TY - BOOK T1 - Essential Tremor - the Facts A1 - Mark Plumb A1 - Peter Bain Y1 - 2007/// VL - First PB - Oxford University Press CY - Oxford, UK N2 - - ER - TY - BOOK T1 - Treating violence: a guide to risk management in mental health A1 - Maden T Y1 - 2007/01// PB - Oxford University Press CY - Oxford SN - 0-1985-2690-3 SP - 1 EP - 200 N2 - - ER - TY - BOOK T1 - Working with children and adolescents: an evidence-based approach to risk and resilience. A1 - Garralda ME A1 - Flament M ED - Garralda ME Flament M Y1 - 2006/// VL - First PB - Rowman and Littlefield CY - New York N2 - - ER - TY - BOOK T1 - Coping with Multiple Sclerosis A1 - Cynthia Benz A1 - Richard Reynolds Y1 - 2005/05// PB - Vermilion CY - London SN - 0091902460 SP - 1 EP - 302 N2 - - ER - TY - BOOK T1 - Guide to Psychiatric Examination A1 - Aquilina C A1 - Warner J Y1 - 2004/// PB - Pastest SN - 1-9046-2714-5 N2 - - ER - TY - BOOK T1 - Clinical Disorders of Posture and Gait A1 - Bronstein AM ED - Bronstein AM; Brandt T; Woollacott MH; Nutt JG Y1 - 2004/// PB - Arnold CY - London SN - 0 340 80657 5 N2 - - UR - http://www.hodderheadline.co.uk/index.asp?url=bookdetails.asp&book=37741 ER - TY - BOOK T1 - How to cope with stress A1 - Tyrer P Y1 - 2003/04// PB - Sheldon Press CY - London SN - 0-85969-880-7 N2 - - ER - TY - BOOK T1 - Textbook of Clinical pain Managment A1 - Rice AS ED - Rice; Warfield; Justins; Eccleston Y1 - 2003/// PB - Arnold CY - London N2 - - ER - TY - BOOK T1 - Managing Children with Psychiatric Problems A1 - Garralda Hualde ME ED - Garralda ME; Hyde C Y1 - 2003/// PB - BMJ N2 - - ER - TY - BOOK T1 - Autonomic Failure: A Textbook of Clinical Disorders of the Autonomic Nervous System A1 - Mathias CJ ED - Mathias CJ; Bannister R Y1 - 2002/// PB - Oxford University Press CY - Oxford SN - 0-1926-2850-X N2 - - ER - TY - BOOK T1 - Dementia: Alzheimer's disease and other dementias A1 - Cayton H A1 - Graham N A1 - Warner J Y1 - 2002/// SN - 1-8595-9075-6 N2 - - ER - TY - BOOK T1 - Outcome of psychiatric admission through the courts. A1 - James D A1 - Farnham F A1 - Moorey H A1 - Lloyd H A1 - Hill K A1 - Blizard R A1 - Barnes TRE Y1 - 2002/// PB - RDS Occasional Paper No. 79. Home Office CY - London SN - 1-84082-804-8 N2 - - ER - TY - BOOK T1 - Neurological Disorders: Course and Management A1 - Brandt, T A1 - Caplan, L R A1 - Dichgans, J A1 - Diener, H C A1 - Kennard , C Y1 - 2002/// VL - 2nd PB - Academic Press CY - San Diego N2 - - ER - TY - BOOK T1 - Current issues in essential tremor. A continuing medical education monograph. A1 - Bain, PG A1 - Brin, MF A1 - Deuschl, G A1 - Elble, RJ A1 - Findley, LJ A1 - Jankovic, J A1 - Koller, WC A1 - Pahwah, R Y1 - 1999/// PB - Embryon, Inc N2 - - ER - TY - CHAP T1 - Choroideremia A1 - MacDonald I A1 - Meltzer MR A1 - Smaoui N T2 - GeneReviews at GeneTests: Medical Genetics Information Resource [database online] 1997-2007 Y1 - 2007/04// N2 - - UR - http://www.genetests.org ER - TY - CHAP T1 - Spindle cell oncocytoma A1 - Fuller GN A1 - Scheithauer BW A1 - Roncaroli F A1 - Wesseling P ED - Louis DN, Ohgaki H, Wiesler OD, Cavanee WK T2 - WHO Classification of Tumours of the Central Nervous System Y1 - 2007/// VL - Third PB - WHO Press - IARC CY - Lyon, France SP - 245 EP - 246 N2 - - ER - TY - CHAP T1 - Treatment options for young people and refugees with posttraumatic stress disorder A1 - Hodes M A1 - Diaz-Caneja A ED - Hosin A T2 - Children, Families and Refugees of Multiple Traumas: Contemporary Issues in Mental Health Y1 - 2006/11// PB - Palgrave Macmillan CY - Basingstoke, Hampshire SN - 1403996806 N2 - - ER - TY - CHAP T1 - Application of MRI to Cell Tracking A1 - Bhakoo, K A1 - Chapon, C A1 - Jackson, J A1 - Jones, W ED - G.A. Webb T2 - Handbook of Modern Magnetic Resonance: Biological Sciences Y1 - 2006/// PB - Springer SP - (in press) N2 - - ER - TY - CHAP T1 - Cannabinoids A1 - Lever, I ED - C Stein T2 - Handbook of Experimental Pharmacology analgesia Y1 - 2006/// PB - Springer CY - Berlin N2 - - ER - TY - CHAP T1 - Epidemiology. A1 - Crawford M ED - C. Freeman, P. Tyrer T2 - Research Methods in Psychiatry Y1 - 2006/// VL - 3rd Edition PB - Gaskell CY - London SP - 53 EP - 72 N2 - - ER - TY - CHAP T1 - New treatments for neuropathic pain A1 - Hill, R T2 - Annual Review of Medicine Y1 - 2006/// VL - 57 SP - 535 EP - 551 N2 - - ER - TY - CHAP T1 - Biomarkers in pain. A1 - Urban, L. A1 - Nagy, I. A1 - Lukacs, K. A1 - Santha, P. ED - James N. Campbell, Allan J. Basbaum, Andre Dray, Ronald Dubner, Robert H. Dworkin and Christine N. Sang, T2 - Emerging Strategies for the Treatment of Chronic Pain Y1 - 2006/// PB - IASP Press CY - Seatle SP - 457 EP - 474 N2 - - ER - TY - CHAP T1 - Functional somatic symptoms and somatoform disorders in children A1 - Garralda ME ED - C Gillberg, R Harrington, HC Steinhausen T2 - A Clinician's Handbook of Child and Adolescent Psychiatry Y1 - 2006/// PB - Cambridge University Press SP - 246 EP - 271 N2 - - ER - TY - CHAP T1 - Control of activity: Relationship between excitatory and inhibitory receptors expressed by nociceptors. A1 - Nagy, I. A1 - Reeh, P. A1 - Srubek Tomassy, G. A1 - Santha, P. ED - Herta Flor, Eija Kalso, and Jonathan O. Dostrovsky T2 - Proceedings of the 11th World Congress on Pain Y1 - 2006/// PB - IASP Press CY - Seatle SP - 109 EP - 110 N2 - - ER - TY - CHAP T1 - Application of MRI to Stem Cell Imaging A1 - Bhakoo, K A1 - Jones, W A1 - Jackson, J A1 - Chapon, C ED - N.A. Habib, M.Y. Gordon, N. Levicar et al T2 - Stem Cell Repair and Regeneration Y1 - 2005/// PB - Imperial College Press CY - London N2 - - ER - TY - CHAP T1 - The Clinical Assessment of Essential Tremor A1 - Bain PG ED - Pahwa & Lyons T2 - Handbook of essential tremor and other tremor disoders Y1 - 2005/// PB - Marcel Dekker SN - 0-8247-2645-6 SP - 93 EP - 115 N2 - - ER - TY - CHAP T1 - Cannabinoids A1 - Rice, A.S.C ED - McMahon, S.B and Koltzenburg, M T2 - Melzack and Wall's Textbook of Pain Y1 - 2005/// VL - 5th PB - Elsvier CY - Amsterdam N2 - - ER - TY - CHAP T1 - Pain in HIV and Aids A1 - Marshall, S.J A1 - Cox, S ED - Ballantyne J T2 - Handbook of Pain Management Y1 - 2005/// VL - 3rd PB - Lippincott, Williams and Wilkins CY - Philadelphia SP - 446 EP - 462 N2 - - ER - TY - CHAP T1 - Refugee children in the UK A1 - Hodes M ED - M Malek & C Joughin T2 - Mental Health Services for Minority Ethnic Children Y1 - 2004/// PB - Jessica Kingsley CY - London SN - 1-84310-236-6 SP - 152 EP - 168 N2 - - ER - TY - CHAP T1 - Extrapyramidal symptoms A1 - Dursun S A1 - Haddad PM A1 - Barnes TRE ED - P Haddad, S Dursun, B Deakin T2 - Adverse syndromes and psychiatric drugs Y1 - 2004/// PB - Oxford University Press CY - Oxford SN - 0-19-852748-9 SP - 1 EP - 20 N2 - - ER - TY - CHAP T1 - Sensory processing: Primary afferent neurons/DRG. A1 - Nagy I ED - Evers; Maze T2 - Anesthetic Pharmacology: Physiologic Principles and Clinical Practice. Y1 - 2004/// PB - Chirchill Livingstone CY - Philadelphia SP - 187 EP - 197 N2 - - ER - TY - CHAP T1 - Neurological eye problems A1 - Hussain, M A1 - Kennard, C T2 - Medicine 32 Y1 - 2004/// SP - 6 EP - 9 N2 - - ER - TY - CHAP T1 - Degenerative and metabolic disorders in adults A1 - Nachev P A1 - Kennard, C ED - N. R. Miller, N. J. Newman, T2 - Walsh and Hoyt's Clinical Neuro-opthalmology Y1 - 2004/// VL - 6th PB - Williams and Wilkins CY - Baltimore SP - 2513 EP - 2550 N2 - - ER - TY - CHAP T1 - Cognitive-behavior therapy for patients with physical illnesses A1 - Sensky T ED - Wright JH T2 - Review of Psychiatry Y1 - 2004/// M2 - 23 No 3 PB - American Psychiatric Press CY - Washington DC SN - 1-58562-178-1 SP - 83 EP - 121 N2 - - ER - TY - CHAP T1 - Glycosylation and Muscular Dystrophy A1 - Brown SC A1 - Muntoni F ED - Winder SJ T2 - Molecular Mechanisms in Muscular Dystrophy Y1 - 2004/// PB - Landes Bioscience N2 - - ER - TY - CHAP T1 - Challenges to psychiatry: antipsychiatry, the user movement and stigma. A1 - Moncrieff J A1 - Byrne P ED - P. Wright, J. Stern, M. Phelan T2 - Core Psychiatry Y1 - 2004/// SN - 0-7020-2718-9 SP - 1 EP - 18 N2 - - ER - TY - CHAP T1 - The Application of Magnetic Resonance Imaging and Spectroscopy to Gene Therapy A1 - Bhakoo, K K A1 - Bell, J D A1 - Cox, I J A1 - Taylor-Robinson, S D T2 - Methods in Enzymology Y1 - 2004/// VL - Imaging in Biological Research M2 - 386 PB - Elsevier Inc. SP - 303 EP - 313 N2 - - UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=15120258&query_hl=7&itool=pubmed_DocSum ER - TY - CHAP T1 - The hypothalamo-pituitary-adrenal axis A1 - John CD A1 - Theogaraj E A1 - Buckingham JC ED - Evers E & Maze M T2 - Anaesthetic Pharmacology: Physiologic Principles and Clinical Practice Y1 - 2004/// PB - Harcourt Health Sciences CY - St Louis, Missouri, USA N2 - - ER - TY - CHAP T1 - Movement disorders in unmedicated schizophrenia A1 - Barbenel DM A1 - Barnes TRE ED - KP Sethi T2 - Drug-Induced Movement Disorders Y1 - 2004/// PB - Marcel Dekker CY - New York SP - 15 EP - 36 N2 - - ER - TY - CHAP T1 - Pituitary carcinoma A1 - Scheithauer BW A1 - Kovacs K A1 - Horvath E A1 - Roncaroli F A1 - Ezzat S A1 - Asa SL A1 - Lloyd RV A1 - Nose V A1 - Watson RE Jr A1 - Lindell EP ED - DeLellis RA, Lloyd RV, Heitz U, Eng C T2 - Pathology & Genetics of Tumours of Endocrine Organs Y1 - 2004/// PB - IARC Press CY - Lyon France SP - 36 EP - 39 N2 - - ER - TY - CHAP T1 - Oculomotor dysfunction in Parkinson's disease A1 - Nachev, P A1 - Kennard, C ED - RF Pfieffer, I Bodis-Wollner T2 - Parkinson's disease and non-motor dysfunction Y1 - 2004/// SP - 235 EP - 256 N2 - - ER - TY - CHAP T1 - Normal and abnormal eye movements A1 - Kennard C ED - L Luxon T2 - A Textbook of Audiological Medicine: Clinical Aspects of Hearing and Balance Y1 - 2003/// PB - Martin Dunitz CY - London SP - 781 EP - 796 N2 - - ER - TY - CHAP T1 - Sex differences in pain A1 - Holdcroft A A1 - Berkley KJ ED - Melzack R, Wall PD T2 - Handbook of Pain Management Y1 - 2003/// PB - Churchill Livingstone CY - Edinburgh SP - 569 EP - 579 N2 - - ER - TY - CHAP T1 - Scales to measure behavioural and emotional adjustment in children and their families A1 - Gledhill J A1 - Garralda ME ED - D Skuse T2 - Child Psychology and Psychiatry: An Introduction Y1 - 2003/// PB - The Medicine Publishing Company CY - Oxon SP - 39 EP - 48 N2 - - ER - TY - CHAP T1 - Vestibular system disorders A1 - Kennard, C T2 - Encyclopaedia of Life Sciences Y1 - 2003/// PB - Macmillan Reference Limited (in press) N2 - - ER - TY - CHAP T1 - Adjustment and psychopathology amongst Afro-Caribbean children and adolescents in the U.K. A1 - Kramer T A1 - Hodes M ED - D. Ndegwa & D. Olajide T2 - Main Issues in Mental Health and Race Y1 - 2003/// PB - Ashgate CY - Aldershot, England SP - 175 EP - 200 N2 - - ER - TY - CHAP T1 - Local Neuroimmune interactions in visceral hyperalgesia. Bradykinin neutrophins and cannabinoids A1 - Rice, A.S.C ED - Bountra, C, Munglani R and Schmid, V.K T2 - Pain: Current understanding, emerging therapies and novel approaches to drug discovery Y1 - 2003/// PB - Marcel Dekker CY - New York SP - 135 EP - 148 N2 - - ER - TY - CHAP T1 - Somatisation and somatoform disorders in childhood and adolescence A1 - Garralda ME ED - D Skuse T2 - Child Psychology and Psychiatry: An Introduction Y1 - 2003/// PB - The Medicine Publishing Company CY - Oxon SP - 129 EP - 132 N2 - - ER - TY - CHAP T1 - Self, identity and acceptance in chronic pain A1 - Crombez G A1 - Morley S A1 - MacCracken L A1 - Sensky T A1 - Pincus T ED - Dostrovsky JO, Carr DB, Koltzenberg M T2 - Progress in Pain Research and Management Y1 - 2003/// PB - International Association for the Study of Pain CY - Seattle WA SN - 0-9310-9246-9 SP - 651 EP - 659 N2 - - ER - TY - CHAP T1 - Tremor A1 - Bain PG A1 - Navan P A1 - Aziz TZ ED - Brandt T, Caplan LR, Dichgans J, Diener HC, Kennard C T2 - Neurological Disorders: Course and Treatment, 2nd Edition Y1 - 2003/// M2 - Ch 86 PB - Academic Press CY - London SP - 1233 EP - 1245 N2 - - ER - TY - CHAP T1 - Mortality and sudden death in schizophrenia A1 - Barnes TRE A1 - Kerwin R ED - J Camm. T2 - Cardiovascular Risk Associated with Schizophrenia and its Treatment Y1 - 2003/// PB - Galliard Healthcare Communications CY - London SN - 0-9544351-0-9 SP - 7 EP - 23 N2 - - ER - TY - CHAP T1 - Lesions of the periphery and spinal cord A1 - Angel MJ A1 - Davey N A1 - Ellaway P A1 - Chen R ED - Boniface S, Ziemann U T2 - Plasticity in the human nervous system Y1 - 2003/// PB - Cambridge University Press CY - Cambridge SN - 0-5110-5752-0 SP - 204 EP - 230 N2 - - ER - TY - CHAP T1 - Family work and family therapy in child mental health A1 - Goldberg D A1 - Hodes M ED - E Garralda & C Hyde T2 - Managing Children with Psychiatric Problems Y1 - 2003/// PB - BMJ Publishing Group Ltd CY - London SP - 111 EP - 123 N2 - - ER - TY - CHAP T1 - Dementing illness and Complementary and Alternative Medicine A1 - McCarney R A1 - Warner J ED - Cherniak P and Cherniak N T2 - Alternative Medicine for the Elderly Y1 - 2003/// PB - Springer CY - Berlin SN - 3-5404-4169-7 SP - 425 EP - 436 N2 - - ER - TY - CHAP T1 - Visual Pathways A1 - Kennard C ED - D A Warrell, T M Cox, J D Firth, E J Benz T2 - The Oxford Textbook of Medicine Y1 - 2003/// VL - 4th M2 - Vol 3 PB - Oxford University Press SP - 972 EP - 978 N2 - - ER - TY - CHAP T1 - Cannabinoids anad Pain Proceedings of the 10th World Congress on Pain A1 - Rice, A.S.C A1 - Farquhar-Smith, W.P A1 - Bridges, D ED - Dostrovsky, J.O. Carr, D.H and Kolztenburg, M T2 - Progress in Pain Control and Management Y1 - 2003/// M2 - 24 PB - IASB Press CY - Seattle SP - 437 EP - 467 N2 - - ER - TY - CHAP T1 - Analgesics: cannabinoids A1 - Rice, A.S.C ED - Evers, A and Maze, M T2 - Anesthetic Pharmacology: Physiologic Principles and Clinical Practice Y1 - 2003/// PB - Harcourt Health Sciences CY - St Louis SP - 491 EP - 506 N2 - - ER - TY - CHAP T1 - Anxiety Disorders in Chilren and Adolescents A1 - Fung G A1 - Garralda ME ED - D Skuse T2 - Child Psychology and Psychiatry: An Introduction Y1 - 2003/// PB - The Medicine Publishing Company CY - Oxon SP - 141 EP - 146 N2 - - ER - TY - CHAP T1 - Immunological Aspects of Multiple Sclerosis with Emphasis on the Potential Use of Autologous Hemopoietic Stem Cell Transplantation A1 - Muraro, P A A1 - McFarland, H F A1 - Martin, R ED - Burt R, Marmont A T2 - Stem Cell Therapy for Autoimmune Diseas Y1 - 2003/// PB - Landes Bioscience CY - Georgetown, TX SN - 1-58706-031-0 SP - 277 EP - 283 N2 - - UR - http://www.landesbioscience.com/books/special/id/812 ER - TY - CHAP T1 - Essential tremor and primary writing tremor A1 - Bain PG ED - Hallet M T2 - the Handbook of Clinical Neurophysiology, Vol 1: Movement Disorders Y1 - 2003/// M2 - Ch 23 PB - Elselvier Science CY - Amsterdam SP - 365 EP - 376 N2 - - ER - TY - CHAP T1 - Risk factors for dyskinesia in the elderly A1 - Barnes TRE T2 - Principles and Practice of Geriatric Psychiatry Y1 - 2002/// M2 - 2nd SN - 0-4719-8197-4 SP - 527 EP - 533 N2 - - ER - TY - CHAP T1 - Investigation of autonomic disorders A1 - Mathias CJ A1 - Bannister R ED - Mathias CJ, Bannister R T2 - Autonomic Failure: A Textbook of Clinical Disorders of the Autonomic Nervous System Y1 - 2002/// M2 - 4th edition PB - Oxford University Press CY - Oxford SP - 169 EP - 195 N2 - - ER - TY - CHAP T1 - Primary Health Care Psychiatry A1 - Garralda ME T2 - Child and Adolescent Psychiatry Y1 - 2002/// M2 - 4th SN - 0-6320-1228-5 SP - 1090 EP - 1100 N2 - - ER - TY - CHAP T1 - Annexin 1 (Lipocortin 1) A1 - Solito E A1 - Mulla A A1 - Flower RJ A1 - Buckingham JC T2 - Wiley Encyclopaedia of Molecular Medicine Y1 - 2002/// SN - 0-4713-7496-2 SP - 1943 EP - 1947 N2 - - ER - TY - CHAP T1 - Introduction and classification of autonomic disorders A1 - Bannister R A1 - Mathias CJ ED - Mathias CJ, Bannister R T2 - Autonomic Failure: A Textbook of Clinical Disorders of the Autonomic Nervous System Y1 - 2002/// M2 - 4th edition PB - Oxford University Press CY - Oxford N2 - - ER - TY - CHAP T1 - Social function, chronic strains and personality difficulties A1 - Tyrer P A1 - Karlsen S A1 - Crawford MJ T2 - Ethnic minority psychiatric illness rates in the community (EMPIRIC) - Quantitative report Y1 - 2002/// SN - 0-1132-2582-2 SP - 63 EP - 71 N2 - - UR - http://www.doh.gov.uk/public/empiric.pdf ER - TY - CHAP T1 - Endocannabinoids and Pain Spinal and Peripheral Analgesia in Inflammation and Neuropathy A1 - Rice, A.S.C A1 - Farquhar-Smith, W.P T2 - Prostaglandins Leukotrienes and Essential Fatty Acids Y1 - 2002/// VL - 66 M2 - 2-3 SP - 243 EP - 256 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 - Social function, chronic strains and personality difficulties A1 - Tyrer P A1 - Karlsen S A1 - Crawford MJ T2 - Ethnic minority psychiatric illness rates in the community (EMPIRIC) - Quantitative report Y1 - 2002/// SN - 0-1132-2582-2 SP - 63 EP - 71 N2 - - UR - http://www.doh.gov.uk/public/empiric.pdf 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 - Cannabimmetric eicosanoids in cancer and inflammation: an update A1 - Melck, D A1 - Bisogno, T A1 - De Petrocellis, L A1 - Beaulieu, P A1 - Rice, A.S.C T2 - Adv Exp Biol Med. Eicosanids and Other bioactive Lipids in Cancer Inflammation and Radiation Injuryry Y1 - 2002/// M2 - 507 SP - 381 EP - 386 N2 - - ER - TY - CHAP T1 - Pain: Sex/Gender Differences A1 - Berkley KJ A1 - Hoffman G A1 - Murry AZ A1 - Holdcroft A T2 - Hormones, Brains and Behaviour Y1 - 2002/// SN - 0-1253-2104-X N2 - - ER - TY - CHAP T1 - Drink, drugs and dependence: from science to clinical practice A1 - Cann W A1 - de Belleroche J Y1 - 2002/// SN - 0-4152-7891-0 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 - Applied physiology of inflammatory pain. A1 - Nagy I A1 - Rice A ED - Rice; Warfield; Justins; Eccleston T2 - Clinical Pain Management Y1 - 2002/// M2 - Acute Pain PB - Arnold CY - London SP - 17 EP - 42 N2 - - ER - TY - CHAP T1 - Postprandial hypotension in autonomic disorders A1 - Mathias CJ A1 - Bannister R ED - Mathias CJ, Bannister R T2 - Autonomic Failure: A Textbook of Clinical Disorders of the Autonomic Nervous System Y1 - 2002/// M2 - 4th edition PB - Oxford University Press CY - Oxford SP - 283 EP - 295 N2 - - ER - TY - CHAP T1 - Indications for Cannabis and THC: Pain Therapy A1 - Holdcroft A T2 - Cannabis, Cannabinoids, Pharmacology, Toxicology and Therapeutic Potential Y1 - 2002/// SN - 0-7890-1507-2 N2 - - ER - TY - CHAP T1 - Promoting continuity of care for people with severe mental illness whose needs span primary, secondary and social care A1 - Freeman G A1 - Crawford MJ A1 - Weaver T A1 - Low J A1 - de Jonge E T2 - Report for the National Co-ordinating Centre for NHS Service Delivery and Organisation R & D (NCCSDO Y1 - 2002/// N2 - - UR - http://www.sdo.lshtm.ac.uk/pdf/coc_mentalillness_freeman.pdf ER - TY - CHAP T1 - Mechanisms of Inflammatory Pain: Role of neurotrophins and cannabinoids A1 - Rice AS Y1 - 2002/// SN - 1-8531-5481-4 SP - 35 EP - 45 N2 - - ER - TY - CHAP T1 - Autonomic function and dysfunction A1 - Mathias CJ T2 - Diseases of the nervous system: Clinical neuorscience and therapeutic principles Y1 - 2002/// M2 - 3rd SN - 0-5217-9351-3 SP - 773 EP - 794 N2 - - ER - TY - CHAP T1 - Disorders of Vision A1 - Morland, A A1 - Kennard, C ED - A.K. Asbury, G.M. McKhann, W.I. McDonald T2 - Diseases of the Nervous System - Clinical Neurobiology Y1 - 2002/// VL - 3rd PB - Saunders CY - Philadelphia SP - 621 EP - 633 N2 - - ER - TY - CHAP T1 - Current treatment opinions in neuropathic pain A1 - Hempenstall, K T2 - Current Opinion in Investigational Drugs Y1 - 2002/// VL - 3 M2 - 3 SP - 441 EP - 448 N2 - - ER - TY - CHAP T1 - CHM (Choroideremia) Gene A1 - van den Hurk, J.A.J.M. A1 - Cremers, F.P.M. A1 - Seabra, M.C. T2 - Wiley Encylopedia of Molecular Medicine Y1 - 2002/// PB - John Wiley & Sons Inc. SP - 750 EP - 752 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/// SN - 0-8799-3499-9 SP - 135 EP - 152 N2 - - ER - TY - CHAP T1 - Pharmacologie des derives cannabinoides: applications au raitement de la douleur? A1 - Rice, A.S.C T2 - Ann Fr Anesth Reanim Y1 - 2002/// VL - 21 M2 - 6 SP - 493 EP - 508 N2 - - ER - TY - CHAP T1 - Alzheimer's disease A1 - Warner JP A1 - Butler RE Y1 - 2001/06// SN - 0-7279-1504-5 SP - 630 EP - 641 N2 - - ER - TY - CHAP T1 - Visual defects as a result of occipital lesions A1 - Pambakian ALM A1 - Kennard, C ED - JE Harrison, AM Owen, Martin Dunitz T2 - Cognitive deficits in brain disorders Y1 - 2001/// CY - London SP - 99 EP - 120 N2 - - ER - TY - CHAP T1 - Cannabinoids and pain A1 - Rice, A.S.C T2 - Current Opinion In Investigational Drugs Y1 - 2001/// VL - 2 M2 - 3 SP - 399 EP - 414 N2 - - ER - TY - CHAP T1 - Neuro-ophthalmology A1 - Kennard C Y1 - 2001/// M2 - 11th edition (8) SN - 0-1926-2618-3 SP - 237 EP - 294 N2 - - ER - TY - CHAP T1 - Abnormalities of smell and taste A1 - Kennard C Y1 - 2001/// VL - 11th SN - 0-1926-2618-3 SP - 311 EP - 316 N2 - - ER - TY - CHAP T1 - Suicide and suicide attempts A1 - Crawford M Y1 - 2001/// SN - 1-8530-2934-3 SP - 259 EP - 262 N2 - - ER - TY - CHAP T1 - Mechanisms of neuropathic pain A1 - Bridges, D A1 - Thompson, S.W.N T2 - British Journal of Anaesthesia Y1 - 2001/// VL - 87 M2 - 1 SP - 12 EP - 26 N2 - - ER - TY - CHAP T1 - The molecular and cellular biology of muscle A1 - Brown SC A1 - Walsh FS A1 - Dickson G ED - Karparti G; Hilton-Jones D; Griggs RC T2 - Disorders of Voluntary Muscle Y1 - 2001/// M2 - 7th PB - Cambridge University Press SN - 0-5216-5062-3 SP - 42 EP - 49 N2 - - ER - TY - CHAP T1 - Tremor behaviour trial design and physiological outcome measures A1 - Alusi SH A1 - Bain PG Y1 - 2001/// M2 - 29 SN - 1-8523-3239-5 SP - 347 EP - 358 N2 - - ER - TY - CHAP T1 - Methods for evaluating community treatments A1 - Tyrer P Y1 - 2001/// SN - 0-1926-2997-2 SP - 63 EP - 72 N2 - - ER - TY - CHAP T1 - Is there a single best surgical procedure for the alleviation of Parkinson's disease? Basal Ganglia and Thalamus A1 - Aziz T A1 - Parkin S A1 - Joint C A1 - Gregory R A1 - Bain PG A1 - Stein JF A1 - Scott R ED - Llinsky K, Llinsky IA T2 - Health and Movement Disorders Y1 - 2001/// PB - Kluwer Academic/Plenum Publishers CY - New York SP - 317 EP - 326 N2 - - ER - TY - CHAP T1 - Congenital muscular dystrophies A1 - Mercuri E A1 - Muntoni F Y1 - 2001/// SN - 0-1926-3291-4 SP - 10 EP - 38 N2 - - ER - TY - CHAP T1 - Genetics of Duchenne muscular dystrophy A1 - Brown SC A1 - Dickson G ED - Reeve E T2 - Encyclopedia of Genetics Y1 - 2001/// PB - Fitzroy Dearborn SN - 1-8849-6434-6 SP - 467 EP - 473 N2 - - ER - TY - CHAP T1 - The functional neuroanatomy of emotional disorders : focus on depression and posttraumatic stress disorder A1 - Lawrence AD A1 - Grasby PM Y1 - 2001/// M2 - 2nd Edition (10) SN - 0-4445-0362-5 N2 - - ER - TY - CHAP T1 - Tremor clinical measurement of impairment, disability and handicap A1 - Alusi SH A1 - Bain PG Y1 - 2001/// M2 - 28 SN - 1-8523-3239-5 SP - 339 EP - 346 N2 - - ER - TY - CHAP T1 - Deafness, vertigo and imbalance A1 - Kennard C Y1 - 2001/// M2 - 11th edition (9) SN - 0-1926-2618-3 SP - 295 EP - 310 N2 - - ER - TY - CHAP T1 - Diplopia and ptosis in a young man A1 - Mort DJ A1 - Kennard C Y1 - 2001/// M2 - (Case 20) SN - 0-7506-4304-8 SP - 165 EP - 175 N2 - - ER - TY - CHAP T1 - The ATP-sensitive potassium channel: a metabolic sensor A1 - F.M. Ashcroft A1 - S. Trapp ED - K.B. Storey T2 - Molecular Mechanisms of Metabolic Arrest; Life in Limbo Y1 - 2001/// PB - BIOS Scientific Publishers Ltd CY - Oxford SN - 1859962122 SP - 43 EP - 58 N2 - - ER - TY - CHAP T1 - Looking and seeing Gordon Holmes - 1936 John Mallet Purser Lecture revisited A1 - Kennard, C ED - R Clifford-Rose T2 - Twentieth Century Neurology Y1 - 2001/// PB - Imperial College Press SP - 107 EP - 114 N2 - - ER - TY - CHAP T1 - Retinitis pigmentosa and allied disorders A1 - Weleber RG A1 - Gregory-Evans K ED - SJ Ryan T2 - Retina Y1 - 2001/// PB - Mosby, Inc. CY - St Louis, Missouri, USA SN - 0-323-00804-6 SP - 362 EP - 460 N2 - - ER - TY - CHAP T1 - Glucocorticoids and the HPA axis A1 - Cowell AM A1 - Buckingham JC Y1 - 2001/// SN - 3-7643-6059-3 SP - 129 EP - 146 N2 - - ER - TY - CHAP T1 - Sexuality and Dementia A1 - Warner JP ED - O'Brien, Ames and Burns T2 - Dementia Y1 - 2000/// PB - Chapman Hall CY - London SN - 0 340 75916 X N2 - - ER - TY - CHAP T1 - Disorders of the autonomic nervous system A1 - Mathias CJ ED - WG Bradley, RB Daroff, GM Fenichel, CD Marsden T2 - Neurology in Clinical Practice Y1 - 2000/// M2 - 3rd edition PB - Butterworth-Heinemann CY - Boston, USA SP - 2131 EP - 2165 N2 - - ER - TY - CHAP T1 - Treating neurogenic orthostatic hypotension A1 - Wieling W A1 - Cortelli P A1 - Mathias CJ ED - PJ Vinken, GW Bruyn T2 - Handbook of Clinical Neurology Y1 - 2000/// M2 - Vol 75 PB - Elsevier NV CY - Amsterdam, The Netherlands SP - 713 EP - 729 N2 - - ER - TY - CHAP T1 - Biochemistry of Rab geranylgeranyl transferase A1 - Seabra, M.C. ED - Tamanoi, F. and Sigman, D. T2 - The Enzymes Y1 - 2000/// M2 - XXI PB - Academic Press CY - New York SP - 131 EP - 154 N2 - - ER - TY - CHAP T1 - Glucocorticoids: Role in stress A1 - Buckingham JC ED - Fink G T2 - The Encyclopaedia of Stress Y1 - 2000/// PB - Academic Press CY - New York SP - 261 EP - 279 N2 - - ER - TY - CHAP T1 - Drug Treatment of Neuropathic Pain A1 - Anonymous (see Drugs and Therapeutics, Bulletin T2 - Drugs and Therapies Bulletin Y1 - 2000/// VL - 38 M2 - 12 SP - 89 EP - 93 N2 - - ER - TY - CHAP T1 - Children of mothers with eating disorders A1 - Reder P A1 - McClure M A1 - Jolley A T2 - Family Matters: Interfaces between Child and Adult Mental Health Y1 - 2000/// PB - Routledge, Taylor & Francis Group. CY - London & Philadelphia SN - 0-415-22218-4 SP - 107 EP - 121 N2 - - ER - TY - CHAP T1 - Neuro-opthamological manifestations of neurodegenerative diseases A1 - Mort, D J A1 - Kennard , C T2 - Neurology of the eye Y1 - 2000/// PB - Optometry Today CY - London N2 - - ER - TY - CHAP T1 - Autonomic dysfunction A1 - Mathias CJ ED - J Grimley-Evans T2 - Oxford Textbook of Geriatric Medicine Y1 - 2000/// M2 - 2nd Edition PB - Oxford University Press CY - Oxford SP - 883 EP - 852 N2 - - ER - TY - CHAP T1 - Lipocortin 1 A1 - Mulla A A1 - Flower RJ A1 - Buckingham JC ED - Fink G T2 - The Encyclopaedia of Stress Y1 - 2000/// PB - Academic Press CY - New York SP - 623 EP - 628 N2 - - ER - TY - CHAP T1 - Glucocorticoids: Effects of stress on A1 - Buckingham JC ED - Fink G T2 - The Encyclopaedia of Stress Y1 - 2000/// PB - Academic Press CY - New York SP - 229 EP - 243 N2 - - ER - TY - CHAP T1 - Autonomic dysfunction and hypotension A1 - Mathias CJ ED - JT Willerson, JN Cohn T2 - Cardiovascular Medicine Y1 - 2000/// M2 - 2nd edition PB - WB Saunders Company SP - 1537 EP - 1560 N2 - - ER - TY - CHAP T1 - The autonomic nervous system and gastrointestinal disorders A1 - Albanese A A1 - Brisinda G A1 - Mathias CJ ED - PJ Vinken, GW Bruyn T2 - Handbook of Clinical Neurology Y1 - 2000/// M2 - Vol 75 PB - Elsevier NV CY - Amsterdam, The Netherlands SP - 613 EP - 663 N2 - - ER - TY - CHAP T1 - Testing the visual system A1 - Pambakian A1 - Kennard, C ED - A Crockard, R Hayward, T Hoff T2 - Neurosurgery the Scientific Basis of Clinical Practice Y1 - 2000/// VL - 3rd PB - Blackwell Science SP - 975 EP - 998 N2 - - ER - TY - CHAP T1 - Non-microelectrode recording guided pallidotomy. Indications, technique and results. A1 - Bowen, J A1 - Munro-Davies, LE A1 - Silburn, P A1 - Gregoy, R A1 - Bain, PG A1 - Scott, R A1 - Joint, C A1 - Hall, B A1 - Stein, J ED - Lozano AM T2 - Movement Disorder Surgery Y1 - 1999/// PB - Karger CY - Basel N2 - - ER - TY - CHAP T1 - Disorders of visual perception A1 - Kennard, C ED - D.L. Easty, J.M. Sparrow T2 - Oxford Textbook of Opthamology Y1 - 1999/// PB - Oxford Medical Publishing SP - 857 EP - 859 N2 - - ER - TY - CHAP T1 - Pain mechanisms and pathways A1 - Rice, A.S.C T2 - Current Anaesthesia and Critical Care Y1 - 1999/// VL - 10 SP - 98 EP - 104 N2 - - ER - TY - CHAP T1 - The naïve and memory MBP-reactive CD4+ T cell repertoire A1 - Muraro, P A A1 - Bielekova, B ED - Gambi D, Muraro PA, Lugaresi A T2 - Advances in the Immunopathogenesis of Multiple Sclerosis Y1 - 1999/// PB - Springer-Verlag CY - Milan SN - 88-470-0067-X SP - 11 EP - 19 N2 - - UR - http://www.springer.de ER - TY - CHAP T1 - Hereditary pigmentary retinal and macular dystrophies A1 - Gregory-Evans G A1 - Bird AC ED - Easty & J Sparrow T2 - Oxford textbook of Ophthalmology Y1 - 1999/// PB - Oxford University Press SP - 607 EP - 612 N2 - - ER - TY - CHAP T1 - Hypoglycaemia and the central nervous system A1 - Fuller, G A1 - Kennard , C ED - E Bryn T2 - Handbook of Clinical Neurology Y1 - 1998/// PB - North Holland Publishing SP - 171 EP - 192 N2 - - ER - TY - CHAP T1 - The neuro-opthamology of Movement Disorders A1 - O'Sullivan, E A1 - Kennard, C ED - J. Jankovic, E. Tolosa T2 - Parkinson's Disease and Movement Disorders Y1 - 1998/// PB - Williams and Wilkins CY - Baltimore SP - 869 EP - 886 N2 - - ER - TY - CHAP T1 - Translating research and technological developments into clinical practice A1 - Blunt, S.B. A1 - Kennard, C ED - A Williams T2 - Care of the common neurological illnesses Y1 - 1998/// PB - OUP CY - Oxford SP - 417 EP - 424 N2 - - ER - TY - CHAP T1 - Developments in the pathophysiology of acute pain A1 - Rice, A.S.C T2 - Acute pain Y1 - 1998/// VL - 1 M2 - 2 SP - 27 EP - 36 N2 - - ER - TY - CHAP T1 - Degenerative and metabolic disorders in adults A1 - Kennard, C ED - N. R Miller, N. J Newman, Williams and Wilkins, T2 - Walsh and Hoyt's Clinical Neuro-opthalmology Y1 - 1998/// VL - 5th CY - Baltimore SP - 2747 EP - 2810 N2 - - ER - TY - CHAP T1 - The use of cannabis and its derivatives for medical and recreational purposes A1 - Lachmann, P.J A1 - Edwards, J.G A1 - Pertwee, R.G A1 - Robbins, I.W A1 - Sykes, Sir R A1 - Wall, P.D T2 - The Royal Society and the Academy of Medical Sciences Y1 - 1998/// N2 - - ER - TY - CHAP T1 - Eye Movements A1 - Shaunack, S A1 - O'Sullivan, E A1 - Kennard, C ED - RAC Hughes T2 - Neurological Investigations Y1 - 1997/// PB - BMJ Publishing CY - London SP - 253 EP - 282 N2 - - ER - TY - CHAP T1 - Prevention of nerve damage in branchial plexus block A1 - Rice, A.S.C ED - A Van Zundert T2 - Highights in Pain and Regional Anaesthesia Y1 - 1997/// M2 - VI PB - Permanver Publications SP - 60 EP - 64 N2 - - ER - TY - CONF T1 - Papillary tumor of the pineal region and spindle cell oncocytoma of the pituitary: New tumor entities in the 2007 WHO classification A1 - Roncaroli, F A1 - Scheithauer, BW U1 - Consensus Conference on Classification of Tumours of the Nervous System Y1 - 2007/07// Y2 - // VL - 17 SP - 314 EP - 318 N2 - - ER - TY - CONF T1 - The role of the pre-supplementary motor area in the control of action A1 - Nachev, P A1 - Wydell, H A1 - O'Neill, K A1 - Husain, M A1 - Kennard, C U1 - Symposium on Cortical Control of Higher Motor Cognition - From Basic Neuroscience to Apraxia Y1 - 2007/02// Y2 - // VL - 36 SP - T155 EP - T163 N2 - - ER - TY - CONF T1 - Quantitative sensory tests (perceptual thresholds) in patients with spinal cord injury A1 - Savic, G A1 - Bergstrom, EMK A1 - Davey, NJ A1 - Ellaway, PH A1 - Frankel, HL A1 - Jamous, A A1 - Nicotra, A U1 - 57th Annual Meeting of the American-Academy-of-Neurology Y1 - 2007/// Y2 - // VL - 44 SP - 77 EP - 82 N2 - - ER - TY - CONF T1 - Development of a hyperspectral fluorescence lifetime imaging microscope and its application to tissue imaging - art. no. 64411K A1 - Owen, DM A1 - Manning, HB A1 - de Beule, P A1 - Talbot, C A1 - Requejo-Isidro, J A1 - Dunsby, C A1 - McGinty, J A1 - Benninger, RKP A1 - Elson, DS A1 - Munro, I A1 - Galletly, NP A1 - Lever, MJ A1 - Stamp, GW A1 - Anand, P A1 - Neil, MAA A1 - French, PMW U1 - Conference on Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues V Y1 - 2007/// Y2 - // VL - 6441 SP - K4411 EP - K4411 N2 - - ER - TY - CONF T1 - Review of physiological motor outcome measures in spinal cord injury using transcranial magnetic stimulation and spinal reflexes A1 - Ellaway, PH A1 - Catley, M A1 - Davey, NJ A1 - Kuppuswamy, A A1 - Strutton, P A1 - Frankel, HL A1 - Jamous, A A1 - Savic, G U1 - 57th Annual Meeting of the American-Academy-of-Neurology Y1 - 2007/// Y2 - // VL - 44 SP - 69 EP - 75 N2 - - ER - TY - CONF T1 - A novel hyperspectral lifetime probe for autofluorescence - art. no. 643303 A1 - De Beule, PAA A1 - Dunsby, C A1 - Owen, DM A1 - Galletly, NP A1 - Anand, U A1 - Benham, CD A1 - Naylor, A A1 - Stamp, GW A1 - Anand, P A1 - French, PMW U1 - Conference on Optical Fibers and Sensors for Medical Diagnostics and Treatment Applications VII Y1 - 2007/// Y2 - // VL - 6433 SP - 43303 EP - 43303 N2 - - ER - TY - CONF T1 - Assessment of autonomic dysfunction following spinal cord injury: Rationale for additions to International Standards for Neurological Assessment A1 - Krassioukov, AV A1 - Karlsson, AK A1 - Wecht, JM A1 - Wuermser, LA A1 - Mathias, CJ A1 - Marino, RJ U1 - 57th Annual Meeting of the American-Academy-of-Neurology Y1 - 2007/// Y2 - // VL - 44 SP - 103 EP - 112 N2 - - ER - TY - CONF T1 - Effectiveness of a vibro-tactile feedback to cue a stepping response to a balance challenge. A1 - Asseman, F A1 - Bronstein, AM A1 - Gresty, MA U1 - 5th IEEE International Workshop on Haptic Audio Visual Environments and Their Applications Y1 - 2006/// Y2 - // SP - 90 EP - 92 N2 - - ER - TY - CONF T1 - Dopamine transporter imaging of tremulous disorders A1 - Hensman DJ A1 - Frank JW A1 - Bain PG A2 - Deuschl G, Goetz CG. U1 - Xth International Congress of Parkinson's Disease and Movement Disorders AD - Kyoto, Japan J1 - Movement Disorders 2006; 21: Suppl 15: P1367. Y1 - 2006/// Y2 - 2006/10/30/ N2 - - ER - TY - CONF T1 - Dopamine transporter imaging of patients with essential tremor and features of parkinsonism A1 - Hensman DJ A1 - Frank JW A1 - Towey DJ A1 - Deeb J A1 - Bain PG A2 - Deuschl G & Goetz CG U1 - Xth International Congress of Parkinson's disease and Movement Disorders AD - Kyoto, Japan J1 - Movement Disorders 2006; 21 (suppl 15): P1369. Y1 - 2006/// Y2 - 2006/10/30/ N2 - - ER - TY - CONF T1 - Is abnormal copper metabolism a significant factor in Parkinson’s disease? A1 - Sampson B A1 - Saifee T A1 - Hensman DJ A1 - Frank JW A1 - Bain PG U1 - 5th International Copper Meeting: Copper and Related Metals in Biology. AD - Alghero, Italy. Y1 - 2006/// N2 - - ER - TY - CONF T1 - Parkinson's disease and caeruloplasmin deficiency - is there any connection? A1 - Saifee T A1 - Hensman DJ A1 - Frank W A1 - Barry S A1 - Bain PG A2 - Deuschl G and Goetz CG U1 - Xth International Congress of Parkinson's Disease and Movement Disorders AD - Kyoto, Japan J1 - Movement Disorders 2006; 21 (suppl 15): P439 Y1 - 2006/// Y2 - 2006/10/30/ N2 - - ER - TY - CONF T1 - Systematic assessment of incongruities in the correlation between the clinical signs and DAT imaging in parkinsonism A1 - Hensman DJ A1 - Frank JW A1 - Bain PG A2 - Deuschl G & Goetz CG U1 - Xth International Congress of Parkinson's Disease and Movement Disorders AD - Kyoto, Japan J1 - Movement Disorders 2006; 21 (suppl 15): P1083 Y1 - 2006/// Y2 - 2006/10/30/ 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 - Assessing dysmetric arm movements in 2D: Task design and result visualisation. A1 - Mueller, A A1 - Bain, PG A1 - Liu, X U1 - 5th Forum of European Neuroscience Societies. AD - Vienna J1 - [FENS Abstr. 2006; Vol 3: A112.13] Y1 - 2006/// Y2 - 2006/// N2 - - ER - TY - CONF T1 - DAT imaging and MR evolution in fragile X-associated tremor/ataxia syndrome associated with 53 CGG repeat expansion A1 - Hensman DJ A1 - Nicholas R A1 - Khawaja F A1 - Deeb J A1 - Towey DJ A1 - Frank JW A1 - Colquhoun IR A1 - Bain PG A2 - Deuschl G & Goetz CG U1 - Xth International Congress of Parkinson's Disease and Movement disorders AD - Kyoto, Japan J1 - Movement Disorders 2006; 21 (suppl 15): P1370. Y1 - 2006/// Y2 - 2006/10/30/ 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 - FENS 2006 AD - Vienna, Austria Y1 - 2006/// N2 - - ER - TY - CONF T1 - Brain imaging in the Renaissance A1 - Paluzzi A A1 - Belli A A1 - Bain P A1 - Viva L U1 - Clinical Neurosciences 2005 AD - Torquay, UK J1 - J Neurol Neurosurg Psychiatry 2006; 77(1): 127 Y1 - 2006/// Y2 - 2005/09/07/ SP - 127 N2 - - ER - TY - CONF T1 - The onset of voluntary reactive movement is temporally influenced by tremor in patients with multiple sclerosis. A1 - Wong MF A1 - Bain PG A1 - Liu X A2 - Deuschl G and Goetz CG U1 - Xth International Congress of Parkinson's Disease and Movement Disorders AD - Kyoto, Japan J1 - Movement Disorders 2006; 21 (suppl 15): P1353. Y1 - 2006/// Y2 - 2006/10/30/ N2 - - ER - TY - CONF T1 - The clinical value of dopamine transporter imaging to the movement disorder specialist in managing tremors. A1 - Hensman, DJ A1 - Bain, PG A1 - Frank, JW U1 - British Nuclear Medicine Society AD - Manchester J1 - Nuclear Medicine Communications 2006; 27 (3): 296 Y1 - 2006/// Y2 - 2006/03/27/ N2 - - ER - TY - CONF T1 - Thalamic deep brain stimulation versus thalamotomy for tremor A1 - Hyam JA A1 - Liu X A1 - Bain PG A1 - Aziz TZ U1 - Clinical Neurosciences 2005 AD - Torquay, UK Y1 - 2005/09// SP - 152 N2 - - ER - TY - CONF T1 - Pregnancy in dystonic women with in situ deep brain stimulators A1 - Paluzzi A A1 - Bain PG A1 - Liu X A1 - Yianni J A1 - Kumarendran K A1 - Aziz TZ U1 - Clinical Neurosciences 2005 AD - Torquay, Uk Y1 - 2005/09// Y2 - 2005/09/07/ SP - 174 N2 - - ER - TY - CONF T1 - Complications of deep brain stimulation A1 - Paluzzi A A1 - Belli A A1 - Bain P A1 - Liu X A1 - Aziz TZ U1 - Clinical Neurosciences 2005 AD - Torquay, UK Y1 - 2005/09// Y2 - 2005/09/07/ SP - 154 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 - Insulin-induced membrane currents in capsaicin-sensitive primary sensory neurones A1 - Santha P A1 - Nagy I U1 - Scientific Meeting of The Physiological Society held at King's College London AD - King's College, London, UK Y1 - 2005/// Y2 - // PB - Blackwell N2 - - ER - TY - CONF T1 - Globus pallidus field potentials in patients with primary dystonia. A1 - Wang, S A1 - Yianni, J A1 - Peden, R A1 - Van Bergen, O A1 - Heinzen, J A1 - Bain, P A1 - Aziz, T A1 - Liu, X A1 - Stein, J U1 - Focussed meeting on Neuroscience of Human Movement in Health and Disease, Physiological Society. AD - London J1 - Proc Physiol Soc 2006; 1: PC6 Y1 - 2005/// Y2 - 2005/// N2 - - ER - TY - CONF T1 - Expression of TRPV1 and TRPV1B in dorsal root ganglia innervating the inflamed rat urinary bladder A1 - Charrua A A1 - Reguenga C A1 - Nagy I A1 - Cruz F A1 - Avelino A U1 - 35th Annual Meeting of the Society for Neuroscience AD - Washington DC Y1 - 2005/// Y2 - // VL - 31 PB - Society for Neuroscience SP - 170.8 N2 - - ER - TY - CONF T1 - Control of activity: Interaction between excitatory and inhibitory receptors in nociceptors A1 - Nagy I U1 - 11th World Congress on Pain AD - Sydney, Australia Y1 - 2005/// Y2 - // PB - IASP Press SP - 526 N2 - - ER - TY - CONF T1 - Insulin-induced activation of nociceptive primary sensory neurons A1 - Santha P A1 - Nagy I U1 - 35th Annual Meeting of the Society for Neuroscience AD - Washington DC Y1 - 2005/// Y2 - // VL - 31 PB - Society for Neuroscience SP - 511.25 N2 - - ER - TY - CONF T1 - Lead migration of deep brain stimulation electrodes-role of the plain skull x-ray. A1 - Samuel M A1 - Bain PG A1 - Jarosz J A1 - Aziz TZ A1 - Brand G A1 - Selway R U1 - Ninth International Congress of Parkinson's Disease and Movement Disorders. AD - New Orleans, Louisiana, USA. J1 - Movement Disorders 2005; 20 (suppl 10): S159 Y1 - 2005/// Y2 - 2005/03/05/ PB - Wiley-Liss SN - 0885-3185 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 - Syncope in patients with autonomic nervous system disturbances: Which diagnosis and treatment? A1 - Mathias, CJ U1 - 9th International Workshop on Cardiac Arrhythmias Y1 - 2005/// Y2 - // SP - 643 EP - 653 N2 - - ER - TY - CONF T1 - Dynamic changes in activity of the subthalamic nucleus and forearm muscles related to interemittent rest tremor. A1 - Liu, X A1 - Wang, S-Y A1 - Stein, J A1 - Bain, PG A1 - Aziz, TZ U1 - XIIth European Congress of Clinical Neurophysiology AD - Stockholm Y1 - 2005/// Y2 - 2005/// 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 - XIIth European Congress of Clinical Neurophysiology A1 - Liu, X A1 - Carroll, CB A1 - Wang, SY A1 - Zajicek, J A1 - Bain, PG U1 - Federation of European Neurological Societies AD - Lisbon J1 - FENS Abstr. 2004; vol 2: A131.3. Y1 - 2004/// Y2 - 2004/// N2 - - ER - TY - CONF T1 - Wavelet Analysis of Gene Expression (WAGE) A1 - Turkheimer, FE A1 - Duke, DC A1 - Moran, LB A1 - Graeber, MB U1 - 2nd IEEE International Symposium on Biomedical Imaging Y1 - 2004/// Y2 - // SP - 1183 EP - 1186 N2 - - ER - TY - CONF T1 - Water drinking to prevent orthostatic hypotension and neurally mediated syncope: Mechanisms and benefits A1 - Mathias, CJ A1 - Young, TM U1 - 8th International Workshop on Cardiac Arhythmias Y1 - 2004/// Y2 - // SP - 625 EP - 631 N2 - - ER - TY - CONF T1 - Effect of GPi DBS on functional imaging of the brain in dystonia. A1 - Yianni J A1 - Bradley K A1 - Bain P A1 - Gregory R A1 - Stein J U1 - Eighth International Congress of Parkinson's Disease and Movement Disorders AD - Rome, Italy J1 - Mov Disord 2004; 19 (suppl 9): S94 Y1 - 2004/// Y2 - 2004/06/14/ PB - Wiley-Liss SN - 0885-3185 N2 - - ER - TY - CONF T1 - Intra-operative monitoring of motor symptoms using surface EMG during electrode implantation for deep brain stimulation of movement disorders A1 - Liu X A1 - Bain PG A1 - Aziz TZ A1 - Stein JF U1 - Eighth International Congress of Parkinson's Disease and Movement Disorders AD - Rome, Italy J1 - Movement Disorders 2004: 19 (suppl 9): S58 Y1 - 2004/// Y2 - 2004/06/14/ PB - Wiley-Liss SN - 0885-3185 N2 - - ER - TY - CONF T1 - An audit of the incidence and types of epilepsy occuring after deep brain stimulation for dystonia. A1 - Saifee T A1 - Johnson M A1 - Yanni J A1 - Aziz TZ A1 - Pearce RKB A1 - Bain PG U1 - Eighth International Congress of Parkinson's Disease and Movement Disorders AD - Rome, Italy J1 - Movement Disorders 2004; 19 (suppl 9): S291 Y1 - 2004/// Y2 - 2004/06/14/ PB - Wiley-Liss SN - 0885-3185 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 - Clinical relevance of quantifying drug induced dyskinesia in the arms using continuous and discrete drawing tasks. A1 - Liu X A1 - Carroll CB A1 - Wang SY A1 - Bain PG U1 - Eighth International Congress of Parkinson's Disease and Movement Disorders AD - Rome, Italy J1 - Movement Disorders 2004; 19 (suppl 9): S159 Y1 - 2004/// Y2 - 2004/06/14/ PB - Wiley-Liss SN - 0885-3185 N2 - - ER - TY - CONF T1 - Ultrastructural analysis by scanning and transmission electron microscopy of brain tissue adherent to explanted electrodes from patients with dystonia and Parkinson's Disease. A1 - Moss J A1 - Ryder T A1 - Graeber MB A1 - Bain PG U1 - Eighth International Congress of Parkinson's Disease and Movement Disorders AD - Rome, Italy J1 - Movement Disorders 2004; 19 (suppl 9): S304-305 Y1 - 2004/// Y2 - 2004/06/14/ PB - Wiley-Liss SN - 0885-3185 N2 - - ER - TY - CONF T1 - Does cannabis have a role in the treatment of Parkinson's disease? A1 - Caroll C A1 - Bain PG A1 - Teare L A1 - Liu X A1 - Wroath C A1 - Parkin S A1 - Fox P A1 - Wright D A1 - Hobart J A1 - Zajicek J U1 - American Academy of Neurology AD - San Francisco, USA J1 - Neurology 2004: 62 (Suppl 5): A330 Y1 - 2004/// Y2 - 2004/04/24/ PB - Neurology N2 - - ER - TY - CONF T1 - Wavelet variance components in image space for spatio-temporal neuroimaging data A1 - Aston, J A1 - Turkheimer, F A1 - Cunningham, V A1 - Gunn, R U1 - Wavelets - Applications in Signal and Image Processing X Conference Y1 - 2003/// Y2 - // VL - 5207 SP - 849 EP - 857 N2 - - ER - TY - CONF T1 - The endogenous TRPV1 ligand anandamide increases in the rat inflamed urinary bladder and may contribute to inflammatory pain A1 - Avelino AA A1 - Dinis P A1 - Charrua A A1 - Nagy I A1 - Yacoob M A1 - Cruz F U1 - 33rd Annual Meeting of the Society for Neuroscience AD - New Orleans Y1 - 2003/// Y2 - // VL - 29 PB - Society for Neuroscience SP - 608.3 N2 - - ER - TY - CONF T1 - Different mechanisms may generate sustained hypertonic and rhythmic bursting muscle activity in dystonia; comparison of pallidal field potentials with surface EMGs. A1 - Liu, X A1 - Wang, S A1 - Yianni, J A1 - Aziz, TZ A1 - Bain, PG A1 - Stein, J U1 - Society for Neurosciences AD - Washington DC J1 - Society for Neurosciences, Washington DC, 2003: Program No. 71.2 abstract viewer/itinery planner CD-ROM Y1 - 2003/// Y2 - 2003/// N2 - - ER - TY - CONF T1 - Insulin induces cobalt - uptake in a sub - population of primary sensory neurons A1 - Sathianathan V A1 - Santha P A1 - Nagy I U1 - 33rd Annual Meeting of the Society for Neuroscience AD - New Orleans, USA Y1 - 2003/// Y2 - // VL - 29 PB - Society for Neuroscience SP - 812.16 N2 - - ER - TY - CONF T1 - Globus pallidus deep brain stimulation in the treatment of dystonia A1 - Yianni J A1 - Gregory R A1 - Bain PG A1 - Joint C A1 - Parkin S A1 - Aziz T U1 - Association of British Neurologists AD - Oxford, UK J1 - J Neurol Neurosurg Psychiatry 2002; 72: 233 Y1 - 2002/// Y2 - 2002/// N2 - - ER - TY - CONF T1 - Cannabinoid 1 receptor- and vanilloid receptor 1-mediated effects on transmitter release from cultured primary sensory neurons A1 - Nagy I A1 - Ahluwalia J A1 - Yaqoob M A1 - Bevan S A1 - Urban L U1 - 32rd Annual Meeting of the Society for Neuroscience AD - Orlando Y1 - 2002/// Y2 - // VL - 28 PB - Society for Neuroscience SP - 114.3 N2 - - ER - TY - CONF T1 - Cold induces cobalt-uptake in a sub-population of rat cultured primary sensory neurons A1 - Thapar A A1 - Nagy I U1 - 32rd Annual Meeting of the Society for Neuroscience AD - Orlando Y1 - 2002/// Y2 - // VL - 28 PB - Society for Neuroscience SP - 46.3 N2 - - ER - TY - CONF T1 - The effect of oral cannabis oil on tremor in patients with multiple sclerosis A1 - Fox PJ A1 - Bain PG A1 - Glickman S A1 - Zajicek J U1 - Sixth Congress of the European Federation of Neurological Societies AD - Vienna, Austria J1 - European J of Neurology 2002; 9 (Suppl 2): 224 Y1 - 2002/// Y2 - 2002/// PB - European J Neurology SP - 224 N2 - - ER - TY - CONF T1 - Anandamide increases the micturition reflex activity via the vanilloid receptor 1 A1 - Silva AA A1 - Charrua A A1 - Nagy I A1 - Cruz F U1 - 32rd Annual Meeting of the Society for Neuroscience AD - Orlando Y1 - 2002/// Y2 - // VL - 28 PB - Society for Neuroscience SP - 49.11 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 - A double-blind cross over study of the effects of pramipexole, pergolide and placebo on tremor and UPDRS (III) in Parkinson's disease. A1 - Navan P A1 - Findley LJ A1 - Pearce RKB A1 - Bain PG U1 - Association of British Neurologists AD - Durham, UK J1 - J Neurol Neurosurg Psychiatry 2002; 72 (1): 138 Y1 - 2002/// Y2 - 2001/// N2 - - ER - TY - CONF T1 - Dual effect of anandamide on nociceptive primary sensory neurons A1 - Nagy I A1 - Ahluwalia J A1 - Urban L U1 - 3rd FENS Forum AD - Paris Y1 - 2002/// Y2 - // N2 - - ER - TY - CONF T1 - A double-blind 3-month parallel study of the effects of pramipexole, pergolide and placebo on tremor in Parkinson's disease. A1 - Navan P A1 - Findley LJ A1 - Pearce RKB A1 - Jeffs J A1 - Bain PG U1 - Seventh International Congress of Parkinson's disease and Movement Disorders AD - Miami, Florida, USA J1 - Movement Disorders 2002; 17 (suppl 5): S83 Y1 - 2002/// Y2 - 2002/11/10/ PB - Wiley-Liss SN - 0885-3185 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 - Measuring what we do - HoNOSCA: a measure for clinicians to rate symptoms and functional impairments in child and adolescent psychiatry patients A1 - Garralda ME U1 - 4th Conference on psychiatric research in the North Y1 - 2002/// Y2 - 2002/// N2 - - ER - TY - CONF T1 - Adrenergic receptors are sites for the analgesic response to general anesthetics A1 - Maze, M U1 - 6th International Conference on Molecular and Basic Mechanisms of Anesthesia Y1 - 2002/// Y2 - // SP - 259 EP - 261 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 - Surgical alleviation of complex action tremor: role of zona incerta and field potentials. A1 - Nandi D A1 - Bain PG A1 - Liu X A1 - Yianni J A1 - Stei JF A1 - Aziz TZ U1 - Seventh International Congress of Parkinson's Disease and Movement Disorders AD - Miami, Florida, USA J1 - Movement Disorders 2002; 17 (suppl 5): S352 Y1 - 2002/// Y2 - 2002/11/10/ PB - Wiley-Liss SN - 0885-3185 N2 - - ER - TY - CONF T1 - The effect of anandamide on calcitonin gene-related peptide release from primary sensory neurons A1 - Ahluwalia J A1 - Urban L A1 - Bevan S A1 - Nagy I U1 - 10th World Congress on Pain AD - San Diego Y1 - 2002/// Y2 - // PB - IASP Press N2 - - ER - TY - CONF T1 - Rapid capsaicin-induced redistribution of the rat vanilloid receptor subtype i in heterologously expressing CHO cells and in DRG neurons A1 - Brown AJH A1 - Hudson LJ A1 - Nagy I A1 - Winter J A1 - McIntyre P U1 - 30th Annual Meeting of the Society for Neuroscience AD - New Orleans, USA Y1 - 2001/// Y2 - // VL - 26 PB - Society For Neuroscience SP - 635.4 N2 - - ER - TY - CONF T1 - Cross correlation techniques used to identify activation of intrafusal fibres by fusimotor axons A1 - Ellaway, PH A1 - Taylor, A A1 - Durbaba, R A1 - Rawlinson, S U1 - NATO Advanced Research Workshop on Sensorimotor Control Y1 - 2001/// Y2 - // VL - 326 SP - 124 EP - 130 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 - Is there a single best surgical procedure for the alleviation of Parkinson's disease? A1 - Aziz, T A1 - Parkin, S A1 - Joint, C A1 - Gregory, R A1 - Bain, P A1 - Stein, JF A1 - Scott, R U1 - International Workshop on Basal Ganglia and Thalamus in Health and Movement Disorders Y1 - 2001/// Y2 - // SP - 317 EP - 325 N2 - - ER - TY - CONF T1 - Expression of cannabinoid 1 receptors and its regulation in primary sensory neurons A1 - Bevan SJ A1 - Ahluwalia J A1 - Nagy I A1 - Urban L U1 - 31st Annual Meeting of the Society for Neuroscience AD - San Diego Y1 - 2001/// Y2 - // VL - 27 PB - Society for Neuroscience SP - 716.2 N2 - - ER - TY - CONF T1 - The management of non-parkinsonian tremors A1 - Bain, PG U1 - World Congress of Neurology AD - London Y1 - 2001/// Y2 - 2001/// N2 - - ER - TY - CONF T1 - A study of the relative reliabilities of different ways of measuring the magnitudes of parkinsonisn tremors. A1 - Navan, P A1 - Findley, LJ A1 - Pearce, RKB A1 - Bain, PG U1 - XIV International Congress of Parkinson's disease AD - Helsinki J1 - Parkinsonism & Related Disorders 2001; 7 (suppl): S124 Y1 - 2001/// Y2 - 2001/07/27/ PB - Elsevier SN - 1353-8020 N2 - - ER - TY - CONF T1 - A physiological probe into the mechanisms underlying tremor in multiple sclerosis. A1 - Alusi,SH A1 - McKinnon, C A1 - Glickman, S A1 - Rothwell, J A1 - Bain, PG U1 - World Congress of Neurology AD - London Y1 - 2001/// Y2 - 2001/// N2 - - ER - TY - CONF T1 - Effects of the endogenous cannabinoid anandamide on excitatory transmission in substantia gelatinosa neurons of the rat spinal cord A1 - Morisset V A1 - Nagy I A1 - Urban L U1 - 31st Annual Meeting of the Society for Neuroscience AD - San Diego Y1 - 2001/// Y2 - // VL - 27 PB - Society for Neuroscience SP - 716.11 N2 - - ER - TY - CONF T1 - Cannabinoid 1 receptors are expressed on primary sensory neurons A1 - Ahluwalia J A1 - Urban L A1 - Capogna M A1 - Bevan S A1 - Nagy I U1 - Scientific Meeting of The Physiologal Society held at the University of Abrdeen AD - Aberdeen, UK Y1 - 2000/// Y2 - // VL - 528 PB - Blackwell N2 - - ER - TY - CONF T1 - Stereotaxic thalamotomy for the treatment of tremor in multiple sclerosis.: a prospective case-controlled trial. A1 - Alusi, SH A1 - Worthington, J A1 - Glickman, S A1 - Bain, PG U1 - 6th International Congress of Parkinson’s Disease and Movement Disorders AD - Barcelona J1 - Movement Disorders 2000; 15 (suppl 3): 60 (P394) Y1 - 2000/// Y2 - 2000/06/11/ PB - Lippincott Williams & Wilkins N2 - - ER - TY - CONF T1 - Alpha-2 adrenergic agonists A1 - Maze, M U1 - Symposium on Molecular Pharmacology of Anasthesia Y1 - 2000/// Y2 - // SP - 232 EP - 240 N2 - - ER - TY - CONF T1 - Clinical aspects of tremor A1 - Bain, PG U1 - European Federation of Neurological Societies AD - Copenhagen Y1 - 2000/// Y2 - 2000/// N2 - - ER - TY - CONF T1 - Distribution of vanilloid receptor (vr-1) immunoreactive fibers in the rat urinary tract. A1 - Cruz F A1 - Avelino A A1 - Cruz C A1 - Nagy I U1 - 30th Annual Meeting of the Society for Neuroscience AD - New Orleans, USA Y1 - 2000/// Y2 - // VL - 26 PB - Society For Neuroscience SP - 629.11 N2 - - ER - TY - CONF T1 - Metallothionein, calmodulin, and trace elements in healing skin wounds A1 - Sampson, B A1 - Lansdown, A A1 - Rowe, A U1 - 10th International Symposium on Trace Elements in Man and Animals Y1 - 2000/// Y2 - // SP - 1038 EP - 1038 N2 - - ER - TY - CONF T1 - Bilateral globus pallidus internus stimulation for the treatment of spasmodic torticollis. A1 - Parkin, SJ A1 - Aziz, TZ A1 - Gregory, R A1 - Bain, PG U1 - Association of British Neurologists AD - Exeter Y1 - 2000/// Y2 - 2000/04/05/ N2 - - ER - TY - CONF T1 - SNS/PN3 and NaN/SNS2 sodium channel immunoreactivity in human pain states A1 - Coward, K A1 - Saldanha, G A1 - Birch, R A1 - Carlstedt, T A1 - Anand, P U1 - 9th World Congress on Pain Y1 - 2000/// Y2 - // VL - 16 SP - 711 EP - 716 N2 - - ER - TY - CONF T1 - Vanilloid receptor 1-mediated and noxious heat-induced currents in noxious heat-sensitive primary sensory neurons A1 - Nagy I A1 - Rang HP U1 - Joint Scientific Meeting of The Physiologal Society and the Hungarian Physiological Society AD - Budapest, Hungary Y1 - 2000/// Y2 - // VL - 526 PB - Blackwell N2 - - ER - TY - CONF T1 - Co-expression of vanilloid 1 and cannabinoid 1 receptors in nociceptive primary sensory neurons A1 - Ahluwalia J A1 - Urban L A1 - Capogna M A1 - Nagy I U1 - 30th Annual Meeting of the Society for Neuroscience AD - New Orleans, USA Y1 - 2000/// Y2 - // VL - 26 PB - Society For Neuroscience SP - 632.8 N2 - - ER - TY - CONF T1 - Identification of the zinc binding protein in a child with hyperzincaemia as calprotectin (MRP8/MRP14) A1 - Sampson, B A1 - Richmond, P A1 - Golden, BE A1 - Fagerhol, MK A1 - Beattie, JH A1 - Kovar, IZ U1 - 10th International Symposium on Trace Elements in Man and Animals Y1 - 2000/// Y2 - // SP - 1031 EP - 1034 N2 - - ER - TY - CONF T1 - Tremor A1 - Bain, PG A1 - Merello, M U1 - 6th International Congress of Parkinson’s Disease and Movement Disorders AD - Barcelona Y1 - 2000/// Y2 - 2000/06/11/ N2 - - ER - TY - CONF T1 - Heat- and capsaicin-activated channels in cultured dorsal root ganglion neurons A1 - Nagy I A1 - Rang HP U1 - 9th World Congress on Pain AD - Wiena, Austria Y1 - 1999/// Y2 - // PB - IASP Press SP - 135 N2 - - ER - TY - CONF T1 - The comparative reliability of rating multiple sclerosis upper limb tremor from videotapes, spirals and handwriting. A1 - Alusi, SH A1 - Worthington, J A1 - Glickman, S A1 - Findley, LJ U1 - Joint Meeting of the Association of Bristish Neurologists & Dutch Neurology Society AD - Rotterdam Y1 - 1999/// Y2 - 1999/// N2 - - ER - TY - CONF T1 - Target board test for quantification of ataxia in tremulous patients. A1 - Alusi, SH A1 - Patel, N A1 - Worthington, J A1 - Glickman, S A1 - Bain, PG U1 - 2nd World Congess in Neurological Rehabilitation AD - Toronto Y1 - 1999/// Y2 - 1999/// N2 - - ER - TY - CONF T1 - The role of alpha(2) agonists in anesthesiology A1 - Maze, M U1 - Postgraduate Course in Clinical Anesthesiology on Anesthesia for the New Millennium Y1 - 1999/// Y2 - // VL - 34 SP - 213 EP - 223 N2 - - ER - TY - CONF T1 - Drug addiction among anesthesiologists A1 - Maze, M U1 - Postgraduate Course in Clinical Anesthesiology on Anesthesia for the New Millennium Y1 - 1999/// Y2 - // VL - 34 SP - 263 EP - 266 N2 - - ER - TY - CONF T1 - Writing speed - a useful quantitative assessment of fine upper limb function. A1 - Findley, M A1 - Reid, H A1 - Findley, LJ A1 - Bain, PG U1 - XIII International Congress on Parkinson's disease AD - Vancouver Y1 - 1999/// Y2 - 1999/// 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 - Dyskinesia & L-dopa responsive Holmes tremor A1 - Alusi, SH A1 - Stern, J A1 - Rakshi, J A1 - Colquhoun, I A1 - Findley, LJ A1 - Brooks, DJ U1 - 5th International Congress of Parkinson’s Disease and Movement AD - New York J1 - Movement Disorders 1998; 13 (suppl 2: 139 (P2.215) Y1 - 1998/// Y2 - 1998/10/10/ PB - Lippincott Williams & Wilkins N2 - - ER - TY - CONF T1 - Noxious heat-activated microscopic currents in rat dorsal root ganglion neurones A1 - Nagy I A1 - Rang HP U1 - Scientific Meeting of The Physiological Society held at Cambridge University AD - Cambridge, UK Y1 - 1998/// Y2 - // VL - 507 PB - Blackwell N2 - - ER - TY - CONF T1 - Noxious heat transduction mechanisms in cultured dorsal root ganglion neurons A1 - Nagy I A1 - Rang HP U1 - 28th Annual Meeting of the Society for Neuroscience AD - Los Angeles, USA Y1 - 1998/// Y2 - // VL - 24 PB - Society for Neuroscience SP - 814.9 N2 - - ER - TY - CONF T1 - Treatment of hereditary essential tremor by combined VIM/VOP thalamotomies - a case report. A1 - McEvoy, AW A1 - Aziz, TZ A1 - Bain, PG U1 - 5th International Congress of Parkinson’s Disease and Movement Disorders AD - New York J1 - Movement Disorders 1998; 13 (suppl 2: 139 (P2.216) Y1 - 1998/// Y2 - 1998/10/10/ PB - Lippincott Williams & Wilkins N2 - - ER - TY - CONF T1 - L-dopa responsive Holmes's tremor and wearing off dyskinesia secondary to a brainstem angioma - a model for parkinsonism. A1 - Alusi, SH A1 - Stern, J A1 - Rakshi, J A1 - Colquhoun, I A1 - Findley, LJ A1 - Brooks, DK A1 - Bain, PG U1 - Association of British Neurologists AD - Leeds J1 - J Neurol Neurosurg Psychiatry Y1 - 1998/// Y2 - 1998/04/16/ 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 - Multidimensional measures of outcome following unilateral and bilateral pallidotomy. A1 - Scott, R A1 - Silburn, R A1 - Bowen, J A1 - Gregory, R A1 - Bain, PG A1 - Hall, B A1 - Hines, N A1 - Harding-Clark, J A1 - Troy, L A1 - Joint, C A1 - Aziz, TZ U1 - 5th International Congress of Parkinson’s Disease and Movement AD - New York J1 - Movement Disorders 1998; 13 (suppl 2: 304 (P5.100) Y1 - 1998/// Y2 - 1998/10/10/ N2 - - ER - TY - CONF T1 - A study of tremor in multiple sclerosis. A1 - Alusi, SH A1 - Glickman, S A1 - Worthington, J A1 - Bain, PG U1 - Association of British Neurologists AD - London J1 - J Neurol Neurosurg Psychiatry 1998 Y1 - 1998/// Y2 - 1998/// 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 - Clinical measurement of tremor A1 - Bain, PG U1 - International Congress: Tremor: Basic Mechanisms and Clinical Aspects AD - Kiel, Germany J1 - Movement Disorders 1998; 13 (suppl 3): 77-81. Y1 - 1998/// Y2 - 1997/06/11/ N2 - - ER - TY - CONF T1 - Ventralis oralis posterior thalamotomy for multiple sclerosis associated tremor - a case report A1 - Alusi, SH A1 - Bain, PG A1 - Aziz, TZ U1 - 5th International Congress of Parkinson’s Disease and Movement Disorders AD - New York J1 - Movement Disorders 1998; 13 (suppl 2: 138 (P2.214) Y1 - 1998/// Y2 - 1998/10/10/ PB - Lippincott Williams & Wilkins N2 - - ER - TY - CONF T1 - Nigrostriatal dysfunction in Holmes's tremor. A1 - Stern, JS A1 - Rakshi, J A1 - Alusi, SH A1 - Findley, LJ A1 - Bain, PG A1 - Brooks, DJ U1 - Association of British Neurologists AD - London J1 - J Neurol Neurosurg 1998 Y1 - 1998/// Y2 - 1998/// 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 - CONF T1 - Membarane responses of rat dorsal root ganglion neurons to noxious heat stimulation A1 - Nagy I A1 - Rang HP U1 - XIIIth World Congtess of Pharmacology AD - Munich, Germany Y1 - 1998/// Y2 - // PB - Springer-Verlag N2 - - ER - TY - CONF T1 - Noxious heat activated currents in rat dorsal root ganglion neurons A1 - Nagy I A1 - Rang HP U1 - Scientific Meeting of The Physiological Society held at King's College London AD - King's College London, London, UK Y1 - 1998/// Y2 - // VL - 506 PB - Blackwell N2 - - ER - TY - CONF T1 - Ion channels activated by noxious heat in rat sensory neurons A1 - Nagy I A1 - Rang HP U1 - XIIIth World Congtess of Pharmacology AD - Munich, Germany Y1 - 1998/// Y2 - // PB - Springer-Verlag N2 - - ER - TY - CONF T1 - Investigations in a child with hyperzincaemia: Partial characterisation of an abnormal zinc binding protein, kinetics and studies of liver pathology A1 - Sampson, B A1 - Kovar, IZ A1 - Beattie, JH A1 - McArdle, HJ A1 - Rauscher, A A1 - Fairweather-Tait, SJ A1 - Jasani, B U1 - 9th International Symposium on Trace Elements in Man and Animals (TEMA 9) Y1 - 1997/// Y2 - // SP - 484 EP - 486 N2 - - ER - TY - CONF T1 - Downregulation of spinal cord NK1 receptor and antinociception by intrathecal treatment with NK1 antisense oligonucleotide and substance P A1 - Hua X.-Y A1 - Chen P A1 - Polgar E A1 - Nagy I A1 - Marsala M A1 - Urban L A1 - Yaskh TL A1 - Webb M U1 - 27th Annual Meeting of the Society for Neuroscience Y1 - 1997/// Y2 - // VL - 23 PB - Society for Neuroscience SP - 267.14 N2 - - ER - TY - CONF T1 - Molecular mechanisms for the analgesic properties of alpha-2 adrenergic agonists A1 - Kingery, WS A1 - Davies, MF A1 - Maze, M U1 - Conference on Molecular Aspects of the Neurobiology of Pain as part of the Celebration to Mark the 150th Anniversary of the First Public Demonstration of Ether Y1 - 1997/// Y2 - // VL - 9 SP - 275 EP - 304 N2 - - ER - TY - CONF T1 - Botulinum toxin (Dysport) treatment of upper leg adductor spasticity in multiple sclerosis; prospective, randomised, double blind, placebo controlled, dose ranging study. A1 - Hyman, N A1 - Barnes, M A1 - Bhakta, B A1 - Cozens, A A1 - Bakheit, M A1 - Krecy-Kleedorfer, B A1 - Poewe, W A1 - Wissel, J A1 - Bain, PG A1 - Glickman, S A1 - Sayer, a A1 - Richardson, A A1 - Dott, C A1 - Cohen, H U1 - European Federation of Neurological Societies AD - Prague Y1 - 1997/// Y2 - 1997/// N2 - - ER - TY - CONF T1 - Pathological laughter in midbrain arterio-venous malformation. A1 - Alusi, SH A1 - Colquhoun, IR A1 - Bain, PG U1 - Association of British Neurologists AD - London J1 - J Neurol Neurosurg Psychiatry 1997 Y1 - 1997/// Y2 - 1997/// N2 - - ER - TY - CONF T1 - Reciprocal inhibition of the H-reflex in musician's painless incoordination syndrome. Evidence for an occupational dystonia. A1 - Bain, PG U1 - Health and Musicians conference AD - York Y1 - 1997/// Y2 - 1997/// N2 - - ER - TY - JFULL T1 - Comparative Analysis of Antisense Oligonucleotide Sequences for Targeted Skipping of Exon 51 During Dystrophin Pre-mRNA Splicing in Human Muscle. A1 - Arechavala-Gomeza, V A1 - Graham, IR A1 - Popplewell, LJ A1 - Adams, AM A1 - Aartsma-Rus, A A1 - Kinali, M A1 - Morgan, JE A1 - Van Deutekom, JC A1 - Wilton, SD A1 - Dickson, G A1 - Muntoni, F J1 - Hum Gene Ther Y1 - 2007/09/03/ SN - 1043-0342 N2 - Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene that result in the absence of functional protein. In the majority of cases these are out-of-frame deletions that disrupt the reading frame. Several attempts have been made to restore the dystrophin mRNA reading frame by modulation of pre-mRNA splicing with antisense oligonucleotides (AOs), demonstrating success in cultured cells, muscle explants, and animal models. We are preparing for a phase I/IIa clinical trial aimed at assessing the safety and effect of locally administered AOs designed to inhibit inclusion of exon 51 into the mature mRNA by the splicing machinery, a process known as exon skipping. Here, we describe a series of systematic experiments to validate the sequence and chemistry of the exon 51 AO reagent selected to go forward into the clinical trial planned in the United Kingdom. Eight specific AO sequences targeting exon 51 were tested in two different chemical forms and in three different preclinical models: cultured human muscle cells and explants (wild type and DMD), and local in vivo administration in transgenic mice harboring the entire human DMD locus. Data have been validated independently in the different model systems used, and the studies describe a rational collaborative path for the preclinical selection of AOs for evaluation in future clinical trials. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17767400&query_hl=1 ER - TY - JFULL T1 - Sexual Dimorphism in Superantigen Shock Involves Elevated TNF-{alpha} and TNF-{alpha} induced Hepatic Apoptosis. A1 - Faulkner, L A1 - Altmann, DM A1 - Ellmerich, S A1 - Huhtaniemi, I A1 - Stamp, G A1 - Sriskandan, S J1 - Am J Respir Crit Care Med Y1 - 2007/09/01/ VL - 176 SN - 1073-449X SP - 473 EP - 482 N2 - Rationale: There is conflicting evidence regarding sex differences in the outcome from severe sepsis and toxic shock. Superantigen-mediated toxic shock affects a higher proportion of female patients. Objectives: The objective of the current study was to investigate sexual dimorphism in superantigen-associated sepsis and in superantigen-mediated shock and to identify the key mechanisms responsible for this sex difference. Methods: We measured mortality and serum cytokines after induction of sepsis with isogenic superantigen-positive and superantigen-negative Streptococcus pyogenes in HLA class II transgenics. During superantigen-mediated toxic shock, we measured mortality, T-cell responses, systemic tumor necrosis factor (TNF)-alpha and TNF receptors, TNF-alpha-induced hepatocyte apoptosis, and conditioning of these responses by tamoxifen treatment. Measurements and Main Results: In both superantigen-associated sepsis and in superantigen-mediated shock, serum TNF-alpha was increased in females compared with males. This was not attributable to a detectable difference in splenic TNF-alpha transcription; rather, serum soluble TNF receptors were higher in males. Pretreatment of females with the estrogen receptor modulator tamoxifen increased serum soluble TNF receptors, reduced the early serum TNF-alpha response, and improved mortality in females challenged with staphylococcal enterotoxin B. Lethal superantigen shock was characterized by hepatocyte apoptosis, and was reproduced by injection of TNF-alpha. Females had enhanced susceptibility to TNF-alpha-mediated lethality. TNF-alpha-induced hepatocyte apoptosis was greater in females, and was reduced by tamoxifen pretreatment. Conclusions: Sexual dimorphism in experimental superantigen toxic shock results from increased systemic TNF-alpha in females, coupled with an increased susceptibility to TNF-alpha-induced hepatocyte apoptosis. Both processes are abrogated by estrogen receptor modulators. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17575097&query_hl=1 ER - TY - JFULL T1 - Quantification of the rat spinal microglial response to peripheral nerve injury as revealed by immunohistochemical image analysis and flow cytometry. A1 - Blackbeard, J A1 - O'dea, KP A1 - Wallace, VC A1 - Segerdahl, A A1 - Pheby, T A1 - Takata, M A1 - Field, MJ A1 - Rice, AS J1 - J Neurosci Methods Y1 - 2007/08/30/ VL - 164 SN - 0165-0270 SP - 207 EP - 217 N2 - Microgliosis is implicated in the pathophysiology of several neurological disorders, including neuropathic pain. Consequently, perturbation of microgliosis is a mechanistic and drug development target in neuropathic pain, which highlights the requirement for specific, sensitive and reproducible methods of microgliosis measurement. In this study, we used the spinal microgliosis associated with L5 spinal nerve transection and minocycline-induced attenuation thereof to: (1) evaluate novel software based semi-quantitative image analysis paradigms for the assessment of immunohistochemical images. Microgliosis was revealed by immunoreactivity to OX42. Several image analysis paradigms were assessed and compared to a previously validated subjective categorical rating scale. This comparison revealed that grey scale measurement of the proportion of a defined area of spinal cord occupied by OX42 immunoreactive cells is a robust image analysis paradigm. (2) Develop and validate a flow cytometric approach for quantification of spinal microgliosis. The flow cytometric technique reliably quantified microgliosis in spinal cord cell suspensions, using OX42 and ED9 immunoreactivity to identify microglia. The results suggest that image analysis of immunohistochemical revelation of microgliosis reliably detects the spinal microgliosis in response to peripheral nerve injury and pharmacological attenuation thereof. In addition, flow cytometry provides an alternative approach for quantitative analysis of spinal microgliosis elicited by nerve injury. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17553569&query_hl=1 ER - TY - JFULL T1 - Characterization of rodent models of HIV-gp120 and anti-retroviral-associated neuropathic pain. A1 - Wallace, VC A1 - Blackbeard, J A1 - Segerdahl, AR A1 - Hasnie, F A1 - Pheby, T A1 - McMahon, SB A1 - Rice, AS J1 - Brain Y1 - 2007/08/30/ SN - 1460-2156 N2 - A distal symmetrical sensory peripheral neuropathy is frequently observed in people living with Human Immunodeficiency Virus Type 1 (HIV-1). This neuropathy can be associated with viral infection alone, probably involving a role for the envelope glycoprotein gp120; or a drug-induced toxic neuropathy associated with the use of nucleoside analogue reverse transcriptase inhibitors as a component of highly active anti-retroviral therapy. In order to elucidate the mechanisms underlying drug-induced neuropathy in the context of HIV infection, we have characterized pathological events in the peripheral and central nervous system following systemic treatment with the anti-retroviral agent, ddC (Zalcitabine) with or without the concomitant delivery of HIV-gp120 to the rat sciatic nerve (gp120+ddC). Systemic ddC treatment alone is associated with a persistent mechanical hypersensitivity (33% decrease in limb withdrawal threshold) that when combined with perineural HIV-gp120 is exacerbated (48% decrease in threshold) and both treatments result in thigmotactic (anxiety-like) behaviour. Immunohistochemical studies revealed little ddC-associated alteration in DRG phenotype, as compared with known changes following perineural HIV-gp120. However, the chemokine CCL2 is significantly expressed in the DRG of rats treated with perineural HIV-gp120 and/or ddC and there is a reduction in intraepidermal nerve fibre density, comparable to that seen in herpes zoster infection. Moreover, a spinal gliosis is apparent at times of peak behavioural sensitivity that is exacerbated in gp120+ddC as compared to either treatment alone. Treatment with the microglial inhibitor, minocycline, is associated with delayed onset of hypersensitivity to mechanical stimuli in the gp120+ddC model and reversal of some measures of thigmotaxis. Finally, the hypersensitivity to mechanical stimuli was sensitive to systemic treatment with gabapentin, morphine and the cannabinoid WIN 55,212-2, but not with amitriptyline. These data suggests that both neuropathic pain models display many features of HIV- and anti-retroviral-related peripheral neuropathy. They therefore merit further investigation for the elucidation of underlying mechanisms and may prove useful for preclinical assessment of drugs for the treatment of HIV-related peripheral neuropathic pain. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17761732&query_hl=1 ER - TY - JFULL T1 - Neurabin-I Is Phosphorylated by Cdk5: Implications for Neuronal Morphogenesis and Cortical Migration. A1 - Causeret, F A1 - Jacobs, T A1 - Terao, M A1 - Heath, O A1 - Hoshino, M A1 - Nikolic, M J1 - Mol Biol Cell Y1 - 2007/08/15/ SN - 1059-1524 N2 - Monitoring Editor: Paul Forscher The correct morphology and migration of neurones, which is essential for the normal development of the nervous system, is enabled by the regulation of their cytoskeletal elements. We reveal that Neurabin-I, a neuronal specific F-actin binding protein, has an essential function in the developing forebrain. We show that gain and loss of Neurabin-I expression affect neuronal morphology, neurite outgrowth and radial migration of differentiating cortical and hippocampal neurones, suggesting that tight regulation of Neurabin-I function is required for normal forebrain development. Importantly, loss of Neurabin-I prevents pyramidal neurones from migrating into the cerebral cortex, indicating its essential role during early stages of corticogenesis. We demonstrate that in neurones Rac1 activation is affected by the expression levels of Nb1. Furthermore, the Cdk5 kinase, a key regulator of neuronal migration and morphology, directly phosphorylates Neurabin-I and controls its association with F-actin. Mutation of the Cdk5 phosphorylation site reduces the phenotypic consequences of Neurabin-I overexpression both in vitro and in vivo, suggesting that Neurabin-I function depends, at least in part on its phosphorylation status. Together our findings provide new insight into the signaling pathways responsible for controlled changes of the F-actin cytoskeleton that are required for normal development of the forebrain. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17699587&query_hl=1 ER - TY - JFULL T1 - Localized activation of p21-activated kinase controls neuronal polarity and morphology. A1 - Jacobs, T A1 - Causeret, F A1 - Nishimura, YV A1 - Terao, M A1 - Norman, A A1 - Hoshino, M A1 - Nikolić, M J1 - J Neurosci Y1 - 2007/08/08/ VL - 27 SN - 1529-2401 SP - 8604 EP - 8615 N2 - In the developing forebrain, neuronal polarization is a stepwise and initially reversible process that underlies correct migration and axon specification. Many aspects of cytoskeletal changes that accompany polarization are currently molecularly undefined and thus poorly understood. Here we reveal that the p21-activated kinase (Pak1) is essential for the specification of an axon and dendrites. In hippocampal neurons, activation of Pak1 is spatially restricted to the immature axon despite its uniform presence in all neurites. Hyperactivation of Pak1 at the membrane of all neurites or loss of Pak1 expression disrupts both neuronal morphology and the distinction between an axon and dendrites. We reveal that Pak1 acts on polarity in a kinase-dependent manner, by affecting the F-actin and microtubule cytoskeleton at least in part through Rac1 and cofilin. Our data are the first to demonstrate the importance of localized Pak1 kinase activation for neuronal polarization and differentiation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17687038&query_hl=1 ER - TY - JFULL T1 - Arts therapies for people with schizophrenia: an emerging evidence base. A1 - Crawford, MJ A1 - Patterson, S J1 - Evid Based Ment Health Y1 - 2007/08// VL - 10 SN - 1362-0347 SP - 69 EP - 70 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17652554&query_hl=1 ER - TY - JFULL T1 - Extrastriatal D2 and striatal D2 receptors in depressive illness: pilot PET studies using [11C]FLB 457 and [11C]raclopride. A1 - Montgomery, AJ A1 - Stokes, P A1 - Kitamura, Y A1 - Grasby, PM J1 - J Affect Disord Y1 - 2007/08// VL - 101 SN - 0165-0327 SP - 113 EP - 122 N2 - BACKGROUND: Reduced dopaminergic function may occur in depressive disorders. In this paper the results of two pilot studies examining different aspects of the dopamine system in depression are presented. First, the binding of [(11)C]FLB 457 to extrastriatal D(2) receptors was measured in a group of depressed patients. Second, the hypothesis that selective serotonin reuptake inhibiting (SSRI) antidepressants affect the striatal binding of [(11)C]raclopride was tested. METHODS: In the first study the binding of [(11)C]FLB 457 was compared between 7 people with depression and 7 healthy controls. In the second study the binding of [(11)C]raclopride to striatal D(2/3) receptors was compared between 8 people taking SSRI antidepressant medication and 8 healthy controls. RESULTS: There was no difference in the binding of [(11)C]FLB 457 between the two groups. [(11)C]raclopride binding was reduced in the dorsal striatum of people taking antidepressants suggesting either that D(2/3) expression was reduced, or that dopamine release was increased, compared to untreated controls. LIMITATIONS: The depressed patients were not severely depressed and were not matched for gender with controls. In the raclopride group the patients and controls were not matched by gender and were taking different SSRI antidepressants. CONCLUSION: We found no support for the hypothesis that dopamine D(2) receptor expression is altered in extrastriatal brain regions in depression. SSRI antidepressants were associated with reduced [(11)C]raclopride binding in the dorsal striatum supporting the hypothesis that therapeutic effects of such drugs may, in part, be due to changes in the dopamine system. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17197036&query_hl=1 ER - TY - JFULL T1 - The effect of nicotine on striatal dopamine release in man: A [11C]raclopride PET study. A1 - Montgomery, AJ A1 - Lingford-Hughes, AR A1 - Egerton, A A1 - Nutt, DJ A1 - Grasby, PM J1 - Synapse Y1 - 2007/08// VL - 61 SN - 0887-4476 SP - 637 EP - 645 N2 - In common with many addictive substances and behaviors nicotine activates the mesolimbic dopaminergic system. Brain microdialysis studies in rodents have consistently shown increases in extrasynaptic DA levels in the striatum after administration of nicotine but PET experiments in primates have given contradicting results. A recent PET study assessing the effect of smoking in humans showed no change in [(11)C]raclopride binding in the brain, but did find that "hedonia" correlated with a reduction in [(11)C]raclopride binding suggesting that DA may mediate the positive reinforcing effects of nicotine. In this experiment we measured the effect of nicotine, administered via a nasal spray, on DA release using [(11)C]raclopride PET, in 10 regular smokers. There was no overall change in [(11)C]raclopride binding after nicotine administration in any of the striatal regions examined. However, the individual change in [(11)C]raclopride binding correlated with change in subjective measures of "amused" and "happiness" in the associative striatum (AST) and sensorimotor striatum (SMST). Nicotine concentration correlated negatively with change in BP in the limbic striatum. Nicotine had significant effects on cardiovascular measures including pulse rate, systolic blood pressure (BPr), and diastolic BPr. Baseline [(11)C]raclopride binding potential (BP) in the AST correlated negatively with the Fagerström score, an index of nicotine dependence. These results support a role for the DA system in nicotine addiction, but reveal a more complex relationship than suggested by studies in animals. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17492764&query_hl=1 ER - TY - JFULL T1 - Human muscle precursor cells give rise to functional satellite cells in vivo. A1 - Ehrhardt, J A1 - Brimah, K A1 - Adkin, C A1 - Partridge, T A1 - Morgan, J J1 - Neuromuscul Disord Y1 - 2007/08// VL - 17 SN - 0960-8966 SP - 631 EP - 638 N2 - Mouse satellite cells have been shown to be functional muscle stem cells, in that they are able to regenerate skeletal muscle and to reconstitute the satellite cell pool. Although human muscle precursor cells are able to contribute to skeletal muscle regeneration following transplantation into host mouse muscles, it is uncertain whether they also give rise to functional satellite cells. Here, we transplant human fetal muscle precursor cells into cryodamaged muscles in C(5)-/gamma-chain-/Rag2-host mice. The donor cells gave rise to muscle fibres that persisted for up to 6 months after grafting. Isolated muscle fibres, bearing satellite cells, were prepared from muscles 4 weeks after grafting. When placed in culture, a small proportion of these fibres gave rise to muscle precursor cells of human origin, indicating that the originally grafted cells had formed satellite cells as well as regenerated muscle fibres. These satellite cell-derived human muscle precursor cells were expanded in culture and formed muscle following their transplantation into a second series of host mice. This provides evidence that human, as well as mouse, muscle precursor cells, are capable of forming functional satellite cells in vivo. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17588754&query_hl=1 ER - TY - JFULL T1 - Use of blood alcohol concentration in resuscitation room patients. A1 - Csipke, E A1 - Touquet, R A1 - Patel, T A1 - Franklin, J A1 - Brown, A A1 - Holloway, P A1 - Batrick, N A1 - Crawford, MJ J1 - Emerg Med J Y1 - 2007/08// VL - 24 SN - 1472-0213 SP - 535 EP - 538 N2 - OBJECTIVE: To clarify the use of blood alcohol concentration (BAC) in the emergency department resuscitation room, by comparing it with a subsequent alcohol questionnaire and by surveying patients' attitudes to BAC testing. DESIGN: Observational study. PARTICIPANTS: 273 resuscitation room patients at St Mary's Hospital, Paddington between August 2005 and February 2006. MAIN OUTCOME MEASURES: BAC comparison to questionnaire results, and attitudes to BAC testing. RESULTS: The level of agreement between positive screening by questionnaire and a BAC of >80 mg/100 ml was low (kappa = 0.29, 95% confidence interval 0.12 to 0.46) because each test measures different aspects of drinking. Patients accepted the use of BAC tests in detecting alcohol use, though a small minority reported concerns over confidentiality. CONCLUSION: Use of BAC testing complements later questionnaire screening to identify alcohol misuse in patients initially brought to the emergency department resuscitation room, providing results are fed back to the patient. Potential ethical, judicial and insurance concerns should not prevent the use of BAC when judged to be in the patient's best interest. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17652671&query_hl=1 ER - TY - JFULL T1 - Gaze strategies during planning in first-episode psychosis. A1 - Huddy, VC A1 - Hodgson, TL A1 - Kapasi, M A1 - Mutsatsa, SH A1 - Harrison, I A1 - Barnes, TR A1 - Joyce, EM J1 - J Abnorm Psychol Y1 - 2007/08// VL - 116 SN - 0021-843X SP - 589 EP - 598 N2 - Eye movements were measured during the performance of a computerized Tower of London task to specify the source of planning abnormalities in patients with 1st-episode schizophrenia or schizoaffective disorder. Subjects viewed 2 arrays of colored balls in the upper and lower parts of the screen. They were asked to plan the shortest sequence of moves required to rearrange the balls in the lower screen to match the upper arrangement. Compared with healthy controls, patients made more planning errors, and decision times were longer. However, the patients showed the same gaze biases as controls prior to making a response, indicating that they understood the requirements of the task, approached the task in a strategic manner by identifying the nature of the problem, and used appropriate fixation strategies to plan and elaborate solutions. The patients showed increased duration of long-gaze periods toward both parts of the screen. This suggests that the patients had difficulty in encoding the essential features of the stimulus array. This finding is compatible with slowing of working memory consolidation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17696714&query_hl=1 ER - TY - JFULL T1 - The effect of the palmitoylethanolamide analogue, palmitoylallylamide (L-29) on pain behaviour in rodent models of neuropathy. A1 - Wallace, VC A1 - Segerdahl, AR A1 - Lambert, DM A1 - Vandevoorde, S A1 - Blackbeard, J A1 - Pheby, T A1 - Hasnie, F A1 - Rice, AS J1 - Br J Pharmacol Y1 - 2007/08// VL - 151 SN - 0007-1188 SP - 1117 EP - 1128 N2 - BACKGROUND AND PURPOSE: Cannabinoids are associated with analgesia in acute and chronic pain states. A spectrum of central cannabinoid (CB(1)) receptor-mediated motor and psychotropic side effects limit their therapeutic potential. Here, we investigate the analgesic effect of the palmitoylethanolamide (PEA) analogue, palmitoylallylamide (L-29), which via inhibition of fatty acid amide hydrolase (FAAH) may potentiate endocannabinoids thereby avoiding psychotropic side effects. EXPERIMENTAL APPROACH: The in vivo analysis of the effect of L-29 on measures of pain behaviour in three rat models of neuropathic pain. KEY RESULTS: Systemically administered L-29 (10 mg kg(-1)) reduced hypersensitivity to mechanical and thermal stimuli in the partial sciatic nerve injury (PSNI) model of neuropathic pain; and mechanical hypersensitivity in a model of antiretroviral (ddC)-associated hypersensitivity and a model of varicella zoster virus (VZV)-associated hypersensitivity. The effects of L-29 were comparable to those of gabapentin (50 mg kg(-1)). The CB(1) receptor antagonist SR141716a (1 mg kg(-1)) and the CB(2) receptor antagonist SR144528 (1 mg kg(-1)) reduced the effect of L-29 on hypersensitivity in the PSNI and ddC models, but not in the VZV model. The peroxisome proliferator-activated receptor-alpha antagonist, MK-886 (1 mg kg(-1)), partially attenuated the effect of L-29 on hypersensitivity in the PSNI model. L-29 (10 mg kg(-1)) significantly attenuated thigmotactic behaviour in the open field arena without effect on locomotor activity. CONCLUSIONS AND IMPLICATIONS: L-29 produces analgesia in a range of neuropathic pain models. This presents L-29 as a novel analgesic compound that may target the endogenous cannabinoid system while avoiding undesirable side effects associated with direct cannabinoid receptor activation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17558434&query_hl=1 ER - TY - JFULL T1 - Molecular mechanisms and phenotypic variation in RYR1-related congenital myopathies. A1 - Zhou, H A1 - Jungbluth, H A1 - Sewry, CA A1 - Feng, L A1 - Bertini, E A1 - Bushby, K A1 - Straub, V A1 - Roper, H A1 - Rose, MR A1 - Brockington, M A1 - Kinali, M A1 - Manzur, A A1 - Robb, S A1 - Appleton, R A1 - Messina, S A1 - D'Amico, A A1 - Quinlivan, R A1 - Swash, M A1 - Müller, CR A1 - Brown, S A1 - Treves, S A1 - Muntoni, F J1 - Brain Y1 - 2007/08// VL - 130 SN - 1460-2156 SP - 2024 EP - 2036 N2 - Dominant mutations in the skeletal muscle ryanodine receptor (RYR1) gene are well-recognized causes of both malignant hyperthermia susceptibility (MHS) and central core disease (CCD). More recently, recessive RYR1 mutations have been described in few congenital myopathy patients with variable pathology, including multi-minicores. Although a clinical overlap between patients with dominant and recessive RYR1 mutations exists, in most cases with recessive mutations the pattern of muscle weakness is remarkably different from that observed in dominant CCD. In order to characterize the spectrum of congenital myopathies associated with RYR1 mutations, we have investigated a cohort of 44 patients from 28 families with clinical and/or histopathological features suggestive of RYR1 involvement. We have identified 25 RYR1 mutations, 9 of them novel, including 12 dominant and 13 recessive mutations. With only one exception, dominant mutations were associated with a CCD phenotype, prominent cores and predominantly occurred in the RYR1 C-terminal exons 101 and 102. In contrast, the 13 recessive RYR1 mutations were distributed evenly along the entire RYR1 gene and were associated with a wide range of clinico-pathological phenotypes. Protein expression studies in nine cases suggested a correlation between specific mutations, RyR1 protein levels and resulting phenotype: in particular, whilst patients with dominant or recessive mutations associated with typical CCD phenotypes appeared to have normal RyR1 expression, individuals with more generalized weakness, multi-minicores and external ophthalmoplegia had a pronounced depletion of the RyR1 protein. The phenomenon of protein depletion was observed in some patients compound heterozygous for recessive mutations at the genomic level and silenced another allele in skeletal muscle, providing additional information on the mechanism of disease in these patients. Our data represent the most extensive study of RYR1-related myopathies and indicate complex genotype-phenotype correlations associated with mutations differentially affecting assembly and function of the RyR1 calcium release channel. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17483490&query_hl=1 ER - TY - JFULL T1 - SNP genome scanning localises oto-dental syndrome to chromosome 11q13 and microdeletions at this locus implicate FGF3 in dental and inner ear disease and FADD in ocular coloboma. A1 - Gregory-Evans, CY A1 - Moosajee, M A1 - Hodges, MD A1 - Mackay, DS A1 - Game, L A1 - Vargesson, N A1 - Bloch-Zupan, A A1 - Rüschendorf, F A1 - Santos-Pinto, L A1 - Wackens, G A1 - Gregory-Evans, K J1 - Hum Mol Genet Y1 - 2007/07/25/ SN - 0964-6906 N2 - We ascertained three different families affected with oto-dental syndrome, a rare but severe autosomal dominant craniofacial anomaly. All affected patients had the unique phenotype of grossly enlarged molar teeth (globodontia) segregating with a high frequency sensorineural hearing loss. In addition, ocular coloboma segregated with disease in one family (oculo-oto-dental syndrome). A genome-wide scan was performed using the Affymetrix GeneChip10K 2.0 Array. Parametric linkage analysis gave a single LOD score peak of 3.9 identifying linkage to chromosome 11q13. Haplotype analysis revealed three obligatory recombination events defining a 4.8 Mb linked interval between D11S1889 and SNP rs2077955. Higher resolution mapping and Southern blot analysis in each family identified overlapping hemizygous microdeletions. SNP expression analysis and real-time qRT-PCR in patient lymphoblast cell lines excluded a position effect on the flanking genes ORAOV1, PPFIA1 and CTTN. The smallest 43 kb deletion resulted in the loss of only one gene, FGF3, which was also deleted in all other otodental families. These data suggest that FGF3 haploinsufficiency is likely to be the cause of otodental syndrome. In addition, the Fas-associated death domain gene (FADD) was also deleted in the one family segregating ocular coloboma. Spatiotemporal in situ hybridisation in zebrafish embryos established for the first time that fadd is expressed during eye development. We therefore propose that FADD haploinsufficiency is likely to be responsible for ocular coloboma in this family. This study therefore implicates FGF3 and FADD in human craniofacial disease. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17656375&query_hl=1 ER - TY - JFULL T1 - Using vibrotactile feedback of instability to trigger a forward compensatory stepping response. A1 - Asseman, F A1 - Bronstein, AM A1 - Gresty, MA J1 - J Neurol Y1 - 2007/07/25/ SN - 0340-5354 N2 - We evaluated the effectiveness of vibrotactile feedback to enhance protective stepping with a view to developing a prosthesis for patients with balance disorders. Subjects standing on a moving walkway were exposed to an unpredictable, abrupt backwards translation of the support surface that required a step response to remain standing. The subjects were 15 normal young, 15 normal elderly and 9 patients with either bilateral vestibular loss or peripheral neuropathy. The initial passive displacement of the body was recorded by a gyroscope placed on the leg which triggered a vibration pulse to the trigeminal distribution on the forehead to cue a forwards step. Stepping responses and postural sway, with and without vibration feedback, were compared. Vibration produced significantly shorter stepping reaction times only in the elderly normals with naturally slower stepping. Patients did not benefit in any way. We conclude that the effectiveness of vibration biofeedback appears limited. Any enhancement of compensatory stepping might be triggered by speeding the decision to step rather than by creating a specific stimulus-response loop. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17641814&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 - Determinants of the anesthetic sensitivity of two-pore domain acid-sensitive potassium channels: molecular cloning of an anesthetic-activated potassium channel from lymnaea stagnalis. A1 - Andres-Enguix, I A1 - Caley, A A1 - Yustos, R A1 - Schumacher, MA A1 - Spanu, PD A1 - Dickinson, R A1 - Maze, M A1 - Franks, NP J1 - J Biol Chem Y1 - 2007/07/20/ VL - 282 SN - 0021-9258 SP - 20977 EP - 20990 N2 - Certain two-pore domain K(+) channels are plausible targets for volatile general anesthetics, yet little is known at the molecular level about how these simple agents cause channel activation. The first anesthetic-activated K(+) current I(K(An)) that was characterized was discovered in the mollusk Lymnaea stagnalis and is remarkable for both its sensitivity to general anesthetics and its stereoselective responses to anesthetic enantiomers (Franks, N. P., and Lieb, W. R. (1988) Nature 333, 662-664 and Franks, N. P., and Lieb, W. R. (1991) Science 254, 427-430). Here we report the molecular cloning of a two-pore domain K(+) channel LyTASK from L. stagnalis and show that, when expressed in HEK-293 cells, it displays the same biophysical characteristics as the anesthetic-activated K(+) current I(K(An)). Sequence analysis and functional properties show it to be a member of the TASK family of channels with approximately 47% identity at the amino acid level when compared with human TASK-1 and TASK-3. By using chimeric channel constructs and site-directed mutagenesis we have identified the specific amino acid 159 to be a critical determinant of anesthetic sensitivity, which, when mutated to alanine, essentially eliminates anesthetic activation in the human channels and greatly reduces activation in LyTASK. The L159A mutation in LyTASK disrupts the stereoselective response to isoflurane while having no effect on the pH sensitivity of the channel, suggesting this critical amino acid may form part of an anesthetic binding site. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17548360&query_hl=1 ER - TY - JFULL T1 - Kisspeptin-54 Stimulates Gonadotrophin Release Most Potently During The Preovulatory Phase Of The Menstrual Cycle In Women. A1 - Dhillo, WS A1 - Chaudhri, OB A1 - Thompson, EL A1 - Murphy, KG A1 - Patterson, M A1 - Ramachandran, R A1 - Nijher, GK A1 - Amber, V A1 - Kokkinos, A A1 - Donaldson, M A1 - Ghatei, MA A1 - Bloom, SR J1 - J Clin Endocrinol Metab Y1 - 2007/07/17/ SN - 0021-972X N2 - Context: Kisspeptin, the endogenous ligand of the GPR54 receptor, is a key regulator of the hypothalamo-pituitary-gonadal (HPG) axis. GPR54-null mice exhibit reproductive dysfunction and exogenous kisspeptin potently stimulates the HPG axis in rodents, primates and human males. The effects of kisspeptin administration to human females are unknown. Objective: To investigate the effects of kisspeptin on LH release during the menstrual cycle in female volunteers. Design: Bolus subcutaneous (sc) kisspeptin-54 to female volunteers and measurement of plasma gonadotrophins. Setting: Hospital clinical research facility. Volunteers: Healthy female volunteers with regular menstrual cycles. Intervention: (i) Volunteers received a sc bolus injection of kisspeptin-54 (0, 0.2, 0.4, 0.8, 1.6, 3.2 and 6.4 nmol/kg, n=3-4 per dose) in the follicular phase. (ii) Volunteers (n=8) received a sc bolus injection of either kisspeptin-54 (0.4 nmol/kg) or saline in random order during each phase of the menstrual cycle. Main outcome measures: plasma gonadotrophins. Results: (i) Kisspeptin-54 caused a dose-dependent increase in mean LH over time at doses from 0.2-6.4 nmol/kg. (ii) Kisspeptin-54 increased plasma LH compared to saline injection in all phases of the cycle. The effect of kisspeptin was greatest in the preovulatory phase and least in the follicular phase of the cycle [mean increase in LH over baseline (IU/L)+/-S.E.M.: follicular phase: 0.12+/-0.17; preovulatory phase: 20.64+/-2.91 (P<0.001 vs follicular phase); luteal phase: 2.17+/-0.79 (P<0.01 vs follicular phase)]. Conclusion: Elevation of plasma kisspeptin in human females potently stimulates LH release in the preovulatory phase and provides a novel mechanism for manipulation of the HPG axis in women. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17635940&query_hl=1 ER - TY - JFULL T1 - Neuronal Markers in Allergic Rhinitis: Expression and Correlation With Sensory Testing. A1 - O'hanlon, S A1 - Facer, P A1 - Simpson, KD A1 - Sandhu, G A1 - Saleh, HA A1 - Anand, P J1 - Laryngoscope Y1 - 2007/07/17/ VL - Publish Ahead of Print SN - 0023-852X N2 - INTRODUCTION:: Although the role of immunoglobulin E-mediated hypersensitivity reactions in allergic rhinitis is well known, the relative contribution of sensory nerves to the symptoms of rhinitis is uncertain. This study looked at the level of specific neuronal markers including the nerve marker protein gene product 9.5 (PGP 9.5), sensory and autonomic neuropeptides, the capsaicin/heat receptor TRPV1, and nerve growth factor (NGF) in patients with allergic rhinitis and controls and their correlation with nasal sensitivity. MATERIALS AND METHODS:: Forty patients (23 controls, 17 rhinitis) having nasal surgery were recruited. Nasal sensitivity was tested using graded monofilaments. Inferior turbinate biopsies were collected and studied using immunohistology, with measurement of nerve fibers by direct observation or computerized image analysis. RESULTS:: Nerve fibers (PGP 9.5) in the epithelium, subepithelium, and glandular/vascular regions were significantly increased in allergic rhinitis (P = .037, <.01, and .04, respectively), as were subepithelial and glandular/vascular fibers immunoreactive for neuropeptide substance P (P = .04 subepithelium; .02 glandular/vascular) and neuropeptide tyrosine (P < .01 glandular/vascular), markers for sensory and sympathetic nerves, respectively. TRPV1 epithelial fiber counts were higher in rhinitis, but thiswas not statistically significant. Epithelial NGF immunoreactivity (% area) was significantly increased in rhinitis (P = .027). Nasal sensitivity was correlated significantly with PGP 9.5 subepithelial innervation (control touch P = .023, irritation P = .046; rhinitis touch P = .042, irritation P = .043). A correlation was also observed between epithelial NGF and subepithelial PGP 9.5 innervation, which included all subjects (P = .044). CONCLUSION: The increased number and specific phenotypical changes of sensory nerves may play a role in nasal hypersensitivity and provide new targets for the treatment of rhinitis. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17667132&query_hl=1 ER - TY - JFULL T1 - Cortical control of erector spinae muscles during arm abduction in humans. A1 - Kuppuswamy, A A1 - Catley, M A1 - King, NK A1 - Strutton, PH A1 - Davey, NJ A1 - Ellaway, PH J1 - Gait Posture Y1 - 2007/07/16/ SN - 0966-6362 N2 - Abduction of one arm preferentially activates erector spinae muscles on the other side to stabilise the body. We hypothesise that the corticospinal drive to the arm abductors and the erector spinae may originate from the same hemisphere. In 18 subjects, transcranial magnetic stimulation (TMS) was applied using an angle double-cone coil placed symmetrically over the vertex. Motor evoked potentials (MEP) could not be evoked systematically seated at rest but could be evoked bilaterally in erector spinae muscles during unilateral arm abduction. TMS was applied at 110% and 120% motor threshold (MT) for the contralateral erector spinae muscle when an arm was abducted against resistance. The electromyographic (EMG) activity in the erector spinae at L4 vertebral level during contralateral arm abduction was significantly higher (P<0.05) than in the ipsilateral erector spinae. The mean (+/-S.E.M.) latencies of MEPs in the contralateral muscle to TMS at 120%MT (left 16.0+/-0.8ms; right 17.0+/-0.8ms) were significantly (P<0.05) longer than in the ipsilateral erector spinae (13.9+/-1.0ms; 16.6+/-0.4ms). In two of six subjects from the same group, it was possible to elicit MEPs by TMS applied selectively to one hemisphere using a figure-of-eight coil. MEPs ipsilateral to the TMS had longer latencies than contralateral MEPs. The study revealed an unexpectedly longer rather than shorter latency of the MEP recorded from the lumbar erector spinae muscles when co-activated during abduction of the opposite arm. A speculative explanation is that TMS might activate back muscles contralateral to arm abduction via an uncrossed, ipsilateral corticospinal tract that is slower conducting than the conventional crossed corticospinal tract. The study has implications for the design of measures to promote recovery and rehabilitation of motor function in disorders such as stroke and spinal cord injury. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17644335&query_hl=1 ER - TY - JFULL T1 - Neurochemical characterization of insulin receptor-expressing primary sensory neurons in wild-type and vanilloid type 1 transient receptor potential receptor knockout mice. A1 - Baiou, D A1 - Santha, P A1 - Avelino, A A1 - Charrua, A A1 - Bacskai, T A1 - Matesz, K A1 - Cruz, F A1 - Nagy, I J1 - J Comp Neurol Y1 - 2007/07/10/ VL - 503 SN - 0021-9967 SP - 334 EP - 347 N2 - The insulin receptor (IR) is expressed by a subpopulation of primary sensory neurons (PSN), including a proportion of cells expressing the nociceptive transducer vanilloid type 1 transient receptor potential receptor (TRPV1). Recent data suggest functional links between the IR and other receptors, including TRPV1, which could be involved in the development of PSN malfunctions in pathological insulin secretion. Here we used combined immunohistochemical labelling on sections from L4-5 dorsal root ganglia of wild-type (WT) and TRPV1 knockout (KO) mice to examine the neurochemical properties of IR-expressing PSN and the possible effect of deletion of TRPV1 on those characteristics. We found that antibodies raised against the high-molecular-weight neurofilament (NF-200) and the neurofilament protein peripherin distinguished between small and large neurons. We also found that the IR was expressed predominantly by the small peripherin-immunopositive cells both in the WT and in the KO animals. IR expression, however, did not show any preference between the major subpopulations of the small cells, the calcitonin gene-related peptide (CGRP)-expressing and Bandeiraea simplicifolia isolectin B4 (IB4)-binding neurons, either in the WT or in the KO mice. Nevertheless, a significant proportion of the IR-expressing cells also expressed TRPV1. Comparison of the staining pattern of these markers showed no difference between WT and KO animals. These findings indicate that the majority of the IR-expressing PSN are small neurons, which are considered as nociceptive cells. Furthermore, these data show that deletion of the TRPV1 gene does not induce any additional changes in neurochemical phenotype of nociceptive PSN. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17492627&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 - Taking the sting out of pain. A1 - Nagy, I A1 - Paule, C A1 - White, J A1 - Urban, L J1 - Br J Pharmacol Y1 - 2007/07// VL - 151 SN - 0007-1188 SP - 721 EP - 722 N2 - While the role of the brain kallikrein-kinin system in the development of various pathological processes, such as oedema formation following brain injury or induction of central hypertonia has generated major interest, the possible role of this system in nociceptive processing has received little attention. In their present paper, Mortari et al. (2007) show that bradykinin B2 receptor activation in the brain by the bradykinin analogue, Thr(6)-bradykinin, isolated from the venom of the social wasp, Polybia occidentalis potently reduces acute, noxious heat-evoked reflex responses in naive rats. The unknown underlying mechanism of this powerful antinociceptive effect reminds us that the supraspinal antinociceptive system is still a "black box" in many aspects and awaits thorough investigation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17533427&query_hl=1 ER - TY - JFULL T1 - Papillary tumor of the pineal region and spindle cell oncocytoma of the pituitary: new tumor entities in the 2007 WHO Classification. A1 - Roncaroli, F A1 - Scheithauer, BW J1 - Brain Pathol Y1 - 2007/07// VL - 17 SN - 1015-6305 SP - 314 EP - 318 N2 - We have reviewed the features of two recently described intracranial tumors, which have been formally recognized as distinct entities by the 2007 WHO Classification of Brain Tumours: Papillary tumor of the pineal region and spindle cell oncocytoma of the pituitary gland. Their salient clinicopathological features, differential diagnosis, histogenetic hypothesis and outcome are discussed. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17598824&query_hl=1 ER - TY - JFULL T1 - Disease progression after bone marrow transplantation in a model of multiple sclerosis is associated with chronic microglial and glial progenitor response. A1 - Cassiani-Ingoni, R A1 - Muraro, PA A1 - Magnus, T A1 - Reichert-Scrivner, S A1 - Schmidt, J A1 - Huh, J A1 - Quandt, JA A1 - Bratincsak, A A1 - Shahar, T A1 - Eusebi, F A1 - Sherman, LS A1 - Mattson, MP A1 - Martin, R A1 - Rao, MS J1 - J Neuropathol Exp Neurol Y1 - 2007/07// VL - 66 SN - 0022-3069 SP - 637 EP - 649 N2 - Multiple sclerosis (MS), the most common nontraumatic cause of neurologic disability in young adults in economically developed countries, is characterized by inflammation, gliosis, demyelination, and neuronal degeneration in the CNS. Bone marrow transplantation (BMT) can suppress inflammatory disease in a majority of patients with MS but retards clinical progression only in patients treated in the early stages of the disease. Here, we applied BMT in a mouse model of neuroinflammation, experimental autoimmune encephalomyelitis (EAE), and investigated the kinetics of reconstitution of the immune system in the periphery and in the CNS using bone marrow cells isolated from syngeneic donors constitutively expressing green fluorescent protein. This approach allowed us to dissect the contribution of donor cells to the turnover of resident microglia and to the pathogenesis of observed disease relapses after BMT. BMT effectively blocked or delayed EAE development when mice were treated early in the course of the disease but was without effect in mice with chronic disease. We found that there is minimal overall replacement of host microglia with donor cells in the CNS and that newly transplanted cells do not appear to contribute to disease progression. In contrast, EAE relapses are accompanied by the robust activation of endogenous microglial and macroglial cells, which further involves the maturation of endogenous Olig2 glial progenitor cells into reactive astrocytes through the cytoplasmic translocation of Olig2 and the expression of CD44 on the cellular membrane. The observed maturation of large numbers of reactive astrocytes from glial progenitors and the chronic activation of host microglial cells have relevance for our understanding of the resident glial response to inflammatory injury in the CNS. Our data indicate that reactivation of a local inflammatory process after BMT is sustained predominantly by endogenous microglia/macrophages. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17620989&query_hl=1 ER - TY - JFULL T1 - Modified Overt Aggression Scale (MOAS) for people with intellectual disability and aggressive challenging behaviour: A reliability study A1 - Oliver, PC A1 - Crawford, MJ A1 - Rao, B A1 - Reece, B A1 - Tyrer, P J1 - J APPL RES INTELLECT Y1 - 2007/07// VL - 20 SP - 368 EP - 372 N2 - Background Reliable measures of aggressive challenging behaviour are required if interventions aimed at reducing this behaviour among people with intellectual disability (ID) are to be formally evaluated. The present authors examined the reliability of the Modified Overt Aggression Scale (MOAS), an instrument not yet formally tested in those with ID, in a sample of people who participated in a randomized trial of neuroleptic medication for aggressive challenging behaviour.Method Sixty interviews using the MOAS were carried out by two interviewers 2-5 days apart with 23 carers of 14 people who had shown aggressive challenging behaviour. Level of agreement between these two ratings was examined for four subscales of aggression and for total MOAS score.Results The level of agreement between the raters was high for verbal aggression (intraclass correlation coefficient, ICC = 0.90), physical aggression against others (ICC = 0.90) and for total MOAS score (ICC = 0.93). Levels of agreement on the other two subscales were lower but still in the good/moderate range.Conclusion The MOAS provides a reliable measure of verbal and physical aggression among people with ID who reside in community settings and is suitable for use in studies evaluating the effectiveness of interventions aimed at reducing aggressive challenging behaviour in this group. 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 - Brain opioid receptor binding in early abstinence from opioid dependence: positron emission tomography study. A1 - Williams, TM A1 - Daglish, MR A1 - Lingford-Hughes, A A1 - Taylor, LG A1 - Hammers, A A1 - Brooks, DJ A1 - Grasby, P A1 - Myles, JS A1 - Nutt, DJ J1 - Br J Psychiatry Y1 - 2007/07// VL - 191 SN - 0007-1250 SP - 63 EP - 69 N2 - BACKGROUND: Although opioid receptor function in humans is clearly reduced during opioid dependence, what happens to the receptor in early abstinence is not understood. AIMS: This study sought to examine changes in opioid receptor availability in early abstinence from opioid dependence. METHOD: Ten people with opioid dependence who had completed in-patient detoxification and 20 healthy controls underwent [11C]-diprenorphine positron emission tomography. Clinical variables were assessed with structured questionnaires. Opioid receptor binding was characterised as the volume of distribution of [11C]-diprenorphine using a template of predefined brain volumes and an exploratory voxel-by-voxel analysis. RESULTS: Compared with controls, participants with opioid dependence had increased [11C]-diprenorphine binding in the whole brain and in 15 of the 21 a priori regions studied. CONCLUSIONS: This study suggests that opioid receptor binding is increased throughout the brain in early abstinence from dependent opioid use. These data complement the findings in cocaine and alcohol dependence. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17602127&query_hl=1 ER - TY - JFULL T1 - Post-deep brain stimulation - gradual non-stimulation dependent decrease in strength with attenuation of multiple sclerosis tremor. A1 - Hyam, JA A1 - Aziz, TZ A1 - Bain, PG J1 - J Neurol Y1 - 2007/07// VL - 254 SN - 0340-5354 SP - 854 EP - 860 N2 - Tremor in multiple sclerosis is considered to be a persistent and progressive sign. We describe five patients with multiple sclerosis in whom upper limb tremor severity gradually decreased over a period of several years after deep brain stimulation. In every case this attenuation of tremor was accompanied by increasing pyramidal weakness in the relevant upper limb. In two patients this attenuation of tremor remained after stimulation was permanently switched off. In one other patient, where upper limb strength remained normal, tremor severity gradually worsened in spite of continuing stimulation. There was a highly significant difference (p = 0.0007) between the changes in intention tremor severities when the arms with increasing pyramidal weakness (n = 9) were compared to those in which normal strength was retained throughout follow-up period (n = 3); intention tremor decreased in the former and increased in the latter by means of -3.66 and +4.0 points of a 0-10 tremor scale respectively. There was also a significant correlation (0.699; p = 0.0359) between decreasing upper limb strength and decreasing intention tremor severity for the upper limbs of patients that had undergone contralateral DBS. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17431703&query_hl=1 ER - TY - JFULL T1 - Natural killer cells, killer immunoglobulin-like receptors and human leucocyte antigen class I in disease. A1 - Boyton, RJ A1 - Altmann, DM J1 - Clin Exp Immunol Y1 - 2007/07// VL - 149 SN - 0009-9104 SP - 1 EP - 8 N2 - Natural killer cells constitute a potent, rapid part of the innate immune response to infection or transformation, and also generate a link to priming of adaptive immunity. Their function can encompass direct cytotoxicity as well as the release of cytokines and chemokines. In humans, a major component of natural killer (NK) cell target recognition depends mainly on the surveillance of human leucocyte antigen (HLA) class I molecules by killer immunoglobulin-like receptors (KIR). Different KIR can transmit inhibitory or activatory signals to the cell, and effector function is considered to result from the balance of these contributing signals. The regulation of NK cell responses depends on a number of variables: KIR genotype, HLA genotype, heterozygosity versus homozygosity for these, whether there is cognate recognition between the HLA and KIR products carried by an individual, clonal variation between individual NK cells in KIR expression, and the specific modulation of HLA expression by infection, transformation or peptide binding. Different HLA/KIR genotypes can impart different thresholds of activation to the NK cell repertoire and such genotypic variation has been found to confer altered risk in a number of diseases including human immunodeficiency virus (HIV) susceptibility and progression, hepatitis C virus clearance, idiopathic bronchiectasis, autoimmunity and cancer. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17521317&query_hl=1 ER - TY - JFULL T1 - Investigating the mechanisms of deep brain stimulation: Computational modelling approaches – A commentary. A1 - N Yousif A1 - X Liu J1 - Current Medical Literature: Neurology Y1 - 2007/07// VL - 23 SP - 29 EP - 34 ER - TY - JFULL T1 - The size and distribution of midbrain dopaminergic populations are permanently altered by perinatal glucocorticoid exposure in a sex- region- and time-specific manner. A1 - McArthur, S A1 - McHale, E A1 - Gillies, GE J1 - Neuropsychopharmacology Y1 - 2007/07// VL - 32 SN - 0893-133X SP - 1462 EP - 1476 N2 - Central dopaminergic (DA) systems appear to be particularly vulnerable to disruption by exposure to stressors in early life, but the underlying mechanisms are poorly understood. As endogenous glucocorticoids (GCs) are implicated in other aspects of neurobiological programming, this study aimed to characterize the effects of perinatal GC exposure on the cytoarchitecture of DA populations in the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA). Dexamethasone was administered non-invasively to rat pups via the mothers' drinking water during embryonic days 16-19 or postnatal days 1-7, with a total oral intake circa 0.075 or 0.15 mg/kg/day, respectively; controls received normal drinking water. Analysis of tyrosine hydroxylase-immunoreactive cell counts and regional volumes in adult offspring identified notable sex differences in the shape and volume of the SNc and VTA, as well as the topographical organization and size of the DA populations. Perinatal GC treatments increased the DA population size and altered the shape of the SNc and VTA as well as the organization of the DA neurons by expanding and/or shifting them in a caudal direction. This response was sexually dimorphic and included a feminization or demasculinization of the three-dimensional cytoarchitecture in males, and subtle differences that were dependent on the window of exposure. These findings demonstrate that inappropriate perinatal exposure to GCs have enduring effects on the organization of midbrain DA systems that are critically important for normal brain function throughout life. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17164817&query_hl=1 ER - TY - JFULL T1 - Alterations in presenilin 1 processing by amyloid-beta peptide in the rat retina. A1 - Watts, HR A1 - Vince, V A1 - Walsh, DT A1 - Bresciani, LG A1 - Gentleman, SM A1 - Jen, LS A1 - Anderson, PJ J1 - Exp Brain Res Y1 - 2007/07// VL - 181 SN - 0014-4819 SP - 69 EP - 77 N2 - Accumulating evidence indicates that mutations in the presenilin 1 (PS1) gene are responsible for most cases of familial Alzheimer's disease (AD). Although its biological functions are not yet fully understood, it appears that PS1 plays a role in the processing and trafficking of the amyloid precursor protein (APP). However, little is known about factors that are involved in regulating the metabolism of PS1 especially in relation to AD pathology. In this study, we have examined the effect of optic nerve crush, intravitreal injection of the inflammatory agent lipopolysaccharide (LPS) or injection of amyloid beta(1-42) (Abeta(1-42)) on the expression and processing of PS1 in the rat retina. We found that 48 h after injection of Abeta(1-42) there was a dramatic alteration in the banding pattern of PS1 on Western blots, as indicated by marked changes in the levels of expression of some of its C- and N-terminal fragments in retinal homogenates. These results suggest an Abeta(1-42)-induced potentiation of a non-specific stress-related but inflammation-independent alteration of processing of PS1 in this in vivo model. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17333007&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 - Human medial frontal cortex mediates unconscious inhibition of voluntary action. A1 - Sumner, P A1 - Nachev, P A1 - Morris, P A1 - Peters, AM A1 - Jackson, SR A1 - Kennard, C A1 - Husain, M J1 - Neuron Y1 - 2007/06/07/ VL - 54 SN - 0896-6273 SP - 697 EP - 711 N2 - Within the medial frontal cortex, the supplementary eye field (SEF), supplementary motor area (SMA), and pre-SMA have been implicated in the control of voluntary action, especially during motor sequences or tasks involving rapid choices between competing response plans. However, the precise roles of these areas remain controversial. Here, we study two extremely rare patients with microlesions of the SEF and SMA to demonstrate that these areas are critically involved in unconscious and involuntary motor control. We employed masked-prime stimuli that evoked automatic inhibition in healthy people and control patients with lateral premotor or pre-SMA damage. In contrast, our SEF/SMA patients showed a complete reversal of the normal inhibitory effect--ocular or manual--corresponding to the functional subregion lesioned. These findings imply that the SEF and SMA mediate automatic effector-specific suppression of motor plans. This automatic mechanism may contribute to the participation of these areas in the voluntary control of action. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17553420&query_hl=1 ER - TY - JFULL T1 - Remyelination can be extensive in multiple sclerosis despite a long disease course. A1 - Patani, R A1 - Balaratnam, M A1 - Vora, A A1 - Reynolds, R J1 - Neuropathol Appl Neurobiol Y1 - 2007/06// VL - 33 SN - 0305-1846 SP - 277 EP - 287 N2 - Experimental studies using models of multiple sclerosis (MS) indicate that rapid and extensive remyelination of inflammatory demyelinated lesions is not only possible, but is the normal situation. The presence of completely remyelinated MS lesions has been noted in numerous studies and routine limited sampling of post mortem MS material suggests that remyelination may be extensive in the early stages but eventually fails. However, visual macroscopic guided sampling tends to be biased towards chronic demyelinated lesions. Here we have extensively sampled cerebral tissue from two MS cases to investigate the true extent of remyelination. Sections were cut from 185 cerebral tissue blocks and stained with haematoxylin and eosin (H&E), luxol fast blue and cresyl fast violet (LFB/CFV) and anti-myelin oligodendrocyte glycoprotein, human leucocyte antigen-DR (HLA-DR) and 200 kDa neurofilament protein antibodies. Demyelinated areas were identified in 141 blocks, comprising both white matter (WMLs) and/or grey matter lesions. In total, 168 WMLs were identified, 22% of which were shadow plaques, 73% were partially remyelinated and only 5% were completely demyelinated. The average extent of lesion remyelination for all WMLs investigated was 47%. Increased density of HLA-DR(+) macrophages and microglia at the lesion border correlated significantly with more extensive remyelination. Results from this study of two patients with long standing disease suggest that remyelination in MS may be more extensive than previously thought. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17442065&query_hl=1 ER - TY - JFULL T1 - Vagal and sympathetic heart rate and blood pressure control in adult onset PHOX2B mutation-confirmed congenital central hypoventilation syndrome A1 - Diedrich, A A1 - Malow, BA A1 - Antic, NA A1 - Sato, K A1 - McEvoy, RD A1 - Mathias, CJ A1 - Robertson, D A1 - Berry-Kravis, EM A1 - Weese-Mayer, DE J1 - CLIN AUTON RES Y1 - 2007/06// VL - 17 SN - 0959-9851 SP - 177 EP - 185 N2 - Background Children with Congenital Central Hypoventilation Syndrome (CCHS) typically present as newborns with alveolar hypoventilation. With the advent of genetic testing, parents of affected children and other unrelated adults, all heterozygous for the disease-defining PHOX2B polyalanine expansion mutation with the 20/25 genotype, are being identified in adulthood. Though children with PHOX2B mutation-confirmed CCHS demonstrate ANS dysregulation, including altered heart rate and blood pressure control, it is unknown if adults with CCHS have similarly affected autonomic function in blood pressure control. Methods and Results An autonomic profile of blood pressure control has been studied with recording of muscle sympathetic activity and spectral analysis of heart rate and blood pressure variability of one adult patient with alveolar hypoventilation and the 20/25 PHOX2B genotype. All parameters of heart rate variability were reduced. Cardiac baroreflex sensitivity was decreased. Sympathetic responses to Valsalva maneuver, hypoxemia, isometric exercise and cold pressor were blunted. Conclusion In summary, we found a reduced cardiac baroreflex and a blunted sympathetic mediated response in the individual with adult-onset CCHS, possibly due to dysfunction in the afferent pathway. Our results confirm that PHOX2B affects the development of the autonomic nervous system, possibly causing absence of normal maturation of carotid body and visceral sensory ganglia and leading to autonomic dysfunction in adult-onset CCHS. 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 - Involvement of prefrontal cortex in visual search. A1 - Anderson, EJ A1 - Mannan, SK A1 - Husain, M A1 - Rees, G A1 - Sumner, P A1 - Mort, DJ A1 - McRobbie, D A1 - Kennard, C J1 - Exp Brain Res Y1 - 2007/06// VL - 180 SN - 0014-4819 SP - 289 EP - 302 N2 - Visual search for target items embedded within a set of distracting items has consistently been shown to engage regions of occipital and parietal cortex, but the contribution of different regions of prefrontal cortex remains unclear. Here, we used fMRI to compare brain activity in 12 healthy participants performing efficient and inefficient search tasks in which target discriminability and the number of distractor items were manipulated. Matched baseline conditions were incorporated to control for visual and motor components of the tasks, allowing cortical activity associated with each type of search to be isolated. Region of interest analysis was applied to critical regions of prefrontal cortex to determine whether their involvement was common to both efficient and inefficient search, or unique to inefficient search alone. We found regions of the inferior and middle frontal cortex were only active during inefficient search, whereas an area in the superior frontal cortex (in the region of FEF) was active for both efficient and inefficient search. Thus, regions of ventral as well as dorsal prefrontal cortex are recruited during inefficient search, and we propose that this activity is related to processes that guide, control and monitor the allocation of selective attention. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17310377&query_hl=1 ER - TY - JFULL T1 - Vestibular perception and navigation in the congenitally blind. A1 - Seemungal, BM A1 - Glasauer, S A1 - Gresty, MA A1 - Bronstein, AM J1 - J Neurophysiol Y1 - 2007/06// VL - 97 SN - 0022-3077 SP - 4341 EP - 4356 N2 - Vestibular input is required for accurate locomotion in the dark, yet blind subjects' vestibular function is unexplored. Such investigation may also identify visually dependent aspects of vestibular function. We assessed vestibular function perceptually in six congenitally blind (and 12 sighted) subjects. Cupula deflection by a transient angular, horizontal acceleration generates a related vestibular nerve signal that declines exponentially with time constant approximately 4-7 s, which is prolonged to 15 s in the evoked vestibular-ocular reflex by the brain stem "velocity storage." We measured perceptual velocity storage in blind subjects following velocity steps (overall perceptual vestibular time constant, experiment 1) and found it to be significantly shorter (5.34 s; range: 2.39-8.58 s) than in control, sighted subjects (15.8 s; P < 0.001). Vestibular navigation was assessed by subjects steering a motorized Bárány-chair in response to imposed angular displacements in a path-reversal task, "go-back-to-start" (GBS: experiment 2); and a path-completion task, "complete-the-circle" (CTC: experiment 3). GBS performances (comparing response vs. stimulus displacement regression slopes and r(2)) were equal between groups (P > 0.05), but the blind showed worse CTC performance (P < 0.05). Two blind individuals showed ultrashort perceptual time constants, high lifetime physical activity scores and superior CTC performances; we speculate that these factors may be inter-related. In summary, the vestibular velocity storage as measured perceptually is visually dependent. Early blindness does not affect path reversal performance but is associated with worse path completion, a task requiring an absolute spatial strategy. Although congenitally blind subjects are overall less able to utilize spatial mechanisms during vestibular navigation, prior extensive physical spatial activity may enhance vestibular navigation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17392406&query_hl=1 ER - TY - JFULL T1 - Deep brain stimulation: a new treatment for hypertension? A1 - Green, AL A1 - Wang, S A1 - Bittar, RG A1 - Owen, SL A1 - Paterson, DJ A1 - Stein, JF A1 - Bain, PG A1 - Shlugman, D A1 - Aziz, TZ J1 - J Clin Neurosci Y1 - 2007/06// VL - 14 SN - 0967-5868 SP - 592 EP - 595 N2 - We report a 61-year-old hypertensive man who underwent deep brain stimulation of the periventricular/periaqueductal grey area for the relief of chronic neuropathic pain affecting his oral cavity and soft palate. During intraoperative stimulation, we were able to modulate his blood pressure up or down, depending on electrode location. This is the first evidence that hypertension could be effectively treated with electrical stimulation of the midbrain. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17430783&query_hl=1 ER - TY - JFULL T1 - Results of forty years Yellow Card reporting for commonly used perioperative analgesic drugs. A1 - Richardson, J A1 - Holdcroft, A J1 - Pharmacoepidemiol Drug Saf Y1 - 2007/06// VL - 16 SN - 1053-8569 SP - 687 EP - 694 N2 - BACKGROUND: A variety of analgesics are used perioperatively and associated adverse drug reactions (ADRs) may complicate anaesthesia and recovery. METHODS: We aimed to measure the demographics of reported suspected ADRs to alfentanil, fentanyl, ketorolac, morphine, nalbuphine, papaveretum, pethidine and remifentanil. We report a retrospective analysis of Yellow Card reports of suspected ADRs from 1965-2004 as classified in the Adverse Drug Reaction On-line Tracking database (ADROIT) of the Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: In total, 1312 reactions were retrieved. A single drug was reported in 908, 39 were fatal and 219 categorised as 'allergic'. Allergic phenomenon varied from 2/33 (6%) for remifentanil to 11/53 (21%) for alfentanil. 'Cardiovascular' reactions were reported frequently with remifentanil (18/33, 55%) and alfentanil (19/53, 36%) and these generated a signal for possible hazards from proportional reporting ratios (PRRs). The opioid fentanyl was associated with similar hazard signals for muscular and psychiatric ADRs. CONCLUSIONS: Perioperative vigilance may reduce morbidity and mortality from preventable ADRs to analgesic drugs. Denominator and diagnostic data are essential for prospective studies. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17436358&query_hl=1 ER - TY - JFULL T1 - Altered emotional decision-making in prisoners with borderline personality disorder. A1 - Kirkpatrick, T A1 - Joyce, E A1 - Milton, J A1 - Duggan, C A1 - Tyrer, P A1 - Rogers, RD J1 - J Personal Disord Y1 - 2007/06// VL - 21 SN - 0885-579X SP - 243 EP - 261 N2 - Previous studies have identified neuropsychological deficits in individuals with antisocial personality disorder and/or psychopathy. Few studies have examined neuropsychological functioning in individuals with borderline personality disorder (BPD), and no studies have yet investigated cognitive and emotional function in male prisoners with BPD. In this study, we compared the risky decision-making of 17 participants with a history of serious violent or sexual offenses and a diagnosis of DSM-IV BPD with that of 17 participants with similar offending histories but personality disorders other than BPD. Those with BPD exhibited altered processing of information about potential losses (punishment) when the probability of gains (reward) was high; they also increased their choice of risky options even in circumstances where this was clearly avoidable. These data suggest that individuals with a diagnosis of BPD and a history of serious offenses have problems integrating different reinforcement signals when choosing between risky actions, perhaps reflecting corticolimbic dysfunction as an underlying mechanism in BPD. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17536938&query_hl=1 ER - TY - JFULL T1 - Authors' reply:. A1 - Burns, T A1 - Yiend, J A1 - Tyrer, P J1 - Br J Psychiatry Y1 - 2007/06// VL - 190 SN - 0007-1250 SP - 538 EP - 538 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17541121&query_hl=1 ER - TY - JFULL T1 - Giving voice to contrary opinions A1 - Tyrer, P J1 - BRIT J PSYCHIAT Y1 - 2007/06// VL - 190 SN - 0007-1250 SP - 546 EP - 546 ER - TY - JFULL T1 - Mechanical and cold hypersensitivity in nerve-injured C57BL/6J mice is not associated with fear-avoidance- and depression-related behaviour. A1 - Hasnie, FS A1 - Wallace, VC A1 - Hefner, K A1 - Holmes, A A1 - Rice, AS J1 - Br J Anaesth Y1 - 2007/06// VL - 98 SN - 0007-0912 SP - 816 EP - 822 N2 - BACKGROUND: Neuropathic pain is associated with significant co-morbidity, including anxiety and depression, which impact considerably on the overall patient experience. However, pain co-morbidity symptoms are rarely assessed in animal models of neuropathic pain. To improve the clinical validity of a widely used rodent model of traumatic peripheral neuropathy, we have investigated fear-avoidance- and depression-related behaviours in nerve-injured and sham-operated mice over a 4 week period. METHODS: Male C57BL/6J mice were subjected to partial sciatic nerve ligation (PSNL) or sham surgery and were assessed on days 7, 14, and 28 after operation. Withdrawal thresholds to punctate mechanical and cooling stimuli were measured. Mice were tested on the novel open-field and elevated plus-maze tests for fear-avoidance behaviour, and on the tail suspension test for depression-related behaviour. RESULTS: Hypersensitivity to punctate mechanical and cool stimuli was evident up to day 28 after PSNL. However, there was no change in fear-avoidance- or depression-related behaviours regardless of interval after-surgery. CONCLUSION: These data demonstrate that pain behaviour in nerve-injured C57BL/6J mice was not associated with alterations in emotion-related behaviours. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17478455&query_hl=1 ER - TY - JFULL T1 - Issues in SMA clinical trial design. The International Coordinating Committee (ICC) for SMA Subcommittee on SMA Clinical Trial Design. A1 - Kaufmann, P A1 - Muntoni, F A1 - International Coordinating Committee for SMA Subcommittee on SMA Clinical Trial Design J1 - Neuromuscul Disord Y1 - 2007/06// VL - 17 SN - 0960-8966 SP - 499 EP - 505 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17300938&query_hl=1 ER - TY - JFULL T1 - A personalised genetic treatment for DMD A1 - Fletcher, S A1 - Adams, AM A1 - Harding, PL A1 - McClorey, G A1 - Muntoni, F A1 - Iversen, PL A1 - Wilton, SD J1 - J GENE MED Y1 - 2007/06// VL - 9 SN - 1099-498X SP - 529 EP - 529 ER - TY - JFULL T1 - The neuroprotective properties of heat shock protein 27 in experimental models of epilepsy, nerve injury and amyotrophic lateral sclerosis A1 - Sharp, P A1 - Senda, A A1 - Joshi, K A1 - Akbar, T A1 - De Belleroche, J J1 - J NEUROCHEM Y1 - 2007/06// VL - 101 SN - 0022-3042 SP - 15 EP - 16 ER - TY - JFULL T1 - Naturalistic follow-up of co-morbid substance use in schizophrenia: the West London first-episode study. A1 - Harrison, I A1 - Joyce, EM A1 - Mutsatsa, SH A1 - Hutton, SB A1 - Huddy, V A1 - Kapasi, M A1 - Barnes, TR J1 - Psychol Med Y1 - 2007/05/29/ SN - 0033-2917 SP - 1 EP - 10 N2 - Background. The impact of co-morbid substance use in first-episode schizophrenia has not been fully explored.Method. This naturalistic follow-up of a cohort of 152 people with first-episode schizophrenia examined substance use and clinical outcome in terms of symptoms and social and neuropsychological function.Results. Data were collected on 85 (56%) of the patient cohort after a median period of 14 months. Over the follow-up period, the proportion of smokers rose from 60% at baseline to 64%. While 30% reported lifetime problem drinking of alcohol at baseline, only 15% had problem drinking at follow-up. Furthermore, while at baseline 63% reported lifetime cannabis use and 32% were currently using the drug, by the follow-up assessment the latter figure had fallen to 18.5%. At follow-up, persistent substance users had significantly more severe positive and depressive symptoms and greater overall severity of illness. A report of no lifetime substance use at baseline was associated with greater improvement in spatial working memory (SWM) at follow-up.Conclusions. Past substance use may impede recovery of SWM performance in people with schizophrenia in the year or so following first presentation to psychiatric services. The prevalence of substance use other than tobacco tends to diminish over this period, in the absence of specific interventions. Persistent substance use in first-episode schizophrenia is associated with more severe positive and depressive symptoms but not negative symptoms, and should be a target for specific treatment intervention. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17532864&query_hl=1 ER - TY - JFULL T1 - The lack of expression of the peripheral benzodiazepine receptor characterises microglial response in anaplastic astrocytomas. A1 - Takaya, S A1 - Hashikawa, K A1 - Turkheimer, FE A1 - Mottram, N A1 - Deprez, M A1 - Ishizu, K A1 - Kawashima, H A1 - Akiyama, H A1 - Fukuyama, H A1 - Banati, RB A1 - Roncaroli, F J1 - J Neurooncol Y1 - 2007/05/23/ SN - 0167-594X N2 - The peripheral benzodiazepine receptor (PBR) is a 18 kDa molecule mainly involved in cholesterol transport through the mitochondrial membrane. In microglia, PBR is expressed from the earliest stages of activation and appears to exert a pro-inflammatory function. This molecule is commonly up-regulated in inflammatory, degenerative, infective and ischaemic lesions of the central nervous system but it has never been reported in glioma-infiltrating microglia. We examined two anaplastic astrocytomas showing minimal contrast-enhancement and therefore little damage of the blood brain barrier to minimise the presence of blood borne macrophages within tumour tissue. The two lesions were studied in vivo using positron emission tomography (PET) with the specific PBR ligand [(11)C](R)-PK11195 and the corresponding tumour tissue was investigated with an anti-PBR antibody. Glioma-infiltrating microglia were characterised for molecules involved in antigen presentation and cytotoxic activity. As comparison, PBR was investigated in three brains with multiple sclerosis (MS) and three with Parkinson's disease (PD). The expression profile of four anaplastic astrocytomas was also exploited and results were compared to the profile of eleven samples of normal temporal lobe and nine cases of PD. PET studies showed that [(11)C](R)-PK11195 binding was markedly lower in tumours than in the contralateral grey matter. Pathological investigation revealed that glioma-infiltrating microglia failed to express PBR and cytotoxic molecules although some cells still expressed antigen presenting molecules. PBR and cytotoxic molecules were highly represented in MS and PD. Evaluation of microarray datasets confirmed these differences. Our results demonstrated PBR suppression in glioma-infiltrating microglia and suggested that PBR may have a relevant role in modulating the anti-tumour inflammatory response in astrocytic tumours. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17520179&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 - 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 - A UK Audit of Screening for the Metabolic Side Effects of Antipsychotics in Community Patients. A1 - Barnes, TR A1 - Paton, C A1 - Cavanagh, MR A1 - Hancock, E A1 - Taylor, DM J1 - Schizophr Bull Y1 - 2007/05/04/ SN - 0586-7614 N2 - Reviews of the association between psychotic disorder, the metabolic syndrome, diabetes, and antipsychotic drugs conclude that there is a need for active, routine physical health screening of patients' prescribed antipsychotic drugs. From published guidelines, we derived the audit standard that all such patients should, as a minimum, have their blood pressure, body mass index (BMI) (or other measure of obesity such as waist circumference), blood glucose (or HbA(1c)), and plasma lipids measured at least once a year. We conducted an audit of the clinical records of 1966 eligible patients under the care of 48 multidisciplinary, assertive outreach clinical teams in 21 mental health services across the United Kingdom. This revealed a recorded measurement within the previous year for blood pressure in 26% of the patients, obesity in 17%, blood glucose (or HbA(1c)) in 28% and plasma lipids in 22%, with all 4 measures documented in 11%. In the total national sample, 6% had a documented diagnosis of diabetes, 6% hypertension, and 6% dyslipidemia. Extrapolating from the prevalence of these disorders in similar populations suggests that for every patient with a known diagnosis of diabetes, another had not been recognized, for every known case of hypertension, 4 had been missed, and for every known case of dyslipidemia, 7 had been missed. The responses of the clinical teams to a questionnaire yielded information on obstacles to screening in routine practice, revealing uncertainty about whose responsibility this was, a lack of confidence about the interpretation of abnormal screening results, and limited access to basic equipment. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17483101&query_hl=1 ER - TY - JFULL T1 - Dangerous and severe personality disorder: antecedents and origins A1 - Maden, A J1 - BRIT J PSYCHIAT Y1 - 2007/05// VL - 190 SN - 0007-1250 SP - S8 EP - S11 N2 - The origins of the Dangerous and Severe Pesonality Disorder (DSPD) Programme can be traced to developments in structured assessment and services for the cognitive-behavioural treatment of sexual and violent offenders in other countries. A comparison with these other services highlights the strengths and weaknesses of DSPD. The decision to use a medical model raises ethical and financial questions that may jeopardise the Programme's future. ER - TY - JFULL T1 - An agitation of contrary opinions A1 - Tyrer, P J1 - BRIT J PSYCHIAT Y1 - 2007/05// VL - 190 SN - 0007-1250 SP - S1 EP - S2 N2 - Those people who are dangerous often have personality disorders. Should these individuals be dealt with by criminal justice or mental health services? England (note not Scotland) has taken the mental health route with the Dangerous and Severe Personality Disorder Programme. Is this bold move wise or foolish? To answer this question we have both evidence and opinion - neither is conclusive. ER - TY - JFULL T1 - The ternary Rab27a-Myrip-Myosin VIIa complex regulates melanosome motility in the retinal pigment epithelium. A1 - Lopes, VS A1 - Ramalho, JS A1 - Owen, DM A1 - Karl, MO A1 - Strauss, O A1 - Futter, CE A1 - Seabra, MC J1 - Traffic Y1 - 2007/05// VL - 8 SN - 1398-9219 SP - 486 EP - 499 N2 - The retinal pigment epithelium (RPE) contains melanosomes similar to those found in the skin melanocytes, which undergo dramatic light-dependent movements in fish and amphibians. In mammals, those movements are more subtle and appear to be regulated by the Rab27a GTPase and the unconventional myosin, Myosin VIIa (MyoVIIa). Here we address the hypothesis that a recently identified Rab27a- and MyoVIIa-interacting protein, Myrip, promotes the formation of a functional tripartite complex. In heterologous cultured cells, all three proteins co-immunoprecipitated following overexpression. Rab27a and Myrip localize to the peripheral membrane of RPE melanosomes as observed by immunofluorescence and immunoelectron microscopy. Melanosome dynamics were studied using live-cell imaging of mouse RPE primary cultures. Wild-type RPE melanosomes exhibited either stationary or slow movement interrupted by bursts of fast movement, with a peripheral directionality trend. Nocodazole treatment led to melanosome paralysis, suggesting that movement requires microtubule motors. Significant and similar alterations in melanosome dynamics were observed when any one of the three components of the complex was missing, as studied in ashen- (Rab27a defective) and shaker-1 (MyoVIIa mutant)-derived RPE cells, and in wild-type RPE cells transduced with adenovirus carrying specific sequences to knockdown Myrip expression. We observed a significant increase in the number of motile melanosomes, exhibiting more frequent and prolonged bursts of fast movement, and inversion of directionality. Similar alterations were observed upon cytochalasin D treatment, suggesting that the Rab27a-Myrip-MyoVIIa complex regulates tethering of melanosomes onto actin filaments, a process that ensures melanosome movement towards the cell periphery. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17451552&query_hl=1 ER - TY - JFULL T1 - Comparison of alternative methods of collection of service use data for the economic evaluation of health care interventions. A1 - Byford, S A1 - Leese, M A1 - Knapp, M A1 - Seivewright, H A1 - Cameron, S A1 - Jones, V A1 - Davidson, K A1 - Tyrer, P J1 - Health Econ Y1 - 2007/05// VL - 16 SN - 1057-9230 SP - 531 EP - 536 N2 - Economic evaluation of health care interventions usually requires the collection of service use data to estimate the total cost of participants in an evaluation. There are a number of methods available to measure the quantity of services used but little is known about the relative accuracy of alternative methods. In a multicentre randomised controlled trial of interventions for the treatment of adults with recurrent episodes of deliberate self-harm (the POPMACT trial), health service data were collected by patient self-report after six and twelve months and also from GP records by independent investigators. Agreement for overall costs was relatively high. However, this hides substantial variation in agreement between the two sources of information for different services. The results suggest that GP records provide more accurate data on the use of general practice-based contacts than patient report, but less reliable information on contacts with other health services. Thus reliance on GP records for data on hospital services and other community health services based outside of general practice surgeries is not recommended. Future research should explore the level of agreement between patient report and other providing sector records, such as hospital records. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17001749&query_hl=1 ER - TY - JFULL T1 - Rapid hyperspectral fluorescence lifetime imaging. A1 - De Beule, P A1 - Owen, DM A1 - Manning, HB A1 - Talbot, CB A1 - Requejo-Isidro, J A1 - Dunsby, C A1 - McGinty, J A1 - Benninger, RK A1 - Elson, DS A1 - Munro, I A1 - John Lever, M A1 - Anand, P A1 - Neil, MA A1 - French, PM J1 - Microsc Res Tech Y1 - 2007/05// VL - 70 SN - 1059-910X SP - 481 EP - 484 N2 - We report a rapid hyperspectral fluorescence lifetime imaging (FLIM) instrument that exploits high-speed FLIM technology in a line-scanning microscope. We demonstrate the acquisition of whole-field optically sectioned hyperspectral fluorescence lifetime image stacks (with 32 spectral bins) in less than 40 s and illustrate its application to unstained biological tissue. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17366615&query_hl=1 ER - TY - JFULL T1 - Continuous infusion of the cannabinoid WIN 55,212-2 to the site of a peripheral nerve injury reduces mechanical and cold hypersensitivity. A1 - Lever, IJ A1 - Pheby, TM A1 - Rice, AS J1 - Br J Pharmacol Y1 - 2007/05// VL - 151 SN - 0007-1188 SP - 292 EP - 302 N2 - BACKGROUND AND PURPOSE: Cannabinoids have analgesic and anti-inflammatory properties but their use is limited by psychotropic activity at CNS receptors. Restricting cannabinoid delivery to peripheral tissues at systemically inactive doses offers a potential solution to this problem. EXPERIMENTAL APPROACH: WIN 55,212-2 was continuously delivered to the site of a partial ligation injury to the sciatic nerve via a perineural catheter connected to a mini-osmotic pump implanted at the time of injury. Bilateral reflex limb withdrawal behaviour was measured in adult male Wistar rats in response to mechanical and cooling stimulation of the hind paw. KEY RESULTS: Compared with vehicle treatment, WIN 55,212-2 (1.4 microg microl(-1) hr(-1)) reduced hypersensitivity to stimuli applied to the injured limb at 2, 4 and 6 days after injury. The effects of WIN 55,212-2 (0.6-2.8 microg microl(-1) hr(-1)) were dose-dependent. Estimated EC(50) values for reduction in mean responses to mechanical and cooling stimulation (day 4 post-surgery) were 1.55 (95% C.I, [1.11-2.16]) microg microl(-1) hr(-1) and 1.52 (95% C.I, [1.07-2.18]) microg microl(-1) hr(-1), respectively. When delivered to the contralateral side to injury, WIN 55,212-2 (1.4 or 2.8 microg microl(-1) hr(-1)) did not significantly affect nerve injury-associated hypersensitivity. Co-perineural application of a CB(1) receptor antagonist SR141716a and WIN 55,212-2 prevented the effects of WIN 55,212-2 on hypersensitivity. Co-application of CB(2) receptor antagonist SR144528 reversed WIN 55,212-2's effect on mechanical hypersensitivity on day 2 only. CONCLUSIONS AND IMPLICATIONS: These data support a peripheral antihyperalgesic effect of WIN 55,212-2 when delivered directly to the site of a nerve injury at systemically inactive doses. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17375083&query_hl=1 ER - TY - JFULL T1 - Intervention following deliberate self-harm: enough evidence to act? A1 - Crawford, MJ A1 - Kumar, P J1 - Evid Based Ment Health Y1 - 2007/05// VL - 10 SN - 1362-0347 SP - 37 EP - 39 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17459970&query_hl=1 ER - TY - JFULL T1 - Middle meningeal artery hemorrhage: An incorrect name A1 - Fishpool, SJC A1 - Suren, N A1 - Roncaroli, F A1 - Ellis, H J1 - CLIN ANAT Y1 - 2007/05// VL - 20 SN - 0897-3806 SP - 371 EP - 375 N2 - Extradural hemorrhage is most commonly assumed to result from a middle meningeal artery rupture. This article challenges that assumption. The meningeal vasculature of 29 cadaveric specimens was examined macroscopically and microscopically at the level of the greater wing of the sphenoid bone and foramen spinosum. It was observed that the middle meningeal artery is accompanied by a pair of dural sinuses throughout the majority of its course, thus making exclusively arterial rupture an anatomical improbability. Furthermore, as these dural sinuses pass caudally through the foramen spinosum with the middle meningeal artery, they were seen to diverge to form a plexiform arrangement around the artery. This has not been reported before. ER - TY - JFULL T1 - Altered memory and affective instability in prisoners assessed for dangerous and severe personality disorder. A1 - Kirkpatrick, T A1 - Joyce, E A1 - Milton, J A1 - Duggan, C A1 - Tyrer, P A1 - Rogers, RD J1 - Br J Psychiatry Suppl Y1 - 2007/05// VL - 49 SN - 0960-5371 SP - s20 EP - s26 N2 - BACKGROUND: Previous studies of borderline personality disorder report neuropsychological impairments in several domains, including memory. No studies have compared memory functioning in high-risk prisoners with borderline personality disorder with similar prisoners with other personality disorders. AIMS: To explore mnemonic impairments in prisoners undergoing personality assessment as part of the dangerous and severe personality disorder initiative or detained in a medium secure facility. METHOD: We investigated memory function in 18 prisoners with borderline personality disorder and 18 prisoners with other personality disorders. RESULTS: Prisoners with borderline personality disorder exhibited a pattern of multi-modal impairments in the immediate and delayed recall of verbal and visual information, with some association with affective instability. These deficits were not associated with the severity of personality disturbance. CONCLUSIONS: These data suggest that memory deficits have some specificity in relation to the constituent traits of borderline personality disorder and indicate that neuropsychological assessment may be a source of useful adjunctive information for distinguishing between the cognitive and psychological difficulties of individual prisoners. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17470938&query_hl=1 ER - TY - JFULL T1 - Apparent diffusion coefficient changes and lesion evolution in Balo's type demyelination-correlation with histopathology. A1 - Ball, T A1 - Malik, O A1 - Roncaroli, F A1 - Quest, RA A1 - Aviv, RI J1 - Clin Radiol Y1 - 2007/05// VL - 62 SN - 0009-9260 SP - 498 EP - 503 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17398278&query_hl=1 ER - TY - JFULL T1 - T cell responses to a non-glycosylated epitope predominate in type II collagen-immunised HLA-DRB1*0101 transgenic mice. A1 - von Delwig, A A1 - Altmann, DM A1 - Charlton, FG A1 - McKie, N A1 - Isaacs, JD A1 - Holmdahl, R A1 - Robinson, JH J1 - Ann Rheum Dis Y1 - 2007/05// VL - 66 SN - 0003-4967 SP - 599 EP - 604 N2 - AIM: To study collagen-induced arthritis in human leucocyte antigen (HLA)-DR1 transgenic mice lacking endogenous major histocompatibility complex class II molecules (MHC-II) and to determine T cell specificity against the arthritogenic CII(259-273) epitope of type II collagen either unmodified or post-translationally glycosylated at Lys(264). METHODS: Arthritis was induced by immunisation with human type II collagen in complete Freund's adjuvant and measured by footpad swelling, clinical score and histology. T cell responses were assessed by proliferation of spleen and lymph node cells and in antigen presentation assays, using T cell hybridomas specific for the glycosylated and non-glycosylated CII(259-273) epitope. RESULTS: The incidence of arthritis was 50% in DR1-transgenic mice lacking endogenous MHC-II molecules. Recall T cell responses in draining lymph nodes and spleen were consistently greater against the non-glycosylated epitope than to the glycosylated CII(259-273). Most of the T cell hybridomas generated from CII-immunised mice recognised the non-glycosylated CII epitope and this form of the epitope was also presented with 100-fold higher efficiency and 1 h faster kinetics by both macrophages and dendritic cells. CONCLUSION: This study shows that T cell responses to the non-glycosylated epitope of heterologous (human) CII are dominant in HLA-DR1 transgenic mice lacking MHC-II, which could contribute to the pathogenicity of autoimmune arthritis. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17114189&query_hl=1 ER - TY - JFULL T1 - Hsp27 overexpression in the R6/2 mouse model of Huntington's disease: chronic neurodegeneration does not induce Hsp27 activation. A1 - Zourlidou, A A1 - Gidalevitz, T A1 - Kristiansen, M A1 - Landles, C A1 - Woodman, B A1 - Wells, DJ A1 - Latchman, DS A1 - de Belleroche, J A1 - Tabrizi, SJ A1 - Morimoto, RI A1 - Bates, GP J1 - Hum Mol Genet Y1 - 2007/05/01/ VL - 16 SN - 0964-6906 SP - 1078 EP - 1090 N2 - Huntington's disease (HD) is caused by an expanded polyglutamine tract in the huntingtin protein. Mitochondrial dysfunction and free radical damage occur in both R6/2 mice and HD patient brains and might play a role in disease pathogenesis. In cell culture systems, heat-shock protein 27 (Hsp27), a small molecular chaperone, suppresses mutant huntingtin-induced reactive oxygen species formation and cell death. To investigate this in vivo, we conducted an extensive phenotypic characterization of mice arising from a cross between R6/2 mice and Hsp27 transgenic mice but did not observe an improvement of the R6/2 phenotype. Hsp27 overexpression had no effect in reducing oxidative stress in the R6/2 brain, assessed by measuring striatal aconitase activity and protein carbonylation levels. Native protein gel analysis revealed that transgenic Hsp27 forms active, large oligomeric species in heat-shocked brain lysates, demonstrating that it is efficiently activated upon stress. In contrast, Hsp27 in double transgenic brains exists predominantly as a low molecular weight, inactive species. This suggests that Hsp27, which is otherwise activatable upon heat shock, remains inactive in the R6/2 model of chronic neurodegeneration. Hsp27 transgenics had been previously shown to be protected from acute stresses such as kainate administration, ischemia/reperfusion heart injury and neonatal nerve injury. Our study is the first to suggest a differential modulation of Hsp27 activation in vivo and, importantly, it illustrates the diverse effect of Hsp27 on acute versus chronic models of disease. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17360721&query_hl=1 ER - TY - JFULL T1 - Critical developments in the assessment of personality disorder. A1 - Tyrer, P A1 - Coombs, N A1 - Ibrahimi, F A1 - Mathilakath, A A1 - Bajaj, P A1 - Ranger, M A1 - Rao, B A1 - Din, R J1 - Br J Psychiatry Suppl Y1 - 2007/05// VL - 49 SN - 0960-5371 SP - s51 EP - s59 N2 - BACKGROUND: The assessment of personality disorder is currently inaccurate, largely unreliable, frequently wrong and in need of improvement. AIMS: To describe the errors inherent in the current systems and to indicate recent ways of improving personality assessment. METHOD: Historical review, description of recent developments, including temporal stability, and of studies using document-derived assessment. RESULTS: Studies of interrater agreement and accuracy of diagnosis in complex patients with independently established personality status using document-derived assessment (PAS-DOC) with a four personality cluster classification, showed very good agreement between raters for the flamboyant cluster B group of personalities, generally good agreement for the anxious/dependent cluster C group and inhibited (obsessional) cluster D group, but only fair agreement for the withdrawn cluster A group. Overall diagnostic accuracy was 71%. CONCLUSIONS: Personality function or diathesis, a fluctuating state, is a better description than personality disorder. The best form of assessment is one that uses longitudinal repeated measures using a four-dimensional system. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17470943&query_hl=1 ER - TY - JFULL T1 - Predictive factors for the development of scoliosis in Duchenne muscular dystrophy. A1 - Kinali, M A1 - Main, M A1 - Eliahoo, J A1 - Messina, S A1 - Knight, RK A1 - Lehovsky, J A1 - Edge, G A1 - Mercuri, E A1 - Manzur, AY A1 - Muntoni, F J1 - Eur J Paediatr Neurol Y1 - 2007/05// VL - 11 SN - 1090-3798 SP - 160 EP - 166 N2 - OBJECTIVE: Scoliosis is a frequent complication (68-90%) of Duchenne muscular dystrophy (DMD). Prevention of limb deformities, rehabilitation in knee-ankle-foot-orthoses (KAFOs) and glucocorticoids prolong walking and standing, and might reduce scoliosis. We evaluated possible predictive factors for scoliosis development in a large DMD population. METHODS: Case notes of 123 DMD boys, > or = 17 years, followed at our centre between 1992 and 2002 were reviewed. Univariate analysis was used to relate two outcome measures (age at onset of scoliosis and severity at 17 years) with (i) glucocorticoids treatment; (ii) ages at (a) loss of independent ambulation, (b) rehabilitation into KAFOs, (c) loss of standing, (iii) forced vital capacity (FVC) (%) between 11 and 12 years and (iv) lower limb contractures. RESULTS: In total, 37/123 boys (30%) received intermittent prednisolone (0.75 mg/kg/day, 10 day/month) for a median 1-year (2 months-9 years), starting between 7.7 and 12.4 years (mean 9.5). About 96/123 (78%) were rehabilitated into KAFOs at 10.2+/-1.6 years. Age at loss of ambulation in KAFOs was 12.3+/-1.9 years and at loss of standing 12.8+/-2.1 years. About 95/123 (77%) boys developed scoliosis (Cobb angle >30 degrees ). Mean age+/-S.D. at scoliosis onset was 12.7+/-1.6 years. Forty-three boys (35%) had scoliosis surgery by 15+/-1.2 years. Later age at loss of ambulation (p<0.0001) and longer duration of prednisolone treatment (p=0.01) related to later scoliosis onset. Ages at loss of ambulation and standing were inversely related to scoliosis severity at 17 years (p<0.005). Hip asymmetry and %FVC at 11-12 years were directly related to scoliosis severity (p=0.02). CONCLUSIONS: Our data indicate a significant association between prolonged ambulation and a reduced risk of scoliosis development. Glucocorticoid administration, in our series, appear to be associated with a later onset of scoliosis, but did not alter the severity at 17 years, probably reflecting the shorter overall glucocorticoid exposure in this population. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17257866&query_hl=1 ER - TY - JFULL T1 - Gastrostomy placement in paediatric patients with neuromuscular disorders: indications and outcome. A1 - Ramelli, GP A1 - Aloysius, A A1 - King, C A1 - Davis, T A1 - Muntoni, F J1 - Dev Med Child Neurol Y1 - 2007/05// VL - 49 SN - 0012-1622 SP - 367 EP - 371 N2 - Studies of children with neurodevelopmental disorders have shown that receiving nutrition through a gastrostomy can improve clinical outcomes and quality of life. However, there is little information on gastrostomy and its effect in patients with neuromuscular disorders. A retrospective casenote review of all patients with a gastrostomy, followed-up at the Hammersmith Hospital, London, was undertaken to assess the indications for, and outcomes of, gastrostomy placement. Notes for 32 patients (17 males, 15 females) were reviewed (age range 32mo-31y; median age 12y 5mo). We found three main groups of diagnoses: congenital muscular dystrophy (n=15), structural congenital myopathies (n=11), and other neuromuscular disorders (n=6). Two main patterns of feeding problems were identified before gastrostomy: swallowing difficulties, and nutrition and growth problems. The follow-up period after gastrostomy was from 12 months to 19 years (mean 5y). Weight faltering was reversed in 17 out of 22 patients, and height faltering in 9 out of 14, where data were available. Twenty-six patients had a reduced frequency of chest infections. No significant complication of gastrostomy placement was documented. Twenty-eight patients or their families were happy with the results of the gastrostomy. Gastrostomy seems to have a substantial positive impact in patients with neuromuscular disease and feeding difficulties. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17489811&query_hl=1 ER - TY - JFULL T1 - Increased NKCC1 expression in refractory human epilepsy A1 - Sen, A A1 - Martinian, L A1 - Nikolic, M A1 - Walker, MC A1 - Thom, M A1 - Sisodiya, SM J1 - EPILEPSY RES Y1 - 2007/05// VL - 74 SN - 0920-1211 SP - 220 EP - 227 N2 - Cation-chloride co-transporters; (CCTs), particularly NKCC1, may be important in epileptogenesis. We have performed a detailed histological examination of NKCC1 in large samples of patients with hippocampal sclerosis (HS) or focal cortical dysplasia (FCD), pathologies both commonly associated with pharmacoresistant epilepsy. We consistently found increased immunoreactivity for NKCC1 in HS and FCD, but not in adjacent histologically normal cortex. Our results suggest that NKCC1 might contribute to the pathogenesis or pathophysiology of HS and FCD, thereby potentially offering a new therapeutic target in the treatment of pharmacoresistant epilepsy. (C) 2007 Elsevier B.V. All rights reserved. ER - TY - JFULL T1 - Low-dose oral tri-iodothyronine does not directly increase food intake in man. A1 - Martin, NM A1 - Small, CJ A1 - Lee, JL A1 - Ellis, S A1 - Dhillo, WS A1 - Smith, KL A1 - Kong, WM A1 - Frost, GS A1 - Bloom, SR J1 - Diabetes Obes Metab Y1 - 2007/05// VL - 9 SN - 1462-8902 SP - 435 EP - 437 N2 - Previously, we have shown that low-dose tri-iodothyronine (T3) increases food intake in rodents. This randomised, double-blind, placebo-controlled study aimed to investigate the effects of low-dose T3 on food intake in normal body weight individuals. However, despite an elevation in fT3 comparable to our earlier studies, administration of low-dose T3 in the fasted state did not stimulate food intake in man. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17391172&query_hl=1 ER - TY - JFULL T1 - Imaging microglial activation in Huntington's disease. A1 - Tai, YF A1 - Pavese, N A1 - Gerhard, A A1 - Tabrizi, SJ A1 - Barker, RA A1 - Brooks, DJ A1 - Piccini, P J1 - Brain Res Bull Y1 - 2007/04/30/ VL - 72 SN - 0361-9230 SP - 148 EP - 151 N2 - Activated microglia have been proposed to play a major role in the pathogenesis of Huntington's Disease (HD). PK11195 is a ligand which binds selectively to peripheral benzodiazepine binding sites, a type of receptor selectively expressed by activated microglia in the central nervous system. Using (11)C-(R)-PK11195 positron emission tomography (PET), we have recently shown in vivo evidence of increased microglial activation in both symptomatic and presymptomatic HD gene carriers and that the degree of microglial activation in the striatum correlates with the severity of striatal dopamine D2 receptor dysfunction measured with (11)C-raclopride PET. Our findings indicate that microglial activation is an early process in the HD pathology, occurring before the onset of symptoms. The close spatial and temporal relationship between microglial activation and neuronal dysfunction lends further support to the pathogenic link between the two processes in HD. Further longitudinal studies are needed to fully elucidate this link. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17352938&query_hl=1 ER - TY - JFULL T1 - Spinal projection of spindle afferents of the longissimus lumborum muscles of the cat. A1 - Durbaba, R A1 - Taylor, A A1 - Ellaway, PH A1 - Rawlinson, S J1 - J Physiol Y1 - 2007/04/15/ VL - 580 SN - 0022-3751 SP - 659 EP - 675 N2 - The connections and monosynaptic projections of muscle spindle afferents of individual heads of the longissimus lumborum have been studied in cats by natural stimulation, by electrical stimulation and by spike-triggered averaging from single identified afferents. The spindle afferents were classified by sensitivity to vibration and by the effect of succinylcholine on their response to ramp-and-hold muscle stretches. Axonal conduction and synaptic effects were recorded as field potentials and focal synaptic potentials during systematic exploration of the spinal cord in segments L1 to L4 with extracellular metal microelectrodes, singly and in linear arrays. Ascending branches of afferent axons within the cord had a significantly higher mean conduction velocity (CV: 56.5 m s(-1)) than descending branches (40.8 m s(-1)). The CV of ascending branches was significantly positively correlated with a measure of the strength of intrafusal bag(2) muscle fibre contacts, but not to a measure of bag(1) contacts. Two sites of monosynaptic excitatory projection in the cord were identified, namely to the intermediate region (laminae V, VI and VII) and to ventral horn region (laminae VIII and IX). In tests of 154 single afferents, signs of central projection were detected for 60, providing 122 regions of maximum negative focal synaptic potentials (FSPs) of mean amplitude 7.51 microV. Their longitudinal spacing indicated that axons gave off descending collaterals at intervals of 1.5-3.5 mm. Based on the amplitude of FSPs, the projection of secondary afferents is stronger than that of primaries in the intermediate region and possibly also in the ventral horn region. Evidence is also presented that spindle afferent input from different heads of the longissimus converges into any given spinal segment and that input in one spinal root projects to adjacent segments. It is concluded that the organization of the longissimus monosynaptic spindle input favours relatively tonic and diffuse stretch reflexes. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17255163&query_hl=1 ER - TY - JFULL T1 - Pharmacological, behavioural and mechanistic analysis of HIV-1 gp120 induced painful neuropathy. A1 - Wallace, VC A1 - Blackbeard, J A1 - Pheby, T A1 - Segerdahl, AR A1 - Davies, M A1 - Hasnie, F A1 - Hall, S A1 - McMahon, SB A1 - Rice, AS J1 - Pain Y1 - 2007/04/11/ SN - 1872-6623 N2 - A painful neuropathy is frequently observed in people living with human immunodeficiency virus type 1 (HIV-1). The HIV coat protein, glycoprotein 120 (gp120), implicated in the pathogenesis of neurological disorders associated with HIV, is capable of initiating neurotoxic cascades via an interaction with the CXCR4 and/or CCR5 chemokine receptors, which may underlie the pathogenesis of HIV-associated peripheral neuropathic pain. In order to elucidate the mechanisms underlying HIV-induced painful peripheral neuropathy, we have characterised pathological events in the peripheral and central nervous system following application of HIV-1 gp120 to the rat sciatic nerve. Perineural HIV-1 gp120 treatment induced a persistent mechanical hypersensitivity (44% decrease from baseline), but no alterations in sensitivity to thermal or cold stimuli, and thigmotactic (anxiety-like) behaviour in the open field. The mechanical hypersensitivity was sensitive to systemic treatment with gabapentin, morphine and the cannabinoid WIN 55,212-2, but not with amitriptyline. Immunohistochemical studies reveal: decreased intraepidermal nerve fibre density, macrophage infiltration into the peripheral nerve at the site of perineural HIV-1 gp120; changes in sensory neuron phenotype including expression of activating transcription factor 3 (ATF3) in 27% of cells, caspase-3 in 25% of cells, neuropeptide Y (NPY) in 12% of cells and galanin in 13% of cells and a spinal gliosis. These novel findings suggest that this model is not only useful for the elucidation of mechanisms underlying HIV-1-related peripheral neuropathy but may prove useful for preclinical assessment of drugs for the treatment of HIV-1 related peripheral neuropathic pain. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17433546&query_hl=1 ER - TY - JFULL T1 - Cortical 5-HT1A receptor binding in patients with homozygous D90A SOD1 vs sporadic ALS A1 - Turner, MR A1 - Rabiner, EA A1 - Al-Chalabi, A A1 - Shaw, CE A1 - Brooks, DJ A1 - Leigh, PN A1 - Andersen, PM J1 - NEUROLOGY Y1 - 2007/04/10/ VL - 68 SN - 0028-3878 SP - 1233 EP - 1235 ER - TY - JFULL T1 - Rab27b regulates number and secretion of platelet dense granules. A1 - Tolmachova, T A1 - Abrink, M A1 - Futter, CE A1 - Authi, KS A1 - Seabra, MC J1 - Proc Natl Acad Sci U S A Y1 - 2007/04/03/ VL - 104 SN - 0027-8424 SP - 5872 EP - 5877 N2 - The Rab27 GTPase subfamily consists of two closely related homologs, Rab27a and Rab27b. Rab27a has been shown previously to regulate organelle movement and regulated exocytosis in a wide variety of secretory cells. However, the role of the more restrictedly expressed Rab27b remains unclear. Here we describe the creation of Rab27b knockout (KO) strain that was subsequently crossed with the naturally occurring Rab27a KO line, ashen, to produce double KO (Rab27a(ash/ash) Rab27b(-/-)) mice. Rab27b KO (and double KO) exhibit significant hemorrhagic disease in contrast to ashen mice. In vitro assays demonstrated impaired aggregation with collagen and U46619 and reduced secretion of dense granules in both Rab27b and double KO strains. Additionally, we detected a 50% reduction in the number of dense granules per platelet and diminished platelet serotonin content, possibly due to a dense granule packaging defect into proplatelets during megakaryocyte maturation. The presence of Rab27a partially compensated for the secretory defect but not the reduced granule number. The morphology and function of platelet alpha-granules were unaffected. Our data suggest that Rab27b is a key regulator of dense granule secretion in platelets and thus a candidate gene for delta-storage pool deficiency in humans. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17384153&query_hl=1 ER - TY - JFULL T1 - A population of myogenic stem cells that survives skeletal muscle aging. A1 - Collins, CA A1 - Zammit, PS A1 - Ruiz, AP A1 - Morgan, JE A1 - Partridge, TA J1 - Stem Cells Y1 - 2007/04// VL - 25 SN - 1066-5099 SP - 885 EP - 894 N2 - Age-related decline in integrity and function of differentiated adult tissues is widely attributed to reduction in number or regenerative potential of resident stem cells. The satellite cell, resident beneath the basal lamina of skeletal muscle myofibers, is the principal myogenic stem cell. Here we have explored the capacity of satellite cells within aged mouse muscle to regenerate skeletal muscle and to self-renew using isolated myofibers in tissue culture and in vivo. Satellite cells expressing Pax7 were depleted from aged muscles, and when aged myofibers were placed in culture, satellite cell myogenic progression resulted in apoptosis and fewer total differentiated progeny. However, a minority of cultured aged satellite cells generated large clusters of progeny containing both differentiated cells and new cells of a quiescent satellite-cell-like phenotype characteristic of self-renewal. Parallel in vivo engraftment assays showed that, despite the reduction in Pax7(+) cells, the satellite cell population associated with individual aged myofibers could regenerate muscle and self-renew as effectively as the larger population of satellite cells associated with young myofibers. We conclude that a minority of satellite cells is responsible for adult muscle regeneration, and that these stem cells survive the effects of aging to retain their intrinsic potential throughout life. Thus, the effectiveness of stem-cell-mediated muscle regeneration is determined by both extrinsic environmental influences and diversity in intrinsic potential of the stem cells themselves. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17218401&query_hl=1 ER - TY - JFULL T1 - Xenon mitigates isoflurane-induced neuronal apoptosis in the developing rodent brain. A1 - Ma, D A1 - Williamson, P A1 - Januszewski, A A1 - Nogaro, MC A1 - Hossain, M A1 - Ong, LP A1 - Shu, Y A1 - Franks, NP A1 - Maze, M J1 - Anesthesiology Y1 - 2007/04// VL - 106 SN - 0003-3022 SP - 746 EP - 753 N2 - BACKGROUND: Anesthetics, including isoflurane and nitrous oxide, an antagonist of the N-methyl-D-aspartate subtype of the glutamate receptor, have been demonstrated to induce apoptotic neurodegeneration when administered during neurodevelopment. Xenon, also an N-methyl-D-aspartate antagonist, not only lacks the characteristic toxicity produced by other N-methyl-D-aspartate antagonists, but also attenuates the neurotoxicity produced by this class of agent. Therefore, the current study sought to investigate xenon's putative protective properties against anesthetic-induced neuronal apoptosis. METHOD: Separate cohorts (n = 5 or 6 per group) of 7-day-old rats were randomly assigned and exposed to eight gas mixtures: air, 75% nitrous oxide, 75% xenon, 0.75% isoflurane, 0.75% isoflurane plus 35% or 75% nitrous oxide, 0.75% isoflurane plus 30% or 60% xenon for 6 h. Rats were killed, and cortical and hippocampal apoptosis was assessed using caspase-3 immunostaining. In separate cohorts, cortices were isolated for immunoblotting of caspase 3, caspase 8, caspase 9, and cytochrome c. Organotypic hippocampal slices of postnatal mice pups were derived and cultured for 24 h before similar gas exposures, as above, and subsequently processed for caspase-3 immunostaining. RESULTS: In vivo administration of isoflurane enhances neuronal apoptosis. When combined with isoflurane, nitrous oxide significantly increases whereas xenon significantly reduces apoptosis to a value no different from that of controls. In vitro studies corroborate the ability of xenon to attenuate isoflurane-induced apoptosis. Isoflurane enhanced expression of indicators of the intrinsic and common apoptotic pathways; this enhancement was increased by nitrous oxide but attenuated by xenon. CONCLUSIONS: The current study demonstrates that xenon prevents isoflurane-induced neonatal neuronal apoptosis. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17413912&query_hl=1 ER - TY - JFULL T1 - Identifying cardiorespiratory neurocircuitry involved in central command during exercise in humans A1 - Green, A A1 - Wang, SW A1 - Purvis, S A1 - Owen, SLF A1 - Bain, PG A1 - Stein, JF A1 - Guz, A A1 - Aziz, TZ A1 - Paterson, DJ J1 - FASEB J Y1 - 2007/04// VL - 21 SN - 0892-6638 SP - A566 EP - A566 ER - TY - JFULL T1 - Exploring the physiological effects of double-cone coil TMS over the medial frontal cortex on the anterior cingulate cortex: an H2(15)O PET study. A1 - Hayward, G A1 - Mehta, MA A1 - Harmer, C A1 - Spinks, TJ A1 - Grasby, PM A1 - Goodwin, GM J1 - Eur J Neurosci Y1 - 2007/04// VL - 25 SN - 0953-816X SP - 2224 EP - 2233 N2 - Transcranial magnetic stimulation (TMS) using a double-cone coil over the medial frontal cortex has the potential to clarify the function of the anterior cingulate cortex (ACC) in cognition, emotion and mood disorders. Following demonstration of disruption of performance on psychological tasks closely linked to cingulate function using this TMS technique, the current study aimed to directly measure the regional distribution of physiological effects of stimulation in the brain with H2(15)O PET. Experiment 1 assessed the effect of increasing numbers of pulse trains of TMS on regional cerebral blood flow (rCBF). Experiment 2 assessed the capacity of medial frontal TMS to modulate brain activity associated with the Stroop task using medial parietal TMS as a control site of stimulation. SPM99 analyses, using the ACC as a region of interest, revealed clusters of increased rCBF during medial frontal TMS in Brodmann area 24 and reduced rCBF in more ventral ACC, the latter occurring in both experiments. In a whole-brain analysis, striking changes in rCBF were observed distal to the ACC following medial frontal TMS. Although TMS reliably affected Stroop task performance in early trials, there was no interaction between TMS and Stroop condition in rCBF. Our results suggest that medial frontal TMS using the double-cone coil can affect ACC activity. However, a number of more distal cortical areas were also affected in these experiments. These additional changes may reflect either 'downstream' effects of altered cingulate cortex activity or direct effects of the coil. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17439499&query_hl=1 ER - TY - JFULL T1 - Upregulation of opioid receptor binding following spontaneous epileptic seizures. A1 - Hammers, A A1 - Asselin, MC A1 - Hinz, R A1 - Kitchen, I A1 - Brooks, DJ A1 - Duncan, JS A1 - Koepp, MJ J1 - Brain Y1 - 2007/04// VL - 130 SN - 1460-2156 SP - 1009 EP - 1016 N2 - Animal and limited human data suggest an important anticonvulsant role for opioid peptides and their receptors. We aimed to provide direct human in vivo evidence for changes in opioid receptor availability following spontaneous seizures. We scanned nine patients within hours of spontaneous temporal lobe seizures and compared their postictal binding of the non-subtype selective opioid receptor PET radioligand [11C]diprenorphine (DPN), quantified as a volume-of-distribution (VD), with interictal binding and with binding changes in 14 healthy controls, controlling for a range of behavioural variables associated with opioid action. A regionally specific increase of opioid receptor availability was evident in the temporal pole and fusiform gyrus ipsilateral to the seizure focus following seizures (Z 5.01, P < 0.001, 16 432 mm3). Within this region, there was a negative correlation between VD and log10 time since last seizure (r = -0.53, P < 0.03), compatible with an early increase and gradual return to baseline. [11C]DPN VD did not undergo systematic changes between time points in controls. This study provides direct human in vivo evidence for changes in opioid receptor availability over a time course of hours following spontaneous seizures, emphasizing an important role of the opioid system in seizure control. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17301080&query_hl=1 ER - TY - JFULL T1 - Expression of gamma-synuclein in Parkinson's disease A1 - Slonimsky, A A1 - Hickey, L A1 - Christian, L A1 - Dexter, DT A1 - Pearce, RKB A1 - Graeber, MB A1 - Moran, LB J1 - NEUROPATH APPL NEURO Y1 - 2007/04// VL - 33 SN - 0305-1846 SP - 256 EP - 256 ER - TY - JFULL T1 - Expression profiling in Alzheimer's disease A1 - Gentleman, SM J1 - NEUROPATH APPL NEURO Y1 - 2007/04// VL - 33 SN - 0305-1846 SP - 251 EP - 252 ER - TY - JFULL T1 - Unkind selves A1 - Tyrer, P J1 - BRIT J PSYCHIAT Y1 - 2007/04// VL - 190 SN - 0007-1250 SP - 370 EP - 370 ER - TY - JFULL T1 - Rab27a regulates phagosomal pH and NADPH oxidase recruitment to dendritic cell phagosomes. A1 - Jancic, C A1 - Savina, A A1 - Wasmeier, C A1 - Tolmachova, T A1 - El-Benna, J A1 - Dang, PM A1 - Pascolo, S A1 - Gougerot-Pocidalo, MA A1 - Raposo, G A1 - Seabra, MC A1 - Amigorena, S J1 - Nat Cell Biol Y1 - 2007/04// VL - 9 SN - 1465-7392 SP - 367 EP - 378 N2 - To prevent excessive degradation of internalized antigens, which could destroy the peptides recognized by T lymphocytes, dendritic cells have developed several strategies that limit proteolytic activity in phagosomes. The recruitment of the NADPH oxidase NOX2 prevents acidification of phagosomes, limiting antigen degradation. Here, we show that dendritic cells derived from Rab27a-deficient ashen mice show increased phagosome acidification and antigen degradation, causing a defect in antigen cross-presentation. Enhanced acidification results from a delay in the recruitment to phagosomes of a subset of lysosome-related organelles containing the membrane subunits of NOX2. The Rab27a-dependent recruitment of these "inhibitory lysosome-related organelles" to phagosomes continuously limits acidification and degradation of ingested particles in dendritic cells, thus promoting antigen cross-presentation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17351642&query_hl=1 ER - TY - JFULL T1 - Formyl peptide receptors and the regulation of ACTH secretion: targets for annexin A1, lipoxins, and bacterial peptides. A1 - John, CD A1 - Sahni, V A1 - Mehet, D A1 - Morris, JF A1 - Christian, HC A1 - Perretti, M A1 - Flower, RJ A1 - Solito, E A1 - Buckingham, JC J1 - FASEB J Y1 - 2007/04// VL - 21 SN - 1530-6860 SP - 1037 EP - 1046 N2 - The N-formyl peptide receptors (FPRs) are a family of G-protein coupled receptors that respond to proinflammatory N-formylated bacterial peptides (e.g., formyl-Met-Leu-Phe, fMLF) and, thus, contribute to the host response to bacterial infection. Paradoxically, a growing body of evidence suggests that some members of this receptor family may also be targets for certain anti-inflammatory molecules, including annexin A1 (ANXA1), which is an important mediator of glucocorticoid (GC) action. To explore further the potential role of FPRs in mediating ANXA1 actions, we have focused on the pituitary gland, where ANXA1 has a well-defined role as a cell-cell mediator of the inhibitory effects of GCs on the secretion of corticotrophin (ACTH), and used molecular, genetic, and pharmacological approaches to address the question in well-established rodent models. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis identified mRNAs for four FPR family members in the mouse anterior pituitary gland, Fpr-rs1, Fpr-rs2, Fpr-rs6, and Fpr-rs7. Functional studies confirmed that, like dexamethasone, ANXA1 and two ANXA1-derived peptides (ANXA1(1-188) and ANXA1(Ac2-26)) inhibit the evoked release of ACTH from rodent anterior pituitary tissue in vitro. Fpr1 gene deletion failed to modify the pituitary responses to dexamethasone or ANXA1(Ac2-26). However, lipoxin A4 (LXA4, 0.02-2 microM, a lipid mediator with high affinity for Fpr-rs1) mimicked the inhibitory effects of ANXA1 on ACTH release as also did fMLF in high (1-100 microM) but not lower (10-100 nM) concentrations. Additionally, a nonselective FPR antagonist (Boc1, 100 microM) overcame the effects of dexamethasone, ANXA1(1-188), ANXA1(Ac2-26), fMLF, and LXA4 on ACTH release, although at a lower concentration (50 microM), it was without effect. Together, the results suggest that the actions of ANXA1 in the pituitary gland are independent of Fpr1 but may involve other FPR family members, in particular, Fpr-rs1 or a closely related receptor. They thus provide the first evidence for a role of the FPR family in the regulation of neuroendocrine function. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17218541&query_hl=1 ER - TY - JFULL T1 - Can deficits in social problem-solving in people with personality disorder be reversed? A1 - Crawford, MJ J1 - BRIT J PSYCHIAT Y1 - 2007/04// VL - 190 SN - 0007-1250 SP - 283 EP - 284 N2 - Research evidence is beginning to emerge that social problem-solving can improve the social functioning of people with personality disorder. This approach is particularly important because it may be relatively easy to train healthcare workers to deliver this intervention. However, the costs and cost-effectiveness of social problem-solving need to be established if it is to be made more widely available. ER - TY - JFULL T1 - Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology. A1 - Magliozzi, R A1 - Howell, O A1 - Vora, A A1 - Serafini, B A1 - Nicholas, R A1 - Puopolo, M A1 - Reynolds, R A1 - Aloisi, F J1 - Brain Y1 - 2007/04// VL - 130 SN - 1460-2156 SP - 1089 EP - 1104 N2 - Intrathecal antibody production is a hallmark of multiple sclerosis and humoral immunity is thought to play an important role in the inflammatory response and development of demyelinated lesions. The presence of lymphoid follicle-like structures in the cerebral meninges of some multiple sclerosis patients indicates that B-cell maturation can be sustained locally within the CNS and contribute to the establishment of a compartmentalized humoral immune response. In this study we examined the distribution of ectopic B-cell follicles in multiple sclerosis cases with primary and secondary progressive clinical courses to determine their association with clinical and neuropathological features. A detailed immunohistochemical and morphometric analysis was performed on post-mortem brain tissue samples from 29 secondary progressive (SP) and 7 primary progressive (PP) multiple sclerosis cases. B-cell follicles were detected in the meninges entering the cerebral sulci of 41.4% of the SPMS cases, but not in PPMS cases. The SPMS cases with follicles significantly differed from those without with respect to a younger age at multiple sclerosis onset, irreversible disability and death and more pronounced demyelination, microglia activation and loss of neurites in the cerebral cortex. Cortical demyelination in these SPMS cases was also more severe than in PPMS cases. Notably, all meningeal B-cell follicles were found adjacent to large subpial cortical lesions, suggesting that soluble factors diffusing from these structures have a pathogenic role. These data support an immunopathogenetic mechanism whereby B-cell follicles developing in the multiple sclerosis meninges exacerbate the detrimental effects of humoral immunity with a subsequent major impact on the integrity of the cortical structures. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17438020&query_hl=1 ER - TY - JFULL T1 - Revealing the dynamic causal interdependence between neural and muscular signals in Parkinsonian tremor A1 - Wang, S A1 - Chen, Y A1 - Ding, M A1 - Feng, J A1 - Stein, J A1 - Aziz, T A1 - Liu, X J1 - Journal of the Franklin Institute Y1 - 2007/04// VL - 344 SP - 180 EP - 195 UR - http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6V04-4KW5WKM-1-1M&_cdi=5636&_user=217827&_orig=search&_coverDate=09%2F12%2F2006&_sk=999999999&view=c&wchp=dGLbVlb-zSkWb&md5=5529a808e2f0b7af961 ER - TY - JFULL T1 - Augmentation with a second antipsychotic in patients with schizophrenia who partially respond to clozapine: a meta-analysis. A1 - Paton, C A1 - Whittington, C A1 - Barnes, TR J1 - J Clin Psychopharmacol Y1 - 2007/04// VL - 27 SN - 0271-0749 SP - 198 EP - 204 N2 - OBJECTIVES: To conduct a meta-analysis of randomized placebo-controlled trials (RCTs) of clozapine augmentation with another antipsychotic drug in patient with schizophrenia who partially respond to clozapine and compare the results with the findings of relevant open studies. METHODS: A systematic literature search was conducted to identify eligible RCTs. All baseline, posttreatment, and change scores in these trials were included in the meta-analysis. For change in Brief Psychiatric Rating Scale/Positive and Negative Syndrome Scale total scores, the effect size was calculated, and for the proportion of patients with a reduction in Brief Psychiatric Rating Scale/Positive and Negative Syndrome Scale scores of 20% or more, the relative risk was calculated. RESULTS: There was a total of 166 participants in the 4 eligible RCTs. Pooling effect sizes across these studies revealed clinically important heterogeneity (I = 63.5%). Analyzing by duration accounted for the heterogeneity (I = 0%), whereas analyzing by drug did not (I = 57.5%). The 2 RCTs lasting 10 weeks or more gave an odds ratio of response to treatment of 4.41 (95% confidence interval, 1.38 to 14.07). In 8 open studies identified, the same pattern of response was seen. The main treatment-emergent side effects reported were extrapyramidal side effects and raised serum prolactin. CONCLUSIONS: Augmentation of clozapine with another antipsychotic drug in patients with schizophrenic illness that has partially responded to clozapine is worthy of an individual clinical trial. This trial may need to be longer than the 4 to 6 weeks usually recommended for acute antipsychotic monotherapy. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17414246&query_hl=1 ER - TY - JFULL T1 - New insights into the patho-anatomical basis of hallucinations in Parkinson's disease A1 - Kalaitzakis, ME A1 - Christian, LM A1 - Graeber, MB A1 - Pearce, RKB A1 - Gentleman, SM J1 - NEUROPATH APPL NEURO Y1 - 2007/04// VL - 33 SN - 0305-1846 SP - 266 EP - 266 ER - TY - JFULL T1 - Widespread distribution and muscle differentiation of human fetal mesenchymal stem cells after intrauterine transplantation in dystrophic mdx mouse. A1 - Chan, J A1 - Waddington, SN A1 - O'Donoghue, K A1 - Kurata, H A1 - Guillot, PV A1 - Gotherstrom, C A1 - Themis, M A1 - Morgan, JE A1 - Fisk, NM J1 - Stem Cells Y1 - 2007/04// VL - 25 SN - 1066-5099 SP - 875 EP - 884 N2 - Duchenne muscular dystrophy (DMD) is a common X-linked disease resulting from the absence of dystrophin in muscle. Affected boys suffer from incurable progressive muscle weakness, leading to premature death. Stem cell transplantation may be curative, but is hampered by the need for systemic delivery and immune rejection. To address these barriers to stem cell therapy in DMD, we investigated a fetal-to-fetal transplantation strategy. We investigated intramuscular, intravascular, and intraperitoneal delivery of human fetal mesenchymal stem cells (hfMSCs) into embryonic day (E) 14-16 MF1 mice to determine the most appropriate route for systemic delivery. Intramuscular injections resulted in local engraftment, whereas both intraperitoneal and intravascular delivery led to systemic spread. However, intravascular delivery led to unexpected demise of transplanted mice. Transplantation of hfMSCs into E14-16 mdx mice resulted in widespread long-term engraftment (19 weeks) in multiple organs, with a predilection for muscle compared with nonmuscle tissues (0.71% vs. 0.15%, p < .01), and evidence of myogenic differentiation of hfMSCs in skeletal and myocardial muscle. This is the first report of intrauterine transplantation of ontologically relevant hfMSCs into fully immunocompetent dystrophic fetal mice, with systemic spread across endothelial barriers leading to widespread long-term engraftment in multiple organ compartments. Although the low-level of chimerism achieved is not curative for DMD, this approach may be useful in other severe mesenchymal or enzyme deficiency syndromes, where low-level protein expression may ameliorate disease pathology. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17185606&query_hl=1 ER - TY - JFULL T1 - Agonist-dependent internalization of D2 receptors: Imaging quantification by confocal microscopy. A1 - Goggi, JL A1 - Sardini, A A1 - Egerton, A A1 - Strange, PG A1 - Grasby, PM J1 - Synapse Y1 - 2007/04// VL - 61 SN - 0887-4476 SP - 231 EP - 241 N2 - In positron emission tomography and single photon emission computed tomography studies using D2 dopamine (DA) receptor radiotracers, a decrease in radiotracer binding potential (BP) is usually interpreted in terms of increased competition with synaptic DA. However, some data suggest that this signal may also reflect agonist (DA)-induced increases in D2 receptor (D2R) internalization, a process which would presumably also decrease the population of receptors available for binding to hydrophilic radioligands. To advance interpretation of alterations in D2 radiotracer BP, direct methods of assessment of D2R internalization are required. Here, we describe a confocal microscopy-based approach for the quantification of agonist-dependent receptor internalization. The method relies upon double-labeling of the receptors with antibodies directed against intracellular as well as extracellular epitopes. Following agonist stimulation, DA D2R internalization was quantified by differentiating, in optical cell sections, the signal due to the staining of the extracellular from intracellular epitopes of D2Rs. Receptor internalization was increased in the presence of the D2 agonists DA and bromocriptine, but not the D1 agonist SKF38393. Pretreatment with either the D2 antagonist sulpiride, or inhibitors of internalization (phenylarsine oxide and high molarity sucrose), blocked D2-agonist induced receptor internalization, thus validating this method in vitro. This approach therefore provides a direct and streamlined methodology for investigating the pharmacological and mechanistic aspects of D2R internalization, and should inform the interpretation of results from in vivo receptor imaging studies. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17230553&query_hl=1 ER - TY - JFULL T1 - Papillary meningioma: clinicopathological features of 42 cases A1 - Barker, JV A1 - Scheithauer, BW A1 - Giannini, C A1 - Moss, J A1 - Farrar, M A1 - Katsarou, A A1 - Perry, A A1 - Roncaroli, F J1 - NEUROPATH APPL NEURO Y1 - 2007/04// VL - 33 SN - 0305-1846 SP - 260 EP - 260 ER - TY - JFULL T1 - Motor recovery and the breathing arm after brachial plexus surgical repairs, including re-implantation of avulsed spinal roots into the spinal cord. A1 - Htut, M A1 - Misra, VP A1 - Anand, P A1 - Birch, R A1 - Carlstedt, T J1 - J Hand Surg [Br] Y1 - 2007/04// VL - 32 SN - 0266-7681 SP - 170 EP - 178 N2 - Forty-four patients with severe traction brachial plexus avulsion injuries were studied following surgical repairs. In eight patients, re-implanting avulsed spinal roots directly to the spinal cord was performed with other repairs and motor recovery in the proximal limb was similar to that achieved by conventional nerve grafts and transfers when assessed using the MRC clinical grades, Narakas scores, EMG and Transcranial Magnetic Stimulation (TMS). Thirty-four of the 37 patients had co-contractions of agonist and antagonist muscle groups. Spontaneous contractions of limb muscles in synchrony with respiration, the "breathing arm", were noted in 26 of 37 patients: in three patients, the source of the breathing arm was from spinal cord re-connection, providing evidence of regeneration from the CNS to the periphery. Our study shows that re-connection of avulsed spinal roots can produce good motor recovery and provides a clinical model for developing new treatments which may enhance nerve regeneration. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17224225&query_hl=1 ER - TY - JFULL T1 - Increased trpv1 expressing nerve fibres in colonic biopsies from irritable bowel syndrome patients correlate with the degree of abdominal pain A1 - Akbar, A A1 - Yiangou, Y A1 - Facer, P A1 - Anand, P A1 - Ghosh, S J1 - GUT Y1 - 2007/04// VL - 56 SN - 0017-5749 SP - A19 EP - A19 ER - TY - JFULL T1 - CD163: a marker of peripheral blood macrophages in traumatic brain injury A1 - Christian, LM A1 - Moran, LM A1 - Vince, V A1 - Graham, DI A1 - Gentleman, SM J1 - NEUROPATH APPL NEURO Y1 - 2007/04// VL - 33 SN - 0305-1846 SP - 258 EP - 258 ER - TY - JFULL T1 - Desmin immunolocalisation in autosomal dominant Emery-Dreifuss muscular dystrophy. A1 - Piercy, RJ A1 - Zhou, H A1 - Feng, L A1 - Pombo, A A1 - Muntoni, F A1 - Brown, SC J1 - Neuromuscul Disord Y1 - 2007/04// VL - 17 SN - 0960-8966 SP - 297 EP - 305 N2 - Autosomal dominant Emery-Dreifuss muscular dystrophy (AD-EDMD) is one of a number of allelic disorders caused by mutations in the nuclear lamina proteins, lamins A and C. The disorder is characterised by the early onset of skeletal muscle weakness and joint contractures and later, by dilated cardiomyopathy and cardiac arrythmias. Although the pathophysiology is not understood, one theory suggests that disordered structural organisation at weakened nuclei in contractile cells may underlie the disease. Previous work shows that mice deficient in lamin A/C develop similar skeletal and cardiac muscle signs to patients with AD-EDMD and ultrastructural examination of muscle from these mice shows abnormal localisation of desmin. We hypothesised therefore that desmin localisation may be abnormal in muscle or cells from patients with AD-EDMD and/or in cells expressing mutant lamins. In order to evaluate this, desmin immunolocalisation was determined in skeletal muscle biopsy sections from patients with AD-EDMD and cell lines including MyoD-transfected fibroblast-derived myotubes from AD-EDMD patients and murine embryonic stem cell-derived cardiomyocytes stably transfected with mutant human lamin A. Ultrastructural examination of patient muscle was also performed. Desmin was expressed and localised normally in patient muscle and cell lines and ultrastructural examination was similar to controls. These results fail to provide any evidence that dominant mutations in lamin A/C lead to a disorganisation of the desmin associated cytoskeleton. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17329105&query_hl=1 ER - TY - JFULL T1 - Centronuclear myopathy due to a de novo dominant mutation in the skeletal muscle ryanodine receptor (RYR1) gene. A1 - Jungbluth, H A1 - Zhou, H A1 - Sewry, CA A1 - Robb, S A1 - Treves, S A1 - Bitoun, M A1 - Guicheney, P A1 - Buj-Bello, A A1 - Bönnemann, C A1 - Muntoni, F J1 - Neuromuscul Disord Y1 - 2007/04// VL - 17 SN - 0960-8966 SP - 338 EP - 345 N2 - Centronuclear myopathy is a genetically heterogeneous congenital myopathy. Whilst mutations in the myotubularin (MTM1) gene are implicated in the X-linked variant, mutations in the dynamin 2 (DNM2) gene have been recently associated with dominant inheritance. We report a 16-year-old girl with clinical features of a congenital myopathy and external ophthalmoplegia. Multiple central nuclei affecting up to 50% of fibres and central accumulation of oxidative enzyme stains were the most prominent findings on muscle biopsy obtained at 1 year. However, some core-like areas appeared on repeat biopsy 8 years later; in addition, muscle MRI was compatible with the pattern we previously reported in patients with mutations in the skeletal muscle ryanodine receptor (RYR1) gene. Mutational analysis identified a de novo dominant RYR1 missense mutation (c.12335C>T; Ser4112Leu) affecting a highly conserved domain of the protein. Our findings expand the phenotypical spectrum associated with RYR1 mutations and indicate that RYR1 screening should be considered in centronuclear myopathy patients without MTM1 or DNM2 mutations; muscle MRI may aid selection of appropriate genetic testing. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17376685&query_hl=1 ER - TY - JFULL T1 - October 2006: A 37-year old male with headache - Diagnosis - Cerebellar low grade astroblastoma A1 - Chopra, I A1 - Roncaroli, F A1 - Apostolopoulos, V A1 - Moss, J A1 - Peston, D A1 - O'Neill, K J1 - BRAIN PATHOL Y1 - 2007/04// VL - 17 SN - 1015-6305 SP - 251 EP - + N2 - Astroblastoma is a rare tumor of glial lineage usually occurring in young adults and involving the supratentorial compartment. Brain stem and cerebellar examples are uncommon. We report a 37-year-old patient who presented with 2-month history of headache and balance impairment. Pre-operative MR scans showed a cystic, contrast-enhanced lesion involving the cortex of the left cerebellar hemisphere. Histologically, the tumor showed compressive margins, appeared rich in vessels and featured compact architecture with no fibrillary background. It contained perivascular pseudorosettes composed of columnar cells with short cytoplasmic processes and eccentric nuclei. Mitoses were rare and necrosis was absent. Tumor cells expressed GFAP, S-100 protein and NSE. Immunoreactions for cytokeratin CAM5.2, cytokeratins AE1/AE3, smooth muscle actin, CD31, EMA, chromogranin and synaptophysin were negative. Electron microscopy showed capillaries with grossly thickened basal lamina. Cell junctions of tumor cells were primitive and intermediate. There were no intracytoplasmic lumina, ciliary bodies and microvilli. A diagnosis of low grade astroblastoma was made. Low grade astroblastoma has an excellent long term survival when gross totally resection. High grade examples have an unfavorable outcome, often similar to glioblastoma. Mitoses, cellular atypia and microvascular proliferation appear to be poor prognostic indicators. ER - TY - JFULL T1 - Increased immunoreactivity of cdk5 activators in hippocampal sclerosis A1 - Sen, A A1 - Thom, M A1 - Martinian, L A1 - Yogarajah, M A1 - Nikolic, M A1 - Sisodiya, SM J1 - NEUROREPORT Y1 - 2007/03/26/ VL - 18 SN - 0959-4965 SP - 511 EP - 516 N2 - Cyclin-dependent kinase 5 is important in several in-vitro neurodegeneration paradigms. Whether cyclin-dependent kinase 5 contributes to cell death in human neuro-degenerative diseases remains uncertain, particularly because post-mortem delay and other extrinsic factors might influence cyclin-dependent kinase 5 activity Here we demonstrate increased immunoreactivity for the activators of cyclin-dependent kinase 5 in post-mortem human hippocampi affected by the neurodegenerative condition hippocampal sclerosis, but not in histologically normal hippocampi. Moreover, in post-mortem brain tissue from patients with unilateral hippocampal sclerosis, increased immunoreactivity for cyclin-dependent kinase 5 activators was detected in the hippocampus with sclerosis, but not in the contralateral hippocampus, suggesting that extrinsic factors are unlikely to account for the differential staining observed. Our findings suggest that deregulation of cyclin-dependent kinase 5 might contribute to the pathogenesis of hippocampal sclerosis. ER - TY - JFULL T1 - A review of the functional role and of the expression profile of retinoid signaling and of nuclear receptors in human spinal cord. A1 - Malaspina, A A1 - Turkheimer, F J1 - Brain Res Bull Y1 - 2007/03/15/ VL - 71 SN - 0361-9230 SP - 437 EP - 446 N2 - Spinal cord degenerative pathologies in humans cause extensive disability and require a broad range of specialist and palliative medical interventions. In amyotrophic lateral sclerosis (ALS), motor cell loss leads to extensive paralysis and to death from respiratory failure in 3-5 years form disease onset. A wide range of molecular changes forms the basis of spinal cord involvement in ALS, including the reactivation of molecular pathways with potentially neurorestorative properties. Central to this tissue repair mechanism is the differential regulation of components of the retinoid signaling (ReS), a molecular pathway encompassing a variety of proteins functioning as transporters, signaling factors and metabolizing enzymes for retinoic acid. In this paper, we review the strong body of experimental evidence supporting retinoid signaling's primary role in spinal cord embryonic differentiation and its likely survival-promoting function in ALS. We discuss the potential involvement in ALS pathogenesis of a subgroup of nuclear receptors (NRs) that act as functional partners of retinoid receptors in human spinal cord. We also provide a review of the expression profile of 25 ReS and NRs genes in human adult spinal cord and in motor neurons of healthy and ALS individuals, using data retrieved from independent datasets obtained through serial analysis of gene expression and array investigations. Based on published expression data, we outline a tentative expression profile of ReS and functionally synergic NR genes in human spinal cord that could guide further experiments to clarify the role of these molecules in mature nervous tissue and suggest potential treatment strategies that could have therapeutic potentials in ALS. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17259011&query_hl=1 ER - TY - JFULL T1 - Digitised spirography as an evaluation tool for intention tremor in multiple sclerosis. A1 - Feys, P A1 - Helsen, W A1 - Prinsmel, A A1 - Ilsbroukx, S A1 - Wang, S A1 - Liu, X J1 - J Neurosci Methods Y1 - 2007/03/15/ VL - 160 SN - 0165-0270 SP - 309 EP - 316 N2 - This study investigated validity and reliability of digitised circle and square spiral drawing for quantifying intention tremor severity and related disability in patients with multiple sclerosis (MS). The tremor amplitude was measured as the standard deviation of the drawing velocity of the arm in the radial and tangential direction for circle spiral drawing, and in the horizontal and vertical direction for square spiral drawing. Results were compared with those of MS patients without tremor and healthy controls, and correlated with clinical assessments of tremor severity and arm functionality including Fahn's tremor rating scale, Test d'Evaluation des Membres supérieurs des Personnes Agées (TEMPA) and the nine-hole-peg test to examine validity. Comparison of patient's performance between four repeated trials examined short-term test-retest reliability. All digitised spirography variables discriminated between the MS-tremor and both MS-no-tremor and healthy control groups. Validity was also shown by high spearman correlation coefficients between spirography variables and clinical ratings. Tremor appeared to be most profound in the radial and vertical direction during circle and square spiral drawing, respectively. The consistency and high correlations between four repeated executions indicated short-term test-retest reliability. We conclude that the digitised spirography provide a useful instrumentation for quantifying MS intention tremor. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17113154&query_hl=1 ER - TY - JFULL T1 - Ionic currents underlying the response of rat dorsal vagal neurones to hypoglycaemia and chemical anoxia. A1 - Balfour, RH A1 - Trapp, S J1 - J Physiol Y1 - 2007/03/15/ VL - 579 SN - 0022-3751 SP - 691 EP - 702 N2 - A proportion of dorsal vagal neurones (DVN) are glucosensors. These cells respond to brief hypoglycaemia either with a K(ATP) channel-mediated hyperpolarization or with depolarization owing to an as yet unknown mechanism. K(ATP) currents are observed not only during hypoglycaemia, but also in response to mitochondrial inhibition. Here we show that similarly to the observations for K(ATP) currents, both hypoglycaemia and inhibition of mitochondrial function elicited a small inward current that persisted in TTX in DVN of rat brainstem slices. Removal of glucose from the bath solution induced this inward current within 50 +/- 4 s in one subpopulation of DVN and in 279 +/- 36 s in another subpopulation. No such subpopulations were observed for the response to mitochondrial inhibition. Biophysical analysis revealed that mitochondrial inhibition or hypoglycaemia inhibited an openly rectifying K+ conductance in 25% of DVN. In the remaining cells, either an increase in conductance, with a reversal potential between -58 and +10 mV, or a parallel inward shift of the holding current was observed. This current most probably resulted from inhibition of the Na+-K+-ATPase and/or the opening of an ion channel. Recordings with electrodes containing 145 mm instead of 5 mm Cl- failed to shift the reversal potential of the inward current, indicating that a Cl- channel was not involved. In summary, glucosensing and non-glucosensing DVN appear to use common electrical pathways to respond to mitochondrial inhibition and to hypoglycaemia. We suggest that differences in glucose metabolism rather than differences in the complement of ion channels distinguish these two cell types. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17218356&query_hl=1 ER - TY - JFULL T1 - Relationship between appearance and psychological distress in rheumatic diseases. A1 - Monaghan, SM A1 - Sharpe, L A1 - Denton, F A1 - Levy, J A1 - Schrieber, L A1 - Sensky, T J1 - Arthritis Rheum Y1 - 2007/03/15/ VL - 57 SN - 0004-3591 SP - 303 EP - 309 N2 - OBJECTIVE: To examine the relationship between physical appearance concerns and psychological distress in patients with rheumatic diseases. METHODS: A total of 60 patients with systemic lupus erythematosus (SLE), 44 with chronic rheumatoid arthritis (RA), and 53 with recent-onset RA were evaluated for levels of appearance concern and a range of illness-specific measures to determine how these demographic and clinical variables were related to the dependent variable psychological distress. RESULTS: Using hierarchical multiple regression analyses, we found that both appearance concerns and levels of disability were predictive of depression in patients with RA. In the SLE sample, physical disability was predictive of depression when appearance concerns were not included in the analysis. However, disability did not predict depression when appearance concerns were entered into the analysis. This indicates that appearance concerns mediated the relationship between disability and depression in SLE. There was no association between appearance concerns and anxiety in either sample. CONCLUSION: The results suggest that appearance concerns are strongly related to depression in patients with rheumatic diseases and should be routinely assessed. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17330287&query_hl=1 ER - TY - JFULL T1 - Activation of the subventricular zone in multiple sclerosis: Evidence for early glial progenitors A1 - Nait-Oumesmar, B A1 - Picard-Riera, N A1 - Kerninon, C A1 - Decker, L A1 - Seilhean, D A1 - Hoglinger, GU A1 - Hirsch, EC A1 - Reynolds, R A1 - Baron-Van Evercooren, A J1 - P NATL ACAD SCI USA Y1 - 2007/03/13/ VL - 104 SN - 0027-8424 SP - 4694 EP - 4699 N2 - In multiple sclerosis (MS), oligodendrocyte and myelin destruction lead to demyelination with subsequent axonal loss. Experimental demyelination in rodents has highlighted the activation of the subventricular zone (SVZ) and the involvement of progenitor cells expressing the polysialylated form of neural cell adhesion molecule (PSA-INCAM) in the repair process. In this article, we studied the distribution of early PSA-NCAM(+) progenitors in the SVZ and MS lesions in human postmortem brains. Compared with controls, MS SVZ showed a 2- to 3-fold increase in cell density and proliferation, which correlated with enhanced numbers of PSA-NCAM+ and glial fibrillary acidic protein-positive (GFAP+) cells. PSA-NCAM+ progenitors mainly were Sox9(+), and a few expressed Sox10 and Olig2, markers of oligodendroglial specification. PSA-NCAM+ progenitors expressing Sox10 and Olig2 also were detected in demyelinated MS lesions. In active and chronic active lesions, the number of PSA-NCAM+ progenitors was 8-fold higher compared with chronic silent lesions, shadow plaques, and normal-appearing white matter. In active and chronic active lesions, PSA-NCAM+ progenitors were more frequent in periventricular lesions (30-50%) than in lesions remote from the ventricular wall. These data indicate that, as in rodents, activation of gliogenesis in the SVZ occurs in MS and suggest the mobilization of SVZ-derived early glial progenitors to periventricular lesions, where they could give rise to oligodendrocyte precursors. These early glial progenitors could be a potential target for therapeutic strategies designed to promote myelin repair in MS. ER - TY - JFULL T1 - Personality diatheses: a superior explanation than disorder. A1 - Tyrer, P J1 - Psychol Med Y1 - 2007/03/12/ SN - 0033-2917 SP - 1 EP - 5 N2 - Diatheses confer vulnerability to disorder but are not necessarily manifest overtly or consistently. It is suggested that the main empirical findings of studies with abnormal personality support the notion that they are diatheses rather than disorders. This includes their onset early in life, their variability of expression dependent on setting, their greater association with more severe disorders and their acceptance as intrinsic components of functioning by most suffering from these conditions. It is argued that a separate axis of classification for personality diatheses rather than disorders is justified. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17349102&query_hl=1 ER - TY - JFULL T1 - Pure autonomic failure followed by amyotrophy A1 - Irani, SR A1 - Mathias, CJ A1 - Orrell, RW J1 - NEUROLOGY Y1 - 2007/03/06/ VL - 68 SN - 0028-3878 SP - 792 EP - 793 ER - TY - JFULL T1 - Expression and externalization of annexin 1 in the adrenal gland: structure and function of the adrenal gland in annexin 1-null mutant mice. A1 - Davies, E A1 - Omer, S A1 - Buckingham, JC A1 - Morris, JF A1 - Christian, HC J1 - Endocrinology Y1 - 2007/03// VL - 148 SN - 0013-7227 SP - 1030 EP - 1038 N2 - Annexin 1 (ANXA1) is a member of the annexin family of phospholipid- and calcium-binding proteins with a well demonstrated role in early delayed (30 min to 3 h) inhibitory feedback of glucocorticoids in the hypothalamus and pituitary gland. This study used adrenal gland tissue from ANXA1-null transgenic mice, in which a beta-galactosidase (beta-Gal) reporter gene was controlled by the ANXA1 promoter, and wild-type control mice to explore the potential role of ANXA1 in adrenal function. RT-PCR and Western blotting revealed strong expression of ANXA1 mRNA and protein in the adrenal gland. Immunofluorescence labeling of ANXA1 in wild-type and beta-Gal expression in ANXA1-null adrenals localized intense staining in the outer perimeter cell layers. Immunogold electron microscopy identified cytoplasmic and nuclear ANXA1 labeling in outer cortical cells and capsular cells. Exposure of adrenal segments in vitro to dexamethasone (0.1 mum, 3 h) caused an increase in the amount of ANXA1 in the intracellular compartment and attached to the surface of the cells. The N-terminal peptide ANXA1(Ac2-26) inhibited corticosterone release. Corticosterone release was significantly greater from ANXA1-null adrenal cells compared with wild type in response to ACTH (10 pm to 5 nm). In contrast, basal and ACTH-stimulated aldosterone release from ANXA1-null adrenal cells was not different from wild type. Morphometry studies demonstrated that ANXA1 null adrenal glands were smaller than wild-type, and the cortical/medullary area ratio was significantly reduced. These results suggest ANXA1 is a regulator of adrenocortical size and corticosterone secretion. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17158208&query_hl=1 ER - TY - JFULL T1 - The cadherincatenin complex in meningiomas A1 - Kastarou, A A1 - Barker, JV A1 - Farrar, M A1 - Essex, D A1 - O'Neill, K A1 - Roncaroli, F J1 - MODERN PATHOL Y1 - 2007/03// VL - 20 SN - 0893-3952 SP - 298A EP - 298A ER - TY - JFULL T1 - The neuroendocrine physiology of kisspeptin in the human. A1 - Dhillo, WS A1 - Murphy, KG A1 - Bloom, SR J1 - Rev Endocr Metab Disord Y1 - 2007/03// VL - 8 SN - 1389-9155 SP - 41 EP - 46 N2 - Kisspeptin is a 54-amino acid peptide, encoded by the KiSS-1 gene, which activates the G protein-coupled receptor GPR54. Recent evidence suggests the kisspeptin/GPR54 system is a key regulator of reproduction. GPR54-deficient mice have abnormal sexual development. Central or peripheral administration of kisspeptin stimulates the hypothalamic-pituitary-gonadal (HPG) axis in animal models. This review discusses the evidence that kisspeptin also plays a key role in human reproduction. Inactivating GPR54 mutations cause normosmic hypogonadotrophic hypogonadism in humans. Mutations which increase GPR54 signaling are associated with gonadotrophin-dependent premature puberty. Acute intravenous administration of kisspeptin to healthy human male volunteers potently increased plasma LH levels and significantly increased plasma FSH and testosterone without side effects. Plasma kisspeptin is found at low concentrations in the circulation of men and non-pregnant women, but is markedly increased in pregnancy. The placenta is believed to be the source of these high levels of circulating kisspeptin. The kisspeptin-GPR54 system is also implicated in tumour biology. Consistent with this role, plasma kisspeptin concentrations are elevated in patients with abnormal proliferation of placental tissue (gestational trophoblastic neoplasia or GTN) at presentation and fall after treatment with chemotherapy. The kisspeptin/GPR54 system therefore appears to play an important role in the regulation of reproduction in humans. Kisspeptin represents a novel tool for the manipulation of the HPG axis in humans and plasma kisspeptin may be a novel tumour marker in patients with GTN. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17323132&query_hl=1 ER - TY - JFULL T1 - Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: clinical trial design. A1 - Lammertse, D A1 - Tuszynski, MH A1 - Steeves, JD A1 - Curt, A A1 - Fawcett, JW A1 - Rask, C A1 - Ditunno, JF A1 - Fehlings, MG A1 - Guest, JD A1 - Ellaway, PH A1 - Kleitman, N A1 - Blight, AR A1 - Dobkin, BH A1 - Grossman, R A1 - Katoh, H A1 - Privat, A A1 - Kalichman, M A1 - International Campaign for Cures of Spinal Cord Injury Paralysis J1 - Spinal Cord Y1 - 2007/03// VL - 45 SN - 1362-4393 SP - 232 EP - 242 N2 - The International Campaign for Cures of Spinal Cord Injury Paralysis established a panel tasked with reviewing the methodology for clinical trials for spinal cord injury (SCI), and making recommendations on the conduct of future trials. This is the fourth of four papers. Here, we examine the phases of a clinical trial program, the elements, types, and protocols for valid clinical trial design. The most rigorous and valid SCI clinical trial would be a prospective double-blind randomized control trial utilizing appropriate placebo control subjects. However, in specific situations, it is recognized that other trial procedures may have to be considered. We review the strengths and limitations of the various types of clinical trials with specific reference to SCI. It is imperative that the design and conduct of SCI clinical trials should meet appropriate standards of scientific inquiry to insure that meaningful conclusions about efficacy and safety can be achieved and that the interests of trial subjects are protected. We propose these clinical trials guidelines for use by the SCI clinical research community. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17179970&query_hl=1 ER - TY - JFULL T1 - Mural cells paint a new picture of muscle stem cells. A1 - Morgan, J A1 - Muntoni, F J1 - Nat Cell Biol Y1 - 2007/03// VL - 9 SN - 1465-7392 SP - 249 EP - 251 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17330116&query_hl=1 ER - TY - JFULL T1 - Regionally increased efflux of R-[11C] verapamil occurs in some patients with therapy refractory epilepsy A1 - Bauer, M A1 - Langer, O A1 - Hammers, A A1 - Karch, R A1 - Pataraia, E A1 - Zimprich, F A1 - Koepp, M A1 - Abrahim, A A1 - Luurtsema, G A1 - Kletter, K A1 - Baumgartner, C A1 - Muller, M J1 - EPILEPSIA Y1 - 2007/03// VL - 48 SN - 0013-9580 SP - 61 EP - 62 ER - TY - JFULL T1 - Analysis of alpha-synuclein, dopamine and parkin pathways in neuropathologically confirmed parkinsonian nigra. A1 - Moran, LB A1 - Croisier, E A1 - Duke, DC A1 - Kalaitzakis, ME A1 - Roncaroli, F A1 - Deprez, M A1 - Dexter, DT A1 - Pearce, RK A1 - Graeber, MB J1 - Acta Neuropathol (Berl) Y1 - 2007/03// VL - 113 SN - 0001-6322 SP - 253 EP - 263 N2 - The identification of mutations that cause familial Parkinson's disease (PD) provides a framework for studies into pathways that may be perturbed also in the far more common, non-familial form of the disorder. Following this hypothesis, we have examined the gene regulatory network that links alpha-synuclein and parkin pathways with dopamine metabolism in neuropathologically verified cases of sporadic PD. By means of an in silico approach using a database of eukaryotic molecular interactions and a whole genome transcriptome dataset validated by qRT-PCR and histological methods, we found parkin and functionally associated genes to be up-regulated in the lateral substantia nigra (SN). In contrast, alpha-synuclein and ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) gene expression levels were significantly reduced in both the lateral and medial SN in PD. Gene expression for Septin 4, a member of the GTP-binding protein family involved in alpha-synuclein metabolism was elevated in the lateral parkinsonian SN. Additionally, catalase and mitogen-activated protein kinase 8 and poly(ADP-ribose) polymerase family member 1 (PARP1) known to function in DNA repair and cell death induction, all members of the dopamine synthesis pathway, were up-regulated in the lateral SN. In contrast, two additional PD-linked genes, glucocerebrosidase and nuclear receptor subfamily 4, group A, member 2 (NR4A2) showed reduced expression. We show that in sporadic PD, parkin, alpha-synuclein and dopamine pathways are co-deregulated. Alpha-synuclein is a member of all three gene regulatory networks. Our analysis results support the view that alpha-synuclein has a central role in the familial as well as the non-familial form of the disease and provide steps towards a pathway definition of PD. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17203291&query_hl=1 ER - TY - JFULL T1 - Befriending patients with medication-resistant schizophrenia: can psychotic symptoms predict treatment response? A1 - Samarasekera, N A1 - Kingdon, D A1 - Siddle, R A1 - O'Carroll, M A1 - Scott, JL A1 - Sensky, T A1 - Barnes, TR A1 - Turkington, D J1 - Psychol Psychother Y1 - 2007/03// VL - 80 SN - 1476-0835 SP - 97 EP - 106 N2 - OBJECTIVES: Supportive interventions are used in schizophrenia, but little research has been conducted into whether any baseline variable predicts treatment response. The aim of this study was to establish if baseline delusions or hallucinations are associated with changes in overall symptoms in patients who received a befriending intervention. DESIGN: The sample consisted of 44 patients with schizophrenia. These patients comprised the befriending arm of a multicentre randomized controlled trial which compared the efficacy of using CBT against befriending as an adjunct to routine care for patients with medication-resistant schizophrenia. METHODS: Scores for auditory hallucinations and delusions relating to persecution or control were entered into two regression models. The dependent variables were change in overall symptoms (1) between baseline and end of the intervention, and (2) between baseline and 9 months post-intervention. RESULTS: Baseline delusions predicted a good response and auditory hallucinations predicted a poor response at 9 months. CONCLUSIONS: Baseline psychotic symptoms strongly predicted outcome in this sample. The finding that hallucinations predicted a poor outcome is consistent with previous research. These results may help to determine which patients would benefit from supportive interventions. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17346383&query_hl=1 ER - TY - JFULL T1 - Guidelines for the conduct of clinical trials for spinal cord injury (SCI) as developed by the ICCP panel: clinical trial outcome measures. A1 - Steeves, JD A1 - Lammertse, D A1 - Curt, A A1 - Fawcett, JW A1 - Tuszynski, MH A1 - Ditunno, JF A1 - Ellaway, PH A1 - Fehlings, MG A1 - Guest, JD A1 - Kleitman, N A1 - Bartlett, PF A1 - Blight, AR A1 - Dietz, V A1 - Dobkin, BH A1 - Grossman, R A1 - Short, D A1 - Nakamura, M A1 - Coleman, WP A1 - Gaviria, M A1 - Privat, A A1 - International Campaign for Cures of Spinal Cord Injury Paralysis J1 - Spinal Cord Y1 - 2007/03// VL - 45 SN - 1362-4393 SP - 206 EP - 221 N2 - An international panel reviewed the methodology for clinical trials of spinal cord injury (SCI), and provided recommendations for the valid conduct of future trials. This is the second of four papers. It examines clinical trial end points that have been used previously, reviews alternative outcome tools and identifies unmet needs for demonstrating the efficacy of an experimental intervention after SCI. The panel focused on outcome measures that are relevant to clinical trials of experimental cell-based and pharmaceutical drug treatments. Outcome measures are of three main classes: (1) those that provide an anatomical or neurological assessment for the connectivity of the spinal cord, (2) those that categorize a subject's functional ability to engage in activities of daily living, and (3) those that measure an individual's quality of life (QoL). The American Spinal Injury Association impairment scale forms the standard basis for measuring neurologic outcomes. Various electrophysiological measures and imaging tools are in development, which may provide more precise information on functional changes following treatment and/or the therapeutic action of experimental agents. When compared to appropriate controls, an improved functional outcome, in response to an experimental treatment, is the necessary goal of a clinical trial program. Several new functional outcome tools are being developed for measuring an individual's ability to engage in activities of daily living. Such clinical end points will need to be incorporated into Phase 2 and Phase 3 trials. QoL measures often do not correlate tightly with the above outcome tools, but may need to form part of Phase 3 trial measures. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17179972&query_hl=1 ER - TY - JFULL T1 - The cadherincatenin complex in meningiomas A1 - Kastarou, A A1 - Barker, JV A1 - Farrar, M A1 - Essex, D A1 - O'Neill, K A1 - Roncaroli, F J1 - LAB INVEST Y1 - 2007/03// VL - 87 SN - 0023-6837 SP - 298A EP - 298A ER - TY - JFULL T1 - Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: spontaneous recovery after spinal cord injury and statistical power needed for therapeutic clinical trials. A1 - Fawcett, JW A1 - Curt, A A1 - Steeves, JD A1 - Coleman, WP A1 - Tuszynski, MH A1 - Lammertse, D A1 - Bartlett, PF A1 - Blight, AR A1 - Dietz, V A1 - Ditunno, J A1 - Dobkin, BH A1 - Havton, LA A1 - Ellaway, PH A1 - Fehlings, MG A1 - Privat, A A1 - Grossman, R A1 - Guest, JD A1 - Kleitman, N A1 - Nakamura, M A1 - Gaviria, M A1 - Short, D J1 - Spinal Cord Y1 - 2007/03// VL - 45 SN - 1362-4393 SP - 190 EP - 205 N2 - The International Campaign for Cures of Spinal Cord Injury Paralysis (ICCP) supported an international panel tasked with reviewing the methodology for clinical trials in spinal cord injury (SCI), and making recommendations on the conduct of future trials. This is the first of four papers. Here, we examine the spontaneous rate of recovery after SCI and resulting consequences for achieving statistically significant results in clinical trials. We have reanalysed data from the Sygen trial to provide some of this information. Almost all people living with SCI show some recovery of motor function below the initial spinal injury level. While the spontaneous recovery of motor function in patients with motor-complete SCI is fairly limited and predictable, recovery in incomplete SCI patients (American spinal injury Association impairment scale (AIS) C and AIS D) is both more substantial and highly variable. With motor complete lesions (AIS A/AIS B) the majority of functional return is within the zone of partial preservation, and may be sufficient to reclassify the injury level to a lower spinal level. The vast majority of recovery occurs in the first 3 months, but a small amount can persist for up to 18 months or longer. Some sensory recovery occurs after SCI, on roughly the same time course as motor recovery. Based on previous data of the magnitude of spontaneous recovery after SCI, as measured by changes in ASIA motor scores, power calculations suggest that the number of subjects required to achieve a significant result from a trial declines considerably as the start of the study is delayed after SCI. Trials of treatments that are most efficacious when given soon after injury will therefore, require larger patient numbers than trials of treatments that are effective at later time points. As AIS B patients show greater spontaneous recovery than AIS A patients, the number of AIS A patients requiring to be enrolled into a trial is lower. This factor will have to be balanced against the possibility that some treatments will be more effective in incomplete patients. Trials involving motor incomplete SCI patients, or trials where an accurate assessment of AIS grade cannot be made before the start of the trial, will require large subject numbers and/or better objective assessment methods. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17179973&query_hl=1 ER - TY - JFULL T1 - Chemokines as modulators of neuroendocrine functions A1 - Rostene, W A1 - Buckingham, JC J1 - J MOL ENDOCRINOL Y1 - 2007/03// VL - 38 SN - 0952-5041 SP - 351 EP - 353 N2 - Chemokines are small secreted proteins with chemoattractant properties for immune cells. Besides their role in the immune system, chemokines and their receptors may play important roles in the central nervous system. Neurodegenerative disorders that involve neuroinflammation such as multiple sclerosis, stroke, Alzheimer's disease, Parkinson's disease and HIV-associated dementia are commonly associated with local upregulation and release of chemokines. However, recent work has established that certain chemokines, constitutively expressed in the brain, exert functions in the brain that are distinct from inflammation. These chemokines regulate neuronal migration during brain development, modulate neuronal activity and play a role in various neurodegenerative diseases, pain and more recently in neuroendocrine functions. All these novel aspects, mainly focused on the chemokine stromal cell-derived factor-1/CXCL12 and its receptor CXCR4, were presented by pioneers in the field during the symposium held at the sixth International Congress of Neuroendocrinology in Pittsburgh, Pennsylvania, USA in June 2006. ER - TY - JFULL T1 - Pre-synaptic striatal dopamine synthesis capacity in subjects at risk of psychosis A1 - Howes, OD A1 - Montgomery, AJ A1 - Asselin, M A1 - Murray, RM A1 - Grasby, PM A1 - McGuire, PK J1 - SCHIZOPHRENIA BULL Y1 - 2007/03// VL - 33 SN - 0586-7614 SP - 371 EP - 371 ER - TY - JFULL T1 - Cognitive functioning in psychosis: Relationship to objective and subjective measures of outcome A1 - Jabben, N A1 - Krabbendam, L A1 - Burns, T A1 - Tatton, T A1 - Green, J A1 - Tyrer, P A1 - Murray, R A1 - Van Os, J J1 - SCHIZOPHRENIA BULL Y1 - 2007/03// VL - 33 SN - 0586-7614 SP - 591 EP - 591 ER - TY - JFULL T1 - UK drug analysis prints and anaesthetic adverse drug reactions. A1 - Holdcroft, A J1 - Pharmacoepidemiol Drug Saf Y1 - 2007/03// VL - 16 SN - 1053-8569 SP - 316 EP - 328 N2 - PURPOSE: Anaesthetic drugs were selected from the Medicines and Healthcare products Regulatory Agency Drug Analysis Prints in order to determine the number and types of reported reactions and associated mortality. METHODS: The chosen drug groups were the intravenous induction agents, the neuromuscular blocking drugs and neostigmine, the inhalational anaesthetic agents and nitrous oxide, local anaesthetic agents and a selection of analgesics agents, naloxone and midazolam and its antagonist flumazenil. From each drug file, the number and type of reactions were analysed. Mortality was calculated as a percentage of the number of deaths against patient reports. RESULTS: A total of 11,199 reactions were analysed from 6603 patients of whom 620 (9%) died. Few drug records reported reactions from multiple constituent formulations. The majority of reactions were not allergic. The highest mortality was in the inhalational anaesthetic group. Although the greatest number of fatal events was associated with halothane, this drug is no longer used. Nevertheless the percentage remains high because cardiovascular mortality is still being reported. Local anaesthetic use was associated with the smallest percentage mortality (3%). The highest reported number of reactions was associated with the intravenous induction agents and idiosyncratic neurological and peripheral vascular reactions were linked with the use of etomidate. CONCLUSIONS: The reporting of allergic reactions was low. The data demonstrate that induction of anaesthesia presents the highest risk of adverse drug reaction; there is also mortality from newer drugs for example, desflurane, remifentanil as well as from drugs for which there is no alternative, for example, suxamethonium. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16767795&query_hl=1 ER - TY - JFULL T1 - Postoperative impairment of cognitive function in rats: a possible role for cytokine-mediated inflammation in the hippocampus. A1 - Wan, Y A1 - Xu, J A1 - Ma, D A1 - Zeng, Y A1 - Cibelli, M A1 - Maze, M J1 - Anesthesiology Y1 - 2007/03// VL - 106 SN - 0003-3022 SP - 436 EP - 443 N2 - BACKGROUND: Postoperative cognitive dysfunction is being increasingly reported as a complication. The authors investigated the role of cytokine-mediated inflammation within the central nervous system in the development of cognitive dysfunction in a rat model. METHODS: Adult rats were subjected to neuroleptic anesthesia (20 microg/kg fentanyl plus 500 microg/kg droperidol, intraperitoneal) for splenectomy or no surgery. On postanesthetic days 1, 3, and 7, cognitive function was assessed in a Y maze. To evaluate the immune response in the hippocampus, the authors measured glial activation, as well as transcription and expression of key proinflammatory cytokines interleukin 1beta and tumor necrosis factor alpha. To determine propensity for apoptosis, they measured expression of Bax and Bcl-2. RESULTS: Cognitive function in splenectomized animals was impaired at days 1 and 3 after surgery compared with cognitive function in nonanesthetized rats. At all times, anesthetized rats that were not subjected to surgery were no different from control rats. Glial activation was observed in the hippocampus only in splenectomized rats at postsurgery days 1 and 3. Interleukin-1beta messenger RNA (mRNA) was significantly increased at postsurgery days 1 and 3, with an increase in protein expression detected on day 1. There was a significant increase in tumor necrosis factor-alpha mRNA on day 1 after surgery, although this was not associated with an increase in protein expression. The ratio of Bcl-2:Bax was significantly decreased in the splenectomized animals. CONCLUSION: These results suggest that splenectomy performed during neuroleptic anesthesia triggers a cognitive decline that is associated with a hippocampal inflammatory response that seems to be due to proinflammatory cytokine-dependent activation of glial cells. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17325501&query_hl=1 ER - TY - JFULL T1 - Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP Panel: clinical trial inclusion/exclusion criteria and ethics. A1 - Tuszynski, MH A1 - Steeves, JD A1 - Fawcett, JW A1 - Lammertse, D A1 - Kalichman, M A1 - Rask, C A1 - Curt, A A1 - Ditunno, JF A1 - Fehlings, MG A1 - Guest, JD A1 - Ellaway, PH A1 - Kleitman, N A1 - Bartlett, PF A1 - Blight, AR A1 - Dietz, V A1 - Dobkin, BH A1 - Grossman, R A1 - Privat, A A1 - International Campaign for Cures of Spinal Cord Injury Paralysis J1 - Spinal Cord Y1 - 2007/03// VL - 45 SN - 1362-4393 SP - 222 EP - 231 N2 - The International Campaign for Cures of Spinal Cord Injury Paralysis established a panel tasked with reviewing the methodology for clinical trials for spinal cord injury (SCI), and making recommendations on the conduct of future trials. This is the third of four papers. It examines inclusion and exclusion criteria that can influence the design and analysis of clinical trials in SCI, together with confounding variables and ethical considerations. Inclusion and exclusion criteria for clinical trials should consider several factors. Among these are (1) the enrollment of subjects at appropriate stages after SCI, where there is supporting data from animal models or previous human studies; (2) the severity, level, type, or size of the cord injury, which can influence spontaneous recovery rate and likelihood that an experimental treatment will clinically benefit the subject; and (3) the confounding effects of various independent variables such as pre-existing or concomitant medical conditions, other medications, surgical interventions, and rehabilitation regimens. An issue of substantial importance in the design of clinical trials for SCI is the inclusion of blinded assessments and sham surgery controls: every effort should be made to address these major issues prospectively and carefully, if clear and objective information is to be gained from a clinical trial. The highest ethical standards must be respected in the performance of clinical trials, including the adequacy and clarity of informed consent. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17179971&query_hl=1 ER - TY - JFULL T1 - From the Editor's desk A1 - Tyrer, P J1 - BRIT J PSYCHIAT Y1 - 2007/03// VL - 190 SN - 0007-1250 SP - 282 EP - 282 ER - TY - JFULL T1 - Characterization of dopaminergic dysfunction in familial progressive supranuclear palsy: an 18F-dopa PET study. A1 - Tai, YF A1 - Ahsan, RL A1 - de Yébenes, JG A1 - Pavese, N A1 - Brooks, DJ A1 - Piccini, P J1 - J Neural Transm Y1 - 2007/03// VL - 114 SN - 0300-9564 SP - 337 EP - 340 N2 - We analyzed (18)F-dopa PET data from 11 members of kindreds with familial progressive supranuclear palsy (PSP) to characterize their cerebral dopaminergic dysfunction. Three clinically-affected PSP patients showed reduced (18)F-dopa uptake in the striatum, orbitofrontal cortex and amygdala. One asymptomatic subject exhibited progressive putamen dopaminergic dysfunction. 60% of subjects with abnormal (18)F-dopa scans developed PSP subsequently. This is the first in vivo documentation of cortical dopaminergic deficiency in PSP. Reduced striatal (18)F-dopa uptake in susceptible relatives may predict later clinical disease. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16897607&query_hl=1 ER - TY - JFULL T1 - Using activity data to explore the influence of case-load size on care patterns. A1 - Burns, T A1 - Yiend, J A1 - Doll, H A1 - Fahy, T A1 - Fiander, M A1 - Tyrer, P J1 - Br J Psychiatry Y1 - 2007/03// VL - 190 SN - 0007-1250 SP - 217 EP - 222 N2 - BACKGROUND: A limited case-load size is considered crucial for some forms of intensive case management and many countries have undertaken extensive reorganisation of mental health services to achieve this. However, there has been limited empirical work to explore this specifically. AIMS: To test whether there is a discrete threshold for changes in intensive case management practice determined by case-load size. METHOD: "Virtual" case-load sizes were calculated for patients from their actual contacts over a 2-year period and were compared with the proportions of contacts devoted to medical and non-medical care (as a proxy for a more comprehensive service model). RESULTS: There were 39 025 recordings for 545 patients over 2 years, with a mean rate of contacts per full-time case manager per month of 48 (range 35-60). There was no variation in the proportion of non-medical contacts when case-load sizes were over 1:20 but there was a convincing linear relationship when sizes were between 1:10 and 1:20. CONCLUSIONS: Case-load size between 1:10 and 1:20 does affect the practice of case management. However, there is no support for a paradigm shift in practice at a discrete level. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17329741&query_hl=1 ER - TY - JFULL T1 - Increased opiold receptor binding in early abstinence from dependent opioid and alcohol use and relationship to craving A1 - Williams, TM A1 - Lingford-Hughes, A A1 - Daglish, MRC A1 - Taylor, LG A1 - Hammers, A A1 - Brooks, DJ A1 - Grasby, P A1 - Nutt, DJ J1 - EUR NEUROPSYCHOPHARM Y1 - 2007/03// VL - 17 SN - 0924-977X SP - S78 EP - S79 ER - TY - JFULL T1 - The V beta specific response to bacterial superantigens is determined by concentration and HLA class II A1 - Llewelyn, M A1 - Sriskandan, S A1 - Terrazzini, N A1 - Cohen, J A1 - Altmann, DM J1 - IMMUNOLOGY Y1 - 2007/03// VL - 120 SN - 0019-2805 SP - 77 EP - 77 ER - TY - JFULL T1 - Postoperative cognitive dysfunction after noncardiac surgery: a systematic review. A1 - Newman, S A1 - Stygall, J A1 - Hirani, S A1 - Shaefi, S A1 - Maze, M J1 - Anesthesiology Y1 - 2007/03// VL - 106 SN - 0003-3022 SP - 572 EP - 590 N2 - This article describes a systematic review on the research into postoperative cognitive dysfunction (POCD) in noncardiac surgery to ascertain the status of the evidence and to examine the methodologies used in studies. The review demonstrated that in the early weeks after major noncardiac surgery, a significant proportion of people show POCD, with the elderly being more at risk. Minimal evidence was found that patients continue to show POCD up to 6 months and beyond. Studies on regional versus general anesthesia have not found differences in POCD. Many studies were found to be underpowered, and a number of other methodologic difficulties were identified. These include the different types of surgery in studies and variations in the number and range of neuropsychological tests used. A particular issue is the variety of definitions used to classify individuals as having POCD. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17325517&query_hl=1 ER - TY - JFULL T1 - Screening for the metabolic syndrome in people receiving antipsychotic medication in assertive outreach teams: Results of the POMH-UK baseline audit A1 - Barnes, TR A1 - Paton, C A1 - Hancock, E A1 - Cavanagh, M A1 - Taylor, D A1 - Lelliott, P A1 - POMH-UK Project Team J1 - SCHIZOPHRENIA BULL Y1 - 2007/03// VL - 33 SN - 0586-7614 SP - 494 EP - 494 ER - TY - JFULL T1 - Special issue on postoperative cognitive dysfunction: selected reports from the journal-sponsored symposium. A1 - Maze, M A1 - Todd, MM J1 - Anesthesiology Y1 - 2007/03// VL - 106 SN - 0003-3022 SP - 418 EP - 420 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17325497&query_hl=1 ER - TY - JFULL T1 - Hypothalamic mapping of orexigenic action and Fos-like immunoreactivity following relaxin-3 administration in male Wistar rats. A1 - McGowan, BM A1 - Stanley, SA A1 - White, NE A1 - Spangeus, A A1 - Patterson, M A1 - Thompson, EL A1 - Smith, KL A1 - Donovan, J A1 - Gardiner, JV A1 - Ghatei, MA A1 - Bloom, SR J1 - Am J Physiol Endocrinol Metab Y1 - 2007/03// VL - 292 SN - 0193-1849 SP - E913 EP - E919 N2 - The insulin superfamily, characterized by common disulphide bonds, includes not only insulin but also insulin-like peptides such as relaxin-1 and relaxin-3. The actions of relaxin-3 are largely unknown, but recent work suggests a role in regulation of food intake. Relaxin-3 mRNA is highly expressed in the nucleus incertus, which has extensive projections to the hypothalamus, and relaxin immunoreactivity is present in several hypothalamic nuclei. In the rat, relaxin-3 binds and activates both relaxin family peptide receptor 1, which also binds relaxin-1, and a previously orphaned G protein-coupled receptor, RXFP3. These receptors are extensively expressed in the hypothalamus. The aims of these studies were twofold: 1) map the hypothalamic site(s) of the orexigenic action of relaxin-3 and 2) examine the site(s) of neuronal activation following central relaxin-3 administration. After microinjection into hypothalamic sites, human relaxin-3 (H3; 180 pmol) significantly stimulated 0- to 1-h food intake in the supraoptic nucleus (SON), arcuate nucleus (ARC), and the anterior preoptic area (APOA) [SON 0.4+/-0.2 (vehicle) vs. 2.9+/-0.5 g (H3), P<0.001; ARC 0.7+/-0.3 (vehicle) vs. 2.7+/-0.2 g (H3), P<0.05; and APOA 0.8+/-0.1 (vehicle) vs. 2.2+/-0.2 g (H3), P<0.05]. Cumulative food intake was significantly increased1.5 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. ER - TY - JFULL T1 - Analgesia with sevoflurane during labour: ii. Sevoflurane compared with Entonox for labour analgesia. A1 - Yeo, ST A1 - Holdcroft, A A1 - Yentis, SM A1 - Stewart, A A1 - Bassett, P J1 - Br J Anaesth Y1 - 2007/01// VL - 98 SN - 0007-0912 SP - 110 EP - 115 N2 - BACKGROUND: We determined the optimal inspired sevoflurane concentration for use during labour as 0.8% in our previous study. This study compared sevoflurane at a concentration of 0.8% and Entonox((R)) (nitrous oxide 50%: oxygen 50%) for analgesia during labour in 32 healthy parturients. METHODS: Each mother underwent two open-label, three-part sequences in random order, Entonox-sevoflurane-Entonox or sevoflurane-Entonox-sevoflurane. In each part the agent was self-administered during 10 contractions. A 100 mm visual analogue scores for pain relief and sedation was completed immediately after each contraction. RESULTS: Two patients withdrew during administration of sevoflurane (because of its odour) and five during Entonox (requesting epidural analgesia). Of the remaining women, data were available for analysis from 29 participants: median (IQR [range]) pain relief scores were significantly higher for sevoflurane 67 (55-74 [33-100]) mm than for Entonox 51 (40-69.5 [13-100]) mm (P<0.037). Nausea and vomiting were more common in the Entonox group [relative risk 2.7 (95% CI 1.3-5.7); P=0.004]. No other adverse effects were observed in the mothers or babies. There was significantly more sedation with sevoflurane than with Entonox {74 (66.5-81 [32.5-100]) and 51 (41-69.5 [13-100]) mm, respectively; P<0.001}. Twenty-nine patients preferred sevoflurane to Entonox and found its sedative effects helpful. CONCLUSIONS: We conclude that self-administered sevoflurane at subanaesthetic concentration (0.8%) can provide useful pain relief during the first stage of labour, and to a greater extent than Entonox. Although greater sedative effects were experienced with sevoflurane, it was preferred to Entonox. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17158129&query_hl=1 ER - TY - JFULL T1 - Alpha2-adrenoceptor agonists. A1 - Sanders, RD A1 - Maze, M J1 - Curr Opin Investig Drugs Y1 - 2007/01// VL - 8 SN - 1472-4472 SP - 25 EP - 33 N2 - Alpha2-Adrenoceptor agonists have an immensely diverse utility in peri-operative and critical care medicine. In particular, their application as premedicants, analgesics and hypnotics/sedatives is becoming increasingly popular with delivery to a wide spectrum of patients. The ability of these agents to provide renal, cardiac and neurocognitive protection is only just being realized and requires further study. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17263182&query_hl=1 ER - TY - JFULL T1 - Validation of a tracer kinetic model for the quantification of 5-HT(2A) receptors in human brain with [(11)C]MDL 100,907. A1 - Hinz, R A1 - Bhagwagar, Z A1 - Cowen, PJ A1 - Cunningham, VJ A1 - Grasby, PM J1 - J Cereb Blood Flow Metab Y1 - 2007/01// VL - 27 SN - 0271-678X SP - 161 EP - 172 N2 - The positron emission tomography (PET) ligand [(11)C]MDL 100,907 has previously been introduced to image the serotonin 2A (5-HT(2A)) receptor in human brain. The aim of this work was to contribute to the verification of the tracer kinetic modelling in human studies. Five healthy volunteers were scanned twice after intravenous bolus injection of approximately 370 MBq [(11)C]MDL 100,907 using dynamic PET. One scan was performed under baseline condition, the other scan commenced 90 mins after a single oral dose of 30 mg of the antidepressant mirtazapine, which binds to the 5-HT(2A) receptor. There did not appear to be radiolabelled metabolites of [(11)C]MDL 100,907 in human plasma, which are likely to cross the blood-brain barrier. Total volumes of distribution VD in 11 different brain regions were estimated using a reversible, two tissue, four rate constants compartment model with a variable fractional blood volume term and the metabolite-corrected plasma input function. There were no significant changes of the VD in the cerebellum between the baseline and the blocked scans confirming the cerebellum as a region devoid of displaceable binding. Regional estimates of binding potential were then obtained indirectly using the cerebellar VD and occupancies calculated. The mean occupancy with this clinically effective dose of mirtazapine was 60% without significant regional differences. This study confirmed the use of an arterial input kinetic model for the quantification of 5-HT(2A) receptor binding with [(11)C]MDL 100,907 and the use of the cerebellum as a reference region for the free and nonspecific binding. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16685260&query_hl=1 ER - TY - JFULL T1 - Review of physiological motor outcome measures in spinal cord injury using transcranial magnetic stimulation and spinal reflexes A1 - Ellaway, PH A1 - Catley, M A1 - Davey, NJ A1 - Kuppuswamy, A A1 - Strutton, P A1 - Frankel, HL A1 - Jamous, A A1 - Savic, G J1 - J REHABIL RES DEV Y1 - 2007/// VL - 44 SN - 0748-7711 SP - 69 EP - 75 N2 - This article reviews methods that have been developed as part of a clinical initiative on improving outcome measures for motor function assessment in subjects with spinal cord injury (SCI). Physiological motor outcome measures originally developed for limbs-transcranial magnetic stimulation (TMS) of the motor cortex to elicit motor-evoked potentials (MEPs) and mechanical stimulation to elicit spinal reflexes-have been extended to muscles of the trunk. The impetus for this development is the lack of a motor component in the American Spinal Injury Association clinical assessment for the thoracic myotomes. The application of TMS to the assessment of limb muscles is reviewed, followed by consideration of its application to the assessment of paravertebral and intercostal muscles. Spinal reflex testing of paravertebral muscles is also described. The principal markers for the thoracic SCI motor level that have emerged from this clinical initiative are (1) the threshold of MEPs in paravertebral muscles in response to TMS of the motor cortex, (2) the facilitation pattern and latency of MEPs in intercostal muscles during voluntary expiratory effort, and (3) the absence of long-latency reflex responses and the exaggeration of short-latency reflex responses in paravertebral muscles. ER - TY - JFULL T1 - Competitive Inhibition at the Glycine Site of the NMDA Receptor by the Anesthetics Xenon and Isoflurane: Evidence from Molecular Modeling and Electrophysiology A1 - Dickinson R A1 - Peterson B A1 - Banks P A1 - Simillis C A1 - Martin JC A1 - Valenzuela CA A1 - Maze M A1 - Franks NP J1 - Anesthesiology Y1 - 2007/// VL - xx SP - xxx EP - xxx ER - TY - JFULL T1 - From the editor's desk A1 - Tyrer, P J1 - BRIT J PSYCHIAT Y1 - 2007/01// VL - 190 SN - 0007-1250 SP - 90 EP - 90 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 - Analgesia with sevoflurane during labour: i. Determination of the optimum concentration. A1 - Yeo, ST A1 - Holdcroft, A A1 - Yentis, SM A1 - Stewart, A J1 - Br J Anaesth Y1 - 2007/01// VL - 98 SN - 0007-0912 SP - 105 EP - 109 N2 - BACKGROUND: Sevoflurane has favourable physical qualities for inhaled analgesia during labour pain. The aim of this preliminary study was to identify its optimum concentration. METHODS: In this open-labelled escalating-dose study, 22 parturients in labour self-administered sevoflurane at 10 contractions using an Oxford Miniature Vaporiser. The inspired concentration was increased by 0.2% after each contraction from 0% to 1.4% or decreased if sedation occurred. Visual analogue scores (0-100 mm) for pain intensity, pain relief, sedation, mood and coping were measured after each contraction. RESULTS: The median (IQR [range]) pain relief and sedation scores increased from 44 (43-56 [4-93]) mm and 55 (43-56 [0-98]) mm at 0.2% sevoflurane, to 74 (72-78 [50-80]) mm and 71 (71-73 [33-97]) mm at 1.2% sevoflurane, respectively. Pain relief scores did not show any significant increase above 0.8% whilst sedation continued to increase, with excessive sedation occurring at 1.2% sevoflurane. No significant changes in other scores were measured. CONCLUSIONS: We concluded that the optimal sevoflurane concentration in labour was 0.8%. This concentration allows a safety margin and balances the risk of sedation with the benefit of pain relief in labour. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17158128&query_hl=1 ER - TY - JFULL T1 - The role of the pre-supplementary motor area in the control of action. A1 - Nachev, P A1 - Wydell, H A1 - O'neill, K A1 - Husain, M A1 - Kennard, C J1 - Neuroimage Y1 - 2007/// VL - 36 Suppl 2 SN - 1053-8119 SP - T155 EP - T163 N2 - Although regions within the medial frontal cortex are known to be active during voluntary movements their precise role remains unclear. Here we combine functional imaging localisation with psychophysics to demonstrate a strikingly selective contralesional impairment in the ability to inhibit ongoing movement plans in a patient with a rare lesion involving the right pre-supplementary motor area (pre-SMA), but sparing the supplementary motor area (SMA). We find no corresponding delay in simple reaction times, and show that the inhibitory deficit is sensitive to the presence of competition between responses. The findings demonstrate that the pre-SMA plays a critical role in exerting control over voluntary actions in situations of response conflict. We discuss these findings in the context of a unified framework of pre-SMA function, and explore the degree to which extant data on this region can be explained by this function alone. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17499162&query_hl=1 ER - TY - JFULL T1 - Progression of dysautonomia in multiple system atrophy: a prospective study of self-perceived impairment A1 - Koellensperger, M A1 - Stampfer-Kountchev, M A1 - Seppi, K A1 - Geser, F A1 - Frick, C A1 - Del Sorbo, F A1 - Albanese, A A1 - Gurevich, T A1 - Giladi, N A1 - Djaldetti, R A1 - Schrag, A A1 - Low, PA A1 - Mathias, CJ A1 - Poewe, W A1 - Wenning, GK J1 - EUR J NEUROL Y1 - 2007/01// VL - 14 SN - 1351-5101 SP - 66 EP - 72 N2 - To assess severity and progression of self-perceived dysautonomia and their impact on health-related quality of life (Hr-QoL) in multiple system atrophy (MSA), twenty-seven patients were recruited by the European MSA Study Group (EMSA-SG). At baseline, all patients completed the Composite Autonomic Symptom Scale (COMPASS) and the 36 item Short Form Health Survey (SF-36), and they were assessed using the 3-point global disease severity scale (SS-3) and the Unified MSA Rating Scale (UMSARS). After 6 months follow-up, the self completed COMPASS Change Scale (CCS), the SF-36, SS-3, and UMSARS were obtained. MSA patients showed marked self-perceived dysautonomia at baseline visit and pronounced worsening of dysautonomia severity on the CCS at follow-up. Severity and progression of dysautonomia did not correlate with age, disease duration, motor impairment and overall disease severity at baseline. There were no significant differences between genders and motor subtypes. Baseline COMPASS scores were, however, inversely correlated with SF-36 scores. Progression of self-perceived dysautonomia did not correlate with global disease progression. Hr-QoL scores were stable during follow-up. This is the first study to investigate self-perceived dysautonomia severity in MSA and its evolution over time. Our data suggest that dysautonomia should be recognized as a key target for therapeutic intervention in MSA. ER - TY - JFULL T1 - Quantitative sensory tests (perceptual thresholds) in patients with spinal cord injury. A1 - Savic, G A1 - Bergström, EM A1 - Davey, NJ A1 - Ellaway, PH A1 - Frankel, HL A1 - Jamous, A A1 - Nicotra, A J1 - J Rehabil Res Dev Y1 - 2007/// VL - 44 SN - 0748-7711 SP - 77 EP - 82 N2 - This article was presented at the Premeeting Workshop on Outcome Measures at the American Spinal Injury Association (ASIA) Annual Scientific Meeting in Dallas, Texas, in May 2005. The article summarizes preliminary findings of three quantitative sensory tests that were evaluated as part of the International Spinal Research Trust Clinical Initiative study: perceptual thresholds to electrical, vibration, and thermal stimulation. The results gathered so far suggest that the three tests are simple, reproducible, and applicable in a clinical setting. The tests seem to add resolution and sensitivity to the standard clinical testing and could be useful adjuncts in longitudinal monitoring of spinal cord injury for research purposes. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17551861&query_hl=1 ER - TY - JFULL T1 - Psychiatric adjustment in the year after meningococcal disease in childhood A1 - Shears D A1 - Nadel S A1 - Gledhill J A1 - Gordon F A1 - Garralda ME J1 - Journal of the American Academy of Child and Adolescent Psychiatry Y1 - 2007/// IS - 1 VL - 46 SN - 0890-8567 SP - 76 EP - 82 ER - TY - JFULL T1 - Implications of changes in the impact factors of psychiatric journals. A1 - Tyrer, P J1 - Epidemiol Psichiatr Soc Y1 - 2007/01// VL - 16 SN - 1121-189X SP - 71 EP - 72 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17427606&query_hl=1 ER - TY - JFULL T1 - Generalised anxiety disorder. A1 - Tyrer, P A1 - Baldwin, D J1 - Lancet Y1 - 2006/12/16/ VL - 368 SN - 1474-547X SP - 2156 EP - 2166 N2 - Generalised anxiety disorder is a persistent and common disorder, in which the patient has unfocused worry and anxiety that is not connected to recent stressful events, although it can be aggravated by certain situations. This disorder is twice as common in women than it is in men. Generalised anxiety disorder is characterised by feelings of threat, restlessness, irritability, sleep disturbance, and tension, and symptoms such as palpitations, dry mouth, and sweating. These symptoms are recognised as part of the anxiety syndrome rather than independent complaints. The symptoms overlap greatly with those of other common mental disorders and we could regard the disorder as part of a spectrum of mood and related disorders rather than an independent disorder. Generalised anxiety disorder has a relapsing course, and intervention rarely results in complete resolution of symptoms, but in the short term and medium term, effective treatments include psychological therapies, such as cognitive behavioural therapy; self-help approaches based on cognitive behavioural therapy principles; and pharmacological treatments, mainly selective serotonin reuptake inhibitors. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17174708&query_hl=1 ER - TY - JFULL T1 - Structurally distinct membrane nanotubes between human macrophages support long-distance vesicular traffic or surfing of bacteria. A1 - Onfelt, B A1 - Nedvetzki, S A1 - Benninger, RK A1 - Purbhoo, MA A1 - Sowinski, S A1 - Hume, AN A1 - Seabra, MC A1 - Neil, MA A1 - French, PM A1 - Davis, DM J1 - J Immunol Y1 - 2006/12/15/ VL - 177 SN - 0022-1767 SP - 8476 EP - 8483 N2 - We report that two classes of membrane nanotubes between human monocyte-derived macrophages can be distinguished by their cytoskeletal structure and their functional properties. Thin membrane nanotubes contained only F-actin, whereas thicker nanotubes, i.e., those > approximately 0.7 microm in diameter, contained both F-actin and microtubules. Bacteria could be trapped and surf along thin, but not thick, membrane nanotubes toward connected macrophage cell bodies. Once at the cell body, bacteria could then be phagocytosed. The movement of bacteria is aided by a constitutive flow of the nanotube surface because streptavidin-coated beads were similarly able to traffic along nanotubes between surface-biotinylated macrophages. Mitochondria and intracellular vesicles, including late endosomes and lysosomes, could be detected within thick, but not thin, membrane nanotubes. Analysis from kymographs demonstrated that vesicles moved in a stepwise, bidirectional manner at approximately 1 microm/s, consistent with their traffic being mediated by the microtubules found only in thick nanotubes. Vesicular traffic in thick nanotubes and surfing of beads along thin nanotubes were both stopped upon the addition of azide, demonstrating that both processes require ATP. However, microtubule destabilizing agents colchicine or nocodazole abrogated vesicular transport but not the flow of the nanotube surface, confirming that distinct cytoskeletal structures of nanotubes give rise to different functional properties. Thus, membrane nanotubes between macrophages are more complex than unvarying ubiquitous membrane tethers and facilitate several means for distal interactions between immune cells. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17142745&query_hl=1 ER - TY - JFULL T1 - Gut hormones and the regulation of energy homeostasis. A1 - Murphy, KG A1 - Bloom, SR J1 - Nature Y1 - 2006/12/14/ VL - 444 SN - 1476-4687 SP - 854 EP - 859 N2 - Food intake, energy expenditure and body adiposity are homeostatically regulated. Central and peripheral signals communicate information about the current state of energy balance to key brain regions, including the hypothalamus and brainstem. Hunger and satiety represent coordinated responses to these signals, which include neural and hormonal messages from the gut. In recent years our understanding of how neural and hormonal brain-gut signalling regulates energy homeostasis has advanced considerably. Gut hormones have various physiological functions that include specifically targeting the brain to regulate appetite. New research suggests that gut hormones can be used to specifically regulate energy homeostasis in humans, and offer a target for anti-obesity drugs. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17167473&query_hl=1 ER - TY - JFULL T1 - Positive emotions preferentially engage an auditory-motor "mirror" system. A1 - Warren, JE A1 - Sauter, DA A1 - Eisner, F A1 - Wiland, J A1 - Dresner, MA A1 - Wise, RJ A1 - Rosen, S A1 - Scott, SK J1 - J Neurosci Y1 - 2006/12/13/ VL - 26 SN - 1529-2401 SP - 13067 EP - 13075 N2 - Social interaction relies on the ability to react to communication signals. Although cortical sensory-motor "mirror" networks are thought to play a key role in visual aspects of primate communication, evidence for a similar generic role for auditory-motor interaction in primate nonverbal communication is lacking. We demonstrate that a network of human premotor cortical regions activated during facial movement is also involved in auditory processing of affective nonverbal vocalizations. Within this auditory-motor mirror network, distinct functional subsystems respond preferentially to emotional valence and arousal properties of heard vocalizations. Positive emotional valence enhanced activation in a left posterior inferior frontal region involved in representation of prototypic actions, whereas increasing arousal enhanced activation in presupplementary motor area cortex involved in higher-order motor control. Our findings demonstrate that listening to nonverbal vocalizations can automatically engage preparation of responsive orofacial gestures, an effect that is greatest for positive-valence and high-arousal emotions. The automatic engagement of responsive orofacial gestures by emotional vocalizations suggests that auditory-motor interactions provide a fundamental mechanism for mirroring the emotional states of others during primate social behavior. Motor facilitation by positive vocal emotions suggests a basic neural mechanism for establishing cohesive bonds within primate social groups. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17167096&query_hl=1 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 - Time-specific effects of perinatal glucocorticoid treatment on anterior pituitary morphology, annexin 1 expression and adrenocorticotrophic hormone secretion in the adult female rat. A1 - John, CD A1 - Theogaraj, E A1 - Christian, HC A1 - Morris, JF A1 - Smith, SF A1 - Buckingham, JC J1 - J Neuroendocrinol Y1 - 2006/12// VL - 18 SN - 0953-8194 SP - 949 EP - 959 N2 - Perinatal glucocorticoid (GC) treatment is increasingly associated with long-term disturbances in hypothalamo-pituitary-adrenocortical function. In the male rat, such treatment induces profound molecular, morphological and functional changes in the anterior pituitary gland at adulthood. To determine whether these effects are sex-specific, we have examined the effects of perinatal dexamethasone treatment on the female pituitary gland, focusing on (i) the integrity of the annexin 1 (ANXA1) dependent regulatory effects of GCs on adrenocorticotrophic hormone (ACTH) release and (ii) corticotroph and folliculo-stellate (FS) cell morphology. Dexamethasone was given to pregnant (gestational days 16-19) or lactating (days 1-7 post partum) rats via the drinking water (1 microg/ml); controls received normal drinking water. Pituitary tissue from the female offspring was examined ex vivo at adulthood (60-90 days). Both treatment regimes reduced the intracellular and cell surface ANXA1 expression, as determined by western blot analysis and quantitative immunogold electron microscopic histochemistry. In addition, they compromised the ability of dexamethasone to suppress the evoked release of ACTH from the excised tissue in vitro, a process which requires the translocation of ANXA1 from the cytoplasm to the cell surface of FS cells. Although neither treatment regime affected the number of FS cells or corticotrophs, both altered the subcellular morphology of these cells. Thus, prenatal dexamethasone treatment increased while neonatal treatment decreased FS cell size and cytoplasmic area. By contrast, corticotroph size was unaffected by either treatment, as also was the size of the secretory granules. Corticotroph granule density and margination were, however, increased markedly by the prenatal treatment, while the neonatal treatment had no effect on granule density but decreased granule margination. Thus, perinatal dexamethasone treatment exerts long-term effects on the female pituitary gland, altering gene expression, cell morphology and the ANXA1-dependent GC regulation of ACTH secretion. The changes are similar but not identical to those reported in the male. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17076770&query_hl=1 ER - TY - JFULL T1 - From the editor's desk A1 - Tyrer, P J1 - BRIT J PSYCHIAT Y1 - 2006/12// VL - 189 SN - 0007-1250 SP - 576 EP - 576 ER - TY - JFULL T1 - The differential effects of nitrous oxide and xenon on extracellular dopamine levels in the rat nucleus accumbens: a microdialysis study. A1 - Sakamoto, S A1 - Nakao, S A1 - Masuzawa, M A1 - Inada, T A1 - Maze, M A1 - Franks, NP A1 - Shingu, K J1 - Anesth Analg Y1 - 2006/12// VL - 103 SN - 1526-7598 SP - 1459 EP - 1463 N2 - Dopamine release in the nucleus accumbens (NAC) plays a crucial role in the action of various psychotropic and addictive drugs, such as antagonists of the N-methyl-D-aspartate subtype of the glutamate. Although both nitrous oxide and xenon are N-methyl-D-aspartate receptor antagonists, they differ in their potential for producing neuropsychological toxicity; therefore, we decided to examine their effects on both spontaneous and ketamine-induced extracellular dopamine levels in the NAC. A microdialysis probe was implanted into the NAC in each of 35 rats, which were randomly assigned to one of six groups: exposure to 40% O2, exposure to 60% nitrous oxide (0.27 MAC), exposure to 43% xenon (0.27 MAC) for 60 min, and three groups exposed to either 40% O2, 60% nitrous oxide, or 43% xenon for 70 min and 80 mg/kg ketamine was given i.p. 10 min after the initiation of gas exposure. Perfusate samples were collected every 20 min, and the dopamine levels were measured using a high-performance liquid chromatography system. Nitrous oxide, but not xenon, significantly increased the dopamine level. Ketamine significantly increased the dopamine level, and this was significantly inhibited by xenon, but not by nitrous oxide. These data suggest that the difference in neuropsychological activity between nitrous oxide and xenon is partly due to their differential effects on the mesolimbic dopamine system. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17122223&query_hl=1 ER - TY - JFULL T1 - A new syndrome of congenital insensitivity to pain diagnosed by skin biopsy and contact heat evoked potentials (CHEPS) A1 - Facer, P A1 - Atherton, D A1 - Roberts, K A1 - Misra, VP A1 - Kinali, M A1 - Manzur, AY A1 - Muntoni, F A1 - Anand, P J1 - J NEUROL NEUROSUR PS Y1 - 2006/12// VL - 77 SN - 0022-3050 SP - 1400 EP - 1400 ER - TY - JFULL T1 - Correction of head movement on PET studies: comparison of methods. A1 - Montgomery, AJ A1 - Thielemans, K A1 - Mehta, MA A1 - Turkheimer, F A1 - Mustafovic, S A1 - Grasby, PM J1 - J Nucl Med Y1 - 2006/12// VL - 47 SN - 0161-5505 SP - 1936 EP - 1944 N2 - Head movement presents a continuing problem in PET studies. Head restraint minimizes movement but is unreliable, resulting in the need to develop alternative strategies. These include frame-by-frame (FBF) realignment or use of motion tracking (MT) during the scan to realign PET acquisition data. Here we present a comparative analysis of these 2 methods of motion correction. METHODS: Eight volunteers were examined at rest using (11)C-raclopride PET with the radioligand administered as a bolus followed by constant infusion to achieve steady state. Binding potential (BP) was estimated using the ratio method during 2 periods of the scan at steady state. Head movement was compensated by using coregistration between frames (FBF) and 3 methods using MT measurements of head position acquired with a commercially available optical tracking system. RESULTS: All methods of realignment improved test-retest reliability and noise characteristics of the raw data, with important consequences for the power to detect small changes in radiotracer binding, and the potential to reduce false-positive and false-negative results. MT methods were superior to FBF realignment using coregistration on some indices. CONCLUSION: Such methods have considerable potential to improve the reliability of PET data with important implications for the numbers of volunteers required to test hypotheses. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17138736&query_hl=1 ER - TY - JFULL T1 - Gut peptides in the regulation of food intake and energy homeostasis. A1 - Murphy, KG A1 - Dhillo, WS A1 - Bloom, SR J1 - Endocr Rev Y1 - 2006/12// VL - 27 SN - 0163-769X SP - 719 EP - 727 N2 - Gut hormones signal to the central nervous system to influence energy homeostasis. Evidence supports the existence of a system in the gut that senses the presence of food in the gastrointestinal tract and signals to the brain via neural and endocrine mechanisms to regulate short-term appetite and satiety. Recent evidence has shown that specific gut hormones administered at physiological or pathophysiological concentrations can influence appetite in rodents and humans. Gut hormones therefore have an important physiological role in postprandial satiety, and gut hormone signaling systems represent important pharmaceutical targets for potential antiobesity therapies. Our laboratory investigates the role of gut hormones in energy homeostasis and has a particular interest in this field of translational research. In this review we describe our initial studies and the results of more recent investigations into the effects of the gastric hormone ghrelin and the intestinal hormones peptide YY, pancreatic polypeptide, glucagon-like peptide-1, and oxyntomodulin on energy homeostasis. We also speculate on the role of gut hormones in the future treatment of obesity. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17077190&query_hl=1 ER - TY - JFULL T1 - Nodal, paranodal and juxtaparanodal axonal proteins during demyelination and remyelination in multiple sclerosis A1 - Coman, I A1 - Aigrot, MS A1 - Seilhean, D A1 - Reynolds, R A1 - Girault, JA A1 - Zalc, B A1 - Lubetzki, C J1 - BRAIN Y1 - 2006/12// VL - 129 SN - 0006-8950 SP - 3186 EP - 3195 N2 - Saltatory conduction in myelinated fibres depends on the specific molecular organization of highly specialized axonal domains at the node of Ranvier, the paranodal and the juxtaparanodal regions. Voltage-gated sodium channels (Na-v) have been shown to be deployed along the naked demyelinated axon in experimental models of CNS demyelination and in multiple sclerosis lesions. Little is known about aggregation of nodal, paranodal and juxtaparanodal constituents during the repair process. We analysed by immunohistochemistry on free-floating sections from multiple sclerosis brains the expression and distribution of nodal (Na-v channels), paranodal (paranodin/Caspr) and juxtaparanodal (K-v channels and Caspr2) molecules in demyelinated and remyelinated lesions. Whereas in demyelinated lesions, paranodal and juxtaparanodal proteins are diffusely distributed on denuded axons, the distribution of Na-v channels is heterogeneous, with a diffuse immunoreactivity but also few broad Na-v channel aggregates in all demyelinated lesions. In contrast to the demyelinated plaques, all remyelinated lesions are characterized by the detection of aggregates of Na-v channels, paranodin/Caspr, K-v channels and Caspr2. Our data suggest that these aggregates precede remyelination, and that Na-v channel aggregation is the initial event, followed by aggregation of paranodal and then juxtaparanodal axonal proteins. Remyelination takes place in multiple sclerosis tissue but myelin repair is often incomplete, and the reasons for this remyelination deficit are many. We suggest that a defect of Na-v channel aggregation might be involved in the remyelination failure in demyelinated lesions with spared axons and oligodendroglial cells. ER - TY - JFULL T1 - Intraspinal microstimulation excites multisegmental sensory afferents at lower stimulus levels than local alpha-motoneuron responses. A1 - Gaunt, RA A1 - Prochazka, A A1 - Mushahwar, VK A1 - Guevremont, L A1 - Ellaway, PH J1 - J Neurophysiol Y1 - 2006/12// VL - 96 SN - 0022-3077 SP - 2995 EP - 3005 N2 - Microstimulation within the motor regions of the spinal cord is often assumed to activate motoneurons and propriospinal neurons close to the electrode tip. However, previous work has shown that intraspinal microstimulation (ISMS) in the gray matter activates sensory afferent axons as well as alpha-motoneurons (MNs). Here we report on the recruitment of sensory afferent axons and MNs as ISMS amplitudes increased. Intraspinal microstimulation was applied through microwires implanted in the dorsal horn, intermediate region and ventral horn of the L(5)-L(7) segments of the spinal cord in four acutely decerebrated cats, two of which had been chronically spinalized. Activation of sensory axons was detected with electroneurographic recordings from dorsal roots. Activation of MNs was detected with electromyographic (EMG) recordings from hindlimb muscles. Sensory axons were nearly always activated at lower stimulus levels than MNs irrespective of the stimulating electrode location. EMG response latencies decreased as ISMS stimulus intensities increased, suggesting that MNs were first activated transsynaptically and then directly as intensity increased. ISMS elicited antidromic activity in dorsal root filaments with entry zones up to 17 mm rostral and caudal to the stimulation sites. We posit that action potentials elicited in localized terminal branches of afferents spread antidromically to all terminal branches of the afferents and transsynaptically excite MNs and interneurons far removed from the stimulation site. This may help explain how focal ISMS can activate many MNs of a muscle even though they are distributed in long thin columns. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16943320&query_hl=1 ER - TY - JFULL T1 - Disruption of neurofascin localization reveals early changes preceding demyelination and remyelination in multiple sclerosis. A1 - Howell, OW A1 - Palser, A A1 - Polito, A A1 - Melrose, S A1 - Zonta, B A1 - Scheiermann, C A1 - Vora, AJ A1 - Brophy, PJ A1 - Reynolds, R J1 - Brain Y1 - 2006/12// VL - 129 SN - 1460-2156 SP - 3173 EP - 3185 N2 - Saltatory conduction in the nervous system is enabled through the intimate association between the leading edge of the myelin sheath and the axonal membrane to demarcate the node of Ranvier. The 186 kDa neuron specific isoform of the adhesion molecule neurofascin (Nfasc186) is required for the clustering of voltage gated Na+ channels at the node, whilst the 155 kDa glial specific isoform (Nfasc155) is required for the assembly of correct paranodal junctions. In order to understand the relationship between these vital structures and how they are affected in multiple sclerosis we have examined the expression of Nfasc155 and Nfasc186 in areas of inflammation, demyelination and remyelination from post-mortem brains. Fourteen cases of neuropathologically confirmed multiple sclerosis (8 female and 6 male; post-mortem delay 7-24 h; age 37-77 years; and disease duration 15-40 years), comprising 20 tissue blocks with 32 demyelinating or remyelinating lesions, were used in this study. A significant early alteration in Nfasc155+ paranodal structures occurs within and adjacent to actively demyelinating white matter lesions that are associated with damaged axons. Shaker-type Kv1.2 channels, normally located distally to the paranode, overlapped with the disrupted Nfasc155+ structures. In the absence of Nfasc155, Kv1.2 channels abutted normally clustered Nfasc186+ nodes, indicating that complete disruption of the paranodal structure and movement of Kv1.2 channels precede alterations at the node itself. Within areas of partial remyelination, a number of atypical triple-Nfasc155+ structures were noted that may represent transient oligodendrocyte-axonal contacts during the process of myelin repair or aberrant interactions. Within shadow plaques discretely clustered Na+v, Nfasc186+ and Nfasc155+ domains indicated the restoration of normal nodal architecture. The alterations in oligodendrocyte Nfasc155 expression that accompany inflammation and demyelination suggest an ongoing disruption to the axonal-oligodendrocyte complex within newly forming as well as established lesions in multiple sclerosis, resulting in destruction of the Nfasc186+/Na+v nodal complex vital to successful fast neurotransmission in the CNS. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17041241&query_hl=1 ER - TY - JFULL T1 - Gene deletion reveals roles for annexin A1 in the regulation of lipolysis and IL-6 release in epididymal adipose tissue. A1 - Warne, JP A1 - John, CD A1 - Christian, HC A1 - Morris, JF A1 - Flower, RJ A1 - Sugden, D A1 - Solito, E A1 - Gillies, GE A1 - Buckingham, JC J1 - Am J Physiol Endocrinol Metab Y1 - 2006/12// VL - 291 SN - 0193-1849 SP - E1264 EP - E1273 N2 - In this study, epididymal adipose tissue from male annexin 1 (ANXA1)-null and wild-type control mice were used to explore the potential role of ANXA1 in adipocyte biology. ANXA1 was detected by Western blot analysis in wild-type tissue and localized predominantly to the stromal-vascular compartment. Epididymal fat pad mass was reduced by ANXA1 gene deletion, but adipocyte size was unchanged, suggesting that ANXA1 is required for the maintenance of adipocyte and/or preadipocyte cell number. Epididymal tissue from wild-type mice responded in vitro to noradrenaline and isoprenaline with increased glycerol release, reduced IL-6 release, and increased cAMP accumulation. Qualitatively similar but significantly attenuated responses to the catecholamines were observed in tissue from ANXA1-null mice, an effect that was not associated with changes in beta-adrenoceptor mRNA expression. Lipopolysaccharide (LPS) also stimulated lipolysis in vitro, but its effects were muted by ANXA1 gene deletion. By contrast, LPS failed to influence IL-6 release from wild-type tissue but stimulated the release of the cytokine from tissue from ANXA1-null mice. ANXA1 gene deletion did not affect glucocorticoid receptor expression or the ability of dexamethasone to suppress catecholamine-induced lipolysis. It did, however, augment IL-6 expression and modify the inhibitory effects of glucocorticoids on IL-6 release. Collectively, these studies suggest that ANXA1 supports aspects of adipose tissue mass and alters the sensitivity of epididymal adipose tissue to catecholamines, glucocorticoids, and LPS, thereby modulating lipolysis and IL-6 release. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16835395&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 - The potential role of nerve growth factor (NGF) in painful neuromas and the mechanism of pain relief by their relocation to muscle. A1 - Atherton, DD A1 - Taherzadeh, O A1 - Facer, P A1 - Elliot, D A1 - Anand, P J1 - J Hand Surg [Br] Y1 - 2006/12// VL - 31 SN - 0266-7681 SP - 652 EP - 656 N2 - Painful neuromas have been successfully treated by surgical procedures including relocation to muscle, but the underlying molecular mechanism remains unclear. Nerve growth factor (NGF) is secreted by tissues and promotes the expression of ion channels and neuropeptides in sensory neurons involved in pain transmission. We hypothesised that excess of NGF may lead to pain in neuromas and that the efficacy of surgical relocation results from deprivation of NGF, i.e. translocation from NGF-rich regions, particularly sub-cutaneous structures associated with injury or inflammation, to NGF-poor structures such as muscle or bone. Using immunohistological methods with primary antibodies to rhNGF, we report that NGF levels were elevated in 13 painful neuromas in comparison with six control nerves. However, in four painful neuromata re-located into muscle with pain relief, the NGF level was similar to that of controls. NGF levels suggest an explanation for the development of painful neuromas and the efficacy of relocation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16928414&query_hl=1 ER - TY - JFULL T1 - The role of nerve growth factor in painful neuromas and the mechanism of pain relief by their relocation to muscle A1 - Atherton, D A1 - Taherzadeh, O A1 - Facer, P A1 - Elliot, D A1 - Anand, P J1 - J NEUROL NEUROSUR PS Y1 - 2006/12// VL - 77 SN - 0022-3050 SP - 1391 EP - 1391 ER - TY - JFULL T1 - Neuroprotective interaction produced by xenon and dexmedetomidine on in vitro and in vivo neuronal injury models. A1 - Rajakumaraswamy, N A1 - Ma, D A1 - Hossain, M A1 - Sanders, RD A1 - Franks, NP A1 - Maze, M J1 - Neurosci Lett Y1 - 2006/12/01/ VL - 409 SN - 0304-3940 SP - 128 EP - 133 N2 - Xenon, an NMDA receptor antagonist and dexmedetomidine (Dex), an alpha(2)-adrenoceptor agonist, both exhibit neuroprotective effects. We investigated the nature of their interaction. In vitro: a primary co-culture of neuronal and glial cells derived from neonatal mice was exposed to oxygen and glucose deprivation (OGD) and the resulting neuronal injury was assessed by the release of lactate dehydrogenase (LDH). In vivo: Postnatal rats aged 7 days underwent right common carotid artery ligation followed by 90 min of hypoxia. The area of infarction was assessed at four days post-injury by morphological criteria. Long-term neurological function was evaluated at 30 days post-injury by testing co-ordination on rotarod. Both xenon and Dex concentration-dependently reduced LDH release with IC50 values of 42% atm (95% CI: 35-52) and 0.10 microM (95% CI: 0.08-0.16), respectively. Isobolographic analysis showed that combined effect of xenon and Dex in vitro was additive. In vivo, a combination of xenon and Dex, at doses that are individually not neuroprotective, produced significant neuroprotective effect as measured by reduction in area of infarction. The long-term neurological function data corroborated these morphological data. Our study demonstrates that the combination of xenon and Dex offers neuroprotection additively in vitro and synergistically in vivo. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17052852&query_hl=1 ER - TY - JFULL T1 - Pain phenomena and sensory recovery following brachial plexus avulsion injury and surgical repairs. A1 - Htut, M A1 - Misra, P A1 - Anand, P A1 - Birch, R A1 - Carlstedt, T J1 - J Hand Surg [Br] Y1 - 2006/12// VL - 31 SN - 0266-7681 SP - 596 EP - 605 N2 - Seventy-six patients with severe brachial plexus avulsion injuries were studied using pain questionnaires and quantitative sensory testing. There was significant correlation between pain intensity and the number of roots avulsed prior to surgery (P=0.0004) and surgical repairs were associated with pain relief. Sensory recovery to thermal stimuli was observed, mainly in the C5 dermatome. Allodynia to mechanical and thermal stimuli was observed in the border zone of affected and unaffected dermatomes in 18% of patients assessed early (<6 months) and 37% patients at later stages. Pain and sensations referred to the original source of afferents occurred at a later stage (>6 months) in 12% of patients and were related to nerve regeneration. By contrast, "wrong-way" referred sensations (e.g. down the affected arm while shaving or drinking cold fluids) were reported by 44% of patients and often occurred early, suggesting CNS plasticity. Understanding sensory mechanisms will help develop new treatments for severe brachial plexus injuries. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16822598&query_hl=1 ER - TY - JFULL T1 - Drug-induced exacerbation of glomus tumour pain. A1 - Daghir, A A1 - Anand, P A1 - Gabra, H A1 - Elliot, D J1 - J Hand Surg [Br] Y1 - 2006/12// VL - 31 SN - 0266-7681 SP - 692 EP - 692 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16766103&query_hl=1 ER - TY - JFULL T1 - Multiple sclerosis conference synopsis and discussion: cellular therapy for treatment of autoimmune diseases (October 2005). A1 - Openshaw, H A1 - Atkins, HL A1 - Chen, JT A1 - de Bittencourt, PR A1 - Griffith, LM A1 - Kerr, DA A1 - Khoury, SA A1 - Muraro, PA A1 - Nash, RA A1 - Saccardi, R J1 - Mult Scler Y1 - 2006/12// VL - 12 SN - 1352-4585 SP - 824 EP - 825 N2 - At a conference held in October 2005, participants presented studies on high dose immunosuppression with hematopoietic cell transplant (HCT) for multiple sclerosis (MS), including neuroimmunological and magnetic resonance imaging (MRI) mechanistic approaches, clinical registry reports, and ongoing or newly-designed protocols. A discussion panel considered questions on how to define success, timing of controlled clinical trials, difficulty in patient recruitment, and future direction of high dose therapy. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17263013&query_hl=1 ER - TY - JFULL T1 - Severe childhood SMA and axonal CMT due to anticodon binding domain mutations in the GARS gene A1 - James, PA A1 - Cader, MZ A1 - Muntoni, F A1 - Childs, AM A1 - Crow, YJ A1 - Talbot, K J1 - NEUROLOGY Y1 - 2006/11/14/ VL - 67 SN - 0028-3878 SP - 1710 EP - 1712 N2 - We screened 100 patients with inherited and sporadic lower motor neuron degeneration and identified three novel missense mutations in the glycyl-tRNA synthetase (GARS) gene. One mutation was in the anticodon binding domain and associated with onset in early childhood and predominant involvement of the lower limbs, thus extending the phenotype associated with GARS mutations. 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 - The human ClC-4 protein, a member of the CLC chloride channel/transporter family, is localized to the endoplasmic reticulum by its N-terminus. A1 - Okkenhaug, H A1 - Weylandt, KH A1 - Carmena, D A1 - Wells, DJ A1 - Higgins, CF A1 - Sardini, A J1 - FASEB J Y1 - 2006/11// VL - 20 SN - 1530-6860 SP - 2390 EP - 2392 N2 - Despite considerable similarity in their amino acid sequences and structural features, the mammalian members of the CLC chloride channel/transporter family have different subcellular locations. The subcellular location and function of one of these members, hClC-4, is controversial. To characterize its cellular function, we investigated its tissue distribution and subcellular location. Expression was high in excitable tissues such as the nervous system and skeletal muscle. When heterologously expressed in HEK293 cells and in skeletal muscle fibers, hClC-4 localizes to the endoplasmic/sarcoplasmic reticulum (ER/SR) membranes, in contrast to hClC-3, which localizes to vesicular structures. This location was confirmed by identification of endogenous ClC-4 in membrane fractions from mouse brain homogenate enriched for the sarco-endoplasmic reticulum ATPase SERCA2, an ER/SR marker. To identify the motif responsible for ER localization of hClC-4, we generated hClC-4 truncations and chimeras between hClC-4 and hClC-3 or the unrelated plasma membrane protein Ly49E. A stretch of amino acids, residues 14-63, at the N-terminus constitutes a novel motif both necessary and sufficient for targeting hClC-4 and other membrane proteins to the ER. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17023393&query_hl=1 ER - TY - JFULL T1 - Unexplained syncope--is screening for carotid sinus hypersensitivity indicated in all patients aged >40 years? A1 - Humm, AM A1 - Mathias, CJ J1 - J Neurol Neurosurg Psychiatry Y1 - 2006/11// VL - 77 SN - 1468-330X SP - 1267 EP - 1270 N2 - OBJECTIVE: To determine the frequency, age distribution and clinical presentation of carotid sinus hypersensitivity (CSH) among 373 patients (age range 15-92 years) referred to two autonomic referral centres during a 10-year period. METHODS: Carotid sinus massage (CSM) was performed both supine and during 60 degree head-up tilt. Beat-to-beat blood pressure, heart rate and a three-lead electrocardiography were recorded continuously. CSH was classified as cardioinhibitory (asystole > or = 3 s), vasodepressor (systolic blood pressure fall > or = 50 mm Hg) or mixed. All patients additionally underwent autonomic screening tests for orthostatic hypotension and autonomic failure. RESULTS: CSH was observed in 13.7% of all patients. The diagnostic yield of CSM was nil in patients aged < 50 years (n = 65), 2.4% in those aged 50-59 years (n = 82), 9.1% in those aged 60-69 years (n = 77), 20.7% in those aged 70-79 years (n = 92) and reached 40.4% in those > 80 years (n = 57). Syncope was the leading clinical symptom in 62.8%. In 27.4% of patients falls without definite loss of consciousness was the main clinical symptom. Mild and mainly systolic orthostatic hypotension was recorded in 17.6%; evidence of sympathetic or parasympathetic dysfunction was found in none. CONCLUSIONS: CSH was confirmed in patients > 50 years, the incidence steeply increasing with age. The current European Society of Cardiology guidelines that recommend testing for CSH in all patients > 40 years with syncope of unknown aetiology may need reconsideration. Orthostatic hypotension was noted in some patients with CSH, but evidence of sympathetic or parasympathetic failure was not found in any of them. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16735395&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 - Apolitical psychiatry A1 - Tyrer, P J1 - BRIT J PSYCHIAT Y1 - 2006/11// VL - 189 SN - 0007-1250 SP - 478 EP - 478 ER - TY - JFULL T1 - Podcasts for the British Journal of Psychiatry A1 - Tyrer, P J1 - BRIT J PSYCHIAT Y1 - 2006/11// VL - 189 SN - 0007-1250 SP - 478 EP - 478 ER - TY - JFULL T1 - Epigenetic allele silencing unveils recessive RYR1 mutations in core myopathies. A1 - Zhou, H A1 - Brockington, M A1 - Jungbluth, H A1 - Monk, D A1 - Stanier, P A1 - Sewry, CA A1 - Moore, GE A1 - Muntoni, F J1 - Am J Hum Genet Y1 - 2006/11// VL - 79 SN - 0002-9297 SP - 859 EP - 868 N2 - Epigenetic regulation of gene expression is a source of genetic variation, which can mimic recessive mutations by creating transcriptional haploinsufficiency. Germline epimutations and genomic imprinting are typical examples, although their existence can be difficult to reveal. Genomic imprinting can be tissue specific, with biallelic expression in some tissues and monoallelic expression in others or with polymorphic expression in the general population. Mutations in the skeletal-muscle ryanodine-receptor gene (RYR1) are associated with malignant hyperthermia susceptibility and the congenital myopathies central core disease and multiminicore disease. RYR1 has never been thought to be affected by epigenetic regulation. However, during the RYR1-mutation analysis of a cohort of patients with recessive core myopathies, we discovered that 6 (55%) of 11 patients had monoallelic RYR1 transcription in skeletal muscle, despite being heterozygous at the genomic level. In families for which parental DNA was available, segregation studies showed that the nonexpressed allele was maternally inherited. Transcription analysis in patients' fibroblasts and lymphoblastoid cell lines indicated biallelic expression, which suggests tissue-specific silencing. Transcription analysis of normal human fetal tissues showed that RYR1 was monoallelically expressed in skeletal and smooth muscles, brain, and eye in 10% of cases. In contrast, 25 normal adult human skeletal-muscle samples displayed only biallelic expression. Finally, the administration of the DNA methyltransferase inhibitor 5-aza-deoxycytidine to cultured patient skeletal-muscle myoblasts reactivated the transcription of the silenced allele, which suggests hypermethylation as a mechanism for RYR1 silencing. Our data indicate that RYR1 undergoes polymorphic, tissue-specific, and developmentally regulated allele silencing and that this unveils recessive mutations in patients with core myopathies. Furthermore, our data suggest that imprinting is a likely mechanism for this phenomenon and that similar mechanisms could play a role in human phenotypic heterogeneity. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17033962&query_hl=1 ER - TY - JFULL T1 - Air bubble growth in water. A1 - Franks, NP A1 - Benavides, R A1 - Maze, M J1 - Anesthesiology Y1 - 2006/11// VL - 105 SN - 0003-3022 SP - 1059 EP - 1060 N2 - L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17065903&query_hl=1 ER - TY - JFULL T1 - Plasma kisspeptin is raised in patients with gestational trophoblastic neoplasia and falls during treatment. A1 - Dhillo, WS A1 - Savage, P A1 - Murphy, KG A1 - Chaudhri, OB A1 - Patterson, M A1 - Nijher, GM A1 - Foggo, VM A1 - Dancey, GS A1 - Mitchell, H A1 - Seckl, MJ A1 - Ghatei, MA A1 - Bloom, SR J1 - Am J Physiol Endocrinol Metab Y1 - 2006/11// VL - 291 SN - 0193-1849 SP - E878 EP - E884 N2 - Kisspeptin is a 54-amino acid peptide, encoded by the anti-metastasis gene KiSS-1, that activates G protein-coupled receptor 54 (GPR54). The kisspeptin-GPR54 system is critical to normal reproductive development. KiSS-1 gene expression is increased in the human placenta in normal and molar pregnancies. Circulating kisspeptin is dramatically increased in normal pregnancy, but levels in GTN have not previously been reported. The present study was designed to determine whether plasma kisspeptin levels are altered in patients with malignant GTN. Thirty-nine blood samples were taken from 11 patients with malignant GTN at presentation during and after chemotherapy. Blood was also sampled from nonpregnant and pregnant volunteers. Plasma kisspeptin IR and hCG concentrations were measured. Plasma kisspeptin IR concentration in nonpregnant (n = 16) females was <2 pmol/l. Plasma kisspeptin IR in females was 803 +/- 125 pmol/l in the first trimester of pregnancy (n = 13), 2,483 +/- 302 pmol/l in the third trimester of pregnancy (n = 7), and <2 pmol/l on day 15 postpartum (n = 7). Plasma kisspeptin IR and hCG concentrations in patients with malignant GTN were elevated at presentation and fell during and after treatment with chemotherapy in each patient (mean plasma kisspeptin IR: prechemotherapy 1,363 +/- 1,076 pmol/l vs. post-chemotherapy <2 pmol/l, P < 0.0001; mean plasma hCG: prechemotherapy 227,191 +/- 152,354 U/l vs. postchemotherapy 2 U/l, P < 0.0001). Plasma kisspeptin IR strongly positively correlated with plasma hCG levels (r(2) = 0.99, P < 0.0001). Our results suggest that measurement of plasma kisspeptin IR may be a novel tumor marker in patients with malignant GTN. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16757546&query_hl=1 ER - TY - JFULL T1 - Lentiviral vector expressing retinoic acid receptor beta2 promotes recovery of function after corticospinal tract injury in the adult rat spinal cord. A1 - Yip, PK A1 - Wong, LF A1 - Pattinson, D A1 - Battaglia, A A1 - Grist, J A1 - Bradbury, EJ A1 - Maden, M A1 - McMahon, SB A1 - Mazarakis, ND J1 - Hum Mol Genet Y1 - 2006/11/01/ VL - 15 SN - 0964-6906 SP - 3107 EP - 3118 N2 - Spinal cord injury often results in permanent and devastating neurological deficits and disability. This is due to the limited regenerative capacity of neurones in the central nervous system (CNS). We recently demonstrated that a transcription factor retinoic acid receptor beta2 (RARbeta2) promoted axonal regeneration in adult sensory neurones located peripherally. However, it is not known if RARbeta2 can promote axonal regeneration in cortical neurones of the CNS. Here, we demonstrate that delivery of RARbeta2 via a lentiviral vector to adult dissociated cortical neurones significantly enhances neurite outgrowth on adult cortical cryosections, which normally provide an unfavourable substrate for growth. We also show that lentiviral-mediated transduction of corticospinal neurones resulted in robust transgene expression in layer V corticospinal neurones and their axonal projections in the corticospinal tract (CST) of the spinal cord. Expression of RARbeta2 in these neurones enhanced regeneration of the descending CST fibres after injury to these axons in the mid-cervical spinal cord. Furthermore, we observed functional recovery in sensory and locomotor behavioural tests in RARbeta2-treated animals. These results suggest that a direct and selective delivery of RARbeta2 to the corticospinal neurones promotes long-distance functional regeneration of axons in the spinal cord and may thus offer new therapeutic gene strategy for the treatment of human spinal cord injuries. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16984961&query_hl=1 ER - TY - JFULL T1 - Music therapy for in-patients with schizophrenia: exploratory randomised controlled trial. A1 - Talwar, N A1 - Crawford, MJ A1 - Maratos, A A1 - Nur, U A1 - McDermott, O A1 - Procter, S J1 - Br J Psychiatry Y1 - 2006/11// VL - 189 SN - 0007-1250 SP - 405 EP - 409 N2 - BACKGROUND: Music therapy may provide a means of improving mental health among people with schizophrenia, but its effects in acute psychoses have not been explored. AIMS: To examine the feasibility of a randomised trial of music therapy for inpatients with schizophrenia, and explore its effects on mental health. METHOD: Up to 12 weeks of individual music therapy plus standard care were compared with standard care alone. Masked assessments of mental health, global functioning and satisfaction with care were conducted at 3 months. RESULTS: Of 115 eligible patients 81 (70%) were randomised. Two-thirds of those randomised to music therapy attended at least four sessions (median attendance, eight sessions). Multivariate analysis demonstrated a trend towards improved symptom scores among those randomised to music therapy, especially in general symptoms of schizophrenia. CONCLUSIONS: A randomised trial of music therapy for in-patients with schizophrenia is feasible. The effects and cost-effectiveness of music therapy for acute psychosis should be further explored in an explanatory randomised trial. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17077429&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 - Lack of annexin 1 results in an increase in corticotroph number in male but not female mice A1 - Morris, JF A1 - Omer, S A1 - Davies, E A1 - Wang, E A1 - John, C A1 - Afzal, T A1 - Wain, S A1 - Buckingham, JC A1 - Flower, RJ A1 - Christian, HC J1 - J NEUROENDOCRINOL Y1 - 2006/11// VL - 18 SN - 0953-8194 SP - 835 EP - 846 N2 - Annexin 1 (ANXA1) is a member of the annexin family of phospholipid- and calcium-binding proteins with a well demonstrated role in early delayed (30 min to 3 h) inhibitory feedback of glucocorticoids in the pituitary. We have examined corticotrophs in wild-type and ANXA1 knockout mice to determine the effects of lack of ANXA1 in male and female animals. Anterior pituitary tissue from ANXA1 wild-type, heterozygote and null mice was fixed and examined (i) by confocal immunocytochemistry to determine the number of corticotrophs and (ii) by electron microscopy to examine the size, secretory granule population and secretory machinery of corticotrophs. No differences in these parameters were detected in female mice. In male ANXA1 null mice, there were approximately four-fold more corticotrophs than in wild-type animals. However, the corticotrophs in ANXA1 null mice were smaller and had reduced numbers of secretory granules (the reduction in granules paralleled the reduction in cell size). No differences in the numerical density of folliculo-stellate, gonadotroph, lactotroph or somatotroph cells were detected in male ANXA1 null mice. Plasma corticosterone, adrenocorticotrophic hormone (ACTH) and pituitary pro-opiomelanocortin mRNA were unchanged but pituitary ACTH content was increased in male ANXA1 null mice. Interleukin (IL)-6 pituitary content was significantly elevated in male and reduced in female ANXA1 null mice compared to wild-type. In conclusion, these data indicate that ANXA1 deficiency is associated with gender-specific changes in corticotroph number and structure, via direct actions of ANXA1 and/or indirect changes in factors such as IL-6. ER - TY - JFULL T1 - The mechanistic classification of addictive drugs. A1 - Lüscher, C A1 - Ungless, MA J1 - PLoS Med Y1 - 2006/11// VL - 3 SN - 1549-1676 SP - e437 EP - e437 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17105338&query_hl=1 ER - TY - JFULL T1 - Annexin 1, glucocorticoids, and the neuroendocrine-immune interface. A1 - Buckingham, JC A1 - John, CD A1 - Solito, E A1 - Tierney, T A1 - Flower, RJ A1 - Christian, H A1 - Morris, J J1 - Ann N Y Acad Sci Y1 - 2006/11// VL - 1088 SN - 0077-8923 SP - 396 EP - 409 N2 - Annexin 1 (ANXA1) was originally identified as a mediator of the anti-inflammatory actions of glucocorticoids (GCs) in the host defense system. Subsequent work confirmed and extended these findings and also showed that the protein fulfills a wider brief and serves as a signaling intermediate in a number of systems. ANXA1 thus contributes to the regulation of processes as diverse as cell migration, cell growth and differentiation, apoptosis, vesicle fusion, lipid metabolism, and cytokine expression. Here we consider the role of ANXA1 in the neuroendocrine system, particularly the hypothalamo-pituitary-adrenocortical (HPA) axis. Evidence is presented that ANXA1 plays a critical role in effecting the negative feedback effects of GCs on the release of corticotrophin (ACTH) and its hypothalamic-releasing hormones and that it is particularly pertinent to the early-onset actions of the steroids that are mediated via a nongenomic mechanism. The paracrine/juxtacrine mode of ANXA1 action is discussed in detail, with particular reference to the significance of the secondary processing of ANXA1, the processes that control the intracellular and transmembrane trafficking of the protein of the molecule and the mechanism of ANXA1 action on its target cells. In addition, the role of ANXA1 in the perinatal programming of the HPA axis is discussed. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17192583&query_hl=1 ER - TY - JFULL T1 - Direction of tremor oscillation in spiral drawings reveals proximal versus distal muscle involvement. A1 - Liu, X A1 - Bain, PG J1 - Mov Disord Y1 - 2006/11// VL - 21 SN - 0885-3185 SP - 2032 EP - 2032 L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16991146&query_hl=1 ER - TY - JFULL T1 - The human prion protein residue 129 polymorphism lies within a cluster of epitopes for T cell recognition. A1 - Isaacs, JD A1 - Ingram, RJ A1 - Collinge, J A1 - Altmann, DM A1 - Jackson, GS J1 - J Neuropathol Exp Neurol Y1 - 2006/11// VL - 65 SN - 0022-3069 SP - 1059 EP - 1068 N2 - T cell immune responses to central nervous system-derived and other self-antigens are commonly described in both healthy and autoimmune individuals. However, in the case of the human prion protein (PrP), it has been argued that immunologic tolerance is uncommonly robust. Although development of an effective vaccine for prion disease requires breaking of tolerance to PrP, the extent of immune tolerance to PrP and the identity of immunodominant regions of the protein have not previously been determined in humans. We analyzed PrP T cell epitopes both by using a predictive algorithm and by measuring functional immune responses from healthy donors. Interestingly, clusters of epitopes were focused around the area of the polymorphic residue 129, previously identified as an indicator of susceptibility to prion disease, and in the C-terminal region. Moreover, responses were seen to PrP peptide 121-134 containing methionine at position 129, whereas PrP 121-134 [129V] was not immunogenic. The residue 129 polymorphism was also associated with distinct patterns of cytokine response: PrP 128-141 [129M] inducing IL-4 and IL-6 production, which was not seen in response to PrP 128-141 [129V]. Our data suggest that the immunogenic regions of human PrP lie between residue 107 and the C-terminus and that, like with many other central nervous system antigens, healthy individuals carry responses to PrP within the T cell repertoire and yet do not experience deleterious autoimmune reactions. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17086102&query_hl=1 ER - TY - JFULL T1 - Chronic subcutaneous administration of kisspeptin-54 causes testicular degeneration in adult male rats. A1 - Thompson, EL A1 - Murphy, KG A1 - Patterson, M A1 - Bewick, GA A1 - Stamp, GW A1 - Curtis, AE A1 - Cooke, JH A1 - Jethwa, PH A1 - Todd, JF A1 - Ghatei, MA A1 - Bloom, SR J1 - Am J Physiol Endocrinol Metab Y1 - 2006/11// VL - 291 SN - 0193-1849 SP - E1074 EP - E1082 N2 - The kisspeptins are KiSS-1 gene-derived peptides that signal through the G protein-coupled receptor-54 (GPR54) and have recently been shown to be critical regulators of reproduction. Acute intracerebroventricular or peripheral administration of kisspeptin stimulates the hypothalamic-pituitary-gonadal (HPG) axis. This effect is thought to be mediated via the hypothalamic gonadotropin-releasing hormone (GnRH) system. Chronic administration of GnRH agonists paradoxically suppresses the HPG axis after an initial agonistic stimulation. We investigated the effects of continuous peripheral kisspeptin administration in male rats by use of Alzet minipumps. Initially we compared the effects of acute subcutaneous administration of kisspeptin-10, -14, and -54 on the HPG axis. Kisspeptin-54 produced the greatest increase in plasma LH and total testosterone at 60 min postinjection and was used in the subsequent continuous administration experiments. Chronic subcutaneous long-term administration of 50 nmol kisspeptin-54/day for 13 days decreased testicular weight. Histological examination showed degeneration of the seminiferous tubules associated with a significant decrease in the circulating levels of the testes-derived hormone, inhibin B. Plasma free and total testosterone were also lower, although these changes did not reach statistical significance. Further studies examined the effects of shorter periods of continuous kisspeptin administration. Subcutaneous administration of 50 nmol kisspeptin-54 for 1 day increased plasma LH and testosterone. This effect was lost after 2 days of administration, suggesting a downregulation of the HPG axis response to kisspeptin following continuous administration. These findings indicate that kisspeptin may provide a novel tool for the manipulation of the HPG axis and spermatogenesis. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16787965&query_hl=1 ER - TY - JFULL T1 - A coiled-coil domain of melanophilin is essential for Myosin Va recruitment and melanosome transport in melanocytes. A1 - Hume, AN A1 - Tarafder, AK A1 - Ramalho, JS A1 - Sviderskaya, EV A1 - Seabra, MC J1 - Mol Biol Cell Y1 - 2006/11// VL - 17 SN - 1059-1524 SP - 4720 EP - 4735 N2 - Melanophilin (Mlph) regulates retention of melanosomes at the peripheral actin cytoskeleton of melanocytes, a process essential for normal mammalian pigmentation. Mlph is proposed to be a modular protein binding the melanosome-associated protein Rab27a, Myosin Va (MyoVa), actin, and microtubule end-binding protein (EB1), via distinct N-terminal Rab27a-binding domain (R27BD), medial MyoVa-binding domain (MBD), and C-terminal actin-binding domain (ABD), respectively. We developed a novel melanosome transport assay using a Mlph-null cell line to study formation of the active Rab27a:Mlph:MyoVa complex. Recruitment of MyoVa to melanosomes correlated with rescue of melanosome transport and required intact R27BD together with MBD exon F-binding region (EFBD) and unexpectedly a potential coiled-coil forming sequence within ABD. In vitro binding studies indicate that the coiled-coil region enhances binding of MyoVa by Mlph MBD. Other regions of Mlph reported to interact with MyoVa globular tail, actin, or EB1 are not essential for melanosome transport rescue. The strict correlation between melanosomal MyoVa recruitment and rescue of melanosome distribution suggests that stable interaction with Mlph and MyoVa activation are nondissociable events. Our results highlight the importance of the coiled-coil region together with R27BD and EFBD regions of Mlph in the formation of the active melanosomal Rab27a-Mlph-MyoVa complex. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16914517&query_hl=1 ER - TY - JFULL T1 - Fukutin gene mutations in steroid-responsive limb girdle muscular dystrophy. A1 - Godfrey, C A1 - Escolar, D A1 - Brockington, M A1 - Clement, EM A1 - Mein, R A1 - Jimenez-Mallebrera, C A1 - Torelli, S A1 - Feng, L A1 - Brown, SC A1 - Sewry, CA A1 - Rutherford, M A1 - Shapira, Y A1 - Abbs, S A1 - Muntoni, F J1 - Ann Neurol Y1 - 2006/11// VL - 60 SN - 0364-5134 SP - 603 EP - 610 N2 - OBJECTIVE: Defects in glycosylation of alpha-dystroglycan are associated with several forms of muscular dystrophy, often characterized by congenital onset and severe structural brain involvement, collectively known as dystroglycanopathies. Six causative genes have been identified in these disorders including fukutin. Mutations in fukutin cause Fukuyama congenital muscular dystrophy. This is the second most common form of muscular dystrophy in Japan and is invariably associated with mental retardation and structural brain defects. The aim of this study was to determine the genetic defect in two white families with a dystroglycanopathy. METHODS: The six genes responsible for dystroglycanopathies were studied in three children with a severe reduction of alpha-dystroglycan in skeletal muscle. RESULTS: We identified pathogenic fukutin mutations in these two families. Affected children had normal intelligence and brain structure and shared a limb girdle muscular dystrophy (LGMD) phenotype, had marked elevation of serum creatine kinase, and were all ambulant with remarkable steroid responsiveness. INTERPRETATION: Our data suggest that fukutin mutations occur outside Japan and can be associated with much milder phenotypes than Fukuyama congenital muscular dystrophy. These findings significantly expand the spectrum of phenotypes associated with fukutin mutations to include this novel form of limb girdle muscular dystrophy that we propose to name LGMD2L. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17044012&query_hl=1 ER - TY - JFULL T1 - Rab38 and Rab32 control post-Golgi trafficking of melanogenic enzymes. A1 - Wasmeier, C A1 - Romao, M A1 - Plowright, L A1 - Bennett, DC A1 - Raposo, G A1 - Seabra, MC J1 - J Cell Biol Y1 - 2006/10/23/ VL - 175 SN - 0021-9525 SP - 271 EP - 281 N2 - A mutation in the small GTPase Rab38 gives rise to the mouse coat color phenotype "chocolate" (cht), implicating Rab38 in the regulation of melanogenesis. However, its role remains poorly characterized. We report that cht Rab38(G19V) is inactive and that the nearly normal pigmentation in cht melanocytes results from functional compensation by the closely related Rab32. In cht cells treated with Rab32-specific small interfering RNA, a dramatic loss of pigmentation is observed. In addition to mature melanosomes, Rab38 and Rab32 localize to perinuclear vesicles carrying tyrosinase and tyrosinase-related protein 1, consistent with a role in the intracellular sorting of these proteins. In Rab38/Rab32-deficient cells, tyrosinase appears to be mistargeted and degraded after exit from the trans-Golgi network (TGN). This suggests that Rab38 and Rab32 regulate a critical step in the trafficking of melanogenic enzymes, in particular, tyrosinase, from the TGN to melanosomes. This work identifies a key role for the Rab38/Rab32 subfamily of Rab proteins in the biogenesis of melanosomes and potentially other lysosome-related organelles. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17043139&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 - Self-initiated gait increases susceptibility to the moving platform after-effect. A1 - Reynolds, RF A1 - Bronstein, AM J1 - Neuroreport Y1 - 2006/10/02/ VL - 17 SN - 0959-4965 SP - 1503 EP - 1505 N2 - Walking onto a stationary platform previously experienced as moving results in a large forward sway, despite awareness of the changing context. This after-effect demonstrates aberrant motor prediction. Here, we compared after-effect magnitude when gait initiation was either externally triggered or self-initiated. Both participant groups adapted their walking speed similarly when walking onto the moving platform. When it was kept stationary however, after-effect magnitude was more than doubled in the self-initiated group. We attribute this to a stronger association made between the action (gait initiation) and its consequence (platform movement) when the action is initiated by oneself. This increased sense of agency reduces the ability to switch off the acquired motor response when it is no longer appropriate. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16957597&query_hl=1 ER - TY - JFULL T1 - Operative and hardware complications of deep brain stimulation for movement disorders. A1 - Paluzzi, A A1 - Belli, A A1 - Bain, P A1 - Liu, X A1 - Aziz, TM J1 - Br J Neurosurg Y1 - 2006/10// VL - 20 SN - 0268-8697 SP - 290 EP - 295 N2 - The objective of this investigation was to present the operative and hardware complications encountered during follow-up of patients with in situ deep brain stimulators. The study took the form of a retrospective chart review on a series of consecutive patients who were treated successfully with insertion of deep brain stimulators at a single centre by a single surgeon between 1999 and 2005. During the study period, a total of 60 patients underwent 96 procedures for implantation of unilateral or bilateral DBS electrodes. The mean follow-up period was 43.7 months (range 6-78 months) from the time of the first procedure. No patients were lost to follow-up or died. Eighteen patients (30%) developed 28 adverse events, requiring 28 electrodes to be replaced. Seven patients developed two adverse events and two patients developed three adverse events. The rate of adverse events per electrode-year was 8%. We observed a higher proportion of early complications (<6 months postoperatively) in patients with Parkinson's disease, while dystonic patients had more late complications (>6 months postoperatively) and no early complications. Thirty per cent of our patients developed an adverse event that could potentially lead to revision of the implanted hardware. In patients with Parkinson's disease most of the complications tend to occur during the first 6 months postoperatively, while in dystonic patients most occur between 12 and 24 months postoperatively. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17129876&query_hl=1 ER - TY - JFULL T1 - Is there a relationship between hamstring length and function in ambulant boys with Duchenne muscular dystrophy? A1 - Nicholson, C A1 - Main, M A1 - Mercuri, E A1 - Muntoni, F J1 - NEUROMUSCULAR DISORD Y1 - 2006/10// VL - 16 SN - 0960-8966 SP - 719 EP - 719 ER - TY - JFULL T1 - A phase I/II clinical trial in Duchenne muscular dystrophy using IM and IV delivered antisense oligonucleotides: The MDEX consortium A1 - Arechavala, V A1 - Bushby, K A1 - Dickson, G A1 - Graham, I A1 - Kinali, M A1 - Liu, K A1 - Morgan, J A1 - Muntoni, F A1 - Popplewell, L A1 - Partridge, T A1 - Thorogood, F A1 - Wells, K A1 - Wells, N A1 - Wood, M A1 - Yin, H J1 - NEUROMUSCULAR DISORD Y1 - 2006/10// VL - 16 SN - 0960-8966 SP - 685 EP - 685 ER - TY - JFULL T1 - RYR1 genotype-phenotype correlative and functional studies in a large cohort of core myopathy patients with RYR1 mutations A1 - Zhou, H A1 - Jungbluth, H A1 - Treves, S A1 - Bertini, E A1 - Straub, V A1 - Bushby, K A1 - Sewry, C A1 - Muntoni, F J1 - NEUROMUSCULAR DISORD Y1 - 2006/10// VL - 16 SN - 0960-8966 SP - 687 EP - 687 ER - TY - JFULL T1 - The use of FRET analysis to look at the interaction of glycosyltransferases responsible for dystroglycanopathies A1 - Kaluarachchi, M A1 - Skordis, L A1 - Brockington, M A1 - Muntoni, F A1 - Brown, SC J1 - NEUROMUSCULAR DISORD Y1 - 2006/10// VL - 16 SN - 0960-8966 SP - 679 EP - 679 ER - TY - JFULL T1 - The cost-effectiveness of cognitive behavior therapy for borderline personality disorder: results from the BOSCOT trial. A1 - Palmer, S A1 - Davidson, K A1 - Tyrer, P A1 - Gumley, A A1 - Tata, P A1 - Norrie, J A1 - Murray, H A1 - Seivewright, H J1 - J Personal Disord Y1 - 2006/10// VL - 20 SN - 0885-579X SP - 466 EP - 481 N2 - Borderline personality disorder places a significant burden on healthcare providers and other agencies. This study evaluated the cost-effectiveness of cognitive behavior therapy plus treatment as usual compared to treatment as usual alone for patients with borderline personality disorder. The economic analysis was conducted alongside a multi-center, randomized controlled trial. The costs of primary and secondary healthcare utilization, alongside the wider economic costs, were estimated from medical records and patient self-report. The primary outcome measure used was the quality-adjusted life year (QALY), assessed using EuroQol. On average, total costs per patient in the cognitive behavior therapy group were lower than patients receiving usual care alone (-689 pounds sterling), although this group also reported a lower quality of life (-0.11 QALYs). These differences were small and did not approach conventional levels of statistical significance. The use of cognitive therapy for borderline personality disorder does not appear to demonstrate any significant cost-effective advantage based on the results of this study. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17032159&query_hl=1 ER - TY - JFULL T1 - Brain structure and function in the At Risk Mental State A1 - McGuire, P A1 - Woolley, J A1 - Broome, M A1 - Howes, O A1 - Picchioni, M A1 - Barker, G A1 - Riecher, A A1 - Borgwardt, S A1 - Grasby, P A1 - Murray, R A1 - Chitnis, X A1 - Williams, S J1 - SCHIZOPHR RES Y1 - 2006/10// VL - 86 SN - 0920-9964 SP - S9 EP - S9 ER - TY - JFULL T1 - Randomized controlled trial of effect of prescription of clozapine versus other second-generation antipsychotic drugs in resistant schizophrenia. A1 - Lewis, SW A1 - Barnes, TR A1 - Davies, L A1 - Murray, RM A1 - Dunn, G A1 - Hayhurst, KP A1 - Markwick, A A1 - Lloyd, H A1 - Jones, PB J1 - Schizophr Bull Y1 - 2006/10// VL - 32 SN - 0586-7614 SP - 715 EP - 723 N2 - There is good evidence that clozapine is more efficacious than first-generation antipsychotic drugs in resistant schizophrenia. It is less clear if clozapine is more effective than the other second-generation antipsychotic (SGA) drugs. A noncommercially funded, pragmatic, open, multisite, randomized controlled trial was conducted in the United Kingdom National Health Service (NHS). Participants were 136 people aged 18-65 with DSM-IV schizophrenia and related disorders whose medication was being changed because of poor clinical response to 2 or more previous antipsychotic drugs. Participants were randomly allocated to clozapine or to one of the class of other SGA drugs (risperidone, olanzapine, quetiapine, amisulpride) as selected by the managing clinician. Outcomes were assessed blind to treatment allocation. One-year assessments were carried out in 87% of the sample. The intent to treat comparison showed no statistically significant advantage for commencing clozapine in Quality of Life score (3.63 points; CI: 0.46-7.71; p = .08) but did show an advantage in Positive and Negative Syndrome Scale (PANSS) total score that was statistically significant (-4.93 points; CI: -8.82 to -1.05; p = .013) during follow-up. Clozapine showed a trend toward having fewer total extrapyramidal side effects. At 12 weeks participants who were receiving clozapine reported that their mental health was significantly better compared with those receiving other SGA drugs. In conclusion, in people with schizophrenia with poor treatment response to 2 or more antipsychotic drugs, there is an advantage to commencing clozapine rather than other SGA drugs in terms of symptom improvement over 1 year. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16540702&query_hl=1 ER - TY - JFULL T1 - Report of the 2005 RSPCA/UFAW rodent welfare group meeting A1 - Hawkins, P A1 - Felton, LM A1 - van Loo, P A1 - Maconochie, M A1 - Wells, DJ A1 - Dennison, N A1 - Hubrecht, R A1 - Jennings, M J1 - LAB ANIMAL Y1 - 2006/10// VL - 35 SN - 0093-7355 SP - 29 EP - + ER - TY - JFULL T1 - The role of the cellular prion protein in the immune system. A1 - Isaacs, JD A1 - Jackson, GS A1 - Altmann, DM J1 - Clin Exp Immunol Y1 - 2006/10// VL - 146 SN - 0009-9104 SP - 1 EP - 8 N2 - Prion protein (PrP) plays a key role in the pathogenesis of prion diseases. However, the normal function of the protein remains unclear. The cellular isoform (PrP(C)) is expressed widely in the immune system, in haematopoietic stem cells and mature lymphoid and myeloid compartments in addition to cells of the central nervous system. It is up-regulated in T cell activation and may be expressed at higher levels by specialized classes of lymphocyte. Furthermore, antibody cross-linking of surface PrP modulates T cell activation and leads to rearrangements of lipid raft constituents and increased phosphorylation of signalling proteins. These findings appear to indicate an important but, as yet, ill-defined role in T cell function. Although PrP(-/-) mice have been reported to have only minor alterations in immune function, recent work has suggested that PrP is required for self-renewal of haematopoietic stem cells. Here, we consider the evidence for a distinctive role for PrP(C) in the immune system and what the effects of anti-prion therapeutics may be on immune function. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16968391&query_hl=1 ER - TY - JFULL T1 - The TCR Vbeta signature of bacterial superantigens spreads with stimulus strength. A1 - Llewelyn, M A1 - Sriskandan, S A1 - Terrazzini, N A1 - Cohen, J A1 - Altmann, DM J1 - Int Immunol Y1 - 2006/10// VL - 18 SN - 0953-8178 SP - 1433 EP - 1441 N2 - Superantigens (Sags) induce large-scale stimulation of T lymphocytes by a mechanism distinct from conventional antigen presentation, involving direct MHC binding and stimulation of TCR families based on Vbeta gene usage. The specific Vbeta targets of a given Sag have, since the earliest studies in murine models, been considered a hallmark of that toxin. Bacterial Sags are implicated in the aetiology of a wide range of human diseases, although their role has been most clearly defined in toxic shock syndrome. While Sags have been defined by the Vbeta-specific changes in T cell repertoire they induce, human studies of in vitro stimulation or analysis of cells from infected patients have produced inconsistent findings. Here we have evaluated the contribution of HLA allelic polymorphisms and strength of stimulus to this response. We show that there are differences in binding and presentation of the staphylococcal Sag, staphylococcal enterotoxin A (SEA), by different HLA-DR alleles. We also show that the TCR Vbeta response, previously thought to be a fixed property defining a given Sag, varies with stimulus strength such that a broader repertoire of response is seen at higher concentrations or following presentation by high-binding class II types. Responses of human Vbeta8 and Vbeta1 to SEA, Vbeta5 to SEB and of Vbeta12 and Vbeta13 to streptococcal pyrogenic exotoxin A are absolutely dependent on stimulus strength. These findings have important implications for heterogeneity in the response to Sags and the consequent differences in susceptibility to severe toxic shock. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16893924&query_hl=1 ER - TY - JFULL T1 - IFN gamma and CXCR-1 gene polymorphisms in idiopathic bronchiectasis. A1 - Boyton, RJ A1 - Reynolds, C A1 - Wahid, FN A1 - Jones, MG A1 - Ozerovitch, L A1 - Ahmad, T A1 - Chaudhry, A A1 - Jewell, DP A1 - Kon, OM A1 - Smith, J A1 - Rose, M A1 - Newman-Taylor, AJ A1 - Cole, P A1 - Wilson, R A1 - Altmann, DM J1 - Tissue Antigens Y1 - 2006/10// VL - 68 SN - 0001-2815 SP - 325 EP - 330 N2 - Idiopathic bronchiectasis is a disease of chronic, bacterial lung infection, unresolving inflammation and progressive lung damage. Bronchiectasis can be associated with autoimmune diseases including ulcerative colitis. Defects of both innate and adaptive immunity have been proposed. The airway inflammation is characterized by interleukin-8 (IL-8) expression and infiltration by neutrophils and T cells. Here we investigated two candidate gene polymorphisms that may contribute to disease susceptibility: a CXCR-1 (+2607 G/C) gene polymorphism that is implicated in IL-8 binding and neutrophil trafficking as well as the interferon-gamma (IFNgamma) (+874 T/A) polymorphism which is linked to levels of IFNgamma production. These polymorphisms were distributed similarly in the idiopathic bronchiectasis group and controls, suggesting that these two candidate gene polymorphisms are not associated with disease susceptibility. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17026468&query_hl=1 ER - TY - JFULL T1 - Molecular genetic analysis of 6 glycosyltransferases in a large population of dystroglycanopathy patients significantly widens the spectrum of phenotypes resulting from POMT1, POMGnT1 and Fukutin mutations A1 - Godfrey, C A1 - Mein, R A1 - Brockington, M A1 - Elson, E A1 - Topaloglu, H A1 - Smith, J A1 - Escolar, D A1 - Bertini, E A1 - Merlini, I A1 - Mercuri, E A1 - Bushby, K A1 - Straub, V A1 - North, K A1 - Abbs, S A1 - Muntoni, F J1 - NEUROMUSCULAR DISORD Y1 - 2006/10// VL - 16 SN - 0960-8966 SP - 683 EP - 683 ER - TY - JFULL T1 - The pre-synaptic dopaminergic system before and after the onset of psychosis: Initial results from an ongoing [F-18]fluoro-DOPA PET study A1 - Howes, OD A1 - Montgomery, AJ A1 - Asselin, MC A1 - Murray, RM A1 - Grasby, PM A1 - McGuire, PK J1 - SCHIZOPHR RES Y1 - 2006/10// VL - 86 SN - 0920-9964 SP - S11 EP - S11 ER - TY - JFULL T1 - More than our share of happiness A1 - Tyrer, P J1 - BRIT J PSYCHIAT Y1 - 2006/10// VL - 189 SN - 0007-1250 SP - 390 EP - 390 ER - TY - JFULL T1 - Interactions between retinoic acid, nerve growth factor and sonic hedgehog signalling pathways in neurite outgrowth. A1 - So, PL A1 - Yip, PK A1 - Bunting, S A1 - Wong, LF A1 - Mazarakis, ND A1 - Hall, S A1 - McMahon, S A1 - Maden, M A1 - Corcoran, JP J1 - Dev Biol Y1 - 2006/10/01/ VL - 298 SN - 0012-1606 SP - 167 EP - 175 N2 - Many studies have shown a role of retinoid signalling in neurite outgrowth in vitro, and that the retinoic acid receptor (RAR) beta2 is critical for this process. We show here that RARbeta2 is expressed predominantly in dorsal root ganglia (DRG) neuronal subtypes that express neurofilament (NF) 200 and calcitonin gene-related peptide (CGRP), and that these neurons extend neurites in response to RA. We demonstrate that retinoid signalling has a role in neurite outgrowth in vivo, by showing that in a peripheral nerve crush model there is less neurite outgrowth from RARbeta null DRG compared to wild-type. We identify sonic hedgehog (Shh) as a downstream target of the RARbeta2 signalling pathway as it is expressed in the injured DRG of wild-type but not RARbeta null mice. This regulation is direct as when RARbeta2 is overexpressed in adult motoneurons Shh is induced in them. Finally we show that Shh alone cannot induce neurite outgrowth but potentiates RARbeta2 signalling in this process. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16860305&query_hl=1 ER - TY - JFULL T1 - Predictive factors for the development of scoliosis in Duchenne muscular dystrophy A1 - Kinali, M A1 - Knight, RK A1 - Main, M A1 - Mercuri, E A1 - Messina, S A1 - Manzur, AY A1 - Muntoni, F J1 - NEUROMUSCULAR DISORD Y1 - 2006/10// VL - 16 SN - 0960-8966 SP - 719 EP - 719 ER - TY - JFULL T1 - Mutations in SIL1 cause Marinesco-Sjogren syndrome, a cerebellar ataxia with cataract and myopathy A1 - Senderek, J A1 - Krieger, M A1 - Stendel, C A1 - North, K A1 - Muntoni, F A1 - Quijano-Roy, S A1 - Ebinger, F A1 - Schroder, JM A1 - Voit, T A1 - Weis, J A1 - Topaloglu, H A1 - Zerres, K J1 - NEUROMUSCULAR DISORD Y1 - 2006/10// VL - 16 SN - 0960-8966 SP - 683 EP - 683 ER - TY - JFULL T1 - Microinjection of galanin-like peptide into the medial preoptic area stimulates food intake in adult male rats. A1 - Patterson, M A1 - Murphy, KG A1 - Thompson, EL A1 - Smith, KL A1 - Meeran, K A1 - Ghatei, MA A1 - Bloom, SR J1 - J Neuroendocrinol Y1 - 2006/10// VL - 18 SN - 0953-8194 SP - 742 EP - 747 N2 - Galanin-like peptide (GALP) is a neuropeptide implicated in the regulation of feeding behaviour, metabolism and reproduction. GALP is an endogenous ligand of the galanin receptors, which are widely expressed in the hypothalamus. GALP is predominantly expressed in arcuate nucleus (ARC) neurones, which project to the paraventricular nucleus (PVN) and medial preoptic area (mPOA). Intracerebroventricular or intraparaventricular (iPVN) injection of GALP acutely increases food intake in rats. The effect of GALP injection into the mPOA on feeding behaviour has not previously been studied. In the present study, intra-mPOA (imPOA) injection of GALP potently increased 0-1-h food intake in rats. The dose-response effect of imPOA GALP administration on food intake was similar to that previously observed following iPVN administration. The effects of GALP (1 nmol) or galanin (1 nmol) on food intake were then compared following injection into the PVN, mPOA, ARC, dorsal medial nucleus (DMN), lateral hypothalamus and rostral preoptic area (rPOA). GALP (1 nmol) increased food intake to a similar degree when injected into the imPOA or iPVN, but produced no significant effect when injected into the ARC, DMN, lateral hypothalamus or rPOA. Similarly, galanin (1 nmol) significantly increased food intake following injection imPOA and iPVN. However, the effect was significantly smaller than that following administration of GALP (1 nmol). Galanin also had no significant effect on food intake when administered into the ARC, DMN, lateral hypothalamus and rPOA. These data suggest that the mPOA and the PVN may have specific roles in mediating the orexigenic effect of GALP and galanin. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16965292&query_hl=1 ER - TY - JFULL T1 - Limitation of neck movement may be a feature of most of the childhood neuromuscular disorders A1 - Main, M A1 - Kinali, M A1 - Muntoni, F J1 - NEUROMUSCULAR DISORD Y1 - 2006/10// VL - 16 SN - 0960-8966 SP - 664 EP - 664 ER - TY - JFULL T1 - Thermal perception thresholds: assessing the level of human spinal cord injury. A1 - Nicotra, A A1 - Ellaway, PH J1 - Spinal Cord Y1 - 2006/10// VL - 44 SN - 1362-4393 SP - 617 EP - 624 N2 - STUDY DESIGN: Controlled, cross-sectional, observational. OBJECTIVES: To investigate whether quantitative sensory testing (QST) is able to reveal subclinical deficits at the neurological level of lesion in subjects with chronic spinal cord injury (SCI). SETTING: National Spinal Injuries Centre, Stoke Mandeville Hospital and Imperial College London, UK. METHODS: QST and clinical assessments were carried out on 18 subjects with complete SCI (American Spinal Injury Association (ASIA) grade A) and 10 subjects with incomplete SCI (ASIA grades B, C or D). A total of 10 healthy subjects acted as controls. RESULTS: At the level of lesion perceptual thresholds to monofilaments, cold pain and heat pain were similar to values in control subjects but cool and warm thresholds were significantly raised. A correlation between cool and warm thresholds was observed at the level of lesion in complete SCI and between heat and cold pain thresholds at the level of lesion in complete SCI, incomplete SCI and in control subjects. In the zone of partial preservation in complete SCI and below the level of lesion in incomplete SCI, thresholds for all modalities were all different compared to controls. CONCLUSION: QST reveals impaired thermal sensation in dermatomes clinically defined as normal with ASIA standards. Quantitative thermal testing therefore permits a discriminating assessment of preserved sensation and subclinical deficit and has the potential to improve upon the clinical detection of natural recovery or changes in level of injury following interventions designed to repair SCI. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16432532&query_hl=1 ER - TY - JFULL T1 - A randomized controlled trial of cognitive behavior therapy for borderline personality disorder: rationale for trial, method, and description of sample. A1 - Davidson, K A1 - Tyrer, P A1 - Gumley, A A1 - Tata, P A1 - Norrie, J A1 - Palmer, S A1 - Millar, H A1 - Drummond, L A1 - Seivewright, H A1 - Murray, H A1 - Macaulay, F J1 - J Personal Disord Y1 - 2006/10// VL - 20 SN - 0885-579X SP - 431 EP - 449 N2 - This paper describes the rationale for a randomized controlled trial, comparing cognitive behavior therapy in addition to treatment as usual with treatment as usual alone, for borderline personality disorder. Previous pioneering randomized controlled trials of psychotherapies have suffered from methodological weaknesses and have not always been reported clearly to allow adequate evaluation of either the individual study or comparisons across studies to be undertaken. We report on the recruitment and randomization, design, and conduct of an ongoing randomized controlled trial of one hundred and six patients with borderline personality disorder. Primary and secondary hypotheses and their planned analyses are stated. The baseline characteristics of 106 patients meeting diagnostic criteria for borderline personality disorder are described. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17032157&query_hl=1 ER - TY - JFULL T1 - Differential expression of FOXO1 and FOXO3a confers resistance to oxidative cell death upon endometrial decidualization. A1 - Kajihara, T A1 - Jones, M A1 - Fusi, L A1 - Takano, M A1 - Feroze-Zaidi, F A1 - Pirianov, G A1 - Mehmet, H A1 - Ishihara, O A1 - Higham, JM A1 - Lam, EW A1 - Brosens, JJ J1 - Mol Endocrinol Y1 - 2006/10// VL - 20 SN - 0888-8809 SP - 2444 EP - 2455 N2 - The integrity of the feto-maternal interface is critical for survival of the conceptus. This interface, consisting of the maternal decidua and the invading placental trophoblast, is exposed to profound changes in oxygen tension during pregnancy. We demonstrate that human endometrial stromal cells become extraordinarily resistant to oxidative stress-induced apoptosis upon decidualization in response to cAMP and progesterone signaling. This differentiation process is associated with the induction of the forkhead transcription factor FOXO1, which in turn increases the expression of the mitochondrial antioxidant manganese superoxide dismutase. However, silencing of FOXO1 did not increase the susceptibility of decidualized cells to oxidative cell death. Comparative analysis demonstrated that hydrogen peroxide, a source of free radicals, strongly induces FOXO3a mRNA and protein expression in undifferentiated human endometrial stromal cells but not in decidualized cells. Expression of a constitutively active FOXO3a mutant elicited apoptosis in decidualized cells. Furthermore, silencing of endogenous FOXO3a in undifferentiated cells abrogated apoptosis induced by hydrogen peroxide. These results suggest that the induction of FOXO1 may enhance the ability of decidualized cells to prevent oxidative damage while the simultaneous repression of FOXO3a expression disables the signaling pathway responsible for oxidative cell death. The differential regulation of FOXO expression provides the decidua with a robust system capable of coping with prolonged episodes of oxidative stress during pregnancy. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16709600&query_hl=1 ER - TY - JFULL T1 - A comparative analysis of collagen VI production in muscle, skin and fibroblasts from 14 Ullrich congenital muscular dystrophy patients with dominant and recessive COL6A mutations. A1 - Jimenez-Mallebrera, C A1 - Maioli, MA A1 - Kim, J A1 - Brown, SC A1 - Feng, L A1 - Lampe, AK A1 - Bushby, K A1 - Hicks, D A1 - Flanigan, KM A1 - Bonnemann, C A1 - Sewry, CA A1 - Muntoni, F J1 - Neuromuscul Disord Y1 - 2006/10// VL - 16 SN - 0960-8966 SP - 571 EP - 582 N2 - Ullrich congenital muscular dystrophy (UCMD) is caused by recessive and dominant mutations in COL6A genes. We have analysed collagen VI expression in 14 UCMD patients. Sequencing of COL6A genes had identified homozygous and heterozygous mutations in 12 cases. Analysis of collagen VI in fibroblast cultures derived from eight of these patients showed reduced extracellular deposition in all cases and intracellular collagen VI staining in seven cases. This was observed even in cases that showed normal collagen VI labelling in skin biopsies. Collagen VI immunolabelling was reduced in all the available muscle biopsies. When comparisons were possible no correlation was seen between the extent of the reduction in the muscle and fibroblast cultures, the mode of inheritance or the severity of the clinical phenotype. Mutations affecting glycine substitutions in the conserved triple helical domain were common and all resulted in reduced collagen VI. This study expands the spectrum of collagen VI defects and shows that analysis of skin fibroblasts may be a useful technique for the detection of collagen VI abnormalities. In contrast, immunohistochemical analysis of skin biopsies may not always reveal an underlying collagen VI defect. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16935502&query_hl=1 ER - TY - JFULL T1 - UK physicians' attitudes and practices in long-term non-invasive ventilation of Duchenne Muscular Dystrophy. A1 - Kinali, M A1 - Manzur, AY A1 - Mercuri, E A1 - Gibson, BE A1 - Hartley, L A1 - Simonds, AK A1 - Muntoni, F J1 - Pediatr Rehabil Y1 - 2006/10// VL - 9 SN - 1363-8491 SP - 351 EP - 364 N2 - Previous studies have shown that long-term non-invasive ventilation (NIV) is not always routinely offered by all physicians in Duchenne Muscular Dystrophy (DMD), despite evidence that this treatment improves quality of life and survival. This study examined UK physicians' practices related to respiratory follow-up and DMD ventilation. A mailed questionnaire was used. Thirty-eight of the 59 (64%) UK physicians identified via the Muscular Dystrophy Campaign (MDC) responded. Eighty-one per cent of respondents felt ethically obliged to discuss NIV with families while 13% believed that NIV results in poor quality of life. Forty-seven per cent of physicians discuss in-depth the use of NIV when the patient is in respiratory failure. Eighty-four ventilated DMD patients in the respondents' practice use NIV (via Bi-Pap Nasal mask). Nearly 66% of physicians do not consider the public cost to be an impediment to offering NIV, despite significant problems with resources' allocation in their area. While the majority of UK physicians have comparable attitudes and practices regarding NIV, the questionnaire highlighted that not all specialists were aware of the existence of consensus guidelines regarding respiratory monitoring. In addition, different practices of disclosure of life-prolonging ventilation options were used by different physicians. Seventy-one per cent of physicians wished for national consensus guidelines for different DMD age groups. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17111551&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 - Randomized controlled trial of the effect on Quality of Life of second- vs first-generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1). A1 - Jones, PB A1 - Barnes, TR A1 - Davies, L A1 - Dunn, G A1 - Lloyd, H A1 - Hayhurst, KP A1 - Murray, RM A1 - Markwick, A A1 - Lewis, SW J1 - Arch Gen Psychiatry Y1 - 2006/10// VL - 63 SN - 0003-990X SP - 1079 EP - 1087 N2 - CONTEXT: Second-generation (atypical) antipsychotics (SGAs) are more expensive than first-generation (typical) antipsychotics (FGAs) but are perceived to be more effective, with fewer adverse effects, and preferable to patients. Most evidence comes from short-term efficacy trials of symptoms. OBJECTIVE: To test the hypothesis that in people with schizophrenia requiring a change in treatment, SGAs other than clozapine are associated with improved quality of life across 1 year compared with FGAs. DESIGN: A noncommercially funded, pragmatic, multisite, randomized controlled trial of antipsychotic drug classes, with blind assessments at 12, 26, and 56 weeks using intention-to-treat analysis. SETTING: Fourteen community psychiatric services in the English National Health Service. PARTICIPANTS: Two hundred twenty-seven people aged 18 to 65 years with DSM-IV schizophrenia and related disorders assessed for medication review because of inadequate response or adverse effects. INTERVENTIONS: Randomized prescription of either FGAs or SGAs (other than clozapine), with the choice of individual drug made by the managing psychiatrist. MAIN OUTCOME MEASURES: Quality of Life Scale scores, symptoms, adverse effects, participant satisfaction, and costs of care. RESULTS: The primary hypothesis of significant improvement in Quality of Life Scale scores during the year after commencement of SGAs vs FGAs was excluded. Participants in the FGA arm showed a trend toward greater improvements in Quality of Life Scale and symptom scores. Participants reported no clear preference for either drug group; costs were similar. CONCLUSIONS: In people with schizophrenia whose medication is changed for clinical reasons, there is no disadvantage across 1 year in terms of quality of life, symptoms, or associated costs of care in using FGAs rather than nonclozapine SGAs. Neither inadequate power nor patterns of drug discontinuation accounted for the result. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17015810&query_hl=1 ER - TY - JFULL T1 - The effectiveness of cognitive behavior therapy for borderline personality disorder: results from the borderline personality disorder study of cognitive therapy (BOSCOT) trial. A1 - Davidson, K A1 - Norrie, J A1 - Tyrer, P A1 - Gumley, A A1 - Tata, P A1 - Murray, H A1 - Palmer, S J1 - J Personal Disord Y1 - 2006/10// VL - 20 SN - 0885-579X SP - 450 EP - 465 N2 - The outcome of a randomized controlled trial of cognitive behavior therapy in addition to treatment as usual (CBT plus TAU) compared with TAU alone (TAU) in one hundred and six participants meeting diagnostic criteria for borderline personality disorder is described. We anticipated that CBT plus TAU would decrease the number of participants with in-patient psychiatric hospitalizations or accident and emergency room contact or suicidal acts over twelve months treatment and twelve months follow-up, compared with TAU. We also anticipated that CBT plus TAU would lead to improvement in a range of secondary outcomes of mental health and social functioning compared to TAU. Of the 106 participants randomized, follow-up data on 102 (96%) was obtained at two years. Those randomized to CBT were offered an average of 27 sessions over 12 months and attended on average 16 (range 0 to 35). We found that the global odds ratio of a participant in the CBT plus TAU group compared with the TAU alone group having any of the outcomes of a suicidal act, in-patient hospitalization, or accident and emergency contact in the 24 months following randomization was 0.86 (95% confidence interval [CI] 0.45 to 1.66, p = 0.66). The corresponding global odds ratio, excluding accident and emergency room contact, was 0.75 (95% CI 0.37 to 1.54, p = 0.44). In terms of the number of suicidal acts, there was a significant reduction over the two years in favor of CBT plus TAU over TAU, with a mean difference of -0.91 (95% CI -1.67 to -0.15, p = 0.020). Across both treatment arms there was gradual and sustained improvement in both primary and secondary outcomes, with evidence of benefit for the addition of CBT on the positive symptom distress index at one year, and on state anxiety, dysfunctional beliefs and the quantity of suicidal acts at two year follow-up. CBT can deliver clinically important changes in relatively few clinical sessions in real clinical settings. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17032158&query_hl=1 ER - TY - JFULL T1 - Detecting time-dependent coherence between non-stationary electrophysiological signals--a combined statistical and time-frequency approach. A1 - Zhan, Y A1 - Halliday, D A1 - Jiang, P A1 - Liu, X A1 - Feng, J J1 - J Neurosci Methods Y1 - 2006/09/30/ VL - 156 SN - 0165-0270 SP - 322 EP - 332 N2 - Various time-frequency methods have been used to study time-varying properties of non-stationary neurophysiological signals. In the present study, a time-frequency coherence estimate using continuous wavelet transform (CWT) together with its confidence intervals are proposed to evaluate the correlation between two non-stationary processes. The approach is based on averaging over repeat trials. A systematic comparison between approaches using CWT and short-time Fourier transform (STFT) is carried out. Simulated data are generated to test the performance of these methods when estimating time-frequency based coherence. In contrast to some recent studies, we find that CWT based coherence estimates do not supersede STFT based estimates. We suggest that a combination of STFT and CWT would be most suitable for analysing non-stationary neural data. Tests are presented to investigate the time and frequency discrimination capabilities of the two approaches. The methods are applied to two experimental data sets: electroencephalogram (EEG) and surface electromyogram (EMG) during wrist movements in a healthy subject, and local field potential (LFP) and surface EMG recordings during resting tremor in a Parkinsonian patient. Supporting software is available at and . L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16563517&query_hl=1 ER - TY - JFULL T1 - Characterization of recessive RYR1 mutations in core myopathies. A1 - Zhou, H A1 - Yamaguchi, N A1 - Xu, L A1 - Wang, Y A1 - Sewry, C A1 - Jungbluth, H A1 - Zorzato, F A1 - Bertini, E A1 - Muntoni, F A1 - Meissner, G A1 - Treves, S J1 - Hum Mol Genet Y1 - 2006/09/15/ VL - 15 SN - 0964-6906 SP - 2791 EP - 2803 N2 - We have characterized at the molecular level, three families with core myopathies carrying apparent recessive mutations in their RYR1 gene and studied the pharmacological properties of myotubes carrying endogenous mutations as well as the properties of mutant channels expressed in HEK293 cells. The proband of family 1 carried p.Ala1577Thr+p.Gly2060Cys in trans, having inherited a mutation from each parent. Immunoblot analysis of proteins from the patient's skeletal muscle revealed low levels of ryanodine receptor (RyR1) but neither substitution alone or in combination affected the functional properties of RyR1 channels in a discernable way. Two affected siblings in family 2 carried p.Arg109Trp+p.Met485Val substitutions in cis, inherited from the unaffected father. Interestingly, both affected siblings only transcribed the mutated paternal allele in skeletal muscle, whereas the maternal allele was silent. Single-channel measurements showed that recombinant, mutant RyR1 channels carrying both substitutions lost the ability to conduct Ca2+. In this case as well, low levels of RyR1 were present in skeletal muscle extracts. The proband of family 3 carried p.Ser71Tyr+p.Asn2283His substitutions in trans. Recombinant channels with Asn2283His substitution showed an increased activity, whereas recombinant channels with p.Ser71Tyr+p.Asn2283His substitution lost activity upon isolation. Taken together, our data suggest major differences in the ways RYR1 mutations may affect patients with core myopathies, by compromising RyR1 protein expression, stability and/or activity. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16940308&query_hl=1 ER - TY - JFULL T1 - Free innervated sole of foot transfer for contralateral lower limb salvage. A1 - Irwin, MS A1 - Jain, A A1 - Anand, P A1 - Nanchahal, J J1 - Plast Reconstr Surg Y1 - 2006/09/15/ VL - 118 SN - 1529-4242 SP - 93e EP - 97e L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16980840&query_hl=1 ER - TY - JFULL T1 - Effects of acute and chronic relaxin-3 on food intake and energy expenditure in rats. A1 - McGowan, BM A1 - Stanley, SA A1 - Smith, KL A1 - Minnion, JS A1 - Donovan, J A1 - Thompson, EL A1 - Patterson, M A1 - Connolly, MM A1 - Abbott, CR A1 - Small, CJ A1 - Gardiner, JV A1 - Ghatei, MA A1 - Bloom, SR J1 - Regul Pept Y1 - 2006/09/11/ VL - 136 SN - 0167-0115 SP - 72 EP - 77 N2 - The effects of acute and repeated intraparaventricular (iPVN) administration of human relaxin-3 (H3) were examined on food intake, energy expenditure, and the hypothalamo-pituitary thyroid axis in male Wistar rats. An acute high dose iPVN injection of H3 significantly increased food intake 1 h post-administration [0.4+/-0.1 g (vehicle) vs 1.6+/-0.5 g (180 pmol H3), 2.4+/-0.5 g (540 pmol H3) and 2.2+/-0.5 g (1,620 pmol H3), p<0.05 for all doses vs vehicle]. Repeated iPVN H3 injection (180 pmol/twice a day for 7 days) significantly increased cumulative food intake in ad libitum fed animals compared with vehicle [211.8+/-7.1 g (vehicle) vs 261.6+/-6.7 g (ad libitum fed H3), p<0.05]. Plasma leptin was increased in the H3 ad libitum fed group. Plasma thyroid stimulating hormone was significantly decreased after acute and repeated administration of H3. These data suggest H3 may play a role in long-term control of food intake. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16764952&query_hl=1 ER - TY - JFULL T1 - Role of corticotrophin releasing factor (CRF) in NMDAR-mediated responses and firing rate of ventral tegmental neurons A1 - Bonci, A A1 - Ungless, M A1 - Wanat, M J1 - ALCOHOL CLIN EXP RES Y1 - 2006/09// VL - 30 SN - 0145-6008 SP - 93A EP - 93A ER - TY - JFULL T1 - Mutation detection in a large cohort of muscular dystrophy patients widens the clinical spectrum associated with dystroglycanopathy genes A1 - Godfrey, C A1 - Mein, R A1 - Jimenez-Mallebrera, C A1 - Feng, L A1 - Brockington, M A1 - Muntoni, F A1 - Abbs, S J1 - J MED GENET Y1 - 2006/09// VL - 43 SN - 0022-2593 SP - S84 EP - S84 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 - Adherence in adolescents and young adults following heart or heart-lung transplantation. A1 - Wray, J A1 - Waters, S A1 - Radley-Smith, R A1 - Sensky, T J1 - Pediatr Transplant Y1 - 2006/09// VL - 10 SN - 1397-3142 SP - 694 EP - 700 N2 - To assess the prevalence and some potential correlates of non-adherence to medications in adolescent and young adult transplant patients. Fifty patients who had undergone heart or heart-lung transplantation 1.4-14.9 yr (mean 8.8 yr) previously completed the Beliefs about Medication Questionnaire (BMQ), Perceived Illness Experience (PIE) scale and a demographics questionnaire. Medical notes were reviewed for information regarding previous psychiatric referral, rejection episodes and complications and noted concerns about adherence. Forty (80%) completed questionnaires were received. Non-adherence determined from the questionnaires was associated with forgetting to take medication and was classified as unintentional non-adherence. Such non-adherence was reported by 11 (28%) patients. Seven patients (18%) showed evidence from their records of deliberate non-adherence, which was classified as intentional. Whilst intentional non-adherence was associated with depression and transplant-related lymphoma, unintentional non-adherence and perceived difficulties with medications were associated with high scores on the PIE preoccupation with illness and BMQ concerns subscale and with drinking alcohol. Future research is required to determine whether unintentional non-adherence results in significant medical complications in the longer term and how a reduction in the prevalence of non-adherence can be facilitated. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16911493&query_hl=1 ER - TY - JFULL T1 - Identification of 45 novel mutations in the nebulin gene associated with autosomal recessive nemaline myopathy. A1 - Lehtokari, VL A1 - Pelin, K A1 - Sandbacka, M A1 - Ranta, S A1 - Donner, K A1 - Muntoni, F A1 - Sewry, C A1 - Angelini, C A1 - Bushby, K A1 - Van den Bergh, P A1 - Iannaccone, S A1 - Laing, NG A1 - Wallgren-Pettersson, C J1 - Hum Mutat Y1 - 2006/09// VL - 27 SN - 1098-1004 SP - 946 EP - 956 N2 - Nemaline myopathy (NM) is a clinically and genetically heterogeneous disorder of skeletal muscle caused by mutations in at least five different genes encoding thin filament proteins of the striated muscle sarcomere. We have previously described 18 different mutations in the last 42 exons of the nebulin gene (NEB) in 18 families with NM. Here we report 45 novel NEB mutations detected by denaturing high-performance liquid chromatography (dHPLC) and sequence analysis of all 183 NEB exons in NM patients from 44 families. Altogether we have identified, including the deletion of exon 55 identified in the Ashkenazi Jewish population, 64 different mutations in NEB segregating with autosomal recessive NM in 55 families. The majority (55%) of the mutations in NEB are frameshift or nonsense mutations predicted to cause premature truncation of nebulin. Point mutations (25%) or deletions (3%) affecting conserved splice signals are predicted in the majority of cases to cause in-frame exon skipping, possibly leading to impaired nebulin-tropomyosin interaction along the thin filament. Patients in 18 families had one of nine missense mutations (14%) affecting conserved amino acids at or in the vicinity of actin or tropomyosin binding sites. In addition, we found the exon 55 deletion in four families. The majority of the patients (in 49/55 families) were shown to be compound heterozygous for two different mutations. The mutations were found in both constitutively and alternatively expressed exons throughout the NEB gene, and there were no obvious mutational hotspots. Patients with more severe clinical pictures tended to have mutations predicted to be more disruptive than patients with milder forms. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16917880&query_hl=1 ER - TY - JFULL T1 - Subretinal membranes are associated with abnormal degrees of pupil "evasion": an index of clinical macular dysfunction. A1 - Zaidi, FH A1 - Bremner, FD A1 - Gregory-Evans, K A1 - Cocker, KD A1 - Moseley, MJ J1 - Br J Ophthalmol Y1 - 2006/09// VL - 90 SN - 0007-1161 SP - 1115 EP - 1118 N2 - AIM: To assess whether macular dysfunction caused by unilateral subretinal neovascular membranes (SRNs) is associated with pupil "evasion" (that is, increased initial rate of re-dilation following a brief light stimulus). METHODS: Comparative observational series. 20 eyes of 10 participants, all with unilateral SRNs and healthy fellow eyes. Dynamic infrared pupillography at seven stimulus intensities (duration 1100 ms, intensities over 2 log unit range). Pupil evasion ratio (PEVR; defined as the ratio of light response amplitude to amount of recovery at the mid-time point of re-dilation expressed as a percentage) was calculated for each stimulus intensity (mean of five recordings). RESULTS: Inter-eye PEVR is significantly reduced in eyes with SRN (that is, greater pupil evasion in SRN eyes: range p = 0.002 to p = 0.05 (paired t test)) and is most apparent at higher stimulus intensities. CONCLUSIONS: PEVR is a novel parameter that is analogous to the pupil escape ratio, but measured following a short rather than a sustained light stimulus. PEVR is significantly altered by macular disease. Clinically PEVR may be used to detect occult unilateral or asymmetric maculopathy in situations such as ocular media opacities like cataract, when pupil reactions are unaffected or augmented, while other tests of retinal function are diminished. PEVR represents altered neuronal firing in cones and macular ganglion cells. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16929060&query_hl=1 ER - TY - JFULL T1 - The long-term effects of perinatal glucocorticoid exposure on the host defence system of the respiratory tract. A1 - Theogaraj, E A1 - John, CD A1 - Dewar, A A1 - Buckingham, JC A1 - Smith, SF J1 - J Pathol Y1 - 2006/09// VL - 210 SN - 0022-3417 SP - 85 EP - 93 N2 - Glucocorticoids are used to mature the fetal lung at times of threatened premature delivery. These drugs modify leukocyte profiles when administered in adulthood, but their effects on the mature host defence system following administration during the perinatal period are incompletely understood. In this study, the long-term effects of perinatal dexamethasone exposure on rodent host defence cells in the pulmonary airspaces, the perivascular compartment of the lung, and the blood were investigated. Rats were treated prenatally (gestational days 16-19) or neonatally (postnatal days 1-7) by inclusion of dexamethasone in the mothers' drinking water (1 microg/ml). The pups were then allowed to develop to adulthood (P60-80), at which time respiratory tissues were collected for light and electron microscopy and bronchoalveolar lavage (BAL), and blood for cell count and fluorescent activated cell-sorting (FACS) analysis. Prenatal treatment had no effect on any parameter examined. Following neonatal dexamethasone exposure, light microscopy of the lung tissue revealed a significant reduction in the number of cells in the perivascular space in both the central and the peripheral regions of the adult lung, but no differences in the number of cells in the airspaces. Neonatal dexamethasone exposure was also characterized by a significant reduction in the total number of white cells in the peripheral blood in adulthood and in particular, the number of lymphocytes relative to neutrophils was significantly reduced at maturity in these animals. The results show that neonatal, but not prenatal, dexamethasone exposure significantly alters the distribution of host defence cells in the blood and lung at maturity compared with control animals. The early neonatal period is characterized by the stress hyporesponsive period in the rat, when endogenous glucocorticoid levels are very low. Therefore, exogenous glucocorticoids administered during this time are likely to have marked "programming" effects on glucocorticoid-sensitive tissues. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16924656&query_hl=1 ER - TY - JFULL T1 - The pre-synaptic dopaminergic system before and after the onset of psychosis: initial results A1 - Howes, OD A1 - Montgomery, AJ A1 - Asselin, MC A1 - Murray, RM A1 - Grasby, PM A1 - McGuire, PK J1 - EUR NEUROPSYCHOPHARM Y1 - 2006/09// VL - 16 SN - 0924-977X SP - S177 EP - S177 ER - TY - JFULL T1 - Whole genome expression profiling reveals involvement of the cerebral cortex in Parkinson's disease A1 - Moran, LB A1 - Duke, DC A1 - Croisier, E A1 - Slonimsky, A A1 - Kalaitzakis, M A1 - Deprez, M A1 - Dexter, DT A1 - Pearce, RK A1 - Graeber, MB J1 - BRAIN PATHOL Y1 - 2006/09// VL - 16 SN - 1015-6305 SP - S8 EP - S8 ER - TY - JFULL T1 - Violent deliberate self-harm amongst adolescent refugees. A1 - Patel, N A1 - Hodes, M J1 - Eur Child Adolesc Psychiatry Y1 - 2006/09// VL - 15 SN - 1018-8827 SP - 367 EP - 370 N2 - Investigation of frequency and characteristics of violent deliberate self-harm (DSH) amongst adolescents. Study was retrospective, over 3-year period, based on records of attendees at child and adolescent mental health clinics in North West London. Nine adolescents showed violent self-harm out of 982 DSH cases (frequency 0.92%). The nine cases included five female asylum seekers, who experienced war related events, were significantly more likely to have affective disorders and post-traumatic stress disorder (PTSD), compared with the four males (none asylum seekers), who were significantly more likely to have conduct and substance misuse disorders. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16680410&query_hl=1 ER - TY - JFULL T1 - Accumulation of alpha-synuclein in the CA2 sector of the hippocampus: Correlates with dementia in Parkinson's disease A1 - Gentleman, SM A1 - Green, G A1 - Kalaitzakis, ME A1 - Pearce, R A1 - Roncaroli, F A1 - Trojanowski, JQ A1 - Graeber, MB J1 - BRAIN PATHOL Y1 - 2006/09// VL - 16 SN - 1015-6305 SP - S7 EP - S7 ER - TY - JFULL T1 - Perceptual threshold to cutaneous electrical stimulation in patients with spinal cord injury. A1 - Savic, G A1 - Bergström, EM A1 - Frankel, HL A1 - Jamous, MA A1 - Ellaway, PH A1 - Davey, NJ J1 - Spinal Cord Y1 - 2006/09// VL - 44 SN - 1362-4393 SP - 560 EP - 566 N2 - STUDY DESIGN: Prospective experimental. OBJECTIVES: The aim of this study was to develop a quantitative sensory test (QST) that could be used for assessing the level and the density (degree of impairment) of spinal cord injury (SCI) and for monitoring neurological changes in patients with SCI. SETTING: National Spinal Injuries Centre, Stoke Mandeville Hospital, Buckinghamshire Hospitals NHS Trust, UK. METHODS: Perceptual threshold to 3 Hz cutaneous electrical stimulation was measured in 30 control subjects and in 45 patients with SCI at American Spinal Injuries Association (ASIA) sensory key points for selected dermatomes between C3 and S2 bilaterally. Electrical perceptual threshold (EPT) was recorded as the lowest ascending stimulus intensity out of three tests at which the subject reported sensation. The level of SCI according to EPT results was established for right and left sides as the most caudal spinal segment at which patient's EPT was within the control range (mean +/- 2 standard deviation (SD)). The level of SCI, according to EPT, was then compared with clinical sensory level derived according to ASIA classification. RESULTS: In the control group, EPT depended on the dermatome tested and was lowest for T1 (1.01 +/- 0.23 mA, mean +/- SD) and highest for L5 (3.32 +/- 1.14 mA). There was strong correlation between corresponding right and left dermatomes and between repeated assessments. In the SCI group, the level of lesion according to EPT and clinical testing was the same in 43 of the 90 tests (48%). In 37 cases (41%), the EPT level was higher than the clinical level, and in 10 cases (11%), it was lower. Below the level of lesion in incomplete SCI and in the zone of partial preservation in complete SCI, the EPT values in most dermatomes were raised compared with the control group. CONCLUSIONS: EPT is a simple, reproducible QST that can assess both the level and the density of SCI. It seems to add sensitivity and resolution to the standard clinical testing and could be a useful adjunct in longitudinal monitoring of patients with SCI for research purposes during natural recovery and therapeutic interventions. SPONSORSHIP: International Spinal Research Trust (ISRT), UK, Grant CLI001. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16568143&query_hl=1 ER - TY - JFULL T1 - beta-adrenergic receptor blockers and the treatment of vasovagal syncope: more nails in the coffin! A1 - Mathias, CJ J1 - Clin Sci (Lond) Y1 - 2006/09// VL - 111 SN - 0143-5221 SP - 189 EP - 191 N2 - beta-Adrenergic receptor blockers are one of a number of therapeutic agents promoted as having beneficial effects in vasovagal syncope. In this issue of Clinical Science, Eldadah and co-workers have investigated the effect of the beta-adrenergic receptor blocker propranolol in preventing syncope in a double-blind cross-over trial in eight subjects with a diagnosis based on tilt table testing and elevated plasma adrenaline levels during syncope. Of these, seven did not respond and the authors therefore suggest that this drug has no role in the management of vasovagal syncope. Their laboratory-based study, however, raises a number of issues regarding terminology, choice of subjects, the value and role of investigations directed towards diagnosis and in understanding pathophysiological mechanisms, and the relevance of such trials to individual subjects with vasovagal syncope. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16848762&query_hl=1 ER - TY - JFULL T1 - [Improving the publication rate of Spanish researchers in good journals] A1 - Tyrer, P J1 - Actas Esp Psiquiatr Y1 - 2006/09// VL - 34 SN - 1139-9287 SP - 283 EP - 286 N2 - Five obstacles are described that currently prevent Spanish researchers in the psychological sciences from publishing more frequently in journals of high impact factor. These are: a) a general lack of confidence in your ability; b) a tendency for your papers to be driven more by speculation rather than data; c) excessive length of submitted manuscripts; d) higher than expected rates of drop-out and non-participation in studies, and e) lack of independence from pharmaceutical companies. Although many of these problems will require long-term structural changes, others can be addressed immediately and yield improvement rapidly. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16991015&query_hl=1 ER - TY - JFULL T1 - The effect of trial number on the emergence of the 'broken escalator' locomotor aftereffect. A1 - Bunday, KL A1 - Reynolds, RF A1 - Kaski, D A1 - Rao, M A1 - Salman, S A1 - Bronstein, AM J1 - Exp Brain Res Y1 - 2006/09// VL - 174 SN - 0014-4819 SP - 270 EP - 278 N2 - Walking onto a stationary platform, which had been previously experienced as moving generates a locomotor aftereffect (LAE), which resembles the 'broken escalator' phenomenon. Experimentally, this is achieved by having subjects walk initially onto a stationary sled (BEFORE condition), then onto a moving sled (MOVING condition, or adaptation trials) and then again onto the stationary sled (AFTER condition). Subjects are always appropriately warned of the change in conditions. In this paper, we ask how many adaptation trials are needed to produce such a LAE. Thus, in two experiments, the number of MOVING trials was varied between 20 and 5 (Experiment 1) and between 8 and 1 (Experiment 2). Gait velocity, trunk position, foot contact timing and EMG of the ankle flexor-extensors muscles were measured. In comparison with BEFORE trials all groups in the AFTER trials walked inappropriately fast, experienced a large overshoot of the trunk and showed increased leg EMG, indicating that all groups showed a LAE. In each experiment, and for all variables, no significant difference between the groups (i.e. 20 down to one MOVING trials) was found. The study shows that this LAE, in contrast to other motor aftereffects reported in the literature, can be generated with only one or two adaptation trials and without requiring unexpected 'catch' trials. The fast aftereffect generation observed is likely to depend on two types of mechanisms: (1) the nature of the sensorimotor adaptation process, involving multiple sensory feedbacks (visual, vestibular and proprioceptive), anticipatory control and large initial task errors and (2) the involvement of two phylogenetically old neural mechanisms, namely locomotion and fear. Fear-relevant mechanisms, which are notably resistant to cognitive control, may be recruited during the adaptation trials and contribute to the release of this LAE. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16639502&query_hl=1 ER - TY - JFULL T1 - Attenuation of severe multiple sclerosis tremor coincident with progressive upper limb pyramidal weakness after thalamic surgery A1 - Hyam, JA A1 - Aziz, TZ A1 - Bain, PG J1 - EUR J NEUROL Y1 - 2006/09// VL - 13 SN - 1351-5101 SP - 76 EP - 76 ER - TY - JFULL T1 - EFNS guidelines on the diagnosis and management of orthostatic hypotension A1 - Lahrmann, H A1 - Cortelli, P A1 - Hilz, M A1 - Mathias, CJ A1 - Struhal, W A1 - Tassinari, M J1 - EUR J NEUROL Y1 - 2006/09// VL - 13 SN - 1351-5101 SP - 930 EP - 936 N2 - Orthostatic (postural) hypotension (OH) is a common, yet under diagnosed disorder. It may contribute to disability and even death. It can be the initial sign, and lead to incapacitating symptoms in primary and secondary autonomic disorders. These range from visual disturbances and dizziness to loss of consciousness (syncope) after postural change. Evidence based guidelines for the diagnostic workup and the therapeutic management (non-pharmacological and pharmacological) are provided based on the EFNS guidance regulations. The final literature research was performed in March 2005. For diagnosis of OH, a structured history taking and measurement of blood pressure (BP) and heart rate in supine and upright position are necessary. OH is defined as fall in systolic BP below 20 mmHg and diastolic BP below 10 mmHg of baseline within 3 min in upright position. Passive head-up tilt testing is recommended if the active standing test is negative, especially if the history is suggestive of OH, or in patients with motor impairment. The management initially consists of education, advice and training on various factors that influence blood pressure. Increased water and salt ingestion effectively improves OH. Physical measures include leg crossing, squatting, elastic abdominal binders and stockings, and careful exercise. Fludrocortisone is a valuable starter drug. Second line drugs include sympathomimetics, such as midodrine, ephedrine, or dihydroxyphenylserine. Supine hypertension has to be considered. ER - TY - JFULL T1 - Febrile temperatures enhance antigen processing of type II collagen for presentation to CD4 T cells. A1 - von Delwig, A A1 - Wilson, A A1 - Altmann, DM A1 - Holmdahl, R A1 - Harding, CV A1 - McKie, N A1 - Isaacs, JD A1 - Lakey, JH A1 - Robinson, JH J1 - ARTHRITIS RHEUM Y1 - 2006/09// VL - 54 SN - 0004-3591 SP - S37 EP - S37 ER - TY - JFULL T1 - Booming tunes of gloom A1 - Tyrer, P J1 - BRIT J PSYCHIAT Y1 - 2006/09// VL - 189 SN - 0007-1250 SP - 294 EP - 294 ER - TY - JFULL T1 - Increased 5-HT(2A) receptor binding in euthymic, medication-free patients recovered from depression: a positron emission study with [(11)C]MDL 100,907. A1 - Bhagwagar, Z A1 - Hinz, R A1 - Taylor, M A1 - Fancy, S A1 - Cowen, P A1 - Grasby, P J1 - Am J Psychiatry Y1 - 2006/09// VL - 163 SN - 0002-953X SP - 1580 EP - 1587 N2 - OBJECTIVE: A previous positron emission tomography (PET) study reported increased serotonin 5-HT(2A) receptor binding in unmedicated depressed patients with high scores on the Dysfunctional Attitudes Scale. The purpose of the present study was to use the highly selective 5-HT(2A) receptor ligand [(11)C]MDL 100,907 in a PET imaging paradigm to assess 1) 5-HT(2A) receptor binding potential in euthymic subjects with a history of recurrent depression and 2) the relationship between receptor binding and scores on the Dysfunctional Attitudes Scale. METHOD: Cortical 5-HT(2A) receptor binding was measured in 20 unmedicated, fully recovered unipolar depressed patients and 20 age- and gender-matched comparison subjects. Regional estimates of binding potential were obtained using a reversible plasma input function compartmental model and the cerebellum as a reference region to estimate the free and non-specifically bound [(11)C]MDL 100,907 in brain tissue. RESULTS: Relative to the comparison subjects, the recovered depressed patients demonstrated significantly higher 5-HT(2A) receptor binding potential in the frontal cortex (mean increase: 19%), parietal cortex (mean increase: 25%), and occipital cortex (mean increase: 19%). 5-HT(2A) receptor binding potential correlated negatively with age in both patients and comparison subjects and positively with the Dysfunctional Attitudes Scale in the recovered patients. CONCLUSIONS: These findings should be considered preliminary but suggest that recovered subjects with a history of recurrent major depression have elevated binding potential of cortical 5-HT(2A) receptors. The correlation of increased 5-HT(2A) receptor binding potential with increased scores on Dysfunctional Attitudes Scale supports earlier work suggesting that increased 5-HT(2A) receptor availability characterizes a group of depressed patients with high levels of dysfunctional attitudes. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16946184&query_hl=1 ER - TY - JFULL T1 - Combining imaging and genotypes in depression: fact or fiction? A1 - Grasby, PM J1 - EUR NEUROPSYCHOPHARM Y1 - 2006/09// VL - 16 SN - 0924-977X SP - S169 EP - S169 ER - TY - JFULL T1 - Relationship between insight, cognitive function, social function and symptomatology in schizophrenia: the West London first episode study. A1 - Mutsatsa, SH A1 - Joyce, EM A1 - Hutton, SB A1 - Barnes, TR J1 - Eur Arch Psychiatry Clin Neurosci Y1 - 2006/09// VL - 256 SN - 0940-1334 SP - 356 EP - 363 N2 - OBJECTIVE: To examine the nature and clinical correlates of insight in first-episode schizophrenia, and how these differ from findings in established schizophrenia. METHOD: Insight (and insight dimensions), clinical symptoms, neurocognitive function and social function were assessed in 94 patients with first-episode schizophrenia or schizophreniform disorder according to DSM-IV criteria. RESULTS: Greater global insight was associated with more severe depression. Poor overall insight was associated significantly with more severe negative and disorganisation symptoms as well as poor working memory, and at a trend level with lower current IQ. Patients with poor insight perceived themselves to have a better level of independent performance at daily living activities. CONCLUSION: In first-episode psychosis, the clinical correlates of poor insight are similar to those reported for established schizophrenia. Those patients with greater insight may be at risk of depression. The complex relationships between insight, positive and negative symptoms, neurocognitive dysfunction and social function may reflect the multidimensional nature of insight. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16902732&query_hl=1 ER - TY - JFULL T1 - Breathlessness measured by clamping end-tidal carbon dioxide: Limitations of the breathing system A1 - Pickering, E A1 - Guz, A A1 - Semple, S A1 - Murphy, K A1 - Holdcroft, A J1 - BRIT J ANAESTH Y1 - 2006/09// VL - 97 SN - 0007-0912 SP - 437P EP - 437P ER - TY - JFULL T1 - Effective immune depletion following novel lymphoablative regimen for autologous hematopoietic stem cell transplantation (AutoHSCT) in systemic lupus erythematosus (SLE). A1 - Nikolov, NP A1 - Illei, GG A1 - Yarboro, C A1 - Hakim, F A1 - Leitman, S A1 - Read, E A1 - Khuu, H A1 - Gramrner, A A1 - Fischer, R A1 - Balow, J A1 - Austin, H A1 - Gea-Banacloche, J A1 - Muraro, P A1 - Babb, R A1 - Krumlauf, M A1 - Sportes, C A1 - Lipsky, P A1 - Gress, R A1 - Pavletic, S J1 - ARTHRITIS RHEUM Y1 - 2006/09// VL - 54 SN - 0004-3591 SP - S790 EP - S790 ER - TY - JFULL T1 - Structural anatomy of pure and hemianopic alexia. A1 - Leff, AP A1 - Spitsyna, G A1 - Plant, GT A1 - Wise, RJ J1 - J Neurol Neurosurg Psychiatry Y1 - 2006/09// VL - 77 SN - 1468-330X SP - 1004 EP - 1007 N2 - BACKGROUND: The two most common types of acquired reading disorder resulting from damage to the territory of the dominant posterior cerebral artery are hemianopic and pure alexia. Patients with pronounced hemianopic alexia have a right homonymous hemianopia that encroaches into central or parafoveal vision; they read individual words well, but generate inefficient reading saccades when reading along a line of text. Patients with pure alexia also often have a hemianopia but are more disabled, making frequent errors on individual words; they have sustained damage to a brain region that supports efficient word identification. OBJECTIVE: To investigate the differences in lesion site between hemianopic alexia and pure alexia groups, as rehabilitative techniques differ between the two conditions. METHODS: High-resolution magnetic resonance images were obtained from seven patients with hemianopic alexia and from six patients with pure alexia caused by a left occipital stroke. The boundary of each lesion was defined and lesion volumes were then transformed into a standard stereotactic space so that regional comparisons could be made. RESULTS: The two patient groups did not differ in terms of damage to the medial left occipital lobe, but those with pure alexia had additional lateral damage to the posterior fusiform gyrus and adjacent tissue. CONCLUSIONS: Clinicians will be able to predict the type of reading disorder patients with left occipital lesions have from simple tests of reading speed and the distribution of damage to the left occipital lobe on brain imaging. This information will aid management decisions, including recommendations for reading rehabilitation. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16801352&query_hl=1 ER - TY - JFULL T1 - Febrile temperatures enhance antigen processing of type II collagen for presentation to CD4 T cells. A1 - von Delwig, A A1 - Wilson, AJ A1 - Altmann, DM A1 - Holmdahl, R A1 - Harding, CV A1 - Mckie, N A1 - Isaacs, JD A1 - Lakey, JH A1 - Robinson, JH J1 - ARTHRITIS RHEUM Y1 - 2006/09// VL - 54 SN - 0004-3591 SP - S639 EP - S639 ER - TY - JFULL T1 - Role of a 5'-enhancer in the transcriptional regulation of the human endothelial cell protein C receptor gene. A1 - Mollica, LR A1 - Crawley, JT A1 - Liu, K A1 - Rance, JB A1 - Cockerill, PN A1 - Follows, GA A1 - Landry, JR A1 - Wells, DJ A1 - Lane, DA J1 - Blood Y1 - 2006/08/15/ VL - 108 SN - 0006-4971 SP - 1251 EP - 1259 N2 - The endothelial cell protein C receptor (EPCR) is expressed by endothelial cells of large blood vessels and by hematopoietic stem cells. DNaseI hypersensitive (DH) site mapping across 38 kb of the human EPCR gene (hEPCR) locus identified 3 potential regulatory elements. By itself, the DH region spanning the proximal promoter (PP) was unable to direct cell-specific transcription in transgenic mice. A second DH element, located upstream of PP and termed -5.5HS was hypersensitive only in endothelial cells (ECs) and immature hematopoietic cell lines. Transgenes expressing LacZ under the control of -5.5HS coupled to either PP or the SV40 promoter were able to direct beta-galactosidase activity to the endothelium of large vessels during embryogenesis and adulthood. The -5.5HS exhibited enhancer activity that was conferred by the interplay of transcription factors interacting with conserved Ets and composite GATA/Tal1 motifs. The third DH element, located in intron 2, was primarily hypersensitive in EPCR-negative cells, and capable of initiating antisense transcription, suggesting a role in hEPCR silencing. This study identifies critical elements required for the tissue specificity of hEPCR and suggests a mechanism for endothelial and hematopoietic stem cell-specific transcriptional regulation that reflects the common origin of these cell types. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16627757&query_hl=1 ER - TY - JFULL T1 - Overlapping regional distribution of CCK and TPPII mRNAs in Cynomolgus monkey brain and correlated levels in human cerebral cortex (BA 10). A1 - Radu, D A1 - Tomkinson, B A1 - Zachrisson, O A1 - Weber, G A1 - de Belleroche, J A1 - Hirsch, S A1 - Lindefors, N J1 - Brain Res Y1 - 2006/08/09/ VL - 1104 SN - 0006-8993 SP - 175 EP - 182 N2 - Tripeptidyl peptidase II (TPPII) is a high molecular weight exopeptidase important in inactivating extracellular cholecystokinin (CCK). Our aims were to study the anatomical localization of TPPII and CCK mRNA in the Cynomolgus monkey brain as a basis for a possible functional anatomical connection between enzyme (TPPII) and substrate (CCK) and examine if indications of changes in substrate availability in the human brain might be reflected in changes of levels of TPPII mRNA. Methods: mRNA in situ hybridization on postmortem brain from patients having had a schizophrenia diagnosis as compared to controls and on monkey and rat brain slices. Results: overlapping distribution patterns of mRNAs for TPPII and CCK in rat and monkey. High amounts of TPPII mRNA are seen in the neocortex, especially in the frontal region and the hippocampus. TPPII mRNA is also present in the basal ganglia and cerebellum where CCK immunoreactivity and/or CCK B receptors have been found in earlier studies, suggesting presence of CCK-ergic afferents from other brain regions. Levels of mRNAs for CCK and TPPII show a positive correlation in postmortem human cerebral cortex Brodmann area (BA) 10. TPPII mRNA might be affected following schizophrenia. Discussion: overall TPPII and CCK mRNA show a similar distribution in rat and monkey brain, confirming and extending earlier studies in rodents. In addition, correlated levels of TPPII and CCK mRNA in human BA 10 corroborate a functional link between CCK and TPPII in the human brain. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16822484&query_hl=1 ER - TY - JFULL T1 - Identification of an oculomotor biomarker of preclinical Huntington disease. A1 - Golding, CV A1 - Danchaivijitr, C A1 - Hodgson, TL A1 - Tabrizi, SJ A1 - Kennard, C J1 - Neurology Y1 - 2006/08/08/ VL - 67 SN - 1526-632X SP - 485 EP - 487 N2 - The authors examined oculomotor function to identify a biomarker of disease progression in genetically confirmed preclinical and early clinical Huntington disease (HD). Initiation deficits of voluntary-guided, but not reflexive, saccades were characteristic of preclinical HD. Saccadic slowing and delayed reflexive saccades were demonstrated in clinical but not preclinical HD. Saccadic measures provide biomarkers of disease progression in both preclinical and early clinical stages of HD. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16625001&query_hl=1 ER - TY - JFULL T1 - Pharmacological management of acute mania - does current prescribing practice reflect treatment guidelines? A1 - Streeruwitz, A A1 - Barnes, TR A1 - Fehler, J A1 - Ohlsen, RI A1 - Curtis, V J1 - J Psychopharmacol Y1 - 2006/08/04/ SN - 0269-8811 N2 - The records of 70 inpatients with an acute manic episode were audited, to examine the relationship between current prescribing practice, the recommendations of recent clinical guidance and short-term clinical outcomes. Overall, 38 combinations of medication were prescribed. Within the first 24 hours of treatment, monotherapy with a second generation antipsychotic was favoured. At discharge, combination treatment (a mood stabilizer and a second generation antipsychotic) predominated. Early initiation of medication was significantly associated with an earlier clinical decision to discharge. Prescribing was generally in accord with published guidelines. The findings reinforce the value of prescribing surveys in mental health and the need to share understanding of the constraints that may lead to deviation from prescribing guidelines. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16891337&query_hl=1 ER - TY - JFULL T1 - Listening to narrative speech after aphasic stroke: the role of the left anterior temporal lobe. A1 - Crinion, JT A1 - Warburton, EA A1 - Lambon-Ralph, MA A1 - Howard, D A1 - Wise, RJ J1 - Cereb Cortex Y1 - 2006/08// VL - 16 SN - 1047-3211 SP - 1116 EP - 1125 N2 - The dorsal bank of the primate superior temporal sulcus (STS) is a polysensory area with rich connections to unimodal sensory association cortices. These include auditory projections that process complex acoustic information, including conspecific vocalizations. We investigated whether an extensive left posterior temporal (Wernicke's area) lesion, which included destruction of early auditory cortex, may contribute to impaired spoken narrative comprehension as a consequence of reduced function in the anterior STS, a region not included within the boundary of infarction. Listening to narratives in normal subjects activated the posterior-anterior extent of the left STS, as far forward as the temporal pole. The presence of a Wernicke's area lesion was associated with both impaired sentence comprehension and a reduced physiological response to heard narratives in the intact anterior left STS when compared to aphasic patients without temporal lobe damage and normal controls. Thus, in addition to the loss of language function in left posterior temporal cortex as the direct result of infarction, posterior ablation that includes primary and early association auditory cortex impairs language function in the intact anterior left temporal lobe. The implication is that clinical studies of language on stroke patients have underestimated the role of left anterior temporal cortex in comprehension of narrative speech. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16251507&query_hl=1 ER - TY - JFULL T1 - Transient receptor potential vanilloid receptor subtype 1 in painful bladder syndrome and its correlation with pain. A1 - Mukerji, G A1 - Yiangou, Y A1 - Agarwal, SK A1 - Anand, P J1 - J Urol Y1 - 2006/08// VL - 176 SN - 0022-5347 SP - 797 EP - 801 N2 - PURPOSE: Painful bladder syndrome is a chronic, debilitating bladder hypersensitivity disorder characterized by urinary frequency, urgency and bladder pain without an identifiable cause. Recent advances in understanding the molecular basis of hypersensitivity provide an opportunity to advance the understanding of and treatment for painful bladder syndrome. We studied the heat and capsaicin receptor transient receptor potential vanilloid receptor subtype 1 in the bladder in patients with painful bladder syndrome and their relationship to pain symptoms. MATERIALS AND METHODS: Bladder biopsies were obtained from 20 characterized subjects with painful bladder syndrome and 25 with asymptomatic microscopic hematuria as controls. Specimens were immunostained using specific antibodies to transient receptor potential vanilloid receptor subtype 1 and neurofilaments as a structural maker. Nerve fiber and urothelial staining were quantified with computerized image analysis. The results of immunohistochemistry were correlated with the pain score. RESULTS: There was a marked increase in suburothelial nerve fibers expressing transient receptor potential vanilloid receptor subtype 1 in painful bladder syndrome in comparison with that in controls (p <0.0001). The ratio of transient receptor potential vanilloid receptor subtype 1 fibers to neurofilaments was also significantly increased in painful bladder syndrome, suggesting over expression of transient receptor potential vanilloid receptor subtype 1 (p <0.0001). When all specimens studied were included, the pain score correlated significantly with the relative nerve fiber density of transient receptor potential vanilloid receptor subtype 1 in the suburothelium (r = 0.6862, p = 0.0002) as well as the ratio of transient receptor potential vanilloid receptor subtype 1 fibers to neurofilaments (r = 0.5554, p = 0.004). Urothelial transient receptor potential vanilloid receptor subtype 1 showed a tendency toward an increase in the painful bladder syndrome group but it did not achieve statistical significance. No correlation was found between transient receptor potential vanilloid receptor subtype 1 immunoreactivity of urothelium or neurofilament fibers and the pain score. CONCLUSIONS: This study shows increased transient receptor potential vanilloid receptor subtype 1 in nerve fibers of the bladder in painful bladder syndrome and a correlation of the pain score with the relative density of transient receptor potential vanilloid receptor subtype 1 nerve fibers. Transient receptor potential vanilloid receptor subtype 1 may have a role in the pathophysiology of painful bladder syndrome and it is a potential target for novel therapeutic agents. L1 - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16813950&query_hl=1 ER - TY - JFULL T1 - Gender differences in reoffending after discharge from medium-secure units - National cohort study in England and Wales A1 - Maden, A A1 - Skapinakis, P A1 - Lewis, G A1 - Scott, F A1 - Jamieson, E J1 - BRIT J PSYCHIAT Y1 - 2006/08// VL - 189 SN - 0007-1250 SP - 168 EP - 172 N2 - Background: Previous research has shown that there are gender differences in reoffending after discharge from medium-secure units, but these have not been adequately explained.Aims: To investigate ge