Phd Day 13 January 2006

UNIVERSITY OF AARHUS GRADUATE SCHOOL OF HEALTH SCIENCES

PhD Day 13 January 2006

2 Welcome

The PhD Day is the annual gathering of PhD students enrolled at the University of Aarhus Graduate School Health Sciences. As evident from the present volume containing all submitted abstracts, our Faculty has a large and thriving research environment covering a multitude of clinical, biomedical and public health areas. The studies span contributions from basic investigations in molecular medicine to contributions which address significant challenges to public health.

The PhD students perform an important part of the research carried out under the auspices of the Faculty. More than 350 students are enrolled in the Graduate School. Their projects, although firmly rooted in the research activities in Aarhus and Aalborg, have wide international collaboration, emphasizing the Faculty’s high international rating. Students in our Graduate School are thus well-prepared to meet with international leaders in health science research.

The program for PhD Day 2006 arranged by the Organizing Committee has focused on the criteria for excellence in research and how scientific results should be published. We therefore welcome the distinguished panel of speakers who have accepted our invitation to contribute.

We believe that this PhD Day will, as in previous years, demonstrate the strength of our PhD program, and provide students and supervisors alike with encouragement for their continued scientific activity.

On behalf of the Faculty of Health Sciences, The Graduate School of Medicine, and the Organizing Committee, we offer you an enthusiastic welcome to the PhD Day 2006.

Michael John Mulvany Thomas Vorup-Jensen Director, Graduate School of Health Sciences Chairman, Organizing Committee

Søren Mogensen Dean, Faculty of Health Sciences

3 4 Contents

Welcome 3

Information 7

Program 8

Free communication program - oral 10 - posters 11

Invited speakers 33

Abstracts 34

Index 228

Information from the PhD Association 232

5 6 Information

Practical information:

• Lunch will be held in Lake Auditorium Building

• Posters will be shown in Lake Auditorium 5; Bartholin Building reading room and auditoria 3 and 4; Victor Albeck Building

• Posters must be set up at 7.30 before the start of the conference, and taken down immediately after the close.

• Oral presenters for sessions O1-O4 must meet in the auditorium concerned between 07.30 and 08.00 to put their powerpoint presentation onto the auditorium hard disk. Other oral presenters should meet in auditorium 1 at the first coffee-break 9.25 to load their presentations.

Organizing committee:

• Thomas Vorup-Jensen (chairman) , Institute of Medical Microbiology • Niels Trolle Andersen, Department of Biostatistics, Institute of Public Health • Birgit Bonefeld, Chairman, PhD Association • Helene Nørrelund, Department of Medicine, Clinical Institute • Louise Østergaard Petersen, Board member, PhD Association • Troels Staehelin Jensen, co-Director of PhD studies • Michael Mulvany, Director of PhD studies

Prize committee: • Chairman, Jens Chr. Djurhuus • Co-chairman, Helene Nørrelund • Coordinators: o Oral sessions, Torben Ørntoft o Poster sessions Lake Auditorium 5 (groups 1-6), Michael Hasenkam Bartholin Building (groups 7-14), Raben Rosenberg Victor Albeck Building (groups 15-27), Jens Sandahl Christensen

Secretariat:

Inge Haislund Andersen, Forskeruddannelsen, The Faculty of Health Sciences, Vennelyst Boulevard 9, 8000 Aarhus C. [email protected]

7 Programme

Welcome

8.30 Søren Mogensen (Dean of the Faculty of Health Sciences) Michael Mulvany (Director, PhD studies) Birgit Bonefeld (Chairman, PhD Association) Thomas Vorup-Jensen (Chairman, organizing committee)

Health science research process. Chairman Troels Staehlin Jensen, co-Director PhD studies

8.45 Tomas Hökfelt, Karolinska Institute, Neuropeptides: from basics to the clinic

9.25 Tea/coffee

Medical publishing. Chairmen Povl Riis, former editor Journal of the Danish Medical Association (Ugeskrift for Læger), Michael Mulvany, Director PhD studies

9.55 Fiona Godlee, Editor British Medical Journal. Protecting medical publishing from bias

10.35 Torben Schroeder, Editor Journal of the Danish Medical Association Ethics of medical publishing

10.55 Discussion - 11.10

Oral communications

11.20 Parallel sessions Session O1. Chairmen: Mogens Kilian, Lise Wogensen Bach Auditorium 1 Session O2 Chairmen: Søren Moestrup, Leif Mosekilde Auditorium 2 Session O3 Chairmen: Torsten Toftegaard, Christian Aalkjær Auditorium 3 Session O4 Chairmen: Hans Gregersen, Ebba Nexø Auditorium 4

12.35 Lunch

Poster session

13.00 Poster viewing

13.30 Poster visits (for chairmen see poster programme) Groups P1-P6 Auditorium 5 Groups P7-P14 Bartholin Building Teaching Wing Groups P15-P27 Victor Albeck Building

Training in health science research. Chairmen: Hans Jørn Kolmos, Director of PhD studies, University of Southern Denmark Jørgen Vinten, Director of PhD studies, University of Copenhagen

14.45 Seppo Meri, Helsinki University Research training: an international perspective

15.15 Discussion

Special lecture. Chairman Søren Nielsen, Institute of Anataomy, University of Aarhus

15.30 Peter Agre, Duke University, Nobel Laureate. What is good research?

Closing remarks

16.15 Søren Mogensen

Social programme

18.30 Dinner, Entertainment and Dance, Stakladen. Jens Christian Djurhuus: Announcement of the prizes Lars Bolund; Festive speech

9 Free communications program

Presenting authors and title. For co-authors and affiliation see abstracts.

Oral session O1. Chairmen: Mogens Kilian, Lise Wogensen Bach

O1.01 Hanne Vebert Olesen. VIRAL AND ATYPICAL BACTERIAL INFECTIONS IN CHILDREN WITH CYSTIC FIBROSIS

O1.02 Mette Skytte Tetsche. PROGNOSIS OF OVARIAN CANCER ASSOCIATED WITH VENOUS THROMBOEMBOLISM: A NATIONWIDE DANISH COHORT STUDY

O1.03 Irene Dige. QUANTITATIVE MEASUREMENT OF BACTERIA IN DENTAL BIOFILMS: A PILOT STUDY

O1.04 Mette Møller-Kristensen. DEFICIENCY OF MANNAN-BINDING LECTIN GREATLY INCREASES SUSCEPTIBILITY TO POST-BURN INFECTION WITH PSEUDOMONAS AERUGINOSA

O1.05 Thomas Nielsen. RELATIONSHIP BETWEEN COMBRETASTATIN INDUCED CHANGES IN DCEMRI PARAMETERS AND RADIATION RESPONSE IN A MURINE TUMOUR MODEL

Oral session O2. Chairmen: Søren Moestrup, Leif Mosekilde

O2.01 Anja Pernille Einholm. MUTATION OF GLY94 IN TRANSMEMBRANE SEGMENT M1 OF THE NA+,K+-ATPASE INTERFERES WITH NA+ AND K+ BINDING IN E2P CONFORMATION

O2.02 Ramune Aleksyniene. EFFECTS OF PARATHYROID HORMONE TREATMENT ON DISTRACTION OSTEOGENESIS IN THE RABBIT TIBIAL LENGTHENING MODEL

O2.03 Marianne Jensby Nielsen. MOLECULAR CHARACTERIZATION OF THE HAPTOGLOBIN-HEMOGLOBIN RECEPTOR CD163: ENDOCYTIC PROPERTIES OF THE CYTOPLASMIC TAIL OF PHYSIOLOGICAL CD163 VARIANTS

O2.04 Mathias Hauge Bünger. THE EFFECTS OF STRONTIUM ON BONE ULTRASTRUCTURE: INSIGHTS FROM LABORATORY SCANNING SMALL ANGLE X- RAY SCATTERING (SSAXS)

O2.05 Bjarke Moosgaard. VITAMIN D STATUS AND SEASONAL VARIATIONS IN PRIMARY HYPERPARATHYROIDISM

10 Oral session O3. Torsten Toftegaard, Christian Aalkjær

O3.01 Kim Holmgaad Jensen. THE IMPAIRMENT OF RETINAL VASOCONSTRICTION CAUSED BY PERIVASCULAR TISSUE CAN BE BLOCKED BY INHIBITION OF THE GLUTAMATE NMDA RECEPTOR AND COX

O3.02 Niels Jessen. ALTERED SUBSTRATE METABOLISM AND ABLATED AMPKΑ2 ACTIVITY IN LKB1 KNOCKOUT HEARTS

O3.03 Rikke Nørregaard. SEGMENTAL AQP2 REGULATION BY SELECTIVE COX-2 INHIBITION IN AFTER RELEASE OF BILATERAL URETERAL OBSTRUCTION IN RATS

O3.04 Søren Dalager-Pedersen. PERIADVENTITIAL INFLAMMATION - A MARKER OF SYSTEMIC INFLAMMATORY ACTIVATION AND CORONARY DEATH?

O3.05 Lars Riisgaard Ribe. MOTION ANALYSIS FOR SHORTER SCAN TIMES IN CARDIAC MRI

Oral session O4. Hans Gregersen, Ebba Nexø

O4.01 Trine Munk-Olsen. RISK OF POSTPARTUM MENTAL DISORDERS, WOMEN ARE AT RISK, BUT WHAT ABOUT MEN?

O4.02 Ellen M. Mikkelsen. PSYCHOSOCIAL CONDITIONS OF WOMEN WHO ANTICIPATE GENETIC COUNSELING: A POPULATION-BASED STUDY

O4.03 Karen Johanne Pallesen. EMOTION PROCESSING IN THE HUMAN BRAIN: AN fMRI STUDY

O4.04 Brent M. Witgen. INHIBITORY INTERNEURONS FOLLOWING EXPERIMENTAL BRAIN INJURY

O4.05 Anita Rethmeier. THE USE OF OLIGONUCLEOTID ARRAYS IN SEARCH OF NEW MOLECULAR MARKERS IN AML

Poster session 01. Chairmen: Flemming Winther Bach, Lars Bolund

P01.01 Jane Clemmensen. TELEMEDICAL HOME TREATMENT OF PATIENTS WITH DIABETIC FOOT ULCERS: VIDEO PHONE AS A DIAGNOSTIC AID

P01.02 Lars Uhrenholt . INJURIES TO THE CERVICAL SPINE FACET JOINTS OF A ROAD TRAFFIC CRASH FATALITY – A CASE REPORT

P01.03 Christian Lodberg Hvas. IMPAIRED CYTOKINE RESPONSE IN INTESTINAL CD4+ T CELLS FROM CROHN DISEASE PATIENTS

P01.04 Rikke Søgaard. SOCIOECONOMIC EVALUATION OF LUMBAR SPINAL FUSION IN CHRONIC LOW BACK PAIN PATIENTS

P01.05 Ashfaque Ahmed Memon. ACTIVITY OF THE EPIDERMAL GROWTH FACTOR RECEPTOR DELAYS THE ONSET OF CALCIUM-INDUCED APOPTOSIS IN BLADDER CANCER CELLS

P01.06 Jianguo Chen. STEVIOSIDE DOES NOT CAUSE INCREASED BASAL INSULIN SECRETION OR ß-CELL DESENSITISATION LIKE THE SULPHONYLUREA, GLIBENCLAMIDE: STUDIES IN VITRO

P01.07 AnetteTorvin Møller. NEUROPATHIC PAIN AND SENSORY DISTURBANCES IN HETEROZYGOTE PATIENTS WITH FABRY DISEASE

P01.08 Mimi Kjærsgaard. TREATMENT OF IDIOPATHIC THROMBOCYTOPENIC PURPURA IN CHILDREN WITH SUBCUTANEOUS ADMINISTERED ANTI-D

P01.09 Bodil Øster. HUMAN HERPESVIRUS 6B INDUCES P53 ACCUMULATION AND CELL CYCLE ARREST IN T CELLS

P01.10 Anja Fjorback. A ROLE FOR M6B IN THE FUNCTIONAL REGULATION OF THE HUMAN SEROTONIN TRANSPORTER

Poster session 02. Chairmen: Jens Overgaard, Gunna Christiansen

P02.01 Guixian Wang. DOWNREGULATION OF KEY RENAL ACID BASE TRANSPORT PROTEINS EXPLAINS THE URINARY ACIDIFICATION DEFECT IN RESPONSE TO URINARY TRACT OBSTRUCTION

P02.02 Cecilia Høst Ramlau-Hansen. SMOKING DURING PREGNANCY AND RISK OF LOW SEMEN QUALITY IN THE MALE OFFSPRING

P02.03 Jørgen Baas. RECONSTITUTED BOVINE BONE PROTEIN LYOPHILLISATE ENHANCES FIXATION OF ALLOGRAFTED GAP IMPLANTS

P02.04 Lene Baad-Hansen. BLINK REFLEXES IN PATIENTS WITH ATYPICAL ODONTALGIA AND MATCHED HEALTHY CONTROLS

P02.05 Thomas Baad-Hansen. ALTERATION OF HIP JOINT CENTRE DURING ACETABULAR REAMING

P02.06 Annette Ø. Jensen. NON MELANOMA SKIN CANCER AND MORTALITY IN DENMARK – A 10 YEAR FOLLOW UP STUDY

P02.07 Jing Hong. STEVIOSIDE COUNTERACTS THE ALPHA CELL HYPERSECRETION CAUSED BY LONG-TERM PALMITATE EXPOSURE

12 P02.08 Phuong Le Quach. PREDICTORS OF MEDICATION COMPLIANCE AMONG PATIENTS WITH FIRST EPISODE OF SCHIZOPHRENIA SPECTRUM DISORDER

P02.09 Sukru Oguzkan Topcu. CANDESARTAN PREVENTS LONG TERM CHANGES INRESPONSE TO NEONATAL URETERAL OBSTRUCTION

P02.10 Lisbeth Uhrenfeldt. CLINICAL WISDOM AND RESPONSIBILITY AMONG PROFICIENT NURSES

Poster session 03. Chairmen: Ulrik Baandrup, Torben Clausen

P03.01 Tina R. Kilburn. A NEW METHOD FOR TESTING SPEED OF INFORMATION PROCESSING IN YOUNG CHILDREN BASED ON STERNBERG’S PARADIGM

P03.02 Lars Riber Zebis. PERORAL ADMINISTRATED AMIODARONE PROPHYLAXIS FOR ATRIAL FIBRILLATION AFTER INTRAVENEOUS LOADING FOR PATIENTS UNDERGOING CORONARY ARTERY BYPASS GRAFTING: A RANDOMIZED, DOUBLE BLIND, PLACEBO-CONTROLLED TRIAL

P03.03 Anne C. Vingård Olesen. BIRTH WEIGHT AS A CORRELATE OF BLOOD PRESSURE: UNEXPECTED ASSOCIATION BETWEEN SPOUSES

P03.04 Iben Søgaard Jacobsen. T(4;12) TRANSLOCATION IN A PATIENT WITH BIPOLAR AFFEKTIVE DISORDER

P03.05 Esben Thyssen Vestergaard. THE GHRELIN RESPONSE TO EXERCISE BEFORE AND AFTER GH ADMINISTRATION

P03.06 Nina Ank. THE INTERFERON-Λ – A NOVEL INTERFERON – IS PRODUCED DURING VIRAL INFECTIONS AND EXERTS ANTIVIRAL ACTIVITY

P03.07 Ole Eschen. SOLUBLE ADHESION MOLECULES IN HEALTHY SUBJECTS: A DOSE- RESPONSE STUDY WITH N-3 FATTY ACIDS

P03.08 Astrid Heide Petersen. ABSORPTION OF INHALED INSULIN DRAMATICALLY INCREASES BY LARGE TIDAL VOLUME VENTILATION IN RABBITS

P03.09 Brian Dall Schyth. RNA INTERFERENCE IN FISH CELLS – SMALL INTERFERING RNAS TARGETING VIRAL GENES FROM A FISH PATHOGENIC VIRUS

P03.10 Inger Mechlenburg. CARTILAGE THICKNESS IN THE HIP JOINT MEASURED BY MRI AND STEREOLOGY

Poster session 04. Chairmen: Asbjørn Drewes, Niels Ehlers

P04.01 Charlotte Buchard Norager. CAFFEINE IMPROVES ENDURANCE IN 75-YEAR OLD CITIZENS. A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, CROSS- OVER STUDY

P04.02 Emad Eddin Ayesh. HYPERSENSITIVITY TO PIN-PRICK STIMULI FOLLOWING NOCICEPTIVE ELECTRICAL STIMULATION OF THE HUMAN TMJ

P04.03 Ingolf Mølle. SELECTED GENETIC POLYMORPHISMS OF THE INNATE IMMUNE SYSTEM AND CHEMOTHERAPY-RELATED INFECTIONS IN PATIENTS WITH MULTIPLE MYELOMA

P04.04 TINA PARKNER. CLINICAL ASPECTS OF BASAL INSULIN PUMP THERAPY FOR 8 HOURS VERSUS 24 HOURS IN PATIENTS WITH TYPE 2 DIABETES

P04.05 Zahra Nourian. COMPARATIVE STUDY ON THE FUNCTIONAL α1-ADRENOCEPTOR AFFINITY OF ANTIPSYCHOTIC DRUGS IN RAT SMALL MESENTERIC ARTERIES AND THORACIC AORTA

P04.06 Susanne Lerche. NEW POTENTIAL EFFECTS OF GLP-1, WITH A SPECIAL FOCUS ON THE CNS AND HEART

P04.07 Anne Sofie Brems-Eskildsen. ALTERNATIVE SPLICING IN BLADDER CANCER

P04.08 Torben H. Thygesen. SPATIAL AND TEMPORAL ASSESSMENT OF OROFACIAL SOMATOSENSORY SENSITIVITY: A METHODOLOGICAL STUDY

P04.09 Ann Suhl Kristensen. THE STRUCTURE OF ANXIETY SYMPTOMS – AN INVESTIGATION OF DIMENSIONAL SUBTYPES OF ANXIETY AND OF THE RELATIONSHIP BETWEEN SYMPTOM SUBTYPES AND AETIOLOGICAL FACTORS

P04.10 Rasmus Beedholm . INVESTIGATION OF THE RECEPTOR-MEDIATED ENDOCYTOSIS OF TRANSCOBALAMIN/INTRINSIC FACTOR-VITAMIN B12 COMPLEXES

Poster session 05. Chairmen: Per Klausen Fink, Jørgen Frøkiær

P05.01 Thomas Holm Pedersen. REPETITIVE FIRING OF ACTION POTENTIALS SHIFTS THE EXCITABILITY OF RAT MUSCLES VIA A REDUCTION IN THE RESTING CL- CONDUCTANCE

P05.02 Manhai Long. DIOXIN-LIKE ACTIVITIES IN BLOOD ACROSS EUROPEAN AND INUIT POPULATIONS

P05.03 Britta Hørdam. CLINICAL RESEARCH – NURSING INTERENTION: DYSFUNCTION AND GENERAL HEALTH STATUS OF PATIENTS OVER 65 YEARS UNDERGOING TOTAL HIP-REPLACEMENT

P05.04 Martin Eivindson. LOW INSULIN-LIKE GROWTH FACTOR-I (IGF-I) AND IGF BINDING PROTEIN-3 LEVELS IN ACTIVE ULCERATIVE COLITIS AND CROHN’S DISEASE: PARTIAL NORMALIZATION DURING PREDNISOLONE TREATMENT

P05.05 Mette Ebbesen. WHICH BIOETHICAL PRINCIPLES SHOULD BE USED WITHIN BIOMEDICINE?

P05.06 Louise Henriette Pedersen. PHARMACOLOGICAL CHARACTERISATION OF A PLACE ESCAPE / AVOIDANCE PARADIGM (PEAP) IN RATS WITH NEUROPATHIC PAIN

P05.07 Søren Kildeberg Paulsen. GROWTH HORMONE (GH) SUBSTITUTION IN GH DEFICIENT PATIENTS INHIBITS 11Β-HSD1 MRNA EXPRESSION IN ADIPOSE TISSUE

P05.08 Mette Krintel Petersen. EFFICACY OF MULTIMODAL, INTERDISCIPLINARY INTERVENTION AFTER TOTAL HIP ARTHROPLASTY: A PROSPECTIVE, RANDOMISED CONTROLLED TRIAL

P05.09 Mahmoud Ashkanian. HYPEROXIA- AND HYPERCAPNIA-INDUCED CHANGES OF CBF AND CMRO2 IN ISCHEMIC PENUMBRA

P05.10 Grete Moth. ORGANIZATION AND COST-EFFECTIVENESS OF CARE OF SCHOOL- AGE CHILDREN WITH ASTHMA: A REGISTER-BASED STUDY

Poster session 06. Chairmen: Albert Gjedde, Niels Gregersen

P06.01 Peter Brynningsen. IMPROVED NUTRITIONAL STATUS IN ELDERLY PATIENTS 6 MONTHS AFTER ISCHEMIC STROKE

P06.02 Kenneth Jensen. DO SMOKERS REALLY HAVE MORE FUN?

P06.03 Gitte Juhl. SENSITIZATION PHENOMENA AFTER THIRD MOLAR SURGERY: A QUANTITATIVE SENSORY TESTING STUDY

P06.04 Louise Gyldensted. PERFUSION-WEIGHTED MAGNETIC RESONANCE IMAGING IN ALZHEIMER’S DISEASE AND MILD COGNITIVE IMPAIRMENT

P06.05 Lone Bruhn Madsen. ANIMAL MODELS FOR HUMAN NEURODEGENERATIVE DISEASES

P06.06 Mette Asbjørn Neergaard. CANCER PALLIATION IN PRIMARY CARE –WHAT IS GOOD AND BAD?

P06.07 Mette Underbjerg Dyrskog. PRENATAL ALCOHOL EXPOSURE: NEUROPSYCHOLOGICAL FUNCTIONS AT AGE 5 – WITH PARTICULAR REFERENCE TO ATTENTION

P06.08 Allan Carle´. A POPULATION-BASED STUDY OF THYROID AUTO-ANTIBODIES IN OVERT HYPOTHYROIDISM

P06.09 Vibeke Sejer Hansen. GENDER DIFFERENCES IN HIPPOCAMPAL ATROPHY IN EPILEPSY

P06.10 Hanne Stubbe Teglbjærg. EXPRESSIVE ARTS THERAPY FOR SCHIZOPHRENIA, A QUALITATIVE RESEARCH OF A FENOMENOLOGICAL BASED TREATMENT IN A LOCAL PSYCHIATRIC CENTER

Poster session 07. Chairmen: Cai Grau, Peter Hokland

P07.01 Bo Eskerod Madsen. SEARCHING FOR INTERACTING GENETIC VARIANTS THAT PREDISPOSE FOR DISEASES OR RESPONSE TO TREATMENT

P07.02 Bente Høy. SELF-CARE AS A HEALTH RESOURCE OF THE ELDERLY

P07.03 Mette Søgaard. SHORT- AND LONG-TERM PROGNOSIS OF COMMUNITY- ACQUIRED BACTERAEMIA IN PATIENTS ADMITTED TO MEDICAL DEPARTMENTS IN NORTH JUTLAND COUNTY

P07.04 Pia Pinholt Madsen. MIS-CLASSIFICATION OF MISSENSE, NONSENSE AND SILENT MUTATIONS – CODING REGION MUTATIONS MAY INSTEAD CAUSE ABERRANT MRNA SPLICING

P07.05 Mia Færch. CHARACTERIZATION OF A MUTANT V2 RECEPTOR ASSOCIATED WITH PARTIAL CONGENITAL NEPHROGENIC DIABETES INSIPIDUS

P07.06 Him Shing Ng. VISUAL VALIDATION OF EMBOLI DETECTION USING DOPPLER ULTRASOUND AND WAVELET TRANSFORMATION

P07.07 Marianna Lalla. AN EXPERIMENTAL HYPOSPADIA REPAIR IN RABBITS: A BIOMECHANICAL STUDY OF THE URETHRA

P07.08 Andreas Schröder. HOW TO DEFINE CRITERIA FOR SEVERE SOMATIZATION FOR A INTERVENTION STUDY IN TERTIARY CARE

P07.09 Anne Toftegaard Funding. MITOGEN- AND STRESS- ACTIVATED PROTEIN KINASE 1 IS ACTIVATED IN LESIONAL PSORIATIC EPIDERMIS S

P07.10 Hanne Busk Andersen. OPTIMIZATION OF CULTURE METHODS; CORD BLOOD DERIVED MASTCELLS

Poster session 08. Chairmen: Henning Grønbæk, Per Høllsberg

P08.01 Mett Marri Lægsgaard Madsen. ATTITUDES TOWARDS PSYCHIATRIC GENETIC RESEARCH AND TESTING: FEARS, HOPES, AND INTENTIONS

P08.02 Jette Ammentorp. COMMUNICATION IN HEALTH CARE – CAN IT BE IMPROVED ?

P08.03 Anna Mrowiec. THE NBCN1 PROTEIN EXPRESSION IS INCREASED THROUGH DIFFERRENT MECHANISMS IN TWO MODELS OF ENHANCED RENAL DISTAL TUBULAR NH4+ DELIVERY

P08.04 Gang Chen. ANTIVASCULAR THERAPY EVALUATED BY PWI AND DWI

16 P08.05 Tomasz Brudek. HERPES VIRUS ANTIGENS ACTIVATE ENDOGENOUS RETROVIRUSES: IMPLICATIONS FOR MULTIPLE SCLEROSIS

P08.06 Søren Peter Jørgensen. REMISSION-KEEPING AND REMISSION-INDUCING EFFECT OF VITAMIN-D IN CROHNS DISEASE

P08.07 Jonathan Gardi. USING BIASED IMAGE ANALYSIS FOR IMPROVING UNBIASED STEREOLOGIC NUMBER ESTIMATION

P08.08 Mie Wiese Petersen. ACCURACY OF MORPHOLOGICAL CHANGES IN TMJ- TOMOGRAMS WITH THREE IMAGING SYSTEMS

P08.09 Jakob Udby Blicher. EVIDENCE OF SHORT-TERM PLASTICITY IN A STROKE PATIENT, MEASURED BY TRANSCRANIAL MAGNETIC STIMULATION OF THE MOTOR-CORTEX

P08.10 Inge Errebo Agerholm. SEQUENTIAL FISH ANALYSIS USING COMPETITIVE DISPLACEMENT OF LABELED PEPTIDE NUCLEIC ACID PROBES FOR 8 CHROMOSOMES IN HUMAN BLASTOMERES

Poster session 09. Chairmen: Elisabeth Hall, Poul Henning Jensen

P09.01 Helle Terkildsen Maindal. A HEALTH PROMOTION PATIENT EDUCATION PROGRAM FOR SCREEN-DETECTED PATIENTS WITH NEWLY DIAGNOSED TYPE 2 DIABETES, IMPAIRED FASTING GLUCOSE AND IMPAIRED GLUCOSE TOLERANCE

P09.02 Anne Kirkeby Hansen. ELECTIVE CESAREAN SECTIO AND RESPIRATORY MORBIDITY IN THE NEONATAL PERIOD

P09.03 Thomas Dyrsø Jensen. HIGH-RESOLUTION SCREENING OF COLORECTAL CANCER USING ARRAY COMPARATIVE GENOMIC HYBRIDIZATION

P09.04 Charlotte Graugaard-Jensen. REGULATION OF URINE PRODUCTION: DIFFERENCES BETWEEN GENDERS

P09.05 Christina Bak Pedersen. SYNERGISTIC ROLE OF IBD (ACAD8) MUTATIONS AND THE PREVALENT 625G>A SCAD SUSCEPTIBILITY VARIATION IN ELEVATED C4- CARNITINE EXCRETION DETECTED BY MS/MS NEWBORN SCREENING

P09.06 Kari Tanderup. GEOMETRIC STABILITY OF RADIOACTIVE SOURCES DURING RADIATION THERAPY

P09.07 Ole Gade Sørensen. DIFFERENT FIXATION METHODS IN RECONSTRUCTION OF THE ANTERIOR CRUCIATE LIGAMENT

P09.08 Bettina Jørgensen. REPRODUCIBILITY OF MR RENOGRAPHY IN CHILDREN

P09.09 Sigitas Urbonavicius. IDENTIFICATION OF PROTEINS AND PEPTIDES PREDICTING THE NATURAL HISTORY OF ABDOMINAL AORTIC ANEURYSMS

P09.10 Fenghua Chen. PLASTICITY AT THE SYNAPSE: NEURON AND SYNAPSE NUMBER IN THE SUBREGIONS OF RAT HIPPOCAMPUS AFTER IMIPRAMINE TREATMENT

Poster session 10. Chairmen: Kjeld Hermansen, Susanne Keiding

P10.01 Kristian Larsen. EFFICACY OF A PROACTIVE PERIOPERATIVE CARE AND REHABILITATION INTERVENTION IN PATIENTS UNDERGOING PRIMARY TOTAL HIP OR KNEE REPLACEMENT

P10.02 Jeppe Sylvest Nielsen. ACTIVATED PROTEIN C’S ANTI-INFLAMMATORY EFFECTS ON ACUTE ENDOTOXEMIC PIGS

P10.03 Maciej Bogdan Maniecki. NEW PROTEINS INVOLVED IN THE IRON METABOLISM – STUDY OF HEPCIDIN IN RELATION TO FUNCTION, EXPRESSION AND SHEDDING OF CD163

P10.04 Anne Barklin. INFLAMMATORY RESPONS TO BRAIN DEATH. A PORCINE EXPERIMENTAL STUDY

P10.05 Vivian Langagergaard. BIRTH OUTCOME IN WOMEN WITH BREAST CANCER

P10.06 Susanne Maigaard Axelsen. UROGYNECOLOGIC DYSFUNCTION AFTER RADICAL HYSTERECTOMY

P10.07 Karsten Bork Nielsen. GENE EXPRESSION IN THE DEVELOPING PIG BRAIN

P10.08 Hanne Lou. LONG-TERM IMPACT OF EXTREMELY PREMATURE CHILDBIRTH. PARENTS´ EXPERIENCES WHEN THE CHILDREN REACH SCHOOL AGE

P10.09 Thomas Munk Laursen. EXCESS MORTALITY ASSOCIATED WITH PSYCHIATRIC ADMISSION

P10.10 Golnosh Bahrami. RISK INDICATORS FOR MARGINAL BONE LOSS IN THE INDIVIDUAL

Poster session 11. Chairmen: Vibeke Hjortdahl, Torben Laursen

P11.01 Stig Storgaard Jakobsen. PROSTHESES SURFACES GENERATE AN INFLAMMATORY RESPONSE

P11.02 Sophie de Seigneux. IMPORTANCE OF ALDOSTERONE IN SODIUM RETENTION AND SODIUM TRANSPORTERS DYSREGULATIONS IN PUROMYCIN INDUCED NEPHROTIC SYNDROME

P11.03 Ole Mathiassen. FOREARM PLETHYSMOGRAPY IN THE ASSESSMENT OF VASCULAR RESISTANCE: NEW METHODOLOGICAL INSIGHTS

18 P11.04 Jesper Noer Petersen. PSYCHOSOCIAL, FUNCTIONAL AND AESTHETIC PERSPECTIVES IN ORTHOGNATHIC SURGICAL TREATMENT OF JAWANOMALIE

P11.05 Niels Hjort. ARE MRI-BASED PREDICTIVE MODELS COMPARABLE AMONG STROKE CENTERS?

P11.06 Joanna Wieclaw. OCCUPATIONAL RISK OF DEPRESSION AND STRESS IN THE DANISH WORK FORCE

P11.07 Stig Åvall Severinsen. 2,3-DIHYDROXYBENZOIC ACID ATTENUATES KANAMYCIN- INDUCED VOLUME REDUCTION IN MOUSE UTRICULAR TYPE I HAIR CELLS

P11.08 Kirsten Ejskjær. INCREASED EXPRESSION OF THE EPIDERMAL GROWTH FACTOR SYSTEM IN ENDOMETRIOID ENDOMETRIAL CANCER COMPARED TO HEALTHY ENDOMETRIUM.

P11.09 Birgit Drews. IMPROVING MOTIVATION AND GOAL SETTING FOR RETURN TO WORK IN A POPULATION ON SICK LEAVE: A CONTROLLED STUDY

P11.10 Lasse Solskov Jensen. METFORMIN ACTIVATES AMP-ACTIVATED PROTEIN KINASE (AMPK) IN THE RAT HEART AND REDUCES MYOCARDIAL INFARCT SIZE 24 HOURS LATER

Poster session 12. Chairmen: Arvid Maunsbach, Therese Ovesen

P12.01 Ditte M. S. Lundvig. P25α - A NOVEL MOLECULAR LINK TO DEMYELINATING DISORDERS

P12.02 Bettina S. Nedergaard. QUANTITATIVE STUDIES OF THE CELLULAR IMMUNE RESPONSE IN CANCER

P12.03 Hanne Kronborg. BREASTFEEDING AND EARLY BONDING: A RANDOMISED COMMUNITY BASED TRIAL

P12.04 Morten Krag. GROWTH HORMONE TENDED TO INCREASE INTRAMYOCELLULAR TRIGLYCERIDE IRRESPECTIVE OF AMBIENT FREE FATTY ACID LEVELS

P12.05 Lars Gormsen. DOSE-RESPONSE EFFECTS OF FREE FATTY ACIDS ON INSULIN SENSITIVITY IN HUMANS

P12.06 Mandana Ghisari. IMPACT OF ENVIRONMENTAL CHEMICALS ON THE THYROID HORMONE FUNCTION IN PITUITARY RAT GH3 CELLS

P12.07 Jeanne Elisabeth Debess. COGNITIVE FUNCTION AMONG WOMEN WITH BREAST CANCER IN RELATION TO ADJUVANT THERAPY

P12.08 Josefine Gradman. KNEMOMETRIC ASSESSMENT OF SHORT TERM GROWTH IN CHILDREN WITH ECZEMA TREATED WITH TOPICAL MOMETASONE FUROATE AND TACROLIMUS

P12.09 Morten Sig Ager Jensen. MODERATE AGREEMENT BETWEEN CLINICAL ECG INTERPRETATION AND MINNESOTA CODING

P12.10 Anne Birgitte Als. MOLECULAR PROGNOSTIC MARKERS FOR SURVIVAL AFTER CHEMOTHERAPY IN ANDVANCED BLADDER CANCER

Poster session 13. Chairmen: Jens Otto Lunde Jørgensen, Jesper Vuust Møller

P13.01 Karsten Zieger. CHARACTERISING GENOMIC CHANGES IN SUPERFICIAL BLADDER CANCER

P13.02 Hanne Aagaard. NURSING AND CARING OF PREMATURE INFANTS

P13.03 Marianne Kyndi. PREDICTIVE MARKERS OF RESPONSE TO ADJUVANT RADIOTHERAPY IN HIGH-RISK BREAST CANCER

P13.04 Lene Unmack Larsen. FETAL CARDIAC EJECTION FRACTION ASSESSED FROM 4D ULTRASOUND: SPATIO TEMPORAL IMGAE CORRELATION AND VOLUME CALCULATION

P13.05 Birgitte Oxlund-Mariegaard. IS PRETERM DELIVERY ASSOCIATED WITH A CONSTITUTIONAL DECREASE IN THE MECHANICAL COMPETENCE AND COLLAGEN CONCENTRATION OF THE CERVICAL CONNECTIVE TISSUE?

P13.06 Henriette Schou Hansen. PREDICTORS OF THE COURSE OF FUNCTIONAL DIASESE IN GENERAL PRACTICE – PREVENTION OF CHRONICITY

P13.07 Tanja Krüger. XENOANDROGENIC ACTIVITIES IN SERUM ACROSS EUROPEAN AND INUIT POPULATIONS

P13.08 Søren Rytter. KNEE DISORDERS AMONG A DANISH COHORT OF FLOOR LAYERS

P13.09 Donata Cibulskyte. FUNCTIONAL AND STRUCTURAL RENAL EFFECTS OF CICLOSPORIN A IN A PIG MODEL

P13.10 Naja Becher. MMP-9 AND MMP-8 ACTIVITY IN THE CERVICAL MUCUS PLUG AT TERM OF PREGNANCY

Poster session 14. Chairmen: Jørn Koch, Anne Møller-Larsen

P14.01 Marianne Ingerslev Holt. STEREOTACTIC BODY RADIOTHERAPY FOR LIVER TUMORS

P14.02 Lars H. Pedersen. PHARMACOLOGICAL TREATMENT OF DEPRESSION IN PREGNANCY

P14.03 Randi Abrahamsen. EFFECT OF HYPNOSIS IN TREAMENT OF OROFACIAL PAIN IN A NEUROBIOLOGICAL PERSPECTIVE

P14.04 Steffen Lund Hokland. ASSESING THE EFFICACY OF THE NEW VASCULAR TARGETING AGENT – OXI 4503 – IN COMBINATION WITH MODERATE HYPERTHERMIA – A PRELIMINARY STUDY

P14.05 Samuel Alberg Kock. MOTIONAL EFFECT ON WALL SHEAR STRESSES IN A COMPUTATIONAL FLUID DYNAMICS MODEL OF THE COMMON CAROTID ARTERY

P14.06 Bente Martinsen. PERMANENT DEPENDENCE ON OTHERS DURING MEALS. A PHENOMENOLOGICAL STUDY OF PATIENTS’ EXPERIENCES

P14.07 Lone Duval. ADOPTIVE IMMUNOTHERAPY WITH ALLOGENEIC, CYTOTOXIC, HLA-A2 RESTRICTED T-LYMPHOCYTES TRANSDUCTED WITH A MART-1 RECEPTOR-ENCODING GENE: A PHASE I STUDY IN MELANOMA

P14.08 Hanne Birke Sørensen. FREE JEJUNAL FLAPS FOR OESOPHAGUS RECONSTRUCTION: METABOLISM AND MONITORING USING MICRODIALYSIS

P14.09 Birgitte Mahler. THE CIRCADIAN RHYTHM OF URINE OUTPUT IN INFANTS. UNIVERSITY OF AARHUS GRADUATE SCHOOL OF HEALTH SCIENCES, 13 JANUARY 2006

P14.10 Jesper Kelsen. PARECOXIB IS NEUROPROTECTIVE IN SPONTANEOUSLY HYPERTENSIVE RATS AFTER TRANSIENT MIDDLE CEREBRAL ARTERY OCCLUSION

Poster session 15. Chairmen: Michael Rehling, Jens Randel Nyengaard

P15.01 Gitte Jacobsen. TRENDS IN EXPOSURE AND RESPIRATORY SYMPTOMS IN THE DANISH WOOD WORKING INDUSTRY

P15.02 Tina Senholt Videbæk. CIRCUMFERENTIAL FUSION IMPROVES LONG-TERM OUTCOME IN COMPARISON TO INSTRUMENTED POSTEROLATERAL FUSION

P15.03 Karen-Marie Pedersen. FROM GENE TO FUNCTION: CONDITIONAL KNOCKOUT OF FOUR DIFFERENT SPLICE VARIANTS OF THE MURINE SORCS1 GENE

P15.04 Mette Ørskov Sjøland. MIGRATION PATTERNS IN TWO TYPES OF CEMENTED HIP PROSTHESES – A CLINICAL INTERVENTION STUDY

P15.05 Mette Drasbek. INHIBITING THE ADHESION OF MYCOPLASMA PNEUMONIAE TO HEP-2 CELLS

P15.06 Morten Ølgaard Jensen. THE EFFECT OF MITRAL ANNULOPLASTY RINGS ON MITRAL VALVE 3D GEOMETRY AND STRESS DISTRIBUTION

P15.07 Jacob Fog Bentzon. SMOOTH MUSCLE CELLS OF ATHEROSCLEROTIC PLAQUES ARE DERIVED FROM THE LOCAL VESSEL WALL IN APOLIPOPROTEIN E- DEFICIENT MICE

P15.08 Jian Li. CHROMOSOMAL IMBALANCES MAPPED BY ARRAY-BASED COMPARATIVE GENOMIC HYBRIDIZATION IN AN INTEGRATED APPROACH TO COMBAT BREAST CANCER IN DENMARK

P15.09 Agata Baczynska. PREVALENCE OF MYCOPLASMA HOMINIS INFECTIONS AMONG INFERTILE WOMEN AND WOMEN UNDERGOING INDUCED TERMINATION OF THE PREGNANCY

P15.10 René Christiansen. PERIAPICAL BONE HEALING AFTER APICECTOMY WITH AND WITHOUT RETROGRADE ROOT FILLING

Poster session 16. Chairmen: Anders Nykjær, Frede Olesen

P16.01 Birgit E. Bonefeld. SELECTION OF STABLY EXPRESSED REFERENCE GENES FOR NORMALIZATION OF QPCR DATA OBTAINED FROM BRAIN TISSUE FROM THE GENETIC ANIMAL MODEL OF DEPRESSION, THE FLINDERS RATS

P16.02 Thomas Dissing. EXPERIMENTAL UNILATERAL URETEROBSTRUCTION IN THE LATE PART OF THE NEPHROGENESIS PERIOD

P16.03 Ramkumar Menon. ETHNIC CHARACTERIZATION OF CANDIDATE GENES FOR SPONTANEOUS PRETERM DELIVERY

P16.04 Mads Heilskov Rasmussen. EPIGENETIC DETERMINANTS OF ONCOGENE ACTIVATION

P16.05 Kirsten Pugdahl. SENSORY NERVE INVOLVEMENT IN ALS - FREQUENCY EVALUATED IN A EUROPEAN MULTICENTER STUDY

P16.06 Pernille Bøttger. CELLULAR DOWN-REGULATION OF THE TYPE III SODIUM- DEPENDENT INORGANIC PHOSPHATE TRANSPORTER, PIT2, IN RESPONSE TO HYPERPHOSPHATEMIC CONDITIONS

P16.07 Thomas Lind-Hansen. STABILITY AND HEALING IN PROXIMAL TIBIAL OPEN WEDGE OSTEOTOMI IN THE TREATMENT OF UNICOMPARTMENTAL OSTEOARTHRITIS. A SERIES OF CLINICAL AND BIOMECHANICAL STUDIES.

P16.08 Mette Stylsvig. A PROSPECTIVE INVESTIGATION OF NEUROPSYCHOLOGICAL IMPAIRMENT AFTER TRAUMATIC BRAIN INJURY IN CHILDREN AND ADOLESCENTS

P16.09 Charlotte Christie Petersen. T-CELL-MEDIATED IMMUNITY IN PATIENTS WITH LEUKEMIA DURING HCMV REACTIVATION

22 P16.10 Mette Slot Nielsen. ENCAPSULATED CELL BIODELIVERY OF NGF TO THE BASAL FOREBRAIN IN THE GÖTTINGEN MINIPIG

Poster session 17. Chairmen: Svend Juul, Erling Bjerregaard Pedersen

P17.01 Nicoline Marie Hall. ACTIVITY IN MEDIAL PARIETAL AREAS DURING MENTAL IMAGERY IS INDEPENDENT OF RETRIEVAL INTENTIONALITY: A PET STUDY ON INVOLUNTARY AND VOLUNTARY EPISODIC MEMORY

P17.02 Eduardo Castrillon. INFLUENCE OF ORAL CONTRACEPTIVES ON GLUTAMATE- EVOKED PAIN AND PRESSURE PAIN IN MASSETER MUSCLE

P17.03 Erik Elgaard Sørensen. NURSING MANAGEMENT

P17.04 Sune Straszek. ACOUSTIC RHINOMETRY: A DIFFERENT APPROACH TO MEASURING CHANGES IN AIRWAY GEOMETRY. UNIVERSITY OF AARHUS GRADUATE SCHOOL OF HEALTH SCIENCES, 13 JANUARY 2006

P17.05 Isa Niemann. RECURRENT MOLAR EVENTS – REPETITIVE OR RETAINED?

P17.06 Jolanta Hansen. SAFETY AND EFFICACY OF COMPUTED TOMOGRAPHY

P17.07 Martin Roelsgaard Jakobsen. SENSITIVE HIV-1 GENOTYPE METHOD VALIDATING VIRAL RESISTANCE FROM PATIENTS WITH A LOW VIRAL LOAD

P17.08 Louise Østergaard Petersen. HYPOXIA-INDUCED ENDOTHELIAL DYSFUNCTION IN HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS

P17.09 Kristin Skogstrand. SIMULTANEOUS DETERMINATION OF 25 INFLAMMATORY MARKERS AND NEUROTROPHINS IN NEONATAL DRIED BLOOD SPOTS BY IMMUNOASSAY

P17.10 Kirstine Stochholm. THE INCIDENCE OF GROWTH HORMONE DEFICIENCY – A NATIONWIDE STUDY

Poster session 18. Chairmen: Finn Skou Pedersen, Henrik Schønheyder

P18.01 Niels Christian Bjerregaard. DETECTION OF COLORECTAL NEOPLASIA IN SYMPTOMATIC DANISH OUTPATIENTS WITHOUT VISIBLE RECTAL BLEEDING: VALIDITY OF FAECAL OCCULT BLOOD TEST

P18.02 Lars Kroløkke Hviid. REMITTED DEPRESSED PATIENTS, VISUOSPATIAL MEMORY AND CBF IN THE RIGHT HIPPOCAMPUS

P18.03 Torsten Munch-Hansen. SATISFACTION WITH PSYCHOSOCIAL WORK CONDITIONS AND SICKNESS ABSENCE

23 P18.04 Thorbjørn H. Mikkelsen. CANCER REHABILITATION WITH PARTICULAR FOCUS ON THE PRESENT AND FUTURE ROLE OF GENERAL PRACTICE – RESULTS FROM A QUALITATIVE STUDY

P18.05 Lotte Ebdrup. DOES ATORVASTATIN AFFECT THE SYSTEMIC INFLAMMATORY RESPONSE SYNDROME (SIRS) ELICITED BY ENDOTOXIN IN PIGS?

P18.06 Line Bille Madsen. DOES TELEMONITORING OF HOME BLOOD PRESSURE IMPROVE BLOOD PRESSURE CONTROL IN HYPERTENSION?

P18.07 Christian Wejse. A CLINICAL SCORE SYSTEM FOR MONITORING TB TREATMENT IN A LOW RESSOURCE SETTING

P18.08 Kim Mouridsen. BAYESIAN ESTIMATION OF PERFUSION PARAMETERS BASED ON A PHYSIOLOGICAL MODEL FOR THE VASCULATURE

P18.09 Susanna Deutch. BROAD-RANGE REAL-TIME PCR AND DNA-SEQUENCING FOR THE DIAGNOSIS OF BACTERIAL MENINGITIS

P18.10 Karen Madsen. DEVELOPMENT OF A CLASSIFICATION AND GRADING SYSTEM FOR SPONDYLARTHROPTHY WITH MRI

Poster session 19. Chairmen: Erik Berg Schmidt, Hans Stødkilde-Jørgensen

P19.01 Dea Kehler. EVALUATION OF THE PREVENTIVE CARDIOVASCULAR CONSULTATION IN GENERAL PRACTICE

P19.02 Thomas Jakobsen. TOPICAL BISPHOSPHONATE TREATMENT INCREASES FIXATION OF IMPLANTS INSERTED WITH BONE COMPACTION. 12 WEEKS CANINE STUDY

P19.03 My Svensson. OMACOR AS SECONDARY PREVENTION AGAINST CARDIOVASCULAR EVENTS IN PATIENTS UNDERGOING CHRONIC HEMODIALYSIS: A RANDOMISED, PLACEBO CONTROLLED INTERVENTION STUDY

P19.04 Ljubica Vukelic Andersen . ACUTE UPPER LIMB ISCHEMIA AND ATRIAL FIBRILLATION/-FLUTTER IN DENMARK FROM 1990 TILL 2002

P19.05 Rie Stokholm. BONE REACTION AROUND IMMEDIATE LOADED IMPLANTS – ANIMAL EXPERIMENTAL STUDY

P19.06 Søren Hagstrøm. THE EFFECT OF SLEEP ON NOCTURNAL URINE OUTPUT

P19.07 Jesper Stentoft. MINIMAL RESIDUAL CORE BINDING FACTOR AMLS BY REAL TIME QUANTITATIVE PCR – INITIAL RESPONSE TO CHEMOTHERAPY PREDICTS EVENT FREE SURVIVAL AND CLOSE MONITORING OF PERIPHERAL BLOOD UNRAVELS THE KINETICS OF RELAPSE

24 P19.08 Louise Sørensen. A ROLE FOR TOLL-LIKE RECEPTOR (TLR)-2 AND -9 IN ANTIVIRAL IMMUNITY AGAINST HERPES SIMPLEX VIRUS

P19.09 Martin C. Sassen. CYCLOSPORINE TREATMENT IS ASSOCIATED WITH INCREASED Α-ENAC EXPRESSION AND SODIUM RETENTION IN RATS

P19.10 Anders Bergström. STRESS AND ANTIDEPRESSANT RESISTANCE IN THE CHRONIC MILD STRESS ANIMAL MODEL OF DEPRESSION

Poster session 20. Chairmen: Ulf Simonsen, Peter Svensson

P20.01 Puk Sandager. PREDICTION OF PRETERM BIRTH

P20.02 Frederikke Rosendal. EVALUATION OF THE SUBTHALAMIC CONNECTIVITY IN THE GÖTTINGEN MINIPIG AND APPLAYING DIFFUSION TENSOR IMAGING TO THE MINIPIG MODEL. SPECIAL EMPHASIS ON PARKINSON DISEASE

P20.03 Martin Tolstrup. CYSTEINE 138 MUTATION IN HIV-1 NEF FROM PATIENTS WITH DELAYED DISEASE PROGRESSION

P20.04 Lise Gormsen. PAIN THRESHOLDS DURING AND AFTER TREATMENT OF SEVERE DEPRESSION WITH ELECTROCONVULSIVE THERAPY

P20.05 Mikkel Lyngholm . LIMBAL CORNEAL STEM CELL INSUFFICIENCY- CLINICAL AND EXPERIMENTAL STUDIES

P20.06 Jakob Hansen. EXPRESSION OF PROTEIN QUALITY CONTROL GENES IN CELL MODELS OF SPASTIC PARAPLEGIA.

P20.07 Sanne Angel. TO GET ON WITH YOUR LIFE AFTER A MAJOR CHANGE. A QUALITATIVE STUDY OF HOW THE SPINAL CORD INJURY PATIENT RECREATE MEANING DURING THE LONG REHABILITATION PERIOD TOWARDS A CHANGED LIFE

P20.08 Per Borghammer. PARKINSON’S DISEASE: CEREBRAL METABOLISM EVALUAED BY [15O] OXYGEN AND [15O] WATER POSITRON EMISSION TOMOGRAPHY (PET)

P20.09 Henrik Pedersen. REAL-TIME CORRECTION OF RESPIRATORY MOTION FOR IMPROVING MR MYOCARDIAL PERFUSION IMAGING

P20.10 Vibeke Koudahl. THE EFFECT OF ERYTHROPOIETIN ON WOUND HEALING

Poster session 21. Chairmen: Kristian Stengaard-Pedersen, Poul Thorsen

P21.01 Jesper Frandsen. REGULARIZATION OF DIFFUSION TENSOR FIELDS

P21.02 Ole Ingemann Hansen. PRESENTATION OF THE WESTERN DANISH SEXUAL ASSAULT CENTER

P21.03 Jacob Koefoed-Nielsen. A METHOD TO EXPERIMENTALLY INDUCE SOLITARY LOBE ATELECTASIS

P21.04 Anelia Larsen. OCCUPATIONAL PSYCHIATRY: MENTAL DDISORDERS IN A DANISH WORKING POPULATION

P21.05 Malene Herbsleb. IDENTIFICATION OF NEW TRANSCRIPTIONAL CORRELATIONS IN CANCER USING ARRAY DATABASES AND FUNCTIONAL IN VITRO STUDIES

P21.06 Mette Spliid Ludvigsen. PATIENT LIFE. A NURSING STUDY BASED ON ETHNOGRAPHIC METHODOLOGY OF INFORMAL RELATIONSHIPS BETWEEN PATIENTS DURING HOSPITALISATION AT A SURGICAL GASTROENTEROLOGICAL DEPARTMENT IN DENMARK

P21.07 Michael Sørensen. DYNAMIC 18F-LABELED GALACTOSE PET AS A MEASURE OF REGIONAL LIVER FUNCTION IN PIGS

P21.08 Rikke Riber-Hansen. THE OPTIMAL NUMBER OF SENTINEL LYMPH NODES IN MALIGNANT MELANOMA WHEN EXTENSIVE HISTOPATHOLOGICAL EXAMINATION IS APPLIED

P21.09 Signe Engkjær Christensen. THE CALCIUM-CREATININE CLEARANCE RATIO (CCCR) IS INSUFFICIENT IN SEPARATING FAMILIAL HYPOCALCIURIC HYPERCALCAEMIA (FHH) FROM PRIMARY HYPERPARATHYROIDISM (PHPT)

P21.10 Tina Aaen Geest. GENERAL PRACTITIONERS ROLE IN HELPING PATIENTS TO COPE WITH CANCER

Poster session 22. Chairmen: Kjeld Søballe, Ann Wenzel

P22.01 Christine Petersen. P25Α INDUCES Α-SYNUCLEIN-DEPENDENT TOXICITY IN CELLULAR MODELS OF NEURODEGENERATIVE DISORDERS

P22.02 Kristian Otkjær Nielsen. THE P38 MAPK IS A KEY REGULATOR OF IL-20 EXPRESSION IN HUMAN KERATINOCYTES

P22.03 Thomas Harbo. SYMPTOMS AND SIGNS OF NEUROPATHY IN A LONG-TERM FOLLOW-UP OF PATIENTS WITH CHRONIC INFLAMMATORY DEMYELINATING POLYRADICULONEUROPATHY

P22.04 Mogens Stender. VENOUS THROMBOEMBOLISM AND HAEMOSTATIC ALTERATIONS IN PATIENTS WITH COLORECTAL CANCER – EFFECT OF RADIATION THERAPY

P22.05 Vibeke Hvidberg. IDENTIFICATION OF THE RECEPTOR SCAVENGING HEMOPEXIN- HEME COMPLEXES

26 P22.06 Jakob Nielsen. DECREASED RESPONSE TO ALDOSTERONE IN KIDNEY CORTICAL COLLECTING DUCT IN RATS WITH LITHIUM-INDUCED NEPHROGENIC DIABETES INSIPIDUS .

P22.07 Maik Stiehler. OPTIMIZING VIRAL AND NON-VIRAL GENE TRANSFER METHODS FOR GENETIC MODIFICATION OF MESENCHYMAL STEM CELLS

P22.08 Anne Fredsted. THE CAUSE OF MUSCLE DAMAGE: MECHANICAL STRAIN OR CELLULAR CALCIUM OVERLOAD?

P22.09 Philippe Lamy. GENOTYPING AND ANNOTATION OF AFFYMETRIX SNP PROBE SETS

P22.10 Elena V Bouzinova. THE NA+ DEPENDENT HCO3- UPTAKE INTO THE RAT CHOROID PLEXUS EPITHELIUM IS PARTIALLY DIDS-SENSITIVE

Poster session 23. Chairmen: Per Vestergaard, Lars Østergaard

P23.01 Søren Aagaard. THE IMPACT OF REMOTE PRECONDITIONING ON MYOCARDIAL STUNNING IN PIGS

P23.02 Jens Rolighed. ASPECTS OF ANESTHETIC PRECONDITIONING IN A PORCINE MODEL

P23.03 Nikolaos Karamperis. CHARACTERIZATION OF CALCINEURIN PHOSPHATASE DURING ALLOGRAFT TRANSPLANTATION IN A RAT REJECTION MODEL

P23.04 Henriette Nørmølle Buttenschøn. THE GLUTAMATE DECARBOXYLASE GENE 1 AS A POTENTIAL CANDIDATE GENE FOR AUTISM

P23.05 Signe Gjedde. MUSCULAR MANIFESTATIONS IN HYPOTHYROID PATIENTS

P23.06 Helle Friis Svenstrup. MYCOPLASMA GENITALIUM, CHLAMYDIA TRACHOMATIS AND TUBAL FACTOR INFERTILITY – A PROSPECTIVE STUDY

P23.07 Walther Fledelius. SWARM BASED MEDICAL IMAGE ANALYSIS: APPLIED TO IN- VIVO CORNEAL CONFOCAL MICROSCOPY

P23.08 Alma Becic Pedersen. PATIENT CHARACTERISTICS AND SURVIVAL OF TOTAL HIP ARTHROPLASTIE

P23.09 Mette Nørgaard. SHORT-TERM MORTALITY OF BACTERAEMIA IN ELDERLY PATIENTS WITH HAEMATOLOGICAL MALIGNANCIES

P23.10 Henrik Kold-Petersen. CORONARY ARTERY MYOGENIC RESPONSE IN A MOUSE MODEL OF HYPERTROPHIC CARDIOMYOPATHY AND THE ROLE OF ENDOTHELIN-1

27 Poster session 24. Chairmen: Torsten Lauritzen, Steffen Thiel

P24.01 Majken K. Jensen. GENE-DIET INTERACTIONS IN THE REGULATION OF CHOLESTEROL METABOLISM AND RISK OF ACUTE CORONARY SYNDROME

P24.02 Jacob Tauris. CUBILIN AND MEGALIN EXPRESSION IN THE INNER EAR

P24.03 Simon Buus. INDIVIDUAL RADIATION RESPONSE OF PAROTID GLANDS INVESTIGATED BY DYNAMIC 11C-METHIONINE PET

P24.04 Jesper Karmisholt. QUALITY OF LIFE, BODY COMPOSITION, RESTING ENERGY EXPENDITURE AND LEVEL OG PHYSICAL ACTIVITY IN PATIENTS WITH SUBCLINICAL HYPOTHYROIDISM

P24.05 Ripudaman Singh. HEAT SHOCK PROTEIN 70 GENE IN ASSOCIATION WITH HUMAN LONGEVITY IN DANISH POPULATION

P24.06 Donna Marie Briggs. THE CALCIUM-ACTIVATED CYCLIC-GMP DEPENDENT CHLORIDE CHANNEL CONTRIBUTES TO RAT MESENTERIC RESISTANCE ARTERY VASOMOTION

P24.07 Borja Ballarín-González. DEVELOPMENT OF KNOCK-IN MOUSE MODELS CARRYING AN AKV 1-99 LTR INTO THE N-RAS/UNR LOCUS

P24.08 Xiao-Yue Zhai. RECONSTRUCTION OF MOUSE NEPHRONS

P24.09 Søren Cristensen. THE PHYSIOLOGICAL SIGNIFICANCE OF THE TMAX PARAMETER IN BOLUS TRACKING MRI

P24.10 Peter Michael Kragh . PORCINE BLASTOCYSTS PRODUCED BY HANDMADE CLONING WITH A COMBINED ELECTRICAL AND CHEMICAL ACTIVATION

Poster session 25. Chairmen: Svend Birkelund Andersen, Anders Børglum

P25.01 Mads Vilhelm Hollegaard. METHOD DEVELOPING AND BASIC RESEARCH FOR SNP DETECTION AND FUNCTIONALITY WITH SPECIAL INTEREST IN ASSOCIATIONS TO PRETERM BIRTH

P25.02 Erik Langer Madsen. CHANGES IN ENDOTHELIAL FUNCTION AND ADIPOKINES IN RELATION TO GASTRIC BANDING INDUCED WEIGHT LOSS. A STUDY DESIGN

P25.03 Andrey Azov. POSITION EFFECTS ON GENE EXPRESSION AS STUDIED ON A BALANCED TRANSLOCATION MODEL

P25.04 Maiken Møller-Pedersen. THE PRECISION AND INFLUENCE OF FLEXION FOR BMD MEASUREMENTS OF THE PROXIMAL TIBIA FOLLOWING TOTAL KNEE ARTHROPLASTY. A METHODOLOGICAL DEXA STUDY

P25.05 Yuelian Sun. APGAR SCORES AND LONG-TERM RISK OF EPILEPSY

P25.06 Claus Olesen. DEPHOSPHORYLATION OF THE CALCIUM PUMP COUPLED TO COUNTERION OCCLUSION

P25.07 Anette Jørgensen. HYALURONAN INTRA-ARTICULAR IS WITHOUT LONG-TERM CLINICAL EFFECT IN KNEE OSTEOARTHRITIS (OA). A MULTICENTER, RANDOMIZED, PLACEBO-CONTROLLED DOUBLE-BLIND STUDY OF 335 PATIENTS WITH MODERATE TO SEVERE KNEE OA

P25.08 Birgitte Brandsborg. CHRONIC PAIN FOLLOWING HYSTERECTOMY: A NATIONWIDE STUDY OF CHRONIC PAIN COMBINING QUESTIONNAIRE AND SURGICAL DATA

P25.09 Henriette Nørmølle Buttenschøn. THE GLUTAMATE DECARBOXYLASE GENE 1 AS A POTENTIAL CANDIDATE GENE FOR AUTISM

P25.10 Kai Wang. DEVELOPMENT OF BIOINFORMATICS TOOLS FOR DIAGNOSTIC PROCEDURES INVOLVING ARRAY ANALYSES OF DEGENERATIVE DISEASE PROCESSES

Poster session 26. Chairmen: Michael Væth, Morten Frydenberg

P26.01 Lijin Zou. THE EFFECT OF HYALURONAN ON OSTEOGENESIS OF PORCINE BONE MARROW STROMAL CELLS IN VITRO

P26.02 Mads Vilhelm Hollegaard. METHOD DEVELOPING AND BASIC RESEARCH FOR SNP DETECTION AND FUNCTIONALITY WITH SPECIAL INTEREST IN ASSOCIATIONS TO PRETERM BIRTH

P26.03 Mads Aaboe Jensen. HUMAN TRANSCRIPTION FACTOR SOX4

P26.04 Magdalena Janina Laska. THE ROLE OF GENE RAI IN APOPTOSIS AND CANCER. CULTURES OF LYMPHOCYTES FROM NORMAL AND CANCEROUS INDIVIDUALS

P26.05 Malene Rohr Andersen Dahl. LOWER LEVELS OF ADMA AND INCREASED ENDOTHELIUM-DEPENDENT NO-MEDIATED RELAXATION OF UTERINE SMALL ARTERIES FROM PREGNANT WOMEN

P26.06 Søren Hjortshøj. PREVALENCE OF ISCHEMIA MODIFIED ALBUMIN IN ISCHAEMIC HEART DISEASE

P26.07 Yutao Du. HIGH OVERALL IN VITRO EFFICIENCY OF PORCINE HANDMADE CLONING COMBINING OOCYTE TRISECTION WITH SEQUENTIAL CULTURE

P26.08 Claus Olesen. DEPHOSPHORYLATION OF THE CALCIUM PUMP COUPLED TO COUNTERION OCCLUSION

P26.09 Mette Rylev Agerbæk. IDENTIFICATION OF DOMINANT IMMUNOGENIC BACTERIA AND BACTERIAL PROTEINS IN PERIODONTITIS.

P26.10 Jacob Severinsen. ASSOCIATION ANALYSIS SUGGESTING GPR24 AS A SHARED SUSCEPTIBILITY GENE FOR BIPOLAR AFFECTIVE DISORDER AND SCHIZOPHRENIA

Poster session 27. Chairmen: Thomas Ledet, Thomas Juhl Corydon

P27.01 Esben Buhl. GLUCOCORTICOID RECEPTOR ANTAGONISM REVERSES HEPATIC INSULIN RESISTANCE IN LOW BIRTH WEIGHT RATS DISPLAYING HYPOTHALAMUS-PITUITARY-ADRENAL-AXIS HYPERACTIVITY.

P27.02 Kasper Kyng. GENE EXPRESSION AND DNA DAMAGE RESPONSES IN HUMAN AGING AND PREMATURE AGING SYNDROMES

P27.03 Preben Larsen. MICROBIOLOGICAL PESTICIDES IN GREENHOUSES - A POSSIBLE HEALTH RISK?.

P27.04 Carsten Stengaard. AN ANIMAL MODEL FOR PARTIAL THICKNESS CHONDRAL DEFECTS

P27.05 Anders Husted Madsen. RISK STRATIFICATION AFTER INTRODUCTION OF SENTINEL LYMPH NODE BIOPSY TECHNIQUE

P27.06 Jane Agergaard. DIPHTERIA-TETANUS-PERTUSSIS (DTP) VACCINATION AND CHILD SURVIVAL: RANDOMISED STUDY OF NOT PROVIDING DTP VACCINATION SIMULTANIOUSLY WITH OR AFTER MEASLES VACCINATION (MV)

P27.07 Hanne Heje. PATIENT EVALUATION IN GENERAL PRACTICE

P27.08 Vibeke Guldbrand Rasmussen VALVULAR HEART DISEASE ASSOCIATED WITH THE USE OF ERGOT DOPAMINE AGONISTS IN TREATMENT OF PATIENTS WITH PARKINSON’S DISEASE

P27.09 Reziwanggu Abudula. REBAUDIOSIDE A DIRECTLY STIMULATES INSULIN SECRETION FROM PANCREATIC BETA CELLS: A GLUCOSE-DEPENDENT ACTION VIA INHIBITION OF ATP-SENSITIVE K+-CHANNELS.

P27.10 Mette Møller. DYNAMIC CHANGES OF THE CORTICOSPINAL TRACT AFTER ISCHEMIC STROKE DETECTED BY MRI FIBERTRACKING

P27.11 Niels Juul. ASSOCIATION BETWEEN LEVELS OF ICP AND CPP AND MORTALITY IN PATIENTS WITH SEVERE HEAD INJURIES

P27.12 Thomas Andersen. DALLAS PAIN QUESTIONNAIRE CLASSIFICATION PREDICTS OUTCOME IN LOW BACK PAIN PATIENTS UNDERGOING SPINAL FUSION

30 Additional abstracts, which will not be presented

X01.01 Claus Svane Søndergaard. EVALUATING THERAPEUTIC POTENTIAL OF HUMAN STEM AND PROGENITORS CELLS IN IMMUNODEFICEINT RODENT MODELS OF ACUTE MYOCARDIAL INFACTION

X01.02 Astrid From Frøhlich. EFFECT OF IMPERMEABLE INTERFACES ON APPARENT DIFFUSION COEFFICIENT IN HETEROGENEOUS MEDIA

X01.03 Dorte Kjær. ANTIEPILEPTIC DRUGS, FOLIC ACID AND CONGENITAL ABNORMALITIES: A POPULATION BASED CASE-CONTROL STUDY

X01.04 Esben Hjorth Madsen. ACETYLSALICYLIC ACID AND CLOPIDOGREL. COMPARISON OF METHODS FOR EVALUATING PLATELET RESPONSE AND RESISTANCE IN HEALTHY MEN AND PATIENTS WITH ATHEROSCLEROSIS. PROGNOSTIC SIGNIFICANCE OF RESISTANCE IN PATIENTS WITH ATHEROSCLEROSIS

X01.05 Hanne Krogh Jensen. NO CORRELATION BETWEEN TUMOR-EXPRESSION OF CAIX AND INFILTRATION OF CD57+NK CELLS IN RENAL CELL CARCINOMA

X01.06 Hanne M. Søndergaard. IMPACT OF TYPE 2 DIABETES ON MYOCARDIAL INSULIN SENSITIVITY TO GLUCOSE UPTAKE AND PERFUSION IN PATIENTS WITH CORONARY ARTERY DISEASE

X01.07 Hanne Melgaard Nielsen. FAILURE PATTERN AMONG HIGH-RISK BREAST CANCER PATIENTS RANDOMIZED TO PLUS MINUS POSTMASTECTOMY RADIOTHERAPY

X01.08 Iver Nordentoft. HOW DOES THE HISTONE ACETYLTRANSFERASE PROTEIN TIP60 INFLUENCE THE INSULIN SECRETION CASCADE IN BETA CELLS

X01.09 Kristine C. Tvedegaard. GENETIC MARKERS FOR DEVELOPMENT OF AUTISTIC DISORDER BASED ON MULTIPLEX GENOTYPING

X01.10 Line Petersen. NK-CELL MEDIATED IMMUNITY DURING CYTOMEGALOVIRUS REACTIVATION IN PATIENTS WITH BLOOD MALIGNANCIES

X11.01 Marianne Bjerager. DELAY IN DIAGNOSE AND TREATMENT OF LUNG CANCER

X11.02 Pia Holland Hansen. INCREASED NOCTURNAL LEVELS OF ENDOTHELIN IN PLASMA AND SODIUM IN URINE IN RELATION TO BLOOD PRESSURE AND SEVERITY OF OBSTRUCTIVE SLEEP APNOEA

X11.03 Ruta Kuzminskyte. CEREBRAL RESPONSE PATTERN TO PAIN AND ANTICIPATION OF PAIN IN PATIENTS WITH MULTISYMPTOMATIC FUNCTIONAL DISORDER

X11.04 Stine Johnsen. ABSENCE OF PCOS FEATURES IN HIV-INFECTED WOMEN DESPITE SIGNIFICANT HYPERINSULINEMIA AND TRUNCAL ADIPOCITY

X11.05 Thomas Urban. IMMEDIATE IMPLANT PLACEMENT IN THE MOLAR REGIONS - A RANDOMIZED CLINICALLY CONTROLLED STUDY

X11.06 Trine Madsen. INTRAVENOUS OMEGA-3 FATTY ACIDS AND HEART RATE VARIABILITY IN HAEMODIALYSIS PATIENTS

X11.07 Vanda Turcanova. EXPRESSION OF HERV-K18 ENVELOPE GENE DURING HHV-6B INFECTION

32 Invited Speakers

Prof. Peter C. Agre, MD, Nobel Laureate Vice Chancellor, Science & Technology Professor of Cell Biology Duke University 108A Green Zone, Davison Building DUMC Box 3701 Durham, NC 27710 USA

Dr Fiona Godlee Editor, BMJ BMJ Publishing Group BMA House Tavistock Square London, WC1H 9JR UK

Prof. Tomas Hökfelt Institute for Neurosciences Retzius väg 8, Solna Karolinska Institutet 171 77 Stockholm Sweden

Prof. Seppo Meri Haartman Institute Department of Bacteriology and Immunology University of Helsinki Haartmaninkatu 3 (P.O. Box 21) FIN-00014 University of Helsinki Helsinki Finland

Professor, overlæge, dr.med Torben Veith Schroeder Editor, Journal of the Danish Medical Association (Ugeskrift for Læger) Klinisk Institut for Kirurgi og Anæstesiologi Klinisk Universitetscenter Karkirurgisk afdeling RK 3111, Rigshospitalet Blegdamsvej 9 2100 København Ø

33 Abstracts

Abstracts for oral presentations (O1-O4) and poster sessions (P01-P26)

session. Presenting Abstract number Author

O1.01 Hanne VIRAL AND ATYPICAL BACTERIAL INFECTIONS IN CHILDREN WITH Vebert CYSTIC FIBROSIS. Olesen H.V. Olesen*, L. P. Nielsen§, P. O. Schiotz* *Pediatric Dept. A, Aarhus University Hospital, Skejby Sygehus, DK-8200 Aarhus N, Denmark, § Dept. of Clinical Microbiology, Odense University Hospital, DK-5000 Odense, Denmark Background: Respiratory viral and atypical bacterial infections are associated with pulmonary exacerbations and hospitalisations in cystic fibrosis patients. We wanted to study the impact of such infections on children attending the outpatient clinic. Methods: 75 children were followed for 12 months at regular clinic visits. Routine sputum/laryngeal aspirations were tested with PCR for 7 respiratory viruses. Antibodies against C. pneumoniae, M. pneumoniae and

B. pertussis were measured every 3-4 months. FEV-1, FEF25-75 and specific airway resistance, “viral” symptoms and bacterial culture were recorded. Results: 97 viral and 21 atypical bacterial infections were found. FEV-1 was significantly reduced during viral infection (-12.5%, p=0.048), with the exception of rhinovirus infection. A small change in FEV-1 (-3%) was seen during atypical bacterial infection (p=0.039). Viral and atypical bacterial infections caused no change in type and frequency of bacterial culture. Positive predictive value of “viral symptoms” was low (0.64%). 8 patients received “unnecessary” antibiotics because of viral symptoms. Conclusions: Some viral infections and atypical bacterial infections affect FEV-1 acutely. Viral infections did not precipitate bacterial infection or change of colonisation. Clinical symptoms failed to predict viral infection accurately. Routine surveillance for virus or atypical bacteria seems not to be justified in this patient category.

O1.02 Mette Skytte PROGNOSIS OF OVARIAN CANCER ASSOCIATED WITH VENOUS Tetsche THROMBOEMBOLISM: A NATIONWIDE DANISH COHORT STUDY M.S. Tetsche, M. Nørgaard, L. Pedersen, H.T. Sørensen Dept. of Clinical Epidemiology, Aalborg Hospital, Aarhus University Hospital, Sdr. Skovvej 15, 9000 Aalborg, Denmark Objective: Few data exist on the prognosis of ovarian cancer discovered during or after an episode of venous thromboembolism (VTE). Our aim was to estimate the impact of VTE on survival of ovarian cancer. Materials & Methods: We identified all ovarian cancer patients diagnosed during 1980-2003 in the Danish Cancer Registry and obtained information on hospitalization with VTE in the Danish National Registry. Mortality was

34 determined through the Civil Registration System. The prevalence ratio was calculated as the proportion of patients with a certain stage of ovarian cancer and VTE divided by the proportion of patients with the same stage and no VTE. Survival of ovarian cancer patients who had VTE at the time of or before the cancer were compared with that of all other Danish ovarian cancer patients. We used Cox-regression analysis to compute the mortality rate ratios adjusted for age, stage of disease and calendar period. Results: Of 88 patients who had cancer at the same time as an episode of VTE, 38.6 % (83 patients) had stage IV disease, as compared with 32.1 % of 12,778 control ovarian cancer patients (prevalence ratio, 1.2; 95% confidence interval (CI), 0.9 to 1.6). For 53 patients diagnosed within one year after an episode of VTE 43 % had stage IV disease (prevalence ratio, 1.4; 95 % CI, 1.0 to 1.8). VTE patients had increased mortality compared with control patients. The adjusted mortality ratios were 2.7 (95% CI, 2.0-3.5) for patients with VTE at the time as cancer and 1.2 (95% CI, 0.8-1.7) in patients with VTE within one year before the cancer diagnosis. Conclusion: The prognosis of ovarian cancer is associated with the complication VTE. Ovarian cancer discovered at the same time as venous thromboembolism tends to be at an advanced stage with a poor prognosis.

O1.03 Irene Dige QUANTITATIVE MEASUREMENT OF BACTERIA IN DENTAL BIOFILMS: A PILOT STUDY. I. Dige, J.R. Nyengaard, H. Nilsson, M. Kilian, B. Nyvad. Faculty of Health Sciences, University of Aarhus, 8000 Århus C, Denmark. The purpose of the study was to visualize and quantify the proportion of streptococci relative to other bacteria in initial in-situ grown dental biofilms as a function of time. The hypothesis was that the relative proportion of streptococci decreases with time over the initial 48 hours of dental biofilm formation. Two healthy volunteers were recruited according to the rules of the Ethical Committee. Biofilms were collected on custom-made glass slabs with a surface roughness of 1200 grit. Two slabs were mounted in intra-oral appliances and worn for 6, 12, 24 and 48 hours, respectively. After intra-oral exposure the biofilms were labelled with 16S rRNA-targeted oligonucleotide probes EUB338 (for detection of all bacteria) and STR405 (for detection of streptococci). Specimens were analysed by Confocal Laser Scanning Microscopy. Quantification of EUB338-labelled and STR405- labelled bacteria was performed by stereological tools; an unbiased counting frame and the 2D fractionator. The results showed considerable intra- and inter-individual variation in the bacterial populations at each time interval. Overall there was a 26-73-fold increase in the total number of bacteria and a 21-80-fold increase in the number of streptococci from 6 to 48 hours. The proportion of streptococci relative to total bacteria did not differ markedly over time. These pilot studies have shown that it is possible to visualize and quantify specific bacterial populations over a range of time intervals in in-situ dental biofilms by the use of FISH-techniques and stereological tools. The results suggest that the present stereological sampling conditions are suitable for future studies of biofilm formation. However, due to large biological variations between individuals the total number of test persons in the final study should be around ten.

35 O1.04 Mette DEFICIENCY OF MANNAN-BINDING LECTIN GREATLY INCREASES Møller- SUSCEPTIBILITY TO POST-BURN INFECTION WITH PSEUDOMONAS Kristensen AERUGINOSA. Mette Møller-Kristensen*‡, Eddie Ip*, Lei Shi*, Lakshmi D. Gowda*, Michael R. Hamblin†, Steffen Thiel‡, Jens Chr. Jensenius‡, R. Alan B. Ezekowitz*, Kazue Takahashi*. *Laboratory of Developmental Immunology, Department of Pediatrics, and †Wellman Laboratory of Photomedicine, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 ‡Department of Medical Microbiology and Immunology, University of Aarhus, DK-8000 Aarhus C, Denmark. Burn injury disrupts the mechanical and biological barrier that the skin presents against infection by symbionts like the Pseudomonas aeruginosa, Gram-negative bacteria. A combination of local factors, antimicrobial peptides and resident effector cells form the initial response to mechanical injury of the skin. This is followed by an inflammatory response that includes influx of phagocytes and serum factors, such as complement and the mannose-binding lectin (MBL), which is a broad-spectrum pattern recognition molecule that plays a key role in innate immunity. A growing consensus from studies in humans and mice suggest that lack of MBL together with other comorbid factors predisposes the host to infection. In this study we examined whether MBL deficiency increases the risk of P. aeruginosa infection in a burned host. We found that both wild type and MBL null mice were resistant to a 5% total body surface area burn alone or subcutaneous infection alone with P. aeruginosa. However, when mice were burned then inoculated subcutaneously with P. aeruginosa at the burn site, all MBL null mice died by 42 h from septicemia, while only one third of wild type mice succumbed (p = 0.0005). This result indicates that MBL plays a key role in containing and preventing a systemic spread of P. aeruginosa infection following burn injury and suggests that MBL deficiency in human maybe a premorbid variable in the predisposition to infection in burn victims.

O1.05 Thomas RELATIONSHIP BETWEEN COMBRETASTATIN INDUCED CHANGES Nielsen IN DCEMRI PARAMETERS AND RADIATION RESPONSE IN A MURINE TUMOUR MODEL T. Nielsen1,2, R. Murata1, R.J. Maxwell3, H. Stødkilde-Jørgensen4, L. Østergaard2, M.R. Horsman1 1Dept. of Experimental Clinical Oncology and 2Dept. of Neuroradiology, Aarhus University Hospital, DK-8000 Aarhus C, Denmark; 3Gray Cancer Institute, Northwood, Middlesex HA6 2JR, U.K.; 4 MR Research Center, Aarhus University Hospital, DK-8200 Aarhus N, Denmark Introduction: Combretastatin is a leading vascular disrupting agent in clinical trials that induces tumour vascular damage and necrosis. Dynamic contrast enhanced magnetic resonance imaging (DCEMRI) allows in vivo characterization of tumour vasculature blood flow, vessel permeability, and plasma volume. The purpose of this study was to correlate DCEMRI measurements in a murine tumour after CA4DP treatment with radiation response. Methods: The C3H mammary carcinoma was grown in the right

36 3 rear foot of female CDF1 mice and treated when at 200 mm in size. DCEMRI was performed before and 3 hours after intraperitoneal (i.p.) CA4DP administration at doses from 10 to 250 mg/kg. Radiation response was assessed by treating groups of mice with graded radiation doses. The mice were given either radiation alone or 30 minutes later i.p. injected with

CA4DP. The TDC50 value (the radiation dose producing local tumour control in 50 % of treated animals) was calculated for each of the CA4DP doses. Results: Post treatment DCEMRI values were significantly lower than

pre treatment values at all drug doses except 10 mg/kg. The TCD50 at 25 and 250 mg/kg were significantly different from radiation alone, but at 10 and 100 mg/kg it was not. By both assays no further dose response was seen by increasing the dose above 25 mg/kg. Conclusions: The curve shapes

of TCD50 and the DCEMRI parameters showed the same trend, which indicates that DCEMRI parameters supply information about the underlying mechanism of the CA4DP contribution to the tumour control.

O2.01 Anja Pernille MUTATION OF GLY94 IN TRANSMEMBRANE SEGMENT M1 OF THE + + + + Einholm Na ,K -ATPASE INTERFERES WITH Na AND K BINDING IN E2P CONFORMATION A.P. Einholm, M. Toustrup-Jensen, J.P. Andersen, and B. Vilsen Department of Physiology, University of Aarhus, 8000 Aarhus C, Denmark. The importance of Gly93 and Gly94 in transmembrane segment M1 of the Na+,K+-ATPase for interaction with Na+ and K+ was demonstrated by functional analysis of mutants Gly93Ala and Gly94Ala. Steady-state and transient kinetic measurements of overall and partial reactions were performed using manual mixing or a quench-flow module (QFM-5 or SFM- 400/Q). In the crystal structures of the Ca2+-ATPase, the corresponding residues, Asp59 and Leu60, are located right where M1 bends. Rapid kinetic measurements of K+-induced dephosphorylation allowed + determination of the affinity of the E2P phosphoenzyme intermediate for K . In Gly94Ala, the K+ affinity was reduced 9-fold, i.e., to the same extent as seen for mutation of the cation binding residue Glu329. Furthermore, 94 Gly Ala showed strongly reduced sensitivity of the E1P-E2P equilibrium to + + Na , with accumulation of E2P even at 600 mM Na , indicating that + interaction of E2P with extracellular Na is impaired. On the contrary, in 93 + Gly Ala the affinity for K was slightly increased and the E1P-E2P

equilibrium was displaced in favor of E1P. In both mutants, the affinity of + the cytoplasmically facing sites of E1 for Na was reduced, but this effect 94 was relatively small compared with the effects seen for E2P in Gly Ala. Comparison with Ca2+-ATPase mutagenesis data (Einholm AP, Vilsen B, Andersen JP, J Biol Chem 2004; 279: 15888-15896) suggests that the role of M1 in binding of the transported ions is universal among P-type ATPases, despite the low sequence homology in this region. Structural modeling of Na+,K+-ATPase mutant Gly94Ala indicates that the alanine side chain comes 287 close to Ile of M3, particularly in E2P, thus resulting in a steric clash that may explain the present observations.

O2.02 Ramune EFFECTS OF PARATHYROID HORMONE TREATMENT ON Aleksyniene DISTRACTION OSTEOGENESIS IN THE RABBIT TIBIAL

37 LENGTHENING MODEL R.Aleksyniene, H.Eckardt, K.G.Bundgaard, M.Lind, I.Hvid Otopædkirurgi Nordjylland, Sdr.Skovvej 11, 9000 Aalborg Objectives: The overall purpose of the study is to determine the effects of parathyroid hormone on bone formation in regenerated and surrounding bone of distracted callus during limb lengthening in rabbits. Additionally, the aim of the pilot study is to titrate the optimal dose of PTH (1-34) for distraction osteogenesis treatment in rabbits tibial lengthening model. Materials and methods: in a pilot study 18 rabbits underwent right tibia lengthening by callus distraction. Lenghtening was started 5 days postoperatively 1mm/day for 10 days period. Rabbits were divided into 3 groups: gr. 1-received PTH(1-34) treatment in a dose of 5µg/kg/day, gr. 2- received PTH (1-34) 25 µg/kg/day treatment, gr. 3 rabbits were treated with saline. After sacrifice tibiae of both legs were dissected free, kept frozen and underwent x-ray analysis, DEXA scanning, microcomputed tomography scanning and three-dimensional evaluation. Biomechanical test followed. Results : Pilot study has been performed and the overall results indicate, that during distraction osteogenesis in a new regenerated bone, PTH (1-34) treatment with two different doses of 5µg/kg/day and 25 µg/kg/day increased callus cross – sectional area, callus bone mineral density and bone mineral content, bone volume density, dramatically increased trabecular number with slight increase in trabecular thickness, whereas decreased trabecular separation, bone surface density and decreased degree of anisotropy when compared with control group animals. Conclusion: PTH (1-34) treatment improved mineralization, structural indices of regenerated distracted rabbit tibia, whereas treatment with dose of 25g/kg/day PTH(1-34) was significantly more effective than 5 g/kg/day PTH(1-34) dose treatment when compared to control group. Bigger dose has been chosen for the main study.

O2.03 Marianne MOLECULAR CHARACTERIZATION OF THE HAPTOGLOBIN- Jensby HEMOGLOBIN RECEPTOR CD163: ENDOCYTIC PROPERTIES OF THE Nielsen CYTOPLASMIC TAIL OF PHYSIOLOGICAL CD163 VARIANTS. Marianne Jensby Nielsen, Mette Madsen, Holger J. Møller, and Søren K. Moestrup. Department of Medical Biochemistry, University of Aarhus, 8000 Aarhus C, Denmark. CD163 is the monocyte/macrophage-specific receptor for haptoglobin- hemoglobin (Hp-Hb) complexes. The cytoplasmic tail of human CD163 exists as a short tail variant and two long tail variants. RT-PCR analysis indicated that all three CD163 variants are substantially expressed in blood, liver, and spleen, with the short tail variant being the predominant mRNA species. Using cell transfectants in which cDNA encoding the CD163 variants was inserted at the same site in the genome, we evaluated the expression and endocytic properties of the tail variants. Ligand uptake analysis showed that cells expressing the CD163 short tail variant exhibited a higher capacity for ligand endocytosis than cells expressing the CD163 long tail variants. The difference in endocytic activity was explained by

38 confocal microscopic analysis showing marked deviations in subcellular distribution. Surface expression was far most pronounced for the CD163 short tail variant, whereas the long tail variants were most abundant in Golgi/endosomes. Mutational change of a putative signal for endocytosis (Tyr-Arg-Glu-Met) present in a common part of the cytoplasmic tail of the variants almost completely inactivated the endocytic activity of the short tail variant. In conclusion, the three physiological tail variants of CD163 may contribute to Hp-Hb endocytosis by means of the common ligand binding region and endocytic signal. However, the high mRNA expression level and relatively high endocytic capacity of the short tail variant suggest that it accounts for the majority of Hp-Hb uptake from the circulation, whereas the long tail variants may have yet unknown intracellular roles.

O2.04 Mathias THE EFFECTS OF STRONTIUM ON BONE ULTRASTRUCTURE: Hauge INSIGHTS FROM LABORATORY SCANNING SMALL ANGLE X-RAY Bünger SCATTERING (SSAXS) M.H. Bünger [1,2], T.P.K. Hansen [1], F. Besenbacher [1], B. Langdahl [2], H. Oxlund [1], J.S. Pedersen [1], H. Birkedal [1]. [1] University of Aarhus, Aarhus, DK, [2] Department of Endocrinology and Metabolism C, Aarhus University Hospital, DK-8000 Aarhus, DK Strontium salts have attracted strong interest as a possible anabolic drug for the treatment of osteoporosis. Sr is believed to substitute Ca in the apatite crystal lattice. However, detailed knowledge about possible effects of Sr treatment on the bone ultrastructure is still missing. Here we use scanning Small Angle X-ray Scattering (sSAXS) to study the effects of a strontium treatment regime in a rat model. The SAXS signal from bone samples originates from differences in electron density between the mineral and organic phase. SAXS offers unique information about mineral particle thickness, orientation and shape. We studied the effect of Sr on the treatment of ovariectomy induced osteoporosis in 6 month old female Wistar rats. The animals were treated

with 4 mmol SrCl2(aq)/kg/day or placebo for a period of 140 days and labelled with flourochromes at days 7, 126 and 136. Cross sections from the midshaft femur from four animals (-ov/-Sr, +ov/-Sr , -ov/+Sr and +ov/+Sr) were studied in detail using fluorescence microscopy and scanning electron microscopy including element mapping by energy dispersive X-ray analysis (EDAX) and sSAXS. The new bone, identified by fluorescence microscopy, was found to contain increased levels of Sr by EDAX analysis in the two +Sr animals. The SAXS survey scans, with a ~50 m lateral resolution, revealed a large variation in the SAXS intensity in the central part of the individual sections, while they were more homogeneous toward the periost in agreement with current models of bone maturation. Qualitatively, the sSAXS results illustrated the osteoinductive behaviour of Sr. Detailed SAXS investigations of selected regions covering both pre- and post-treatment bone were used to determine crystallite orientation, shape and thickness. We will compare +Sr and –Sr bone to bring to light any possible effects of Sr treatment on the crystallite properties and distribution.

39 O2.05 Bjarke VITAMIN D STATUS AND SEASONAL VARIATIONS IN PRIMARY Moosgaard HYPERPARATHYROIDISM B. Moosgaard, P. Vestergaard, L. Heickendorff, F. Melsen, P. Christiansen, L. Mosekilde Department of Endocrinology and Metabolism C, Aarhus University Hospital, DK-8000 Aarhus C, Denmark Background: Primary hyperparathyroidism (PHPT) and vitamin D insufficiency are common conditions that may occur in combination. Aim: To compare the risk of vitamin D insufficiency and deficiency stratified by age-, sex- and season between PHPT patients and controls. Design: Cross-sectional study. Material: 289 consecutive Caucasian patients with PHPT aged 65.9 (24 – 94) years, 289 sex-, age-, and season-matched normocalcaemic controls and 187 healthy adult blood donors. PHPT diagnosis was confirmed in 214 by neck exploration. Results: Vitamin D insufficiency (P-25OHD < 50 nmol/l) was observed in 81% of PHPT patients compared with 60% of sex- and age-matched controls (p < 0.001) and 35% of blood donors (p< 0.001). During summer 77% versus 53% (p< 0.001) and 4% (p< 0.001), respectively, had vitamin D insufficiency. During winter 86% versus 66% (p< 0.001) and 71% (p< 0.05) respectively, had vitamin D insufficiency. Vitamin D deficiency (P-25OHD < 25 nmol/l) was observed in 33% of PHPT patients compared with 20% of age- and sex- matched controls (p< 0.001) and 13% of blood donors (p< 0.001). Both PHPT-patients and controls showed seasonal variations in 25OHD related to average number of sun hours, but values were lower in PHPT patients at all calendar months. Conclusion: Vitamin D insufficiency and deficiency is a common finding in PHPT and occur more often than in a sex- and age-matched control group referred from GP and in normal blood donors irrespective of season.

O3.01 Kim THE IMPAIRMENT OF RETINAL VASOCONSTRICTION CAUSED BY Holmgaad PERIVASCULAR TISSUE CAN BE BLOCKED BY INHIBITION OF THE Jensen GLUTAMATE NMDA RECEPTOR AND COX. Kim Holmgaard Jensen*, Christian Aalkjær#, John D.C. Lambert#, and Toke Bek*. (Correspondence should be sent to: [email protected].) *Dept. of Ophthalmology, ÅKH. #Dept of Physiology, AU. Introduction: To disclose interactions between the arteriole and the surrounding perivascular cells, in vitro model complexity should be increased form isolated arterioles to arterioles surrounded by perivascular retinal tissue. However, previous studies have shown that perivascular tissue causes the retinal arterioles to be less responsive to vasoconstrictors. In order to interpret studies of retinal vascular tone regulation, it is important to elucidate the physiological role and the causative mechanisms of this phenomenon. Methods: Porcine retinal arterioles (Ø ~ 150 µm, length ~ 1.8 mm) with 2 mm adjacent tissue on each side of the vessels were mounted in a wire myograph for isometric tone measurements. Concentration-response experiments were carried out with the vasoconstrictor U46619 before and after removal of the perivascular retina, and it was tested whether the response was affected by the glutamate rec. subtype agonist NMDA, the

40 NMDA antagonist DL-APV, and the COX inhibitor Ibuprofen. Results: The presence of retinal tissue impaired the contractile effect of U46619 in about 60 % of the arterioles. In the remaining arterioles, the contractile effect of U46619 was impaired by application of NMDA. This impairment was eliminated by blocking the glutamate NMDA receptor (p<0.01) and by inhibition of COX (p<0.01). The NMDA induced impairment of vasoconstriction was abolished when the perivascular retinal tissue was removed from the arterioles and could not be reinduced by application of NMDA. Conclusion: Retinal tissue causes impairment of vasoconstriction by a mechanism which involves activation of the NMDA rec. and COX.

O3.02 Niels Jessen ALTERED SUBSTRATE METABOLISM AND ABLATED AMPKΑ2 ACTIVITY IN LKB1 KNOCKOUT HEARTS Niels Jessen1,2, Ho-Jin Koh2, Bo Løfgren1, Sten Lund1, Laurie J. Goodyear2 1Medical Research Lab, Aarhus Sygehus, Bygn. 3, 8000 Århus C 2Joslin Diabetes Center, Harvard Medical School, MA-02215 Boston, USA AMP-activated protein kinase (AMPK) plays a critical role in maintaining energy homeostasis and cardiac function. When activated, AMPK phosphorylates and inactivates acetyl CoA carboxylase (ACC); this results in increased fatty acid oxidation. Multiple AMPK kinases have been postulated to exist in cardiac muscle, and recently LKB1 has been identified as an upstream kinase of AMPK in vitro. To examine LKB1 as an AMPK kinase in vivo, we generated a skeletal muscle- and cardiac-specific LKB1 knockout mouse using the Cre-LoxP system. Hearts from LKB1 knockout (KO) and control (CON) littermates were studied in the basal state and in response to 2 min of hypoxia. AMPKα1 and α2 subunit phosphorylation of the regulatory Thr172 site was assessed by immunoblotting. Basal and hypoxia-stimulated Thr172 phosphorylation was reduced by >95% in KO hearts. There was complete ablation of AMPKα2 activity in KO hearts, but surprisingly, AMPKα1 activity was normal in both the basal state and during hypoxia. ACC phosphorylation in the basal state and during hypoxia was reduced by 75% in KO hearts. Basal glycogen levels were unaltered, but during hypoxia, glycogen breakdown in KO mice was significantly greater. Glucose uptake in KO hearts was 30- fold greater than CON during a glucose tolerance test with radioactive labeled glucose. Both results indicate a preference for carbohydrate utilization in KO hearts, possibly due to reduced ACC phosphorylation. In conclusion, LKB1 is essential for AMPKα2 activity, but not AMPKα1 activity, in cardiac muscle. Knockout of LKB1 in heart leads to reduced ACC phosphorylation and profound changes in substrate metabolism.

O3.03 Rikke SEGMENTAL AQP2 REGULATION BY SELECTIVE COX-2 INHIBITION Nørregaard IN AFTER RELEASE OF BILATERAL URETERAL OBSTRUCTION IN RATS Rikke Nørregaard1,3, Maria Diget1,3, Boye L. Jensen4, Søren Nielsen1,2 and Jørgen Frøkiær1,3. 1The Water and Salt Research Center, 2Institute of Anatomy, and 3 Clinical Institute University of Aarhus, Aarhus and 4Physiology and Pharmacology,

41 University of Southern Denmark, Odense, Denmark. Previously we demonstrated that bilateral ureteral obstruction (BUO) for 24 hours was associated with a marked increase in the inner medullary (IM) expression of (COX-2) and that selective COX-2 inhibition prevents downregulation of AQP2. Now we examined the effect of the selective COX-2 inhibitor parecoxib (PCOX) on COX-2 and AQP2 expression 3 days after release of BUO (BUO-3DR). Rats were subjected to 24h BUO followed by release and observed during the next 3 days and sham-operated control rats were examined in parallel. Clearance experiments were performed after 3 days and kidneys were removed and prepared for immunoblotting. In a subset of animals, kidneys were perfusion fixed for immunocytochemistry. Urinary PGE2 excretion was measured. Release of BUO was associated with marked polyuria and a significant decreased GFR compared to SHAM. After release of BUO urinary PGE2 excretion was significantly stimulated (1.5 ± vs. 2.9 ± 0.6 ng/min/day). Administration of PCOX completely abolished this stimulation. COX-2 expression increased in both C+OM and IM of kidneys in BUO-3DR. However, PCOX treatment significantly increased AQP2 abundance in IM (arbitary units: 2.01±0.6 vs. 5.88±0.9, n=6; p<0.01) in BUO- 3DR rats. Immunohistochemistry showed increased apical labeling of AQP2 after treatment with PCOX in IM. In conclusion, PCOX only prevents dysregulation of AQP2 in IM. These data indicate that inhibition of COX-2 activity may contribute to altered segmental AQP2 expression.

O3.04 Søren PERIADVENTITIAL INFLAMMATION - A MARKER OF SYSTEMIC Dalager- INFLAMMATORY ACTIVATION AND CORONARY DEATH? Pedersen S. Dalager-Pedersen, E. Falk, I.B. Kristensen, W.P. Paaske Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Skejby Sygehus, 8200 Aarhus N, Denmark. Periadventitial inflammation (PAI) may be important in atherosclerotic plaque growth and complications. We explored the distribution of PAI in different arterial territories and the association with coronary death. Predefined segments of left anterior descending (LAD), right coronary (RCA), and bilateral carotid, and superficial femoral arteries were obtained prospectively from 100 autopsies (70 men; 20-82 years). One subject dying with chronic lymphatic leukemia was excluded. Coronary atherosclerosis was the cause of death in 27 cases. The segments were sectioned and processed (hematoxylin and eosin stain) for microscopic examination. All sections (n=4755) were analysed blindly with identification of plaque (type ≥IV, American Heart Association classification) and a plaque burden was calculated (the fraction of sections with plaque in a segment). PAI was quantified as the number of periadventitial high power fields (HPF, x400 magnification) with ≥25 mononuclear round cells in the vessel perimeter. The number of PAI HPFs was significantly increased in coronary death in all artery segments. The coronary arteries were most severely affected followed by the carotid and the femoral arteries. Plaque burden was also increased in coronary death and correlated with the degree of PAI. The association between coronary death and PAI remained significant in the

42 coronary and carotid arteries after adjustment by plaque burden in multiple logistic regression analysis. Our results suggest inflammatory activation beyond the coronary arteries in coronary death independent of plaque burden. Quantification of carotid artery PAI may be a new target for identification of high-risk patients.

O3.05 Lars MOTION ANALYSIS FOR SHORTER SCAN TIMES IN CARDIAC MRI Riisgaard L. R. Ribe, S. Ringgaard, E. M. Pedersen Ribe MR Research Center, Aarhus University Hospital, Aarhus N, Denmark In high-resolution cardiac MR imaging, motion artifacts from the intrinsic cardiac motion is traditionally minimized by scanning only during a 60-100 ms time window in mid-diastole. It is possible, however, to correct the motion retrospectively if the motion is an affine transformation. Therefore, it is of interest to examine the extension of the time window where the cardiac motion is affine. Seven healthy volunteers were imaged. The motion of all pixels within the cardiac muscle was calculated and subsequently fitted to an affine transformation. Three different motion correction models were defined: 1) no motion correction, 2) correction for translation, and 3) correction for an affine transformation. We defined the model error as the average length of the motion vector of the remaining motion after correction with a given motion model. The model error is a function of the time window used to calculate the motion. The differences between the different model errors were estimated by linear regression. The slope of the difference between no correction and translation was 0.39 meaning that 39% of the model error was removed when correcting for translation. The slope of the difference between no correction and affine was 0.83. For both situations, the probability of a zero slope was less than 0.01. The time window where the motion error was below 1 mm was 1) no correction: 100 ms, 2) translation: 140 ms, and 3) 450 ms. We have shown that the cardiac motion in a long-axis slice may be described by a simple affine transformation in a time window substantially larger than the time window used presently in high resolution cardiac imaging. This indicates that retrospective motion correction would allow a substantial increase of the time window for high-resolution cardiac imaging with subsequent decrease of the scan time.

O4.01 Trine Munk- RISK OF POSTPARTUM MENTAL DISORDERS, WOMEN ARE AT RISK, Olsen BUT WHAT ABOUT MEN? Trine Munk-Olsen MSc 1, Thomas Munk Laursen MSc 1, Carsten B. Pedersen MSc 1, Ole Mors MD PhD 2, Preben Bo Mortensen DrMedSc 1. 1 National Centre for Register-based Research, University of Aarhus, Taasinge-gade 1, 8000 Aarhus C, Denmark. 2 Psychiatric Hospital in Aarhus, University Hospital of Aarhus, Skovagervej 2, 8240 Risskov, Denmark. Background: Incidence of psychotic illnesses rises dramatically for women in the first weeks and months after childbirth, and there is some indication

43 that men also experience postpartum depressive symptoms, but do paternal postpartum mental disorders exist? Method: A cohort comprising all persons born in Denmark January 1st 1955 until February 1st 1988 were followed from 1973 to 2003 in a register based study. The main outcome variable was first admission or outpatient contact with a mental disorder during the first year period after becoming a parent. Estimates of relative risks were calculated using Poisson regression. Results: A total of 1,063,308 people became parents during the study period, and 10,218 mothers and 7,347 fathers had a first-time admission during the study period. Women had a high relative risk of psychiatric admission after childbirth, the relative risk was especially high 11 – 20 days after childbirth, RR: 7.97 (5.83-10.88) compared with women who gave birth 11 – 12 moths earlier. Similar to this the highest risk of an outpatient contact was 11 – 20 days postpartum, RR: 2.64 (1.85-3.77). Men did not have an increased relative risk of psychiatric admission or outpatient contact during the first year after becoming a father. Conclusion: Becoming a parent has a significantly different effect on women’s and men’s mental health; diverse mechanisms are likely to explain these differences. Both men and women aged 25 years or more who did not become parents during the study period had an increased risk of psychiatric admission compared to parents, and further studies should focus on a potential protective effect of parenthood or a possible selection into becoming a parent.

O4.02 Ellen M. PSYCHOSOCIAL CONDITIONS OF WOMEN WHO ANTICIPATE Mikkelsen GENETIC COUNSELING: A POPULATION-BASED STUDY E.M. Mikkelsen, L. Sunde, C. Johansen, P. Johnsen Klinisk Epidemiologisk Afd., Ole Worms Allé 150, 8000 Århus C. The aim of this study was to compare the psychosocial conditions of women who anticipate genetic counseling with two reference groups, further to examine the possible differences in clinical and socioeconomic characteristics between respondents and non-respondents. We are conducting an on-going population based follow-up study of 568 women referred consecutively to genetic counseling for hereditary risk of breast or ovarian cancer. In addition, we have included 689 women referred consecutively to mammography (Reference Group I), and a random sample of 2000 women from the general population (Reference Group II). Data are collected by questionnaires including e.g. standardized measures of anxiety, depression, and cancer specific distress. Baseline data were collected one to four weeks before the first counseling. We used register data from 6 nationwide public registries to compare respondents and non-respondents. We found no substantial differences in anxiety and depression when comparing the genetic group with the reference groups. Fifty-four percent of the non-cancer affected women and 64 % of the cancer affected women awaiting genetic counseling experienced cancer specific distress, and both affected and non-affected women in the Genetic Group had a substantially higher prevalence of cancer specific distress compared to the reference groups. We found no striking differences between respondents and non- respondents in the entire study-population.

44 Our findings underline that anticipating genetic counseling can be burdensome for both affected and non-affected women and cancer specific distress is relevant to address at the first counseling.

O4.03 Karen EMOTION PROCESSING IN THE HUMAN BRAIN: AN fMRI STUDY Johanne Karen Johanne Pallesen Pallesen PET centre, Aarhus Hospital, 8000 Aarhus C, Denmark

Behavioral studies have shown that music fragments and even isolated musical chords may elicit emotional effects in listeners (Pallesen K.J. et al., Brain and Cognition 2003, 51:188-90). Dissonance in melodies has previously been associated with activity in right parahippocampal and right precuneus brain areas (Blood A.J. et al., Nat. Neurosci. 2001 2(4): 382-387). We wished to study whether simple musical stimuli such as isolated chords would activate brain structures previously associated with emotion analysis. Moreover, we wanted to test the hypothesis, already proved in the visual modality (Hariri A.R. et al., Neuroreport 2000, 11 (1): 43-8), that cognition down-regulates the emotional responses, and the potential influence of stimulus familiarity. To this aim, we mapped the blood oxygenation level dependent (BOLD) response in 11 musicians and 10 non- musicians who listened passively or memorized the pitch of major, minor and dissonant musical chords. Minor and dissonant chords, compared to major chords, elicited enhanced responses in areas including the brainstem, amygdala and retrosplenial cortex, during passive listening but not during memorization of the chords, indicating that 1. neural processing in brain areas implicated in emotions is activated even by single chords, 2. emotion processing is enhanced in the absence of cognitive requirements. Musical competence did not influence the neural responses during passive listening, although musicians were better at recognizing the conventional emotional connotations of the stimuli.

O4.04 Brent M. INHIBITORY INTERNEURONS FOLLOWING EXPERIMENTAL BRAIN Witgen INJURY BM Witgen, J Lifshtiz, MS Grady, JR Nyengaard Stereology and Electron Microscopy Research Laboratory, Aarhus University, Building 1185, Aarhus 8000 Denmark Susceptibility of hippocampal neurons to human traumatic brain injury (TBI) can also be identified in experimental models. After lateral fluid percussion brain injury in the mouse, a uniform loss of 25-35% of all neurons occurs in the four major subregions of the hippocampus by one week post-injury. Since excitatory and inhibitory networks combine to establish hippocampal function, the neuronal loss could be exclusively excitatory neurons, all inhibitory neurons, or a combination of the two populations. To further address the nature of hippocampal neuronal loss after TBI, GFP-GAD (FVB-TgN(GadGFP)45704Swn) transgenic mice were employed to quantify the remaining population of somatostatin-positive inhibitory interneurons in the hippocampus using combined transgenic-

45 fluorescent-stereology. At one week, the brains of brain-injured and uninjured control mice were processed for vibratome sectioning and the optical fractionator for estimation of GFP-positive somatostatin-positive inhibitory interneurons in the hilus and area CA. Uninjured control mice possess 1140 (CV=0.06) somatostatin-positive interneurons in the hilus and 3050 (CV=0.06) in area CA. Whereas brain-injured mice had 900 (CV=0.05) somatostatin-positive interneurons in the hilus, and 3300 (CV=0.06) in area CA. In the hilus, one week after injury, a significant 21% of these cells are lost, but previous data shows a 34% total neuronal loss. No significant loss is observed in area CA. Consequently, the proportion of somatostatin- positive inhibitory interneurons in the hilus shifts after brain injury with potential functional implications. Remarkably, the number of somatostatin- positive inhibitory interneurons in area CA does not decrease following injury. Further studies will address the other inhibitory interneuron subpopulations in the brain injured hippocampus.

O4.05 Anita THE USE OF OLIGONUCLEOTID ARRAYS IN SEARCH OF NEW Rethmeier MOLECULAR MARKERS IN AML A. Rethmeier1, C. Juhl-Christensen1, C.G. Nyvold1, T. Thykjær2, L.H. Olesen1 and P. Hokland1. Departments of Hematology1 and Clinical Biochemistry2; University Hospital of Aarhus, 8000 Aarhus, DK Acute Myeloid Leukaemia (AML) is heterogeneous in relation to the wide number of molecular abnormalities present in this disease. Some of these changes, especially balanced translocations, are used as markers in regard to prognosis and follow-up. However, in a larger part of the patients molecular markers cannot be identified. In order to search for new markers in AML, we compared the transcription profile of bone marrow (BM) cells from 14 patients with balanced translocation and four healthy individuals to BM cells from six AML patients lacking a series of well-defined genetic and epigenetic changes. Expression profiles were obtained employing oligonucleotide-based microarrays. The method has the advantage of presenting a massive amount of information of expression of well-characterized genes as well as genes with unknown function. Nevertheless, the huge data sets acquired can be difficult to handle and should therefore be validated by other methods. We used real-time quantitative PCR to validate the expression of candidate genes that we selected using microarray. We found that transcription of the “IQ motif containing GTPase activating protein” (IQGAP) gene was up-regulated in four of the six patients without known molecular changes; this was not seen in either healthy individuals or patients with balanced translocation. Subsequently, the transcriptional status of the gene was investigated in 28 AML patients, where X showed increased expression of IQGAP. Next we want to test if the transcriptional increase in IQGAP is caused by gene amplification and, if positive, these data will be correlated to clinical data such as survival.

P01.01 Jane TELEMEDICAL HOME TREATMENT OF PATIENTS WITH DIABETIC

46 Clemmensen FOOT ULCERS: VIDEO PHONE AS A DIAGNOSTIC AID Jane Clemensen, Simon B. Larsen, Marit Kirkevold, Niels Ejskjær Centre for Pervasive Healthcare, Aabogade 34, 8200 Aarhus University, [email protected] The aim was to investigate if it is possible to move experts from hospital to the patient’s home by the use of technology We have used the qualitative method: Participatory Design. The study has involved a close cooperation with 5 patients, 3 relatives, 5 visiting nurses, 3 expert nurses and 1 expert doctor from the Medical Department, Aarhus University Hospital. A pilot test was conducted where the intervention was to replace traditional visits in the out patient clinic with a video consultation in the patients own home. The results showed that the doctor and expert nurses are able to evaluate the ulcer on a distance and to prescribe further treatment. The visiting nurse experienced increased security in treating the foot ulcer and furthermore the visiting nurses characterized the consultations as a learning situation. The patients expressed satisfaction and security being treated by the experts on a distance and avoiding waiting time and transportation was a great advantage. The conclusion is that the combination of video phones and online ulcer record holds promise as a diagnostic aid in that the technology and the close collaboration between home and hospital made up a conclusive alternative to a visit in the out patient clinic in the cases encountered in the study.

P01.02 Lars INJURIES TO THE CERVICAL SPINE FACET JOINTS OF A ROAD Uhrenholt TRAFFIC CRASH FATALITY – A CASE REPORT L. Uhrenholt, E. Nielsen, A. Vesterby Charles, M. Gregersen and F. Melsen Department of Forensic Medicine, University of Aarhus, Denmark Nordic Institute of Chiropractic and Clinical Biomechanics, Odense Department of Pathology, Aarhus Sygehus, University Hospital of Aarhus Department of Neuroradiology, University Hospital of Aarhus The aim of this case report is to present the application of a specialised histological method in the post-mortem evaluation of the cervical spine facet joint injuries. Specialised post-mortem examination included diagnostic imaging procedures of the lower cervical spine segments. The specimen was prepared un-decalcified, unfrozen and by alcohol fixation with immersion in methyl methacrylate from which histological sections 10µm thick were produced and stained with Goldner-Trichrome. Autopsy findings revealed injuries to the face, skull and brain. No injuries in the lower cervical spine were detected on autopsy or diagnostic imaging. Histological examination identified discrete injuries to the cervical spine facet joints, including capsular tears, subchondral fractures and haemarthrosis. We present a case of a road traffic crash fatality whose lower cervical spine was examined with specialised histological methods that identified discrete injuries despite negative diagnostic imaging procedures.

47 P01.03 Christian IMPAIRED CYTOKINE RESPONSE IN INTESTINAL CD4+ T CELLS Lodberg FROM CROHN DISEASE PATIENTS Hvas C.L. Hvas, J. Kelsen, J. Agnholt, P. Höllsberg, J.K. Møller, M. Tvede, J.F. Dahlerup Gastro-Immuno Research Laboratory (GIRL), Department of Medicine V, Aarhus University Hospital. Tel. 8949 3828, e-mail [email protected]. Crohn disease (CD) results from a lack of tolerance to commensal bacteria, but a functional immuno-regulatory defect remains to be identified. We investigated the response .of intestinal T cells from CD patients and healthy controls to microbial antigens in the presence or absence of dendritic cells. We cultured intestinal CD4+ T cells from CD patients (n=9) and from healthy controls (HC) (n=6) and differentiated dendritic cells from their peripheral monocytes. Intestinal T cells were stimulated with Lactobacillus strains or autologous intestinal bacteria with or without the presence of dendritic cells. Cytokine levels of interleukin (IL)-10 and interferon (IFN)-γ were measured on day 4. When CD intestinal T cells were stimulated with bacterial products in the presence of dendritic cells, they produced more IFN-g (mean 6.4 ng/ml +/- standard error 1.1 ng/ml) and less IL-10 (0.7 ng/ml +/- 0.1 ng/ml) than HC intestinal T cells (IFN-g 3.9 ng/ml +/- 0.8 ng/ml, p=0.06; IL-10 4.6 ng/ml +/- 0.9 ng/ml, p=0.0001). In the absence of dendritic cells, cytokine concentrations were low except in CD intestinal T cells which responded to autologous bacterial products with an increased IFN-g production (2.3 +/- 1.3 vs. 0.3 +/- 0.2 ng/ml in HC). We conclude that Crohn disease intestinal CD4+ T cells respond to bacterial antigens with an enhanced IFN- γ production, whereas they fail to upregulate a regulatory response (IL-10) to both tolerogenic (Lactobacilli) and immunogenic antigens (autologous intestinal bacteria).

P01.04 Rikke HEALTH ECONOMIC EVALUATION OF LUMBAR SPINAL FUSION IN Søgaard CHRONIC LOW BACK PAIN PATIENTS R. Soegaard, F.B. Christensen, T. Christiansen, C. Bünger Orthopaedic Research Lab., Institute of Clinical Medicine, University Hospital of Aarhus, Denmark / Health Economics Unit, Institute of Public Health, University of Southern Denmark, Denmark Cost-effectiveness is the ultimate criterion for health services management. The evidence of value-for-money in the treatment of chronic low back pain, however, is lacking. The aim of this PhD project is to improve the decision-analytic foundation for health service management in lumbar spinal fusion by investigating cost-effectiveness of 1) surgical techniques and 2) various rehabilitation that follow surgery. Two randomized trials are conducted. Trial I (n=148) compares two surgical techniques (posterolateral vs. posterolateral and anterior fusion in combination). Trial II (n=90) compares three rehabilitation protocols (hospital’s usual vs. intensive training exercise vs. a bio-psycho-social approach). The cost-effectiveness of posterolateral and anterior fusion in combination (in comparison with posterolateral fusion alone) was found moderate with a

48 2-year follow up. Two-year follow up of patients’ extra-hospital health service utilization after fusion surgery showed a reduced service utilization of factor 4.7 (95% CI 4.64;4.77) in the bio-psycho-social randomization group as compared with the group randomized to hospital’s usual approach. The rehabilitation study underlines the importance of a broad view when evaluating an intervention in chronic low back pain. A minor cognitive extension to the hospital’s usual rehabilitation approach significantly reduced patients’ service utilization in the primary health sector. The moderate cost-effectiveness of the combined surgical technique needs to be further investigated in a randomized design with a follow up longer than 2 years.

P01.05 Ashfaque ACTIVITY OF THE EPIDERMAL GROWTH FACTOR RECEPTOR Ahmed DELAYS THE ONSET OF CALCIUM-INDUCED APOPTOSIS IN Memon BLADDER CANCER CELLS Ashfaque A. Memon, Mathias M. Sorensen, Ebba Nexo and Boe S. Sorensen Department of Clinical Biochemistry, NBG, AS, Aarhus University Hospital, Norrebrogade 44, 8000 Aarhus C, Denmark Calcium uptake regulates several biological systems. In the present study, we demonstrate that calcium uptake induce apoptosis in bladder cancer cells by a mechanism involving the epidermal growth factor (EGF) system. Exposure of the RT4 bladder cancer cell line to 10mM calcium resulted in apoptosis after 12hrs. Real time PCR results show that mRNA levels of EGFR (two folds) and its ligands especially epiregulin, heparin binding EGF like growth factor (HB-EGF) and transforming growth factor alpha (TGFα) were increased approx: 120, 10 and 3 folds respectively, 30 min after calcium treatment. Western blotting analysis with the specific phospho- tyrosine EGFR (p-EGFR, Y1173) antibody showed that the activity of the EGFR was increased more than five folds during early calcium treatment. However induction of EGFR activity and mRNA expression of its ligands was suppressed at 12 hrs after calcium treatment at the same time as the cells entered apoptosis. These results suggest that, activation of the EGFR may protect the cells from calcium-induced apoptosis at the onset of calcium treatment. To confirm this early survival effect of the EGFR during calcium treatment, we blocked the activity of the EGFR by Iressa (Gefitinib, ZD1839), a specific EGFR tyrosine kinase inhibitor. This demonstrated that the effect of calcium-induced apoptosis was significantly augmented by co- treatment with iressa (1.5 folds), while Iressa alone did not induce any significant changes in the level of apoptosis in these cells. To further examine the role of EGFR in protecting the cells from calcium induced apoptosis we treated the well-observed EGFR over-expressing cell line A431 with calcium. Unlike RT4 cells which express comparatively low EGFR, no significant apoptosis was observed with calcium treatment to these cells for 24 hrs. However, co-treatment with iressa induced a significant apoptotic response to calcium. These findings show that the EGF system protects cells from the onset of calcium induced apoptosis and suggest that the loss of EGFR activity after 12 hrs of calcium treatment could be responsible for the onset of apoptosis.

49 P01.06 Jianguo Chen STEVIOSIDE DOES NOT CAUSE INCREASED BASAL INSULIN SECRETION OR ß-CELL DESENSITISATION LIKE THE SULPHONYLUREA, GLIBENCLAMIDE: STUDIES IN VITRO. Jianguo Chen, Per Bendix Jeppesen, Reziwanggu Abudula, Stig E.U. Dyrskog, Michele Colombo, Kjeld Hermansen Department of Endocrinology and Metabolism, Aarhus Sygehus THG, Aarhus University Hospital, Tage-Hansens Gade 2, DK-8000 Aarhus C, Denmark Type 2 diabetes (T2DM) is characterised by abnormal ß-cell function with increased basal insulin secretion (BIS) and reduced glucose-stimulated insulin secretion (GSIS). Unfortunately, the classic anti-diabetic sulphonylureas (SU) e.g. glibenclamide (GB) have undesirable effects on ß- cells i.e. they stimulate BIS and/or cause desensitisation of ß-cells. We have shown that stevioside (SVS) possesses a potential role as antihyperglycemic agents in the treatment of type 2 diabetes mellitus. However, whether SVS acts on ß-cells like the SU is not known. To explore and compare the effects of SVS pre-treatment with those of GB and glucagon-like peptide-1 (GLP-1), we exposed isolated mouse islets to low or high glucose for 1-h after short-term (2-h) or long-term (24-h) pre- treatment with SVS, GB or GLP-1, respectively. The gene expression of glucose transporter 2 (GLUT2), glucokinase (GCK) and pancreatic and duodenal homeobox 1 (PDX-1) was measured by RT-PCR. At 3.3 or 5.5 mM glucose BIS was not changed after short-term pre- treatment with SVS (10-7 M), while BIS was increased about three fold after pre-treatment with GB (10-7 M). GSIS (16.7 mM) increased dose-dependently after long-term pre-treatment with SVS (10-7 - 10-5 M). A 24-h pre-treatment with GB (10-7 M) increased BIS (3.3 mM glucose) (p<0.001), but decreased GSIS (16.7 mM glucose) (p <0.001). In contrast SVS (10-7 M) and GLP-1 (10-7 M) did not stimulate BIS but both substances enhanced GSIS (16.7 mM glucose) (p <0.05 and p <0.05, respectively). While SVS pre-treatment increased the intracellular insulin content, GB pre-treatment decreased the insulin content. Gene expression of GLUT2, GCK and PDX-1 was upregulated by SVS pretreatment. Our results suggest that short-term and long-term pre-treatment of isolated mouse islets with SVS does not increase BIS while a long-term pre- treatment enhances GSIS. This enhanced GSIS is both glucose and SVS dose dependent. Increased insulin biosynthesis and glucose-sensing elements may play a role in this GSIS stimulation. In conclusion, SVS pre-treatment does not cause a stimulation of BIS neither desensitises ß-cells i.e. SVS seems to have advantageous characteristics to GB as a potential treatment of T2DM.

P01.07 AnetteTorvin NEUROPATHIC PAIN AND SENSORY DISTURBANCES IN Møller HETEROZYGOTE PATIENTS WITH FABRY DISEASE A.T.Moeller1, F.W. Bach1, Å.K.Rasmussen2, Steen Kølvraa3, U. Feldt- Rasmussen2, T.S. Jensen1 1Danish Pain Research Center, University hospital of Aarhus, 8000 Aarhus, Denmark. Background: Fabry disease is a rare X-linked lysosomal storage disorder.

50 Deficiency of the enzyme α-galactosidase causes accumulation of glycosphingolipids in the vascular endothelial cells and many other tissues. An early sign of the disease is painful small fibre neuropathy Aim: The aim of the study is to evaluate pain and somatosensory disturbances in heterozygote Fabry patients with an assessment of C-fibre evoked allodynia, hyperalgesia and cutaneous blood flow Methods: Topical application of 100 µl capsaicin (5%) in a closed chamber was carried out on the lower limb 5 cm above the medial malleole in females with known Fabry mutations and in healthy sex-and age-matched volunteers. The evoked pain following application for 30 min and the area of allodynia to brush and pinprick in the secondary hyperalgesic area was measured. The area of brush evoked allodynia and pinprick hyperalgesia was determined using a camel hair brush and a von Frey hair no. 5.88, respectively. Laser Doppler scanning was used to determine the area and magnitude of the capsaicin-induced flare response. Results: So far 13 females with known Fabry mutations have been examined. All in the index group had signs of neuropathy. By comparison to an age and gender matched healthy control group, female Fabry patients showed signs of reduced central sensitisation induced by topical applied capsaicin. The flare response was likewise decreased. Conclusion: The results document that C-fiber function is deficient in heterozygote Fabry patients. This is the first time an objective method has been used to determine C-fiber function in homozygote or heterozygote Fabry patients.

P01.08 Mimi TREATMENT OF IDIOPATHIC THROMBOCYTOPENIC PURPURA IN Kjærsgaard CHILDREN WITH SUBCUTANEOUS ADMINISTERED ANTI-D M. Kjaersgaard Skejby Hospital, Department of Pediatrics, University of Aarhus, Brendstrupgaardsvej 100, 8200 Aarhus N, Denmark In children idiopathic thrombocytopenic purpura (ITP) is often acute, post infectious and self limiting but the course can be diverse. Around 20% of ITP children will experience prolonged low platelet counts, and some will need medical treatment. To day’s drug of choice is intravenous immunoglobulin G (IVIG) or intravenous anti-D. Anti-D administered subcutaneously could be easier to administer, associated with fewer side effects, and have the same efficacy compared with intravenous anti-D or IVIG (Meyer O, Kiesewetter H, Hermsen M, Salama A, Eur. J. Haematol. 2004; 73; 71-72). Objective: To document the effect of subcutaneous Anti-D treatment emphasizing the time it takes to obtain clinical improvement and platelet counts above 20, 50 and 150•109/L. Method: Children admitted to a pediatric department in Denmark for diagnosis, observation or treatment of acute or chronic ITP, between 1 and 14 years of age, and with a platelet count below 30•109 /L are eligible. In the primary observation period, the children’s bleeding manifestations are systematic scored according to Buchanan & Adix, 2002. There is indication for treatment if the bleeding manifestations during this period continuously increase significantly, equaling a bleeding score 3. If the child is rhesus-D

51 positive, s/he receive 50µg/kg anti-D subcutaneously. If the child is rhesus- D negative s/he receive standard treatment. After treatment the child is followed with bleeding score and blood samples (i.a. platelet count, reticulocyte count, LDH, and hemoglobin). After discharge the child has at least two ambulatory visits after approximately 6 months and 1 year.

P01.09 Bodil Øster HUMAN HERPESVIRUS 6B INDUCES P53 ACCUMULATION AND CELL CYCLE ARREST IN T CELLS B. Øster, B. Bundgaard and P. Höllsberg Institute of Medical Microbiology and Immunology, University of Aarhus, DK-8000 Aarhus C, Denmark In response to various forms of cellular stress, the tumour suppressor p53 is an important regulator of several cellular pathways, including cell cycle arrest and apoptosis. The availability of the protein is mainly regulated by its stabilization, subcellular localization and posttranslational modifications. T cells infected by human herpesvirus 6B (HHV-6B) are arrested in the G1/S and G2/M phases of the cell cycle concomitant with an aberrant accumulation of p53. Most of the accumulated p53 localizes to the nucleus, but in contrast to uninfected cells, a significant proportion is found in the cytoplasm. The accumulated p53 has DNA-binding activity and is phosphorylated at Ser15 and Ser20. However, the known p53-induced mediator of cell cycle arrest, p21 is not upregulated, nor is PUMA, the p53- induced protein involved in apoptosis. Approximately 100% of the cells express the viral p41 protein which is indicative of infection, but only a minority of the infected cells undergo apoptosis. The molecular mechanisms by which HHV-6B interferes with host cell growth arrest are largely unknown and it remains to be elucidated whether the cell cycle arrest observed here is associated with phosphorylation and accumulation of p53.

P01.10 Anja A ROLE FOR M6B IN THE FUNCTIONAL REGULATION OF THE Fjorback HUMAN SEROTONIN TRANSPORTER Anja W Fjorback1, Heidi Müller2, Jana Haase2 , and Ove Wiborg1 1Department of Basic Psychiatric Research, Aarhus Psychiatric 2University Hospital Denmark. University of College Dublin, Conway Institute for Biomolecular and Biomedical Research, Dublin, Ireland The serotonin transporter (SERT) is regulated by various signalling mechanisms that may operate to maintain appropriate levels of synaptic serotonin (5-HT). SERT is a 630 amino acid long protein and is believed to have 12 trans-membrane domains with N- and C-termini facing the intracellular compartment. The function of the N- and C termini is not yet fully established, but they are known to associate with other proteins We identified, using two yeast hybrid screening, M6B as a novel binding partner of the N-terminal end of SERT. This interaction was confirmed using pull down experiments using GST tagged N-and C-terminal SERT constructs as bait. This interaction was further investigated to determine if M6B had an impact on 5-HT uptake. This was investigated by co- transfection in HEK cells followed by up-take studies. M6B was shown to decrease the 5-HT uptake significantly in a doses dependent manner. Using confocal microscopy we furthermore, showed that M6B and SERT

52 co-localise in transfected cell lines. The future aim would be to elucidate the interaction with M6B and SERT, by performing co-immunoprecipitation from cell lines endogenous expressing the proteins and from rat brain tissue. The interaction between M6B and SERT could be interesting because members of glucoprotein M6 family have been shown to be up-regulated in the hippocampus of stressed mice, a regulation that can be inverted by treatment with tianeptine a serotonin selective reuptake inhibitor.

P02.01 Guixian DOWNREGULATION OF KEY RENAL ACID BASE TRANSPORT Wang PROTEINS EXPLAINS THE URINARY ACIDIFICATION DEFECT IN RESPONSE TO URINARY TRACT OBSTRUCTION. Gui Xian Wang, Jens Christian Djurhuus, Søren Nielsen and Jørgen Frøkiær The Water and Salt Research Center, University of Aarhus and Institute of Clinical Medicine, Aarhus University Hospital-Skejby, DK-8200 Aarhus N Urinary tract obstruction results in renal defect in urinary acidification. + ¯ This is thought to be caused by diminished net H secretion and/or HCO3 reabsorbtion. To clarify the molecular mechanisms of these defects, expression levels of acid-base transporters were examined along renal nephron and collecting duct of rats with 24h bilateral ureteral obstruction (BUO), 4 days after release of BUO (BUO-R), and under the condition of experimental metabolic acidosis (BUO-A). BUO-24h resulted in acidosis. ¯ The plasma pH and HCO3 levels were dramatically reduced by NH4Cl loaded for 2 days in BUO-A, but no changes in sham rats with same acid treatment (Sham-A). Combined with the changes in urine pH, manifests the + ¯ defect in H excretion and HCO3 reabsorption after release of BUO. Immunoblotting analysis revealed that BUO-24h resulted in significant downregulation of type 3 Na+/H+ exchanger (NHE3) to 21 ± 4%, + ¯ electrogenic Na / HCO3 cotransporter (NBC1) to 71±5%, type 1 bumetanide-sensitive Na+-K+-2Cl- cotransporter (BSC-1) to 3 ± 1%, + ¯ electroneutral Na / HCO3 cotransporter (NBCn1) to 46±7%, Na-K-ATPase to 71 ± 4%, and anion exchanger (pendrin) to 87 ± 2%. Some changes were conformed by immunocytochemistry. BUO-A caused a upregulation of NHE3 to 115 ± 16%, NBC1 to 94 ± 6% NBCn1 to 88 ± 6%, BSC-1 to 106 ± 5%, and Na-K-ATPase to 194 ± 17%, whereas, most of which were still in lower levels in BUO-R. Persistent downregulation of pendrin to 69 ± 5% was observed. With the same treatment of acid on sham rats (Sham-A), the results showed that NHE3 in Sham-A was increased to153± 10%, NBC1 to 157 ± 8%, NBCn1 to 164 ± 6% of sham levels. Analysed those results between two groups with same acid treatment found that the compensating ability in BUO rats is apparently incomplete. In conclusion, downregulation of acid-base transporters in BUO and release of BUO are likely to contribute to the associated urinary acidification defect. The incomplete compensating ability in rats under the condition of acid loaded may be another reason of + ¯ decreased H excretion and HCO3 reabsorption.

P02.02 Cecilia Høst SMOKING DURING PREGNANCY AND RISK OF LOW SEMEN Ramlau- QUALITY IN THE MALE OFFSPRING Hansen C.H. Ramlau-Hansen1, A.M. Thulstrup1, L. Storgaaarad2, G. Toft1, J. Olsen3,

53 J.P. Bonde1 Department of 1Occupational Medicine and of Gynaecology and 2Obstetrics, Aarhus University Hospital, Nørrebrogade 44, bygn 2C, 8000 Århus C, Denmark. 3 Department of Epidemiology, School of Public Health, UCLA Aim: The objective of this prospective follow-up study is to investigate the effect of exposure to cigarette smoke in utero on the semen quality in the male offspring. Methods: Participants are 350 adult sons of mothers, who during pregnancy provided information about smoking and other lifestyle factors. Men are included in six different strata according to prenatal tobacco smoke exposure. Each man provides a semen sample, a blood sample, and answers a questionnaire, which is collected in a mobile laboratory. Results: Until now, a total of 265 men have been included. The participation rate is 52%. The percentage of men with decreased sperm concentration (<20 mill/ml) is 23%. The unadjusted median (25-75% percentile) sperm concentrations and total sperm counts in the six groups are listed below: Prenatal exposure Sperm conc. , Total sperm count, mill/ml mill Non-exposed 49 (23-86) 136 (68-285) (n=90) 1-4 cig/day (n=33) 54 (17-94) 145 (36-358) 5-9 cig/day (n=48) 28 (18-68) 83 (39-258) 10-14 cig/day 40 (21-101) 111 (44-305) (n=35) 15-19 cig/day 30 (19-52) 98 (57-132) (n=33) >19 cig/day (n=26) 33 (12-63) 64 (26-182) Conclusion: These preliminary results suggest that smoking 15 or more cigarettes per day during pregnancy decreases the sons’ sperm concentration and total sperm count.

P02.03 Jørgen Baas RECONSTITUTED BOVINE BONE PROTEIN LYOPHILLISATE ENHANCES FIXATION OF ALLOGRAFTED GAP IMPLANTS J. Baas, A. Lamberg, B. Elmengaard, T. B. Jensen, K. Søballe Orthopedic Research Laboratory, AUH, Norrebrogade 44, Build. 1a, 8000 Aarhus C, Denmark Insufficient bone stock in implant situations can be managed with bone allografting. This study investigates whether the fixation of grafted orthopedic implants can be improved by adding an extract of bovine cortical bone, Colloss (Ossacur AG, Germany) containing reconstituted collagen type 1 and a range of bone-specific proteins. In a controlled paired animal study, cylindrical (6x10mm) unloaded porous-coated Ti with a 2,5mm gap was inserted in the femoral condyles of 16 dogs. The 64 implants were divided into to four groups: The control group with allograft alone and three groups with allograft mixed with 10, 20 or 40 mg Colloss. One ccm of morselled bone allograft was used for each gap in all implantation sites. The implants were evaluated by blinded mechanical pushout test and histomorphometry after a 4-week observation

54 time. Superior mechanical fixation was seen for implants with allograft added Colloss. Furthermore, we found the best mechanical fixation in the 10 and 20 mg Colloss groups. In these concentrations, mechanical fixation improved significantly by 50 to 100% in all mechanical parameters. By histomorphometry, we found a 10-fold decrease in fibrous tissue formation in the Colloss-treated implants, along with an increased new bone formation. This was seen both on the implant surface as well as in the surrounding gap. Colloss enhanced the fixation of allografted implants. It nearly eliminated fibrous tissue formation and increased new bone ongrowth and ingrowth. This could prove useful in clinical settings where allograft is needed for implant support in sites with insufficient bone.

P02.04 Lene Baad- BLINK REFLEXES IN PATIENTS WITH ATYPICAL ODONTALGIA AND Hansen MATCHED HEALTHY CONTROLS. L. Baad-Hansen, T. List, H. Kaube, T.S. Jensen, P. Svensson Department of Clinical Oral Physiology, School of Dentistry, University of Aarhus, Aarhus, Denmark The aim of this study was to investigate signs of neuronal hyperexcitability in the brainstem in atypical odontalgia (AO) by studying the blink reflex (BR) in patients with AO and matched healthy controls, before, during, and after an intraoral pain provocation test with capsaicin. 38 patients with AO and 27 matched healthy controls participated. Electrical stimuli were applied using a ”nociceptive-specific” electrode on the skin overlying the painful trigeminal (V) branch and contralateral branch. Recording surface EMG electrodes were placed bilaterally on mm. orbicularis oculi. The BR responses were quantified as root mean square values (RMS) of the R2 component of the BR (27 to 87 ms) and onset latencies of ipsilateral (R2i) and contralateral R2 (R2c). 30 L of 5% capsaicin was topically applied in an oral bandage to the painful intraoral area of the patients. Mixed-model analyses of variance (ANOVAs) with Tukey HSD post hoc analyses were used. Patients showed significantly lower R2i responses and prolonged R2i latencies compared with controls (P < 0.046). R2c responses were not different between groups (P = 0.152). There was no main effect on R2i or R2c responses of stimulation side (P > 0.757), but capsaicin significantly inhibited the R2i and R2c responses in both groups (P < 0.001), and R2i and R2c significantly increased with increasing stimulus intensity (P < 0.001). There were no indications of increased excitability of brainstem reflex pathways on the painful side in AO patients. In contrast, the ipsilateral BR responses appear to be tonically suppressed in AO patients compared to healthy controls. Capsaicin-evoked pain effectively triggers inhibitory circuits with connections to the BR arch in both groups.

P02.05 Thomas ALTERATION OF HIP JOINT CENTRE DURING ACETABULAR Baad-Hansen REAMING. T. Baad-Hansen*, S. Kold*, W. Fledelius*, PT. Nielsen**, K. Soballe* * Department of Orthopaedic Surgery, Aarhus University Hospital, 8000

55 Århus C, Denmark ** Northern Orthopaedic Division, Aalborg University Hospital, 9000 Aalborg, Denmark Change of the hip joint centre location during preparation of the acetabular cavity for the acetabular component can affect the outcome of total hip arthroplasty. Deviations from the preoperative geometry can compromise an otherwise successful operation with regard to hip dislocations, leg length inequality and range of motion of the hip joint. 18 cadaver acetabuli were measured before and after acetabular reaming to determine the change of hip centre location. Two different acetabular reamers were applied to the acetabular cavity, a chamfered reamer dome intended for minimal invasive hip surgery (MIS) and a conventional hemispherical reamer dome. A 3D optical scanning system – ATOS II SO, created 3D models of the cavities prior to, and after the reaming procedure. The two 3D models were merged into a single 3D model and displacements in all 3 dimensions were calculated. No significant difference between MIS and conventional reaming was found with regard to resulting vector length (P=0.9). The mean measured medial, cranial and dorsal displacement was 2,9mm (SD. 2,2 mm), 1,8mm (SD. 1,2mm) and 0,8mm (SD. 0.4mm), respectively. The mean length of the resulting vector was 3,6mm (SD. 2,4mm), range 0,6 - 9,2mm. The alteration of the hip centre location is not influenced by the changes made to the MIS reamer domes in comparison with conventional reamer domes. In comparison with previous studies the drift of the hip centre caused by the acetabular reaming is reduced due to new techniques and prosthesis designs.

P02.06 Annette Ø. NON MELANOMA SKIN CANCER AND MORTALITY IN DENMARK – Jensen A 10 YEAR FOLLOW UP STUDY A. Ø. Jensen, * A. B. Olesen, *, C. Dethlefsen, ‡ and H. T. Sørensen §¤ *The Department of Dermatology, Aarhus University Hospital, Aarhus C, Denmark; ‡ Center for Cardiovascular Research, Aarhus University Hospital, Aalborg Hospital, Denmark; § The Department of Clinical Epidemiology, Aarhus University Hospital, Denmark; ¤Institute of Preventive Medicine, H:S, Copenhagen, Denmark. The aim of this study was to investigate long term follow up on survival among patients with non melanoma skin cancer (NMSC) in Denmark, using a complete population-based cohort of 4779 NMSC patients seen by Danish Dermatologists in the year 1995 and 47191 population controls. Cohort members and controls were followed throughout 2004 and mortality was determined through the Central Population Registry. Among patients with nodular and ulcerative basal cell carcinoma we found a reduced mortality rate ratio (MRR) at 0.85 [95% CI, 0.80-0.90] and among patients with superficial basal cell carcinoma we found a reduced mortality rate ratio at 0.63 [95% CI, 0.56-0.71]. Both ratios were further reduced if the carcinomas was distributed on the truncus (MRR = 0.71 [95% CI, 0.59-0.85] for nodular and ulcerative basal cell carcinoma and MRR = 0.58 [95% CI, 0.49-0.69] for superficial basal cell carcinoma). Among patients with squamous cell carcinoma we found an increased mortality rate ratio at

56 1.39 [95% CI, 1.14-1.69] which was reduced if the carcinoma was distributed on the face and neck (MRR = 1.34 [95% CI, 1.06-1.69]). These findings raise the question of whether NMSC patients are protected against fatal diseases or our results are due to bias.

P02.07 Jing Hong STEVIOSIDE COUNTERACTS THE ALPHA CELL HYPERSECRETION CAUSED BY LONG-TERM PALMITATE EXPOSURE J. Hong 1, L. Chen 2, P. B. Jeppesen 1, I. Nordentoft 1, K. Hermansen 1. 1Department of Endocrinology and Metabolism, Aarhus Sygehus THG, Aarhus University Hospital, Tage-Hansens Gade 2, 8000 Aarhus C, Denmark 2The Molecular Endocrinology Unit (KMEB), Medical Biotechnology Centre, Odense University Hospital, Winsløwparken 25, 5000 Odense C, Denmark Long-term exposure to fatty acids impairs beta cell function in type 2 diabetes while little is known about the chronic effects of fatty acids on alpha cell. We therefore studied the prolonged impact of palmitate on alpha cell function and on the expression of genes related to fuel metabolism. We also investigated if the antihyperglycaemic agent, stevioside, was able to counteract these effects of palmitate. Clonal alpha TC1-6 cells were cultured with palmitate in the presence or absence of stevioside. After 72h we evaluated glucagon secretion, glucagon content, triglyceride content and changes in the gene expression. Glucagon secretion was dose-dependently increased after 72h culture with palmitate at concentrations 0.25 mM (P<0.05). Palmitate (0.5mM) enhanced triglyceride content of alpha cells by 73% (P<0.01). Interestingly, stevioside (10-8 and 10-6 M) reduced palmitate- stimulated glucagon release by 22% and 45%, respectively (P<0.01). There was no significant change in glucagon content after 72h culture with palmitate and/or stevioside. Palmitate increased CPT-1 mRNA level while stevioside enhanced CPT-1, PPAR gamma and SCD gene expressions in the presence of palmitate (P<0.05). In conclusion, long-term exposure to elevated fatty acids leads to a hypersecretion of glucagon and an accumulation of triglyceride content in clonal alpha TC1-6 cells. Stevioside was able to counteract the alpha cell hypersecretion caused by palmitate and enhanced the expression of genes involved in fatty acid metabolism. This indicates that stevioside may be a promising antidiabetic agent in treatment of type 2 diabetes.

P02.08 Phuong Le PREDICTORS OF MEDICATION COMPLIANCE AMONG PATIENTS Quach WITH FIRST EPISODE OF SCHIZOPHRENIA SPECTRUM DISORDER P. Le Quach and 14 others Psykiatrisk Hospital i Aarhus, Skovagervej 2 8240 Risskov, DK Less than half of the patients with schizophrenia are compliant with the medication, although the effectiveness of antipsychotic drugs is well- documented. Non-compliance results in relapse, rehospitalization, poor prognosis and increased financial and personal strain. It is therefore of outmost clinical importance to identify predictors of medical compliance. Aims: to identify important factors (e.g. insight into the illness, psychopatology and effect of integrated treatment) for medication compliance among patients with first episode of schizophrenia spectrum

57 disorder. Methods: 547 patients with first episode of schizophrenia spectrum disorder were randomised to integrated or standard treatment. The integrated treatment lasted for two years and consisted of assertive community treatment with programmes for family involvement and social skills training. Standard treatment offered contact with a community mental health centre. Both groups were treated with antipsychotic drugs as required and assessed at baseline, 1, 2 & 5 year follow-ups. Based on interviews, available data sources from official registers, medical records and plasma levels monitoring, the medication compliance rates will be estimated and predictors of adherence to medical treatment evaluated. Results & conclusion: Not yet available.

P02.09 Sukru CANDESARTAN PREVENTS LONG TERM CHANGES INRESPONSE TO Oguzkan NEONATAL URETERAL OBSTRUCTION Topcu Sukru Oguzkan Topcu, Michael Pedersen, Guixian Wang, Mark A. Knepper, Søren Nielsen, Troels Munch Jørgensen and Jørgen Frøkiær Institute of Clinical Medicine, The Water and Salt Research Center, Aarhus University Angiotensin II (ANG II) plays a predominant role for numerous cellular and hemodynamic changes in various types of progressive renal damage. AT1 receptor blockers provide a direct means of protecting against influences of excessive Ang II levels. To evaluate the role of novel type 1 receptor antagonist, candesartan cilexetil in response to chronic (PUUO), newborn rats were subjected to severe PUUO or sham operated within the first 48hr of life. Candesartan (CAN) was provided in the drinking water in a subset of rats with PUUO, Sham from the 21th day of life until 10 weeks of age when rats were sacrificed. Renal blood flow (RBF) and GFR were measured using MRI and renal clearance of EDTA, respectively, and the

renal expression of Na-K-ATPase, AQP1, COX-1, COX-2, p-AQP2 and AQP2 were examined by semiquantitative immunoblotting and immunocytochemistry. RBF was significantly reduced in response to PUUO (0.8±0.1 vs.1.6±0.1 ml/min/100g bw, p<0.05), Likewise, GFR was impaired on the obstructed side (37±16 vs. 448±111 ul/min/100gbw, p<0.05). Furthermore, severe neonatal PUUO is associated with significant natriuresis(89±9 vs. 26±5 mmol/L, p<0.05), impairment in fractional sodium excretion(35.9±9.6 vs. 3.2±0.6 %, p<0.05) and caused a reduction in total protein concentration(3.6±0.4 vs.14.0±0.9 ug/ul, p<0.05) Consistent with these, the expression of AQP2 (52±15% vs.100±4%, p<0.05) and Na-K-ATPase (75±12% vs.100±5%, p<0.05) was downregulated in response to PUUO. CAN attenuated the pronounced hydronephrotic and obstructive changes. Moreover, CAN prevented the downregulation of AQP2 (74±13% vs.100±4%) and Na-K-ATPase (103±8% vs. 100±5%).In conclusion, CAN attenuates the reduction in RBF, GFR and prevents the dysregulation of AQP2, Na-K-ATPase in response to congenital PUUO.

P02.10 Lisbeth CLINICAL WISDOM AND RESPONSIBILITY AMONG PROFICIENT Uhrenfeldt NURSES University of Aarhus Graduate School of Health Sciences, 13 January 2006

58 Background: Recruitment of nursing students has been stable in the period 1970-1990. In Denmark nursing schools had an applicant increase of 16% from 2004 till 2005. Danish nurses are employed in the public production with tasks in health service, care of the elderly and disabled persons. Since 2001 Danish nurses have been in a bachelor program. Nordic as well as US scholars influence undergraduate and graduate programs. The scholars address retention effort towards proficient nurses because of their independence and clinical wisdom. Purpose: This study examined one theme that emerged from a broader interpretive hermeneutical study with the purpose to gain deeper knowledge of proficient nurses´ clinical wisdom. Design: Proficient nurses with variation in experience, employment and age from two Danish hospitals participated in a qualitative study. Methods: Data were collected through 20 semi-structured interviews with clinical nurses and stepwise analyzed using a hermeneutical approach. Findings: Clinical wisdom contained three elements: thinking, action, and responsibility. Conclusion: Knowledge is gained about experienced proficient Danish nurses and their clinical practise. Clinical wisdom was constituted based on individual professional’s thinking, action and responsibility but also showed working conditions that might press proficient nurses into non- proficient performance.

P03.01 Tina R. A NEW METHOD FOR TESTING SPEED OF INFORMATION Kilburn PROCESSING IN YOUNG CHILDREN BASED ON STERNBERG’S PARADIGM. TR Kilburn, U Kesmodel U, P Thorsen, NI Landrø, EL Mortensen, L Bakketeig NANEA at the Institute of Public Health, Department of Epidemiology, University of Aarhus, Vennelyst Boulevard 6, 8000 Århus, Denmark Background: In 1966, Sternberg suggested the existence of an internal serial-comparison process when retrieving and processing sequential information from recent memory. In adults, the mean reaction time increased linearly with the length of the set size. We have developed a new method to test information processing speed in young children with the aim to investigate whether young children use the same kind of process when making decisions regarding stored information as older children and adults do. Methods: Sternberg originally used nine digits in a computer based program. Since five year old children are not necessarily familiar with the digits, we developed a new version of the method with pictures familiar to this age group. Versions using either coloured fruits or black and white drawings of wild animals were used in strings of 1-2-3 as well as 2-3-4. A total of 50 children were tested with either combination. Results: The colour version did not show the expected linear trend, probably due to colour preference. For the black and white version, it was found that with the 2-3-4 version results were very similar to the linear results Stenberg obtained with adults. The linear increase with the length of set size was significant. The 1-2-3 version showed a similar tendency, but the confusion associated with the presentation of just one item resulted in a non-linear increase.

59 Conclusion: The speed with which information processing is carried out is an important ability in order to react quickly and make swift and correct decisions built on the collected information. We have developed a promising method that can measure this ability in children. In a clinical setting it can be used to differentiate whether intervention might be suggestible in aiding the child’s development.

P03.02 Lars Riber PERORAL ADMINISTRATED AMIODARONE PROPHYLAXIS FOR Zebis ATRIAL FIBRILLATION AFTER INTRAVENEOUS LOADING FOR PATIENTS UNDERGOING CORONARY ARTERY BYPASS GRAFTING: A RANDOMIZED, DOUBLE BLIND, PLACEBO-CONTROLLED TRIAL. L.R. Zebis, T.D. Christensen, L. Folkersen, M.M. Mikkelsen, H.T. Sørensen, V.E. Hjortdal Department of Cardio Thoracic and Vascular Surgery and Department of Intensive Care, Skejby Sygehus, Aarhus University Hospital, Brendstrupgaardsvej 100, DK-8200 Aarhus N, Denmark The aim of the study is to test whether a 5 day postoperative course of amiodarone treatment reduce the frequency of postoperative atrial fibrillation (AF) after Coronary Artery Bypass Grafting (CABG). Randomized, controlled, double blinded trial monitored by the GCP unit. The patient received a bolus infusion of 300 mg of amiodarone or placebo (dextrose 5% in water) over 20 minutes the morning after surgery in the intensive care unit together with the first 600 mg dose of oral amiodarone or placebo. The oral administration dose of 600 mg amiodarone/ placebo was then continued twice a day at 8 a.m. and 6 p.m. for five days. Out of 271 consecutive patients enlisted for CABG, 21 were excluded (18 met the exclusion criterias, 3 refused participation). 250 were rando-mized. Dropout: conversion to Off Pump Coronary Artery Bypass (OPCAB) 20, missing medicine 7, preoperative AF 6, PCI 4, patient request 3, double procedure 3, bradycardi 2, reoperation 2, hypotension 1, dead 1, no operation 1, ICD 1, ventricle aneurism 1, perioperative AMI 1. Dropout rate was estimated to 53/250 = 21%. The conclusion so far is that the necessary number of patients is included. The dropout rate was higher than expected especially due to OPCAB, missing medication and due to inclusion even when the exclusion criteria were met. Data analysis is ongoing.

P03.03 Anne C. BIRTH WEIGHT AS A CORRELATE OF BLOOD PRESSURE: Vingård UNEXPECTED ASSOCIATION BETWEEN SPOUSES Olesen Olesen AV, Parner ET, Overvad K, Olsen J Dept of Epidemiology, University of Aarhus, DK-8000 Århus C, Denmark Objective: Both lifestyle and uterine growth retardation are considered indicators of high blood pressure. This study addressed the well-known association between low birth weight and blood pressure in adult life by comparing spouses to adjust for confounding by lifestyle and norms in adult life. Methods: A matched cross-sectional study with historical data on birth weight from archived midwife records. Totally, 472 co-habiting couples of opposite sex, aged 50 to 65 years, and all born in Denmark were included.

60 The spouses were recruited through the Danish Diet, Cancer, and Health Study, providing measurements of blood pressure and total serum- cholesterol. Results: Birth weight was negatively correlated with blood pressure in both husbands and wives. Unexpectedly, data also displayed a positive correlation between blood pressure of one spouse and birth weight of the other. Conclusions: One should be careful when comparing data collected decades apart as it is needed within life-course epidemiology.

P03.04 Iben Søgaard t(4;12) TRANSLOCATION IN A PATIENT WITH BIPOLAR AFFEKTIVE Jacobsen DISORDER IS Jacobsen1, Z Tümer2, N Tommerup2, A Borglum3, H Horsboel1, O Mors1 1Centre for Basic Psychiatric Research, Aarhus, Denmark 2Wilhelm Johannsen Centre, Panum Institute, Copenhagen, Denmark 3Institute of Human Genetics, Aarhus University, Denmark Mapping of chromosomal breakpoints of apparently balanced translocations has been applied to find new potential susceptibility genes for psychiatric disorders in candidate regions suggested by linkage analysis. The DISC1 (Disrupted in Schizophrenia 1) gene is an example of a gene located within a breakpoint in a t(1:11) translocation co-segregating with schizophrenia and depression in a large Scottish kindred. We identified an apparently balanced t(4:12) translocation in a female patient affected by bipolar affective disorder, fulfilling the ICD-10 criteria. Both translocation breakpoints were located within or close to chromosomal regions suggested by linkage studies and were investigated with FISH (fluorescence in situ hybridization) analysis. The breakpoint on chromosome 4 is within a region with a gene desert where the nearest gene PCDH7 is at a 2.4 Mb distance. The breakpoint on chromosome 12 is located 122 kbp upstream to the PPFIA2 gene, which encodes liprin alpha 2. Liprin alpha proteins could be important for trafficking of synaptic vesicles, and the influence on both pre- and post-synaptic morphology could be more indirectly. Both translocation breakpoints have been located some distance away from any known genes. However long range effect of translocations on regulation of down- and/or upstream genes is a known phenomenon (SOX9 and Campomelic dysplesia) and could also apply to the present case. Another possibility is presence of a yet unknown gene at the translocation breakpoints.

P03.05 Esben THE GHRELIN RESPONSE TO EXERCISE BEFORE AND AFTER GH ADMINISTRATION Thyssen E. T. Vestergaard, T. K. Hansen, R. Dall, J. Frystyk, J. S. Christiansen, J. O. L. Vestergaard Jørgensen. Medicinsk Afdeling M, Århus Sygehus, Nørrebrogade 44, 8000 Århus C. (a) Ghrelin is a recently described peptide hormone produced by the enteroendocrine cells of the mucosal epithelial layer in the ventricle. Ghrelin stimulates pituitary growth hormone (GH) release. We have previously shown that exercise-induced GH release is not mediated by ghrelin, but it remains to be studied whether this increase in GH may suppress post-

61 exercise ghrelin levels. The aim of this study was to characterise systemic ghrelin levels post- exercise with and without concomitant GH administration. (b) In a double blind, placebo-controlled, parallel study, thirty-two healthy subjects (age: 18 to 33 yrs) were randomized to placebo, rhGH 0.1 IU/kg per day, or rhGH 0.2 IU/kg per day for four weeks followed by an eight weeks wash-out period. The subjects performed a multistage fitness

test to asses VO2-max at baseline and after four weeks. We measured total circulating ghrelin levels immediately after exercise and at 15, 30, 60, 90, and 120 minutes post-exercise. (c) Exercise at baseline was associated with a significant lowering of ghrelin levels post-exercise (p < 0.0001). In addition, high dose GH was

followed by ~25% reduction in AUCghrelin (µg/l x min): 168.0 (range 69.2 - 377.0) vs. 127.9 (range 59.0 - 368.6), p < 0.05. (d) Conclusions: 1) ghrelin levels decrease significantly post-exercise in healthy subjects, 2) high dose GH suppresses ghrelin levels, 3) these data support the hypothesis that GH feed-back inhibits ghrelin secretion. Acknowledgements: This study was supported by research grants from the World Anti-Doping Agency. The study was derived from the Danish part of the GH-2000 project and we thank the members of GH-2000 team.

P03.06 Nina Ank THE INTERFERON- – A NOVEL INTERFERON – IS PRODUCED DURING VIRAL INFECTIONS AND EXERTS ANTIVIRAL ACTIVITY Nina Ank and Søren R. Paludan Medical Microbiology and Immunology, University of Aarhus, DK-8000 Aarhus C, Denmark For several years interferons (IFN) have been known to have antiviral

activity. Recently three novel IFNs were discovered and named IFN- 1 &

IFN- 2/3. We report here that IFN- can be induce by many viruses, including Herpes Simplex Virus type 2 (dsDNA), Encephalomyocaditisvirus (+ssRNA), Sendai virus (-ssRNA), Reovirus (dsRNA), and Influenza virus (Seg. – ssRNA). But not only did we see an up-regulation of IFN- after stimulation with the mentioned viruses, we are also able to demonstrate that IFN- , unlike IFN- and IFN- , is produced in both lymphoid cells and

non-immune cells. Furthermore, we report that stimulation with IFN- causes an up-regulation of mRNA of PKR, OAS and ISG56, but not IFN- / , thus suggesting the antiviral activity of IFN- to be independent of type I IFN. A number of studies have demonstrated that IFN- has antiviral activity against several RNA viruses in vitro, but antiviral activity against DNA viruses such as herpesviruses has until now not been demonstrated. We report here that not only has IFN- antiviral activity against the +ssRNA virus Encephalomyocarditisvirus but also against the dsDNA virus herpes simplex virus type 2. Thus, our data show for the first time that IFN- s do have antiviral activity against herpesviruses, and also that this novel class of IFNs are indeed a bona fide antiviral cytokine.

62 P03.07 Ole Eschen SOLUBLE ADHESION MOLECULES IN HEALTHY SUBJECTS: A DOSE- RESPONSE STUDY WITH N-3 FATTY ACIDS Ole Eschena, Jeppe Hagstrup Christensen b, Raffaele De Caterina c, Erik Berg Schmidt a. Department of aCardiology or bNephrology, Aalborg Hospital, 9100 Aalborg , Denmark. cChair of Cardiology, “G. d’Annunzio” University, Chieti, and C.N.R. Institute of Clinical Physiology, Pisa, Italy. Background: Dietary intake of long-chained n-3 polyunsaturated fatty acids (PUFA) may protect against atherosclerotic disease. Serum levels of soluble cellular adhesion molecules (sCAMs) may reflect the inflammatory process underlying atherosclerosis. Purpose of the study: 1) To examine the correlation between the levels of sP-selectin, sICAM-1 and sVCAM-1 and the content of marine n-3 fatty acids in granulocyte membranes in healthy subjects and 2) to assess whether dietary n-3 PUFA in different doses affect serum levels of sCAMs. Design: Sixty healthy volunteers were randomly assigned to three treatment groups in a double blind design. The subjects received a daily supplement of 6.6 g n-3 PUFA, 2.0 g n-3 PUFA, or olive oil. Serum levels of sCAMs and the fatty acid content of granulocyte membranes and serum lipids were measured at entry and after 12 weeks of supplementation. Results: A significant negative correlation was found between serum levels of sICAM-1 and the content of DHA in granulocyte membranes at entry (r=-0.28, p<0.05). After supplementation with 6.6g of n-3 PUFA, a significant decrease in sCAMs was found only for sP-selectin (81±23 vs 73±20, p<0.01). Conclusion: The study showed a significant decrease in sP-selectin after supplementation with 6.6g n-3 PUFA. This may indicate a beneficial effect of n-3 PUFA from fish with respect to atherosclerosis.

P03.08 Astrid Heide ABSORPTION OF INHALED INSULIN DRAMATICALLY INCREASES BY Petersen LARGE TIDAL VOLUME VENTILATION IN RABBITS A. H. Petersen1,2,3, T. Laursen2, P. Clauson3, P. Wollmer4; 1Dept. of Internal Medicine, Medical University Graz, A-8010 Graz, Austria, 2 University of Aarhus, Aarhus, Denmark, 3Novo Nordisk A/S, Bagsvaerd, Denmark, , 4 Lund University, Malmö, Sweden. The objective of this study was to investigate the effect of large tidal volume ventilation (LTVV) on the absorption of inhaled insulin in rabbits. Ventilated rabbits inhaled human insulin (5U) via a nebuliser system, and plasma insulin levels were measured for the following 120 min. Ventilation was adjusted according to randomization in the four groups (N=8 each): 1) Normal tidal volume ventilation (NTVV, 40 breaths/min and an inspiratory

pressure of 10 cmH2O over a positive end-expiratory (PEEP) of 2 cmH2O)

during the entire 120 min [NTVV], 2) LTVV (20 breaths/min, and 23 cmH2O over PEEP) during the entire 120 min [LTVV], 3) NTVV except for 15 min LTVV immediately after dosing [Early LTVV], and 4) NTVV except for 15 min LTVV starting at 60 min post dosing [Late LTVV].

Total insulin absorption (AUCins(0-120min)) was significantly greater (149%) in the [LTVV] group compared to the [NTVV] group (p<0.01) as was the

maximal insulin concentration (Cmax) (106%, p=0.03), while the time to Cmax

63 was not statistically significantly different. [Early LTVV] led to changed absorption profile. For [Late LTVV] an increase in insulin levels was observed after the LTVV period (n.s. compared to [NYVV]). In conclusion, LTVV during the whole period increased absorption of

inhaled insulin in rabbits, with a significantly increased AUCins(0-120min) and

Cmax, and even short periods of LTVV changed the absorption profiles. These data could potentially have implications for patients using inhaled insulin in situations where a change in breathing pattern is seen, such as exercise.

P03.09 Brian Dall ANTIVIRAL ACTIVITY OF SMALL INTERFERING RNAS: SPECIFICITY Schyth TESTING USING TARGET-HETEROLOGOUS VIRUS REVEALS IFN RELATED EFFECTS OVERLOOKED BY CONVENTIONAL MISMATCH CONTROLS B. D. Schyth1*, N. Lorenzen1 & F. S. Pedersen2 1Danish Food and Veterinary Research, Århus, Denmark 2Molecular Biology, Aarhus University, C.F. Møllers Alle, 8000 Århus C RNA interference (RNAi) is a cellular defence mechanism, activated when double stranded RNA (dsRNA) enters the eukaryotic cell. Briefly, the dsRNA is cut into smaller 21 base pair pieces by an intracellular enzyme called Dicer and delivered to the RNA-induced silencing complex (RISC), where the small RNA strands are used in a primer-like fashion to bind to complementary single stranded RNAs in the cell cytoplasm, and degrade these by nuclease activity of the RISC complex. In gene functional studies RNAi can be used to down regulate expression of specific genes, by delivering small dsRNAs designed to have one strand complementary to an mRNA target. Because high specificity can be achieved, RNAi is also exploited as a treatment of diseases, where genes essential to the survival of a pathogen can be targeted at the transcriptional level. The presented study is focusing on RNAi in fish cells, where the mechanism is only partly described. It is the aim to set up protocols for using siRNAs in fish cells and whole fish and more specific to study the ability of siRNAs in interfering with viral replication of the fish pathogenic rhabdovirus Viral Haemorrhagic Septicaemia Virus (VHSV). In the first attempts we have used in vitro produced siRNAs against the envelope G gene of VHSV. Viral replication of VHSV was strongly inhibited in fish cells treated with selected siRNAs before inoculation of virus on cells. However the siRNA treatment also inhibited replication of heterologous rhabdoviruses. The protective effect was correlated with the abilities of the siRNA to stimulate the antiviral interferon response. Experiments with synthetic siRNAs against VHS G are now carried out in order to check the ability of the siRNAs to specifically interfere with VHSV G expression.

P03.10 Inger CARTILAGE THICKNESS IN THE HIP JOINT MEASURED BY MRI AND Mechlenburg STEREOLOGY I Mechlenburg1, JR Nyengaard2, J Gelineck3, K Søballe1 1Department of Orthopaedics, University Hospital of Aarhus, Denmark 2 Stereology and Electron Microscopy Laboratory, University of Aarhus,

64 Denmark 3 Department of Radiology, University Hospital of Aarhus, Denmark Introduction. Periacetabular osteotomy is performed in dysplastic hips and the result of surgery is largely dependent on the degree of preoperative osteoarthritic involvement. As periacetabular osteotomy is performed on dysplastic hips to prevent osteoarthritic progression, changes in the thickness of the articular cartilage is a central variable to evaluate. For this purpose we developed a method by which the thickness of the articular cartilage in the hip joint can be quantified based on Magnetic Resonance Imaging (MRI) and 3D design-based sampling principles (stereology). Material and methods. Twenty six dysplastic hips on twenty two females and four males were MR scanned preoperatively. The first 13 patients were examined twice, with complete repositioning of the patient and set-up in order to obtain an estimate of precision of the method used. To show the acetabular and femoral cartilages separately, an ankle traction device was used during MRI. This device pulled the leg distally with a load of 10 kg. Results. The mean thickness of the acetabular cartilage was 1.26 mm, SD 0.04 mm and CV 0.03. The mean thickness for the femoral cartilage was 1.18 mm, SD 0.06 mm and CV 0.05. The precision calculated as the coefficient of error of the mean was estimated for the thickness of the acetabular cartilage 0.01 and femoral cartilage 0.02. The measurements took 15-20 minutes per hip to carry out. Conclusion. The described method is an unbiased and precise method for quantifying the thickness of the articular cartilage in the hip joint. We suggest that the method can be advantageous for assessing the progression of osteoarthritis in dysplastic hips after periacetabular osteotomy.

P04.01 Charlotte CAFFEINE IMPROVES ENDURANCE IN 75-YEAR OLD CITIZENS. A Buchard RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, CROSS- Norager OVER STUDY. C.B. Norager, M.B. Jensen, M.R. Madsen, S. Laurberg Surgical Research Department, Herning Hospital, Gl. Landevej 61, DK-7400 Herning, Denmark. This study investigated the effect of caffeine on physical performance in healthy citizens aged 70 years. The randomized, double-blind, placebo-controlled cross-over study was conducted in 15 males and 15 females recruited by their general practitioner. Participants abstained from caffeine for 48 hours and were randomized to receive one capsule of placebo then caffeine (6 mg/kg) or caffeine then placebo with one week in between. One hour after intervention we measured reaction and movement times, postural stability, walking speed, cycling at 65% of expected maximal heart rate, perceived effort (RPE) during cycling, maximal isometric arm flexion strength and endurance. Analysis was by intention-to-treat and p<0.05 was regarded as significant. Caffeine increased cycling endurance by 25% (95% CI: 13-38; p=0.0001), and isometric arm flexion endurance by 54% (95% CI: 29-83; p=0.0001). Caffeine also reduced the RPE after five minutes of cycling by 11% (95% CI: 5-17; P=0.002), and postural stability with eyes open by 25% (95% CI: 2-53;

65 p=0.03). Caffeine ingestion did not affect muscle strength, walking speed, reaction and movement times. At the end of the study 46% of participants correctly identified when they received caffeine and placebo. Caffeine increased exercise endurance in healthy citizens aged 70 years, but the participant’s reasons for stopping the test may have varied between subjects as the cycling test was done at approximately 55% of maximal oxygen consumption. Further studies are required to investigate whether caffeine can be utilized to improve the physical performance of elderly citizens.

P04.02 Emad Eddin HYPERSENSITIVITY TO PIN-PRICK STIMULI FOLLOWING Ayesh NOCICEPTIVE ELECTRICAL STIMULATION OF THE HUMAN TMJ Ayesh EE1, Jensen TS2, Svensson P1 1School of Dentistry, University of Aarhus, 2Danish Pain Research Center The overall goal of this Ph.D.-project is to develop a technique to study nociception in the human temporomandibular joint (TMJ) by application of electrical stimulation. This first study aimed to compare the sensitivity after painful skin stimulation and intra-articular stimulation of the TMJ. A total of 43 subjects (24 and 19 ) without TMDs participated. Two unipolar needle electrodes were inserted into the skin or into the TMJ. Electrical pulses were used to determine sensory detection threshold (SDT), pain detection threshold (PDT) and summation threshold (SumT). Repetitive electrical stimuli (0.5 ms duration, 5 Hz) were adjusted to generate a pain sensation around 5 on a 0-10 cm visual analogue scale for 20 min. Von Frey filaments (5.16 g = tactile and 84.96 g = pin-prick) were used to assess the sensitivity to mechanical stimuli at 11 points before stimulation (baseline), after 20-min, and 15 min after end of stimulation. Intensity of von Frey filaments was rated on a 0-100 numerical rating scale. ANOVA was used to test the data. SDT, PDT and SumT (P<0.01) were lower in skin compared to TMJ without gender difference (P>0.7). After TMJ stimulation, ANOVAs indicated moderate, but significant pin-prick hyperesthesia in the TMJ area after 20 min, and 15 min post-stimulation compared to baseline values (P<0.001), without gender differences. Tactile sensation was significantly decreased after 20 min, and 15 min post-stimulation compared to baseline values (P<0.001), without gender differences. There were no significant changes after skin stimulation. The TMJ appears to be less sensitive to electrical stimuli compared to the skin, however, continous nociceptive input to TMJ is associated with hyperesthesia to pin-prick stimuli and decrease in tactile sensation in the area around TMJ, without gender differences.

P04.03 Ingolf Mølle SELECTED GENETIC POLYMORPHISMS OF THE INNATE IMMUNE SYSTEM AND CHEMOTHERAPY-RELATED INFECTIONS IN PATIENTS WITH MULTIPLE MYELOMA Ingolf Mølle, Charlotte Nyvold, Steffen Thiel, Rudi Steffensen Department of Haematology, Aarhus Sygehus, THG Patients with multiple myeloma frequently suffer from severe infections

66 during chemotherapy courses. This significantly affects morbidity and mortality. The aim of this project is to seek to identify genetic variants of the innate immune system as possible risk factors for infections. Polymorphisms of the mannose-binding lectin promotor gene, the MBL2 gene, the MASP-2 gene, and the Fc gamma receptor IIa-, IIIa-, and IIIb- genes will be identified with molecular biological methods using frozen stem cells or paraffin embedded trephine samples. Information about infections during chemotherapy courses is found in a project database, which was established in the beginning of the project period.

P04.04 TINA CLINICAL ASPECTS OF BASAL INSULIN PUMP THERAPY FOR 8 PARKNER HOURS VERSUS 24 HOURS IN PATIENTS WITH TYPE 2 DIABETES T. Parkner1, M.K. Møller1, J-W. Chen1, T. Laursen1, H.F. Thomsen, C. Jørgensen, J. Smedegaard, T. Lauritzen and J.S. Christiansen1 1Department M, Aarhus University Hospital, 8000 Aarhus C, Denmark The aim of the present study was to compare the effect of basal insulin supplementation by means of continuous subcutaneous insulin infusion (CSII) therapy for 8 hours at night and 24 hours, employing the short-acting insulin aspart analogue, in patients with type 2 diabetes. Ten type 2 diabetic patients with poor plasma glucose control in response to oral anti-diabetic (OAD) treatment were included in this randomized cross-over study. Following an initial 24 hours control day, two 3-day periods with basal CSII therapy, employing insulin aspart infusion at a rate of 1.5 IU/h, for 8 hours (night) versus 24 hours, were compared. The two periods were separated by a 2 week wash-out period. The patients received usual OAD treatment throughout the study. Plasma glucose and serum insulin profiles were recorded. Compared to the control day, the 8 hours infusion period significantly improved fasting plasma glucose (FPG) and post-prandial plasma glucose (PPG) after breakfast, whereas 24 hours infusion improved FPG and all three PPG values. Compared with the 8 hours infusion, the 24 hours infusion significantly improved PPG after breakfast (1.49±0.46 mmol/L; P = 0.0014), after lunch (1.60±0.47 mmol/L; P = 0.0007), and after dinner (1.84 ±0.46 mmol/L; P = 0.0001). No major hypoglycaemic episodes occurred. Basal insulin therapy administered at fixed subcutaneous infusion rate of 1.5 IU/h for 8 hours (overnight) or 24 hours substantially improves glycaemic control in OAD treated type 2 diabetic patients. The effect on the FPG was equivalent, whereas the effect on PPG was superior during the 24 hour treatment as compared to the 8 hours over-night infusion. Fixed basal subcutaneous insulin therapy lowers the FPG levels, and has a profound effect on PPG control as well.

P04.05 Zahra COMPARATIVE STUDY ON THE FUNCTIONAL α1-ADRENOCEPTOR Nourian AFFINITY OF ANTIPSYCHOTIC DRUGS IN RAT SMALL MESENTERIC ARTERIES AND THORACIC AORTA Z. Nourian, J. Matz1, M.J. Mulvany Department of Pharmacology, University of Aarhus, Aarhus, and 1H. Lundbeck A/S, Copenhagen, Denmark

67 The therapeutic action of most antipsychotic drugs in the treatment of schizophrenia is attributed to their central dopamine antagonist effect, but

they also have effects on α1-adrenoceptors (AR) in blood vessels. Here we have determined the affinity of antipsychotic drugs (haloperidol, sertindole, risperidone, clozapine, ziprasidone, domperidone, olanzapine and

aripiprazole) in male Wistar rat small mesenteric arteries (mainly α1A–AR)

and rat aorta (prominent α1D–AR). Segments of rat small mesenteric arteries (SMA) and thoracic aorta were mounted on a wire myograph for isometric tension recording. Cumulative concentration response curves were constructed to phenylephrine (PE) in absence and presence of the antipsychotics. Appropriate vehicle controls

and blockers were used throughout. pA2 values were calculated by Schild analysis. Cumulative concentration-contraction curves for PE were

competitively antagonized by prazosin in the SMA (pA2=9.52) and rat aorta

(pA2=10.1). Risperidone had the highest and domperidone had the lowest

functional affinity for both α1-AR subtypes. The responses to PE in the SMA were also antagonized by the presence of sertindole, ziprasidone, clozapine,

haloperidol, olanzapine, and aripiprazole (pA2 values 8.78, 7.98, 7.64, 7.64, 7.35, and 7.17, respectively). On rat aorta, sertindole and haloperidol gave Schild slopes significantly different from unity. Endothelial removal did not

affect either pA2 values or the Schild slopes in the presence of sertindole and risperidone in SMA. We conclude that all the investigated antipsychotics exhibited moderate to

high functional α1A- and α1D–AR affinity except sertindole, aripiprazole, and

haloperidol which had little affinity for α1D– AR.

P04.06 Susanne NEW POTENTIAL EFFECTS OF GLP-1, WITH A SPECIAL FOCUS ON Lerche THE CNS AND HEART Susanne Lerche MD, Birgitte Brock, MD, Ph.d., Albert Gjedde, Professor,dr.med, Ole Schmitz, Professor,dr.med. Department of Pharmacology, Bartholinbygningen, University of Aarhus, 8000 Aarhus C, Denmark and The PET-center, Aarhus Sygehus NBG, 8000 Aarhus C Type 2 diabetes mellitus (T2D), is a disease characterized by an immense growing prevalence world wide. It is associated with a 3-fold increase in cardiovascular complications. The British Prospective Diabetes Study (UKPDS) showed that neither diet alone nor the pharmaceutical treatment utilized were able to affect these complications. Also intensive treatment with insulin is limited by the risk of hypoglycaemia. (Glucagon-like-peptide-1)GLP-1 is an incretin hormone with convincing effects on glycaemia in type 2 diabetic patients with little or no risk of hypoglycaemia. Recent research in animal models has shown a potential protective effect in the brain and heart. The mechanism behind these protective effects however is not known. The effect of GLP-1 on glucose uptake in the brain and heart will be visualized by PET-scan with FDG as tracer during normo- and hypoglycaemia using clamp techniques in healthy young men. The hypothesis is that GLP-1 directly will stimulate glucose uptake independent of the islet hormones and through this mechanism

68 exert its protective actions. Also the effect of GLP-1 on glyceamia and counterregulatory hormones during 48 hours of fasting will be evaluated in healthy young men. The hypothesis is that GLP-1 will not induce hypoglycaemia during long time fasting. The studies will give considerable knowledge about the potential mechanism behind these protective effects of GLP-1, and also give important information about its safety regarding hypoglycaemia. Already one GLP-1 agonist is available for the treatment of T2D in the USA.

P04.07 Anne Sofie ALTERNATIVE SPLICING IN BLADDER CANCER. Brems- A. S. Brems-Eskildsen. Eskildsen Department of Clinical Biochemistry, University of Aarhus, Brenstrupgårdsvej, Skejby, 8200 Århus N. Malignant transformation is known to involve changes both at the chromosomal and DNA level and thereby development of tumours and progression to different stages. One of the mechanisms, which might be of importance in the malignant transformation, is splicing of exons during the transcription/translation process from DNA to protein. Splicing is hypothesized to play a role in production of different, but similar proteins that might be inactive or have opposite functions compared to their normal variant. There may be as many as 5-10 splice variants per gene. Splicing might also function as a regulatory mechanism. The aim of my research is to investigate: Has alternative splicing a correlation to the level of gene expression of certain genes? The aim is to detect splice variants by Exon Array form Affymetrix and establish an rtPCR method to validate the results. The aim is to: 1 identifies known splice variants in cell lines in a reproducible way. 2 detect splice variants in bladder cancer. 3 discover new splice variants in bladder cancer. 4 identify differences in splice variants between different stages of disease. Materials are tissue from the MOB tissue bank at Skejby Hospital. In this bank there are bladder cancer patients, and follow up are possible with journals. Cell lines are established in the laboratory and these have been characterized by sequencing of key genes and expression profiling. Methods: Use Exon arrays form Affymetrix to discover splice variants in bladder cancer. Validate the results with rtPCR and cell lines. Work with model genes in cell lines. Perspectives: The general aim is to get insight into splicing events in bladder cancer and characterise differences, during the progression of bladder cancer, and in the long run to discover new markers for bladder cancer and new targets for therapy.

P04.08 Torben H. SPATIAL AND TEMPORAL ASSESSMENT OF OROFACIAL Thygesen SOMATOSENSORY SENSITIVITY: A METHODOLOGICAL STUDY T.H. Thygesen, J. Jensen, S.E. Noerholt, P Svensson. Department of Oral and Maxillofacial Surgery, Aarhus University Hospital, DK-8000 Aarhus C, Denmark. Department of Clinical Oral Physiology, School of Dentistry, University of Aarhus, DK-8000 Aarhus C, Denmark The overall aim of the Ph.D.-project is to describe somatosensory function of the maxillary nerve in patients before and after orthognathic surgery on

69 the maxilla. The aim of the present sub-project was to evaluate the sensitivity and reproducibility of four different psychophysical techniques for the assessment of both spatial and temporal changes in somatosensory function before and after an infraorbital nerve block. Sixteen healthy subjects participated in two experimental sessions separated by 2 weeks. The subjects rated the perceived intensity of four standardized psychophysical stimuli applied to 5 x 5 points in the infraorbital region using a numerical rating scale (NRS) to encompass non-painful and painful scores. An acrylic mask with adjustable settings was used to allow stimulation of the same points in both sessions. ANOVA analysis of mean NRS scores, number of points, and center-of-gravity coordinates for all test stimuli showed no significant effects of session. Post-hoc tests for all stimuli demonstrated significantly lower mean NRS scores and significantly higher number of points with hyposensitivity at 30 min and 60 min post-injection compared to baseline (Tukey tests: P < 0.002). Our findings indicate that the psychophysical method is sufficiently reproducible. All stimuli demonstrated adequate sensitivity since local anesthesia was associated with significant changes in psychophysical measures. Furthermore, measurement of 5 x 5 points allowed a spatial description of somatosensory sensitivity. We suggest that the present method may be valuable for clinical studies on changes in somatosensory sensitivity following trauma or orthognathic surgery on the maxilla.

P04.09 Ann Suhl THE STRUCTURE OF ANXIETY SYMPTOMS – AN INVESTIGATION OF Kristensen DIMENSIONAL SUBTYPES OF ANXIETY AND OF THE RELATIONSHIP BETWEEN SYMPTOM SUBTYPES AND AETIOLOGICAL FACTORS A. S. Kristensen, PhD-stud, MSc (Psych), & O. Mors, Professor, PhD, MD Centre for Basic Psychiatric Research, Aarhus University Hospital, Skovagervej 2, 8240 Risskov, E-mail: [email protected] Both genetic studies and studies of treatment response are starting to subdivide and redefine existing diagnostic categories of anxiety in order to identify more homogeneous subtypes. The investigation of possible subtypes of anxiety disorders is also of great importance to the development of new, more valid diagnostic entities. One way of subdividing the present descriptive phenotypes into potentially more homogeneous subtypes is through structural equation modeling. The aim of this study is to explore sub-dimensions of anxiety symptoms in patients with panic disorder, agoraphobia or social phobia, to investigate whether these sub-dimensions are replicable and to examine whether they are differentially related to co-morbidity or to psychological risk factors, such as personality. 200 patients with early onset of panic disorder, agoraphobia and/or social phobia are included as part of a genetic study. Furthermore, 200 patients, who fulfil the diagnostic criteria for panic disorder, agoraphobia and/or social phobia, are included in the replication study. Patients are diagnosed using Schedules for Clinical Assessment in Neuropsychiatry. Anxiety symptoms are further assessed through a self-completion questionnaire with 187 anxiety symptoms. Personality questionnaires, the TCI and the

70 NEO PI-R, are also completed. Preliminary results will be presented at the PhD Day 2006 concerning the factor structure of ICD-10 anxiety symptoms, subdivided into 28 questionnaire items. The factor structure is examined through principal component analysis, eigenvalue > 1, scree test, and oblique rotation.

P04.10 Rasmus INVESTIGATION OF THE RECEPTOR-MEDIATED ENDOCYTOSIS OF

Beedholm TRANSCOBALAMIN/INTRINSIC FACTOR-VITAMIN B12 COMPLEXES R. Beedholm1, C. B. Grissom2, S. N. Fedosov3, E. Nexø4 and S. K. Moestrup1 1Department of Medical Biochemistry, University of Aarhus, Denmark. 2Department of Chemistry, University of Utah, Utah. 3Department of Molecular Biology, University of Aarhus, Denmark and 4Clinical Biochemistry, Aarhus University Hospital, Denmark.

The transport of vitamin B12 (B12)/cobalamin in the tissue-fluids is facilitated by three different binding-proteins: Intrinsic factor (IF), transcobalamin (TC) and haptocorrin. Especially the first two are important

for the cellular uptake of B12. Intrinsic factor is produced in the ventricle and

is essential for the B12 uptake in the distal part of ileum by the receptor

complex cubilin/amionless. TC is important for the uptake of B12 from

plasma. In the kidney, megalin is the receptor for the TC- B12 complex,

whereas uptake of TC- B12 in the extrarenal tissue occurs by means of a still unknown receptor structure. This receptor is suggested to be regulated by

the vitamin B12 level in the cells, which is interesting in relation to cancer

growth. The cellular endocytosis of TC- B12 complex by this unknown receptor is being investigated, using confocal microscopy. Fluorescently

labeled B12 molecules (Origon green linked to B12) have been synthesized to

determine the B12 uptake level in normal and various tumour-derived cells (e.g. Hela cells from cervix epithelioid carcinoma and BN- cells from rat

yolk sac sarcoma). Costaining of the B12 binders has been performed using fluorescently labeled secondary antibodies recognising primary antibodies against IF and TC. The data show a cell growth-regulated uptake of free

fluorescent B12 but a strong inducement of uptake by TC and IF. After

uptake the B12 fluorochrome colocalizes with the B12 binders.

P05.01 Thomas REPETITIVE FIRING OF ACTION POTENTIALS SHIFTS THE Holm EXCITABILITY OF RAT MUSCLES VIA A REDUCTION IN THE RESTING Pedersen CL- CONDUCTANCE T. H. Pedersen, O. B. Nielsen Institute of Physiology and Biophysics, University of Aarhus, Denmark In skeletal muscle fibres, the tendency for action potentials (AP) to be initiated is dampened by a high passive Cl- conductance that enables large leak currents, which tend to clamp the resting membrane potential. In resting muscles, this serves to prevent uncontrolled muscle contractions and myotonia. In contracting muscles, however, excitability may for several reasons by reduced, making a high Cl- conductance a hindering for the initiation of muscle APs in response to motor activity. Based on this, the aim of this study was to examine, if a compensatory decrease in the Cl- conductance takes place during trains of APs in fibers from rat extensor digitorum longus. Intact muscles from 12 week old rats were placed in

71 Krebs-Ringer bicarbonate buffer at 30 oC containing 50 µM BTS to specifically inhibit the contractile apparatus and fibre movement. Change in Cl- conductance was estimated from measurements of the input resistance

(Rin) of the membrane: Individual fibres were impaled by two glass microelectrodes 50 µm apart. One electrode injected constant current pulses and the other electrode recorded the membrane potential. By changing

polarity, duration and amplitude of the current pulses, recordings of Rin and trains of AP could be alternated as required. The fibres were stimulated by

30 Hz trains of 100 AP separated by 3.3 s rest periods during which Rin was

determined. After 500 AP, Rin was increased from 0.21±0.02 to 0.27±0.03, - n=7. After reducing the Cl concentration from 127 to 50 mM, however, Rin only increased from0.37±0.01 to 0.38±0.01, n=4. These results show that during repetitive AP, Cl- channels are closed which could help maintain muscle fibre excitability during contractions

P05.02 Manhai Long DIOXIN-LIKE ACTIVITIES IN BLOOD ACROSS EUROPEAN AND INUIT POPULATIONS M Long1, BS. Andersen1, C Lindh, L Hagmar, JP Bonde, EC Bonefeld- Jorgensen1 and the IUUEDO group* 1 Department of Environmental and Occupational Medicine, Institute of Public Health, University of Aarhus, Denmark; * www.inuedo.dk Exposure to certain persistent organic pollutants (POPs) such as polychlorinated dibenzo-p-dioxins/furans (PCDD/PCDFs), polychlorinated biphenyls (PCBs) and organochlorine pesticides can cause a series of negative effects in animal and human including adverse effects on reproduction, neurobehavior, many of which involve the aryl hydrocarbon receptor (AhR). The aim of the present study is to compare the actual and integrated serum level of dioxin-like activity among European and Inuit populations and to evaluate whether the dioxin-like activity is correlated to the proxy markers of bio-accumulated POPs, 2,2’,4,4’,5,5’-hexachlorobiphenyl (PCB153) and 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p’-DDE). The AhR-mediated activities in lipophillic serum extracts containing the POPs of 338 males from Inuits (n= 75), Warsaw (n=99), Sweden (n=78) and Kharkiv (n=86) were determined by using the chemical activated luciferase gene expression (CALUX) bioassay. Significant differences of agonistic AhR- activities were observed among the study groups but these differences could not be explained by PCB153 and p,p’-DDE levels alone. The three European groups had higher CALUX- TEQs (TCDD toxic equivalents) compared to Inuits. The Inuit serum extracts showed higher further increased TCDD induced AhR activity than that of three European groups. No significant correlations between CALUX-TEQ and PCB153 or p,p’-DDE levels were observed. Significant negative correlation between competitive AhR activity, which was assessed in the presence of TCDD, and PCB153 was found on Kharkiv men. PCB153 and p,p’-DDE seemed not to be suitable key compounds as global POP marker for dioxin-like compounds. Our data suggest that serum dioxin-like activity reflects the pattern of POP and can contribute to assessment of chemical body burden and health risks.

72 P05.03 Britta CLINICAL RESEARCH – NURSING INTERENTION: DYSFUNCTION Hørdam AND GENERAL HEALTH STATUS OF PATIENTS OVER 65 YEARS UNDERGOING TOTAL HIP-REPLACEMENT. Britta Hørdam Introduction: Total hip replacement is regarded as a very efficient operation in terms of pain-relief and improvement of walking ability. However, after the operation many of the patients still suffer from dysfunctions and low general health status leading to reduced functional ability. A rehabilitation programme which focuses on self-care might improve the outcome of THR. Aim of the study: To describe self-rated physical and general health and types of dysfunctions among patients undergoing THR. To analyze the associations between type of dysfunctions and general health status according to gender, age, living alone and dependency on others for help. Material and methods: A cross-sectional-study including 287 patients above 65 years undergoing THR during a period of 12 months was performed. Patients from five counties in Denmark were included. Self- rated physical dysfunction and general health status were recorded using SF-36. Results: Women, patients living alone, patients dependent on help from others and patients above the age of 75 experienced a significantly higher risk of dysfunctions. Patients, who depended on help from others and patients living alone had a significantly lower general health status. Conclusion: The results obtained with respect to self-rated physical dysfunction and general health status are unsatisfactory in some specific groups of patients undergoing THR. The results from an ongoing intervention study (RCT) will facilitate the development of clinical guidelines to enhance the clinical outcome after THR.

P05.04 Martin LOW INSULIN-LIKE GROWTH FACTOR-I (IGF-I) AND IGF BINDING Eivindson PROTEIN-3 LEVELS IN ACTIVE ULCERATIVE COLITIS AND CROHN’S DISEASE: PARTIAL NORMALIZATION DURING PREDNISOLONE TREATMENT Martin Eivindson 1, Henning Grønbæk 1, Allan Flyvbjerg 2, Jan Frystyk 2, Jens Frederik Dahlerup 1 1Medical Department V, Aarhus University Hospital, Aarhus, E-mail:[email protected] 2Medical Research Laboratories, Aarhus University Hospital, Aarhus Objectives: Metabolic bone disease (MBD) and muscle wasting (MW) are serious complications in adults suffering from Inflammatory Bowel Disease (IBD). Patients with Crohn’s Disease (CD) are at higher risk of osteoporotic bone fractures than patients with Ulcerative Colitis (UC). The inflammatory process and corticosteroid treatment may lead to changes in the IGF-system involving MBD and MW. Methods: We studied 37 IBD patients with severe exacerbation (20 with UC and 17 with CD) before and during high dose prednisolone treatment (1 week) and tapering (8-12 weeks). Ten healthy subjects served as controls. The aim of the present study was to assess changes in circulating total and

73 free IGF-I and IGF binding proteins (IGFBPs) along with clinical and biochemical markers of IBD. Results: Total IGF-I was significantly reduced by 36% (p<0.01) in CD and 41% (p<0.001) in UC before treatment and normalized after 1 week of treatment. IGFBP-3 was significantly reduced by 38% (p<0.001) in CD and 32% (p<0.001) in UC prior to treatment with only partial normalization after treatment was stopped (CD: 20% p<0.01 and UC: 28% p<0.001). Free IGF-I and IGFBP-1 were unchanged throughout the study period. Harvey Bradshaw index (HBI), CRP and albumin normalised during prednisolone treatment and tapering. There were no differences in the IGF-system between CD and UC during the study period. Conclusions: Marked changes in total IGF-I and IGFBP-3 were demonstrated in CD and UC patients in exacerbation with only partial normalization during high dose prednisolone treatment and tapering. These changes may be part of the catabolic state in active IBD.

P05.05 Mette WHICH BIOETHICAL PRINCIPLES SHOULD BE USED WITHIN Ebbesen BIOMEDICINE? Mette Ebbesen Centre for Bioethics & Faculty of Health Sciences, University of Aarhus. Email: [email protected] There is extensive discussion on which principles should be used within biomedicine to analyse ethical problems. By performing a phenomenological analysis, the Danish philosophers Jacob Rendtorff & Peter Kemp indicate that the principles of respect for autonomy, dignity, integrity, and vulnerability are the four basic principles in biomedicine and biolaw in Europe (Basic Ethical Principles in European Bioethics and Biolaw. Vol. 1: Autonomy, Dignity, Integrity and Vulnerability. Denmark: Centre for Ethics and Law, 2000, p. 19). However, by examining considered moral judgements within biomedicine two American bioethicisists, Tom L. Beauchamp & James F. Childress, are convinced that the principles of respect for autonomy, nonmaleficence, beneficence, and justice are central to and play a vital role in biomedicine (Principles of Biomedical Ethics. 5th ed. Oxford: Oxford University Press, 2001, pp. 12-13). Although, Beauchamp claims that the efficacy of these principles can be tested empirically and that it can be determined whether they are part of a cross- cultural common morality, he does not present any empirical data generated systematically by qualitative research methods to support his position. Though, Beauchamp asks for a design of an empirical research project to investigate the subject (A Defence of the Common Morality. Kennedy Institute of Ethics Journal, 13(3), 259-274, 2003). Therefore, there is a need to construct an empirical study to investigate the ethical reasoning within biomedicine. In this paper we present the set-up of an empirical study to explore the ethical reasoning of physicians and molecular biologists. The aim of the study is to explore which ethical considerations or principles are at stake within biomedicine in Denmark.

P05.06 Louise PHARMACOLOGICAL CHARACTERISATION OF A PLACE ESCAPE / Henriette AVOIDANCE PARADIGM (PEAP) IN RATS WITH NEUROPATHIC PAIN

74 Pedersen Louise H. Pedersen and Gordon Blackburn-Munro, Dep. of Pharmacology, NeuroSearch A/S, Ballerup, Denmark [email protected] Aim of investigation: Classical pain tests performed in animals require the experimenter to evoke a reflex nociceptive response. This measure may exclusively reflect sensory processing of nociceptive transmission. PEAP may possibly be used in rats with chronic pain to selectively assess drug effects on affective pain processing (LaBuda and Fuchs, Exp Neurol, 2000). We have investigated the effect of morphine, gabapentin, duloxetine (dual-

reuptake inhibitor) and THIP (gaboxadol; GABAA agonist) in neuropathic rats using the PEAP and compared the results with those obtained using evoked nociceptive responses. Methods: Adult male Sprague-Dawley CCI (Bennet and Xie, Pain, 1988) rats with established mechanical allodynia were used. With the PEAP method rats were stimulated with a 69 g von Frey filament every 15 s for 30 min. The injured paw was stimulated if the rat was in the dark area, and the non-injured paw if the rat was in the light area. Escape / avoidance behavior was defined as a shift from the dark area of the chamber to the light area. Mechanical allodynia was determined prior to and after PEAP testing. Results: Morphine (3 and 6 mg/kg, sc) and gabapentin (50 and 100 mg/kg, ip) reduced the % time spent in the light area of the chamber

compared to controls [F(10,90)=3,542, P= 0,001; F(10,75)=5,419, P=0,001, respectively]. Duloxetine (10 and 30 mg/kg, ip) also reduced the time spent

in the light [F(10,90)=3,481, P=0,001], although the 30 mg/kg dose was sedative and prevented sufficient exploration. THIP (1 and 3 mg/kg, ip) showed no effect at either dose tested. Mechanical allodynia was reduced

compared to controls with morphine and gabapentin [F(2,18)=13,234, P=

0,001; F(2,15)=33,271, P=0,01, respectively]. Duloxetine and THIP showed no effects on mechanical allodynia at the doses tested. Conclusions: The PEAP method may enable discrimination between selected drug classes on distinct components of sensory and affective pain processing in rats with peripheral nerve injury. Acknowledgements: LHP is supported by The Danish Academy of Technical Sciences.

P05.07 Søren GROWTH HORMONE (GH) SUBSTITUTION IN GH DEFICIENT Kildeberg PATIENTS INHIBITS 11 -HSD1 MRNA EXPRESSION IN ADIPOSE Paulsen TISSUE S.K. Paulsen, S.B. Pedersen, J.O.L. Jørgensen, S. Fisker, J.S. Christiansen, A. Flyvbjerg and B. Richelsen Central obesity is associated with insulin resistance, dyslipidaemia, cardiovascular morbidity and the metabolic syndrome. The features of the metabolic syndrome have apparent similarities those of Cushing’s syndrome, which has led to the assumption that cortisol excess may be a contributor to the metabolic syndrome. Patients suffering from growth hormone deficiency (GHD) share these clinical features and central obesity is associated with a decrease in GH-secretion. Local tissue activity of glucocorticoids is in part determined by the isoenzymes 11-ßHSD1 and 11- ßHSD2, interconverting inert cortisone and active cortisol.

75 In the present study we investigated the effects of GH-treatment and increased levels of IGF-I on adipose tissue 11 -HSD mRNA, in 23 GHD patients. Patients were randomized to four months of GH-treatment (n=11) or placebo-treatment (n=12). Adipose tissue biopsies were obtained before and after treatment with GH or Placebo. IGF-I, 11 -HSD1 and 11 -HSD2 mRNA was determined by real-time RT-PCR. In the GH-treated group S-IGF-I and IGF-I mRNA increased significantly, and the mRNA expression of 11 -HSD1 increased 66% (p<0.01) and increased 11 -HSD2 mRNA by 167% (p<0.05).11- HSD1 mRNA was negatively correlated with s-IGF1 (R=-0.433, p<0.005) and IGF-I mRNA (R=- 0.348, p<0.05). 11- HSD2 mRNA was positively correlated to IGF-I mRNA (R=0,686, p<0.00001) and to s-IGF-I(R=0.376, p<0.05). Thus GH and/or IGF-I is able to inhibit 11 -HSD1 mRNA and possibly reduce the amount of cortisol locally in the adipose tissue. We propose that the clinical features of GHD and the metabolic syndrome may in part be due to changes in 11 -HSD activity in adipose tissue, as a consequence of relative or complete deficiency of GH and/or IGF-I.

P05.08 Mette Krintel EFFICACY OF MULTIMODAL, INTERDISCIPLINARY INTERVENTION Petersen AFTER TOTAL HIP ARTHROPLASTY: A PROSPECTIVE, RANDOMISED CONTROLLED TRIAL M.K Petersen, C. Madsen, N.T. Andersen, K.Søballe Adress of coresponding author: Snærildvej 64 B, 8300 Odder, [email protected] Background: A multi-modal regimen combinating epidural anaesthesia and postoperative epidural analgesia with local anaesthetics and opioids, enforced mobilisation and nutrition has been reported to reduce convalescence and hospital stay in small series of unselected patients in uncontrolled studies. We evaluated the efficacy of this regimen in patients undergoing primary total hip arthroplasty (THA) in a randomised, controlled trial. Method: Eighty THA patients participated in a prospective, randomised study. All patients were given epidural anaesthesia and postoperative epidural analgesia with local anaesthetics and opioids. Length of stay, postoperative complications, pain, oral energy intake, time out of bed, walking distance, and independence in personal activities of daily living (PADL) were registered during the first 6 postoperative days. Results: Fifty-seven patients fulfilled the study protocol:27 in the intervention and 30 in the control group. Length of stay was moderately reduced in the intervention group compared with the control group (7.0 versus 8.2 days). We found no differences in complication rates between the two groups. Mobilisation and energy intake were significantly better in the intervention group than in the control group. A minor, non-significant difference was observed regarding independence in PADL function. Conclusion: This study suggests that a multi-modal intervention can reduce hospitalisation without increasing complications and provide better mobilisation and energy intake.

P05.09 Mahmoud HYPEROXIA- AND HYPERCAPNIA-INDUCED CHANGES OF CBF AND

76 Ashkanian CMRO2 IN ISCHEMIC PENUMBRA M. Ashkanian1, G. Andersen2, M. Vafaee 1, L. Østergaard1 1: CFIN, Århus University Hospital. Bygn 30 Nørrebrogade 44, 8000 Århus C. Denmark 2: Department of Neurology, Århus University Hospital, Nørrebrogade 44, 8000 Århus C. Denmark Background: Ischemic penumbra is defined as a hypoperfused brain tissue with maintained membrane potential and ion homestasis [Astrup J, Siesjo BK, Symon L, Stroke 1981;12(6):723-5]. Studying neurometabolic and neurovascular behaviour of penumbral cells is essential to achieve adequate understanding of stroke pathophysiology. BOLD signal in fMRI is a product of both regional Cerebral Metabolic Rate of Oxygen (CMRO2) and Cerebral Blood Flow (CBF). With concomitant Flow-sensitive Alternating Inversion Recovery (FAIR) it is possible to isolate and study each of these vital parameters. Objectives: To study CMRO2 and CBF separately by MRI in patients with severe carotid stenosis and healthy controls. Methods: During the scan time the subject is breathing via a mask, which is connected to an electronically controlled gas application unit. The gas application system is designed to supply the subject with a semirandom sequence of 100% O2 (hyperoxia), 5% CO2 (mild hypercapnia), and Carbogen (95% O2 + 5% C02) each for a duration of one minute, followed by three minutes inhalation of normal atmospheric air. Discussion: Animal experiments show that either oxygen therapy or mild hypercapnia reduce final infarct volume [Flynn EP, Auer RN, Ann.Neurol. 2002;52(5):566-72 and Simon RP, Niro M, Gwinn R, J Pharmacol.Exp.Ther. 1993;267(3):1428-31]. The present study determines whether we can detect and manipulate changes in CMRO2 and CBF.

P05.10 Grete Moth ORGANIZATION AND COST-EFFECTIVENESS OF CARE OF SCHOOL- AGE CHILDREN WITH ASTHMA: A REGISTER-BASED STUDY G.Moth Danish Paediatric Asthma Centre, Aarhus University Hospital, Skejby Sygehus, 8200 Århus N Within the area of childhood asthma, Danish counties vary considerably in hospital admission rates and in number of visits to paediatric specialists. This means that the amount of resources allocated to care of asthmatic children is very different and counties in which a great number of asthmatic children were being treated by specialists in 2001, did not have fewer hospital admissions than counties in which the majority of children were being treated by general practitioners. In this PhD project two register-based studies will be performed by use of linked data on an individual level from The Medicinal Product Statistics, The National Hospital Register, The National Health Insurance Service Registry, and Statistics Denmark. Furthermore a health-economic analysis of the costs in the counties of management of childhood asthma care will be carried out. The aim of these studies is 1) to map out how management of care of asthmatic children in the Danish counties is organized and between

77 the hospitals, the practicing paediatric specialists and the general practitioners and 2) on the basis of this mapping to develop indicators to monitor the quality of care of asthmatic children in the counties. The mentioned studies will be preceded by a study of the validity of data from The National Hospital Register and by a study which aims to develop a method to define asthmatic children on the bass of register data on use of medication

P06.01 Peter IMPROVED NUTRITIONAL STATUS IN ELDERLY PATIENTS 6 Brynningsen MONTHS AFTER ISCHEMIC STROKE P. Brynningsen, E.M.S Damsgaard, S.E. Husted Geriatric Department G, Aarhus Sygehus, P.P. Ørumsgade 11, 8000 Århus Introduction: Nutritional status among stroke patients has received limited attention despite the fact, that it may have an influence on clinical outcome. Previous studies estimate that 15-20 % of patients suffer from malnutrition in the acute phase of stroke, but so far no studies have focused on the late rehabilitation phase after stroke. Aims: To determine the prevalence of malnutrition during 6 months and to investigate the association between nutritional status, functional score, length of stay in hospital and infectious complications. Subjects and Methods: 89 patients consecutively admitted to a geriatric stroke unit had their nutritional status evaluated in the hospital at 1 week and 5 weeks after stroke, and in their own home at 3 months and 6 months. Nutritional status was evaluated by body weight, body mass index, midupper arm circumference, triceps skinfold thickness and serum concentrations of albumin and transferrin. Malnutrition was considered present if the patients had 2 or more abnormal nutritional variables. Results: We found a significant increase in albumin from 1 week to 6 months (P<0.0001), and a significant increase in transferrin (P<0.05). There was no significant change in weight or BMI from 1 week to 6 months. The number of patients with 2 or more abnormal nutritional variables was 31 (35 %) at 1 week and was reduced to 20 (22 %) at 6 months. Conclusion: 35 % of elderly patients with ischemic stroke were malnourished 1 week after stroke. During the rehabilitation period serum proteins improved, and 22 % of the patients were malnourished 6 months after stroke. No association was found between malnutrition and low functional score, increased length of stay or number of infectious complications.

P06.02 Kenneth DO SMOKERS REALLY HAVE MORE FUN? Jensen Kenneth Jensen, Anders Bonde Jensen and Cai Grau Department of Oncology, Aarhus University Hospital Background: Smoking is an important etiologic factor in the development of head and neck cancer. Smoking during radiotherapy influences survival and acute side-effects. Smoking after therapy influences the rate of second cancers. Nevertheless, some patients continue to smoke after diagnosis and treatment because they feel that smoking is associated with pleasure and quality of life. Materials and methods: A cross sectional quality of life and morbidity study was performed using EORTC C30 and H&N35 as well as

78 the DAHANCA morbidity scoring system. Patients were attending follow up after single modality treatment. Results: Fifty-two of 114 patients, with available smoking information, were registered as self reported smokers at follow up. Smoking status was not significantly correlated with any of the tumour or patient related endpoints including age, gender, tumour site, stage, time since therapy or therapy. Nevertheless smokers invariable have the lowest function scores and the highest symptoms scores in both DAHANCA and EORTC QLQ except fibrosis and HN Weight gain. This difference was significant in 20 of the 33 QoL scales, but none of the morbidity scores. The difference was apparent in both general and organ specific endpoints. When dividing the non-smokers (N=62) in patients admitting to smoke during initial therapy (N=48) and never smokers (N=14) a “dose” dependent effect could be seen with smokers having more symptoms than former smokers that had more symptoms than never smokers. Conclusion: Smokers had a significantly reduced score of many items of the EORTC C30 and H&N35 quality of life questionnaires. There was a clear tendency towards a dose effect with previous smokers constituting an intermediate group between present-smokers and never- smokers. These indicate that there could be an immediate benefit to the patient’s health related quality of life of smoking cessation since former smokers did better than current smokers.

P06.03 Gitte Juhl SENSITIZATION PHENOMENA AFTER THIRD MOLAR SURGERY: A QUANTITATIVE SENSORY TESTING STUDY. G.I.Juhl, T.S.Jensen, S.E.Norholt, P.Svensson. Department of Neurology and Danish Pain Research Center, Aarhus University Hospital, Norrebrogade 44, DK-8000 Aarhus C, Denmark. Background: Surgical removal of third molars may carry a risk of development of persistent orofacial pain and central sensitization appears to play an important role in the transition of acute pain to chronic pain. Aim: The aim of this study was to investigate sensitization after orofacial trauma using quantitative sensory tests (QST). Materials and methods: A total of 32 healthy men (16 patients and age- matched 16 controls subjects) underwent a battery of QST tests adapted to the trigeminal area at baseline and 2 days, 7 days, and 30 days following the surgical removal of a lower impacted third molar. Results: We found signs of sensitization of the trigeminal nociceptive system for at least one week after the surgery; sensitization was indicated by significantly increased pain intensity evoked by intraoral repetitive pinprick and electrical stimulation (P<0.05) including facilitation of temporal summation mechanisms (P<0.05), extraoral repetitive electrical stimulation (P<0.001), significantly more frequent aftersensation in patients (P=0.0002), extraoral hyperalgesia due to single pinprick stimulation (P<0.05) and larger pain areas to intranasal stimulation (P<0.001). Peripheral sensitization was indicated by intraoral hyperalgesia due to single pinprick (P<0.05). Conclusion: These results in a human oral pain model are comparable to animal and human experimental studies demonstrating perturbed mechanosensitivity after trauma. Our results indicate that even a minor

79 orofacial surgical procedure may be sufficient to evoke signs of central and peripheral sensitization, which may play a role in the transition from acute to chronic pain in susceptible individuals.

P06.04 Louise PERFUSION-WEIGHTED MAGNETIC RESONANCE IMAGING IN Gyldensted ALZHEIMER’S DISEASE AND MILD COGNITIVE IMPAIRMENT Louise Gyldensted, Jamila Ahdidan, Anders Rodell, Kim Mouridsen, Leif Østergaard, Carsten Gyldensted, Department of Neuroradiology and CFIN, Aarhus University Hospital, Nørrebrogade, 8000 Aarhus, Denmark, E-mail: [email protected] Alzheimer’s disease (AD) associates with several vascular risk factors pointing to microvascular insufficiency of gray and white matter in AD pathogenesis [de la Torre, Neurosci.Behav.Rev.,1994;18:397-401, Brown, Ann.NYAcad.Sci.,2000; 903:39-45]. PET and SPECT studies have shown hypoperfusion in Hippocampus, temporo-parietal and frontal cortices [Friedland, JCAT 1983;7:590-98, Waldemar, Cerebrovasc.BrainMetab. Rev. 1995;7:89-130]. We aim to study microvascular perfusion abnormalities across AD patients with PWI-MRI and have scanned twenty patients clinically suspected of mild to moderate AD or mild cognitive impairment and 23 healthy age-matched controls with contrast bolus PW MRI in a 1.5 T GE Scanner. Mean transit time (MTT) maps where calculated [Østergaard L, MRM,1996;36:715-25&726-36]. A voxel by voxel t-test was performed on coregistrered MTT maps to identify areas with significant MTT differences between groups. MTT was higher (p<<0.04) among patients than among controls in the following areas: Right, medial, parietal gray matter and right posterior, temporal white and gray matter. Our finding of prolonged MTT indicates low perfusion pressure in accordance with PET findings of low CBF and the high incidence of watershed infarcts known from post-mortem AD studies. By analysing perfusion data such as cerebral blood flow and cerebral blood volume, we hope to further address the vascular and neurodegenerative pathogenesis of AD and MCI.

P06.05 Lone Bruhn ANIMAL MODELS FOR HUMAN NEURODEGENERATIVE DISEASES Madsen L.B. Madsen1, B. Thomsen1, K. Larsen1, A. L. Jørgensen2, A. L. Nielsen2 and C. Bendixen1. 1Department of Genetics and Biotechnology, Danish Institute of Agricultural Sciences, PO Box 50, DK-8830 Tjele, Denmark. 2Department of Human Genetics, Bartholin Building, University of Aarhus, DK-8000 Aarhus C, Denmark. Many diseases are hard to investigate in humans and especially the early stages of a disease are difficult to examine. Therefore, the establishment of lifelike animal models for studying the pathophysiology of the neurodegenerative diseases and for developing and evaluating existing and new therapeutic agents and diagnostic methods would be of great value. Since the pig in many ways resembles humans, this project seeks to establish porcine models for human neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS), Parkinson’s (PD) and Alzheimer ’s

80 disease (AD). Due to the great similarity between human and pig, it can’t be ruled out that naturally occurring porcine models with said diseases exist. Therefore, key genes for the aforementioned disorders are characterized and examined in a large porcine material, regarding single nucleotide polymorphisms, which could be potential disease causing mutations. Furthermore, by means of site directed mutagenesis, mutations are introduced into the porcine orthologous of genes known to cause familial forms of ALS, PD, and AD and the mutagenised genes are cloned into vectors, which are applied in cellular assays. In addition, constructs harboring the aforementioned mutations are created, and are to be used to establish transgenic pigs with neurodegenerative diseases.

P06.06 Mette CANCER PALLIATION IN PRIMARY CARE –WHAT IS GOOD AND Asbjørn BAD? Neergaard MA Neergaard, MD, specialist in general medicine, PhD student* F Olesen, general practitioner, Dr.Med.Sci., professor* J Soendergaard, general practitioner, senior researcher, PhD* AB Jensen, MD, consultant in oncology, PhD** *The Research Unit for General Practice, University of Aarhus, Vennelyst Boulevard 6, 8000 Århus C, DK. **Department of Oncology / The Palliative Team, Aarhus Hospital, DK. Background. Palliative care for cancer patients is an important part of a general practitioner’s work. Although every general practitioner is frequently involved in care for terminally ill cancer patients, only little is known about how the palliation efforts are perceived, a knowledge that is vital to make improvements. We aimed to analyse the quality of palliative home care based on evaluations by the relatives and the primary and secondary health care sectors. Methods. A series of focus group interviews is presently being conducted with participation of relatives of recently deceased cancer patients, GPs, community nurses and hospital physicians working with palliative patients. The interviews are transcribed and analysed according to the phenomenological approach. The interviews will form the basis of a survey of 500 episodes of palliative home care as evaluated by relatives, GPs and district nurses. Results. These results are the preliminary results from the first interviews with GPs. Three themes emerged from the interviews: 1) The key persons in palliative home care, 2) the desire for personal contact, and 3) barriers to working with palliation. Conclusion. Our study provides important knowledge that can help form the basis for suggestions to optimize the organisation of palliative home care.

P06.07 Mette PRENATAL ALCOHOL EXPOSURE: NEUROPSYCHOLOGICAL Underbjerg FUNCTIONS AT AGE 5 – WITH PARTICULAR REFERENCE TO Dyrskog ATTENTION M.U. Dyrskog1, P.Thorsen, U. Kesmodel, E.L. Mortensen, T. Manly

81 1NANEA, at the Institute of Public Health, Department of Epidemiology, Aarhus University, Vennelyst Boulevard 6, 8000 Aarhus C Objectives: 1) to develop and validate a new test of attention in young children 2) to examine the relationship between low-moderate average alcohol intake during pregnancy and cognitive development at age five 3) to examine the relationship between prenatal exposure to binge drinking (intake of 5 or more alcohol containing drinks on a single occasion) and cognitive development at age 5. Methods: A new theoretically founded test of attention has been developed and a sample of 160 5-year-old children is being tested in order to investigate the psychometric properties of the test. In a separate study 1500 participants are recruited from The Danish National Birth Cohort (DNBC) consisting of 100,000 women and their offspring enrolled during pregnancy. Sample selection is based on information from DNBC on the number of drinks the mother consumed per week before and during pregnancy and on the number and timing of binge drinking episodes. At age five the children are administered an extensive neuropsychological test battery intended to assess both global cognition (IQ) as well as more specific cognitive functions (e.g. attention). Tests of motor development, anthropometrical measurements and control of vision and hearing are also carried out and the mothers are asked to undergo a brief IQ test. Further- more a project developed questionnaire and two standardised questionnaires are completed by the mother and a person from the child's day care. Perspectives: The study will have global public health implications as the results will contribute substantially to resolve the issue of whether there is a safe level of drinking during pregnancy.

P06.08 Allan Carle´ A POPULATION-BASED STUDY OF THYROID AUTO-ANTIBODIES IN OVERT HYPOTHYROIDISM. 1)Allan Carlé, (1)Peter Laurberg, (1)Inge Bülow Pedersen, (2)Nils Knudsen, (2)Hans Perrild, (3)Lars Ovesen, (4)Lone Banke Rasmussen, (5)Torben Jorgensen. (1)Department of Endocrinology & Medicine, Aalborg Hospital,Aarhus University Hospital; (2)Endocrine Unit, Medical Clinic I, Bispebjerg Hospital, Copenhagen; (3)the National Heart Foundation, Copenhagen; (4)Department of Nutrition, Danish Institute for Food and Veterinary Research, Copenhagen; (5)Research Centre for Disease Prevention and Health, Glostrup Hospital, Copenhagen, Denmark. Correspondence: [email protected] Thyroid autoimmunity is a major cause for hypothyroidism. However, no population-based study has described thyroid auto-antibodies in the various nosological subtypes of hypothyroidism.We established a laboratory-linked monitoring system to identify 685 patients with incident primary, overt hypothyroidism: spontaneous (presumably of autoimmune origin, n=578) and non-spontaneous (n=107, patients with prior treatment with amiodarone or lithium, delivery within one year, prior neck-radiation of euthyroid disorders, subacute thyroiditis and congenital hypothyroidism). 186 patients (61% of those invited) underwent an

82 extensive investigation program, including thyroid ultrasonography and measurements of TPO-Ab and Tg-Ab (Brahms). TPO-Ab (but not Tg-Ab) was more common in spontaneous than in non-spontaneous hypothyroidism: TPO-Ab+ 96/71% (p<0.001), Tg-Ab+ 81/78% (p=0,71), TPO-Ab+ or Tg-Ab+ 99/83%, TPO-Ab+ and Tg-Ab+ 77/66%. Among spontaneously hypothyroid patients, with both antibodies present, we found a significant positive correlation between the two antibodies. In a multivariate regression model both TPO-Ab and Tg-Ab were positively associated with thyroid volume (p<0.001). No association was found with sex, age, iodine deficiency level or degree of biochemical hypothyroidism (TSH). All variables were similar in patients with relative high TPO-Ab/Tg- Ab ratio vs. low TPO-Ab/Tg-Ab ratio. In the population, more than 99% of spontaneously hypothyroid patients were antibody positive. This was less common in the heterogeneous group of non-spontaneous hypothyroidism. In spontaneous hypothyroidism both TPO-Ab and Tg-Ab were positively associated with thyroid size. TPO-Ab and Tg-Ab showed only modest positive correlation. We found no clue to why some patients predominantly developed TPO-Ab, and others mainly generated Tg-Ab.

P06.09 Vibeke Sejer GENDER DIFFERENCES IN HIPPOCAMPAL ATROPHY IN EPILEPSY Hansen V.S. Hansen, T. Christensen, F.T. Jensen, and P. Sidenius. Department of Neurology, Aarhus University Hospital, Aarhus, Denmark. Recently it has been suggested that men may be more vulnerable to the damaging effect of epileptic seizures than women. We wished to examine whether hippocampal atrophy progresses at a faster rate in male than in female epilepsy patients. One hundred and eighty persons aged 15-50 years (women, n=107, men, n=73) with a diagnosis of epilepsy had MR scans of the brain including volumetry of the hippocampus. Clinical information was obtained from the Epibase database at the outpatient clinic, Aarhus University Hospital, where our epilepsy patients have been systematically registered since 1999. Linear regression analysis was used to calculate the rate of volume reduction as a function of epilepsy duration. Multiple regression analysis was applied to estimate the influence from gender, age and ongoing seizure activity. The mean duration of epilepsy was 14.0 ±11.7 years in men and 14.4 ± 12.6 years in women. Seizure freedom was equally frequent in men and women (26.0% and 34.6%, p=0.22). The left hippocampal volumes correlated with the duration of epilepsy in men (p=0.001) and women (p=0.02). The right hippocampal volume correlated with the duration in men (p<0.001), but not in women (p=0.053). The linear reduction in left hippo-campal volume as a function of epilepsy duration was larger in men than in women ( = -0.04 and -0.01 cm3/year, p<0.05). The linear reduction in right hippocampal volume also seemed to be larger in men than in women ( = -0.02 and -0.01 cm3/year), but this was not statistically significant. Multiple regression analysis showed a significant influence from disease duration and gender on the left hippocampal volume, but not from age and seizure freedom. On the right side only disease duration significantly influenced the hippocampal volume. Our findings suggest that hippocampal disease may progress faster in men than in women, irrespective of seizure control.

83 P06.10 Hanne EXPRESSIVE ARTS THERAPY FOR SCHIZOPHRENIA, A QUALITATIVE Stubbe RESEARCH OF A FENOMENOLOGICAL BASED TREATMENT IN A Teglbjærg LOCAL PSYCHIATRIC CENTER. Hanne Stubbe Teglbjærg Centre for Basic Psychiatric Research, Psychiatric Hospital in Aarhus, 8240 Risskov, Denmark. There is some theoretical evidence for assuming that artmaking can bring patients with schizophrenia in better contact with themselves and their world by strengthening the ability of making sense and form in artistic materials. To test this hypothesis a group of schizophrenic patients is offered art therapy once a week for one year. Another group of patients with other diagnoses is given the same treatment for comparison. Data is collected from log-books, pictures, ratings and interviews before and after treatment in a one year follow-up. To analyse the connection between artmaking and psychopathology in the empirical data, a theoretical framework will be built on the ground of philosophical phenomenology The collected data will be analysed by means of phenomenological hermeneutics to search answers to the following questions: What happens in terms of psychopathology when schizophrenic patient are engaged in art making? How does the psychopathology of the schizophrenia affect the artmaking? And what is the relationship between the art-piece and the artist /patient? Hopefully, the project will give an answer to the question whether expressive arts therapy has a place in the future treatment of schizophrenia.

P07.01 Bo Eskerod SEARCHING FOR INTERACTING GENETIC VARIANTS THAT Madsen PREDISPOSE FOR DISEASES OR RESPONSE TO TREATMENT B. E. Madsen BiRC – Building 1090, University of Aarhus, DK-8000 Aarhus C. The aim of the project is to develop new statistical and bioinformatics methods for analysing and designing association studies. The project will use real data sets generated by collaborators at the university or found in the literature, and data sets generated by simulation. Real data sets are used 1) to learn about the limitations of current methods used for association studies and 2) to guide us in developing new methods. Simulated data sets are used 1) to evaluate the efficiency of methods and 2) to make guidelines for the design of future studies. Two problems are of special interest in this project: A) Many statistical methods have very low power. The power might be improved by correctly adjusting for the correlation structure in the data, and by limiting the number of tests performed (use search strategies). B) Current methods poorly handle interactions between genetic variants. New mathematical models, incorporating non-genetic information (such as protein-protein interaction network or expression arrays) might be able to handle interactions more efficiently. I am 3 months into this project, so no results are available at this point.

P07.02 Bente Høy SELF-CARE AS A HEALTH RESOURCE OF THE ELDERLY

84 A review and reinterpretation of health-oriented concepts of self-care Bente Høy, RN, MPH, doctoral student, Institute of Public Health, Department of Nursing Science, Aarhus University E-mail: [email protected] Lis Wagner, RN, Dr.PH, Professor, Elisabeth O.C. Hall, RN, MScN, Ph.D., Associate Professor The aim of the study was twofold; to explore health-oriented concepts of self-care for the elderly in nursing and health care literature and to develop a theoretical understanding of self-care as a health-resource of the elderly. Background. Self-care, as a health-related concept used in caring and health promotion studies of the elderly, has the potential for a health-promoting approach enhancing and mobilizing health-resources of the elderly. Paradoxically there seems to be a lack of clarity about the meaning of self- care as a health-resource in everyday life. The studies have until 1990 been dealing more with self-care deficit than with individuals’ health needs, and self-care has primarily been regarded as a supplementary approach to health care, and not the scope of health-promoting. The study was designed as integrative literature review and reinterpretation of health-oriented concepts of self-care of the elderly from a salutogenic perspective. Studies published between 1990 and 2005 in nursing and health care journals were identified, and the selected studies consisted of qualitative or concept development approaches. A concept analysis following methods described by Morse and colleagues was applied.Findings. Twenty one relevant studies were explored and reinterpreted. Self-care as a health-resource can be understood as human capabilities encompassing four action levels; practice, performance, power, and fundamental and as a salutogenic approach of three life-building processes encompassing: process of life experience and educational and ecological process. Conclusions. The study provide and understanding of health as a potential for self-care in daily life and not just as an idealistic goal or absence of disease. Keywords: salutogensis, self-care, elderly, concept, health promotion, review

P07.03 Mette SHORT- AND LONG-TERM PROGNOSIS OF COMMUNITY-ACQUIRED Søgaard BACTERAEMIA IN PATIENTS ADMITTED TO MEDICAL DEPARTMENTS IN NORTH JUTLAND COUNTY M. Søgaard, M. Nørgaard, A. Riis, H.T. Sørensen, H.C. Schønheyder Departments of Clinical Microbiology and Clinical Epidemiology Aarhus University Hospital, Aalborg and Aarhus, Denmark. Bacteraemia defines a group of patients of particular interest. The 30-day case fatality is 10-40 %, but information is sparse concerning short-term (0-7 days) and long-term (1-6 months) prognosis. Registry-based studies are an option for addressing this group of patients, since many bacteraemia patients in medical care would not be eligible for clinical trials because they are elderly with multiple morbidities. The ph.d. study aims to examine the following hypotheses: Pre-admission use of antibiotics is a prognostic factor for death in community-acquired bacteraemia. The prognosis differs dependent on whether patients are selected for

85 blood culture or not. Community-acquired bacteraemia has a long-term impact on prognosis (up to 6 months). Prognostic factors may be time-dependent and their weigh may differ during the course of infection. Each hypothesis is addressed in a population-based cohort study. Data are obtained from The Bacteraemia Research Registry of North Jutland, laboratory information systems at Aalborg Hospital, the Hospital Discharge Regi- stry and the Danish Civil Registration System. The main outcome measure will be time to death and Kaplan-Meier Survival curves will be constructed. Cox’s regression analysis is used to compare mortality rate ratios. Statistical analysis will be adjusted for potential confounders including focus of infection, age, and comorbidity.

P07.04 Pia Pinholt MIS-CLASSIFICATION OF MISSENSE, NONSENSE AND SILENT Madsen MUTATIONS – CODING REGION MUTATIONS MAY INSTEAD CAUSE ABERRANT mRNA SPLICING Pia Pinholt Madsen1,2, Thomas J. Corydon1, Lisbeth Schrøder1,2, Niels Gregersen2, Brage Storstein Andresen1,2 1Department of Human Genetics, Aarhus University, 2Research Unit for Molecular Medicine, Aarhus University Hospital, Denmark Disease-causing mutations, which based on the genetic code have been predicted to be missense (amino acid substitution), nonsense (introduction of a stop codon) and even silent, sometimes cause exon skipping. Because, the mature mRNA defines the nature of the encoded protein, exon skipping during pre-mRNA splicing has serious consequences. Recently it has become clear that not only the splice sites are required for correct splicing of an exon, but also exonic splicing enhancer (ESE) and exonic splicing silencer (ESS) elements are necessary. Mutations that affect ESE and ESS elements may thus dramatically compromise splicing. Therefore, increased knowledge about the characteristics and mode of function of these elements is necessary if we shall achieve a better understanding of how mutations may cause disease and avoid mis-classification of mutations in the future. We have characterized a general regulatory element that controls splicing in two different genes. In both SBCAD exon 10 and ATR exon 9 a disease- causing A>G mutation located in an identical 7 bp. motif causes exon skipping in patient cells thereby implying that a general regulatory element is disrupted. On basis of comprehensive in vivo minigene studies and RNA in vitro assays (UV-crosslinking, band shifts), we conclude that a bi- functional regulatory element with both ESE and ESS activity controls splicing of both exons. We hope that our ongoing experiments (RNA pull- down and 2D gel electrophoresis) will reveal the identity of the regulatory proteins that binds to this general element. Our latest results shows that the carrier frequency of the SBCAD mutation is as high as 1:10 in an ethnic group (Hmong Chinese) who lives in countries in North Vietnam/east Asia.

P07.05 Mia Færch CHARACTERIZATION OF A MUTANT V2 RECEPTOR ASSOCIATED WITH PARTIAL CONGENITAL NEPHROGENIC DIABETES INSIPIDUS M.Færch1, J.H.Christensen3, K.Kamperis2, T.J.Corydon4, N.Gregersen3, F. de

86 Zegher5, W.Proesmans5, S.Rittig2 1Pediatric Research Laboratory, 2Department of Pediatrics, and 3Research Unit for Molecular Medicine, Skejby Sygehus, Denmark; 4Department of Human Genetics, University of Aarhus, Denmark; 5Department of Pediatrics, University of Leuven, Belgium Objectives of Study: A novel mutation in the AVPR2 gene resulting in a S329R substitution of the V2 receptor is remarkable in that it is one of only four mutations known to cause partial congenital nephrogenic diabetes insipidus (CNDI). The affected amino acid residue (S329) is located in the intracellular C-terminal of the V2 receptor. In order to investigate the cellular handling of the mutant V2 receptor, human wild type (WT) or mutant AVPR2 cDNAs were expressed in human embryotic kidney cells. Methods and Results: Western blotting showed no significant difference in protein production suggesting that similar amounts of receptor protein are produced in both mutant and WT cells. Immunostaining and confocal laser scanning microscopy established that WT receptors were localized mainly on the cell surface whereas the majority of the mutant receptors seemed to accumulate in a diffuse pattern within the cells partly co-localizing with the endoplasmic reticulum (ER). Ligand binding assay with radiolabeled AVP

demonstrated no significant difference in AVP affinity (1/Kd) between the

WT and mutant receptors. However, the Bmax of the mutant receptor was significantly lower further indicating that the surface expression is reduced compared to WT. Displacement analysis with AVP or dDAVP demonstrated a slightly lower affinity of both WT and mutant receptors towards dDAVP than AVP. Conclusion: The S329R substitution of the V2 receptor associated with partial CNDI seems not to affect the affinity of the V2 receptor towards AVP and dDAVP but rather the efficiency of its intracellular trafficking.

P07.06 Him Shing VISUAL VALIDATION OF EMBOLI DETECTION USING DOPPLER Ng ULTRASOUND AND WAVELET TRANSFORMATION Him Shing Ng1,2, Hans Nygaard1,2, J. Michael Hasenkam2, Peter Johansen1,2 1Centre for Biomedical Technology, Engineering College of Aarhus 2Department of Cardiothoracic Surgery and Institute of Clinical Medicine, Aarhus University Hospital, Skejby Sygehus Address: Aarhus University Hospital, Skejby Sygehus, 100 Brendstrupgaardsvej, Aarhus, DK 8200, Denmark Transcranial Doppler ultrasound can detect asymptomatic emboli. Wavelet transform had been suggested as a Doppler signal-processing tool. However, the results are sensitive to predetermined algorithm. The aim of this study was to optimize wavelet algorithm and to develop a novel visual validation method. Gaseous emboli were generated using electrolysis within a flow loop. At a common measuring point, both high-speed imaging and Doppler data were acquired. Wavelet analysis was performed and validated visually. Results: Percent difference (%d)= (Doppler count- Visual count)/Visual count in percent. For large emboli (400-600µm), low count (n=38), %d= 0; medium count (n=66), %d = 3; high count (n=122), %d = -7.4. For small emboli (200-370µm), low count (n=75), %d = 2.7; high count

87 (n=114), %d= -3.5. The results showed good agreement between Doppler and video counts. Wavelet transformation may offer high detectability. Cooperation with visual validation may offer many advantages in development of emboli detection.

P07.07 Marianna AN EXPERIMENTAL HYPOSPADIA REPAIR IN RABBITS: A Lalla BIOMECHANICAL STUDY OF THE URETHRA M. Lalla, C.C. Danielsen, H. Austevoll, L.H. Olsen, T. M. Jørgensen. Klinisk Institut, Skejby Sygehus, Brendstrupgårdsvej 100 8200 Århus N To investigate the biomechanical properties of a hypospadiac urethra. 38 NZ white rabbits underwent experimental hypospadia creation and acute repair. In the first group ventral urethra and dorsal plate were longitudinally incised, half of the ventral urethral wall was excised creating hypospadia-like defect and the incised urethra was tubularized. In the second group the urethra was mobilized from corpora cavernosa, excised in its distal end mimicking hypospadia and advanced to glanular tip. Other two groups were sham operated and controls. After 23 weeks the animals were sacrificed. One-mm high urethral ring samples were mechanically tested and collagen content was determined. Data from 32 rabbits were analysed. The maximal strength and maximal stiffness of urethra and the percent collagen were not significantly different among the groups. In the advancement group, the urethral diameter was larger and the total collagen was higher (p<0.05), partly due to more collagen in the dorsal part of urethra. The mechanical quality of the urethral collagen (maximal load and maximal stiffness normalized with mg collagen per mm) was reduced in the advancement group (p<0.05) compared to controls and shams. In the tubularized incised urethra the mechanical quality of the collagen was non-significantly reduced. No fibrosis was present. As urethra is subject mostly to circular stresses, the urethral plate preservation, even if incised, seems to give better results than urethral mobilization and advancement, which shows more collagen of lower mechanical quality tested in circular direction, indicating an increased collagen formation with fibre re-orientation to resist the longitudinal stress. This method may be used on a hypospadia animal model to test functional results after a hypospadia repair technique before its clinical use.

P07.08 Andreas HOW TO DEFINE CRITERIA FOR SEVERE SOMATIZATION FOR A Schröder INTERVENTION STUDY IN TERTIARY CARE Andreas Schröder, MD, Tomas Toft, MD, PhD, Per Fink, Assoc. Prof., DMSc. The Research Clinic for Functional Disorders and Psychosomatics, Aarhus University Hospital, Noerreborgade 44, DK-8000 Aarhus C, Denmark We are conducting a RCT of specialized treatment of patients with chronic multiple functional somatic symptoms. ICD-10 and DSM-IV criteria for Somatization Disorder (SD) are shown to be unsatisfactory both from a nosological and clinical point of view. We have therefore explored other definitions of multiple functional somatic symptoms in accordance to relevant literature.

88 The aim of this study was to compare patients with SD (defined by ICD-10 and DSM-IV criteria, respectively), Functional Somatic Distress Disorder (FSDD, defined by our own diagnostic algorithm) and other constructs with regard to physical and social functioning and emotional problems. A stratified sample of 701 consecutive primary care patients (age 18-65) consulting their GP with a new health problem was examined for functional somatic complaints and emotional symptoms by means of the WHO-SCAN diagnostic instrument. Assessment included health related quality of life (measured by the MOS SF-36 questionnaire), impairment (interviewer- rating), and frequency of GP-consultations due to functional somatic symptoms (GP-rating). Patients fulfilling criteria for severe Functional Somatic Distress Disorder showed the lowest values for SF-36 summary scores (mean PCS 34.8, MCS 38.8), indicating a poor health related quality of life. 54 % of the FSDD- patients were severely impaired in daily life, and 23 % had frequent GP- consultations due to functional somatic symptoms. 24 % had a comorbid major depressive episode. The prevalence of severe FSDD in primary care was comparable to ICD-10 SD (both 0.03), and there was considerable diagnostic overlap with both ICD-10 and DSM-IV SD. Severe Functional Somatic Distress Disorder is a suitable concept for selection of somatizing patients for treatment in tertiary care.

P07.09 Anne MITOGEN- AND STRESS- ACTIVATED PROTEIN KINASE 1 IS Toftegaard ACTIVATED IN LESIONAL PSORIATIC EPIDERMIS Funding A Funding1, C Johansen1, K Kragballe1, K Otkjær1, U Jensen2, M Madsen3, M Fjording3, J Finnemann3, T Skak-Nielsen3, S Paludan4 and L Iversen1 1Department of Dermatology, Aarhus Inviversity Hospital, DK-8000 Aarhus C, 2Institute of Human Genetics, Aarhus University Hospital, DK-8000 Aarhus C, 3Department of Medical Chemistry, LEO Pharma, Industriparken 55, DK-2750 Ballerup, 4Institute of Medical Microbiology and Immonology, Aarhus University, DK-8000 aarhus C Mitogen- and stress- activated protein kinase 1 (MSK1) is a down stream target of both the p38 and ERK1/2 MAPKs. MSK1 stimulates transcription of different pro-inflammatory genes through activation of transcription factors. The purpose of this study was, to investigate the expression and activation of MSK1 in lesional psoriatic skin and its role in cytokine production in cultured normal human keratinocytes. Western blotting revealed a consistent and significant increase in phosphorylated (activated) MSK1 in lesional psoriatic skin. Immunofluorescence staining revealed phosphorylated MSK1 localized in the basal layers of the epidermis in lesional psoriatic skin. No staining was found in non-lesional psoriatic skin. Cultured human keratinocytes incubated with the p38-activator, anisomycin or IL-1 resulted in phosphorylation of the p38 MAPK and MSK1. MSK1 phosphorylation was inhibited by pre-incubation with the p38 inhibitor SB 202190. Transfection of the keratinocytes with specific MSK1 siRNA resulted in 82% reduction of MSK1 expression and 51%, 40% and 31% decrease in IL-6, IL-8 and TNF- protein production, respectively.

89 This study demonstrates for the first time expression of MSK1 in epidermal keratinocytes and increased activation focally in psoriatic epidermis. Because MSK1 regulates the production of proinflammatory cytokines, it may play a role in the pathogenesis of psoriasis.

P07.10 Hanne Busk OPTIMIZATION OF CULTURE METHODS; CORD BLOOD DERIVED Andersen MASTCELLS. H.B. Andersen, M. Holm, C. Dahl, T. Hetland, S. Junker, HJ. Hoffmann , P.O. Schioetz A-Research Lab, Department of Pediatric, University Hospital of Aarhus, Brendstrupgaardsvej 100, 8200 Aarhus N, Denmark Mast cells (MC) are effectors of both innate and adaptive immunity. In vitro differentiation of human MCs is influenced by numerous factors including stem cell factor, interleukins, IgE and fetal calf serum. We have compared the resulting MC phenotype from three different culture protocols. Methods: CD133+ cord blood derived human MCs were cultured under serum-free conditions for 7 or 12 weeks in the presence of IL-6, SCF, and initially IL-3 for 1 or 3 weeks. Final differentiation was induced by fetal calf serum for respectively 1 or 2 weeks. The influence of IL-4 for 3 days on mature MCs was investigated measuring Fc RI and CD117 expression by FACS analysis. IgE/anti-IgE mediated histamine release was quantitated. Results: More than 50% of mature cells stained positive for CD117 at both 7 and 12 weeks cultures, and more than 60% for Fc RI . IL-4 resulted in modest decrease in CD117 expression, but had no effect on Fc RI . Histamine content in 7 or 12 weeks cultures was 24 pg/cell. IgE/anti-IgE mediated release of histamine (HR) in 7 weeks cultured cells showed batch variation but always increased by 15% in the presence of IL-4. No significant HR was found in 12 weeks cultured cells. Conclusions: Significant variations of phenotypes were observed between culture batches. It is unclear whether the in vitro phenotype heterogeneity reflects the in vivo heterogeneity of MCs or whether it is the result of culture conditions. Short term cultured cells were functionally superior and comparable to 12 weeks cultured MC.

P08.01 Mett Marri ATTITUDES TOWARDS PSYCHIATRIC GENETIC RESEARCH AND Lægsgaard TESTING: FEARS, HOPES, AND INTENTIONS Madsen Mett Marri Laegsgaard, Ole Mors Centre for Basic Psychiatric Research, Aarhus University Hospital Knowledge of attitudes towards psychiatric genetics and factors influencing these attitudes will be necessary when the results of psychiatric genetic research are to be integrated into the healthcare services. Psychiatric genetic research raises ethical questions, and the application of the methods and the knowledge gained will touch on legal, social and psychological issues. We constructed a questionnaire to assess attitudes towards psychiatric genetics and towards the legal and ethical issues inherent to genetic knowledge, as pointed out by the Nuffield Council on Bioethics. We

90 included 661 patients diagnosed with either recurrent depression (n=79), anxiety (n=105), bipolar disorder (n=29), schizophrenia (n=35), unknown diagnoses (n=149), 164 relatives of these persons, and 100 medical or psychology students. SCAN 2.1 was used for psychiatric diagnoses. Intention to use psychiatric genetic testing is expressed by 80.25%, while 71.56% would test their children. Fears of psychiatric genetic research bringing on increased discrimination are anticipated by 44%. Hopes of psychiatric genetic research leading to decreased shamefulness are expressed by 68%, 43% expect less guilt and 56% anticipates testing leading to preparedness to fight disorder. Hypothetic interest in genetic testing for other than psychiatric diseases has been shown to be a poor predictor of actual test uptake. To make the results on attitudes applicable in a future counselling situation, we analyzed which factors influence intentions to test. We found intentions to be related to age, experience with mental illness, and attitudes towards psychiatric genetic research and testing. Results from the survey will be followed up by a qualitative study, exploring issues of relevance for a future psychiatric genetic counselling service.

P08.02 Jette COMMUNICATION IN HEALTH CARE – CAN IT BE IMPROVED ? Ammentorp Ammentorp J, Mainz J, Sabroe S Institute of Public Health , University of Aarhus Skullebjerg Alle 33, 7000 Fredericia Communication is a component of healthcare services that has important impact on the patient’s experience of healthcare service as well as the outcome. Review of the literature shows that lack of information and responsiveness are among the problem most often reported. Few randomised trial has shown that it is possible to integrate key communication skills into clinical practice through training in communication skills. The results so far underline the need for well design studies investigating the effect of communication courses. The purpose of the study is to investigate if communication-skills training for doctors and nurses can improve: Parents’ and children’s perception of the communication Doctors’ and nurses’ experience of self-efficacy Reduce asthma symptoms in children with asthma The study is conducted as a controlled randomised trial in the Paediatric Outpatients clinic at Kolding Hospital, including physicians and nurses. The intervention group receives a 5 days communication course and the control group receives no intervention. The impact of the intervention will be evaluated by comparing physicians and nurses’ improvement in communication skills. Perception of the communication will be measured by the parents and children/ adolescent in questionnaires. As a measure of self-efficacy doctor and nurses assessment of confidence in executing certain skills related to communication with children and parents will be measured in questionnaires. Among children with asthma symptoms peek flow and asthma symptoms, will be registered.

91 P08.03 Anna THE NBCn1 PROTEIN EXPRESSION IS INCREASED THROUGH Mrowiec DIFFERRENT MECHANISMS IN TWO MODELS OF ENHANCED RENAL + DISTAL TUBULAR NH4 DELIVERY A. Mrowiec1, B. Jensen2, J. Praetorius3, C. Buus4, Ch. Aalkjaer1 1Water and Salt Research Center, Institute of Physiology, Ole Worms Alle 1160, University of Aarhus, Denmark; 2Institute of Medical biology- Physiology and Pharmacology, University of Southern Denmark, Odense, Denmark; 3Water and Salt Research Center, Institute of Anatomy, University of Aarhus, Denmark; 4Institute of Pharmacology, University of Aarhus, Denmark We have studied the mechanisms controlling expression of the bicarbonate transporter NBCn1 (SLC4A7).

Male rats were treated with NH4Cl in the drinking water for 1 and 2 weeks or given a K+-deficient diet for 1 and 4 days. This produces metabolic acidosis (CMAc) and alkalosis (CMAl), respectively but in both cases cause + increased NH4 delivery to the kidney thick ascending limb (TAL). NBCn1 protein levels from different kidney zones were analysed by Western Blotting and mRNA levels by quantitative PCR (QPCR) and by RNA protection assay. The results showed increased protein levels of NBCn1 in the inner stripe of outer medulla of NH+ loaded and K+-deficient rats, but not in cortex or inner medulla. The results suggest that NBCn1 is regulated at the translational or + posttranslational level during NH4 -loading while NBCn1 is regulated at the transcriptional level in the K-depleted rats. Hence, increased delivery of + NH4 to the TAL can not be the only factor controlling NBCn1 expression.

P08.04 Gang Chen ANTIVASCULAR THERAPY EVALUATED BY PWI AND DWI Gang Chen MR Research Center, Aarhus University Hospital, DK8200 Aarhus N Introduction: Tumor neovasculature has been identified as a target of new drugs for cancer treatment. This study uses magnetic resonance perfusion and diffusion imaging to validate the changes in tumor regional flow patterns induced by the anti vascular drugs CA4DP and DMXAA. Methods and Materials: CDF1 mice, implanted in the right rear foot with a C3H mammary carcinoma, received either CA4DP (250 mg/kg) or DMXAA (20 mg/kg), intraperitoneally. Repeated fluid diffusion and blood perfusion weighted images were performed before and up to 6-hours after treatment. The image area representing the whole tumor; the central part; and the peripheral part of the tumor were identified. Results: The blood perfusion in the peripheral tumor areas and whole tumor samples decreased immediately after the administration of CA4DP; however this did not occur in the central part. The peripheral part of tumor showed decreased blood perfusion soon after DMXAA while in the whole tumor, the decreasing could only be detected 3 hours after administration. The fluid diffusion decreased immediately in all three tumor areas after CA4DP, however the same pattern was observed increasing after DMXAA. Conclusion: Both CA4DP and DMXAA show their abilities to block the blood supply and damage cells in tumors. CA4DP showed a typical

92 ischemia-necrosis process. Although there is a substantial decrease in blood perfusion, cells in the peripheral part of the tumor obtain their nutrient and oxygen needs, and thus survived for a long time compared to those in central part. In contrary, in the DMXAA treated group, blood perfusion decrease and cell death could be detected at the same time, due to the effect caused by TNF. Blood perfusion changes are not always followed by substantial cell death, thus when the anti-vascular therapy is administered, it could be considered some supplement treatments, such as chem- or radiotherapy, should be given.

P08.05 Tomasz HERPES VIRUS ANTIGENS ACTIVATE ENDOGENOUS RETROVIRUSES: Brudek IMPLICATIONS FOR MULTIPLE SCLEROSIS T. Brudek1, P. Lühdorf1, T. Christensen1, H. J. Hansen2, A. Møller-Larsen1 1Department of Medical Microbiology and Immunology, 2Department of Neurology, University of Aarhus, DK-8000 Aarhus C, Denmark Multiple Sclerosis (MS), the neurological inflammatory disease, affects and incapacitates a large number of people worldwide. It is well established that genetic and environmental factors are involved in the etiology of MS. Several human endogenous retroviruses (HERV) and herpes viruses have been associated with development of MS. These groups are known to interact with each other by inducing synergistic immune responses and herpes viruses are capable of transactivating HERVs. Considering the possible role of herpes viruses as cofactors in activation of HERVs, which in consequence maybe leading to the development of MS, we present further evidence of a significant interaction between these two viral groups. Using a highly sensitive method, product enhanced reverse transcriptase assay (PERT), for detection of reverse transcriptase (RT) activity, we have shown the ability of herpes antigens to induce HERV expression in peripheral blood mononuclear cells (PBMC) from MS patients and healthy controls. The level of RT activity was similar in both groups. The effect was predominantly observed with HHV-6A and VZV antigens after day 9 post antigen stimulation, persisting through the following days of the experiments up to day 21. HSV-1 antigens were also found to significantly increase HERV expression but for a short period. Intriguingly we did not find correlation between HERV activation and cell proliferation in response to herpes antigens. The significant RT activities were observed in the days following the peak responses in the cellular reactivity. This may indicate that the activating immune response is different from or may follow the analyzed lymphocyte reactions towards herpes antigens. The present results contribute to the theory that herpes viruses and HERVs, by their unique relationship, may play a role in the pathogenesis of MS.

P08.06 Søren Peter REMISSION-KEEPING AND REMISSION-INDUCING EFFECT OF Jørgensen VITAMIN-D IN CROHNS DISEASE. Jorgensen SP, Agnholt J, Glerup H, Lyhne Nielsen S, Christensen LA and Dahlerup JF. Department V (hepato- and gastroenterology), Aarhus University Hospital, V-science, Nørrebrogade 44, buil. 1C, 1., 8000.

93 Background: Recent years scientists have hypothesized low blood vitamin-D levels playing a role in the development of autoimmune disease, including Crohns disease. Cutaneous biosynthesis upon exposure of the skin to sunlight is a major source of vitamin-D for most people. Epidemiological studies show higher prevalence of Crohns disease in the northern hemisphere compared to the southern. Furthermore studies have shown an effect of vitamin-D treatment in animal models with eksperimental inflammatory bowel disease. Methods: Double blind placebo controlled randomized trial. 100 patients with inactive Crohns disease are allocated to a daily intake of either 1200 I.U. of kalciferol or placebo. Follow up period: 1 year. Primary endpoint: Flair-up. Time to flair-up will be measured within the two groups and survivalanalysis will be made. Patient who flair up, i.e. reach primary endpoint, will openlabelled receive 100.000 I.U. of kalciferol and the role of vitamin-D treatment in active Crohns disease will be evaluated. Peripheral blood mononuclear cells (PBMC) and intestinal mucosal T-cells (only when flair up), will be collected, cultured, analyzed and frozen. Blood samples will be frozen for latter analysis of 25- and 1,25-hydroxyvitamin-D and parathyroid hormone. Results/study-plan: October 2005: 11 patients with inactive Crohns disease enrolled in the study. No flair ups has been reported.

P08.07 Jonathan USING BIASED IMAGE ANALYSIS FOR IMPROVING UNBIASED Gardi STEREOLOGIC NUMBER ESTIMATION – A PILOT SIMULATION STUDY OF THE SMOOTH FRACTIONATOR J.E. Gardi, J.R. Nyengaard, H.J.G. Gundersen Stereology and Electron Microscopy Research Laboratory and MIND Center, University of Aarhus, Aarhus, Denmark The viewing, sampling and estimation process in tissue with sparse or non-homogeneous cell distributions can be improved by introducing computerized image analysis into existing stereology procedures. The smooth fractionator was introduced in 2002 (Gundersen HJG. The smooth fractionator. J. Microscopy. 207, 191-210). The combination of a smoothing protocol with a computer assisted stereology tool provides better precision and less workload. This study uses simulation for comparing fractionator sampling based on the smoothing design, the commonly used systematic uniformly random sampling design, and the ordinary simple random sampling design. The smoothing is performed using the biased information from crude (but fully automatic) image analysis of the fields of view. The different design paradigms are compared using simulation in three different cell distributions with reference to sample size, noise and counting frame position. Regardless of clustering, sample size or noise, the fractionator based on smoothing design is more efficient than the fractionator based on systematic uniform random design, which is more efficient than a fractionator based on simple random design. The fractionator, based on a smooth design, is up to four times more efficient than a simple random design. Apparently, the smooth fractionator can improve the efficiency of cell

94 counting.

P08.08 Mie Wiese ACCURACY OF MORPHOLOGICAL CHANGES IN TMJ-TOMOGRAMS Petersen WITH THREE IMAGING SYSTEMS M. WIESE, H. HINTZE, A. WENZEL Department of Oral Radiology, School of Dentistry, University of Aarhus and University of Copenhagen, Denmark. Aim: To compare diagnostic accuracy of tomograms obtained with film and two digital imaging systems for detection of morphological changes in the TMJ. Methods: 50 dry human skulls were examined with corrected lateral and frontal TMJ tomography performed in a Cranex Tome™ x-ray unit. The images were obtained with two PSP systems, Digora (D) and Vista Scan (V) and with conventional film (F). Three observers examined individually the tomograms for the presence of flattening, osteophytes and defects of the condyle, mandibular fossa and articular tubercle. The presence of morphological bone changes was validated by naked-eye inspection of the skulls performed by the same three observers. The “gold standard” was defined as an observation reported by at least two observers. The diagnostic

accuracy was expressed as ROC curve areas (Azs), and differences between the imaging systems were analysed by two-way ANOVA.

Results: Using both lateral and frontal tomograms mean Azs were: condylar flattening: 0.69 (D), 0.73 (V) and 0.74 (F) (p<0.02 between D and F); condylar defects: 0.63 (D), 0.67 (V) and 0.65 (F) (p<0.03 between D and V); articular tubercle flattening: 0.83 (D), 0.84 (V) and 0.88 (F) (p>0.05); articular tubercle defects: 0.64 (D), 0.63 (V) and 0.66 (F) (p>0.05). Using the lateral

tomograms only, mean Azs were: fossa flattening: 1.00 (D), 1.00 (V) and 0.96 (F) (p>0.05); fossa defects: 0.73 (D), 0.73 (V) and 0.75 (F) (p>0.05); condyle osteophyte: 0.62 (D), 0.65 (V) and 0.60 (F) (p>0.05). Conclusion: For assessment of bone changes in the mandibular fossa and the articular tubercle no difference in diagnostic accuracy was found between the three systems, but for assessment of condyle flattening and defects the Digora-system was less accurate than the other two systems.

P08.09 Jakob Udby EVIDENCE OF SHORT-TERM PLASTICITY IN A STROKE PATIENT, Blicher MEASURED BY TRANSCRANIAL MAGNETIC STIMULATION OF THE MOTOR-CORTEX. J.U. Blicher, J.F. Nielsen, J. Jakobsen Hammel Neurocenter, [email protected] The aim of the study was to demonstrate use dependent plasticity in the motor-cortex of a chronic stroke patient. A stroke patient (21 months after stroke) was examined with Transcranial Magnetic Stimulation (TMS). The size of the Motor Evoked Potential (MEP) and the response to paired-pulse stimulation in the abductor pollicis brevis muscle were measured before and after a 15 minutes session of repetitive thumb movements. The results show a change in the response to paired-pulse stimulation indicating a change in the synaptic efficacy of the inhibitory circuitry at the level of the motor-cortex.

95 The presence of short-term plasticity in the motor-cortex of stroke patients after motor training might indicate a possibility for further motor- learning/rehabilitation in these patients. In healthy volunteers the amount

of short-term plasticity after motor-training is decreased by GABAA receptor agonists like lorazepam and increased by methylphenidate. This might be of importance for the rehabilitation of brain injured patients in the future.

P08.10 Inge Errebo SEQUENTIAL FISH ANALYSIS USING COMPETITIVE DISPLACEMENT Agerholm OF LABELED PEPTIDE NUCLEIC ACID PROBES FOR 8 CHROMOSOMES IN HUMAN BLASTOMERES. I.E.Agerholm1 , S.Ziebe , B.Williams, C.Berg, D.G.Crüger, G.Bruun Petersen , S.Kølvraa 1Fertilitetsklinikken, Brædstrup sygehus, 8740 Brædstrup, Denmark The objective was to introduce a new strategy for fluorescence in situ hybridization (FISH) analysis in single cells based on Peptide Nuclei Acid (PNA) probes and competitive displacement . Sequential FISH analysis with peptide nucleic acid probes and competitive displacement was performed using three different probe sets. The first set consisted of labeled probe only. The second and third set included labeled as well as unlabeled probe corresponding to the labeled probes in the previous cycles. The probes for enumeration were for chromosome 1, 13, 16, 17, 18, 21, X and Y. The performance of peptide nucleic acid probes was similar to the established DNA probes. The strategy of competitive displacement resulted in a destabilization of already bound probe before the next FISH cycle at only 50 º C, which allowed for up to 5 sequential FISH cycles without loss of signal. Peptide nucleic acid probes are a good alternative to DNA probes since the low temperature required both for binding and destabilization of PNA probes minimizes the loss of signal and several FISH cycles can therefore be done before FISH errors occur. As a consequence more chromosomes can be enumerated in a single cell resulting in a more accurate analyze of IVF produced human embryos before replacement.

P09.01 Helle A HEALTH PROMOTION PATIENT EDUCATION PROGRAM FOR Terkildsen SCREEN-DETECTED PATIENTS WITH NEWLY DIAGNOSED TYPE 2 Maindal DIABETES, IMPAIRED FASTING GLUCOSE AND IMPAIRED GLUCOSE TOLERANCE Helle Terkildsen, Institut for Folkesundhed, afdeling for Almen Medicin, Vennelyst Boulevard 6, st 8000 Århus C In Denmark more than 300.000 suffer from T2 DM, and among these 50% are unaware of their condition. The disease can be prevented by lifestyle interventions ex. weight loss, increased exercise and smoking cessation. The ADDITION-study (Anglo-Danish-Dutch study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care), is a two-phase population-based study conducted in DK; UK and The Netherlands aiming at evaluating screening for prevalent undiagnosed Type 2 Diabetes and intensive treatment and care of diabetes and associated risk factors. The

96 intervention study is a 5-year prospective randomised study, where a health promotion patient education program will be part of the future intervention. The aim of this study is to develop and evaluate a health promotion patient education program with the goal of empowering patients in everyday self-care decision-making in the context of a complicated chronic disease. The intervention will be patient-centred, systematic and focused on providing the patients with adequate competencies and skills. Important elements will be problem-solving, decision-making, utilisation of resources, action-planning and attitudes to the health system. The intervention will be planned as nurse-led group-based sessions in primary health care. A randomized, clinically controlled trial will be carried out in 200 patients with T2 DM, IGT and IFG from one Danish county. There will be pre- and post-tests and 1-year follow-up including the outcome measures: self- management skills in diabetes health behaviours, self-efficacy, healthcare utilization and HbA1c, BP and cholesterol. Data sources will be self- administered questionnaires and blood samples. Results will be of relevance to policy decision makers concerning screening and treatment of T2 DM in local settings and add a new approach to health promotion activities.

P09.02 Anne ELECTIVE CESAREAN SECTIO AND RESPIRATORY MORBIDITY IN Kirkeby THE NEONATAL PERIOD. Hansen A.K.Hansen, M.D, Ph.D-student. The Perinatal Epidemiological Research Unit, Department of Obstetrics and Pediatrics, Aarhus University Hospital, 8240 Aarhus, Denmark. Elective caesarean section has been associated with an increased risk of respiratory problems in the neonatal period. There may be several explanations to this finding; 1) “iatrogen immaturity” (invers relation between the frequency of respiratory morbidity and gesational age), 2) lack of natural physiological changes in the fetal cardiopulmonary system in relation to labour. 3) caesarean section pr se. The aim of this study is to investigate the association between elective caesarean section and the risk of respiratory morbidity in the neonatal period. This cohort study is based on data from The Aarhus Birth Cohort, Aarhus Unversity Hospital, and includes information about 65.000 deliveries. Information on exposure (elective caesarean section in gestational week 37, 38, 39 and 40) is extracted from this database. Information about neonatal morbidity, i.e respiratory distress syndrome, transient tachypnea of the newborn, persistent pulmonary hypertension of the newborn, pneumothorax, perinatal asphyxia and sepsis will be obtained from the Neobase (discharge data from children admitted to The Neonatal Care Unit at Skejby Hospital) and The Danish Hospital Register. The statistical analyses will be conducted as multiple regression, and logistic regression analyses with elective caesarean section as independent variable, and admission to neonatal care unit and specific neonatal morbidity as dependent variables.

P09.03 Thomas HIGH-RESOLUTION SCREENING OF COLORECTAL CANCER USING Dyrsø Jensen ARRAY COMPARATIVE GENOMIC HYBRIDIZATION

97 T.D. Jensen1,2, J. Li2, K. Wang2, S. Li2, X. Zhang2, L. Bolund2, S. Kølvraa1, G.B. Petersen1 1Dep. of Clinical Genetics, Vejle Hospital, 7100 Vejle; 2Institute of Human Genetics, University of Aarhus, 8000 Aarhus C Colorectal cancer is one of the most common cancers in the western world and the prognosis is generally poor. Choice of therapy and prognostic considerations still depend on pathological staging. However, in recent years array-based technologies have proved to be very promising tools in future treatment of all cancers. In this project, tumor DNA from newly operated colorectal cancer patients is investigated using array comparative genomic hybridization (array-CGH) in a set-up that allows detection of small-scale aberrations (deletions, duplications and amplifications) in the tumor genome at a 1 megabase resolution. The project has two main aims: 1) To identify regions of the genome where aberrations are frequent, i.e. where DNA breaks are more prone to take place. The hypothesis is that such regions contain repetitive DNA segments, so-called low copy repeats (LCR’s) and that regions which are frequently duplicated or amplified contain oncogenes and regions that are frequently deleted contain tumor supressor genes. 2) To classify colorectal cancers according to aberrational patterns and correlate that with clinical and pathological findings. The hope is that such genomic screenings of colorectal cancer patients in the future will become a valuable tool, improving treatment and prognostic precision.

P09.04 Charlotte REGULATION OF URINE PRODUCTION: DIFFERENCES BETWEEN Graugaard- GENDERS. Jensen Graugaard-Jensen C, Frøkiær J, Hvistendahl G, Djurhuus JC. Institute of Clinical Medicine, AArhus University Hospital Skejby, 8200 Aarhus N, Denmark [email protected] In healthy adults, a circadian secretion of AVP with a nighttime peak has been demonstrated. With increasing age, the nocturnal phase of AVP secretion seems to diminish to a level close to daytime levels. A gender difference also seems to occur. Several studies have shown that the relatively high oestrogen levels in pregnancy and in the luteal phase of the menstrual cycle reduce the osmotic thresholds for thirst and vasopressin release. This osmostat resetting also occurs when young women are given oestrogen substitution (oral contraception). Aquaporin-2 water channels (AQP2) are essential for the renal concentration mechanisms. Aquaporin-2 is shed in the urine and varies according to the menstrual cycle. More AQP2 is shed in the urine when oestrogen is high. During pregnancy the amount of AQP2 excretion in the urine also varies, with a peak in week 36, but interestingly, no increase in AVP occurs. A non-AVP factor may therefore play a role in the regulation of the urine production and we designed a study to elucidate the regulating mechanisms during the different levels of naturally occurring oestrogen (ie, during the menstrual cycle and during the perimenopause). Sixty participants, 40 young women and men and 20 middle aged women and men will be included. The young women will be admitted twice just

98 before and after ovulation. The middle aged will be admitted three times during two years. Men serve as controls. Every admission will be 24 hours. Seven times during the 24 hours a blood sample will be drawn through an intravenous catheter. Every third hour the bladder will be emptied. This will give us the opportunity to characterize the circadian rhythm of the water and salt-regulating hormones under the influence of oestrogen and may give us new knowledge about the non-AVP factor.

P09.05 Christina SYNERGISTIC ROLE OF IBD (ACAD8) MUTATIONS AND THE Bak Pedersen PREVALENT 625G>A SCAD SUSCEPTIBILITY VARIATION IN

ELEVATED C4-CARNITINE EXCRETION DETECTED BY MS/MS NEWBORN SCREENING CB Pedersen1, C Bishoff1, E Christensen2, H Simonsen3, A Lund2, SP Young4, DD Koeberl4, DS Millington4, CR Roe5, DS Roe5, RJ Wanders6, JP Ruiter6, LD Keppen7, Q Stein7, I Knudsen1, N Gregersen1, BS Andresen1,8 1Res. Unit for Mol. Med., Skejby Sygehus,2Dept.Clin. Gen., Rigshospitalet, 3Statens Serum Inst., 4Duke Univ., N. Carolina, USA, 5Baylor College, Texas, USA, 6Academic Med. Center, Amsterdam, The Netherlands, 7Univ. of S. Dakota, USA, 8Dept. of Hum. Gen., Aarhus University. The acyl-CoA dehydrogenases (ACADs) are a family of nuclear encoded, mitochondrial enzymes involved in the metabolism of fatty acids and branched chain amino acids. Inherited deficiencies of ACADs are important causes of metabolic disorders. Isobutyryl-CoA dehydrogenase (IBD) is involved in the catabolism of valine, whereas short-chain acyl-CoA dehydrogenase (SCAD) is involved in the fatty acid metabolism. IBD deficiency results in accumulation of isobutyryl-CoA, whereas SCAD

deficiency results in accumulation of butyryl-CoA. Both of these C4-CoA’s are detoxified by conjugation to carnitine and glycine, and excreted in blood and urine. In this study we demonstrate IBD deficiency in four newborns

with elevated C4-carnitine identified by tandem mass spectrometry (MS/MS) based screening. We present seven new mutations in the IBD gene. Functional studies showed that some of the mutations disturb protein folding and reduce the IDB enzyme activity. Interestingly, all four newborns and a previously described patient with clinically manifested IBD deficiency were heterozygous for the prevalent SCAD 625G>A susceptibility variation. Accordingly, we speculate that a synergistic effect of mutations in the IBD gene together with the prevalent SCAD susceptibility variation is necessary for IBD deficiency to become clinically relevant, and if isolated IBD deficiency may thus be a benign condition.

P09.06 Kari GEOMETRIC STABILITY OF RADIOACTIVE SOURCES DURING Tanderup RADIATION THERAPY K.Tanderup, J.J.Christensen, J.Granfeldt, C.Grau & J.Lindegaard. Dept. of Oncology, Aarhus University Hospital, 8000 Aarhus C, Denmark Background and purpose: Displacements of radioactive source or critical organs during internal radiotherapy can lead to misadministrations of radiation dose. The purpose of this study was to evaluate the stability of radioactive source and the rectum during 10 hours of radiotherapy of

99 cervical cancer. Materials and methods: A total of 18 treatments each consisting of 10 hourly radiation pulses were analyzed. Holders for the radioactive source were placed in the uterine channel and on the cervix. Additionally, five diodes were placed in the rectum for dose measurements. A mathematical model was developed that could transform the dose measurements into the geometry of source holder and rectal diodes. The displacement of the source relative to diodes during a patient treatment was determined together with the uncertainty of the method. The method was validated by phantom measurements. Results: Phantom measurements confirmed that the model could determine changes in geometry with an uncertainty of less than 1 mm. The mean measurement uncertainty in patients was below 0.8 ± 0.5 mm in all directions. The relative geometry of applicator and diodes was very stable during the treatment since the standard deviation of displacements was below 2.8 mm in all directions for all patients. The mean displacements in lateral, longitudinal and anterior-posterior directions were 1.2 ± 0.7 mm, 1.2 ± 0.7 mm and 0.9 ± 0.6 mm respectively. Conclusions: A new mathematical method has been developed, enabling us to quantify and monitor the geometry of radioactive source and rectal diodes during radiotherapy. The spatial relation between source holder and rectal dosimeter was very stable during extended treatments.

P09.07 Ole Gade DIFFERENT FIXATION METHODS IN RECONSTRUCTION OF THE Sørensen ANTERIOR CRUCIATE LIGAMENT. Sørensen OG(1+2), Jakobsen BW(1), Kold S(1), Hansen TB(2), Mortensen JS(2), Søballe K(1). (1)Department of Orthopedics, Hospital of Århus, County of Århus, Denmark. (2)Department of Orthopedics, County of Ringkøbing, Denmark. Background: Anterior cruciate ligament(ACL) injury is a common consequence of knee injury. This may lead to a decrease in joint stability with risk of damage to the intraarticular structures leading to osteoarthrosis. ACL reconstruction aims to re-establish joint stability. Earlier the patella tendon was chosen as graft in most cases. In the recent years the hamstring tendon has become increasingly popular due to minimal donor site morbidity. However especially the tibial fixation of the hamstring graft is considered problematic due to numerous reasons. Objective: To investigate a new tibial transverse fixation method, which may reduce some of the problems in fixation of hamstring grafts. Material and methods: 1) In-vitro biomechanical study using a bovine model. The strength of two new transverse fixation methods and two already known fixation devices, are evaluated after cyclic loading and single cycle pullout tests. 2) The strongest transverse fixation method is compared to the strongest of the known procedures in a clinical randomized trial. Tantalum beads are inserted in both the femur, tibia and graft. The knee laxity and graft motion inside the bone tunnel are evaluated using roentgen stereometric analysis and a Telos stress apparatus.

P09.08 Bettina REPRODUCIBILITY OF MR RENOGRAPHY IN CHILDREN.

100 Jørgensen Bettina Jørgensen, A Keller, S Rittig, F Taagehøj-Jensen, J Frøkiær, TM Jørgensen,Michael Pedersen. Institute for Clinical Medicine, Aarhus University Hospital, 8200 Århus N, Denmark. Email:[email protected] Purpose: Patients in risk of renal deterioration are followed with serial examinations. It would be advantageously to replace destructive methods with non-destructive modalities such as magnetic resonance imaging (MRI). The purpose of this study was to evaluate the reproducibility of MRI renography for quantitative calculation of renal parameters. Methods and materials: 10 healthy volunteers, age 13-16 years, were examined 3 times within 10 weeks, including one session with increased fluid intake. In each MRI procedure a bolus of contrast agent was administrated intravenously during a fast renography sequence. Images were acquired in the coronal plan and 1200 images were recorded in approximately 15 minutes. Renal data were analyzed to estimate absolute and differential values of renal parameters by converting signal intensities into quantitative units. Results: Using the simple approach that a change in MRI signal is linearly related to the change in Gd-DTPA concentration, we found reproducibilities in the range of 1-5% in all calculations of the split renal function. When calculating the quantitative renal parameters, the relative glomerular ultrafiltration (rGU) assigned in ml/min/cm3 kidney parenchyma, we found a reproducibility of 7% for rGU using a model based on deconvolution. Calculations of absolute measures in parameters as TP (time to peak) and MTT (mean transit time) resulted in reproducibilities < 10 %. Increased hydration showed significant changes in most parameters. Conclusion:MR renography is fully comparable to conventional renographic measures of split renal function. When calculating absolute measures, it is important to employ the correct method. Hydration should be standardized in order to produce reproducible results.

P09.09 Sigitas IDENTIFICATION OF PROTEINS AND PEPTIDES PREDICTING THE Urbonavicius NATURAL HISTORY OF ABDOMINAL AORTIC ANEURYSMS S.Urbonavicius, J.S.Lindholt, H.Vorum, E.W.Henneberg, B.Honoré Department of Medical Biochemistry, Ole Worms Allé, bldg.1170, Aarhus University, Denmark Abdominal aortic aneurysm (AAA) is an abnormality prone to expansion and rupture, causing death. We aim to prevent death due to AAA rupture by early detection of high-risk factors for the disorder. Serum samples and abdominal aortic wall material from 12 cases of ruptured (RAAA) and 12 cases of unruptured abdominal aortic aneurysms (Viborg study, Denmark) have been selected and prepared. Samples were analyzed for protein composition by two-dimensional gel electrophoresis. Image analysis was used to detect protein spots, which were differentially regulated at least 1.5-fold in ruptured AAA samples as compared with unruptured AAA. Significant spots were excised subjected to in-gel digestion and identified by mass spectrometry. Seven proteins were differentially regulated in wall material from patients with ruptured as compared with unruptured AAA. Three proteins were

101 identified, two down-regulated, vitronectin and gamma-fibrinogen, and one up-regulated, peroxiredoxin-2. Experiments are currently conducted to identify the remaining proteins. Gamma-fibrinogen in serum correlated with AAA expansion rate (Spearman’s r=0.649). Several albumin fragments were detected showing positive as well as negative correlation. The proteomic composition of wall material differs from patients with ruptured and unruptured AAA. The identified proteins initially suggest that the changes in AAA wall are due to at least two different mechanisms, destruction and weakening of extracellular matrix and inflammation.

P09.10 Fenghua PLASTICITY AT THE SYNAPSE: NEURON AND SYNAPSE NUMBER IN Chen THE SUBREGIONS OF RAT HIPPOCAMPUS AFTER IMIPRAMINE TREATMENT Fenghua Chen1, 2, Gregers Wegener2, Torsten M. Madsen2, Jens R. Nyengaard11Stereology and Electron Microscopy Research Lab. and MIND Center, Aarhus University; 2Center for Basic Psychiatric Research, Psychiatric Hospital, Aarhus University Depression covers a wide spectrum of diseases, which are different with respect to incidence, severity and prognosis. The underlying pathophysiological mechanisms of depression and the neurobiological basis for antidepressant therapy are still poorly understood. The hippocampus is thought to play an important role in the pathophysiology of depression. Depression may result from an impairment of neurons in the hippocampus which makes it impossible to make appropriate adaptations and / or synaptic connections. Chronic antidepressant therapy increases levels of neurotrophic factors, cell proliferation and neurogenesis; it possibly stimulates outgrowth and regeneration of dendrites and axons, as well as promoting synaptogenesis in the hippocampus. We investigated whether chronic antidepressant treatment increases the rate of neurogenesis and synaptogenesis in the subregions of hippocampus in normal rats. The physical disector stereological method was used to quantify neurogenesis and synaptogenesis in subregions of the hippocampus after imipramine (a classic tricyclic antidepressant) injection for 14 days on normal rats. The results showed that the volume, numerical density and the total number of neurons in the various hippocampal subregions are not different between imipramine and vehicle treatment after 14 days (n=14, 7 for treatment, 7 for control). Synapses density and total synapse number in the CA1 stratum radiatum were statistically indistinguishable in these two groups. It could be explained by the clinically observed effect of imipramine treatment where symptoms relief occur usually after 21 days. We conclude that administration of imipramine for 14 days in rats does not increase numbers of either synapses or neurons in hippocampus.

P10.01 Kristian EFFICACY OF A PROACTIVE PERIOPERATIVE CARE AND Larsen REHABILITATION INTERVENTION IN PATIENTS UNDERGOING PRIMARY TOTAL HIP OR KNEE REPLACEMENT Larsen K*, Søballe K†, Hansen TB*, Christiansen T‡. *The Musculoskeletal Research Unit, Department of Orthopedic, County of

102 Ringkoebing, Denmark. †Department of Orthopedic, County of Aarhus, Denmark. ‡ISF University of Southern Denmark. Background: When scrutinising the literature there seems to be a great potential in reducing the costs and improving the effect of optimizing the perioperative period for patients undergoing total hip or knee replacement. But since only one randomized clinical trial looking at a clinical pathway for hip and knee replacement could be identified and because this study was not reporting cost data the level of evidence for the cost efficacy of this intervention is low. Materials & Methods: Randomized controlled intervention trial with cost utility analysis. Eighty patients are estimated to be sufficiently for the study to show an anticipated reduction in length of stay of 2 days. At baseline the patients are given written and oral information and after content they fill in a baseline questionnaire and are randomised to a control group receiving the current perioperative care and rehabilitation or to an intervention group where the intervention is given according to the regime advocated by The Unit for Perioperative Nursing Care, Rigshospitalet. In this regimen the perioperative care and rehabilitation is organized in a new proactive special care and rehabilitation unit where the patients are gathered and the health care staff are focusing on optimizing four areas: 1) information including a preselected discharge day, 2) pain reduction, 3) nutrition and 4) mobilisation. Costs for the perioperative period are collected using DRG taxes and costs for the postoperative period are collected from diaries. Effect data is collected from questionnaires using EQ-5D at 3 and 12 months follow-up. Primary outcome measure is the incremental cost efficacy ratio.

P10.02 Jeppe Sylvest Activated Protein C’s Anti-inflammatory Effects on Acute Endotoxemic Nielsen Pigs Jeppe S. Nielsen, Rasmus Sørensen, Thomas Rix, Thomas Ledet, Anders Larsson, Else Tønnesen Dept. Anaesthesiology and Intensive Care, Clinical Institute Introduction: Beneficial effects of Activated Protein C (APC) on mortality and morbidity have been demonstrated in patients with severe sepsis and septic shock. The anti-inflammatory properties of APC remain unsettled. Aim: In this study we assessed the anti-inflammatory effects of APC in a porcine model of acute endotoxemia. Materials and methods: The study was approved by the Ethical Committee on Animal Research. 18 female landrace pigs were studied. Animals in group I (LPS, n=9) were subjected to anaesthesia and lipopolysaccharide (LPS) infusion for 5 h. In group II (LPS+APC, n=9) the animals were exposed to LPS and APC for 5 h. LPS infusion was started at a rate of 2.5 µg·kg-1·h-1 and increased stepwise to 15 µg·kg-1·min-1 during the following 30 min's. For the remaining trial period the infusion continued at a rate of 2.5 µg·kg-1·h-1. The APC infusion was commenced at 100 µg.kg-1.h-1. Blood for cytokine analysis (IL-1, IL-6, IL-8, IL-10, TNF- ) was drawn at -15 min, 60, 120, 180, 240, and 300 min. Measurements of the coagulation parameters APC, TAT, and PAI-1 were performed according to the manufactures instructions. Results: In both groups endotoxemia elicited a marked pro-(TNF- , IL-1,

103 IL-6 and IL-8) and anti-inflammatory (IL-10) cytokine response but without significant differences between the groups. There was a tendency towards decreased TAT levels in the APC treated group but this was not statistical significant. The same tendency was found for the PAI-1 levels with decreased levels in the APC treated animals. Discussion: Endotoxemia elicited a well defined cytokine response, but we were unable to show any significant differences in plasma cytokine levels between APC and non-APC treated animals. Furthermore, we did not find the expected anti-coagulative and pro-fibrinolytic effects of APC. A contributing factor to our results may be that the porcine coagulation system is different from the human. In addition, data may indicate that our study is underpowered. Conclusion: We did not find any modifying effects of APC on pro- or anti- inflammatory cytokines. Our results suggest that the anti-inflammatory effects of APC are not elicited through cytokines.

P10.03 Maciej NEW PROTEINS INVOLVED IN THE IRON METABOLISM – STUDY OF Bogdan HEPCIDIN IN RELATION TO FUNCTION, EXPRESSION AND Maniecki SHEDDING OF CD163 M.B. ManieckI1, B.K. Møller2, S.K. Moestrup1,3, H.J. Møller1 1 Department of Clinical Biochemistry, Aarhus University Hospital, DK- 8000 Aarhus C. 2 Department of Clinical Immunology, Aarhus University Hospital, DK-8000 Aarhus C. 3 Institute of Medical Biochemistry, University of Aarhus, DK-8000 Aarhus C. Introduction: Through the past few years, there has been a research breakthrough with regard to identification of proteins involved in the iron metabolism. This research has radically expanded our knowledge on the progression of iron related diseases. The two endocytic macrophage receptors CD163 and CD91 are both known to be essential players in iron metabolism; CD163 by scavenging haptoglobin-hemoglobin complexes by endocytosis for the removal and metabolism of hemoglobin, and LRP/CD91 by binding and mediating the endocytic clearance of hemopexin-hem complexes resulting in cellular heme uptake and lysosomal hemopexin degradation. The key regulator of iron metabolism, however, is the newly discovered liver-produced hormone hepcidin. This hepatic peptide controls plasma iron levels by regulating the absorption of dietary iron from the intestine, and the release of recycled hemoglobin iron by macrophages. Hepcidin seems to play a crucial role in hemochromatosis, iron deficiency anemia and anemia of chronic disease. Aim of study: The primary aim of this forthcoming study is to investigate the relationship of the two macrophage receptors CD163 and CD91, which play an essential role in iron uptake in macrophages, with the hepatic peptide hepcidin. Additionally an LCMS technology based assay will be developed for measurement of hepcidin in biological fluids. Materials and methods: Hepcidin will be synthesized commercially. Hepcidin will be measured in blood serum with electrospray tandem mass spectrometry after chromatographic purification. Hepcidin induced

104 ferroportin uptake will be characterized by confocal laser scanning microscopy, application of recombinant hepcidin-GFP fusion protein, radioactive conjugated hepcidin, monoclonal antibody inhibition and siRNA technology. Cell culture will be performed using monocytes purified from human buffy-coats and followed by real-time quantitative reverse transcription polymerase chain reaction, fluoresecence-activated cell sorting analysis, and enzyme-linked immunosorbent assay. Perspectives: The study will provide new knowledge on the relationship between proteins involved in the iron metabolism. Identification of a co- factor for ferroportin internalization will open novel therapeutic possibilities in hemochromatosis and anemia of chronic disease. The development of a hepcidin serum assay will open novel diagnostic possibilities with regard to differentiating iron deficiency anemia from anemia of chronic disease.

P10.04 Anne Barklin INFLAMMATORY RESPONS TO BRAIN DEATH. A PORCINE EXPERIMENTAL STUDY. A. Barklin, Chr. Vestergaard, A. Larsson, E. Tønnesen. Department of Anaestesiology and Intensive care, University Hospital of Aarhus, Nørrebrogade, N-forskning, bygn. 1C, 8000 Aarhus C, Denmark. Organs transplanted from brain dead donors show a poorer survival than organs from living donors. Brain death leads to changes in circulation and hormonal status. It is less clear, if brain death per se leads to systemic inflammation. In a porcine model we have previously induced an acute inflammation, with a cytokine response analogous to the response in humans. The aim of this study is to establish a porcine model to investigate inflammatory changes induced by brain death with particular emphasis on the organs: heart, lung, liver, and kidney. Brain death is induced by increasing the intracranial pressure, by infusion of saline water into the balloon of a Foley catheter, placed frontoparietal, epidural in the pig. The pigs develop a brain stem response (severe increaseof blood pressure and heart rate). Hereafter brain death is defined when the cerebral perfusion pressure becomes negative (intracranial pressure is higher than middle artery pressure). Bloodsamples are analysed for cytokines (TNF-a, IL-6, IL-8 and IL-10), hormones, free fatty acids, lactate, etc. Biopsies from the organs are taken six hours after brain death. Cytokine mRNA is analysed by PCR-technique, and the cytokine-proteins by Elisa-technique. The results of cytokines are still being analysed and will not be presented. This experimental model will be used for intervention-studies (insulin, hypothermia, steroids etc.), with the aim to minimise inflammation, after brain death, in organs, relevant for transplantation.

P10.05 Vivian BIRTH OUTCOME IN WOMEN WITH BREAST CANCER Langagergaa Vivian Langagergaard, Mette Gislum, Mette V. Skriver, Bente Nørgård, Tim rd L. Lash, Kenneth J. Rothman, Henrik T. Sørensen. Department of Clinical Epidemiology, Aarhus University Hospital, Ole Worms Allé 150, 8000 Aarhus C.

105 Maternal breast cancer may affect birth outcome. We studied the associations between maternal breast cancer and the risk of adverse birth outcomes. Using Danish population registries, we conducted a nationwide cohort study of 695 births from 1973 to 2002 of women diagnosed with breast cancer from 1943 to 2002. We measured the occurrence of preterm birth, low birth weight at term, stillbirth and congenital abnormalities as well as mean birth weight, compared with the outcomes of 33,443 births from unaffected mothers. Adjusted prevalence odds ratios were estimated by logistic regression and differences in mean birth weight by multiple linear regression. There was no excess risk of adverse birth outcome for 216 newborns of women diagnosed with breast cancer before pregnancy. Stratification by child’s gender or mother’s treatment did not change the results. For 37 newborns of women diagnosed during pregnancy, the prevalence ratio (PR) of preterm birth was 8.1 (95 % confidence interval (CI): 3.8-17). However, 10 of the 12 preterm deliveries among these women were elective early deliveries. Among 442 births of women diagnosed from time of delivery until two years later, the PR of preterm birth was 1.4 (95 % CI: 1.0-2.0). In this group only boys had an increased odds of low birth weight at term. (PR= 2.9; 95 % CI: 1.3-6.3). Overall, our results are reassuring regarding the risks of adverse birth outcome for women with breast cancer.

P10.06 Susanne UROGYNECOLOGIC DYSFUNCTION AFTER RADICAL HYSTERECTOMY Maigaard S.M. Axelsen, L.K. Petersen Axelsen Department of Gynecology and Obstetrics, Skejby Hospital, Brendstrupgaardsvej, DK-8200 Aarhus N Objective: To identify urogynecologic symptoms in women treated for cervical cancer by radical hysterectomy. Methods: All patients (n = 396) received a questionnaire. Results: The response rate was 84%. The mean age at follow up was 52.5 (+/- 12.2) years. The mean time after the operation was 9.6 (+/- 7.7) years. Symptoms of urinary incontinence were reported by 37% of the patients, and 37% had symptoms related to urinary retention. Twenty-eight percent reported cystitis at least once. Multiple logistic regression analysis identified BMI, at least one delivery, preoperative urinary incontinence, and pulmonary disease as predictors of significance for development of postoperative urinary incontinence. Significant predictive variables for urinary retention symptoms were age, cystitis and or dysuria, previous rupture of the anal sphincter, fetal weight at delivery > 4000 g, sensation of vaginal dryness, and preoperative urinary retention symptoms. Considering postoperative cystitis and or dysuria, fetal weight > 4000 g, sensation of vaginal dryness, cystitis and or dysuria before the operation, and physical activity were significant predictive variables. Conclusion: Based on the symptoms described by this study, patients can be informed and advised about possible urinary tract symptoms. Moreover, special attention in the pre- and postoperative period can be paid to a subgroup of patients at high risk of later urogynecological problems.

106 P10.07 Karsten Bork GENE EXPRESSION IN THE DEVELOPING PIG BRAIN Nielsen K.B. Nielsen, A.L. Jørgensen and A.L. Nielsen Dept. Of Human Genetics, Aarhus University, Aarhus, Denmark. The aim of my project is to identify and characterize genes that regulate neuron morphology and migration in the developing porcine brain. The porcine brain will be used as a model system, since the availability of human embryonic brains is very limited. The embryonic pig brain represents an attractive non-primate animal model for studies of brain development, since the similarity between the human and the pig embryonic brain is high. The embryogenesis of the porcine brain (end volume 100 cm3) is regarded as a highly relevant recapitulation of neuron migration and plasticity of the human brain as it develops a convoluted surface (gyri) and a similar cyto-architecture, not modelled for example in the small (1 cm3) and smooth (lissencephalic) rodent brain. A better knowledge of the genes that are involved in the development of the brain and how they migrate is very important because it is envisaged that malfunction of these fundamental processes in the embryonic brain is the cause of a wide spectrum of neurodevelopmental and neurological disorders and that stimulation of the processes in the mature brain promotes plasticity by recruitment of the neuronal stem cells from the ventricular regions. The studies of the gene expression during embryogenesis have been performed using the Affymetrix GeneChip Porcine genome array. Total RNA from two different periods in the gestation were purified and were hybridized to the Chip. The two periods of choice are 60 days after conception, where no convoluted surface is present, and 80 days after conception, which represents the first part of the third trimester where the gyri is almost fully convoluted. The genes that show differences in the expression profile between day 60 and day 80 in the gestation are being verified using RT-PCR. The localisation will be determined using RNA in situ hybridization on cryosections from embryogenic tissue from pigs.

P10.08 Hanne Lou LONG-TERM IMPACT OF EXTREMELY PREMATURE CHILDBIRTH. PARENTS´ EXPERIENCES WHEN THE CHILDREN REACH SCHOOL AGE H. Lou Perinatal Epidemiological Research Unit, Aarhus University Hospital, Skejby Sygehus, Denmark. Aim: To elucidate the impact of extremely premature birth on the family and assess its potential need for professional and social support. Methods: The study is explorative and based on qualitative research interviews. Information on the premature birth originates from the Birth Cohort of Aarhus University Hospital. 11 mothers and 9 fathers are interviewed. Nvivo software is used to support systematisation of the data, which are analysed according to the editing strategy. ( Crabtree B F, Miller W L, Doing qualitative Research, 1999). Results: Analyses are ongoing, but preliminary results will be presented at the Ph. D. Day. Of particular interest are the strong contrasts appearing in the data. The parents seem to have many feelings and reactions in common

107 at the birth of the premature child and in parenting during childhood, but disparities are found among both sexes in relation to attachment, parenting competences and coping-strategies. Conclusion: Involving the fathers, targeting the family and having a long- term perspective this investigation fills a gap in a poorly elucidated area thereby supplementing other scientific studies on physical, psychological and social impacts on the children.

P10.09 Thomas EXCESS MORTALITY ASSOCIATED WITH PSYCHIATRIC ADMISSION. Munk T.M. Laursen MSc, T. Munk-Olsen MSc, M. Nordentoft MNPh.D, P.B Laursen Mortensen DrMedSc. National Centre for Register-based Research, University of Aarhus, Denmark Patients suffering from schizophrenia, schizoaffective disorder, unipolar disorder, or bipolar disorder face increased mortality. Our aims were to analyze mortality rate differences between these four illnesses and to analyze mortality impact of family history of psychiatric admission. A population-based cohort established from the CPR register was used. Psychiatric admission was assessed merging the cohort with the Psychiatric Central Register. Mortality rate ratios were estimated by log-linear Poisson regression with person years as offset variable. Persons admitted with a psychiatric disorder had much higher mortality rates than persons never admitted. Age was a strong predictor: young admitted cohortees had higher excess mortality rate than older cohortees. Men had a higher mortality rate ratio of natural death after admission with schizophrenia than men admitted with schizoaffective, unipolar, or bipolar disorder. The opposite applied to unnatural death. The same pattern was seen in women. A family history of psychiatric admission was associated with an excess mortality rate of 1.40 (1.35 - 1.46) for persons never admitted and 1.11 (1.05 - 1.18) for those admitted. To conclude: Unipolar disorder, bipolar disorder, schizoaffective disorder, and schizophrenia were associated with high excess mortality. Schizophrenia was associated with a higher excess mortality from natural causes, but with lower excess mortality from unnatural causes than the 3 other illnesses. Family history of psychiatric admission was associated with an excess mortality rate.

P10.10 Golnosh RISK INDICATORS FOR MARGINAL BONE LOSS IN THE INDIVIDUAL Bahrami Golnosh Bahrami, Ann Wenzel, Lise-Lotte Kirkevang, Flemming Isidor, Michael Væth Department of Oral Radiology, Institute of Odontology, University of Aarhus, 8000 Aarhus C, Denmark Purpose: The aim of this study was to assess risk indicators for marginal bone loss in the individual, with emphasis on apical periodontitis. Materials and methods: 616 randomly selected Danish adults (304 women and 312 men), mean age of 42 years underwent a full-mouth radiographic survey. The marginal bone level was measured from the cemento-enamel junction to the marginal bone. The measurements were performed at the

108 mesial (Am) and distal (Ad) aspect of the tooth. The marginal bone level for each individual was calculated: A(ind) = A(teeth) / N(teeth), and A(ind) > 4 mm was considered as manifest bone loss. The periapical status was assessed by the Periapical Index (PAI), which was dichotomised (healthy = PAI score 1 and 2, and diseased = PAI score 3, 4 and 5). Coronal restorations (crowns, fillings + inlays) and smoking status were also recorded. All variables were analysed in a logistic regression model with manifest bone loss as the outcome. Results: Coronal restorations were not statistically significant (p > 0.05) as risk indicators. The impact of age (OR = 3.3), smoking (OR = 10.5) and apical periodontitis (OR = 4.7) on bone loss was statistically significant (p < 0.01). Conclusions: Not surprisingly, this study showed that smoking and older age, were risk indicators for having marginal bone loss > 4 mm. Even when adjusted for these factors, individuals with > 1 teeth with apical periodontitis were five times more at risk of having a marginal bone loss than those with no periapical infection.

P11.01 Stig PROSTHESES SURFACES GENERATE AN INFLAMMATORY RESPONSE Storgaard S.S. Jakobsen, A. Larsen, M. Stoltenberg, K. Soballe Jakobsen Department of Neurobiology, The Institute of Anatomy, University of Aarhus and Department of Orthopaedic Surgery, Aarhus University Hospital, Aarhus Sygehus, Tage-Hansens Gade 2, 8000 Århus C. Aseptic loosening is a major concern in total hip arthroplasty. Strong evidence link ultra high molecular weight polyethylene (UHMWPE) particulate wear-debris to aseptic loosening. Radiographs of initial well-fixed cement less implants show radiolucent areas close to the distal part of the femur prosthesis, indicating stimuli other than UHMWPE particles play an important role in aseptic loosening. We hypothesize, that the presence of prosthesis surface in the body generates an inflammatory response also capable of producing osteolysis leading to aseptic loosening. A murine macrophage cell line (J774) was incubated with different kinds of prosthesis materials. (Discs of cast high and low carbon CoCr alloy,

Wrought Ti6A14V, and UHMWPE.) The inflammatory cytokine response were determined in the supernatant with ELISA and in the cells with Real Time rt-PCR. The inflammatory response (TNF- , TGF- , IL-6) to Cast high carbon CoCr alloy, Cast low carbon CoCr alloy, and Wrought CoCr alloy was

significantly larger than the response generated by Wrought Ti6A14V, UHMWPE. Bone-regulating cytokines OPG and MCP-1 does not show any significant differences between any of the materials. We cannot measure any differences in the response between the different CoCr alloys. Discs of commonly used prosthesis material generate an inflammatory response. The Inflammatory response from CoCr discs is greater than the response from UHMWPE and Titanium discs. This supports the existing literature.

P11.02 Sophie de IMPORTANCE OF ALDOSTERONE IN SODIUM RETENTION AND

109 Seigneux SODIUM TRANSPORTERS DYSREGULATIONS IN PUROMYCIN INDUCED NEPHROTIC SYNDROME S. de Seigneux, S.W. Kim, S.C. Hemmingsen, J. Frøkiær and S. Nielsen Department of Anatomy, University of Aarhus, 8000 Aarhus C, Denmark. The role of Aldosterone on sodium retention and on the sodium epithelial channel apical targeting in nephrotic syndrome is unclear. We aimed at defining more precisely the impact of this hormone on puromycin (PAN) induced nephrotic syndrome in rats. 15 male whistar rats were adrenalectomized and supplemented with dexamethasone. They were injected with either PAN or vehicle. They were followed in metabolic cages and offered saline to drink and sacrificed five and half days after the injection. Immunoblotting and immunochemistry studies were performed. Sodium retention was apparent as ascites and relative decrease in FeNa in the PAN adrenalectomized rats whereas the control adrenalectomized rats were free of ascites. PAN treated adrenalectomized rats presented decreased sodium excretion at the time of sacrifice. The epithelial sodium channel (ENaC) seemed not more apically targeted in the absence of Aldosterone but the three subunits were increased in abundance The 70 KdA band of the gamma ENaC subunit was absent in both groups. The abundance of the aquaporins 2 channel was maintained whereas its targeting was increased in the PAN treated group. Other sodium transporters were downregulated. In conclusion sodium epithelial channel enhanced apical targeting is due to aldosterone stimulation in the puromycin model of nephrotic syndrome. In absence of aldosterone and enhanced apical targeting of the sodium epithelial channel sodium retention still takes place. Sodium epithelial channel enhanced targeting is therefore compensated by other factors and is not a primary dysregulation of the kidney in the nephrotic condition.

P11.03 Ole FOREARM PLETHYSMOGRAPY IN THE ASSESSMENT OF VASCULAR Mathiassen RESISTANCE: NEW METHODOLOGICAL INSIGHTS. 1 ON Mathiassen, 1,3 NH Buus, 1 MJ Mulvany, 1,2 KL Christensen 1Dept of Pharmacology, University of Aarhus, and 2Dept of Medicine and Cardiology A, 3Dept of Nephrology C, Aarhus University Hospital. High peripheral resistance and structural alteration in resistance arteries are central phenomena in essential hypertension and has been widely examined by venous occlusion plethysmography applied to the human forearm; at rest when concerning vascular tone, and during reactive hyperaemia when concerning vascular structure. We studied influences of intravenous pressure and myogenic tone on hyperaemic vascular resistance, and measured reproducibility of hyperaemic and resting vascular resistance, when based on auscultatory blood pressure measurement. In 4 healthy subjects, intravenous and intraarterial blood pressures were measured along with plethysmographic recordings of hyperaemic and resting forearm blood flow. Reproducibility was examined in 15 young and 14 middle aged healthy subjects, and in 21 untreated hypertensive subjects. During reactive hyperaemia vascular resistance remained low in the first cardiac cycle following venous occlusion, but rose in the second in spite of

110 venous pressure correction. High reproducibility was found, except for a significant reduction between days in the young subjects. A significant gender difference was observed. Forearm resting vascular resistance stabilized from the first to the second measurement performed 30 min later on each day, and in general showed considerable day-to-day variation.. We conclude that during reactive hyperaemia, vascular resistance should be measured in the first cardiac cycle following venous occlusion to minimize influences of venous congestion and an apparently myogenic response. Assessment of resting vascular resistance should await 30 min of rest and a pilot measurement. Sample size may be substantially reduced if measurements are performed on two different days instead of just one.

P11.04 Jesper Noer PSYCHOSOCIAL, FUNCTIONAL AND AESTHETIC PERSPECTIVES IN Petersen ORTHOGNATHIC SURGICAL TREATMENT OF JAWANOMALIES. J.N.Petersen, J.Jensen, A.Elklit, B.Melsen, Department of Oral and Maxillofacial Surgery, Department of Orthodontics & Institute of Psychology, University of Aarhus, 8000 Aarhus, Denmark. Orthognathic surgery is the art and science of maxillofacial correction by combining orthodontic movements of teeth with surgical movements of jaws. This treatment is indicated when a persons jaw deformity is so severe, that orthodontic growth modification or conventional orthodontic camouflage wont do. The aim of the treatment is to (re) establish an overall good oral function (chewing, talking, phonetics, movement of jaw etc) together with a satisfactory psychosocial appearance of the treated person. Orthognatic surgery most often changes the appearance of the patients dramatically. This will demand a lot of the treated patient’s adaptive skills. It is known that even positive changes in appearance can be very stressful to a person. The main objective of this study is to analyse the psychosocial, functional and orthognathic changes that patients undergo in relation to orthognathic surgery. The prospective study comprises 170 consecutive patients that started treatment between January 2001 and December 2002. Psychosocial, functional and aesthetic parameters are assembled before start of treatment, after surgery and a minimum of 2 years after surgery or at removal of braces. The data are obtained through clinical examination and the compilation of specially developed questionnaires. The qualitative and quantitative parameters collected before, during and after treatment will be statistically described and compared. Preliminary results indicate that the motive for treatment change during the course of treatment from being primarily focused on function to placing more on the psychosocial aspect

P11.05 Niels Hjort ARE MRI-BASED PREDICTIVE MODELS COMPARABLE AMONG STROKE CENTERS? Niels Hjort, Ona Wu, Mahmoud Ashkanian, Christine Sølling, Kim Mouridsen, Joachim Röther, Grethe Andersen, and Leif Østergaard Dept. of Neuroradiology, Aarhus University Hospital, Århus, Denmark Previous studies have shown that MRI-based algorithms predicting risk of infarction can assess efficacy of thrombolytic therapy in acute stroke. This study explores the applicability in multi-center studies by comparing predictive models from two centers, University Hospital Hamburg

111 Eppendorf (C1) and Aarhus University Hospital (C2). Two separate models, based on acute perfusion- and diffusion MRI acquired prior to thrombolytic therapy, were formed using generalized linear model (GLM). Voxel-wise risk of infarction was based on T2, ADC, DWI, CBF, CBV, MTT, and delay. Model parameters were estimated by jack-knifing (C1: n=29, median time-to-MRI 3.0 h, follow-up (F/U) 7days; C2: n=9, 2.0 h, 3 mth). Models from C1 and C2 were applied separately on the dataset from C2. Predicted lesion volumes (PLV) were compared with measured (MLV) at F/U. Areas under ROC curves were calculated to assess accuracy of predictions. No significant differences in AUC between models were found. PLV were comparable between models, although both models overestimated final infarct size. This was especially pronounced in reperfusers. GLM parameter coefficients showed similar patterns among models, but differed significantly, except for CBV. MRI-based algorithms trained on data from one institution can potentially be used to predict risk of infarction in patients admitted to other centers - despite differences in MRI protocols, patient characteristics, etc. Reperfusion is presumably the most important determinant of tissue destiny, although unpredictable. Our models were trained on both reperfusers and non-reperfusers; future large scale subgroup analysis may improve predictive power.

P11.06 Joanna OCCUPATIONAL RISK OF DEPRESSION AND STRESS IN THE DANISH Wieclaw WORK FORCE. J Wieclaw1, E Agerbo2, P B Mortensen2, J P Bonde1 1 Aarhus University Hospital Dep. of Occupational Medicine, DK 2 Aarhus University National Centre for Register-based Research, DK Occupation and psychosocial working conditions may be important contributing factors to development of mental health problems, but epidemiological studies based on independent measures are few and inconclusive. The aim of the study was to investigate the risk of affective and stress-related disorders across occupations. A population-based nested case-control prospective study included all hospital in- and outpatients, age 18-65, treated for affective (ICD10, F30-39) or stress-related disorders (ICD10, F40-48) in 1995 -1998 (cases n= 28.971), selected from The Danish Psychiatric Central Research Register, matched for age, date of birth and gender with 5 controls (n=144.855) drawn from Statistics Denmark’s Integrated Database for Labour Market Research. Occupation held 1 year before treatment, according to the Danish version of International Standard Classification of Occupations-88, was the exposure measure. Among 27 occupational groups, 8 occupations among women and 1 among men had significantly elevated risk of depression and stress-related conditions (women, RR range 1.20-1.58) compared to a reference group of clerical staff. On the contrary the risk were reduced in 8 occupations in men (RR range 0.50-0.76) and only in 1 occupation in women. We found highest risk in teaching (RR 1.58) and health professions (RR 1.53). Only professionals caring for mentally and physically disable had elevated risks

112 in both women (RR 1.72 CI 1.38-2.16) and men (RR 2.09 CI 1.38-3.15). The increased risk of depression and stress related disorders related to occupation and gender.

P11.07 Stig Åvall 2,3-DIHYDROXYBENZOIC ACID ATTENUATES KANAMYCIN- Severinsen INDUCED VOLUME REDUCTION IN MOUSE UTRICULAR TYPE I HAIR CELLS Stig Å. Severinsen1*, Mette Kirkegaard2 Jens R. Nyengaard1 1Stereology and Electron Microscopy Research Laboratory and MIND Center, Institute of Clinical Medicine, University of Aarhus, Denmark and 2Center for Hearing and Communication Research, Karolinska University Hospital, Stockholm, Sweden The aminoglycoside kanamycin is a commonly used antibiotic, but unfortunately it is oto- and nephrotoxic in large doses. The negative effects are thought to be due to the formation of free radicals which is why strong antioxidants and iron chelators like 2,3-dihydroxybenzoic acid (DHB) are of great interest. This study estimates cellular quantitative changes in the utricular macula of mice following systemic treatment with kanamycin alone or in combination with DHB. The animals were injected with either saline, kanamycin or kanamycin + DHB for 15 days and perfusion fixed three weeks after last injection. Total volume of the utricle, as well as total number of hair and supporting cells, were estimated on light microscopic sections. Total volume and mean volume of hair cell type I & II and supporting cells were estimated on digital transmission electron micrographs. Total volume of the utricular macula, hair cell type I and supporting cells decreased significantly in animals injected with kanamycin but not in animals co-treated with DHB. Hair and supporting cell numbers remained unchanged in all three groups. In conclusion, the kanamycin-induced volume reduction of type I hair cells was attenuated by DHB. Keywords: Inner ear; mice; stereology; utricular macula; volume; otoprotection.

P11.08 Kirsten INCREASED EXPRESSION OF THE EPIDERMAL GROWTH FACTOR Ejskjær SYSTEM IN ENDOMETRIOID ENDOMETRIAL CANCER COMPARED TO HEALTHY ENDOMETRIUM. Kirsten Ejskjær1, Boe Sandahl Sorensen1, Steen Seier Poulsen2, Ole Mogensen3, Axel Forman4 and Ebba Nexø1 1Dept. of Clinical Biochemistry, NBG, Århus University Hospital; 2Dept. of Medical Anatomy, Panum Institute, University of Copenhagen; 3Dept. of Gynecology and Obstetrics, Odense University Hospital; and 4Dept. of Gynecology and Obstetrics, Århus University Hospital; Denmark. Background: The epidermal growth factor (EGF) system consists of four receptors, and a number EGF-related peptide growth factors or ligands. Besides being ubiquitous in human organs, playing fundamental roles in embryogenesis, development, proliferation and differentiation, the EGF system is involved in malignant transformation. Cyclical variation of the

113 EGF-system in human endometrium suggests a role in control of normal endometrial growth. As cancer represents abnormal growth, we hypothesise differences in the expression of the EGF system in endometrial cancer compared to normal endometrium. Methods: RNA was extracted from fifty-two endometrial cancer samples (patients; age 67.6 (39.6 – 92); FIGO staging: 5 stage IA; 27 IB; 13 IC; 2 II; 4 III and 1 stage IV) and forty-two endometrial samples from 14 healthy women (controls, age 24 - 41 years). The four receptors HER1, HER2, HER3 and HER4 and the 6 ligands: epidermal growth factor (EGF), epiregulin (EPI), amphiregulin (AR), transforming growth factor alpha (TGFα), betacellulin (BCL) and heparinbinding-EGF (HB-EGF) were analysed by real-time PCR. Results: All receptors and ligands except EGF and BCL are detectable in patient and control endometrium. HER3 show significantly lower expression (p < 0.0001) and HER4 higher expression (p < 0.0001) in patient endometrium. AR (p < 0.0001), TGF- (p < 0.0001), and HB-EGF (p = 0.0171) show higher expression in cancer tissue. Conclusions: mRNA of all EGF-receptors and four ligands, AR, TGF , HB- EGF and EPI are present in endometrioid endometrial cancer. HER3 and HER4, and three ligands show significantly altered expression in cancer compared to healthy endometrium.

P11.09 Birgit Drews IMPROVING MOTIVATION AND GOAL SETTING FOR RETURN TO WORK IN A POPULATION ON SICK LEAVE: A CONTROLLED STUDY B.Drews1, C. Vinther Nielsen1, M. Skou Rasmussen2, J.P.Bonde2 1Department of Public Health, Oluf Palmes Allé 17, 8200 Aarhus N 2Department of Occupational Medicine, Aarhus University Hospital, Nørrebrogade 44, 8000 Aarhus C. Limited knowledge precludes evidence-based interventions targeting return to work among sick-listed employees. The objective of this study was to examine the vocational effect of an intervention focused on motivation, goal setting and planning of return to work. 2795 people, across 6 municipalities, sick-listed for at least 21 days received a questionnaire. 1256 with a self-assessed poor prognosis for fast return to work were eligible for the study. An examination by a specialist in social medicine followed by additional counselling by a social worker was offered to 510 residents in two municipalities and accepted by 264 (52%). The goal was to enhance motivation, goal setting and planning of return to work. Residents in the remaining municipalities (n=746) received the standard case management offered by the municipalities (referents). 845 (67%) persons completed a follow-up questionnaire gathering data on general health and employment status. The duration of the sick leave was analysed by Cox regression, and the chance of being gainfully employed was analysed by logistic regression analysis; both adjusted for several covariates. The intervention neither shortened sick leave periods nor increased the likelihood of gainful employment after one year [OR 0.76; 95% CI 0.45-1.28]. A low-cost counselling program addressing motivation, goal setting and planning of return to work did not improve vocational outcomes or reduce the duration of sick leave periods.

114 P11.10 Lasse METFORMIN ACTIVATES AMP-ACTIVATED PROTEIN KINASE Solskov (AMPK) IN THE RAT HEART AND REDUCES MYOCARDIAL INFARCT Jensen SIZE 24 HOURS LATER L. S. Jensen2,3, J. M. Nielsen3, B. Løfgren3, S. B. Kristiansen3, N. Jessen1, T. T. Nielsen3, H. E. Botker3, O. Schmitz1,2, S. Lund1; 1Medical Research Laboratory, Medical Department M, Aarhus University Hospital, Aarhus C, Denmark, 2Department of Clinical Pharmacology, University of Aarhus, Aarhus C, Denmark, 3Department of Cardiology, Aarhus University Hospital, Skejby Sygehus, Aarhus N, Denmark. Cardiovascular disease is the main cause of mortality in patients with diabetes, and risk reduction is an important goal in the treatment of diabetes. AMP-activated protein kinase (AMPK) is an important enzyme concerning glucose and lipid metabolism, which has recently been found to play an important protective role in the ischemic heart. Previous studies have provided evidence that some of the beneficial effects of metformin in liver and skeletal muscle might be through activation of AMPK. The aim of this study was to determine whether a single dose of metformin was capable of protecting the myocardium against experimentally induced ischemia 24 hours after the intervention, and if so to assess whether the AMPK system might be involved. Wistar rats were allocated into two groups: a metformin group given a single oral dose of metformin and a control group given a single oral dose of vehicle. After 24 hours the hearts were perfused in a Langendorff model and subjected to 45 minutes left main coronary artery occlusion followed by 120 minutes reperfusion. Infarct size was determined by tetrazolium staining and expressed as a percentage of the risk zone (I/R%). Isoform specific AMPK-alpha2 activity was measured 2 hours after administration of metformin or vehicle. Infarct size was significantly reduced in the metformin treated (I/R: 20±4% vs. 38±4%, p < 0.01, n=8) compared to the control group. A single oral dose of metformin resulted in an approximately 2-fold increase in AMPK-alpha2 activity (p<0.01, n=4-8). A single dose of metformin significantly increases AMPK-activity 2 hours after administration and reduces the infarct size seen after a coronary artery occlusion 24 hours after administration.

P12.01 Ditte M. S. P25α - A NOVEL MOLECULAR LINK TO DEMYELINATING DISORDERS Lundvig D. Lundvig, P.H. Jensen Institute of Medical Biochemistry, University of Aarhus, DK-8000 Aarhus, Denmark The axons of neurons in the central nervous system (CNS) are wrapped with myelin sheaths that facilitate rapid transmission of nerve impulses. Demyelinating diseases are characterised by degradation of the myelin sheath and compromised neuronal transmission. Myelin basic protein (MBP) accounts for ~30% of the total protein content of the myelin sheath in the CNS and it is involved in myelination of the CNS neurons. During our investigations on functional characterization of brain-specific protein p25α, we identified brain-specific protein p25α as a binding partner of MBP by affinity chromatography and demonstrate the existence of a

115 high-affinity binding by BiaCore investigations. The existence of a MBP- p25α complex in vivo has further been supported by sucrose density gradient analysis, demonstrating an overlapping density distribution of MBP and p25α. When affinity-purifying MBP from porcine brain preparations an unknown protease co-elutes with the MBP-p25α complex that digests MBP rapidly. However, the presence of p25α increases MBP’s protease resistance markedly, implying a protective role of p25α through shielding of amino acids from the protease or by inducing conformational changes of both proteins, thereby hindering protease access. We demonstrate that p25α interacts with MBP and thereby increases MBP’s protease resistance. This suggests that p25α is important for the stabilization of the myelin sheath and that dysregulation or mislocation of p25α contributes to MBP degradation. In vivo, MBP degradation would result in destabilization of the myelin sheet. p25α might thus be considered a novel molecular link to the pathogenesis of demyelinating disorders.

P12.02 Bettina S. QUANTITATIVE STUDIES OF THE CELLULAR IMMUNE RESPONSE IN Nedergaard CANCER. B.S. Nedergaard Department of Oncology, Aalborg Hospital, Aarhus University Hospital, Hobrovej 18-22, 9100 Aalborg, Denmark. Background: “Tumor-Infiltrating Lymphocytes” (TIL) may accumulate in malignant tumors, a part of the lymphocytes being specific tumor-antigen- reactive T cells. The density and composition of TIL may be correlated to prognosis, tumor characteristics and effect of immunotherapy. It is, however, poorly known which tumors of different subtypes are immunogenic and may raise a cellular immune response at an early stage. This knowledge is important for the feasibility assessment of immunotherapy for early cancers, including adjuvant immunotherapy. Materials and Methods: Initially, to develop quantitative methods for assessment of TIL, paraffin-embedded cone-biopsies from 25 consecutive, stage 1, cervical squamous cell carcinomas have been collected. 4 m thick sections were cut and immunostained for CD1a, CD3, CD4, CD8, CD20, CD45RA, CD45RO, CD57, CD68 and GrB. Estimates of stereologic reference volume and of densities, total numbers and distribution of lymphocyte subtypes are obtained. Using these methods, I will furthermore quantitatively describe TIL in archival material from patients with several types of cancer. I will focus on “early” cancers, obtaining basic data regarding the intensity, nature, and localization of TIL and its clinical- biological-pathological correlation, the study hopefully resulting in an “immunogenicity grading scheme” for various common cancer types.

P12.03 Hanne BREASTFEEDING AND EARLY BONDING: A RANDOMISED Kronborg COMMUNITY BASED TRIAL H. Kronborg, M. Væth, L. Iversen, J. Olsen, I. Harder Department of Nursing Science, University of Aarhus, 8000 Aarhus C. e-mail: [email protected]

116 Evidence is needed on how to support the breastfeeding mother in the postnatal period in the most effective way. The effect of a breastfeeding intervention within the first five weeks was compared to usual practice. The intervention accounted for the role of the psychosocial factors and consisted of 1-3 homevisits. Women were enrolled in a cluster randomised trial. The 52 health visitors assigned to the intervention group were trained in an 18 hour course. The primary outcome was duration of exclusive breastfeeding within six months of follow up. Comparison was accoring to the intention to treat principle. The study included 781 mothers in the intervention- and 816 mothers in the comparison group. Mothers in the intervention group had a breastfeeding cessation rate 14% lower than the comparison group (HR=0.86 CI: 0.75-0.99). Similar results were seen among primiparous (HR=0.87 CI:0.75- 1.2), and multiparous with previously short breastfeeding experience (HR=0.74 CI: 0.56-0.99). Mothers in the intervention group reported that they had received: first home visit earlier after delivery (p<0.001), more visits within the first five weeks after delivery (p<0.001), more practical breastfeeding training (p<0.001). Babies in the intervention group received more frequently breastfeeding (p<0.001), they used less pacifier (p=0.01), and mothers reported more confidence in not knowing the exact amount of milk their baby had had (p<0.001). Postnatal breastfeeding by homevisits in the first five weeks following birth may raise the rate of exclusive breastfeeding. Primiparous and multiparous with previously short breastfeeding experience need special attention with focus on improving self-efficacy and practical skills.

P12.04 Morten Krag GROWTH HORMONE TENDED TO INCREASE INTRAMYOCELLULAR TRIGLYCERIDE IRRESPECTIVE OF AMBIENT FREE FATTY ACID LEVELS Morten Krag1, Lars Gormsen1, Zengkui Guo2, Jens S. Christiansen1, Michael Jensen2, Søren Nielsen1, Jens O.L. Jørgensen1. 1. Medical Department M, Aarhus University Hospital, Denmark, 2. Mayo Foundation, Endocrine Research Unit, Rochester, United States Mobilisation of free fatty acids (FFA) from adipose tissue is a pivotal metabolic effect of GH (growth hormone) in human subjects. Mobilisation of FFA requires activation of the hormone sensitive lipase (HSL). Previous experimental data from our group, however, indicate that GH may stimulate lipid oxidation independently of ambient FFA levels. The aim of this study was to assess the impact of growth hormone on intramyocellular triglyceride (IMTG) content, lipid oxidation, and insulin sensitivity in healthy subjects during concomitant pharmacological inhibition of the HSL with acipimox. Nine male subjects underwent three 8-days treatment arms in a randomised, double-blind, crossover design: A) Placebo, B) GH (2 mg/day), C) GH + Acipimox (250 mg x 3/day). At the end of each period fat and muscle biopsies were obtained followed by a hyperinsulinemic euglycemic clamp. Acipimox abrogated the GH-induced increase in basal serum FFA levels (P<0.0001, ANOVA), mirrored by a similar reduction of basal lipid oxidation. GH treatment tended to increase IMTG irrespective of

117 concomitant Acipimox: A: 4.16±0.57; B: 6.03±0.61 C: 5.39±0.61 mol/gram wet weight muscle tissue (P=0.09, ANOVA). Insulin sensitivity estimated by glucose infusion rate during clamp was significantly suppressed during GH and GH+Acipimox compared to placebo [4.29±0.59 and 3.80±0.81 vs 6.29±0.68 mg/kg/min, P<0.001, ANOVA]. Conclusion: GH tended to increase intramyocellular triglyceride irrespective of ambient FFA levels. GH induced insulin resistance also during conditions of low basal FFA levels. We speculate that IMTG could be a determinant of GH-induced insulin resistance

P12.05 Lars DOSE-RESPONSE EFFECTS OF FREE FATTY ACIDS ON INSULIN Gormsen SENSITIVITY IN HUMANS L.C.Gormse1, J. Gjedsted1, N. Jessen1, J.S. Christiansen1, S. Nielsen1 and N. Møller1. 1Department M, Aarhus University Hospital, Denmark. Increased plasma free fatty acids (FFAs) is common in insulin resistant states (e.g. type 2 diabetes, visceral obesity). Experimental elevation of plasma FFAs produces many of the metabolic complications of insulin resistance, however, the mechanism is not known in detail. This study was designed to gain further insight into the relationship between FFA and glucose metabolism by studying the dose-response relationship between plasma FFA and insulin mediated glucose metabolism. Eight lean, healthy men were examined on 4 occasions using variable infusion of intralipid/Heparin and saline to create different plasma FFA concentrations: 1) without intralipid infusion (LOW FFA), 2) 0.003 ml/kg/min intralipid (NORMAL FFA), 3) 0.006 ml/kg/min intralipid (HIGH FFA), and 4) 0.012 ml/kg/min intralipid (SUPRA FFA). A hyperinsulinaemic-euglycaemic clamp (0.6 mU/kg/min) in combination with somatostatin suppression and hormone replacement (GH, glucagon, and insulin) and acipimox to suppress endogenous lipolysis was performed to assess insulin resistance/sensitivity. FFA levels (endclamp) were significantly different on the four study days (LOW 0.02 0.01, NORMAL 0.34 0.03, HIGH 0.68 0.09, SUPRA 1.78 0.39 mmol/liter, ANOVA p<0.00001). Insulin sensitivity, assessed by the glucose infusion rate, (GIR (mg/kg/min)) exhibited clear dose dependency with plasma FFA (ANOVA p<0.005): GIR was significantly reduced at high FFA levels (SUPRA 4.6 0.9 vs NORMAL 9.4 1.0, p = 0.008), whereas the initial slope of the curve (i.e. FFA concentrations between 0.02 and 0.68 mM) was close to zero.We conclude that there is a clear inverse dose-response relationship between FFA levels and insulin sensitivity in the range between 0.68 and 1.8 mM. Below 0.68 mM no such relationship could be detected.

P12.06 Mandana IMPACT OF ENVIRONMENTAL CHEMICALS ON THE THYROID Ghisari HORMONE FUNCTION IN PITUITARY RAT GH3 CELLS M. Ghisari and E.C. Bonefeld-Jørgensen Unit of Environmental Biotechnology, Department of Environmental and Occupational Medicine, University of Aarhus, Vennelyst Boulevard 6, DK- 8000 Aarhus, Denmark

118 Endocrine disrupting chemicals (EDCs) are widespread in the environment and suspected to interfere with the function of thyroid hormones (THs). Thyroid hormones regulate a number of biological events and are essential for proper neuronal proliferation, cell migration, and differentiation in the developing mammalian brain. Furthermore, estrogen and THs play critical roles in reproduction and growth in mammals. We did investigate the potential TH disrupting activity of different classes of EDCs including plasticizers, alkylphenols, pesticides, hydroxylated metabolites of Poly Chlorinated Biphenyls and brominated flame retardants by analyzing the effect on cell proliferation of the TH dependent rat pituitary cell line GH3. All chemicals significantly interfered with the cell proliferation alone or upon co-treatment with the natural ligand T3. The growth of GH3 cells was stimulated by most chemicals, but 4-n-nonylphenol, 4-octylphenol, prochloraz and iprodion elicited an inhibitory effect on cell growth. Exposure of GH3 cells to estrogen showed a weak stimulation of GH3 proliferation, which could be blocked by ICI that is a strong antiestrogen. Our results indicate that the estrogen receptor is involved in basal and T3- induced growth of GH3 cells. In conclusion, these EDCs have the potential to exert TH disruption increasing the risk for e.g. a negative impact on the fetus brain development resulting in cognitive dysfunctions.

P12.07 Jeanne COGNITIVE FUNCTION AMONG WOMEN WITH BREAST CANCER IN Elisabeth RELATION TO ADJUVANT THERAPY Debess J.E. Debess, M. Ewertz Department of Oncology, Aalborg Hospital, Hobrovej 18-22, DK-9000 Aalborg, Denmark. The aim of the study is to examine cognitive function in women who receive adjuvant therapy for early breast cancer. Background: Today around eighty percent of women with early breast cancer (BC) receive adjuvant treatment such as chemotherapy, radiotherapy and anti-hormonal therapy. Recently, some studies have shown that chemotherapy and / or Tamoxifen can affect cognitive functions especially verbal learning, concentration, and memory function. Design: The study is designed as a longitudinal cohort study. The study population will include approximately 150 women under the age of sixty years who had surgery for primary BC in North Jutland county during the period 1st May 2004 to 30th June 2006 In addition, a reference group of 200 healthy age matched women will be included in the study. Data on cognitive function are collected by questionnaires including socioeconomic data, side effects to chemotherapy, Quality of Life (EORTC QLQ C30), Self- efficacy (GPS-E), Stress, Anxiety, and Depression (POMS), Coping with Cancer (MAC). In addition, neuropsychological tests (Danish Adult Reading Test, Visual Verbal Learning Test, Concept Shifting Test, Letter Digit Coding Test and Stroop Colour Word Test) are performed at baseline, and after six and twelve months. By October 2005, 80 patients and 175 healthy controls have been included into the study. The data collection will continue until June 2007. Results of the baseline tests are expected to be

119 available late in 2006.

P12.08 Josefine KNEMOMETRIC ASSESSMENT OF SHORT TERM GROWTH IN Gradman CHILDREN WITH ECZEMA TREATED WITH TOPICAL MOMETASONE FUROATE AND TACROLIMUS J.Gradman, O.D.Wolthers Children´sClinicRanders, Dytmærsken 9, 8900 Randers, Denmark Anti-inflammatory treatment with topical glucocorticoids is widely used for management of eczema in children. To some extent, however, topical glucocorticoids may be absorbed and become systemically active causing adverse effects, of which growth suppression may be a concern in children. By measuring the growth of the lower leg short term knemometry has been developed for sensitive assessment of systemic activity of exogenous glucocorticoids in children. The objective of the present study was to assess whether the topical glucocorticoid mometasone furoate or the new non- glucocorticoid anti-inflammatory topical drug tacrolimus affects knemometric growth rate. 17 prepubertal children ( / : 10/7) aged 5-12 years with eczema were studied in a single blind, randomised 5-period cross over study with two treatments, a run in, a wash out and a run out of 2 weeks duration. Active treatments were mometasone furoate ointment 0.1% (Elocon®) once daily and tacrolimus ointment 0.1% (Protopic®) twice daily. Lower leg length was measured by knemometry. As compared to run in (0.40 mm/week) lower leg growth rates were not statistically significantly affected during treatment with mometasone furoate (0.36 mm/week (p=0.61)) or wash out (0.49 mm/week (p=0.40)); or during treatment with tacrolimus (0.33 mm/week (p=0.49)) or wash out (0.52 mm/week (p=0.22)). Treatment with topical mometasone furoate or tacrolimus does not affect short term growth in children with eczema. Sponsor and investigator: O.D. Wolthers. The study was supported by a grant from Astellas Pharma.

P12.09 Morten Sig MODERATE AGREEMENT BETWEEN CLINICAL ECG Ager Jensen INTERPRETATION AND MINNESOTA CODING M.S.A. Jensen1, J.L. Thomsen1, S.E. Jensen2, T. Lauritzen1, M. Engberg1 1 Institute of Public Health, Department of General Practice, University of Aarhus, Vennelyst Boulevard 6, 8000 Århus C, Denmark. 2 Department of Cardiology, Ribe County Hospital, Finsensgade 35, 6700 Esbjerg, Denmark. The Minnesota Code (MC) of electrocardiographic findings is the standard for electrocardiogram interpretation in epidemiologic research. Little is, however, known about the value of clinical ECG diagnostics in population based research. We aimed to examine the correspondence between the clinical diagnoses made by a cardiologist and the MC by applying them to the same sample of ECGs. A random sample of 380 ECGs obtained from the Copenhagen Male Study was interpreted blindly by a cardiologist. The diagnoses made by the cardiologist were then compared to the Minnesota Codes originally

120 assigned to the ECGs. The two classification systems agreed on 75.53% ECGs. Sensitivities of clinical ECG diagnoses made by the cardiologist with the MC as the reference standard ranged from 0.21 (95% CI: 0.07-0.42) to 1.00 (95% CI: 0.48-1.00). The specificities ranged from 0.93 (95% CI: 0.89-0.96) to 1.00 (95% CI: 0.99-1.00). Predictive value of a positive test for the cardiologists diagnoses ranged from 0.53 (95% CI: 0.28-0.77) to 1.00 (95% CI: 0.48-1.00) and predictive value of a negative test ranged from 0.80 (95% CI: 0.75-0.85) to 1.00 (95% CI: 0.99-1.00). The kappa coefficient estimate was 0.50 (95% CI: 0.42-0.58) indicating a moderate agreement between the two classification systems. There was only a moderate concordance between the MC and clinical diagnoses made by a cardiologist. Good agreement was observed for right bundle branch blocks and atrial fibrillation, whereas poor agreement was observed for ischemic ECG findings.

P12.10 Anne MOLECULAR PROGNOSTIC MARKERS FOR SURVIVAL AFTER Birgitte Als CHEMOTHERAPY IN ANDVANCED BLADDER CANCER. Als AB, Koed K, Jensen JL, Dyrskjot L, Orntoft TF, von der MaaseH Department of Oncology, Aarhus University Hospital, 8000 Aarhus C In patients with advanced bladder cancer, cisplatin-containing chemotherapy yields response rates around 50%, with a median survival around 12 months. Poor performance status (PS≥2) and presence of visceral metastases are identified as independent poor prognostic factors for survival in several studies. The Aim of this study is to identify differentially expressed genes with a prognostic impact on survival after the cisplatin- containing regimens MVAC or GC. We identified 30 tumors sampled less than four months prior to chemotherapy. Patients had a follow-up time of more than 15 months. Gene expression data were generated using Affymetrix GeneChip® HU133A. Genes that correlated significant with survival were identified using SAM (Significance Analysis of Microarrays; Stanford University Labs) Fifty-one genes correlated highly significantly with survival. We selected five genes well annotated and with biological relevance. The genes encode proteins involved in apoptosis regulation, DNA-damage-repair and extracellular matrix modulation. Expression values were dichotomized and analyzed in combination with clinical prognostic factors. Patients with (n=9) or without (n=22) visceral metastases had a median survival of 8 months vs. 12.5 months, respectively (p=0.014). This group could be further subdivided by adding the gene expression values. For gene “39” patients with low expression values had a median survival time of 30.5 months vs. 10 months for patients with high expression values (p=0.0001). Addition of further gene expression profiles resulted in further separation of the survival curves. The conclusion is that we have identified five genes with a stronger prognostic impact than the known clinical prognostic factors. Confirmation of results is ongoing.

P13.01 Karsten CHARACTERISING GENOMIC CHANGES IN SUPERFICIAL BLADDER Zieger CANCER

121 K. Zieger, L.Dyrskjøt, K. Møller, T.F. Ørntoft Departments of Urology and Clinical Biochemistry, Aarhus University Hospital in Skejby, DK 8200 Århus N, Denmark Objective: The development of bladder cancer follows different molecular pathways. The individual course of superficial bladder cancer is difficult to predict. The objective of this study is to characterise different forms of superficial bladder cancer with respect to the clinical courses, including recurrence and progression to muscle-invasive, life-threatening stages. Methods: The study is based on a tissue bank with clinical follow-up data of 2,000 patients, prospectively collected since 1994. The study focuses on superficial invasive bladder cancer (stage T1); the material includes 50 patients with progressing disease and 50 patients with at least five years progression free survival and no radical treatment. The examined genomic changes include mutational analysis of cancer relevant genes (TP53, RAS, FGFR3) by (re-)sequencing, and genome-wide analysis of loss-of heterozygosity and DNA copy number changes using an SNP microarray. Results: Preliminary results indicate that at least two different forms of bladder cancer can be distinguished, with good correlation to the clinical phenotypes (papillary – CIS/invasive). Molecular differences between non- progressing and progressing cases in both forms include chromosomal instability and TP53 mutations. Further analyses are currently performed and will be presented. Conclusions: The characterisation of different forms of bladder cancer development opens up for improved individualised risk assessment and prediction of clinical course. Further analyses will guide our way towards a tailor-suited treatment approach.

P13.02 Hanne NURSING AND CARING OF PREMATURE INFANTS. Aagaard Aagaard, H. Jørgensen, Department of Nursing Science, Institute of Public Health, Faculty of Health Sciences, University of Aarhus, 8000 Aarhus C, Denmark The study is a longitudinal case-controlled study designed as aquasi- experimental multi-centre study involving two neonatal units at university hospitals. The aim is to investigate the effect of neonatal developmental care according to NIDCAP® in the infant and the mother. Moreover, to test the hypothesis that there is no difference in NIDCAP nursing and ordinary developmental nursing care. The main variables in the infant group: The infant’s self-control and self regulation growth, medical disease and complications; respiratory dysfunction, use of oxygen and time for admission. Current the group of the mothers the variables is: Maternal self- esteem; staff's support of parents; assessment of being a new parent; parent's support from different networks and demographic data. Participants will be 60 infants in the intervention and 60 in the control group and their mothers. The intervention consists of educ ation sessions of the nursing staff about the principle of NIDCAP® and repeated supervision of the nurses when caring for mother and infant. Data collection takes place during one year from October 2005 through repeated structured observations of the infants´ behaviour and repeated structured Likert-type

122 questionnaires concerning maternal capabilities. The PhD-student and a research assistant (EJ) will collect the data and regularly test the interrater reliability of the infant observations. Data analysis is quantitative. The expectations of the results are to show a significant advantage in the intervention group. Infants in the intervention group will be more mature; more stable in their self-control; earlier admission and the mothers will be more competent.

P13.03 Marianne PREDICTIVE MARKERS OF RESPONSE TO ADJUVANT Kyndi RADIOTHERAPY IN HIGH-RISK BREAST CANCER Kyndi M¹ ², Sørensen FB², Alsner J¹, Overgaard J¹ ¹Department of Exp.Clinical Oncology, and 2Department of Pathology, Aarhus University Hospital, Nørrebrogade 44, 8000 Århus C, Denmark The DBCG82 b and c protocols examined the effect of adding adjuvant radiotherapy to 3,083 Danish high-risk breast cancer patients who had a mastectomy. Patients were defined as high risk if they had tumour size larger than 50 mm, metastases to lymph nodes, or tumour invasion in the surrounding tissue. After mastectomy, the pre-menopausal women (DBCG82b) were randomized to receive CMF-chemotherapy plus radiotherapy or CMF only. The postmenopausal women (DBCG82c) were randomized to receive Tamoxifen plus radiotherapy or Tamoxifen only. Overall, the addition of adjuvant radiotherapy improved the overall survival by approximately 10%, and resulted in an 80% reduction of loco- regional recurrences. The two protocols have provided a major part of the information on indications for radiotherapy in high-risk patients. The aim of this PhD study is to confine the indication area for post-mastectomy radiotherapy by finding new molecular markers predictive of the group of patients responding to the treatment. Approx. 1,250 patients who had more than 7 axillary lymph nodes surgically removed were included in this study. So far, paraffin embedded tumour samples from approximately 1,100 patients have been collected and invasive tumour cell have been verified for 1,000 patients by histology, grade of malignancy has been updated and TMA's (tissue microarrays) have been constructed. Currently immunohistochemical staining for oestrogen receptor, progesterone receptor and HER2 is performed to up-date this old study to present standard. Future perspectives are to examine cell proliferation, apoptosis, metastasis, angiogenesis and microenvironment including MIB-1, cyclin D1, isoforms of cyclin E1, Survivin, VEGF, HIF-1 , osteopontin, CaIX, and S100-A4.

P13.04 Lene FETAL CARDIAC EJECTION FRACTION ASSESSED FROM 4D Unmack ULTRASOUND: SPATIO TEMPORAL IMGAE CORRELATION AND Larsen VOLUME CALCULATION L.U. Larsen, O.B. Petersen, K. Sorensen, E. Sloth and N. Uldbjerg Dept. Of Obstetrics and Gynecology, Aarhus University Hospital, Skejby Hospital, Brendstrupgaardsvej, 8200 Aarhus N High frame rates are crucial when evaluating the diastolic and systolic events of the fetal heart. The introduction of spatio-temporal image correlation (STIC) in fetal 4D echocardiography has solved the problem of low frame rates in realtime 3D ultrasound. The aim of this study was to

123 assess the feasibility of STIC and volume calculation software (VOCAL II) in estimating fetal ejection fraction (EF) based on systolic and diastolic volume of the left ventricle. 39 STIC recordings from a total of 21 normal fetuses with the gestational ages 19+0 to 39+1 were included in the study. The end-diastolic and end- systolic volumes of the left ventricle were calculated on an external work station using dedicated software. Two techniques for volume calculation were used: Manual outlining of the endocardial border and volume based on greyscale threshold values. Our conclusion is that asessment of EF based on STIC and VOCAL II is feasible in the fetus. Mean EF was 60.6 % (SD 10.8) in the manual outlined group and 61.5 % (SD 8.3) in the threshold group. Values did not change significantly with gestational age (Lines of regression: y=-0.007x+61 and y=- 0,12x+65) With these new techniques it is possible to assess the ejection fraction of the fetal heart. This may be valuable in the evaluation and monitoring of fetuses at risk and fetuses with congenital heart defects.

P13.05 Birgitte IS PRETERM DELIVERY ASSOCIATED WITH A CONSTITUTIONAL Oxlund- DECREASE IN THE MECHANICAL COMPETENCE AND COLLAGEN Mariegaard CONCENTRATION OF THE CERVICAL CONNECTIVE TISSUE? B. S. Oxlund-Mariegaard, G. Ørtoft, H. Oxlund, N. Uldbjerg. Department of Gynaecology and Obstetrics, Aarhus University Hospital and Department of Connective Tissue Biology, University of Aarhus, Denmark. The aim of the present study is to investigate the collagen concentration, collagen cross-linking pattern and biomechanical strength of the cervical connective tissue in non-pregnant women with a history of cervical incompetence. Materials. Pilot-study: 10 women with no prior history of preterm delivery. Project 1: 70 normal non-pregnant women. Project 2: 60 non-pregnant women with previous cervical incompetence. Methods. Three cervical biopsies will be taken from each cervix. Two biopsies will be used for hydroxyproline and cross-link analyses and for mechanical testing. The third biopsy will be used for histological examination and determination of collagen fibre density and orientation. Our hypothesis is that women with previous cervical incompetence have less hydroxyproline and low biomechanical strength compared with normal women. Keywords: Cervix, Collagen, Hydroxyproline, Biomechanical strength, Cervical incompetence, preterm delivery.

P13.06 Henriette PREDICTORS OF THE COURSE OF FUNCTIONAL DIASESE IN Schou GENERAL PRACTICE – PREVENTION OF CHRONICITY Hansen H.S. Hansen Research Clinic for Functional Disorders, Århus University Hospital, Barthsgade 5,1. 8200 Århus N Patients with medically unexplained symptoms or functional disorders account for a large part of contacts in general practice, with an incidence of 25-30%, here of 30-50% will become chronically ill. The treatment process

124 will often be prolonged and futile. Functional disorders can be seen as an interaction between the doctor and the patient and/or the patient’s family. Several persons and factors have an influence on how the course of the disease will develop, and whether it will become chronic. The aim of this project is to investigate, what circumstances can predict the course of the disease for patients with functional disorders. The issue will be examined with a quantitative and a qualitative approach. The quantitative part takes its starting point in register data and questionnaires from patients and their GPs (collected in an earlier project about medically unexplained symptoms in general practice), and will examine if any conditions with the patient and/or the doctor can predict the course of the functional disorder, measured on self rated health, health care utilisation and at sick leave. The qualitative part, will consist of focus groups with GPs, and will analyse interaction between the doctor and the patient and examine how the interaction affects the course of the disease. At the end there will be a interdisciplinary analysis, where results from the quantitative and qualitative studies are analysed together. The perspective is to give the GPs better criteria for diagnostics and better opportunity to estimate the prognosis for the patients. A greater knowledge about predictors could also help in further development of intervention with patients with functional disorders.

P13.07 Tanja Krüger XENOANDROGENIC ACTIVITIES IN SERUM ACROSS EUROPEAN AND INUIT POPULATIONS T Krüger1, PS Hjelmborg1, BAG Jönsson, L Hagmar, JP Bonde, EC Bonefeld- Jorgensen1 and the INUENDO group* 1Department of Environmental and Occupational Medicine, Institute of Public Health, University of Aarhus, Denmark; * www.inuendo.dk Epidemiological studies have indicated that human male reproductive disorders are increasing while sperm counts appear to be declining. There are evidences that these disorders can arise as a result of environmental chemicals, such as polychlorinated biphenyls (PCBs), dioxins and 1,1- dichloro-2,2-bis (p-chlorophenyl)-ethylene (p, p’-DDE), disrupting normal androgen receptor (AR) signalling. The aim was to compare total integrated xeno-androgenic activity in the hormone free, lipophilic POP fraction of human serum among European and Inuit groups and to evaluate whether the activity is correlated to the level of the POP markers PCB-153 and p,p’-DDE. Serum samples were collected from 262 adult males (35 Inuits from Greenland (GRL), 58 from Sweden (SE), 83 from Warsaw (PL) and 76 from Kharkiv (UA)). The xeno-androgenic activity was determined as the effect of serum extract alone (XAR) and in the presence of the AR agonist R1881 (XARcomp) using the AR transactivated luciferase reporter gene assay in the CHO-K1 cells. Positive correlations between XARcomp and p, p’-DDE were found in the GRL and PL groups, having similar median p, p’-DDE levels. However, GRL XARcomp activity was significantly higher than the European groups. Highest antagonistic XARcomp activity was found in UA, having the

125 highest median p, p’-DDE level. For the combined data no interaction between AR-activity and the POP markers was observed across the study groups suggesting that the selected POP markers alone can not predict the integrated xeno-AR serum activity.

P13.08 Søren Rytter KNEE DISORDERS AMONG A DANISH COHORT OF FLOOR LAYERS. S. Rytter, L. Kirkeskov Jensen, N. Egund, J.P. Bonde Department of Occupational Medicine Viborg Hospital, Resenvej 25, DK 7800 Skive, Denmark Objective: Floor layers have a high frequency of knee complaints mainly caused by spending more than half of the working time in kneeling work positions. The present study is a ten years follow-up study among a cohort of floor layers and graphic designers (controls). The purpose of the study is to investigate the dose-response relationship between knee straining work positions and the development of knee osteoarthrosis and anterior knee disorders. Materials: Floor layers (N=169) and graphic designers (N=214) between ages 40-70 years, employed as well as unemployed and retired. Methods: 1. Questionnaire. Registration of self-reported musculoskeletal complaints, present and previous employment, medical disorders, knee accidents and operations, participation in sports plus height and weight. 2. Clinical knee and ultrasound examination and X-rays of the hip and knees estimating and graduating signs of osteoarthrosis and changes in the periarticular soft tissue. 3. Knee MRI among a random sample of 50 floor layers to estimate the prevalence of meniscus and lig. cruciatae lesions and furthermore to evaluate the locations of cartilage lesions. 4. Exposure study. The temporal amount of knee straining work positions will be measured with pressure sensitive contacts in the knee pads coupled with a data logger. Perspectives: Knee osteoarthrosis is a potential disabling disease with wide personal and social consequences. It is important to clear the connection between the amount of knee stressing work and the development of both acute and chronic knee disorders. The perspective will be to arrange appropriate preventive actions and thereby prevent wearing- down and exclusion from the trade but also to transfer new knowledge to other trades in the construction industry with knee straining work positions.

P13.09 Donata FUNCTIONAL AND STRUCTURAL RENAL EFFECTS Cibulskyte OF CICLOSPORIN A IN A PIG MODEL Donata Cibulskyte1, Daniel Hanefelt Kristensen2, Michael Pedersen3, Arne Hørlyck4, Niels Marcussen5, Hans Erik Hansen1, Melvin Madsen1, Jens Mortensen2 1Department of Renal Medicine, 2Clinical Institut, 3MR Research Centre, 4Department of Radiology, 5Department of Pathology, Aarhus University Hospital, Aarhus, Denmark Background. Ciclosporin A (CsA) is a keystone in the management of organ transplantation and some immunomediated diseases. The use of CsA is limited by side effects, especially chronic nephrotoxicity. Most studies on

126 this issue have been done in rodents, but the pig possesses several advantages due to similarities in anatomy and physiology to the human. The aim of first 2 studies was to evaluate renal effects of CsA in a pig model. Methods. 1) six Gøttingen minipigs were given 10 mg/kg/d CsA for 6 months and 5 untreated pigs served as controls. Body weight, blood pressure, serum creatinine, glomerular filtration rate (GFR), renal blood flow (RBF), renal vascular resistance (RVR), kidney dimensions and renal histological changes were estimated at baseline and then with 5 weeks intervals; 2) six pigs received 20 mg/kg/d CsA for 6 months and 4 untreated pigs were control animals; Results. 1) Whole blood trough CsA levels were lower in pigs than in humans. The study demonstrated no renal histological changes or impairment in kidney function during the treatment with CsA 10 mg/kg/d. Surprisingly, there was a significant increase in GFR and kidney volume. 2) Administration of CsA 20 mg/kg/d caused an increase in serum creatinine, blood pressure, RVR and a decrease in RBF. Structurally, we found kidney enlargement and no histological changes. Conclusions. CsA causes deterioration of kidney function in a pig model. Higher CsA doses are necessary in pigs than in humans. The hyperfiltration and renal enlargement warrants further investigation.

P13.10 Naja Becher MMP-9 AND MMP-8 ACTIVITY IN THE CERVICAL MUCUS PLUG AT TERM OF PREGNANCY. Becher N1, Hein M1, Danielsen CC2, Uldbjerg N1. Department of Obstetrics and Gynecology, Skejby University Hospital1, 8200 Aarhus N and Department of Connective Tissue Biology, University of Aarhus2, 8000 Aarhus, Denmark. Background: The cervical mucus plug (CMP) is a semi-solid structure (mean weight 6 g) which fills the cervical canal during pregnancy. It is bactericidal towards a broad spectrum of bacteria and contains several antimicrobial peptides including secretory leukoprotease ihibitor (SLPI), defensins, and lysosyme. Forming a physical and immunological barrier to microbial entry into the sterile uterine cavity, it protects the fetus from ascending infection. It contains large amounts of matrix metalloproteinase 9 (MMP-9), matrix metalloproteinase 8 (MMP-8), and tissue inhibitor of metalloproteinase 1 (TIMP-1) indicating a potential to degrade extracellular matrix components. Method: Cervical mucus plugs from 20 healthy women in normal active labor were homogenized, extracted, and analyzed by MMP-9 and MMP-8 activity assay (GE healthcare). Results: High concentrations of MMP-9 and MMP-8 were detected in all samples. The MMP-9 activity assay demonstrated that all 20 samples contained its active form. The concentration of active MMP-9 was 0.287 ng/mg (0.241-0.342), equivalent to 10.5% (6.5-17.0) of the total endogenous MMP-9 (2.73 ng/mg (1.88-4.01)). In 18 of the 20 samples, we detected no active MMP-8. In the remaining 2 samples, the proportion of active MMP-8 was 4%. The total amount of endogenous MMP-8 was 5.75 ng/mg (4.11-8.05). The concentration of total endogenous MMP-9 was directly proportional to total endogenous MMP-8 (R=0.75, p<0.001) indicating a common cellular origin.

127 Conclusion: The results suggest that the presence of MMP is important to the biochemical functions of the cervical mucus plug. MMP in the cervical mucus plug may play a part in the ripening of the cervix and in the modulation of the fetal membranes prior to both term and preterm labor.

P14.01 Marianne STEREOTACTIC BODY RADIOTHERAPY FOR LIVER TUMORS Ingerslev Holt, M.I., Høyer, M., Grau C., von der Maase, H. Holt Departments of Oncology, Århus Sygehus, Nørrebrogade 44, 8000 Århus C, Denmark. Stereotactic Body Radiotherapy (SBRT)was introduced as an experimental therapy in the department in 1999 and is now used as routine in treatment of a variety of tumour types. Due to lack of evidence on toxicity profiles for the liver, however, treatment is based on very conservative selection criteria based on tumour volume and number. The increased focus on local treatment of liver tumours underlines the need for documentation on effect and toxicity of SBRT. The objective of the PhD. project is to optimise patient selection and treatment based on risk assessments by characterising survival, morbidity and certain technical aspects of SBRT and treatment planning. The project consists of three elements: Perspectives on the use of PET/CT scanning in SBRT treatment planning, a prospective study with 15 patients. A methodological study on validation of PET/CT for targetdefinition compared to pathology will be performed prior to the prospective study. Perspectives on 18FD-Galactose as a new tracer in PET for description of liver function and morphology following SBRT, a prospective study with 15 patients. A pilot study on 4 pigs will be performed prior to the clinical study in order to assess when to perform the PET/CT scan following SBRT. An analysis of a phase II trial on SBRT of hepatocellular carcinoma and cholangio-carcinoma (25 patients in each group) following SBRT with respect to local tumour control, time-to-progression, survival and toxicity. The characterization of risk assessments will lead to better, more precise and potentially wider selection criteria. The knowledge on hepatic toxicity profiles will be essential for future treatments with high-dose radiotherapy.

P14.02 Lars H. PHARMACOLOGICAL TREATMENT OF DEPRESSION IN PREGNANCY Pedersen Lars H. Pedersen, MD, PhD student Danish Epidemiological Science Centre, Department of Epidemiology, University of Aarhus, DK-8000 Aarhus C, Denmark Treatment of depression in pregnancy is a balance between the potential harmful effects of the disease and the adverse effects of the medication. Depression in itself is associated with increased morbidity and mortality for both mother and child. On the other hand, the possible adverse effects of the medication on both short and long term are insufficiently investigated. The aim of this project is to investigate the effects of the use of antidepressant medication in pregnancy. The study uses data from the National Danish Birth Cohort in which information on 100,000 women and their offspring has been prospectively recorded. Of these women approx. 1200 are exposed to medications with

128 potential effect on the brain including 600 exposed to antidepressant. Endpoints will be complications in pregnancy and during the neonatal period and markers for brain development up too 7 years of age, including milestones, motor development, and behavioral problems. The study is ongoing and no definite results are available.

P14.03 Randi EFFECT OF HYPNOSIS IN TREAMENT OF OROFACIAL PAIN IN A Abrahamsen NEUROBIOLOGICAL PERSPECTIVE R.Abrahamsen, R. Zachariae, P.Svensson Department of Clinical and Oral Physiology, School of Dentistry, University of Aarhus, Aarhus, Denmark A recent study on hypnosis in the treatment of chronic orofacial pain has shown a marginal reduction in self estimated daily pain and no significant changes in somatosensory thresholds. One explanation could be a high incidence of psychological disorders in this study group. The aim of this PhD project is to explore the effect of hypnotically induced analgesia on postoperative pain after third molar surgery (POST-OP) – a pain condition which neurobiologically is well characterized - and to contrast that to persistent myofascial TMD pain (TMD). The possible influence of genetic and psychological factors on pain will be tested. Changes in the blink reflex (BR) during hypnosis will be measured and fMRI scans will be used to show activation of the different levels of the trigeminal system (trigeminal ggl. brainstem, prefrontal lobe) during hypnosis. 40 TMD and 40 POST-OP patients will be randomised to active hypnotic intervention or relaxation. Self estimated pain, various psychological test and somatosensory function (pressure pain, heat / cold, pressure pain, laser stimuli, capsaicin and menthol responses) will be recorded before and after treatment. Blood samples will be used to determine genotype of catechol-o-methyltransferase (COMT). The overall hypothesis is that highly suggestible individuals during various pain stimuli under hypnosis have a greater pain reduction than the lower suggestible and that this may be related to COMT genotype. Furthermore, differences in somatosensory function, BR and in the activation of the different levels of the trigeminal system will exist between the groups.

P14.04 Steffen Lund ASSESING THE EFFICACY OF THE NEW VASCULAR TARGETING Hokland AGENT – OXI 4503 – IN COMBINATION WITH MODERATE HYPERTHERMIA – A PRELIMINARY STUDY S.L. Hokland 1 2, M. Pedersen 2, H. Stødkilde-Jørgensen 2 & M.R. Horsman 1 1: Department of Experimental Clinical Oncology, University of Aarhus, Aarhus Hospital NBG, DK-8000 Aarhus C. 2: The MR-Research Centre, Inst. Clin. Medicine, Aarhus Hosp. Skejby, DK- 8200 Aarhus N The aim of the Ph.D. project is to establish a working setup of Magnetic Resonance Imaging (MRI)-guided Focused Ultrasound (FUS). This novel technique employs FUS to induce non-invasive local hyperthermia, under active temperature monitoring and control by MRI. Here we present preliminary animal studies using conventional hyperthermia techniques.

129 Therapy seeking to disrupt tumour blood flow has been shown to enhance the effect of other anticancer treatments such as radio- and/or chemotherapy or hyperthermia. The vascular targeting agent (VTA) Combretastatin A-1 disodium phosphate (Oxi4503) is a new potent Combretastatin derivative. Experiments were performed using the C3H mammary carcinoma grown in the rear right foot of female CDF1 mice. Heating was performed using a thermostat regulated waterbath in which the tumour bearing foot was submerged during 1 hour. Oxi4503 was administered intraperitoneally at a dose of 50mg/kg either at 6, 3, 1 or 0.5 hours or immediately before or after heat treatment. Treatment groups also included sham groups with either no treatment at all or exclusive hyperthermia or Oxi4503, respectively. Treatment was performed when tumours reached 200mm**3 in size. Tumour sizes were measured 5 times a week and the time where tumour size reached 5 times treatment size calculated. Statistics were performed using students ttest and analysis of variance. Results show that Oxi4503 substantially reduces tumour growth time.

P14.05 Samuel MOTIONAL EFFECT ON WALL SHEAR STRESSES IN A Alberg Kock COMPUTATIONAL FLUID DYNAMICS MODEL OF THE COMMON CAROTID ARTERY S.A. Kock, E.T. Fründ The majority of CFD studies performed on human arteries simulate vessels as rigid tubes. The objective of the current study was to include real- life deformation of vessel walls into CFD simulations to study the impact of motion on wall shear stress (WSS) levels. These are a major factor in the development of atherosclerosis which is the cause of cardiovascular disorders, the number 1 killer in the western world. High WSS levels lead to endothelial denudening while low and oscillating WSS levels allow blood to stagnate causing increased tendencies towards clotting resulting in complications in the form of myocardial infarctions and stroke. The deformation was measured using magnetic resonance (MR) scans. The radius of the common carotid artery (CCA) was measured 21 times during a single heart-phase along with velocity measurements of the blood flow. The expansion and velocity data were applied to a 3D model of the CCA through the use of user-defined-functions using the finite-volume CFD solver Fluent 6.2.22. Models with 3 different degrees of stenosis were analysed, namely 50%, 70% and 90%. WSS levels were averaged along radial sections of the stenosis and exported to Matlab R14 for further analysis. The results indicate marked differences from rigid simulations to simulations taking the wall motion into account. The mean difference for the 50% stenosis was 28.3%, 70% stenosis 26.1% and 90% stenosis 42.9%. The maximum difference occurred in the central part of the model with a maximal degree of stenosis and decreased towards either end. The present study clearly indicates that treatment of human vessels as rigid tubes in CFD simulations introduces a sizeable error in WSS estimations. One should therefore take care to simulate human vessel walls as deformable elastic entities instead of rigid entities.

130 P14.06 Bente PERMANENT DEPENDENCE ON OTHERS DURING MEALS. A Martinsen PHENOMENOLOGICAL STUDY OF PATIENTS’ EXPERIENCES. B. Martinsen. Institute of Public Health, Department of Nursing Science, University of Aarhus, Hoegh Guldbergsgade 6A, 8000 Aarhus C, Denmark. The purpose of this study is to investigate how people, suffering from spinal cord injuries, may experience being helped by others during meals. The main questions are: How does the dependence affect the self esteem of the patients? Which consequences may it have for their social lives? How is the importance of the relationship between helper and patient? Which changes may happen over time regarding the patients’ self esteem, their daily lives and their relations to assistants. The data will be collected by interviewing 16 persons three times within the first year of the study. Between every round of interviews the transcriptions shall be analysed as described below. The plan is that the material from first round may give rise to questions for the second round etc. As this is a phenomenological study the aim is to describe the essence of the participant’s lifeworld, i.e. to grasp the essence of the experince being dependent on help from others during meals. The work is inspired by Van Manen’s phenomenological approach. Broadly speaking, the analysis process consists of four steps: First, a holistic step where the interviews will be read several times to gain an overall understanding of the phenomenon being dependent on help during meals. Secondly, a selective reading has to be done by highlighting phrases and quotes that seem to be thematic. Each of these meaning units will be scrutinized to find out what they reveal about being dependent on others during meals. The third step will be a detailed approach where the researcher interprets each meaning unit in a way that is pertinent for the discipline of nursing. Finally, the aim is to create a coherent, sensitive phenomenological text that seeks to capture the essence of being helped by others during meals.

P14.07 Lone Duval ADOPTIVE IMMUNOTHERAPY WITH ALLOGENEIC, CYTOTOXIC, HLA-A2 RESTRICTED T-LYMPHOCYTES TRANSDUCTED WITH A MART-1 RECEPTOR-ENCODING GENE: A PHASE I STUDY IN MELANOMA L Duval, H Schmidt, T Steiniche, K Kaltoft, K Fode, J J Jensen, S Mellerup Sørensen, M I Nishimura and H Von der Maase Department of Oncology, University Hospital of Aarhus, Aarhus, Denmark We performed a phase I dose-escalation trial to evaluate the feasibility and safety of intra-tumoral injections of C Cure 709, an allogeneic, continuous cytotoxic T lymphocyte cell line that, restricted by HLA-A2, recognizes MART-1 positive tumor cells through transduction with a T-cell receptor encoding gene. Cells were administered intra-tumorally in 4 dose levels ranging from 108 to 109cells per day on days 1, 4, 7, 10, 14 and 28 of each treatment cycle to patients with metastatic melanoma. Main inclusion criteria were HLA-A2 tissue type, MART-1 positive tumor cells and metastases suitable for ultrasound-guided injections. Patients were assessed for toxicity and response. Three to six patients were treated per dose level. Patients without

131 progressive disease were offered up to three treatment cycles. Fifteen patients received a total of 24 treatment cycles with a total of 266 injections of C Cure 709. Toxicity was minor to moderate and most commonly injection site reactions, fever, fatigue, nausea/vomiting, and arthralgia/myalgia. Side effects disappeared in general within 24 hours. Toxicity was not dose dependent. One patient had a partial response (PR). Remaining patients did not achieve an overall response. Three patients including the PR patient had significant local tumor regression of lesions used for injections, and two patients of lesions not used for injections. Intra-tumoral injections of C Cure 709 are feasible, safe and capable of inducing tumor regression. Signs of anti-tumor activity and tolerability of this treatment hold promise for further investigation in a phase II trial.

P14.08 Hanne Birke FREE JEJUNAL FLAPS FOR OESOPHAGUS RECONSTRUCTION: Sørensen METABOLISM AND MONITORING USING MICRODIALYSIS H.B. Sørensen Department of Plastic surgery, Århus University Hospital, 8000 Århus, Denmark. e-mail: [email protected] One of the challenges when reconstructing the upper part of oesophagus using free jejunal flaps is to avoid necrosis. Upon revascularisation there is a risk of impaired blood supply leading to local ischemia, moreover impaired cardiovascular function might lead to general ischemia. The jejunal tissue is sensitive to ischemia and a neglected ischemic situation might lead to leakage and/or necrosis, which are life-threatening complications. Microdialysis might provide information concerning the interstitial fluid. Distinctive metabolic profiles have been documented in muscle as well as subcutaneous tissue during ischemia. Animal studies have indicated characteristic metabolic changes in the bowel a few hours after induction of local or general ischemia. In a clinical study including twelve patients admitted for oesophageal reconstruction after resection of cancer, the metabolism has been monitored in the free jejunal flap using microdialysis. In concordance with these metabolic values reoperation has been performed in two cases. A study has been designed to investigate the metabolism in jejunum and reference tissue during ischemia, and to identify any differences in response to local ischemia compared to general ischemia. The study is based on one clinical and two experimental trials. I: A clinical trial including consecutive patients admitted for reconstruction of the upper oesophagus. The free jejunal flap will be monitored. Reference catheters will be inserted subcutaneously and intra abdominally. II+III: Characterisation of the metabolic profiles in isolated jejunal flaps during arterial and venous ischemia. Two trials will be performed analogous in normovolemic and hypovolemic pigs.

P14.09 Birgitte THE CIRCADIAN RHYTHM OF URINE OUTPUT IN INFANTS. Mahler University of Aarhus Graduate School of Health Sciences, 13 JANUARY 2006 B. Mahler MD, S. Rittig MD, K.Kamperis MD PhD, JC Djurhuus Professor MD.

132 Clinical Institute, Pediatric department, Skejby sygehus, Aarhus University hospital. Background: Healthy children, above 3 years, and adults decreases the urine output and the excretion of osmotically active substances during the night. The circadian rhythm of urine output with a decreased night time diureses reduce the need for night time voiding and allow us to sleep uninterrupted through the night. Circadian rhythm of urine output in infants has not been investigated. We are planning a prospective study of the natural history in the development of circadian rhythm in quality and quantity of urine output in healthy children. The children will be followed during the first three years of life. Circadian variation is defined as a 30% decrease in night time compared to daytime values. Material: 30 healthy infants born at Aarhus university hospital. Methods: 24-hours urine collection and observation chart with sleep/wake patterns and feeding amount and type. The measurements are repeated every second to sixth months during the first three years of the participants’ life. Planned urine analyses: electrolytes, urea, creatinine, osmolality, vasopressin, aquaporine 2, prostaglandin E2. Recruiting from October 2005.

P14.10 Jesper Kelsen PARECOXIB IS NEUROPROTECTIVE IN SPONTANEOUSLY HYPERTENSIVE RATS AFTER TRANSIENT MIDDLE CEREBRAL ARTERY OCCLUSION J. Kelsen1, K. Kjær4, G. Chen2, M. Pedersen2, L. Røhl2, J. Frøkiær1, S. Nielsen1, J.R. Nyengaard3, and L.C.B. Rønn4 1Water and Salt Research Centre, 2MR Research Centre, 3Stereology Research Lab, University of Aarhus, and 4NeuroSearch A/S, Denmark Anti-inflammatory treatment affects ischemic damage and neurogenesis in rodent models of cerebral ischemia. We investigated the potential benefit of COX-2 inhibition in Spontaneous Hypertensive Rats (SHRs) subjected to transient Middle Cerebral Artery occlusion (tMCAo). Forty seven male SHRs were randomized to ninety minutes of tMCAo or sham surgery. Parecoxib (10mg/kg BW) or saline were administered IP during the procedure, and twice daily thereafter. Thirteen animals were euthanized after 24 hrs, and each hemisphere was examined for mRNA expression of pro-inflammatory cytokines and COX enzymes by quantitative PCR.

tMCAo animals were studied with MR (diffusion and T2 weighted imaging) before sacrifice. Thirty four SHRs were given BrdU twice daily on day four to seven after tMCAo. On day eight the animals were euthanized and the brains were studied immunohistochemically for an activated microglia marker (ED-1) and hippocampal neurogenesis. Infarct volume on MR images, ED-1 and BrdU positive cells were estimated with design-based stereologic methods. There was a significant up-regulation of IL-1 , TNF- , IL-6, IL-10 and COX-2 24 hrs after tMCAo, whereas COX-1 was unaffected. No difference in cytokine expression and MRI parameters was found between saline and parecoxib groups. Hippocampal granule cell BrdU incorporation one week after tMCAo was not affected by parecoxib treatment. A pronounced effect on infarct volume was seen in the parecoxib treated animals. IP administration of parecoxib was neuroprotective, as

133 evidenced by a large reduction of infarct volume. Proinflammatory cytokine levels remained unaffected. Parecoxib is acting downstream in the inflammatory cascade, and does not influence cytokine expression.

P15.01 Gitte TRENDS IN EXPOSURE AND RESPIRATORY SYMPTOMS IN THE Jacobsen DANISH WOOD WORKING INDUSTRY Authors: Jacobsen G1, Schlünssen, V2, Schaumburg I1, Sigsgaard T2. 1Department of Occupational and Environmental Medicine, Sygehus Viborg, Denmark, 2Institute of Public Health, Department of Environmental and Occupational Medicine, Aarhus University, Denmark. Introduction: In an ongoing study among Danish woodworkers we investigated the relation between wood dust exposure and respiratory symptoms in two cross sectional studies conducted 6 years apart. This abstract presents preliminary data on respiratory symptoms and exposure, comparing the two study populations. Methods: 2.033 workers from 54 plants returned a questionnaire on respiratory symptoms in study one and 1.886 workers from 52 plants in study two. Exposure measurements were in both studies carried out using a personal passive dust monitor resulting in 1.687 personal measurements from 54 plants (study one) and 1.036 measurements from 41 plants (study two). In study two exposure measurements were performed on all "new" plants and a random sample of plants also participating in study one. Results: No difference in smoking (47%) was seen between the two studies. Participants in study two were older (40 versus 36 years) and more women participated, 23 versus 18%. The prevalence of asthma symptoms, self reported asthma and doctor-diagnosed asthma were equal in the 2 populations. A decrease in coughing during the day was seen among male non-smokers and female smokers. A decrease in nasal symptoms was seen among all, significantly for male smokers and female non-smokers. No significant differences were seen in inhalable wood dust levels between study one GM (GSD) 0.94 mg/m3 (2.1) and study two 0.96 mg/m3 (1.7). A significant increase in percentage of measurements being above arithmetic concentration 0.5 mg/m3 (9.8 versus 13.1%) and below 1.0 mg/m3 (50.1 versus 44.7%) was found. Conclusion: The prevalence of nasal symptoms has decreased during the study period. The prevalence of coughing has decreased among male non- smokers and female smokers. The overall wood dust concentration in the Danish furniture industry has not changed, but there are fewer subjects exposed to levels above 1.0 mg/m3.

P15.02 Tina Senholt CIRCUMFERENTIAL FUSION IMPROVES LONG-TERM OUTCOME IN Videbæk COMPARISON TO INSTRUMENTED POSTEROLATERAL FUSION. T. S. Videbæk, F.B. Christensen, R. Søgaard, E. S. Hansen, K. Høy, P. Helmig,B. Niedermann, S.P. Eiskjær, C. Bünger. Spine Unit, Dept. of Orthopaedics, University Hospital of Aarhus, Nørrebrogade 44, DK-8000 Aarhus C, Denmark Study design. Prospective randomized clinical study with a 5-9 year follow-up period. Objective: To analyze the long-term outcome; functional disability, pain

134 and general health of circumferential lumbar fusion in comparison to instrumented posterolateral lumbar fusion. Methods: From April 1996 to November 1999 a total of 148 patients with severe chronic low back pain were randomly selected for either posterolateral lumbar fusion or circumferential lumbar fusion. Outcome measure was the Dallas Pain Questionnaire (DPQ), the Oswestry Disability Index, the SF-36 instrument and the Low Back Pain Rating Scale. Results: The available follow-up rate was 93%. The circumferential group showed a significantly better improvement (p<0.05) in comparison to the posterolateral group with respect to all four DPQ categories: daily activities, work/leisure, anxiety/depression and social interest. The Oswestry Disability Index supported these results (p<0.01). General health as assessed by SF-36 also showed significantly better physical health (p<0.01) in the circumferential group where as no significant difference was found with respect to mental health compared to the posterolateral group. The circumferential group experienced significantly less back pain (p<0.05) in comparison to the posterolateral group. No significant difference was found regarding leg pain. Conclusion: Circumferential lumbar fusion demands more extensive operative resources compared to posterolateral lumbar fusion. However, 5- 9 years after surgery the circumferentially fused patients had a significantly improved outcome compared to posterolateral fusion alone.

P15.03 Karen-Marie FROM GENE TO FUNCTION: CONDITIONAL KNOCKOUT OF FOUR Pedersen DIFFERENT SPLICE VARIANTS OF THE MURINE SorCS1 GENE. Background: SorCS1 is a type-1 transmembrane protein belonging to a subgroup of the mammalian Vps10p-domain receptor family characterized by an N-terminal Vps10p-domain, a leucine-rich domain, a single transmembrane domain and a short cytoplasmic tail. SorCS1, which is strongly expressed in neuronal tissues, exist in several splice variants that code for identical extracellular and transmembrane domains but a cytoplasmic tail that differ significantly in length and sequence. Three splice variants have been identified in humans and 4 in mice. The receptor isoforms are differentially expressed within the nervous system indicating that each SorCS1 splice variant exhibit a distinct biological function. The aim of the present study is to unravel the biological function of SorCS1 and to clarify the physiological role of each receptor variant. Methods: Firstly, a targeting vector is constructed in which the C-terminal part of SorCS1 is replaced by a neomycin cassette flanked by Flp-recombinase cleavage sites. The targeting vector is subsequently used to generate a transgenic mouse lacking expression of all SorCS1 isoforms (full knockout). Secondly, a shuttle plasmid containing one mutated splice variant flanked by Flp- recombinase cleavage sites is used to generate knockouts devoid in one of the four murine tail isoforms by Flp-induced recombination. Findings: The full knockout of SorCS1 has been established and the phenotypic analysis of the mice has been initiated. ES cells devoid in each of the 4 tail isoforms have recently been generated and the cells will be used for blastocyst injection to generate knockout mice lacking expression of the respective splice variants.

135 P15.04 Mette MIGRATION PATTERNS IN TWO TYPES OF CEMENTED HIP Ørskov PROSTHESES – A CLINICAL INTERVENTION STUDY Sjøland M.Ø. Sjøland1, P. Riegels-Nielsen1, A. Zawadzski1, C. Schlanbusch1, C. Smidt-Sivertsen2, K. Søballe3. Departments of Orthopaedics (1) and Radiology (2), Ribe County Hospital, Esbjerg, Denmark, and Department of Orthopaedics (3), Århus University Hospital, Denmark Artificial hip prostheses used in hip arthrosis surgery consist of a femoral component (stem) and an acetabular component (cup). The stems used vary greatly, and detailed information on the durability is scarce. An increased migration of a stem over time is associated with increased risk of aseptic loosening and thus need for revision surgery. In the present study we set out to investigate the migration pattern of a cemented stem made from titanium versus cobalt-chrome in hip arthrosis surgery. Forty patients (ages between 60 and 75 years) were randomized to receive a stem of either titanium (n=20) or cobalt-chrome (n=20). The patients were followed using radiostereometry (RSA) post-operatively, and after 3, 6, 12 and 24 months. In addition, bone densitometry X-ray scans (DEXA) were performed post-operatively and after 12 months to assess periprosthetic bone loss. Visual analogue scale scores (VAS) for pain, and Harris hip scores (HHS) for function were also recorded. At present all patients have completed their 12 months follow-up visit. Data is presently being analyzed, but no conclusive results have emerged so far. Preliminary results, however, indicate no significant differences in periprosthetic bone loss (DEXA). RSA results obtained during the first year of follow-up are likely to be inconclusive, as pathologic migration patterns usually are not recognisable before a minimum of 2 years follow-up. However, data awaits further analysis.

P15.05 Mette INHIBITING THE ADHESION OF MYCOPLASMA PNEUMONIAE TO Drasbek HEP-2 CELLS M. Drasbek, S. Birkelund, G. Christiansen Department of Medical Microbiology and Immunology, University of Århus, 8000 Århus C, Denmark Mycoplasma pneumoniae is a human pathogen that colonizes the mucosal surfaces of the respiratory tract. It is characterized by the tip-like organelle which plays a important role in the adhesion of the mycoplasmas to the host. The P1 protein, which is clustered at the tip, is one of the major adhesion in M. pneumoniae. The aim of the study is to determine whether ten synthetic peptides covering the immnunogenic part of the P1 protein or antibodies raised against two of these peptides inhibit the adherence of M. pneumoniae to host cells (HEp-2 cells). M. pneumoniae cells were incubated with the 10 synthetic peptides or the antibodies. The HEp-2 cells were infected with the mycoplasma/peptide/antibody suspension and incubated over night. The infected HEp-2 cells were fixed and incubated with a primary antibody raised against M. pneumoniae and visualized using a FITC-conjugated

136 secondary antibody. The amount of mycoplasmas attached to single HEp-2 cells were determined. Comparison of the positive control with the peptide experiments showed that five of the 10 peptides inhibited the adhesion of M. pneumoniae to HEp-2 cells with more than 60%. It also showed that the two antibodies inhibited the adhesion. These observations suggest a direct role for P1 in receptor binding. Furthermore, experiments with fluorescent beads showed that the peptides binds to receptors on the the HEp-2 cells.

P15.06 Morten THE EFFECT OF MITRAL ANNULOPLASTY RINGS ON MITRAL VALVE Ølgaard 3D GEOMETRY AND STRESS DISTRIBUTION Jensen M. Jensen, S. L. Nielsen, H. Nygaard, M. Hasenkam Experimental Cardiac Surgery (T-Forskning), Skejby Sygehus, Aarhus, DK New insight into the 3D dynamic behavior of the mitral valve (MV) apparatus has prompted a reevaluation of mitral annuloplasty ring design, that allow sufficient flexibility to adapt a systolic "saddle-shape" and a diastolic flat configuration, while offering sufficient stability to ensure proper leaflet coaptation. We hypothesize that 1) Mitral annular shape changes are associated with a non-uniform stress distribution along the annulus. 2) Accordingly, implantation of a flat rigid ring generates high local annular stresses during systole, diminishing curvature and increasing leaflet stresses and tensile forces of adjoining chordae tendineae (CT). In contrast, a saddle-shaped rigid ring generates high local stresses during diastole while maintaining normal leaflet curvature in systole, preventing increased leaflet stresses and tensile forces of adjoining chords. 3) Implantation of a flat rigid mitral ring with individual flexible parts interimposed at the focal stress points reduces stress distribution in the annulus and tensile forces of adjoining CT while maintaining mitral annular cross-sectional area and principal cross- diameters. Therefore, in acute porcine models, 3D geometry and relative force distribution of the normal mitral annulus and chordal tension (reflecting leaflet stresses) will be assessed 1) before and 2) after implantation of rigid flat and saddle-shaped rings. 3) Based on these results, a quasi-flexible ring prototype will be developed and optimized in a pulsatile in-vitro model. Then, following ring implantation in acute porcine models, the 3D geometry, relative annulus force distribution, and chordal tension will be assessed. This biomechanical approach enables innovative mitral ring designs, improving the MV stress distribution and repair durability.

P15.07 Jacob Fog SMOOTH MUSCLE CELLS OF ATHEROSCLEROTIC PLAQUES ARE Bentzon DERIVED FROM THE LOCAL VESSEL WALL IN APOLIPOPROTEIN E- DEFICIENT MICE J.F. Bentzon, C. Weile, C. S. Sondergaard, J. Hindkjaer, M. Kassem, E. Falk. Dept. Cardiology, Research Unit, Skejby Hospital, Brendstupgaardsvej, 8200 Aarhus N. Recent reports have concluded that hematopoietic stem cells contribute to smooth muscle cells (SMC) in atherosclerotic plaques of apolipoprotein E deficient (apoE-/-) mice. Here, we reexamined the origin of SMC by a series

137 of bone marrow and vessel wall transplantations. To trace hematopoetic stem cell progeny, apoE-/- mice were lethally irradiated and reconstituted with unfractionated bone marrow cells from enhanced green fluorescent protein (eGFP) transgenic eGFP+ apoE-/- mice. To trace cell migration from the local vessel wall, we developed a novel model of rapid atherogenesis in orthotopically transplanted artery segments. Briefly, segments of common carotid artery were transplanted between apoE-/- and eGFP+ apoE-/- mice, and atherosclerosis was induced inside the graft by placement of a slightly constrictive perivascular collar. Mice were sacrificed and perfusion-fixed and the aortic root, aortic arch, brachiocephalic trunk and common carotids were removed, cryoprotected and snap-frozen. Sections were immunostained for SMC ( SMA, clone 1A4), and analyzed by combined DIC and epifluorescence microscopy. All mice developed fibrofatty lesions. We did not find a single occurrence of SMA+eGFP+ cells in plaques of bone marrow transplanted mice or in apoE-/- vessels anastomosed to eGFP+apoE-/- recipients. Conversely, in plaques developing in eGFP+ apoE-/- artery segments that were grafted to apoE-/- recipients, all SMC were eGFP+. This concludes that atherosclerotic plaque SMC in apoE-/- mice do not derive from hematopoietic stem cells, but exclusively from cells of the local vessel wall.

P15.08 Jian Li CHROMOSOMAL IMBALANCES MAPPED BY ARRAY-BASED COMPARATIVE GENOMIC HYBRIDIZATION IN AN INTEGRATED APPROACH TO COMBAT BREAST CANCER IN DENMARK Jian Li, Xiuqing Zhang, Thomas Dyrsoe Jensen, Kai Wang, Steen Kølvraa & Lars Bolund Institute of Human Genetics, University of Aarhus, Denmark Comparative genomic hybridization (CGH) has revolutionized the detection and mapping of chromosomal imbalances in neoplasias. However, conventional CGH is handicapped by its low resolution. Array- based CGH brings the resolution towards a molecular level. With a capillary printer we produce arrays on CodeLink slides with 3158 BAC clones, which randomly represent the whole genome. With our home-made arrays, we can detect and map numerical aberrations in a single experiment with about 1-Mb resolution. Furthermore, we have optimized printing, labeling, hybridization, scanning and analysis tools. Reverse-labeling (exchanging the tumor and reference DNA labeling dyes) gives us reliable results even in samples with substantial admixture of normal cells. In the Danish Centre for Translational Breast Cancer Research (DCTB) a five–year project involving 500 high-risk patients is underway. Both prospective and retrospective studies are planned with a systems biological approach involving a multitude of analyses, including array-CGH. 20 breast cancer samples have been analyzed in a preliminary study. Chromosome 1q (15/20), 8 (14/20), 11(5/20), 17q (9/20) and 20q (6/20) gains (duplications and amplifications), and chromosome 22 (7/20) deletions are the most frequent aberrations, which is consistent with the previously published conventional CGH results. Our findings will continuously be integrated with all the other results from the same tumors.

138 P15.09 Agata PREVALENCE OF MYCOPLASMA HOMINIS INFECTIONS AMONG Baczynska INFERTILE WOMEN AND WOMEN UNDERGOING INDUCED TERMINATION OF THE PREGNANCY A. Baczynska, J. Fedder, S. Birkelund and G. Christiansen Department of Medical Microbiology and Immunology, University of Aarhus, 8000C, Denmark. Introduction: M. hominis is associated with the genito-urinary tract infections. This opportunistic pathogen is a common inhabitant of female lower genital tract and it is believed to be sexually transmitted. Association with development of female infertility has also been suggested. Studies made on women undergoing in vitro fertilization showed the presence of M. hominis only in 2.1% of the women (Witkin SS, Kligman I, J Assist Reprod Genet 1995, 12: 610-614). Serological studies, show however, presence of antibodies to M. hominis in 30% of infertile patient compared to 9.6% among healthy controls (Baczynska A, Svenstrup H, Hum Reprod 2005; 20 1277–1285).The aim of our study was to compare the prevalence of M. hominis among infertile women and women undergoing abortion. Methods: We investigated 223 and 49 cervical swab samples from infertile and abortion patients. The culture in BEa medium was preformed on all of the samples. The quantitative LightCycler PCR method was used to find a bacterial DNA in the samples (Baczynska A, Svenstrup H, BMC Microbiol 2004; 4: 35). Results: Of 223 (3.1%) infertile patients, seven carried M. hominis at the time of analyzes, which was confirmed by positive culture and LightCycler PCR. Of 49 abortion patients, eleven (22%) were positive for M. hominis analyzed by both methods. Conclusions: Infertile women carry Mycoplasma hominis significantly less often than women undergoing abortion. Results from cultivation and LightCycler PCR were identical, which was a good conformation of the positive results.

P15.10 René PERIAPICAL BONE HEALING AFTER APICECTOMY WITH AND Christiansen WITHOUT RETROGRADE ROOT FILLING. René Christiansen Institute of Odontology, Faculty of Health Sciences, University of Aarhus, 8000 Århus C, Denmark Objectives: Dental treatment of chronic infection in the bone around a root apex. The purpose of this study is to evaluate two apicectomy treatments with and without a sealing material after removal of 1-3 mm of the root tip. It is believed that bacteria in the pulp delta causes the chronic infection in the bone. Design: A clinical randomised trial,60 patients with apical periodontitis on a root-filled tooth will be randomised into the following two groups: • Group A will be treated with MTA (mineral trioxide aggregate) as the root end sealing material after apicectomy. Group B will be left with the gutta-percha root filling after apicectomy. Radiographs will be taken one week, 3, 6 and 12 months after the surgical treatment. A 3D dental CT-scan will be performed one week and 12 months after the surgical treatment. These methods will provide the data for evaluating healing of the infected

139 bone.Patient interviews, clinical photos and clinical registrations before, during and after the treatment will be analysed and used for describing factors associated with the healing of the chronic infection and the surgical treatment. To consider: Compared to treatment with only gutta-percha, sealing with MTA is more difficult and time consuming as it involves more clinical steps. Our study will provide general clinical practitioners with results, which can facilitate treatment decision in patients with apical peridontitis. Schedule: 10 patients have been treated so far, 6 with MTA and 4 with gutta-percha. In January 2006 we will evaluate: • How the patient experienced the treatment • Bone healing 6 months after treatment.

P16.01 Birgit E. SELECTION OF STABLY EXPRESSED REFERENCE GENES FOR Bonefeld NORMALIZATION OF qPCR DATA OBTAINED FROM BRAIN TISSUE FROM THE GENETIC ANIMAL MODEL OF DEPRESSION, THE FLINDERS RATS B.E. Bonefeld, G. Wegener, D.H. Overstreet, R.Rosenberg When examining gene expression by quantitative polymerase chain reaction (qPCR) with endogenous normalization, it is essential that the endogenous controls for relative quantification of target genes are chosen to be as representative for the mRNA amount as possible. Lately, it has turned out that the house keeping genes typical used for normalization, like b- actin, gapdh and 18sRNA, are not stably expressed under several experimental conditions. This study was undertaken in order to select the most stably expressed housekeeping gene for normalization of qPCR data. The experimental material was dissected brain tissue from a genetic animal model of depression, the Flinders rats. Brain tissue from hippocampus (Hip) and cerebellum (Cer) from male as well as female rats were included. qPCR was performed to determine the expression of mRNA of 8 housekeeping genes, namely 18sRNA, ACTB, CYCA, GAPD, HMBS, HPRT1, RPL13A, and YWHAZ. The SYBR-green technology and optimized primers were used. In order to determine the most stably expressed housekeeping gene, the data was analyzed with NormFinder software. In Cer and Hip in female Flinders rats, CycA was identified selected as the most stably expressed housekeeping gene. In male Flinders rats, the most stably expressed genes in Cer and Hip were CycA and Hprt, respectively. When normalizing gene expression data of target genes with the identified housekeeping genes, a different result was obtained than when normalizing with e.g. b-actin. These findings emphasizes the importance of selecting a stably expressed house keeping gene, for normalization

P16.02 Thomas EXPERIMENTAL UNILATERAL URETEROBSTRUCTION IN THE LATE Dissing PART OF THE NEPHROGENESIS PERIOD. T.H. Dissing, A. Eskild-Jensen, J. Frokiaer, M. Rehling, T. Munch Jorgensen, J.C. Djurhuus. Institute of Clinical Medicine, University of Aarhus.

140 In the pig nephrogenesis continues three weeks after birth (Friis C, J. Anat. 130:513, 1980). Previously, our group has characterised renal functional changes when an obstruction was induced in pigs two days of age (Eskild-Jensen A., Christensen H., Lindvig M., et al. J urol163, 2000).The study showed an initial reduced function, which later normalised or vice versa. The purpose of this study was to examine the effect on kidney function of inducing an obstruction later in the nephrogenic phase. Methods: Twenty pigs 14 days of age were included in the study. Fifteen animals were randomized to unilateral partial obstruction a.m. Ulm and Miller (Ulm A. H., and Miller, F. J. Urol. 88: 337, 1962. Five animals were sham operated. The pigs were examined at the age of 4, 12 and 24 weeks using 99mTc- DTPA renography and plasma clearance of 99mTc-DTPA. Data are given as mean ± SEM and compared using one-way ANOVA. Statistical significance is considered as p<0.05. When evaluated by magnetic resonance imaging obstructed kidneys were hydronephrotic (mild to severe) at the age of 4 weeks. At this age functional share of the obstructed kidneys varied from 17 to 47 % (32 % ± 3) making the average functional share significantly lower than in the sham operated kidneys (49 ± 2 p=0.001). The functional share at age 4 weeks of 11 of the obstructed kidneys were below 40% and 4 were above. Six of the 11 obstructed kidneys with functional share below 40% at 4 weeks of age had an increase in functional share. Five of these to above 40% at 12 and 24 weeks of age. Three of the obstructed kidneys with functional share below 40% at age 4 weeks had decreasing function. One of these only from 39% at 4 weeks to 33% at 24 weeks of age. The other two deteriorated from a functional share of 17 % and 20 % at 4 weeks to a 11% and a virtual zero, respectively, at 12 weeks. At 24 weeks of age both of these had practically no functional share (values measured to 5% and 4%, respectively). One of the 4 obstructed kidneys with functional share above 40% deteriorated through 40% at 12 weeks to 32% at 24 weeks. The rest of the obstructed kidneys remained stable. GFR/kg bodyweight did not differ between the two groups at neither 4, 12 nor 24 weeks of age (2.7 ± 0.2 ml/min/kg vs. 2.5 ± 0.3 ml/min/kg p=0.66 at 4 weeks, 2.3 ± 0.1 ml/min/kg vs. 2.1 ± 0.2 ml/min/kg p=0.24 at 12 weeks and 1.8 ± 0.1 vs. 1.6 ± 0.1 at 24 weeks p=0.46). The above leads us to conclude that partial obstruction induced in the late nephrogenesis period shows the variability in long term functional outcome as previously shown in neonatally induced obstruction.

P16.03 Ramkumar ETHNIC CHARACTERIZATION OF CANDIDATE GENES FOR Menon SPONTANEOUS PRETERM DELIVERY Ramkumar Menon, Poul Thorsen, Ida Vogel, Bo Jacobsson, Scott Williams, Digna Velez, Stephen J Fortunato. The objective of this study is to characterize 19 single nucleotide polymorphisms (SNPs) in 3 candidate genes (TNF- ), TNF-Receptor 1, and TNF Receptor 2 in order to define SNPs that may associate with preterm

141 labor (PTL) and ethnic disparity. For each polymorphism, we compared allele and genotype frequencies between African-Americans (AA) and European-Americans (EA) in a case-control study. Maternal and fetal genotypes were compared separately as well as to each other in 102 PTL EA cases and 325 controls, and 46 AA PTL cases and 181 AA controls. Both maternal and fetal genotypes were studied from these birth pairs, as it is unclear whether one or both of these are important in the etiology of PTL. Allelic and genotypic frequency differences are compared. Descriptive statistics, tests for Hardy-Weinberg equilibrium, exact tests for genetic differentiation and Fishers exact tests were performed using TFPGA and RxC statistical software. Multiple comparisons were made and Bonferroni corrections were applied. Majority of the SNPs differed significantly between ethnic groups in at least one of the comparisons (p <0.01). For TNF- , three of six SNPs; for TNF-R1, 5/6; and for TNFR2 6/7 showed significant differences between ethnic groups. Data demonstrate highly significant and common ethnic genetic differences in genes that affect PTL. In several comparisons the maternal and fetal genotype and /or allele frequencies differ within ethnic groups. Specifically, the findings suggest that transmission of some alleles from mother to child may not be at random, and that this lack of random transmission may act to confer either increased or decreased risk of PTL.

P16.04 Mads EPIGENETIC DETERMINANTS OF ONCOGENE ACTIVATION Heilskov M.H. Rasmussen (1), F.S. Pedersen (2), A.L. Nielsen (1). Rasmussen Department of Human Genetics (1) and Molecular Biology (2), University of Aarhus, DK-8000. The aims of the study using a murine model for lymphomagenesis are i) to examine epigenetic changes in genetic loci frequently targeted by insertional mutagenesis in murine leukemia virus (MLV) induced lymphomas in mice and ii) to functionally characterize the tumorigenic genes encoded by the loci. Mice will be injected with lymphoma cells with integration into selected loci (Fos/Jdp2/Batf and cMyv/Pvt1) that have been isolated from MLV inoculated syngenic mice. Upon development of clonal tumors these shall iteratively be cultured and developed in vivo as well as cultured in vitro before being subjected to analyses. We will i) use chromatin immunoprecipitation (ChIP) and chromatin conformation capture (3C) to investigate how the insertion of an actively transcribing provirus changes the chromatin structure of a locus; ii) apply siRNA to look for any dependence of provirus transcription on gene activation (and vice versa); and iii) functionally describe the activated genes functionally using in vivo propagation and siRNA. The project is anticipated to enlighten on epigenetic changes associated with enhancer-mediated activation of proto-oncogenes as is typical for a long range of cancer-linked chromosomal imbalances in man, and given the reversible nature of most epigenetic modifications such insights may have therapeutic implications.

P16.05 Kirsten SENSORY NERVE INVOLVEMENT IN ALS - FREQUENCY EVALUATED

142 Pugdahl IN A EUROPEAN MULTICENTER STUDY K. Pugdahl, A. Fuglsang-Frederiksen, B. Johnsen Department of Clinical Neurophysiology, University Hospital of Aarhus, Aarhus Sygehus, Nørrebrogade 44, DK-8000 Århus C Amyotrophic lateral sclerosis (ALS) is a rapidly progressive, fatal neurological disorder of the brain, spinal cord and nerves, caused by degeneration of the upper and lower motor neurons, which are responsible for controlling voluntary muscles. ALS is traditionally described as a disease solely attacking the motor system with no intellectual or sensory impairment. The etiology of the disease is unknown. Since 1992 physicians from six European centres have prospectively collected samples of their electrodiagnostic patient cases for regular peer review and the building of a multicenter database. A pilot study reviewing ALS cases from the database has suggested the existence of a subgroup of ALS patients with pronounced affection of the sensory system. The frequency of cases with electrophysiological abnormalities in at least two different sensory nerves was determined from 89 cases extracted from the database. These cases represented all cases with a consensus diagnosis of non-familial ALS, which were confirmed by clinical follow-up in case of doubt. In addition cases with systemic disease or other potential causes of neuropathy were excluded. Affection of the sensory system was indicated in 19 of the 89 ALS cases (21.3%). The mean age for this group was 65.2 years (range 50 to 81) and the mean time from onset of symptoms was 10.5 months (range 2-36 months). These results suggest that a subgroup of patients with acquired ALS have additional peripheral neuropathy, which is supported by several neuropathological studies, although the literature is conflicting. More detailed studies addressing this issue is planned.

P16.06 Pernille CELLULAR DOWN-REGULATION OF THE TYPE III SODIUM- Bøttger DEPENDENT INORGANIC PHOSPHATE TRANSPORTER, PIT2, IN RESPONSE TO HYPERPHOSPHATEMIC CONDITIONS. P. Bøttger, L. Pedersen Institute of Clinical Medicine, University of Aarhus, 8000 Aarhus C, Denmark. Type III sodium-dependent inorganic phosphate (Pi) co-transporters, PiT1 and PiT2, are housekeeping Pi transporters and additionally suggested involved in normal and pathologic mineralization in bone and blood vessels, respectively. Both proteins exhibit dual function, thus, besides being transporters they also serve as receptors for a diverse group of retroviruses. A large intracellular domain present in human PiT1 and PiT2 (PiT2 amino acids 236 to 483) are smaller - or not present - in related proteins from primitive species. This suggests that the domain might affect regulation of the PiT-proteins - since additional regulatory functions ought to develop as a consequence of evolution from simple archaea and bacteria to the complex body of mankind. A battery of human PiT2 mutants were made – including deletion of sequences in the large intracellular domain as well as point-mutations

143 introduced by site-directed mutagensis (PiT2 254-483, PiT2 260-273, PiT2 277-335,

PiT2 260-335, PiT2 L224A L225A, and PiT2 D406K D412K). The cellular regulation of PiT2 – and mutant proteins in response to hyperphosphatemic conditions (Pi above 1.4 mM) was studied in a transient transfection and infection assay using receptor function for a PiT2 cognate virus – the 10A1 murine leukemia virus - as a valuable tool for tracing of the proteins. Three sequences in the large intracellular domain are indeed involved in cellular down-regulation of PiT2 in response to high Pi levels. Moreover, a PiT2-specific transmenbranic di-leucine motif also affects the ability of PiT2 to down-regulate in response to hyperphosphatemia.

P16.07 Thomas STABILITY AND HEALING IN PROXIMAL TIBIAL OPEN WEDGE Lind-Hansen OSTEOTOMI IN THE TREATMENT OF UNICOMPARTMENTAL OSTEOARTHRITIS. A SERIES OF CLINICAL AND BIOMECHANICAL STUDIES. Thomas Lind-Hansen 1), Poul Torben Nielsen 1) and Martin Carøe Lind 2) 1) Northern Orthopaedic Division, Aarhus Univerity Hospital 2) Department of Orthopaedics, Aarhus University Hospital. In the treatment of osteoartritis of the medial compartment of the knee, open wedge high tibial osteotomi is a good choice of treatment for the young and active patient. However it leaves an open gap in the bone, the healing of which are essential for a good long lasting result. The objective of this PhD.-study is to gain further knowledge of the biomechanical properties and healing in open wedge osteotomies. Methods: 3 studies are performed: 1) A retrospective study of open wedge osteotomies performed from 2001-2005. A survival analysis (Kaplan Meier) will be performed. 2) A clinical prospective randomised study including 45 patients randomised to either a) no graft in the bone gap b) autograft from the hip (crista iliaca) or c) the injectable calciumphospate cement Calcibon®. The principal effect- parameter is migration of the distal bone segment measured in mm using RSA (Roentgen Stereophotometric Analysis). Migration suggests delayed healing. 3) A biomechanical cadaver bone study. 16 (8x2) medial open wedge tibia osteotomies of 10 mm are performed in the pilot and main study. In 8 bones the bone gaps are filled with Calcibon® - other 8 serves as controls. Biomechanical testing is then performed in an Instron material testing machine. The loads will mimic the load found during level walking (up to 3 times bodyweight). The stiffness of the construct can then be calculated and used in mobilisation of future patients. Results: The PhD. was initiated in February 2005 and so far no results are available. We hope to present the results from the biomechanical pilot study at the PhD-day.

P16.08 Mette A PROSPECTIVE INVESTIGATION OF NEUROPSYCHOLOGICAL Stylsvig IMPAIRMENT AFTER TRAUMATIC BRAIN INJURY IN CHILDREN AND ADOLESCENTS. Mette Stylsvig, neuropsychologist. The Department of Neurosurgery, Aarhus University Hospital. Traumatic brain injury in children is usually mild. nevertheless, we need consistent terminology for classifying such injuries and reliable estimates of cognitive deficits in children. At present, such procedures are lacking.

144 We hypothesize that no reliable relationship exists in children between the degree of head injury and the severity of neuropsychological impairment at one year. All children and adolescents (from one month to eighteen years old) with newly aquired head injury in Aarhus county were included from 1. april 2003 – 31. march 2004. The prospective follow-up study are based on questionnaires at baseline and a half and one year after the diagnose. In other studies the applied questionnaires have demonstrated satisfactory reliability and validity. The applied neuropsychological test are choosen, because they have been tested in numerous international investigations. The normmaterial for the applied test will provide the control group for the study-population. The investigation is expected to contribute to a more valid knowledge of the incidence of paediatric traumatic brain injury than previously published nationally as well as internationally. Furthermore the perspective will be to identify riskfactors in relation to neuropsychological impairment after head trauma in children and adolescents with special reference to secondary and tertiary prevention.

P16.09 Charlotte T-CELL-MEDIATED IMMUNITY IN PATIENTS WITH LEUKEMIA Christie DURING HCMV REACTIVATION Petersen C.C. Petersen, M. Hokland Institute of Medical Microbiology and Immunology, University of Aarhus, 8000 Aarhus C, Denmark. Human Cytomegalovirus (HCMV) is highly prevalent (ca. 50% in the adult Danish population). Although usually entirely sub-clinical, reactivated virus can be potentially fatal in immunocompromised individuals. For this reason, patients with latent HCMV-infection, who are undergoing treatment for malignant leukemias, are at risk. The project aims to identify an early diagnostic marker for HCMV reactivation in these patients, and to establish a protocol for expansion of HCMV-specific T cells for treatment of reactivated virus infection. Blood samples from patients will be evaluated both directly and after short-time antigen-stimulation. T cells will be evaluated with respect to CMV specificity using antigen-specific tetramers, phenotype (CD3, CD4, CD8, CD27, CD28, CD45RA/RO, CD62L, CCR7), cytotoxic potential (perforin and granzyme B), cytokine profile (intracellular IFN-gamma, TNF- alpha, IL-2, IL-10, IL-21), and proliferation (CFSE) using multi-parameter flow cytometry. The data will be correlated to viral load and clinical status. In addition, a protocol for generating autologous HCMV specific T cells will be established. The culture and expansion will follow Good Laboratory Practice (GLP) standards as far as possible and cell cultures will be validated for phenotype, functionality and specificity.

P16.10 Mette Slot ENCAPSULATED CELL BIODELIVERY OF NGF TO THE BASAL Nielsen FOREBRAIN IN THE GÖTTINGEN MINIPIG M.S. Nielsen, J.C. Sørensen, C.R. Bjarkam, K.S. Ettrup, F. Rosendal, B. Juliusson, J. Tornøe, L. Fjord-Larsen, L.U. Wahlberg Department of Neurobiology, Institute of Anatomy, University of Aarhus,

145 8000 Århus C, Denmark Nerve growth factor (NGF) has been shown to protect and restore cholinergic function in animal models of Alzheimer’s disease. Translation of these results to human therapy has been difficult as both systemic and intracerebroventricular infusions have been associated with painful side effects. Rodent and primate animal models and human pilot trials have demonstrated the therapeutic potential of local intraparenchymal NGF delivery to the basal forebrain using gene therapy approaches. However, current ex vivo or in vivo approaches do not allow for gene regulation or the ability to stop NGF treatment if side effects occur. Encapsulated cell biodelivery (ECB) of NGF could overcome this limitation by combining the efficacy of gene-based NGF delivery with that of the safety of a retrievable device. In order to study delivery and scale-up issues of NGF to the brain, we have utilized the Göttingen minipig. Clinical-sized ECB devices containing a clonal human cell line engineered to secrete human NGF and empty control devices were placed stereotaxically using MRI guidance in the basal forebrain of six animals. The animals showed no evidence of toxicity and had normal weight gain. Retrieval at 3 months was successful and the devices could be explanted without complications. Postexplantation NGF secretion was stable at preimplantation levels. Diffusion of NGF in the basal forebrain was measured by immunohistochemistry and ELISA. This study shows that ECB devices containing human cells secreting NGF can be implanted in the non-immunosuppressed minipig brain and can secrete therapeutic levels of NGF in the basal forebrain for at least 3 months without untoward effects. Support contributed by NsGene A/S.

P17.01 Nicoline ACTIVITY IN MEDIAL PARIETAL AREAS DURING MENTAL IMAGERY Marie Hall IS INDEPENDENT OF RETRIEVAL INTENTIONALITY: A PET STUDY ON INVOLUNTARY AND VOLUNTARY EPISODIC MEMORY. N.M. Hall, R. Kupers & A. Gjedde Center for Functionally Integrative Neuroscience, Bygning 30, Århus Kommunehospital, Nørrebrogade 44, 8000 Århus C. Episodic memory is usually associated with activity in right lateral/anterior prefrontal cortex (PFC), medial temporal lobe and medial parietal lobe. This knowledge is primarily obtained from neuropsychological and neuroimaging studies focusing on intentional memory retrieval. However, episodic memories can also occur without any prior attempt at retrieval; we call this phenomenon involuntary conscious memory (ICM). Very little knowledge exists on the contributions of the neural network involved in voluntary conscious memory (VCM) to ICM, and the objective of the present study is to investigate this issue. We used positron emission tomography to measure blood flow (rCBF) in twelve healthy subjects during the auditory presentation of cue words which were used to recall pictures that had previously been associated with these cues. Three conditions with identical stimulation involved intentional cued recall (VCM); semantic evaluation and unintentional cued recall (ICM); or semantic evaluation without recall (control). Post-scan reports suggested that recall of pictures was near ceiling level in

146 both recall conditions. An increased rCBF in posterior cingulate gyrus and precuneus in the medial parietal lobe occurred during both ICM and VCM compared to control. In right dorsolateral PFC, rCBF showed an increase during VCM compared to both ICM and control. These results confirm the involvement of dorsolateral PFC in intentional episodic retrieval processes. Contrary to earlier findings, activity in the medial parietal cortex seems to be independent of retrieval intentionality. Medial parietal activity does however seem to depend on whether retrieval is episodic or semantic.

P17.02 Eduardo INFLUENCE OF ORAL CONTRACEPTIVES ON GLUTAMATE-EVOKED Castrillon PAIN AND PRESSURE PAIN IN MASSETER MUSCLE Eduardo Castrillon, Malin Ernberg, Kelun Wang, Brian Cairns, Barry Sessle, Lars Arendt-Nielsen, Peter Svensson. Clinical Oral Physiology, School of Dentistry, Aarhus University, Vennelyst Boulevard 9, 8000 Århus C, Denmark. The aim of the PhD project is to get a better understanding of pathobiological mechanisms underlying on orofacial muscle pain with a particular emphasis on the role of peripheral glutamate receptors. In this part of the study, we hypothesized that women taking oral contraceptives (W+OC) would differ from women not taking (W-OC) in deep-pain sensitivity. Twenty five W+OC and 22 W-OC without temporomandibular disorders (TMD) participated. Pressure-pain thresholds (PPTs) and Pressure-pain tolerance levels (PPTOLs) were determined in the masseter muscle (MM). Then 0.2 ml glutamate (1mol/lL) was injected into the MM and subjects scored pain levels on an electronic visual analog scale (VAS) for 15 min. PPTs were assessed every 5 min and PPTOLs 15 min after the injection. Also, all subjects filled out the McGill Pain Questionnaire (MPQ). Groups were compared with analyses of variance (ANOVAs). ANOVAs for PPTs and PPTOLs showed no significant difference between groups (P>0.96) but a significant decrease after glutamate injections (P<0.001). Injection of glutamate caused moderate levels of pain in all subjects, but no differences between groups were found in VAS peak pain scores, area under the curve or pain duration (P>0.656). Analysis of MPQ data in glutamate-evoked pain did not reveal any pain rating differences for sensory, affective, evaluative neither miscellaneous indices (P>0.158). Results indicated that the use of oral contraceptives did not influence MM pain sensitivity, even though there were significant increases in mechanical sensitivity over time.

P17.03 Erik Elgaard NURSING MANAGEMENT Sørensen Erik Elgaard Sørensen Department of Nursing Science, Institute of Public Health, Faculty of Health Sciences, University of Aarhus, 8000 Aarhus C, Denmark Background: In Danish hospital care system, nurses have not only carried out professional tasks. They have also occupied key executive and management functions. As a result, executive leadership and management have relied upon those with a nursing education together with experience

147 from clinical practice. New models of management are now being tested, and there is an emerging trend for those managers with professional nursing backgrounds to be supplanted by those with specific managerial skills and training. On one hand it is said, that professional skills may act as an impediment to good management with the risk of bringing into administrative practice various dilemmas, loyalty-problems, limitations and negative consequences. On the other hand, professional skills beneficial for good leadership and organisational management. Aim: The purpose of this project is to investigate the interaction between administrative/managerial and professional competence at central, departmental and sectional levels in Danish hospitals. The investigation is restricted to the field of management of patient care in hospitals, based as it is on the assumption of the need for leaders with sufficient background, insight, skills and understanding of patient care and based on experience with clinical practice. It is therefore assumed, that nurse-managers both have the ability to communicate and get on socially with different types of employees and the ability to create conditions and circumstances for optimum care of persons, whose lives are affected by illness and disease. Making the empirical foundation: The investigation has taken place in five Danish hospitals. A total of twelve nurse-trained managers are included in the study, all women with an average on 48 years, of which two are head nurses at central organs, five heads of department and five heads of sections. The empirical data derives from participant observation, participant accounts, interviews and fieldnotes. Each informant has been followed for a one week period.

P17.04 Sune ACOUSTIC RHINOMETRY: A DIFFERENT APPROACH TO MEASURING Straszek CHANGES IN AIRWAY GEOMETRY. UNIVERSITY OF AARHUS GRADUATE SCHOOL OF HEALTH SCIENCES, 13 JANUARY 2006. S. P. Straszek Objective: 1) To validate Acoustic Rhinometry (AR) in small laboratory animals post mortem. 2) Optimize AR for in vivo studies of nasal congestion. 3) Adapt AR to in vivo measurements of nasal mucosal response to airborne irritants in guinea pigs. Method: AR is a non-invasive method that measures cross-sectional area as a function of distance in a cavity by reflection of sound. Measurements of nasal airway geometry post mortem in guinea pigs and rats are validated by comparison to CT, MR and a Fluid-Displacement-Method (FDM). AR is used in vivo on guinea pigs to compare changes in nasal congestion before and after a response to inhaled irritants, e.g. glucanes and LPS. Results: AR underestimates the true volume of a nasal cavity compared to MR, CT and FDM but have a high reproducibility. The study will show the effect of nasal irritants on nasal mucosa of guinea pigs in vivo. Conclusion: AR is a simple, non-invasive method that reliably can measure relative changes in nasal airway geometry before and after application of histamine and decongestants making it suitable for screening of pharmaceuticals and possibly irritants or allergens in vivo. Areas for improvement include scaling of equipment and optimized algorithm for data handling.

148 P17.05 Isa Niemann RECURRENT MOLAR EVENTS – REPETITIVE OR RETAINED? Isa Niemann, Lone Sunde Department of Clinical Genetics, Bartholin Bygningen, Aarhus Sygehus, 8000 Aarhus C, Denmark. The aims of this study were to assess whether repeated molar pregnancies in six women were representing recurrent moles or retained molar pregnancies. Also, we wanted to examine the effect on future pregnancies and to estimate the risk of persistent trophoblastic disease in women with recurrent hydatidiform moles. 17 polymorphic microsatellite markers with high heterozygosity were used to determine the genetic constitution in the repeated molar pregnancies and in the parents. Data on hCG-levels, pathology reports and clinical features were collected from hospital files. All analysed moles were diploid, but had inconsistent morphology. Two patients had biparental molar pregnancies, the others androgenetic moles. The time span between moles varied from 5 to 79 months. All patients had 1-3 normal obstetric events. Two were treated with chemotherapy to obtain remission after their second mole. One mole was retained despite of negative hCG levels, when analyzed with microsatellite markers. Cases of repetitive molar pregnancies within a shorter time span could possibly represent retained molar tissue, which cannot be revealed by morphological examination. The risk of subsequent molar pregnancies may vary greatly depending on the genetic origin of the moles. The prognosis of normal future reproduction is supposedly not impaired after two androgenetic molar events. Furthermore, the retained mole calls upon cautiousness with respect to shorten the surveillance period for diploid moles.

P17.06 Jolanta SAFETY AND EFFICACY OF COMPUTED TOMOGRAPHY Hansen Jolanta Hansen Department of Radiology and Medical Physics, Aarhus University Hospital Background: Computed Tomography (CT) scanners have gone through a rapid evolution since their introduction in 1973. CT examinations account for about 3-6 % of all examinations performed using x-ray in Europe, while radiation doses from CT constitute 30 - 40% of the collective radiation dose from medical exposures. Purpose: 1) to evaluate radiation dose and associated risk in multislice CT (MSCT), 2) to analyse the possibilities for optimising MSCT to obtain a dose as low as reasonably achievable, and 3) to evaluate the justification of MSCT compared to MRI for 2-3 disorders or anatomical areas, resulting in evidence-based diagnostic strategies based on prospective studies. Material and methods: Existing practices regarding clinical indications for CT will be collected in a database including evaluation of dose and risk. Protocols for the optimisation study will be chosen based on these data to secure inclusion of high dose MSCT examinations which have the potential for a dose reduction e.g. MSCT of multi-trauma patients. The needed image quality will be established by radiologists. The selection of disorders or anatomical areas for the prospective study will be based on the results of phases 1 and 2. Current suggestions are: a) to analyse the possibility for

149 converting MSCT of the sternoclavicular joint to MRI and b) to evaluate the possibility for converting MSCT of the abdomen to MRI of retroperitoneum in the follow-up of patients with stage 1 testicular cancer. The diagnostic potential of MSCT and MRI will be evaluated separately, in a blind manner, each by two radiologists. Perspectives: Optimisation and justification of MSCT examinations, and the analysis of the usefulness of other examination techniques will contribute to reduce patient doses. Selection of optimal diagnostic imaging can potentially reduce radiation induced cancer incidence. This project is part of a CEC SPECIFIC TARGETED RESEARCH PROJECT.

P17.07 Martin SENSITIVE HIV-1 GENOTYPE METHOD VALIDATING VIRAL Roelsgaard RESISTANCE FROM PATIENTS WITH A LOW VIRAL LOAD. Jakobsen M.R. Jakobsen, L.S. Bertelsen, J. Kjems, & Østergaard, L Department of Infectious disease, Skejby Hospital, Brenstrupgaardvej 100, 8200 Aarhus N, email: [email protected] Background: HIV-1 drug resistance testing is a standard methodology when HIV-patient fails to react on HAART treatment. Unfortunately, limitations in the assay exclude analysis of developed resistance in patients with low level of virus in the blood stream (referred to viral load) or in samples where mutant species populations are below 20%. This has become a fundamental clinical problem, since drug resistance diagnosed as early as possibly will result in better compliance and lowers the risk for multidrug resistant viruses to evolve. Method: We have developed a method specific for purifying viral RNA and the detection of single nucleotide polymorphism (SNP) from patients with a low viral load. Moreover, to minimize the time of the analysis we intend to develop an alternative resistance measurement that instead of sequencing uses a Taqman and LightCycler technical approach, referred to amplification refractory mutation system (ARMS). Results: The first method has been evaluated against the general genotype method at SSI. Out of 6 patients with a high viral load the resistance pattern were similar. Currently, we are estimating the lower limit of the assay in regards of viral load. The ARMS method has earlier been tested against a dual mutation set called N103K – M184V. This method are now renewed with further mutations and tested for possibly measuring multiple resistances. Conclusion: The data obtained shows that a general molecular biology approach can be used as screening method for HIV resistance genotypes in patient with low viral load. Further, utilizing the ARMS method could lead to faster genotype measurement. Thus the combined method could improve the genotype analytical tools in order to establish developed resistance much earlier that what is at this time present.

P17.08 Louise HYPOXIA-INDUCED ENDOTHELIAL DYSFUNCTION IN HUMAN Østergaard UMBILICAL VEIN ENDOTHELIAL CELLS Petersen *L. Østergaard, *U. Simonsen, #T. Ledet, §M.R. Andersen, ¤H. Vorum, *M.J. Mulvany

150 *Department of Pharmacology, University of Aarhus, 8000 Århus C, #Research Laboratory for Biochemical Pathology, Aarhus Sygehus, 8000 Århus C, §Dept. of Obstetrics and Gynaecology, Aarhus Sygehus, 8200 Aarhus, ¤Department of Medical Biochemistry, University of Aarhus, 8000 Århus C, Denmark The object of this study was to investigate the changes occurring in endothelial cells exposed to 5% hypoxia for 24 hours. The changes in protein expression were studied in primary cultures of human umbilical vein endothelial cells (HUVECs) using proteomics. Hypoxic incubations

were carried out in an airtight chamber flushed with N2 and the O2

concentration was measured continuously using an O2-electrode. Two separate 2D gel experiments (n=5) revealed several identical proteins that were up-regulated. This included Grp78, cyclophilin A, cofilin, calmodulin and tubulin, which has also been confirmed with immunoblotting. Furthermore, immunoblotting showed an up-regulation of other proteins related to Grp78 such as caspase 12 and Grp94. A stabilizer of HIF-1 was also able to up-regulate many of the proteins indicating a role, either direct or indirect, for this transcription factor. Present findings show that hypoxia can induce several changes in primary endothelial cells. The up-regulation of Grp78, Grp94 and caspase12 indicates the presence of ER stress, which is a novel finding. The up- regulation of cofilin and tubulin suggests migration or angiogenesis of the endothelial cells, while the up-regulation of cyclophilin A suggests migration, caspase activation and protein folding. We conclude that hypoxia has direct effects on endothelial cells, effects which may account for some of the vascular changes associated with low oxygen levels.

P17.09 Kristin SIMULTANEOUS DETERMINATION OF 25 INFLAMMATORY Skogstrand MARKERS AND NEUROTROPHINS IN NEONATAL DRIED BLOOD SPOTS BY IMMUNOASSAY xMAP TECHNOLOGY K.Skogstrand, P.Thorsen, B.Nørgaard-Pedersen, D.Schendel, L.Sørensen, D.Hougaard, Serum Institut, Artillerivej 5,84/147, 2300 København S Background: Inflammatory reactions and other events in early life may be part of the etiology of late-onset diseases, including cerebral palsy, autism and type-1 diabetes. Most neonatal screening programs for congenital disorders are based on analysis of dried blood spot samples (DBSS), and stored residual DBSS constitute a valuable resource for research into the etiology of these diseases. The small amount of blood available however confines the number of analytes that can be determined using traditional immunoassay methodology. Methods: A new multiplexed sandwich immunoassays based on flow metric Luminex® xMAP technology. Results: The high capacity 25-plexed multianalyte method determine 23 inflammatory and trophic cytokines, triggering receptor expressed on myeloid cells-1 (TREM-1) and C-reactive protein (CRP) in two 3.2 mm punches from DBSS. It can also be used for determination of 26 cytokines and TREM-1 in serum. The low end of the working range for all 25 analytes covers concentrations found in DBSS from normal newborns. In DBSS routinely collected day 5-7 from 8 newborns with documented inflammatory reactions at birth the method demonstrated

151 significantly changed levels of inflammatory cytokines. Measurements on DBSS stored at -24°C for up till more than 20 years showed that most cytokines are detectable in equal concentrations over time. Conclusion: The method can reliably determine 25 inflammatory markers and growth factors in DBSS. It has a large potential for high capacity analysis of DBSS in epidemiological case-control studies and with further refinements also in neonatal screening. (Skogstrand et.al Clinical Chemistry. 2005;51:1854-1866)

P17.10 Kirstine THE INCIDENCE OF GROWTH HORMONE DEFICIENCY – A Stochholm NATIONWIDE STUDY K. Stochholm, C. Gravholt, T. Laursen, J. S. Christiansen, M. Frydenberg, A. Green Medical Department M, Aarhus Sygehus, NBG, 8000 Aarhus The incidence of Growth Hormone Deficiency (GHD) was estimated in the Denmark using national registries. A cohort of 9,131 patients with a high a priori risk of having GHD was identified. All available hospital files (representing 90.2% of the patients) were traced, and a verification of the diagnosis of GHD was based on a combination of clinical and biochemical definitions. We identified 2,205 patients in total whereof 1823 patients were incident during 1980-1999. The incidence was stable for males and females with CO and AO, but increasing for total CO GHD. Three-hundred-and-three males and 191 females had childhood onset (CO) GHD, 744 males had adult onset (AO) GHD, and 585 females had AO. Significantly more males than females had GHD (both CO and AO GHD, p<0.00002). In three diagnoses males (m) had a significantly higher absolute number of GHD than females (f): non-functioning pituitary adenoma (244 m, 135 f), germinoma (22 m, 5 f), and birth trauma (11 m, 1 f). The higher number of males with GHD in AO has not been described previously. The difference in absolute numbers in the two genders is well known among CO. Assessment of mortality and prevalence in this cohort will be performed.

P18.01 Niels DETECTION OF COLORECTAL NEOPLASIA IN SYMPTOMATIC Christian DANISH OUTPATIENTS WITHOUT VISIBLE RECTAL BLEEDING: Bjerregaard VALIDITY OF FAECAL OCCULT BLOOD TEST Bjerregaard N.C., MD; Tøttrup A., MD, DMsc; Sørensen H.T., PhD, DMSC; Laurberg S.,MD, DMSc. Department of Surgery L, Aarhus Hospital, Aarhus University Hospital. Email: [email protected] The aim of this study was to assess the validity of Hemoccult Sensa® in detecting colorectal neoplasia in symptomatic outpatients without visible rectal bleeding, with no known risk factors for colorectal cancer other than age (low-risk patients), and without visible rectal bleeding. This observational study focused on low-risk patients aged 40 or older referred by general practitioners for symptoms consistent with colorectal cancer. The Hemoccult Sensa® test was performed before endoscopic examination. Colorectal cancer was diagnosed at endoscopy (colonoscopy or flexible sigmoidoscopy) or identified through follow-up using hospital

152 discharge registries. Patients completed a questionnaire about symptoms and signs before their first hospital appointment. Two hundred and fifty-six patients were included. Eight patients were found to have colorectal cancer. Median patient age was 63 years (range 40 – 94 years), and 42.2% were men. The positive predictive value of Hemoccult Sensa® was 10.5% for CRC, 21.1% for significant neoplasia (CRC or an adenoma > 10 mm), 11.8% for adenomas 10 mm or larger, and 19.6% for adenomas of any size. The negative predictive value of Hemoccult Sensa® for colorectal cancer was 99.0%. Sensitivity and specificity of Hemoccult Sensa® for CRC were 75.0% and 79.4%. Hemoccult Sensa® does not appear to be an acceptable alternative to endoscopy as the initial examination in symptomatic low-risk patients without rectal bleeding.

P18.02 Lars REMITTED DEPRESSED PATIENTS, VISUOSPATIAL MEMORY AND Kroløkke CBF IN THE RIGHT HIPPOCAMPUS Hviid L.K.Hviid, P.B.Videbech, B.Ravnkilde, R.Rosenberg Center for Basic Psychiatric Research, Psychiatric Hospital in Aarhus, Skovagervej 2, 8240 Risskov, Denmark We plan to measure regional cerebral blood flow (rCBF) in the right hippocampus of remitted depressed patients during a visuospatial memory activation task. A group of depressed patients have in a previous positron emission tomography (PET) study been assessed to have a significant increased level of rCBF in the right hippocampus whilst in a resting state. In this study we aim to compare the rCBF of: 10 remitted depressed patients that in the previous study displayed high level of rCBF, 10 remitted depressed patients that displayed a low level of rCBF and 10 healthy participants with an average level of rCBF in the right hippocampus during a rest state, while the participants (during PET) perform a visuospatial memory activation task specific for right hippocampus cognitive functioning. All participants will in addition undergo PET rest measurements for baseline assessments, 3-dimensional magnetic resonance imaging (MRI), in order to allow for volumetric assessment, and neuropsychological testing. Neuropsychological testing will serve to rule out potential confounders in terms of cognitive deficits not directly related to right hippocampus functioning. A research plan of the study and preliminary result will be presented at the PH.D. Day. The assessment of the level of rCBF in the right hippocampus of remitted depressed patients is important in terms of evaluating to what extent major depression causes impairment to right hippocampus cognitive functioning, whether the previously observed rCBF is a state or trait of major depression, as well as, giving an indication of prognosis for depressed patients with increased rCBF in the hippocampus beyond their depressive illness.

P18.03 Torsten Satisfaction with Psychosocial Work Conditions and Sickness Absence Munch- Authors: T. Munch-Hansen, M. Rosenkilde, J. Wieclaw, J.P. Bonde Hansen Background: Sickness absence has been shown to be associated with a

153 variety of psychosocial work conditions but cross-sectional design and lack of independent measurement of exposure and outcome precludes causal inference. Objective: To examine sickness absence as a function of satisfaction with psychosocial work conditions in public service-workplaces. Methods: The participants were 1542 employees from 106 different psychiatric care-service-workplaces in the County of Aarhus. The study is part of a larger project including different types of public service- workplaces and several dimensions of the psychosocial work environment. Satisfaction with psychosocial work conditions was rated on a scale from 0 till 10 in surveys administered by the County of Aarhus in February 2005. Measures were used at a work-place level to reduce reporting bias. Average values for the overall satisfaction with psychosocial work conditions and the average number of days of sickness absence during the 6 months around the collection of exposure data were calculated for each workplace- unit. Linear regression was used to perform the analysis. Results: No association was found between the satisfaction with psychosocial work conditions and the proportion of employees who had any cases of sickness-absence. Among those who had been absent we found a 1.30 decrease (β= -1.30 (CI: -2.63 – 0.03)) in the number of sickness absence-days with one-unit increase in satisfaction with psychosocial work. Conclusion: The average level of sickness-absence decreased with increasing satisfaction with the psychosocial work conditions at the workplace-level. However, cautious interpretation is warranted, as the association found is cross-sectional. Subsequent follow-up-analysis will adjust for potential confounders.

P18.04 Thorbjørn H. CANCER REHABILITATION WITH PARTICULAR FOCUS ON THE Mikkelsen PRESENT AND FUTURE ROLE OF GENERAL PRACTICE – RESULTS FROM A QUALITATIVE STUDY. Thorbjørn H. Mikkelsen MSc (soc.) PhD-student. Frede Olesen MD, PhD, Professor, Research Director. Jens Søndergaard, senior researcher, MD, GP, PhD. The Research Unit for General Practice, University of Aarhus, Vennelyst Boulevard 6, 8000 Århus C. Anders Bonde Jensen, consultant, PhD, Department of Oncology, Århus Kommunehospital, Nørrebrogade 44, 8000 Århus C. Rehabilitation is the process of helping a person to achieve the greatest possible physical, psychological, social, educational and vocational performance in relation to impairments, environmental limitations, desires and life plans. Rehabilitation is an essential and integrated part of cancer treatment primarily taking place after hospital treatment when the main medical responsibility again rests with general practice. The aim of this study is: -To investigate to what extent cancer patients are rehabilitated to a well- functioning life - physically, psychologically and socially. -To investigate cancer patients’ and doctors’ evaluation of the rehabilitation process. -To suggest initiatives to improve the rehabilitation process. The research questions are investigated through a combination of

154 qualitative and quantitative methods including focus group interviews and questionnaires. The analysis of the focus group interviews is ongoing. Results from our focus group interviews with patients, general practitioners, oncologists and surgeons regarding their evaluation of the rehabilitation process, including their proposals for improvements will be presented.

P18.05 Lotte Ebdrup DOES ATORVASTATIN AFFECT THE SYSTEMIC INFLAMMATORY RESPONSE SYNDROME (SIRS) ELICITED BY ENDOTOXIN IN PIGS? L. Ebdrup, J. Krog, M. Hokland, E. Toennesen Dept. of Anaesthesiology and Intensive Medicine, Research Lab., Building 1C, 1st floor, Aarhus Hospital, NBG 44, DK-8000 Aarhus C SIRS and sepsis (SIRS + infection) are potentially deleterious conditions, involving an activated immune system. Atorvastatin, a well known cholesterol-lowering agent, has immune modulating effects. We hypothesize, that Atorvastatin given before an endotoxemic insult can modulate the immune response. We estimate the modulation by 1) concentrations of cytokines in plasma and tissue, 2) changes in subtypes of leucocytes in blood, 3) changes in expression of selected adhesion molecules. Finally we hypothesize, that Atorvastatin causes changes in renal clearance. Methods: Pigs (n=24) are randomised to pre-treatment with Atorvastatin 80 mg or placebo for 21 days. To elicit SIRS we use a porcine endotoxemic model based on LPS-infusion under general anaesthesia. Detection of cytokines (IL6, IL8, IL10, TNF ): sandwich immunoassays, Western Blot and immunhistochemistry. Subtyping of leucocytes and detection of adhesion molecules: Multicolour Flowcytometri. Renal clearance hourly: 51Crom EDTA clearance. Results of pilot study (n=6): Endotoxemia elicits a reproducible insult with increasing pulmonary artery pressure, increasing oxygen demand and hypotension. A tendency towards lower values of cytokines in the Atorvastatin treated group is seen. Atorvastatin is well tolerated in pigs.

P18.06 Line Bille DOES TELEMONITORING OF HOME BLOOD PRESSURE IMPROVE Madsen BLOOD PRESSURE CONTROL IN HYPERTENSION? L.B. Madsen, E.B. Pedersen Department of Medical Research, Aarhus University, Holstebro Hospital, 7500 Holstebro, Denmark. Despite available effective antihypertensive treatment only 25% of hypertensive patients have their blood pressure (BP) optimally controlled. Home BP monitoring has been shown to be more reliable than monitoring clinical BP and trials of telemedical home BP monitoring indicate a more effective BP control. The aim of this study is to compare telemedical and conventional BP treatment in regards to effectiveness to control BP, quality of life for the treated patients, and cost-effectiveness. 400 patients with elevated clinical BP (>/= 150/90 mmHg) are recruited by general practitioners. If the patients have an elevated 24-hour

155 ambulatory BP they are randomly allocated to either telemedical or conventional antihypertensive treatment for 26 weeks, after which the 24- hour ambulatory BP is repeated. The change in 24-hour ambulatory BP in the two groups will be compared. Analysis of health-related quality of life is based on the SF-36 questionnaire. Analysis of cost-effectiveness will compare the estimated health care costs in the two groups. If telemonitoring of BP proves to lead to better BP control, provide better quality of life and / or better cost-effectiveness the results may influence future guidelines for management of hypertensive patients.

P18.07 Christian A CLINICAL SCORE SYSTEM FOR MONITORING TB TREATMENT IN A Wejse LOW RESSOURCE SETTING. Christian Wejse (CW), Morten Sodemann (MS), Jens Nielsen (JS), Peter Aaby (PA), Paul Andersen (PA), Per Gustafson (PG) Bandim Health Project, Guinea Bissau (CW, MS, JS, PA, PG). BHP, Statens Serum Institut Copenhagen ((JS, PA) Dep. Infectious Diseases, Malmö, Sweden (MS, PG), Dep. Infectious Diseases, Skejby, Aarhus University Hospital, Denmark (CW, PA). Corresponding author: Christian Wejse, Dep. Inf. Dis, Aarhus University Hospital, Skejby, Brendstrupgaardsvej, 8200 Århus N. E-mail: [email protected] Apart from sputum conversion in initially smear positive patients, there is no gold standard for measuring clinical outcomes in tuberculosis (TB) patients. A score system based on repeatedly measured clinical parameters has been developed and tested in a cohort of 713 tuberculosis patients from Guinea Bissau enrolled in an epidemiological study 1996-2001. A principal component analysis measured which factors were explanatory among chosen clinical variables (at time=0) and was used to generate the score. The score was tested for ability to show change, estimate cure and predict mortality at later clinical visits. Most important factors were: Self reported cough, dyspnoea, chest pain and weight loss and findings of anaemia, abnormal lung stethoscopy, low Body Mass Index and low Middle Upper Arm Circumference. The TBscore was found to be sensitive to change after start of TB treatment, with a similar pattern for HIV positive and HIV negative patients. At 5 months of treatment all initially smear positive patients with smear status were smear negative and thus cured by WHO definitions. Ninety six percent of initially smear positive and 95% of initially smear negative patients had at 5 months a score below 6 points. An initial score above 8 points meant a higher mortality at 8 months follow up (23% vs. 11%, p<0.001). A score of 8 points predicts later mortality with a sensitivity of 0,42, a specificity of 0,77 and a predictive value of 0,23 The TBscore is potentially useful as an outcome measure for patients in clinical trials. The TBscore is a useful supplement to determine cure for TB and to predict mortality.

P18.08 Kim BAYESIAN ESTIMATION OF PERFUSION PARAMETERS BASED ON A Mouridsen PHYSIOLOGICAL MODEL FOR THE VASCULATURE

156 Kim Mouridsen1, Karl Friston2, Louise Gyldensted1, Leif Østergaard1, Stefan Kiebel2. 1Center for Functionally Integrative Neuroscience, Aarhus University Hospital, Denmark. 2Wellcome Department of Imaging Neuroscience, Institute of Neurology, London, UK. Perfusion weighted MRI has proven very useful for deriving haemodynamic parameters such as CBF, CBV and MTT. These quantities are important diagnostic tools, e.g. in acute stroke, where they are used to identify ischemic regions. In this study, we estimate perfusion parameters based on a vascular model specifically representing heterogeneous capillary flow. We use a fully Bayesian approach in order to obtain posterior probability distributions for all parameters. This allows us to perform inference on perfusion parameters at the voxel level, either within or between subjects. We test our algorithm on simulated data as well as data from a healthy subject and a stroke patient. In simulations the estimated CBF values are in excellent agreement with simulated values. Contrary to the traditional singular value decomposition (SVD) method of calculating CBF [Østergaard et. al. MRM 1996], our algorithm does not underestimate high flows. In the healthy subject, the VM CBF map shows good grey/white matter discrimination and high flow components are well reproduced. For the stroke patient the MTT map shows a markedly hyper-intense area corresponding to the ischemic region. The major advantage of our model, compared to the SVD-based approach, is its parameterization in terms of physiological states. This allows us to use existing physiological prior knowledge. Using prior knowledge can increase sensitivity when classifying ischemic tissue. We have demonstrated in simulations that with this model we obtain CBF estimates with negligible bias compared to SVD estimates, and we have shown in clinically acquired MRI data that the model can be used to identify ischemic tissue.

P18.09 Susanna BROAD-RANGE REAL-TIME PCR AND DNA-SEQUENCING FOR THE Deutch DIAGNOSIS OF BACTERIAL MENINGITIS Deutch S, Pedersen L B, Pødenphant L, Olesen R Schmidt M B, Møller J K, Ostergaard L Department of Infectious Diseases, Skejby Hospital, Brendstrupgårdsvej 100, 8200 Aarhus N Rapid etiologic diagnosis of bacterial meningitis is crucial for the early targeting of antimicrobial and adjuvant therapy. Broad-range polymerase chain reaction (PCR) targeting the 16S rRNA gene allows etiologic diagnosis of bacterial meningitis when applied to cerebrospinal fluid (CSF). We assessed the additional diagnostic effect of applying a novel broad-range real-time PCR and subsequent DNA-sequencing to culture, microscopy, and broad-range conventional PCR on CSF in patients with suspected bacterial meningitis. Broad-range conventional PCR and broad-range real-time PCR with subsequent DNA-sequencing were applied to 206 CSF specimens collected consecutively from 203 patients aged six days to 86 years. Patients’ charts were reviewed for clinical information.Seventeen pathogens were identified by PCR and DNA-sequencing or culture. Three specimens were negative by culture but positive by broad-range real-time PCR. Three

157 specimens were positive by culture but negative by broad-range real-time PCR. Compared with culture, the sensitivity of broad-range real-time PCR was 86%, and the specificitiy 98 %. Conventional PCR resulted in a sensitivity of 64% and specificity of 98%. Broad-range real-time PCR was generally comparable to culture of CSF and may be a useful supplement, particularly when antimicrobial therapy has been administered. Broad- range real-time PCR was more sensitive than broad-range conventional PCR and microscopy.

P18.10 Karen DEVELOPMENT OF A CLASSIFICATION AND GRADING SYSTEM FOR Madsen SPONDYLARTHROPTHY WITH MRI . K. Madsen A. Jurik and B. Schiottz-Christensen. Arhus sygehus, Denmark Contact mail : [email protected] The rheumatic disease spondylarthropthy (SpA) is primarily involving the sacroiliac and spinal joints. The classification of SpA is based on bone changes observed on ordinary radiography, meaning destruction of bone and joint has already occurred. It has been proven that changes within the bone and joint can be established earlier by means of MRI, but it has not yet become the golden standard to include this examination in the classification of SpA. The need for early detection and detailed diagnostic imaging of the disease has arisen, as the possibilities for treatment have become more efficient. More over it is important to distinguish between the different subtypes of SpA at an early stage because the treatment differ, and are not always free of side effects. Hypothesis: 1) The types of SpA can be detected at an early stage by means of MRI. 2) The change of sacroiliaca abnormalities over time is related to their appearance and location. 3) A redefined grading system, will give improved monitoring during treatment. Material and method: In our study, 130 participants will have MRI of the sacroiliac joints and the spine, radiographs of the spine. The study group will be examined by the same rheumatologist , to determine the exact SpA diagnosis. Results from these examinations will be compared with examinations made 2-7 years previously. The participants enrolled, will either have participated in a study 7 years ago, or have had an MRI preformed as part of their clinical treatment. The two MRI will be compared and related to the clinical diagnosis. The purpose is to determining the feasibility of MRI to distinguish specific abnormalities for the different subtypes of SpA, depending on stages of the disease. All the MRI will be used to test the validity to further develop the redefined grading system of SpA.

P19.01 Dea Kehler EVALUATION OF THE PREVENTIVE CARDIOVASCULAR CONSULTATION IN GENERAL PRACTICE. D Kehler, Christensen B, Bondo M, Lauritzen T and M Risør. Department of general Practice, University of Aarhus, Denmark. Department of Public Health and Primary Care. Objective: the overall aims of the study are to evaluate the preventive cardio-vascular consultation in general practice with focus on; risk communication, motivation, preferred doctor-patient relationship and

158 patient benefits. Design: Triangulation between qualitative and quantitative methods. Participants: In the qualitative study 20 general practitioners selected strategic and 20 persons with 20 % or higher risk of cardiovascular disease participate from Århus and Vejle county. In the quantitative study 500 general practitioners and 500 patients in risk of cardio-vascular disease will be invited from Århus and Vejle county on the basis of extension from the health insurance register. Methods: Qualitative: Videotaping and individual interviews with the doc-tors and the persons in risk. Quantitative: a questionnaire. Models and conceptions: The following analyse models and conceptions are used to evaluate the preventive cardiovascular consultation in general practi-ce: A. Risk communication by use of risk conceptions and strategies based on Patient-Cente-red Interviewing. B. Motivational interviewing by use of manual for the Motivational inter-viewing Skill Code. C. Use of standards of a good doctor-patient relationship based on PEARLS. D. The participants benefits of the preventive cardiovascular consultation in the light of 4 defined measures. Perspectives: In the light of this study, it will be possible to describe, how general practitioners communicate risk, motivation and which relationship they prefer as a frame in their preventive cardiovascular together with know-ledge about the benefits for the person in risk. The results might be an impor-tant supplement to the development of the preventive consultation in general practice in the future. Furthermore the study might be the basis of a randomi-sed investigation of a preventive cardiovascular program, where specific com-municative strategies together with medical treatment are tested against each other with the aim to help more persons in risk for cardiovascular disease to change their unhealthy lifestyle.

P19.02 Thomas TOPICAL BISPHOSPHONATE TREATMENT INCREASES FIXATION OF Jakobsen IMPLANTS INSERTED WITH BONE COMPACTION. 12 WEEKS CANINE STUDY Jakobsen, T; Kold, S; Elmengaard, B; Bechtold, J; Søballe K Orthopaedic Research lab, Aarhus Hospital, Nørrebrogade 44, building 1A, DK-8000 Aarhus A new bone preparation technique, bone compaction, has shown to increase implant fixation. Bisphosphonate (BP), a potent inhibitor of bone resorption, has shown to increase the amount of bone around implants inserted with the bone compaction technique after four weeks. Even though mechanical implant fixation was not increased after four weeks, it may be that the non-vital bone, due to osteoconductive properties, will increase longer-term implant fixation. Therefore, this study investigated whether topical application of bisphosphonate combined with compaction would improve mechanical implant fixation after 12 weeks. Ten dogs were used in this paired study. Two porous coated titanium implants were inserted in each dog, one in each proximal tibia. The bone was prepared with the compaction technique; by radially enlarging an initial 5.0 mm drill hole to 8.0 mm. Before insertion of the implants, the right cavities were soaked for 1 minute with alendronate solution (BP) and the

159 left cavities with saline (control). The observation period was 12 weeks. Implants were evaluated by biomechanical push-out test and histomorphometry. Topical bisphosphonate treatment resulted in a two-fold improvement of biomechanical implant fixation. Histomorphometrical results are still pending. The improvement in implant fixation after 12 weeks suggests a positive effect of adding topical bisphosphonate to the compaction technique. Histomorphometrical results may enlighten some of the mechanisms behind the increased biomechanical implant fixation.

P19.03 My Svensson OMACOR AS SECONDARY PREVENTION AGAINST CARDIOVASCULAR EVENTS IN PATIENTS UNDERGOING CHRONIC HEMODIALYSIS: A RANDOMISED, PLACEBO CONTROLLED INTERVENTION STUDY M Svensson1 , KA Jorgensen2 , EB Schmidt3 and JH Christensen1on behalf of the OPACH study group 1. Department of Nephrology, Aalborg Hospital, Aarhus University Hospital, Aalborg.2. Department of Renal Medicine C, Skejby Hospital, Aarhus University Hospital, Aarhus3. Department of Preventive Cardiology, Aalborg Hospital, Aarhus University Hospital, Aalborg. Patients with chronic renal failure (CRF) have a high incidence of cardiovascular disease (CVD) and an increased premature mortality. n-3 polyunsaturated fatty acids (n-3 PUFA) are known to have cardioprotective effects in subjects with normal renal function. The aim of the present study was to examine the effect of n-3 PUFA on the incidence of cardiovascular events and death in patients undergoing chronic hemodialysis (HD). Patients were recruited from 11 dialysis wards in Denmark and were eligible for inclusion if they had previously experienced a cardiovascular event and had been treated with HD for a minimum of 6 months. Patients were randomly assigned to treatment with n-3 PUFA (Omacor) or placebo (olive oil) for two years. Compliance was assured by measuring the content of n-3 PUFA in plasma phospholipids. Patients were evaluated with blood samples four times during the study period (0, 3, 12 and 24 months). Primary endpoints were a composite of: 1) acute myocardial infarction, 2) angina pectoris requiring cardiologic intervention, 3) transitory cerebral ischaemia, 4) cerebral infarction, 5) peripheral vascular disease requiring surgical intervention, and 6) death. This is the first randomised, placebo- controlled study of n-3 PUFA as secondary prevention against CVD in patients undergoing chronic HD. The results will have an impact on whether HD patients should be advised to increase their intake of n-3 PUFA.

P19.04 Ljubica ACUTE UPPER LIMB ISCHEMIA AND ATRIAL FIBRILLATION/- Vukelic FLUTTER IN DENMARK FROM 1990 TILL 2002 Andersen Ljubica Vukelic Andersen1, MD, Lars Frost1, MD, PhD, Ole Færgeman1, Professor, dr.med., Jes Lindholt2, MD, PhD, Leif Spange Mortensen3, Chief consultant, MSc Correspondence: Ljubica Vukelic Andersen, Department of Cardiology,

160 Aarhus Sygehus, Aarhus University Hospital, Denmark. tel. +45 8949 7575; fax +45 8949 7619, E-mail: [email protected] There is not much knowledge about acute upper limbs ischemia. The aim of this nationwide study is to up light potential risk factors, prognosis and historical development of incidence of this disease. This is a cohort study and data sources are Medical journals and different Danish national databases. It will generate knowledge, which is necessary for future prophylaxes. The following aspects are considered as most important: a) Incidence of acute upper limb ischemia in the Danish population. b) An analysis of the importance of sex, age, co-morbidity and anticoagulation therapy as prophylaxis for development of upper limb ischemia among patients with atrial fibrillation/-flutter. c) An analysis of prognosis (survival, stroke, arm amputation) after surgery demanding upper limb ischemia. d) Seasonal variation in the occurrence of acute occlusion of artery in upper limb. e) Validating of the medical database The Danish National Vascular Registry (KarBasen), a quality control in Danish vascular surgery.

P19.05 Rie Stokholm BONE REACTION AROUND IMMEDIATE LOADED IMPLANTS – ANIMAL EXPERIMENTAL STUDY R. Stokholm, F. Isidor, J. Nyengaard Department of Prosthetic Dentistry, School of Dentistry, University of Aarhus, Vennelyst Boulevard 9, 8000 Aarhus C, Denmark The aim of the study is to compare the clinical, radiographic and histological bone reaction around immediate and delayed loaded single tooth implants in the lower jaw of monkeys. The study is carried out on six monkeys (Macaca Fascicularis). Firstly, one premolar and one molar were extracted in both sides of the lower jaw. Three months later two implants were inserted in the tooth-less area in the one side of the lower jaw. One of the implants was submerged the other one was provided with a composite crown. After three months of healing, the submerged implant was provided with a composite crown. The crown was in occlusion, but without supra-contact. At the same time two implants are inserted in the other side of the lower jaw. The one is submerged and the other one is provided with a composite crown. Once a week the implants were cleaned. Radiological examinations were performed at baseline i.e. when the implants were inserted, and then every third month. After 6 months of healing of the first inserted implants, the animals were sacrificed. Tissue blocks containing the implants were removed and approximately 50 Φm thick slides of the implants and surrounding tissues from the buccal aspect and in the long axis of the implants were made. A minimum of two sections through the mid-portion of the proximal surfaces are available. At present the histological evaluation is carried out and the main parameters are: bone-to-implant contact and bone density (i.e. the proportion of mineralized bone tissue from the implant surface and to a distance of 1 mm lateral to this surface).

161 All implants osseointegrated and none were lost during the study period.

P19.06 Søren THE EFFECT OF SLEEP ON NOCTURNAL URINE OUTPUT Hagstrøm Hagstroem S, Kamperis K, Rittig S, Radvanska E, Djurhuus J C. Clinical Institute, University of Aarhus. The aim was to elucidate the impact of sleep on the quantity and quality of the nocturnal urine production in healthy individuals. 20 healthy volunteers were admitted in the hospital for two 24-hour periods under standardized conditions. Blood samples taken every 3 hours and urine was fractionally collected. During 1 of the 2 periods subjects were deprived from sleep and the sequence was randomized. During nights participants were in a lying position in a dimly lit room and physical activities, food and fluid intake were not allowed. Electrolytes, creatinine, urea, osmolarity and Arginine vasopressin (AVP) were measured in plasma and urine. Blood pressure and heart rate were monitored. Prostaglandin E2 (PGE2) and 6-sulfatoxy-melatonin (MEL) was measured in urine. Clearances, excretions and fractional excretions were calculated for electrolytes, creatinine, urea, osmoles and solute free water. The circadian rhythm of AVP, PGE2 and MEL was evaluated at baseline and during sleep deprivation. No significant differences were found in the urinary production at daytime between the two 24-h periods. During night time and on the nights of sleep deprivation, both males and females produced markedly larger amounts of urine. A similar effect was found for the urinary excretion of sodium, potassium and urine osmolality. The circadian rhythm in AVP was not influenced by sleep deprivation. In accordance with this, solute free water reabsorption was not significantly different between nights. A significant correlation between hemodynamics and the degree of nocturnal polyuria following sleep deprivation was seen. Concluding message. Sleep seems to be a major regulator of urine production at night and its deprivation leads to natriuresis, kaliuresis and the production of excess amounts of urine. Altered hemodynamics induced by the deprivation of sleep, seem partly responsible for these processes.

P19.07 Jesper MINIMAL RESIDUAL CORE BINDING FACTOR AMLS BY REAL TIME Stentoft QUANTITATIVE PCR – INITIAL RESPONSE TO CHEMOTHERAPY PREDICTS EVENT FREE SURVIVAL AND CLOSE MONITORING OF PERIPHERAL BLOOD UNRAVELS THE KINETICS OF RELAPSE J. Stentoft, MD, P. Hokland, MD, PhD, M. Østergaard, MSci, PhD, H. Hasle, MD, PhD, and C. G. Nyvold, MSci, PhD. Depts.of Haematology and Paediatrics, Aarhus University Hospital. Minimal residual disease (MRD) detection in core binding factor (CBF) AMLs by RQ-PCR has shown great promise, but crucial basic and translational issues remain unresolved. Objectives: to 1) elucidate key methodological issues (use of blood (PB) v. bone marrow (BM); assay sensitivities during treatment); 2) assess clinical correlates (prognostic significance of post-induction MRD levels; detailed kinetics of relapse). Material and methods: 24 patients (11 AML1/ETO, 13 CBF /MYH11)

162 analysed at diagnosis, after induction chemotherapy, and at subsequent visits. Results: Median detection limits were 1:50.000 (range 1:400.000 to 1:3.000) for AML1/ETO and 1:10.000 (range 125.000 to 1.000) for CBF /MYH11. In 64/103 samples MRD was detectable and highly correlated in PB and BM. In 38/103 samples, where MRD was only detectable in BM, median BM MRD was 3.5 log lower than at diagnosis. Event free survival (EFS) was inferior in case of post-induction MRD < 2 log reduction (hazard ratio = 8.6, p< 0.01). Persistent MRD was always followed by haematological relapse. Molecular progression rate in relapsing CBF /MYH11 cases was surprisingly slow (one log increase/100 days) with a time lag from molecular to haematological relapse approaching 1 year. Conclusion: In CBF AMLs RQ-PCR is a powerful tool for clinical decision-making and for unravelling the biology of relapse.

P19.08 Louise A ROLE FOR TOLL-LIKE RECEPTOR (TLR)-2 AND -9 IN ANTIVIRAL Sørensen IMMUNITY AGAINST HERPES SIMPLEX VIRUS. Louise N. Sørensen og Søren R. Paludan Department of Medical Microbiology and Immunology, University of Aarhus, DK-8000 Aarhus C., Denmark The development of immunological memory and immunity is crucial for defence against many pathogens. However, much is still unknown about which mechanisms control the differentiation of T-cells towards memory T cells. Toll-like receptors (TLRs) is one class of pathogen recognition receptors (PRRs) recognizing different pathogen-associated molecular patterns (PAMPs) thereby detecting pathogens. So far 13 different TLRs have been identified, expressed mainly on dendritic cells and macrophages, and TLRs have been shown to play an important role in initiating the innate immune response and subsequently the adaptive immune response toward different pathogens. Recently, a role for TLRs in development of immunological memory has been described, implicating IL-6 and other soluble factors as important for T cell memory differentiation. We are examining the development of immunity towards a generalized herpes simplex virus (HSV) infection in mice. Immunization with an attenuated HSV-strain induces immunity against HSV-2 in wildtype C57bl/6 mice. TLRs 2 and 9 have been shown to be recognition molecules for different herpesviruses and the induction and maintenance of immunity in TLR 2 and 9-deficient mice will be investigated. Furthermore, the role of TLR 2 and 9 and their ligands in T cell function and differentiation will be examined.

P19.09 Martin C. CYCLOSPORINE TREATMENT IS ASSOCIATED WITH INCREASED - Sassen ENAC EXPRESSION AND SODIUM RETENTION IN RATS Martin C. Sassen1, Soo Wan Kim1, Mark A. Knepper2, Jørgen Frøkiær1, and Søren Nielsen1 1The Water and Salt Research Center, University of Aarhus, DK-8000 Aarhus C, Denmark; 2LKEM, NHLBI, NIH, Bethesda, Maryland 20892, USA Cyclosporine (CsA) treatment is known to be associated with sodium

163 retention and salt-dependent hypertension. We hypothesize that dysregulation of the epithelial sodium channel (ENaC) and/or renal sodium (co)transporters may be responsible for sodium retention associated with CsA treatment. Male Wistar rats were treated with CsA (15 mg/kg/d s.c., n=7) for two weeks; controls (n=7) received vehicle only. The expression of ENaC subunits and sodium (co)transporters was determined by immunoblotting and immunocytochemistry. Water and food/sodium intake was identical in both groups. Urinary sodium excretion (0.48.±0.08 vs. 1.12±0.07 mmol/d in controls, p<0.01), fractional excretion of sodium (0.27±0.03 vs. 0.55±0.02 % in controls, p<0.01) and urinary Na/K ratio (0.17±0.02 vs. 0.3±0.01 in controls, p<0.01) were significantly decreased, whereas creatinine clearance, urinary potassium excretion, plasma sodium, plasma potassium, and plasma aldosterone levels were unchanged in CsA- treated compared to control rats. Moreover, CsA treatment dramatically increased urinary magnesium and calcium excretion. Immunoblotting revealed a significant upregulation of -ENaC in cortex/outer stripe of outer medulla (CTX/OSOM) (124±7 vs. 100±5 % in controls, p<0.05), whereas the abundance of - and -ENaC remained unchanged. Immunocytochemistry confirmed the increase in -ENaC, and moreover revealed labeling of apical plasma membrane domains of all ENaC subunits with no overall change in the subcellular localization between CsA-treated and control rats. Immunoblotting and immunocytochemistry revealed that the expression of the thiazide-sensitive Na-Cl cotransporter (NCC) was markedly decreased in CTX/OSOM (54±3 vs. 100±9 % in controls, p<0.01), whereas the protein expression of the Na-K-2Cl cotransporter NKCC2, the type 3 Na+/H+ exchanger and the -1 subunit of the Na-K-ATPase remained unchanged. In conclusion, the results suggest that the upregulation of - ENaC contributes to sodium retention associated with CsA treatment. In contrast, proximal tubule and thick ascending limb sodium transporters are not upregulated in abundance and are therefore unlikely to be involved in the decreased urinary sodium excretion. The downregulation of NCC may play a compensatory role to promote sodium excretion in CsA-treated rats. Key words: ENaC, sodium retention, cyclosporine

P19.10 Anders STRESS AND ANTIDEPRESSANT RESISTANCE IN THE CHRONIC MILD Bergström STRESS ANIMAL MODEL OF DEPRESSION A.Bergström1, A.Mørk2, O.Wiborg1. 1Dept. of Biological Psychitry, Psychiatric Hospital, Aarhus. 2Dept. of Psychopharmacology, H. Lundbeck A/S, Copenhagen. Correspondance to [email protected] The goal of this ph.d.-project is to examine the correlation between stress, depression and regulation of the Hypothalamic-Pituitary-Adrenocortical (HPA) axis using a respected and validated rodent model known as the Chronic Mild Stress (CMS) model of depression. This model allows for analysis of mechanisms of antidepressant drug resistance and mechanisms of resistance to stress i.e. resilience, focusing on changes in gene expression leves (mRNA). Microarray analysis of total rat hippocampus with Affymetrix gene chips have revealed 16 mRNA sequences to be differentially (more than 2-fold

164 change in expression level) regulated between the antidepressant responding and antidepressant non-responding animals. However, RT-PCR could only verify some of these sequences. Moreover, 156 genes/sequences were more than 2-fold differentially regulated between the stressed and resilient animals in the microarray study. Real-Time RT-PCR on total hypothalamus revealed the mRNA of 4 genes with relevance to regulation of the HPA-axis to be differentially regulated between stress and control animals. No genes were found to be differentially regulated with respect to either of the two resistance phenomena discussed above. Currently, in situ hybrididation is being performed on whole brain sections to examine possible molecular mecahnisms of stress resilience in paraventricular nucleus, ventral hippocampus and the nuclues accumbens. These are all areas of the brain of interest in the etiology of unipolar depression. A set of oligonucleotide probes was selected based on literature and relevance to depression and regulation of the HPA-axis.

P20.01 Puk PREDICTION OF PRETERM BIRTH Sandager P. Sandager, I. Vogel, T.B. Henriksen, P. Thorsen, N. Uldbjerg. Department of Obstetrics and Gynaecology, Aarhus University Hospital, DK-8200 Aarhus N. Background: Preterm birth occurs in about 7% of all pregnancies and in about 5% of singleton pregnancies in Denmark, and is the leading course of perinatal morbidity and death. Despite intensive research it is still not possible to identify women at high risk of preterm birth, but previously studies have identified several individual risk factors or biological markers for preterm birth. Objective: The aim of the study is to evaluate the ability of a combination of biomarkers and risk factors to predict preterm birth. Study design: A prospective cohort study based on a study population of 1.100 women with singleton pregnancies. Methods: Serum samples were obtained twice, at gestational weeks 12 and 19. In week 19 a sample of vaginal fluid and a urine sample were furthermore obtained, as well as a transvaginal ultrasound examination to determine the length of cervix. Anamnesis (previous pregnancy history, information about demography and daily habits) were obtained from questionnaire in early pregnancy. Serum and vaginal fluid samples will be analysed for a range of cytokines using luminex multiplex technology, and additionally serum samples for the hormone relaxin. Results: In the cohort 4.7% of the women have delivered preterm (before 37+0 weeks gestation). Samples will be analysed in December 2005. Conclusion: We anticipate creating a prediction model for preterm birth subsequently to be tested in other cohorts.

P20.02 Frederikke EVALUATION OF THE SUBTHALAMIC CONNECTIVITY IN THE Rosendal GÖTTINGEN MINIPIG AND APPLAYING DIFFUSION TENSOR IMAGING TO THE MINIPIG MODEL. SPECIAL EMPHASIS ON PARKINSON DISEASE.

165 F.Rosendal, C.R. Bjarkam, K.Østergaard and J.C.Sørensen CENSE, Department of Neurosurgery, 8000, Aarhus University Hospital. Denmark. The subthalamic nucleus is a functionally important structure of the basal ganglia modulating basal ganglia output. The exact mechanism of action is unknown, but there is consensus among scientists, that the STN is disinhibited and becomes hyperactive with loss of dopamine action, seen in Parkinson disease. STN is likewise an essential structure in surgical treatment for Parkinson disease, deep brain stimulation as the electrode is placed herein. Currently a valid, affordable and ethically acceptable animal model is lacking. We are currently establishing a porcine model of subthalamic DBS in Göttingen minipigs. However, data about the STN connectivity, supposed to play a key role in PD are still lacking. Though STN is clearly seen and well defined in histological preparations from the minipig brain, it has not yet been possible to visualize it using the available neuroimaging techniques. This renders the coordinate calculation, essential for stereotactic surgery on the nucleus, complicated and the coordinates imprecise. Various magnetic resonance imaging sequences, such as T2*- weighted gradient-echo images and diffusion weighed images of the brain are currently not available in the minipig due to artifacts from the adjacent air filled sinuses. The occurrence of image distortions and signal losses is caused by susceptibility artifacts at air/tissue interfaces. Aims. To determine the afferent and efferent connections between the STN and other components of the basal ganglia and the sensor motor cerebral cortex in the model. To apply MRI Diffusion Tensor Imaging to the minipig model, finding a solution to the air artefact problem. If MRI data of good quality are obtained, we will apply fibre-tracking algorithms to the diffusion tensors may visualize well-known fibre tracts surrounding the STN. Thereby STN will be delineated. Visualizing STN will enable significantly more reliable calculation of coordinates for stereotactic surgery on the STN in the minipig model.

P20.03 Martin Cysteine 138 mutation in HIV-1 Nef from patients with delayed disease Tolstrup progression. Tolstrup, M.1,2, Laursen, AL.1, Gerstoft, J3., Pedersen, FS.2,4*, Ostergaard L.1, and Duch, M2 1) Department of Infectious Disease, Skejby Hospital, DK-8200 Aarhus. 2)Department of Molecular Biology, University of Aarhus, DK-8000 Aarhus. 3 Department of Epidemiology, Rigshospitalet, DK-2100 Copenhagen 4)Department of Medical Microbiology and Immunology, University of Aarhus, DK-8000 Aarhus. Background: The nef gene of the primate lentiviruses has been studied extensively because of the multiple immunsuppressive and replicative effects exerted by this gene. Patient studies have revealed important virulence capacities of the gene and the role of Nef is a vital aspect of HIV pathogenesis. We set out to assess the polymorphism in the nef gene in Danish patients.

166 Methods: We have established a patient cohort of long term non- progressors (LTNP) -14 patients with well controlled HIV-1 infections (median infected time 15.3 year) with a stable CD4+ cell count (median count in 2004: 571; median decline (1997-2004) 17.4 CD4+ cells/year). As a control group 15 patients randomly chosen from the out-clinic were included and the nef gene was amplified. Results: The patients in the LTNP cohort were stratified according to the CD4 cell decline over a 7-years period from 1997-2004. The results revealed 4 patients with a T138C mutation previously reported to confer decreased replicative capacities in cell culture settings. None of the patients in the control group harbored the T138C mutation. A search in GeneBank of nef sequences containing the cysteine mutation gave multiple hits. Selecting solely sequences that contained a description of patient disease status, the data revealed a high prevalence of T138C among AIDS patients with a long asymptotic infection history.

P20.04 Lise PAIN THRESHOLDS DURING AND AFTER TREATMENT OF SEVERE Gormsen DEPRESSION WITH ELECTROCONVULSIVE THERAPY Gormsen,L., Ribe,A.R., Raun,P,Rosenberg,R.,Videbech,P., Vestergaard,P., Bach, F.W., Jensen,T.S. Danish Pain Research Centre, Aarhus University, Noerrebrogade 44, 1A, 8000 Aarhus C, Denmark. Background: Pain and depression are often associated. This association may be the result of disturbances in common neurotransmitter systems e.g. the monoamines in the brain and spinal cord. Aim of the Study:Determination of the association between pain parameters and depression. Materials and Methods: Depressed patients with a Hamilton depression score > 18 were included from Aarhus University Hospital of Psychiatry. The patient’s reaction time was measured. Subsequently pain perception thresholds and pain tolerance thresholds were measured with pressure algometry. Furthermore pain tolerance threshold to the Cold Pressure Test by exposure to ice-water was performed. Patients were examined when electroconvulsive therapy (ECT) for depression were initiated and after recovery. The patients were gender and age matched with non-depressed control persons. Results: While ECT significantly improved Hamilton Depression Scale (from mean 23.9 (SD:5.7) to mean 12.5 (SD:5.7)) there was no significant change in pain thresholds during and after ECT in the patient group. However, depressed patients had significantly lower pain tolerance in the Cold Pressor Test on both examinations and on pressure pain tolerance on the second examination day than their corresponding control subjects. Conclusion: The differential effect of ECT on depression score and pain procession indicate that mood and noxious procession are not medicated directly by the same systems but that a complex relationship between pain and depression exist. Reference: European Journal of pain 8 (2004) 487-493.

P20.05 Mikkel LIMBAL CORNEAL STEM CELL INSUFFICIENCY- CLINICAL AND Lyngholm EXPERIMENTAL STUDIES.

167 M. Lyngholm, H. Vorum, K Nielsen, N. Ehlers. Department of Ophthalmology,University of Aarhus,8000C, Denmark. The cornea is covered by 5-7 layers of non-keratinising squamous epithelium, which are continuously being regenerated. The cell division takes place basally in the epithelium, predominantly at the limbal cornea. Researchers agree that a corneal epithelial stem cell exists, and for decades they have tried to identify a protein marker for the corneal epithelium stem cell. Many proteins have been analysed, but so far no specific marker has been found. Clinically the discovery of a stem cell marker would be most welcome. The stem cell could subsequently be identified and isolated, and the cultivated pure stem cells used for treating patients with stem cell insufficiencies including alkali burns, ocular pemphigoid, Stevens Johnson’s syndrome, aniridia etc. The purpose of this PhD-study is to select and identify corneal epithelial proteins isolated from both the limbal and the central region of the human cornea. This will be done using the latest proteomic technology (2-dimensional gel electrophoresis combined with protein identification by mass spectrometry). We will use tissue from the Cornea Bank, Department of Ophthalmology Aarhus University Hospital and tissue from eyes removed following severe of trauma or desease in the posterior pole. The differential expression of proteins in tissue from the limbal and the central part of the cornea are potential candidates for markers or antimarkers (i.e. a protein not expressed in the stem cells) of the limbal stem cell. We will attempt to separate the stem cells from the other epithelial cells using a fluorescence-activated cell sorter (FACS) or a magnetic activated cell sorter (MACS). To test the clinical correlation, the expression of these marker proteins will be examined in corneal biopsies from patients with stem cell insufficiency. The marker proteins will then be quantified using corneal epithelial stem cell cultures produced in international laboratories.

P20.06 Jakob EXPRESSION OF PROTEIN QUALITY CONTROL GENES IN CELL Hansen MODELS OF SPASTIC PARAPLEGIA. J. Hansen, T.J Corydon, N. Gregersen, and P. Bross. Research Unit for Molecular Medicine, University of Aarhus Faculty of Health Sciences, Skejby Sygehus, Brendstrupgaardsvej, 8200Aarhus N. Hereditary Spastic Paraplegia (HSP) causes a progressive weakness and spasticity of the lower limbs mediated by death of specific motor neurons in the central nervous system. Two HSP causative genes (Hsp60 and paraplegin) encode proteins localised in mitochondria. The Hsp60 protein is a highly expressed and essential protein whose fundamental role is to assist and supervise folding of mitochondrial matrix proteins. Hsp60 is a part of a network of chaperones, proteases, and other co-factors, entitled the protein quality control system, that promotes correct folding, inhibits protein aggregation and eliminates proteins that fail to fold correctly. We have the hypothesis that the disease-associated variant Hsp60(V72I) has functional deficits resulting in increased accumulation of misfolded proteins and mitochondrial dysfunction. In this project we have investigated if the expression levels of mitochondrial chaperones and proteases are up-regulated in order to

168 compensate Hsp60(V72I) mediated mitochondrial dysfunction in patient cells. We have measured the mRNA levels in cultured lymphoblastoid and fibroblast cells from spastic paraplegia patients and from control persons by quantitative RT-PCR. Our data indicate that the patient cells have a significantly decreased expression level of the proteases Lon and ClpP whereas the expression of all other mitochondrial chaperones and proteases are similar to the levels detected in control cells. In conclusion, we were unable to detect a compensatory up-regulation of genes encoding the chaperones and proteases involved in handling of misfolded mitochondrial proteins, but instead we observed a decreased expression level of two mitochondrial proteases.

P20.07 Sanne Angel TO GET ON WITH YOUR LIFE AFTER A MAJOR CHANGE. A QUALITATIVE STUDY OF HOW THE SPINAL CORD INJURY PATIENT RECREATE MEANING DURING THE LONG REHABILITATION PERIOD TOWARDS A CHANGED LIFE Sanne Angel. Afdeling for Sygeplejevidenskab. Institut for Folkesundhed. Det Sundhedsvidenskabelige Fakultet. Aarhus Universitet. Høegh-Guldbergsgade 6A. 8000 Århus C. A traumatic spinal cord injury change life suddenly. Often there are persistent negative consequences. The patients are in a very vulnerable situation. Nevertheless it is necessary that they actively take part in the rehabilitation process. The purpose is to investigate the patients´ experiences of the process they are going through in order to understand how the patients get on with their life and how it best can be facilitated by the rehabilitation team. The approach is narrative inspired by Paul Ricoeur. About 12 patients with a spinal cord injury after an accident where the injury is expected to result in a handicap. The method is qualitative, longitude and combine field observation and interviews: Field observation in about 5 days, where the patient is followed in the different situation during day and night. Interviews 6 times during the first year after the accident where I ask the patient to tell about his/ hers situation.The analysis has three steps: Naive reading, structure analysis, where themes and patterns are led out and then critical interpreted. The study has been running since 1.th.of Marts 2005 and there are no results yet. Knowledge about the process the patient are going through with focus on how the patient get on with his/ her life support/ guide nurses and other healthcare professionals in adjusting their support to the patient.

P20.08 Per PARKINSON’S DISEASE: CEREBRAL METABOLISM EVALUAED BY [15O] Borghammer OXYGEN AND [15O] WATER POSITRON EMISSION TOMOGRAPHY (PET). Albert Gjedde, Karen Østergaard, Paul Cumming CFIN, Aarhus University Hospital, Nørrebogade 44, bygn.30, 8000, Århus C Background: Parkinson’s disease (PD) has a complex aetiology and it is getting increasingly clear that disturbances in cerebral metabolism plays a

169 significant part in the pathogenesis. Nevertheless only few brain imaging studies on cerebral metabolism has recently been conducted. Since the development of neuroprotective drugs for PD has become the focus of much attention, we wish to examine the cerebral metabolism in the brain of patients with early PD, as they would be the target population for neuroprotective therapies. Methods: We mapped the Cerebral Blood Flow (CBF) and Cerebral

Metabolic Rate of Oxygen (CMRO2) using PET in 10 early PD patients and 16 healthy age-matched controls. Findings: The preliminary analysis shows hyperactivity in the Globus Pallidus internus (GPi) and mesencephalon in the patients on the oxygen scans but not on the waterscans. Moreover, there was asymmetry in the thalami with hyperactivity on the less lesioned side. Discussion: Although it is a well-established fact that PD patients show hyperactivity in the GPi and in mesencephalic structures it has not been shown before using PET techniques measuring oxygen consumption. There was no concurrent rise in CBF in these structures which suggests a possible dissociation between bloodflow increase and oxygen consumption (extraction fraction increase) The mesencephalic hyperactivity could be an interesting target for neuroprotective treatment, using drugs that decrease hyperactivity and thereby prevent formation of toxic oxygen radicals.

P20.09 Henrik REAL-TIME CORRECTION OF RESPIRATORY MOTION FOR Pedersen IMPROVING MR MYOCARDIAL PERFUSION IMAGING H. Pedersen, S. Ringgaard, W.Y. Kim MR Research Centre, Skejby Sygehus, Aarhus University Hospital, 8200 Aarhus N, Denmark. Time-series of magnetic resonance (MR) images acquired during injection of a contrast agent can be used for assessment of myocardial perfusion. However, respiratory induced motion of the heart occurring during the data acquisition results in gross image misalignments, which severely limits methods of myocardial perfusion quantification. Thus, it becomes imperative to correct the misalignments of the images prior to their use for quantification. Conventionally, this procedure is carried out manually which is both tedious and time-consuming due to the relatively large number of images involved (typically 300-400). Therefore, the purpose of this study was to develop a fully automated method of respiratory motion correction. The implemented approach uses real-time slice-following to position each imaging slice according to the respiratory induced displacement of the heart, as determined by a preceding navigator echo (which monitors the motion of the diaphragm). For optimum prediction of the motion the underlying motion model is calibrated to each individual patient by means of a short free-breathing calibration scan. The efficiency of the strategy was evaluated in 8 normal subjects and 2 patients with stable angina pectoris undergoing MR myocardial perfusion examinations. Residual left ventricular in-plane misalignments were reduced from 2.5±0.8mm to 0.7±0.3mm (mean±SD) as compared to the non-corrected images. This reduction is sufficient to give the desired decrease in signal

170 variability that produces reliable perfusion measurements. In addition, since the approach is fully automated, conventional manual motion correction can be avoided. This will reduce the total duration and cost of these examinations considerably.

P20.10 Vibeke THE EFFECT OF ERYTHROPOIETIN ON WOUND HEALING Koudahl Vibeke Koudahl Clinical Institute, University of Aarhus, Brendstrupgaardsvej 100, 8200 Aarhus N, Denmark Although originally identified for its role in erythropoiesis Erythropoietin is now known to be a multifunctional cytokine and is related to cytokines concerned with growth and inflammation. Erythropoietin is involved in the process of neo-vascularization, where Erythropoietin has been shown to have a positive effect on angiogenesis and erythropoietin is able to mobilize endothelial progenitor cells from the bone marrow to sites of neo-vascularization, where they participate in the formation of new vessels. Furthermore Erythropoietin has an effect on formation of granulation tissue. It is the hypothesis of this study, that erythropoietin has a positive effect on wound healing. The effect of erythropoietin on wound healing will be evaluated in two experimental models: The Hairless-Mouse-Ear-Wound model and the ePTFE model. In the Hairless-Mouse-Ear-Wound model epitheliazation and neo- vascularization of a wound is followed by microscopy until wound healing is complete providing information on healing time. In the ePTFE-model a porous tube is implanted subcutaneously allowing in-growth of granulation tissue. After 18 days the tubes are removed and the amount of granulation tissue and content of hydroxyproline is determined. Results are not yet available.

P21.01 Jesper REGULARIZATION OF DIFFUSION TENSOR FIELDS Frandsen J. Frandsen1, A. Hobolth2, E. B. Jensen3, P. Vestergaard-Poulsen1, L. Østergaard1. 1Centre for Functionally Integrative Neuroscience, Aarhus University Hospital, Denmark. 2Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark, 3Laboratory for Computational Stochastics, Aarhus University, Aarhus, Denmark. The integrity and course of white matter fibre tracts is of key importance in understanding the structural basis of functional integration of cortical centres in complex cognitive tasks. Due to the inherent noise of MR diffusion measurements the direction and size of diffusion tensor may be inaccurate, leading to erroneous results in terms of the derived white matter fibre paths. Regularization of the tensor field using all information stored in the diffusion tensor can potentially improve the fibre tracking in areas with low anisotropy due to e.g. crossing white matter fibre bundles. We used a Bayesian approach to combine the observation model and the a

171 priori knowledge (low curvature of axonal fibres) to give an a posteriori density. Simulating from the posterior density using Markov Chain Monte Carlo methodology produces a regularized field of MRI tensors. After regularization, the eigensystem was calculated from the tensor using diagonalization. The regularization method proved stable, converged rapidly while tested in human as well as synthetic data (a torus model resembling curving fibre bundles in isotropic tissue). Our test showed no tendency for the algorithm to “over-regularize”, i.e. discard small fibre structures. We have shown that regularizing the field of diffusion tensors provides an effective noise reduction in DTI data and preliminary results indicate that directional information even in smaller well-defined bundles is retained. Furthermore we believe this will be a valuable tool in the work of creating a gold standard for fibre tracking.

P21.02 Ole PRESENTATION OF THE WESTERN DANISH SEXUAL ASSAULT Ingemann CENTER Hansen O. Ingemann-Hansen, A. Vesterby, M. Knudsen, A. Elklit, O. Brink Institute of Forensic Medicine, University of Aarhus, Peder Sabroes Gade 15, 8000 Aarhus C, Denmark. November 1999 the first Center for (adult) Victims of Sexual Assault in Denmark opened in the town of Aarhus in cooperation with the Aarhus County’s Health Service, Aarhus University Hospital, the police and the Institute of Forensic Medicine, University of Aarhus. The Center is located at the emergency department, open 24-hours a day and no referral is needed nor police notification. The victim can talk to specially trained nurses and get a medical examination with collection of forensic evidence performed by a specially trained physician. The day after the acute treatment and crisis care a psychologist will contact the victim. At the moment the victims are offered follow-up by the psychologist, at the department of gynaecology or by their own general practitioner. The Center covers an area of 890.000 people. From 1999 to 2004 the Center received 523 victims. 330 (63%) were seen by the physician - the others were taken care of by the nurses and/or the psychologist. 256 victims examined by the physicians were reported to the police (78%). The Aarhus Center is now well established, and there is an excellent cooperation in the region between the Center and the affiliated partners: the police, the forensic scientists, the department of gynaecology, the county’s general practitioners and the university institutes of psychology and forensic medicine. The prevention of sexual assault is a difficult issue, but the fact that half the cases happens in privacy or at work, and that only 25% of the assailants are not previously known by the victims could indicate, that information to both females and males not to bring themselves in precariously situations might be the right implement.

P21.03 Jacob A METHOD TO EXPERIMENTALLY INDUCE SOLITARY LOBE Koefoed- ATELECTASIS.

172 Nielsen Jacob Koefoed-Nielsen, Jonas Nielsen, Lars Kjærsgaard Hansen, Erik Sloth , Per Lambert , Søren Lunde, Anders Larsson. Dept. Anaesthesia & Intensive Care, Aalborg hospital, Aarhus Universityhospital, Denmark. E-mail:[email protected] .dk Background: Solitary collapse of a lobe, e.g., the left lower lobe is common after cardiac surgery. It has been difficult to experimentally study therapeutic interventions for lobar atelectasis due to lack of suitable animal models. The aim of this study was therefore to develop a reproducible model of lobar atelectasis in pigs. Methods: Ten anesthetized pigs were intubated and ventilated. A bronchial blocker (Cook C-AEBS-7.0) was inserted in the right lower lobe (about 50 cm from the ET-tube opening) by the use of a fiberoptic bronchoscope. End-expiratory lung volume (EELV), quasistatic compliance of the respiratory system (Crs) were measured and blood gases (mixed venous and arterial) were obtained. The balloon of the bronchial blocker was inflated, the air of the isolated lobe exsufflated and measured (“lobe volume”). The lobe was selectively lavaged with 37 C saline. EELV, Crs and blood gases were obtained. CT thorax was done in one pig and another pig was thoracotomized. Results: The “lobe volume” was 66±21 ml. Before lavage After lavage p EELV (ml) 886±170 698±166 p<0.002

PaO2 (mm 76±9 40±14 p< 0.004 Crs 32±6 22±7 p<0.002 All results is mean±SD. Both CT and the inspection of the lung showed atelectasis of the right lower lobe. Conclusion: A reproducible experimental lobe atelectasis can be obtained by selective lobe lavage in pigs. This method may be used experimentally for studying methods treating atelectasis.

P21.04 Anelia OCCUPATIONAL PSYCHIATRY: Larsen MENTAL DDISORDERS IN A DANISH WORKING POPULATION Anelia Larsen Enheden for Psykiatrisk Forskning, Aalborg Psykiatriske Sygehus, Mølleparkvej 10, 9000 Aalborg Background. Approx. 10% of a working population experience minor, usually mixed anxiety and depression. Screening for psychiatric morbidity often shows methodological weaknesses. Aim. To estimate the prevalence of psychiatric morbidity within a working population in Denmark. Method. A cross-sectional multicentre study utilizing a two-phase design was carried out in two counties in Denmark Feb 2002 - Nov 2004. Ten enterprises within private and public sectors were included. At step one a questionnaire was administrated to 1500 employees aged 18+. At step two a Present State Examination (PSE) interview was conducted with selected respondents according to their scores on SCL-90-R (screening for psychopathology) and CAGE(screening for alcohol problems). Diagnoses were given based on PSE ratings. Results. 975 (65%) employees responded. SCL-90-R and CAGE screening:

173 26,7% scored above GSI cut-off 1,00 and/ or subscale cut-off 1,25 and/or above threshold on CAGE. 188(19%)PSE interviews were conducted; 77 respondents fulfilled diagnostic criteria for depression or anxiety. Conclusion. The presence of symptoms and diagnoses is remarkably high among people active on the Danish labour market.

P21.05 Malene IDENTIFICATION OF NEW TRANSCRIPTIONAL CORRELATIONS IN Herbsleb CANCER USING ARRAY DATABASES AND FUNCTIONAL IN VITRO STUDIES M. Herbsleb, T. Thykjær Andersen, C. Wiuf, T.F. Ørntoft Molecular Diagnostic Laboratory, Aarhus University Hospital, Brendstupgaardsvej 100, DK-8200 Aarhus N, [email protected] In cancer progression the expression level of single genes is often changed and the consequence can be a changed expression of other genes which can facilitate the malignant development. To understand the consequences of the altered expression level of single genes it is important to know and understand the relationship among genes, the gene networks. The aim of this project is to identify new gene networks with relevance for a malignant development. Based on microarray analyses of the gene expression in 300 bladder cancer samples we have identified some interesting target genes which demonstrate significant changed expression from the benign to malignant stages. By use of RNA interference we try in vitro to reveal the function of these genes for the tumorigenesis. The RNAi technique makes it possible to down-regulate the expression of one or more genes and the effect of this down-regulation on other genes is measured with microarray analyses. The consequences are further analysed using advanced softwares. The functional impact of the target genes in relationship to cancer specific parameters like proliferation, apoptosis and invasion will also be investigated. Finally, we will analyse whether some of the in vitro identified relationships between genes are present in the clinical material.

P21.06 Mette Spliid PATIENT LIFE. A NURSING STUDY BASED ON AN ETHNOGRAPHIC Ludvigsen METHODOLOGY OF INFORMAL RELATIONSHIPS BETWEEN PATIENTS DURING HOSPITALISATION AT A SURGICAL GASTROENTEROLOGICAL DEPARTMENT IN DENMARK Ludvigsen MS, Pedersen BD, Risør MB Department of Nursing Science, Institute for Public Health, Faculty of Health Sciences, University of Aarhus, DK-8000 Aarhus C. Denmark, and Department of Surgical Gastroenterology, Aarhus University Hospital. [email protected] With a specific focus on contrasting experiences the purpose of this study is to analyse informal relationships between patients as manifested in concrete situations in the wards of a surgical gastroenterological department. The research design is qualitative and based on ethnographic fieldwork. Extended fieldwork over a period of 2 1/2years, and 18 in- depths interviews with nine male and nine female patients aged between 24

174 and 84 years old was carried out. The analytical approach is hermeneutical- phenomenological and inspired by the French philosopher Paul Picoeur. Analysis and interpretation is a process involving three steps; naïve reading, structural analysis, and critical interpretation. Preliminary findings indicate that even though patients are hospitalised for very different reasons they share a condition of being diseased, as described by the metaphor “We are all in the same boat”. The inherent tensions that exist between differing values and beliefs among patients are synthesised into four central empirically derived themes and approaches that characterise the informal relationships. These are: “patience- impatience”, “concern-indifference”, “privacy-company”, and “consideration-selfishness”. Conclusions suggest that these dichotomies are also dilemmas to be dealt with, given that they are at stake in relationships between patients. Determinations of outcomes of patients’ informal relationships are dependent on how they balance these dilemmas during hospitalisation.

P21.07 Michael DYNAMIC 18F-LABELED GALACTOSE PET AS A MEASURE OF Sørensen REGIONAL LIVER FUNCTION IN PIGS Sørensen M, Bender D, Mortensen FV, Olsen AK, Keiding S PET Center, Aarhus University Hospital, Noerrebrogade 44, DK-Aarhus C, Denmark There is an unmet need for a method that can quantify regional liver function in cirrhotic patients. As a first step towards solving this problem we tested if 18F-deoxy-galactose (FDGal) PET can be used to measure the regional liver galactose metabolism. Galactose is routinely used for measuring the total liver function. Methods. Eight anaestisized pigs underwent a 90 min dynamic FDGal PET scan with successive blood samples from an artery and the portal vein (PV) for radioactivity concentration determinations. Ultrasound transit time flowmetres were placed around the hepatic artery (HA) and the PV for contineous flow measurements. Four of the eight pigs had a constant i.v. infusion of un-labeled, cold galactose during the scan to saturate galactokinase enzyme. Kinetics was calculated by linear fitting of a FDGal metabolism model to the time course of liver tissue activity using flow- weighted input ([FHA CHA + FPV CPV]/[FHA + FPV]). Results: In the four pig livers without cold galactose, K-values (net metabolic clearance of FDGal) was 0.6 ±0.05 ml/min/ml tissue (mean ±SD) and the extraction fraction higher than 0.96. K-values were 0.07 ± 0.01 ml/min/ml tissue in the four pigs with cold galactose. Conclusion: FDGal follows saturation kinetics. Dynamic FDGal PET is suitable for measuring specific regional galactose metabolism in liver tissue.

P21.08 Rikke Riber- THE OPTIMAL NUMBER OF SENTINEL LYMPH NODES IN Hansen MALIGNANT MELANOMA WHEN EXTENSIVE HISTOPATHOLOGICAL EXAMINATION IS APPLIED R Riber-Hansen, S Hamilton-Dutoit, T Steiniche Institute of Pathology, Aarhus University Hospital, 8000 Aarhus C, Denmark.

175 The sentinel lymph node biopsy (SLN) has become the standard approach for staging lymph node involvement in malignant melanoma. The SLN can be visualized by injecting radioactive colloid around the tumour or the biopsy scar, the colloid will enter the lymphatic vessels and the first draining node(s) is termed the SLN. In the operating theatre the surgeon can localize the SLNs by a handheld gamma camera measuring gamma counts. Controversy exists as to how one should define a SLN in a clinical setting resulting in various protocols among which the 10% rule is often used. This rule states that all lymph nodes with a count of 10% or more of the SLN with the highest count should be considered additional SLNs. This yielded during the period of interest in our institution a mean of 2.7 SLNs per patient, with a range of SLNs submitted of 1-9. Our protocol for histopathology includes exhaustive step sectioning of all SLNs resulting in a mean of 24.4 steps and 61.0 sections per patients. We wish to establish if such an extensive workup is required for all SLN submitted from the same lymphatic basin regardless of the individual counts. Pathology records of the 243 patients having undergone SLN biopsy at Aarhus University Hospital during the period of Jan 2003- Dec 2005 will be retrieved. All data concerning the number, steps, counts and metastases of SLNs will be analysed along with the characteristics of the patients undergoing SLN biopsy.

P21.09 Signe THE CALCIUM-CREATININE CLEARANCE RATIO (CCCR) IS Engkjær INSUFFICIENT IN SEPARATING FAMILIAL HYPOCALCIURIC Christensen HYPERCALCEMIA (FHH) FROM PRIMARY HYPERPARATHYROIDISM (PHPT) Signe Engkjær Christensen, Peter H. Nissen, Peter Vestergaard, Bjarke Moosgaard, Lene Heickendorff, Leif Mosekilde. Department of Medicine C, Aarhus Hospital (THG), 8000 Aarhus C Introduction: The CCCR is important in separating Familial Hypocalciuric Hypercalcemia (FHH) from Primary Hyperparathyroidism (PHPT). CCCR<0.01 indicates FHH and CCCR>0.02 indicates PHPT. Objective: To compare the CCCR in FHH and PHPT patients and to test the discriminative power of CCCR. Materials: FHH: 57 patients, hypercalcemia (mean of 3 measurements), mutation(s) in the calcium sensing receptor gene (CaSR-gene). FHH subgroup I (n=36), mutations with obvious effect on the FHH fenotype. FHH subgroup II (n=21), mutations with less effect on the FHH fenotype. PHPT: 58 patients, surgically verified PHPT, all participants had a plasma creatinine level < 140 pmol/l. Methods: Calcium-Creatinine Clearance Ratio was calculated as (P-Ca/24hU-Ca) x (24hU-Cr/P-Cr). Calcium-Sensing Receptor Gene: All exons, including a minimum of 10 bp of flanking intron sequence, were sequenced and aligned to GenBank reference sequence NM_000388. Results: We found a significant difference between the mean values of the CCCR in patients with FHH (0.011 ± 0.007 (SD)) and PHPT (0.023 ± 0.009), 2p<0.001. The positive predictive value of CCCR < 0.01 for FHH was 0.97, and 0.90 for PHPT with CCCR>0.02. ROC curve analysis showed that CCCR <0.015 is the optimal point for separating between FHH and PHPT.

176 The sensitivity for FHH at this point was only 0.79 with a specificity of 0.84. In the FHH subgroup I and in the FHH subgroup II, we found the mean value of the CCCR to be 0.009 (± 0.005) and 0.014 (± 0.008), respectively. Both are significantly different from the PHPT group with a two-sided P- value < 0.001 in each subgroup. Conclusions: The CCCR is insufficient in discriminating between FHH and PHPT. It is important also to consider pedigree, mutations in the CaSR gene, p-PTH, ultrasound, and parathyroid scintigraphy.

P21.10 Tina Aaen GENERAL PRACTITIONERS ROLE IN HELPING PATIENTS TO COPE Geest WITH CANCER Geest, TA Research Unit for General Practic, University of Aarhus, Vennelyst Boulevard 6, DK-8000 Aarhus C, Denmark Patients’ ways of coping with cancer may influence not only their quality of life but may also affect biomedical aspects of their disease and their recovery. It has been shown that the GPs can influence cancer patients’ coping processes, however only little is known about what GPs know about coping and what they actually do to influence cancer patients’ coping processes. The aim of this study is to explore and document GPs’ theoretical knowledge of coping, their use of coping diagnostics and actual actions to help cancer patients coping with their disease. 12 patients and their GPs are interviewed individually using a semi- structured interview guide. Patients are interviewed about the course of their cancer disease; changes in their lives due to their disease; their expectations to help from their GP; and actual interaction with their GP during the course of their disease. GPs are interviewed about their perceptions of the course with the specific patient and with older cancer patients in general. Further they are interviewed about their theoretical knowledge of coping; use of coping diagnostics in their care and treatment of cancer patients; and their attitudes to help cancer patients with matters related to their disease but beyond pure biomedical matters. The results from the study will provide data about GPs’ knowledge of and use of coping diagnostics, and cancer patients’ wishes and expectations for treatment and care in general practice. This will provide a basis for development of pre- as well as postgraduate educational courses aimed at fitting and optimising the theoretical and practical training of GPs in the use of knowledge abut coping in patient care. The study is in progress, but results are not yet available.

P22.01 Christine P25 INDUCES -SYNUCLEIN-DEPENDENT TOXICITY IN CELLULAR Petersen MODELS OF NEURODEGENERATIVE DISORDERS. C.L. Petersen, P.H. Jensen Institute of Medical Biochemistry, University of Aarhus, 8000 Aarhus C, Denmark The neurodegenerative disorders, Parkinson’s disease (PD) and multiple system atrophy (MSA), belong to the group of -synucleinopathies. Their unifying hallmark is the presence of intracellular inclusions containing

177 aggregates of -synuclein (Asyn). The inclusions comprise neuronal Lewy bodies in PD and glial cytoplasmic inclusions in MSA. The mechanisms underlying Asyn aggregation are still not clear but are likely to involve an altered expression of pro-aggregatory factors. We have identified the brain-specific protein, p25 , as an accelerator of Asyn aggregation suggesting a role for p25 in the neurodegenerative process. The cellular expression of p25 is abnormal in the degenerating neurons and oligodendrocytes in PD and MSA where it co-localises with Asyn in Lewy bodies and glial cytoplasmic inclusions. Here we have investigated the role of p25 in two cell lines stably transfected with Asyn. By immunofluorescence and different biochemical assays we show that p25 induces Asyn-dependent cell death in an oligodendrocyte cell line. However, expression of p25 in a neuroblastoma cell line does not cause cell death but leads to formation of inclusions, which are positive for both Asyn and p25 . Accordingly, cell specific factors appear to determine the functional outcome of p25 ’s action on Asyn; either a cytotoxic effect or a protective sequestration of the aggregates in inclusions. Understanding the molecular and cellular mechanisms whereby i) Asyn exerts its neurotoxicity and ii) cells raise a successful protective response may help to develop novel neuroprotective strategies for diseases caused by Asyn aggregation. Understanding the molecular and cellular mechanisms whereby aggregated AS contributes to neurotoxicity may help to develop new treatments for diseases caused by AS aggregation.

P22.02 Kristian THE P38 MAPK IS A KEY REGULATOR OF IL-20 EXPRESSION IN Otkjær HUMAN KERATINOCYTES. Nielsen K.Otkjær, L. Iversen, A. Funding, C. Johansen, H. Just and K.Kragballe Dept. of Dermatology, Aarhus Hospital, P.P. Ørumsgade11, 8000 Århus C Interleukin-20 (IL-20) is a member of the IL-10 cytokine family. IL-20 over expressing transgenic mice have skin changes that resemble those seen in human psoriatic skin. Furthermore, it has been demonstrated that keratinocytes in the basal layer of lesional psoriatic skin express increased levels of IL-20 mRNA. Therefore IL-20 is believed to be a key cytokine in the pathogenesis of psoriasis. The aim of the present study was to identify important signalling pathways controlling IL-20 gene expression in human keratinocytes. Cultured normal human keratinocytes were stimulated with IL-1 , UVB, IFN or TNF- . In separate experiments cells were pre-incubated with inhibitors of PKC, p38 MAPK or ERK and then stimulated for one hour with IL-1 (10 ng/ml) or vehicle. Incubation with IL-1 or UVB lead to a significant increase in IL-20 mRNA expression in human keratinocytes, whereas IFN and TNF- did not induce IL-20 mRNA expression. Pre-incubation with the p38 MAPK inhibitor, SB 202190 dramatically decreased IL-20 mRNA expression to a level below vehicle treated cells. Inhibition of ERK with PD 98059 resulted in a moderate although statistically significant decrease in IL-20 gene-expression whereas inhibition of PKC did not affect IL-20 gene expression significantly.

178 These data demonstrate p38 MAPK as a key regulator of IL-20 gene expression in human keratinocytes. Because IL-20 is believed to be an essential cytokine in the pathogenesis of psoriasis, p38 MAPK may also be a possible target in the treatment of this disease.

P22.03 Thomas SYMPTOMS AND SIGNS OF NEUROPATHY IN A LONG-TERM Harbo FOLLOW-UP OF PATIENTS WITH CHRONIC INFLAMMATORY DEMYELINATING POLYRADICULONEUROPATHY T. Harbo, H. Andersen and J. Jakobsen. Department of Neurology, University Hospital of Aarhus, 8000 Aarhus C, Denmark. Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a severe autoimmune disease of peripheral nerves characterized by demyelination, which causes muscle weakness and sensory loss. The long- term outcome in CIDP however has not been studied in details. Methods: In a cross-sectional follow-up study of patients with CIDP diagnosed at our Department from 1992-2002, isokinetic muscle-strength (IMS) was measured at the ankle, knee, hip, wrist elbow, and shoulder. Furthermore patients were evaluated with the Neuropathy Symptom Score (NSS) (ranging from 0-17, scores over 1 abnormal), and with a standardized clinical examination (Neuropathy Impairment Scale (NIS)) (ranging from 0- 240, scores over 3 abnormal). Results: Twelve patients with a median follow up time of 8.7 years (range 2.5-11.4 years) have been studied. There was a significant reduction of muscle-strength in CIDP patients; Mean IMS at all measured joints is 84% of normal (95% CI=70-97%). Median NSS was 3.5 (5th-95th percentile=0-10) and median NIS was 38.5 (5th-95th percentile 2-143). IMS was closely related to NSS (r=-0.62, p=0.03) and the NIS (r=-0.85, p=0.0005). Conclusions: At long-term follow-up we found that almost all CIDP patients had residual symptoms and signs of neuropathy. Furthermore their isokinetic motor performance was significant reduced.

P22.04 Mogens VENOUS THROMBOEMBOLISM AND HAEMOSTATIC ALTERATIONS Stender IN PATIENTS WITH COLORECTAL CANCER – EFFECT OF RADIATION THERAPY Stender M, Nielsen S, Frøkjær JB, Larsen TB, Elbrønd H, Thorlacius-Ussing O. Dept. of Gastrointestinal Surgery, Aalborg Hospital, DK-9000 Aalborg. Background: Venous thromboembolism (VTE) is a well known complication to cancer. Autopsy studies have shown that pulmonary embolism (PE) is the second most common cause of death in cancer patients. Deep venous thrombosis (DVT) is the main cause PE. The postoperative prevalence of DVT in patients with colorectal cancer is 20-40%. Hypothetically, a number of these DVT´s are present pre-operatively resulting in high risk of PE post-operatively, but the literature concerning this issue is surprisingly sparse. A Swedish study has shown that the postoperative prevalence of symptomatic DVT in patients with rectal cancer - who have undergone pre-operative radiation therapy - is 7,5 % vs. 3,6 % in non-irradiated patients. The aim of the study is to answer the following

179 questions: 1)•What is the pre-operative prevalence of DVT in patients with colorectal cancer? 2)•What is the clinical utility of D-dimer for the diagnosis of DVT in patients with colorectal cancer undergoing surgery? 3)•Does radiation therapy activate the coagulation- and fibrinolysis system as assessed by sensitive biochemical markers? Material and Methods: 200 patients with colorectal cancer and 100 healthy controls will be included. The patients will be examined with ultrasonography for DVT before and after radiation therapy and surgery. Blood samples will be analyzed for markers of coagulation and fibrinolysis. Perspectives: In case of a high prevalence of thrombosis before surgery and/or radiation induced coagulation activation, considerations about changing the current antithrombotic prophylaxis regimen should be done.

P22.05 Vibeke IDENTIFICATION OF THE RECEPTOR SCAVENGING HEMOPEXIN- Hvidberg HEME COMPLEXES V. Hvidberg, M.B. Maniecki, C. Jacobsen, P. Højrup, H.J. Møller, S.K. Moestrup Department of Medical Biochemistry, University of Aarhus, Ole Worms Allé, bldg. 170, DK-8000 Aarhus C, Denmark Heme released from heme-binding proteins on internal hemorrhage, hemolysis, myolysis, or other cell damage is highly toxic due to oxidative and proinflammatory effects. Complex formation with hemopexin, the high-affinity heme-binding protein in plasma and cerebrospinal fluid, dampens these effects and is suggested to facilitate cellular heme metabolism. Using a ligand-affinity approach, we purified the human hemopexin-heme receptor and identified it as the low-density lipoprotein receptor-related protein (LRP)/CD91, a receptor expressed in several cell types including macrophages, hepatocytes, neurons, and syncytiotrophoblasts. Binding experiments, including Biacore analysis, showed that hemopexin-heme complex formation elicits the high receptor affinity. Uptake studies of radiolabeled hemopexin-heme complex in LRP/CD91-expressing COS cells and confocal microscopy of the cellular processing of fluorescent hemopexin-heme complex established the ability of LRP/CD91 to mediate hemopexin-heme internalization resulting in cellular heme uptake and lysosomal hemopexin degradation. Uptake of hemopexin-heme complex induced LRP/CD91-dependent heme-oxygenase 1 mRNA transcription in cultured monocytes. In conclusion, hemopexin- heme complexes are removed by a receptor-mediated pathway showing striking similarities to the CD163-mediated haptoglobin-hemoglobin clearance in macrophages. Furthermore, the data indicate a hitherto unknown role of LRP/CD91 in inflammation. (Blood. 2005;106:2572-2579)

P22.06 Jakob DECREASED RESPONSE TO ALDOSTERONE IN KIDNEY CORTICAL Nielsen COLLECTING DUCT IN RATS WITH LITHIUM-INDUCED NEPHROGENIC DIABETES INSIPIDUS . Jakob Nielsen, Tae-Hwan Kwon, Jørgen Frøkiær, Mark Knepper Søren Nielsen. Water and Salt Research Center, Institute of Anatomy, University of Aarhus. Lithium-induced nephrogenic diabetes insipidus (Li-NDI) is associated

180 with increased urinary sodium excretion and decreased responsiveness to aldosterone and vasopressin. Dysregulation of the epithelial sodium channel (ENaC) is thought to play an important role in the sodium wasting. W P<0.05) compared to rats treated with lithium only. Plasma lithium concentration was decreased by aldosterone-treatment compared to rats treated with lithium only (0.31±0.03 mmol/l vs. 0.54±0.04 mmol/l, P<0.05). Immunoblotting showed increased protein expression of ENaC, the 70kDa from of ENaC and NCC in the kidney cortex in aldosterone-treated rats compared to rats treated with lithium only. Immunohistochemical analysis confirmed the increased expression of ENaC in the late DCT and CNT and also revealed increased apical targeting of all three ENaC subunits ( ,ß and ) after aldosterone treatment. In the CCD aldosterone treatment did not induce any changes in overall labeling or trafficking which remained very weak or absent in contrast to the observed changes in DCT and CNT. This study demonstrates a segment-specific lack of effect of aldosterone selectively in the CCD, but not in CNT and DCT, affecting both ENaC protein expression and trafficking of the ENaC complex to the apical plasma membrane. The selective downregulation and reduced aldosterone responsiveness in the CCD may explain the increased sodium wasting associated with chronic lithium treatment.

P22.07 Maik Stiehler OPTIMIZING VIRAL AND NON-VIRAL GENE TRANSFER METHODS FOR GENETIC MODIFICATION OF MESENCHYMAL STEM CELLS M. Stiehler1,2*, M. Duch2, T. Mygind1, H. Li1, M. Ulrich-Vinther1, C. Modin2, M. Lind 1, F. S. Pedersen2, C. Bünger1 1Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Aarhus University Hospital, Aarhus, Denmark; 2Interdisciplinary Nanoscience Center (iNANO) and Department of Molecular Biology, University of Aarhus, Aarhus, Denmark; *[email protected] Ex vivo cell-mediated gene therapy using mesenchymal stem cells (MSCs) over expressing osteogenic growth factors is an attractive therapeutic strategy for the treatment of musculoskeletal disorders. The aim of this study was to evaluate optimized viral and non-viral ex vivo gene delivery systems using primary porcine MSCs. Gene transfer vectors expressing eGFP reporter gene and bone morphogenetic protein(BMP)-2 gene were transferred to porcine MSCs by different non-viral methods and by use of adeno-associated virus (AAV)- mediated and retroviral gene delivery. Gene transfer efficiencies were evaluated by flow cytometry and by BMP-2 gene expression assays. The low efficiency of non-viral gene delivery observed in this study demands further improvement of existing non-viral methods. High-titer AAV gene delivery resulted in efficient, though transient, genetic modification of porcine MSCs. Retroviral gene delivery combining high efficiency and long-term transgene expression was significantly enhanced by centrifugation of retroviral particles onto the target cell layer. Porcine MSCs that were BMP-2 transduced by optimized retroviral gene delivery demonstrated a significant increase in BMP-2 gene expression and showed increased osteogenic differentiation. Ex vivo gene therapy protocols using MSCs should consider differences in gene transfer efficiency and duration

181 of transgene expression depending on the gene transfer system used.

P22.08 Anne THE CAUSE OF MUSCLE DAMAGE: MECHANICAL Fredsted STRAIN OR CELLULAR CALCIUM OVERLOAD? A. Fredsted, U.R. Mikkelsen, H. Gissel & T. Clausen Institute of Physiology and Biophysics, University of Aarhus, Ole Worms Allè 160, DK-8000 Århus C. Prolonged or unaccustomed exercise leads to muscle cell damage, detectable as a release of the intracellular enzyme lactic acid dehydrogenase (LDH). This was correlated to excitation-induced influx of Ca2+ (Gissel & Clausen, Am. J. Physiol. 279:R917-R924, 2000), but it cannot be excluded that mechanical strain contributes to the damage. We here explore this question using a chemical tool, N-benzyl-p-toluene sulphonamide (BTS), which specifically blocks muscle contraction (Macdonald et al., Exp. Physiol. 2005). Isolated extensor digitorum longus (EDL) muscles were prepared from 4 wk old rats and mounted on holders for isometric contractions. Muscles were stimulated intermittently at 40 Hz for 15, 30 or 60 min or exposed to the Ca2+ ionophore A23187. Electrical stimulation increased 45Ca influx 3-4 fold within 15 min. This was followed by a progressive release of LDH, which was correlated to the influx of Ca2+. In the presence of BTS at a concentration (50 M) causing 90% inhibition of contractile force, excitation induced the same increase in 45Ca influx, but the increased release of LDH was completely suppressed, both at normal extracellular Ca2+ and elevated Ca2+ (5 mM). Passive mechanical stretching up to 40 g, which is comparable to the tension developed during electrical stimulation, caused no release of LDH. Both in the absence and the presence of BTS, A23187 markedly increased 45Ca influx and LDH-release, but caused no increase in tension. In conclusion, muscle excitation is associated with an influx of Ca2+. The degree of cell damage, assessed by LDH release depends on the size of Ca2+ influx and the energy status of the cell, and not on mechanical stretch.

P22.09 Philippe GENOTYPING AND ANNOTATION OF AFFYMETRIX SNP PROBE SETS Lamy Philippe Lamy *, Claus L. Andersen † and Carsten Wiuf *† *Bioinformatics Research Center, University of Aarhus, Hoegh- Guldbergsgade 10, Bldg 1090 8000 Aarhus C, Denmark †Molecular Diagnostic Laboratory, Aarhus University Hospital, Brendstrupgaardsvej 8000 Aarhus N, Denmark Affymetrix SNP array technology is today widely used for whole-genome scans of polymorphic genetic markers. Affymetrix has developed software for genotyping Single Nucleotide Polymorphisms (SNPs) based on intensities measuring DNA abundance and the derived genotypes are used for further analysis of the data. Here we developed a different method to genotype SNPs which further allow us to annotate 1) SNPs that experimentally have bad quality or 2) SNPs (or alleles) that would perform poorly when used for copy number analysis in abnormal genomes. We show that our method agrees well with Affymetrix’method (99.23% agreement). In many cases where the two methods disagree, we can show

182 that our method give a better result. Currently, we work on extending the method in order to perform allele specific copy number analysis.

+ - P22.10 Elena V THE NA DEPENDENT HCO3 UPTAKE INTO THE RAT CHOROID Bouzinova PLEXUS EPITHELIUM IS PARTIALLY DIDS-SENSITIVE. EV Bouzinova, J Praetorius, S Nielsen, C Aalkjær Inst. for Physiology and Biophysics, The Water & Salt Research Center University of Aarhus, 8000 Aarhus C, Denmark + - Several studies suggest the involvement of Na and HCO3 transport in + - the formation of cerebrospinal fluid. Two Na dependent HCO3 transporters were recently localized to the epithelial cells of the rat choroid plexus (NBCn1 and NCBE), and the mRNA for a third protein was also detected (NBCe2) (Praetorius et al., 2004b). We aimed to immunolocalize the NBCe2 to the choroid plexus by immunohistochemistry and immuno- gold electronmicroscopy as well as to functionally characterize the bicarbonate transport in the isolated rat choroid plexus by measurements of intracellular pH (pHi) using a dual excitation wavelength pH sensitive dye (BCECF). Both antisera derived from c-terminal and n-terminal NBCe2 peptides localized NBCe2 to the brush border membrane domain of choroid

plexus epithelial cells. Steady state pHi in choroidal cells increased from 7.03 ± 0.02 to 7.38 ± 0.02 (n = 41) after addition of CO2/HCO3- into the bath solution. This increase was Na+ dependent and inhibited by the Cl- and HCO3- transport inhibitor, DIDS (200 M). This suggests the presence of Na+ dependent partially DIDS sensitive - HCO3 uptake. The pHi recovery after acid loading revealed an initial Na+ and HCO3- dependent net base flux of 0.828 ± 0.116 mM/s (n = 8). The initial flux in presence of CO2/HCO3- was unaffected by DIDS. Our data support the existence of both DIDS-sensitive and -insensitive Na+ and HCO3- dependent base loaders uptake into the rat choroid plexus epithelial cells. This is consistent with the localization of the three base transporters NBCn1, NCBE, and NBCe2 in this tissue.

P23.01 Søren THE IMPACT OF REMOTE PRECONDITIONING ON MYOCARDIAL Aagaard STUNNING IN PIGS. S.R. Aagaard, J.S. Berg, J.M. Hasenkam. T-forskning, Skejby Sygehus, Brendstrupgaardsvej 100, DK-8200 Aarhus N If the myocardium is exposed to a short period of ischaemia (13-20 min.) followed by reperfusion, as during an OPCAB procedure, there is a risk of myocardial stunning, which is a temporary loss of the myocardium’s contractile capability. This condition can hamper the cardiac pump function and thereby cause cardiac failure. The study is investigating the possibilities to reduce stunning by the use of remote delayed preconditioning. The study was conducted on 80 kg pigs. 20 animals were randomized to three groups, with 10 animals in each The intervention group was exposed to two days of surgery and the control only to the second day of surgery. The remote delayed preconditioning was induced by a balloon catheter placed in the abdominal aorta. And inflated for 4 times 5 min or 30 min depending of the group. The myocardial

183 ischemia was induced by clamping the LAD for 15 min and the ischemic period was followed by 180 min reperfusion. The myocardial contraction was measured by a sonomicrometry method. The three groups were comparable regarding baseline haemodynamic values and myocardial contraction. In all three groups a significant fall in contraction from baseline to 180 min reperfusion were seen, this shows that the myocardium in all three groups was stunned. But there were no significant difference between the degrees of stunning when the groups were compared with each other. The study shows that remote delayed preconditioning does not have any effect on myocardial stunning in pigs, neither with a multiple short or a prolonged preconditioning ischaemia.

P23.02 Jens ASPECTS OF ANESTHETIC PRECONDITIONING IN A PORCINE Rolighed MODEL Jens Rolighed Clinical Institute, Faculty of Health Sciences, University of Aarhus, 8000 Aarhus C, Denmark Background: The preconditioning phenomenon is well-documented in many species, but has yet to be concluded in human studies. Anesthetic preconditioning has been established in rodents and canine models. The canine (dog) model has a significant collateral coronary artery circulation, possibly explaining the extent of preconditioning in this model. In order to establish anesthetic preconditioning in a model with little or no collateral circulation, akin to human coronary anatomy, pigs were introduced into an ischemia-reperfusion model and prior to ischemic insult subjected to sevoflurane, a halogenated inhalational anesthetic known to precondition. Additionally, tissue Doppler echocardiography was introduced in the model to evaluate this method’s ability to determine alterations in left ventricle contractility. Methods:We pre-anesthetized twenty-four 20-25 kg danish landrace pig using midazolam 2mg kg-1 intramuscular inj. Prior to general anaesthesia with pentobarbital intravenous (iv) 20 mg kg-1, random allocation to either one of three groups took place. Group A: (Controls) Mebumal anesthesia with 40 min PTCA-based occlusion of the LAD artery distal to the 2nd diagonal, followed by 2.5 hr reperfusion, then risk area delineation by Evans blue dye injection in the left atrium after reocclusion, then euthanasia, heart excision and staining by the tetrazolium method. Group B: (Ischemic preconditioning) as A, but prior to LAD occlusion animals were subjected to twice 5 min ischemia followed by 5 min reperfusion. Group C: (Sevoflurane) as A, but prior to LAD occlusion animals were given inhaled sevoflurane 4% vol/vol twice for 5 min followed by 5 min reperfusion. The primary end-point was a comparison of the infarct size:risk area ratio between groups. Tissue Doppler echocardiography was performed at baseline, after 10 min ischemia, and each min after reperfusion until 15 min.

184 Results: no data available Participants: Larsen-JR, Aagaard-S, Sloth-E, Sorensen-M, Hasenkam-MJ (prof). Investigation site: Clinical Institute, Skejby Sygehus, AUH. Time table: commencement August 2005. Publication: Spring 2006. Acknowledgements: This investigation is supported by the following contributors; The Danish Heart Foundation (www.Hjerteforeningen.dk) Aarhus Universitetshospitals Forskningsinitiativ Abbott, Denmark have donated investigation pharmaceuticals. Contact: [email protected]

P23.03 Nikolaos CHARACTERIZATION OF CALCINEURIN PHOSPHATASE DURING Karamperis ALLOGRAFT TRANSPLANTATION IN A RAT REJECTION MODEL N. Karamperis1, Ø. Østraat2, K.A. Jørgensen1 1Dept. of Renal Medicine C, 2Dept. of Urology K, Skejby, Aarhus University Hospital The intracellular protein-phosphatase Calcineurin (CaN) plays a central role as a key molecule in T-cell activation, during allograft transplantation and rejection. Our aim will be to investigate CaN from three different aspects, thereby acquiring an overall view of its “behavior” under transplantation and rejection. Methods: First we will estimate the enzymatic (phosphatase) activity/capacity of the enzyme utilizing the ‘CaN activity assay’; CaN activity is measured as the release of radiolabelled phosphate from a previously phosphorylated 19 amino acid peptide that mimics NFAT, the natural substrate of CaN. The second objective of this study it will be to quantify the amount of CaN by means of Western Blot and/or ELISA technique. Finally, we will study the production/expression of enzyme’s m- RNA, utilizing Reverse-Transcription Polymerase Chain Reaction. Study Design: Our aim is to apply all the above-mentioned techniques on whole blood, isolated T-cells and also homogenized tissues from the rejected organ; all these samples will be obtained from heart transplanted rats undergoing rejection (utilizing the ‘Heterotopic heart transplantation’ rat-model). The overall number of rats, used in this study, will be 200. Rats will be divided into 3 groups: Group A: n=20, control-normal rats. Group B: n=90, 45 control-isogenic heart transplantations. (5 transplantations for each, of the 9, subgroups). Group C: n=90, 45 allogenic heart transplantations (5 transplantations for each, of the 9, subgroups). The whole study population will be divided into 9 subgroups based on the time after transplantation, at which the rats will be sacrificed and the blood and tissue samples will be collected: after 4, 8 and 24 hours and after 2, 3, 4, 5, 6 and 7 days. Rats on group A will be used for determination of the CaN’s ‘normal’ levels on healthy, not transplanted, animals. Blood samples will be obtained from the sacrificed animals and after that the rejected heart will be removed. Heart-tissue samples will be send for histological termination/gradation of the rejection .The rest of the rejected organ will be homogenized and used for tissue CaN determination.

185 P23.04 Henriette THE GLUTAMATE DECARBOXYLASE GENE 1 AS A POTENTIAL Nørmølle CANDIDATE GENE FOR AUTISM Buttenschøn H. N. Buttenschøn1, T. D. Als1, A. El Daoud1, A. G. Wang2,3, A. D. Børglum4, T A Kruse5, M B Lauritsen1, O Mors1 1Centre for Basic Psychiatric Research, Aarhus University Hospital, Denmark 2Dept. of Psychiatry, Copenhagen University Hospital, Denmark 3Dept. of Psychiatry, National Hospital, Faroe Islands 4Inst. of Human Genetics, University of Aarhus, Denmark 5Dept. of Clinical Biochemistry and Genetics, Odense University Hospital, Denmark Based on several previous genome-wide scans and screenings of possible candidate genes, 2q31-33 has been suggested as a candidate region for autism. According to several studies, the glutamate decarboxylase gene (GAD1) located within this region is an interesting functional and positional candidate susceptibility gene for autism. The gene encodes the enzyme, gamma-aminobutyric acid synthetic enzyme, GAD67, which synthesizes the inhibitory neurotransmitter GABA from the excitatory neurotransmitter glutamate. We performed a genome-wide scan in a search for susceptibility genes for autism of the isolated population of the Faroe Islands. In order to investigate whether GAD1 is involved in the development of autism, we genotyped ten SNPs spanning the gene in cases and controls. Among other regions, chromosome 2q31 appeared to be a potential candidate region for autism. We found association between autism and marker D2S2381 (empirical CLUMP p values (T1 and T4) of 0.00515 and 0.01256, respectively). Chromosome region 2q31 harbouring the GAD1 gene appeared as a likely candidate region/gene for autism.

P23.05 Signe Gjedde MUSCULAR MANIFESTATIONS IN HYPOTHYROID PATIENTS S. Gjedde, L. Gormsen, T. Clausen, A.G. Jurik, A.L.D.Riis, N. Møller, J. Rungby, J. Weeke Medical Department M, Aarhus Sygehus, Nørrebrogade 44, 8000 Århus C Muscular symptoms such as stiffness, cramps, aches and weakness are frequent complaints in hypothyroid patients. Trying to clarify muscular aspects of hypothyroid disease, we monitored muscle mass, strength, energy expenditure and the level of Ca2+ pumps in the muscle in hypothyroid patients. We studied five parameters at baseline and after treatment in eight newly diagnosed hypothyroid patients and in eight healthy volunteers: namely muscle area, assessed by computer tomography (CT); muscle strength, assessed by means of a dynamometer; thyroid hormones measured in a blood sample; resting energy expenditure (REE), asessed by indirect calorimetry; and the level of Ca2+ pumps determined in a needle biopsy from the vastus lateralis muscle. Myopathy is well known in hypothyroid patients and muscle enlargement has been described. We therefore expect that muscle area may be increased in these patients. Furthermore we expect decreased muscle strength and

186 REE. Increased levels of thyroid hormones have been shown to increase Ca2+ pumps in skeletal muscle, we therefore expect them to be decreased in these hypothyroid patients.

P23.06 Helle Friis MYCOPLASMA GENITALIUM, CHLAMYDIA TRACHOMATIS AND Svenstrup TUBAL FACTOR INFERTILITY – A PROSPECTIVE STUDY H. F. Svenstrup, J. Fedder, S. Birkelund and G. Christiansen Department of Medical Microbiology and Immunology, Aarhus University, 8000 Aarhus C, Braedstrup Fertility Clinic, 8740 Braedstrup, Denmark The objective of the study was to determine the prevalence of M. genitalium and C. trachomatis in women attending infertility clinics and to follow the women prospectively over 20 months to study the effect of previous infection on tubal damage, pregnancy rate and outcome. Serum and swab specimens were obtained from 212 infertile women and tested for M. genitalium and C. trachomatis IgG antibodies and DNA. All women were examined by culdoscopy/laparoscopy to assess the tubal status. No M. genitalium DNA was found in the swabs and only one woman was found positive by PCR for C. trachomatis. The seroprevalence of M. genitalium IgG antibodies among women with TFI were 17% (5/30) as compared to 4% (10/164) of women with normal tubes (OR = 4.5, CI =1.3- 15.2, P = 0.016). Of Women with TFI 7 (23%) were seropositive to C. trachomatis compared to 24 (15%) of women with normal tubes. Surprisingly, C. trachomatis IgG antibodies were not associated with TFI (OR = 2.2, CI = 0.8-5.8, P = 0.111). C. trachomatis antibodies was more prevalent in women with a history of PID than in women without previous PID (P = 0.001). Of M. genitalium seropositive women with TFI 3/5 had suffered from PID as compared to none among the seropositive women with normal tubes. There was no association between M. genitalium or C. trachomatis seropositivity and spontaneous- or treated pregnancy or to adverse pregnancy outcome. This study indicates that C. trachomatis is no longer a sure predictor of TFI in Denmark and we ascribe the increased diagnostic and improved treatment since the mid 1990s to cause this effect. Despite of this we show that M. genitalium is still associated with TFI and thus emphasise the importance of studying the role of this pathogen in acute PID and long-term sequela.

P23.07 Walther SWARM BASED MEDICAL IMAGE ANALYSIS: APPLIED TO IN-VIVO Fledelius CORNEAL CONFOCAL MICROSCOPY. Walther Fledelius (1), Niels Ehlers (1), Brian Mayoh (2). (1)Department of Ophthalmology, Århus University Hospital, Nørrebrogade 44, 8000 Århus C, Denmark. (2) Department of Computer Science, University of Aarhus, IT-parken, Aabogade 34, 8200 Aarhus N, Denmark. We seek to combine the advantages of swarm based computing [E. Bonabeau, M. Dorigo and Guy Theraulaz, Swarm Intelligence: From Natural to Artificial Systems, (New York, Oxford University Press, 1999)] with the difficulties faced by medical images. Medical images are necessarily subject to biological variation, not only with respect to shape

187 and position, but also various types of noise that are induced by differences in the patient, such as intensities and signal distortion. Secondly the sensitivity of the human body will often limit imaging parameters such as radiation, radioactivity, and light, giving medical images a lower signal to noise ratio than their non-medical counterparts. The robustness and stability that are characteristic of a swarm based algorithm would thus be ideal for processing medical images. A framework, Snowstorm, was constructed to facilitate a rapid construction and application of swarms to real medical image data. Proof of concept was achived by applying the method to different types of medical images obtained from the human cornea, human retina, and MR scans of the human brain. The method will finally be applied to clinical studies for quantification of the human corneal endothelium and stroma, obtained by In-Vivo confocal microscopy.

P23.08 Alma Becic PATIENT CHARACTERISTICS AND SURVIVAL OF TOTAL HIP Pedersen ARTHROPLASTIES A.B.Pedersen, S.P.Johnsen, S.Overgaard, K.Søballe, H.T.Sørensen, U.Lucht. Department of Orthopaedics and Department of Clinical Epidemiology, Aarhus University Hospital, and Department of Orthopaedics, Odense University Hospital, Denmark. Introduction: We examined factors associated with short and long term implant survival after primary total hip arthroplasties according to different patient’s characteristics. Material and methods: We identified patients in the Danish Hip Arthroplasty Registry between 1995 and 2002. The Cox regression analyses were used to estimate the risk of revision (RR) and 95% Confidence interval (CI) adjusting for possible confounding. Results: In the long term period, males and patients with several comorbidities were in increased risk of revision compared to females and patients without comorbidities (RR=1.2; 95% CI 1.1-1.4 and RR=2.7; 95% CI 2.4-3.2, respectively). Patients with avascular necrosis, paediatric diseases and older than 74 years had an increased risk of revision in the first 30 days postoperatively compared to primary arthrosis or age 60-73 years; however, the difference in survival according to diagnosis disappear in the long term period. Long term risk of revision for patients older than 74 years was decreased (RR=0.8; 95% CI 0.7-0.9), and for patients between 10-49 and 50- 59 was increased compared to 60-73 years (RR=1.7; 95% CI 1.3-2.2 and RR=1.3; 95% CI 1.1-1.6, respectively). Conclusions: Males and patients having several comorbidities were identified as risk factors of revision in the long term period. More efforts should be done to recognize avascular necrosis, paediatric diseases, and age older than 74 years as risk factors of revision in the first 30 postoperative days.

P23.09 Mette SHORT-TERM MORTALITY OF BACTERAEMIA IN ELDERLY PATIENTS Nørgaard WITH HAEMATOLOGICAL MALIGNANCIES M Nørgaard, H Larsson, G Pedersen, HC Schønheyder, KJ Rothman, HT Sørensen.

188 Department of Clinical Epidemiology, Aalborg Hospital, Aarhus University Hospital, 9100 Aalborg, Denmark Bacterial infections are important complications in patients with haematological malignancies. We compared the outcome of bacteraemia among elderly and younger patients with haematological malignancies, and evaluated the impact of comorbidity on this association using population- based registries from 1992-2002. Among 358 patients with an incident haematological malignancy and an episode of bacteraemia, 207 (58%) were older than 60 years and 37 (10%) older than 80 years. The 7-day mortality was 10% among patients younger than 60 years, 21% among patients age 60-79 years, and 27% for patients older than 80 years. When compared with patients younger than 60 years adjusted mortality rate ratios (MRRs) were 1.9 (95% CI: 0.9-3.8) for patients age 60-79 and 1.6 (95% CI: 0.6-4.2) for patients older than 80 years. The 30- day mortality was 23% among patients younger than 60 years of age, 35% among patients age 60-79, and 54% among patients 80 years or older. Adjusted MRRs were 1.7 (95% CI: 1.1-2.7) and 2.3 (95% CI: 1.2-4.3), respectively. Differences in comorbidity did not have any major impact on the estimates. We found that increasing age was associated with increased mortality from bacteraemia in patients with haematological malignancies. An increased burden of comorbidity among elderly did not explain this association.

P23.10 Henrik Kold- CORONARY ARTERY MYOGENIC RESPONSE IN A MOUSE MODEL OF Petersen HYPERTROPHIC CARDIOMYOPATHY AND THE ROLE OF ENDOTHELIN-1. H. Kold-Petersen, H. Nilsson, C. Aalkjær Dept. of Physiology and Biophysics, Build. 1160, University of Aarhus, Ole Worms Allé, DK-8000 Aarhus. The aim of this study is to see if the inhibition of the endothelin-1 receptor by bosentan (non-selective ETa/ETb receptor blocker) will have an effect on the myogenic response in the coronary arteries, and if it will decrease cardiac hypertrophy in a mouse model of hypertrophic cardiomyopathy (HCM). We have previously shown that at the age of 10 months the coronary arterty myogenic response is impaired in mice with HCM compared to wild type (WT), (WT: 46±4%; HCM:32±4%). After in vitro inhibition of endothelin receptors with Bosentan, both WT and HCM mice had similar increases in myogenic constriction. Also, the sensitivity to exogenous endothelin was significantly reduced in HCM mice, suggesting that the reduced myogenic constriction in HCM was due to reduced receptor sensitivity. There have been reports of doubling of the endothelin-1 concentration in serum in patients with HCM and in some patients mRNA for pre-proendothelin-1 is markedly increased. Endothelin-1 is known to increase fibrosis through the ETb receptor and hypertrophy through the ETa receptor. In this study we will orally feed HCM mice with Bosentan over a time period of 9 months. We will then try to elucidate what effect endothelin-1 inhibition has on cardiac hypertrophy, cardiac haemodynamics, cardiac fibrosis, the coronary artery myogenic

189 reponse, and to see if the decreased sensitivity to exogenous endothelin-1 in the vasculature can be reversed. The main methods used will be pressure myography (Mulvany-Halpern myograph), catheterization to assess cardiac haemodynamics, and Western blotting to quantify possible differences in ETa/ETb receptor amounts.

P24.01 Majken K. GENE-DIET INTERACTIONS IN THE REGULATION OF CHOLESTEROL Jensen METABOLISM AND RISK OF ACUTE CORONARY SYNDROME – Description of a PhD project. Majken K. Jensen, Kim Overvad and Erik Berg Schmidt. Department of Clinical Epidemiology, Aalborg Hospital, Aarhus University Hospital, 9100 Aalborg, Denmark. Objective: The aim of this PhD project is to investigate whether variation in three candidate genes involved in cholesterol metabolism is associated with risk of acute coronary syndrome, and whether dietary factors associated with plasma concentrations of cholesterol sub-classes modifies inherent genetic risks. Study population: A case-cohort study is designed within the Danish ‘Diet, Cancer and Health’ study population. A total of 1500 cases of acute coronary syndrome have been identified among 57,053 men and women who participated in a baseline examination between 1993-1997 when they were aged 50-64 years. A random sample of 1500 participants will be drawn as the ‘control’ population. Exposures: All members of the cohort have filled out a detailed 192-item food frequency questionnaire and a questionnaire concerning lifestyle factors. Participants were asked to provide a blood sample and fat biopsies were also obtained. Candidate genes for acute coronary syndrome have been selected among those involved in cholesterol transport (ATP-binding cassette transporter A1, Cholesterol-ester transfer protein, and acyl- CoA:cholesterol acyltransferase 2). Five single nucleotide polymorphisms (SNPs) will be genotyped within each gene. SNPs will be selected among those with demonstrated functional importance, as assessed in public databases. Methods: Statistical analyses of association between genetic variation in the three chosen genes and risk of acute coronary syndrome will be performed in SAS. Explorations of biological interaction, as defined by Rothman, will be of particular focus in the thesis.

P24.02 Jacob Tauris CUBILIN AND MEGALIN EXPRESSION IN THE INNER EAR J. Tauris, E.I. Christensen, A. Nykjaer, C. Jakobsen, T. Ovesen Dept. of Otorhinolaryngology, Aarhus University Hospital, Noerrebrogade 44, 8000 Aarhus C, Denmark, email:[email protected] Cubilin and megalin are two important multifunctional endocytic receptors expressed in many absorptive epithelia and acting together in concert to perform significant physiological functions in several tissues of the organism. The aim of the present study was to investigate the expression of cubilin in the inner ear of neonatal rats and to compare the results to the expression of megalin, since megalin has previously been shown to act as a drug receptor for aminoglycosides (AG) and other

190 polybasic substances, well known ototoxic drugs. In the cochlea immunohistochemical labelling of cubilin showed expression corresponding to the apical surface of the strial marginal cells, epithelial cells at the spiral prominence and epithelial cells of Reissners membrane facing the cochlear duct. In the vestibular apparatus positive labelling was found in vestibular dark cells of the utriculus and cells flanking the hair cell regions of the semicircular ducts. The exact same tissue distribution was found for megalin. Specific antibody reactivity was confirmed with immunoblotting. Our results demonstrate that cubilin completely colocalizes with megalin in the cochlea as well as in the vestibular apparatus. These findings support the prevailing view that cubilin and megalin comprise a dual-receptor complex facilitating the function of each other. The physiological role of this dual-receptor complex in the inner ear remains unclear. However, the distribution of the receptors in the inner ear combined with the multiligand binding properties of both cubilin and megalin could indicate, that these receptors act as a high capacity – low affinity system for scavenging of macromolecules from the endolymph. Furthermore we investigated the binding properties of six different AG to cubilin and megalin respectively. These studies interestingly show that all six AG bind to both cubilin and megalin with the same affinity. The impact of these results is discussed.

P24.03 Simon Buus INDIVIDUAL RADIATION RESPONSE OF PAROTID GLANDS INVESTIGATED BY DYNAMIC 11C-METHIONINE PET Simon Buus, M.D. 1, 2, Cai Grau, M.D., D.M.Sc. 2, Ole Lajord Munk, Ph.D.1, Anders Rodell, Ph.D. 1,3, Kenneth Jensen, M.D. 2, Kim Mouridsen M.Sc. 3 and Susanne Keiding, M.D., D.M.Sc.,1, 4 1PET Center, 2Department of Oncology, 3Center for Functionally Integrative Neuroscience (CFIN), 4Department of Medicine V, Aarhus University Hospital, Aarhus, Denmark The purpose was to investigate by dynamic 11C-methionine PET the individual radiation dose-function relationship of parotid glands in head and neck cancer patients. Previously, we showed that net the metabolic clearance of 11C-methionine of the parotid gland, K, calculated from dynamic 11C-methionine PET, can be used as a measure of parotid gland function. The study included twelve head and neck cancer patients that were examined by dynamic 11C-methionine PET after radiotherapy (RT). Parametric images of K were generated, co-registered and compared voxel- by-voxel with the 3D radiation dose plan within the parotid gland to assess the individual radiation dose function relationship. In each patient, voxel-values of K decreased with increasing radiation dose. Population based analysis showed a sigmoid dose response relationship of parotid gland, from which we estimated a threshold radiation dose of 16 Gy, and mean TD50 of 28 Gy. TD50 ranged from 7 to 50 Gy. In conclusion, individual radiation dose response of parotid glands can be measured by dynamic 11Cmethionine PET. The dose-response analysis revealed a sigmoid relationship, a threshold radiation dose at 16 Gy, and a

191 mean TD50 of 28 Gy; values are relevant for treatment planning in order to spare parotid gland function during RT.

P24.04 Jesper QUALITY OF LIFE, BODY COMPOSITION, RESTING ENERGY Karmisholt EXPENDITURE AND LEVEL OG PHYSICAL ACTIVITY IN PATIENTS WITH SUBCLINICAL HYPOTHYROIDISM Jesper Karmisholt, Peter Laurberg, Dept. of endocrinology, Aalborg Hospital, Århus University Hospital, 9000 Aalborg Thyroid hormones have effect on most organ systems including the central nerve system, skeletal muscle- and cardiopulmonary function. It is discussed whether patients with subclinical hypothyroidism (SH) should receive thyroid hormone substitution, as there is doubt whether this mild hormonal imbalance affects health. A negative effect on self rated perception of health is significant to patients, and important to recognize. The level of physical activity is not investigated in patients with SH. As thyroid hormones have influence on skeletal muscle- and cardiopulmonary function, it is relevant to investigate if the level of physical activity is altered. It is well know that a decreased level of physical activity has negative health impact. The investigation will provide information on whether SH patients differ from euthyroid individuals on the measured parameters. It will also give information on the variation through the year of the measured parameters in SH patients. Twenty patients with SH will be investigated every month for a period of one year. Investigations constitute measurement of thyroid hormones, quality of life (SF-36), resting energy expenditure (indirect calorimetry), physical activity level (pedometers and questionnaire) and body weight. The first and last investigation includes a measurement of body composition by DXA-scan. Examination of thyroid size, structure and function by ultrasound and scintigraphy is also performed. The SH patients is compared to 20 age matched euthyroid controls.

P24.05 Ripudaman HEAT SHOCK PROTEIN 70 GENE IN ASSOCIATION WITH HUMAN Singh LONGEVITY IN DANISH POPULATION Ripudaman Singh, Suresh I. S. Rattan, Peter Bross and Steen Kølvraa. Department of Human Genetics. University of Aarhus. 8000. Aarhus C. Denmark. We have studied the possible association of alleles, genotypes, and haplotypes derived from single nucleotide polymorphisms in three heat shock protein genes (HSP70A1A, HSP70A1B and HSP70A1L) with human longevity in the Danish population. The involvement of HSPs in the cellular maintenance and repair mechanisms make them suitable candidates for studying their association with ageing and longevity. DNA samples from different age-related cohorts from Danish registeries were genotyped using real-time PCR (light cycler). We observed an significant association between HSP70A1A(A-110AC) polymorphism with ‘self-rated health’ and ‘relative self rated health’ (p=0.0046 and 0.018, respectively) in 400 individuals from the “Longitudinal Study of

192 Danish Twins” (LSADT). We employed a novel method of measuring the haplotype relative risk (HRR) and observed an age dependant decrease in the frequency of haplotype A-A-C and increase the frequency of A-A- T in males (p=0.02). Another observation showed that the carriers of haplotype A-A-T survived better (p<0.001), whereas the carriers of haplotype A-A-C (p<0.001) survived worse than the non-carriers substantiating our above observations. We also used a novel method and performed a longitudinal study of human survival on one of the cohorts of Danish population. We observed that the female carriers of genotypes HSP70A1A-AA and HSP70A1B-AA were bad survivors (p=0.005 and 0.003 respectively) as compared to the non-carriers. We have also studied the age-dependant ability to respond to stress, the process called ‘heat shock response’ (HSR), and shown that the carriers of alleles which decrease with age also show decreased HSR.

P24.06 Donna Marie THE CALCIUM-ACTIVATED CYCLIC-GMP DEPENDENT CHLORIDE Briggs CHANNEL CONTRIBUTES TO RAT MESENTERIC RESISTANCE ARTERY VASOMOTION D.M. Briggs, V.M. Matchkov, H. Nilsson, and C. Aalkjær. Department of Physiology, Institute for Physiology and Biophysics, University of Aarhus. Vasomotion, defined as oscillatory vascular tone, is present in most resistance artery vasculatures. Mesenteric resistance arteries, which contribute significantly to the control of systemic blood pressure, have been extensively studied and many of the known cellular mechanisms of vasomotion have been elucidated from them (Peng H, et al. Circ Res 2001; 88: 810–815). One component of the mesenteric model of vasomotion requiring exploration is a plasma membrane ion channel that could depolarise vascular smooth muscle cells (VSMCs). A candidate channel,

possibly integrating other important signals in the model, is ICl(Ca-cGMP): a Ca2+-activated cGMP-dependent chloride-current. The purpose of this study

was to explore ICl(Ca-cGMP) in vasomotion of isolated rat mesenteric resistance arteries stimulated with noradrenaline. The effects of classic Cl- channel blockers in intact preparations are difficult to interpret due to their non-specific effects via other channels and transporters. An alternative is chloride substitution where the properties of other anions are exploited. The ability of the anion thiocyanate (SCN-) to permeate (i.e. enter) the channel, without passing through it (i.e. conduct current), results in an “anion block”. When SCN- is substituted for Cl-, vasomotion is inhibited in a concentration-dependent and fully reversible manner. The specificity of the chaotrope SCN- has been questioned in other preparations. However, the effect of SCN- on vasomotion occurred here without other important intracellular factors being affected: gap-junction 2+ 2+ coupling, [Ca ]i, Ca -store release, pHi, and excitation-contraction coupling were unaffected when 36 mM SCN- was present. Therefore, we conclude

that ICl(Ca-cGMP) and chloride conductance contributes to the noradrenaline- stimulated vasomotion in rat mesenteric arteries.

P24.07 Borja DEVELOPMENT OF KNOCK-IN MOUSE MODELS CARRYING AN AKV

193 Ballarín- 1-99 LTR INTO THE N-RAS/UNR LOCUS González B.Ballarín-González, E.M.Fuchtbauer, J.Martín-Hernández, A.C.Fuchtbauer F.S.Pedersen. Department of Molecular Biology, University of Aarhus, 8000 Aarhus C, Denmark Induction of mouse tumourigenesis by retroviruses has been extensively used in the identification and characterization of cancer-involved genes. One of such experiments conducted in our laboratory highlighted the overexpression of N-ras as an important factor in the development of B-cell lymphomas induced by the murine leukemia virus Akv1-99 (Martin- Hernadez J, Sorensen AB, Petersen FS, Journal of Virology 2001; 75 (23): 11907-11912). The aim of our project is to study the effect of inserting a single Akv1-99 LTR at the exactly same three positions as the previously identified Akv1-99 viral integrations. Insertion, at these positions, of the single LTR in the same and opposite transcriptional orientation as the N-ras gene might help us to better understand viral-induced tumourigenesis by promoter or enhancer insertion, respectively. Additionally these mouse models could also be used to study genes cooperating with N-ras in lymphoma induction. Finally, another possible outcome could be the study of viral silencing by methylation. At present, three of the constructs have been cloned by recombineering (phage-based E.coli recombination system) and transfected into embryonic stem cells and we are screening by southern blot analysis for those cells that have been targeted by our constructs, incorporating the LTR into their N-ras/unr locus. The right clones will be introduced into the blastocoel cavity of 4-5 days old embryos followed by surgical implantation into pseudo-pregnant mice.

P24.08 Xiao-Yue RECONSTRUCTION OF MOUSE NEPHRONS Zhai X.Y. Zhai, J.S. Thomsen, H. Birn, I.B. Kristoffersen, A. Andreasen, E.I. Christensen Department of Cell Biology, Institute of Anatomy, University of Aarhus, DK 8000, Denmark. Renal function is crucially dependent on renal microstructure providing the basis for the regulatory mechanisms controlling the transport of water and solutes between filtrate and plasma and the urinary concentration. A 3D reconstruction of 200 nephrons and collecting ducts was performed on aligned digital images, obtained from 2.5-µm-thick serial sections of mouse kidneys. A series of custom-made computer programs which ran on a Linux system made the tracing of the renal tubules possible. Detailed information on mouse renal architecture have been obtained, including the spatial course of the renal tubules, lengths of different segments of nephrons, histotopography of tubules and vascular bundles, and epithelial ultrastructure at well-defined positions along the nephrons. Important novel findings include: 1. A tortuous course of the descending thin limbs of the long-looped nephrons and a winding course of the thick ascending limbs of the short-looped nephrons contributed both to a 27% average increase in the lengths of the corresponding segments. 2. The thick-walled tubules incorporated in the central part of the vascular bundles in the inner stripe of the outer medulla have been identified as thick ascending limbs of

194 long-looped nephrons. The descending thin limbs of all short-looped nephrons are integrated into the vascular bundle in the outer part of the inner stripe of the outer medulla. 3. Three type bends of the short-looped nephrons are identified and shown to relate to the spatial path and lengths of the nephrons and their corresponding corpuscles. 4. The ultrastructure of the thin limbs of Henle’s loop is characterized by four type epithelia, which suggests important implications for renal transport mechanism, and should be considered when evaluating the segmental distribution of receptors, and water and solute transporters within the normal and diseased kidney.

P24.09 Søren THE PHYSIOLOGICAL SIGNIFICANCE OF THE TMAX PARAMETER IN Cristensen BOLUS TRACKING MRI S. Christensen, O. Wu, H. Karstoft, N. Hjort, K. Butcher, S. Davis, L. Ostergaard CFIN, Aarhus Sygehus, Nørrebrogade 44, 8000 Århus C. The Tmax parameter used in Bolus tracking MRI has proved to be a promising penumbra pseudo marker [K.S. Butcher et al. Stroke 2005; 1153-9. Ludy C. Shih et al. Stroke 2003 Jun;34(6):1425-30], yet the physical parameters it reflects have not been examined in detail. We performed simulations to determine influence of cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT) and bolus time to travel (TTT) on Tmax. The simulations covered: Range/interval TTT = 0-10 / 0.5 s, MTT= 4-16/ 2 s. CBV=2% and 4%. Residue function shapes were, boxcar, linear and exponential. Noise generation was as in [O. Wu et al. MRM 2003 ;50(1):164-74]; k-values and SNR were set to reflect our 3T-data. The results showed that Tmax was well described as a linear combination of MTT and TTT p for the regression was <0.001 for all residue functions and CBV. The MTT and TTT coefficients vary across residue functions, but in all cases Tmax is mainly influenced by TTT and to a lesser extent MTT. The implications are that Tmax is not just a measure of acutely disturbed hemodynamics; due to its sensitivity to delay in general, chronic changes such as ICA stenosis will affect Tmax. If slice acquisition timing differences are not corrected for they will also bias the measure. In the light of these findings it is conceivable that Tmax is sensitive mainly to phenomena of macrovascular origin that introduce delay downstream of the site of arterial input function selection. In conclusion, Tmax reflects mainly TTT and to a lesser extent MTT. The maps should be interpreted with caution due to the potentially biasing delay sensitivity.

P24.10 Peter PORCINE BLASTOCYSTS PRODUCED BY HANDMADE CLONING Michael WITH A COMBINED ELECTRICAL AND CHEMICAL ACTIVATION Kragh P.M. Kragh, Y. Du, T.J. Corydon, G. Vajta and L. Bolund Department of Human Genetics, University of Aarhus, DK-8000 Aarhus C, Denmark, and Section of Population Genetics and Embryology, Institute of Agricultural Sciences, DK-8830 Tjele, Denmark. Email: [email protected] The purpose of our work was to establish an efficient protocol for activation of porcine nuclear transfer (NT) embryos produced by the Handmade Cloning (HMC) technique. Firstly, we investigated a combined electrical and chemical activation protocol for parthenogenetic development

195 of in vitro matured zona-free oocytes. Oocytes were activated by a single DC pulse and subsequently cultured in cytochalasin B (CB) and cycloheximide (CHX). Developmental rates of blastocysts from activated oocytes were in average (mean ± s.e.m.) 49 ± 1% and 40 ± 2%, when using a pulse of 0.85 or 1.25 kV/cm for 80 µs, respectively. Secondly, the activation protocol was applied in the HMC technique. Zona-free porcine oocytes were bisected and halves containing no chromatin, i.e. the cytoplasts, were selected. Reconstructed embryos were produced by a two step fusion procedure. First, one cytoplast was fused to one fibroblast by a single pulse of 1.25 kV/cm for 80 µsec, and after one hour, the cytoplast-fibroblast pair and another cytoplast were fused and activated simultaneously by a single pulse of 0.85 kV/cm for 80 µsec, and subsequently cultured in CB and CHX. The development of reconstructed embryos to the blastocyst stage was in average 21 ± 4%. Thus, a combined electrical and chemical activation procedure resulted in efficient blastocyst development in the HMC technique.

P25.01 Mads METHOD DEVELOPING AND BASIC RESEARCH FOR SNP DETECTION Vilhelm AND FUNCTIONALITY WITH SPECIAL INTEREST IN ASSOCIATIONS Hollegaard TO PRETERM BIRTH Mads V. Hollegaard1,2,3, David M. Hougaard2, Susanne Mandrup3 and Poul Thorsen1. 1NANEA, Dept. of Epi. Soci. Med. AU, 2 Dept. Clin. Biochem., SSI. 3 Dept. Biochem. Mol. Biol. SDU, Denmark. Preterm birth (PTB) is a major cause of infant morbidity and mortality. Several observations support the hypothesis that preterm birth is influenced by genetics. To further investigate this we designed a large candidate gene Single Nucleotide Polymorphism (SNP) genotype study of PTB. Our study, consisting of both PTB and Cerebral Palsy (CP) cases and controls, covers 1,152 SNPs located in the promoter and coding sequences of 139 different genes. The main purpose of the assay is to select SNPs of special interest in PTB and CP and to describe the haplotypes, genotypes, and allele patterns of the different SNPs in a Danish Caucasian population. The SNPs of special interest will be included into several “in house” genotyping assays. These assays will be designed and developed with one or several different methods, padlock probes, Allele Specific Oligonucleotides (ASO) or Allele Specific Primer Extension (ASPE). The methods will be adapted to the Luminex platform (Luminex corp. Austin, TX, USA). These assays will be used for genotyping a large PTB cohort study including 3,500 patients, drawn from the “Bedre Sundhed for Mor Barn” (BSMB) cohort. Earlier studies have shown that SNPs in the regulatory region of TNFA and IL1B is associated with PTB. To investigate the molecular mechanism of these SNPs transcient transfection assays on different haplotypes, Chromatin Immuno Precipitation and direct stimulation of PMBC’s followed by quantification of the secreted proteins will be carried out. We hope that these studies can give us a tool for identifying women at high risk of PTB so that it may be possible to initiate pertinent preventive actions focusing directly or indirectly on the dys-regulated protein or cytokine balance and in that way reduce neonatal mortality and morbidity.

196 P25.02 Erik Langer CHANGES IN ENDOTHELIAL FUNCTION AND ADIPOKINES IN Madsen RELATION TO GASTRIC BANDING INDUCED WEIGHT LOSS. A STUDY DESIGN. UNIVERSITY OF AARHUS GRADUATE SCHOOL OF HEALTH SCIENCES, 13 JANUARY 2006 E.L. Madsen Department of Medical Endocrinology C, Aarhus University Hospital - THG, Tage Hansensgade 2, DK 8000 Aarhus C, Denmark. The aim of the study is to investigate the effect of surgically induced weight loss on a) the cardiovascular health marker: endothelial function and b) inflammatory markers released by human adipose tissue (adipokines). In a population of 30 non-diabetic obese subjects age 20 - 60 years, without overt cardiovascular disease or uncontrolled hypertension measures of endothelial function and circulating adipokine levels will be investigated before and after (6 + 12 months) weight loss induced by gastric banding. Endothelial function will be assessed non-invasively by ultrasound in the brachial artery and measures of circulating adipokines: Tumor Necrosis Factor , interleukin 6 and 8 will be assessed by ELISA.

P25.03 Andrey POSITION EFFECTS ON GENE EXPRESSION AS STUDIED ON A Azov BALANCED TRANSLOCATION MODEL A.G. Azov Laboratory of Molecular Pathology, University of Aarhus, 8000 Aarhus C, Denmark It is remarkable how cells in a complex multicellular organism, although sharing the same genes, exhibit a variety of structure and function. Obviously, complex regulatory mechanisms must be involved. It is our intention to investigate one such mechanism—the position where genes end up inside the nucleus of the functional cell. The material for research is cell lines derived from a Danish family with a balanced translocation between the short arm of chromosome 6 and the long arm of chromosome 14. Despite the absence of any genetic gains or losses (as shown by array comparative genomic hybridization), the translocation affects the phenotype of the carriers and manifests itself clinically with a spectrum of autoimmune disorders grouped as autoimmune polyglandular syndrome. Moreover, global gene expression profiling performed by a collaborating group showed major changes in gene expression compared with control cells. Using fluorescence in situ hybridization (FISH), we plan to visualize the breakpoint regions and examine their positions in interphase nuclei. Furthermore, as FISH is a rather crude technique in the sense that it detects only sufficiently large portions of DNA, we are working on new methods that will allow visualization of individual genes and thus help us examine in more detail the fate of those genes whose expression is affected by the translocation.

P25.04 Maiken THE PRECISION AND INFLUENCE OF FLEXION FOR BMD Møller- MEASUREMENTS OF THE PROXIMAL TIBIA FOLLOWING TOTAL Pedersen KNEE ARTHROPLASTY. A METHODOLOGICAL DEXA STUDY. M. Møller-Pedersen, O. Rahbek, K. Søballe.

197 Department of Orthopaedics, Århus University Hospital, THG, Denmark. Background: Bone quality is very important for the success of joint prostheses implantation and the assessment of the periprosthetic bone density after total knee arthroplasty (TKA) is currently being compared to monitoring implant stability by RSA and is expected to become an important method of implant survival evaluation. Protocols for DEXA knee scans often suggest that the knee be positioned in full extension, but according to physiotherapist reports extension deficit often prohibits this position during the first postoperative week where the baseline bone mass density (BMD) scan, used in clinical studies, is performed. Methods: Using a Lunar Prodigy Advance DEXA scanner periprostetic BMD was measured in 7 regions of interest in close relation to the tibia components fixed with bone cement in dry phantom bone. Two different stem designs were compared (Biomet Maxim wedge stem vs. I-beam stem). BMD measurements were repeated 5 times at every 5° of interval change in flexion from 0 degrees to 20 degrees of flexion. The position of the bone was secured in a clamp set up design. Findings: The precision error of the scanner was 1-2% (coefficient of variation of the mean BMD). The I-beam implant BMD significantly changed between 10-15 degrees of flexion and the Wedge implant BMD significantly changed between 0-5 degrees of flexion. Discussion: The aim of this study was to suggest a validated analysis protocol for the assessment of BMD in the proximal tibia after TKA. This study underlines that adequate positioning of the knee in a standardized manner during DEXA scans is important for obtaining a reliable precision in prospective clinical studies.

P25.05 Yuelian Sun APGAR SCORES AND LONG-TERM RISK OF EPILEPSY -A Population-based Cohort Study Y. Sun1, M. Vestergard1, C.B. Pedersen2, J. Christensen3, J. Olsen1 1 Department of Epidemiology, University of Aarhus 2 National Centre for Register-based Research, University of Aarhus 3 Department of Neurology and Department of Clinical Pharmacology, Aarhus University Hospital We examined if a low Apgar score can predict epilepsy in childhood and early adulthood. An association between low Apgar scores and epilepsy could support the view that pre- or perinatal factors play a role in the etiology of epilepsy. We carried out a population-based cohort study of 1,538,732 infants born alive in Denmark between January 1, 1978 and December 31, 2002 by using national registers. The one- and five-minute Apgar scores were recorded by midwives following standardized procedures. The endpoint was registered hospitalizations and outpatients with epilepsy according to International Classification of Disease (ICD-8 before 1994 and ICD-10 from 1994). Outpatients were included in the register from 1995. The incidence rate of epilepsy increased with decreasing one- and five- minute Apgar scores and the incidence rate decreased when the Apgar scores improved from one to five minutes. The incidence rate of epilepsy was 628 per 100,000 person-years for those with five-minute Apgar scores of

198 1 to 3 and 86 for those with a score of 10 (incidence rate ratio: 7.14, 95%CI: 5.79-8.81). The risks of epilepsy associated with low Apgar scores were particularly high in early childhood. The association between Apgar scores and epilepsy did not change in children without cerebral palsy, congenital malformation and a parental history of epilepsy. The Apgar score was strongly associated with the risk of epilepsy throughout childhood and early adulthood. More attention should be given to the pre- and perinatal time period when evaluating causes of epilepsy.

P25.06 Claus Olesen DEPHOSPHORYLATION OF THE CALCIUM PUMP COUPLED TO COUNTERION OCCLUSION. Claus Olesen1#, Thomas Lykke-Møller2 Sørensen, Rikke C. Nielsen2, Anne- Marie L. Jensen2, Jesper Vuust Møller1 and Poul Nissen2. 1Department of Physiology and Biophysics Ole Worms Alle 185 DK-8000 University of Aarhus, Denmark. 2Centre for Structural Biology, University of Aarhus, Denmark. #e-mail [email protected] To understand the dephosphorylation mechanism and to reveal the intramolecular coupling between cation transport and ATP hydrolysis, we crystallized sarcoplasmic reticulum Ca2+-ATPase (SERCA1a) in complex with aluminium fluoride. This represents the transition state of hydrolysis of the counterion-bound (protonated) phosphoenzyme (Olesen et al Science 306, 2251). The planar aluminium fluoride group is located between the conserved Asp351 side chain and a water molecule, thus representing the transition state of hydrolysis of the phosphoenzyme. The water molecule is positioned and activated for a nucleophilic attack by Ser181 and Glu183 of the conserved TGES motif of the A-domain. This arrangement overlaps - with the position of ADP:AlF4 in phosphoryl transfer in the E1~P structure (Sorensen et al Science 304,1672). The domain movements associated with the formation of the dephosphorylation site depend on the release ADP after ATP phosphorylation, and the dephosphorylation reaction cannot proceed before the bound Ca2+ ions have been exchanged for protons that become occluded. The helix bundle constituting the proper arrangement of the dephosphorylation site for catalytic activity is stabilized by an integral K+-site (Sorensen et al., J Biol Chem 279(45) 46355-8), explaining the stimulatory effect of monovalent cations on dephosphorylation. The new structure provides a rationale for the vectorial transport of Ca2+ and couples it with the counterion exchange needed for dephosphorylation.

P25.07 Anette HYALURONAN INTRA-ARTICULAR IS WITHOUT LONG-TERM Jørgensen CLINICAL EFFECT IN KNEE OSTEOARTHRITIS (OA). A MULTICENTER, RANDOMIZED, PLACEBO-CONTROLLED DOUBLE- BLIND STUDY OF 335 PATIENTS WITH MODERATE TO SEVERE KNEE OA A.Jørgensen,1 K.Stengaard-Pedersen,1 and the Hyalgan® study group.2 1Department of Rheumatology, Aarhus University Hospital, 2Department of Orthopaedics, Hjørring Hospital, Clinic of Rheumatology, Parker Institute/Frederiksberg Hospital, Department of Orthopaedics, Odense University Hospital, Department of Orthopaedics, Herlev University Hospital, King Christian X’s Hospital for Rheumatic Diseases, Department

199 of Orthopaedics , Holstebro Hospital, Department of Radiology, Aarhus University Hospital, Larix Aps., Værløse. Sponsored by Nycomed Denmark A/S Aim of study: To examine long-term efficacy and safety of five intra- articular injections with Hyalgan®, a natural hyaluronan extracted from rooster (MW 500 – 730 kDa), for the treatment of knee osteoarthritis. Methods: A multi-center, randomized, placebo-controlled double blind study of 335 patients who full-filled the American College of Rheumatology (ACR) criteria for osteoarthritis with moderate to severe disease activity. These patients were randomized with 165 patients to hyaluronan and 170 patients to placebo intra-articular injections. Intra-articular injections of 2 ml Hyalgan® (20mg/2ml) or 2 ml placebo (saline) were administered once a week for 5 weeks. The study duration was 1 year. Time to recurrence (defined as ”Time from start of improvement until either: a) Lequesne algo- functional Index (LFI) recording is higher by at least 1 than any of the recordings at visit 1 to 6 and the patient confirm that her/his condition is at least back to baseline, or b) Patient wants to withdraw or investigator wants to withdraw patient to start other therapy ”) was primary efficacy parameter. Pain during 50 meters walk (100 mm VAS), patients global assessment, acetaminophen consumption, Nottingham Health Profile Questionnaire and volume of joint effusion were evaluated as secondary efficacy parameters. All adverse events were registered and analyzed. An Intention To Treat (ITT) analysis and a Per Protocol (PP) analysis was conducted for primary efficacy parameter, VAS and acetaminophen consumption. A Per Protocol (PP) analysis was conducted for remaining secondary efficacy parameters. Results: Time to recurrence showed no significant treatment effect (ITT analysis P= 0,26 and PP analysis P= 0,20). Change from baseline in LFI showed no treatment effect as mean difference (95% confidence limits CL) was 0,29 (-0,34 to 0,93) after 3 months, 0,66 (-0,23 to 1,55) after 6 months and 1,12 (-0,47 to 2,71) after 12 months. Change from baseline on visual analog scale (VAS) (Pain on walking) was equal in the hyaluronan and the placebo treated groups with a mean difference (95% CL) of 0,07 (-0,34 to 0,48) after 3 months, 0,17 (-0,37 to 0,72) after 6 months and 0,39 (-0,57 to 1,35) after 12 months. Patients global assessment showed no treatment effect, actually there was a significant difference in favour of placebo after 6 months (p=0,04) but not after 3 (p=0,44) or 12 months (p=0,69). Concerning acetaminophen consumption the Hyalgan® group took slightly fewer tablets per day compared to baseline than placebo patients, however the difference was not significant, mean difference (95% CL) was -0,16 (-0,59 to 0,26) after 3 months, -0,23 (-0,75 to 0,29) after 6 months and -0,48 (-1,36 to 0,39) after 12 months. At least one adverse event was registered in155 patients and 93 patients had at least one adverse drug reaction but no difference between Hyalgan® and placebo group was found. Twenty-one serious adverse events was reported but again no difference between Hyalgan® and placebo group. Conclusion: In patients full-filling the ACR-criteria for OA of the knee and with moderate to severe disease activity five intra-articular injections with Hyalgan® did not improve pain, function, acetaminophen consumption or

200 other efficacy parameters 3, 6, 9, and 12 months after the treatment.

P25.08 Birgitte CHRONIC PAIN FOLLOWING HYSTERECTOMY: A NATIONWIDE Brandsborg STUDY OF CHRONIC PAIN COMBINING QUESTIONNAIRE AND SURGICAL DATA. B. Brandsborg, L. Nikolajsen, C.T. Hansen, H. Kehlet, T.S. Jensen Danish Pain Research Center, Aarhus University Hospital, Noerrebrogade 44, bldg.1A, 8000 Aarhus C, Denmark. Background: Chronic post-operative pain is a potential complication after major surgical procedures like amputation or thoracotomy, but it is also increasingly recognized in minor surgery. Little is known about chronic pain following gynaecological procedures, but a recently published questionnaire study described pain in 12.3% of women one year after caesaerean section. We studied the prevalence of pain one year following benign hysterectomy in relation to clinical data from the time of surgery. Methods: A questionnaire concerning the present pain experience one year following hysterectomy was sent to 1299 women consecutively included from the Danish Hysterectomy Database. We included 1147 women (88.3%), and pain data were combined with clinical data from the time of surgery extracted from the database. Results: Pain in the pelvic area was reported one year after hysterectomy by 364 women (31.7%), and 54 (14.8%) of these did not recall having pain before the operation. Mean pain intensity on a visual analogue scale (VAS 0-10) was 4.2 (2.0 SD) and maximum was 6.1 (2.5 SD). Pain was more common in women who had an abdominal hysterectomy compared to women who had a vaginal hysterectomy (OR 1.6, CI 1.2-2.1). Chronic pain was not related to the type of incision or anaesthesia. There was a higher prevalence of previous caesaerean section among the women with chronic pain (OR 1.8, CI 1.3-2.5), and women with chronic pain had a higher prevalence of pain problems elsewhere (OR 3.4, CI 2.5-4.6). Conclusion: 31.7 % still have pain one year following hysterectomy. Some risk factors are identified, but further clinical examination is needed.

P25.09

P25.10 Kai Wang DEVELOPMENT OF BIOINFORMATICS TOOLS FOR DIAGNOSTIC PROCEDURES INVOLVING ARRAY ANALYSES OF DEGENERATIVE DISEASE PROCESSES K. Wang, C. Wiuf, and L. Bolund Institute of Human Genetics, The Bartholin Building, Wilhelm Meyers Allé, Building 240, University of Aarhus, DK-8000 Aarhus Degenerative disorders are a growing medical problem in the aging populations of the world. Two aspects of biological maintenance seem to be of particular medical importance: 1. DNA stability and repair; 2. Protein folding and quality control. Array technologies have opened up new possibilities for obtaining large amounts of data regarding the integrity of the genetic material and the expression of its genes. Thus, genomic fragment arrays can reveal aberrations by CGH and oligonucleotide arrays can reveal the expression patterns of importance for cellular protein quality

201 control, stress responses and death processes. Accurate identification of degenerative disorders from thousands of array CGH and gene expression measurements requires robust computational tools. The array CGH data will be collected in collaboration with PhD student Jian Li. The oligonucleotide arrays design and data collection will be a joint effort with DTU and BGI. A major problem in the study is to obtain the large amounts of data needed and to extract relevant information about instability and stress as well as regulatory processes and biological networks (systems biology). Bioinformatics tools should thus be developed to handle, analyze and integrate different data types in a common framework, and bioinformatics classifiers should be built to perform molecular diagnosis and obtain prognostic outcomes of potential treatments. An important aspect is to develop tools for understanding the sequential order of chromosomal rearrangements and mutations leading to the development of degenerative disorders and the potential consequences of misfolded proteins in pathways. Tools should rely on current state-of-the-art statistical techniques, such as Bayesian Networks, genetic algorithms and multiple testing procedures.

P26.01 Lijin Zou THE EFFECT OF HYALURONAN ON OSTEOGENESIS OF PORCINE BONE MARROW STROMAL CELLS IN VITRO Lijin Zou, Xuenong Zou, Haisheng Li, Tina Mygind, Cody Bünger Orthopaedic Research Lab, Aarhus University Hospital, 8000 Aarhus, Denmark The aim of the present study is to investigate if the prolonged presence of high concentration (4.0mg/ml) 800 KDa hyaluronan(HA) can modify osteogenesis of pBMSC. Methods: pBMSC were cultured in basic medium or basic medium plus HA for 7days. Then basic medium group was subdivided into basic medium group and osteogenic medium (Dex+ -GP/Asc) group. The latter was subdibided into four group: basic medium group, osteogenic medium group, HA alone group and osteogenic medium plus HA group. Cell proliferation, ALP activity assay and mineralization were evaluated. Expression of differentiation-related genes was analysed by real-time PCR. Results: HA alone or plus osteogenic medium increased cell proliferation, whereas osteogenic medium alone had no effect. HA alone increased endogenic HA. ALP activity was increased in osteogenic medium during culture. At day14, HA plus osteogenic medium increased ALP activity compared with osteogenic medium alone. At day21, calcium deposit was increased compared with osteogenic medium. There is no difference in osteogenesis between pre-treatment of HA and non pre-treatment. Bone marker genes such as cbfa1, ALP, Osterix were decreased at day7 in HA alone, whereas at day14 HA plus osteogenic medium increased these genes expression compared with osteogenic medium alone. Osteocalcin expression result was the same to calcium deposit evaluation. Conclusion: 1. HA alone or associated with dex stimulates pBMSC proliferation. 2. HA associated with Dex can synergetically increases osteogenic differentiation.

202 P26.02 Mads METHOD DEVELOPING AND BASIC RESEARCH FOR SNP DETECTION Vilhelm AND FUNCTIONALITY WITH SPECIAL INTEREST IN ASSOCIATIONS Hollegaard TO PRETERM BIRTH Mads V. Hollegaard1,2,3, Poul Thorsen1, David M. Hougaard2, and Susanne Mandrup3. 1NANEA, Dept. of Epidemiology and Social Medicine, Aarhus University, Paludan Moellersvej 17, 8000 Aarhus C, Denmark. 2 Dept. Clinical Biochemistry, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen, Denmark. 3 Dept. Biochemestry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark. Preterm birth (PTB) is a major cause of infant morbidity and mortality. Several observations support the hypothesis that preterm birth is influenced by genetics. To further investigate this we designed a large candidate gene Single Nucleotide Polymorphism (SNP) genotype study of PTB. The assay is developed in cooperation with Illumina Corp., San Diego, CA, USA. Our study, consisting of both PTB and Cerebral Palsy (CP) cases and controls, covers 1,152 SNPs located in the promoter and coding sequences of 139 different genes. The main purpose of the assay is to select SNPs of special interest in PTB and CP and to describe the haplotypes, genotypes, and allele patterns of the different SNPs in a Danish Caucasian population. After a statistical and descriptive evaluation of the data the SNPs of special interest will be included into several “in house” genotyping assays. These assays will be designed and developed with one or several different methods, for instance padlock probes, Allele Specific Oligonucleotides (ASO) or Allele Specific Primer Extension (ASPE). The methods will be designed so that they can be detected on the Luminex platform (Luminex corp. Austin, TX, USA) which is suited for cheap high throughput assays. We plan on using these assays for genotyping a large PTB cohort study including 3,500 patients, drawn from the “Bedre Sundhed for Mor Barn” (BSMB) cohort. An early pilot study has shown that SNPs in the regulatory region of TNFA and IL1B is associated with PTB. To investigate the molecular mechanism of the SNPs found to be associated to PTB, different approaches have been planned. First, transcient transfection assays on different haplotypes with and without LPS stimulation will be done to see if there is any direct effect of the variations in a controlled system. Secondly, Chromatin Immuno Precipitation (ChIP) will be done on PMBC from different patients to quantify binding of proteins or protein complexes to DNA in its natural context embedded in chromatin. Thirdly, LPS stimulation of PMBC’s followed by quantification of the secreted proteins with a Luminex protein assay will be carried out to see the “in vivo” protein response of the different genotypes. We hope that these association studies in SNPs can give us a tool for identifying women at high risk of PTB so that it may be possible to initiate pertinent preventive actions focusing directly or indirectly on the dys- regulated protein or cytokine balance and in that way reduce neonatal mortality and morbidity. Hopefully the investigations will also help us

203 understand the patho-physiological mechanisms behind PTB.

P26.03 Mads Aaboe HUMAN TRANSCRIPTION FACTOR SOX4 Jensen M. Aaboe1, K. Birkenkamp-Demtroder1, C. Wiuf1,2, F.B. Sørensen3, T. Thykjaer1, G. Sauter4, K. Møller-Ernst Jensen5, L. Dyrskjøt1 and T. Ørntoft1. 1Molecular Diagnostic Laboratory, Department of Clinical Biochemistry, Aarhus University Hospital / Skejby Sygehus, 8200 Aarhus N, Denmark. 2Bioinformatics Research Center, University of Aarhus, 8000 Aarhus C, Denmark. 3Institute of Pathology, Aarhus University Hospital, Aarhus Sygehus, 8000 Aarhus C, Denmark. 4Department of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. 5Department of Urology, Aarhus University Hospital Skejby, 8200 Aarhus N, Denmark. We have shown that the human transcription factor SOX4 is 5-fold upregulated in bladder tumors compared to normal tissue. This was done by whole-genome expression profiling of 166 clinical bladder tumor samples and 27 normal urothelium samples using microarrays. Using a SOX4-specific antibody we found cancer cells to express SOX4 protein in bladder tumors. This led us to perform an evaluation of SOX4 protein expression in 2360 bladder tumors using a tissue microarray associated with clinical annotation. We found a correlation (p<0.05) between strong SOX4 expression and increased patient survival. This led us to conduct an analysis of SOX4 over-expression in the human bladder cell line HU609 with focus on cell survival, and identification of target genes. When induced in bladder cells SOX4 strongly impaired cell viability and promoted apoptosis. To characterize downstream target genes and to identify possible SOX4- induced pathways, we used a time-course global expression study of the effect of SOX4 over-expression in HU609 bladder cells. Analysis of microarray data showed 130 novel SOX4 related genes. Among the genes regulated by SOX4, 25 contained at least one SOX4-binding motif in the promoter sequence, suggesting a direct binding of SOX4. The gene set identified in vitro was analyzed in the clinical bladder material, and a small subset of the genes showed a high correlation to SOX4 expression. The present data suggest a role of SOX4 in the bladder cancer disease.

P26.04 Magdalena THE ROLE OF GENE RAI IN APOPTOSIS AND CANCER. CULTURES OF Janina Laska LYMPHOCYTES FROM NORMAL AND CANCEROUS INDIVIDUALS. M.J.Laska, B.A.Nexo, U.B.Jensen, U.B.Vogel. Institute of Human Genetics, University of Aarhus, DK-8000 Aarhus C. National Institute of Occupational Health, DK-2100, Copenhagen, Denamrk. We have shown that region of human chromosome 19 around the gene RAI contains DNA sequences modulating the risk for cancer in young and middle-aged persons. By identifying the function of RAI that influences the occurrence of breast cancer we will gain an important insight into protective mechanisms against this and other cancer forms. We will perform functional studies of the gene RAI in relation to cell survival and apoptosis. Specifically, we will develop cell cultures from person carrying the causative RAI variant and suitable controls and study RAI function. We will

204 pursue studies of mRNA levels in response to a number of apoptosis- inducing stimuli, and also manipulate mRNA RAI levels with siRNA and follow the consequences for survival and apoptosis. Conversely, we will introduce RAI cDNA under a suitable promoter in cells from normal and cancer-prone individuals and study the results. In this way we will gain insight into the normal function of RAI as well as the aspects of function that differ between cancer-prone individuals and normal persons. When functional studies are combined with the genetic results, we expect to learn much about apoptosis-related anti-cancer protection. This may in turn provide us with clues as to which other genes have potential to influence cancer risk.

P26.05 Malene Rohr LOWER LEVELS OF ADMA AND INCREASED ENDOTHELIUM- Andersen DEPENDENT NO-MEDIATED RELAXATION OF UTERINE SMALL Dahl ARTERIES FROM PREGNANT WOMEN M.R. Andersen,a U. Simonsen,b M. Hedegaard,a S. Stender,c C. Aalkjær.d aDept. of Obstetrics & Gynecology, Skejby Hospital, Aarhus University (AU), bDept. of Pharmacology, AU, cDept. of Clinical Biochemistry, Gentofte University Hospital, dDept. of Physiology & Biophysics, AU. The study aimed to investigate whether changes in blood biochemistry and small artery structure and function contribute to the increased uterine blood flow during pregnancy. Twenty-two pregnant undergoing elective caesarean section and 20 nonpregnant undergoing hysterectomy were included. Plasma L-arginine (NO synthase (NOS) substrate), asymmetric dimethylarginine (ADMA, NOS inhibitor), and symmetric dimethylarginine (SDMA, inactive ADMA isomer) were determined. Small myometrial arteries were isolated from isthmus. Isometric responses were assessed in a small vessel myograph after normalization of the artery diameter. Pregnant had a lower L-arginine and ADMA level, than nonpregnant, but the SDMA levels were similar. Normalized lumen diameters of arteries from pregnant were larger than from nonpregnant, but the concentration-dependent

tension development to the thromboxane A2 analog U46619 was not different. Preconstricted arteries from pregnant demonstrated enhanced concentration- and endothelium-dependent relaxation to bradykinin compared with those from nonpregnant. The bradykinin-induced relaxation was attenuated in the presence of the NOS inhibitor N-nitro-L-arginine, so that it became similar, and was unaffected by the cyclooxygenase inhibitor indomethacin. Endothelium-independent relaxation induced by the NO donor sodium nitroprusside was not different between groups. The findings suggest that the increased uterine blood flow during pregnancy is at least partly due to changes in NOS substrates and inhibitors, small artery compliance and function.

P26.06 Søren PREVALENCE OF ISCHEMIA MODIFIED ALBUMIN IN ISCHAEMIC Hjortshøj HEART DISEASE S. Hjortshoej Dept. of Cardiology, Aarhus University Hospital, DK-9000 Aalborg Biochemical markers of necrosis such as cardiac troponins and CK-MB mass are widely used to diagnose acute cardiac ischemia and thrombosis.

205 These markers are, however, detected in blood at a late stage – when irreversible damage to myocardial cells has occurred. Ischemia Modified Albumin (IMA) is a new marker, based on the principle that ischemia in the myocardium produces free radicals. By means of a colorimetric assay albumin's binding capacity for cobalt can be measured and characterized as normal (negative test) or decreased (positive test) as a marker for reversible ischemia. This study will investigate IMA in different settings of ischemic heart disease 1.IMA in patients suspected of acute coronary syndrome (ACS) 550 patients admitted to the dept. of cardiology for observation. All suspected of ACS. Blood samples have been drawn on arrival, after 6-9 hours, and after 16-24 hours. 2.IMA in patients undergoing Percutaneous Coronary Intervention (PCI) Blood samples were drawn from 3 x 25 patients undergoing PCI at our dept. (1. patients with stable angina; 2. patients with ACS referred for subacute PCI; 3. patients with ACS referred for acute PCI). As the IMA test is fast reacting, samples were collected before, during, and after PCI. Furthermore samples have been collected every 15 minutes in the first two hours, at 6-9 h, and at 16-24 h post PCI. In total 11 samples from each patient has been collected. 3.Reference population (blood donors) 255 healthy blood donors. All blood samples have been collected. Analysis of data is ongoing.

P26.07 Yutao Du HIGH OVERALL IN VITRO EFFICIENCY OF PORCINE HANDMADE CLONING COMBINING OOCYTE TRISECTION WITH SEQUENTIAL CULTURE Y Du,1,2 P M. Kragh,1,2 X Zhang,2 H Yang,3 L Bolund2 and G Vajta1 1Danish Institute of Agricultural Sciences, Tjele, Denmark; 2Aarhus University, Aarhus, Denmark; 3Beijing Genomics Institute, Beijing, China The aim of this work was to investigate the in vitro developmental competence of porcine embryos using improved parthenogenetic activation (PA) and handmade cloning (HMC). Embryos were cultured in modified North Carolina State University (NCSU37) media. Firstly, we compared the developmental competence between oocytes from sows and gilts through zona-intact (ZI) PA and zona-free (ZF) PA in 3 replicates. A single DC pulse of 0.85 or 1.25 KV/cm for 80 s was applied to ZF or ZI oocytes, following 4 h treatment with cytochalasin B and cycloheximide. Higher (p<0.05) blastocyst rates were obtained from sow oocytes (42 and 55% for ZF and ZI) than gilt oocytes (20% and 27% for ZF and ZI). Secondly, sow oocytes were used in 6 replicates of modified HMC that was based on an improved enucleation with trisection of porcine oocytes and using 3 cytoplasts and one somatic cell for embryo reconstruction. Three in vitro fertilization (IVF) replicates together with either ZF or ZI PA in parallel to HMC were used as the control systems. After trisection, more than 90% oocyte fragments were recovered, resulting in an average of 37 reconstructed embryos from 100 oocytes. Blastocyst rates of HMC, IVF, ZI PA and ZF PA embryos were 18%, 30%, 47% and 60% respectively. Our results prove that HMC in pigs

206 may result in high in vitro developmental efficiency especially with sow oocytes. In vivo developmental competence should be confirmed with embryo transfer experiments.

P26.08 Claus Olesen DEPHOSPHORYLATION OF THE CALCIUM PUMP COUPLED TO COUNTERION OCCLUSION. Claus Olesen1#, Thomas Lykke-Møller2 Sørensen, Rikke C. Nielsen2, Anne- Marie L. Jensen2, Jesper Vuust Møller1 and Poul Nissen2. 1Department of Physiology and Biophysics Ole Worms Alle 185 DK-8000 University of Aarhus, Denmark. 2Centre for Structural Biology, University of Aarhus, Denmark. #e-mail [email protected] To understand the dephosphorylation mechanism and to reveal the intramolecular coupling between cation transport and ATP hydrolysis, we crystallized sarcoplasmic reticulum Ca2+-ATPase (SERCA1a) in complex with aluminium fluoride. This represents the transition state of hydrolysis of the counterion-bound (protonated) phosphoenzyme (Olesen et al Science 306, 2251). The planar aluminium fluoride group is located between the conserved Asp351 side chain and a water molecule, thus representing the transition state of hydrolysis of the phosphoenzyme. The water molecule is positioned and activated for a nucleophilic attack by Ser181 and Glu183 of the conserved TGES motif of the A-domain. This arrangement overlaps - with the position of ADP:AlF4 in phosphoryl transfer in the E1~P structure (Sorensen et al Science 304,1672). The domain movements associated with the formation of the dephosphorylation site depend on the release ADP after ATP phosphorylation, and the dephosphorylation reaction cannot proceed before the bound Ca2+ ions have been exchanged for protons that become occluded. The helix bundle constituting the proper arrangement of the dephosphorylation site for catalytic activity is stabilized by an integral K+-site (Sorensen et al., J Biol Chem 279(45) 46355-8), explaining the stimulatory effect of monovalent cations on dephosphorylation. The new structure provides a rationale for the vectorial transport of Ca2+ and couples it with the counterion exchange needed for dephosphorylation.

P26.09 Mette Rylev IDENTIFICATION OF DOMINANT IMMUNOGENIC BACTERIA AND Agerbæk BACTERIAL PROTEINS IN PERIODONTITIS. M.R. Agerbaek, D. Haubek, S. Birkelund & M. Kilian Institute of Medical Microbiology and Immunology, Aarhus University. Background: Periodontitis is an infectious disease which triggers host immune responses resulting in destruction of the tooth supporting tissues. Some species have been identified as putative pathogens, but only a limited proportion of the microflora has been examined Aim: To identify bacterial proteins to which the organism reacts in relationship to the development of periodontitis. To compare the antibody reaction towards two putative pathogens and member of the commensal microflora. Methods: A 2 dimensional gelelectroforesis will be carried out of proteins extracted from the following bacterial strains: Porphyromonas gingivalis (P.g) strain W83, Actinobacillus atinomycetemcomitans (A.a) strain HK1651 and Streptococcus gordonii, which serves as control. All three strains are

207 genome sequenced and the sequences are available in databases. The gels will be analysed by immunoblotting with sera from periodontitis patients and healthy control individuals. The proteins, which are of interest on account of their immunogenic property, will be identified by mass spectrometry with the genome sequence as reference. Rabbit antisera against A.a, P.g and S.g will be prepared and will be used as reference in the analyses. Conclusion: It is expected that this part of the project will be able to identify immunodominant proteins by bacteria which are thought to play a pathogenetic role in the development of periodontitis. Future aspects: To analyse antibodies against the whole oral microbial plaque in general concerning the identification immunodominant proteins and bacteria which have not yet been cultivated?

P26.10 Jacob ASSOCIATION ANALYSIS SUGGESTING GPR24 AS A SHARED Severinsen SUSCEPTIBILITY GENE FOR BIPOLAR AFFECTIVE DISORDER AND SCHIZOPHRENIA JE Severinsen1, TD Als2, H Binderup1, AG Wang3-4, WJ Muir5, DHR Blackwood5, O Mors2 and AD Børglum1. 1. Institute of Human Genetics, University of Aarhus, Aarhus, Denmark, 2. Department of Psychiatric Demography, Centre for Basic Psychiatric Research, Psychiatric Hospital in Aarhus, Aarhus University Hospital, Risskov, Denmark, 3. Department of Psychiatry, National Hospital, Torshavn, Faeroe Islands, 4. Department of Psychiatry, Amager Hospital, Copenhagen University Hospital, Copenhagen, Denmark, 5. Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, United Kingdom Linkage analyses suggest that chromosome 22q12-13 may harbor a shared susceptibility locus for bipolar affective disorder (BPD) and schizophrenia (SZ) ( Schwab SG, Wildenauer DB., Am J Med Genet 1999;88(3):276-8.). In a study of bipolar and schizophrenic cases from the Faeroe Islands we have previously reported association between both disorders and microsatellite markers in a 3.6 cM segment on 22q13 ( Jorgensen TH, Borglum AD, Mors O, Wang AG, Pinaud M, Flint TJ, et al.,Am J Med Genet 2002;114(2):245-52.). The present study investigated three candidate genes located in this segment: GPR24, ADSL, and ST13. Eight SNPs located in these genes and one microsatellite marker (D22S279) were applied in an association analysis of two samples: An extension of the previously analyzed Faeroese sample comprising 28 distantly related cases (17 BPD, 11 SZ subjects) and 44 controls, and a Scottish sample including 162 patients with BPD, 103 with SZ and 202 controls. In both samples significant associations were observed in both disorders with predominantly GPR24 SNPs and haplotypes. In the Faeroese sample overall p-values as low as 0.0009, 0.0054 and 0.0023 were found for haplotypes in BPD, SZ and combined cases, respectively, and in the Scottish sample overall p-values of 0.0002, 0.0135, and 0.0079 were observed for the same groups. Specific haplotypes showed associations with lowest p-values of 7x10-5 and 0.0005 in the combined group of cases from the Faeroe Islands and Scotland, respectively. This is the first study reporting association between GPR24 and BPD and

208 SZ, suggesting that GPR24 variants may confer susceptibility to both disorders.

P27.01 Esben Buhl GLUCOCORTICOID RECEPTOR ANTAGONISM REVERSES HEPATIC INSULIN RESISTANCE IN LOW BIRTH WEIGHT RATS DISPLAYING HYPOTHALAMUS-PITUITARY-ADRENAL-AXIS HYPERACTIVITY Esben S. Buhl1, Kitt Falk Petersen1, Shin Yonemitsu1, Jurg Rossbacher1, John Geisler3, Susanne Neschen1, Dongyan Zhang1, Varman Samuel1, Jung Kim2, and Gerald I. Shulman1. 1 Yale School of Medicine, Internal Medicine, Section of Endocrinology, New Haven, CT, USA. 2 Yale School of Medicine, Yale-New Haven Hospital, Department of Pathology, New Haven, CT, USA. 3 ISIS Pharmaceuticals, Carlsbad, CA. Low birth weight (LBW) is associated with insulin resistance and an increased risk of type 2 diabetes but the mechanism remains unknown. Fetal exposure to glucocorticoids leading to elevated hypothalamus- pituitary-adrenal-axis (HPA-axis) activity and insulin resistance has been suppositioned as being the mechanism. We studied a rat model for LBW implying prenatal dexamethasone exposure and during hyperinsulinemic euglycemic clamp conditions we found impaired insulin mediated suppression of hepatic glucose production associated with elevated levels of the gluconeogenetic enzymes phosphoenolpyruvate carboxy-kinase (PEPCK) and glucose-6-phosphatase (G6Pase), respectively. Rats displayed elevated expression of corticotrophin-releasing hormone at a hypothalamic level and hyperplasia of ACTH secreting cells within the pituitary gland, increased 8 a.m. plasma ACTH, exaggerated corticosterone secretion during restraint stress and more importantly there was a ~73% increase in 24 hour urine corticosterone excretion. Using an ASO-technique knock-down of the hepatic glucocorticoid receptor (GCCR), however, fully restored hepatic insulin sensitivity and the disturbances observed regarding insulin- stimulated levels of PEPCK and G6Pase were completely recovered. These data provide evidence that hepatic insulin resistance seen after glucocorticoid induced fetal growth retardation is caused by HPA-axis hyperactivity resulting in up-regulation of hepatic gluconeogenesis. Furthermore, GCCR antagonism may be a new strategy for the treatment of LBW associated insulin resistance.

P27.02 Kasper Kyng GENE EXPRESSION AND DNA DAMAGE RESPONSES IN HUMAN AGING AND PREMATURE AGING SYNDROMES K.J. Kyng Danish Center for Molecular Gerontology, Department of Molecular Biology, University of Aarhus, DK-8000 Aarhus C, Denmark. The main goal of this work was to learn more about the aging process on a celllular level. This was pursued in a number of studies using different approaches, all designed to investigate age-associated gene expression changes using DNA microarray technology. Proceeding from the framework of the DNA damage theory of aging, a chief objective was to explore a possible role of gene expression changes in the age-associated

209 accumulation of DNA mutations and decline in DNA repair capacity. The underlying hypothesis was that the mechanisms regulating gene expression, in particular after DNA damage, change with age and play a role in aging. To explore different human aging model systems we used both isogenic transformed wildtype and Cockayne Syndrome cells lines, and primary cell lines from normal aged donors and Werner Syndrome or Cockayne Syndrome patients. This setup enabled us to evaluate the extent to which premature aging syndromes resemble normal, biological aging with respect to gene expression. The role of DNA damage and stress response in aging was addressed by exposing cells to one or more types of DNA damaging agents before expression analysis. The project has resultet in three published original papers (I-III), a review (IV) and two studies in the manuscript preparation phase, I. Kyng K.J, et al. Oncogene 2003. Feb 27;22(8):1135-49. II. Kyng K.J, May,A., Kølvraa, S., & Bohr,V.A. Proc Natl Acad Sci U S A 2003. Oct 14;100(21):12259-64. III. Kyng K.J, May,A., Stevnsner,T., Becker,K.G., Kolvra,S., Bohr,V.A. Oncogene 2005. 24, 5026-5042. IV. Kyng K.J, & Bohr,V.A. Ageing Res Rev. 2005 Nov;4(4):579-602.

P27.03 Preben “MICROBIOLOGICAL PESTICIDES IN GREENHOUSES - A POSSIBLE Larsen HEALTH RISK?”. P.Larsen , Section of Respiratory Diseases, Department of Medicine C, Odense University Hospital, DK-5000 Odense C, Denmark In order to reduce the exposure of chemical pesticides both to greenhouse- workers and to the general population, the chemical pesticides have gradually been replaced by microbiological pesticides (MP) A 3- year follow-up study to evaluate the health effects on workers in greenhouses started in 1997, in 31 different enterprises in which the four different MPs were used to a varying extent. The subjects were examined annually with interview about working conditions and health with emphasis on respiratory complaints. Besides, skin prick tests to standard aero-allergens, spirometry, and histamine challenge were made, and blood was drawn for IgE-antibodies against the four MP. 456 workers were included in the run 0 in 1997. In run 1 the cohort was supplied with 123 additional persons. In total the cohort consisted of 579 persons, 184 males and 395 females. There was a loss of 140 (31 %) persons between run 0 and run 1. Among the 123 persons included in run 1 70 % participated in run 2. Of the persons participating two times 85% participated in the third while 99 % percent of those having participated three times also were included in the fourth. In all 262 persons were followed for three years, 342 were followed for at least two years, while 402 were followed for at least one year. This gave 1585 single observations and 1006 observations of incidence data covering 1146 person years. The Ph.D. reports data of the cohort of 579 persons and the data from the 1. year of follow up incl.: exposure profile of MP, respiratory and general symptoms, lung function and specific IgE in relation to exposure. In conclusion the preliminary results did not show any effects on the workers of the four microbiological pesticides. However, more definite

210 results may rise from the results of the last two years follow-up.

P27.04 Carsten AN ANIMAL MODEL FOR PARTIAL THICKNESS CHONDRAL Stengaard DEFECTS Carsten Stengaard Traumatic lesions in the articular cartilage are a major cause of osteoarthritis among young people. Thus, a vast effort is conducted in research ensuring complete regeneration of the articular surface. Yet, the definite method is still to be developed, emphasizing the complexity of cartilage regeneration suggesting the involvement of numerous yet to be understood processes. When boarding animal studies, the model must allow these processes to be isolated, permitting thorough and pinpointed analysis of the utilised treatment. Still, most studies involve osteochondral lesions where marrow stem cells and growth factors invade the joint cavity and “contaminate” the result and analysis of the treatment. We present an animal model of cartilage defects, with the defect only reaching the deep cartilage, yet deep enough for implantation of regenerative substances. 8 cadaver goat femora were used. A custom designed drilling tool was firmly attached to the distal femur. The tool allowed precise ultra sonic measurement (US) of the cartilage thickness prior to drilling. The drilling tool was adjusted accordingly. A defect attempting to reach 75% of the cartilage thickness was established in the medial femoral condyle. The relative depth of the defect was estimated histological using stereology. We were able to produce cartilage defects with a mean depth of 74%

CI95[0.66;0.81]. One defect showed a small penetration of the subchondral bone. Double measurements of cartilage thickness using US showed a CV of 1.8%. We have developed an animal model with a drilling tool based on US measurements for establishing reproducible chondral defects in the goat. The device will be used in studies of treatment response in cartilage regeneration.

P27.05 Anders RISK STRATIFICATION AFTER INTRODUCTION OF SENTINEL LYMPH Husted NODE BIOPSY TECHNIQUE Madsen Anders Husted Madsen Introduction: Risk stratification is used to allocate patient to adjuvant chemotherapy. Commonly used models to stratify a patients risk include lymph node status but also other prognostic factors are used. Sentinel Lymph Node Biopsy (SLNB) technique results in increased probality of detecting lymph node metastases because sentinel lymph nodes are examined more extensively using serial sectioning and immunohistochemisty staining. Studies suggests that 10 – 20 % more metastases are detected. It is often argued in favour of introducing SLNB that these additional metastases will lead to more adjuvant therapy and subsequently better survival of the patients. Aim: The aim of the present study was to examine the impact of additional metastases on risk stratification and allocation to adjuvant therapy after introducing sentinel lymph node biopsy technique according to three commonly used prognostic indexes.

211 Methods: All patients (n=1913) with age 70 or younger were identified in three different counties in Denmark using the Danish Cancer Registry and the database of the Danish Breast Cancer Cooperative Group. Two periods (1996-97 vs. 2002) were compared in the counties of Funen, Aarhus and Northern Jutland. None of the three counties had introduced SLNB in the first period, however in 2002 only Northern Jutland had not implemented SLNB. Algorithms for risk stratification were made for the Nottingham Prognostic Index, The St. Gallen criteria and the criteria used in the Danish Breast Cancer Cooperative Group. Results: A significant increase in the number of patients with metastasis were seen in Aarhus and Funen but not in Northern Jutland (p=0.40) and the odds ratio for detecting lymph node metastasis increased significantly in Aarhus (OR=1.36 95 % CI 1.01 – 1.86) and Funen (OR=1.59 95 % CI 1.16 – 2.17) but not in Northern Jutland (1.23 95 % CI 0.87 – 1.72). Despite the increased number of metastases only 4.2 % in Funen, 3.4 % in Aarhus and 1.3 % in Northern Jutland received adjuvant therapy because of the finding of additional metastasis. Conclusion: Despite significantly increased numbers of patients with additional metastases after introducing SLNB were seen the method had only little impact on allocating patients to adjuvant therapy. Other factors like tumor size and malignancy grade plays a major role in this allocation.

P27.06 Jane DIPHTERIA-TETANUS-PERTUSSIS (DTP) VACCINATION AND CHILD Agergaard SURVIVAL: RANDOMISED STUDY OF NOT PROVIDING DTP VACCINATION SIMULTANIOUSLY WITH OR AFTER MEASLES VACCINATION (MV) J. Agergaard, C. S. Benn, A. Rodrigues, L. Østergaard, P. Aaby Dept. Infectious Diseases, Skejby Sygehus and Bandim Health Project at Dept. of Epidemiology Statens Serum Institut / Guinea Bissau Background: Infectious diseases are the main cause of high child mortality in Africa. In several non-randomised studies, routine childhood vaccinations have been observed to have non-targeted effects. Live vaccines like measles vaccine (MV) seem to protect against overall mortality, whereas killed vaccines, like DTP, may have no beneficial effects, especially for girls. DTP provided with or after MV may be associated with increased mortality. The mechanisms behind these effects are unknown. Hypothesis: Not providing DTP together with or after MV is associated with a 35% reduction in overall mortality and 23% reduction in hospitalisations. Objectives: To examine in a randomised study of 6000 children the effect of not administering DTP simultaneously with or after MV on 1) Overall child mortality 2) Hospitalisation rates and major causes of hospitalisation 3) The immunological profile after vaccination 4) Sex- differences in the above mentioned outcomes Methods: 6000 children are randomised as they come for DTP3 or DTP booster with or after MV at the health centre. The children are followed for adverse effects, morbidity, hospital admission and mortality. With a total of 7500 person-years of follow-up, we will be able to document a 35% reduction in mortality. A subgroup of children will be examined for

212 possible differences in immunological profile after vaccination. Perspectives: The project may document that DTP may that changes in vaccination policy might have major implications for child survival.

P27.07 Hanne Heje PATIENT EVALUATION IN GENERAL PRACTICE H. Heje, P. Vedsted, F. Olesen Research Unit for General Practice, University of Aarhus, DK-8000 Aarhus C. The aims of this project were to study associations between patients’ evaluations of their GP and characteristics of the patients and the GPs and to evaluate the effect on the GPs of being evaluated by their patients. Lastly we wanted to study the effect on the evaluations of different questionnaire distribution methods and of using reminders. We performed a questionnaire survey among the patients of voluntarily participating GPs in a descriptive cross-sectional design, a cluster- randomised trial and a non-comparative intervention study. The questionnaire was an international validated instrument for measuring patient experienced quality in general practice. We included 673 GPs and obtained valid replies from more than 50.000 patients. 79% of the GPs replied to the questionnaire evaluating their participation. We found that the questionnaire distribution method did influence the assessment level, while reminders added only little to the assessments. Older patients, frequently attending patients and patients with chronic illnesses were more satisfied with their care, while patients with a low self-rated health were less satisfied. Patients were more satisfied with younger GPs and experienced accessibility better in singlehanded practices. Through the GPs’ evaluation of their participation in the project, we found that the GPs were able to interpret the results of the evaluation in relation to daily practice, that they learned from it and used the results to change and improve practice. Most of the GPs would recommend an evaluation to a colleague and would like to repeat it themselves. We conclude that this study have provided us with valuable information that can be used for possible future implementation of patient evaluation in the continuing quality improvement of general practice care.

P27.08 Vibeke VALVULAR HEART DISEASE ASSOCIATED WITH THE USE OF ERGOT Guldbrand DOPAMINE AGONISTS IN TREATMENT OF PATIENTS WITH Rasmussen PARKINSON’S DISEASE. V. G. Rasmussen¶, S. H. Poulsen¶, E. Dupont¥, H. Egeblad¶ ¶Department of Cardiology, Århus University Hospital, Skejby Sygehus, 8200 Århus N, Denmark ¥Department og Neurology, Århus University Hospital, Århus Sygehus, 8000 Århus C, Denmark. Background: The ergot dopamine agonists (EDA), pergolide and cabergolin, has recently been associated with cardiac valvulopathy. Aims: In a cross-sectional study to compare the prevalence of valvular heart disease in two groups of Parkinson patients treated with either EDA or non ergot derived dopamine agonists (non-EDA). Methods: 160 Parkinson patients treated with either EDA or non-EDA.

213 Time of diagnosis (British Brain Bank Criteria), Hoehn & Yahr status, actual and former antiparkinsonistic treatment and cumulative doses is registered by the neurologists. Cardiologic examination is performed including echocardiography with recording of all relevant valvular views according to the ACC guidelines, ventricular dimensions and Simpson’s biplane for estimation of ejection fraction. Systolic pulmonary artery pressure is derived from the tricuspid gradient. Tissue Doppler Imagine is performed to estimate function of the longitudinal myocardial fibres. The echocardiography is digitally saved for later second opinion analysis. The cardiologist is blinded for the medical treatment for Parkinson’s disease. Results: The study is ongoing. Without unblinding for the given Parkinson treatment we have in the first 75 patients (50 men, 25 women; median age 64 (43-82)) found moderate or severe aortic insufficiency in 14 patients and altogether at least moderately regurgitation of the aortic, mitral or tricuspid valves in 23 patients (31%), which seams high if the treatment (or Parkinson’s disease) is without influence on the valves.

P27.09 Reziwanggu REBAUDIOSIDE A DIRECTLY STIMULATES INSULIN SECRETION Abudula FROM PANCREATIC BETA CELLS: A GLUCOSE-DEPENDENT ACTION VIA INHIBITION OF ATP-SENSITIVE K+-CHANNELS. Reziwanggu Abudula1, Vladimir V. Matchkov2, Per Bendix Jeppesen1, Holger Nilsson2, Christian Aalkjær2, Kjeld Hermansen1 1 Department of Endocrinology and Metabolism C, Aarhus University Hospital, 8000 Aarhus C, Denmark 2 Institute for Physiology and Biophysics, Department of Physiology, Aarhus University, 8000 Aarhus C, Denmark Aims/hypothesis: We have shown that rebaudioside A potently stimulates the insulin secretion from isolated mouse islets in a dose- , glucose- and Ca2+ -dependent manner. Little is known about the mechanisms underlying the insulinotropic action of rebaudioside A. The

aim of this study was to define the signaling system centered in KATP channels by which rebaudioside A acts and especially to see if the action is different from that of SU. Methods: Isolated mouse islets were used in the cAMP[125I] scitillation proximity assay to measure total cAMP level and in a luminometric method to measure intracellular ATP and ADP concentrations. Whole-cell configuration of the patch-clamp technique was used to verify the effect of rebaudioside A on ATP-sensitive K+-channels from dispersed single cells from isolated mouse islets. Insulin was measured by RIA from insulinoma MIN6 cells. Results: In the presence of 16.7 mmol/l glucose, the addition of the maximally effective concentrion of rebaudioside A (10-10M or 10-9M) increased the ATP/ADP ratio significantly while it did not change the intracellurlar cAMP level. Rebaudioside A (10-9 M) and stevioside (10-6 M)

reduced the ATP-sensitive potassium channel (KATP) conductance in a

critically glucose-dependent manner. The effect of rebaudioside A on KATP channel disappeared at low glucose and in the absence of intracellular Na+. Moreover, rebaudioside A stimulated the insulin secretion from MIN6 cells in a dose- and glucose dependent manner.

214 Conclusion: The insulinotropic effect of rebaudioside A is mediated via inhibition of ATP-sensitive K+-channels and requires the presence of high glucose. The results indicate that rebaudioside A may offer a distinct therapeutic advantage over sulphonylureas due to less risk of causing hypoglycemia.

P27.10 Mette Møller DYNAMIC CHANGES OF THE CORTICOSPINAL TRACT AFTER ISCHEMIC STROKE DETECTED BY MRI FIBERTRACKING M. Møller, MD1,2, J. Frandsen1,3 MsCs, G. Andersen MD, PhD4, D. Zeidler, RT1,3, A. Gjedde, MD, PhD1,2, P. Vestergaard-Poulsen MSc, PhD1,3, L. Østergaard, MD, PhD1,3. 1Center of Functionally Integrative Neuroscience, Aarhus University, Denmark, 2PET-Center, Aarhus University Hospital, Denmark, 3Department of Neuroradiology, Aarhus University Hospital, Denmark, 4Department of Neurology, Aarhus University Hospital, Denmark. The integrity of motor pathways and functional connectivity patterns are important in assessing plastic changes related to successful recovery, to obtain prognostic information, and to monitor future therapeutic strategies of stroke patients. We tested the hypotheses; 1) that changes in axonal integrity along the corticospinal tract after stroke can be detected as a reduction of fractional anisotropy and 2) that sustained low fractional anisotropy is indicative of axonal loss, and therefore is correlated with poor motor outcome. We used magnetic resonance diffusion tensor imaging (DTI) in conjunction with 3D fiber tracking and specific neurological motor scores to test the hypotheses in five stroke patients within the first week and 30 and 90 days post-stroke. The study demonstrated the feasibility of fibertracking as a segmentation tool for mapping distal parts of the corticospinal motor pathways and showed that fractional anisotropy is a sensitive measure of structural changes after stroke. The results reveal that reduction in fractional anisotropy within the first weeks after stroke reflects decline of axonal integrity leading to Wallerian degeneration. The results demonstrate a correlation between the temporal evolution of fractional anisotropy and motor function in patients with poor motor outcome.

P27.11 Niels Juul ASSOCIATION BETWEEN LEVELS OF ICP AND CPP AND MORTALITY IN PATIENTS WITH SEVERE HEAD INJURIES Juul N, Labouriau R, Mass AIR, Marshall LF and Sorensen HT. Introduction: Intracranial pressure (ICP) and cerebral perfusion pressure (CPP) monitoring are the cornerstones in the ICU treatment of head injured patients. The acceptable limits for these pressure parameters have been debated. We examined the mortality rate according to levels of ICP and CPP in patients after traumatic brain injury with two different diagnostics from the CT scanning at hospital admission: 1) diffuse axonal injuries and 2) evacuated mass lesions. Material and methods: We studied 1,188 patients with severe head injury (GCS < 9) from the international and American (USA) Tirilazad trial. The time from injury to death (or loss by follow up after one year) was analyzed

215 as a right-censored variable in a Cox proportional model. Four time- dependent covariates described the patient’s state in terms of their hourly measured ICP and CPP during the first 5 days at the ICU (after initial stabilization). The analyses were stratified according to the two CT- scanning diagnostic and adjusted for the Glasgow motor score at hospital arrival, occurrence of hypoxia, and a combination of gender and age. Results: The table below displays the estimates of the mortality rate obtained using the Cox proportional model.

Mortality rate ratio Mortality rate ratio for patients with for patients with diffuse axonal lesion evacuated mass lesion (n=723) (n=465) ICP < 20 and CPP > 70* 1.0 (reference) 1.0 (reference) ICP < 20 and CPP < 70* 1.06 CI (0.55-2.04) 1.15 CI (0.63-2.12) ICP > 20 and CPP > 70* 1.46 CI (0.41-5.20) 1.23 CI (0.45-3.38) ICP > 20 and CPP < 70* 4.54 CI (1.71-12.07) 1.39 CI (0.54-3.58) * ICP and CPP in mm Hg, CI: 95% Confidence Interval.

The only statistically significant increase in the mortality rate detected was for the state characterized by high ICP and low CPP for patients with diffuse axonal lesion. Conclusion: Our results show that different patterns in terms of mortality appear for groups of patients with different diagnostics. This might be relevant for recommendations of medical practices and certainly deserves further investigations.

P27.12 Thomas DALLAS PAIN QUESTIONNAIRE CLASSIFICATION PREDICTS Andersen OUTCOME IN LOW BACK PAIN PATIENTS UNDERGOING SPINAL FUSION Thomas Andersen, Finn Bjarke Christensen, Ebbe Stender Hansen, Peter Helmig, Kristian Høy, Bent Niedermann, Cody Bünger Spine Section, Department of Orthopaedics, Aarhus Kommunehospital Introduction. Ozguler et al. described a classification tool for low back pain patients using the Dallas Pain Questionnaire (DPQ) (Spine 2002). Our aim was to evaluate the ability of this classification to predict outcome in spinal fusion patients. Material and methods. 578 patients (246 men, 332 women; mean age 46, range 18-81) operated between 1992 and 2001, with a complete DPQ preoperatively and after a minimum of one year follow-up, were included. They were classified preoperatively and at follow-up into four groups: Group 1 (slight disability), Group 2 (intermediate disability), Group 3 (major disability) and Group 4 (major disability and emotional distress). 250 patients with low back pain rating scale scores at follow-up were used for prediction of back and leg pain at follow-up. Using logistic regression 7 predictor variables were investigated: Age (18- 59 years/60+ years), Gender (male/female), Diagnosis (listhesis/degeneration), Previous back surgery (yes/no), Work status

216 (working/not working), Duration of pain (less than 2 years/more than 2 years) and Disability/distress (disability (group 1-3)/disability and distress (group 4)). Outcome variables consisted of disability (low=group1+2 at follow-up/high=group 3+4 at follow-up) and for the subset of patients leg pain (low/high) and back pain (low/high). Results. Preoperative classification was Group 1: 1%, Group 2: 14%, Group 3: 36%, Group 4: 49%. Variables found to predict high disability at follow- up were female gender OR 1.39 (p=0.083), previous back surgery OR 2.00 (p<0.0005), not working OR 2.94 (p<0.0005) and emotional distress OR 2.49 (p<0.0005). Emotional distress predicted back pain OR 2.22 (p.=0.007) and leg pain OR 2.90 (p.=0.002) at follow-up. Previous back surgery predicted leg pain at follow-up OR 1.97 (p.=0.037). Conclusion. These results show that this classification based on DPQ- scores predicts outcome in spinal fusion patients and that the largest risk factors for inferior outcome in is emotional distress, previous surgery and a status as not working.

X01.01 Claus Svane EVALUATING THERAPEUTIC POTENTIAL OF HUMAN STEM AND Søndergaard PROGENITORS CELLS IN IMMUNODEFICEINT RODENT MODELS OF ACUTE MYOCARDIAL INFACTION C.S. Sondergaard1,4,5, J.H. Bonde4,5, D. Maxwell7, D. Hess5, I. Rosova5, F. Dagnæs-Hansen2, C. Weinheimer6, J.M. Nielsen1,3, J. Nolta5, E. Falk1,3, L. Pedersen1,4. 1Clinical Institute; 2Dep. of Medical Microbiology and Immunology; 3Dep. of Cardiology, Skejby University Hospital; Faculty of Health Sciences and 4Dep. of Molecular Biology, Faculty of Science; Aarhus University, 8000 Aarhus C, Denmark. Dep. of Internal Medicine, 5Div. of Oncology, Section of Hematopoietic Development and Malignancy; 6Div. of Cardiology, Mouse Physiology Core; 7Dep. of Radiology, Molecular Imaging Center; Washington University, School of Medicine, St. Louis, MO, USA. In recent years a number of reports have documented improved cardiac function following transplantation of hematopoietically derived stem and progenitor cells in rodent models for both acute and chronic myocardial infarction. Clinical trials exploring the safety and feasibly of this treatment are currently under way, but more detailed preclinical trials are needed in order to optimize treatment regimes. We have established models for acute myocardial infarction (AMI) in immunodeficient nude rats and NOD/SCID 2-Microblobulinnull mice and are currently evaluating the ability of human hematopoietically derived stem and progenitor cells to home to the site of injury and confer functional improvement. Using the nude rat AMI model we found little or no engraftment and functional improvement following intramyocardial injection of human CD34+ cells purified from cytokine mobilized peripheral blood. Recently, using a combined Kodak 4000MM CCD/X-ray imaging station, we found that Aldefluor positive cord blood cells labelled with 655nm light emitting Quantum Dot nano crystals homed to the site of injury following tail vein injection to immunodeficient mice with AMI. Further studies exploring the in vivo fate of transplanted cells and their ability to confer functional improvement are currently under way.

217 X01.02 Astrid From EFFECT OF IMPERMEABLE INTERFACES ON APPARENT DIFFUSION Frøhlich COEFFICIENT IN HETEROGENEOUS MEDIA A.F. Frøhlich, L1,2. Østergaard1 and V.G. Kiselev2 1Dept. of Neuroradiology, CFIN, Aarhus University Hospital, Nørrebrogade 44, bygn 30, 8000 Aarhus C, Denmark. 2 Sect. of Medical Physics, Dept. of Diagnostic Radiology, University Hospital Freiburg, Freiburg, Germany. The short-time behavior of the apparent diffusion coefficient measured by NMR provides a measure of the specific surface, S/V, of porous samples filled with an NMR-detectable fluid (1, 2). The potential applications of this method to living tissues such as neuronal fibers is of great interest. However the medium surrounding neuronal fibers is not homogeneous as in porous media and might result in a pattern of temporal dynamics of the diffusion coefficient similar to that of the impermeable surface studied. Here, an approach to describe diffusion and the boundary effect of an impermeable surface in heterogeneous media is presented in the framework of a cumulant expansion of the NMR signal. The leading term of this expansion is determined by the velocity autocorrelation function which is expressed in terms of properties of microscopic transport in the medium Given the properties of the bulk medium, the apparent diffusion coefficient can be calculated for an arbitrary sequence of gradient pulses. Application of this model to neuronal fibers reveals a bulk term 1/2 proportional to (D0t) just like the surface-to-volume term studied. This term can in principle can be subtracted from the apparent diffusion coefficient by comparing eigenvalues of the diffusion tensor. However, to find the surface-to-volume ratio of neuronal fibers, diffusion measurements should be complemented with an account for the possible difference in spatial organization of Glia cells close to and far from the fibers. References: (1) Mitra, P.P. et al ; Phys.Rev.Lett. 1992; 68: 3555-3558 (2) Mitra, P.P. et al 1993; Phys.Rev.B, 47: 8565-8574

X01.03 Dorte Kjær ANTIEPILEPTIC DRUGS, FOLIC ACID AND CONGENITAL ABNORMALITIES: A POPULATION BASED CASE-CONTROL STUDY. D. Kjær, E. Puho, J. Christensen, A.E. Czeizel, M. Vestergaard, H.T. Sørensen, J. Olsen. Danish Epidemiology Science Centre, Institute of Public Health, University of Aarhus. Centre for Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark. Carbamazepine (CBZ), Phenytoin (PHT), Phenobarbital (PB), and Primidone (PRI) increase the risk of congenital abnormalities (CAs). We examine whether folic acid supplementation (FAS) reduces the CA risk following exposure to antiepileptic drugs (AEDs) during early pregnancy. The Hungarian Case-Control Surveillance of Congenital Abnormalities (1980-1996) database contains disease and exposure data on 22,843 mothers of children with CAs (cases), and 38,151 mothers to unaffected children (controls). We assessed effect of AEDs taken during pregnancy at the time of organogenesis, i.e. second and third month of gestation, with or without FAS. Children exposed to CBZ, PHT, PB or PRI in the absence of FAS had an

218 increased risk of CAs compared to nonaffected children, OR 1.5 (95% CI: 1.2-1.9). FAS reduced this slightly, OR 1.2 (95% CI: 0.8-1.8). The risk of CAs increased with number of AEDs used. Compared to children exposed to neither AEDs nor FAS, OR for children exposed to one AED and no FAS was 1.33 (95% CI: 1.12-1.57), one AED and FAS 1.06 (95% CI: 0.79-1.42), two or more AEDs without FAS 3.46 (95% CI: 1.20-9.96), and two or more AEDs and FAS 2.21 (95% CI: 0.49-9.88). While these results are strongly suggestive of a protective effect, FAS did not show a statistically significant effect modification. FAS during the second and third month may have a protective effect on development of CAs among offspring of mothers taking CBZ, PHT, PB, and / or PRI.

X01.04 Esben Hjorth ACETYLSALICYLIC ACID AND CLOPIDOGREL. COMPARISON OF Madsen METHODS FOR EVALUATING PLATELET RESPONSE AND RESISTANCE IN HEALTHY MEN AND PATIENTS WITH ATHEROSCLEROSIS. PROGNOSTIC SIGNIFICANCE OF RESISTANCE IN PATIENTS WITH ATHEROSCLEROSIS. E.H. Madsen, E.B. Schmidt, E. Maurer-Spurej, S.R. Kristensen Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Devine/Maurer Lab., Vancouver BC, V6T 1Z3, Canada Some patients do not respond well to aspirin (ASA) and/or clopidogrel (Clo) treatment. This is often referred to as resistance. Definition of resistance and the impact of resistance on prognosis are not clear. Study 1: 20 healthy men received ASA and Clo in random order each for a ten day period separated by ten days without treatment. During treatment platelet function was measured at baseline (before treatment), at 24 hours, day 5 and 10. This study was recently finished. Results are not yet analyzed. Study 2: 50 patients undergoing elective coronary angioplasty at Vancouver General Hospital are followed for 12 months. Blood samples are drawn at baseline (before initiation of Clo treatment), at 24 hours, 1, 6 and 12 months. Clo is continued throughout the study. All patients are treated with ASA indefinitely. Patient enrolment has just begun. Study 3: 1000 patients with peripheral atherosclerotic disease referred to the Dept. of Vascular Surgery in Aalborg Hospital will be followed for 6 years after assessment of platelet function upon study entry. All of these patients are treated with ASA as a part of the standard treatment. 100 patients will receive Clo for 14 days instead of aspirin, followed by measurement of platelet function. Description of the population after the first year of enrolment will be included in the PhD thesis. Methods for assessment of platelet function: The PFA-100™, aggregation in platelet rich plasma and flow cytometry.

X01.05 Hanne NO CORRELATION BETWEEN TUMOR-EXPRESSION OF CAIX AND Krogh Jensen INFILTRATION OF CD57+NK CELLS IN RENAL CELL CARCINOMA. H.K.Jensen, F.Donskov, M.Nordsmark, N.Marcussen, F.Lundbeck, H.Von Der Maase, Dep. of Oncology, Universityhospital of Aarhus, 8000 Aarhus C, Denmark [email protected]

219 In clearcell renal cell carcinoma CAIX (Carbonic Anhydrase IX) is a tumor antigen that predicts for a better overall survival, in both localized and metastatic setting. It is probably a downstream marker of VHL-mutation reflecting significant changes in tumorbiology. In the present study we evaluated the correlation between tumor CAIX expression and tumor- infiltrating CD57+NK cells in order to assess an immune-modulatory effect. Formalinfixed, parraffin embedded tissue-samples from 98 pts, radically nephrectomized for clearcell renal cell carcinoma, stage I – IV, were processed using standard IHC procedure and stained with the antibodies CA IX (M75) and CD57 (DAKO, M1014). Assessment of the leukocytes was done by an unbiased counting technique using a counting frame and a computerized counting-system. CA IX was assessed as positive membrane staining in more or less than 85% of the tumor cells, according to the litterature. CAIX and CD57+NKcells were correlated with clinical factors and overall survival. High staining of CAIX (>/=85%) was present in 86 pts (87,8%). It was an independent good prognostic factor for overall survival (p<0.05) CD57+NK cells were present with a large inter-tumor variability, median 25,52 cells/mm2 (range 1,09 - 579,78 cells/mm2). Dichotomized according to the median value there was no impact on overall survival (p=0.54). There was no correlation between the expression of CAIX in tumor cells and tumor infiltrating CD57+NK-cells (Spearman’s rho 0.115, p=0.269) Conclusion: The impact of CAIX as a good prognostic factor is not related to the presence of CD57+NK cells. Further studies concerning other immune-parameters are ongoing.

X01.06 Hanne M. IMPACT OF TYPE 2 DIABETES ON MYOCARDIAL INSULIN Søndergaard SENSITIVITY TO GLUCOSE UPTAKE AND PERFUSION IN PATIENTS WITH CORONARY ARTERY DISEASE Hanne M. Søndergaard MD1,2, Morten Bøttcher MD1, Mette Marie Madsen MD1, Ole Schmitz MD2,3, Søren B. Hansen MSc 4, Torsten T. Nielsen MD1, and Hans Erik Bøtker MD 1 Department of Cardiology B 1, Department of Clinical Pharmacology 2, Department of Endocrinology3, The PET Center4, Aarhus University Hospital, Aarhus University, Denmark. Myocardial insulin resistance (IR) is a feature of coronary artery disease (CAD) with reduced left ventricular ejection fraction (LVEF). Whether type 2 diabetes mellitus (T2DM) with CAD and preserved LVEF induces myocardial IR and whether insulin is a myocardial vasodilator is debated. We studied 27 CAD-patients (LVEF > 50%): twelve with T2DM (CAD+DM), fifteen without T2DM (CAD-NoDM). Regional myocardial (MGU) and skeletal (SGU) glucose uptake, myocardial (MBF) and skeletal muscle (SBF) perfusion were measured with positron emission tomography. MBF was measured at rest and during hyperemia in non-stenotic and stenotic regions with and without acute hyperinsulinemia. MGU was similar in CAD+DM and CAD-NoDM in non-stenotic regions (0.38±0.08 and 0.36±0.11 µmol/g/min, P=0.56) and stenotic regions (0.35±0.09 and 0.37±0.13 µmol/g/min, P=0.56). SGU was reduced in

220 CAD+DM (0.05±0.04 vs. 0.10±0.05 µmol/g/min, P=0.02), and likewise whole-body glucose uptake was reduced in CAD+DM (4.0±2.8 vs. 7.0±2.4 mg/kg/min, P=0.01). Insulin did not alter MBF at rest or during hyperemia. Insulin increased SBF in CAD-NoDM (0.11±0.03 vs. 0.06±0.03 ml/g/min, P=0.02), but not in CAD+DM (0.08±0.04 and 0.09±0.05 ml/g/min, P=0.75) In conclusion, myocardial IR is not an inherent feature in T2DM patients with preserved LVEF. Acute physiological insulin exposure exerts no coronary vasodilation in CAD-patients irrespective of T2DM.

X01.07 Hanne FAILURE PATTERN AMONG HIGH-RISK BREAST CANCER PATIENTS Melgaard RANDOMIZED TO PLUS MINUS POSTMASTECTOMY RADIOTHERAPY Nielsen H.M. Nielsen, M. Overgaard, C. Grau, A.R. Jensen, J. Overgaard Department of Experimental Clinical Oncology, Department of Oncology, Aarhus University Hospital Purpose. Postmastectomy radiotherapy (RT) in high-risk breast cancer patients can reduce loco-regional recurrences (LRR) and improve disease- free and overall survival. The aim of the present analysis was to examine the overall failure pattern among patients randomized to +/- RT. Patients and methods. A long term follow-up was performed among the 3083 patients from the Danish Breast Cancer Cooperative Group (DBCG) 82 b&c trials, except in those already recorded with distant metastases (DM) or contralateral breast cancer (CBC). The endpoints were LRR, DM and CBC, and the follow-up continued until DM, CBC, emigration or death. Information was selected from medical records, general practitioners and the National Causes of Death Registry. The median potential follow-up time was 18 years. Results. The 18-year probability of any first breast cancer event was 73% and 59% after no-RT and RT, respectively (RR: 0.68; 0.63-0.75, p<0.001). The 18-year probability of LRR (with or without DM) was 49% and 14% (p<0.001) after no RT and RT, respectively (RR: 0.23; 0.19-0.27). The 18-year probability of DM subsequent to LRR was 35% and 6% (p<0.001) after no RT and RT, respectively (RR: 0.15; 0.11-0.20), whereas the probability of any DM was 64% and 53% (p<0.001) after no RT versus RT, respectively (RR: 0.78; 0.71-0.86). Conclusion. Postmastectomy RT changes the failure pattern in high risk breast cancer patients with especially less patients having LRR as first site of failure, and overall less patients having DM.

X01.08 Iver HOW DOES THE HISTONE ACETYLTRANSFERASE PROTEIN TIP60 Nordentoft INFLUENCE THE INSULIN SECRETION CASCADE IN BETA CELLS. Iver Nordentoft, Per Bendix Jeppesen, Poul Jørgensen, Anders Lade Nielsen, Kjeld Hermansen. Department of Endocrinology and Metabolism C, Aarhus Sygehus, Aarhus University, Tage Hanssens Gade 2, 8000 Aarhus C, Denmark. Aim: To characterize the presence and distribution of the histone acetyltransferase (HAT) protein Tip60 in the beta cell and to clarify the functional role of Tip60 in the normal and diabetic beta cell. Hypothesis: Tip60 is present in β-cells and regulates the glucose stimulated insulin secretion in the normal and diabetic state via binding to

221 and regulation of cPLA2 activity. Tip60 influences the insulin sensitivity and the propensity to develop type 2 diabetes. Material: Islets from normal non-diabetic mice (c57Bl/6J) and type 2 diabetic animals (KKAy). Clonal murine pancreatic beta cell line MIN6 and clonal rat beta cell line INS-1. Methods: Transient and stable transfection of MIN6/INS-1 beta cells with Tip60 constructs. RNAi silencing of Tip60 in MIN6/INS-1 cells. RNA purification from islets and transfected beta cells and evaluation of Tip60

and cPLA2 expression with Real time RT-PCR. Visualization of Tip60 localization in MIN6/INS-1 cells using immunohistochemistry. Measure the level of Tip60 mRNA in β-cells and isolated islets after 24 h incubation at different glucose concentrations. Characterization of glucose stimulated insulin secretion (GSIS) and insulin content in Tip60 over-expressing cells, Tip60 silenced cells, c57Bl/6J mice islets and KKAy mice islets. Perspective: To disentangle the potential role of Tip60 on beta-cell function and the susceptibility to develop type 2 diabetes.

X01.09 Kristine C. GENETIC MARKERS FOR DEVELOPMENT OF AUTISTIC DISORDER Tvedegaard BASED ON MULTIPLEX GENOTYPING K.C. Tvedegaard, E. Parner, J. Attermann, N. Gregersen, P. Thorsen NANEA at Department of Epidemiology, Institute of Public Health, University of Aarhus, 8000 Aarhus C, Denmark High rates of concordance of autism are found in monozygotic twins (82 %) compared with dizygotic twins (10 %), indicating a strong genetic influence. Moreover, there is an overlap between clinical symptoms in individuals with autism and individuals with abnormal fatty acid and phospholipid metabolism We hypothesize that genetic factors are predisposing for infantile autism. These genetic factors include a) hereditable enzyme defects in the fatty acid metabolism, and b) variations in select neuropeptides and other biologically relevant biomarkers. In this project we will study differences in the prevalence of selected Single Nucleotide Polymorphisms (SNPs) between a group of individuals with infantile autism, born from 1990 through 1999, and identified in the Danish Psychiatric Central Research Registry, and a group of matched controls randomly selected from the Danish Civil Registration System . We expect to identify approximately 400 cases. Whole genome amplified DNA from PKU cards from the biobank at Statens Seruminstitut will be used to estimate the prevalence of the selected SNPs and genotyping of SNPs in candidate genes will be based on Multi- Code™ Multiplexed Analysis from EraGen and processed on Luminex®100™ IS Total System. This study will contribute to a better understanding of the aetiology and pathogenesis of autism and thereby open possibilities for better treatment and possibly prevention.

X01.10 Line Petersen NK-CELL MEDIATED IMMUNITY DURING CYTOMEGALOVIRUS REACTIVATION IN PATIENTS WITH BLOOD MALIGNANCIES L. Petersen, M. Hokland

222 Department of Medical Microbiology and Immunology, University of Aarhus, DK-8000 Aarhus C, Denmark Reactivation of latent Cytomegalovirus is a serious complication arising when patients suffering from blood malignancies are treated with immuno- suppressive drugs. The viral infection can cause mortality in these patients. The project aims to establish methods to describe the load of CMV in these patients and to identify diagnostic markers on the NK cells, which will be able to predict the reactivation of CMV before onset of the disease. Specifically, CMV load in plasma from patients with blood malignancies will be examined using a real time quantitative PCR. The findings will then be correlated to the phenotype (CD3, CD56, NKp30, NKp44, NKp46, NKG2D, DNAM-1, CRTAM) and activation status (cytokine stimulation, cytokine profiling and 51Cr release) of the NK cells measured by flow cytometric assays. In addition, CMV load and the immunological markers on the NK cells will be correlated to the clinical status of the patient.

X11.01 Marianne DELAY IN DIAGNOSE AND TREATMENT OF LUNG CANCER Bjerager Marianne Bjerager1, Torben Palshof2 Ronald Dahl3 and Frede Olesen1 1Research Unit for General Practice, University of Aarhus, Denmark, 2Department of Oncology, Aarhus University Hospital, 3Department of Respiratory Diseases, Aarhus University Hospital, Denmark. Objectives: Delay of diagnose and treatment of lung cancer is known to be a problem and earlier studies have showed room for improvements in both primary and secondary health care. The aim of this study was to analyse the causes of delay in diagnose and treatment of lung cancer and to point out possible areas of improvements within the health care system. Methods: A systematic review of the time from the initial symptom until treatment or decision not to treat of a group of consecutive lung cancer patients who where diagnosed in 2003 and were living in the County of Aarhus. For each patient a detailed case history was made based on medical records and interviews with the patient and the patient’s GP. In the analysis we distinguish between patient delay, doctor delay and system delay, system delay being defined as time intervals that can be ascribed to waiting times related to investigations of cancer related symptoms and administration. Results: 92 patients were included. The median patient delay was 24 days, the median doctor delay was 13 days (inter-quartile range 0-65 days) and the median system delay was 75 days (inter-quartile range 60-92 days). In primary health care the median delay was 29 days (inter-quartile range 10- 63 days), and in secondary care 58 days (inter-quartile range 42-70 days). 17 patients (18 %) had taken a thoracic x-ray that failed to raise the suspicion of cancer. The total delay in health care was 254 days for patients with a false negative chest x-ray and 79 days for the rest of the patients. Conclusion: System delay is a key problem in delay in diagnosis and treatment of lung cancer, and increased focus on this issue is necessary if we want to shorten delay. False negative chest x-ray often results in substantial delay for patients with lung cancer.

X11.02 Pia Holland INCREASED NOCTURNAL LEVELS OF ENDOTHELIN IN PLASMA

223 Hansen AND SODIUM IN URINE IN RELATION TO BLOOD PRESSURE AND SEVERITY OF OBSTRUCTIVE SLEEP APNOEA P H Hansen, L Sadauskiene, J Wessels, O. Nyvad, B Strunge, E B Pedersen. Department of Medical Research, Holstebro Hospital, 7500 Holstebro, Denmark. Background: The mechanisms involved in development and maintenance of hypertension in obstructive sleep apnoea (OSA) are not clarified. We hypothesize that patients with OSA have an abnormal nocturnal level of some vasoactive hormones and an abnormal renal handling of sodium and water during the night. Methods: We studied 32 patients with OSA and 19 healthy control subjects during night time with serial determinations of endothelin (ENDO), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), arginine vasopressin (AVP), angiotensin II (AT II), fractional urinary

excretion of sodium (FENa), free water clearance (CH2O), urinary excretion of aquaporin 2 (u-AQP2), blood pressure (BP) and oxygen saturation (SatO2).

Results: Patients with OSA had a higher plasma level of ENDO, FENa, and BP than healthy controls during night time. No significant differences were

measured in ANP, BNP, AT II, CH2O and u-AQP2. The average level of AVP during the whole night was slightly higher in OSA than controls. ENDO was significantly correlated to the apnoea-hypopnoea index (AHI) as a measure of the severity of OSA. This correlation remained statistically significant after statistical analysis in a general linear model with correction for confounders. Conclusions: Endothelin is a pathogenic factor in OSA. The higher fractional excretion of sodium in OSA most likely can be attributed to pressure natriuresis.

X11.03 Ruta CEREBRAL RESPONSE PATTERN TO PAIN AND ANTICIPATION OF Kuzminskyte PAIN IN PATIENTS WITH MULTISYMPTOMATIC FUNCTIONAL DISORDER R.Kuzminskyte, R.Kupers, P.Fink, P.Videbeck, A.Gjedde Aim of Investigation: Multisymptomatic functional disorder (MFD) is a syndrome characterised by pain and many physical complaints from various organ systems that cannot adequately be explained by known pathophysiological mechanisms. Behavioral studies have shown that MFD patients respond differently to painful stimuli. The aim of this study was to examine cerebral response patterns to painful and non-painful heat stimulation and to the anticipation of pain in MFD patients and to compare these with responses in healthy controls. Methods: 14 MFD patients and 14 healthy controls matched for age, sex and education were included. All subjects had undergone a psychiatric (SCAN) interview, a thorough somatic check-up and quantitative sensory testing. We used PET to measure changes in regional cerebral blood flow (rCBF). Subjects were scanned 3 times in each of following conditions: rest, innocuous heat, noxious heat and anticipation of pain. The heat stimulus was selected individually according to each subject's pain thresholds. After every scan, patients rated pain intensity. Results: There were no significant differences in pain and warmth ratings

224 between patients and controls. Nonetheless, rCBF patterns differed significantly in both groups. Controls showed bilateral activations in thalamus, SII and insular cortex in response to painful stimulation. In contrast, MFD patients only showed a contralateral activation in these areas. rCBF patterns in response to pain and anticipation of pain were clearly distinct in controls, but overlapped to a large extent in MFD patients. Patients showed a significant rCBF increase in dorsolateral prefrontal cortex during anticipation of pain. Conclusions: Differences in brain activity during pain and anticipation of pain in the two groups suggest an altered pain processing in MFD patients.

X11.04 Stine Johnsen ABSENCE OF PCOS FEATURES IN HIV-INFECTED WOMEN DESPITE SIGNIFICANT HYPERINSULINEMIA AND TRUNCAL ADIPOCITY Stine Johnsen, M.D., Sara E. Dolan, ANP., Kathleen Fitch, FNP., Kathleen Killilea, B.S., Jan L. Shifren, M.D. and Steven K. Grinspoon, M.D. Program in Nutrition and Metabolism (S.J., K.K., S.D., S.G), Department of Infectious Diseases, Aarhus University Hospital, 8200 Aarhus, Denmark (S.J) and Vincent Memorial Obstetrics and Gynecology Service (J.S.), Massachusetts General Hospital and Harvard Medical School, Boston, MA. A growing number of HIV infected women demonstrate metabolic abnormalities including insulin resistance and fat redistribution Among non HIV-infected women, insulin resistance and truncal adiposity are associated with features of the polycystic ovary syndrome (PCOS). In this study, we characterized and compared ovarian morphology and reproductive indices in HIV-infected women (N = 88) and age and BMI-matched healthy control subjects (N = 94). HIV-infected women demonstrated more visceral adipose tissue (VAT), a trend toward decreased abdominal subcutaneous adipose tissue and increased VAT: SAT. Fasting insulin and 2-hour glucose post OGTT were also significantly increased in the HIV-infected women. Despite significant hyperinsulinemia and visceral adiposity, HIV-infected women did not demonstrate irregular menses or an increased number of small ovarian follicles. Rather, SHBG (124 ± 10 vs. 84 ± 4 nmol/L, p = 0.0002) was increased significantly in HIV-infected women, and free testosterone by equilibrium dialysis was significantly reduced (2.2 ± 0.2 vs. 2.7 ± 0.2 pg/mL, p = 0.04), as was LH: FSH ratio. Menstrual function, androgen levels and ovarian morphology by ultrasonography were not different between the lipodystrophic subjects and healthy controls. These data demonstrate that among HIV-infected subjects with severe abdominal fat accumulation and hyperinsulinemia, common features of PCOS are not seen.

X11.05 Thomas IMMEDIATE IMPLANT PLACEMENT IN THE MOLAR REGIONS - A Urban RANDOMIZED CLINICALLY CONTROLLED STUDY Urban, T. Department of Oral Radiology & Department of Oral Surgery, Royal Dental College Aarhus, Vennelyst Boulevard, DK-8000 Aarhus C Usually a patient has to wait at least 3-6 month for bone healing after extraction before a dental implant can be inserted to replace an extracted tooth. Inserting the implant immediately after extraction would therefore

225 benefit the patient in reducing overall treatment time significantly. Immediat implant placement replacing one-rooted teeth has been investigated thoroughly contrary to replacement of two- or three-rooted teeth(molars). By means of a special preparation technique the molar extraction socket can be fitted with an implant, but still there are huge defects left not filled out by the implant. 90 patients are to have a molar extracted and replaced with an implant. The patients are randomised into 3 groups according to how the perimarginal bone defects around the placed implants are being treated: 1. Bonechips 2. Membrane 3. Bonechips+Membrane. The bone healing of the defects in the groups is compared, and the amount of newly formed bone in every case is being assessed by clinical measurements and advanced

radiographic methods. The H0-hypothesis states that there is no difference in bone healing between the three groups. So far, 5 patients have had an implant inserted. All 5 had swelling and oedema because of the necessity of raising a bigger flap to be able to close the wound. It has yet to be determined if the reduced treatment time can justify the seemingly more unpleasant postoperative days.

X11.06 Trine INTRAVENOUS OMEGA-3 FATTY ACIDS AND HEART RATE Madsen VARIABILITY IN HAEMODIALYSIS PATIENTS T. Madsen, E.B. Schmidt, J.H. Christensen Department of Nephrology and Cardiovascular Research Centre, Aalborg Hospital, Aarhus University Hospitals, 9100 Aalborg, Denmark. Haemodialysis patients are at high risk of sudden cardiac death (SCD). An attenuated heart rate variability (HRV) is a strong predictor of arrhythmic events and SCD. Dietary supplementation with omega-3 fatty acids has previously been shown to increase HRV in haemodialysis patients. It is not known whether these fatty acids need to be incorporated into cell membranes to exert this effect. An acute rise in the plasma concentration of omega-3 fatty acids might also increase HRV. A placebo controlled, single-blinded study is planned to investigate the acute effect of intravenous infusion with omega-3 fatty acid in haemodialysis patients. Seventy patients with end stage renal disease undergoing haemodialysis three times weekly will be randomized to a single infusion with 100 ml of an omega-3 fatty acid emulsion prepared for intravenous use or placebo (saline). The infusion will be administered during the course of a dialysis treatment. A 48-hour Holter recording will be obtained from each patient starting at the beginning of the dialysis. The Holter recordings will be analyzed with respect to HRV and the occurrence of ventricular arrhythmias. The content of omega-3 fatty acids in plasma and platelets will be determined in blood samples drawn at t=0, 4 and 48 hours. Possible outcome: HRV is increased in patients given omega-3 fatty acids compared to placebo and the frequency of ventricular tachyarrhythmias is diminished. The content of omega-3 fatty acids in plasma is increased where as the content in platelets is unchanged. This will suggest that the effect of omega-3 fatty acids can be attributed to the plasma concentration of free fatty acids in plasma rather than to fatty acids incorporated into

226 membrane phospholipids.

X11.07 Vanda EXPRESSION OF HERV-K18 ENVELOPE GENE DURING HHV-6B Turcanova INFECTION. UNIVERSITY OF AARHUS GRADUATE SCHOOL OF HEALTH SCIENCES, 13 JANUARY 2006 V. Turcanova, P. Höllsberg Department of Medical Microbiology and Immunology, University of Aarhus, Bartholin Building 1240, University Park, 8000 Århus C, Denmark The K18-Env, an envelope protein of human endogenous retrovirus (HERV-) K18, displays superantigen-like properties. As such, it may play a role in the development of autoimmune diseases by antigen-non-specific activation of autoagressive T cells. HERV-K18 mRNA levels are known to be upregulated during an EBV infection, or following IFN-α treatment in B cells. This upregulation is coupled with a functional superantigen-like activity. In our study, we investigate the expression of K18-env gene on the mRNA and functional level during infection by another herpesvirus, HHV-6B, also implicated in the autoimmunity. mRNA levels in peripheral blood mononuclear cells are studied by real-time quantitative PCR. Results show an upregulated expression of K18-env mRNA. This upregulation appears to be dependent on the active expression of HHV-6B genes and de novo protein synthesis, either viral or induced cellular, and independent of replication of HHV-6B DNA. To ascertain, whether the increased mRNA levels are coupled with the expression of a functional superantigen, T-cell activation will be tested on a panel of T-cell clones bearing different TCR-Vβ chains, primarily by flow cytometry. This study will apart from clarifying some of the mechanisms of herpervirus-induced HERV-K18 expression also bring more light into the potential connection between viral infections and autoimmune reactions in a fully human testing system.

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Index of oral and poster presentations

Oral presentations are arranged in four sessions O1-O4 Poster presentations are arranged in 26 groups P01-P26 Additional abstracts not presented X01, X11

Abstract session Presenter Abstract session Presenter and number and number

P15.09 Agata Baczynska P24.07 Borja Ballarín-González P06.08 Allan Carle O4.04 Brent M. Witgen P23.08 Alma Becic Pedersen P03.09 Brian Dall Schyth P19.10 Anders Bergström P05.03 Britta Hørdam P27.05 Anders Husted Madsen P27.04 Carsten Stengaard P07.08 Andreas Schröder P02.02 Cecilia Høst Ramlau- P25.03 Andrey Azov Hansen P21.04 Anelia Larsen P04.01 Charlotte Buchard Norager P25.07 Anette Jørgensen P16.09 Charlotte Christie Petersen P01.07 AnetteTorvin Møller P09.04 Charlotte Graugaard- O4.05 Anita Rethmeier Jensen P01.10 Anja Fjorback P01.03 Christian Lodberg Hvas O2.01 Anja Pernille Einholm P18.07 Christian Wejse P04.09 Ann Suhl Kristensen P09.05 Christina Bak Pedersen P08.03 Anna Mrowiec P22.01 Christine Petersen P12.10 Anne Birgitte Als P25.06 Claus Olesen P10.04 Anne Barklin X01.01 Claus Svane Søndergaard P03.03 Anne C. Vingård Olesen P19.01 Dea Kehler P22.08 Anne Fredsted P12.01 Ditte M. S. Lundvig P09.02 Anne Kirkeby Hansen P13.09 Donata Cibulskyte P04.07 Anne Sofie Brems- P24.06 Donna Marie Briggs Eskildsen X01.03 Dorte Kjær P07.09 Anne Toftegaard Funding P17.02 Eduardo Castrillon P02.06 Annette Ø. Jensen P22.10 Elena V Bouzinova P01.05 Ashfaque Ahmed Memon O4.02 Ellen M. Mikkelsen X01.02 Astrid From Frøhlich P04.02 Emad Eddin Ayesh P03.08 Astrid Heide Petersen P17.03 Erik Elgaard Sørensen P07.02 Bente Høy P25.02 Erik Langer Madsen P14.06 Bente Martinsen P27.01 Esben Buhl P09.08 Bettina Jørgensen X01.04 Esben Hjorth Madsen P12.02 Bettina S. Nedergaard P03.05 Esben Thyssen Vestergaard P11.09 Birgit Drews P09.10 Fenghua Chen P16.01 Birgit E. Bonefeld P20.02 Frederikke Rosendal P25.08 Birgitte Brandsborg P08.04 Gang Chen P14.09 Birgitte Mahler P15.01 Gitte Jacobsen P13.05 Birgitte Oxlund-Mariegaard P06.03 Gitte Juhl O2.05 Bjarke Moosgaard P10.10 Golnosh Bahrami P07.01 Bo Eskerod Madsen P05.10 Grete Moth P01.09 Bodil Øster P02.01 Guixian Wang

228 P13.02 Hanne Aagaard P02.03 Jørgen Baas P14.08 Hanne Birke Sørensen P12.08 Josefine Gradman P07.10 Hanne Busk Andersen P25.10 Kai Wang P27.07 Hanne Heje O4.03 Karen Johanne Pallesen X01.05 Hanne Krogh Jensen P18.10 Karen Madsen P12.03 Hanne Kronborg P15.03 Karen-Marie Pedersen P10.08 Hanne Lou P09.06 Kari Tanderup X01.06 Hanne M. Søndergaard P10.07 Karsten Bork Nielsen X01.07 Hanne Melgaard Nielsen P13.01 Karsten Zieger P06.10 Hanne Stubbe Teglbjærg P27.02 Kasper Kyng O1.01 Hanne Vebert Olesen P06.02 Kenneth Jensen P23.06 Helle Friis Svenstrup O3.01 Kim Holmgaad Jensen P09.01 Helle Terkildsen Maindal P18.08 Kim Mouridsen P23.04 Henriette Nørmølle P11.08 Kirsten Ejskjær Buttenschøn P16.05 Kirsten Pugdahl P13.06 Henriette Schou Hansen P17.10 Kirstine Stochholm P23.10 Henrik Kold-Petersen P10.01 Kristian Larsen P20.09 Henrik Pedersen P22.02 Kristian Otkjær Nielsen P07.06 Him Shing Ng P17.09 Kristin Skogstrand P03.04 Iben Søgaard Jacobsen X01.09 Kristine C. Tvedegaard P08.10 Inge Errebo Agerholm P12.05 Lars Gormsen P03.10 Inger Mechlenburg P14.02 Lars H. Pedersen P04.03 Ingolf Mølle P18.02 Lars Kroløkke Hviid O1.03 Irene Dige P03.02 Lars Riber Zebis P17.05 Isa Niemann O3.05 Lars Riisgaard Ribe X01.08 Iver Nordentoft P01.02 Lars Uhrenholt P15.07 Jacob Fog Bentzon P11.10 Lasse Solskov Jensen P21.03 Jacob Koefoed-Nielsen P02.04 Lene Baad-Hansen P24.02 Jacob Tauris P13.04 Lene Unmack Larsen P20.06 Jakob Hansen P26.01 Lijin Zou P22.06 Jakob Nielsen P18.06 Line Bille Madsen P08.09 Jakob Udby Blicher X01.10 Line Petersen P26.10 Jacob Severinsen P02.10 Lisbeth Uhrenfeldt P27.06 Jane Agergaard P20.04 Lise Gormsen P01.01 Jane Clemmensen P19.04 Ljubica Vukelic Andersen P12.07 Jeanne Elisabeth Debess P06.05 Lone Bruhn Madsen P23.02 Jens Rolighed P14.07 Lone Duval P10.02 Jeppe Sylvest Nielsen P18.05 Lotte Ebdrup P21.01 Jesper Frandsen P06.04 Louise Gyldensted P24.04 Jesper Karmisholt P05.06 Louise Henriette Pedersen P14.10 Jesper Kelsen P17.08 Louise Østergaard Petersen P11.04 Jesper Noer Petersen P19.08 Louise Sørensen P19.07 Jesper Stentoft P10.03 Maciej Bogdan Maniecki P08.02 Jette Ammentorp P26.03 Mads Aaboe Jensen P15.08 Jian Li P16.04 Mads Heilskov Rasmussen P01.06 Jianguo Chen P25.01 Mads Vilhelm Hollegaard P02.07 Jing Hong P26.02 Mads Vilhelm Hollegaard P11.06 Joanna Wieclaw P26.04 Magdalena Janina Laska P17.06 Jolanta Hansen P05.09 Mahmoud Ashkanian P08.07 Jonathan Gardi P22.07 Maik Stiehler

229 P25.04 Maiken Møller-Pedersen P27.11 Niels Juul P24.01 Majken K. Jensen P23.03 Nikolaos Karamperis P21.05 Malene Herbsleb P03.06 Nina Ank P26.05 Malene Rohr Andersen P03.07 Ole Eschen Dahl P09.07 Ole Gade Sørensen P12.06 Mandana Ghisari P21.02 Ole Ingemann Hansen P05.02 Manhai Long P11.03 Ole Mathiassen P07.07 Marianna Lalla P20.08 Per Borghammer X11.01 Marianne Bjerager P16.06 Pernille Bøttger P14.01 Marianne Ingerslev Holt P06.01 Peter Brynningsen O2.03 Marianne Jensby Nielsen P26.10 Mette Rylev Agerbæk P13.03 Marianne Kyndi P24.10 Peter Michael Kragh P19.09 Martin C. Sassen P22.09 Philippe Lamy P05.04 Martin Eivindson P02.08 Phuong Le Quach P17.07 Martin Roelsgaard X11.02 Pia Holland Hansen Jakobsen P07.04 Pia Pinholt Madsen P20.03 Martin Tolstrup P27.03 Preben Larsen O2.04 Mathias Hauge Bünger P20.01 Puk Sandager P08.01 Mett Marri Lægsgaard P16.03 Ramkumar Menon Madsen O2.02 Ramune Aleksyniene P06.06 Mette Asbjørn Neergaard P14.03 Randi Abrahamsen P15.05 Mette Drasbek P04.10 Rasmus Beedholm P05.05 Mette Ebbesen P27.09 Reziwanggu Abudula P05.08 Mette Krintel Petersen P15.10 René Christiansen P27.10 Mette Møller P19.05 Rie Stokholm O1.04 Mette Møller-Kristensen O3.03 Rikke Nørregaard P23.09 Mette Nørgaard P21.08 Rikke Riber-Hansen P15.04 Mette Ørskov Sjøland P01.04 Rikke Søgaard P26.09 Mette Rylev Agerbæk P24.05 Ripudaman Singh O1.02 Mette Skytte Tetsche X11.03 Ruta Kuzminskyte P16.10 Mette Slot Nielsen P14.05 Samuel Alberg Kock P07.03 Mette Søgaard P20.07 Sanne Angel P21.06 Mette Spliid Ludvigsen P09.09 Sigitas Urbonavicius P16.08 Mette Stylsvig P21.09 Signe Engkjær Christensen P06.07 Mette Underbjerg Dyrskog P23.05 Signe Gjedde P07.05 Mia Færch P24.03 Simon Buus P21.07 Michael Sørensen P11.02 Sophie de Seigneux P08.08 Mie Wiese Petersen P23.01 Søren Aagaard P20.05 Mikkel Lyngholm P24.09 Søren Cristensen P01.08 Mimi Kjærsgaard O3.04 Søren Dalager-Pedersen P22.04 Mogens Stender P19.06 Søren Hagstrøm P12.04 Morten Krag P26.06 Søren Hjortshøj P15.06 Morten Ølgaard Jensen P05.07 Søren Kildeberg Paulsen P12.09 Morten Sig Ager Jensen P08.06 Søren Peter Jørgensen P19.03 My Svensson P13.08 Søren Rytter P13.10 Naja Becher P14.04 Steffen Lund Hokland P17.01 Nicoline Marie Hall P11.07 Stig Åvall Severinsen P18.01 Niels Christian Bjerregaard P11.01 Stig Storgaard Jakobsen P11.05 Niels Hjort X11.04 Stine Johnsen O3.02 Niels Jessen P02.09 Sukru Oguzkan Topcu

230 P17.04 Sune Straszek P03.01 Tina R. Kilburn P18.09 Susanna Deutch P15.02 Tina Senholt Videbæk P04.06 Susanne Lerche P08.05 Tomasz Brudek P10.06 Susanne Maigaard Axelsen P04.08 Torben H. Thygesen P13.07 Tanja Krüger P18.03 Torsten Munch-Hansen P27.12 Thomas Andersen X11.06 Trine Madsen P02.05 Thomas Baad-Hansen O4.01 Trine Munk-Olsen P16.02 Thomas Dissing X11.07 Vanda Turcanova P09.03 Thomas Dyrsø Jensen P27.08 Vibeke Guldbrand P22.03 Thomas Harbo Rasmussen P05.01 Thomas Holm Pedersen P22.05 Vibeke Hvidberg P19.02 Thomas Jakobsen P20.10 Vibeke Koudahl P16.07 Thomas Lind-Hansen P06.09 Vibeke Sejer Hansen P10.09 Thomas Munk Laursen P10.05 Vivian Langagergaard O1.05 Thomas Nielsen P23.07 Walther Fledelius X11.05 Thomas Urban P24.08 Xiao-Yue Zhai P18.04 Thorbjørn H. Mikkelsen P25.05 Yuelian Sun P21.10 Tina Aaen Geest P26.07 Yutao Du P04.04 Tina Parkner P04.05 Zahra Nouria

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