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
Director, Graduate School of Health Sciences
Thomas Vorup-Jensen
Chairman, Organizing Committee
Søren Mogensen
Dean, Faculty of Health Sciences
3
4
Contents
Welcome
3
Information
7
Program
8
Free communication program
- oral
- posters
10
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
ƒ Lake Auditorium 5 (groups 1-6), Michael Hasenkam
ƒ Bartholin Building (groups 7-14), Raben Rosenberg
ƒ 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. tahiha@adm.au.dk
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
- 11.10
Discussion
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
8
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 XRAY 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
11
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 DOSERESPONSE 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, CROSSOVER STUDY
13
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 CLCONDUCTANCE
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?
14
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 SCHOOLAGE 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
15
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 COMMUNITYACQUIRED 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 TMJTOMOGRAMS 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 C4CARNITINE 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
17
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 KANAMYCININDUCED 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
19
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
20
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
21
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 SODIUMDEPENDENT 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 GLUTAMATEEVOKED 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
25
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 HEMOPEXINHEME 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 INVIVO 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
28
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.
29
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
31
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
number Author
Abstract
O1.01
Hanne
Vebert
Olesen
VIRAL AND ATYPICAL BACTERIAL INFECTIONS IN CHILDREN WITH
CYSTIC FIBROSIS.
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
Tetsche
PROGNOSIS OF OVARIAN CANCER ASSOCIATED WITH VENOUS
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 STR405labelled 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
MøllerKristensen
DEFICIENCY OF MANNAN-BINDING LECTIN GREATLY INCREASES
SUSCEPTIBILITY TO POST-BURN INFECTION WITH PSEUDOMONAS
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
Nielsen
RELATIONSHIP BETWEEN COMBRETASTATIN INDUCED CHANGES
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
1
Dept. 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
rear foot of female CDF1 mice and treated when at 200 mm3 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
Einholm
MUTATION OF GLY94 IN TRANSMEMBRANE SEGMENT M1 OF THE
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 SFM400/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,
Gly94Ala 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
Gly93Ala 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
was relatively small compared with the effects seen for E2P in Gly94Ala.
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
close to Ile287 of M3, particularly in E2P, thus resulting in a steric clash that
may explain the present observations.
O2.02
Ramune
Aleksyniene
EFFECTS OF PARATHYROID HORMONE TREATMENT ON
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. 2received 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
38
Marianne
Jensby
Nielsen
MOLECULAR CHARACTERIZATION OF THE HAPTOGLOBINHEMOGLOBIN RECEPTOR CD163: ENDOCYTIC PROPERTIES OF THE
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 haptoglobinhemoglobin (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
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
Hauge
Bünger
THE EFFECTS OF STRONTIUM ON BONE ULTRASTRUCTURE:
INSIGHTS FROM LABORATORY SCANNING SMALL ANGLE X-RAY
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
Moosgaard
VITAMIN D STATUS AND SEASONAL VARIATIONS IN PRIMARY
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 sexmatched 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
Holmgaad
Jensen
THE IMPAIRMENT OF RETINAL VASOCONSTRICTION CAUSED BY
PERIVASCULAR TISSUE CAN BE BLOCKED BY INHIBITION OF THE
GLUTAMATE NMDA RECEPTOR AND COX.
Kim Holmgaard Jensen*, Christian Aalkjær#, John D.C. Lambert#, and Toke
Bek*. (Correspondence should be sent to: khj@akhphd.au.dk.)
*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
1
Medical 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 30fold 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
Nørregaard
SEGMENTAL AQP2 REGULATION BY SELECTIVE COX-2 INHIBITION
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.
1
The 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 BUO3DR 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
42
Søren
DalagerPedersen
PERIADVENTITIAL INFLAMMATION - A MARKER OF SYSTEMIC
INFLAMMATORY ACTIVATION AND CORONARY DEATH?
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
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
Riisgaard
Ribe
MOTION ANALYSIS FOR SHORTER SCAN TIMES IN CARDIAC MRI
L. R. Ribe, S. Ringgaard, E. M. Pedersen
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 MunkOlsen
RISK OF POSTPARTUM MENTAL DISORDERS, WOMEN ARE AT RISK,
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
44
Ellen M.
Mikkelsen
PSYCHOSOCIAL CONDITIONS OF WOMEN WHO ANTICIPATE
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 nonrespondents in the entire study-population.
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
Johanne
Pallesen
EMOTION PROCESSING IN THE HUMAN BRAIN: AN fMRI STUDY
Karen Johanne 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 nonmusicians 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.
Witgen
INHIBITORY INTERNEURONS FOLLOWING EXPERIMENTAL BRAIN
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 somatostatinpositive inhibitory interneurons in the hilus shifts after brain injury with
potential functional implications. Remarkably, the number of somatostatinpositive 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
Rethmeier
THE USE OF OLIGONUCLEOTID ARRAYS IN SEARCH OF NEW
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
P01.02
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,
janec@daimi.au.dk
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.
Lars
Uhrenholt
INJURIES TO THE CERVICAL SPINE FACET JOINTS OF A ROAD
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
Lodberg
Hvas
IMPAIRED CYTOKINE RESPONSE IN INTESTINAL CD4+ T CELLS
FROM CROHN DISEASE PATIENTS
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 chvas@as.aaa.dk.
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 IFNγ production, whereas they fail to upregulate a regulatory response (IL-10)
to both tolerogenic (Lactobacilli) and immunogenic antigens (autologous
intestinal bacteria).
P01.04
Rikke
Søgaard
HEALTH ECONOMIC EVALUATION OF LUMBAR SPINAL FUSION IN
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
Ahmed
Memon
ACTIVITY OF THE EPIDERMAL GROWTH FACTOR RECEPTOR
DELAYS THE ONSET OF CALCIUM-INDUCED APOPTOSIS IN
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 phosphotyrosine 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 cotreatment 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 ßcells 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) pretreatment 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 pretreatment 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 pretreatment 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
Møller
50
NEUROPATHIC PAIN AND SENSORY DISTURBANCES IN
HETEROZYGOTE PATIENTS WITH FABRY DISEASE
A.T.Moeller1, F.W. Bach1, Å.K.Rasmussen2, Steen Kølvraa3, U. FeldtRasmussen2, T.S. Jensen1
1
Danish Pain Research Center, University hospital of Aarhus, 8000 Aarhus,
Denmark.
Background: Fabry disease is a rare X-linked lysosomal storage disorder.
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
Kjærsgaard
TREATMENT OF IDIOPATHIC THROMBOCYTOPENIC PURPURA IN
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 rhesusD 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 p53induced 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
Fjorback
A ROLE FOR M6B IN THE FUNCTIONAL REGULATION OF THE
HUMAN SEROTONIN TRANSPORTER
Anja W Fjorback1, Heidi Müller2, Jana Haase2 , and Ove Wiborg1
1
Department 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 cotransfection 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
Wang
DOWNREGULATION OF KEY RENAL ACID BASE TRANSPORT
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
RamlauHansen
SMOKING DURING PREGNANCY AND RISK OF LOW SEMEN
QUALITY IN THE MALE OFFSPRING
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
54
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
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 BaadHansen
BLINK REFLEXES IN PATIENTS WITH ATYPICAL ODONTALGIA AND
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
Baad-Hansen
ALTERATION OF HIP JOINT CENTRE DURING ACETABULAR
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
56
Annette Ø.
Jensen
NON MELANOMA SKIN CANCER AND MORTALITY IN DENMARK –
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
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.
1
Department of Endocrinology and Metabolism, Aarhus Sygehus THG,
Aarhus University Hospital, Tage-Hansens Gade 2, 8000 Aarhus C,
Denmark
2
The 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 palmitatestimulated 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
Quach
PREDICTORS OF MEDICATION COMPLIANCE AMONG PATIENTS
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 welldocumented. 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
Oguzkan
Topcu
CANDESARTAN PREVENTS LONG TERM CHANGES INRESPONSE TO
NEONATAL URETERAL OBSTRUCTION
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
Uhrenfeldt
CLINICAL WISDOM AND RESPONSIBILITY AMONG PROFICIENT
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 nonproficient performance.
P03.01
Tina R.
Kilburn
A NEW METHOD FOR TESTING SPEED OF INFORMATION
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
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.
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.
Vingård
Olesen
BIRTH WEIGHT AS A CORRELATE OF BLOOD PRESSURE:
UNEXPECTED ASSOCIATION BETWEEN SPOUSES
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 serumcholesterol.
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
Jacobsen
t(4;12) TRANSLOCATION IN A PATIENT WITH BIPOLAR AFFEKTIVE
DISORDER
IS Jacobsen1, Z Tümer2, N Tommerup2, A Borglum3, H Horsboel1, O Mors1
1
Centre for Basic Psychiatric Research, Aarhus, Denmark
2
Wilhelm Johannsen Centre, Panum Institute, Copenhagen, Denmark
3
Institute 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 preand 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
Thyssen
Vestergaard
THE GHRELIN RESPONSE TO EXERCISE BEFORE AND AFTER GH ADMINISTRATION
E. T. Vestergaard, T. K. Hansen, R. Dall, J. Frystyk, J. S. Christiansen, J. O. L.
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 postexercise 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
62
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 IFNcauses 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.
P03.07
Ole Eschen
SOLUBLE ADHESION MOLECULES IN HEALTHY SUBJECTS: A DOSERESPONSE 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
Petersen
ABSORPTION OF INHALED INSULIN DRAMATICALLY INCREASES BY
LARGE TIDAL VOLUME VENTILATION IN RABBITS
A. H. Petersen1,2,3, T. Laursen2, P. Clauson3, P. Wollmer4;
1
Dept. 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
Schyth
ANTIVIRAL ACTIVITY OF SMALL INTERFERING RNAS: SPECIFICITY
TESTING USING TARGET-HETEROLOGOUS VIRUS REVEALS IFN
RELATED EFFECTS OVERLOOKED BY CONVENTIONAL MISMATCH
CONTROLS
B. D. Schyth1*, N. Lorenzen1 & F. S. Pedersen2
1
Danish Food and Veterinary Research, Århus, Denmark
2
Molecular 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
Mechlenburg
CARTILAGE THICKNESS IN THE HIP JOINT MEASURED BY MRI AND
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
Buchard
Norager
CAFFEINE IMPROVES ENDURANCE IN 75-YEAR OLD CITIZENS. A
RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, CROSSOVER 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
Ayesh
P04.03
Ingolf Mølle
HYPERSENSITIVITY TO PIN-PRICK STIMULI FOLLOWING
NOCICEPTIVE ELECTRICAL STIMULATION OF THE HUMAN TMJ
Ayesh EE1, Jensen TS2, Svensson P1
1
School 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.
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 IIIbgenes 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
PARKNER
CLINICAL ASPECTS OF BASAL INSULIN PUMP THERAPY FOR 8
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
1
Department 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
Nourian
COMPARATIVE STUDY ON THE FUNCTIONAL α1-ADRENOCEPTOR
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
68
Susanne
Lerche
NEW POTENTIAL EFFECTS OF GLP-1, WITH A SPECIAL FOCUS ON
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
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
BremsEskildsen
ALTERNATIVE SPLICING IN BLADDER CANCER.
A. S. Brems-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.
Thygesen
SPATIAL AND TEMPORAL ASSESSMENT OF OROFACIAL
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
70
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
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: ask@psykiatri.aaa.dk
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
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
Beedholm
INVESTIGATION OF THE RECEPTOR-MEDIATED ENDOCYTOSIS OF
TRANSCOBALAMIN/INTRINSIC FACTOR-VITAMIN B12 COMPLEXES
R. Beedholm1, C. B. Grissom2, S. N. Fedosov3, E. Nexø4 and S. K. Moestrup1
1
Department of Medical Biochemistry, University of Aarhus, Denmark.
2
Department 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
Holm
Pedersen
REPETITIVE FIRING OF ACTION POTENTIALS SHIFTS THE
EXCITABILITY OF RAT MUSCLES VIA A REDUCTION IN THE RESTING
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 Clconductance 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
72
Manhai Long
DIOXIN-LIKE ACTIVITIES IN BLOOD ACROSS EUROPEAN AND INUIT
POPULATIONS
M Long1, BS. Andersen1, C Lindh, L Hagmar, JP Bonde, EC BonefeldJorgensen1 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 AhRactivities 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.
P05.03
Britta
Hørdam
CLINICAL RESEARCH – NURSING INTERENTION: DYSFUNCTION
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. Selfrated 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
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
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:DocMartin@dadlnet.dk
2
Medical 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
Ebbesen
WHICH BIOETHICAL PRINCIPLES SHOULD BE USED WITHIN
BIOMEDICINE?
Mette Ebbesen
Centre for Bioethics & Faculty of Health Sciences, University of Aarhus.
Email: meb@teo.au.dk
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 crosscultural 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
Henriette
PHARMACOLOGICAL CHARACTERISATION OF A PLACE ESCAPE /
AVOIDANCE PARADIGM (PEAP) IN RATS WITH NEUROPATHIC PAIN
74
P05.07
Pedersen
Louise H. Pedersen and Gordon Blackburn-Munro, Dep. of Pharmacology,
NeuroSearch A/S, Ballerup, Denmark LHP@neurosearch.dk
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 (dualreuptake 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.
Søren
Kildeberg
Paulsen
GROWTH HORMONE (GH) SUBSTITUTION IN GH DEFICIENT
PATIENTS INHIBITS 11 -HSD1 MRNA EXPRESSION IN ADIPOSE
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 11ßHSD2, 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
Petersen
EFFICACY OF MULTIMODAL, INTERDISCIPLINARY INTERVENTION
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,
mekp@mail.dk
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
P05.10
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.
Grete Moth
ORGANIZATION AND COST-EFFECTIVENESS OF CARE OF SCHOOLAGE 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
Brynningsen
IMPROVED NUTRITIONAL STATUS IN ELDERLY PATIENTS 6
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
Jensen
DO SMOKERS REALLY HAVE MORE FUN?
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 neversmokers. 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 agematched 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
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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
Gyldensted
PERFUSION-WEIGHTED MAGNETIC RESONANCE IMAGING IN
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: lg@pet.auh.dk
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
Madsen
ANIMAL MODELS FOR HUMAN NEURODEGENERATIVE DISEASES
L.B. Madsen1, B. Thomsen1, K. Larsen1, A. L. Jørgensen2, A. L. Nielsen2 and
C. Bendixen1.
1
Department of Genetics and Biotechnology, Danish Institute of
Agricultural Sciences, PO Box 50, DK-8830 Tjele, Denmark.
2
Department 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
Asbjørn
Neergaard
CANCER PALLIATION IN PRIMARY CARE –WHAT IS GOOD AND
BAD?
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
Underbjerg
Dyrskog
PRENATAL ALCOHOL EXPOSURE: NEUROPSYCHOLOGICAL
FUNCTIONS AT AGE 5 – WITH PARTICULAR REFERENCE TO
ATTENTION
M.U. Dyrskog1, P.Thorsen, U. Kesmodel, E.L. Mortensen, T. Manly
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1
NANEA, 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. Furthermore 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
82
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: carle@dadlnet.dk
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
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/TgAb 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
Hansen
GENDER DIFFERENCES IN HIPPOCAMPAL ATROPHY IN EPILEPSY
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
Stubbe
Teglbjærg
EXPRESSIVE ARTS THERAPY FOR SCHIZOPHRENIA, A QUALITATIVE
RESEARCH OF A FENOMENOLOGICAL BASED TREATMENT IN A
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
Madsen
SEARCHING FOR INTERACTING GENETIC VARIANTS THAT
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:
bh@sygeplejevid.au.dk
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 selfcare 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
Søgaard
SHORT- AND LONG-TERM PROGNOSIS OF COMMUNITY-ACQUIRED
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 Registry 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
Madsen
MIS-CLASSIFICATION OF MISSENSE, NONSENSE AND SILENT
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
1
Department 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 diseasecausing 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 bifunctional regulatory element with both ESE and ESS activity controls
splicing of both exons. We hope that our ongoing experiments (RNA pulldown 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
1
Pediatric 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
Ng
VISUAL VALIDATION OF EMBOLI DETECTION USING DOPPLER
ULTRASOUND AND WAVELET TRANSFORMATION
Him Shing Ng1,2, Hans Nygaard1,2, J. Michael Hasenkam2,
Peter Johansen1,2
1
Centre for Biomedical Technology, Engineering College of Aarhus
2
Department 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 countVisual 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
Lalla
AN EXPERIMENTAL HYPOSPADIA REPAIR IN RABBITS: A
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
Schröder
HOW TO DEFINE CRITERIA FOR SEVERE SOMATIZATION FOR A
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 (interviewerrating), 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 FSDDpatients were severely impaired in daily life, and 23 % had frequent GPconsultations 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
Toftegaard
Funding
MITOGEN- AND STRESS- ACTIVATED PROTEIN KINASE 1 IS
ACTIVATED IN LESIONAL PSORIATIC EPIDERMIS
A Funding1, C Johansen1, K Kragballe1, K Otkjær1, U Jensen2, M Madsen3, M
Fjording3, J Finnemann3, T Skak-Nielsen3, S Paludan4 and L Iversen1
1
Department 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 TNFprotein 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
Andersen
OPTIMIZATION OF CULTURE METHODS; CORD BLOOD DERIVED
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
Lægsgaard
Madsen
ATTITUDES TOWARDS PSYCHIATRIC GENETIC RESEARCH AND
TESTING: FEARS, HOPES, AND INTENTIONS
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
Ammentorp
COMMUNICATION IN HEALTH CARE – CAN IT BE IMPROVED ?
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
Mrowiec
THE NBCn1 PROTEIN EXPRESSION IS INCREASED THROUGH
DIFFERRENT MECHANISMS IN TWO MODELS OF ENHANCED RENAL
DISTAL TUBULAR NH4+ DELIVERY
A. Mrowiec1, B. Jensen2, J. Praetorius3, C. Buus4, Ch. Aalkjaer1
1
Water and Salt Research Center, Institute of Physiology, Ole Worms Alle
1160, University of Aarhus, Denmark; 2Institute of Medical biologyPhysiology 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
Brudek
HERPES VIRUS ANTIGENS ACTIVATE ENDOGENOUS RETROVIRUSES:
IMPLICATIONS FOR MULTIPLE SCLEROSIS
T. Brudek1, P. Lühdorf1, T. Christensen1, H. J. Hansen2, A. Møller-Larsen1
1
Department 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
Jørgensen
REMISSION-KEEPING AND REMISSION-INDUCING EFFECT OF
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
94
Jonathan
Gardi
USING BIASED IMAGE ANALYSIS FOR IMPROVING UNBIASED
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
counting.
P08.08
Mie Wiese
Petersen
ACCURACY OF MORPHOLOGICAL CHANGES IN TMJ-TOMOGRAMS
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
Blicher
EVIDENCE OF SHORT-TERM PLASTICITY IN A STROKE PATIENT,
MEASURED BY TRANSCRANIAL MAGNETIC STIMULATION OF THE
MOTOR-CORTEX.
J.U. Blicher, J.F. Nielsen, J. Jakobsen
Hammel Neurocenter, neujbl@sc.aaa.dk
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 motorlearning/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
Agerholm
SEQUENTIAL FISH ANALYSIS USING COMPETITIVE DISPLACEMENT
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
1
Fertilitetsklinikken, 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
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
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: selfmanagement skills in diabetes health behaviours, self-efficacy, healthcare
utilization and HbA1c, BP and cholesterol. Data sources will be selfadministered 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
Kirkeby
Hansen
ELECTIVE CESAREAN SECTIO AND RESPIRATORY MORBIDITY IN
THE NEONATAL PERIOD.
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
Dyrsø Jensen
HIGH-RESOLUTION SCREENING OF COLORECTAL CANCER USING
ARRAY COMPARATIVE GENOMIC HYBRIDIZATION
97
T.D. Jensen1,2, J. Li2, K. Wang2, S. Li2, X. Zhang2, L. Bolund2, S. Kølvraa1, G.B.
Petersen1
1
Dep. 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
98
Charlotte
GraugaardJensen
REGULATION OF URINE PRODUCTION: DIFFERENCES BETWEEN
GENDERS.
Graugaard-Jensen C, Frøkiær J, Hvistendahl G, Djurhuus JC.
Institute of Clinical Medicine, AArhus University Hospital Skejby, 8200
Aarhus N, Denmark
graugaard@ki.au.dk
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
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
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
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
1
Res. Unit for Mol. Med., Skejby Sygehus,2Dept.Clin. Gen., Rigshospitalet,
3
Statens 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
Tanderup
GEOMETRIC STABILITY OF RADIOACTIVE SOURCES DURING
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
Sørensen
DIFFERENT FIXATION METHODS IN RECONSTRUCTION OF THE
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
P09.09
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:bettina.jorgensen@ki.au.dk
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.
Sigitas
Urbonavicius
IDENTIFICATION OF PROTEINS AND PEPTIDES PREDICTING THE
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
Chen
PLASTICITY AT THE SYNAPSE: NEURON AND SYNAPSE NUMBER IN
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
Larsen
EFFICACY OF A PROACTIVE PERIOPERATIVE CARE AND
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
Nielsen
Activated Protein C’s Anti-inflammatory Effects on Acute Endotoxemic
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 antiinflammatory cytokines. Our results suggest that the anti-inflammatory
effects of APC are not elicited through cytokines.
P10.03
104
Maciej
Bogdan
Maniecki
NEW PROTEINS INVOLVED IN THE IRON METABOLISM – STUDY OF
HEPCIDIN IN RELATION TO FUNCTION, EXPRESSION AND
SHEDDING OF CD163
M.B. ManieckI1, B.K. Møller2, S.K. Moestrup1,3, H.J. Møller1
1
Department of Clinical Biochemistry, Aarhus University Hospital, DK8000 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
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 cofactor 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
Langagergaa
rd
BIRTH OUTCOME IN WOMEN WITH BREAST CANCER
Vivian Langagergaard, Mette Gislum, Mette V. Skriver, Bente Nørgård, Tim
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
106
Susanne
Maigaard
Axelsen
UROGYNECOLOGIC DYSFUNCTION AFTER RADICAL HYSTERECTOMY
S.M. Axelsen, L.K. Petersen
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.
P10.07
Karsten Bork
Nielsen
GENE EXPRESSION IN THE DEVELOPING PIG BRAIN
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 longterm 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
Munk
Laursen
EXCESS MORTALITY ASSOCIATED WITH PSYCHIATRIC ADMISSION.
T.M. Laursen MSc, T. Munk-Olsen MSc, M. Nordentoft MNPh.D, P.B
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
Bahrami
RISK INDICATORS FOR MARGINAL BONE LOSS IN THE INDIVIDUAL
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
Storgaard
Jakobsen
PROSTHESES SURFACES GENERATE AN INFLAMMATORY RESPONSE
S.S. Jakobsen, A. Larsen, M. Stoltenberg, K. Soballe
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
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P11.03
110
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.
Ole
Mathiassen
FOREARM PLETHYSMOGRAPY IN THE ASSESSMENT OF VASCULAR
RESISTANCE: NEW METHODOLOGICAL INSIGHTS.
1
ON Mathiassen, 1,3 NH Buus, 1 MJ Mulvany, 1,2 KL Christensen
1
Dept 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
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
Petersen
PSYCHOSOCIAL, FUNCTIONAL AND AESTHETIC PERSPECTIVES IN
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
112
Joanna
Wieclaw
OCCUPATIONAL RISK OF DEPRESSION AND STRESS IN THE DANISH
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 out- patients, 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
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
Severinsen
2,3-DIHYDROXYBENZOIC ACID ATTENUATES KANAMYCININDUCED VOLUME REDUCTION IN MOUSE UTRICULAR TYPE I HAIR
CELLS
Stig Å. Severinsen1*, Mette Kirkegaard2 Jens R. Nyengaard1
1
Stereology and Electron Microscopy Research Laboratory and MIND
Center, Institute of Clinical Medicine, University of Aarhus, Denmark and
2
Center 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
Ejskjær
INCREASED EXPRESSION OF THE EPIDERMAL GROWTH FACTOR
SYSTEM IN ENDOMETRIOID ENDOMETRIAL CANCER COMPARED
TO HEALTHY ENDOMETRIUM.
Kirsten Ejskjær1, Boe Sandahl Sorensen1, Steen Seier Poulsen2, Ole
Mogensen3, Axel Forman4 and Ebba Nexø1
1
Dept. 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 , HBEGF 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
114
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
1
Department of Public Health, Oluf Palmes Allé 17, 8200 Aarhus N
2
Department 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.
P11.10
Lasse
Solskov
Jensen
METFORMIN ACTIVATES AMP-ACTIVATED PROTEIN KINASE
(AMPK) IN THE RAT HEART AND REDUCES MYOCARDIAL INFARCT
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;
1
Medical 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.
Lundvig
P25α - A NOVEL MOLECULAR LINK TO DEMYELINATING DISORDERS
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 MBPp25α 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.
Nedergaard
QUANTITATIVE STUDIES OF THE CELLULAR IMMUNE RESPONSE IN
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-antigenreactive 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 clinicalbiological-pathological correlation, the study hopefully resulting in an
“immunogenicity grading scheme” for various common cancer types.
P12.03
Hanne
Kronborg
BREASTFEEDING AND EARLY BONDING: A RANDOMISED
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: HK@nursingscience.au.dk
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:0.751.2), 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
Gormsen
DOSE-RESPONSE EFFECTS OF FREE FATTY ACIDS ON INSULIN
SENSITIVITY IN HUMANS
L.C.Gormse1, J. Gjedsted1, N. Jessen1, J.S. Christiansen1, S. Nielsen1 and N.
Møller1.
1
Department 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
Ghisari
IMPACT OF ENVIRONMENTAL CHEMICALS ON THE THYROID
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, DK8000 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 T3induced 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
Elisabeth
Debess
COGNITIVE FUNCTION AMONG WOMEN WITH BREAST CANCER IN
RELATION TO ADJUVANT THERAPY
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), Selfefficacy (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
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available late in 2006.
P12.08
Josefine
Gradman
KNEMOMETRIC ASSESSMENT OF SHORT TERM GROWTH IN
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 nonglucocorticoid 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
Ager Jensen
MODERATE AGREEMENT BETWEEN CLINICAL ECG
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
Birgitte Als
MOLECULAR PROGNOSTIC MARKERS FOR SURVIVAL AFTER
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 cisplatincontaining 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
Zieger
CHARACTERISING GENOMIC CHANGES IN SUPERFICIAL BLADDER
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 nonprogressing 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
122
Hanne
Aagaard
NURSING AND CARING OF PREMATURE INFANTS.
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 aquasiexperimental 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 selfesteem; 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
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
Kyndi
PREDICTIVE MARKERS OF RESPONSE TO ADJUVANT
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 locoregional 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
Unmack
Larsen
FETAL CARDIAC EJECTION FRACTION ASSESSED FROM 4D
ULTRASOUND: SPATIO TEMPORAL IMGAE CORRELATION AND
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 endsystolic 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
OxlundMariegaard
IS PRETERM DELIVERY ASSOCIATED WITH A CONSTITUTIONAL
DECREASE IN THE MECHANICAL COMPETENCE AND COLLAGEN
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
Schou
Hansen
PREDICTORS OF THE COURSE OF FUNCTIONAL DIASESE IN
GENERAL PRACTICE – PREVENTION OF CHRONICITY
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 BonefeldJorgensen1 and the INUENDO group*
1
Department 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 1,1dichloro-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
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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 wearingdown 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
Cibulskyte
FUNCTIONAL AND STRUCTURAL RENAL EFFECTS
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
1
Department of Renal Medicine, 2Clinical Institut, 3MR Research Centre,
4
Department 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
Ingerslev
Holt
STEREOTACTIC BODY RADIOTHERAPY FOR LIVER TUMORS
Holt, M.I., Høyer, M., Grau C., von der Maase, H.
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.
Pedersen
PHARMACOLOGICAL TREATMENT OF DEPRESSION IN PREGNANCY
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
Abrahamsen
EFFECT OF HYPNOSIS IN TREAMENT OF OROFACIAL PAIN IN A
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
Hokland
ASSESING THE EFFICACY OF THE NEW VASCULAR TARGETING
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, DK8200 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
130
Samuel
Alberg Kock
MOTIONAL EFFECT ON WALL SHEAR STRESSES IN A
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 reallife 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.
P14.06
Bente
Martinsen
PERMANENT DEPENDENCE ON OTHERS DURING MEALS. A
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
Sørensen
FREE JEJUNAL FLAPS FOR OESOPHAGUS RECONSTRUCTION:
METABOLISM AND MONITORING USING MICRODIALYSIS
H.B. Sørensen
Department of Plastic surgery, Århus University Hospital, 8000 Århus,
Denmark.
e-mail: hanne.birke@ki.au.dk
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
Mahler
THE CIRCADIAN RHYTHM OF URINE OUTPUT IN INFANTS.
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
1
Water 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
Jacobsen
TRENDS IN EXPOSURE AND RESPIRATORY SYMPTOMS IN THE
DANISH WOOD WORKING INDUSTRY
Authors: Jacobsen G1, Schlünssen, V2, Schaumburg I1, Sigsgaard T2.
1
Department 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 nonsmokers 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
Videbæk
CIRCUMFERENTIAL FUSION IMPROVES LONG-TERM OUTCOME IN
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, 59 years after surgery the circumferentially fused patients had a significantly
improved outcome compared to posterolateral fusion alone.
P15.03
Karen-Marie
Pedersen
FROM GENE TO FUNCTION: CONDITIONAL KNOCKOUT OF FOUR
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 Flprecombinase 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
Ørskov
Sjøland
MIGRATION PATTERNS IN TWO TYPES OF CEMENTED HIP
PROSTHESES – A CLINICAL INTERVENTION STUDY
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
Drasbek
INHIBITING THE ADHESION OF MYCOPLASMA PNEUMONIAE TO
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
Ølgaard
Jensen
THE EFFECT OF MITRAL ANNULOPLASTY RINGS ON MITRAL VALVE
3D GEOMETRY AND STRESS DISTRIBUTION
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 crossdiameters.
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
Bentzon
SMOOTH MUSCLE CELLS OF ATHEROSCLEROTIC PLAQUES ARE
DERIVED FROM THE LOCAL VESSEL WALL IN APOLIPOPROTEIN EDEFICIENT 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
138
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. Arraybased 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.
P15.09
Agata
Baczynska
PREVALENCE OF MYCOPLASMA HOMINIS INFECTIONS AMONG
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
Christiansen
PERIAPICAL BONE HEALING AFTER APICECTOMY WITH AND
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.
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
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 bactin, 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
Dissing
EXPERIMENTAL UNILATERAL URETEROBSTRUCTION IN THE LATE
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 99mTcDTPA 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
Menon
ETHNIC CHARACTERIZATION OF CANDIDATE GENES FOR
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
Heilskov
Rasmussen
EPIGENETIC DETERMINANTS OF ONCOGENE ACTIVATION
M.H. Rasmussen (1), F.S. Pedersen (2), A.L. Nielsen (1).
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
P16.06
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.
Pernille
Bøttger
CELLULAR DOWN-REGULATION OF THE TYPE III SODIUMDEPENDENT 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
Lind-Hansen
STABILITY AND HEALING IN PROXIMAL TIBIAL OPEN WEDGE
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 effectparameter 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
Stylsvig
A PROSPECTIVE INVESTIGATION OF NEUROPSYCHOLOGICAL
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
Christie
Petersen
T-CELL-MEDIATED IMMUNITY IN PATIENTS WITH LEUKEMIA
DURING HCMV REACTIVATION
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, TNFalpha, 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
Nielsen
ENCAPSULATED CELL BIODELIVERY OF NGF TO THE BASAL
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
146
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.
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
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
Castrillon
INFLUENCE OF ORAL CONTRACEPTIVES ON GLUTAMATE-EVOKED
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
Sørensen
NURSING MANAGEMENT
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
148
Sune
Straszek
ACOUSTIC RHINOMETRY: A DIFFERENT APPROACH TO MEASURING
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.
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
Hansen
SAFETY AND EFFICACY OF COMPUTED TOMOGRAPHY
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
Roelsgaard
Jakobsen
SENSITIVE HIV-1 GENOTYPE METHOD VALIDATING VIRAL
RESISTANCE FROM PATIENTS WITH A LOW VIRAL LOAD.
M.R. Jakobsen, L.S. Bertelsen, J. Kjems, & Østergaard, L
Department of Infectious disease, Skejby Hospital, Brenstrupgaardvej 100,
8200 Aarhus N, email: mrj@sks.aaa.dk
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
Østergaard
Petersen
HYPOXIA-INDUCED ENDOTHELIAL DYSFUNCTION IN HUMAN
UMBILICAL VEIN ENDOTHELIAL CELLS
*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 upregulation 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
Skogstrand
SIMULTANEOUS DETERMINATION OF 25 INFLAMMATORY
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
Stochholm
THE INCIDENCE OF GROWTH HORMONE DEFICIENCY – A
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
Christian
Bjerregaard
DETECTION OF COLORECTAL NEOPLASIA IN SYMPTOMATIC
DANISH OUTPATIENTS WITHOUT VISIBLE RECTAL BLEEDING:
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: rlg07ncb@as.aaa.dk
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
Kroløkke
Hviid
REMITTED DEPRESSED PATIENTS, VISUOSPATIAL MEMORY AND
CBF IN THE RIGHT HIPPOCAMPUS
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
MunchHansen
Satisfaction with Psychosocial Work Conditions and Sickness Absence
Authors: T. Munch-Hansen, M. Rosenkilde, J. Wieclaw, J.P. Bonde
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 serviceworkplaces 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 workplaceunit. 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
154
Thorbjørn H.
Mikkelsen
CANCER REHABILITATION WITH PARTICULAR FOCUS ON THE
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 wellfunctioning 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
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:
51
Crom 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
Madsen
DOES TELEMONITORING OF HOME BLOOD PRESSURE IMPROVE
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 24hour 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
Wejse
A CLINICAL SCORE SYSTEM FOR MONITORING TB TREATMENT IN A
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:
wejse@dadlnet.dk
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
Mouridsen
BAYESIAN ESTIMATION OF PERFUSION PARAMETERS BASED ON A
PHYSIOLOGICAL MODEL FOR THE VASCULATURE
156
Kim Mouridsen1, Karl Friston2, Louise Gyldensted1, Leif Østergaard1, Stefan
Kiebel2.
1
Center 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
Deutch
BROAD-RANGE REAL-TIME PCR AND DNA-SEQUENCING FOR THE
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. Broadrange real-time PCR was more sensitive than broad-range conventional
PCR and microscopy.
P18.10
Karen
Madsen
DEVELOPMENT OF A CLASSIFICATION AND GRADING SYSTEM FOR
SPONDYLARTHROPTHY WITH MRI .
K. Madsen A. Jurik and B. Schiottz-Christensen. Arhus sygehus, Denmark
Contact mail : kbmad@as.aaa.dk
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
Jakobsen
TOPICAL BISPHOSPHONATE TREATMENT INCREASES FIXATION OF
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, placebocontrolled 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
Vukelic
Andersen
ACUTE UPPER LIMB ISCHEMIA AND ATRIAL FIBRILLATION/FLUTTER IN DENMARK FROM 1990 TILL 2002
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: ljubica@stofanet.dk
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
Hagstrøm
THE EFFECT OF SLEEP ON NOCTURNAL URINE OUTPUT
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
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
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
Sørensen
A ROLE FOR TOLL-LIKE RECEPTOR (TLR)-2 AND -9 IN ANTIVIRAL
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.
Sassen
CYCLOSPORINE TREATMENT IS ASSOCIATED WITH INCREASED ENAC EXPRESSION AND SODIUM RETENTION IN RATS
Martin C. Sassen1, Soo Wan Kim1, Mark A. Knepper2, Jørgen Frøkiær1, and
Søren Nielsen1
1
The 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 CsAtreated 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
164
Anders
Bergström
STRESS AND ANTIDEPRESSANT RESISTANCE IN THE CHRONIC MILD
STRESS ANIMAL MODEL OF DEPRESSION
A.Bergström1, A.Mørk2, O.Wiborg1.
1
Dept. of Biological Psychitry, Psychiatric Hospital, Aarhus.
2
Dept. of Psychopharmacology, H. Lundbeck A/S, Copenhagen.
Correspondance to absm@lundbeck.com
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
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
Sandager
PREDICTION OF PRETERM BIRTH
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
Rosendal
EVALUATION OF THE SUBTHALAMIC CONNECTIVITY IN THE
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
166
Martin
Tolstrup
Cysteine 138 mutation in HIV-1 Nef from patients with delayed disease
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.
Methods: We have established a patient cohort of long term nonprogressors (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
Gormsen
PAIN THRESHOLDS DURING AND AFTER TREATMENT OF SEVERE
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
Lyngholm
LIMBAL CORNEAL STEM CELL INSUFFICIENCY- CLINICAL AND
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
168
Jakob
Hansen
EXPRESSION OF PROTEIN QUALITY CONTROL GENES IN CELL
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
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
Borghammer
PARKINSON’S DISEASE: CEREBRAL METABOLISM EVALUAED BY [15O]
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
170
Henrik
Pedersen
REAL-TIME CORRECTION OF RESPIRATORY MOTION FOR
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
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
Koudahl
THE EFFECT OF ERYTHROPOIETIN ON WOUND HEALING
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 neovascularization 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
Frandsen
REGULARIZATION OF DIFFUSION TENSOR FIELDS
J. Frandsen1, A. Hobolth2, E. B. Jensen3, P. Vestergaard-Poulsen1, L.
Østergaard1.
1
Centre 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
Ingemann
Hansen
PRESENTATION OF THE WESTERN DANISH SEXUAL ASSAULT
CENTER
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
Koefoed-
A METHOD TO EXPERIMENTALLY INDUCE SOLITARY LOBE
ATELECTASIS.
172
P21.04
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:koefoed-nielsen@ki.au .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.
Anelia
Larsen
OCCUPATIONAL PSYCHIATRY:
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
Herbsleb
IDENTIFICATION OF NEW TRANSCRIPTIONAL CORRELATIONS IN
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, herbsleb@ki.au.dk
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
Ludvigsen
PATIENT LIFE. A NURSING STUDY BASED ON AN ETHNOGRAPHIC
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.
msl@nursingscience.au.dk
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 indepths interviews with nine male and nine female patients aged between 24
174
and 84 years old was carried out. The analytical approach is hermeneuticalphenomenological 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: “patienceimpatience”, “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
Sørensen
DYNAMIC 18F-LABELED GALACTOSE PET AS A MEASURE OF
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 flowweighted 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 RiberHansen
THE OPTIMAL NUMBER OF SENTINEL LYMPH NODES IN
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
176
Signe
Engkjær
Christensen
THE CALCIUM-CREATININE CLEARANCE RATIO (CCCR) IS
INSUFFICIENT IN SEPARATING FAMILIAL HYPOCALCIURIC
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.
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 Pvalue < 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
Geest
GENERAL PRACTITIONERS ROLE IN HELPING PATIENTS TO COPE
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 semistructured 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
Petersen
P25 INDUCES -SYNUCLEIN-DEPENDENT TOXICITY IN CELLULAR
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
178
Kristian
Otkjær
Nielsen
THE P38 MAPK IS A KEY REGULATOR OF IL-20 EXPRESSION IN
HUMAN KERATINOCYTES.
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.
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
Harbo
SYMPTOMS AND SIGNS OF NEUROPATHY IN A LONG-TERM
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 longterm 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 0240, 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
Stender
VENOUS THROMBOEMBOLISM AND HAEMOSTATIC ALTERATIONS
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
Hvidberg
IDENTIFICATION OF THE RECEPTOR SCAVENGING HEMOPEXINHEME 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, hemopexinheme 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
Nielsen
DECREASED RESPONSE TO ALDOSTERONE IN KIDNEY CORTICAL
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
1
Orthopaedic 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; *maik.stiehler@ki.au.dk
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
Fredsted
THE CAUSE OF MUSCLE DAMAGE: MECHANICAL
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
Lamy
GENOTYPING AND ANNOTATION OF AFFYMETRIX SNP PROBE SETS
Philippe Lamy *, Claus L. Andersen † and Carsten Wiuf *†
*
Bioinformatics Research Center, University of Aarhus, HoeghGuldbergsgade 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
Bouzinova
THE NA+ DEPENDENT HCO3- UPTAKE INTO THE RAT CHOROID
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 HCO3transporters 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 immunogold 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
Aagaard
THE IMPACT OF REMOTE PRECONDITIONING ON MYOCARDIAL
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
184
Jens
Rolighed
ASPECTS OF ANESTHETIC PRECONDITIONING IN A PORCINE
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.
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: jens.rolighed@dadlnet.dk
P23.03
Nikolaos
Karamperis
CHARACTERIZATION OF CALCINEURIN PHOSPHATASE DURING
ALLOGRAFT TRANSPLANTATION IN A RAT REJECTION MODEL
N. Karamperis1, Ø. Østraat2, K.A. Jørgensen1
1
Dept. 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 mRNA, 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
Nørmølle
Buttenschøn
THE GLUTAMATE DECARBOXYLASE GENE 1 AS A POTENTIAL
CANDIDATE GENE FOR AUTISM
H. N. Buttenschøn1, T. D. Als1, A. El Daoud1, A. G. Wang2,3, A. D. Børglum4,
T A Kruse5, M B Lauritsen1, O Mors1
1
Centre for Basic Psychiatric Research, Aarhus University Hospital,
Denmark
2
Dept. of Psychiatry, Copenhagen University Hospital, Denmark
3
Dept. of Psychiatry, National Hospital, Faroe Islands
4
Inst. of Human Genetics, University of Aarhus, Denmark
5
Dept. 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
Svenstrup
MYCOPLASMA GENITALIUM, CHLAMYDIA TRACHOMATIS AND
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 =1.315.2, 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
Fledelius
SWARM BASED MEDICAL IMAGE ANALYSIS: APPLIED TO IN-VIVO
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
Pedersen
PATIENT CHARACTERISTICS AND SURVIVAL OF TOTAL HIP
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 5059 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
Nørgaard
SHORT-TERM MORTALITY OF BACTERAEMIA IN ELDERLY PATIENTS
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 populationbased 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 30day 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 KoldPetersen
CORONARY ARTERY MYOGENIC RESPONSE IN A MOUSE MODEL OF
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.
Jensen
GENE-DIET INTERACTIONS IN THE REGULATION OF CHOLESTEROL
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 acylCoA: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:tauris@dadlnet.dk
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
1
PET 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 voxelby-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
Karmisholt
QUALITY OF LIFE, BODY COMPOSITION, RESTING ENERGY
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
Singh
HEAT SHOCK PROTEIN 70 GENE IN ASSOCIATION WITH HUMAN
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-AT 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
Briggs
THE CALCIUM-ACTIVATED CYCLIC-GMP DEPENDENT CHLORIDE
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
coupling, [Ca2+]i, Ca2+-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 noradrenalinestimulated vasomotion in rat mesenteric arteries.
P24.07
Borja
DEVELOPMENT OF KNOCK-IN MOUSE MODELS CARRYING AN AKV
193
P24.08
194
BallarínGonzález
1-99 LTR INTO THE N-RAS/UNR LOCUS
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 (MartinHernadez 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.
Xiao-Yue
Zhai
RECONSTRUCTION OF MOUSE NEPHRONS
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
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
Cristensen
THE PHYSIOLOGICAL SIGNIFICANCE OF THE TMAX PARAMETER IN
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
Michael
Kragh
PORCINE BLASTOCYSTS PRODUCED BY HANDMADE CLONING
WITH A COMBINED ELECTRICAL AND CHEMICAL ACTIVATION
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: pmk@humgen.au.dk
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
196
Mads
Vilhelm
Hollegaard
METHOD DEVELOPING AND BASIC RESEARCH FOR SNP DETECTION
AND FUNCTIONALITY WITH SPECIAL INTEREST IN ASSOCIATIONS
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.
P25.02
Erik Langer
Madsen
CHANGES IN ENDOTHELIAL FUNCTION AND ADIPOKINES IN
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
Azov
POSITION EFFECTS ON GENE EXPRESSION AS STUDIED ON A
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
MøllerPedersen
THE PRECISION AND INFLUENCE OF FLEXION FOR BMD
MEASUREMENTS OF THE PROXIMAL TIBIA FOLLOWING TOTAL
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
198
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 fiveminute 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
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, AnneMarie L. Jensen2, Jesper Vuust Møller1 and Poul Nissen2.
1
Department of Physiology and Biophysics Ole Worms Alle 185 DK-8000
University of Aarhus, Denmark. 2Centre for Structural Biology, University
of Aarhus, Denmark. #e-mail co@biophys.au.dk
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
Jørgensen
HYALURONAN INTRA-ARTICULAR IS WITHOUT LONG-TERM
CLINICAL EFFECT IN KNEE OSTEOARTHRITIS (OA). A
MULTICENTER, RANDOMIZED, PLACEBO-CONTROLLED DOUBLEBLIND STUDY OF 335 PATIENTS WITH MODERATE TO SEVERE KNEE
OA
A.Jørgensen,1 K.Stengaard-Pedersen,1 and the Hyalgan® study group.2
1
Department 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 intraarticular 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 algofunctional 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
Brandsborg
CHRONIC PAIN FOLLOWING HYSTERECTOMY: A NATIONWIDE
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.
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
P25.09
P25.10
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
202
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.
P26.02
Mads
Vilhelm
Hollegaard
METHOD DEVELOPING AND BASIC RESEARCH FOR SNP DETECTION
AND FUNCTIONALITY WITH SPECIAL INTEREST IN ASSOCIATIONS
TO PRETERM BIRTH
Mads V. Hollegaard1,2,3, Poul Thorsen1, David M. Hougaard2, and Susanne
Mandrup3.
1
NANEA, 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 dysregulated 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
Jensen
HUMAN TRANSCRIPTION FACTOR SOX4
M. Aaboe1, K. Birkenkamp-Demtroder1, C. Wiuf1,2, F.B. Sørensen3, T.
Thykjaer1, G. Sauter4, K. Møller-Ernst Jensen5, L. Dyrskjøt1 and T. Ørntoft1.
1
Molecular Diagnostic Laboratory, Department of Clinical Biochemistry,
Aarhus University Hospital / Skejby Sygehus, 8200 Aarhus N, Denmark.
2
Bioinformatics 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.
5
Department 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 SOX4induced 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
Janina Laska
THE ROLE OF GENE RAI IN APOPTOSIS AND CANCER. CULTURES OF
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 apoptosisinducing 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
Andersen
Dahl
LOWER LEVELS OF ADMA AND INCREASED ENDOTHELIUMDEPENDENT NO-MEDIATED RELAXATION OF UTERINE SMALL
ARTERIES FROM PREGNANT WOMEN
M.R. Andersen,a U. Simonsen,b M. Hedegaard,a S. Stender,c C. Aalkjær.d
a
Dept. 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
Hjortshøj
PREVALENCE OF ISCHEMIA MODIFIED ALBUMIN IN ISCHAEMIC
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
206
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
1
Danish 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
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, AnneMarie L. Jensen2, Jesper Vuust Møller1 and Poul Nissen2.
1
Department of Physiology and Biophysics Ole Worms Alle 185 DK-8000
University of Aarhus, Denmark. 2Centre for Structural Biology, University
of Aarhus, Denmark. #e-mail co@biophys.au.dk
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
Agerbæk
IDENTIFICATION OF DOMINANT IMMUNOGENIC BACTERIA AND
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
208
Jacob
Severinsen
ASSOCIATION ANALYSIS SUGGESTING GPR24 AS A SHARED
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
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 hypothalamuspituitary-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 insulinstimulated 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
210
Preben
Larsen
“MICROBIOLOGICAL PESTICIDES IN GREENHOUSES - A POSSIBLE
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 greenhouseworkers 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
results may rise from the results of the last two years follow-up.
P27.04
Carsten
Stengaard
AN ANIMAL MODEL FOR PARTIAL THICKNESS CHONDRAL
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
Husted
Madsen
RISK STRATIFICATION AFTER INTRODUCTION OF SENTINEL LYMPH
NODE BIOPSY TECHNIQUE
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
212
Jane
Agergaard
DIPHTERIA-TETANUS-PERTUSSIS (DTP) VACCINATION AND CHILD
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) Sexdifferences 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
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 clusterrandomised 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
Guldbrand
Rasmussen
VALVULAR HEART DISEASE ASSOCIATED WITH THE USE OF ERGOT
DOPAMINE AGONISTS IN TREATMENT OF PATIENTS WITH
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
214
Reziwanggu
Abudula
REBAUDIOSIDE A DIRECTLY STIMULATES INSULIN SECRETION
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.
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.
1
Center of Functionally Integrative Neuroscience, Aarhus University,
Denmark,
2
PET-Center, Aarhus University Hospital, Denmark,
3
Department of Neuroradiology, Aarhus University Hospital, Denmark,
4
Department 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 timedependent 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 CTscanning 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
216
Thomas
Andersen
DALLAS PAIN QUESTIONNAIRE CLASSIFICATION PREDICTS
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 (1859 years/60+ years), Gender (male/female), Diagnosis
(listhesis/degeneration), Previous back surgery (yes/no), Work status
(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 followup 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 DPQscores 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
Søndergaard
EVALUATING THERAPEUTIC POTENTIAL OF HUMAN STEM AND
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.
1
Clinical Institute; 2Dep. of Medical Microbiology and Immunology; 3Dep. of
Cardiology, Skejby University Hospital; Faculty of Health Sciences and
4
Dep. 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
Frøhlich
EFFECT OF IMPERMEABLE INTERFACES ON APPARENT DIFFUSION
COEFFICIENT IN HETEROGENEOUS MEDIA
A.F. Frøhlich, L1,2. Østergaard1 and V.G. Kiselev2
1
Dept. 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
proportional to (D0t)1/2 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
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.
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
Krogh Jensen
NO CORRELATION BETWEEN TUMOR-EXPRESSION OF CAIX AND
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
hkrje@as.aaa.dk
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 tumorinfiltrating 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
220
Hanne M.
Søndergaard
IMPACT OF TYPE 2 DIABETES ON MYOCARDIAL INSULIN
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
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
Melgaard
Nielsen
FAILURE PATTERN AMONG HIGH-RISK BREAST CANCER PATIENTS
RANDOMIZED TO PLUS MINUS POSTMASTECTOMY RADIOTHERAPY
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 diseasefree 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
Nordentoft
HOW DOES THE HISTONE ACETYLTRANSFERASE PROTEIN TIP60
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.
Tvedegaard
GENETIC MARKERS FOR DEVELOPMENT OF AUTISTIC DISORDER
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 MultiCode™ 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 immunosuppressive 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
Bjerager
DELAY IN DIAGNOSE AND TREATMENT OF LUNG CANCER
Marianne Bjerager1, Torben Palshof2 Ronald Dahl3 and Frede Olesen1
1
Research Unit for General Practice, University of Aarhus, Denmark,
2
Department 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 1063 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
X11.03
224
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.
Ruta
Kuzminskyte
CEREBRAL RESPONSE PATTERN TO PAIN AND ANTICIPATION OF
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
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
Urban
IMMEDIATE IMPLANT PLACEMENT IN THE MOLAR REGIONS - A
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
226
Trine
Madsen
INTRAVENOUS OMEGA-3 FATTY ACIDS AND HEART RATE
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
membrane phospholipids.
X11.07
Vanda
Turcanova
EXPRESSION OF HERV-K18 ENVELOPE GENE DURING HHV-6B
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.
227
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
and number
P15.09
P06.08
P23.08
P19.10
P27.05
P07.08
P25.03
P21.04
P25.07
P01.07
O4.05
P01.10
O2.01
P04.09
P08.03
P12.10
P10.04
P03.03
P22.08
P09.02
P04.07
P07.09
P02.06
P01.05
X01.02
P03.08
P07.02
P14.06
P09.08
P12.02
P11.09
P16.01
P25.08
P14.09
P13.05
O2.05
P07.01
P01.09
228
Presenter
Agata Baczynska
Allan Carle
Alma Becic Pedersen
Anders Bergström
Anders Husted Madsen
Andreas Schröder
Andrey Azov
Anelia Larsen
Anette Jørgensen
AnetteTorvin Møller
Anita Rethmeier
Anja Fjorback
Anja Pernille Einholm
Ann Suhl Kristensen
Anna Mrowiec
Anne Birgitte Als
Anne Barklin
Anne C. Vingård Olesen
Anne Fredsted
Anne Kirkeby Hansen
Anne Sofie BremsEskildsen
Anne Toftegaard Funding
Annette Ø. Jensen
Ashfaque Ahmed Memon
Astrid From Frøhlich
Astrid Heide Petersen
Bente Høy
Bente Martinsen
Bettina Jørgensen
Bettina S. Nedergaard
Birgit Drews
Birgit E. Bonefeld
Birgitte Brandsborg
Birgitte Mahler
Birgitte Oxlund-Mariegaard
Bjarke Moosgaard
Bo Eskerod Madsen
Bodil Øster
Abstract session
and number
P24.07
O4.04
P03.09
P05.03
P27.04
P02.02
P04.01
P16.09
P09.04
P01.03
P18.07
P09.05
P22.01
P25.06
X01.01
P19.01
P12.01
P13.09
P24.06
X01.03
P17.02
P22.10
O4.02
P04.02
P17.03
P25.02
P27.01
X01.04
P03.05
P09.10
P20.02
P08.04
P15.01
P06.03
P10.10
P05.10
P02.01
Presenter
Borja Ballarín-González
Brent M. Witgen
Brian Dall Schyth
Britta Hørdam
Carsten Stengaard
Cecilia Høst RamlauHansen
Charlotte Buchard Norager
Charlotte Christie Petersen
Charlotte GraugaardJensen
Christian Lodberg Hvas
Christian Wejse
Christina Bak Pedersen
Christine Petersen
Claus Olesen
Claus Svane Søndergaard
Dea Kehler
Ditte M. S. Lundvig
Donata Cibulskyte
Donna Marie Briggs
Dorte Kjær
Eduardo Castrillon
Elena V Bouzinova
Ellen M. Mikkelsen
Emad Eddin Ayesh
Erik Elgaard Sørensen
Erik Langer Madsen
Esben Buhl
Esben Hjorth Madsen
Esben Thyssen Vestergaard
Fenghua Chen
Frederikke Rosendal
Gang Chen
Gitte Jacobsen
Gitte Juhl
Golnosh Bahrami
Grete Moth
Guixian Wang
P13.02
P14.08
P07.10
P27.07
X01.05
P12.03
P10.08
X01.06
X01.07
P06.10
O1.01
P23.06
P09.01
P23.04
P13.06
P23.10
P20.09
P07.06
P03.04
P08.10
P03.10
P04.03
O1.03
P17.05
X01.08
P15.07
P21.03
P24.02
P20.06
P22.06
P08.09
P26.10
P27.06
P01.01
P12.07
P23.02
P10.02
P21.01
P24.04
P14.10
P11.04
P19.07
P08.02
P15.08
P01.06
P02.07
P11.06
P17.06
P08.07
Hanne Aagaard
Hanne Birke Sørensen
Hanne Busk Andersen
Hanne Heje
Hanne Krogh Jensen
Hanne Kronborg
Hanne Lou
Hanne M. Søndergaard
Hanne Melgaard Nielsen
Hanne Stubbe Teglbjærg
Hanne Vebert Olesen
Helle Friis Svenstrup
Helle Terkildsen Maindal
Henriette Nørmølle
Buttenschøn
Henriette Schou Hansen
Henrik Kold-Petersen
Henrik Pedersen
Him Shing Ng
Iben Søgaard Jacobsen
Inge Errebo Agerholm
Inger Mechlenburg
Ingolf Mølle
Irene Dige
Isa Niemann
Iver Nordentoft
Jacob Fog Bentzon
Jacob Koefoed-Nielsen
Jacob Tauris
Jakob Hansen
Jakob Nielsen
Jakob Udby Blicher
Jacob Severinsen
Jane Agergaard
Jane Clemmensen
Jeanne Elisabeth Debess
Jens Rolighed
Jeppe Sylvest Nielsen
Jesper Frandsen
Jesper Karmisholt
Jesper Kelsen
Jesper Noer Petersen
Jesper Stentoft
Jette Ammentorp
Jian Li
Jianguo Chen
Jing Hong
Joanna Wieclaw
Jolanta Hansen
Jonathan Gardi
P02.03
P12.08
P25.10
O4.03
P18.10
P15.03
P09.06
P10.07
P13.01
P27.02
P06.02
O3.01
P18.08
P11.08
P16.05
P17.10
P10.01
P22.02
P17.09
X01.09
P12.05
P14.02
P18.02
P03.02
O3.05
P01.02
P11.10
P02.04
P13.04
P26.01
P18.06
X01.10
P02.10
P20.04
P19.04
P06.05
P14.07
P18.05
P06.04
P05.06
P17.08
P19.08
P10.03
P26.03
P16.04
P25.01
P26.02
P26.04
P05.09
P22.07
Jørgen Baas
Josefine Gradman
Kai Wang
Karen Johanne Pallesen
Karen Madsen
Karen-Marie Pedersen
Kari Tanderup
Karsten Bork Nielsen
Karsten Zieger
Kasper Kyng
Kenneth Jensen
Kim Holmgaad Jensen
Kim Mouridsen
Kirsten Ejskjær
Kirsten Pugdahl
Kirstine Stochholm
Kristian Larsen
Kristian Otkjær Nielsen
Kristin Skogstrand
Kristine C. Tvedegaard
Lars Gormsen
Lars H. Pedersen
Lars Kroløkke Hviid
Lars Riber Zebis
Lars Riisgaard Ribe
Lars Uhrenholt
Lasse Solskov Jensen
Lene Baad-Hansen
Lene Unmack Larsen
Lijin Zou
Line Bille Madsen
Line Petersen
Lisbeth Uhrenfeldt
Lise Gormsen
Ljubica Vukelic Andersen
Lone Bruhn Madsen
Lone Duval
Lotte Ebdrup
Louise Gyldensted
Louise Henriette Pedersen
Louise Østergaard Petersen
Louise Sørensen
Maciej Bogdan Maniecki
Mads Aaboe Jensen
Mads Heilskov Rasmussen
Mads Vilhelm Hollegaard
Mads Vilhelm Hollegaard
Magdalena Janina Laska
Mahmoud Ashkanian
Maik Stiehler
229
P25.04
P24.01
P21.05
P26.05
P12.06
P05.02
P07.07
X11.01
P14.01
O2.03
P13.03
P19.09
P05.04
P17.07
P20.03
O2.04
P08.01
P06.06
P15.05
P05.05
P05.08
P27.10
O1.04
P23.09
P15.04
P26.09
O1.02
P16.10
P07.03
P21.06
P16.08
P06.07
P07.05
P21.07
P08.08
P20.05
P01.08
P22.04
P12.04
P15.06
P12.09
P19.03
P13.10
P17.01
P18.01
P11.05
O3.02
230
Maiken Møller-Pedersen
Majken K. Jensen
Malene Herbsleb
Malene Rohr Andersen
Dahl
Mandana Ghisari
Manhai Long
Marianna Lalla
Marianne Bjerager
Marianne Ingerslev Holt
Marianne Jensby Nielsen
Marianne Kyndi
Martin C. Sassen
Martin Eivindson
Martin Roelsgaard
Jakobsen
Martin Tolstrup
Mathias Hauge Bünger
Mett Marri Lægsgaard
Madsen
Mette Asbjørn Neergaard
Mette Drasbek
Mette Ebbesen
Mette Krintel Petersen
Mette Møller
Mette Møller-Kristensen
Mette Nørgaard
Mette Ørskov Sjøland
Mette Rylev Agerbæk
Mette Skytte Tetsche
Mette Slot Nielsen
Mette Søgaard
Mette Spliid Ludvigsen
Mette Stylsvig
Mette Underbjerg Dyrskog
Mia Færch
Michael Sørensen
Mie Wiese Petersen
Mikkel Lyngholm
Mimi Kjærsgaard
Mogens Stender
Morten Krag
Morten Ølgaard Jensen
Morten Sig Ager Jensen
My Svensson
Naja Becher
Nicoline Marie Hall
Niels Christian Bjerregaard
Niels Hjort
Niels Jessen
P27.11
P23.03
P03.06
P03.07
P09.07
P21.02
P11.03
P20.08
P16.06
P06.01
P26.10
P24.10
P22.09
P02.08
X11.02
P07.04
P27.03
P20.01
P16.03
O2.02
P14.03
P04.10
P27.09
P15.10
P19.05
O3.03
P21.08
P01.04
P24.05
X11.03
P14.05
P20.07
P09.09
P21.09
P23.05
P24.03
P11.02
P23.01
P24.09
O3.04
P19.06
P26.06
P05.07
P08.06
P13.08
P14.04
P11.07
P11.01
X11.04
P02.09
Niels Juul
Nikolaos Karamperis
Nina Ank
Ole Eschen
Ole Gade Sørensen
Ole Ingemann Hansen
Ole Mathiassen
Per Borghammer
Pernille Bøttger
Peter Brynningsen
Mette Rylev Agerbæk
Peter Michael Kragh
Philippe Lamy
Phuong Le Quach
Pia Holland Hansen
Pia Pinholt Madsen
Preben Larsen
Puk Sandager
Ramkumar Menon
Ramune Aleksyniene
Randi Abrahamsen
Rasmus Beedholm
Reziwanggu Abudula
René Christiansen
Rie Stokholm
Rikke Nørregaard
Rikke Riber-Hansen
Rikke Søgaard
Ripudaman Singh
Ruta Kuzminskyte
Samuel Alberg Kock
Sanne Angel
Sigitas Urbonavicius
Signe Engkjær Christensen
Signe Gjedde
Simon Buus
Sophie de Seigneux
Søren Aagaard
Søren Cristensen
Søren Dalager-Pedersen
Søren Hagstrøm
Søren Hjortshøj
Søren Kildeberg Paulsen
Søren Peter Jørgensen
Søren Rytter
Steffen Lund Hokland
Stig Åvall Severinsen
Stig Storgaard Jakobsen
Stine Johnsen
Sukru Oguzkan Topcu
P17.04
P18.09
P04.06
P10.06
P13.07
P27.12
P02.05
P16.02
P09.03
P22.03
P05.01
P19.02
P16.07
P10.09
O1.05
X11.05
P18.04
P21.10
P04.04
Sune Straszek
Susanna Deutch
Susanne Lerche
Susanne Maigaard Axelsen
Tanja Krüger
Thomas Andersen
Thomas Baad-Hansen
Thomas Dissing
Thomas Dyrsø Jensen
Thomas Harbo
Thomas Holm Pedersen
Thomas Jakobsen
Thomas Lind-Hansen
Thomas Munk Laursen
Thomas Nielsen
Thomas Urban
Thorbjørn H. Mikkelsen
Tina Aaen Geest
Tina Parkner
P03.01
P15.02
P08.05
P04.08
P18.03
X11.06
O4.01
X11.07
P27.08
P22.05
P20.10
P06.09
P10.05
P23.07
P24.08
P25.05
P26.07
P04.05
Tina R. Kilburn
Tina Senholt Videbæk
Tomasz Brudek
Torben H. Thygesen
Torsten Munch-Hansen
Trine Madsen
Trine Munk-Olsen
Vanda Turcanova
Vibeke Guldbrand
Rasmussen
Vibeke Hvidberg
Vibeke Koudahl
Vibeke Sejer Hansen
Vivian Langagergaard
Walther Fledelius
Xiao-Yue Zhai
Yuelian Sun
Yutao Du
Zahra Nouria
231