Abstrakter for postere Tema: Somatisk forskning, kirurgi nevrologi hjerte/kar

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1 Abstrakter for postere Tema: Somatisk forskning, kirurgi nevrologi hjerte/kar Posterpresentasjon torsdag 26. mars: Alders- og kjønnsfordeling av creatin kinase (CK) i en normalbefolkning Bekkelund, SI Abeler K, Nevrologisk avdeling, Universitetssykehuset Nord-Norge (UNN), Tromsø, Norge, Bekkelund SI, Nevrologisk avdeling, UNN Tromsø og Universitetet i Tromsø (UiTø), Norge, Figenschau Y, Avdeling for medisinsk biokjemi, UNN Tromsø og UiT, Norge, Johnsen SH, Nevrologisk avdeling, UNN Tromsø og UiT, Norge, Jorde R, Endokrinologisk avdeling, UiT og UNN Tromsø, Norge Kvitnes AK, Nevromuskulært kompetansesenter (NMK), nevrologisk avdeling, UNN Tromsø, Norge Lilleng H, Nevrologisk avdeling, UiT og UNN Tromsø, Norge, Lindal S, Patologisk avdeling, UNN Tromsø og UiT, Norge, Lund I, Nevromuskulært kompetansesenter (NMK), nevrologisk avdeling, UNN Tromsø, Norge, Løseth S, Nevrologisk avdeling, nevrofysiologisk seksjon, UNN Tromsø og UiT, Norge Stensland E, Nevrologisk avdeling, UNN Tromsø og UiT, Norge Formål Undersøke alders- og kjønnsfordeling av muskelenzymet creatin kinase (CK) i en normalbefolkning. Metode Resultatene er hentet fra Tromsøundersøkelsen som ble gjennomført fra oktober 2007 til desember 2008 i regi av Institutt for samfunnsmedisin, UiT (ISM). Et utvalg av personer i Tromsø ble invitert til å delta i undersøkelsen. Dataene er ikke korrigert for fysisk aktivitet eller andre forhold som kan påvirke CK-verdiene. Resultat CK er målt på av deltakere i Tromsøundersøkelsen. Av dem var 6930 kvinner og 6054 menn. Gjennomsnittlig CK-verdi for hele gruppen var 127,9 (Standardavvik, SD = 224). I gruppen av menn var gjennomsnittsverdien på 160 (SD=313), mens tilsvarende resultat for kvinner var 100 (SD=79). For kvinner var i liten grad aldersavhengighet, mens det var større aldersvariasjon i den mannlige gruppen. Verdiene var lavere for kvinner i aldersgruppen år sammenlignet med de mellom år. Deretter viste CK økende verdi hos de over 50 år for deretter å stabilisere seg blant de høyeste aldersgruppene. CK viste jevnt fallende verdier for de over 50 år i den mannlige gruppen. Det var også større spredning i dataene for menn, særlig i aldersgruppene år og år. Konklusjon Menn har høyere CK-verdier og større variasjon i CK enn kvinner. I motsetning til menn, holder CK-verdiene seg omtrent på samme nivå med økende alder blant kvinner. Det er derfor større grunn til å kontrollere en forhøyet CK-prøve hos en mann enn hos en kvinne.

2 Molecular Characterization of FKRP related Limb-Girdle type 2I Muscular Dystrophy Alhamidi, M 1,2 Alhamidi M, 2 Kjeldsen Buvang E, 1 Fagerheim T, 1 Brox V, 1 van Ghelue M and 1,2 Nilssen Ø. Department of Medical Genetics, 1 University Hospital of North-Norway, NO-9038 Tromsø, Norway, and 2 Institute of Clinical Medicine, NO-9037 University of Tromsø, Norway. Aim Limb-Girdle Muscular Dystrophy type 2I (LGMD2I) is a recessive disorder caused by mutations in the FuKutin-Related Protein gene (FKRP). Muscle biopsies from LGMD2I patients show incomplete/aberrant O-glycosylation of the membrane/extra-cellular-matrix protein alpha-dystroglycan. However, further clues to the FKRP function are lacking. Hence, the underlying molecular aetiology of LGMD2I is unknown. As a part of the effort to fully characterise the biological role of FKRP (495aa), we provide preliminary data on posttranslational modification and molecular self-interaction. Anti FKRP antibodies were generated against peptides FKRP and FKRP Other methods employed were; Immunogold Transmission Electron Microscopy (TEM), molecular cloning, FKRP expression in mammalian cells, Western Blot analysis and Yeast 2- Hybrid (Y2H) analysis. Immunogold TEM of muscle sections indicated that anti FKRP antibodies co-localize with Golgi markers. Deglycosylation of FKRP with EndoH or PNGaseF resulted in an FKRP MW shift from 58 to 54 kda. Upon expression in mammalian cells, FKRP assembled into DTT sensitive complexes of kda that became DTT insensitive upon in vivo and in vitro chemical cross-linking. Pair-wise Y2H experiments with FKRP/FKRP in bait/pray combination demonstrated growth of yeast on selective medium. FKRP appears to localize close to, or within the Golgi compartment, at the Z-lines between the myofibrils. FKRP contains two potential N-glycosylation sites. Both are occupied with high mannose (and/or hybrid) oligosaccharides. FKRP self-interaction, indicated by chemical cross-linking, was demonstrated by pair-wise Y2H analysis. FKRP involvement in higher MW complexes was also observed. The content of these complexes remains to be investigated.

3 Female and male rat hearts are equally affected by chronic exogenous angiotensin II Aljabri, B Aljabri, M. B., Lund, T., Ytrehus, K. Faculty of Medicine, Institute of Medical Biology, University of Tromsø, Norway Purpose Circulating ang II is part of the mechanism behind heart hypertrophy. Gender-dependent difference in heart hypertrophy due to pressure overload has been established in clinical and experimental studies. In the present study we examined if chronic ang II overexposure leads to a milder response in female compared to male hearts with respect to gene expression changes and ischemic injury. 16 female and male age and litter matched rats received ang II 200 ng/kg/min (miniosmotic pumps) or sham treatment. After 14 days hearts were excised, buffer-perfused and subjected to 30 minutes ischemia and 30 minutes reperfusion. Left ventricular developed pressure (LVDP), coronary flow and hearts rate were monitored. Hearts were harvested for expression of 18 different genes using RT-PCR. Statistics: TwoWay ANOVA, p 0.05, mean ± SD. Hearts treated with ang II had significantly higher LVDP prior to ischemia (sham 124±32 vs ang II 170±36 mmhg) and significantly higher end diastolic pressure at the end of reperfusion (26±17 in sham vs 68±22 mmhg in ang II). No significant gender difference was detected in heart function. Ang II increased expression of hypertrophy, fibrosis, apoptosis and inflammation related genes. Subgroup analysis revealed slightly more significant expression response to ang II in female compared to male hearts. Ang II leads to significant increase in gene expression related to hypertrophy, interstitial fibrosis, inflammation and apoptosis and to increase in contractile force and reduced tolerance to ischemia in the heart. In rat heart, female gender seems not to protect against these changes.

4 Demographical characteristics according to recruiting methods and gender distribution in The Dementia Study in Rural Northern Norway. Andersen, F Anders, F, Steigen Medical Center, Leinesfjord, Norway Background Dementia is the most challenging geriatric problem in public health for years to come. Identifying risk factors, reliable diagnosing criteria and suited screening methods are crucial for prevention and treatment of early diseased stage. Objectives This issue is derived from The Dementia Study in Rural Northern Norway, which provided examination of the effect of structured stimulation therapy on cognitive functions in patients with a recent diagnosis of Alzheimer s disease. The paper focuses on demographical characteristics of samples recruited by population-based screening and routine clinical practice. Gender differences are also elucidated. Method The study was designed as a non-randomized 1-year intervention with structured stimulation compared to routine care in five and four municipalities, respectively. To this a block randomized double-blind donepezil study was added. As a consequence of low inclusion rate in routine general practice the study population was exposed to a postal screening of cognitive impairment followed by a clinical examination and diagnosing. One hundred patients were recruited by screening and 87 in general practice. Screening recruited younger patients with a higher MMSE-score, and relatively more men. All over, women were older and at a more serious disease stage. After age adjusting significantly more women were living single and required more support from the community nursery. Population based screening of cognitive function recruits younger patients with early stage dementia compared to recruitment in general clinical practice. Single living elderly women should be paid more attention to prevent progress of cognitive impairment.

5 Vektøkning i svangerskapet Flo, K. Flo, K. ¹, ³, Wilsgaard, T.², Acharya, G.¹, ³ ¹Kvinneklinikken, Universitetssykehuset i Nord- Norge,Tromsø, ²Institutt for Samfunnsmedisin, Med.Fak. Universitetet i Tromsø, ³Institutt for Klinisk Medisin, Med.Fak. Universitetet i Tromsø Formål Forekomst av overvekt og fedme har i Norge økt 2-3 ganger i løpet av en generasjon. Overvektige gravide har større risiko for svangerskapsdiabetes, preeklampsi, langvarig fødsel og operativ forløsning. Enkelte studier tyder på at stor vektøkning i svangerskapet øker risikoen for varig overvekt. Det intrauterine miljø har betydning for barnets senere helse. Føtal makrosomi gir økt risiko for overvekt hos barnet i tenårene og diabetes senere i livet. Det finnes ingen gode data av norske kvinners vektøkning i graviditet og det er ikke klart hva som er den optimale vektøkning kg økning hos normalvektige regnes som veiledende. Hensikten med denne studien var å undersøke økning i vekt og kroppsmasseindeks (KMI) fra første svangerskapskontroll til termin hos friske lav- risikogravide. Metode Dette er en del av en langsgående observasjonsstudie av 53 lav-risikogravide uten intervensjon. Opplysninger om vekt på første gangs svangerskapskontroll ble notert fra helsekortet. Kvinnene ble undersøkt fra svangerskapsuke 22 med omtrent 4 ukers intervall, og hver kvinne ble undersøkt 4-5 ganger. Resultat Gjennomsnittlig vekt og KMI ved første gangs svangerskapskontroll var henholdsvis 65,9 kg og 23,5 kg/m². Vekt og KMI økte til henholdsvis 78 kg og 27,7 kg/m² ved termin. Gjennomsnittlig vektøkning fra første gangs svangerskapskontroll til termin var 12,1 kg. Det var ingen alvorlige komplikasjoner hos mødrene eller barna. Konklusjon Studien viser vektøkning innenfor angitte anbefalinger. Det er behov for en større studie som kartlegger normal vektøkning gjennom hele graviditeten hos norske kvinner.

6 Elevated glucose and insulin improve cardiac efficiency and post-ischemic functional recovery in perfused hearts from type 2 diabetic mice Aasum, E Hafstad AD, Khalid AM, How OJ, Larsen TS and Aasum E Department of medical physiology, Institute of Medical Biology, Faculty of Medicine, University of Tromsø, Norway Aim Perfused hearts from type 2 diabetic (db/db) mice demonstrate over-reliance on fatty acid oxidation (FAox) as well as reduced resistance to ischemic injury. Relationships between ventricular pressure-volume area (PVA) and myocardial oxygen consumption (MVO 2 ), have also revealed reduced cardiac efficiency in these hearts. Although db/db mice show overall insulin resistance in vivo, we recently reported that insulin induces a marked shift in myocardial metabolism towards glucose oxidation (GLUox) in perfused db/db hearts. We therefore hypothesized that such a shift in metabolism should improve cardiac efficiency and post-ischemic functional recovery in this model. Method Hearts from non-diabetic (db/+) and diabetic mice were perfused with 0.7 mm palmitate and either 5 mm glucose and no insulin (G), 5 mm glucose mu/ml insulin (GI) or 33 mm glucose mu/ml insulin (HGHI). In addition to pre-ischemic myocardial FAox and GLUox, ventricular function was measured before and after ischemia. Cardiac efficiency was assessed by examination of the PVA-MVO 2 relationships obtained in these hearts. While HGHI had only modest effects on metabolism and recovery in db/+ hearts, it produced a marked metabolic shift towards GLUox in db/db hearts. HGHI significantly increased cardiac efficiency and post-ichemic functional recovery in db/db, but not in db/+ hearts. Insulin and glucose normalize cardiac metabolism, restore efficiency, and improve postischemic functional recovery in type 2 diabetic mouse hearts. These findings may in part explain the beneficial effect of glucose-insulin-potassium therapy in diabetic patients with cardiac complications.

7 Rosiglitazone Treatment Improves Cardiac Efficiency in Hearts from Diabetic Mice Larsen, T How O-J, Larsen TS, Hafstad AD, Khalid AM, Myhre ESP, Severson DL and Aasum E Department of Medical Physiology, University of Tromsø, Norway Aim Isolated perfused hearts from type 2 diabetic (db/db) mice show impaired ventricular function, as well as altered cardiac metabolism. Measurements of myocardial oxygen consumption (MVO 2 ) and cardiac work (pressure-volume area, PVA) have also revealed reduced cardiac efficiency in these hearts. In this study we hypothesized that lipid-lowering treatment (administration of the PPARγ agonist, rosiglitazone) would improve cardiac metabolism and cardiac efficiency in db/db hearts. Method Rosiglitazone (RSG, ~ 20 mg/kg body weight/day) was administered as a food admixture to db/db mice for five weeks. Ventricular function and PVA was assessed using a miniaturized (1.4 Fr) pressure-volume catheter; MVO 2 was measured using a fibre-optic oxygen sensor. RSG treatment of db/db mice normalized plasma glucose and lipid concentrations, restored rates of cardiac glucose and fatty acid oxidation, and improved cardiac efficiency. The improved cardiac efficiency was due to a significant decrease in unloaded MVO 2, while contractile efficiency was unchanged. RSG-treatment also improved the recovery of cardiac function after low-flow ischemia. In conclusion, the present study demonstrates that in vivo PPARγ-treatment restored cardiac efficiency and increased the myocardial tolerance to ischemia of perfused hearts from type 2 diabetic mice.

8 Vasopressin, but not norepinephrine, causes ventriculoarterial mismatch in experimental post ischemic cardiogenic shock Anders Kildal Ole-Jakob How, Assami Røsner, Anders Kildal, Petter Gjessing, Stig E Hermansen, Truls Myrmel, Laboratory of surgical research, University of Tromsø and Department of thoracic and cardiovascular surgery, University hospital Northern Norway. Introduction There is a lack of scientific evidence supporting the efficacy and safety of inotropic and vasopressor support in treatment of cardiogenic shock (CS). Hypothesis: Vasoconstrictors given in cardiogenic shock will increase the ventriculoarterial mismatch and thus lead to reduced cardiac output In a closed chest pig model we tested the inodilator (dobutamine, Dobut) alone and combined with either an inoconstrictor (norepinephrine, NE) or a pure vasopressor (arginine vasopressin, AVP). In anesthetized animals, CS was induced by coronary microembolization. In post ischemic CS, energy transfer from the ventricle to the arterial system (Ea/Ees 1.8 ± 0.2, PRSW 26 ± 2 and Ejection fraction 42 ± 6 %) was partly restored by Dobut (1.4 ± 0.2, 46 ± 2 and 47 ± 6%) unaffected by further adding NE (1.5 ± 0.2, 53 ± 2 and 45 ± 5%), but impaired after adding AVP (2.0 ± 0.1, 43 ± 1 and 34 ± 4%). Consequently, Dobut improved the shock by increasing cardiac output (CO) and SVO2 from 74 ± 3 ml/kg and 37 ± 2% to 103 ± 8 ml/kg and 49 ± 3%. Adding NE resulted in a further improvement of CO (125 ± 9 ml/kg) and SVO2 (59 ± 4%). In contrast AVP further worsened the shock state by decreasing CO (70 ± 6 ml/kg) and SVO2 (45 ± 5%) compared to Dobut alone. A pure afterload increasing substance in acute ischemic hearts with cardiogenic shock aggravate the shock state by causing a ventriculoarterial mismatch.

9 Ung mann med alvorlig hodeskade, hjerneødem, komplisert med septisk sjokk og femorgansvikt, et håpløst tilfelle? Haavind, A Haavind, A, Universitetssykehuset Nord-Norge Formål Vise hvor vanskelig vurdering av intensivpasienter er. Vår pasient hadde svært dårlige prognostiske markører, hvor avslutning av behandling ble vurdert. Vi valgte i en kritisk fase å intensivere behandlingen og pasienten lever med godt funksjonsnivå i dag. Metode Kasuistikk: Pasienten var en 21 år gammel mann som kjørte av veien i stor fart. Han ble funnet bevisstløs hengende opp ned i bilen, selvpustende. Undersøkelse på skadestedet viste Glasgow Coma Score 4, ekstensjonsbevegelser i alle ekstremiteter, dilatert høyre pupille og ingen lysreaksjon bilateralt. Ved ankomst til lokalsykehus ble han sedert og intubert. CT caput viste skallebasisfraktur og subaraknoidalblødning occipitalt, samt to kontusjonsblødninger temporalt venstre side. Mannen ble overflyttet til UNN Tromsø for neurokirurgisk behandling. Intrakraniell trykkmåling ble etablert og pasienten holdt sedert, normoventilert med sirkulatorisk støtte ved Noradrenalin og Dopamin. Intrakranielt trykk steg på dag 3 til 30 mmhg og transkraniell doppler viste patologisk flow i arteria cerebri media høyre side.cefotaxim ble startet for påvist infiltrat høyre lunge. Dag 7 var begge pupiller dilaterte, de var ikke lysreagerende og hadde ingen cornearefleks. Klinisk forelå et ARDS bilde i lungene og Pa02/Fi02 falt fra 16 til 7,7 kpa, samtidig forelå et hyperdynamisk septisk sjokk. Det var dialysekrevende nyresvikt og koagulasjonssvikt med halverte trombocytter siste døgn. Konvensjonell respiratorbehandling ble erstattet med oscillerende ventilasjon og det ble gjort antibiotikaskifte til Meronem samt oppstart av steroider. Neste dag var situasjonen kritisk og etter tverrfaglig vurdering ble det valgt å starte aktivert protein C, til tross for kontraindikasjon som hjerneblødning og koagulasjonssvikt. 36 timer etter oppstart av behandling med aktivert Protein C begynte en gradvis bedring i alle organsystemer. Vasoaktive medikamenter og CRP halvert, oksygenering i bedring. Dag 13 kunne pasienten overføres til rehabilitering. I dag 2 ½ år etter kjører han bil. Konklusjon Intensivpasienter kan ha svært dårlige parametre å vise til som både klinikk, røngtendiagnostikk og labaratoriprøver, men likevel vise seg å overleve med et godt funksjonsnivå. Særlig hos pasienter med traumatisk hodeskade skal man være varsom med å uttale seg om prognose og nevrologisk utfall, så lenge pasienten befinner seg i intensivavdelingen.

10 Increased gene expression diversity between female and male mice hearts after transverse aortic constriction (TAC) Lund, T Trine Lund, Margareth Bergesen Hals, Ruth H Paulssen, Kirsti Ytrehus Institute of Medical Biology and Institute of Clinical Medicine, Faculty of Medicine, University of Tromsø, Norway Purpose Gender-dependent difference in heart hypertrophy due to pressure overload has been widely recognized using different experimental models and in clinical studies. The present study examines how increase in afterload affects gene expression in female hearts compared to male hearts. 32 female and male balb/c mice were randomized to TAC or sham operation using minimal invasive procedure. After 1 week hearts were subjected to gene expression analysis (32K mouse genome survey v2.0 ABI microarrays) and at 1 and 2 weeks RT-PCR for genes selected based on previous reports and pilot studies. Heart/ body wt was significantly increased by TAC and male gender (3.2±0.3 and 4.3±0.6 in sham versus 4.3±0.6 and 6.3±0.5 g/kg in TAC, females and males respectively). Microarrays revealed a total of 601 genes differently expressed (p<0.05) by gender or TAC. Only 8.5 % of the differently expressed genes were associated with gender difference in sham. In contrast, 49.9 % were differently expressed in male vs female TAC hearts. The rest (41.6 %) were common genes regulated in both gender due to TAC. Gender difference in TAC induced gene expression was sorted according to biological processes. Male hearts showed changes in gene expression related to apoptosis, carbohydrate and nucleic acid metabolism, and protein transport whereas gene expression related to these processes appeared unaltered in female hearts. Female hearts showed changes in cell adhesion genes, whereas these appeared unaltered in male TAC hearts. Increase in afterload leads to significant diversity in gene expression between female and male mice hearts.

11 Atlet studien kan personer med inkomplett ryggmargsskade lære å gå? Piira A, Knutsen SF Piira A, Knutsen SF. Rehabiliteringssenteret Nord-Norges Kurbad, Tromsø, Norge Formål Hvert år får 100 nordmenn ryggmargsskade. De fleste blir effektivt rehabilitert til et liv i rullestol. Studien tester den primære hypotesen at pasienter med motorisk inkomplett ryggmargsskade, ved hjelp av vektavlastet intens stå- og gangtrening på tredemølle, kan gjenvinne disse funksjoner helt eller delvis, bedre sin ADL-funksjon og dermed sin livskvalitet og føre til besparelse med hensyn til bruk av norske helsekroner. Metode Singel blindet randomisert klinisk intervensjonsstudie. To metoder for intensiv gangtrening vil bli testet: 1) manuell ledning av føtter og bekken under trening (4-5 terapeuter, Tromsø) eller 2) poliklinisk robot-assistert gangtrening (Asker). Hver delstudie består av 30 personer fordelt på intervensjons- og kontrollgruppe. Intervensjonen i begge gruppene består av 60 treningsdager med intens vektavlastet gangtrening. Kontrollgruppen får tradisjonell behandling/trening (usual care). Objektiv, blindet evaluering av pasientene før og etter intervensjon skjer ved Sunnaas sykehus. Studien er et samarbeidsprosjekt mellom Rehabiliteringssenteret Nord-Norges Kurbad, Sunnaas sykehus, Universitetene i Oslo og Tromsø, Friskvernklikken og Norges Idrettshøyskole. Resultat Studien pågår og man har derfor ikke resultater fra denne. Det vil fremlegges resultater fra pilotprosjektet. Det forventes at ATLET-studien vil gi tallmateriale og danne grunnlag for fremtidige retningslinjer for rehabilitering av ryggmargsskadde. Konklusjon Studien samler ulike rehabiliteringsmiljø i Norge. Studien vil gi betydelig erfaring med behandling av tverrsnittskadde og vil også kunne dokumentere hvorvidt slik intensiv rehabilitering er kostnadseffektiv.

12 Low-dose adrenomedullin-epinephrine cotreatment: A new inodilator treatment approach that increases cardiac output without inducing hypotension Stenberg, T.A. Stenberg, TA. 1 Kildal, AB. 1 Sanden, E. 1 Hermansen, SE. 1,2 How, OJ. 1 Myrmel, T. 1,2 1 Surgical Research Laboratory, Institute of Clinical Medicine, University of Tromsoe, Tromsoe, Norway; 2 Department of Cardiothoracic and Vascular Surgery, University Hospital North Norway, Tromsoe, Norway Purpose Adrenomedullin (AM) reduces mortality in the acute phase of experimental murine myocardial infarction. However, the hemodynamic profile of AM is potentially deleterious in human AMI and cardiogenic shock as the peptide is vasodilative and inotropically neutral. We hypothesized that low-dose cotreatment with AM and epinephrine (EPI) would increase cardiac output while maintaining perfusion pressure. 15 open-chest pigs were employed. Left ventricular (LV) function was measured using a pressure-volume catheter, transit-time flow probes and coronary sinus blood sampling. LV energetics was analyzed in the PVA-MVO 2 framework. After baseline recordings, the AM group (n=9) was infused with 15 ng kg -1 min -1 AM while controls (n=6) received saline as vehicle (VE). Following measurements at +2 h, EPI (50 ng kg -1 min -1 ) was added in both groups and final recordings were obtained (AM-EPI/VE-EPI). AM increased CO (16±13%; mean±sd) and HR (25±16%) with a parallel reduction in SVR by 14±12% (p<.01) while controls were unaffected. AM-EPI increased CO and HR by 48±26 and 57±35% (p<.01) vs. 13±12 and 19±17% by VE-EPI (NS). PRSWi and dp/dt max were increased by 34±23 and 29±12% by AM-EPI (p<.01) vs. 23±27 and -2±14% by VE-EPI (NS). MAP was maintained by AM-EPI (93±10 vs. 91±16 mmhg), whereas it tended to decrease with VE-EPI (89±10 vs. 78±6 mmhg; NS). PVA-MVO 2 was unaffected. s Low-dose AM is inotropically neutral and increases CO primarily through chronotropy and vasodilation. Cotreatment with low-dose epinephrine constitutes a new inodilator that maintains perfusion pressure and moderately augments LV function beyond that achieved by epinephrine alone.

13 Can psychomotor decline on speech production in mild Alzheimer s disease be due to reduced cerebellar gray matter? Vangberg, T.R. Vangberg, T.R. 1, Jota, C. 2, Bakken Arnesen, R.E. 2, Eldevik, P. 1, Johnsen, S.H. 4, Sparr, S. 3, Waterloo K. 2,4, Rodríguez-Aranda, C. 2 1 Dept. Radiology, Medical Faculty, University of Tromsø, Tromsø, Norway 2 Dept. Psychology, University of Tromsø, Tromsø, Norway 3 Dept. Geriatrics, University Hosp N Norway, Tromsø, Norway 4 Dept. Neurology, University Hosp N Norway, Tromsø, Norway Objective indicate that declines on psychomotor functions occur prior to serious cognitive impairment at early stages of Alzheimer s disease (AD). These changes are related to complex motor functions requiring involvement of mental capacities for their execution such as speech articulation. Evidence suggests that the cerebellum may play a crucial role in these functions. Because little is known about psychomotor changes on speech production in mild AD and its relationship to the cerebellum, the present study seeks to evaluate aspects of word generation and the extent to which speech articulation measures correlate to gray matter (GM) volume in the cerebellum. Participants were 15 healthy elderly and 15 mild AD patients. A test battery was utilized to assess cognitive capacity. From the battery, four verbal tasks were recorded and further employed for analysis of psychomotor parameters in word production. Spectrographic analyses of verbal tasks quantified reaction times (RT), word articulation time and voice intensity. Magnetic resonance (MR) scans optimized for voxel based morphometry were collected. From these images the cerebellum was extracted and normalized to a cerebellum template. Linear regression analysis was performed between GM segments and speech scores. Spectrographic results show declines in RT, word articulation and principally on voice intensity in the AD group. The morphometric analyses show positive correlation between speech data and GM volume in the lateral area of the cerebellum. suggest that psychomotor declines on speech production are identifiable changes present in mild AD that relates to structural changes in the cerebellum.

14 Visual acuity in VLBW adolescents correlates to FA-values in corpus callosum Vangberg, T.R. Vangberg, T.R. 1, Lindqvist, S. 2, Haraldseth, O. 3, Brubakk, A.M. 2, Vik, T. 4, Skranes, J. 2 1 Dept. Radiology, Medical Faculty, University of Tromsø, Tromsø, Norway 2 Dept. LabMedicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway 3 Dept. Circulation and Medical Imaging, Medical Faculty, Norwegian University of Science and Technology, Trondheim, Norway 4 Dept of Public health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway Objective To assess the correlations between visual acuity and the microstructural organization of the brain as indicated by fractional anisotropy (FA) values. Visual acuity is often reduced in very low birth weight (VLBW) adolescents, even in the absence of ocular pathology. Periventricular leucomalacia (PVL) is an important risk factor for visual impairment in VLBW children. However, visual impairment is also seen in expremature children with no PVL, and more subtle brain pathology is thought to be responsible. Diffusion tensor imaging (DTI) provides information about the microstructural organization of cerebral white matter and is well suited to detect subtle neuronal pathology. 30 adolescents with VLBW and a control group of 45 term born adolescents were examined at 15 years of age. Subjects underwent MRI examination including DTI. FA values were correlated to distance visual acuity using linear regression (p < 0.001, extent threshold 10 voxels). Visual acuity correlated significantly with FA values in the splenium part of the corpus callosum in VLBW subjects, but not in the control group Reduced FA values, indicating reduced axonal integrity in the corpus callosum, was found to correlate with reduced visual acuity in adolescents with VLBW. This is, to our knowledge, the first study to prove a correlation between visual function and the structural integrity of the corpus callosum, supporting the hypothesis that slightly reduced visual acuity often encountered in ex-prematures with no obvious retinal pathology, may be caused by subtle damage of the brain.

15 Neuropathological changes in pigs with acute liver failure: Evidence of blood brain barrier breakdown Ytrebø, L.M. Kristiansen, RG. 1, Lindal, S. 2, Myreng, K. 2, Revhaug, A. 3, Ytrebø, LM. 1, Rose, C. 4 1 Departments of Anesthesiology, 2 Pathology, and 3 Digestive Surgery, University Hospital of North Norway and University of Tromsø, Norway. 4 Neuroscience Research Unit, Hopital Saint-Luc (CHUM), University of Montreal, Canada. Aims Intracranial hypertension is a serious complication of fulminant hepatic failure which accounts for 30 % of deaths of patients. We have previously demonstrated an increase in intracranial pressure is associated with an accumulation of water in the brain of pigs with acute liver failure (ALF). An accepted tenet has been that the blood-brain barrier is intact and that brain edema is primarily caused by a cytotoxic etiology. The aim of this study was to investigate the ultrastructural changes in three different areas (frontal lobe, cerebellum, and brain stem) of the brain following eight hours of ALF. Sixteen female pigs weighing kg were randomised using the sealed envelope system into two groups: ALF (n=8) and sham operated controls (n=8). ALF was induced with an endto-side portacaval shunt followed by ligation of the hepatic arteries. Brain biopsies were prepared for electron microscopic investigation and scored by using a semiquantitative method. We found profound perivascular and interstitial edema in all three areas as well as disruption of the astrocytic foot processes in pigs with ALF. Furthermore, neurons and axons were edematous and surrounded by vesicles. Severe damage to Purkinje neuron (necrosis) and damaged myelin were seen in the cerebellum and brain stem, respectively. Biopsies from sham operated animals were normal. Vasogenic brain edema plays an important role in the development of intracranial hypertension in ALF. Severe cellular injury may lead to irreversible brain damage, which may explain persisting neurological complications following liver transplantation in patients with ALF.

16 Intensiv gangtrening av barn med CP. En case serie. Jørgensen, A.H. Knutsen, S.F. Jørgensen, A.H., Knutsen R, Agnalt E., Hansen A. M., Knutsen, S. F. Rehabiliteringssenteret Nord-Norges Kurbad AS Formål Et økende antall studier tyder på at barn med cerebral parese kan forbedre og lære nye motoriske funksjoner gjennom intensiv motorisk trening med avlastet kroppsvekt. På bakgrunn av dette og erfaringer fra et pilotprosjekt gjennomført ved RNNK AS, var det ønskelig å gjøre en mer kontrollert studie med intensiv gangtrening av barn med CP. Metode Dette er en intervensjonsstudie på til sammen 12 barn (alder 4-12 år) med CP (GMFM 1-3). Deltakerne fikk intens lokomotorisk trening på tredemølle med kroppsavlastning i 2 timer per dag fordelt på 2 økter, i til sammen 12 uker, fordelt på uker i løpet av 20 uker. Inngående testing av ulike funksjoner ved start, etter endt trening og 6 måneder etter avsluttet trening. Resultat De tre barn som hittil har gjennomført hele studien, viser klar bedring i gangfunksjon med tanke på bruk av ganghjelpemidler, balanse, gangdistanse og ganghastighet. Kasus nr. 1 bedret sin gangfunksjon fra å benytte to 3-punkts stokker til selvstendig gangfunksjon med én 1-punkts stokk. Kasus nr. 2 viste en bedring i gangfunksjon (distanse og hastighet) på om lag 400 %. Kasus nr. 3 gikk fra gangfunksjon med NF-walker med tilsyn til gangfunksjon med rullator med tilsyn. Konklusjon Preliminære data fra intensiv avlastet gangtrening hos 3 barn med CP, viser lovende effekt på gangfunksjonen. En bedring i gangfunksjon og bruk av ganghjelpemidler, vil potensielt ha stor effekt på livskvaliteten til det enkelte barn. Endelig resultat av studien vil rapporteres når alle 12 barn er ferdig trent.

17 Aqueous tissue volume as assessed by computed tomography correlates with extravascular lung water Suborov, E. Kuzkov V.V., Kirov M.Y., Waerhaug K., Mortensen R., Kuklin V.N., Nordhus K., Bjertnaes L.J. Anesthesiology Dept. Medical Faculty, University of Tromsø, Tromsø, Norway Aims We compared extravascular lung water (EVLW), as determined by transpulmonary single thermodilution (EVLW STD ), thermal-dye dilution (EVLW TDD ), and postmortem gravimetry (EVLW G ), with lung aeration assessed by spiral lung computed tomography (CT), before and after oleic acid (OA) induced acute lung injury (ALI) in sheep. Eleven yearling sheep were enrolled in a prospective study. Seven animals were infused oleic acid (OA group) intravenously over 30 min (0.08 ml/kg) and four served as a control (control group). All sheep underwent CT before and after 2 hrs experiment. EVLW STD and EVLW TDD were determined by PiCCOplus and COLD-Z021, respectively (Pulsion Medical Systems, Germany). An approximated volume (tissue volume index TVI) of aqueous density lung tissues was calculated by means of Pulmo CT program (Siemens, Germany). p < 0.05 was regarded statistically significant. EVLW STD and EVLW DTD showed close correlations with reference EVLW G (r = 0.85, and r = 0.89, p<0.001, respectively). After OA, these variables increased by 67 % and 127 %, respectively (p < 0.05) while remaining stable in the control group. Tissue volume index showed a close agreement with reference EVLW G values(r = 0.88 ; p < 0.01; bias 4.0±3.0 ml/kg). s In acute lung injury pulmonary edema is associated with reduced well-aerated- and increased poorly- and non-aerated lung volumes. In this model of inhomogeneous ALI, the volume of tissue with aqueous radiographic density correlates closely with the extravascular lung water content.

18 Sheep model of postpneumonectomy VILI Suborov, E. Suborov, E., Kondratiev, T., Sobhkhez, M., Bjertnæs, L. Universitetet i Tromsø, IKM, anestesiforskning, Tromsø, Norge Aim Mechanical ventilation, important tool in patients with lung injury, per se can result in ventilator-induced lung injury (VILI). One of the possible mechanisms can be a nitric oxide synthesis (NOS). In our ovine model of VILI after removal of one lung, we tested the hypothesis that 7-nitroindazole (7-NI) an inhibitor of NOS could prevent the lung injury after pneumonectomy (PE). After PE, 19 sheep were randomized to a protectively ventilated sham group (Sh) (n=6), and two excessively ventilated groups, a control group (C) (n=7) and a 7-NI+VILI group (n=6) receiving 7-NI intravenously. Hemodynamnics were assessed by thermal-dye dilution. The measurements were performed before- and after lung root ligation, after PE, and at 8 hrs postoperatively. Lung tissue was colected for histological examination. In both the C and 7-NI+VILI groups, EVLW increased compared with the Sh group from 5 hrs after PE and throughout (p<0.05). In all groups hemodynamic was stable. Histological samples show mild inflammation in Sh and severe injury in C groups. In 7-NI+VILI group degree of inflammation was less than in C group. We conclude that 7-NI decrease the severity of lung edema after PE in ovine model of VILI.

19 A rapid method for the simultaneous detection of the m.8344a>g and m.8356t>c mutations using real-time PCR Strand, H. Strand H. 1, Ingebretsen O.C. 1,2 and Nilssen Ø. 3, 4 1 Department of Medical Biochemistry, 3 Department of Medical Genetics, University Hospital of North- Norway, 9038 Tromsø, Norway. 2 Department of Medical Biochemistry, Institute of Medical Biology, 4 Department of Medical Genetics, Institute of Clinical Medicine, University of Tromsø, 9037 Tromsø, Norway Aim The m.8344a>g and m.8356t>c mutations are main causes of the MERRF syndrome. Mutation testing based on clinical suspicion can often confirm the diagnosis without the need for muscle biopsy or other invasive examinations. Additional phenotypes associated with the m.8344a>g have been revealed, thus broadening the indications for mutation analysis. As the number of test inquiries increases, there is a growing need for rapid and robust methods for mutation analysis. Amplification primers and fluorescence labeled probes were designed for detection of the m.8344a>g and m.8356t>c mutations by melting curve analysis on the LightCycler realtime PCR instrument. Tree plasmid standards were generated containing the wild type and the two mutated sequences respectively. Simultaneous detection of both mutations in a single tube were achieved by a single set of primers and probes. Analyzing mixtures of wild type and mutated plasmid standards revealed a detection limit of 20 % heteroplasmy. The heteroplasmic detection limit of this method equals that of the more laborious conventional methods like sequencing and restriction fragment analysis by gel electrophoresis. The easy set-ut (25 min) and rapid analysis (35 min) of up to 30 samples simultaneously makes this method useful for both diagnostic and epidemiological purposes.

20 Adrenomedullin enhance proliferation and angiogenetic potential of late outgrowth endothelial progenitor cells. Hermansen, S.E. Hermansen SE., Institute of Clinical Medicine, UiT, Tromsø, Norway, Dept. of Cardiothoracic and Vascular Surgery, University Hospital of North Norway, Tromsø, Norway, Lund T.,Institute of Medical Biology, UiT, Tromsø, Norway, Ytrehus K., Institute of Medical Biology, UiT, Tromsø, Norway Myrmel T., Institute of Clinical Medicine, UiT, Tromsø, Norway, Dept. of Cardiothoracic and Vascular Surgery, University Hospital of North Norway, Tromsø, Norway Purpose Endothelial progenitor cells (EPCs) represent a potential treatment option in cardiovascular diseases through its ability to replenish damaged endothelium and enhance neovascularisation at sites of ischemia. The utility of therapeutic EPC transplantation is hampered by their low number in the circulation and inhibitory factors causing low levels of engraftment and reduced cell survival. The endogenous vasoactive peptide adrenomedullin (AM) has been found to promote angiogenesis in various experimental models. Therefore, we sought to investigate the effects of AM on EPCs in culture. To obtain EPCs, peripheral blood MNCs were cultured with endothelial growth media. Highly proliferative colonies with cobblestone morphology appeared within 3 weeks. Phenotypic characterisation was done by rt-pcr. Proliferation was assessed using a colorimetric MTS cell proliferation assay. A matrigel matrix was used to assess the angiogenetic potential of EPCs stimulated by either AM or VEGF (vascular endothelial growth factor). Cells expressed VEGFR-2, VE-cadherin, CD31, CD146, but not CD45. They also expressed the AM1 receptor (CLRL/RAMP2) mrna. AM (10-7 M) stimulated EPC proliferation compared to control (0.535 vs , p=0.006). VEGF (50 ng/ml) increased growth compared to both control and AM alone (0.636, p=0.037 and 0.003). Both AM and VEGF increased tubule formation on matrigel by respectively 48% (p=0.001) and 54% (p=0.016). The addition of both agents resulted in a more pronounced increase compared to control 105% (p=0.004). Late outgrowth EPCs express the adrenomedullin receptor (AM1) gene. In addition, AM stimulates proliferation and in vitro differentiation into tubular structures suggesting a proangiogenetic effect on EPCs.

21 Dobutamine and levosimendan are both energetically neutral in therapeutic doses in vivo. Sanden, E. Stig Műller MD, Ole-Jakob How PhD, Espen Sanden Med.Stud, Øyvind Jakobsen MD, Stig Eggen Hermansen MD, Thor Allan Stenberg Med.Stud, Truls Myrmel MD PhD. Department of Cardiothoracic and Vascular Surgery, University Hospital North Norway, Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway Aims We addressed the hypothesis that levosimendan has a more efficient energetic profile than an equipotent therapeutic dose of dobutamine. Postischaemically reduced left ventricular function (stunning) was created by repetitive left coronary occlusions in 16 pigs. This contractile dysfunction was reversed by infusion of either levosimendan (24 µg/kg loading, 0.04 µg/kg/min infusion) or an equipotent dose of dobutamine (1.25 µg/kg/min). Contractility and cardiac output were normalized by both drug regimens. The energy cost of drug induced contractility enhancement was assessed by myocardial oxygen consumption related to the mechanical indexes tension-time index (TTI), pressure-volume area (PVA) and total mechanical energy (TME). Analysis of covariance did not reveal any increased oxygen cost of contractility for either drug in these doses. Dobutamine at supratherapeutic levels (10 µg/kg/min) induced a 30% increase in heart rate, a doubling of the contractility indexes and a highly significant increase in oxygen consumption related to mechanical work compatible with the established oxygen waste of inotropy (p<0.001 for all mechanical indexes). Therapeutic levels of neither levosimendan nor dobutamine demonstrate inotropic oxygen waste in this in vivo pig model. This is in line with their equal effect on survival in the acute heart failure studies.

22 Signifikante forskjeller i inflammasjon og komplement-faktorer mellom ulike filtre ved LDL-aferese. Lappegård, KT Hardersen, R 1,, Hovland, A 1, Sexton, J 2 og Lappegård, KT 1, Mollnes,TE 1, 1 Nordlandssykehuset Bodø, 2 Universitetet i Oslo, Norge. Formål Low density lipoprotein (LDL) aferese er en etablert behandling ved hyperkolesterolemi der LDL-kolesterolet ikke kan kontrolleres med diett og medikamentell behandling alene. Utover senkning av LDL kolesterol er det kjent at inflammasjonsmarkører og komplementfaktorer kan påvirkes av aferese, men få studier har sammenlignet ulike aferese-filtre systematisk med tanke på dette. Metode Tre pasienter med genetisk verifisert familiær hyperkolesterolemi og intoleranse for statiner gjennomgikk en cross-over studie i form av seks fortløpende behandlinger med tre ulike filtre: DL75 (fullblod-system), EC50W og LA15 (begge plasmaseperasjons-systemer). Blodprøver ble tatt fra AV-fistlene direkte før og etter aferese, og en rekke inflammatoriske markører ble målt. Resultat Alle filtrene gav et betydelig fall i LDL som forventet, uten signifikante forskjeller mellom filtrene. Det var betydelige ulikheter med hensyn til påvirkning av inflammatoriske markører mellom de ulike filtrene. Middelverdier og standardavvik for utvalgte markører er vist i tabellen under. EC50W DL75 LA15 Før Etter Før Etter Før Etter LDL-kolesterol 5.58± ± ± ± ± ±1.01 (mmol/l) Hs-CRP 1.29± ± ± ± ± ±0.25 (mg/l) C3 0.94± ±0.10* 0.95± ± ± ± 0.12 (g/l) IL-8 33±26 17±16 39±37 47±62. 45±45 55±73* (pg/ml) MCP-1 20±9 29±18 17±5 15±5 17±4 28±12 (pg/ml) IL-1b 6.7± ± ± ± ± ±1.3 (pg/ml) TNF-α 98±64 93±99 89±49 28±19. 97±55 29±15 (pg/ml) *p<0.05, p<0.001 Konklusjon Filtrene DL75, EC50W og LA15 senker alle LDL-kolesterolet signifikant. Inflammatoriske markører ble påvirket ulikt av de forskjellige filtrene, noe som kan tenkes å ha betydning for den aterosklerotiske prosessen hos disse pasientene.