Download MEDISIN- OG ODONTOLOGISTUDENTENES

MEDISIN- OG ODONTOLOGISTUDENTENES
FORSKNINGSKONFERANSE
21.-23. okt 2016, Bergen
2
Contents
Contents........................................................................................................ 3
Dear participant, .......................................................................................... 4
Committee .................................................................................................... 5
Program ......................................................................................................... 6
Information ................................................................................................... 8
Maps ............................................................................................................ 10
Academic content ..................................................................................... 12
Friday ....................................................................................................... 13
Saturday .................................................................................................. 14
Program for oral presentations .......................................................... 16
Abstracts in clinical medicine ............................................................. 17
Abstracts in basal research and genetics ......................................... 32
Abstracts in cancer research .............................................................. 47
Abstracts in epidemiology ................................................................... 55
Poster presentations ............................................................................ 62
Saksliste til generalforsamling ................................................................ 68
Participants ................................................................................................. 69
Sponsors 2016 .......................................................................................... 73
3
Dear participant,
Finally, the day has come, and we are proud and excited to welcome you to
Frampeik 2016 in Bergen!
As you may or may not have noticed, this year we have changed the sub-title of
Frampeik to include the beloved and devoted odontology students, as they have
been a substantial part of The Medical Student Research Program for years, and
we hope that research during the professional education will continue to inspire
interdisciplinary collaboration and friendships, and we hope that you as a
participant will make some new friends and contacts this weekend!
We are happy to announce that our program this year includes both local and
external speakers, and we´ll start Friday off with Gunnar Tjomlid, who has a
book release the week after Frampeik, but gives you the chance to buy his book
here today! We also have the leader of the hypochondriac clinic, Ingvard
Wilhelmsen, talking about being in control in your own life. Hopefully, the
program reflects on the topics of self-judgment and worst-case-thinking, and
how we should cope with this.
This Saturday we can tempt you with a special treat of West Side culinary
experience, as we have a Gala event at the sea-food restaurant Cornelius, a
mere boat ride away from bryggen. After a delicious three-course dinner, the
party continues in Kalfaret, a 3 minutes’ walk from Hotel Terminus.
We wish you all an enjoyable conference, we hope to see you seize the
opportunity to make this a learning experience for yourself and others,
discussing ideas, results and experience from your line of research. And good
luck to all the presenters!
Lastly, but not least: we really appreciate everyone who has contributed to this
conference, and a big thank you to our sponsors, this would not be
accomplished without your engagement in this project!
On behalf of the Committee,
Tony Elvegaard,
Chairman of the committee
4
Committee
Chairman
Tony Elvegaard
Academic program
Christiane H.
Gjerde
Economics
Lisa Willassen
Social program
Amalie Svanøe
Social program
Benedicte Sjo
Tislevoll
Sponsorship
Hanne Borge
Sponsorship
Vera Ericher
PR
Martha Rolland
Jacobsen
5
Program
Friday 21th of October 2016
Store Auditorium, 3.etg,
Haukeland universitetssykehus (HUS)
14:30-15:30 Registration
15:30:16:15 Welcome to Frampeik 2016
Opening speech by rector Dag Rune Olsen
Introduction by dean Nina Langeland
Presentation of LVS by Tiina Rekand
16:15-17:15: Key lecture by Gunnar Tjomlid
17:30-18:15: Key lecture by Ingvard Wilhelmsen
18:15-19:00: Information about the programme
Guided walk from HUS to Overlegen
19:00-01:00: Tapas dinner and socializing at Overlegen
Saturday 22nd of October 2016
Ground floor, small auditoriums,
Odontologen (OD)
10:00-12:00:
12:00-12:30:
12:30-13:30:
13:30-14:20:
14:30-16:00:
Parallel symposia 1 (with introductory lectures)
Poster session
Lunch
Lecture by Trond Nordseth
Parallel symposia 2
18:30:
19:00:
Bus from Grand Hotel Terminus to Bryggen
Boat ride to sea-food restaurant Cornelius
6
19.30:
23:30:
00:30-late
Gala dinner event
Entertainment by the Magician Snorre Sævraas
Boat ride back to Bryggen, bus to Terminus
Party at Nord-Norge huset (a 3 min walk)
Sunday 23rd of October 2016
Ground floor, small auditoriums,
Odontologen (OD)
11:00-13:00: Parallel symposia 3
13:00-14:00: General Assembly of Frampeik
Closing of Frampeik
14:00-14:30: Lunch
7
Information
Internet access
There is wireless internet in both Store Auditorium at Haukeland
Universitessykehus, and at doontologen. At Haukeland you should log
onto ”gjest ihelse” and get a username and password sent by SMS. At
odontologen, Eduroam is provided, so feel free to go wild.
Access to the conference building
The front door and all the rooms at Odontologen is closed outside of
working hours. All UiB students should have access to all buildings and
rooms. The main entrance will be manned before lectures start and at
break time. Should the door be closed, this would be a perfect time to
befriend a Bergenser, or call or text 41445857 to get someone to open
for you.
Organised transport
At Saturday, the transport from Terminus to Bryggen will be by bus, and
transport over the sea will be by boat. The same procedure on the way
back.
Food
We will provide some coffee and fruits and stuff at registration time
Friday, and an amazing tapas dinner in the evening. Saturday you will be
provided lunch, snacks, lots of coffee and dinner in the night time, and a
lunch on Sunday as well. Enjoy the hotel breakfast (or your regular
oatmeal/knekkebrød/leverpostei-kitchen-breakfast for those living here).
Anything else you might wish can be purchased at Rema 1000 at
Haukeland (indicated on the map), or in any other shop of your choosing.
Drink
Water is in the sink or machines, coffee and some mineral water will be
provided. There is a water machine in the main floor of odontologen, but
it tends to go on strike sometimes; in that case there are plenty more of
them in the floor above. Friday night, a small amount of alcoholic and
non-alcoholic beverages will be provided, should you wish anything else,
we will pass Rema 1000 on our way to Overlegen, so you can buy there.
8
Or bring from home. Saturday you will get three glasses of wine at the
restaurant. We´re allowed to bring our own drink at Nord Norge-huset.
On our way back from the restaurant, we´ll have a pit stop at the hotel
so you can collect anything you want to bring. Remember that polet
closes at 3pm Saturday, when we´re still at Odontologen, so either make
sure you can buy provisions on Friday, or bring from home.
Cornelius sjømatrestaurant
Extracted directly from their webpage;
”Just outside the City of Bergen, you will find one of the most exotic
attractions in the whole of Western Norway’s archipelago. Cornelius is one of
Norway’s best seafood restaurants. It is situated right by the sea on a small
island with spectacular views of the fjord, mountains, skerries and passing
boats and ships.”
Inspired by the weather of the day, Cornelius serves its famous
Meteorological Menu of exquisite seafood and trimmings, prepared using
innovative culinary techniques and with a genuine passion for seafood.
All those who´ve registered with special diets or allergies will be provided food
according to this. Please let us know asap if you forgot to register your allergy,
or developed one during the last few weeks.
Any questions?
Please contact us by message on Facebook, this is where we are most
active, or call or send a text to 41445857.
9
Maps
Busstopp for flybussen
Grand Hotel Terminus
Busstopp for buss 2/3/80 til Haukeland
Nord-Norgehuset selskapslokale (festlokale lørdag)
Rema 1000
Overlegen (festlokale fredag)
Odontologen (konferanse lørdag og søndag,
Busstopp: Statsarkivet)
Busstopp Haukeland universitetssykehus nord
10
11
Academic content
12
Friday
16:15-17:15: Gunnar Tjomlid
”La meg se litt nærmere på akkurat det...”
Gunnar Tjomlid has a half degree in most
subjects, and describes himself as a bit of a
nerd. He´s got a day-job as a web
developer in Thin AS, but as soon as he
quits work he becomes a blogger, a writer,
and a lecturer. Many of you might know
him as the writer of Placebodefekten, where
he explains why alternative medicine does not work, which is not the
easiest task, but he does it, and he does it well. He also runs the blog at
Saksynt, where he comments on every aspect of the society. His writing
is amazing, always critical, and (almost) always on the point.
Right now he´s actual with his new book Håndbok i krisemaksimering,
where he debates the fact that based on the headlines in the paper, the
world and humans has never been worse off, when actually it´s quite the
opposite. We are more healthy and safer than ever, but somehow we
always seem to think that the world is going to end tomorrow. With this
book, Tjomlid tries to provide us with a tool for critical thinking,
especially when it comes to the media. Hopefully he will tell us more
about this in the lecture!
17:30-18:50: Ingvard Wilhelmsen
We are proud to present our very own, and
greatly appreciated professor Wilhelmsen.
Wilhelmsen finished his medical studies in
1976, and has since taken specialities in
internal medicine, digestive disorders and
psychiatry. He now works in the field of
hypochondria, and runs the only clinic of
hypochondria in the Norway. Due to his competence in several fields of
medicine, he is especially interested in connecting the body to the spirit.
13
He compared hypochondria to having a loaded gun pointing towards you
at all times, and suggests that it can and should be treated.
Wilhelmsen has published several books during his career, where his
latest one published in 2011 with the title “Det er ikke mer synd på deg
enn andre” got excellent reviews.
If you´de like to learn more about Wilhelmsen,, we recommend to watch
his interview with Torp at nrk.no.
Saturday
13:30-14:20 Trond Nordseth
Trond Nordseth is currently working as an
associate professor and consultant at the
department of circulation and medical
imaging at NTNU.
He has studied heart rhythms in people
who are about to die of cardiac arrest,
and that's got a little chance to come back
to life because health professionals have
started resuscitation with
cardiopulmonary resuscitation. When the
defibrillator is connected to the patient's
chest, it will monitor the different heart signals and stores them. Such
data has Nordseth researched.
Trond Nordseth defended his PhD at NTNU in 2014, with the title:
Clinical state transitions during the Provision of advanced life support
(ALS) Patients in cardiac arrest.
He also went forskerlinjen during his medical studies at NTNU, which is
of course one of the reasons why we like him so much.
14
Introductory lectures
The remaining topics will be presented Saturday.
Daniela Costea; Cancer research
Daniela Costea has a degree in odontology, and
is positioned as professor at the pathology
department at Haukeland. Her research group
are studying the interactions between epithelial
cells and the surrounding tissue, and between
epithelium/connective tissue cells and
microbiota in normal conditions and during
cancer development. Daniela is an expert in
establishing friendships and collaborative
agreements with other universities, both I
Norway and abroad. She is a motivating and
enthusiastic researcher, lecturer and supervisor, and is loved by all her
students.
Cecilie Gjerde; basal research and
genetics
Cecilie has a master in dentistry, has
specialised in oral surgery, and is currently
doing her PhD here at UiB. She is appreciated
and admired by all our students, and the role
model for what a researcher ought to be like.
She is a fabulous presenter, just so good that
she won forsknings grand prix last year. Her
project involves stem cells from the spinal cord of the patient being used
to regrow bone in the mandibula. So yeah, she basically grows bone,
which is pretty exciting.
15
Program for oral presentations
Saturday 10.00-12.00 – Parallel symposia 1
Clinical medicine
10.30 Giriteka
10.45 Bremnes
11.00 Amundsen
11.15 Willassen
11:30: Lund
Epidemiology
10.30 Madsen
10.45 Ellingsen
11:00 MClean
Cancer research
10.30 Skjefstad
10.45 Barua
11.00 Jacobsen
11.15 Grindstad
Basal research and genetics
10.30 Solvin
10.45 Willems
11.00 Schanche
11.15 Johansen
Saturday 14.30-16.00 – Parallel symposia 2
Clinical Medicine
Cancer research
14.30 Taraldsen
14.45 Staniszewski
15.00 Olsen
15.15 Sulen
14.30 Knutsen
14.45 Svanøe
15.00 Yi
14.30 Pannu
14.45 Tran
15.00 Warlo
14.30 Schanche
14.45 Myklebust
15.00 Radunovic
15.15 Aarebrot
Epidemiology
Basal research and genetics
Sunday 11.00-13.00 – Parallel symposia 3
Clinical medicine
Basal research and genetics
11.00 Koppen
11.15 Halvåg
11.30 Larsen
11.45 Stangeland
12.00 Runde
12.15 Leiten
11.00 Bakken
11.15 Hoel
11.30 Hjøllo
11.45 Kristiansen
12.00 Korkosh
12.15 Klæstad
16
Abstracts in clinical medicine
Giriteka, Lionel
UiB
[email protected]
Bremnes, Thomas
UiT
[email protected]
Amundsen, Vivian S.
UiO
[email protected]
Willassen, Lisa
UiB
[email protected]
Lund, Anders
UiB
[email protected]
Taraldsen, Maria Dalen
NTNU
[email protected]
Staniszewski, Kordian
UiB
[email protected]
Olsen, Eirik Birkelund
UiT
[email protected]
Sulen, Åsta
UiB
[email protected]
Koppen, Elias
NTNU
[email protected]
Halvåg, Ranghild
UiB
[email protected]
Larsen, Christopher Storm
UiO
[email protected]
Stangeland, Marcus
UiB
[email protected]
Runde, Henrik Alexander
NTNU
[email protected]
Leiten, Elise Orvedal
UiB
[email protected]
17
Multimodal Neuroimaging: A study of brain activity in patients with IBS
Lionel Giriteka
Objective: We want to see if we can replicate previous findings of altered brain
structure in IBS using soup as a trigger for discomfort. Primarily we will
research on PI-IBS patients. Experience show that patients get symptoms with
this soup, and this will make a more realistic approach then triggering pain
using, for instance, a balloon.
It is interesting to see whether we can observe differences between HC and
IBS patients during resting state. Using DTI we can look upon the connectivity
between different brain structures.
Pre stimulus: 3DT1 SPGR
DTI (6 b=0, 30 b=1000)
Post stimulus: 3DT1 SPGR
Stimulus:
RS-fMRI (240 volumes, TR=2 s)
RS-fMRI (240 volumes, TR=2 s)
500 ml Toro meat soup per os
(outside magnet)
Repositioning in scanner:
3T GE Signa Excite HD
fMRI_111005_suppe_kk
Materials and methods:
We will start with fMRI uptakes
of 10 HCs before we start with
the IBS patients. Our exact
protocol for the fMRI uptakes is:
1. Localizer - ca 30 sec
2. 3D T1-w anatomy – ca 8 min
3. Resting state 240 volumes (TR=2
sec) - 8 min 10 sec
4. DTI – ca 9 min
5. Soup, 500 ml, outside of scanner ca 4 min
6. Localizer - ca 30 sec
7. 3D T1-w anatomy – ca 8 min
8. Resting state 240 volumes (TR=2
sec) - 8 min 10 sec
Figure'1.'Multimodal'MR'imaging'protocol'pre'–stimulus'and'post7stimulus.'Blue'='DTI'overlay'on'3D'anatomy,'Red'='
fMRI'overlay'on'3D'anatomy.
Future: A larger study is in the making. A bigger team consisting of both
reginal, national and international collaborators is ready. The goal is to take
scientific understanding from several domains into account and integrates
them through a multidisciplinary and multivariate approach (including MRI),
providing a more comprehensive and broader understanding of IBS and its
pathophysiological mechanisms.
!
Brain-Gut-Microbiota Interaction in Irritable Bowel Syndrome: A Multidimensional
Approach
Project manager: Trygve Hausken
National collaborators: Lovisenberg Diakonale Sykehus Jørgen Valeur
Regional collaborators: Arvid Lundervold, Jan G. !Hatlebakk, Odd Helge Gilja, Gülen
Arslan Lied, Magdy El Salhy, Astri J. Lundervold, Synne Ystad, Harald Wiker, Dag Arne
Hoff, Tarek Mazzawi, Eivind Valestrand, Kiniena F Tekie, Lionel Giriteka.
18
PCI - a Theoretically Based Index of Consciousness
Assessing Human Consciousness with TMS-EEG
Thomas René Bremnes, UiT, Professor Johan Frederik Storm, M.D.-Ph.D., UiO, Pål
Gunnar Larsson, M.D.-Ph.D., OUS, Professor II Rune Otto Hennig, M.D., UNN, UiT
Research group: Brain Signalling – Institute of Basic Medical Sciences, Faculty of
Medicine, UiO
One clinical challenge in the care of patients with disorders of consciousness
(DOC) is the lack of methods for assessing the level of consciousness in an
objective way. Nowadays, the clinical evaluation is based on the patients ability
to somehow demonstrate her own subjective experience, but this can be
misleading since experience shows that unresponsiveness not always equal
unconsciousness. Recently, a theory-driven index of the level of consciousness
called the perturbational complexity index (PCI) has been developed. It has
shown good power for classifying the level of consciousness of test subjects in
the lab. Our aim is to further develop this objective measure of consciousness
independent of sensory processing and behavior using electroencephalography
(EEG). EEG is recorded while perturbing the cortex with transcranial magnetic
stimulation (TMS) during different conscious states (awake, sleep, anesthesia
and brain injured patients). From a data-driven algorithm, the PCI is calculated
by compressing the TMS-EEG data of the electrocortical responses to find the
complexity (value between 0 – 1) of the cortical pattern. The results so far
show that conscious subjects (awake) have high PCI values (~ 0,4 – 0,6), while
unconscious subjects (sleep and anesthesia) have low PCI values (~ 0,1 – 0,3).
PCI is in the future expected to be used in the clinical assessment of brain
injured, unresponsive patients to determine the level of consciousness.
19
Skin microvascular assessemnts of periheral oxygen delivery in severe
heart faiure
a
Vivian Shubira Amundsena,b, Lars Gullestadb,d and Knut Kverneboa,b,c
Circulation laboratory, Department of Cardio-thoracic Surgery, Oslo University Hospital, Ullevaal,
Norway
b
Medical Faculty, University of Oslo, Norway
c Department of Cardiothoracic Surgery, Oslo University Hospital, Ullevål, Oslo, Norway
d Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
Introduction: All cells are dependent on delivery of nutrients and oxygen from
the microcirculation, and circulatory failure can be defined as insufficient
capacity for peripheral oxygen delivery. Chronic sever heart failure leads to
systemic circulatory failure. Our group has developed a concept: an oxygen
delivery index (ODIN) where a microscope and a spectroscope are used for
3
microvascular assessments in a tissue volume of 0.1mm . From the files
information of capillary density, blood flow velocities and microvascular oxygen
saturation are extracted.
Aim: In this study we will examine skin nutritive microcirculation of patients
with severe heart failure who are candidates for heart transplant (HTx), as
compared with healthy controls. Follow up examinations will be performed
post HTx.
Methods: Study 1) 24 patients with terminal heart failure above 18 years are
examined with skin computer assisted video microscope (CAVM) and diffuse
reflectance spectroscopy (DRS), before and following HTx or established
treatment with “Left ventricle assist device” (LVAD) treatment. Subjects are
their own controls. 10 healthy sex and age-adjusted controls are also
examined.
Results: Regional ethics committee approval is obtained, and data collection
start in September 2016.
Implications: Published and ongoing studies of ODIN findings in acute heart
failure treated with extra corporeal membrane oxygenations (ECMO) have
shown that the ODIN concept is a sensitive and reliable measure of circulatory
failure.
The present study will clarify the sensitivity for skin application of the ODIN
concept for assessing systemic circulatory failure caused by heart failure.
If this study confirms the sensitivity and reproducibility of the concept, we
have added a diagnostic tool that can be used for assessing of effect of
treatment of drug and operative therapy for chronic heart failure.
20
Temporomandibular disorders assessed with provoked and experienced
pain measurements: a case-control study
§
§
Willassen L,* Kvinnsland S,* Helgeland E,* Staniszewski K,* Johansson A, * Berge T, *
§
Rosén A, *
§
Department of Oral and Maxillofacial Surgery , Haukeland University Hospital, Bergen;
Department of Clinical Dentistry, University of Bergen*.
Aims of Investigation: Temporomandibular disorders (TMD) involves moderate
to severe pain in the masticatory muscles as well as an impaired mandibular
function. A healthy control group was recruited for comparison with a TMD
patient group that was evaluated in a TMD/TMJD project. The aim of the
study was to investigate if the TMD patients differed from the controls in
terms of pain detection threshold. The hypothesis was that TMD patients have
a lower pain detection threshold than healthy subjects.
Methods: The present study was a part of a multidisciplinary project on
TMD/TMJD initiated by the Norwegian Ministry of Health. Sixty healthy
controls were recruited, without TMD symptoms or other musculoskeletal
symptoms in the head and neck area, matched to the cohort of patients with
TMD. The mean age of the control group was forty-six years and it consisted
of fifty women and ten men. The TMD group with sixty patients had a mean
age of forty-five years and consisted of fifty-one women and nine men. All
subjects underwent a clinical examination which included muscle palpation
(pain intensity), PainMatcher and pressure algometry (in a sub group of twelve
matched pairs) in order to obtain an objective measurement of the pain
threshold. Furthermore, the controls answered a questionnaire that was a
shortened version of the same questionnaire answered by the TMD patients.
General Pain Intensity (NRS-scale) and Roland Morrison Scale (disability scale)
were some of the assessment methods included in the questionnaire used to
measure the subjects experienced pain.
Preliminary results: Preliminary results indicate that the TMD patients have
higher disability because of pain and had lower pain thresholds than the
controls, with significant differences between the two groups with regards to
Roland Morrison Scale (p<0.0001), General Pain Intensity (p <0.0001), pressure
algometry (p<0.05-p<0.0001) and the muscle palpation (p<0.0001). The
PainMatcher did not indicate a significant difference between the two groups.
Conclusions:The primary results indicate that the TMD patients have higher
disability because of pain and experience more intense general pain andintense
pain in muscle palpation while pain magnitude matching and pain thresholds
(PainMatcher) did not differed compared to healthy controls. The hypothesis
that TMD patients have lower pain detection threshold was in part fulfilled.
21
Antibodies to signaling molecules and receptors relate to apoptosis and
inflammation in heart failure
1
1,2
1,3
Anders Lund, Medical Student* , Lasse M. Giil, MD , Einar Kristoffersen, MD, PhD ,
4
5,6
Christian Vedeler, MD, PhD , Ralf Dechend, MD, PhD , Gabriela Riemekasten, MD,
7
8
1
PhD Harald Heidecke, MScPharm, PhD , Jan Erik Nordrehaug, MD, PhD
1
2
Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Internal
3
Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway; Department of Immunology and
4
Transfusion Medicine, Haukeland University Hospital, Bergen, Norway; Institute of Clinical Medicine,
5
6
University of Bergen, Bergen, Norway; HELIOS-Klinikum Berlin-Buch, Berlin, Germay; Experimental and
Clinical Research Center, Charité Medical Faculty and the Max-Delbruck Center for Molecular Medicine,
7
Berlin, Germany; Department of Rheumatology, University Hospital Schleswig-Holstein, Lübeck,
8
Germany; CellTrend GmbH, Luckenwalde, Berlin, Germany
Background. Antibodies to signaling molecules and receptors form networks of
correlated antibodies to multiple receptors, even in healthy individuals.
Physiological antibodies have been linked to inflammation and apoptosis, both
important pathophysiological processes in heart failure (HF). We investigated if
there is a link between antibodies to a broad range of signaling molecules and
receptors and biomarkers of inflammation and apoptosis.
Methods. Antibodies (ab) in pre-analytically randomized sera from patients
(n=202) with ischemic cardiomyopathy (ICM) (n = 166) and non-ICM (n = 36)
were measured with full-receptor sandwich enzyme-linked immunosorbent
assays. Non-parametric statistics were used for analysis of association,
reported as effect size (r) and corrected for multiple testing. Troponin-T (TNT)
elevation not due to ischemia was used as a marker for myocardial apoptosis. C
reactive protein (CRP), leukocyte count, kynurenine-tryptophan ratio, (KTR, a
marker of interferon-g activity), fibrinogen (coagulation and inflammation) and
neopterin (a marker of activated monocytes) were measured as immunemarkers.
Results. TNT correlated with Stabilin1-ab (r 0.29, p < 0.001). CRP correlated
with soluble endoglin-ab (sENG-ab, r 0.20, p = 0.01), fibrinogen with sENG-ab
(r 0.28, p < 0.001), neopterin with platelet-derived growth factor β-ab (r 0.27, p
< 0.001). There were both positive (dopamin D2s receptor, r 0.26, p < 0.001)
and negative (soluble pro-renin receptor, r -0.32, p < 0,001) correlations with
KTR.
Conclusion. Antibodies to vascular and immune-related receptors were
correlated with apoptosis and innate immune activation in patients with
predominantly ICM. These processes, linked to physiological antibodies, are
also important mediators of disease progression in HF. Both endoglin and the
pro-renin receptors are linked to myocardial fibrosis. Depending on which
effects these antibodies have on their receptor-antigens, they could provide
new links to key pathophysiological processes in HF.
*corresponding author
22
Coronary artery wall shear stress and the impact on coronary
atherosclerosis and response to aerobic exercise
Stud.med Maria Dalen Taraldsen, Faculty of Medicine, NTNU
Supervisor: Erik Madssen, MD, PhD, Department of Cardiology, St.Olavs Hospital
Assistant supervisor: Rune Wiseth, MD, PhD, Department of Circulation and Medical
Imaging, NTNU and Department of Cardiology, St.Olavs Hospital
Background: Coronary atherosclerosis is a leading cause of morbidity and
mortality. Treatment of coronary artery disease (CAD) includes either
percutaneous coronary intervention with stent implantation or coronary artery
bypass surgery, as well as drug therapy. Several studies have demonstrated
beneficial effects of physical exercise on the vasculature and heart function in
patients with CAD, but the mechanisms behind these positive effects are not
known in detail. Although the entire circulatory system is exposed to
cardiovascular risk factors that leads to inflammation, oxidative stress, and
endothelial dysfunction, it is recognized that changes in coronary flow and wall
shear stress (WSS) play an important role for the development of the focal
distribution of coronary plaques.
Aims: The primary aim of this study is to correlate WSS with the degree and
extent of coronary atherosclerosis measured with intravascular ultrasound
(IVUS) in patients with CAD. Our hypothesis is that WSS is an important factor
for the distribution and composition of coronary plaques. The secondary aim is
to correlate WSS and IVUS findings after patients have undergone an aerobic
exercise intervention. Our hypothesis is that coronary segments with the
lowest WSS at baseline have the biggest potential for beneficial changes after
exercise, compared with coronary segments with high WSS at baseline. This
study may increase our knowledge of the dynamics of plaque development in
coronary arteries.
Methods: This project is based on a single-center, open, parallel, randomized
controlled trial that was performed between 2011 and 2013. Thirty-six
patients with significant CAD on optimal medical treatment underwent 12
weeks of aerobic exercise after stent implantation. Coronary angiography and
grayscale and radiofrequency IVUS was performed at baseline and follow- up.
Calculation of WSS will be performed by computational fluid dynamics
modelling based on a 3D model of the index coronary vessel, before correlating
WSS to IVUS data.
23
Temporomandibular disorders with a psychosocial approach:
Preliminary data from a clinical case-control study
§
§
§
Staniszewski K,* Kvinnsland S,* Helgeland E,* Willassen L,* Berge T, * Johansson A, *
¤
¤
¤
#
!&
§
Schjødt B, Bell RF, Paulsberg AG, Geitung JT, Aandal G, * Lygre H,* Rosén A, *
¤
Department of Oral and Maxillofacial Surgery, Centre for Pain Management and Palliative Care ,
Haukeland University Hospital, Bergen; *Department of Clinical Dentistry, University of Bergen*;
&
Department of Radiology, Haraldsplass Deaconess University Hospital , Bergen; Department of
#
!
Radiology, Akershus University Hospital and University of Oslo , Oslo, Norway; Department of
Clinical Science
Introduction: Temporomandibular disorders (TMD) may cause severe pain, jaw
dysfunction, social withdrawal, and a reduced quality of life. Psychosocial
factors as somatic awareness, psychosocial stress and catastrophizing,
additionally to pain amplification, has been associated with TMD.
Aims of study: To detect risk factors that can be associated with the onset and
maintenance of severe TMD. Specific aims were to investigate TMD patients
stress- and catastrophizing scores, social factors, and cortisol levels as well as
cortisol/cortisone ratio in saliva, with the purpose of examining HPA-axis
function.
Material and Methods: This is a study which is part of a multidisciplinary
investigation of TMD patients at Haukeland University Hospital. Our study
population consists of 60 TMD patients (51 women and 9 men), and 60 healthy
individuals gender- and age-matched in a control group. Fill-in questionnaires
included the Hospital Anxiety and Depression scale (HADS) schemes, two-item
version of the Coping Strategies Questionnaire schemes regarding
catastrophizing, and several other questionnaires regarding social, economic
and health related factors. Saliva-samples were taken by Salivette Cortisol
Code Blue (Sarstedt) for tandem mass spectrometry (LC-MSMS) analysis of
cortisol as a stress marker. A clinical examination of jaw function, muscle pain
and tenderness, and dental status was performed. Blood sampling and MR
imaging of the TMJ was taken.
Results: Preliminary results show that TMD patients compared to healthy
individuals have a significantly higher anxiety- and depression- scores (HADS)
(p<0.0001), and catastrophizing scores (p<0.0001). The frequency of selfconsidered poor economy as well as pain related sleeping disorders are also
remarkably higher in the TMD group.
Conclusion: Preliminary results indicate that patients with severe TMD can be
associated with significant higher levels of stress, including anxiety, depression
and catastrophizing. The TMD patients also seems to have a higher frequency
of pain related sleeping disorders, as well as an undesirable self-consideration
of their own social and economic status compared with healthy individuals.
24
From insulin injections to sulfonylurea tablets in a child with neonatal
diabetes
1
1,2
Authors: Åsta Nordsveen Sulen , Pål R. Njølstad
Supervisor: Pål R. Njølstad, Professor MD, PhD
1
Department of Clinical Science, University of Bergen, Bergen, Norway
2
Department of Paediatrics, Haukeland University Hospital, Bergen, Norway
Introduction: Children with diabetes are dependent on life-long insulin
injections to control their disease. About 1-3% of all diabetes cases are
monogenic, i.e. resulting from mutations in one single gene. Neonatal diabetes
mellitus is a monogenic form of diabetes that occurs in the first 6 months of
life. This form of diabetes can be treated with sulfonylurea (SU) instead of
insulin because SU works directly on the ATP-sensitive potassium (K-ATP)
channels where the mutated protein is found.
Aims: To perform a treatment trial switching from insulin to oral SU treatment
in a 6 year old girl with a mutation in the SUR1 subunit of the K-ATP channel.
Methods: Before the trial started we did an oral glucose tolerance test, a meal
challenge and an intravenous glucose tolerance test. For the treatment
protocol, we gradually lowered the insulin dose and raised the SU dose, and
after 10 days the girl was treated with SU alone. The patient was followed up
for one year with oral glucose tolerance tests and intravenous glucose
tolerance tests every third month to monitor changes in beta cell function.
Results: The patient was successfully converted from insulin injections to SU
tablets. During the trial, the HbA1c dropped from 6.4% to 5.3%. The beta cell
function increased every third month up to 9 months, and after 9 months it
was stabilized.
Conclusion: Genetic testing is advised on children that debut with diabetes
before 6 months of age. If their diabetes is caused by mutations in the K-ATP
channel, treatment can be successfully changed from insulin injections to
sulfonylurea tablets, with a concomitant increase in metabolic control and
quality of life. This study is a great example of personalized medicine, not
everyone with diabetes needs insulin injections to survive.
25
Troponin T course before and after coronary artery bypass grafting
1
2,3
2,4
2,4
2,5
2,3
E. Koppen , E. Madssen , R. Stenseth , G. Greiff , H. Pleym , R. Wiseth , A.
2,6
1,7
Wahba and V. Videm
Corresponding author e-mail: [email protected]
1
Department of Laboratory Medicine, Children’s and Women’s Health, NTNU,
2
Department of Circulation and Medical Imaging, NTNU,
3
Department of Cardiology, St. Olavs Hospital,
4
Department of Cardiothoracic Anaesthesia and Intensive Care, St. Olavs Hospital,
5
Clinic of Anaesthesia and Intensive Care, St. Olavs Hospital,
6
Clinic of Cardiothoracic Surgery, St. Olavs Hospital,
7
Department of Immunology and Transfusion Medicine, St. Olavs Hospital,
Introduction: Troponin T (cTnT) is a biomarker used to diagnose of myocardial
infarction. After open heart surgery, the values are difficult to interpret
because of tissue damage. We hypothesized that increased knowledge about
factors affecting postoperative concentrations will contribute to more accurate
diagnostics of myocardial infarction after open heart surgery. The aim of the
study was to investigate associations between perioperative cTnT
concentrations and important clinical and operative variables.
Methods: 645 patients who underwent isolated coronary artery bypass
grafting (CABG) between April 2008 and April 2010 were included in the
study. Perioperative variables were prospectively registered in a database. The
degree of diffuse coronary atherosclerosis and number of significant stenoses
were assessed by preoperative coronary angiography and scored as an
“atherosteno score”. Mixed model analysis was used to construct a statistical
model to explain the course of troponin T concentrations. The model was
adjusted for intra- and postoperative myocardial infarction.
Results: The cTnT course was associated with complex interactions between
C-reactive protein, “atherosteno score” and intraoperative transfusion of red
blood cells. Factors associated with increased cTnT concentrations after
surgery were longer times on cardiopulmonary bypass (p<0.01) and high
preoperative creatinine concentrations (p<0.001). A large body surface area
(p<0.001) and intraoperative treatment with inotropic drugs (p<0.05) were
variables associated with lower cTnT concentrations.
Conclusion: A possible interpretation of the results is that increased
inflammation (longer operation times with larger tissue damage) gives
increased release of cTnT, independent of myocardial infarction. It is known
that the elimination of cTnT depends on the kidney function. Intraoperative
transfusion of red blood cells may have a dilution effect and may also protect
against tissue damage. The tissue damage may be larger than the cTnT
concentration suggests in larger patients who have received an intraoperative
transfusion of red blood cells.
26
Exploring the feasibility and acceptability of introducing symphysiotomy
in emergency obstetric care in Ethiopia: A formative qualitative WHO
associated study.
Ragnhild Sørbøen Halvåg, Karen Marie Moland, Astrid Blystad, Torvid Kiserud, Mulu
Muleta.
Associated with the research group: Global Health Anthropology.
Background: Eight percent of all maternal deaths in Ethiopia is caused by
obstructed labor, which can also cause obstetric fistula that is associated with a
stillbirth rate of 92%. Obstructed labor is when the fetus cannot progress into
the birth canal because of disproportion between the fetal head and the size of
the pelvic ring. Cesarean section (CS) is the standard procedure for obstructed
labor. However, this procedure is not widely accessible in low-income settings,
where potential harms also are more likely to occur. Symphysiotomy may imply
an alternative to improve the outcome for mother and child in low-income
settings.
Objective: This formative study explores the feasibility and acceptability of
introducing symphysiotomy in order to evaluate whether a RCT (randomized
test control trial) can be initiated in Ethiopia.
Method: This is a formative qualitative study. Data collection took place from
February to May 2015 in Gondar University Hospital and in rural communities
in North Gondar zone. 50 in-depth-interviews were conducted from
informants with different backgrounds: health care providers in maternity
wards in the hospital, health care providers in rural communities and rural and
urban women who had given birth. Systematic text condensation was applied
in the analysis.
Results: Symphysiotomy appears to be an unknown practice in and around
Gondar University Hospital. No health worker has practical experience of the
procedure, while knowledge of the procedure varies significantly. When
describing knowledge and perceptions of symphysiotomy there is a
discrepancy trend between the informant groups in the study. Principally the
hospital health workers perceive CS as the golden standard in emergency
obstetric care, whereas symphysiotomy is described as an outdated and
complicated procedure. Amongst the rural health workers and mothers
symphysiotomy is considered easy, lifesaving and preferable to CS when
planning more children.
Conclusion: This formative study found that lack of knowledge and a general
skepticism towards symphysiotomy makes initiation of a RCT in Gondar
University Hospital little feasible.
27
Probiotic intervention in HIV decreases gut microbial genes related to
biosynthesis of lipopolysaccharide
3,8,11
, Birgitte Stiksrud , Kristian Holm , Piotr Nowak , Dag Kvale ,
4
4
7
6
Felix C Nwosu , Anders Thalme , Anders Sonnerborg , Stein-Erik Birkeland , Knut Rudi , Anne-Ma
1,2,5
2,3,5,8,9
1,5,8,10
Dyrhol-Riise , Johannes R Hov*
, Marius Trøseid*
Christopher Storm-Larsen
1, 2
3
4
1,2,5
6
Introduction: Microbial translocation and chronic inflammation may contribute to
non-AIDS morbidity in patients with HIV. Several strategies have been applied to
reduce microbial translocation, however none of them have been showed to be
successful. In a recent paper our group reported reduced levels of inflammatory
markers d-dimer and CRP after probiotic intervention in HIV-Infected individuals
on stable anti-retroviral treatment, but no change in levels of serum markers of
microbial translocation. In this study we aimed to expand the analyses of microbial
translocation by investigating gut microbial functions.
Methods: Data from the subgroup of patients with 16S rRNA based gut microbiota
profiles available were included (n=10 in the probiotics and n=12 in the combined
control/placebo group). The PiCRUST software was used to predict the functional
genetic composition of the microbiota and an in-house method to distinguish
between bacteria producing hexa- and penta-acylated LPS, which have different
pro-inflammatory potential.
Results: In patients receiving probiotics, there was a significant reduction in both
KEGG-categories related to LPS biosynthesis (-23%, P = 0,05 and –18%, P = 0,03).
The decrease correlated positively with s-LPS (r = 0.68, P = 0,03 and r = 0.73, P =
0,02) and sCD14 (r = 0.63, P = 0.05 and r = 0.65 and P = 0.04). The relative
abundance of gram-negative bacteria decreased from 0.39 to 0.19 (p = 0.05) and
bacteria producing penta-acylated LPS reduced from 0.38 to 0.18 (p = 0.05). No
significant change where seen in hexa-acylated bacteria. At baseline, increased
ratio of Hexa-/penta-acylated LPS was associated with increased levels of
Kyn/Trp-ratio and Neopterin.
Conclusions: Functional profiling of the metagenome showed a decrease in genes
related to LPS biosynthesis, which correlated with a reduction in circulating
markers. However, the reduction was primarily related to the non-inflammatory
penta-acylated LPS, suggesting that other mechanisms than LPS are responsible for
the inflammatory activity.
1 Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway;
2 Department of Infectious Diseases, Institute of Clinical Medicine,University of Oslo, Oslo, Norway;
3 Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital
4 Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden;
5 K.G. Jebsen Center for Inflammation Research, Institute of Clinical Medicine, University of Oslo
6 Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences;
7 TINE SA, TINE R&D, Oslo, Norway
8 Research Institute of Internal Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo
University Hospital
9 Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital
10 Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Oslo, Norway.
11 Institute of Clinical Medicine, University of Oslo, Oslo, Norway
28
Interobserver variation of the bolus-and-burst method for pancreatic
perfusion with dynamic contrast-enhanced ultrasound
1
1, 2
3
4
Marcus Stangeland , Trond Engjom , Martin Mezl , Radovan Jirik , Odd Helge Gilja
2, 1
1, 2
2
, Georg Dimcevski , Kim Nylund
1) Department of Clinical Medicine, University of Bergen, Norway
2) National Centre of Ultrasound in Gastroenterology, Department of Medicine, Haukeland
University Hospital, Bergen
3) Dept. of Biomedical Engineering, Brno Univ. of Technology, Brno, Czech Rep.
4) Institute of Scientific Instruments, AS CR, Brno, Czech Rep.
Introduction/background: Dynamic contrast-enhanced ultrasound (DCE-US)
can be used for calculating organ perfusion. By combining bolus injection with
burst replenishment the arterial input function can be estimated and thus the
actual mean transit time (MTT). Blood volume (BV) can be obtained by scaling
the data to a vessel in the imaging plane.
Objectives/aims: The study aim was to test interobserver agreement for
repeated recordings using the same ultrasound scanner and agreement
between results on two different scanner systems.
Methods: Ten patients under evaluation for exocrine pancreatic failure were
included. Each patient was scanned two times on a GE Logiq E9 scanner, by
two different observers, and once on a Philips IU22 scanner, after a bolus of
1.5 ml Sonovue. A 60 second recording of contrast enhancement was
performed before the burst and the scan continued for another 30 seconds for
reperfusion. Data-analysis was performed using MATLAB-based DCE-US
software (http://www.isibrno.cz/perfusion/). An artery in the same depth as
the region of interest (ROI) was used for scaling. The measurements were
compared using the intraclass correlation coefficient (ICC) and Bland Altman
plots.
Results: There was excellent interobserver agreement on the Logiq E9 for MTT
(ICC=0.83, confidence interval (CI) 0.46-0.96). Between the Logiq E9- and the
IU22 there was poor agreement for MTT (ICC=-0.084, CI -0.68-0.58). The
overall agreement for blood volume measurements was excellent (ICC=0.86, CI
0.50-0.98).
Conclusion: Interobserver agreement was excellent using the same scanner for
both parameters and between scanners for BV, but the comparison between
two scanners did not yield acceptable agreement for MTT. This was probably
due to incomplete bursting of bubbles in some of the recordings on the IU22.
29
Mortality, physical performance & quality of life of patients treated
within the standardized patient care Fast-track hip fractures – a
prospective cohort study
Runde, Henrik Alexander; Johnsen, Lars G.; Basso, Trude; Foss, Olav.
Introduction/background: Elderly patients with hip fractures are especially
vulnerable as a patient group. From the total 9-10.000 of Norwegians that
break their hip per year, one out of four will die within one year. Less than half
recover to the level of function they had before the fracture and therefore
many loose their ability to live an independent life. Hip fracture is one of the
most expensive diagnoses for the Norwegian health care and one hip fracture
alone costs half a million NOK only the first year. One of the main targets for
“Fast-track hip fractures” is to reduce the time before operation, which is
shown to have a connection with postoperative morbidity and mortality. The
introduction of “Fast-track hip fractures” at St. Olavs hospital in 2011 gave a
reduction in the length of a hospital stay from 11 to 8 days. A new Swedish
register study with data from 116.000 patients found that for each day shorter
hospital stay than the threshold value of 10 days, the risk of dying within 30
days increased by 16 %. To improve the outcome after a hip fracture it is
necessary to constantly evaluate and improve the process chain and further
produce new knowledge about factors that can affect patients’ morbidity after
the fracture.
Objectives/aims: The study will follow a group of 120 patients with hip
fractures treated at the Department of Orthopaedic Surgery, St. Olavs hospital
from admission to one year after the fracture. The purpose is to evaluate how
the effective Fast-track process affects mortality and further identify factors
that may be of importance for physical performance and independence in the
patient group.
Methods: The study is organized within the frame of two tasks. In the first task
we will evaluate the effect of the days of hospitalization on early mortality for
patients treated within the Fast-track patient care. In the second task we will
evaluate how change in the hip’s biomechanics affects physical performance
and independence after a hip fracture with Short Physical Performance Battery
scores and life quality with EuroQol EQ-5D-5L. We will do the latter by
studying X-rays of the hip and examining the gait pattern in a laboratory at a
one-year control.
30
Complications and discomfort of bronchoscopy; a systematic review.
1
1
1
Elise Orvedal Leiten , Einar Marius Hjellestad Martinsen , Per Sigvald Bakke , Tomas
1,2
2
Mikal Lind Eagan , and Rune Grønseth
1
Department of Clinical Science, University of Bergen, Norway
2
Department of Thoracic Medicine, Haukeland University Hospital, N-5021 Bergen,
Norway
Background: Bronchoscopy is a cornerstone of respiratory medicine. We
depend on diagnostic bronchoscopy in the diagnosis of several conditions of
the lung, and the procedure is considered as safe. However, no current
systematic review on the safety aspects of bronchoscopy exists.
Objective: To identify complications and discomfort, meaningful complication
rates, and predictors related to diagnostic bronchoscopy.
Method: We conducted a systematic literature search in PubMed on February
th
8 2016, using a search strategy including the PICO model, on complications
and discomfort related to bronchoscopy and related sampling techniques.
Results: The search yielded 1707 hits, of which 45 publications were eligible
for full review. Rates of mortality and severe complications were low. Other
complications, for instance hypoxaemia, bleeding, pneumothorax and fever,
were usually not related to patient characteristics or aspects of the procedure,
and complication rates showed considerate ranges. Measures of patient
discomfort differed considerably, and results were difficult to compare
between different study populations.
Conclusion: More research on safety aspects of bronchoscopy is needed to
conclude on complication rates and patient and procedure-related predictors
of complication and discomfort.
31
Abstracts in basal research and
genetics
Solvin, Åshild Øksnevad
NTNU
[email protected]
Willems, Aron
UiB
[email protected]
Schanche, Torstein
UiT
[email protected]
Johansen, Silje Susanne
Pettersen
UiT
[email protected]
Schanche, Torstein
UiT
[email protected]
Myklebust Ernø, Inger Thea
UiO
[email protected]
Radunovic, Matej
UiB
[email protected]
Krogh Aarebrot, Anders
UiB
[email protected]
Bakken, Rasmus
UiB
[email protected]
Hoel, Fredrik
UiB
[email protected]
Hjøllo, Torunn
UiB
[email protected]
Kristiansen, Elise
UiO
[email protected]
Korkosh, Mohammed Bayar
UiO
[email protected]
Klæstad, Elise
NTNU
[email protected]
32
Establishing a biobank for gene expression studies of psoriasis
1
1
1,2
1,2
Åshild Øksnevad Solvin , Ellen Heilmann Modalsli , Ingrid Snekvik , Maiken Elvestad
1
1
2,3
1
1,2
Gabrielsen , Oddgeir Lingaas Holmen , Marit Saunes , Kristian Hveem , Mari Løset
2
Department of Public Health and General Practice, DMF, NTNU; Department of Dermatology, St.
3
Olavs Hospital, Trondheim; Department of Cancer Research and Molecular Medicine, DMF, NTNU
Introduction: Psoriasis is a chronic inflammatory disease of the skin that results
from an interplay between multiple genetic and environmental factors. Several
genes have been identified to affect the disease, however, much of the genetic
contribution to psoriasis remains to be explained. Global gene expression
studies are proven as powerful strategies for identification of disease-related
genes and pathways, and studies of psoriatic skin have contributed to an
increased understanding of psoriasis pathology. However, the sample sizes are
often limited (<18 samples) and no large transcriptional studies have been
performed on Norwegian samples.
Objectives: Our overall goal is to carefully collect and store skin biopsies and
blood samples from 50 psoriatic cases and 50 non-psoriatic controls and
perform investigations on gene expression through RT-PCR and/or RNA
sequencing of 150 skin biopsies (50 cases, both affected and unaffected skin,
and 50 controls). Further, we will investigate protein levels and cellular
localization of the most central differentially expressed transcripts identified by
western blot and immunohistochemistry.
Materials and Methods: All participants will be asked to fill out a questionnaire
concerning their health status, and anthropometric traits will be recorded. We
will have skin biopsies taken from the psoriatic cases and from the nonpsoriatic controls for RNA- and protein studies. All biopsies will be snap frozen
in liquid nitrogen and stored in -80°C. The biopsies for immunohistochemistry
will be placed in a container with formalin and further prepared for analysis. A
blood sample will be taken from all participants, opening for additional analysis
in future studies.
Results/Conclusion: We have obtained preliminary RNA extraction data on
four skin biopsies that show high-quality RNA, and similar RNA extraction
procedures will be followed in the study. We have studied slide sections from
four participants, which show that the morphology of the skin is well
preserved, and this makes a good starting point for future
immunohistochemical analysis. We hope that our psoriasis biobank will give us
the opportunity to gain new insight in the genetic basis of psoriasis, which
further have the potential to identify new drug targets for treatment and
prevention.
33
SLC7A10 - A Novel Transcription Factor in the Understanding of
Obesity-Related Pathogenesis
1,2
,2,3
1,2,3
1,2
Willems A , Fernø J1 , Sagen JV , Mellgren G
2
Department of Clinical Science, University of Bergen; Hormone Laboratory, Haukeland
3
University Hospital, Bergen; and KG Jebsen Center for Diabetes Research, University of
Bergen
1
Background: Obesity (BMI > 30) is increasing worldwide. Although related
to a number of diseases, it remains unclear why the individual risk of
developing disease varies so greatly. Genetic variation is believed to be
important in understanding the relationship between obesity and obesityrelated diseases. Waist-to-hip ratio (WHR) has been used as an indicator of
health, and the risk of developing disease. This is also reflected by the
stronger correlation between visceral fat and development of obesityrelated diseases.
The candidate gene SLC7A10 has been selected from micro-array studies
of adipose tissue taken from patients who have undergone bariatric
surgery. SLC7A10 strongly correlates with WHR. The gene is also
correlated with metabolic parameters, such as triglyceride/HDL-serum
levels and parameters of mitochondrial function. It has been selected due
to high adipocyte-specific expression, and little known role in adipocyte
function.
Aims and Objectives: The aim for the project is to examine the effects of
SLC7A10 in adipocyte function (both in cultured murine adipocytes and in
primary adipocytes from humans). SLC7A10 will be silenced using siRNA,
and subsequent down-stream effects on genetic expression, differentiation
and adipocyte function will be measured. The ultimate goal is to uncover
and characterize SLC7A10s role in obesity and development of obesityrelated diseases.
Materials and Methods: Human preadipocytes isolated from liposuction
material, in addition to cultured murine adipocytes (3T3-L1), is the primary
material. This will be used as in vitro cell models for investigation of the
function of SLC7A10. siRNA/shRNA – small interfering – and small hairpin
RNA will be used to knock down the gene. qCR (quantative polymerase
chans reaction) will be used for validation of changes in genetic up- or
downregulation. Changes in global genetic expression will be measured
using micro array studies of silenced primary human adipocytes
34
Platelet function during hypothermia and rewarming in an intact pig
model
1
1
1
1
Torstein Schanche , Timofei Kondratiev , Magnus Torstensson , Hans Husum , Bjarne
2,3
1,4
Østerud , Torkjel Tveita
1.
Anesthesia and Critical Care Research Group, Department of Clinical Medicine, UiT, The Arctic
University of Norway, Tromsø, Norway
2.
Molecular Inflammation Research Group, Department of Medical Biology, UiT, The Arctic University of
Norway, Tromsø, Norway
3.
K. G. Jebsen TREC – Thrombosis Research and Expertise Center, Department of Clinical Medicine, UiT,
The Arctic University of Norway, Tromsø, Norway
4.
Division of Surgical Medicine and Intensive Care, University Hospital of North Norway, Tromsø,
Norway
Introduction: Due to functional alteration of blood platelets and
coagulation enzymes at low temperatures, excess bleeding is a wellrecognized complication in victims of accidental hypothermia. Thus,
bleeding in the hypothermic multi-trauma patient is a great clinical
challenge. The aim of this study was to investigate platelet function after
rewarming from hypothermia using an experimental intact porcine model.
Methods: The animals were randomized to cooling and rewarming (n=9), or
to serve as normothermic, time-matched controls (n=3). Animals in the
hypothermic group were immersion cooled in ice water to 25°C,
maintained at 25°C for one hour, and rewarmed to 38°C (normal Tp in pigs)
using warm (40°C) water. Platelet function was assessed indirectly at
different temperatures during cooling and rewarming using a whole blood
coagulometer (ReoRox®4, Medirox AB, Nyköping, Sweden), which
measures clotting time of blood without adding anticoagulant at 38°C.
Results: After rewarming from hypothermia, clotting time was significantly
shortened compared to pre-hypothermic control values. Also, platelet
count was significantly increased.
Conclusion: A reduction in clotting time after rewarming from hypothermia
was observed. This may indicate that rewarming from severe hypothermia
induces a hypercoagulable state, in which thrombus formation is more
likely to occur. The contribution of platelet activation to the observed
decrease in clotting time is a subject for future studies.
35
Mesenchymal stromal cells from human umbilical cords display poor
chondrogenic potential in scaffold-free three dimensional cultures
A. Islam, A.K. Hansen, C. Mennan and I. Martinez-Zubiaurre
Background: The question of whether or not stromal cells harvested from
foetal tissue is suitable for allogenic cell transplantation therapies or tissue
engineering.
Objective: In this study, we have investigated the chondrogenic potential of
mesenchymal stromal cells (MSCs) isolated from whole sections of human
umbilical cord or mixed cord (UCSCs-MC), and compared them with cells
isolated from synovial membrane (SMSCs), Hoffa’s fat pad (HFPSCs) and
cartilage. All MSCs were positive for surface markers including CD73, CD90,
CD105, CD44, CD146 and CD166, but negative for CD11b, CD19, CD34,
CD45 and HLA-DR in addition to CD106 and CD271.
Method: Chondrogenic potential of all cell sources was studied using 3D pellet
cultures incubated in the presence of different combinations of anabolic
substances such as dexamethasone, IGF-1, TGF-β1, TGF-β3, BMP-2 and BMP7.
Results: BMP-2 and dexamethasone in combination with TGF-β1 or TGF-β3
excelled at inducing chondrogenesis on SMSCs, HFPSCs and chondrocytes, as
measured by glycosaminoglycans and collagen type II staining of pellets,
quantitative glycosaminoglycan expression, quantitative PCR of cartilage
signature genes and electron microscopy. In contrast, none of the tested
growth factor combinations was sufficient to induce chondrogenesis on
UCSCs-MC. Moreover, incubation of UCSCs-MC spheroids in the presence of
cartilage pieces or synovial cells in co-cultures did not aid chondrogenic
induction.
Conclusion: We show that in comparison with MSCs harvested from adult joint
tissues, UCSCs-MC display poor chondrogenic abilities. This observation
should alert researchers at the time of considering UCSCs-MC as cartilage
forming cells in tissue engineering or repair strategies.
36
Colloid prime increases blood volume and improves organ blood flow in
extracorporeal rewarming from deep hypothermic circulatory arrest in
rats
1
1.
1
Torstein Schanche , Timofei Kondratiev , Torkjel Tveita
1,2
Anesthesia and Critical Care Research Group, Department of Clinical Medicine, UiT, The Arctic
University of Norway, Tromsø, Norway
2.
Division of Surgical Medicine and Intensive Care, University Hospital of North Norway, Tromsø,
Norway
Introduction: Severe accidental hypothermia (core temperature ≤ 28°C) is
frequently accompanied by cardiac instability. Although recommended
treatment include rewarming by extracorporeal circulation (ECC), scientific
data on how to manage hypothermic patients on ECC is limited.
Hypothermia, along with initiation of ECC introduces major changes to
fluid homeostasis and blood flow. No current guidelines exists concerning
choice of priming fluid for the extracorporeal circuit. This study aimed to
investigate effects of two different fluid protocols on fluid balance, regional
blood flow and hemodynamics during rewarming from severe hypothermia
with cardiac arrest.
Methods: A rat model of conduction cooling and extracorporeal rewarming
was used. All rats were cooled to hypothermic cardiac arrest, and
rewarmed by ECC. During cooling, rats were randomized to two groups: (1)
extracorporeal circuit was primed with saline, or (2) hydroxyethyl starch
(HES). Plasma volume (PV), organ blood flow (OBF), tissue water content
and blood gases was measured. Circulating blood volume (CBV) and tissue
oxygenation was calculated, whereas hemodynamics were continuously
recorded during experiments.
Results: During and after rewarming, pump flow rate, mean arterial
pressure, pulse pressure, PV and CBV was significantly higher in HES
treated compared to saline treated rats. After rewarming, the HES group
had significantly increased OBF to brain, cerebellum and both kidneys
compared to the saline group. Tissue water content in HES treated rats was
significantly lower in both kidneys, skeletal muscle and lung.
Conclusion: Compared to a crystalloid priming solution, the use of an isooncotic colloid prime significantly increases PV and CBV, as well as OBF to
vital organs during and after rewarming. Animals receiving HES also
demonstrated a more favorable fluid balance and improved hemodynamics
compared to saline priming
37
Transportation of cultured oral mucosal epithelial sheets for worldwide
treatment of limbal stem cell deficiency
1
1
1
Inger Thea Myklebust Ernø , Mohammed Bayar Korkosh , Ngoc Ky Cuong Khuu , Linda
1
2
1,3
1
Hildegard Bergersen , Zina Kristiansen , Tor Paaske Utheim and Amer Sehic
1
Department of Oral Biology, Faculty of Dentistry, University of Oslo, Norway
2
Homansbyen Dental Office, Oscars gate 20, 0353 Oslo, Norway
3
Department of Medical Biochemistry, Oslo University Hospital, Norway
The cornea is critical for normal vision by allowing light transmission to the
retina. The corneal epithelium is renewed by limbal epithelial cells (LEC),
which are located in the periphery of the cornea, the limbus. Damage or
disease involving LEC may lead to various clinical presentations of limbal
stem cell deficiency (LSCD). Both severe pain and blindness may result.
Transplantation of cultured oral mucosal epithelial cells (OMEC) represents
the first use of a cultured non-limbal autologous cell types to treat this
disease. Most of the patients suffering from this eye disease live in
developing countries such as India where about 1.5 million people are
affected. The necessary expertise however, is mainly found in the
industrialized countries, including Norway. Furthermore, the optimal
culture method and substrate for OMEC is not established. The importance
of establishing good culture methods and methods for transportation has
been highlighted following the recent European Medicine Agency`s (EMA)
recommendation of approving LEC therapy in Europe. This decision is a
major step for regenerative medicine in Europe and limbal regenerative
therapy in particular as it represents the first recommendation by EMA for
any stem cell therapy in Europe. The decision also reflects that corneal
regenerative medicine is in the forefront of regenerative medicine. Despite
numerous reports on the various aspects of storage of cultured OMEC,
there are hitherto no full reports on the feasibility of transportation of
cultured OMEC. Thus, this study aims to bridge the current gap of
knowledge between culture, storage, and transplantation of OMEC, by
investigating different culture additives and by simulating transportation of
cultured OMEC in sealed storage containers.
Research group
PhD Ngoc Ky Cuong Khuu, PhD Catherine Jackson, Professor, MD PhD
Tor Paaske Utheim, Professor, PhD Julie Daniels, DDS Zina Kristiansen,
Professor, PhD May Griffith, Professor, PhD Darlene A. Dartt, Professor,
PhD Majlinda Lako, Student Inger Thea Myklebust, Student Mohammed
Bayar Korkosh, Associate Professor, PhD Amer Sehic
38
Identifying genetic variation in two potential vaccine candidates against
Giardia Lamblia
Radunovic M, Saghaug C, Langeland N, Hanevik K
Klinisk institutt 2, University of Bergen
Background: Giardia lamblia is the most commonly identified intestinal
parasite in the world. It causes giardiasis, a disease characterized by nausea,
vomiting, watery diarrhea and epigastric pain. Commonly found in day-care
centers, the parasite is now more prevalent due to increased traveling to
endemic areas. There is no known human vaccine against this parasite to
date. Recently there have been studies showing that Giardia proteins
Alpha-1 Giardin and Cyst Wall Protein 2 can act as potentially protective
vaccine candidates in mice. However, these studies have not taken into
account the genomic variation of Giardia. There are eight (A-H) different
genotypes, or assemblages, of Giardia and several assemblages are further
divided into subgroups. Assemblages A and B are known to infect humans.
Genomic differences between assemblages are well known and locating
potential antigens with conserved sequences across assemblages will help
to pinpoint good vaccine candidates.
Aim of the study: We wish to identify the genomic variation of two
antigenic proteins, Alpha-1 Giardin (α-1-g) and Cyst Wall Protein-2 (CWP2)
in Giardia isolates from infected humans.
Methods: We have gathered stool samples from Giardia-infected patients
in Norway. The samples have been processed with sucrose flotation in
order to isolate Giardia cysts. Cyst isolates were then typed in to
assemblage A or B. By using PCR, and custom made primers for α-1g and
CWP2 sequences, we will amplify these genes and sequence them. A
sequence alignment software (Geneious) will then be used to align the
genes and locate single nucleotide polymorphisms (SNPs) between isolates
and also reference sequences. Investigation of these SNPs will be done and
divided into synonymous or non-synonymous SNPs. This will provide
insight into the degree of sequence and amino acid variability between
assemblages, and thereby the suitability of these proteins as antigens. We
have so far managed to successfully amplify and sequence α-1-g in 12 out
of 20 isolates.
Further sequencing is ongoing and we will present data from α-1g and
CWP2 at the conference.
39
Phospho-specific flow cytometry for analysis of TNF signaling
1
1,2
1
1
Anders Krogh Aarebrot , Silje Michelsen Solberg , Richard Davies , Marianne Eidsheim ,
1
3
3
1,4
1
Kjerstin Jakobsen , Lucius Bader , Sonia Gavasso , Yenan Bryceson , Tim D. Holmes , Lene
2,5
1,3
1
Frøyen Sandvik , Roland Jonsson , Silke Appel
1
Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen,
Norway
2
Department of Dermatology, Haukeland University Hospital, Bergen, Norway
3
Department of Rheumatology, Haukeland University Hospital, Bergen, Norway
4
Centre for Hematology and Regenerative Medicine, Department of Medicine, Karolinska
Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
5
Department of Clinical Medicine, University of Bergen, Norway
Background: Flow cytometry is a laser-based technology used to analyze
characteristics of cells and particles on a single cell basis. It is a widely used
method for analyzing the expression of cell surface proteins, by measuring
fluorescence intensity produced by fluorescent-labeled antibodies. By staining
the phosphorylated state of intracellular proteins, we can use the fluorescence
intensity to measure their activation. Thus, flow cytometry can be used to
measure the activation of intracellular signaling cascades.
Aims: Develop a robust assay for measuring phosphorylated proteins mediated
by tumor necrosis factor (TNF), in T-cells, B-cells, monocytes and NK-cells.
Methods: We isolated and cryopreserved peripheral blood mononuclear cells
(PBMCs) from 25 psoriasis patients and 19 healthy controls. The cells were
stimulated with TNF, fixed with 1,5% PFA and permeabilized with 100%
methanol. After permeabilization we added fluorochrome-coupled antibodies
specific for surface antigens (CD3, CD20 and CD56) and phosphorylated NF-kB
(pNF-kB), before analyzing the median fluorescence intensity (MFI) of pNF-kB
in the different cell populations using flow cytometry.
Results:TNF stimulation increased MFI of pNF-kB in T-cells, monocytes and NKcells. This reflects the increased level of phosphorylated NF-kB in cells
stimulated with TNF. Thus, phosphoflow can be used to measure relative activity
of NF-kB.
Conclusions: Phospho-specific flow cytometry can be used to robustly analyze
phosphorylation levels of NF-kB in PBMC.
40
Transcription profiling of a novel TB vaccine-induced responses in a
Phase I Clinical Trial in India
1
1
2
Rasmus Bakken , Dhanasekaran Sivakumaran , Christian Ritz , and Harleen MS
1,3
Grewal
1
Authors’ Affiliations: Department of Clinical Science, Faculty of Medicine and Dentistry,
2
University of Bergen, Norway. Department of Nutrition, Exercise and Sports, University of
3
Copenhagen, Denmark. Department of Microbiology, Haukeland university hospital,
University of Bergen, Norway.
Introduction/background Tuberculosis (TB) remains a leading cause of
morbidity and mortality globally, with an estimated incidence of 9.6 million
people and causing 1.5 million mortalities in 2014. No new effective
vaccine has been brought to marked since the introduction of the BacilleCalmette-Guérin (BCG) in 1921, and 2012 saw the first novel TB drug
approved in 40 years. With the rise of multi drug resistant (MDR) strains,
despite good BCG vaccination coverage, much effort is put into the
development of new vaccines and drugs, as well as improved diagnostic
and prognostic tools to improve the efficiency of TB detection and
treatment. The AERAS-402, a recombinant, replication-deficient Ad35,
which expressing the mycobacterial antigens Ag85A, Ag85B, and TB10.4, is
one such candidate TB vaccine. AERAS-402 underwent a phase I clinical
trial in Bangalore, India, in 2012.
Objectives/aims: Nested within a phase I clinical trial of evaluating the
safety of the AERAS-402 vaccine, the present study aimed to look at
transcriptional markers of vaccine immunogenicity, by comparing RNA
expression between vaccinated and placebo subjects to genes known to
play a role in anti-mycobacterial immunity.
Methods Peripheral blood mononuclear cells (PBMCs) were collected from
the twelve study participants (2:1 ratio active vaccine and placebo
injections) at study days 0, 7, 14, 28, 35, 42, 56, and 182. From these
samples RNA for dual colour Reverse Transcription Multiplex Ligation
Probe Amplification (dcRT-MLPA) was obtained. Gene by gene
comparisons of expression of these biomarkers between the intervention
groups and evaluation of potential biosignatures combining several markers
were undertaken using publically available packages in R statistics.
Results and Conclusion: The results will be presented for the first time during
the conference.
41
A study on mitochondrial dysfunction in cell models of
neurodegenerative disease
1
2
2,3
Fredrik Hoel , Jui-Chih Chan , Chin-San Liu , Karl J. Tronstad
1
1
Department of Biomedicine, University of Bergen, Norway
Vascular and Genomic Center, Changhua Christian Hospital, Changhua, Taiwan
3
Department of Neurology, Changhua Christian Hospital, Changhua, Taiwan
2
Background: The mitochondria are the site of oxidative phosphorylation
(OXPHOS), a process that is responsible for the bulk of the cellular ATP
production. Impaired mitochondrial function results in aberrant ROS
production, insufficient supply of ATP, cellular damage and cell death. Cell
models have indicated the central role of mitochondrial function in the
development of neurodegenerative diseases. Mitochondrial toxins have been
used to model pathological mechanisms of neurodegenerative diseases such as
Parkinson’s Disease (PD). Expression of mutated Ataxin-3 causes mitochondrial
dysfunction in SCA3, while an mtDNA mutation recapitulates the MELAS cell
pathology. There are limited options for interventions aimed at restoring
mitochondrial function, and novel therapeutic approaches are in high demand.
Far-infrared radiation (FIR) and peptide-mediated mitochondrial delivery (PMD)
are two novel approaches that have shown beneficial effects in cell studies.
Aims: This project aims to explore the mechanisms linking mitochondrial
defects to degenerative diseases. Furthermore, we will investigate the
potential of FIR and PMD in restoring mitochondrial dysfunction in cell models
of SCA3 and MELAS, and the associated effects on mitochondrial function.
Methods: Mechanisms of mitochondrial toxins were studied in SH-SY5Y
neuroblastoma cells. Potential rescuing effects of FIR and PMD on
mitochondrial function were investigated in cell models SCA3 and MELAS,
respectively.
Results: Mitochondrial dysfunction caused by electron transport chain
inhibitors caused changes in gene expression in SH-SY5Y cells compatible with
metabolic stress response. FIR protected cell viability via autophagy and
improved mitochondrial function in a SCA3 cell model. PMD had rescuing
effects on mitochondrial function and cell stress tolerance in MELAS cybrid
cells.
Conclusion: Mitochondrial toxins induce mechanisms of metabolic stress that
may present in neurodegenerative diseases such as PD. FIR and PMD was
found to improve aspects of mitochondrial function in cell models of
degenerative disorders. Further studies are required to evaluate the
therapeutic potential of these interventions.
42
Giardia lamblia variant-specific surface proteins, a longitudinal study of
Immunoglobulin A and G responses
Torunn Hjøllo, Eirik Bratland, Matej Radunovic, Nina Langeland and Kurt Hanevik
Department of Clinical Science, University of Bergen
Center for Tropical Infectious Diseases, Department of Medicine, Haukeland University
Hospital, Bergen, Norway
Introduction/Aims: Giardia lamblia is an intestinal parasite that causes
giardiasis, and the duration of the antibody responses after natural
infection is not well described. The aim of this study was to evaluate the
longitudinally Immunoglobulin A and G (IgA and IgG) responses towards
conserved Giardia specific surface proteins and the effect of the duration of
infection on the response.
Methods: We set up two enzyme linked immunosorbent assays (ELISAs)
measuring Giardia specific IgA and IgG based on two recombinant antigens
from G. lamblia, variant-specific surface proteins 3 and 5 (VSP3 and VSP5).
We included serum samples from travellers returning to Norway with
confirmed positive giardiasis by PCR of stool. Samples were collected in the
acute phase, and then at 6 weeks, 6 and 12 months after effective
treatment, and were compared to a group of Norwegians with a low risk of
ever having had giardiasis.
Results: Serum levels of VSP5 IgA and IgG and VSP3 IgG in exposed
individuals were significantly higher than the low risk group in the acute
giardiasis phase, 6 weeks and 6 months. The general trend is different for
IgG and IgA, with levels of IgG stably elevated at the acute phase and 6
weeks, decreased at 6 months and normalized at 12 months. IgA levels
declined rapidly after the acute phase. A short duration of infection (≤8
weeks) gives a significantly higher value for the VSP5 assay for IgA, but not
for the other assays.
Conclusion: IgG antibody levels against Giardia in serum can be detected
until about 6 months after infection, while IgA declines within 6 weeks but
is still detectable. A short duration gives higher values in one of the assays.
43
The oxidation resistance gene protects against apoptosis and tissue loss
after hypoxic ischemia in brain
Kristiansen ES, Yang M, Xiaolin L, Rolseth V, Wang W, Bjørge M, Eide L, Bjørås M
Introduction: Every second our cells are exposed to oxidative stress from
internal metabolic processes. The cells have several defense mechanisms to
prevent and repair damage caused by oxidative stress. Disturbances in these
processes make us vulnerable to many diseases, including cancer, diabetes and
major neurological diseases. The Oxidation Resistance gene 1 (Oxr1) encodes
for a mitochondrial protein protecting the mitochondrial DNA against oxidative
stress. The Oxr1 protein has several known isoforms, among them Oxr1A. This
isoform is only expressed in the brain. In this study we induce cerebral hypoxic
ischemia in mouse pubs to investigate the function of Oxr1A under these
circumstances. We aim to examine the role of Oxr1A for protection against
stroke-induced cell death, tissue loss and regeneration.
Methods: Generated black 6 Oxr1A knock outs and wild type mice are used.
We operated the pubs (P9) ligating their common left carotid artery before
placing them in a low oxygen chamber. This treatment induces a stroke in the
left hemisphere. After recovery, the mice were euthanized at different time
points (3 hours, 1 day, 7 days and 42 days). For immunohistochemistry, their
brains were fixated and embedded in paraffin before sectioning. To quantify
apoptotic cell death, we used a TUNEL kit and counterstained the nucleus with
DAPI. To study the differences between the groups, we measured the average
number of cell death in each area and performed a student T-test to test for
significance.
To study tissue loss after one day, sections were stained with
tetrazoliumchloride (TTC). We also looked at nevrogenesis and regeneration in
the brains. To do this we used markers for neuronal progenitors as well as
markers for mature neurons and astrocytes. We also measured tissue loss 42
days post injury, when the regeneration is complete.
Results: In three different brain regions, there was a significant increase of
apoptotic cell death in the Oxr1A knock-out mice (n=4) compared to the wild
type (n=6). Two of these areas are in the ischemia-susceptible hippocampus;
dentate gyrus and Ca3 (P=0,020 and P=0,012, respectively). The third area is in
the thalamus (P=0,002). TTC staining showed significantly increased tissue loss
1 day after ischemia. After 3 and 7 days we have more neuronal progenitors in
the knock-outs compared to the wild types. There is however no difference in
mature neurons or astrocytes in the genotypes. After 42 days, there is
increased tissue loss in the knock-out mice compared to the wild types.
Conclusion: Oxr1A protects the brain from tissue loss and apoptosis after
hypoxic-ischemia in P9 mice and also when the regeneration is completed.
Oxr1A also has a role in nevrogenesis after brain damage.
44
Optimizing The Storage of Stem cell for Treatment of Limbal stem cell
deficiency
Korkosh, Mohammed Bayar, UiO
Limbal stem cell deficiency (LSCD) is a disease that affects millions of
people all around the world. The disease manifest itself by damaging the
limbus, an area in the eye that renews the cells in the Cornea. Chemical
burns, infections, and autoimmune diseases can cause LSCD. LSCD might
affect both or one of the eyes, and cause blindness and great pain. The
treatment of LSCD has been known for a while now, and it is used in the
developed part of the world. With a biopsy from the mouth of the affected
patient, one can culture the stem cells in a lab and then transplant the stem
cells in the Limbus area in the eye. The treatment has a high success rate of
removing the pain and restoring the vision. The problem is that most
people with LSCD are in third world countries, where treatment is limited.
If we can optimize the storage time and standardize the cultivation of the
stem cells, one can open a new door where we can use the western labs to
culture the cells. So, by taking the biopsies from the affected patient and
flying them to labs that have the ability to culture the stem cells
beforehand, we can fly them back and then use it for treatment for LSCD.
By expanding the storage time without affecting the cells quality and
morphology, we can start treating the disease worldwide.
Research group: Amer Sehic (hovedveileder), Tor Paaske Utheim (medveileder),
Linda Bergersen (medveileder), Ngoc Ky Cuong Khuu, Inger Thea Myklebust
Ernø, Mohammed Bayar Korkosh
45
The interplay between DNA-repair and epigenetics
Elise Klæstad, Geir Slupphaug and Bodil Kavli.
Department of Cancer Research and Molecular Medicine, Norwegian University of
Science and Technology,
Abstract: Epigenetic regulations and DNA-repair are two fundamental
biological processes essential for normal human development and health.
Epigenetic modifications in DNA and DNA –binding histones control gene
expression, and thereby the organism’s phenotype, whilst DNA-repair
removes damaged DNA to prevent mutations and apoptosis. New research
indicates that there could be a link between the two processes.
Understanding how epigenetic modifications in DNA affect processing of
DNA-damage and vice versa could open up for new fields in medical
diagnostics and treatment. The aim of the project is to examine how the
epigenetic modification 5-meC in the presence of the aberrant base uracil
(U) in DNA affects DNA-repair. The task will be implemented by examining
synthetically prepared oligodeoxynucleotides containing 5-meC and uracil,
separate and together, in distinct locations relative to each other and in
specific sequences. DNA-metabolizing enzymes often recognize distinct
primary structures in the DNA. The same has been shown for enzymes
metabolizing DNA uracil and 5-meC. We hypothesize that each of these
factors could affect the enzymatic binding involved in induction and/or
processing of the other in a position dependent manner. The project is
early on in the process and has yet to generate enough results to draw any
conclusions. Any generated results will be presented at Frampeik 2016.
46
Abstracts in cancer research
Skjefstad, Kaja
UiT
[email protected]
Barua, Imon
UiO
[email protected]
Jacobsen, Martha
Rolland
UiB
[email protected]
Grindstad, Thea
UiT
[email protected]
Knutsen, Christina
NTNU
[email protected]
Svanøe, Amalie
Abrahamsen
UiB
[email protected]
Yi, Dag
UiB
[email protected]
47
Prognostic Relevance of Estrogen Receptor α, β and Aromatase
expression in Non-small cell lung cancer
1,*
1
1
Kaja Skjefstad , Thea Grindstad , Mehrdad Rakaee Khanehkenari , Elin
1,2
3,4
2,4
3,4
Richardsen , Tom Donnem , Thomas Kilvaer , Sigve Andersen , Roy M.
3,4
1,2
1,2
Bremnes , Lill-Tove Busund , Samer Al-Saad
1
Department of Medical Biology, UiT – The Arctic University of Norway,
Department of Clinical Pathology, University Hospital of North Norway,
3
Department of Clinical Medicine, UiT – The Arctic University of Norway,
4
Department of Oncology, University Hospital of North Norway,
2
Translational research group, UiT – The Arctic University of Tromsø
Introduction/background: Sex steroids and their receptors are important in the
fetal development of normal lung tissue. In addition emerging evidence reveals
their significance in lung cancer pathogenesis. This encourages the exploitation
of hormone receptors as treatment targets in lung cancer, as it has been
successfully used in breast cancer.
Objectives: This study investigates the prognostic impact of estrogen receptor
(ER) α and β and the aromatase (AR) enzyme in non-small cell lung cancer
(NSCLC) patients.
Methods: Tumor tissue from 335 NSCLC patients was collected and tissue
microarrays (TMAs) were constructed. Immunohistochemical analyses were
performed to evaluate the expression of ERα, ERβ and AR in the cytoplasme
and nuclei of cells in the tumor epithelial and stromal compartment. By use of
survival statistics we investigated the markers impact on disease-specific
survival (DSS).
Results: Nuclear ERβ expression in tumor epithelial cells in female patients (HR
3.03; 95% CI 1.39-6.61) and tumor cell AR expression in all patients (HR 1.55;
95% CI 1.08-2.23) were significant negative prognostic markers of diseasespecific survival in our cohort.
Conclusions: High ERβ expression correlates with worse outcome in female
patients. Further, patients with high AR expression had an unfavorable
prognostic outcome compared with patients expressing low AR levels. These
results emphasize the importance of sex steroids role in NSCLC, and, as antihormonal drugs are widely available, could lead to the development of novel
palliative or even adjuvant treatment strategies in this patient population.
48
Histone deacetylase inhibitors in combined-modality cancer treatment
– experimental studies of normal tissue effects
1,2
1
2
2
1,2
2
Barua IS , Kalanxhi E , Risberg K , Ree AH , Redalen KR
Institute of Clinical Medicine, Campus AHUS, University of Oslo
2
Department of Oncology, Akershus University Hospital
Background: In combined-modality cancer treatment, molecularly targeted
agents may be combined with radiotherapy to increase therapeutic efficacy.
One example is histone deacetylase (HDAC) inhibitors, and in our Pelvic
Radiation and Vorinostat (PRAVO) study we investigated the combination of
radiation with the HDAC inhibitor vorinostat ((suberoylanilide hydroxamic acid
(SAHA)) in gastrointestinal carcinoma. Although such a combination treatment
may result in improved therapeutic efficacy, it may also increase treatment
toxicity, such as diarrhea, and lead to undesired treatment interruptions or
dose limitations. HDAC inhibitors have been regarded as tumor specific,
however, their influence on relevant normal tissues remain poorly investigated.
Aim: To investigate potential treatment toxicity in experimental normal tissue
models treated with the HDAC inhibitor SAHA.
Methods: Two normal tissue models (rat IEC-6 intestinal epithelial cells and
human BJ fibroblasts) and two colorectal cancer cell lines (HCT116 and HT29)
were exposed to SAHA for 24 hours before mechanisms of cell death were
analyzed with flow cytometry, western blot analysis and immunofluorescent
imaging.
Results: By flow cytometry (annexin V and propidium iodide) and western blot
analysis we found that SAHA induced cell death in HCT116 and HT29 cells,
but not in the BJ fibroblasts, and that induction of apoptosis was a main
mechanism of cell death. Intriguingly, the intestinal epithelial IEC-6 cells
responded similarly as the cancer cells to SAHA. In addition to apoptosis we
also found that SAHA induced autophagy, both in the cancer cell lines and the
IEC-6 cells, as reflected by increased expression of autophagy proteins (LC3-II
and p62) on western blot and as visualized by immunofluorescent imaging of
SAHA-treated cells.
Conclusion: Treatment with the HDAC inhibitor SAHA resulted in cell death
through induction of apoptosis and autophagy in a patient-relevant
experimental normal tissue model. The results may contribute to explain
normal tissue adverse events, such as intestinal toxicity, in patients treated
with HDAC inhibitors as part of combined-modality cancer treatment.
49
Estrogen receptors α and β and aromatase as independent predictors for
prostate cancer outcome
Grindstad T 1, Skjefstad K 1, Andersen S 2,3, Ness N 1, Nordby Y 2, Al-Saad S
1,4, Fismen S 4, Donnem T 2,3, Khanehkenari MR 1, Busund LT 1,4, Bremnes RM
1,2, Richardsen E 1,4
1 Dept. of Medical Biology, UiT The Arctic University of Norway, Tromso, Norway.
2 Dept. of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway.
3 Dept. of Oncology, University Hospital of North Norway, Tromso, Norway.
4 Dept. of Clinical Pathology, University Hospital of North Norway, Tromso, Norway
Background
Androgens are considered important in normal prostate physiology and
prostate cancer (PCa) pathogenesis. However, androgen-targeted treatment
preventing PCa recurrence is still lacking. This indicates additional mediators
contributing to cancer development.
Aim
We sought to determine the prognostic significance of estrogen receptors, ERα
and -β, and the aromatase enzyme in PCa.
Methods
Tissue microarrays were created from 535 PCa patients treated with radical
prostatectomy. Expression of ERα, ERβ and aromatase were evaluated using
immunohistochemistry. Representative tumor epithelial (TE) and tumor stromal
(TS) areas were investigated separately. Survival analyses were used to
evaluate the markers correlation to PCa outcome.
Results
In univariate analyses, ERα in TS was associated with delayed time to clinical
failure (CF) (p=0.042) and PCa death (p = 0.019), while ERβ was associated with
reduced time to biochemical failure (BF) (p = 0.002). Aromatase in TS and TE
was associated with increased time to BF and CF respectively (p = 0.016, p =
0.046). Multivariate analyses supported these observations, indicating an
independent prognostic impact of all markers. When stratifying the analysis
according to different surgical centers the results were unchanged.
Conclusion
In conclusion, significant prognostic roles of ERα, ERβ and aromatase were
discovered in the in PCa specimens of our large multicenter cohort.
50
Targeting cancer metabolism to prevent metastasis
Knutsen, Christina, NTNU
Objective: The objective of this project is to explore the relationship between
metabolic characteristics and metastatic potential in breast cancer cell lines of
metastatic and non-metastatic origin. The project is aiming to clarify how
metabolism supports the metastatic process and to evaluate the potential for
preventing metastasis by inhibiting key metabolic pathways.
Background: Breast cancer accounts for approximately 3500 new cancer
diagnoses in Norway each year (Cancer in Norway ref). Although the prognosis
is favourable for many patient groups, there are still as many as 650 breast
cancer deaths in Norway each year. Despite a national screening programme
and significant improvements in surgical and pharmacological treatment of the
primary tumors, a lot of women experience recurrence of their disease and
eventually succumb to distant metastases. It has been suggested that the risk
of recurrence is higher in women with triple negative breast cancer (TNBC),
which accounts for approximately 15-20% of breast cancers, with a higher
incidence in patients younger than 40 years old (1). There is a high therapeutic
potential for breast cancer patients of several subtypes if we can identify
metabolic targets for novel cancer treatment.
Preliminary studies have shown that the isogenic cell lines 67NR and 4T1 has
different metabolic profiles, despite their nearly identical genetic background.
In conclusion, the current knowledge about the 4T1 model system for
metastatic cancer suggests that metastatic cells may be sensitive to drugs that
either inhibit anaplerosis or increase the intracellular oxidative stress. We will
therefore target these mechanisms using clinically relevant drugs; aiming to
confirm the hypothesis that cancer metastasis depends on extracellular
acidification, high citric acid cycle turnover, anaplerosis and/or protection
against oxidative stress.
Methods: Cancer cell cultures grown in the laboratory will be used to put up a
XTT Trans-Well Assay where different enzyme inhibitors will be added. To take
the complexity of tumor/host interaction into account, the efficacy of
metabolic inhibitors must be evaluated in vivo, as animal models will be set up
for spring 2018 (forskertermin 3).
In vitro studies:
96 well plate trans-well assay
Drugs: CB-839: Glutaminase Inhibitor (Phase I trials).
Dichloroacetate: Pyruvat dehydrogenase kinase inhibitor (Generic drug)
AZD-3965: Monocarboxylate transporter 1-inhibitor (AstraZeneca)
51
Animal model: 4T1-model system established at NTNU by Research Scientist
Tonje Steigedal (IKM). Exome sequencing performed by prof. Geir Bjørkøy
(CEMIR) to evaluate genetic heterogeneity.
HR-MAS-MRS performed on cell extracts will be used to measure metabolic
responses to treatment. We will aim to use both 1H and 13C MR-spectroscopy
to analyse polar cell extracts.
Biochemical assays will be used to measure levels of metabolic stress (ROS).
SeaHorse will be used to measure extracellular acidification.
Hypotheses:
In vitro studies:
”4T1 cancer cells are more sensitive than 67NR cells to drugs that contribute
to oxidative stress by blocking glutamine consumption”
Animal model studies:
”Metastatic spread of 4T1 tumors can be inhibited in vivo by drugs that alter
tumor microenvironment or reduce their redox tolerance”
Results and conclusions will be left blank as there are no data to demonstrate.
52
Age-related characteristics in breast cancer
1
1,2
1,2
1
Amalie A. Svanøe , Gøril Knutsvik , Ingunn Stefansson , Kristi Krüger , Monica
1
1
3
3
1,2
1, 2
Mannelqvist , Sura Aziz , Benedicte Davidsen , Turid Aas , Lars A. Akslen , Elisabeth Wik
¹Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, University of
Bergen, Bergen, Norway.
²Department of Pathology, Haukeland University Hospital, Bergen, Norway.
3
Department of Surgery, Haukeland University Hospital, Bergen, Norway
Background: Breast cancer is the most common cancer, and the second most
common cause of cancer related deaths among women in Norway. On average
5,7% of women diagnosed with breast cancer between 2009-2013 were 15-49
years old at the time of diagnosis, and these are referred to as “adolescent and
young adults” (AYAs). Previous studies have shown that this is a group
associated with particularly aggressive subtypes of breast cancer.
Materials and methods: Tumor tissue and patient data from journals were
collected from a population based breast cancer AYA group (n=378). A
previously described population based breast cancer series of patients aged 5069 years old (n=546), was analyzed for comparison (Knutsvik et al, PLoS One
2013). Data from the Cancer Registry and the Cause of Death Registry were
linked to the data and used for survival analyses. A dataset from The Cancer
Genome Atlas (TCGA, n=520), including gene expression and clinico-pathologic
data, was used for further analyses.
The AYA group associated with more aggressive tumor features, such as ER
negativity, high histologic grade, larger tumor size, lymph node metastases and
locally advanced disease (all p<0.0005). Patients in the AYA group experienced
shorter disease specific survival compared to older patients (p=0.001). TCGAdata showed a higher proportion of the basal-like subtype and BRCA1 germline
mutations in the AYA group (both p=0.002). Genes differentially expressed
between AYAs and patients ≥ 50 years identified one cluster within the AYA
cases, that associated with BRCA1 germline mutations (p=0.03) and ER/PR
negative tumors (p<0.0005). All basal-like cases were included in this subcluster.
Gene expression patterns reflecting ER loss, stem cell profiles and hereditary
breast cancer, were enriched in this cluster.
Conclusions: In this large, population based cohort, we confirm aggressive
tumors in AYA breast cancer. A subgroup of the AYA cases is characterized by
the basal-like phenotype and gene expression programs reflecting low ER, stem
cell features and hereditary breast cancer.
53
Monocyte derived dendritic cells stimulated with OK432, TLR 7/8
agonist and PGE2 show mature phenotype with chemotaxis towards
CCR7, secretion of IL-12p70 and strong T-cell stimulatory capacity.
Dag H. Yi, Silke Appel
Dendritic cells (DC) are powerful antigen presenting cells that can promote
both immunogenic and tolerogenic responses from the immune system(1). Ever
since the discovery of DC(2), immunotherapeutic uses of these cells against
cancer have been researched on(3-5). While DC based immunotherapy has
been proven successful in animal models(6-8), it has been disappointing in
clinical trials (9). The aim of this study is to find possible ways to improve upon
current protocols for DC generation from monocytes for immunotherapeutic
purposes.
OK432, manufactured under the name Picibanil, is a streptococcal preparation
against cancer that has been used for decades in Japan. It was discovered that
DC co-cultured with OK432 expressed a mature phenotype as well as an
inflammatory cytokine profile (10-13). The stimulation was shown to be in a
TLR-3 dependent manner (14). Thus our cocktail consists of OK-432, a TLR2
7/8 agonist to in theory further improve stimulation as well as PGE to improve
CCR7 expression. The cocktail matured DCs had their immunostimulatory and
chemotactic motility compared to the gold standard (15). DCs were generated
by culturing monocytes isolated by plastic adherence with IL-4 and GM-CSF
and subsequently stimulated with the two different cocktails. Flow cytometry
was used for phenotyping, autologous mixed lymphocyte reaction with
tuberculin as recall antigen was used to measure T-cell stimulatory capacity,
and chemotaxis was measured using semi permeable membrane chemotaxis
towards CLL19. A 25-plex Luminex assay was used to determine cytokine
secretion profile.
The results shows that the DCs stimulated by the experimental cocktail yielded
mature DCs with higher expression of CCR7, chemotactic motility as well as
increased secretion of IL-12p70. T-cell stimulatory capacity appeared to be
similar to the gold standard. Thus a cocktail consisting of OK432, TLR7/8
2
agonist and PGE appears to be a suitable alternative for maturing DC in
immunotherapy.
(Referances for abstract is in the digital version at frampeik.no)
54
Abstracts in epidemiology
Madsen, Anders
UiB
[email protected]
Ellingsen, Trygve Sølberg
UiT
[email protected]
Mclean, Emily
UiB
[email protected]
Pannu, Mehma
UiB
[email protected]
Tran, Long
NTNU
[email protected]
Warlo, Ellen Mathea Kirsch
UiO
[email protected]
55
Dissecting the hemagglutinin-specific antibody response after pandemic
2009 influenza vaccination
1
1
1
1,2
1
Anders Madsen* , Linda Azimi* , Sarah Tete , Rebecca Cox , Åsne Jul-Larsen
*Equal contributors
1
Influenza Centre, Department of Clinical Science, University of Bergen, Norway
2
Department of Research & Development, Haukeland University Hospital, Bergen, Norway
Background: Influenza is a contagious respiratory infection caused by the
influenza virus. It occurs as seasonal epidemics and occasional pandemics. A
pandemic arises when a novel virus causes worldwide diseases in mainly
immunologically naïve human population. Interestingly, pandemics are known
to have a higher mortality rate among people of younger age, in contrast to
seasonal epidemics.
Frequent mutations on the viral surface protein “hemagglutinin” (HA) is an
important factor for the virus ability to evade hos immunity and reappear
annually. In 2009, parallel to the ongoing “swine-flu”, 250 healthcare workers
at Haukeland University Hospital were recruited to a clinical trial as they were
vaccinated with the pandemic influenza vaccine.
Aim: To investigate how an individual’s previous encounter with different
influenza subtypes influences the humoral response after pandemic vaccination
in 2009.
Methods: Participants were retrospectively chosen, and grouped, based on
their year of birth (reflecting which influenza subtype they were first exposed
to during childhood). We investigated antibodies to the surface protein, HA,
and looked specifically at antibodies binding to the conserved parts of this
protein.
Serum samples were analyzed using hemagglutination inhibition (HI) assay,
microneutralization (MN) assay, and Enzyme-Linked Immunosorbent Assay
(ELISA).
These serological assays are designed to measure the quantity and quality of
influenza-specific antibodies.
Results: Antibody-levels increased significantly after vaccination.
Older subjects had a higher level of preexisting antibodies to conserved parts
of HA, whereas the younger subjects obtained a higher level of strain-specific
antibodies directed to the more variable regions of the HA. Younger subjects
also experienced an overall strong antibody-boost after vaccination.
Conclusion: Our data shows how previous exposure to different influenza
subtypes can affect the immune response to a novel influenza virus. We found
that the more antigenically experienced individuals, who had a broader
antibody repertoire towards novel viruses, obtained higher pre-vaccination
antibody-levels. This was most prominent towards the conserved parts of HA.
On the other hand, the least antigenically experienced individuals achieved the
highest antibody boost in response to vaccination.
56
The association between red cell distribution width and risk of venous
thromboembolism is not mediated by myocardial infarction, stroke or
cancer – a cause-specific analysis
1
1
1,2
Trygve S. Ellingsen , Jostein Lappegård , Tove Skjelbakken , Ellisiv B. Mathiesen
1,5
1,2
1,2
Njølstad , Sigrid K. Brækkan and John-Bjarne Hansen
1,3,4
, Inger
1
K. G. Jebsen – Thrombosis Research and Expertise Center (TREC), Department of Clinical
Medicine, UiT - The Arctic University of Norway, Tromsø, Norway
2
Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
3
Brain and Circulation Research Group, Department of Clinical Medicine, UiT - The Arctic
University of Norway, Tromsø, Norway
4
Department of Neurology and Neurophysiology, University Hospital of North Norway, Tromsø,
Norway.
5
Department of Community Medicine, UiT - The Arctic University of Norway, Tromsø, Norway
Correspondence to: Trygve S. Ellingsen, K.G. Jebsen Thrombosis Research and Expertise Center,
Hematological research group (HERG), Department of Clinical Medicine, University of Tromsø, N9037 Tromsø, Norway
e-mail: [email protected] telephone: +47 958 73 223
Background: Red cell distribution width (RDW) is a risk marker of venous
thromboembolism, myocardial infarction (MI), stroke and cancer. Due to the
established interrelations between these diseases, the apparent association
between RDW and VTE may be mediated by MI, stroke or cancer.
Aims: To investigate whether the effect of RDW on VTE was mediated by MI,
stroke or cancer.
Methods: RDW was measured in 24363 participants of the Tromsø Study in
1994-95. Incident VTE, MI, stroke and cancer were registered until December
31, 2010. Person-time was calculated from inclusion to the date of an incident
outcome, migration, death, or study end, whichever came first. Conventional
and cause-specific Cox-regression models were used to estimate hazard ratios
(HR) for VTE with 95% confidence intervals (CI).
Results: There were 502 first VTEs during a median of 16 years of follow-up. In
conventional Cox regression analysis, RDW in the highest quartile was
associated with a 71% higher risk (HR 1.71, 95% CI 1.09-2.67) and 27% higher
risk (HR 1.27, 95% CI 0.88-1.85) of VTE in men and women, respectively,
compared to subjects in the lowest quartiles. The risk of VTE by the highest
quartile of RDW was similar for men and women of postmenopausal age. In
cause-specific analysis, where each individual contributed with person-time
until the first occurring event only, the risk estimates were essentially similar to
those of the conventional Cox-regression analysis.
Conclusion: Our findings imply that the association between RDW and future
risk of VTE is not mediated by MI, stroke or cancer.
57
Working on the edge of the law: a qualitative study of ethical dilemmas faced
by abortion providers in Addis Ababa, Ethiopia.
Emily McLean, Ingrid Miljeteig, Astrid Blystad and Dawit Desalegn
Introduction and Objectives: In 2005 Ethiopia changed its abortion law in
order to curb the high maternal mortality. Abortion is now legal if the
pregnancy is a result of rape or incest, if the woman's health is in danger or the
foetus has an incurable and serious deformity, and if she suffers from physical
or mental deficiency including if she is under 18. A twist in the law is that the
word of the woman is sufficient to qualify for safe abortion services. The
objective of this study is to enhance the understanding of how abortion
providers in Ethiopia interpret the law, perceive their role as gatekeepers of the
law and experiences potential ethical dilemmas
Method: This is a qualitative study. Data collection took place from March to
May 2016 in Addis Ababa at different health clinics providing abortion
services. 24 in-depth interviews and 3 focus group discussions were conducted
with nurses, midwifes and physicians providing abortion services in
governmental and non-governmental clinics. Systematic text condensation has
been employed in the analysis.
Results: In the interaction with patients seeking abortions the health workers
describe conflicting concerns, a burdensome responsibility and ambiguity
concerning how to interpret the law. They describe efforts to balance their
religious faith and values against their professional obligations and concern for
woman´s health. This negotiation is particularly present in care for women who
fall outside the laws indicators. They usually have to handle these ethical
dilemmas and the decision-makings alone without guidance. Many face stigma
from fellow colleges not performing abortions and keep their job a secret from
family and friends.
Conclusion: The study reveals how health workers in Ethiopia experiencing a
moral workload by balancing on a difficult line trying to manoeuvring between
the abortion law, their personal values and their genuine concerns for woman´s
health.
58
Equality impact analysis of Post Malaria Chemoprevention delivery
mechanisms trial (PMC) in Malawian children under five
Mehmajeet Kaur Pannu, Bjarne Robberstad
1
Department of Global Public Health and Primary Care,
The Research Council of Norway, Global Health and Vaccination Research (GLOBVAC). Project id.:
234487. College of Medicine (CoM), University of Malawi, Private Bag 360, Blantyre, Malawi
Universitetet i Bergen, Bergen, Norge.
Severe anemia is a leading cause of hospital admissions in Africa contributing
substantially to pediatric mortality. Recent case control study in Malawian
children indicated that children aged <5y admitted with severe anemia are not
only at high risk of dying during the acute phase in-hospital (6%) but also for
several months after they leave hospital: 8% had died by 6 months’ discharge,
which is nine times higher than the mortality in community-based, age matched
children with mild anemia. Similar rates are seen in western Kenya and in
Uganda. (c.john et al, unpublished data). Hospitalized children with severe
anemia are particular at risk within the first 3 months post-discharge, likely due
to a combination of environmental, behavioral, nutritional and generic risk
factors.
PMC, or Post Malaria Chemoprevention is the administration of a full
treatment course (Dihydroartemisinin-Piperaquine) of long-acting antimalarials
at pre-defined time intervals (2, 6 & 10 weeks after discharge) irrespective of a
patient’s malaria status. The main objective is to determine the uptake,
effectiveness, cost-effectiveness, acceptability, feasibility and equity/equality
of two different mechanisms for delivering IPTpd: facility vs community-based
approaches and examining the added role of mobile phone text message
reminders.
This is an effort to incorporate equity into cost-effectiveness, and will be
valuable input to decision makers when considering new policies. We will use a
household asset index to differentiate the study population in quintiles, to
examine the differences in a thorough way to answer questions as Does
delivery mechanism affect compliance based on different socioeconomic
variables? Is a specific mechanism superior for a specific part of the population
depending on socioeconomic factors or positions?
Study ongoing, no results yet.
59
The effect of red blood cell transfusion on long-term mortality in adult
patients undergoing isolated coronary artery bypass grafting
1
1
2,3
2,4
2,5
2,3
1,6
Tran L. , Greiff G. , Pleym H. , Wahba A. , Stenseth R. , and Videm V.
Corresponding author e-mail: [email protected]
Department of Laboratory Medicine, Children’s and Women’s Health, NTNU, 7491 Trondheim.
2
Department of Circulation and Medical Imaging, NTNU, 7491 Trondheim.
3
Department of Cardiothoracic Anaesthesia and Intensive Care, St. Olavs Hospital, 7006 Trondheim.
4
Clinic of Anaesthesia and Intensive Care, St. Olavs Hospital, 7006 Trondheim.
5
Clinic of Cardiothoracic Surgery, St. Olavs Hospital, 7006 Trondheim.
6
Department of Immunology and Transfusion Medicine, St. Olavs Hospital, 7006 Trondheim.
Introduction & Aim: Studies have shown a correlation between transfusion of
as little as 1 unit of red blood cell (RBC) and long-term mortality in patients
undergoing CABG[1]. Because the patients receiving transfusion have more
preoperative risk factors, long-term effect of RBC transfusion itself is difficult
to evaluate. We hypothesized that the increased risk is due to pre- and
postoperative morbidity. Our aim was to investigate whether there was a
difference in long-term mortality in a group of patients with fewer confounders
for our primary outcome.
Methods: The study is a part of the Cardiac Surgery Outcome Study at St.
Olavs Hospital. Patient data are collected prospectively in a local database now
consisting of adults undergoing cardiac surgery from 2000 through 2014. We
included patients undergoing primary isolated CABG, excluding those with
preoperative anemia, large intra- or postoperative blood loss and 30-day
mortality. We compared mortality from 1 month postoperatively between
patients receiving transfusion of at least 1 unit of RBC and patients who did
not. We performed multivariate Cox regression analysis and sensitivity analysis
using propensity score matching between RBC transfused and non-transfused
patients.
Results: Of 3550 included patients, 731 (20.6%) received transfusion of at least
1 unit of RBC and 188 (25.7%) died between 1 month and 15 years
postoperatively. In an unadjusted Cox regression model, the hazard ratio (HR)
for long-term mortality was 2.01 (1.69-2.38, p < 0.01). When adjusting for preand intraoperative variables, the HR was 1.28 (1.03-1.59, p = 0.03). With
adjustment also for postoperative complications, RBC transfusion was no
longer significant (HR: 1.15, 0.92-1.43, p = 0.22). These results were supported
in the propensity score-matched patients.
Conclusions: Our study indicated that the association between RBC
transfusion and long-term mortality following CABG was due to confounding,
especially from postoperative complications. The study does not support a
restrictive transfusion policy as a method to reduce long-term mortality in this
patient group.
60
Reduced levels of ADAMTS13 are associated with high on-aspirin
residual platelet reactivity in patients with stable coronary artery
disease.
1
Warlo, E.M.K.
1,2,3
, Seljeflot, I.
1,2,3
, Arnesen, H.
1,2,3
, Pettersen, A-Å.
1,3,4
Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital, Ullevaal, Oslo, Norway
2
Faculty of Medicine, University of Oslo, Oslo, Norway
3
Center for Heart Failure Research, University of Oslo, Norway
4
Department of Medicine, Vestre Viken HF, Ringerike Hospital, Hønefoss, Norway
Introduction: The mechanisms behind residual platelet reactivity (RPR) despite
aspirin treatment are not established. It has been shown that coronary artery
disease (CAD) patients with high on-aspirin RPR have elevated levels of von
Willebrand factor (vWF). ADAMTS13 is a metalloprotease cleaving ultra large
vWF multimers into less active fragments.
Our aim was to investigate whether ADAMTS13 and vWF/ADAMTS13 ratio
were associated with high RPR, and further with clinical endpoints after 2
years.
Materials and methods: Stable aspirin-treated CAD patients (n=1000) from the
ASCET trial. RPR was assessed by PFA-100. ADAMTS13 antigen and activity
were analysed using chromogenic assays. Endpoints were a composite of acute
myocardial infarction, stroke and death.
Results: The number of patients with high RPR was 258 (25.8%). Their serum
thromboxane B2 (TxB2) levels were low, indicating inhibition of COX-1. They
had significantly lower levels of ADAMTS13 antigen compared to patients with
low RPR (517 vs 544ng/mL, p=0.001) and significantly lower ADAMTS13
activity (0.99 vs 1.04IU/mL, p=0.020). The differences were more pronounced
when relating RPR to ratios of vWF/ADAMTS13 antigen and
vWF/ADAMTS13 activity (p<0.001, both). We found an inverse correlation
between vWF and ADAMTS13 antigen (r=-0.14, p<0.001) and ADAMTS13
activity (r=-0.11, p<0.001). No correlations between TxB2 and ADAMTS13
antigen or activity, were observed, implying that ADAMTS13 is not involved in
TxB2 production. Patients who experienced endpoints (n=73) had higher vWF
level (113 vs 105%, p=0.032) and vWF/ADAMTS13 antigen ratio (0.23 vs 0.20,
p=0.012) compared to patients without. When dichotomizing
vWF/ADAMTS13 antigen at median level we observed that patients above
median had higher risk for suffering endpoints, with an adjusted OR of 1.86
(95% CI 1.45, 2.82).
Conclusion: These results indicate that ADAMTS13 is of importance for RPR,
and that it in combination with vWF also is associated with clinical endpoints in
stable CAD patients on aspirin.
61
Poster presentations
Abstracts not included in the following section is presented in the
corresponding section for the topic above.
Shreeram Akerkar
[email protected]
Clinical medicine
Einarsen, Eigir
[email protected]
Clinical medicine
Giriteka, Lionel
[email protected]
Clinical medicine
Larsen, Christopher
Storm
[email protected]
Clinical medicine
Gulliksen, Håkon
[email protected]
Clinical medicine
Bakken, Rasmus
[email protected]
Duus, Inger
Hødnebø
[email protected]
Basal research and
genetics
Basal research and
genetics
Amundsen, Vivian S.
[email protected]
o
[email protected]
o.no
Clinical medicine
Stautland, Andrea
[email protected]
Neuroscience
Tony Elvegaard
[email protected]
Clinical medicine
Bergsmark, Camilla
Basal research and
genetics
62
Olanzapine-induced metabolic effects in female mice
1,2
1,2
1,2
1,2
Duus IH , Ersland KM , Skrede S , Steen VM .
1. Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics
and Molecular Medicine, Haukeland University Hospital, 5021 Bergen, Norway.
2. K.G. Jebsen Center for Psychosis Research, and the Norwegian Center for Mental
Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, 5021
Bergen Norway.
Introduction/background: Schizophrenia is a debilitating mental disorder
associated with great personal suffering and economic burden. The use of
antipsychotics is essential in relieving the symptoms, and today atypical
antipsychotics are in widespread use. Unfortunately, these drugs also have a
tendency to induce severe metabolic side effects, such as weight gain,
dyslipidaemia and deranged glucose metabolism. The molecular mechanisms
underlying these adverse effects are to a large extent unknown.
In order to investigate the biological basis further, the development of an
animal model is important. However, in several rat studies a continuous
problem has been the failure to achieve antipsychotic-induced weight gain.
Further studies on the potential effect of antipsychotics in mice are therefore
worth pursuing.
Objectives/aim: We want to investigate the effects of olanzapine depot
formulation in mice, hopefully increasing our knowledge of the underlying
molecular mechanisms contributing to weight gain.
Methods: In an initial experiment, female mice received intramuscular
injections of olanzapine depot formulation of 25 mg/kg, 50 mg/kg or vehicle
solution. They were fed standard chow. Weight gain and chow intake were
then measured daily for 15 consecutive days. In a second experiment, female
mice received 50 mg/kg olanzapine long-acting injections and were fed a high
fat diet, one group with ad libitum access to food, another group being pair fed.
Weight gain and chow intake were measured as previously described. In both
experiments, the mice received a second injection on day 9 and they were
sacrificed on day 15. Plasma lipid and olanzapine concentrations were
measured, as well as lipogenic gene expression in liver and periovarial fat using
real-time PCR.
Results/conclusion: The results of both experiments are not completely
analysed. Preliminary results show significant weight gain in the 50 mg/kg
group fed standard chow. Also, both experiments induced significant lipogenic
upregulation in liver and periovarial fat.
63
Reduced Serum Lipid Levels in Patients Receiving ECT – Preliminary
Findings
Andrea Stautland (1), Ute Kessler (2), Leif Oltedal (1,3), Jan Haavik (2,4), Ketil J Ødegaard
(1,2)
(1) Department of Clinical Medicine, University of Bergen, Norway, (2) Division of Psychiatry, Haukeland
University Hospital, Bergen, Norway, (3) Department of Radiology, Haukeland University Hospital,
Bergen, Norway, (4) K.G. Jebsen Centre for Neuropsychiatric Disorders; Department of Biomedicine,
University of Bergen, Norway.
Introduction: Major depressive disorder (MDD) is a highly prevalent and
debilitating mental illness. There is evidence for an altered lipid metabolism in
MDD. Electroconvulsive therapy (ECT) is perhaps the most effective acute
treatment of MDD. The mechanisms of action of ECT are not fully understood,
but might include changes in lipid metabolism.
Objectives: The aim of the study was to assess changes in serum lipid
concentrations in MDD patients undergoing ECT. The study is part of a larger,
multidisciplinary trial investigating the mechanisms of ECT.
Methods: Serum lipid levels were measured in 16 patients suffering from
treatment resistant MDD using a non-targeted lipidomics approach. Blood
samples were obtained before first treatment and approximately one week
after the completed treatment series. Ultrahigh performance liquid
chromatography-tandem mass spectrometry (UPLC-MS/MS) technology was
used to detect lipid metabolites. A matched pairs t-test was used to compare
pre and post-treatment samples.
Results: In total, 399 lipid metabolites were detected, of which 69 were
significantly altered after ECT. Post-treatment samples showed reduction of
serum concentration in several classes of lipid metabolites, especially free fatty
acids (FFA). Significant decreases were found in nearly all of the detected
monoacylglycerol species, within several diacylglycerol species, several
lysolipids and other phospholipid breakdown products and a number of fatty
acid dicarboxylates.
The observed changes in lipid levels can be mediated by different processes,
including changes in biosynthesis and breakdown rates of FFAs. This can be
related to altered levels of exercise, distribution and storage of lipids or dietary
changes. More investigations are needed to explore the contributions of these
processes.
Conclusions: The study contributes to elucidate the role of lipid metabolism in
MDD and the effects of ECT. Further investigations in larger samples should be
performed to confirm these results and evaluate the clinical significance of the
findings
64
Asymmetric septal hypertrophy as a prognostic indicator during
progression of aortic valve stenosis
1
2
1
3
4
Einarsen E. , Cramariuc D. , Lonnebakken M.T. , Boman K. , Gohlke-Bärwolf C. ,
5
1
Chambers J.B. , Gerdts E. From 1 University of Bergen, Bergen, Norway; 2Haukeland University
3
4
Hospital, Bergen, Norway; University of Umeaa, Skelefteaa, Sweden; Herz-Zentrum Bad
5
Krozingen, Germany; St. Thomas Hospital, London, United Kingdom.
Objective: Asymmetric septal hypertrophy (ASH) in patients with severe aortic
stenosis (AS) has been associated with increased perioperative morbidity and
mortality in smaller studies with severe aortic stenosis (AS). This association
has not been tested in a large, longitudinal study.
Methods: Clinical, echocardiographic and outcome data from 1730 patients
with asymptomatic AS, participated in the Simvastatin Ezetimibe in Aortic
Stenosis study (SEAS), a randomized placebo controlled study evaluating the
effect of lipid lowering medications on progression of AS, were used. ASH was
considered present if interventricular septal/posterior wall thickness ratio
exceeded 1.5. The association of ASH with rate of major cardiovascular (CV)
events was tested in time-dependent cox-regression analysis.
Results: During a median of 4.3 years follow-up, ASH developed in 17.0 %
of patients, and was associated with higher left ventricular mass (LVM) and
body mass index (BMI) compared to non-ASH patients (all p<0.05). In timevarying Cox regression analysis, ASH predicted a 50% greater incidence of
ischemic CV events (ICE), a 63% greater incidence in the need for coronary
artery bypass grafting (CABG) at the time of aortic valve replacement, and a 2fold higher incidence of hospitalization for heart failure due to progression of
AS (CHFAS) independent of important confounders (all p<0.05) (Table).
Conclusions: Development of ASH during progression of AS was a strong
predictor of major CV events in patients participating in the SEAS-study.
Table. Results are presented as Hazard ratio (95% Confidence Interval).
ICE(n=322)
CABG (n=165)
CHFAS(n=47)
Asymmetric septal hypertrophy
1.44(1-11-1.88)*
1.63 (1.13-2.32)*
2.26(1.21-4.22)*
Aortic valvular velocity (m/sec)
1.25(1.08-1-44)*
1.74(1.44-2.14)ƚ
1.92(1.33-2.78)*
Simvastatin/Ezetimibe treatment
0.77(0.62-0.96)*
0.66(0.46-0.90)*
1.03(0.58-1.82)
Left ventricular mass (g)
1.00(1.00-1.00)*
1.00(0.99-1.00)
Hypertension
1.95(1.36-2.81)ƚ
2.13(1.26-3.64)*
P-value: *<0.05, ƚ <0.001
65
Actigraph-measured Daytime Sleep and Activity of Daily Living in
Norwegian Nursing Home patients. The COSMOS Study (2013-2016)
1
1
1
T. Elvegaard , B.S. Husebo , E. Flo (poster presentation)
Centre for Elderly and Nursing Home Medicine, and Research Group of General Practice,
Department of Global Public Health and Primary Care, University of Bergen, Norway.
1
Background: More than 90% of Nursing Home (NH) patients with dementia
develop neuropsychiatric symptoms (NPS) including agitation, depression,
anxiety, and sleep problems during the course of the disease. Lack of activities
has been associated with reduced mental and physical functioning and Quality
of Life. Contrariwise, structured activities are shown to reduce NPS in NHs.
Aims: To compare the physical activity and circadian rhythms of NH patients
registered with actigraphs with the Proxy-Rater scores of the activity of daily
living (ADL), neuropsychiatric inventory (NPI) and patient-specific activity logs.
Methods: COSMOS is a 4-month effectiveness implementation-hybrid trial
with follow-up at month 9 (data are collected at month 0, 4 and 9). The trial
includes 520 patients from 64 NH units across Norway. The intervention
consists of a 2-day educational program. Guidelines, patient-logs, and flashcards, as well as telephone support and a 2-month evaluation ensure
implementation. The control group continues with current best practice.
Outcome measures include actigraphy, patient-specific activity logs, NPI and
ADL. The patient wears an actigraph on their dominant arm for 7 days at
months 0 and 4. The actigraph objectively records both night- and daytime
activity, yielding data on sleep-wake rhythms and movement. Baseline data
investigate the association between proxy-rated activity, function, NPS and
objective measures of activity by ADL, NPI and actigraphy.
Discussion: Lack of educated staff, and high turnover may lead to a less
systematic activity schedule. The comparison of objective measures of
activities and proxy rating of patient function and activity provides important
insight to the provision of activities in NHs.
66
Monomers Are Released After Orthodontic Bonding
Håkon Gulliksen1, Marit Midtbø1, Inger Kleiven2, Hanne Wellendorf2, Nils
R. Gjerdet1
1
Department of Clinical Dentistry, Faculty of Medicine and Dentistry, University of Bergen,
2
Norway and Nordic Institute of Dental Materials, Oslo, Norway
Objective: The aim of this study was to estimate the release to saliva of
monomers associated with bonding of fixed orthodontic appliances.
Materal and methods: The study group constituted 30 children (mean age 13
years) scheduled for orthodontic treatment at the University Clinic, Bergen,
Norway. Following rinsing with ultrapure water, unstimulated saliva was
collected for 5min immediately before (A-samples), after bonding of brackets
(B-samples), and at 3-6 weeks (C-samples). Brackets precoated with adhesive
(TransbondPlus, 3M-Unitek) were used with the corresponding self-etch
primer. Following the B-sample NiTi-type of achwires and elastomeric ligatures
were placed. Most patients had molar bands cemented with glass-ionomer
cement (Multi-Cure GIC, 3M-Unitek).
The saliva samples were analysed by as chromatography/mass spectrometry
(GC/MS) and liquid chromatography/ mass spectrometry (LC/MS) for different
monomers (HEMA, TEGDMA, Poly-EGDMA, BMAEPH and Bis-GMA).
Stata 13.1 was used for statistics. The clinical study was approved by the
Regional Committee for Research Ethics.
Results: Salivary levels of Poly-EGDMA, BMAEPH and HEMA were detectable
in the B-samples at 42.1µg/m, 10.00µg/ml, and 30.0µg/ml, respectively. These
monomers were not detectable in the A- or C-samples. TEGDMA and Bis-GMA
were not detected in any of the samples.
Conclusion: The release of monomers to saliva from bonded brackets and
molar bands is transient, returning to below detectable amounts for GC/MS
and LC/MS within 3-6 weeks.
67
Saksliste til generalforsamling
Tidspunkt: søndag 23.oktober 2016, kl. 13.00-14.00
Sted: Odontologibygget, Bergen
Sak 01-16
Sak 02-16
Sak 03-16
Sak 04-16
Sak 05-16
Godkjenning av innkalling.
Valg av referent og ordstyrer.
Årsmelding
Regnskap
Valg av vertsby for Frampeik 2017
Eventuelt
Vel møtt til Generalforsamling!
Frampeik-komiteen 2016
V/Tony Elvegaard
Leder
68
Participants
Akerkar
Amundsen
Arctander
Rosenlund
Bakken
Barua
Bergsmark
Boland
Bremnes
Borge
Coucheron
Derouiche
Duus
Einarsen
Ellingsen
Elvegaard
Engebretsen
Fagerholt
Frugård Habiger
Giriteka
Gjerde
Grindstad
Gullhav Hansen
Gulliksen
Hjøllo
Hoel
Hosar
Høigaard
Isaksen
Jacobsen
Johansen
Shreeram
Vivian S.
Ingrid
UiB
UiO
UiT
Rasmus
Imon
Camilla
Solveig
Thomas
Hanne
Tina
Sonja
Inger Hødnebø
Eigir
Trygve Sølberg
Tony
Anja Susanne
Oda Helen Eck
Torstein
Lionel
Christiane Helgestad
Thea
Lisa
Håkon
Torunn
Fredrik
Rannei
Maria
Sylvia Hetlelid
Martha Rolland
Silje Susanne Pettersen
Simon
UiB
UiO
UiO
UiB
UiT
UiB
UiT
UiT
UiB
UiB
UiT
UiB
NTNU
UiB
UiB
UiB
UiB
UiT
UiT
UiB
UiB
UiB
NTNU
NTNU
NTNU
UiB
Tromsø
UiT
69
Kildal
Klæstad
Knutsen
Koppen
Korkosh
Kristiansen
Krogh Aarebrot
Lappegård
Larsen
Leiten
Lund
Løvik
Madsen
Mclean
Myklebust
Myklebust Ernø
Mynarek
Nypan
Næss
Olsen
Pannu
Paulsen
Raa
Radunovic
Runde
Schanche
Skille
Skjefstad
Skjold
Småbrekke
Solvin
Stangeland
Staniszewski
Stautland
Elise
Christina
Elias
Mohammed Bayar
Elise
Anders
Jostein
Christopher Storm
Elise Orvedal
Anders
Katja
Anders
Emily
Ivar
Inger Thea
Maren
Erik
Morten Svendsen
Eirik Birkelund
Mehma
Benedikte
Anette
Matej
Henrik Alexander
Torstein
Hanne
Kaja
Anneli
Silje
Åshild Øksnevad
Marcus
Kordian
Andrea
Åsta
NTNU
NTNU
NTNU
UiO
UiO
UiB
UiT
UiO
UiB
UiB
UiB
UiB
UiB
NTNU
UiO
NTNU
NTNU
UiT
UiT
UiB
UiT
UiB
UiB
NTNU
UiT
UiT
UiT
UiB
UiT
NTNU
UiB
UiB
UiB
UiB
70
Sulen
Svanøe
Svendsen
Taraldsen
Tislevoll
Tran
Uhlving Larsen
Warlo
Willassen
Willems
Xu
Yi
Amalie Abrahamsen
Tuva
Maria Dalen
Benedicte Sjo
Long
Anette
Ellen Mathea Kirsch
Lisa
Aron
Linda Zi Yan
Dag
UiB
UiT
NTNU
UiB
NTNU
UiT
UiO
UiB
UiB
UiB
UiB
71
72
Sponsors 2016
73
74