Læknaneminn - 01.04.2018, Blaðsíða 130

R
an
ns
ók
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i 3
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greindum. Það var tilhneiging til þess að jákvæðir
hlytu blóðhlutameðferð fyrr á rannsóknartímabilinu
en þó var ekki marktækur munur.
Ályktanir: Blóðhlutameðferð virtist tengjast styttri lifun
og tíma að blóðhlutameðferð. Þá fékk um þriðjungur
CLL sjúklinga blóðhlutameðferð og þriðjungur
lyfjameðferð. Skörun var hjá 43 einstaklingum. Jákvætt
Coomb‘s próf hefur tilhneigingu til að tengjast styttri
tíma að rauðkornameðferð. Þá er blóðhlutameðferð
CLL sjúklinga á Íslandi kortlögð en ábendingar fyrir
lyfja­ og blóðhlutameðferðir hafa ekki verið skoðaðar
og vert er að athuga það í framhaldinu.
Validating Genetic Associations
of Asthma in The Consortium
of Asthma among African-
ancestry Populations in the
Americas
Hrafnhildur Bjarnadóttir1, Kathleen C.
Barnes2, Michelle Daya2
1Department of Medicine, University
of Iceland, 2Division of Biomedical
Informatics and Personalized Medicine,
University of Colorado Anschutz Medical
Campus
Introduction. Asthma is a chronic inflammatory
disorder of the respiratory tract estimated to affect
as many as 300 million people worldwide. Asthma
comprises a range of phenotypes with the risk factors
for each phenotype depending on both genetic and
environmental factors as well as their interactions.
Asthma affects people of all ethnic backgrounds
but ethnic minorities, such as African Americans in
the United States, are affected disproportionally. At
present, it is not clear to what extent genetic variation
contributes to these ethnic disparities. Genome­wide
association studies (GWAS) have identified many
risk variants relating to asthma but in these studies,
populations of African ancestry have only been a
small fraction of studied subjects. The Consortium
on Asthma among African­ancestry Populations in
the Americas (CAAPA) performed the largest meta­
analysis of asthma GWAS in individuals of African
ancestry to date. The study yielded a number of loci
that may contribute to risk of asthma specifically
in individuals of African ancestry. The aim of this
study is to replicate the findings of the CAAPA
Consortium in an independent European ancestry
population, and thereby test the generalizability of
associations in non­African ancestry populations.
Materials and methods. The six single nucleotide
polymorphisms (SNPs) that showed strongest
association with asthma in the CAAPA study were
selected for replication. Genotyping was performed in
633 European ancestry samples previously collected for
The Collaborative Studies on the Genetics of Asthma
(CSGA). DNA extraction was performed using an
AutoGen FLEX STAR. Genotyping was performed
using a TaqMan ABI 7900. Hardy Weinberg testing
and tests for Mendelian inconsistencies were performed
using PLINK. Genetic association was tested using the
generalized estimating equations (GEE).
Results. None of the six SNPs showed significant
association with asthma in the replication population.
However, the direction of effect for five of the six SNPs
was the same as in the discovery sample.
Discussion. The CSGA population was selected,
partly, due to the availability of the samples for
genotyping. As the individuals of African ancestry
were not available for a replication study it was decided
to replicate the findings of the CAAPA Consortium
in the portion of the CSGA population that was of
European ancestry. Replication of the CAAPA findings
in a population of European ancestry was of interest
for a number of reasons. The gender distribution
and mean age of subject in the CSGA and CAAPA
populations were similar. The LD patterns for the
SNPs on chromosome 2 were different between the
two populations. It is, however, unlikely that differing
LD patterns contributed to the insignificant results of
this study. Due to the fact that a significant portion
of the CSGA subjects had incomplete phenotype
data, the proportion of cases and controls is the least
comparable factor between study populations. It is
likely that the use of GEE as this study’s analytical
method, in a small sample population with such a
large portion of missing phenotype data, contributed
to the insignificant findings of the study. It is possible
that some of the genotyped SNPs have no association
with asthma in populations of European ancestry. This
study alone can, however, not confirm this and the
role of these SNPs in asthma in European populations
requires further investigation.
Two dimensional measurements
of cell free DNA in plasma of
septic patients
Hróðmar Helgi Helgason1, Jón Jóhannes
Jónsson2, Kristinn Sigvaldason3,
Sigurbergur Kárason4, Gísli Sigurðsson5,
Bjarki Guðmundsson2, Hans Þormar6
1Faculty of Medicine University of
Iceland, 2Faculty of Genetics and
Molecular Sciences Landspítali
University Hospital (LSH), 3ICU­
Fossvogur LSH,4ICU Hringbraut LSH,
5ICU department LSH, 6Lífeind ehf.
Introduction: Elevated levels of cell free DNA
(cfDNA) in plasma is associated with various medical
emergencies such as trauma, stroke, and sepsis. In
septic patients, cfDNA levels have been shown to
correlate with disease severity and hospital mortality].
The goal of this study was to examine if structural
damage in cfDNA is present in septic patients.
Materials and methods: Plasma samples were
collected from nine consenting patients (age >18)
admitted to the two ICU´s of Landspitali due to
severe sepsis from December 2016 until May 2017.
Samples were also collected from five healthy controls.
The sample DNA was isolated using the Genomic
Mini AX kit according to protocol. Northern Lights
assay (two dimensional) was used to detect cfDNA
structural damage such as, single/double strand
breaks, bends, and inter/intra strand crosslinks. The
addition of Fpg (formamidopyrimidine [fapy]­DNA
glycosylase)  which exaggerates damage was also
examined for effect. The study was approved by the
national bioethics committee and the Icelandic Data
Authority.
Results: Elevated plasma levels of cfDNA were
observed in septic patients which in turn decreased
with treatment. Visual analysis of the NLA imaging
results revealed a repeating pattern indicative of
significant single­stranded breaks in nucleosomal
DNA in sepsis patients that was not readily observable
in controls. Fpg enzyme treatment decreased larger
DNA molecules compared to control samples.
Conclusion: The increase in single­stranded DNA
damage in septic patients is possibly the result of
lack of DNA repair associated with cell death. Larger
DNA molecules that are isolated can be assumed to be
necrotic DNA possibly containing increased oxidative
damage. The sample size in this study is too small
to draw concrete conclusions and further research is
warranted.
Sjúkraflutningar nýbura
og tengsl við þróun
fæðingarþjónustu á Íslandi
(1992-2015)
Hugrún Þórbergsdóttir1, Þórður
Þórkelsson1,2, Hildur Harðardóttir1,3 og
Elín Ögmundsdóttir2
1Læknadeild Háskóla Íslands,
2Barnaspítali Hringsins og 3Kvennadeild
Landspítala
Inngangur: Á Íslandi fæðast þrjú af hverjum fjórum
börnum á Landspítalanum (LSH). Sum börn
sem fæðast utan LSH þarf að flytja á Vökudeild
Barnaspítala Hringsins (VBH) vegna veikinda. Á
undan förnum árum hefur fæðingarstöðum hér á
landi fækkað og búast má við að sjúkraflutningum á
veikum nýburum hafi fækkað samhliða en það hefur
ekki verið skoðað. Markmið rannsóknarinnar er að
kanna hvernig sjúkraflutningum á nýburum hefur
verið háttað hér á landi á árunum 1992­2015. Bornar
verða saman sjúkdómsgreiningar og alvarleiki veikinda
barna sem flutt voru á VBH við börn fædd á LSH.
Einnig verður skoðað hvaða breyting hefur átt sér stað
hvað varðar fjölda fæðingarstaða á Íslandi. Loks verður
kannað hverjar áætlaðar ástæður fyrirburafæðinga eru
á landsbyggðinni samanborið við fyrirburafæðingar á
LSH.
Efniviður og aðferðir: Afturskyggn tilfella­ og
viðmiðarannsókn sem náði til allra nýbura sem
fæddust utan LSH og flytja þurfti á VBH á árunum
1992­2015. Klínískra upplýsinga og tegund flutnings
á VBH var aflað úr Vökudeildarskrá og sjúkraskrám
barna og mæðra. Fyrir hvert barn sem flutt var á VBH
voru fundin sem viðmið fjögur (fullburða börn) eða
tvö (fyrirburi) börn sem fæddust á LSH næst á eftir
og á undan tilfellinu. Fyrirburarnir voru paraðir á
meðgöngulengd. Notast var við lýsandi tölfræði og
tilgátuprófanir.
Niðurstöður: Alls fæddust 767 börn utan LSH sem
flytja þurfti á VBH á tímabilinu, 305 stúlkur (39,8%)
og 462 drengir (60,2%). Rannsóknartímabilinu var
skipt í tvö 12 ára tímabil. Meðaltal sjúkraflutninga
á ári lækkaði marktækt á milli tímabilanna (p­gildi=
<,0001*). Á fyrra tímabili þurfti að flytja 2,5% þeirra
barna sem fæddust utan LSH en 2,2% þeirra á seinna
tímabili (p­gildi= 0,235). Fullburða börn sem flutt
voru á VBH voru veikari og þurftu marktækt oftar
súrefnismeðferð, öndunarvélameðferð, niturildi og
sýklalyf samanborið fullburða börn fædd á LSH.
Fyrirburar fluttir á VBH þurftu marktækt oftar
meðferð með öndunarvél, ásamt sýklalyfjum. Á fyrra
tímabili rannsóknar voru að meðaltali sex fyrirburar
fluttir á ári á VBH en að meðaltali fjórir á því seinna
(p­gildi= 0,03). Ekki var markækur munur á áætluðum
ástæðum fyrirburafæðinga kvenna sem fæddu utan
LSH og þeirra sem fæddu á LSH. Fæðingum fækkaði
marktækt á öllum fæðingarstöðum landsins nema á
LSH, Sjúkrahúsinu á Akureyri (SAk), Neskaupsstað,
Akranesi og í heimahúsum.
Ályktanir: Sjúkraflutningar eru mikilvægur hluti af
starfsemi Vökudeildar Barnaspítala Hringsins. Börn
sem flytja þarf sjúkraflutningum eru almennt veikari
en börn sem fæðast á fæðingardeild Landspítalans.
Sjúkraflutningum nýbura hefur fækkað samhliða
fækkun fæðingarstaða og fjölgun fæðinga á LSH.
Fækkun fæðingarstaða er í samræmi við auknar kröfur
um gæði heilbriðgisþjónustu. Þörf fyrir sjúkraflutninga
á fyrirburum hefur minnkað marktækt sem bendir til
bættrar þjónustu við þungaðar konur á landsbyggðinni
þar sem þær eru sendar á Kvennadeildina LSH hafi
þær þekkta áhættuþætti.