The Pathogenesis of Pulmonary Hypoplasia in Congenital Diaphragmatic Hernia: A continuing quest

174 Pages·2012·24.667 MB·English

by  Rhiannon Loenhout

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The Pathogenesis of Pulmonary Hypoplasia in
Congenital Diaphragmatic Hernia:
A continuing quest

Rhiannon Bojoura van Loenhout
The research studies described in this dissertation were conducted at the Lung De-
velopment Programme at the Department of Physiology & Experimental Medicine,
the Hospital for Sick Children, Toronto, Canada, and, the Department of Pediatric
Surgery, Erasmus MC – Sophia Children’s Hospital, Rotterdam, the Netherlands.
The research projects were fi nancially sponsored by the following grants:
Canadian Institute of Health Research (CIHR) (MOP-77751), Erasmus MC Fellowship,
Stichting “Sophia kinderziekenhuis” (project 531), Stichting Prof Michaël – Van Vloten,
Stichting “De Drie Lichten” (project 31/07), Stichting Bekker – La Bastide Fonds,
Schuurman Schimmel – van Outeren Stichting, Trustfonds.
Printing of this dissertation was kindly supported by:
Erasmus Universiteit Rotterdam
Albert Schweitzer ziekenhuis
ISBN: 978-94-6169-256-6
© 2012. Copyright by R. B. van Loenhout, Rotterdam, the Netherlands
No part of this thesis may be reproduced, stored or transmitted in any form or by any
means without prior permission of the auhor, or, where appropriate, the publisher of
the corresponding journal

Cover design: Maple leafs, the national symbol for Canada, which in this design
represent underdeveloped lungs in congenital diaphragmatic hernia
by Detlev van Loenhout & Elena Chochanova
Layout & Print: Optima Grafi sche Communicatie, Rotterdam, the Netherlands
The Pathogenesis of Pulmonary Hypoplasia in
Congenital Diaphragmatic Hernia:
A continuing quest
De pathogenese van pulmonale hypoplasie in
congenitale hernia diafragmatica:
Een voortdurende strijd
Proefschrift
ter verkrijging van de graad van doctor
aan de Erasmus Universiteit Rotterdam
op gezag van de rector magnifi cus
Prof.dr. H.G. Schmidt
en volgens besluit van het College voor Promoties.
De openbare verdediging zal plaatsvinden op
woensdag 30 mei 2012 om 15:30 uur
door
Rhiannon Bojoura van Loenhout
geboren te Dordrecht
PROMOTIECOMMISSIE
Promotoren Prof.dr. D. Tibboel
Prof.dr. M. Post
Overige leden Prof.dr. R.R. de Krijger
Prof.dr. I.K.M. Reiss
Prof.dr. R.M.H Wijnen
Copromotor Dr. R. Keijzer
Paranimfen Annemieke Miedema
Kirsten E. Tijssen
Voor mijn ouders

TABLE OF CONTENTS
Chapter 1 General introduction & Outline of the dissertation 9
Chapter 2 Congenital diaphragmatic hernia: A comparison of 17
animal models and relevance to the human situation
Chapter 3 The pulmonary mesenchymal tissue layer is defective 47
in an in vitro recombinant model of nitrofen-induced
pulmonary hypoplasia
Chapter 4 Apoptosis of fi broblasts is regulated by epithelial cells 73
during fetal rat lung development in a cell recombinant
model
Chapter 5 Epithelial-mesenchymal transition in nitrofen-induced 89
pulmonary hypoplasia in congenital diaphragmatic
hernia: A pilot study
Chapter 6 Postmortem lung biopsy for obtaining lung tissue in 101
congenital diaphragmatic hernia
Chapter 7 The Von Hippel-Lindau pathway in diaphragmatic 119
defects
Chapter 8 General discussion & Future perspectives 133
Chapter 9 English Summary & Nederlandse Samenvatting 151
List of Abbreviations 159
Acknowledgements & Dankwoord 162
Contributing Authors & Technical Assistance 166
PhD Portfolio 168
Curriculum Vitae Auctoris 170