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1.
Olgiati, Simone.
Genetics of Movement Disorders in the Next-Generation Sequencing Era.
Degree: 2016, Erasmus University Medical Center
URL: http://hdl.handle.net/1765/80040 
► markdownabstractMovement disorders are neurologic syndromes in which there is either an excess of movements or a paucity of voluntary and automatic movements, unrelated to weakness…
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▼ markdownabstractMovement disorders are neurologic syndromes in which there is either an excess of movements or a paucity of voluntary and automatic movements, unrelated to weakness or spasticity. These disorders are associated with dysfunctions of the basal ganglia and cerebellum, brain structures that together orchestrate the control of movements. During the last two decades, genetic studies of movement disorders identified many genetics factors associated with these diseases, including rare Mendelian factors, moderately-rare factors with moderate effect size, and common variants with low effect size. In the coming years, the application of novel DNA sequencing technologies to the study of movement disorders promises to unveil even more genetic factors, possibly leading to a full understanding of the genetic architecture of these disorders.
The introduction (Part I) of this thesis reviews the modern strategies for the identification of genetic factors associated with Mendelian forms of movement disorders. After a brief definition of these disorders, we focus on the use of the next-generation sequencing technologies to identify Mendelian mutations in movement disorders (chapter 1.1). Our experimental work is presented in the next three parts of this thesis. Part II is focused on the genetic studies of Parkinson’s disease (PD). In chapter 2.1, for the first time, we report the identification of DNAJC6 mutations in families with early-onset PD. Our work delineate a novel form of autosomal recessive early-onset PD, caused by mutations in the DNAJC6 gene, and has important implications for the diagnostic work-up and genetic counseling of early-onset PD patients. In chapter 2.2, we report genetic and clinical findings in a novel family with early-onset parkinsonism associated with triplication of the SNCA locus. This study contributes to the genetic and clinical characterization of this very rare form. In chapter 2.3, we perform a large exome sequencing project in the isolated population of Sardinia to identify novel risk factors for PD with intermediate or strong effect size. In this study we identify a list of candidate variants highly enriched or exclusively present in PD, a resource of candidates for future studies. Notably, this was the first study analyzing a large cohort of PD patients at exome-wide level.
Part III of this thesis focuses on the study of atypical forms of parkinsonisms. In chapter 3.1, we report the identification of a novel form of early-onset atypical parkinsonism caused by a homozygous mutation in SYNJ1. This study was the first to report the association between a SYNJ1 mutation and parkinsonism. In chapter 3.2, we identify a family with a milder phenotype caused by the same homozygous mutation in a different haplotype, suggesting that the two SYNJ1 mutations originated from different mutational events. Interestingly, the proteins encoded by SYNJ1 and DNAJC6 both act in the molecular pathway of the clathrin-mediated endocytosis, suggesting an involvement of this pathway in the pathogenesis…
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APA (6th Edition):
Olgiati, S. (2016). Genetics of Movement Disorders in the Next-Generation Sequencing Era. (Doctoral Dissertation). Erasmus University Medical Center. Retrieved from http://hdl.handle.net/1765/80040
Chicago Manual of Style (16th Edition):
Olgiati, Simone. “Genetics of Movement Disorders in the Next-Generation Sequencing Era.” 2016. Doctoral Dissertation, Erasmus University Medical Center. Accessed February 26, 2020.
http://hdl.handle.net/1765/80040.
MLA Handbook (7th Edition):
Olgiati, Simone. “Genetics of Movement Disorders in the Next-Generation Sequencing Era.” 2016. Web. 26 Feb 2020.
Vancouver:
Olgiati S. Genetics of Movement Disorders in the Next-Generation Sequencing Era. [Internet] [Doctoral dissertation]. Erasmus University Medical Center; 2016. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/1765/80040.
Council of Science Editors:
Olgiati S. Genetics of Movement Disorders in the Next-Generation Sequencing Era. [Doctoral Dissertation]. Erasmus University Medical Center; 2016. Available from: http://hdl.handle.net/1765/80040
2.
Nijman, Ruud.
Improving diagnostic strategies for predicting serious bacterial infections in children with fever.
Degree: 2014, Erasmus University Medical Center
URL: http://hdl.handle.net/1765/77189
► textabstractThis thesis aimed to improve diagnostic strategies for predicting SBI in febrile children in emergency care settings. Generally, clinical signs and symptoms were of limited…
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▼ textabstractThis thesis aimed to improve diagnostic strategies for predicting SBI in febrile children in emergency care settings. Generally, clinical signs and symptoms were of limited use in detecting SBI, even when using modelling techniques that best reflected their predictive ability. C-reactive protein (CRP) and procalcitonin (PCT) were useful diagnostic tools in the diagnostic management of febrile children, whereas neutrophil CD64 count was not. CRP and PCT had considerable incremental value to clinical signs and symptoms, and a prediction model consisting of clinical signs and symptoms and CRP performed well in derivation and validation studies.
Subjects/Keywords: fever; child; serious bacterial infection; prediction model; vital signs; respiratory rate; lower respiratory tract infections; biomarkers; C-reactive protein; procalcinonin; neutrophil CD64; fever phobia; Manchester Triage System; emergency department
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APA (6th Edition):
Nijman, R. (2014). Improving diagnostic strategies for predicting serious bacterial infections in children with fever. (Doctoral Dissertation). Erasmus University Medical Center. Retrieved from http://hdl.handle.net/1765/77189
Chicago Manual of Style (16th Edition):
Nijman, Ruud. “Improving diagnostic strategies for predicting serious bacterial infections in children with fever.” 2014. Doctoral Dissertation, Erasmus University Medical Center. Accessed February 26, 2020.
http://hdl.handle.net/1765/77189.
MLA Handbook (7th Edition):
Nijman, Ruud. “Improving diagnostic strategies for predicting serious bacterial infections in children with fever.” 2014. Web. 26 Feb 2020.
Vancouver:
Nijman R. Improving diagnostic strategies for predicting serious bacterial infections in children with fever. [Internet] [Doctoral dissertation]. Erasmus University Medical Center; 2014. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/1765/77189.
Council of Science Editors:
Nijman R. Improving diagnostic strategies for predicting serious bacterial infections in children with fever. [Doctoral Dissertation]. Erasmus University Medical Center; 2014. Available from: http://hdl.handle.net/1765/77189
3.
Marsouvanidis, Panteleimon.
Radiopharmaceutical Design for GRPR Targeting in Prostate Cancer.
Degree: 2014, Erasmus University Medical Center
URL: http://hdl.handle.net/1765/77291
► markdownabstract__Abstract__ Molecular imaging is broadly defined as the characterization and measurement of biological processes in living animals at the cellular and molecular level. Bombesin (BBN),…
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▼ markdownabstract__Abstract__
Molecular imaging is broadly defined as the characterization and measurement of biological processes in living animals at the cellular and molecular level.
Bombesin (BBN), an amphibian 14-amino acid peptide, is a homologue of the 27-amino acid mammalian gastrin-releasing peptide (GRP).
These peptides are mostly studied due to their implication in cancer cellular pathways.
It has been proven that various cancer cell lines synthesize bombesin and GRP which in turn stimulate cancer growth through autocrine feedback mechanisms involving the expression of these peptides and that of their receptors in the tumor cells.
During our research we have synthesized a library of GRP/BBN peptide analogs coupled to DOTA or acyclic tetraamines (N4) and have radiolabeled them with the diagnostic radionuclides 111In and 99mTc and/or the therapeutic radionuclides 90Y, 177Lu, and 188Re.
Radiopeptides have been evaluated at the molecular and cellular level (competition, saturation binding assays, internalization-externalization experiments) as well as in experimental animals (metabolism, biodistribution and imaging in SCID/nude mice bearing human xenografts (human prostate or breast carcinomas).
In the figure, the radioactivity uptake of four 111In-labeled truncated analogues of the human 27-mer GRP, conjugated with DOTA at the N-terminus of GRP(13/14/17/18-27) in crucial organs and human xenograft is illustrated.
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APA (6th Edition):
Marsouvanidis, P. (2014). Radiopharmaceutical Design for GRPR Targeting in Prostate Cancer. (Doctoral Dissertation). Erasmus University Medical Center. Retrieved from http://hdl.handle.net/1765/77291
Chicago Manual of Style (16th Edition):
Marsouvanidis, Panteleimon. “Radiopharmaceutical Design for GRPR Targeting in Prostate Cancer.” 2014. Doctoral Dissertation, Erasmus University Medical Center. Accessed February 26, 2020.
http://hdl.handle.net/1765/77291.
MLA Handbook (7th Edition):
Marsouvanidis, Panteleimon. “Radiopharmaceutical Design for GRPR Targeting in Prostate Cancer.” 2014. Web. 26 Feb 2020.
Vancouver:
Marsouvanidis P. Radiopharmaceutical Design for GRPR Targeting in Prostate Cancer. [Internet] [Doctoral dissertation]. Erasmus University Medical Center; 2014. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/1765/77291.
Council of Science Editors:
Marsouvanidis P. Radiopharmaceutical Design for GRPR Targeting in Prostate Cancer. [Doctoral Dissertation]. Erasmus University Medical Center; 2014. Available from: http://hdl.handle.net/1765/77291
4.
Hoen, Lisette.
Outcome Measures in Functional Urology: Towards evaluation through patient reported outcome measures?.
Degree: 2015, Erasmus University Medical Center
URL: http://hdl.handle.net/1765/79283
► markdownabstractAbstract Pelvic floor disorders are characterized by four domains: urinary symptoms, anorectal symptoms, pelvic organ prolapse and sexual dysfunction. The symptoms of the different domains…
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▼ markdownabstractAbstract
Pelvic floor disorders are characterized by four domains: urinary symptoms, anorectal symptoms, pelvic organ prolapse and sexual dysfunction. The symptoms of the different domains have a significant impact on patient’s quality of life. Traditional outcome measures, such as bladder diary, urodynamics, and ultrasound, have been used for the evaluation of pelvic floor disorders and treatment efficacy. These do not take the patient’s perspective into account which has resulted in a discrepancy between patients and physicians about the impact of symptoms and effectiveness of treatment. Patient reported outcome measures (PROMs) have been developed to resolve this discordance between patients and physicians.
The aim of this thesis is to determine the position of PROMs as an outcome measure in functional urology. The first part of this thesis evaluates two additional treatment options using only traditional outcome measures and a combination of PROMs and traditional outcome measures. We have found that onabotulinum toxin-A is effective in the treatment of therapy-refractory children with dysfunctional voiding. Furthermore, the results with intermittent sacral neuromodulation suggest it to be a more cost-effective option than ‘standard’ continuous sacral neuromodulation.
The second part of this thesis focusses on the quality of PROMs used in clinical practice. During the assessment of validation studies and measurement properties using the COSMIN checklist, variable evidence was found for the quality of the PROMs to evaluate sexual function in neurological patients. An essential point of improvement is to adequately assess all measurement properties, specifically responsiveness and minimal important change, before the PROMs can be used in clinical practice.
In the third part of this thesis four Dutch versions of PROMs assessing severity of pelvic floor disorders and their impact on quality of life in children and adults are validated, thereby providing adequate Dutch versions of these PROMs. In conclusion, the findings presented in this thesis support that PROMs in functional urology sufficiently represent the patient’s perspective and PROMs could assist to manage patient expectation and improve patient satisfaction. However, it remains important to guarantee adequate quality of PROMs used in clinical practice. One of the future perspectives for the field of functional urology is to develop a prediction model based on different outcome measure to predict treatment success for individual patients.
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APA (6th Edition):
Hoen, L. (2015). Outcome Measures in Functional Urology: Towards evaluation through patient reported outcome measures?. (Doctoral Dissertation). Erasmus University Medical Center. Retrieved from http://hdl.handle.net/1765/79283
Chicago Manual of Style (16th Edition):
Hoen, Lisette. “Outcome Measures in Functional Urology: Towards evaluation through patient reported outcome measures?.” 2015. Doctoral Dissertation, Erasmus University Medical Center. Accessed February 26, 2020.
http://hdl.handle.net/1765/79283.
MLA Handbook (7th Edition):
Hoen, Lisette. “Outcome Measures in Functional Urology: Towards evaluation through patient reported outcome measures?.” 2015. Web. 26 Feb 2020.
Vancouver:
Hoen L. Outcome Measures in Functional Urology: Towards evaluation through patient reported outcome measures?. [Internet] [Doctoral dissertation]. Erasmus University Medical Center; 2015. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/1765/79283.
Council of Science Editors:
Hoen L. Outcome Measures in Functional Urology: Towards evaluation through patient reported outcome measures?. [Doctoral Dissertation]. Erasmus University Medical Center; 2015. Available from: http://hdl.handle.net/1765/79283
5.
Dulfer, Karolijn.
An Exercise Program in Youngsters with Complex Congenital Heart Disease: does it improve Health Related Quality of Life and Psychosocial Functioning? A randomized controlled trial.
Degree: 2014, Erasmus University Medical Center
URL: http://hdl.handle.net/1765/51287
► markdownabstract__Abstract__ A 12-week standardized exercise program improved self-reported cognitive functioning, and parent-reported social functioning in children and adolescents with complex congenital heart disease. Furthermore, it…
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▼ markdownabstract__Abstract__
A 12-week standardized exercise program improved self-reported cognitive functioning,
and parent-reported social functioning in children and adolescents with complex congenital heart disease. Furthermore, it resulted in a decrease in
passive leisure time spending. In contrast, it had no effect on emotional and behavioural
problems, on sports enjoyment, or on active leisure time spending. Parental mental health
moderated changes in social functioning: adolescents in the exercise group whose parents’
overall mental health was worse, reported a pre-post decrease in social functioning, compared
with controls.
Subjects/Keywords: congenital heart disease; exercise training; quality of life; children; adolescents; young adults
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APA (6th Edition):
Dulfer, K. (2014). An Exercise Program in Youngsters with Complex Congenital Heart Disease: does it improve Health Related Quality of Life and Psychosocial Functioning? A randomized controlled trial. (Doctoral Dissertation). Erasmus University Medical Center. Retrieved from http://hdl.handle.net/1765/51287
Chicago Manual of Style (16th Edition):
Dulfer, Karolijn. “An Exercise Program in Youngsters with Complex Congenital Heart Disease: does it improve Health Related Quality of Life and Psychosocial Functioning? A randomized controlled trial.” 2014. Doctoral Dissertation, Erasmus University Medical Center. Accessed February 26, 2020.
http://hdl.handle.net/1765/51287.
MLA Handbook (7th Edition):
Dulfer, Karolijn. “An Exercise Program in Youngsters with Complex Congenital Heart Disease: does it improve Health Related Quality of Life and Psychosocial Functioning? A randomized controlled trial.” 2014. Web. 26 Feb 2020.
Vancouver:
Dulfer K. An Exercise Program in Youngsters with Complex Congenital Heart Disease: does it improve Health Related Quality of Life and Psychosocial Functioning? A randomized controlled trial. [Internet] [Doctoral dissertation]. Erasmus University Medical Center; 2014. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/1765/51287.
Council of Science Editors:
Dulfer K. An Exercise Program in Youngsters with Complex Congenital Heart Disease: does it improve Health Related Quality of Life and Psychosocial Functioning? A randomized controlled trial. [Doctoral Dissertation]. Erasmus University Medical Center; 2014. Available from: http://hdl.handle.net/1765/51287
6.
Rijen, Susan.
Psychosocial aspects of congenital heart disease in adulthood: A longitudinal cohort study of 20-33 years follow-up.
Degree: 2003, Erasmus University Medical Center
URL: http://hdl.handle.net/1765/51251
► markdownabstract__Abstract__ Adults with congenital heart disease form a rather new phenomenon. Improvements in surgical techniques over the last decades have lead to lower mortality rates…
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▼ markdownabstract__Abstract__
Adults with congenital heart disease form a rather new phenomenon. Improvements in
surgical techniques over the last decades have lead to lower mortality rates for children born
with a congenital heart disease, enabling more of them to grow into adulthood (Sparacino,
1994; Wren & O'Sullivan, 2001). Today, health care professionals encounter the first
generation of adults with congenital heart disease.
Adults with congenital heart disease do not only differ in medical status and history
from the well-known cardiac population with acquired cardiac diseases, but also show
different psychosocial characteristics and needs. Firstly, the age at onset of the cardiac disease
differs considerably for adults with congenital heart disease compared to adults with acquired
cardiac disease. For adults with congenital heart disease, the cardiac anomaly may not only
affect their present adult life, but it may also have left its mark on their childhood.
Experiences of growing up with a congenital heart disease might influence the patient’s
functioning at adult age. Secondly, when growing up into adulthood, patients may be
confronted with new problems associated with congenital heart disease in adulthood. These
problems might concern finding a suitable employment or getting a mortgage (Allen et al.,
1992; Celermajer & Deanfield, 1993; Gersony et al., 1993; Hart & Garson, 1993; Hellstedt,
1994; Mahoney et al., 1991; McGrath & Truesdell, 1994) or they may concern the experience
of uncertainties or restrictions regarding sexuality and childbearing (Gantt, 1992; Mahoney et
al., 1991; Somerville, 1998; Tong & Sparacino, 1994). Adults with congenital heart disease
are in the disadvantageous position of being the first generation to experience these problems,
since little is yet known about relevant medical and psychosocial aspects. For these reasons,
adults with congenital heart disease should be considered as a new and distinct patient
population with unique characteristics. Therefore, the medical course of congenital heart
disease into adulthood, as well as the psychosocial development of adults with congenital
heart disease, deserve special attention.
Subjects/Keywords: heart diseases; adulthood; psychological aspects; congenital heart disease
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APA (6th Edition):
Rijen, S. (2003). Psychosocial aspects of congenital heart disease in adulthood: A longitudinal cohort study of 20-33 years follow-up. (Doctoral Dissertation). Erasmus University Medical Center. Retrieved from http://hdl.handle.net/1765/51251
Chicago Manual of Style (16th Edition):
Rijen, Susan. “Psychosocial aspects of congenital heart disease in adulthood: A longitudinal cohort study of 20-33 years follow-up.” 2003. Doctoral Dissertation, Erasmus University Medical Center. Accessed February 26, 2020.
http://hdl.handle.net/1765/51251.
MLA Handbook (7th Edition):
Rijen, Susan. “Psychosocial aspects of congenital heart disease in adulthood: A longitudinal cohort study of 20-33 years follow-up.” 2003. Web. 26 Feb 2020.
Vancouver:
Rijen S. Psychosocial aspects of congenital heart disease in adulthood: A longitudinal cohort study of 20-33 years follow-up. [Internet] [Doctoral dissertation]. Erasmus University Medical Center; 2003. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/1765/51251.
Council of Science Editors:
Rijen S. Psychosocial aspects of congenital heart disease in adulthood: A longitudinal cohort study of 20-33 years follow-up. [Doctoral Dissertation]. Erasmus University Medical Center; 2003. Available from: http://hdl.handle.net/1765/51251
7.
Berden, Guy.
De ontwikkeling en toepassing van een levensgebeurtenissenvragenlijst en van een levensgebeurtenisseninterview.
Degree: 1992, Erasmus University Medical Center
URL: http://hdl.handle.net/1765/40688
► textabstractWanneer men op zoek is naar een verklaring voor het ontstaan, bij kinderen en jeugdigen, van gevoels- en gedragsproblemen, in dit proefschrift samenvattend probleemgedrag genoemd,…
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▼ textabstractWanneer men op zoek is naar een verklaring voor het ontstaan, bij kinderen en
jeugdigen, van gevoels- en gedragsproblemen, in dit proefschrift samenvattend
probleemgedrag genoemd, verwijst men vaak naar een opeenvolging van gebeurtenissen
in hun voorgeschiedenis zoals: een ziekenhuisopname, het overlijden van een
familielid, een verhuizing of een emstige ziekte van een ouder. Verondersteld wordt
dat deze gebeurtenissen, in de literatuur veelal 'stressvolle levensgebeurtenissen'
genoemd, dermate vee! negatieve invloeden uitoefenen op het kind dat
probleemgedrag hiervan het gevolg kan zijn.
Oat men in de klinische praktijk een relatie veronderstelt tussen een
opeenvolgende reeks 'stressvolle levensgebeurtenissen' en probleemgedrag is zeer
invoelbaar. Zo is er een haast logische samenhang tussen het ontstaan van
scheidingsangsten bij een kind en het gegeven dat dit kind in het nabije verleden
geconfronteerd werd met het verlies van een aantal geliefde personen.
Daze klinische ervaringsgegevens vragen echter om een nadere wetenschappelijke
onderbouwing. Dit proefschrilt beoogt een bijdrage te leveren aan onderzoek
naar de veronderstelde samenhang tussen stressvolle levensgebeurtenissen en
probleemgedrag.
Subjects/Keywords: interviewen; jeugdpsychiatrie; levenservaring; levensloop; psychologie; testconstructie; trauma's; vragenlijsten
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APA (6th Edition):
Berden, G. (1992). De ontwikkeling en toepassing van een levensgebeurtenissenvragenlijst en van een levensgebeurtenisseninterview. (Doctoral Dissertation). Erasmus University Medical Center. Retrieved from http://hdl.handle.net/1765/40688
Chicago Manual of Style (16th Edition):
Berden, Guy. “De ontwikkeling en toepassing van een levensgebeurtenissenvragenlijst en van een levensgebeurtenisseninterview.” 1992. Doctoral Dissertation, Erasmus University Medical Center. Accessed February 26, 2020.
http://hdl.handle.net/1765/40688.
MLA Handbook (7th Edition):
Berden, Guy. “De ontwikkeling en toepassing van een levensgebeurtenissenvragenlijst en van een levensgebeurtenisseninterview.” 1992. Web. 26 Feb 2020.
Vancouver:
Berden G. De ontwikkeling en toepassing van een levensgebeurtenissenvragenlijst en van een levensgebeurtenisseninterview. [Internet] [Doctoral dissertation]. Erasmus University Medical Center; 1992. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/1765/40688.
Council of Science Editors:
Berden G. De ontwikkeling en toepassing van een levensgebeurtenissenvragenlijst en van een levensgebeurtenisseninterview. [Doctoral Dissertation]. Erasmus University Medical Center; 1992. Available from: http://hdl.handle.net/1765/40688
8.
Horst, Maarten.
Gene therapy of Maligant Gliomas.
Degree: Department of Neurology, 2008, Erasmus University Medical Center
URL: http://hdl.handle.net/1765/10864
► textabstractOndanks ontwikkelingen in de neurochirurgie, radiotherapie en chemotherapie is het niet mogelijk om patiënten met maligne gliomen (o.a. glioblastomen) te genezen. Ieder jaar overlijden hieraan…
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▼ textabstractOndanks ontwikkelingen in de neurochirurgie, radiotherapie en chemotherapie is het niet mogelijk om patiënten met maligne gliomen (o.a. glioblastomen) te genezen. Ieder jaar overlijden hieraan 450 patiënten in Nederland (25.000 sterfgevallen per jaar in Europa en Noord-Amerika). Ondanks initiële behandeling krijgen alle patiënten uiteindelijk een recidief. Bij 80% van hen ligt dit binnen een marge van 2-3 cm van de oorspronkelijke tumor op CT/MRI. Zelden is er sprake van een uitzaaiing buiten de schedel. Vanwege het infiltratieve groeipatroon is radicale chirurgische resectie, met oncologische marges, niet mogelijk. De locoregionale aard van maligne gliomen en de slechte prognose maken deze tumoren tot geschikte kandidaten voor adjuvante behandelingstechnieken zoals gentherapie.
In de afgelopen jaren zijn er diverse klinische gentherapie trials, o.a. in Rotterdam, bij maligne gliomen uitgevoerd met adenovirussen die een gen tot expressie kunnen brengen maar die niet kunnen repliceren. In dit proefschrift wordt onderzoek gedaan met als doel het effect van gentherapie te verbeteren. Ten eerste is gekeken naar adenovirussen die kunnen vermenigvuldigen in cellen die voldoen aan een bepaalde voorwaarde (conditioneel replicerende adenovirus). In dit proefschrift wordt de ontwikkeling van een conditioneel replicerend adenovirus onder de controle van een glial fibrillary acidic protein (GFAP) promoter beschreven. Vervolgens is gezocht naar manieren om de adenovirale verspreiding te optimaliseren, waaruit blijkt dat een virus beter verspreid wordt door multiple injecties dan door een enkele injectie of een injectie met een enkele uren durende continue infusie van adenovirus (convection enhanced delivery). Tenslotte wordt ingegaan op nieuwe ontwikkelingen in !
de nucleaire beeldvorming (imaging) van adenovirale vectoren in hersentumoren.
Subjects/Keywords: Adenoviridae; FIAU; FIRU; GFAP; Herpes simplex virus thymidine kinase; SPECT; [99mTc-N40-1,Asp0,Tyr3]octreotate; cancer; convection-enhanced delivery; gene therapy; glioma; oncolytic adenovirus; somatostatin receptor; strocytes; tissue-specific promoter
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APA (6th Edition):
Horst, M. (2008). Gene therapy of Maligant Gliomas. (Doctoral Dissertation). Erasmus University Medical Center. Retrieved from http://hdl.handle.net/1765/10864
Chicago Manual of Style (16th Edition):
Horst, Maarten. “Gene therapy of Maligant Gliomas.” 2008. Doctoral Dissertation, Erasmus University Medical Center. Accessed February 26, 2020.
http://hdl.handle.net/1765/10864.
MLA Handbook (7th Edition):
Horst, Maarten. “Gene therapy of Maligant Gliomas.” 2008. Web. 26 Feb 2020.
Vancouver:
Horst M. Gene therapy of Maligant Gliomas. [Internet] [Doctoral dissertation]. Erasmus University Medical Center; 2008. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/1765/10864.
Council of Science Editors:
Horst M. Gene therapy of Maligant Gliomas. [Doctoral Dissertation]. Erasmus University Medical Center; 2008. Available from: http://hdl.handle.net/1765/10864
9.
Schepper, Evelien.
Diagnostics in Low Back Pain.
Degree: 2016, Erasmus University Medical Center
URL: http://hdl.handle.net/1765/79497
► markdownabstractThe aim of the work presented in this thesis is to gain more insight into the diagnostic tools used in patients with low back pain.…
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▼ markdownabstractThe aim of the work presented in this thesis is to gain more insight into the diagnostic tools used in patients with low back pain.
In recent years, general practitioners in the Netherlands can refer low back pain patients for MRI of the lumbar spine themselves. However, data on the use of MRI by general practitioners in the Netherlands are still lacking. In the first part of this thesis, we examined how lumbar MRI is currently used by general practitioners in the Netherlands.
Identifying subgroups of patients for whom different treatments are superior has been referred to as the ‘Holy Grail’ of low back pain research. One of the possible subgroups based on pathoanatomical findings are patients with degeneration of the spine. In the second part of this thesis, we performed an epidemiological study on the characteristics of lumbar disc degeneration.
Subjects/Keywords: Low back pain; MRI; general practice; lumbar disc degeneration
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APA (6th Edition):
Schepper, E. (2016). Diagnostics in Low Back Pain. (Doctoral Dissertation). Erasmus University Medical Center. Retrieved from http://hdl.handle.net/1765/79497
Chicago Manual of Style (16th Edition):
Schepper, Evelien. “Diagnostics in Low Back Pain.” 2016. Doctoral Dissertation, Erasmus University Medical Center. Accessed February 26, 2020.
http://hdl.handle.net/1765/79497.
MLA Handbook (7th Edition):
Schepper, Evelien. “Diagnostics in Low Back Pain.” 2016. Web. 26 Feb 2020.
Vancouver:
Schepper E. Diagnostics in Low Back Pain. [Internet] [Doctoral dissertation]. Erasmus University Medical Center; 2016. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/1765/79497.
Council of Science Editors:
Schepper E. Diagnostics in Low Back Pain. [Doctoral Dissertation]. Erasmus University Medical Center; 2016. Available from: http://hdl.handle.net/1765/79497
10.
Arends, Lidia.
Multivariate meta-analysis: modelling the heterogeneity mixing apples and oranges; dangerous or delicious?.
Degree: 2006, Erasmus University Medical Center
URL: http://hdl.handle.net/1765/7845
► textabstractMeta-analysis may be broadly defined as the quantitative review and synthesis of the results of related but independent studies. For the simple case where meta-analysis…
(more)
▼ textabstractMeta-analysis may be broadly defined as the quantitative review and synthesis of the results of related but independent studies. For the simple case where meta-analysis concerns only one outcome measure in each study, the statistical methods are well established now. However, in many practical situations there are several outcome
measures presented in the individual studies included in a meta- analysis. In that case analyzing each outcome measure separately in a univariate manner is often suboptimal,
and analyzing all outcome measures jointly using multivariate methods is indicated. For many situations with multivariate outcome, appropriate meta-analytic
methods are still lacking or underdeveloped. The work presented in this thesis aims at the development of statistical methods that are suited to analyse meta-analytic data with a multivariate nature in a right and optimal way. With our proposed methods one can answer more comprehensive research questions than with the standard
univariate methods that are usually used in practice. Our explicit aim is that our suggested statistical methods are relatively easy to use for most researchers.
Chapter 1 is a general introduction to the topic of this thesis. In this chapter some basic terms from the field of meta-analysis are explained and an outline of the thesis is
given. The first situation of a meta-analysis with multivariate outcome in this thesis (Chapter 2) is the analysis of the relationship between treatment effect and baseline risk. A straightforward way of assessing this relationship is to compute the ordinary weighted least squares (WLS) regression line of the treatment effects estimated from the different trials on the estimated so called baseline risks observed in the control groups. This conventional method has potential pitfalls and has been seriously criticised. We propose another method based on a bivariate meta-analysis. Although we did most of the analyses using the BUGS implementation of Markov Chain Monte Carlo (MCMC) numerical integration techniques, we also show for one of the examples how it can be carried out with a general linear mixed model in SAS Proc Mixed. The advantage of using BUGS is that an exact measurement error model can be specified. On the other hand, in practice it is easier to use the procedure P!
roc Mixed of SAS.
In Chapter 3 we discuss the general linear mixed model as a natural and convenient framework for meta-analysis. It is thoroughly pointed out how many existing metaanalysis
methods can be carried out using Proc Mixed of SAS, one of the most important statistical packages. Thus far ad hoc programs had to be used. We discuss several methods to analyse univariate as well as bivariate outcomes in meta-analysis and meta-regression analysis. Several extensions of the models are presented, like exact likelihood, non-normal mixtures and multiple endpoints. All methods are
illustrated by a clinical meta-analysis example for which the complete syntax needed for the software program…
Subjects/Keywords: ROC curves; meta-analysis; multivariate; random effects; survival curves
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APA (6th Edition):
Arends, L. (2006). Multivariate meta-analysis: modelling the heterogeneity mixing apples and oranges; dangerous or delicious?. (Doctoral Dissertation). Erasmus University Medical Center. Retrieved from http://hdl.handle.net/1765/7845
Chicago Manual of Style (16th Edition):
Arends, Lidia. “Multivariate meta-analysis: modelling the heterogeneity mixing apples and oranges; dangerous or delicious?.” 2006. Doctoral Dissertation, Erasmus University Medical Center. Accessed February 26, 2020.
http://hdl.handle.net/1765/7845.
MLA Handbook (7th Edition):
Arends, Lidia. “Multivariate meta-analysis: modelling the heterogeneity mixing apples and oranges; dangerous or delicious?.” 2006. Web. 26 Feb 2020.
Vancouver:
Arends L. Multivariate meta-analysis: modelling the heterogeneity mixing apples and oranges; dangerous or delicious?. [Internet] [Doctoral dissertation]. Erasmus University Medical Center; 2006. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/1765/7845.
Council of Science Editors:
Arends L. Multivariate meta-analysis: modelling the heterogeneity mixing apples and oranges; dangerous or delicious?. [Doctoral Dissertation]. Erasmus University Medical Center; 2006. Available from: http://hdl.handle.net/1765/7845
11.
Mokhles, Mostafa.
Innovative Modeling of Outcome in Cardiac Surgery.
Degree: 2013, Erasmus University Medical Center
URL: http://hdl.handle.net/1765/50204
► markdownabstractIn the normal heart both left and right ventricle have a valve at the atrio-ventricular connection and at the ventriculo-arterial connection. In the left ventricle…
(more)
▼ markdownabstractIn the normal heart both left and right ventricle have a valve at the atrio-ventricular connection
and at the ventriculo-arterial connection. In the left ventricle the inflow valve is
the mitral valve and the outflow valve is the aortic valve. In the right ventricle the inflow
valve is the tricuspid valve and the outflow valve is the pulmonary valve. These heart
valves ascertain that blood only flows in one direction through the heart. The valves
are made of strong, thin flaps of tissue, called leaflets. The valves control the blood flow
through the heart by opening and closing the leaflets during the contractions of the
heart.
Heart valve disease occurs when one or more of the heart valves do not work correctly
because of valvular stenosis or valvular regurgitation, or a combination of the two. Valvular
stenosis occurs when a heart valve doesn’t fully open due to stiff or fused leaflets
or when a valve is congenitally too small. This limits the amount of blood that can flow
through the valve. Valvular regurgitation, also known as valvular insufficiency, occurs
when a valve does not close properly. This will lead to blood leaking back through the
valve when it should be closed. All four heart valves can develop stenosis, regurgitation
of a combination of both stenosis and regurgitation. In case heart valve disease is not
treated, it can have negative impact on a person’s quality of life and may even become
life-threatening. During the past decades, great advances in the surgical treatment of
heart valves disease have been achieved. This thesis will focus on the surgical treatment
of aortic and pulmonary valve disease.
Subjects/Keywords: cardiac surgery; cardiology; heart valve diseases
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APA (6th Edition):
Mokhles, M. (2013). Innovative Modeling of Outcome in Cardiac Surgery. (Doctoral Dissertation). Erasmus University Medical Center. Retrieved from http://hdl.handle.net/1765/50204
Chicago Manual of Style (16th Edition):
Mokhles, Mostafa. “Innovative Modeling of Outcome in Cardiac Surgery.” 2013. Doctoral Dissertation, Erasmus University Medical Center. Accessed February 26, 2020.
http://hdl.handle.net/1765/50204.
MLA Handbook (7th Edition):
Mokhles, Mostafa. “Innovative Modeling of Outcome in Cardiac Surgery.” 2013. Web. 26 Feb 2020.
Vancouver:
Mokhles M. Innovative Modeling of Outcome in Cardiac Surgery. [Internet] [Doctoral dissertation]. Erasmus University Medical Center; 2013. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/1765/50204.
Council of Science Editors:
Mokhles M. Innovative Modeling of Outcome in Cardiac Surgery. [Doctoral Dissertation]. Erasmus University Medical Center; 2013. Available from: http://hdl.handle.net/1765/50204
12.
Hoeboer, Sandra.
Biomarkers of infection and its complications in the critically ill.
Degree: 2015, Erasmus University Medical Center
URL: http://hdl.handle.net/1765/78231
► markdownabstract__Abstract__ Microbial infections, and associated complications, are still an important cause of intensive care (ICU) admissions and mortality Despite the use of antibiotics and guidelines…
(more)
▼ markdownabstract__Abstract__
Microbial infections, and associated complications, are still an important cause of
intensive care (ICU) admissions and mortality Despite the use of antibiotics and
guidelines for supportive care mortality rates are up to 50% depending on disease
severity. The most widely accepted definitions for infection are those of the “International
Sepsis Forum Consensus Conference on Definitions of Infection in the Intensive
Care Unit” (ISFCC).8 According to ISFCC criteria the likelihood of infection is based
mainly on clinical suspicion and/or microbiological cultures.
In clinical practice new onset fever, leukocytosis, tachypnea, tachycardia and elevated
C-reactive protein (CRP) levels raise suspicion about the presence of infectious
disease. They are, however, markers of host inflammation and their value for the
definite diagnosis of infection has considerable limitations, especially in the ICU.
The combination of fever, leukocytosis, tachypnea and tachycardia is considered the
systemic inflammatory response syndrome to infection (SIRS). An infection in the
presence of SIRS is called sepsis (Table 1). The adverse sequelae of infection: sepsis,
septic shock, and organ failure, are partly caused by this host inflammatory response
and each negatively influences outcome. In fear of undertreatment physicians
repeatedly order cultures and start broad spectrum, empiric antibiotic treatment.
However, overtreatment unnecessarily exposes patients to the risk of adverse drug
reactions, amongst other risks. Prolonged antibiotic therapy also results in bacterial
selection in individual patients and microbial resistance on a population level
Subjects/Keywords: biomarkers; infectious diseases; microbial infections
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APA (6th Edition):
Hoeboer, S. (2015). Biomarkers of infection and its complications in the critically ill. (Doctoral Dissertation). Erasmus University Medical Center. Retrieved from http://hdl.handle.net/1765/78231
Chicago Manual of Style (16th Edition):
Hoeboer, Sandra. “Biomarkers of infection and its complications in the critically ill.” 2015. Doctoral Dissertation, Erasmus University Medical Center. Accessed February 26, 2020.
http://hdl.handle.net/1765/78231.
MLA Handbook (7th Edition):
Hoeboer, Sandra. “Biomarkers of infection and its complications in the critically ill.” 2015. Web. 26 Feb 2020.
Vancouver:
Hoeboer S. Biomarkers of infection and its complications in the critically ill. [Internet] [Doctoral dissertation]. Erasmus University Medical Center; 2015. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/1765/78231.
Council of Science Editors:
Hoeboer S. Biomarkers of infection and its complications in the critically ill. [Doctoral Dissertation]. Erasmus University Medical Center; 2015. Available from: http://hdl.handle.net/1765/78231
13.
Koel, Björn.
The molecular basis of influenza virus antigenic change: De moleculaire basis van de antigene evolutie van influenzavirus.
Degree: 2016, Erasmus University Medical Center
URL: http://hdl.handle.net/1765/80138
► markdownabstractInfluenza viruses escape antibody-mediated neutralization by accumulating amino acid substitutions in the hemagglutinin surface protein, necessitating frequent updates of the influenza vaccine. Previous studies identified…
(more)
▼ markdownabstractInfluenza viruses escape antibody-mediated neutralization by accumulating amino acid substitutions in the hemagglutinin surface protein, necessitating frequent updates of the influenza vaccine. Previous studies identified more than 130 potentially important amino acid positions that could cause antibody escape upon mutation. The 20 amino acids that could theoretically occupy each of these positions imply a seemingly endless number of possibilities to escape from antibody recognition. For this thesis the exact amino acid changes responsible for antigenic change of influenza viruses in the past were identified, with the ultimate goal to provide new insights in the evolution of influenza viruses that will help to improve selection of vaccine strains.
All major antigenic differences were due to one or very few substitutions on a small number of key positions near the domain ofthe hemagglutinin responsible for binding to the host cell, and generally involved substantial alterations of the biophysical properties of the amino acids. It was shown that the ability of key substitutions to cause antigenic change is largely independent of the amino acid context, and that substitutions similar to those that caused antibody escape in the past are potentially important for future antigenic change of the influenza viruses responsible for the 2009 influenza pandemic.
These results indicate that the possibilities for influenza viruses to escape antibody-mediated neutralization are limited and that genetically vastly different influenza viruses have analogous ways to change antigenically. The small number of critical positions and restricted amino acid usage decimates the number of possible escape variants from thousands to dozens and thus substantially increases the possibility to predict the antigenic component of influenza virus evolution.
Subjects/Keywords: virology; influenza virus; antibody escape; antigenic evolution
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APA (6th Edition):
Koel, B. (2016). The molecular basis of influenza virus antigenic change: De moleculaire basis van de antigene evolutie van influenzavirus. (Doctoral Dissertation). Erasmus University Medical Center. Retrieved from http://hdl.handle.net/1765/80138
Chicago Manual of Style (16th Edition):
Koel, Björn. “The molecular basis of influenza virus antigenic change: De moleculaire basis van de antigene evolutie van influenzavirus.” 2016. Doctoral Dissertation, Erasmus University Medical Center. Accessed February 26, 2020.
http://hdl.handle.net/1765/80138.
MLA Handbook (7th Edition):
Koel, Björn. “The molecular basis of influenza virus antigenic change: De moleculaire basis van de antigene evolutie van influenzavirus.” 2016. Web. 26 Feb 2020.
Vancouver:
Koel B. The molecular basis of influenza virus antigenic change: De moleculaire basis van de antigene evolutie van influenzavirus. [Internet] [Doctoral dissertation]. Erasmus University Medical Center; 2016. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/1765/80138.
Council of Science Editors:
Koel B. The molecular basis of influenza virus antigenic change: De moleculaire basis van de antigene evolutie van influenzavirus. [Doctoral Dissertation]. Erasmus University Medical Center; 2016. Available from: http://hdl.handle.net/1765/80138
14.
Raats, Jelle.
Frailty and Delirium in the Elderly Surgical Patient.
Degree: 2017, Erasmus University Medical Center
URL: http://hdl.handle.net/1765/94835
markdownabstractThe aims of the research in this thesis were to explore the role of conservative therapies in frail elderly patients in need for (extensive) surgery.
Also, delirium incidence and predictive factors of delirium in elderly patients having surgery were examined.
Subjects/Keywords: Frailty; delirium; elderly; surgery; vascular surgery; predictive factors; conservative treatment
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APA (6th Edition):
Raats, J. (2017). Frailty and Delirium in the Elderly Surgical Patient. (Doctoral Dissertation). Erasmus University Medical Center. Retrieved from http://hdl.handle.net/1765/94835
Chicago Manual of Style (16th Edition):
Raats, Jelle. “Frailty and Delirium in the Elderly Surgical Patient.” 2017. Doctoral Dissertation, Erasmus University Medical Center. Accessed February 26, 2020.
http://hdl.handle.net/1765/94835.
MLA Handbook (7th Edition):
Raats, Jelle. “Frailty and Delirium in the Elderly Surgical Patient.” 2017. Web. 26 Feb 2020.
Vancouver:
Raats J. Frailty and Delirium in the Elderly Surgical Patient. [Internet] [Doctoral dissertation]. Erasmus University Medical Center; 2017. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/1765/94835.
Council of Science Editors:
Raats J. Frailty and Delirium in the Elderly Surgical Patient. [Doctoral Dissertation]. Erasmus University Medical Center; 2017. Available from: http://hdl.handle.net/1765/94835
15.
Witjes, Carlijn.
New Insights in Hepatocellular Carcinoma.
Degree: 2012, Erasmus University Medical Center
URL: http://hdl.handle.net/1765/37371
► textabstractHepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third most common cause of cancer mortality. HCC is one of the few…
(more)
▼ textabstractHepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the
third most common cause of cancer mortality. HCC is one of the few cancers with
well-defined major risk factors. Worldwide, in 80% of the cases HCC develops in
cirrhotic livers, and cirrhosis is the strongest predisposing factor. The incidence
is high in Asia and parts of Africa. Geographical differences in incidence reflect
variations of the main causal factors such as hepatitis B virus infection (HBV) which is
common in Asia and Africa. HBV infection leads to the development of HCC through
direct and indirect pathways. Being an oncogenic virus, it can cause HCC in the absence
of cirrhosis, as it has the ability to integrate into the host genome affecting cellular
signalling and growth control.
Another unique feature of HCC is that it is a vaccine preventable disease. Implementation
of a nationwide HBV vaccination programme for newborns in Taiwan has
convincingly demonstrated a drop in the incidence of HCC in the years thereafter. In
Japan, Europe, and the United States about 60% of the patients with HCC are attributed
to chronic hepatitis C virus (HCV) infection, 20% are attributed to chronic HBV infection
and about 20% are equally divided between cryptogenic and alcoholic liver disease.
Hepatitis C as an infection transmitted by blood or plasma products before 1990 and
is an important factor in the development of HCC in western countries. HCV causes
HCC mainly through indirect pathways: chronic inflammation, cell deaths, and regeneration.
In the pathogenesis the concurrent presence of the use of alcohol, the presence
of diabetes and overweight play also an important role as a co-factor in HCV infection.
Subjects/Keywords: Hepatocellular Carcinoma; gastroenterology; geographical differences; liver cancer
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APA (6th Edition):
Witjes, C. (2012). New Insights in Hepatocellular Carcinoma. (Doctoral Dissertation). Erasmus University Medical Center. Retrieved from http://hdl.handle.net/1765/37371
Chicago Manual of Style (16th Edition):
Witjes, Carlijn. “New Insights in Hepatocellular Carcinoma.” 2012. Doctoral Dissertation, Erasmus University Medical Center. Accessed February 26, 2020.
http://hdl.handle.net/1765/37371.
MLA Handbook (7th Edition):
Witjes, Carlijn. “New Insights in Hepatocellular Carcinoma.” 2012. Web. 26 Feb 2020.
Vancouver:
Witjes C. New Insights in Hepatocellular Carcinoma. [Internet] [Doctoral dissertation]. Erasmus University Medical Center; 2012. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/1765/37371.
Council of Science Editors:
Witjes C. New Insights in Hepatocellular Carcinoma. [Doctoral Dissertation]. Erasmus University Medical Center; 2012. Available from: http://hdl.handle.net/1765/37371
16.
Verweij, Marielle.
Genetic and Nutritional Preconditioning against Ischemia/Reperfusion Injury.
Degree: 2011, Erasmus University Medical Center
URL: http://hdl.handle.net/1765/30631
► textabstractOrgan transplantation is considered to be one of the greatest achievements in modern medicine during the last decades. Improvements in tissue typing for the human…
(more)
▼ textabstractOrgan transplantation is considered to be one of the greatest achievements in modern medicine during the last decades. Improvements in tissue typing for the human leukocyte antigens (HLA) class II antigens, organ preservation, surgery, and the use of immunosuppressive drugs made organ transplantation the treatment of choice for patients with end-stage organ failure.
The success of organ transplantation has led to a marked increase in the number of transplantations. However, with only a limited number of transplantable organs available from living donors, the demand for donor organs has far exceeded the supply. To expand the organ donor pool, the transplant community searched for alternatives e.g. through the use of donors after cardiac death. Organs donated after cardiac death are considered less than optimal. The extended time from the termination of the circulation, to the actual moment of death, to organ recovery, and, finally, to the initiation of perfusion with cold preservation solutions results in the initiation of irreversible ischemia/reperfusion (I/R) injury. On transplantation in the recipient, reperfusion of the graft triggers apoptotic cell death, and promotes the activation of an inflammatory response, resulting in profound injury of the graft. Hence, I/R injury is considered a risk factor for the development of delayed graft function, primary non-function, and acute rejection of the graft.
The treatment of I/R injury is still unsatisfactory. Therefore, new therapeutic interventions to reduce or prevent I/R injury remain warranted.
The studies in this thesis describe two novel treatments to ameliorate I/R injury: genetic and nutritional preconditioning.
Subjects/Keywords: Cockayne syndrome; Ischemia/Reperfusion Injury; dietary restriction; fasting; glucose; hepatectomy; kidney; liver; mice; mitochondria
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APA (6th Edition):
Verweij, M. (2011). Genetic and Nutritional Preconditioning against Ischemia/Reperfusion Injury. (Doctoral Dissertation). Erasmus University Medical Center. Retrieved from http://hdl.handle.net/1765/30631
Chicago Manual of Style (16th Edition):
Verweij, Marielle. “Genetic and Nutritional Preconditioning against Ischemia/Reperfusion Injury.” 2011. Doctoral Dissertation, Erasmus University Medical Center. Accessed February 26, 2020.
http://hdl.handle.net/1765/30631.
MLA Handbook (7th Edition):
Verweij, Marielle. “Genetic and Nutritional Preconditioning against Ischemia/Reperfusion Injury.” 2011. Web. 26 Feb 2020.
Vancouver:
Verweij M. Genetic and Nutritional Preconditioning against Ischemia/Reperfusion Injury. [Internet] [Doctoral dissertation]. Erasmus University Medical Center; 2011. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/1765/30631.
Council of Science Editors:
Verweij M. Genetic and Nutritional Preconditioning against Ischemia/Reperfusion Injury. [Doctoral Dissertation]. Erasmus University Medical Center; 2011. Available from: http://hdl.handle.net/1765/30631
17.
Meyer, Zainna.
Biochemical markers in the surgical intensive care: Identifying critically ill surgical patients with complications.
Degree: 2015, Erasmus University Medical Center
URL: http://hdl.handle.net/1765/78340
► markdownabstract__Abstract__ Introductie Patiënten die postoperatief op de intensive care (IC) worden opgenomen hebben een hogere kans op het ontwikkelen van complicaties. Het is belangrijk om…
(more)
▼ markdownabstract__Abstract__
Introductie
Patiënten die postoperatief op de intensive care (IC) worden opgenomen hebben een hogere kans op het ontwikkelen van complicaties. Het is belangrijk om deze complicaties vroegtijdig te kunnen identificeren bij de kritiek zieke chirurgische patiënten op de IC om tijdig adequate therapie te kunnen starten. Hierom bestudeerden wij de klinische voorspellende waarde van dagelijks gebruikte biomarkers C-reactief proteïne CRP), lactaat, procalcitonine (PCT) en de Sequential Organ Failure Assessment score (SOAF) bij het aantonen van chirurgische complicaties bij de algemene postoperatieve patiënt tijdens de IC-opname.
Resultaten
Er wordt geen significante correlatie tussen stijging van CRP en interventies gevonden. Dit bevestigd het vermoeden dat artsen vaak getriggerd worden door deze markers om interventies te verrichten bij de kritiek zieke postoperatieve patiënten. Toch wordt er geen relatie gevonden tussen stijging in CRP-concentraties en chirurgische complicaties. Wanneer gekeken wordt naar het gebruik van lactaat als voorspeller van complicaties, dan vinden we dat dit marker ook geen geschikt prognostisch instrument is voor chirurgische complicaties op de IC.
Een relatief nieuwere maker is procalcitonine. Ondanks resultaten in eerder studies welke een positieve correlatie tussen PCT-stijging en complicaties toonden, konden we dit niet reproduceren in onze groep algemeen chirurgische patiënten op de IC. In deze studie konden we de conclusie trekken dat PCT geen geschikte marker is om chirurgische complicaties in een heterogene kritiek zieke postoperatieve groep patiënten op de IC te identificeren.
Indien we alle parameters in een regressie model combineren, dan bevestigt het model de eerdere bevindingen waarbij geen enkel parameter afzonderlijk adequaat blijkt te zijn om die kritiek zieke patiënt met verhoogd kans op complicaties te identificeren. Het model benadrukt dat zelfs bij een combinatie van parameters er geen betere voorspellende waardes voor chirurgische complicaties kan worden bereikt bij het gebruik van de huidige biomarkers.
Conclusie
Tot heden worden artsen duidelijk getriggerd door parameters zoals C-reactief proteïne,
lactaat, procalcitonine en het klinische scoringssysteem Sequential Organ Failure
Assessment Score. Echter, deze markers zijn niet geschikt als prognostische testen voor
de vroegtijdige identificatie van chirurgische complicaties in kritiek zieke chirurgische patiënten tijdens de intensive care opname.
Subjects/Keywords: Surgical; complication; critically ill; intensive care; c-reactive protein; procalcitonin; lactate
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APA (6th Edition):
Meyer, Z. (2015). Biochemical markers in the surgical intensive care: Identifying critically ill surgical patients with complications. (Doctoral Dissertation). Erasmus University Medical Center. Retrieved from http://hdl.handle.net/1765/78340
Chicago Manual of Style (16th Edition):
Meyer, Zainna. “Biochemical markers in the surgical intensive care: Identifying critically ill surgical patients with complications.” 2015. Doctoral Dissertation, Erasmus University Medical Center. Accessed February 26, 2020.
http://hdl.handle.net/1765/78340.
MLA Handbook (7th Edition):
Meyer, Zainna. “Biochemical markers in the surgical intensive care: Identifying critically ill surgical patients with complications.” 2015. Web. 26 Feb 2020.
Vancouver:
Meyer Z. Biochemical markers in the surgical intensive care: Identifying critically ill surgical patients with complications. [Internet] [Doctoral dissertation]. Erasmus University Medical Center; 2015. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/1765/78340.
Council of Science Editors:
Meyer Z. Biochemical markers in the surgical intensive care: Identifying critically ill surgical patients with complications. [Doctoral Dissertation]. Erasmus University Medical Center; 2015. Available from: http://hdl.handle.net/1765/78340
18.
Lafranca, Jeffrey.
Shifting Paradigms in Live Kidney Donation and Transplantation.
Degree: 2015, Erasmus University Medical Center
URL: http://hdl.handle.net/1765/78303
► markdownabstract__Abstract__ Although patients with end-stage renal disease (ESRD) can be successfully treated with haemodialysis or peritoneal dialysis, kidney transplantation is by far the best therapeutic…
(more)
▼ markdownabstract__Abstract__
Although patients with end-stage renal disease (ESRD) can be successfully treated with haemodialysis or peritoneal dialysis, kidney transplantation is by far the best therapeutic option for the majority of patients with ESRD. Regretfully, the shortage in donor organs prevails. Despite an impressive societal and governmental investment, the number of deceased donor kidneys that becomes available for transplantation remains insufficient to meet the demand. One of the solutions to this problem is live kidney donation. The advantages of live donor kidney transplantation are numerous and include, among others, that it is an elective operation with short ischemia times. Furthermore, in this way, transplant professionals are able to select good quality kidneys of healthy donors. A uniform approach in the selection of live kidney donors is especially important since the community is seeking for options to further expand the donor pool. Currently, there is a tendency towards accepting so called ‘extended criteria live kidney donors’, which this thesis is about.
Subjects/Keywords: Live kidney donation; transplantation; extended criteria donors
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APA (6th Edition):
Lafranca, J. (2015). Shifting Paradigms in Live Kidney Donation and Transplantation. (Doctoral Dissertation). Erasmus University Medical Center. Retrieved from http://hdl.handle.net/1765/78303
Chicago Manual of Style (16th Edition):
Lafranca, Jeffrey. “Shifting Paradigms in Live Kidney Donation and Transplantation.” 2015. Doctoral Dissertation, Erasmus University Medical Center. Accessed February 26, 2020.
http://hdl.handle.net/1765/78303.
MLA Handbook (7th Edition):
Lafranca, Jeffrey. “Shifting Paradigms in Live Kidney Donation and Transplantation.” 2015. Web. 26 Feb 2020.
Vancouver:
Lafranca J. Shifting Paradigms in Live Kidney Donation and Transplantation. [Internet] [Doctoral dissertation]. Erasmus University Medical Center; 2015. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/1765/78303.
Council of Science Editors:
Lafranca J. Shifting Paradigms in Live Kidney Donation and Transplantation. [Doctoral Dissertation]. Erasmus University Medical Center; 2015. Available from: http://hdl.handle.net/1765/78303
19.
Leur, Kevin.
Surgery in the Elderly: Does age matter?.
Degree: 2015, Erasmus University Medical Center
URL: http://hdl.handle.net/1765/78238
► markdownabstractDe demografische verschuiving in het aantal ouderen zorgt voor een oudere behandelgroep. De chirurgische behandeling van vasculaire en trauma gerelateerde aandoeningen in deze oudere populatie…
(more)
▼ markdownabstractDe demografische verschuiving in het aantal ouderen zorgt voor een oudere behandelgroep. De chirurgische behandeling van vasculaire en trauma gerelateerde aandoeningen in deze oudere populatie is niet eenvoudig. Zorgvuldige patiëntselectie zou wel eens de sleutel kunnen zijn tot betere behandelresultaten van vasculaire en trauma gerelateerde aandoeningen binnen deze oudere bevolkingsgroep.
Het eerste deel van dit proefschrift bespreekt de uitkomst van verschillende vasculaire chirurgische interventies. Oudere dialysepatiënten zijn wellicht beter af zijn met een elleboogshunt gezien de betere patency, hoewel de kwaliteit van leven hierbij nog nader onderzocht dient te worden. Verder wordt aangetoond dat de mortaliteit van perifere bypass chirurgie bij met name 80-plussers erg hoog is met een postoperatieve sterfte van 22%. Met betrekking tot de behandeling van een abdominaal aneurysma is de mortaliteit na electieve endovasculaire behandeling van een abdominaal aneurysma bij patiënten ouder dan 80 jaar significant hoger in vergelijking met een jongere groep, echter als we de mortaliteit van deze behandeling vergelijken met de in de literatuur beschreven mortaliteit na open behandeling van een abdominaal aneurysma lijkt een endovasculaire behandeling in deze populatie gerechtvaardigd.
In het tweede deel worden uitkomsten van verschillende trauma gerelateerde chirurgische behandelingen besproken. De vergrijzing zorgt voor een toename van het aantal ziekenhuisopnames ten gevolge van een bekkenfractuur, om gerelateerde kosten voor de gezondheidszorg in de toekomst te reduceren blijft preventie van vallen bij ouderen en osteoporosescreening belangrijk. Verder zijn de uitkomsten van chirurgische behandeling van een proximale humerusfracturen bij ouderen onderzocht en wordt geconcludeerd dat het veilig en verantwoord is om een osteosynthese van een ernstig gedisloceerde proximale humerusfractuur te verrichtten bij geselecteerde patiënten van 75 jaar en ouder. Tot slot laat dit proefschrift zien dat de mortaliteit na chirurgische behandeling van een heupfractuur bij patiënten van 90 jaar en ouder een mortaliteit kent van 23% in de eerste 3 maanden en dat een heupfractuur bij hoogbejaarde personen grote impact heeft op de mate van onafhankelijk van deze populatie.
Dit proefschrift toont aan dat de oudere patiëntenpopulatie een zeer specifieke groep patiënten is, waarvan de behandeling niet eenvoudig is en moet worden afgestemd op de individuele patiënt. Het blijft moeilijk om co morbiditeit uit te drukken in een specifieke score en zodoende te voorspellen wat het sterfterisico is van een bepaalde behandeling. De ontwikkeling van een beter instrument voor het inschatten van het sterfterisico van chirurgische behandeling is aanbevolen. Verder is er in het algemeen meer aandacht nodig voor het effect van chirurgische behandeling op kwaliteit van leven van de oudere patiëntpopulatie.
Subjects/Keywords: Surgery; Elderly; AAA; dialysis shunt; critical limb ischemia; pelvic fracture; humerus fracture; hip fracture
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APA (6th Edition):
Leur, K. (2015). Surgery in the Elderly: Does age matter?. (Doctoral Dissertation). Erasmus University Medical Center. Retrieved from http://hdl.handle.net/1765/78238
Chicago Manual of Style (16th Edition):
Leur, Kevin. “Surgery in the Elderly: Does age matter?.” 2015. Doctoral Dissertation, Erasmus University Medical Center. Accessed February 26, 2020.
http://hdl.handle.net/1765/78238.
MLA Handbook (7th Edition):
Leur, Kevin. “Surgery in the Elderly: Does age matter?.” 2015. Web. 26 Feb 2020.
Vancouver:
Leur K. Surgery in the Elderly: Does age matter?. [Internet] [Doctoral dissertation]. Erasmus University Medical Center; 2015. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/1765/78238.
Council of Science Editors:
Leur K. Surgery in the Elderly: Does age matter?. [Doctoral Dissertation]. Erasmus University Medical Center; 2015. Available from: http://hdl.handle.net/1765/78238
20.
Slagt, Inez.
Urological Complications in Kidney Transplantation.
Degree: 2015, Erasmus University Medical Center
URL: http://hdl.handle.net/1765/77557
► markdownabstract__Abstract__ The kidney is an essential organ that plays an crucial role in acid-base balance, sodium and potassium balance, calcium metabolism, regulation of blood pressure,…
(more)
▼ markdownabstract__Abstract__
The kidney is an essential organ that plays an crucial role in acid-base balance, sodium
and potassium balance, calcium metabolism, regulation of blood pressure, red blood
cell synthesis and excretion of metabolites. Kidney diseases may result in kidney failure
with the requirement of kidney replacement therapy like dialysis. Hemodialysis and
peritoneal dialysis may extend patient survival but does not cure the kidney failure.
Kidney transplantation is considered the optimal kidney replacement therapy for
patients with end stage kidney failure, resulting in decreased morbidity, improved
quality of life and higher costs effectiveness when compared to dialysis.
In the early years of experimental kidney transplantation, donor kidneys were placed in
the thigh with cutaneous ureterostomy drainage or in the iliac fossa with drainage by
ureteroureterostomy to the recipient native ureter. In January 1951, Rene Kuss placed a
donor kidney into the iliopelvic region of the recipient with cutaneous ureterostomy.1, 2
Soon thereafter another French surgical team established the concept that a kidney placed
in the iliac fossa provides a short ureter with possibilities for drainage to the bladder.
Although these early attempts of kidney transplantation resulted in failure, Joseph
Murray and John Hartwell Harrison completed the first successful kidney transplantation
on identical twins in Boston on December 23, 1954.3 The recipient was prepared with
hemodialysis, and monozygosity was confirmed by the successful exchange of full
thickness skin grafts between the twins. The left donor kidney was transplanted in the
right recipient’s iliac fossa, and a intravesical ureteroneocystostomy with a submucosal
tunnel was established. A small polyethylene catheter was placed up the transplant
ureter and was suprapubicly externalized. After renal vascularization by doctor Murray,
doctor Harrison assisted with the urinary tract reconstruction. The kidney functioned
directly after transplantation and the patient was discharged on day 37 postoperative.
The kidney function maintained good and was functioning until cardiac death 8 years
later occur.4 This successful transplantation between identical twins enhanced the
opinion that the pelvic location with possibilities of bladder drainage was the most
physiological and natural position for the kidney graft.1 Nevertheless, the intervention
of adequate immunosuppressive therapy in the 1960s enabled kidney transplantation
on a larger scale.
Subjects/Keywords: kidney transplantation; urology; kidney failure; quality of life; cost effectiveness; hemodialysis
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APA (6th Edition):
Slagt, I. (2015). Urological Complications in Kidney Transplantation. (Doctoral Dissertation). Erasmus University Medical Center. Retrieved from http://hdl.handle.net/1765/77557
Chicago Manual of Style (16th Edition):
Slagt, Inez. “Urological Complications in Kidney Transplantation.” 2015. Doctoral Dissertation, Erasmus University Medical Center. Accessed February 26, 2020.
http://hdl.handle.net/1765/77557.
MLA Handbook (7th Edition):
Slagt, Inez. “Urological Complications in Kidney Transplantation.” 2015. Web. 26 Feb 2020.
Vancouver:
Slagt I. Urological Complications in Kidney Transplantation. [Internet] [Doctoral dissertation]. Erasmus University Medical Center; 2015. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/1765/77557.
Council of Science Editors:
Slagt I. Urological Complications in Kidney Transplantation. [Doctoral Dissertation]. Erasmus University Medical Center; 2015. Available from: http://hdl.handle.net/1765/77557
21.
Marck, Claudia.
Assessing Barriers to the Involvement of Emergency Departments
in Organ Donation.
Degree: 2015, Erasmus University Medical Center
URL: http://hdl.handle.net/1765/77466
► markdownabstract__Abstract__ Organ transplantation has become increasingly successful in terms of patient survival and is currently the best treatment option for patients with organ failure. With…
(more)
▼ markdownabstract__Abstract__
Organ transplantation has become increasingly successful in terms of patient survival and
is currently the best treatment option for patients with organ failure. With living donor
opportunities only being available for certain organs, most efforts are aimed to increase
donation rates from deceased donors. In various countries, including the Netherlands and
Australia the government has implemented reforms with an aim to increase the number of
organ donations for life saving transplants. In this thesis the Australian approach is being
analysed and compared to the management of organ donation in the Netherlands, and the
involvement of ED clinicians in Australia is analysed in detail in order to find methods that
can be used to optimize the donation rate.
Australia has historically had sub-optimal deceased donation rates and family consent
rates compared to other countries in the developed world. Following the introduction of a
national reform agenda in 2008 and the establishment of the DonateLife network in 2009
the number of organ donors has increased from 11.4 donors per million people in 2009
to 16.9 in 2013, a 48% increase. However, the number of people on the waiting list for
an organ transplant has only decreased slightly from 1768 in 2009 to 1556 in 2013 and
therefore the search for strategies to increase deceased donation continues.
Subjects/Keywords: organ donation; organ transplantation
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APA (6th Edition):
Marck, C. (2015). Assessing Barriers to the Involvement of Emergency Departments
in Organ Donation. (Doctoral Dissertation). Erasmus University Medical Center. Retrieved from http://hdl.handle.net/1765/77466
Chicago Manual of Style (16th Edition):
Marck, Claudia. “Assessing Barriers to the Involvement of Emergency Departments
in Organ Donation.” 2015. Doctoral Dissertation, Erasmus University Medical Center. Accessed February 26, 2020.
http://hdl.handle.net/1765/77466.
MLA Handbook (7th Edition):
Marck, Claudia. “Assessing Barriers to the Involvement of Emergency Departments
in Organ Donation.” 2015. Web. 26 Feb 2020.
Vancouver:
Marck C. Assessing Barriers to the Involvement of Emergency Departments
in Organ Donation. [Internet] [Doctoral dissertation]. Erasmus University Medical Center; 2015. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/1765/77466.
Council of Science Editors:
Marck C. Assessing Barriers to the Involvement of Emergency Departments
in Organ Donation. [Doctoral Dissertation]. Erasmus University Medical Center; 2015. Available from: http://hdl.handle.net/1765/77466
22.
Windt, Dirk.
Islet Xenotransplantation: toward a cure for diabetes.
Degree: 2011, Erasmus University Medical Center
URL: http://hdl.handle.net/1765/23681
► textabstractThe pancreas is an organ with a central anatomical position in the abdomen, and a central role in the processes of food digestion and glucose…
(more)
▼ textabstractThe pancreas is an organ with a central anatomical position in the abdomen,
and a central role in the processes of food digestion and glucose metabolism.
The vast majority of pancreatic tissue (more than 98%) is dedicated to the
production and secretion of digestive enzymes that are released into the
proximal small intestine, and therefore has an exocrine function. The remaining
1-2% is composed of cells producing mainly insulin (by beta cells) and glucagon
(by alpha cells), hormones that are released into the bloodstream to regulate
blood glucose levels. This small part of the pancreas therefore has an endocrine
function. Those hormone-producing cells are organized in small clusters that
appear as ‘small islands’ (islets) in the ‘sea’ of exocrine tissue (Figure 1), as
first described by a German pathologist, Paul Langerhans, in 1869 while he
was still a medical student, although at that time he was unaware of their
function. When later their crucial role in glucose metabolism was discovered,
they became known as islets of Langerhans, in the fields of diabetes and
transplantation (Tx) simply referred to as ‘islets’.
Subjects/Keywords: diabetes; gastroenterology; islets of Langerhans
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APA (6th Edition):
Windt, D. (2011). Islet Xenotransplantation: toward a cure for diabetes. (Doctoral Dissertation). Erasmus University Medical Center. Retrieved from http://hdl.handle.net/1765/23681
Chicago Manual of Style (16th Edition):
Windt, Dirk. “Islet Xenotransplantation: toward a cure for diabetes.” 2011. Doctoral Dissertation, Erasmus University Medical Center. Accessed February 26, 2020.
http://hdl.handle.net/1765/23681.
MLA Handbook (7th Edition):
Windt, Dirk. “Islet Xenotransplantation: toward a cure for diabetes.” 2011. Web. 26 Feb 2020.
Vancouver:
Windt D. Islet Xenotransplantation: toward a cure for diabetes. [Internet] [Doctoral dissertation]. Erasmus University Medical Center; 2011. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/1765/23681.
Council of Science Editors:
Windt D. Islet Xenotransplantation: toward a cure for diabetes. [Doctoral Dissertation]. Erasmus University Medical Center; 2011. Available from: http://hdl.handle.net/1765/23681
23.
Meijer, Vincent.
Fatty Liver: Risks, Regulation and Reversibility.
Degree: Department of Surgery, 2011, Erasmus University Medical Center
URL: http://hdl.handle.net/1765/23495
► textabstractHet doel van de studies die uitmaken van dit proefschrift is om de morbiditeits- en mortaliteitsrisico’s te onderzoeken van patienten met steatose die leverchirurgie ondergaan;…
(more)
▼ textabstractHet doel van de studies die uitmaken van dit proefschrift is om de
morbiditeits- en mortaliteitsrisico’s te onderzoeken van patienten met
steatose die leverchirurgie ondergaan; om het natuurlijk beloop van
niet-alcoholische leververvetting (NAFLD) en obesitas (zwaarlijvigheid) en
de effecten van een voedingsinterventie te onderzoeken in een diermodel;
en om nieuwe farmacologische behandelingen voor NAFLD te identificeren en
te testen. Op experimentele wijze door middel van het gebruik van modellen
van dieet-geinduceerde obesitas en leversteatose in de muis geeft dit
proefschrift nieuwe inzichten in de risico’s, regulering en
omkeerbaarheid van NAFLD.
CONCLUSIES:
Hoofdstuk 2: Na leverchirurgie hebben patienten met leversteatose een ruim
tweemaal verhoogd risico op postoperatieve complicaties en hebben mensen
met overmatige leversteatose een bijna driemaal verhoogd risico om te
overlijden.
Hoofdstuk 3: Het vetgehalte in het dieet is een belangrijke factor in de
ontwikkeling van leversteatose, obesitas en insulineresistentie in de
muis, onafhankelijk van calorische consumptie. Dit werd onder andere
veroorzaakt door een verhoogde opname van vrije vetzuren door de lever en
een verhoogde de novo lipogenese. Tevens konden al deze kenmerken van het
metabole syndroom succesvol worden omgekeerd wanneer obese muizen een
standaard, laag vet dieet werden gevoerd.
Hoofdstuk 4: Obesitas-geinduceerde veranderingen in genexpressieniveaus
van MMP’s in lever- en vetweefsel van obese muizen kunnen bijdragen aan
het ontstaan van veranderingen in de extracellulaire matrix, potentieel
leidend tot een verhoogde kans op het ontwikkelen van fibrose.
Hoofdstuk 5: Behandeling met een farmacologische MMP and TACE-remmer
verbeterde insulinegevoeligheid en keerde leversteatose om in muismodellen
van zowel dieet-geinduceerde obesitas als leptinedeficientie, resulterend
in een afname van postoperatieve leverenzymstoornissen na leverchirurgie.
Hoofdstuk 6: Het gebruik van een orofaryngeale maagknopsonde als methode
van medicijntoediening leidt tot stress, waardoor de ontwikkeling van
leversteatose en het bijbehorende metabool syndroom negatief werd
beinvloed in een muismodel van dieet-geinduceerde obesitas.
Hoofdstuk 7: Effectieve remming van MMP en TACE activiteit tijdens het
toedienen van chronische, toxische leverschade antagoneert de gunstige,
anti-inflammatoire werking resulterend in een versnelde ontwikkeling van
fibrose.
Subjects/Keywords: MMP; fatty liver; fibrosis; obesity; steatosis; tumor necrosis factor alpha converting enzyme
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APA (6th Edition):
Meijer, V. (2011). Fatty Liver: Risks, Regulation and Reversibility. (Doctoral Dissertation). Erasmus University Medical Center. Retrieved from http://hdl.handle.net/1765/23495
Chicago Manual of Style (16th Edition):
Meijer, Vincent. “Fatty Liver: Risks, Regulation and Reversibility.” 2011. Doctoral Dissertation, Erasmus University Medical Center. Accessed February 26, 2020.
http://hdl.handle.net/1765/23495.
MLA Handbook (7th Edition):
Meijer, Vincent. “Fatty Liver: Risks, Regulation and Reversibility.” 2011. Web. 26 Feb 2020.
Vancouver:
Meijer V. Fatty Liver: Risks, Regulation and Reversibility. [Internet] [Doctoral dissertation]. Erasmus University Medical Center; 2011. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/1765/23495.
Council of Science Editors:
Meijer V. Fatty Liver: Risks, Regulation and Reversibility. [Doctoral Dissertation]. Erasmus University Medical Center; 2011. Available from: http://hdl.handle.net/1765/23495
24.
Ginhoven, Tessa.
Beneficial Effects of Preoperative Dietary Restriction.
Degree: 2011, Erasmus University Medical Center
URL: http://hdl.handle.net/1765/22970
► textabstractPeople have always been searching for methods to stay young and live longer. For example, in the European middle ages alchemists were looking for the…
(more)
▼ textabstractPeople have always been searching for methods to stay young and live longer. For
example, in the European middle ages alchemists were looking for the “potion of life”.
This elixir, also known as the elixir of immortality and sometimes equated with the
philosopher’s stone, is a legendary potion, or drink, that grants the drinker eternal life
or eternal youth. So far no elixir has been found. The same holds for the fountain of
youth, a legendary spring that reputedly restores the youth of anyone who drinks of its
waters. Despite all these efforts it was not until the beginning of the twentieth century
that a non-invasive way to prolong life-, and healthspan was found: dietary restriction.
Subjects/Keywords: dietary restriction
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APA (6th Edition):
Ginhoven, T. (2011). Beneficial Effects of Preoperative Dietary Restriction. (Doctoral Dissertation). Erasmus University Medical Center. Retrieved from http://hdl.handle.net/1765/22970
Chicago Manual of Style (16th Edition):
Ginhoven, Tessa. “Beneficial Effects of Preoperative Dietary Restriction.” 2011. Doctoral Dissertation, Erasmus University Medical Center. Accessed February 26, 2020.
http://hdl.handle.net/1765/22970.
MLA Handbook (7th Edition):
Ginhoven, Tessa. “Beneficial Effects of Preoperative Dietary Restriction.” 2011. Web. 26 Feb 2020.
Vancouver:
Ginhoven T. Beneficial Effects of Preoperative Dietary Restriction. [Internet] [Doctoral dissertation]. Erasmus University Medical Center; 2011. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/1765/22970.
Council of Science Editors:
Ginhoven T. Beneficial Effects of Preoperative Dietary Restriction. [Doctoral Dissertation]. Erasmus University Medical Center; 2011. Available from: http://hdl.handle.net/1765/22970
25.
Susa, Denis.
Genetic, Physiological, and Pharmacological Amelioration of Ischemic Injury.
Degree: 2010, Erasmus University Medical Center
URL: http://hdl.handle.net/1765/22638
► textabstractOrgan transplantation is the treatment of choice for end stage organ failure, and in recent decades one year results have greatly improved. Two major problems…
(more)
▼ textabstractOrgan transplantation is the treatment of choice for end stage organ failure, and in recent decades
one year results have greatly improved. Two major problems facing the transplant community
remain; long-term survival of organ grafts has still not reached its full potential, and the shortage
of suitable donor organs is still increasing.
Long-term graft survival is significantly hampered by chronic transplant dysfunction (CTD). This
still poorly defined process of untreatable functional deterioration of an organ following transplantation
accounts for approximately 30 percent of graft loss in the first 5 years after transplantation.
In the kidney CTD, also known as chronic allograft nephropathy (CAN), is clinically
characterized by progressive renal dysfunction, associated with hypertension and proteinuria.
Renal biopsies show characteristic but nonspecific histopathological changes in the vascular, glomerular
and tubulointerstitial compartments of the kidney, which overlap with the histology of
normally aging kidneys. Although the term CAN has been recently replaced by “interstitial fibrosis
and tubular atrophy without evidence of any specific etiology” [3], we continue to use CAN in this
thesis, as this is the terminology used in the majority of the literature available to date.
Increasing evidence suggests that the development of CAN is multifactorial in origin, with alloantigen
dependent and allo-antigen independent factors contributing to the decline of renal
graft function. Of the allo-antigen independent factors, donor age and cold ischemia time
seem to be the major correlate to transplant survival. Clinical observations suggest an inverse
relationship between both donor age and ischemia time and long-term graft survival.
The mechanisms by which donor age or ischemia lead to reduced functional life span are currently
unknown.
Subjects/Keywords: ischemic injury; organ transplantation
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APA (6th Edition):
Susa, D. (2010). Genetic, Physiological, and Pharmacological Amelioration of Ischemic Injury. (Doctoral Dissertation). Erasmus University Medical Center. Retrieved from http://hdl.handle.net/1765/22638
Chicago Manual of Style (16th Edition):
Susa, Denis. “Genetic, Physiological, and Pharmacological Amelioration of Ischemic Injury.” 2010. Doctoral Dissertation, Erasmus University Medical Center. Accessed February 26, 2020.
http://hdl.handle.net/1765/22638.
MLA Handbook (7th Edition):
Susa, Denis. “Genetic, Physiological, and Pharmacological Amelioration of Ischemic Injury.” 2010. Web. 26 Feb 2020.
Vancouver:
Susa D. Genetic, Physiological, and Pharmacological Amelioration of Ischemic Injury. [Internet] [Doctoral dissertation]. Erasmus University Medical Center; 2010. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/1765/22638.
Council of Science Editors:
Susa D. Genetic, Physiological, and Pharmacological Amelioration of Ischemic Injury. [Doctoral Dissertation]. Erasmus University Medical Center; 2010. Available from: http://hdl.handle.net/1765/22638
26.
Mertens Zur Borg, Ingrid.
Anaesthesia and peri-operative care for laparoscopic donor nephrectomy.
Degree: 2008, Erasmus University Medical Center
URL: http://hdl.handle.net/1765/12623
► textabstractA successful renal transplant for patients with kidney failure reduces mortality rate when compared to patients who continue dialysis. Organ donation from living donors has…
(more)
▼ textabstractA successful renal transplant for patients with
kidney failure reduces mortality rate when compared to patients who
continue dialysis. Organ donation from living donors has significant
better results over organ donation from deceased donors. Traditionally
the surgical approach for living donor nephrectomy was performed
through a subcostal lateral incision. Now, laparoscopic donor
nephrectomy has become the method of choice to procure kidneys from
living donors, because of the reduced procedure-related morbidity,
shorter convalescence period, better cosmetic result and a superior
quality of life for the donor compared with open surgery. However,
there are concerns about the transient function deterioration of the
donor graft, compared to the traditional open procedure. The causes
and exact mechanisms of the altered hemodynamic parameters (increase
in systemic vascular resistance and a decrease in cardiac output),
renal blood flow (a decrease up to 75%, with !
subsequent temporary renal ischemia) and reduced urine output during
LDN, and delayed graft function after LDN are probably multifactorial.
Various mechanisms, such as venous compression caused by elevated IAP,
and the pharmacological action of the absorbed CO2, as well as
activation of the sympathetic and neuro-humoral factors have all been
suggested to explain these transient adverse renal effects. Therefore,
it has been advocated to use vigorous hydration up to 2 l/h of
crystalloids during LDN in patients. However, it was shown that this
vigorous hydration could not prevent the impaired creatinine clearance
as observed after LDN.
We developed a protocol that focused on optimal hemodynamic function
and low level of preoperative stress.
Adequate fluid loading before installation of PP, together with
prevention of blood pooling with anti-thrombosis stockings and
adjustment of the position, adequate ventilation with the aim to
minimize elevated intrathoracic pressures, high dose of sufentanil and
adequate depth of anaesthesia results in the prevention of the
hemodynamic and renal compromise encountered due to elevated IAP,
during LDN. Moreover, the differences in stress response between ODN
and LDN have disappeared with this regimen. The use of propofol
anaesthesia and the addition of epidural analgesia further reduced the
stress response and provided a faster and qualitatively better direct
postoperative recovery.
In conclusion, the work presented in this thesis shows that the
anaesthetist is able to improve the outcome for the donor patient, as
well as for the donor kidney.
Subjects/Keywords: anaesthesia; depth of anaesthesia; donor; epidural analgesia; fluid regime; hormones; laparoscopic; nephrectomy; stress
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APA (6th Edition):
Mertens Zur Borg, I. (2008). Anaesthesia and peri-operative care for laparoscopic donor nephrectomy. (Doctoral Dissertation). Erasmus University Medical Center. Retrieved from http://hdl.handle.net/1765/12623
Chicago Manual of Style (16th Edition):
Mertens Zur Borg, Ingrid. “Anaesthesia and peri-operative care for laparoscopic donor nephrectomy.” 2008. Doctoral Dissertation, Erasmus University Medical Center. Accessed February 26, 2020.
http://hdl.handle.net/1765/12623.
MLA Handbook (7th Edition):
Mertens Zur Borg, Ingrid. “Anaesthesia and peri-operative care for laparoscopic donor nephrectomy.” 2008. Web. 26 Feb 2020.
Vancouver:
Mertens Zur Borg I. Anaesthesia and peri-operative care for laparoscopic donor nephrectomy. [Internet] [Doctoral dissertation]. Erasmus University Medical Center; 2008. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/1765/12623.
Council of Science Editors:
Mertens Zur Borg I. Anaesthesia and peri-operative care for laparoscopic donor nephrectomy. [Doctoral Dissertation]. Erasmus University Medical Center; 2008. Available from: http://hdl.handle.net/1765/12623
27.
Rood, Pleunie.
Islet Xenotransplantation and Xeno-antigenicity: studies in a preclinical model.
Degree: Department of Surgery, 2008, Erasmus University Medical Center
URL: http://hdl.handle.net/1765/11732
► textabstractShortage of human donor organs is the major limiting factor for clinical islet allotransplantation. Xenotransplantation, using the pig as the source of islets is considered…
(more)
▼ textabstractShortage of human donor organs is the major limiting
factor for clinical islet allotransplantation. Xenotransplantation,
using the pig as the source of islets is considered a potential
solution to this problem. Since the development of pigs homozygous for
α1,3-galactosyltransferase gene-knockout (GT-KO), renewed interest
exists in the possibility of pig to primate xenotransplantation.
This study involved several aspects of islet xenotransplantation in a
pig to nonhuman primate model, and xenoantigenicity of donor pig tissue.
The first aim was to review the current state of pig to nonhuman
primate islet xenotransplantation.
The second part focused on the presence of preformed (natural) xeno-
antibodies in primate sera against wild-type (WT) pig and GT-KO pig
cells. The xeno-antibodies against WT pigs are directed towards both
Galα1,3Gal (Gal) and nonGalα1,3Gal (nonGal) epitopes on pig cells.
The availability of GT-KO pigs enabled us to study the presence of
nonGal antibodies in baboons, cynomolgus monkeys and humans. Different
aspects have been studied: The incidence and cytotoxicity of preformed
anti-nonGal antibodies have been monitored in these three species. We
investigated the development of an elicited nonGal antibody response
after GT-KO organ transplantation in baboons. Additionally, the
potential difference in anti-nonGal antibody levels in allosensitized
compared to nonsensitized humans have been assessed. And we have
studied specifically the development of nonGal antibodies in infant
humans and infant baboons. The possible implications for clinical
xenotransplantation are addressed.
The next project was to study porcine islet xenotransplantation in
vivo in a nonhuman primate model. The first step was to establish a
safe model for induction of diabetes in cynomolgus monkeys. We were
then able to study the intraportal transplantation of WT and GT-KO pig
islets in diabetic cynomolgus monkeys. An attempt was made to overcome
the destruction of a large number of islets shortly after intraportal
transplantation (described as Instant Blood-Mediated Inflammatory
Reaction [IBMIR] by the Uppsala group), by investigating different
ways to reduce this early graft loss.
The last aim was to evaluate future perspectives. The current position
of clinical islet xenotransplantation is discussed, and a possible
alternative to islet xenotransplantation, i.e. islet cell
regeneration, is described.
Subjects/Keywords: GT-KO; antibodies; diabetes; islets; nonGal; nonhuman primates; xenotransplantation
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APA (6th Edition):
Rood, P. (2008). Islet Xenotransplantation and Xeno-antigenicity: studies in a preclinical model. (Doctoral Dissertation). Erasmus University Medical Center. Retrieved from http://hdl.handle.net/1765/11732
Chicago Manual of Style (16th Edition):
Rood, Pleunie. “Islet Xenotransplantation and Xeno-antigenicity: studies in a preclinical model.” 2008. Doctoral Dissertation, Erasmus University Medical Center. Accessed February 26, 2020.
http://hdl.handle.net/1765/11732.
MLA Handbook (7th Edition):
Rood, Pleunie. “Islet Xenotransplantation and Xeno-antigenicity: studies in a preclinical model.” 2008. Web. 26 Feb 2020.
Vancouver:
Rood P. Islet Xenotransplantation and Xeno-antigenicity: studies in a preclinical model. [Internet] [Doctoral dissertation]. Erasmus University Medical Center; 2008. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/1765/11732.
Council of Science Editors:
Rood P. Islet Xenotransplantation and Xeno-antigenicity: studies in a preclinical model. [Doctoral Dissertation]. Erasmus University Medical Center; 2008. Available from: http://hdl.handle.net/1765/11732
28.
Dor, Frank.
Investigations relating to the induction of immunological tolerance through spleen transplantation in miniature swine.
Degree: Department of Clinical Chemistry, 2006, Erasmus University Medical Center
URL: http://hdl.handle.net/1765/10508
► textabstractThe ultimate goal in transplantation is to achieve donor-specific immunological tolerance. The induction of tolerance would result in the long-term survival of a transplanted organ…
(more)
▼ textabstractThe ultimate goal in transplantation is to achieve donor-specific
immunological tolerance. The induction of tolerance would result in
the long-term survival of a transplanted organ without the need for
continuous immunosuppressive therapy, thus avoiding its many
attendant risks and complications. In this dissertation, spleen
transplantation will be investigated as a method to induce
immunological tolerance.
In the literature, there is evidence for a tolerogenic effect of
spleen transplantation in rodents. However, the relevance of this
phenomenon remained to be demonstrated in large animal models and in
humans. To investigate whether the approach of spleen transplantation
would be clinically applicable, we developed a model in pigs. The
Massachusetts General Hospital miniature swine model was chosen,
based on the fact that the Major Histocompatibility Complex (MHC) is
well-defined, enabling clinically-relevant donor-recipient
combinations to be investigated. During the last 30 years,
considerable experience in transplantation immunology has been gained
in this model.
In miniature swine, a transplanted spleen (a highly immunogenic
organ) is rejected when no immunosuppressive therapy is given.
However, even in the presence of a full MHC-mismatch between donor
and recipient, the transplanted spleen is accepted when a short
course of cyclosporine is administered with pre-transplant low-dose
whole body (100cGy) and thymic (700cGy) irradiation. After successful
spleen transplantation, mixed hematopoietic cell chimerism is induced
in the blood and lymphoid organs of the recipient. Donor cells
migrate from the spleen to recipient lymph nodes, thymus, and bone
marrow, in the absence of graft-versus-host-disease. Meanwhile, the
donor spleen is repopulated with recipient cells.
Creating a state of mixed chimerism is known to be a highly-effective
means of inducing immunological tolerance. When the spleen is
successfully transplanted, the recipient demonstrates donor-specific
T cell tolerance in vitro. After discontinuation of
immunosuppression, T cells remain unresponsive to donor antigen (on
CML and MLR). Regulatory T cells are detected in the circulation of
the recipient, and suppress naïve T cell responses in a donor-
specific manner. Thus, the recipient remains immunocompetent.
We investigated whether in vivo donor-specific tolerance develops. In
pigs tolerized by spleen transplantation, donor-specific kidneys
survived for many months without exogenous immunosuppression, while
in control pigs (without spleen transplants) the grafts were rejected
within 2 weeks.
The fact that donor cells engrafted in recipient bone marrow suggests
that hematopoietic stem cells were present in the donor spleen. We
therefore investigated the presence of hematopoietic stem cells in
adult naïve spleens, using flow cytometry and a variety of
functional stem cell assays. We were able to demonstrate that the
spleens of pigs, baboons, and humans harbor…
Subjects/Keywords: GVHD; T-cells; chimerism; engraftment; immunosuppression; kidney; large animals; pig; regulatory cells; spleen; stem cells; suppression; tolerance; transplantation
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APA ·
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MLA ·
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CSE |
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to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Dor, F. (2006). Investigations relating to the induction of immunological tolerance through spleen transplantation in miniature swine. (Doctoral Dissertation). Erasmus University Medical Center. Retrieved from http://hdl.handle.net/1765/10508
Chicago Manual of Style (16th Edition):
Dor, Frank. “Investigations relating to the induction of immunological tolerance through spleen transplantation in miniature swine.” 2006. Doctoral Dissertation, Erasmus University Medical Center. Accessed February 26, 2020.
http://hdl.handle.net/1765/10508.
MLA Handbook (7th Edition):
Dor, Frank. “Investigations relating to the induction of immunological tolerance through spleen transplantation in miniature swine.” 2006. Web. 26 Feb 2020.
Vancouver:
Dor F. Investigations relating to the induction of immunological tolerance through spleen transplantation in miniature swine. [Internet] [Doctoral dissertation]. Erasmus University Medical Center; 2006. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/1765/10508.
Council of Science Editors:
Dor F. Investigations relating to the induction of immunological tolerance through spleen transplantation in miniature swine. [Doctoral Dissertation]. Erasmus University Medical Center; 2006. Available from: http://hdl.handle.net/1765/10508
29.
Kok, Niels.
Live Kidney Donation: a plea for the laparoscopic approach.
Degree: Department of Surgery, 2007, Erasmus University Medical Center
URL: http://hdl.handle.net/1765/10262
► textabstractIn Chapter One we described the development of live kidney donation. Currently, live donor kidney transplantation is the best solution to attack the persistent organ…
(more)
▼ textabstractIn Chapter One we described the development of live kidney donation. Currently, live donor
kidney transplantation is the best solution to attack the persistent organ shortage in the
Western World. Because of this shortage live kidney donation is still interesting over fifty years
after Joseph Murray and Rene Kuss performed the first live kidney donor transplantations.
The revival of live kidney donation in the 1990s still continues. Developments in immunosuppressive
therapy, crossing the blood barrier, intelligent logistic solutions, improvements of
peri-operative care and last but not least less invasive surgical techniques all attribute to the
successes of live kidney donor transplantations. In this thesis we focused on the latter aspect,
but one have to keep in mind that improvements in surgical and peri-operative care of the
donor can only exist within a solid system providing screening of potential donors, selection
of transplant candidates and accurate medical treatment of the recipients.
In the United States Ratner and colleagues introduced laparoscopic donor nephrectomy in
1995. This technique has greatly revolutionized live kidney donation. Presently the majority
of live kidney donors is operated on using a (modified) laparoscopic approach. However, the
introduction of minimally invasive surgery has also encouraged refinement of open techniques.
Most studies up to now aimed to prove the feasibility of a new surgical technique for
live kidney donation. In this thesis, we compared these novel techniques, therewith addressing
short term surgical outcomes, quality of life, costs and transplant outcome.
Subjects/Keywords: kidney donation
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APA (6th Edition):
Kok, N. (2007). Live Kidney Donation: a plea for the laparoscopic approach. (Doctoral Dissertation). Erasmus University Medical Center. Retrieved from http://hdl.handle.net/1765/10262
Chicago Manual of Style (16th Edition):
Kok, Niels. “Live Kidney Donation: a plea for the laparoscopic approach.” 2007. Doctoral Dissertation, Erasmus University Medical Center. Accessed February 26, 2020.
http://hdl.handle.net/1765/10262.
MLA Handbook (7th Edition):
Kok, Niels. “Live Kidney Donation: a plea for the laparoscopic approach.” 2007. Web. 26 Feb 2020.
Vancouver:
Kok N. Live Kidney Donation: a plea for the laparoscopic approach. [Internet] [Doctoral dissertation]. Erasmus University Medical Center; 2007. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/1765/10262.
Council of Science Editors:
Kok N. Live Kidney Donation: a plea for the laparoscopic approach. [Doctoral Dissertation]. Erasmus University Medical Center; 2007. Available from: http://hdl.handle.net/1765/10262
30.
Klop, Karel.
Tailor-Made Live Kidney Donation.
Degree: 2014, Erasmus University Medical Center
URL: http://hdl.handle.net/1765/51600
► markdownabstract__Abstract__ This thesis describes several aspects of live kidney donation, such as surgical techniques, cost-effectivity, cosmetics en quality of life. Kidney transplantation offer several benefits…
(more)
▼ markdownabstract__Abstract__
This thesis describes several aspects of live kidney donation, such as surgical techniques, cost-effectivity, cosmetics en quality of life.
Kidney transplantation offer several benefits when compared to dialysis. These benefits include better recipient and graft survival, better access to transplantation and pre-emptive transplantation. Eligibility criteria for live kidney donation have been extended in the last decade, leading to an increase in live donors and an increase in donors with mild comorbidities. This development requires continuous innovation evaluation of all aspects of live kidney donation, including selection, peroperative care, surgical techniques, outcome and long-term survival.
There is high quality evidence suggesting that laparoscopic donor nephrectomy is to be preferred over open donor nephrectomy. This thesis describes two randomized controlled trials comparing hand-assisted retroperitoneoscopic donor nephrectomy with full laparoscopic donor nephrectomy. Furthermore, we assess the learning curves of both these techniques in a center with no experience and a center with abundant experience in endoscopic donor nephrectomy.
The second part of the thesis focuses on post-operative outcome. It demonstrates the excellent cosmetic outcome after the procedure. Also, no difference in costs or cost-effectiveness was found between both earlier mentioned techniques. Quality of life after live donor nephrectomy is excellent. Furthermore, elderly donors tend to have higher quality of life scores after donation, and they also return to their baseline values earlier. Also, we try to identify factors that influence postoperative quality of life.
In the final part we describe the ten-year follow-up on quality of life. The protocol of the LOVE-study is also presented. This study aims to assess the functional donor outcome on the long-term.
Subjects/Keywords: Transplantation; Live donors; Kidney; Surgery; Quality of life; Nephrectomy
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APA ·
Chicago ·
MLA ·
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Manager
APA (6th Edition):
Klop, K. (2014). Tailor-Made Live Kidney Donation. (Doctoral Dissertation). Erasmus University Medical Center. Retrieved from http://hdl.handle.net/1765/51600
Chicago Manual of Style (16th Edition):
Klop, Karel. “Tailor-Made Live Kidney Donation.” 2014. Doctoral Dissertation, Erasmus University Medical Center. Accessed February 26, 2020.
http://hdl.handle.net/1765/51600.
MLA Handbook (7th Edition):
Klop, Karel. “Tailor-Made Live Kidney Donation.” 2014. Web. 26 Feb 2020.
Vancouver:
Klop K. Tailor-Made Live Kidney Donation. [Internet] [Doctoral dissertation]. Erasmus University Medical Center; 2014. [cited 2020 Feb 26].
Available from: http://hdl.handle.net/1765/51600.
Council of Science Editors:
Klop K. Tailor-Made Live Kidney Donation. [Doctoral Dissertation]. Erasmus University Medical Center; 2014. Available from: http://hdl.handle.net/1765/51600
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Open Access Theses and Dissertations
