Academic Ceremonies June 2009

“The hypercoagulable state in patients; determining(hyper)coagulability and the role of thrombin generation”

Disorders such as heart infarct or thrombotic leg are characterized by blood with an increased tendency to form coagulated mass. This ‘increased tendency to coagulate’ can be measured with the thrombin generation test. This dissertation describes the standard situation and optimization of this test so that it can be applied in patient studies and in the comparison of results between institutes. Use of the thrombin generation test in patient studies into thrombosis showed that a lowered thrombin generation was associated with the occurrence of complications in patients with a firs heart infarct, while an increased thrombin generation was associated with the repeated occurrence of a thrombotic leg. Possibly this test can be used as a risk predictor in the future. 

Key words:

thrombosis, heart infarct, coagulated mass, thrombin generation test

“Fairness in Multi-Agent System”

“New anti-epileptic drugs in pharmacoresistant epilepsy: retention time as outcome parameter”

Between 1996 and 2001 3 new anti-epileptic drugs were introduced in the market: lamotrigine, topiramat and levetiracetam. This dissertation studies these drugs in a group of 1066 p pharmacoresistant patients. For each patient the retention time was measured, which means the number of days that the patient continued to use the new drug. When a patient stopped, the researcher investigated if this was caused by a lack of effectiveness or by the occurrence of side-effects. In that way relevant differences between these anti-epileptic drugs were determined. It was striking that the effectiveness of the anti-epileptic drugs only limited the retention time to a limited extent. The retention time was mainly determined by the occurrence of side-effects.

Key words:

anti-epileptic drugs, retention time, side-effects

“Seeing Emotion; studies on the processing of facial expressions in normal development and young children with autism”

More and more often, autism is diagnosed at a very early age. However, there is very little known about the brain development of the young child with autism. This research shows that the visual brain, the part of the brains that allows us to see, works differently in the case of autism already at the toddler age. The visual brain of toddlers with autism seems to react excessively to details in his surroundings. This causes deviations in the processing of important social stimuli, such as reading the emotions in facial expressions of others. Current treatments of children with autism particularly focus on training social skills. The results of this research imply that future treatments should particularly also focus on the visual perception. 

Key words:

autism, visual brains, early age

"The threatened brain: magnetic resonance imaging studies into fear and panic"

“Governance Indicators”

“Local pulse wave velocity determination: the arterial distension waveform from foot to crest”

The elasticity of arteries determines to a great extent the effort the heart has to make to pump blood through the body. This dissertation develops a new method, departing from the so-called pulse wave velocity, to determine the elasticity of the carotid artery. The method is low-threshold and distinguishes for example young and elderly people on the basis of elasticity. In patients with cardiovascular diseases the measured elasticity appears to be a factor three lower in the systolic blood pressure than in the diastolic blood pressure. Moreover, the elasticity in the systolic blood pressure is more strongly associated with blood pressure and age. This has consequences for the diagnosis and treatment of patients with a high systolic blood pressure and heart failure. You can earlier detect or exclude a bad vessel condition.

Key words:

elasticity, carotid artery, cardiovascular diseases 

“The treatment of defaecation disorders”

Defecation disorders are disorders where patients have problems holding up their faeces (faecal incontinence) or have constipation of faeces. This dissertation assesses three possibilities of treatment.Retrograde Colon Irrigation (rinsing the intestines via the anus) can be considered if a diet or medication are not effective or after failing surgical interventions.  Retrograde Colon Irrigation (RCI) has a successful result in 59% of the patients with incontinence and 20% of the patients with constipation. Compared to other treatments, sacral neuromodulation (SNM) is the only one that improves the quality of life. Patients who were born with an anorectal malformation (ARM), who are still incontinent at a young age, can be treated with Dynamic Graciloplasty (DGP). Long-term continency for faeces is achieved with DGP in 35% of the patients. 

Key words:

defecation disorders, treatments: RCI, SNM and DGP 

“(Patho) physiology of gut wall integrity in health and disease in man”

Intestinal diseases are hard to diagnose in patients with stomach ache, because many diseases cause stomach ache, even when the intestines are not involved.  Slow diagnostics of intestinal diseases lead to a delayed treatment and therefore to higher morbidity and mortality. That is why there is great need for laboratory tests that can determine if therapy, aimed at recovery, is successful. This dissertation develops and evaluates a series of potential tests that particularly show the damage to the intestinal cells that form a barrier against body-foreign nutrients and micro-organisms. These tests were among others successfully used to early detect infants who are suspected of carrying the serious intestinal inflammation necrotizing enterocolitis.

Key words:

intestinal diseases, diagnostics, laboratory tests

“Experimental ischemia and reperfusion of the small bowel: focus on microvascular events”

“Keep on moving”

“Inhibition of ischemic organ damage with anti-coagulant agents; ASIS and APC in myocardial and renal ischemia/reperfusion”

Cardiovascular diseases are the most common cause of death in the Western world and they are often caused by the formation of atherosclerotic plaques that lead to occlusion of the affected blood vessels. Occlusion of the artery can cause ischemia, i.e. oxygen deficiency in the affected tissue, which in turn can result in cell death or apoptosis. To limit the damage that was caused by the ischemic process, the closed blood vessel has to be opened again; this is called reperfusion. The results from this dissertation show an important role for the anti-coagulant agents ASIS and APC in the protection against heart ischemia/reperfusion damage. Both agents have a protective effect on heart ischemia/reperfusion damage via various action mechanisms and could be used in the future to prevent damage after a heart infarct with a view to limit secondary heart failure. 

The research for this dissertation could be conducted with a subsidy from the Nederlandse Hartstichting.  

Key words:

cardiovascular diseases, ischemic process, reperfusion, anti-coagulant agents

“Dietary folate, genetic variation and DNA methylation in sporadic colorectal cancer”​

“Injection Therapy for Stress Urinary Incontinence in Adult Women”

"Individual Assessment of Children with Profound Intellectual and Multiple Disabilities by Means of Event-related Brain Potentials"

In practice it is extremely difficult to assess the cognitive functioning of serifously disabled children.  This research project investigated if measuring the brain activity (ERP) is a possible alternative for the standard psychological methods. This indeed appears to be the case.  Remarkable was that the obtained research outcomes about the cognitive functioning of these children did for the greater part matched the standard psychological tests, but that some children were seriously underestimated. The suggestion is therefore to expand the existing psychological test batteries for profoundly multiply disabled children with the ERP method. 

Key words:

ERP method, seriously multiply disabled, cognition

“Grens en Gezin; beleidsvorming inzake gezinsmigratie in Nederland, 1955-2005”

The most flexible liberal policy in the field of family reunification and family formation was pursued in the past fifty years by the centre-right governments Van Agt and Lubbers in a time that the economy was bad, whereas particularly in times of economic prosperity right- and left-wing governments chose a strict policy. This is shown by the PhD research into the conditions for family reunification and family formation between 1955 and 2005. This research allows us a look behind the scenes of policymaking in the Netherlands and shows that the influence of civil servants on this policy area has gradually decreased considerably, although the political science and administrative science literature suggests the opposite.   

Key words:

immigration policy, family reunification

"Breinbrekers: de Januskop van psychofarmaca” (‘Brainteasers: the Janushead of Psychofarmaceuticals’). 

“Genetics, Epigenetics and Angiogenesis in Renal Cell Carcinoma”

Angiogenesis (formation of blood vessels) is important for the growth and metastasis of renal carcinoma. This dissertation describes a higher angiogenesis activity in the aggressive clear cell carcinoma, which explains a higher risk of metastasis via the blood vessels. In contrast with angiogenesis there is only a limited tumoural lymph angiogenesis. This could explain the small number of lymph gland metastasis in this tumour. The development of renal cell carcinoma is complex, and besides genetic changes also more and more epigenetic changes (such as DNA promoter hypermethylation) are described. This dissertation illustrates for example that promoter hypermethylation of the gene Gremlin 1 in clear cell renal cell carcinoma is connected to tumour angiogenesis and prognosis. The exact function of Gremlin 1 elimination in the development of renal cancer, however, has to be further investigated. More epigenetic research can lead to the development of early diagnostic and prognostic markers and their new anti-epigenetic therapy forms.

Key words:

Genetics, epigenetics, angiogenesis, renal cell carcinoma  

“Diagnostic and therapeutical aspects of lymphedema”

Lymphedema is a very common chronic disorder from which in the Netherlands alone about 350.000 people suffer. Lymphedema causes a disordered drain of fluid in the body as a result of which the patient gets swollen body parts (mostly arms or legs). This first dissertation on lymphedema in the Netherlands describes new diagnostics of lymphedema on the basis of scientific research, gives an overview of the effectiveness of several (non-) operative treatment methods and gives a guideline for setting up a multidisciplinary care protocol. To prevent irreparable defects and complications and to improve the patient’s quality of life, early diagnostic and treatment are necessary. The treatment is the most effective when (para-) medics cooperate in a multidisciplinary way, also because patients with lymphedema need follow-up and care throughout their lives.

Key words:

lymphedema, diagnostic, treatment

“Haruspices in het heden” (‘Haruspices in the present’)