Academic Ceremonies February 2008

“Relationship between angiogenesis and the immune response against solid tumors”

A promising new anticancer strategy is inhibition of blood vessel formation (angiogenesis) in the tumour. This dissertation shows that tumours also protect themselves against the immune system via the process of angiogenesis. Substances that stimulate angiogenesis inhibit interactions between blood vessel wall and white blood cells, as a result of which the tumour escapes from immune cells that attack the tumour cells. This study confirms the hypothesis that inhibition of angiogenesis makes the tumour more vulnerable again to the immune system, so that the tumour is therefore fought at two fronts. Anti-angiogenesis reinforces the entry of white blood cells and consequently the immune response against the tumour. These results show that inhibition of angiogenesis will reinforce the effect of anti-tumour immune therapy. 

“Neurologic complications in small cell lung cancer”

Metastases to the nervous system are often the most common neurological complications of small cell lung cancer (SCLC). This research tries to give a more adequate description of numbers and to prevent neurological complications in general and brain metastases in particular. Moreover, a contribution is made to the debate about the changes in diagnostics for and the treatment of brain metastases in SCLC. This research shows among others that brain metastases are more often diagnosed thanks to the improvements of imaging techniques (MRI instead of CT), often already before the patient has complaints from these metastases. It turned out that brain metastases reacted less often to chemotherapy than the lung tumour and metastases elsewhere in the body. This dissertation also discusses the optimal treatment strategy for SCLC patients with brain metastases.

Key words:

lung cancer, nervous system, brain metastases

“Radiopaque Bioactive Microspheres as Injectable Biomaterials”

“The development of exhaled breath condensate; a noninvasive method of measuring airway inflammation"

This dissertation describes the development of a new method to simplify the diagnostics of airway inflammation, and to improve its treatment. In a completely painless and harmless way the exhaled breath of a toddler or child is collected and cooled down to drops of exhaled breath condensate. Subsequently, this fluid condensate is analysed for exhaled inflammation substances that can indicate the type and seriousness of an airway inflammation. This method makes it possible to, for example, measure the airway inflammation in asthma in a simple way, and to treat it more effectively. 

Key words:

Children’s lung diseases, airway inflammation

“The Institutional Politics of the European Union; An analysis of administrative governance and constitutional reform in the EU”

The dissertation of Thomas Christiansen studies a few important institutes of the European Union, particularly the way their development is influenced by the tensions and contradictions that are inherent to the making and implementation of European policy. On the basis of a theory that emphasizes the combined action of the political actors and structure characteristics of an organization, the PhD candidate presents the international politics as a process that goes via different dimensions. He applied this theory both to individual institutes, such as the European Commission and the Secretariat-General of the Council of the European Union (the ‘Council of Ministers), as to more general developments in European politics such as the reform of the European Treaty and the constitutional politics.

“Health technology assessment of organizational innovation in health care: the case of shared care in hearing aid provision”

The ageing of the population leads to an increased number of people with impaired hearing. That is one of the reasons why shared care is being developed for elderly people with a hearing impairment. In this shared care audiologists take over tasks from E.N.T. specialists and Audiological Centres  This dissertation evaluates if this improves the care. Both the professionals as the people with a hearing impairment appeared prepared to support shared care. Persons with a hearing impairment preferred a first visit to the audiologist, provided he/she is able to accurately recognize patients who need to be referred, and a hearing aid final check with the E.N.T. specialist. Shared care turned out less expensive than the current care, but less effective and not more efficient. Determining factors that deserve further research are the accuracy of the audiologist and an earlier call for help by the people with impaired hearing.

Key words:

health technology assessment; deafness; organizational innovation

“Explaining Success and Failure in Development.”​

“Tumor cell plasticity: vascularisation beyond angiogenesis”

The growth of tumours is to a great extent determined by the supply of oxygen and nutrients. Tumours sometimes secrete growth factors which stimulates the blood vessels around the tumour in growth; this is called angiogenesis. Besides the aptitude of regular blood vessels, in 1999 it was discovered that aggressive tumour cells are also capable of forming blood vessel type structures themselves, a process that is called vascular mimicry. These vessel structures are co-responsible for the aggressiveness of the tumour. So far, little is known about the role of this secondary circulation system in tumours. This dissertation studies the role of vascular mimicry in the biology of two aggressive tumours: skin melanomas and Ewing sarcomas. The findings make it possible to develop new therapies for aggressive tumours.

Key words:

tumour research, vascular mimicry

“Functionele neurochirurgie: een kwestie van elektrisch evenwicht” (‘Functional neurosurgery: a matter of electrical balance’)

“Breastfeeding and Infant Atopic Manifestations”

“Autobiographical memory retrieval; overgeneral memory and intrusions”

Autobiographical memories can be actively ‘sought’, but they can also suddenly recur in our heads without any effort. These memories play an important role in our identity, goals in life, and problem-solving. It is therefore not surprising that a disturbed retrieval pattern of autobiographical memories is related to psychological problems. This dissertation discusses the question why some people on the one hand find it difficult to consciously retrieve detailed autobiographic memories, whereas at the same time they have constantly recurring and very specific memories of major events in life. One of the reasons appears to be that in traumatized people the active search process seems to be disturbed, while the associative remembering is intact and that the retrieval of one autobiographical memory can cause forgetting the other.

Key words:

autobiographic memory, remembering

“On pediatric delirium in critical illness; a clinical multidisciplinary study in child neuropsychiatry at the PICU”

The delirium, from the Latin word ‘de-lira’ which means ‘disrupted’, is a serious neuropsychiatric disorder in critically ill adults and elderly people. It is related to longer hospitalization, a worse prognosis, and higher mortality, especially in combination with artificial respiration. Children in the home situation become delirious very quickly, especially as a consequence of an infection disease with fever and that has a very good prognosis. The PhD candidate investigated among others how often this phenomenon occurs in the Pediatric Intensive Care Unit of the azM (cumulative 5%, rising at a higher age), how the disorder manifests itself (the so-called presentation), how high the mortality is (12,5%) and how the reaction to medication appears to be (good). However, extensive follow-up research is necessary. 

“Leber’s Hereditary Optic Neuropathy: an interaction between two genomes ?”

“GSK-3B: central regulator of skeletal muscle plasticity”

Loss of muscular mass often occurs in chronic obstructive pulmonary diseases (COPD). Prevention and treatment of this muscular mass loss is increasingly recognized as an important pillar in the treatment of this chronic disease. For this purpose it is essential to understand the mechanisms of muscle degradation and muscle growth. The protein Insulin-Growth-Factor I (IGF-I) has an important role in muscle growth, but the way in which IGF-I is involved in muscle regeneration is still insufficiently clarified. This research shows that one of the signal ), has abproteins of IGF-I, Glycogen Synthase Kinase-3beta (GSK-3 central, inhibiting effect on muscle mass preservation, muscle  withbdifferentiation and regeneration. Targeted inhibition of GSK-3 the help of medication is possibly a promising treatment strategy to prevent loss of muscular mass and to stimulate muscle growth in COPD and other chronic disorders.  
This research was financed by the ‘Nederlands Astma Fonds’ (NAF).

Key words:

COPD, skeletal muscle weakness, treatment strategy

“Managing concerns about falls; Fear of falling and avoidance of activity in older people”

“Implications of cardiac troponin T degradation”

Troponins are proteins that are involved in muscle contraction. They can be found in all muscle cells. In the case of muscle damage these proteins end up in the circulation. The heart is a muscle with troponins that only occur there, the heart-specific troponins. By means of sensitive diagnostic tests these can be measured in the blood to diagnose a heart infarct. This research shows that the troponins in the blood circulation disintegrate. That is why it is not possible to determine for certain what is exactly measured. This has consequences for the comparison of different tests and it can complicate the diagnosis of a heart infarct on the basis of this test.

Key words:

Hartinfarct, Troponine T

“The lipolytic Pathway in the Obese Insulin Resistant State”

Obesity is one of the main health problems of this century. An increased storage of fats in the fatty tissue and the skeletal muscle is an important symptom of obesity and  type 2 diabetes mellitus (geriatric diabetes). This dissertation shows that people with obesity have a reduced ability of mobilising fats from the fatty tissue and the skeletal muscle (lipolysis). Both our genes as environmental factors seem to play an important role here. More insight in the underlying mechanisms for the disturbed lipolysis can lead to the development of new medicines and lifestyle interventions for the prevention of treatment of obesity and geriatric diabetes.

​Key words:

obesity, fatty tissue, skeletal muscle

“Refractive errors: occurrence, aspecific health complaints, and functional problems”