Bij veel te vroeg geboren kinderen blijft prematurenretinopathie (ROP) een belangrijke oorzaak van blind- en slechtziendheid. Dit ondanks uitgebreid onderzoek. De oorzaak hiervan is, dat de... Show moreBij veel te vroeg geboren kinderen blijft prematurenretinopathie (ROP) een belangrijke oorzaak van blind- en slechtziendheid. Dit ondanks uitgebreid onderzoek. De oorzaak hiervan is, dat de leeftijd, waarop deze kinderen geboren en in leven gehouden kunnen worden daalt door een betere neonatologische behandeling. Het aantal kinderen, dat ernstige ROP kan oplopen neemt hierdoor toe. Een vroege opsporing en behandeling van ROP kan de kans op het ontwikkelen van een visuele beperking en de ernst daarvan verminderen. Een evidence-based richtlijn is een belangrijk hulpmiddel om de zorg voor deze hoog-risico prematuren te optimaliseren. Er is echter geen universeel screeningsprotocol op te stellen, omdat het niveau van de neonatologische zorg per land erg kan verschillen. Door middel van de NEDROP studie werden op nationaal niveau het screeningsproces, de invloed van overplaatsingen, de incidentie van ROP, de risicofactoren alsmede de behandelcriteria en de behandeling van ROP ge_nventariseerd. Dit heeft mede geresulteerd in een nieuwe richtlijn geschikt voor allen die betrokken zijn bij de screening (oogartsen, neonatologen, kinderartsen, verpleegkundigen en de ouders) en een uniforme, landelijke ouder-informatie folder. Het uiteindelijke doel van de NEDROP studie is om blind- en slechtziendheid door ROP te doen afnemen in Nederland. Show less
Consumers have many possibilities to undergo a form of screening to acquire health information via the Internet or otherwise by purchasing health checks, medical check-ups, total body scans and... Show moreConsumers have many possibilities to undergo a form of screening to acquire health information via the Internet or otherwise by purchasing health checks, medical check-ups, total body scans and direct-to-consumer (DTC) genetic tests. More and more providers place screenings on the market before they have been assessed properly. In the Netherlands the Act on population screening ( __Wet op het bevolkingsonderzoek__) sets strict quality criteria for screening. In accordance with this Act a licence is required for offering and performing screening with ionising radiation or for detecting (risk factors of) cancer and untreatable diseases. This system, which aims to protect individuals against health damage and also to ensure patients (rights), wards off __commercial screening__ of the Dutch market. In society this meets with criticism. Individuals increasingly perceive the limited access to screening as an unnecessary restriction of their self-determination. However, the Dutch State has a special responsibility regarding the health of individuals. This thesis focuses on the following central question: __What are the normative criteria for the access to and supply of genetic screening from constitutional and European law perspectives?__ As a corollary the author will explore what this means for the Dutch legal framework regulating genetic screening, particularly DTC genetic tests. Show less
The aim of preventive care traditionally refers to measures taken to prevent disease and injury. However, for vulnerable older people the aim to maintain independence and wellbeing seems to be... Show moreThe aim of preventive care traditionally refers to measures taken to prevent disease and injury. However, for vulnerable older people the aim to maintain independence and wellbeing seems to be appropriate. Although a 'gold standard' to stratify for vulnerability in the general older population is lacking, GPs share the same concept of vulnerability for somatic and psychological patient characteristics. However, within the vulnerable older population, there is no evidence (except for physical activity) that a collective screening approach, with a standardized intervention program, will be the most appropriate way to contribute to the maintenance of independence and wellbeing. Moreover, since te majority of vulnerable older people already receive medical care for their chronic disease(s), more benefit can be expected from improving the individual regular care than from a separate screening program. According to GPs, te main topic in the prevention of disease in the general older population is (apart from national programs) cardiovascular risk management. A collective approach, consisting of high risk stratification and treatment, appeared to be possible even at high age. Show less
Being a member of a melanoma family is a major risk factor for cutaneous malignant melanoma. In this thesis clinical characteristics and management of melanoma families are discussed. In the first... Show moreBeing a member of a melanoma family is a major risk factor for cutaneous malignant melanoma. In this thesis clinical characteristics and management of melanoma families are discussed. In the first part of the thesis clinical and histological characteristics of melanoma (patients) from families with a (p16-Leiden) mutation in the high penetrance melanoma susceptibility gene CDKN2A were compared with the general population. Significant differences with respect to several characteristics are reported. In the second part of the thesis the yield, effectiveness, and causes for failure of surveillance of melanoma families are discussed. We report that surveillance is associated with a more favorable tumor stage. Several aspects of surveillance, including interval melanomas, surveillance interval, noncompliance, and overdiagnosis are discussed. Based on analyses of melanoma detection rates in families with different family and genetic characteristics, we propose a risk stratification for members of melanoma families. In the third part of the thesis we investigate the impact of dermoscopy on management decisions. It is demonstrated that dermoscopy by dermoscopy experts in the setting of melanoma family surveillance resulted in a considerable reduction of unnecessary excisions. This effect was considerably less in the setting of dermoscopy non-experts examining patients in general dermatology clinics. Show less
Muntingh, A.D.T.; Heer, E.W. de; Marwijk, H.W.J. van; Ader, H.J.; Balkom, A.J.L.M. van; Spinhoven, P.; Feltz-Cornelis, C.M. van der 2013
Skin cancer is the most common type of cancer in fair-skinned populations. Cutaneous squamous cell carcinoma (SCC) comprises about 15% of all skin cancer diagnoses. Treatment associated with the... Show moreSkin cancer is the most common type of cancer in fair-skinned populations. Cutaneous squamous cell carcinoma (SCC) comprises about 15% of all skin cancer diagnoses. Treatment associated with the high and rising prevalence of cutaneous SCC puts an increasingly high financial burden on society, marking a pressing need for advancements in skin cancer drug development. For screening of novel therapeutics, representative models of human cutaneous SCC are required. The aim of the research described in this thesis was to develop a representative in vitro model of human SCC for screening therapeutics, without the unnecessary use of animals. To this end, we generated three-dimensional in vitro SCC models in which the malignant epidermal cancer cells were either represented by intact primary human cutaneous or by established, spontaneously immortalized cutaneous SCC cell lines. The dermal microenvironment in our models was seeded with either primary normal human dermal fibroblasts or primary SCC-associated fibroblasts. In verifying human cutaneous SCC representation by these in vitro models, we focused on hyperproliferation, cytological and architectural atypia and invasion as three main features of primary SCC. The in vitro skin cancer models presented in this thesis add to the spectrum of available in vitro models for therapeutic screening. Show less
Verweij, E.J.; Oever, J.M.E. van den; Boer, M.A. de; Boon, E.M.J.; Oepkes, D. 2012
Group B Streptococcus (GBS, Streptococcus agalactiae) has been recognized as an important cause of perinatal morbidity and mortality. The frequency of GBS colonization ranges from 10% to 35% in... Show moreGroup B Streptococcus (GBS, Streptococcus agalactiae) has been recognized as an important cause of perinatal morbidity and mortality. The frequency of GBS colonization ranges from 10% to 35% in women of reproductive age. GBS colonization can be transient, intermittent or persistent. Vertical transmission of GBS from mother to child occurs during labor. Studies on vertical GBS transmission in colonized mothers during labor report incidences of colonization of the infant between 16 and 69%. Early-onset group B streptococcal disease (GBS-EOD) occurs in approximately 1% of newborns who are colonized with GBS. Established risk factors for acquiring GBS-EOD are prolonged rupture of membranes, preterm labor, intrapartum fever, GBS bacteriuria during pregnancy or a previous child with GBS-EOD. Intrapartum antibiotic prophylaxis (IAP) given to women at risk of transmitting GBS to their baby may prevent GBS-EOD. Identification of mothers at risk may be performed by screening (taking a culture during pregnancy to detect maternal colonization) and/ or by identifying pregnancies with one or more of the established risk factors for GBS-EOD. Since the overall effect of the Dutch guideline on the incidence of GBS-EOD is disappointing, adaptation of the Dutch guidelines should be reconsidered. The aim of this thesis is to contribute to the information needed for the establishment of an optimal prevention strategy for GBS-EOD. In this thesis, studies on prevalence of GBS carriage, risk factors for GBS-sepsis in relation to GBS carriage, timing of GBS cultures, association of GBS carriage and preterm labor and resistance of GBS for antibiotics are combined. Show less
Receptors tyrosine kinases or RTKs are cell surface receptors that regulate numerous cellular processes, but also have a critical role in the development and progression of many types of cancer.... Show moreReceptors tyrosine kinases or RTKs are cell surface receptors that regulate numerous cellular processes, but also have a critical role in the development and progression of many types of cancer. The overexpression of EphA4, a member of the RTK family, has been observed in a variety of malignant carcinomas. The aim of the research project associated with this thesis was to develop high affinity inhibitors of the tyrosine kinase EphA4. Ligand discovery was based on two complementary approaches, a computational screen and an NMR based screen using Target Immobilized NMR Screening (TINS). In addition, orthogonal biophysical methods including Surface Plasmon Resonance (SPR) and protein observed NMR were employed to analyse fragment binding. The crystal structure of the EphA4 kinase domain was solved and the structure of the kinase domain in complex with dasatinib, a well-known kinase inhibitor, was also elucidated. The in silico approach discovered a potent inhibitor of EphA4 for which the binding mode was elucidated via X-ray crystallography. Moreover, the TINS approach identified two compounds that may constitute starting points for the generation of more potent EphA4 inhibitors. Show less
