The work described in this thesis had two objectives, specifically focusing on people aged 70 years and older: first, we aimed to investigate the associations between several thrombosis-related... Show moreThe work described in this thesis had two objectives, specifically focusing on people aged 70 years and older: first, we aimed to investigate the associations between several thrombosis-related risk factors described in young and middle-aged populations and the risk of venous thrombosis (VT) in the elderly; second, we aimed to provide insight into several long-term consequences (i.e., health-related quality of life (HRQoL) and long-term risk of mortality) after a first VT at old age. Show less
This thesis aimed to identify possible risks associated with erythropoiesis-simulating agent (ESA) use. First, trends in anemia management are described, showing less ESA use in Swedish patients... Show moreThis thesis aimed to identify possible risks associated with erythropoiesis-simulating agent (ESA) use. First, trends in anemia management are described, showing less ESA use in Swedish patients with chronic kidney disease (CKD) and less ESA-treated patients had a hemoglobin above 12 g/dL. Furthermore it is shown that ESA- treated pre-dialysis patients in the Netherlands received more antihypertensive agents than patients without ESA, confirming the hypertensive effect of ESA. However, no relevant difference in routinely measured blood pressure was observed between patients with and without ESA treatment, thus the hypertensive effect of ESAs could be controlled in clinical practice. In addition, no excess of thrombotic events was shown in ESA-treated dialysis patients compared to patients without ESA treatment. In contrast, a higher risk of cardiovascular events with ESA use was indicated in Danish patients with multiple myeloma and myelodyslastic syndrome. Also, with two analytical approaches, a harmful effect of high ESA doses on mortality was indicated in Dutch dialysis patients. Last, it was shown that ESA resistance was associated with mortality in both hemodialysis and peritoneal dialysis patients. To conclude, treatment with high ESA doses was associated with a higher risk of mortality, but the mechanism is largely unknown. Show less
This thesis aims to assess clinical characteristics of paraganglioma (PGLs) patients, with focus on SDH mutation carriers, evaluate psychological aspects in these subjects and to review various... Show moreThis thesis aims to assess clinical characteristics of paraganglioma (PGLs) patients, with focus on SDH mutation carriers, evaluate psychological aspects in these subjects and to review various treatment options for PGLs. Show less
This thesis describes the epidemiology of emerging infections with Clostridium difficile. Outbreaks of severe disease with high mortality were found to be associated with certain types of this... Show moreThis thesis describes the epidemiology of emerging infections with Clostridium difficile. Outbreaks of severe disease with high mortality were found to be associated with certain types of this bacterium and type specific risk factors were identified. Moreover, highly discriminatory typing techniques were useful in understanding clonal disseminations across healthcare institutions. Show less
Op de lijst van potentiële 'hot topics' voor de komende EU-verkiezingen vinden we vergrijzing, economische malaise en de vraag met welke maatregelen Europa's lage geboortecijfers opgekrikt kunnen... Show moreOp de lijst van potentiële 'hot topics' voor de komende EU-verkiezingen vinden we vergrijzing, economische malaise en de vraag met welke maatregelen Europa's lage geboortecijfers opgekrikt kunnen worden. De problematiek van de nog verse 21ste eeuw. Maar die is niet zonder precedenten volgens oud-historici gespecialiseerd in de sociaal-economische en demografische geschiedenis van Romeins Italië. De laatste twee eeuwen voor Christus, toen Rome van een stadstaatje tot een wereldrijk werd, waren roerige tijden voor de burgers van Italië. Zij werden betrokken in oorlogen, waren getuige van grootscheepse politieke veranderingen en leefden met snel groeiende immigranten en slaven in een nog sneller verstedelijkende samenlevering, volop dynamiek, dus. Lang werd gedacht dat het bestaan van de 'oude kern' van Romeinen temidden van deze hectiek van meerdere kanten af werd uitgehold. Met, inderdaad, economische maliase en vergrijzing en ontvolking als gevolg. Deze dissertatie betoogt echter dat het allemaal wel meeviel. Terwijl burgers met in name de landbouwsector in de regio rond Rome getroffen werd, groeiden de kansen in andere sectoren van de Romeinse economie. Gunstige klimaatomstandigheden en de voordelen van imperialise verzachten de problematiek. De economische schade bleef, met andere woorden, beperkt. En die baby's dan? Hier speelden specifieke culturele en sociale omstandigheden een rol. Een 'mamacultuur'en het dorpsleven met familie en buren nabij, ondervingen een goed deel van de potentieel nagatieve gevolgen van armoede voor het Romeinse geboortecijfer. Deze en andere factoren doen vermoeden dat de periode zelfs, in tegenstelling tot wat eerder gedacht werd, ruimte liet voor bevolkingsgroei. Een gedachte die aansluiting vindtin een nieuwe interpretatie van de met raadsels omgeven volkstellingscijfers van Rome's eerste keizer, Augustus. Doemdenkers en pessimisten onder oudere generaties oud-historici lijken daarmee door de geschiedenis te worden ingehaald. Een geruststellend lichtpuntje anno 2009 Show less
Lifespan in under genetic control. In this thesis we translated genes regulating lifespan in model organisms to humans. First we identified DAF-12 as a critical gene for lifespan regulation in the... Show moreLifespan in under genetic control. In this thesis we translated genes regulating lifespan in model organisms to humans. First we identified DAF-12 as a critical gene for lifespan regulation in the nematode worm C. elegans. Then we found that the Liver X Receptors and the Vitamin D Receptor are the most similar human proteins. We tested these genetic variation in these human genes in the Leiden 85-plus Study and found them to associate with with lifespan and cognitive decline respectively. Apolipoprotein E is a target gene of the Liver X Receptor. We found that plasma levels of apolipoprotein E associated with increased risk of cardiovascular mortality, cognitive decline and stroke in a manner independent of classical cardiovascular risk factors. Finally we reviewed the evidence from human candidate gene studies. We conclude that the use of model organisms provides useful directions for research into the genetics of human longevity. However, as the human signalling systems are more complex and our environment is different from that of model organisms, it is unclear to what extent results obtained in model organisms can be extrapolated to humans. Show less
Colorectal cancer is one of the most common malignancies in the world. A family history of colon cancer has been shown to increase an individual’s risk of developing the disease. Approximately 2-3%... Show moreColorectal cancer is one of the most common malignancies in the world. A family history of colon cancer has been shown to increase an individual’s risk of developing the disease. Approximately 2-3% of all colorectal cancers occur in the setting of a well described autosomal dominant inherited syndrome: The Lynch syndrome. It is essential to identify individuals at increased risk to offer adequate surveillance programs to prevent the development of tumors or recognize them at an early stage. This thesis gives a laboratory workup of suspected Lynch syndrome, including analysis of tumor tissue by microsatellite instability analysis and immunohistochemistry, and germline DNA analysis. Several aspects of surveillance in Lynch syndrome are described. The appropriate screening interval is discussed and the effect on mortality because of surveillance is shown. Further, we sought to establish whether individuals from dominant families without mismatch repair deficiency are also at increased risk by examining the incidence of advanced neoplasia during surveillance. Finally, the prevalence of the frequency of a positive family history for CRC, within a random cohort among the Dutch population is presented and also the prevalence of adenomas among young individuals at average risk for colorectal cancer is shown. Show less
