The perinatal mortality rate in The Netherlands is among the highest in the European Union,
with one in 100 babies dying during pregnancy, at birth or shortly thereafter. Low birth
weight, preterm birth, congenital anomalies, perinatal asphyxia, and pre-eclampsia are major
contributors to perinatal mortality. Moreover, pre-eclampsia is not only a major driver for
perinatal mortality but plays a significant role in maternal mortality as well.http://repub.eur.nl/res/pub/20712/100915_Timmermans%2C%20Sarah.pdf
The human intestine contains about 1014 micro-organisms that critically
contribute to
tissue homeostasis, host metabolism and other benefi cial processes.
Despite a continuous
microbial exposure within in the intestine, the mucosal immune system is
able to
maintain a state of tolerance to the microbiota. An aberrant immune
response of the
intestinal immune system results in a defective tolerance in the
intestine, which leads to
a breakdown of intestinal homeostasis. This in turn, can lead to chronic
intestinal infl ammation
or inflammatory bowel disease (IBD).
From an immunological perspective, exaggerated responses by mucosal T and
B cells
(the adaptive immune system) have traditionally been regarded as the key
contributors
to the pathogenesis of IBD. However, discoveries of innate defects that
are associated
with IBD have refocused the attention to this arm of the immune system.
In this thesis we try to answer some of the open questions concerning the
pathogenesis
of IBD and defects in the innate immune system.
Peripheral Arterial Disease (PAD) is a multifactorial syndrome that most commonly
affects people over 60 years of age. With the aging of the population, the
prevalence of atherosclerotic disease and its associated adverse outcomes will
increase. It has to be noted that the process of established atherothrombosis is not
limited to a single arterial location, giving it the character of a systemic and
generalized disease. The Reduction of Atherothrombosis for Continued Health
(REACH) registry demonstrated that one out of six patients with (i) PAD, (ii)
cerebrovascular disease, or (iii) coronary artery disease had involvement of one or
two other arterial beds. Importantly, the presence of multiple affected arterial
territories, called polyvascular disease, has been demonstrated to be an
independent predictor of long-term cardiovascular outcome in the general
population.
In response to studies demonstrating the adverse prognosis of
atherosclerotic disease, the need for adequate risk factor stratification and
reduction has emerged. The importance of risk factor reduction in patients with
PAD has resulted in universally recommended atherothrombotic risk factor
reduction, with the objective of decreasing the high incidence of heart disease and
cerebrovascular disease associated with PAD. In patients with PAD scheduled for
vascular surgery, risk factor stratification is directed at the detection of
(a)symptomatic atherosclerotic disease in other vascular beds than the primary
symptomatic arterial location. Early detection of polyvascular atherosclerotic
disease has important consequences for risk factor reduction strategies, including
life-style interventions and medical therapy.