http://www.ilovelaser.com
Multiple Myeloma (MM) is a malignant plasma cell disorder accounting for 1% of all malignant
diseases and 10% of hematological malignancies. The annual incidence world-wide
of MM is approximately 0.4 to 5 per 100.000, with high incidence rates in North America,
Australia/New Zealand, Northern Europe, and Western Europe compared with Asian
countries. Within the United States, the incidence in African Americans is about double that
in Caucasians, whereas persons of Japanese and Chinese origin have lower rates. In the
Netherlands the annual incidence of MM is 5 per 100.000 and increases progressively with
age, the median age of diagnosis is 70 years.
MM is characterized by clonal expansion of malignant plasma cells in the bone marrow.
The myeloma plasma cell is a post-germinal centre plasma cell which has undergone somatic
hypermutation and immunoglobulin class switching. MM cells secrete a monoclonal
protein (M-protein) which can be detected in serum and/or urine. The M-protein is IgG in
50% of patients, and IgA in 30% of patients or consists of light chain (15%). In rare cases,
secretion of IgD (1%–2%), IgM (0.2%), or IgE (even less frequent), or absence of secretion
(non-secretory MM) is found.
Osteolytic bone lesions are the hallmark of MM. Other characteristic clinical features
include renal injury, anemia, hypercalcemia and immunodeficiency with recurrent
infections. These features may result directly from mass accumulation of plasma cells in
tissues (plasmacytomas) or indirectly from effects of the M-protein and/or cytokines secreted
by the plasma cells. Furthermore a high level of M-protein can cause hyperviscosity, renal
failure and neuropathy.
http://repub.eur.nl/res/pub/37640/121107_Broyl%2C%20Annemiek.pdf
Multiple Myeloma (MM) is a malignant plasma cell disorder accounting for 1% of all malignant
diseases and 10% of hematological malignancies. The annual incidence world-wide
of MM is approximately 0.4 to 5 per 100.000, with high incidence rates in North America,
Australia/New Zealand, Northern Europe, and Western Europe compared with Asian
countries. Within the United States, the incidence in African Americans is about double that
in Caucasians, whereas persons of Japanese and Chinese origin have lower rates. In the
Netherlands the annual incidence of MM is 5 per 100.000 and increases progressively with
age, the median age of diagnosis is 70 years.
MM is characterized by clonal expansion of malignant plasma cells in the bone marrow.
The myeloma plasma cell is a post-germinal centre plasma cell which has undergone somatic
hypermutation and immunoglobulin class switching. MM cells secrete a monoclonal
protein (M-protein) which can be detected in serum and/or urine. The M-protein is IgG in
50% of patients, and IgA in 30% of patients or consists of light chain (15%). In rare cases,
secretion of IgD (1%–2%), IgM (0.2%), or IgE (even less frequent), or absence of secretion
(non-secretory MM) is found.
Osteolytic bone lesions are the hallmark of MM. Other characteristic clinical features
include renal injury, anemia, hypercalcemia and immunodeficiency with recurrent
infections. These features may result directly from mass accumulation of plasma cells in
tissues (plasmacytomas) or indirectly from effects of the M-protein and/or cytokines secreted
by the plasma cells. Furthermore a high level of M-protein can cause hyperviscosity, renal
failure and neuropathy.http://repub.eur.nl/res/pub/37640/121107_Broyl%2C%20Annemiek.pdf
Normal haemostasis requires a delicate balance between procoagulant and anticoagulant
factors. Disruption of this balance may lead to bleeding disorders, such as hemophilia,
or thrombotic disorders, including deep vein thrombosis of the leg. As Virchow
already reported in 1877, properties of the blood vessel wall, the blood flow and blood
constituents contribute to the formation of thrombi in either veins or arteries. However,
through contemporary research the complexity of this process leading to thrombus
formation has become more apparent.
An important player in thrombus formation is von Willebrand Factor (VWF), a large
multifunctional glycoprotein. VWF initiates adherence of platelets to the injured vessel
wall and subsequent platelet aggregation leading inevitably to the formation of
thrombi. In addition, VWF is a carrier protein of coagulation factor VIII (FVIII), thereby
protecting it from clearance.
In healthy subjects normal plasma VWF levels range from 0.60 – 1.40 IU/mL and are
characterized by a large variation. This can be partly attributed to a number of lifestyle
and environmental factors, but most importantly to genetic factors.
The necessity of maintaining normal VWF levels in the circulation is illustrated by
two clinical manifestations that may occur when VWF exceeds its normal range. Low
levels of VWF may lead to bleeding, which is known as von Willebrand Disease (VWD),
the most common inherited bleeding disorder in humans. To the contrary, high VWF
antigen (VWF:Ag) levels are associated with an increased risk of venous thrombosis
and arterial thrombosis, including myocardial infarction (MI) and ischemic stroke.
Multiple sclerosis (MS) is a chronic neurological disease that
affects the brain and spinal cord. It is thought that MS is an
autoimmune disease, where a person’s immune system reacts to
its own body, namely the myelin sheath that surrounds the nerve
cells. Disease symptoms include vision problems, imbalance and
paralysis of the limbs. The exact cause of MS is still unknown, and
therapies without adverse effects are not available. Substantial
evidence suggests that the disease arises as a result of a certain
combination of environmental, genetic and infectious
circumstances. We hypothesize that herpesviruses create a
repertoire of autoreactive T-cells, which play a crucial role in the
demyelination process. To unravel the contribution of these
autoreactive T-cells to the pathogenesis of MS, the common
marmoset is used as an animal model for MS. The common
marmoset is a relevant model with a close genetic and
immunological proximity to humans, and it resembles the
disease in its clinical and pathological presentation. This thesis
describes how the common marmoset model for MS is refined
ethically, mechanistically, and conceptually to better understand
the underlying pathogenic processes, as well as to develop and
improve new targets for MS therapy.
Hepatic Lipase (HL; EC 3.1.1.3) is an extracellular glycoprotein with phospholipase A1 and
triacylglycerol hydrolase activity. The human HL protein is encoded by the LIPC gene on
chromosome 15q21. Most of this protein is synthesized in the parenchymal cells of the liver
and secreted into the space of Disse where it binds to heparin sulfate proteoglycans.
Some synthesis of HL was also observed in macrophages. The HL protein is also present in
the steroidogenic adrenal glands, ovaries and, in small amounts, in the testes. By using
heparin, HL protein is displaced from its binding site. Human HL protein is a homodimer, the
monomer has a molecular weight of 65 kDa. In the metabolism of plasma lipoproteins HL
plays an important role; it mediates the conversion of high density lipoprotein subfraction 2
(HDL2) to high density lipoprotein subfraction 3 (HDL3), the conversion of intermediate density
lipoprotein (IDL) to low density lipoproteins (LDL), and the formation of small dense LDL
(sdLDL) from large buoyant LDL. HL has a role in postprandial lipid transport where it
facilitates the clearance of remnant lipoproteins by the liver. In adrenals and ovaries the HL
enzyme facilitates the delivery of HDL cholesterol for steroidogenesis, at least in the rat.
HL expression is determined by genetic, hormonal and nutritional factors, and by
body composition. HL activity is associated with a risk for Coronary Artery Diseases
(CAD). Whether high HL expression is anti- or pro-atherogenic depends on other genetic or
metabolic factors, e.g. concomitant hypertriglyceridemia [1,19]. Humans with visceral obesity
and insulin resistance or type 2 diabetes show increased levels of HL expression.
How HL gene expression is altered in insulin-resistant conditions is unknown. Relative to the
common LIPC C-allele (referring to the C/T polymorphism at the -514 position), carriers of the
T-allele have reduced post-heparin HL activity, and the T-allele is associated with dyslipidemia
and insulin resistance in healthy controls and in Familial Combined Hyperlipidemia (FCH).
In cell culture experiments using human HepG2 hepatoma cells, HL expression was found to
be increased by elevated levels of fatty acids and glucose, conditions that prevail
in insulin resistance. How these metabolic factors affect HL expression is largely unknown.
At first glance, deciding whether to get the PSA screening
test for prostate cancer seems to be pretty straightforward and attractive. It’s a simple
blood test that can pick up the prostate cancer long before your symptoms appear. After
all, your prostate cancer is earlier treated resulting in cure and better outcome. Therefore
prostate cancer screening seems to be suitable for public commercials. However, many
of the cancers that will be detected by screening are so slow-growing that might never
cause problems during mens life. Moreover, their diagnosis by biopsy, and treatment,
might be worse than the disease itself. Therefore, prostate cancer screening looks favourable;
however, watch out for the prostate cancer bomb.
The World Health Organization (WHO) has played a leading role in developing
http://whqlibdoc.who.int/hq/2003/WHO_CDS_CSR_RMD_2003.2.pdf
Comprehensive quality systems are essential in order to ensure the validity of results from
The continuing emergence of pathogenic microorganisms that are resistant to first-line antimicrobials is a cause of increasing concern. This emergence is associated with higher levels of mortality
Under Dutch law, preventive youth healthcare organisations have a duty to ensure the early
identification of children with health or developmental problems. Similarly, municipalities
have a duty to monitor young people’s health at least every four years. For problem
identification and monitoring, both individual and collective, these organisations often use
self-report questionnaires. The overall aim of this thesis is to study various methodological
and validity issues related to the use of self-report questionnaires among young people in a
preventive youth healthcare setting. Seven specific research questions are derived from the
Rotterdam Youth Monitor (RYM), a longitudinal youth health surveillance system integrated
into preventive youth healthcare in the greater Rotterdam area.
The objective of this thesis was to quantify three-dimensional ocular stability
in response to head movements in healthy human subjects and in patients
with various types of peripheral vestibular disorders. Despite a large increase
in our knowledge from animal and human studies about the neuronal circuitry
that regulates three-dimensional (3D) vestibular organization (for a recent
review see Angelaki and Cullen 2008), its application to clinical practice is still
a long way ahead. In order to bridge this gap, we explored in healthy
subjects the naturally occurring variability in 3D vestibulo-ocular stabilization
and compared these results with changes that occur in 3D vestibulo-ocular
stabilization in patients with various types of unilateral vestibular disorders.
Psoriasis is universal in occurrence, although the worldwide prevalence varies between 0.6%
and 4.8%.The prevalence of psoriasis in people of Caucasian descend is approximately 2%.
In the Netherlands it is therefore estimated that approximately 300,000 people are diagnosed
as having psoriasis. Its prevalence is equal in men and women and can first appear at any age,
from infancy to elderly, although the mean age of development has suggested to be around
30 years old. Some studies suggest the presence of two forms of psoriasis related to the age
at onset. Early onset psoriasis, which comprises approximately 75% of the psoriasis population,
presents itself before the age of 40 mostly with a positive family history and with more severe
disease. While late onset psoriasis presents itself after the age of 40 and may have a less severe
clinical course. However, other studies were not able to confirm the presence of more severe
psoriasis in those subjects with an early age of onset. The extent of body surface area affected
by psoriasis is variable, but in most people the severity of their psoriasis is reasonably stable
over time. Based on a patient survey the prevalence of moderate to severe psoriasis (i.e. more
than 3% of the body surface area affected) was recently estimated to be approximately 17%.