Fibrinogen gamma' in ischemic stroke: a case-control study.

Background And Purpose: To determine the contribution of fibrinogen gamma' levels and FGG haplotypes to ischemic stroke.

Methods: Associations between fibrinogen gamma' levels, fibrinogen gamma'/total fibrinogen ratio, and FGG haplotypes with the risk of ischemic stroke were determined in 124 cases and 125 controls.

Results: Fibrinogen gamma'/total fibrinogen ratio was higher in patients than in controls during the acute phase of the stroke and lower in the convalescent phase 3 months after the stroke.

Platelet receptor P2RY12 haplotypes predict restenosis after percutaneous coronary interventions.

The platelet receptor P2Y12 (gene symbol P2RY12) is involved in several processes that contribute to restenosis after percutaneous coronary interventions (PCI). Therefore, common variation in the P2Y12 gene may serve as a useful marker for risk stratification. We studied whether common variation in the platelet receptor P2Y12 gene affects the risk of restenosis after PCI.

The influence of established genetic variation in the haemostatic system on clinical restenosis after percutaneous coronary interventions.

Since activation of the haemostatic system is an important feature of the wound healing response triggered by arterial injury, variations in genes involved in thrombus formation may play a role in restenosis after percutaneous coronary interventions (PCI). Therefore, our aim was to examine the relationship between polymorphisms that are known to play a role in the haemostatic system and the risk of clinical restenosis in the GENetic DEterminants of Restenosis (GENDER) study, a multicenter prospective study design that enrolled 3,104 consecutive patients after successful PCI. Target vessel revascularization (TVR) was the primary endpoint.

Thrombin-activatable fibrinolysis inhibitor is associated with severity and outcome of severe meningococcal infection in children.

Background And Objectives: In pediatric meningococcal sepsis, an imbalance between coagulation and fibrinolysis and proinflammatory action play major roles. We hypothesized that thrombin activatable fibrinolysis inhibitor (TAFI) and/or TAFI activation markers are involved in the pathogenesis of meningococcal sepsis.

Patients And Methods: Children with severe meningococcal sepsis (n = 112) previously included in Rotterdam-based trials participated in this study.

Epigenetic silencing of cyclooxygenase-2 affects clinical outcome in gastric cancer.

Purpose: Overexpression of cyclooxygenase-2 (COX-2) in gastric cancer has been shown to enhance tumor progression. We investigated whether silencing by promoter region hypermethylation of the COX-2 gene contributes to disease outcome in gastric cancer.

Materials And Methods: COX-2 methylation status was initially assessed by capillary array electrophoresis methylation-specific polymerase chain reaction (CAE-MSP) and COX-2 protein expression by immunohistochemistry (IHC) in 40 primary gastric cancer tissues in a pilot study.

Haplotypes of the fibrinogen gene and cerebral small vessel disease: the Rotterdam scan study.

Objective: Fibrinogen levels and fibrinogen clot structure have been implicated in the pathogenesis of vascular disease. We examined fibrinogen levels and variation in fibrinogen genes (fibrinogen gamma (FGG), alpha (FGA) and beta (FGB)), which have been associated with fibrin clot structure and fibrinogen levels, in relation to cerebral small vessel disease (SVD).

Methods And Results: This study was performed as part of the Rotterdam Scan Study, a population based study in 1077 elderly patients undergoing cerebral MRI.

Improved survival of children with sepsis and purpura: effects of age, gender, and era.

Background: To gain insight into factors that might affect results of future case-control studies, we performed an analysis of children with sepsis and purpura admitted to the paediatric intensive care unit (PICU) of Erasmus MC-Sophia Children's Hospital (Rotterdam, The Netherlands).

Methods: Between 1988 and 2006, all 287 children consecutively admitted with sepsis and purpura were included in various sepsis studies. Data regarding age, gender, ethnicity, serogroup of Neisseria meningitidis, severity, therapy, and survival were collected prospectively.

Prothrombotic coagulation abnormalities in patients with paraprotein-producing B-cell disorders.

Purpose: An increased incidence of thromboembolic complications has been observed in multiple myeloma (MM), especially when patients are treated with anthracycline-based chemotherapy. In patients with MM, plasma levels of several prothrombotic coagulation factors are increased, and this can contribute to the prothrombotic state of these patients. Recently, an increased thrombosis risk has also been described for other plasma cell disorders (PCDs), such as monoclonal gammopathy of uncertain significance (MGUS) and systemic amyloidosis.

No influence of increased intake of orange and blackcurrant juices and dietary amounts of vitamin E on paraoxonase-1 activity in patients with peripheral arterial disease.

Background: Paraoxonase-1 (PON1) is an antioxidative enzyme associated with HDL and its serum activity is associated with risk of cardiovascular disease. The interindividual variation in PON1 activity is partly determined by genetic factors, such as polymorphisms in the PON1 gene, but also by dietary factors like the antioxidants.

Aim Of The Study: We examined the effect of antioxidant-rich orange and blackcurrant juices and vitamin E supplement on PON1 activity in patients with peripheral arterial disease.

Usefulness of combining complement factor H and C-reactive protein genetic profiles for predicting myocardial infarction (from the Rotterdam Study).

Complement factor H (CFH) is an important regulator of the complement cascade. Binding of C-reactive protein (CRP) to CFH augments the ability of CFH to downregulate the effect of complement in atherosclerotic lesions. The CFH Tyr402His polymorphism has been suggested to influence the ability of CFH to bind CRP.

CRP gene haplotypes, serum CRP, and cerebral small-vessel disease: the Rotterdam Scan Study and the MEMO Study.

Background And Purpose: It remains unclear whether C-reactive protein (CRP) is a serum marker for atherothrombotic disease or a causal factor in the pathogenesis of atherosclerosis. We explored the association between CRP gene variations and cerebral small-vessel disease (SVD) in the Rotterdam Scan Study (N=1035) and the MEMO Study (N=268).

Methods: Common haplotypes within the CRP gene were determined by genotype-tagging single-nucleotide polymorphisms.

Drug Interaction of Fluvoxamine and Fluoxetine with Nevirapine in HIV-1-Infected Individuals.

Objective: To evaluate the possible pharmacokinetic interactions between nevirapine and fluvoxamine or fluoxetine in patients with HIV-1 infection.

Patients And Methods: Patients who were using fluvoxamine or fluoxetine concomitantly were chosen from an unselected cohort (n = 173) of HIV-1-infected individuals using a nevirapine-containing regimen (study group). HIV-1-infected patients using nevirapine without fluvoxamine or fluoxetine and non-HIV-infected individuals who were using fluvoxamine and fluoxetine were included as controls.

Assessment of methylation events during colorectal tumor progression by absolute quantitative analysis of methylated alleles.

To date, the epigenetic events involved in the progression of colorectal cancer are not well described. To study, in detail, methylation during colorectal cancer development in high-risk adenomas, we developed an assay combining in situ (on-slide) sodium bisulfite modification (SBM) of paraffin-embedded archival tissue sections with absolute quantitative assessment of methylated alleles (AQAMA). We tested the performance of the assay to detect methylation level differences between paired pre-malignant and malignant colorectal cancer stages.

Specific peptides identified by mass spectrometry in placental tissue from pregnancies complicated by early onset preeclampsia attained by laser capture dissection.

Preeclampsia is a common pregnancy-specific syndrome that is diagnosed by the appearance of both increased blood pressure and proteinuria. Preeclampsia is associated with significant fetal and maternal morbidity and mortality. Although the etiology of preeclampsia is unknown, it is evident that abnormal placentation and trophoblast metabolism plays an important role.

Genetic variation, C-reactive protein levels, and incidence of diabetes.

C-reactive protein (CRP) has been shown to be associated with type 2 diabetes, but whether CRP has a causal role is not yet clear. We examined the association in the Rotterdam Study, a population-based prospective cohort study. The association of baseline serum CRP and incident diabetes during follow-up was investigated, and a meta-analysis was conducted on the BMI-adjusted relation of CRP and diabetes.

Matrix metalloproteinase 3 haplotypes and dementia and Alzheimer's disease. The Rotterdam Study.

Evidence by post-mortem and animal studies suggests that matrix metalloproteinases (MMPs) may play an important role in the pathophysiology of Alzheimer's disease (AD) through degradation of amyloid beta. We investigated in 5999 elderly whether MMP3-haplotypes are associated with cognitive performance over time, dementia and AD. We also explored the association of MMP-3 haplotypes with changes in hippocampal volume and severity of periventricular and subcortical white matter lesions (WML).

Prothrombotic coagulation abnormalities in patients with newly diagnosed multiple myeloma.

Prothrombotic coagulation abnormalities were analyzed in patients with untreated multiple myeloma. Increases in factor VIII, in von Willebrand factor (vWF) and a decrease in protein S were observed and these changes were strongly associated with disease stage. No difference in baseline coagulation parameters was found between patients with and without subsequent venous thromboembolism.

Fibrinogen gene haplotypes in relation to risk of coronary events and coronary and extracoronary atherosclerosis: the Rotterdam Study.

Fibrin network structure has been correlated with coronary disease. Fibrinogen gamma and alpha (FGG and FGA) gene haplotypes (chromosome 4q28) may be associated with fibrin network structure, and thereby with rigidity of the fibrin clot and sensitivity of the fibrin clot to the fibrinolytic system. Through these mechanisms they may influence risk of cardiovascular disease.

Genetic variation in estrogen receptor, C-reactive protein and fibrinogen does not predict the plasma levels of inflammation markers after longterm hormone replacement therapy.

Markers of inflammation, such as C-reactive protein (CRP) and fibrinogen, are associated with the risk of atherothrombosis. Plasma levels of these markers of inflammation are affected by hormone replacement therapy (HRT) and modulated by smoking. We studied whether genetic variation in the estrogen receptor- 1 (ESR1), CRP and fibrinogen-beta genes influences the plasma levels of inflammation markers after HRT.

Genetic variation in thrombin-activatable fibrinolysis inhibitor (TAFI) is associated with the risk of splanchnic vein thrombosis.

Splanchnic vein thrombosis (SVT) has been associated with a hypercoagulable state. Thrombin-activatable fibrinolysis inhibitor (TAFI) may contribute to a hypercoagulable state, and therefore we were interested in the role of TAFI in SVT. Since the disease is frequently associated with liver insufficiency, which affects plasma levels of TAFI, we studied the role of variation in the TAFI gene in SVT.

Plasma triacylglycerol and coagulation factor concentrations predict the anticoagulant effect of dietary fish oil in overweight subjects.

Fish oil, containing (n-3) PUFA, is associated with a moderate reduction in cardiovascular disease through a multifactorial mechanism involving a decrease in plasma lipids and anticoagulant activity. Two intervention studies on subjects at risk were performed to determine the relation of these 2 fish-oil effects. In study 1, 54 overweight subjects consumed 3.

Matrix metalloproteinase-9 gene -1562C/T polymorphism mitigates preeclampsia.

Although the aetiology of preeclampsia is unknown, there is substantial evidence that it finds its roots in abnormal placentation. Prerequisites for successful placentation include trophoblast invasion, degradation and remodelling of the uterine decidual extracellular matrix, and apoptosis without thrombosis. We tested this hypothesis by analysing the effect of functional polymorphisms in the genes coding for MMP9, MMP3 and annexin A5 on the risk of preeclampsia using a case-control design.

Interleukin 10: a new risk marker for the development of restenosis after percutaneous coronary intervention.

Genetic factors appear to be important in the process of restenosis after percutaneous coronary intervention (PCI), as well as in inflammation, a pivotal factor in restenosis. An important mediator in the inflammatory response is interleukin (IL)-10. Our aim was to study whether genetic variants in IL-10 predispose to the risk of restenosis.

Inflammation and apoptosis genes and the risk of restenosis after percutaneous coronary intervention.

Objectives: Genetic factors appear to be important in the development of restenosis after percutaneous coronary intervention, as well as in the process of inflammation, a pivotal factor in restenosis. Caspase-1, interleukin-1-receptor and protein tyrosine phosphatase nonreceptor type 22 are important mediators in the inflammatory response and caspase-1 also in apoptosis. Therefore, we examined whether polymorphisms in these candidate genes are related to the risk of developing restenosis after percutaneous coronary intervention.