Nieuwegein, Netherlands
Nieuwegein, Netherlands

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Harmsze A.M.,Afdeling Klinische Farmacie | Harmsze A.M.,University Utrecht | Van Werkum J.W.,Afdeling Cardiologie | Ten Berg J.M.,Afdeling Cardiologie | And 6 more authors.
Pharmaceutisch Weekblad | Year: 2011

OBJECTIVE: To assess how platelet reactivity and the occurrence of stent thrombosis in patients undergoing percutaneous coronary interventions (PCI) on dual antiplatelet therapy is influenced by genetic variants affecting clopidogrel's absorption (ASCB1 C1236T, G2677T/A, C3435T), metabolism (CYP2C9*2 or *3, CYP2C19*2 or *3, CYP3A4*1B and CYP3A5*3) and pharmacodynamics (P2Y1 A1622G). Clopidogrel plays an important role in the prevention of thrombotic events in patients undergoing PCI. However, a substantial number of atherothrombotic events, including stent thrombosis, still occurs. METHODS: In the first study, platelet function was assessed by two platelet function tests in 428 consecutive patients undergoing elective PCI. Patients were on Clopidogrel maintenance therapy for > 5 days prior to PCI ('75 mg group') or received a 300 mg clopidogrel loading dose 1-5 days prior to PCI ('300 mg group'). In a second study, logistic regression analysis was used to analyse the impact of genetic variations in 176 subjects who developed stent thrombosis while on dual antiplatelet therapy and in 420 control subjects who did not develop atherothrombotic events, including stent thrombosis, within one year post-PCI. RESULTS: In both the 75 mg group and the 300 mg group in the first study, CYP2C19*2 was associated with higher platelet reactivity (p < 0.001) and poor-responder status: OR adj 3.8 (CI95 2.0-7.2) and OR adj 4.1 (CI95 1.6-10.4), respectively. In the 300 mg group, CYP2C9*3 was associated with higher platelet reactivity (p < 0.05) and poor-responder status: OR adj 4.0 (CI95 1.2-13.8). In the second study, CYP2C19*2 and CYP2C9*3 were associated with stent thrombosis: OR adj 1.7 (CI95 1.0-2.6) and OR adj 2.4 (CI95 1.1-5.5), respectively. CONCLUSIONS: Carriage of CYP2C19*2 and CYPC9*3 is associated with heightened platelet reactivity and an increased risk of stent thrombosis after PCI.


Dijkstra I.M.,Afdeling Klinische Chemie | De Keijzer M.H.,Klinisch Chemisch Laboratorium | Van Loon D.,Afdeling Klinische Chemie
Nederlands Tijdschrift voor Klinische Chemie en Laboratoriumgeneeskunde | Year: 2013

Many hospitals and/or medical laboratories collaborate in order to increase efficiency, reduce costs and provide better service and care to patients. The here described collaboration between the St. Antonius Hospital in Nieuwegein and the Rivierenland Hospital in Tiel involves the opening of a dialysis ward in Tiel. Patients from the St. Antonius Hospital who are living in the Tiel area can now be dialysed close to their home. In respect to laboratory testing for these patients, the lab results were requested to be quickly available in the St. Antonius Hospital information system. Therefore, we aimed to perform as many as possible tests in Tiel in order to minimize transport of blood samples. Instead, the laboratory results were transported digitally. Here we describe the comparability of laboratory testing in two distant and separate medical laboratories using different equipment and methods. Moreover, we explain how we dealt with observed differences by means of sigma score calculations and the application of corrective factors.


Muskiet F.A.J.,Universitair Medisch Centrum Groningen | Schuitemaker G.E.,ORTHO Instituut | Van Der Veer E.,Universitair Medisch Centrum Groningen | Wielders J.P.M.,Afdeling Klinische Chemie
Nederlands Tijdschrift voor Klinische Chemie en Laboratoriumgeneeskunde | Year: 2013

In this paper we appraise the new dietary reference intakes, the preferred status and the supplement advices for vitamin D of the Dutch Health Council (GR) of September 26, 2012, and also the underlying rationale. We point at the changes with previous reports of 2000 and 2008 and discuss the most important differences with the recent vitamin D recommendations of the USA 'Institute of Medicine' (IOM) and the German Nutritional Society. Our comment is set out in 11 theses, in which we on the one hand emphasize the limitations that arise from the choice of the GR to exclusively take bone homeostasis as a starting point and, on the other hand, the use of randomized trials as the virtually only criterion for the development of dietary reference intakes. We question the manner by which the recommended dietary allowance and supplemental dosages have been calculated and finish with the advise to adhere for the minimum serum 25-hydroxyvitamin D (25OH)D) concentration of ≥50 nmol/l, as recommended by the USA IOM, the German Nutritional Society and the CBO consensus 'Osteoporosis and Fall Prevention'. We also propose to provide information on the possible benefits of a 25(OH)D concentration of 80-150 nmol/l and how such a vitamin D status might be reached. In a more holistic approach it is emphasized that calcium homeostasis is governed by more (lifestyle) factors than vitamin D and calcium per se.


Van Exel E.,EMGO instituut | Eikelenboom P.,Afdeling Psychiatrie | Comijs H.C.,Afdeling Psychiatrie | Kurniawan C.,Afdeling Psychiatrie | And 6 more authors.
Tijdschrift voor Psychiatrie | Year: 2011

BACKGROUND: It has still not been established unequivocally whether vascular risk factors and inflammatory reactions, determined by heredity, are a cause or a result of Alzheimer's disease (AD). If the offspring of parents with AD have more risk factors and more frequent and severe inflammatory reactions than the offspring of parents without AD, this argues strongly in favor of a causal relationship between vascular risk factors, a pro-inflammatory cytokine response and AD. AIM: To determine whether the offspring of parents with AD have more risk factors and more frequent and severe inflammatory reactions than the offspring of parents without AD. METHOD: Vascular risk-factors, pro-inflammatory cytokines and the APOE genotype were determined in 206 offspring of parents with AD and in zoo offspring of parents without AD. RESULTS: Offspring of parents with AD carried more APOE epsilon4 than offspring of parents without AD (47% vs 21%). Middle-aged offspring of parents with a history of AD also had higher blood pressure and agreater atherosclerotic burden than the offspring of parents without AD. Also their response to the pro-inflammatory cytokine was significantly higher. CONCLUSION: Hypertension and an inherited pro-inflammatory cytokine profile in middle-age are early risk factors that contribute to the development of AD in old age. Offspring with a parental history of AD should therefore be offered screening and treatment for hypertension and have their blood pressure checked so that the development of AD in old age can be prevented.


Dijkstra I.M.,Afdeling Klinische Chemie | Koene H.R.,Interne Geneeskunde | Deneer V.H.M.,Klinische Farmacie | Eland I.A.,Interne Geneeskunde | Wakelkamp I.M.M.J.,Interne Geneeskunde
Nederlands Tijdschrift voor Klinische Chemie en Laboratoriumgeneeskunde | Year: 2013

The use of laxative drugs is highly frequent and increasing every year. These drugs can be obtained with or without a physician's prescription, so called 'over the counter drugs'. Most patients use these drugs for the right purpose, namely complaints of constipation. However, a small minority of patients uses laxatives in an attempt to reduce intake of calories, increase loss of water and thereby achieve weight loss. Prolonged and excessive use of laxatives is associated with many disturbances in human physiologic systems, leading to a variety of clinical symptoms. Abuse of laxatives is not the first diagnose on the physician's list of possible explanations for the observed abnormalities. Moreover, patients often deny using laxatives when physicians suspect and ask about laxative substances. In order to raise awareness, especially for medical laboratory professionals, we here describe a case in which various and sometimes extreme abnormalities were found in the clinical laboratory. The combination of the patient's elaborate medical history and laboratory results pointed towards laxative abuse. This was finally confirmed by positive testing for large amounts of bisacodyl in urine.


Boss D.S.,Afdeling Klinische Chemie | Hackeng C.M.,Afdeling Klinische Chemie | Koene H.R.,Afdeling Interne Geneeskunde | Bikker A.,Afdeling Klinische Chemie | Van Loon D.,Afdeling Klinische Chemie
Nederlands Tijdschrift voor Klinische Chemie en Laboratoriumgeneeskunde | Year: 2014

Analytical interference of M-proteins in the clinical laboratory is a well-known phenomenon. In this article we describe a multiple myeloma patient with an unexplained elevated total bilirubin. Further analyses suggest a reaction between the patient's immunoglobulins and a component in the total bilirubin assay reagents to be the cause of this phenomenon. Reporting of erroneous laboratory results to clinicians can have serious consequences. In situations where an unexplained high total bilirubin is found in patients with monoclonal gammopathy, interference should be considered. Repeating the measurement on another chemistry platform can be helpful in such cases.

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