Polymorphic drug metabolising enzymes:Assessment of activities by phenotyping and genotyping in clinical pharmacology

Drug effects (pharmacodynamics) are determined by drug concentration at target site and the affinity of the drug for a target. Pharmacogenetics describes inherited differences in drug metabolising enzyme activities and differences in drug transporters and receptors.Answers were sought on the following questions:1. What is the value of genotyping on polymorphic drug metabolising enzymes compared to the classical phenotyping stategies?2. What is the situation concerning CYP2D6 and CYP2C19 polymorphism in the Dutch population?3. Is knowledge of the individual metaboliser status of CYP2D6 or CYP2C19 valuable in clinical pharmacological research and practice of pharmacotherap

Paraneoplastic manifestations in children

Paraneoplastic manifestations are signs and symptoms observed in patients with cancer, distant from the tumour or its metastases and not caused by invasion, obstruction or bulk mass. In children with cancer, paraneoplastic manifestations are rare and distinct from those observed in adults. Knowledge about paraneoplastic manifestations can be of great clinical importance because they may be the presenting sign of a tumour or its recurrence and hence facilitate early diagnosis. In contrast, they sometimes mask the symptoms of a tumour and cause diagnostic delay. In this review, paraneoplastic manifestations in children are described, including hypercalcaemia, Cushing syndrome, precocious puberty, opsoclonus/myoclonus, acquired von Willebrand disease, watery diarrhoea syndrome, and hypertension. The mechanisms causing these manifestations are also discussed