This thesis describes clinical, cytological, immunological and pharmacological aspects of acute childhood leukaemia and allogeneic stem cell transplantation(SCT), with the emphasis on the analysis... Show moreThis thesis describes clinical, cytological, immunological and pharmacological aspects of acute childhood leukaemia and allogeneic stem cell transplantation(SCT), with the emphasis on the analysis of potential improvements in risk stratification and possible treatment adaptation, in order to decrease relapse frequency and disease-related death. Firstly, to study the role of chemokine receptor/ligand interactions in the context of extramedullary leukaemia, we analyzed the homing receptor expression on leukemic blast cells in skin or intestine, peripheral blood and bone marrow of patients with T-ALL en AML, respectively. Secondly, the treatment results of 132 children, who received an allogeneic HLA-identical SCT for acute leukaemia was evaluated, showing the effect of biologically effective TBI dose on relapse risk. Thirdly, to optimize the use of Cyclosporin A(CsA) for adequate Graft-versus-host disease(GVHD) prophylaxis and to avoid drug toxicity, we investigated the pharmacokinetics of CsA in children after SCT, and showed that monitoring CsA exposure early after SCT may provide a tool to influence outcome. Finally, to gain a better understanding of the mechanism of chimerism induction of endothelial and epithelial cells following allogeneic SCT, the occurrence of chimerism in relation to the conditioning regimen, time interval after SCT and development of GVHD was studied. Show less
This ethnographic study investigated what wartime children identified as common illnesses which affected them and how they restored normality. The research findings were aimed at providing baseline... Show moreThis ethnographic study investigated what wartime children identified as common illnesses which affected them and how they restored normality. The research findings were aimed at providing baseline information for policies and healthcare interventions consistent with children__s own needs and priorities. Qualitative ethnographic methods suitable for children aged 9-16 years were employed over a one year period in 2004-2005 and through visits to Gulu district in 2006 and 2007. A survey was conducted with 165 children (N=165), in addition to an extensive follow-up of 24 children. Data show that there was a high burden of illnesses among the children. Illnesses were mainly infectious diseases and complaints symptomatic of emotional distress. For infectious illnesses, children used herbal medicines and pharmaceuticals including prescription-only medicines like antibiotics and antimalarials. Coping mechanisms for emotional distress included discouraging open expression of suffering, using tranquilisers, atika plant (Labiate species), and engaging in income generating activities. Findings further highlight epistemological, methodological, theoretical, and policy issues regarding wartime children__s illness experiences and quests for wellbeing. Children readily discussed experiences with infectious illnesses because of their acute onset, primacy, and a priority. Infectious diseases are an immediate need and disorganize a relatively stable condition of emotional distress. Whereas some forms of emotional distress are severe and require immediate redress, there are no simple ways of dealing with them. Although this study underscores the importance of addressing wider socio-economic factors as effective preventive approaches in dealing with infectious diseases and emotional distress, I propose that it is fitting for children to engage in short term curative approaches in illness management, in the context of medical pluralism given the dire context in which they lived. Show less
This thesis deals with emotional and social influences on childhood somatic complaints. Strong support is provided for the idea that negative affect contributes to the development of somatic... Show moreThis thesis deals with emotional and social influences on childhood somatic complaints. Strong support is provided for the idea that negative affect contributes to the development of somatic complaints in childhood. In addition, the studies described give information about the type and levels of negative affect associated with somatic complaints in childhood. When appraisal is characterized by the experience of little control over negative situations and emotions, this is likely to directly cause more feelings of negative affect and also to contribute to a more negative processing of emotions: children who feel little control evidently use more maladaptive emotion regulation strategies. This negative emotional processing further contributes to negative affect and subsequent somatic complaints. These relationships between negative affect and somatic complaints are even present at subclinical levels of emotional problems. With regard to social problems, it is found that they have an effect on somatic complaints that is fully mediated by aspects of children’s emotional functioning: self-perceived social problems indicate lower feelings of control and more maladaptive emotion regulation. Show less
This thesis addressed the physiological impact of fear in 4- and 7-year-old children, induced by media and social fear-inducing tasks (the Trier Social Stress Test for Children). The main question... Show moreThis thesis addressed the physiological impact of fear in 4- and 7-year-old children, induced by media and social fear-inducing tasks (the Trier Social Stress Test for Children). The main question pertained to individual differences in physiological reactivity to fear-inducing stimuli. The possibly relevant factors of attachment security, the child’s temperamental fearfulness, and variations in the serotonin transporter gene (5-HTTLPR; long vs. short allele) were taken into account. Results showed that temperament, attachment, and genetic influences play significant and interactive roles in the expression of fear reactivity. A secure relationship affected the reactivity to media-induced fear stimuli in temperamentally more fearful children but not in less fearful children irrespective of children’s ages. This finding adds to the growing literature showing that children high in negative emotion are more susceptible to positive as well as negative rearing influences. Furthermore, we found evidence that reactivity to the social fear-inducing task was explained by a combination of variations in the serotonin transporter gene and attachment security. Children with a secure attachment representation and two long 5-HTT alleles showed the lowest levels of fear reactivity, indicating that physiological reactivity to a social fear-inducing task is a product of the child’s biology and environment. Show less
The study concentrates on the capabilities of children and young people to cope in child-headed households in Port Elizabeth, South Africa. In contrast to the dominant view of these children as... Show moreThe study concentrates on the capabilities of children and young people to cope in child-headed households in Port Elizabeth, South Africa. In contrast to the dominant view of these children as vulnerable and in need of protection and support by family and community members, this study focuses on the coping strategies of these youngsters and their access to support and its quality. Moreover, it addresses the problematic of conceptualizing child-headed households in the South African context. This new type of information provides us with valuable insights on how such households could be supported in a more effective way. Show less
The overall goal was to develop individualized dosing guidelines for the sedatives propofol and midazolam in infants and in critically ill patients, on the basis of population pharmacokinetic... Show moreThe overall goal was to develop individualized dosing guidelines for the sedatives propofol and midazolam in infants and in critically ill patients, on the basis of population pharmacokinetic-pharmacodynamic (PK-PD) modeling. Both under- and oversedation significantly and adversely affects patient outcome. Due to the high intra- and interindividual variability in dose requirements dosing is complicated. In this thesis the interindividual variability in response has been examined by covariate analysis. In this analysis the effects of bodyweight, cardiac function, severity of illness and liver blood flow and the unexplained interindividual variability have been characterized. It was shown that infants require higher doses of propofol because of differences in pharmacokinetics rather than pharmacodynamics. When comparing the results of the PK-PD model of propofol and midazolam in infants, propofol is preferred over midazolam because of the lower interindividual variability in pharmacodynamics compared to midazolam. In critically ill patients severity of the illness was found to be a major determinant of the level of sedation, with lower propofol dosing requirements with increasing severity of illness. The PK-PD models can be used as a basis for individualized dosing of propofol and midazolam, which is essential for optimizing the quality of sedation in clinical practice and will improve patients__ outcome. Show less
Th e DISABKIDS project is a European collaboration of clinicians and investigators that received funding from the European Commission in 2001. Over the last four years the DISABKIDS project's aim... Show moreTh e DISABKIDS project is a European collaboration of clinicians and investigators that received funding from the European Commission in 2001. Over the last four years the DISABKIDS project's aim was to cross-nationally develop a new European health related quality of life (HRQoL) instrument for children and adolescents with a chronic medical condition 1(Box 1). Some of the steps taken during the developmental process of the European DISABKIDS HRQoL instrument for children and adolescents with a chronic medical condition are described in this thesis. Data from the asthma population is a recurring theme in most chapters as the Dutch DISABKIDS centre operated as asthma consultant Show less
