The overarching aim of this thesis is to illuminate the experience of illness and the meaning of fear of medical care through children’s narratives. A purposive sample of 22 children and youths, aged from 2 to 18 years, narrated through play and conversation their experiences of illness and of their fear of contact with medical care. The data were analysed using thematic qualitative content analysis and the phenomenological hermeneutic method. In childhood, the experience of being ill seems to vary with the child’s age. At the ages of 7 to 10 years, the child’s way of thinking can colour the experience;imagination can produce both problems and opportunities. Children seem to combine imagination and reality, and contrasts in the experience coexist such as being scared/confident, sad/cosy and hurt/having fun. At the age of 11 to 18,being ill seemed to imply being lost, hurt and in need of comfort from themselves and others. Medical care can be frightening to children and what is fearful can differ with age. To a 2-year-old child, medical care seemed to be dangerous; to children aged 7 to 11 years, it seemed threatening, like a monster. To the 2-year-old child, there seemed to be a conflict between, on the one hand, living up to expectations by ‘being good’ and hiding their feelings or, on the other hand, communicating their fear. The narrations by children in the 7–11 year age group, point to the importance of empathy when caring for children, i.e., to be receptive of the child’s fear in order to help the child through and out of the fear. To be afraid for a two-yearold was to have one’s trust broken yet still be searching for a trustful relationship. However, if the child is received along with the fear, this opened up an opportunity for the child to develop courage and to gain control over the fear when under gentle care. The results of this research revealed the possibility of using play to create stories in a creative relationship with the child. To express one’s inner feeling is a gift of trust, a gift of hospitality. Thus when caring for children we can be the ones who are receiving that gift. We can accept the offer of being a guest in the child’s world.

The overall aim of this thesis was to characterize single-channel aEEG/EEG, recorded during the first postnatal days in preterm infants, in relation to brain function and two-year outcome. Study I investigated if aEEG/EEG was associated with neonatal brain injury, inflammation and outcome in 16 very preterm (VPT) infants. The interburst interval (IBI) was prolonged, and aEEG amplitudes were lower in infants with brain injury, and in infants developing handicap. Cord blood TNF-α correlated with IBI. Study II investigated inter-rater agreement of visual burst detection, as compared to automated burst detection based on a non-linear energy operator (NLEO) in an EEG data set from 12 extremely preterm (EPT) and 6 VPT infants. The sensitivity of the NLEO was 64 % and 69 % (EPT and VPT infants, respectively) and the specificity 96 % and 88 %. The algorithm was then modified to further improve the accuracy. Study III investigated if arterial carbon dioxide and plasma glucose is associated with EEG continuity. In 247 sets of samples (PaCO2, plasma glucose, IBI) from 32 EPT infants there was a positive association between PaCO2 and IBI; higher PaCO2 was associated with longer IBI. Corrected for carbon dioxide, plasma glucose had a U-shaped association with IBI in infants with good outcome. Study IV investigated the predictive value of aEEG/EEG in 41 EPT and 8 VPT infants. All VPT infants had good outcome. Predictors of outcome in EPT infants included presence or absence of burst-suppression, continuous activity and cyclicity, median IBI and interburst%. Seizures were associated with neonatal brain damage but not with outcome. Improved preterm brain monitoring may in the future be used for early identification of infants at high risk of brain damage and adverse outcome, which may have implications for direction of care and for early intervention.

Children’s lifestyle has changed significantly during the recent decades, with an increasing prevalence of obesity as one outcome. Parents are usually the most influential people in young children’s lives. The overall aim of this thesis was to investigate parental perspectives on factors associated with 3-6 year-old children’s lifestyle, regarding eating habits and physical activity. Another objective was to compare different approaches to conducting postal questionnaires in terms of response rate, time consumption and cost-efficiency. The samples in the four studies were parents of 6-year-olds (n=158), parents of 3-year-olds (n=873), parents of 4-year-olds (n=30) and parents of 3-year-olds (n=353). In the first study, a questionnaire regarding practices and attitudes towards their child’s lifestyle, perceived obstacles and desired support was used. The second study included the Swedish Parenthood Stress Questionnaire (SPSQ), the Relationship Questionnaire (RQ) and the CFQ (Child Feeding Questionnaire). Parents also reported their child’s TV-viewing habits. The child’s measured height, weight and BMI were obtained from a register, BASTA. In the third study, focus group interviews were performed. The fourth study investigated three types of consent given for participation in a survey. The results showed that parents’ attitudes towards children’s lifestyle, in general, were “healthier” than their reports of their child’s daily practices. The practices differed depending on the parents’ educational background. Significant and dose-dependant associations were found between perceived maternal stress and children’s overweight, but also underweight. Parents felt that they were mainly responsible for their preschool child’s lifestyle. However, parents described challenges that limited and obstructed them from providing their child with a healthy lifestyle, citing the need to receive professional and peer support, while also requesting support from society. Allowing respondents to actively decline participation yielded a higher response rate and proved to be the most cost-efficient method for conducting a postal questionnaire.

<p>Despite major advances in our understanding of the biology of childhood acute myeloid leukemia (AML) and the development of new cytotoxic drugs, the prognosis of long-term survival is still only 60-65 %.</p><p>In the present research, we studied the pharmacokinetics of drugs used in the induction therapy of childhood AML and performed in vitro drug sensitivity testing of leukemic cells from children with AML.</p><p>The aims of the studies were to correlate the results of the analysis to biological and clinical parameters and to identify subgroups of AML with specific drug sensitivity profiles in order to better understand why treatment fails in some patients and how therapy may be improved.</p><p>Blood samples were analysed to study the pharmacokinetics of doxorubicin (n=41), etoposide (n=45) and 6-thioguanine (n=50). Doxorubicin plasma concentration and total body clearance were correlated to the effect of induction therapy, and doxorubicin plasma concentration was an independent factor for complete remission, both in univariate and multivariate analysis including sex, age, and white blood cell count at diagnosis. For etoposide and 6-thioguanine no correlation was found between pharmacokinetics and clinical effect. Children with Down syndrome (DS) tended to reach higher blood concentrations of etoposide and thioguanine nucleotides, indicating that dose reduction may be reasonable to reach the same drug exposure as in children without DS.</p><p>Leukemic cells from 201 children with newly diagnosed AML, 15 of whom had DS, were successfully analysed for in vitro drug sensitivity by the fluorometric microculture cytotoxicity assay (FMCA). We found that samples from children with DS were highly sensitive to most drugs used in AML treatment. In non-DS children, the t(9;11) samples were significantly more sensitive to cytarabine (p=0.03) and doxorubicin (p=0.035) than other samples. The findings might explain the very favorable outcome reported in children with DS and t(9;11)-positive AML. A specific drug resistance profile was found for several other genetic subgroups as well. A detailed study of MLL-rearranged leukemia showed that cellular drug sensitivity is correlated both to partner genes and cell lineage, findings that support the strategy of contemporary protocols to include high-dose cytarabine in the treatment of patients with MLL-rearrangement, both in AML and acute lymphoblastic leukemia (ALL).</p><p>Our results indicate that drug resistance and pharmacokinetic studies may yield important information regarding drug response in different sub-groups of childhood AML, helping us to optimize future chemotherapy in childhood AML.</p>

<p><i>Chlamydia pneumoniae</i> is a human respiratory tract pathogen. Seroepidemiological studies indicate that <i>C. pneumoniae</i> infection is most common in school-aged children and infrequently detected in younger children.</p><p>The aims of this study were to further elucidate the prevalence of <i>C. pneumoniae</i> in paediatric populations and to describe the clinical implications of these infections.</p><p>The study population consisted of 367 children with respiratory tract diseases, 453 presumed healthy children at day-care, 69 children undergoing adenoidectomy and 1585 children from a population based cohort. Family members to infected day-care children were investigated. The laboratory methods used were polymerase chain reaction (PCR) on specimen from upper respiratory tract, serology by microimmunofluorescence (MIF), and immunohistochemistry (IHC) on adenoid tissue specimen. Personal data and medical history were obtained by the means of questionnaires and by the study of patient records.</p><p>In children younger than five years, the prevalence of <i>C. pneumoniae</i> was 17% as detected by PCR. This prevalence started to increase with increasing age from two years of age. The corresponding increase in serology as detected by MIF started at the age of four years. The prevalence at day-care centres varied from 4 to 39%. Both PCR and MIF underestimated the prevalence of <i>C. pneumoniae</i> detected by IHC. Families to infected children were investigated: mothers were more often infected than fathers were.</p><p>Most <i>C. pneumoniae</i> infections in small children were confined to the upper respiratory tract. These infections were usually mild or asymptomatic. Symptomatic disease may be of prolonged nature. No subsequent illness after <i>C. pneumoniae</i> infection was detected at follow-up after four years. In general, no association between <i>C. pneumoniae</i> and asthma was found, but <i>C. pneumoniae</i> may be of importance for asthma in some susceptible individuals. Previous <i>C. pneumoniae</i> infection reduced the risk for later atopy.</p><p>In conclusion, <i>C. pneumoniae</i> is a common finding in small children and most often causes relatively mild disease. If the acquisition of this infection early in life will have any implications for future health remains to be investigated.</p>

<p>Excessive weight gain has frequently been reported in adolescents with type 1 diabetes, especially in girls. In general, puberty is associated with reduced insulin sensitivity that is further diminished by overweight. The causes and consequences of excessive weight gain in adolescents with type 1 diabetes are not fully understood. The studies described in this thesis addressed body composition in adolescents with type 1 diabetes and the relationships between physical activity, energy intake and changes in body composition. Furthermore, the effect of metformin as additional therapy on glycaemic control and insulin sensitivity was examined in a randomised placebo-controlled study. Body mass index (BMI) and percentage body fat (%BF) were significantly higher in girls with type 1 diabetes compared to healthy control girls. Mean HbA1c during puberty, but not mean insulin dose, was positively related to BMI at the age of 18 in girls with diabetes. A centralised fat distribution was associated with poor glycaemic control, increased daily dosage of insulin and elevated cholesterol and triglyceride levels. Neither total physical activity nor total energy intake differed between adolescent girls with type 1 diabetes and healthy age-matched control girls. A high dietary fat intake was positively related to gain in %BF in girls with type 1 diabetes. Additional therapy with metformin for three months improved glycaemic control and peripheral insulin sensitivity in adolescents with poorly controlled type 1 diabetes. The improvement in glycaemic control was related to insulin sensitivity at baseline, implying that the most insulin resistant subjects benefited most from the metformin therapy. It is concluded that the excessive weight gain observed in girls with type 1 diabetes is mainly attributable to an increased fat mass and that dietary fat intake is of importance for this gain in body fat. Additional treatment with metformin improves glycaemic control in adolescents with poorly controlled type 1 diabetes.</p>

<p>The process of β-cell destruction that leads to type 1 diabetes (T1D) is incompletely understood and it is believed to be a result of both genetic and environmental factors. Enterovirus (EV) infections of the β-cells have been proposed to be involved, however, the effects of EV infections on human β-cells have been little investigated. This thesis summarises studies of three different Coxsackie B4 virus strains that have previously been shown to infect human islets. The effects of infections with these EV were studied <i>in vitro</i> in human islets and in a rat insulin-producing cell line. In addition, a pilot study was performed on isolated human islets to investigate the ability to treat such infections with an antiviral compound.</p><p>It was found that one of the virus strains replicated in human β-cells without affecting their main function for at least seven days, which <i>in vivo</i> may increase a virus’s ability to persist in islets.</p><p>Nitric oxide was induced by synthetic dsRNA, poly(IC), but not by viral dsRNA in rat insulinoma cells in the presence of IFN-γ, suggesting that this mediator is not induced by EV infection in β-cells and that poly(IC) does not mimic an EV infection in this respect.</p><p>All three virus strains were able to induce production of the T-cell chemoattractant interferon-γ-inducible protein 10 (IP-10) during infection of human islets, suggesting that an EV infection of the islets might trigger insulitis <i>in vivo</i>.</p><p>Antiviral treatment was feasible in human islets, but one strain was resistant to the antiviral compound used in this study.</p><p>To conclude, a potential mechanism is suggested for the involvement of EV infections in T1D. If EV infections induce IP-10 production in human islet cells <i>in vivo</i>, they might recruit immune cells to the islets. Together with viral persistence and/or virus-induced β-cell damage, this might trigger further immune-mediated β-cell destruction <i>in vivo</i>.</p>

Chlamydia pneumoniae is a human respiratory tract pathogen. Seroepidemiological studies indicate that C. pneumoniae infection is most common in school-aged children and infrequently detected in younger children. The aims of this study were to further elucidate the prevalence of C. pneumoniae in paediatric populations and to describe the clinical implications of these infections. The study population consisted of 367 children with respiratory tract diseases, 453 presumed healthy children at day-care, 69 children undergoing adenoidectomy and 1585 children from a population based cohort. Family members to infected day-care children were investigated. The laboratory methods used were polymerase chain reaction (PCR) on specimen from upper respiratory tract, serology by microimmunofluorescence (MIF), and immunohistochemistry (IHC) on adenoid tissue specimen. Personal data and medical history were obtained by the means of questionnaires and by the study of patient records. In children younger than five years, the prevalence of C. pneumoniae was 17% as detected by PCR. This prevalence started to increase with increasing age from two years of age. The corresponding increase in serology as detected by MIF started at the age of four years. The prevalence at day-care centres varied from 4 to 39%. Both PCR and MIF underestimated the prevalence of C. pneumoniae detected by IHC. Families to infected children were investigated: mothers were more often infected than fathers were. Most C. pneumoniae infections in small children were confined to the upper respiratory tract. These infections were usually mild or asymptomatic. Symptomatic disease may be of prolonged nature. No subsequent illness after C. pneumoniae infection was detected at follow-up after four years. In general, no association between C. pneumoniae and asthma was found, but C. pneumoniae may be of importance for asthma in some susceptible individuals. Previous C. pneumoniae infection reduced the risk for later atopy. In conclusion, C. pneumoniae is a common finding in small children and most often causes relatively mild disease. If the acquisition of this infection early in life will have any implications for future health remains to be investigated.

Excessive weight gain has frequently been reported in adolescents with type 1 diabetes, especially in girls. In general, puberty is associated with reduced insulin sensitivity that is further diminished by overweight. The causes and consequences of excessive weight gain in adolescents with type 1 diabetes are not fully understood. The studies described in this thesis addressed body composition in adolescents with type 1 diabetes and the relationships between physical activity, energy intake and changes in body composition. Furthermore, the effect of metformin as additional therapy on glycaemic control and insulin sensitivity was examined in a randomised placebo-controlled study. Body mass index (BMI) and percentage body fat (%BF) were significantly higher in girls with type 1 diabetes compared to healthy control girls. Mean HbA1c during puberty, but not mean insulin dose, was positively related to BMI at the age of 18 in girls with diabetes. A centralised fat distribution was associated with poor glycaemic control, increased daily dosage of insulin and elevated cholesterol and triglyceride levels. Neither total physical activity nor total energy intake differed between adolescent girls with type 1 diabetes and healthy age-matched control girls. A high dietary fat intake was positively related to gain in %BF in girls with type 1 diabetes. Additional therapy with metformin for three months improved glycaemic control and peripheral insulin sensitivity in adolescents with poorly controlled type 1 diabetes. The improvement in glycaemic control was related to insulin sensitivity at baseline, implying that the most insulin resistant subjects benefited most from the metformin therapy. It is concluded that the excessive weight gain observed in girls with type 1 diabetes is mainly attributable to an increased fat mass and that dietary fat intake is of importance for this gain in body fat. Additional treatment with metformin improves glycaemic control in adolescents with poorly controlled type 1 diabetes.

The process of β-cell destruction that leads to type 1 diabetes (T1D) is incompletely understood and it is believed to be a result of both genetic and environmental factors. Enterovirus (EV) infections of the β-cells have been proposed to be involved, however, the effects of EV infections on human β-cells have been little investigated. This thesis summarises studies of three different Coxsackie B4 virus strains that have previously been shown to infect human islets. The effects of infections with these EV were studied in vitro in human islets and in a rat insulin-producing cell line. In addition, a pilot study was performed on isolated human islets to investigate the ability to treat such infections with an antiviral compound. It was found that one of the virus strains replicated in human β-cells without affecting their main function for at least seven days, which in vivo may increase a virus’s ability to persist in islets. Nitric oxide was induced by synthetic dsRNA, poly(IC), but not by viral dsRNA in rat insulinoma cells in the presence of IFN-γ, suggesting that this mediator is not induced by EV infection in β-cells and that poly(IC) does not mimic an EV infection in this respect. All three virus strains were able to induce production of the T-cell chemoattractant interferon-γ-inducible protein 10 (IP-10) during infection of human islets, suggesting that an EV infection of the islets might trigger insulitis in vivo. Antiviral treatment was feasible in human islets, but one strain was resistant to the antiviral compound used in this study. To conclude, a potential mechanism is suggested for the involvement of EV infections in T1D. If EV infections induce IP-10 production in human islet cells in vivo, they might recruit immune cells to the islets. Together with viral persistence and/or virus-induced β-cell damage, this might trigger further immune-mediated β-cell destruction in vivo.