People with attention-deficit/hyperactivity disorder (ADHD) often experience sleep problems, and these are frequently exacerbated by the methylphenidate they take to manage their ADHD symptoms.... Show morePeople with attention-deficit/hyperactivity disorder (ADHD) often experience sleep problems, and these are frequently exacerbated by the methylphenidate they take to manage their ADHD symptoms. Many of the changes to sleep are consistent with a change in the underlying circadian clock. The present study was designed to determine if methylphenidate alone could alter properties of the circadian clock. Young male mice were examined in light-dark cycles and in constant darkness and recordings were performed on behavioral activity, sleep, and electrical activity in the suprachiasmatic nucleus (SCN) of freely moving mice. Methylphenidate in the drinking water (0.08%) significantly increased activity in the mid-to-late night, and led to a delay in the onset of activity and sleep relative to the light-dark cycle. While locomotor levels returned to baseline after treatment ended, the phase angle of entrainment required at least a week to return to baseline levels. In constant darkness, the free-running period of both wheel-running and general locomotor rhythms was lengthened by methylphenidate. When the treatment ended, the free-running period either remained stable or only partially reverted to baseline levels. Methylphenidate also altered the electrical firing rate rhythms in the SCN. It induced a delay in the trough of the rhythm, an increment in rhythm amplitude, and a reduction in rhythm variability. These observations suggest that methylphenidate alters the underlying circadian clock. The observed changes are consistent with clock alterations that would promote sleep-onset insomnia. Show less
Objectives To estimate the prevalence of children with sickle cell disease (SCD) in The Netherlands. To estimate the annual number of children newly diagnosed as having SCD and the proportion with... Show moreObjectives To estimate the prevalence of children with sickle cell disease (SCD) in The Netherlands. To estimate the annual number of children newly diagnosed as having SCD and the proportion with diagnoses through neonatal screening To estimate the proportion of children with SCD receiving paediatric care in a comprehensive care setting. Design Data from two sources, a survey of paediatric practices (n=107) and a laboratory database (n=20), were analysed by the capture-recapture method. Participants Children with SCD aged <18 years, either born before 2003 or newly diagnosed as having SCD between 2003 and 2007. Main outcome measures Prevalence, annual number of children newly diagnosed as having SCD, proportion of children with diagnoses through neonatal screening, proportion of children receiving paediatric care. Results The prevalence of SCD in children living in The Netherlands on 1 January 2003 was 1: 5152 (95% CI 1: 4513 to 1: 6015). In the next 4 years, the annual incidence was 1: 2011 (95% CI 1: 1743 to 1: 2376). Nearly one-third (27%) of the children newly diagnosed as having SCD immigrated to The Netherlands after birth and would, therefore, be missed by the neonatal screening programme. Approximately 60% of all children with SCD were not reported by paediatricians. Conclusion The number of children with SCD in The Netherlands is much higher than previously estimated, and the majority of these children seem not to be reviewed regularly by a paediatrician. Children born abroad (27% of new cases) do not benefit from neonatal screening and are at high risk of life-threatening complications before SCD is diagnosed. As this introduces disparities in healthcare, the initiation of adequate measures should be considered. Show less
Background: Legg-Calve-Perthes disease is a pediatric disorder characterized by osteonecrosis of the proximal femoral epiphysis. The etiology probably involves successive vascular occlusions, in... Show moreBackground: Legg-Calve-Perthes disease is a pediatric disorder characterized by osteonecrosis of the proximal femoral epiphysis. The etiology probably involves successive vascular occlusions, in which hypercoagulable disorders may play a role. We evaluated the etiologic role of thrombophilia in Legg-Calve-Perthes disease in a pediatric population. Methods: One hundred and sixty-nine consecutive patients who had been diagnosed with Legg-Calve-Perthes disease at two centers in Rotterdam, the Netherlands, when they were between 1.5 and 13.5 years of age were identified between 2000 and 2003. The study also included two control groups: 474 subjects (16.3 to 73.1 years of age) from a population-based case-control study on the etiology of venous thrombosis as well as thirty-eight children (1.8 to 18.8 years of age) who were treated for asthma at one of the centers. We determined levels of protein C, protein S, factor VIII, and fibrinogen and tested for the factor V Leiden and prothrombin G20210A mutations. We calculated age and sex-adjusted odds ratios as measures of the relative risk of the development of Legg-Calve-Perthes disease. Results: The incidence of Legg-Calve-Perthes disease was increased in the presence of the factor V Leiden mutation (odds ratio, 3.3; 95% confidence interval, 1.6 to 6.7), in the presence of the prothrombin G20210A mutation (odds ratio, 2.6; 95% confidence interval, 1.0 to 6.3), in association with elevated levels of factor VIII (>150 IU/dL) (odds ratio, 7.5; 95% confidence interval, 2.2 to 25.2), and in association with protein S deficiency (<67 U/dL) (odds ratio, 2.8; 95% confidence interval, 0.7 to 10.8). Neither high levels of fibrinogen (>4.0 g/L) nor protein C deficiency (! 55 U/dL) had an apparent effect on the risk of Legg-Calve-Perthes disease. (Odds ratios were adjusted forage and sex.) Overall, males had a 2.4 times higher risk of Legg-Calve-Perthes disease developing than did females. The effect of the factor V Leiden mutation, high levels of fibrinogen, and increasing levels of factor VIII was stronger in males than in females. The risk of Legg-Calve-Perthes disease increased with an increasing number of coagulation abnormalities in males but not in females. Conclusions: There appears to be a thrombotic component in the etiology of Legg-Calve-Perthes disease. Show less
