Open-label, long-term safety study of zonisamide administered to children and adolescents with epilepsy

BACKGROUND: Zonisamide is licensed in the EU and USA for the adjunctive treatment of partial-onset seizures in adults but there are few data about its use in children. AIMS: To assess the long-term safety and efficacy of zonisamide in children and adolescents. METHODS: Zonisamide-na?ve patients (n=109, aged 3-15 years, weight >or=12.5 kg) with a clinical diagnosis of epilepsy (>or=4 seizures/month, receiving 1-2 antiepileptic drugs [AEDs] daily) received zonisamide once or twice daily in an open-label trial. The starting dose was 1mg/kg/day, increased by 2 mg/kg/day every 1-2 weeks at the investigator's discretion to an initial maximum of 12 mg/kg/day. The occurrence of adverse events (AEs) was the primary safety measure. Efficacy was measured via the reductions in seizure frequency and via investigator- and carer-rated global assessment ratings. RESULTS: The mean dose received was 8.5 mg/kg/day. Of the 109 children, 52 (48%) completed 15 months' treatment. Treatment-related AEs, mostly mild-to-moderate in severity, were reported by 58 patients. Seven patients discontinued due to treatment-related AEs. Serious AEs (pancreatitis, decreased sweating, and vertigo) were reported by three patients. A significant (p=0.033) median reduction in 'all seizure' frequency of 2.60 seizures per week was observed. Additionally, a significant (p=0.029) median reduction of 1.80 seizures/week in 'complex partial' seizures was reported. Improvements in investigator- and carer-rated global assessments were noted. CONCLUSIONS: Zonisamide treatment was generally well tolerated and was associated with significant reductions in seizure frequency in this pediatric population with a variety of both partial and generalized medically refractory epilepsy syndromes.     

Birthweight and aerobic fitness in adolescents: the Northern Ireland Young Hearts Project

The purpose of this study was to examine relationships between aerobic fitness and birthweight in adolescents. A representative cohort of 1015 males and females aged 12 and 15 y was studied, at baseline, with 89% of the 12-y-olds being re-examined 3 y later.The main outcome measures were an index of aerobic fitness, measured in laps completed at voluntary exhaustion by a twenty-metre shuttle run test, and recorded birthweight. Multiple linear regression, with and without adjustment for known and potential confounding variables, was performed to examine associations between fitness and birthweight.Birthweight and aerobic fitness were positively related so that for each kg decrease in birthweight, there was a mean (95% confidence interval) decrease in fitness score of 4.84 (0.35 to 9.33) laps and 3.21 (0.32 to 6.10) laps, in 12-y-old boys and girls respectively. This relationship is of a similar order to the strength of association between birthweight and adult blood pressure previously reported. Associations between birthweight and physical fitness at the age of 15 were weaker and were not significant.Our findings suggest that aerobic fitness may be involved in mediating the association between birthweight and cardiovascular disease risk later in life. The weakening of the association between birthweight and fitness between the ages of 12 and 15 y is similar to the weaker associations between birthweight and blood pressure seen among adolescents compared to younger children. We are currently re-examining this cohort to see if, as with blood pressure, the association with fitness re-emerges at an older age.     

Rett syndrome from quintuple and triple deletions within the MECP2 deletion hotspot region

Rett syndrome results from mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene, which are nearly always lethal in males and lead to regression and reduced life expectancy in females. Herein we report one propositus with five tandem deletions and a second propositus with three tandem deletions within MECP2 exon 4 that encode truncated protein products resulting in classic Rett syndrome. These deletion breakpoints and single deletions in 3 other patients were all found within a 185-bp region along with 64 of 69 other reported deletion breakpoints in the MECP2 gene. Illegitimate recombination resulting in deletion at a substantial proportion of the shared MECP2 sites is enhanced by repeated guanosine (G) DNA sequences in the antisense direction, consistent with reports at other gene loci that polypurine (multiple guanosine or adenosine (A)) basepairs enhance sequence deletion. Multiple deletions at the same poly G recombination sites confirm the existence of deletion hotspots in this gene region with numerous repeated antisense sites that are enriched 26- to 161-fold. Deletion by illegitimate recombination within a single allele can occur during mitotic or meiotic cell cycles. Although prone to disease-causing deletion, this region is unique in humans and highly conserved among mammals for the last 75 000 000 years to maintain the MECP2 gene's critical function.     

Local and distant recurrences in rectal cancer patients are predicted by the nonspecific immune response; specific immune response has only a systemic effect - a histopathological and immunohistochemical study

Background  

Invasion and metastasis is a complex process governed by the interaction of genetically altered tumor cells and the immunological and inflammatory host reponse. Specific T-cells directed against tumor cells and the nonspecific inflammatory reaction due to tissue damage, cooperate against invasive tumor cells in order to prevent recurrences. Data concerning involvement of individual cell types are readily available but little is known about the coordinate interactions between both forms of immune response.     

Severe cytomegalovirus infections in immunocompetent patients at admission as dengue mimic: Successful treatment with intravenous ganciclovir

Cytomegalovirus (CMV) infection is associated with adverse clinical outcomes in immunosuppressed persons. The incidence and association of CMV reactivation with adverse clinical outcomes in critically ill persons lacking evidence of immunosuppression at ICU admission has received great attention in the practice of critical care medicine. Critically ill patients in ICU who had associated risk factors such as mechanical ventilation, severe sepsis, or blood transfusion are more prone to CMV activation, which in turn led to increased mortality and morbidity in terms of increased ICU stay, longer duration of mechanical ventilation, and higher rates of nosocomial infections. However, severe CMV as initial presentation mimicking dengue infection is rare. We recently came across seven cases with positive CMV serology at ICU admission, which we discuss in the light of current literature.     

Psychometric properties of two physical activity questionnaires, the AQuAA and the PASE, in cancer patients

Background  

This study aimed to evaluate the reliability and validity of two self-report physical activity (PA) questionnaires - the AQuAA (Activity Questionnaire for Adults and Adolescents) and PASE (Physical Activity Scale for the Elderly) - in cancer patients.     

慢性阻塞性肺疾病合并阻塞性睡眠呼吸暂停患者的随访结果

背景和目的:COPD合并阻塞性睡眠呼吸暂停(OSA)的患者,较单独患有其中1种疾病的患者更容易罹患肺动脉高压.本研究旨在评价COPD合并OSA患者的病死率及因COPD急性加重而首次住院的关系,以及持续气道正压通气(CPAP)对患者主要临床结局的影响.