Genetics of epilepsy: epilepsy research foundation workshop report.

The Sixth Epilepsy Research Foundation workshop, held in Oxford in March 2006, brought together basic scientists, geneticists, epidemiologists, statisticians, pharmacologists and clinicians to consider progress, issues and strategies for harnessing genetics to improve the understanding and treatment of the epilepsies. General principles were considered, including the fundamental importance of clear study design, adequate patient numbers, defi ned phenotypes, robust statistical data handling, and follow-up of genetic discoveries. Topics where some progress had been made were considered including chromosomal abnormalities, neurodevelopment, hippocampal sclerosis, juvenile myoclonic epilepsy, focal cortical dysplasia and pharmacogenetics. The ethical aspects of epilepsy genetics were reviewed. Principles and limitations of collaboration were discussed. Presentations and their matched discussions are produced here. There was optimism that further genetic research in epilepsy was not only feasible, but might lead to improvements in the lives of people with epilepsy.     

Postoperative Analgesic Effects of Continuous Wound Infiltration with Diclofenac after Elective Cesarean Delivery

Background: Postoperative pain mostly results from sensitization of afferent fibers at injury sites driving central sensitization. Recently, peripheral processes have gained attention as mechanisms of hyperalgesia, and prostaglandins are among highly sensitizing agents. To date, perioperative administration of a single local dose of nonsteroidal antiinflammatory drugs has shown inconclusive efficacy. Rather than a single bolus, the current study evaluates the postoperative analgesic effect of diclofenac continuous intrawound infusion after elective cesarean delivery.

Methods: Ninety-two parturients were randomly allocated to receive a 48-h continuous intrawound infusion with 240 ml containing 300 mg diclofenac, 0.2% ropivacaine, or saline. In the ropivacaine and saline groups, patients also received 75 mg intravenous diclofenac every 12 h for 48 h. Postoperative evaluation included intravenous morphine consumption by patient-controlled analgesia and visual analog pain scores. Punctate mechanical hyperalgesia surrounding the wound and presence of residual pain after 1 and 6 months were also assessed.

Results: Continuous diclofenac infusion significantly reduced postoperative morphine consumption (18 mg; 95% confidence interval, 12.7-22.2) in comparison with saline infusion and systemic diclofenac (38 mg; 95% confidence interval, 28.8-43.7) (P = 0.0009) without unique adverse effects. Postoperative analgesia produced by local diclofenac infusion was as effective as local ropivacaine infusion with systemic diclofenac.     

Publishing Nutrition Research: A Review of Epidemiologic Methods

The use of epidemiologic research designs and analytical methods is common in dietetics research. Food and nutrition professionals who seek to perform evidence-based practice or participate in research design, analysis, and communication need skills in the essentials of epidemiology. This is one of a series of monographs on research methodology that addresses these needs and supports the goals of the Board of Editors of the Journal of the American Dietetic Association to further enhance competency and skills. This monograph focuses on statistical approaches for univariate analyses used with the primary observational study designs associated with epidemiology. Tables illustrating the presentation and interpretation of these results are included.     

Association between the HOXA1 A218G polymorphism and increased head circumference in patients with autism.

BACKGROUND: The HOXA1 gene plays a major role in brainstem and cranial morphogenesis. The G allele of the HOXA1 A218G polymorphism has been previously found associated with autism. METHODS: We performed case-control and family-based association analyses, contrasting 127 autistic patients with 174 ethnically matched controls, and assessing for allelic transmission disequilibrium in 189 complete trios. RESULTS: A, and not G, alleles were associated with autism using both case-control (chi(2) = 8.96 and 5.71, 1 df, p <.005 and <.025 for genotypes and alleles, respectively), and family-based (transmission/disequilibrium test chi(2) = 8.80, 1 df, p <.005) association analyses. The head circumference of 31 patients carrying one or two copies of the G allele displayed significantly larger median values (95.0th vs. 82.5th percentile, p <.05) and dramatically reduced interindividual variability (p <.0001), compared with 166 patients carrying the A/A genotype. CONCLUSIONS: The HOXA1 A218G polymorphism explains approximately 5% of the variance in the head circumference of autistic patients and represents to our knowledge the first known gene variant providing sizable contributions to cranial morphology. The disease specificity of this finding is currently being investigated. Nonreplications in genetic linkage/association studies could partly stem from the dyshomogeneous distribution of an endophenotype morphologically defined by cranial circumference.     

Evidence of sustained skeletal benefits from impact-loading exercise in young females: a 3-year longitudinal study.

The skeletal effects from intensive exercise throughout puberty are undefined. Forty-five female gymnasts and 52 controls were studied over 3 years, including a heredity aspect. The effects of size, maturity, exercise, and diet were identified using a multilevel regression model. Results demonstrated sustained skeletal benefits resulting from exercise throughout all stages of pubertal development. INTRODUCTION: Weight-bearing exercise is beneficial for peak bone mass development. However, whether skeletal benefits achieved with exercise are maintained if training remains intensive throughout the pubertal years is not entirely clear. The influence of familial resemblance for bone mass remains undefined in physically active versus inactive children. The aim of this study was to investigate the long-term influences of impact-loading exercise on bone quantity and quality in young females after controlling for growth, maturation, and hereditary factors. MATERIALS AND METHODS: At baseline, 45 gymnasts (G) and 52 normally active controls (C) 8-17 years of age were recruited. Anthropometry, diet, physical activity, and quantitative ultrasound (QUS) were measured annually for 3 consecutive years. DXA scans of total body (TB) and lumbar spine (LS) bone mineral content (BMC) and density (BMD) were taken three times at 1-year intervals. A multilevel regression model was fitted, and the independent effects of body size, maturity, physical activity, and diet were identified over time. To assess heredity influences, 27 G mothers and 26 C mothers volunteered for cross-sectional measurements of anthropometry, QUS, and BMC/BMD. RESULTS AND CONCLUSIONS: Gymnasts were smaller and lighter (as were their mothers) than controls, but they had significantly higher QUS and axial and appendicular BMC and BMD, with > 170 g more bone mineral in TB across puberty (after adjustment for maturity [years from peak height velocity], height, weight, energy, and protein intake). Gymnasts had up to 24-51% higher BMC and 13-28% higher BMD, depending on skeletal site. These results provide evidence of sustained skeletal benefits from impact-loading exercise, which are unlikely to result entirely from heredity, throughout pubertal years.