Complex spectrum of phenobarbital effects in a mouse model of neonatal hypoxia-induced seizures.

Seizures in neonates, mainly caused by hypoxic-ischemic encephalopathy, are thought to be harmful to the brain. Phenobarbital remains the first line drug therapy for the treatment of suspected neonatal seizures but concerns remain with efficacy and safety. Here we explored the short- and long-term outcomes of phenobarbital treatment in a mouse model of hypoxia-induced neonatal seizures. Seizures were induced in P7 mice by exposure to 5% O2 for 15 minutes. Immediately after hypoxia, pups received a single dose of phenobarbital (25 mg.kg-1) or saline. We observed that after administration of phenobarbital seizure burden and number of seizures were reduced compared to the hypoxic period; however, PhB did not suppress acute histopathology. Behavioural analysis of mice at 5 weeks of age previously subjected to hypoxia-seizures revealed an increase in anxiety-like behaviour and impaired memory function compared to control littermates, and these effects were not normalized by phenobarbital. In a seizure susceptibility test, pups previously exposed to hypoxia, with or without phenobarbital, developed longer and more severe seizures in response to kainic acid injection compared to control mice. Unexpectedly, mice treated with phenobarbital developed less hippocampal damage after kainic acid than untreated counterparts. The present study suggests phenobarbital treatment in immature mice does not improve the long lasting functional deficits induces by hypoxia-induced seizures but, unexpectedly, may reduce neuronal death caused by exposure to a second seizure event in later life.

Monstrous births and medical networks: debates over forensic evidence, generation theory, and obstetrical authority in France, ca. 1780-1815.

In France between 1780 and 1815, doctors opened a broad correspondence with medical faculties and public officials about foetal anomalies ("monstrosities"). Institutional and legal reforms forced doctors to encounter monstrous births with greater frequency, and they responded by developing new ideas about heredity and embryology to explain malformations to public officials. Though doctors achieved consensus on pathogenesis, they struggled to apply these ideas in forensic cases, especially with doubtful sex. Medical networks simultaneously allowed doctors to explore obstetrical techniques, as licensing regulations forced practitioners into emotional encounters with child anomalies. Doctors thus developed a new ethics for treating monstrosities, viewing them as pathological specimens, forensic objects, and obstetrical tragedies.

Inheriting vice, acquiring virtue: hereditary disease and moral hygiene in eighteenth-century France.

This essay examines the medical debates over hereditary disease and moral hygiene in France between 1748 and 1790. During this time, which was marked by two formal academic exchanges about pathological inheritance, doctors critically studied the existence of hereditary diseases--including syphilis, arthritis, phthisis, scrofula, rickets, gout, stones, epilepsy, and insanity--and the problems that heredity might pose for curing and preventing these diseases. Amid public debate, doctors first treated heredity with formal skepticism and then embraced the idea. Their changing attitudes stemmed less from epistemological or cognitive reasons than from new cultural beliefs about gender, domesticity, and demographic policy. Fearing moral degeneracy and demographic decline, they argued that a number of social pathologies were truly hereditary and that these diseases spread within the family itself. These beliefs were seemingly confirmed by new clinical studies on tuberculosis. Though doctors conceded that hereditary diseases might limit Enlightenment hopes to perfect society, they also suggested that sexual hygiene and physical education could cure hereditary degeneracy and transcend genealogy and descent. Consequently, they stressed that physical regeneration was a dynamic process, one that stretched from the conjugal bed to weaning and beyond. Rather than accepting the accidents of birth, physicians believed that their patients could self-consciously overcome inherited defects and thus regenerate themselves and even all of society itself. Heredity thus gave doctors an idiom with which to diagnose a felt social crisis and to prescribe appropriate hygienic responses.