Post-call performance impairment during a heavy call rotation is comparable with impairment associated with a 0.04 to 0.05 g% blood alcohol concentration during a light call rotation, as measured by sustained attention, vigilance, and simulated driving tasks. Residents' ability to judge this impairment may be limited and task-specific.

Mutations in presenilin 2 are rare causes of early onset familial Alzheimer's disease. Eighteen presenilin 2 mutations have been reported, although not all have been confirmed pathogenic. Much remains to be learned about the range of phenotypes associated with these mutations. We have analysed our unique collection of 146 affected cases in 11 Volga German families, 101 who are likely to have the same N141I mutation in presenilin 2 (54 genotyped confirmed). We have also assessed the detailed neuropathologic findings in 18 autopsies from these families and reviewed the world's literature on other presenilin 2 mutations; presenting a novel mutation that is predicted to lead to a premature truncation codon. Seven presenilin 2 mutations reported in the literature have strong evidence for pathogenicity whereas others may be benign polymorphisms. One hundred and one affected persons, with sufficient historical information from the Volga German pedigrees (N141I mutation), had a mean onset age of 53.7 years+/-7.8 (range 39-75) and mean age at death of 64.2 years+/-9.8 (range 43-88). These figures overlap with and generally fall between the results from the subjects in our centre who have late onset familial Alzheimer's disease or mutations in presenilin 1. Seizures were noted in 20 (30%) of 64 subjects with detailed medical records. Two mutation carriers lived beyond age 80 without developing dementia, representing uncommon examples of decreased penetrance. Two persons had severe amyloid angiopathy and haemorrhagic stroke. Eighteen cases had detailed histopathology available and analysed at our institution. Braak stage was five or six, amyloid angiopathy and neuritic plaques were common and more than 75% had Lewy bodies in the amygdala. TAR DNA-binding protein-43 inclusions were uncommon. In addition, a 58-year-old female with a 2 year course of cognitive decline and no family history of dementia has abnormal fludeoxyglucose-positron emission tomography imaging and a novel 2 base pair deletion in presenilin 2 at nucleotide 342/343, predicted to produce a frame-shift and premature termination. We conclude that mutations in presenilin 2 are rare with only seven being well documented in the literature. The best studied N141I mutation produces an Alzheimer's disease phenotype with a wide range of onset ages overlapping both early and late onset Alzheimer's disease, often associated with seizures, high penetrance and typical Alzheimer's disease neuropathology. A novel premature termination mutation supports loss of function or haploinsufficiency as pathogenic mechanisms in presenilin 2 associated Alzheimer's disease.

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Mice homozygous for a disruption in the alpha-subunit essential for TSH, LH, and FSH activity (alphaGsu-/-) exhibit hypothyroidism and hypogonadism similar to that observed in TSH receptor-deficient hypothyroid mice (hyt) and GnRH-deficient hypogonadal mutants (hpg). Although the five major hormone-producing cells of the anterior pituitary are present in alphaGsu-/- mice, the relative proportions of each cell type are altered dramatically. Thyrotropes exhibit hypertrophy and hyperplasia, and somatotropes and lactotropes are underrepresented. The size and number of gonadotropes in alphaGsu mutants are not remarkable in contrast to the hypertrophy characteristic of gonadectomized animals. The reduction in lactotropes is more severe in alphaGsu mutants (13-fold relative to wild-type) than in hyt or hpg mutants (4.5- and 1.5-fold, respectively). In addition, T4 replacement therapy of alphaGsu mutants restores lactotropes to near-normal levels, illustrating the importance of T4, but not alpha-subunit, for lactotrope proliferation and function. T4 replacement is permissive for gonadotrope hypertrophy in alphaGsu mutants, consistent with the role for T4 in the function of gonadotropes. This study reveals the importance of thyroid hormone in developing the appropriate proportions of anterior pituitary cell types.

Through adverse effects on the developing brain, maternal nutritional deficiency may increase the risk of schizophrenia apart from any genetic predisposition. After the Dutch Hunger Winter in 1944-1945, in which there was a major but time-limited decrease in food intake, the most exposed offspring had a twofold increase in the risk of becoming schizophrenic. The present investigators sought a similar association in the Wuhu region of Anhui, one of the Chinese provinces most affected during an extreme famine in the years [1959][1960][1961]. Rates of schizophrenia were obtained from psychiatric case records for the period 1971 through 2001. Researchers were unaware of exposure status. The Wuhu area has a population of 62 million. Up to the last decease, there has been little migration in or out of the region. The records review also took note of a family history of major mental illness.Birth rates declined by approximately 80% in [1960][1961]. Mortality began to increase in 1959 and peaked in 1960. Overall mortality for Anhui was 12%, and for Wuhu and surrounding counties, 15%. The absolute number of cases of schizophrenia in children born during the famine years decreased but, as a proportion of total births in each year, the cumulative risk increased in the years 1960-1961 compared with the preceding and following years. The sexes were equally affected, and no difference in age at onset of schizophrenia was noted. Cumulative mortality rates were 35% to 40% in children conceived or born during the famine years. The figures for those born in the years just before the famine were 20% to 30%. The mortality-adjusted relative risk of schizophrenia was 2.3 (95% confidence interval [CI], 1.99-2.65) for children born in 1960 and 1.93 (95% CI, 1.68-2.23) for those born in 1961. There was no change in the proportion of familial cases in the years under study.These findings indicate strongly that prenatal exposure to famine conditions increases the risk of schizophrenia later in life. The increase in risk is nearly the same as in the Dutch studies, from an ethnically and culturally distinctive population, but it is based on a much larger sample and on clear evidence of exposure. EDITORIAL COMMENT(This is a fascinating and unique study in which the authors took advantage of a particularly fortuitous convergence of research circumstances to draw conclusions about one aspect of the consequences of the horrific Chinese fam-ine of 1959-1961. Those circumstances included a stable population with minimal immigration or emigration, a single psychiatric hospital serving the entire region, and remarkably complete and continuous inpatient and outpatient psychiatric OBSTETRICS Volume 61, Number 1 OBSTETRICAL AND GYNECOLOGICAL SURVEY ABSTRACT Pregnancy-related stroke is rare, but it can be a devastating event. Apart from mortality estimates of 8% to 15%, survivors may have marked and permanent disability. The authors reviewed data from the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality for the y...