LRRTM1 on chromosome 2p12 is a maternally suppressed gene that is associated paternally with handedness and schizophrenia.

Left-right asymmetrical brain function underlies much of human cognition, behavior and emotion. Abnormalities of cerebral asymmetry are associated with schizophrenia and other neuropsychiatric disorders. The molecular, developmental and evolutionary origins of human brain asymmetry are unknown. We found significant association of a haplotype upstream of the gene LRRTM1 (Leucine-rich repeat transmembrane neuronal 1) with a quantitative measure of human handedness in a set of dyslexic siblings, when the haplotype was inherited paternally (P=0.00002). While we were unable to find this effect in an epidemiological set of twin-based sibships, we did find that the same haplotype is overtransmitted paternally to individuals with schizophrenia/schizoaffective disorder in a study of 1002 affected families (P=0.0014). We then found direct confirmatory evidence that LRRTM1 is an imprinted gene in humans that shows a variable pattern of maternal downregulation. We also showed that LRRTM1 is expressed during the development of specific forebrain structures, and thus could influence neuronal differentiation and connectivity. This is the first potential genetic influence on human handedness to be identified, and the first putative genetic effect on variability in human brain asymmetry. LRRTM1 is a candidate gene for involvement in several common neurodevelopmental disorders, and may have played a role in human cognitive and behavioral evolution.

Strategies and outcomes of PGD of familial adenomatous polyposis.

Owing to adult onset of hereditary cancer, prenatal diagnosis (PND) raises numerous ethical issues on the acceptability to terminate an affected pregnancy (TOP). PND for these disorders is often considered as unacceptable by couples as well as geneticists and legal or ethical authorities, but preimplantation genetic diagnosis (PGD), even if subject to controversy, seems to be a more acceptable option. Therefore, many couples, who do not want to transmit their cancer to their children, consider PGD as their only reproductive option. This article describes our experience of PGD for familial adenomatous polyposis (FAP). Twelve couples were referred between 2000 and 2005. We developed PGD tests to detect the mutation alone, but we rapidly set up multiplex PCR combining mutation detection and indirect diagnosis. Finally, we set up duplex and triplex indirect diagnoses to be able to offer a PGD, whatever mutation was involved in familial cases. PGD strategies were based on (i) a new double allele-specific PCR approach (D-ARMS) allowing the detection of the wild-type and mutated allele; (ii) PCR fragments sizing and (iii) restriction length polymorphisms. For the 12 referrals, we developed eight tests, and 11 cycles have been performed for four couples, resulting in eight embryo transfers and five pregnancies, with the birth of one healthy boy and two ongoing pregnancies. We are now able to propose PGD to most couples at risk of transmitting FAP to their offspring, whether the mutation is familial or occurred de novo.

[Anesthesia for carotid surgery with clamping under residual carotid pressure control]. / Anesthésie pour chirurgie carotidienne avec clampage sous contrôle de la pression résiduelle carotidienne.

Carotid endarterectomy with clamping is performed in 50 patients. Internal carotid artery stump pressure is measured in all cases after clamping at the beginning of the operation. In 35 patients, an increase of systolic pressure is observed which allows a stump pressure more than 70 mmHg in 29 patients. In 15 patients, systolic pressure decreases and a stump pressure more than 70 mmHg is observed in two patients. When the stump pressure is more than 70 mmHg, the clamping is maintained. When the stump pressure is low, the clamping is stopped. A perfusion of Metaraminol increases systolic pressure in all cases: stump pressure is measured again after a second clamping. In 17 cases out of 19, stump pressure increases more than 70 mmHg and the clamping is maintained. In the two cases with a low stump pressure, a shunt is used during intervention.

[Neuroanesthesiology in the child weighing less than 10 kilos: use of Alfatesine combined with a morphinomimetic]. / Neuroanesthésilogie chez l'enfant de moins de dix kilos: intérêts de l'Alfatésine associée a un morphinomimétique.

On the basis of the analysis of fifteen cases of children weighing less than ten kg, in a department of neurosurgery, the authors describe the use of Alfatésine by infusion in association with a morphinomimetic, a technique compatible with the existence of raised intracranial pressure. In view of the weight of the children, availability of a venous line represents a handicap and a danger to such an extent that the authors suggest limited assistance in the form of sedation by a halogenated agent, with the application of strict rules concerning dose and surveillance, bearing in mind its effects on intracranial pressure. The quality of anesthesia and of recovery is emphasised and the doses described. The effects of Alfatesine and of Fentanyl on intracranial pressure, cerebral metabolism and blood flow are reviewed. These favourable effects justify the use of Alfatesine in this context. One case of obvious overdose, responsible for delayed recovery, is discussed.

[Pneumoencephalotomography under diaz-analgesia and narco-analgesia]. / Encéphalotomographie gazeuse sous diazanalgésie et narco-analgésie.

The authors reported 92 observations of anesthesia for gaseous encephalotomography interest the adult. The contrast produce is air. 49 under diazanalgesia and myoresolution. Diazepam, +Fentanyl, pancuronium bromide N2O to 60 p. 100. 25 under diazanalgesia and myoresolution. Diazepam, +Fentanyl, succinylcholine, N2O to 60 p. 100. 18 under narco-analgesia and myoresolution. +Fentyl, pancuronium bromide N2O to 60 p. 100. The conditions of the study are described in the first part. The results and their analysis permit the appreciation of: - the patient confort, the quality of the examination; -the respect of the hemodynamics for this examination, reputed to be "difficult"; -the immediatly noticeable diminution of side effects; -the absence of side effects; -the justification and interesting of the control ventilation; -the quality of waking up. In the conclusion the authors underline the interest of their different techniques and the possibility of using them in operations in sitting position in neurosurgery, and all important chirurgical intervention.