Deficit in memory consolidation (abnormal forgetting rate) in childhood temporal lobe epilepsy. Pre and postoperative long-term observation.

Deficits in memory consolidation have been reported in adult patients with epilepsy but, not to our knowledge, in children. We report the long-term follow-up (9 y. o. to 18 y. o.) of a boy who suffered from temporal lobe epilepsy and underwent a left temporal lobectomy with amygdalo-hippocampal resection at the age of 10. He showed an abnormal forgetting rate when trying to encode new information and a significant deficit for retrieving remote episodic memories (when compared with his twin brother), both consistent with a consolidation disorder. His memory condition slightly improved after cessation of the epilepsy, nevertheless did not normalize. No standard memory assessment could pinpoint his memory problem, hence an adapted methodology was needed. We discuss the nature of the memory deficit, its possible causes and its clinical implications.

Pregabalin in patients with primary brain tumors and seizures: a preliminary observation.

OBJECTIVES: Patients with brain tumors and seizures should be treated with non-enzyme-inducing antiepileptic drugs (AED). Some of the newer drugs seem particularly suited in these patients. METHODS: Here we describe our experience with pregabalin (PGB); its effectiveness was retrospectively studied in nine consecutive patients with primary brain tumors and seizures. RESULTS: Six subjects had secondarily generalized and three simple partial seizures. Patients mostly suffered from WHO grade IV gliomas. PGB replaced enzyme inducing, inefficacious or bad tolerated AED, as add-on or monotherapy. Median follow-up was 5 (2-19) months; three patients died of their tumor. Daily median dosage was 300 mg. All subjects experienced at least a 50% seizure reduction, six were seizure-free. Side effects were reported in four patients, leading to PGB discontinuation in two. CONCLUSION: PGB appears to have a promising effectiveness in this setting, even as a monotherapy. Based on these results we embarked on a prospective controlled trial.

Geological observation in southeastern Zanskar and adjacent Lahul area (northern Himalaya).

The paper deals with the stratigraphic and structural setting of the sedimentary sequence cropping out in southeastern Zanskar and adjacent Lahul areas. The Tibetan Zone succession of southeastern Zanskar consists of about 6000 m of sediments, Late Precambrian~ ?Eocene in age, arranged in two superposed slabs (Pugh tal Unit, below, and Zangla Unit, above) tectonically resting upon the High Himalayan Crystalline. The Pughtal sequence, mostly terrigenous with carbonate units in the Cambrian, Silurian and Carboniferous, is about 2500 m thick. It was deposited from ?Late Precambrian to Carboniferous or ?Early Permian. The Permian Panjal Traps constitute the "sole" of the Zangla Unit, whose sedimentary sequence, about 3000 m thick, mainly carbonatic, spans from Late Permian (Kuling Formation) to Middle Jurassic (Kioto Limestone) in eastern Zanskar. In the Zangla area Late Jurassic/Cretaceous formations (Spiti Shales, Giumal Sandstone, Chikkim Limestone) are also present. Towards northwest, the sequence ranges up to Paleocene (Spanboth Formation) and ?Eocene (Chulung La Slates). Au nord de la Haute Chaine, dans la partie septentrionale de I'Himalaya, la marge continentale indienne a vu plus de 6000 m de sediments se deposer depuis I'Infracambrien jusqu'a I'Eocene. Lors de l'orogenese himalayenne, ces sediments ont ete decolles de leur substratum originel, dMormes et metamorphises de maniere differenciee suivant leur position. Ils reposent en contact tectonique sur la nappe cristalline du Haut-Himalaya. L'unite inferieure ou unite de Pughtal consiste, la ou elle est complete, en plus de 2500 m de sediments en partie detritiques terrigenes mais marque par l'edification de plates-formes carbonatees au Cambrien, Silurien et Carbonifere. Dans cette unite on releve deux grandes sequences sedimentaires separees par l'evenement epirogenique et magmatique tardi-Cambrien (500 rna), contrecoup de l'orogenese pan-africaine. Un niveau massif de vo1canites basaltiques permiennes ~ les Panjal Traps ~ forme la base ou sole de I'unite superieure (nappe de Zangla). Cette unite, plissee de maniere disharmonique, recouvre progressivement vers l'ouest des niveaux de plus en plus anciens de l'unite inferieure, niveaux eux-memes replisses en grands plis couches kilometriques a vergence nord. Dans la partie occidentale (Ringdom) l'unite superieure repose directement sur la nappe cristalline. Cette unite montre une serie sedimentaire avec des carbonates de plate-forme bien developpes au Trias superieur et au Lias puis des sediments surtout pelagiques et en partie detritiques terrigenes au Jurassique superieur et au Cretace. Des la fin du Cretace et jusqu'au Paleocene superieur s'edifie a nouveau une plate-forme peu profonde. La serie se termine par des couches continentales attribuees a l'Eocene. L'evolution geodynamique durant Ie Paleozoique et Ie Mesozoique est analysee. II en ressort que la sedimentation, a partir de I'Ordovicien, est regJee plus par des grands cycles eustatiques que par des mouvements tectoniques ou epirogeniques regionaux (les orogeneses caledoniennes, hercyniennes et cretacees des auteurs).

Store-operated Ca2+ Entry Mediated by Orai1 and TRPC1 Participates to Insulin Secretion in Rat β-Cells.

Store-operated Ca(2+) channels (SOCs) are voltage-independent Ca(2+) channels activated upon depletion of the endoplasmic reticulum Ca(2+) stores. Early studies suggest the contribution of such channels to Ca(2+) homeostasis in insulin-secreting pancreatic β-cells. However, their composition and contribution to glucose-stimulated insulin secretion (GSIS) remains unclear. In this study, endoplasmic reticulum Ca(2+) depletion triggered by acetylcholine (ACh) or thapsigargin stimulated the formation of a ternary complex composed of Orai1, TRPC1, and STIM1, the key proteins involved in the formation of SOCs. Ca(2+) imaging further revealed that Orai1 and TRPC1 are required to form functional SOCs and that these channels are activated by STIM1 in response to thapsigargin or ACh. Pharmacological SOCs inhibition or dominant negative blockade of Orai1 or TRPC1 using the specific pore mutants Orai1-E106D and TRPC1-F562A impaired GSIS in rat β-cells and fully blocked the potentiating effect of ACh on secretion. In contrast, pharmacological or dominant negative blockade of TRPC3 had no effect on extracellular Ca(2+) entry and GSIS. Finally, we observed that prolonged exposure to supraphysiological glucose concentration impaired SOCs function without altering the expression levels of STIM1, Orai1, and TRPC1. We conclude that Orai1 and TRPC1, which form SOCs regulated by STIM1, play a key role in the effect of ACh on GSIS, a process that may be impaired in type 2 diabetes.

Observation and Observing in Economics

Two themes are generative for revealing and understanding the history of observation in economics. First, we argue for the importance of noting that observation is an activity as well as a result, and second that observation is no more identical with quantification than observing is with measuring. These two themes enable us to discuss different historical dimensions of the ways in which economists have observed their economies and so enlarge our understanding of their observational practices. These problematics especially help in delineating the intricate, multilayered, and active interactions between the observer and the observed that take place in all social science observation, and from which our pictures of the economic world emerge.

Aerosol therapy in intensive and intermediate care units: prospective observation of 2808 critically ill patients.

PURPOSE: Unlike in the outpatient setting, delivery of aerosols to critically ill patients may be considered complex, particularly in ventilated patients, and benefits remain to be proven. Many factors influence aerosol delivery and recommendations exist, but little is known about knowledge translation into clinical practice. METHODS: Two-week cross-sectional study to assess the prevalence of aerosol therapy in 81 intensive and intermediate care units in 22 countries. All aerosols delivered to patients breathing spontaneously, ventilated invasively or noninvasively (NIV) were recorded, and drugs, devices, ventilator settings, circuit set-up, humidification and side effects were noted. RESULTS: A total of 9714 aerosols were administered to 678 of the 2808 admitted patients (24 %, CI95 22-26 %), whereas only 271 patients (10 %) were taking inhaled medication before admission. There were large variations among centers, from 0 to 57 %. Among intubated patients 22 % (n = 262) received aerosols, and 50 % (n = 149) of patients undergoing NIV, predominantly (75 %) inbetween NIV sessions. Bronchodilators (n = 7960) and corticosteroids (n = 1233) were the most frequently delivered drugs (88 % overall), predominantly but not exclusively (49 %) administered to patients with chronic airway disease. An anti-infectious drug was aerosolized 509 times (5 % of all aerosols) for nosocomial infections. Jet-nebulizers were the most frequently used device (56 %), followed by metered dose inhalers (23 %). Only 106 (<1 %) mild side effects were observed, despite frequent suboptimal set-ups such as an external gas supply of jet nebulizers for intubated patients. CONCLUSIONS: Aerosol therapy concerns every fourth critically ill patient and one-fifth of ventilated patients.