Class of 2012 Abstract / Specific Aims: During pre-hospital transport, trauma patients may be given a long-acting neuromuscular blocker (NMB) to facilitate endotracheal intubation or to prevent movement. The purpose of this study was to determine the rate of long-acting NMB use and evaluate the concurrent use of sedatives. Methods: This was a retrospective cohort study conducted in a tertiary care, academic emergency department of trauma patients aged 18-89 years who were intubated in the pre-hospital setting. The primary outcome was to determine the rate of long-acting NMB use. The use of post- intubation sedatives was compared between the groups using Wilcoxon rank-sum test or Fisher’s exact test, using an a priori alpha level of 0.05 for all analyses. Main Result: A total of 51 patients were included in final analyses. All patients received etomidate or midazolam for intubation. 86% (n=44) received succinylcholine, 10% (n=5) were given rocuronium and 4% (n=2) did not receive a NMB. After intubation, 75% (n=38) received an additional long-acting NMB to prevent movement (vecuronium (n=22) or rocuronium (n=16)) . Overall, 82% (n=42) of patients received a long- acting NMB during transport. There was no difference in the rate of post-intubation sedative use between groups (79% versus 67%, respectively, p=0.42). The long-acting NMB group received midazolam less promptly after intubation (16 versus 7 minutes, respectively, p=0.04). Conclusions: The use of long-acting NMB is common during the pre-hospital transport of trauma patients. Some of these patients may not be given sedatives or have delays in receiving sedatives following intubation and be at risk of being paralyzed without sedation.

Class of 2012 Abstract / Specific Aims: During pre-hospital transport, trauma patients may be given a long-acting neuromuscular blocker (NMB) to facilitate endotracheal intubation or to prevent movement. The purpose of this study was to determine the rate of long-acting NMB use and evaluate the concurrent use of sedatives. Methods: This was a retrospective cohort study conducted in a tertiary care, academic emergency department of trauma patients aged 18-89 years who were intubated in the pre-hospital setting. The primary outcome was to determine the rate of long-acting NMB use. The use of post-intubation sedatives was compared between the groups using Wilcoxon rank-sum test or Fisher’s exact test, using an a priori alpha level of 0.05 for all analyses. Main Result: A total of 51 patients were included in final analyses. All patients received etomidate or midazolam for intubation. 86% (n=44) received succinylcholine, 10% (n=5) were given rocuronium and 4% (n=2) did not receive a NMB. After intubation, 75% (n=38) received an additional long-acting NMB to prevent movement (vecuronium (n=22) or rocuronium (n=16)) . Overall, 82% (n=42) of patients received a long-acting NMB during transport. There was no difference in the rate of post-intubation sedative use between groups (79% versus 67%, respectively, p=0.42). The long-acting NMB group received midazolam less promptly after intubation (16 versus 7 minutes, respectively, p=0.04). Conclusions: The use of long-acting NMB is common during the pre-hospital transport of trauma patients. Some of these patients may not be given sedatives or have delays in receiving sedatives following intubation and be at risk of being paralyzed without sedation.

臨床上止癢藥物的發展有限,故尋找具有廣泛止癢效果的藥物及探討癢覺傳遞的 神經受體機制是相當重要的。從過去研究中發現,bombesin 能在嚙齒類動物引發強 烈的搔抓行為。另外,bombesin 對 bombesin receptor family 中的 gastrin- releasing peptide receptor(GRPr)和 neuromedin B receptor(NMBr)也有高度親 和力。本研究主要目的為釐清 GRPr 和 NMBr 是否具有獨立調控癢覺搔抓行為的能 力。藉由側腦室於大白鼠中樞給藥並量化大白鼠的後肢搔抓行為,建立 GRP 與 NMB 這兩種胜肽在大白鼠上引發搔抓行為的基本藥理特性,並透過 GRPr 與 NMBr 這兩種受體的專一性拮抗劑探討受體間對於調控癢覺搔抓行為的獨立性。透過每天連 續施打 bombesin、GRP 與 NMB 這三種胜肽探討大白鼠搔抓行為的耐受性及三種胜 肽引發之搔抓行為在長時間觀測上的比較。最後,利用 GRPr 與 NMBr 這兩種受體 的專一性拮抗劑來探討 bombesin 引發搔抓行為的機制。利用側腦室給予 GRP (0.03 - 0.3 nmol)與 NMB(0.1-1 nmol)皆引發劑量相關性的搔抓行為反應。GRPr 的拮抗劑 RC-3095 (0.1-1 nmol)可以劑量相關性地阻斷 GRP 所引發的搔抓行 為,但不能阻斷 NMB 所引發的搔抓行為。相對而言,NMBr 的拮抗劑 PD168368 (0.3-3 nmol)可以劑量相關性地阻斷 NMB 引發的搔抓行為,但不能阻斷 GRP 所引 發的搔抓行為。藉由這些拮抗劑實驗,証實了 GRPr 與 NMBr 兩受體皆調控癢覺的訊 息傳遞並獨立不互相影響。Bombesin、GRP 與 NMB 都能引發搔抓行為,但程度與 持續時間上都有差異。但是每天施打這三種胜肽皆引發搔抓行為的耐受性。然而, RC-3095 與 PD168368 的有效劑量或兩個拮抗劑的組合並不能阻斷 bombesin 所引 發的搔抓行為,意指 bombesin 所引發的搔抓行為可能由其他受體調控。由本研究得 知,GRPr 與 NMBr 分別獨立調控中樞神經系統的癢覺訊息傳遞,並有程度與持續時 間上的差異。更重要的是,綜合先前文獻研究讓我們瞭解 bombesin-recognized neurons 中還有其他重要的受體機制調控於中樞神經系統的癢覺傳遞。 / Bombesin is a pruritogenic agent that causes intense itch-scratching activity in rodents. Bombesin has high affinity for the gastrin-releasing peptide receptor (GRPr) and the neuromedin B receptor (NMBr). The aim of this study was to investigate pharmacologically the ability of GRPr and NMBr to themselves elicit scratching behavior in rats. The intracerebroventricular (i.c.v.) route was selected for drug delivery because the study focused on supraspinal sites of action. The magnitude and duration of scratching produced by the naturally occurring peptides GRP and NMB were characterized. Antagonists selective for GRPr (RC-3095) and NMBr (PD168368) were used to define the role of GRPr and NMBr in the scratching response. After i.c.v. administration, GRP (0.03-0.3 nmol) and NMB (0.1-1 nmol) dose-dependently elicited marked scratching. There was a tolerance to scratching elicited by daily repeated administration of bombesin, GRP, or NMB. Presession administration of RC-3095 (0.1-1 nmol) and PD168368 (0.3-3 nmol) dose- dependently antagonized scratching elicited by GRP and NMB, respectively. More important, 1 nmol of RC-3095 failed to block NMB- elicited scratching and 3 nmol of PD168368 failed to block GRP-elicited scratching. In addition, pretreatment with effective doses of RC-3095 or PD168368 alone or in combination did not block bombesin-elicited scratching. Through the use of the selective antagonists RC-3095 and PD168368, this study demonstrates that central GRPr and NMBr may act independently to elicit scratching behavior. Although the receptor mechanisms underlying bombesin-elicited scratching elude us, this study provides a pharmacological basis for GRPr and NMBr antagonists as potential antipruritics.

Tese de mestrado. Engenharia Biomédica. Faculdade de Engenharia. Universidade do Porto. 2012

Ce travail se proposait, à partir du cas démonstratif de la grotte du Gardon (Ambérieu-en-Bugey, Ain), de dégager le cadre évolutif des industries lithiques néolithiques du Centre-Est de la France. Avec une stratigraphie particulièrement développée et quasiment continue pour la Préhistoire récente la grotte du Gardon constitue un site exceptionnellement favorable à ce genre d'analyse.<br />Cette thèse s'organise en quatre parties principales, regroupant seize chapitres. La première est une présentation générale du travail (cadre géographique et chronologique). Elle est aussi l'occasion d'exposer les concepts à la base des analyses ainsi que la méthodologie employée. La seconde partie consiste en un état des connaissance sur les industries lithiques de l'ensemble du Néolithique haut-rhodanien. La troisième est celle de l'analyse des 17 000 silex taillés néolithiques de la grotte du Gardon. La coexistence de couches d'occupation et de niveaux d'inondation, ainsi que la présence de zone de biseautage impliquent une fiabilité différente des échantillons considérés. Chaque ensemble a été abordé individuellement d'un point de vue technologique et typologique, dans le but de dégager les schémas opératoires propres à chacune des couches. La confrontation de ces résultats à ceux obtenus sur d'autres aspects du système technique et aux données chrono-stratigraphiques permet d'affiner ou de rediscuter les attributions culturelles proposées. Dans la quatrième et dernière partie, les résultats obtenus sur la grotte sont confrontés aux données régionales. Il est alors possible de construire un cadre évolutif général des industries lithiques et, plus largement, des groupes culturels néolithiques du Centre-Est de la France.

S'ha avaluat mitjançant estudis in vitro la viabilitat de la teràpia fotodinàmica antifúngica per al tractament clínic d'infeccions causades per les espècies fúngiques patògenes Candida albicans, Candida parapsilosis, Candida krusei i Trichophyton mentagrophytes. L'objectiu és optimitzar aquesta tècnica per proporcionar una alternativa als fàrmacs antifúngics utilitzats en els tractaments clàssics actuals i eradicar així les micosis superficials. S'ha avaluat la capacitat citotòxica de tres fotosensibilitzadors amb propietats fotoquímiques diferents, la hipericina, la 5,10,15,20-tetraquis(N-metil-4-piridil)-21H,23H-porfina i el clorur de 3,7-Bis(etilamino)-2,8-dimetilfenotiacina-5-io, induint tots la inactivació cel.lular sobre les diferents espècies fúngiques. Per avaluar si la la tècnica produeix danys significatius sobre les cèl.lules epidèrmiques humanes s'han realitzat estudis sobre queratinòcits i fibroblasts humans. S'han avaluat els mecanismes d'acció dels tres fotosensibilitzadors mitjançant estudis espectroscòpics i cinètics de formació i desaparició dels seus estats excitats i oxigen singlet. En el cas de l'hipericina també s'han descrit els intermedis que es formen en irradiar, caracteritzant l'accessibilitat dels triplets a l'oxigen. / Se ha evaluado mediante estudios in vitro la viabilidad de la terapia fotodinámica antifúngica para el tratamiento clínico de infecciones causadas por las especies fúngicas patógenas Candida albicans, Candida parapsilosis, Candida krusei y Trichophyton mentagrophytes. El objetivo es optimizar esta técnica para proporcionar una alternativa a los fármacos antifúngicos usados en los tratamientos clásicos actuales y erradicar así las micosis superficiales. Se ha evaluado la capacidad citotóxica de tres fotosensibilizadores con propiedades fotoquímicas distintas, la hipericina, la 5,10,15,20-tetraquis(N-metil-4-piridil)-21H,23H-porfina y el cloruro de 3,7-Bis(etilamino)-2,8-dimetilfenotiacina-5-io, induciendo todos la inactivación celular sobre las distintas especies fúngicas. Para evaluar si la la técnica produce daños significativos sobre las células epidérmicas humanas se han realizado estudios sobre queratinocitos y fibroblastos humanos. Se han evaluado los mecanismos de acción de los tres fotosensibilizadores mediante estudios espectroscópicos y cinéticos de formación y desaparición de sus estados excitados y oxígeno singlete. En el caso de la hipericina también se han descrito los intermedios que se forman al irradiar, caracterizándose la accesibilidad de los tripletes al oxígeno. / Has been evaluated by in vitro viability studies of photodynamic therapy for clinical fungal infections caused by pathogenic fungal species Candida albicans, Candida parapsilosis, Candida krusei and Trichophyton mentagrophytes. The goal is to optimize this technique to provide an alternative to the antifungal drugs used in current classical treatments and thus eliminate superficial mycoses. We assessed the cytotoxic capacity of three photosensitizers with different photochemical properties, the hypericin, 5,10,15,20-tetrakis(N-methyl-4-pyridyl)-21H,23H-porphine and 3,7-Bis(ethylamino)-2,8-dimethylphenothiazin-5-ium chloride, inducing all cell inactivation on different fungal species. To assess if the technique produces significant damage to human epidermal cells, studies with human fibroblasts and keratinocytes were carried. We evaluated the mechanisms of action of the three photosensitisers by spectroscopic and kinetic studies of formation and disappearance of excited states and singlet oxygen. In the case of hypericin have also been described intermediates formed by irradiating, characterized accessibility of triplet oxygen.