Pneumatic tourniquets are in common use in hospitals to stop the flow of blood to a limb or digit and provide a bloodless surgical site. The risk of injury to the tissue beneath the tourniquet cuff from the high pressure in the cuff could be minimized with a tourniquet system capable of maintaining the cuff pressure at the occlusion pressure, which is defined to be the minimum pressure that will stop the flow of blood past the cuff. In the work described in this thesis, a novel impedance-based method was developed to estimate the occlusion pressure while blood flow is arrested by a tourniquet cuff. This should facilitate the development of actual practical tourniquet systems capable of safely and reliably maintaining the tourniquet cuff pressure near the occlusion pressure for the duration of a surgical procedure. The impedance of the tissue beneath the cuff was measured with a specially designed impedance plethysmograph. The electrode configurations used with the plethysmograph were evaluated with a computer model of the limb. A relationship was found between the impedance of the underlying tissue and the cuff pressure relative to the occlusion pressure that could be used to predict the nearness of the onset of blood flow. Eighteen subjects were used in the trials to establish the relationship. The occlusion pressure was typically 150 mmHg and the standard error of estimation was 16 mmHg. To establish the relationship, the tissue pressure profile along the arm beneath the cuff was measured with a special transducer and controlled by varying the pressures in the bladders of a dual-bladder tourniquet cuff used to arrest blood flow. An algorithm based on the relationship was developed to control the bladder pressures according to the impedance of the underlying tissue. The feasibility of a tourniquet system that uses impedance plethysmography to keep the cuff pressure as close as possible to the occlusion pressure while still preventing blood flow was demonstrated with a single subject by controlling the pressures in a dual-bladder tourniquet cuff placed about his arm using the algorithm. Sources of interference and artifact encountered in the study are discussed, and techniques for removing the artifact presented. The major contributions of the research in this thesis were as follows: 1) the development of a computer model for predicting the performance of electrode configurations; 2) the development, design, implementation, and evaluation of a novel impedance plethysmograph; 3) the measurement of the actual tissue pressure profile along the surface of the arm beneath various occlusive cuffs; 4) the discovery of a quantitative relationship between the pressure in a tourniquet cuff and the impedance of the underlying tissue which for the first time enables the prediction of the occlusion pressure while the tourniquet cuff pressure is above the occlusion pressure; 5) the identification and prioritization of the sources of artifact and interference together with the development of approaches for detecting and handling them; and 6) the establishment of the feasibility of controlling the pressure in a tourniquet cuff by incorporating the above into a practical adaptive tourniquet system. / Applied Science, Faculty of / Electrical and Computer Engineering, Department of / Graduate

Pneumatic tourniquets are widely used in surgery of the extremities to occlude the vessels of the limb, thereby providing a bloodless field for dissection so that the surgeon may operate more quickly and accurately. Over-pressurization of the tourniquet cuff may lead to postoperative complications such as temporary or permanent paralysis of the limb. This motivated the development of adaptive tourniquet systems which could regulate the tourniquet pressure just above the limb occlusion pressure (LOP), or the minimum tourniquet pressure required to prevent blood flow past the cuff for a given duration. Previous adaptive tourniquet systems suffered from several problems which limited their practical utility in the operating room. This thesis describes the adaptation of oscillometry, a technique widely used in the noninvasive estimation of blood pressure, to the estimation of LOP in the surgical environment for application in a clinically practical adaptive tourniquet system. Improved oscillometric LOP estimation performance was obtained through the development of a filter for increasing the signal-to-noise ratio of the oscillometric pulses during periods of limb manipulation, the development of a heuristic real-time pattern recognition algorithm for extracting oscillometric pulses from signal data corrupted by limb movements, and the development of a new method for rapidly estimating the LOP which needs only one-third of the signal data required by a widely-used oscillometric approach to produce an estimate of comparable accuracy. In addition to these contributions, a new tourniquet cuff was developed which achieves an improved fit to the limb, thereby enhancing performance and reliability over that obtained from conventional tourniquets as both an oscillometric occlusion sensor and as a limb-occluding device. An adaptive tourniquet system which integrated these improvements was developed and used in a clinical study involving four orthopaedic surgeons and 16 patients. Clinical trials of the latest system version in which circumstances permitted the use of adaptive control showed that the average limb-applied pressure was reduced by 35%, or from the conventional standard of 250 mm Hg to 162 mm Hg, in the upper limb surgeries, and by 38%, or from the conventional standard of 300 mm Hg to 187 mm Hg, in the lower limb surgeries. These significant reductions in the pressure indicate the potential effectiveness of adaptive tourniquet control and improved cuff design on reducing the risk of patient injuries from excessive tissue compression. Furthermore, unlike all previous implementations, this system is currently being evaluated on a routine basis in orthopaedic surgical procedures performed at Vancouver General Hospital. / Applied Science, Faculty of / Electrical and Computer Engineering, Department of / Graduate

Orientador: Celso Antônio Rodrigues / Banca: Anatonio Carlos Paes / Banca: Rosângela Gonçalves Peccinini / Resumo: Os equinos são acometidos frequentemente por processos sépticos na porção distal dos membros. Dentre as mais variadas condutas terapêuticas, destaca-se a perfusão regional intravenosa de antimicrobianos (PRIVA) utilizada como opção para combater a infecção local. A técnica objetiva proporcionar uma concentração elevada do fármaco no local acometido. O procedimento se baseia no posicionamento de um torniquete na região proximal ao local infectado, proporcionando a oclusão do fluxo sanguíneo venoso e arterial, permitindo que o fármaco permaneça na região acometida por no mínimo 30 minutos. Dentre os antimicrobianos indicados para a PRIVA, destaca-se o sulfato de gentamicina. Objetivou-se com este estudo avaliar e comparar a farmacocinética da gentamicina, no plasma e líquido sinovial da articulação do carpo de equinos, submetidos a PRIVA, utilizando dois modelos de torniquetes. Foram utilizados dez equinos hígidos, divididos aletoriamente em dois grupos de cinco animais, os torniquetes foram aplicados no terço médio do rádio, sempre pelo mesmo aplicador. O grupo GTT recebeu torniquete de látex tubular, enquanto que o grupo GTE, faixa de Esmarch. Após o posicionamento dos torniquetes, acessou-se a veia cefálica e administrou-se 2,2 mg/kg de sulfato de gentamicina, adicionado à solução fisiológica q.s.p. 40 mL. Previamente ao posicionamento do torniquete, procedeu-se avaliação ultrassonográfica color Doppler no membro tratado para visualização da veia cefálica e artéria mediana. Amostras de líquido sinovial do carpo e sangue foram obtidas nos momentos M0, M15', M30', M1h, M2h, M4h, M6h, M8h, M12h, M24h e M48h para a realização da análise de concentração de gentamicina por cromatografia líquida de alta eficiência (CLAE), bem como para os cálculos dos parâmetros farmacocinéticos em modelo monocompartimental. Não foram encontradas diferenças significativas dos parâmetros ... / Abstract: The horses are often affected by septic processes in the distal portions of the limbs. Among the various therapeutic approaches, there is intravenous regional perfusion of antimicrobials (IRPA) used as an option to combat local infection. The technique aims to provide a high concentration of the drug in the affected area. The procedure is based on placing a tourniquet proximal to the infected area in the region of providing the venous and arterial blood flow occlusion, allowing the drug to remain on the affected area at least 30 minutes. Among the antimicrobial agents indicated for IRPA, highlight the gentamicin sulfate. The objective of this study was to evaluate and compare the pharmacokinetics of gentamicin in plasma and synovial fluid of carpal joint of horses undergoing IRPA using two models of tourniquets. Were used ten healthy equines, randomly divided into two groups of five animals, the tourniquets were applied in the middle third of the radius, always by the same applicator. The tourniquet GTT group received latex tube, while the GTE group Esmarch bandage. After positioning the tourniquets, the cephalic vein had been accessed and administered 2.2 mg / kg gentamicin sulfate, added to 40 mL saline q.s.. Prior to placement of the tourniquet, proceeded color Doppler ultrasonographic evaluation in the treated limb for viewing the median artery and cephalic vein. Samples of synovial fluid and blood carpal were obtained in the moments M0, M15 ', M30', M1h, M2h, M4h, M6h, M8h, M12h, M24h and M48h to perform the analysis of concentration of gentamicin by high-performance liquid chromatography (HPLC), as well as calculations of pharmacokinetic parameters in monocompartiment model. No significant differences in pharmacokinetic parameters were found between treatment groups (P>0.05). The results showed that the two types of tourniquets in IRPA can be used in a proximal region of forelimb in horses, if applied properly, both are capable of ... / Mestre

Made available in DSpace on 2015-05-14T16:53:07Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-08-08Bitstream added on 2015-05-14T16:59:24Z : No. of bitstreams: 1 000825120.pdf: 606208 bytes, checksum: 0d2e584d3ba483aa3104ff9ca0511af0 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Os equinos são acometidos frequentemente por processos sépticos na porção distal dos membros. Dentre as mais variadas condutas terapêuticas, destaca-se a perfusão regional intravenosa de antimicrobianos (PRIVA) utilizada como opção para combater a infecção local. A técnica objetiva proporcionar uma concentração elevada do fármaco no local acometido. O procedimento se baseia no posicionamento de um torniquete na região proximal ao local infectado, proporcionando a oclusão do fluxo sanguíneo venoso e arterial, permitindo que o fármaco permaneça na região acometida por no mínimo 30 minutos. Dentre os antimicrobianos indicados para a PRIVA, destaca-se o sulfato de gentamicina. Objetivou-se com este estudo avaliar e comparar a farmacocinética da gentamicina, no plasma e líquido sinovial da articulação do carpo de equinos, submetidos a PRIVA, utilizando dois modelos de torniquetes. Foram utilizados dez equinos hígidos, divididos aletoriamente em dois grupos de cinco animais, os torniquetes foram aplicados no terço médio do rádio, sempre pelo mesmo aplicador. O grupo GTT recebeu torniquete de látex tubular, enquanto que o grupo GTE, faixa de Esmarch. Após o posicionamento dos torniquetes, acessou-se a veia cefálica e administrou-se 2,2 mg/kg de sulfato de gentamicina, adicionado à solução fisiológica q.s.p. 40 mL. Previamente ao posicionamento do torniquete, procedeu-se avaliação ultrassonográfica color Doppler no membro tratado para visualização da veia cefálica e artéria mediana. Amostras de líquido sinovial do carpo e sangue foram obtidas nos momentos M0, M15´, M30´, M1h, M2h, M4h, M6h, M8h, M12h, M24h e M48h para a realização da análise de concentração de gentamicina por cromatografia líquida de alta eficiência (CLAE), bem como para os cálculos dos parâmetros farmacocinéticos em modelo monocompartimental. Não foram encontradas diferenças significativas dos parâmetros ... / The horses are often affected by septic processes in the distal portions of the limbs. Among the various therapeutic approaches, there is intravenous regional perfusion of antimicrobials (IRPA) used as an option to combat local infection. The technique aims to provide a high concentration of the drug in the affected area. The procedure is based on placing a tourniquet proximal to the infected area in the region of providing the venous and arterial blood flow occlusion, allowing the drug to remain on the affected area at least 30 minutes. Among the antimicrobial agents indicated for IRPA, highlight the gentamicin sulfate. The objective of this study was to evaluate and compare the pharmacokinetics of gentamicin in plasma and synovial fluid of carpal joint of horses undergoing IRPA using two models of tourniquets. Were used ten healthy equines, randomly divided into two groups of five animals, the tourniquets were applied in the middle third of the radius, always by the same applicator. The tourniquet GTT group received latex tube, while the GTE group Esmarch bandage. After positioning the tourniquets, the cephalic vein had been accessed and administered 2.2 mg / kg gentamicin sulfate, added to 40 mL saline q.s.. Prior to placement of the tourniquet, proceeded color Doppler ultrasonographic evaluation in the treated limb for viewing the median artery and cephalic vein. Samples of synovial fluid and blood carpal were obtained in the moments M0, M15 ', M30', M1h, M2h, M4h, M6h, M8h, M12h, M24h and M48h to perform the analysis of concentration of gentamicin by high-performance liquid chromatography (HPLC), as well as calculations of pharmacokinetic parameters in monocompartiment model. No significant differences in pharmacokinetic parameters were found between treatment groups (P>0.05). The results showed that the two types of tourniquets in IRPA can be used in a proximal region of forelimb in horses, if applied properly, both are capable of ...

A growing body of evidence shows that presynaptic nerve terminals throughout the nervous system are vulnerable to a range of traumatic, toxic and disease-related neurodegenerative stimuli. The aim of this study was to further characterise this vulnerability by examining the response of mouse α-motor nerve terminals at the neuromuscular junction (NMJ) to hypoxia-reperfusion injury. To address this aim, a novel model system was generated in which ex vivo skeletal muscle preparations could be maintained in an hypoxic environment, at an O2 concentration below in vivo normoxic values (<0.25% O2), for 2hr followed by 2hr reperfusion (2H-2R). Using this model system combined with quantitative assessment of immunohistological preparations as well as some ultrastructural observations, I present evidence to show that α-motor nerve terminals are rapidly and selectively vulnerable to hypoxia-reperfusion injury with no apparent perturbations to postsynaptic endplates or muscle fibres. I show that the severity of α-motor nerve terminal pathology is age and muscle type/location dependent: in 8-12wk old mice, nerve terminals in fast-twitch lumbrical muscles are more vulnerable than predominantly slow-twitch transversus abdominis and triangularis sterni. In 5-6 week old mice however, there is an age dependent increase in vulnerability of α-motor nerve terminals from the predominantly slow-twitch muscles while the fast-twitch lumbricals remained unaffected by age. The functional, morphological and ultrastructural pathology observed in α-motor nerve terminals following 2H-2R is indicative of selective and ongoing nerve terminal disassembly but, occurs via a mechanism distinct from Wallerian degeneration, as the neuroprotective slow Wallerian degeneration (Wlds) gene did not protect nerve terminals from these pathological changes. I also provide provisional evidence to show that 1A/II muscle spindle afferents and γ-motor nerve terminals are more resistant to hypoxia-reperfusion injury compared with α-motor nerve terminals. In addition to this, I also report preliminary finding that indicate that the oxygen storing protein, neuroglobin, maybe expressed at the mouse NMJ and report the difficulties of using mice that express yellow fluorescent protein (YFP) in their neurons for repeat/live imaging studies. Overall, these data show that the model of hypoxia-reperfusion injury developed in this study is robust and repeatable, that it induces rapid, quantitative changes in α-motor nerve terminals and that it can be used to further examine the mechanisms regulating nerve terminal vulnerability in response to hypoxia-reperfusion injuries. These findings have clinical implications for the use of surgical tourniquets and in the aetiology of many neurodegenerative diseases and neuropathic sequelae where mechanisms relating to hypoxia and hypoxia-reperfusion injury have been implicated.

Soucieux de comprendre et de développer une ingénierie moléculaire, les scientifiques ont façonné et produit des objets nanométriques, apparentés à ceux qui nous sont familiers. Le travail présenté ici rassemble les stratégies de synthèse organique mises en œuvre dans la production de tourniquets moléculaires commutables. L'objectif est d'introduire un site catalytique et d'apprécier la modulation de l'activité en fonction de conditions contrôlables. Partant de synthèses multi-étapes optimisées, plusieurs familles ont été préparées, caractérisées et leur performance catalytique a été évaluée. Parallèlement, un intérêt s'est porté sur une question soulevée par la modulation de la cinétique de rotation dans de tels objets. Cette étude a mobilisé une activité de synthèse d'objets isomérisables, d'études RMN, et a été complétée d'un regard photo-physique et théorique. Avec la volonté de structurer les objets, une dernière étude a porté sur l'assemblage de réseaux de coordination construits sur des ligands photo-sensibles. / With a constant desire to understand and develop molecular engineering, scientists have conceived and produced a wealth of systems, similar to the ones we are confronted with everyday. In this work, organic synthesis strategies are presented for the preparation of switchable molecular turnstiles. The goal was to introduce catalytic sites and to follow their activity under controlled conditions. From multi-step and optimized routes, several families were synthesized, characterized and their catalytic activites were evaluated. In the meantime, interest was focused on the modulation of kinetics in such systems. Photo-isomerizable compounds were prepared and characterized by NMR, and later examined with photo-physics and theoretical approaches. Eager to build up organized objects, coordination networks were finally prepared from photo-sensitive ligands.

Le contrôle du mouvement à l’échelle d’une simple molécule est un sujet actuellement florissant et intensément exploré par des chimistes de tous horizons. Le travail présenté dans ce manuscrit s’inscrit dans ce cadre. La conception ainsi que l’étude en solution et à l’état cristallin de tourniquets moléculaires, espèces composées d’un rotor et d’un stator comportant plusieurs sites d’interaction, y sont décrites.Dans une première partie, la synthèse ainsi que le fonctionnement de tourniquets à charnière de Pt(II) sont décrits. La fermeture et l’ouverture de ces systèmes ainsi que les essais de passage d’une station à une autre y sont étudiés. Les sites d’interactions ont été variés sur le rotor et le stator, pour aboutir à des systèmes variant par la dynamique de leur comportement.Dans une seconde partie, une synthèse optimisée de tourniquets à charnière organique est décrite. Les états ouverts et fermés de ces tourniquets ont été caractérisés.Tous les processus décrits pour les tourniquets ont été étudiés par des études RMN mono- et bi-dimensionnelles en solution.Dans un dernier chapitre, des MM’OFs basés sur un tecton comportant un centre Pt(II) et deux sites coordinant de type pyridine sont exposés. Leur utilisation en tant que tecton organométallique avec divers centres métalliques conduit à la formation de réseaux hétérobimétalliques. Un ligand incluant deux centres Pt(II) et un centre Fe(II) entouré par deux terpyridines est décrit. / The control of intramolecular movements has been a topic of high interest for chemists over two decades. Investigations described in this PhD manuscript aim at the design and study, both in solution and in the crystalline state, of molecular turnstiles. These entities are composed of a rotor and a stator, each of these constituents equipped with recognition sites.In the first part, the synthesis and behavior of Pt(II)-based molecular turnstiles are described. The switching between their open and closed states and the migration process between stations are discussed. The recognition sites on both the stator and rotor have been varied, leading to different behaviors, particularly in terms of their dynamics.In solution, 1- and 2-D NMR have been used for the characterization of the dynamic processes.In the last chapter, the use of a Pt(II)-bispyridyl based tecton for the synthesis of MM’OFs is reported. The use of various metal salts as secondary center has led to the construction of networks varying by their geometry and dimensionality. A ligand including two Pt(II) and one Fe(II) complexed by two terpyridyl units is described.