Introdução: A falta de sistemas estruturados de custeio nas organizações hospitalares, principalmente filantrópicas, tem dificultado a análise da cobertura dos custos pelo repasse do Sistema Único de Saúde (SUS) aos procedimentos realizados. Objetivo: Identificar a percentagem de cobertura do repasse de verba do SUS para a cirurgia de revascularização miocárdica (CRM), em um hospital filantrópico do município de São Paulo, que possui um sistema de custeio consolidado. Método: Estudo de abordagem quantitativa, transversal e descritiva. Utilizou-se um banco de dados com registro de CRM denominado REVASC, criado pela instituição em 2009 e de inclusão contínua. As informações para a pesquisa foram coletadas de 13 de março a 30 de setembro de 2012. A escolha do período foi devido ao início da inclusão de informações sobre custo e repasse do SUS. A população alvo foi de 1913 pacientes e amostra de 1362 (71,2%). Resultados: O custo total médio da internação por paciente foi de R$16.196,91. A média de repasse pelo SUS foi de R$6.992,91(48,66%), observando-se um déficit de 9.204,00 (51,34%). A média de idade foi de 61,4 anos e 69,9% eram do sexo masculino. A média do tempo de permanência hospitalar (TPH) foi de 11,23 dias, sendo 2,42 dias na terapia intensiva e 8,49 dias no pós-operatório. A maioria dos pacientes (69,5%) apresentou um TPH maior que sete dias, considerada prolongada pela instituição. Ao comparar o Grupo 1 (TPH7dias) e Grupo 2 (TPH>7dias), este apresentou custo, receita, diferença entre custo-receita e diferença percentual significativamente maiores que os pacientes do Grupo1. Ao associar o TPH com fatores de risco houve diferença apenas no Grupo 2 que apresentou maior idade, maior número de diabetes e de insuficiência renal crônica. Em relação às complicações pós-operatórias houve diferença em relação a transfusão sanguínea, fibrilação atrial, sangramento importante, pneumonia, insuficiência renal aguda, infarto agudo do miocárdio perioperatório, hemodiálise, acidente vascular encefálico, ventilação mecânica prolongada e reoperação por sangramento / mediastinite, também com incidência maior no Grupo2. Conclusão: O repasse do SUS cobriu menos da metade do custo total médio da internação em CRM (48,66%). Embora o valor do repasse do SUS tenha aumentado conforme a elevação do custo, esse ressarcimento foi desproporcional ao custo total, resultando numa diferença percentual de receita cada vez mais negativa a cada aumento do custo e da permanência hospitalar. / Introduction: The lack of structured expense systems in hospital organizations, especially when philanthropic, has hindered the analysis of the coverage of costs by transfer of funds from the Unified Healthcare System (SUS) for the procedures performed. Objective: To identify the percentage of coverage of the transfer of funds from SUS for coronary artery bypass surgery (CABG) in a philanthropic hospital that has a consolidated expense system in the municipality of São Paulo. Method: A quantitative, cross-sectional, and descriptive study. A databank containing data with CABG records called REVASC was used, created by the institution in 2009 with ongoing data inclusion. Information for the research was collected from March 13 to September 30, 2012. The choice of that period was due to the start of inclusion of information on costs and the transfer of funds from SUS. The target population was made up of 1913 patients and a sample of 1362 (71.2%). Results: The total mean cost of hospitalization per patient was R$16,196.91. The mean transfer of funds by SUS was R$6,992.91 (48.66%), with a deficit of 9,204.00 (51.34%). The mean age of the subjects was 61.4 years, and 69.9% of them were men. The mean hospital stay (HS) was 11.23 days, in which 2.42 days were in intensive therapy, and 8.49 days in the postoperative unit. Most of the patients (69.5%) had a HS longer than seven days, considered prolonged by the institution. When comparing Group 1 (HS 7 days) and Group 2 (HS >7 days), the latter group showed costs, revenue, difference between cost and revenue, and percentage difference significantly greater than did the patients from Group 1. In associating the HS with risk factors, there was a greater difference only in Group 2, which showed a higher age, and greater number individuals with diabetes and chronic renal failure. As to postoperative complications, there was a difference as to blood transfusion, atrial fibrillation, significant bleeding, pneumonia, acute renal failure, perioperative acute myocardial infarct, hemodialysis, cerebrovascular accident, prolonged mechanical ventilation, and reoperation due to bleeding/mediastinitis, also with an incidence greater than in Group 2. Conclusion: The financial provision from SUS covered less than half the total mean cost of hospitalization for CABG (48.66%). Although the value transferred from SUS increased according to cost elevation, this reimbursement was disproportional to the total cost, resulting in an increasingly negative percentage difference of revenue for each increase in cost and in hospital stay.

Made available in DSpace on 2017-07-10T14:17:07Z (GMT). No. of bitstreams: 1 Claudia Ebertz.pdf: 1969807 bytes, checksum: 61f18bbc24e26e53d1b8941d93aadc58 (MD5) Previous issue date: 2013-12-17 / Purpose: Bariatric surgeries reduce non-alcoholic fatty liver disease (NAFLD), which is associated with metabolic syndrome co-morbidities; however, the effects of duodenal-jejunal bypass (DJB) have not been investigated. This study aimed to evaluate the effects of DJB on serum and hepatic profiles of obese rats fed on a western diet (WD). Methods: Male Wistar rats were fed a standard rodent chow diet (CTL group) or WD ad libitum. After 10 weeks, WD rats were submitted to sham (WD SHAM) or duodenal-jejunal bypass (WD DJB). Body weight, fat pad depots, glycemia, insulinemia, HOMA-IR, TyG, lipids profile and hepatic analyses were evaluated two months after surgery. Results: The WD SHAM group presented greater obesity, hyperglycemia, hyperinsulinemia, insulin resistance, hypertriglyceridemia and hepatic steatosis than the CTL group. WD DJB rats presented decreased serum glucose and insulin resistance, when compared to WD SHAM animals, without changes in insulinemia. In addition, DJB surgery normalized serum TG and attenuated TG accumulation and steatosis in the liver of the WD DJB group. Hepatic ACC and FAS protein expressions were similar in all groups. Conclusions: DJB attenuates hepatic parameters of NAFLD in obese rats fed on a WD diet / Introdução: Cirurgias bariátricas reducem a doença hepática gordurosa não alcoólica (DHGNA), a qual está associada a comorbidades da síndrome metabólica, entretanto, os efeitos da derivação duodeno-jejunal (DDJ) não foram investigados. Este estudo tem por objetivo avaliar os efeitos da DDJ no perfil sérico e hepático de ratos obesos submetidos à dieta de cafeteria. Métodos: Ratos Wistar foram alimentados com ração padrão para roedores (grupo CTL) ou dieta de cafeteria (grupo CAF) ad libitum. Após 10 semanas de dieta, os animais do grupo CAF foram submetidos à falsa cirurgia (CAF FO) ou à derivação duodeno-jejunal (CAF DDJ). O peso corporal, peso dos depósitos de gorduras, glicemia, insulinemia, HOMA-IR, índice TyG, perfil lipídico e análises hepáticas foram avaliados dois meses após a cirurgia. Resultados: O grupo CAF FC apresentou obesidade, hiperglicemia, hiperinsulinemia, resistência à insulina, hipertrigliceridemia e esteatose hepática em relação ao grupo CTL. Os animais CAF DDJ apresentaram diminuição da glicose sérica e resistência à insulina, sem alterações na insulinemia, quando comparados aos animais CAF FC. Além disso, a DDJ normalizou a concentração sérica de triglicérides e atenuou o acúmulo hepático de triglicérides, bem como a esteatose hepática no grupo CAF DDJ. A expressão proteica de ACC e FAS hepáticas foram similares nos três grupos. Conclusões: A DDJ atenuou os parâmetros hepáticos da DHGNA em ratos obesos por dieta de cafeteria

Made available in DSpace on 2017-07-10T14:17:16Z (GMT). No. of bitstreams: 1 Mariana Carla Mendes.pdf: 1848607 bytes, checksum: 083213cf0c0ad5bc3014210dd258c5e6 (MD5) Previous issue date: 2015-02-02 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This study was designed to evaluate whether DJB in western diet (WD)-obese rats could have effects on pancreatic β-cell morphology and islet responsiveness to potentiating agents involved with the protein kinase A (PKA) and C (PKC) pathway. Male Wistar rats with 8 weeks of life were fed a standard rodent chow diet (CTL group) or WD ad libitum. After 10 weeks, WD rats were submitted to sham operation or DJB, forming WD SHAM and WD DJB group, respectively. After two months, the obesity parameters, insulin resistance (IR), pancreas morphology, insulin secretion stimulate by different secretagogues and islet protein expression were verified. WD SHAM rats displayed obesity, hyperglycemia, hyperinsulinemia, glucose intolerance and IR. In addition, they also presented an increase in islets and β-cells area and mass. The glucose-induced insulin secretion stimulated by 11.1 mM glucose in the presence of carbachol (CCh), PMA, Forskolin or IBMX was higher in WD SHAM islets than CTL islets. DJB surgery did not alter body weight but normalized glucose, insulinemia, IR, and decreased islet and β-cells mass. The insulin release stimulated by glucose in the presence of CCh, PMA, Forskolin or IBMX was too normalized in WD DJB group. The expression of glucokinase, PKC, PKA and sintaxin was not altered in WD SHAM rats, but the M3 receptor was down-regulated. DJB did not influence these protein expressions. DJB surgery normalized glicemia, insulinemia and IR, reduced islets and β-cell mass and normalized insulin secretion by PKC and PKA pathway. / O presente estudo avaliou o efeito da derivação duodeno jejunal (DDJ) em ratos obesos pela dieta de cafeteria (CAF) sobre a morfofisiologia, com enfâse na ação de agentes potencializadores da secreção de insulina. Ratos Wistar com 8 semanas de vida receberam dieta padrão formando o crupo controle (CTL) ou CAF ad libitum. Após 10 semanas, os ratos CAF foram submetidos à falsa operação ou a DDJ, formando os grupos CAF SHAM e CAF DDJ, respectivamente. Após dois meses, foram avaliados os parâmetros de obesidade, resistência à insulina (RI), morfologia do pâncreas, secreção de insulina estimulada por glicose, carbacol (CCh), PMA, IBMX e Forscolina, e a expressão proteica de glicoquinase (GCK), receptor muscarínico M3, proteina quinase C e A (PKC e PKA) e Sintaxina-1, nas ilhotas. Os animais do grupo CAF SHAM tornaram-se obesos, hiperglicêmicos, hiperinsulinêmicos, intolerantes à glicose e resistentes à insulina. Além disso, apresentaram aumento na massa da ilhota e das células β. A secreção de insulina estimulada por 11.1 mM de glicose na presença de CCh, PMA, Forskolin ou IBMX foi significativamente maior no grupo CAF SHAM em relação ao grupo CTL. A DDJ não alterou o peso corporal, mas normalizou a glicemia, insulinemia, a RI e diminuiu a massa das ilhotas e das células β. A secreção de insulina estimulada pelos diferentes secretagogos também foi normalizada no grupo CAF DDJ. A expressão proteica da GCK, PKC, PKA e sintaxina não foi alterada no grupo CAF SHAM em relação ao CTL, todavia a expressão do receptor M3 foi reduzida. A DDJ não influenciou na expressão dessas proteínas. Em conclusão, a cirurgia de DDJ normalizou a glicemia, a insulinemia e a RI, reduziu a massa das ilhotas e das células β bem como, normalizou a secreção de insulina via PKC e PKA.

Introdução: A falta de sistemas estruturados de custeio nas organizações hospitalares, principalmente filantrópicas, tem dificultado a análise da cobertura dos custos pelo repasse do Sistema Único de Saúde (SUS) aos procedimentos realizados. Objetivo: Identificar a percentagem de cobertura do repasse de verba do SUS para a cirurgia de revascularização miocárdica (CRM), em um hospital filantrópico do município de São Paulo, que possui um sistema de custeio consolidado. Método: Estudo de abordagem quantitativa, transversal e descritiva. Utilizou-se um banco de dados com registro de CRM denominado REVASC, criado pela instituição em 2009 e de inclusão contínua. As informações para a pesquisa foram coletadas de 13 de março a 30 de setembro de 2012. A escolha do período foi devido ao início da inclusão de informações sobre custo e repasse do SUS. A população alvo foi de 1913 pacientes e amostra de 1362 (71,2%). Resultados: O custo total médio da internação por paciente foi de R$16.196,91. A média de repasse pelo SUS foi de R$6.992,91(48,66%), observando-se um déficit de 9.204,00 (51,34%). A média de idade foi de 61,4 anos e 69,9% eram do sexo masculino. A média do tempo de permanência hospitalar (TPH) foi de 11,23 dias, sendo 2,42 dias na terapia intensiva e 8,49 dias no pós-operatório. A maioria dos pacientes (69,5%) apresentou um TPH maior que sete dias, considerada prolongada pela instituição. Ao comparar o Grupo 1 (TPH7dias) e Grupo 2 (TPH>7dias), este apresentou custo, receita, diferença entre custo-receita e diferença percentual significativamente maiores que os pacientes do Grupo1. Ao associar o TPH com fatores de risco houve diferença apenas no Grupo 2 que apresentou maior idade, maior número de diabetes e de insuficiência renal crônica. Em relação às complicações pós-operatórias houve diferença em relação a transfusão sanguínea, fibrilação atrial, sangramento importante, pneumonia, insuficiência renal aguda, infarto agudo do miocárdio perioperatório, hemodiálise, acidente vascular encefálico, ventilação mecânica prolongada e reoperação por sangramento / mediastinite, também com incidência maior no Grupo2. Conclusão: O repasse do SUS cobriu menos da metade do custo total médio da internação em CRM (48,66%). Embora o valor do repasse do SUS tenha aumentado conforme a elevação do custo, esse ressarcimento foi desproporcional ao custo total, resultando numa diferença percentual de receita cada vez mais negativa a cada aumento do custo e da permanência hospitalar. / Introduction: The lack of structured expense systems in hospital organizations, especially when philanthropic, has hindered the analysis of the coverage of costs by transfer of funds from the Unified Healthcare System (SUS) for the procedures performed. Objective: To identify the percentage of coverage of the transfer of funds from SUS for coronary artery bypass surgery (CABG) in a philanthropic hospital that has a consolidated expense system in the municipality of São Paulo. Method: A quantitative, cross-sectional, and descriptive study. A databank containing data with CABG records called REVASC was used, created by the institution in 2009 with ongoing data inclusion. Information for the research was collected from March 13 to September 30, 2012. The choice of that period was due to the start of inclusion of information on costs and the transfer of funds from SUS. The target population was made up of 1913 patients and a sample of 1362 (71.2%). Results: The total mean cost of hospitalization per patient was R$16,196.91. The mean transfer of funds by SUS was R$6,992.91 (48.66%), with a deficit of 9,204.00 (51.34%). The mean age of the subjects was 61.4 years, and 69.9% of them were men. The mean hospital stay (HS) was 11.23 days, in which 2.42 days were in intensive therapy, and 8.49 days in the postoperative unit. Most of the patients (69.5%) had a HS longer than seven days, considered prolonged by the institution. When comparing Group 1 (HS 7 days) and Group 2 (HS >7 days), the latter group showed costs, revenue, difference between cost and revenue, and percentage difference significantly greater than did the patients from Group 1. In associating the HS with risk factors, there was a greater difference only in Group 2, which showed a higher age, and greater number individuals with diabetes and chronic renal failure. As to postoperative complications, there was a difference as to blood transfusion, atrial fibrillation, significant bleeding, pneumonia, acute renal failure, perioperative acute myocardial infarct, hemodialysis, cerebrovascular accident, prolonged mechanical ventilation, and reoperation due to bleeding/mediastinitis, also with an incidence greater than in Group 2. Conclusion: The financial provision from SUS covered less than half the total mean cost of hospitalization for CABG (48.66%). Although the value transferred from SUS increased according to cost elevation, this reimbursement was disproportional to the total cost, resulting in an increasingly negative percentage difference of revenue for each increase in cost and in hospital stay.

Abstract Coronary artery bypass grafting (CABG) is the treatment of choice for patients with three-vessel disease or left main stenosis. However, it is associated with considerable risk of perioperative complications such as myocardial infarction, stroke, infections, and mortality to which excessive bleeding is a contributing factor. This thesis aims to determine the factors involved in and clinical implications of bleeding after CABG. The 1st study evaluated the effects of preoperative ASA discontinuation on the patient’s outcome after CABG. The results showed that late or no discontinuation of low-dose ASA before CABG may decrease the risk of postoperative stroke without increasing the risk of postoperative bleeding. In the 2nd study the use of warfarin was found to be a safe during CABG with no excess bleeding nor other major complications. The 3rd study estimated the impact of surgeons´ performances on blood loss and need for re-exploration after CABG. With 2001 study patients, this study clearly demonstrated that an individual surgeon is a powerful determinant of postoperative bleeding and need for re-exploration after CABG. Using systematic review and meta-analysis, we estimated the risk of complications related to re-exploration for bleeding after CABG. In literature search in 2011, 8 articles with 557 923 patients fulfilled the inclusion criteria. Re-exploration for bleeding after cardiac surgery carries a significantly increased risk of postoperative mortality and morbidity, and thus has a major impact on the patient’s immediate postoperative outcome. We also studied the impact of blood transfusion on the development of post-operative stroke after CABG. Of the study population of 2 226 CABG patients, stroke occurred postoperatively in 53 patients (2.4%). The statistical analysis showed that transfusion of blood products after CABG has a strong, dose-dependent association with the risk of stroke. The use of Octaplas® and platelet transfusions seem to have an even larger impact on the development of stroke than red blood cell transfusions. The 6th study investigated the impact of transfusion of blood products on intermediate outcome after CABG in 2001 patients. The findings indicated that transfusion of any blood product is associated with a significant risk of all-cause and cardiac mortality after CABG. / Tiivistelmä Sepelvaltimotauti on yleisin kuolinsyy ja sepelvaltimoiden ohitusleikkaus hyvine pitkäaikaistuloksineen on todettu parhaaksi hoidoksi potilailla, joilla on monen suonen tai vasemman päärungon tauti. Ohitusleikkaukseen liittyy kuitenkin verenvuodon sekä näihin kytkeytyvien komplikaatioiden riski. Tämän väitöskirjan tavoitteena oli määrittää verenvuodon riskitekijöitä sekä verituotteiden siirtojen vaikutusta ohitusleikkauspotilaiden ennusteeseen. Verenhyytymistä estävien lääkkeiden tiedetään lisäävän verenvuotoja. Ensimmäinen tutkimus osoitti, että ASA:n jatkaminen keskeytyksettä ohitusleikkauksissa vähentää aivoinfarktien riskiä lisäämättä silti verenvuodon riskiä. Toisessa tutkimuksessa pitkäaikainen warfariinihoito osoittautui turvalliseksi ohitusleikkauksen aikana eikä sen käyttö lisännyt verenvuotoja eikä muita komplikaatioita. Kolmas tutkimus osoitti kirurgin taidon merkityksen verenvuotojen ja uusintaleikkausten määrään 2001 potilaalla. Verenvuotojen vuoksi tehtävien uusintaleikkausten negatiivinen vaikutus postoperatiiviseen mortaliteettiin sekä morbiditeettiin on todettu yksiselitteisesti useissa tutkimuksissa. Vuonna 2011 tehdyllä systemaattisella kirjallisuuskatsauksella ja meta-analyysillä selvitimme yhteensä 557 923 ohitusleikkauspotilaan aineistosta, että verenvuodon jälkeisiin uusintaleikkauksiin liittyy huomattava kuoleman ja komplikaatioiden riski. Verenvuotoja hoidetaan yleisesti verensiirroilla, vaikkakin useat tutkimukset ovat osoittaneet verituotteiden annon lisäävän mortaliteettia sekä komplikaatioriskiä. Viides tutkimus selvitteli sepelvaltimoleikkauksissa potilaalle annettujen verituotteiden ja leikkauksen yhteydessä sairastettujen aivoinfarktien välistä yhteyttä. Osoittautui, että verituotteiden käyttöön liittyy annosriippuvaisesti lisääntynyt riski saada aivoinfarkti leikkauksen yhteydessä. Varsinkin verihiutale- ja jääplasmasiirtoihin on todettu liittyvän vielä suurempi aivoinfarktin riski kuin punasolusiirtoihin. Kuudes tutkimus selvitteli sepelvaltimoleikkauksien yhteydessä annettujen verituotteiden vaikutusta 2001 potilaan keskipitkään ennusteeseen. Tutkimus osoitti, että minkä tahansa verituotteen antoon sepelvaltimoleikkauksissa liittyy lisääntynyt kuoleman ja sydänkuoleman riski.

Introduction: Coronary artery bypass grafts are most commonly performed using saphenous vein grafts to complement the internal thoracic artery. The saphenous vein will remain popular despite its lower patency rate because it is easily accessible and lengthy enough to perform multiple bypasses. Therefore, several approaches have been studied, with the common goal of finding the optimal conditions that reduce graft failure. They include novel harvest techniques, new preservation preparations, innovative genetic therapies and experimental drugs. We believe a pharmacological pre-conditioning with an anti-oxidative and anti-inflammatory drug during the crucial time of harvest may spark beneficial survival response from the endothelial cells. One particular compound is Celastrol, an HSP90 inhibitor, which displays those antioxidant and anti-inflammatory properties. Methods: Human umbilical vein endothelial cells (HUVEC) were pretreated with various concentrations of Celastrol (10-10M, 10-8M and 10-6M). In order to reproduce oxidative stress found in ischemia/reperfusion, cells were exposed to hydrogen peroxide for a short and extended period (1h and 24h). To mimic storage condition encountered in clinical settings, cells were also exposed in heparinized normal saline. The viability was assessed by LIVE/DEAD assay. As for migrative and proliferative properties, scratch tests were performed. Finally, various protective intracellular pathways were evaluated by Western blot. Results: This study shows that pre-treatment with Celastrol promotes survival in HUVEC submitted to oxidative stress. Notable improvement in cellular viability was detected as early as 1 hour after oxidative stress (H2O2 4 mM), 76.6% vs 66.1% (p=0.005). Significant survival benefits are also reported after prolonged oxidative stress (H2O2 0.5 mM for 24 hours); viability was 93.7% vs 76.9% (p=0.001) for Cel 10- 8 M and 96.6% vs 76.9% (p=0.002) for Celastrol 10-10M when compared to the vehicle. Celastrol, however, did not significantly affect viability of HUVEC stored in heparinized normal saline. Celastrol at 10-6 M promotes faster and more complete wound closure compared to the vehicle or to lower dosages. Celastrol triggers early activation of the RISK pathway, inducing activation of both Akt and ERK1/2 within the first 15 minutes of treatment. Celastrol also induces the expression of HSP70 and HO-1, effectors of the Heat Shock Response and the anti-oxidative response respectively. Conclusion: Pre-treatment by Celastrol provides survival benefits in endothelial cells under oxidative stress. It also stimulates endothelial cell proliferation and migration, promoting faster and more complete re-endothelialisation. Celastrol can potentially be used as an additive to storage solutions to limit endothelial injury and promote graft protection. / Introduction: La chirurgie de pontage coronarien requiert, dans la grande majorité des cas, l’utilisation de l’artère mammaire interne en combinaison avec un ou des greffons provenant de la grande veine saphène. Malgré le taux de perméabilité inférieur aux artères, la veine saphène reste un choix populaire de conduit en raison de son accessibilité et de sa longueur. De ce fait, le greffon veineux devient la cible de multiples approches et le sujet de nombreuses études visant à optimiser sa perméabilité. Celles-ci incluent le raffinement des techniques de prélèvement, les solutions de préservations, les agents pharmacologiques ainsi que la thérapie génique. Il est davantage intéressant de combiner les approches afin de joindre leurs bénéfices, comme, par exemple, ajouter un agent pharmacologique à une solution de préservation. Un agent potentiel serait le Celastrol, connu pour être un inhibiteur du HSP90 et possède des propriétés antioxydantes et anti-inflammatoires. Méthodologie: Des cellules endothéliales humaines provenant de la veine ombilicale (HUVEC) sont pré-conditionnées à de multiples concentrations de Celastrol (10-10M, 10-8M and 10-6M) pendant une heure avant d’être soumises aux conditions de stress. Pour reproduire les conditions per-opératoires de prélèvement, les cellules endothéliales ont été préservées dans du salin (NS) héparinisé. Pour mimer le stress secondaire à l’ischémie/reperfusion, les cellules ont aussi été soumises à diverses concentrations de H2O2. Une analyse de la viabilité cellulaire fut conduite par le test de LIVE/DEAD. La capacité de ré-endothélialisation est étudiée grâce à l’épreuve de scratch test. Les voies intracellulaires de survie telles que le RISK pathway (Akt, ERK1/2), le Heat shock response (HSP70) et la réponse anti-oxydante (via l’activité de HO-1) ont été examinées par immunoblot. Résultats: Les résultats démontrent que la préservation des cellules endothéliales dans du NS héparinisé est associée à une augmentation de la mortalité comparativement au milieu de culture (20.4% vs 1.9%, p=0.004). Toutefois, un traitement au Celastrol n’affecte pas significativement la survie des cellules endothéliales dans le NS héparinisé. Le stress oxydatif induit aussi une augmentation de la mortalité, et ce à dose-dépendante. Suivant un court stress 6 oxydatif (H2O2 4 mM), un pré-traitement au Celastrol 10-10M est associé à une meilleure viabilité comparativement au véhicule (76.6% vs 66.1%, p=0.005). Lorsque soumises à un stress oxydatif prolongé (H2O2 0.5 mM pendant 24h), les HUVEC pré-traitées au Celastrol à 10-8M et 10-10M démontrent une amélioration significative de la viabilité, 93.7% vs 76.9% (p=0.001) et 93.6% vs 76.9% (p=0.002) respectivement. Quant à la ré-endothélialisation, un traitement au Celastrol 10- 6M est associé à une fermeture plus rapide et complète comparativement au véhicule. Un court traitement au Celastrol active précocement les kinases de la voie de RISK (Akt et ERK). Le traitement induit aussi l’expression de HSP70 et HO-1 qui reste soutenue jusqu’à 48 heures posttraitement. Conclusion: Le Celastrol active plusieurs voies de protection intracellulaire tels que le RISK pathway, le Heat Shock Response et la réponse antioxydante via l’activité de HO-1. En corrélation avec cette réponse, il améliore la survie des cellules endothéliales dans un milieu oxydatif. Le Celastrol promeut aussi une ré-endothélialisation plus complète et rapide. Cette étude met en valeur les bénéfices potentiels du Celastrol sur les cellules endothéliales. Afin d’optimiser la protection du greffon, le Celastrol pourrait donc être considéré comme agent adjuvant à une solution de préservation.

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This study aimed at exploring the impact of early traumatic experiences on bariatric patients with the intent to give "voice" to their experiences. The impact of morbid obesity and the lack of quality of life among those suffering from this form of chronic illness can be devastating. Meaningful support systems and bariatric surgery are therefore considered as forced behavioural interventions to remediate the impact of childhood trauma and subsequent development of morbid obesity among this group of bariatric patients. Through a process of social constructivism and dialogue between the researcher and the five participants, the co-construction according to themes was supported by a qualitative research approach and the case study method. For the analysis of the themes according to the participants' "voices", the thematic content analysis method was used to analyse the data and was finally linked to supportive literature. It is hoped that the results from this study will contribute to the development of a unique assessment and support programme to those who have to endure the burden of morbid obesity associated with early childhood trauma; and that the process prior to and post bariatric surgery will be an important contribution to finding quality of life and giving new meaning to patients after suffering through their bodies and traumatised minds. / Psychology / D.Litt. et. Phil (Psychology)

Herzinfarkt und Tod stellen häufige Folgen der koronaren Herzerkrankung dar, die durch eine rechtzeitige aortokoronare Bypassoperation vermieden werden können. Im Gegensatz zur klassischen offenen Operation bieten minimal invasive Verfahren entscheidende Vorteile. Die erschwerte Orientierung stellt jedoch eine große Herausforderung in der minimal invasiven Herzchirurgie dar, insbesondere bei der Verwendung telemanipulatorischer Systeme, wie bei der total endoskopischen Bypassoperation (TECAB). Die Entwicklung des „Surgical Cartographic Navigation System“ (SCNS) verspricht eine deutliche Verbesserung der Orientierung des Chirurgen mithilfe der Nutzung modernster Techniken der Augmentierten Realität. Hierbei wird auf der Basis von CT-Datensätzen ein virtuelles Herzmodell geschaffen, welches als Grundlage der assistierten Navigation dient. Im Speziellen wird bei der durch das SCNS unterstützten TECAB Operation die aufzufindende Koronararterie in das Sichtfeld des Endoskopes projiziert („augmentiert“). Ziel dieses Dissertationsvorhabens war die Evaluation der klinischen Anwendbarkeit des SCNS während einer Simulation einer Inzision mit dem da Vinci™-System auf fünf individuell angefertigten Herzphantomen. Es sollte überprüft werden, ob der Chirurg mit Hilfe der Unterstützung durch die SCNS Sicht mit eingeblendeter Koronararterie einen direkten Kontakt zur LAD (Left Anterior Descending), der häufigsten Zielarterie der TECAB, herstellen kann. In einem Studienkollektiv, bestehend aus zehn medizinisch unerfahrenen Personen und zehn Herzchirurgen, wurde die Treffergenauigkeit der SCNS-gestützten Auffindung der LAD in insgesamt 300 Testversuchen überprüft. Insgesamt konnte die Arterie in 58 % der Fälle korrekt identifiziert werden. Dabei lag kein signifikanter Unterschied zwischen den beiden Gruppen vor. Hiermit konnte die klinische Anwendbarkeit des SCNS für die TECAB erstmals gezeigt werden. Des Weiteren wurden zwei Faktoren als vordringliche Ziele für zukünftige Fortentwicklungen identifiziert: Die Optimierung von Landmarken für die Registrierung des Herzens sowie die verbesserte optische Darstellung der Augmentierten Realität im Endoskopiesichtfeld. Zusammengefasst konnte in diesem Dissertationsvorhaben in einer umfassenden Studie gezeigt werden, dass das SCNS einen erfolgversprechenden Lösungsansatz für die Behebung kritischer Orientierungsprobleme der minimal invasiven Herzchirurgie bei der TECAB bietet. Die hier gewonnenen Erkenntnisse stellen die Grundlage für weitergehende Studien zur Fortentwicklung des SCNS dar, die vor einem klinischen Ersteinsatz erfolgen müssen. / In the therapy of coronary heart disease minimally invasive and endoscopic methods offer considerable benefits to the patient, while for the surgeon difficult orientation and missing haptic feedback are still the leading problems in Endoscopic Bypass Grafting with telemanipulative systems. To support the surgeon with improved vision, a three dimensional model of the coronary artery tree based on CT scans is integrated into the view of the endoscope. The “Surgical Cartographic Navigation System” (SCNS) is a tool which provides this feature called Augmented Reality (AR). Aim of this study was the first technical analysis of the SCNS during a simulation of an incision with the da Vinci™ surgical system on an electronic heart phantom. The hypotheses was that with the guidance of the SCNS augmented reality view, the surgeon can perform a direct contact to the Left Anterior Descending Coronary Artery (LAD). Five anatomically correct heart phantoms were created using the rapid prototyping technology. The heart models were covered with an electrical conducting layer for the detection of the contact with the coronary artery or with the surrounding tissue. A 3D model of the coronary artery tree based on a CT scan was registered to the heart phantom and overlaid into the video screen of the da Vinci™ robot master console. Ten inexperienced medical students and ten experienced heart surgeons used the SCNS in a surgery simulation with the goal of finding the LAD artery and contacting the LAD with robot instruments. In 300 test runs 58 % of both groups hit the LAD correctly. The overlaid information created with the SCNS enables the surgeon to correctly identify the coronary artery. The clinical applicability of the SCNS for the TECAB Operation is hereby demonstrated. These findings are the basis for further studies on the further development of the SCNS, that is necessary before a clinical first-use.

This study aimed at exploring the impact of early traumatic experiences on bariatric patients with the intent to give "voice" to their experiences. The impact of morbid obesity and the lack of quality of life among those suffering from this form of chronic illness can be devastating. Meaningful support systems and bariatric surgery are therefore considered as forced behavioural interventions to remediate the impact of childhood trauma and subsequent development of morbid obesity among this group of bariatric patients. Through a process of social constructivism and dialogue between the researcher and the five participants, the co-construction according to themes was supported by a qualitative research approach and the case study method. For the analysis of the themes according to the participants' "voices", the thematic content analysis method was used to analyse the data and was finally linked to supportive literature. It is hoped that the results from this study will contribute to the development of a unique assessment and support programme to those who have to endure the burden of morbid obesity associated with early childhood trauma; and that the process prior to and post bariatric surgery will be an important contribution to finding quality of life and giving new meaning to patients after suffering through their bodies and traumatised minds. / Psychology / D.Litt. et. Phil (Psychology)