Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Source: Masters Abstracts International, Volume: 46-04, page: 2054. Adviser: Jan M. H. Risser. Includes bibliographical references.

Thesis (M.S.)--Brock University, 2009. / Includes bibliographical references (leaves 34-35).

Orientador: Newton Nunes / Banca: Celina Tie Nishimori Duque / Banca: Paulo Sérgio Patto dos Santos / Resumo: Avaliaram-se os efeitos da anestesia total intravenosa com propofol associado ou não ao tramadol sobre os parâmetros ventilométricos, cardiovasculares, hematológicos e índice biespectral em cães. Utilizaram-se oito animais submetidos a duas anestesias com 15 dias de intervalo, formando-se dois grupos (n=8): grupo controle (GC) e grupo tramadol (GT). Os animais foram induzidos à anestesia geral com propofol (10mg/kg) por via intravenosa. Seguindose, iniciou-se a infusão do fármaco na taxa de 0,7 mg/kg/min. Os cães foram mantidos em ventilação controlada a pressão de maneira a obter-se normocapnia, com FiO2=0,6. No GT os animais receberam, por via intravenosa, tramadol (2 mg/kg), seguido de infusão contínua do fármaco na taxa de 0,5 mg/kg/h, enquanto no GC, foi administrada solução de NaCl a 0,9%, seguido de infusão contínua da mesma solução, em volume idêntico ao empregado no GT. As mensurações das variáveis, exceto as hematológicas, iniciaram-se 30 minutos após o bolus de propofol (M0), e então em intervalos de 15 minutos, durante um período de 60 minutos (M15, M30, M45 e M60). Para os parâmetros hematológicos, uma amostra de sangue foi coletada antes da indução anestésica (Mbasal), 30 minutos após a indução (M0) e em intervalos de 30 minutos durante 60 minutos (M30 e M60). O método estatístico utilizado foi a Análise de Perfil (P<0,05). A associação de propofol e tramadol não promoveu alterações nos parâmetros ventilométricos, cardiovasculares e eletrocardiográficos avaliados e no índice biespectral, mas promoveu diminuição da temperatura corpórea (TC), redução da contagem de hemácias (He), hemoglobina (Hb) e hematócrito (Ht). O sinergismo do tramadol com propofol também reduziu as contagens de leucócitos totais (Le) e linfócitos (Linf). / Abstract: The effects of total intravenous anesthesia with propofol associated or not to tramadol on ventilometric, cardiovascular, hematologic and bispectral index parameters in dogs were evaluated. Eight adult mongrel dogs were anesthetized on 2 occasions, 15 d apart, in a randomized crossover fashion. Two groups were formed: control group (GC) and tramadol group (GT). Propofol was used for induction (10 mg/kg IV) followed by a continuous rate infusion at 0.7 mg/kg/min. The animals were kept in pressure controlled ventilation with FiO2=0.6 with the aim to produce normocapnia. In GT, the tramadol bolus (2 mg/kg) followed by a continuous rate infusion at 0.5 mg/kg/min was administered in dogs via intravenous route. While, in GC, the NaCl to 0.9% was administrated followed by its continuous rate infusion, in the same volume that was used in GT. The measurement of all variables, except the hematologic parameters, was performed 30 minutes after propofol bolus (M0), and then, in intervals of 15 minutes, during 60 minutes (M15, M30, M45 and M60). For hematologic parameters, a blood sample was collected before anesthesia induction (Mbasal), 30 minutes after induction (M0) and, then, in intervals of 30 minutes during 60 minutes (M30 and M60). Numeric data were submitted to Profile analysis (P<0,05). The association of propofol and tramadol did not promote changes in bispectral index, ventilometric, cardiovascular and electrocardiographic parameters, but it promoted corporal temperature (TC) decrease and reduction in counting of hemaceas (He), hemoglobin (Hb) and hematocrit (Ht). The synergism of tramadol with propofol reduced the counting of total leukocytes (Le) and lymphocytes (Lymph). / Mestre

Les immunoglobulines circulantes jouent un rôle critique dans l’homéostasie immune en modulant les fonctions des cellules du système immunitaire. Au cours de ma thèse, j’ai exploré les effets régulateurs des immunoglobulines G thérapeutiques (IVIG) et des immunoglobulines A monomériques circulantes (mIgA) sur l’autophagie et les réponses Th17 respectivement. Les IVIg sont une préparation thérapeutique d’IgG normales poolées. Elles ont utilisées comme agent anti-inflammatoire dans le traitement de maladies auto-immunes et inflammatoires variées. Cependant, les mécanismes ne sont pas complètement élucidés et plusieurs mécanismes mutuels et non exclusifs ont été proposés. L’autophagie est un important processus biologique impliquant la dégradation lysosomale des composants cellulaires endommagés et des protéines mal repliées. Il y a plusieurs preuves montrant l’implication de l’autophagie dans les maladies auto-immunes et auto-inflammatoires incluant la découverte de polymorphismes dans des gènes liés à l’autophagie. J’ai montré que l’induction de l’autophagie par les IVIG représente un nouveau mécanisme d’action permettant leur effet thérapeutique dans les maladies auto-immunes et inflammatoires. Les Th17 représentent une cible attractive pour traiter plusieurs maladies inflammatoires et auto-immunes. Malgré le fait qu’elles sont le deuxième anticorps le plus abondant dans la circulation, la function immunorégulatrice des IgA n’est relativement pas explorée. J’ai montré que les IgA monomériques (mIgA) inhibent la différentiation et l’amplification des cellules Th17 humaines et la production de leur cytokine effectrice IL-17A. / Circulating immunoglobulins play a critical role in the immune homeostasis by modulating the functions of immune cells. In my thesis, I investigated the regulatory effects of therapeutic immunoglobulin G (IVIG) and circulating monomeric immunoglobulin A (mIgA) on autophagy and human Th17 response respectively. IVIG is a therapeutic preparation of pooled normal IgG. It is used as an anti-inflammatory agent in the treatment of a wide variety of autoimmune and inflammatory diseases. However, the mechanisms are not yet fully elucidated and several mutually non-exclusive mechanisms have been proposed. Autophagy is an important biological process involving lysosomal degradation of damaged cellular components and misfolded proteins. There are several evidences that support the involvement of autophagy in autoimmune and auto- inflammatory disorders including the discovery of polymorphisms in autophagy-related genes. I show that induction of autophagy by IVIG represents a novel mechanism of action in achieving therapeutic effect in autoimmune and inflammatory diseases. Th17 cells represent an attractive target to treat several inflammatory and autoimmune diseases. Despite being second most abundant antibody in the circulation, the immunoregulatory function of IgA is relatively unexplored. I have shown that monomeric IgA (mIgA) inhibits differentiation and amplification of human Th17 cells and the production of their effector cytokine IL-17A.

The goal of this research is to analyze the stigmatization of opioid addiction within the framework of emergency care from an ethnographic perspective. Interviews with those who have been swept up in the current opioid epidemic indicate that stigma, or a shame or dishonor, and socioeconomic insecurity emerge often as common themes in their emergency care experiences. In many cases, socioeconomic insecurity most intensely translates into a lack of access to healthcare and emergency rooms across the country often function as primary care for uninsured populations. The central field site selected for this study was the emergency department of an urban trauma-level research hospital in an attempt to document the process of care for those in opioid crisis and the challenges healthcare providers face in facilitating this care. The aim of this research is to discover how stigma affects care in emergency room settings during an acute opioid crisis. This is a moment when patients may be most open to the idea of detoxification and sobriety. In this study, I argue that addiction can be shifted from being viewed as a disgraceful state to a medical condition, by uncovering what experiences overdose victims have while under emergency care, how patients experience stigma related to their opioid crisis, and what challenges healthcare providers describe while facilitating care during crisis. Findings suggest that stigma permeates the interactions drug-addicted patients have with healthcare professionals and that it may have a negative impact on their decision to seek further treatment. Application of results in the form of a community resource guide made available to patients and hospital staff indicate the potential for reducing stigma of intravenous/opioid-related addiction as healthcare providers are more able to discern gaps in care for addicted patients and facilitate greater follow-up care and access to resources. This thesis illustrates the potential for qualitative analysis of acute care to uncover vital next steps in reducing the stigma surrounding opioid addiction. Reducing stigma in the provision of care could foster more integrative approaches to treatment, help inform new protocols for caregivers, uncover resources to aid healthcare providers, and potentially provide a more substantial level of care and access to resources for the patient in crisis—one that may facilitate recovery in lieu of relapse.

Introdução e objetivos: A extensão segura da janela terapêutica para o tratamento do acidente vascular cerebral isquêmico (AVCI) agudo com terapia trombolítica endovenosa (EV) é importante, porque mais pacientes podem ser beneficiados com este tratamento. O objetivo é comparar o benefício da trombólise <3 horas e entre 3 e 4,5 horas no mundo real. Métodos: Avaliamos prospectivamente pacientes com AVCI tratados com trombólise em Porto Alegre entre 2002 a 2011. Até 2008, apenas alguns pacientes selecionados foram tratados com mais de 3 horas. Após o estudo ECASS III, estendemos a janela terapêutica com os mesmos critérios para os pacientes tratados entre 3-4,5 h. Nós comparamos a evolução funcional em 3 meses, hemorragia intracerebral sintomática (HIS) e mortalidade do grupo tratado < 3h com o grupo tratado entre 3-4,5h. Resultados: Foram analisados 487 pacientes com AVCI agudo trombolisados. Neste período, 33% dos pacientes foram tratados entre 3 e 4,5 horas. Pacientes tratados mais precocemente eram mais graves: média de idade 68±14 vs. 65±13, P<0,03, escore do NIHSS 12±6 vs. 11±7, P<0,015, ASPECTS ≤ 7 18% vs. 8,5%, P=0,011, hipodensidade maior 1/3 ACM na tomografia (4% vs. 0,9%, P=0,05). Os resultados no grupo < 3 h comparado com o grupo entre 3-4,5h foram, respectivamente: boa evolução funcional 49% vs. 50%, P= 0,82, mortalidade 12% vs. 11%, P= 0,60 e a HIS 5,9% vs. 3,8%, P= 0,52. Após a extensão da janela terapêutica, houve um aumento de 3,8 vezes no número de pacientes trombolisados. Conclusões: Este estudo sugere que trombólise EV para pacientes com AVCI agudo entre 3-4,5h é segura e apresenta bons resultados funcionais, semelhante a pacientes tratados mais precocemente. Deve ser estimulado o tratamento o mais precoce possível, mas pacientes que chegam tardíamente ao hospital também podem receber o benefício do tratamento. / Background and aims: A safe extension of the therapeutic window for treating acute ischemic stroke (AIS) with intravenous thrombolysis is important because it would mean that more patients could receive the benefit of the treatment. Our goal was to compare the safety and functional outcome of thrombolysis between 3 and 4.5 h and ≤ 3 h in patients in the Real World. Methods: We prospectively evaluated a cohort of thrombolyzed patients treated between 2005 and 2011. Following the publication of the results from ECASS III, we extended the therapeutic window, using the same criteria, to patients treated between 3 and 4.5 h after AIS. We compared functional outcomes at 3 months, symptomatic intracranial hemorrhage (SIH) and mortality of the patients treated until 3 h vs. those treated at between 3 and 4.5 h. Results: We analyzed 487 thrombolyzed patients. During this period, 33% of patients were treated between 3 and 4.5 hours. The patients treated at earlier timepoints were more severely affected than the patients treated at later timepoints: mean ages were 68 vs. 65 (P<0.03), NIHSS scale scores were 12 vs. 11 (P<0.015), ASPECTS ≤ 7 were 18% vs. 8.5% (P =0.011) and hypodensity was observed in more than 1/3 of the middle cerebral artery in 4% vs. 0.9% (P=0.05), respectively. When comparing the group < 3 h vs. between 3 and 4.5h, the results showed favorable outcomes in 49% vs. 50% (P=0.82), mortality in 12% vs. 11% (P=0.60) and SIH in 5.9% vs. 3.8% (P=0.52), respectively. After extending the therapeutic window, the number of thrombolyzed patients increased 3.8-fold. Conclusions: This study suggests that intravenous thrombolysis is safe in AIS patients and that it causes favorable functional outcomes, similar to patients treated at earlier timepoints. Thrombolytic treatment should be initiated as soon as possible; however, patients who arrive late may receive treatment benefits.

Submitted by DANIEL CARVALHO DE MENEZES null (menezesdcc@hotmail.com) on 2016-04-11T00:33:09Z No. of bitstreams: 1 Dissertação - Mestrado - Daniel Carvalho de Menezes.pdf: 1004576 bytes, checksum: ed91db99176a44b0b049ca9ff16a1a70 (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-04-12T17:59:09Z (GMT) No. of bitstreams: 1 menezes_dc_me_bot.pdf: 1004576 bytes, checksum: ed91db99176a44b0b049ca9ff16a1a70 (MD5) / Made available in DSpace on 2016-04-12T17:59:09Z (GMT). No. of bitstreams: 1 menezes_dc_me_bot.pdf: 1004576 bytes, checksum: ed91db99176a44b0b049ca9ff16a1a70 (MD5) Previous issue date: 2016-03-03 / Introdução: a presença de dor pós-operatória é uma grande preocupação quando o remifentanil é usado em Anestesia Venosa Total (AVT) devido à meia-vida muito curta desse fármaco e possíveis mecanismos de hiperalgesia e tolerância. Opioides com duração de ação mais prolongada - como sufentanil – têm sido usados durante a indução da AVT com infusão contínua de remifentanil no intuito de suplantar essa limitação. Contudo, a efetividade desta estratégia carece de evidência decorrente de ensaios clínicos. Objetivo: avaliar a eficácia e a segurança da estratégia de administrar sufentanil durante a indução de AVT com remifentanil na analgesia pós-operatória por meio de ensaio clínico randomizado. Método: quarenta pacientes em programação de cirurgia abdominal aberta eletiva foram randomizados para receber infusão contínua de remifentanil em anestesia venosa total, com ou sem a administração de uma dose única de sufentanil, durante a indução da anestesia. Foram avaliados a intensidade da dor pós-operatória, o consumo de morfina e a ocorrência de complicações como náuseas, vômitos, prurido, agitação, sonolência e depressão respiratória, até 48 horas após a cirurgia. O desfecho primário foi o consumo de morfina durante as primeiras 24 horas após a cirurgia. Resultados: a média do consumo de morfina durante as primeiras 24 horas após a cirurgia foi 21,55 mg e 26,68 mg para o grupo que recebeu a dose única de sufentanil e para o grupo controle, respectivamente (p = 0,31). Os pacientes que receberam sufentanil necessitaram de menor quantidade de morfina durante o tempo na Sala de Recuperação Pós-anestésica (SRPA) (média do consumo de morfina total de 7,77 mg versus 15,63 mg, p= 0,02). As diferenças nos escores de dor durante todo o período de estudo e no consumo de morfina após a alta da SRPA não alcançaram significância estatística. A frequência de efeitos adversos não foi estatisticamente diferente entre os grupos. Conclusão: a administração de sufentanil durante a indução anestésica de anestesia venosa total com remifentanil em infusão contínua apresentou superioridade analgésica pós-operatória no período até a alta da SRPA, sem a ocorrência de uma maior proporção de efeitos adversos em relação ao grupo que não recebeu sufentanil. / Background: the presence of postoperative pain is a major concern when remifentanil is used for Total Intravenous Anesthesia (TIVA) because of the very short half-life of this medication and possible mechanisms of hyperalgesia and tolerance. Longer acting opioids – such as sufentanil – have been used during induction of remifentanil-based TIVA as a means to overcome this shortcoming. However, the effectiveness of the strategy still lacks evidence from randomized clinical trials. Objective: we conducted a randomized clinical trial to assess the postoperative analgesic efficacy and safety of a single dose of sufentanil administered during the induction of remifentanil-based TIVA. Methods: forty patients scheduled for elective open abdominal surgery were randomized to receive remifentanil-based TIVA with or without the administration of a single dose of sufentanil during anesthesia induction. We assessed postoperative pain intensity, morphine consumption and the occurrence of complications such as nausea, vomiting, pruritus, agitation, somnolence and respiratory depression up to 48 hours after surgery. The primary outcome was morphine consumption during the first 24 hours after surgery. Results: the mean morphine consumption during the first 24 hours after surgery was 21,55 mg and 26,68 mg for the group that received sufentanil and the control group, respectively (P=0,31). Patients in the sufentanil group required less morphine during their time in the Post-Anesthetic Care Unit (PACU) (mean total morphine consumption of 7,77 mg versus 15,63 mg, P=0,02). Differences in pain scores during the whole study period and morphine consumption after discharge from PACU were not statistically significant. The frequency of adverse effects did not statistically vary between the groups. Conclusion: the administration of sufentanil during anesthetic induction of remifentanil-based TIVA continuous infusion showed superior postoperative analgesic efficacy in the period until discharge from PACU and did not increase the incidence of adverse effects.

Made available in DSpace on 2014-06-11T19:31:08Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-04-27Bitstream added on 2014-06-13T20:47:25Z : No. of bitstreams: 1 carareto_r_dr_jabo.pdf: 692919 bytes, checksum: c80efafc680f7ae3629e5949745e34a5 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Avaliaram-se os efeitos hemodinâmicos, ventilatórios e hemogasométricos decorrentes da utilização da ventilação controlada a volume ou a pressão, com diferentes valores de pressões positivas expiratórias finais (PEEPs) em cães submetidos ao cefalodeclive. Utilizaram-se 6 animais adultos, machos ou fêmeas, os quais foram induzidos à anestesia com propofol (8 mglkg por via IV), e mantidos sob anestesia total intravenosa com propofol (0,2 rnglkg/rnin) e sufentanil (0,1 f..L9/kg/min). Formaram-se dois grupos que se diferenciaram pela modalidade ventilatória utilizada, ou seja: GO-V ventilação controlada a volume e GO-P ventilação controlada a pressão. Os animais foram mantidos na posição de Trendenlemburg a 30° e submetidos a diferentes valores de PEEP (O, 5 e 10 cmH20). Os dados de cada grupo foram submetidos a uma análise de variância, seguido pelo pós teste de Tukey-Kramer. Para a comparação entre os dois grupos, utilizou-se do teste T pareado. Para todas as análises, considerou-se P<O,OS como estatisticamente significativo. Nos cães ventilados com pressão controlada foi observado variação no Vt, Ppico, Pplat, Vd alv , IS, PAPm, PCPm, 1002 e IV02 ao longo das PEEPs. No grupo dos ventilados com volume controlado houve alteração na Ppico, Pplat, Vd alv e FC. A comparação das diferentes ventilações foi caracterizada por 'variação no Vd alv, FC, PVC, PCPm, CV02, IV02 e Te02. Concluiu-se que os níveis progressivos de PEEP promoveram mínimas alterações hemodinâmicas, ventilatórias e hemogasométricas e ambas as modalidades são igualmente eficientes na manutenção da estabilidade respiratória e cardiovascular nas condições experimentais propostas. / The hemodynamic, ventilatory, and btood gases parameters were evaluated in dogs undergoing either volume-controlled or pressure-controlled ventilatioo and varying PEEPs under head-down tilt. Six mature dogs of eifher sex were used. Anesthesia was induced with propofol (8 mglkg IV), and maintained with propofol (O.2mglkg/min) and sufentanil (0.1 f.1glkglmin). Two groups were constituted with differem ventilatory methods, namely: GD-V volume-controlled ventilation, and GD-P pressurecontrolled ventilation. The animais were maintained in Trendelenburg position at 3iJD aftd underwent increasing PEEP (O, 5 and 10 cmH20). Data from each group was analised statistically through an analysis of variance, which was followed by a post-hoc Tukey-Kramer test To compare groups a paired T test was used. For aD analises, p<O.05 was considered to be significant. In the dogs that underwent pressure-controlled ventilation, significant changes were documented for Vt, Ppico, Pplat, Vd alv, IS, PAPm, PCPm. 1002. and IVÜ2. as PEEPs changed. In the dogs that underwent volumecontrolled ventilation, changes were seen in Ppico, Pplat, Vd alv and FC. When groups were compared, significant differences were detected in Vd alv, FC, PVC, PCPm, CV02, IV02 . and T e02. Increasing PEEPs were concluded to cause minimal changes in the blood gases, and in the hemodynamic and ventilatory parameters. Also, both ventilatory methods were shown to be reliable in maintaining respiratory and cardiovascular stability under the proposed experimental conditions.

Made available in DSpace on 2014-06-11T19:31:08Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-06-21Bitstream added on 2014-06-13T19:01:28Z : No. of bitstreams: 1 barbosa_vf_dr_jabo.pdf: 857896 bytes, checksum: be55354f43cf593758c89ed8d7f0452f (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Avaliaram-se os efeitos respiratórios, hemogasométricos e cardiovasculares do fornecimento de diferentes frações inspiradas de oxigênio (FiO2) em coelhos submetidos ao pneumoperitônio e mantidos em cefalodeclive (“Trendelenburg a 30°). Foram utilizados oito coelhos adultos em cada grupo, os quais foram pré-medicados com acepromazina (0,5 mg/kg) e submetidos a anestesia com propofol (10 mg/kg, seguido de infusão contínua de 1,2 mg/kg/min) e rocurônio (0,6 mg/kg bolus e infusão contínua de 0,6 mg/kg/h), sendo que, cada procedimento anestésico foi diferenciados pela FiO2 fornecida ao paciente, permitindo formar os seguintes grupos: G40 (FiO2 = 0,4), G60 (FiO2 = 0,6) e G100 (FiO2 = 1,0). Os parâmetros foram mensurados uma hora após a indução anestésica (M0) e a cada 20 minutos, durante um período de 100 minutos (M20 a M100). Os animais foram mantidos em ventilação controlada a tempo, e receberam PEEP de 2 cmH2O em M80 e M100. Os dados foram submetidos à Análise de Perfil (p<0,05). A comparação das diferentes frações inspiradas foi caracterizada por aumento da PAO2, PaO2, PvO2 e AaDO2 e redução da relação PaO2/FiO2 quanto mais altas foram as FiO2. Nos grupos tratados com maiores e menores frações inspiradas constatou-se alteração da SaO2, PvCO2 e SvO2 . Conclui-se que as diferentes FiO2 não alteram as variáveis hemodinâmicas e que o fornecimento de oxigênio a 40% é o mais indicado por melhor manter as trocas gasosas e a estabilidade dos parâmetros ventilatórios. A inclusão de PEEP promoveu discretas alterações hemodinâmicas e ventilatórias, e quando associada a elevadas FiO2, resultou em incremento da oxigenação arterial e prejuízos na eliminação de dióxido de carbono / The effects of several inspired oxygen fractions (FiO2) on the blood gases, respiratory and cardiovascular parameters were evaluated in rabbits undergoing pneumoperitoneum under head-down tilt position (“Trendelenburg” position at 30°). Eight adult rabbits were used in each group. The animals were premedicated with acepromazine (0.5 mg/kg) and, thereafter underwent general anesthesia with propofol (10 mg//kg, followed by continuous infusion of 1.2 mg/kg/min) and rocuronium (0.6 mg/kg, followed by continuous infusion of 0.6 mg/kg/h). The patients were distributed into three groups according to the FiO2 regimen during general anesthesia: G40 (FiO2 = 0,4), G60 (FiO2 = 0,6) and G100 (FiO2 = 1,0). The first data sampling (M0) was carried out one hour after anesthesia induction (M0). Additional recordings were performed every 20-minute intervals for 100 minutes (M20 to M100). The animals were maintained in time controlled ventilation. Additionally, PEEP (2 cmH2O) was performed in M80 and M100. Numeric data were submitted to Profile Analysis (p<0.05). The comparison among the different FiO2 regimen was based on the variation of the values of PAO2, PaO2, PvO2 and AaDO2, which increased in patients submitted to higher FiO2 regimen. Significant changes in SaO2, PvCO2 e SvO2 were documented in the patients belonging to the groups that underwent higher and lower FiO2. Results showed that FiO2 does not impair hemodynamic parameters and 40% oxygen is the most suitable for better maintenance of gas exchange and stability of ventilatory parameters. The PEEP inclusion promoted discrete hemodynamic and ventilatory changes and when combined with high FiO2 it resulted in increased blood oxygenation and damage on the elimination of carbon dioxide