1,721,005 research outputs found
Microvascular perfusion and tissue oxygenation during critical illness
Gittata cardiaca, livelli di emoglobina e di ossigeno nel sangue arterioso (SaO2 e PaO2) sono generalmente considerati come i principali determinanti della disponibilità di O2 sistemica. Tuttavia, negli stati critici l’ipossia tissutale può persistere nonostante la normalizzazione dei parametri emodinamici e dell’ossigenazione sistemica, a causa di una compromissione della perfusione microcircolatoria. Negli stati di infiammazione sistemica come la sepsi, lo stress ossidativo e i mediatori infiammatori possono portare a danno endoteliale e disfunzione microvascolare, che possono essere a loro volta responsabili di ipoperfusione e insufficienza d’organo. E’ quindi importante monitorizzare il microcircolo e la sua risposta alle terapie. Negli studi inclusi in questa tesi sono state utilizzate due tecniche non invasive che permettono di valutare la perfusione microcircolatoria e l’ossigenazione tissutale: la tecnica di video-microscopia sublinguale Sidestream Dark Field (SDF) e la Near Infrared Spectroscopy (NIRS) a livello del muscolo scheletrico (eminenza tenar) con test di occlusione vascolare. Questa tesi conferma il valore prognostico del microcircolo nei pazienti critici. Un’alterata capacità del tessuto di estrarre O2 in corso di ischemia e una riduzione della reattività microvascolare nella fase di riperfusione si sono rivelate in grado di predire la mortalità in una popolazione eterogenea di 89 pazienti ricoverati in Terapia Intensiva. Utilizzando la tecnica SDF, abbiamo trovato significative alterazioni del glicocalice endoteliale a livello del microcircolo sublinguale nei pazienti critici in confronto a volontari sani, e tali alterazioni sono apparse più pronunciate in presenza di sepsi. Il monitoraggio del microcircolo può rappresentare un’utile guida terapeutica. In pazienti settici la trasfusione di emazie leucodeplete ha prodotto un effetto più favorevole sul flusso convettivo a livello microcircolatorio rispetto alle emazie non leucodeplete. La trasfusione di emazie vecchie (tempo di conservazione >15 giorni) si è associata ad un aumento
dell’emoglobina libera plasmatica, la quale può aver condotto ad una riduzione della densità microvascolare per la sua attività di scavenger nei confronti dell’ossido nitrico. Dal momento che la perfusione e l’ossigenazione tissutali dipendono principalmente dalla funzione microcircolatoria, è importante tenere in considerazione gli effetti che le terapie comunemente applicate (ad es. l’ossigenoterapia) possono avere sul microcircolo. Una meta-analisi di studi osservazionali ha mostrato un’associazione tra l’esposizione ad iperossia e una più alta mortalità in diverse categorie di pazienti critici. In uno studio prospettico osservazionale su 40 pazienti, l’iperossia ha prodotto una precoce riduzione della densità microvascolare (indice di vasocostrizione), seguita tuttavia da normalizzazione al ritorno ai livelli inspiratori di ossigeno basali. Un’esposizione di 2 ore all’iperossia ha causato un aumento dei radicali liberi, inducendo un aumento della produzione di glutatione: questo meccanismo può essere stato in grado di stimolare la produzione di eritropoietina, secondo la teoria del “normobaric oxygen paradox”. Infine, questa tesi ha messo in luce le difficoltà tecniche relative al monitoraggio del microcircolo sublinguale tramite tecnica SDF e ha sottolineato l’importanza della qualità delle immagini raccolte al fine di ottenere una valutazione del microcircolo attendibile.Cardiac output, haemoglobin levels and arterial oxygen levels (SaO2 and PaO2) are generally considered as the main determinants of systemic O2 delivery. However, during critical illness tissue hypoxia may persist despite normalization of systemic haemodynamics and oxygenation, due to an impairment in microvascular perfusion. During systemic inflammation such as sepsis, endothelial damage and microcirculatory dysfunction may occur due to oxidative stress and inflammatory mediators, leading to hypoperfusion and organ failure. It is thus important to monitor the microcirculation and its response to interventions. In the studies included in this thesis, two non-invasive techniques were applied to evaluate microvascular perfusion and tissue oxygenation: sublingual sidestream dark field (SDF) videomicroscopy and near infrared spectroscopy (NIRS) on the skeletal muscle (thenar eminence) with a vascular occlusion test. This thesis confirms the prognostic value of the microcirculation during critical states. Alterations in tissue O2 extraction capacity during an ischemic challenge and a reduced microvascular reactivity during reperfusion were able to predict mortality in a heterogeneous population of 89 critically ill patients. Using SDF videomicroscopy, we found significant alterations in the sublingual microvascular glycocalyx in critically ill patients as compared to healthy volunteers, which were more pronounced in presence of sepsis. Microvascular monitoring may be a useful tool to guide therapy. In septic patients, the transfusion of leukodepleted red blood cells (RBCs) seemed to produce a more favourable effect on microvascular convective flow in comparison to non-leukodepleted RBCs. The transfusion of old RBCs (storage >15 days) was associated with an increase in plasma free haemoglobin, possibly leading to a reduction in microvascular density due to a nitric oxide-scavenger activity. Since tissue perfusion and oxygenation mainly depend on microvascular function, it is important to
consider the microvascular effects of commonly applied interventions, such as O2 therapy. A meta-analysis of observational studies showed that exposure to arterial hyperoxia was associated with higher mortality in several subsets of critically ill patients. In a prospective observational study on 40 patients, hyperoxia induced an early reduction in microvascular density, suggesting a vasoconstrictive response, which however normalized upon returning to baseline levels of inspired O2. A 2-hour exposure to hyperoxia caused a rise in O2 free radicals, inducing an increased glutathione production: this mechanism may have been able to stimulate erythropoietin production, according to the “normobaric oxygen paradox”. Finally, this thesis highlighted the technical challenges of sublingual SDF monitoring and underlined the importance of microcirculatory image quality for a reliable evaluation of the microcirculation
Approach to Supporting Continuity of Usage in Location-Based Access Control
In location-based access control systems, the location of subjects is a relevant parameter in access control decisions. Those systems however fail in controlling the location of subjects along the period of use of the objects and this can lead to security breaches. To ensure a stronger protection of objects, a continuous control over the movement of subjectsis thus needed. To address this requirement, we have developed GEO-RBAC_C a location-based access control model supporting continuous usage control capabilities. In the paper,we first present the basic concepts of the model and then discuss how the continuous control can be actually enforced
The role of cardiac dysfunction in multiorgan dysfunction
The aim of this review was to examine the main determinants of cardiac dysfunction in critically ill patients, as well as how a reduction in cardiac performance influences other organ function
Prolonged prone positioning in ARDS: No mortality benefit, no increased risk-But what about the reduced ICU staff workload?
Sidestream dark field videomicroscopy for in vivo evaluation of vascularization and perfusion of mammary tumors in HER-2/neu transgenic mice.
Angiogenesis plays a key role in tumor growth and formation of metastases. Angiogenesis inhibitors and anti-vascular agents may prove useful in the treatment of breast cancer. A comprehensive characterization of the vasculature and perfusion of mammary tumors is a prerequisite for developing new specific drugs. We applied sidestream dark field videomicroscopy to evaluate in vivo the vascular network of spontaneous mammary tumors in HER-2/neu transgenic mice. The tumor masses showed higher vessel density as compared to the healthy mammary gland (total vessel density of 16.8 [13.4-20.5] mm/mm(2) versus 9.1 [8.1-10.9] mm/mm(2) , p<0.001). Tumor vessel density was reduced in mice treated with the anti-angiogenesis agent berberine (total vessel density of 12.1 [10.6-13.1] mm/mm(2) ). SDF imaging is a versatile technique that may be useful for understanding the role of angiogenesis in the progression of breast cancer and its relationship with outcome. It may represent a valuable tool for a dynamic monitoring of the effects of new anti-angiogenesis therapies. This article is protected by copyright. All rights reserved
Oxygen in the critically ill: friend or foe?
To examine the potential harmful effects of hyperoxia and summarize the results of most recent clinical studies evaluating oxygen therapy in critically ill patients
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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