Spelling suggestions: "subject:"acute respiratory distress syndrome"" "subject:"scute respiratory distress syndrome""
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The role of platelets in acute inflammationPeters, Mark John January 2001 (has links)
No description available.
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Oxidative damage to extracellular proteins and lipids during acute lung injuryQuinlan, Gregory John January 1995 (has links)
No description available.
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Mediators and mechanisms of persistent pulmonary neutrophilia in acute lung injuryAggarwal, Anjna January 2002 (has links)
No description available.
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The pathogenesis of lung injury following cardiothoracic surgeryJordan, Simon James January 2001 (has links)
No description available.
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Rationale for surfactant replacement therapy in patients with acute lung injuryBaker, Cathy Sue January 1997 (has links)
No description available.
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The role of vascular endothelial growth factor (VEGF) in repair and recovery from acute respiratory distress syndrome (ARDS)Medford, Andrew R. L. January 2007 (has links)
Acute Respiratory Distress Syndrome (ARDS) is the most extreme form of acute lung injury and continues to have a significant morbidity and mortality. Unfortunately, the mechanisms involved in the recovery and repair of the lung following ARDS remain poorly understood. An understanding of these is pivotal to improving outcome from acute lung injury. Several observational studies have suggested a potential relationship between Vascular Endothelial Growth Factor (VEGF) in the lung and the development/outcome of ARDS. In this thesis, three potential mechanisms underlying these observations have been explored: 1. What is the anatomical distribution of VEGF receptor and isoform expression in normal and ARDS lung? How does this change at early and later time points following acute lung injury? 2. Are human type 2 alveolar epithelial (ATII) cells a source of and target for VEGF? How does exposure to a pro-inflammatory milieu modify their expression of VEGF isoforms and receptors? 3. Is there a relationship between a functional VEGF polymorphism and susceptibility to developing and severity of ARDS? I have demonstrated VEGF receptor expression on both sides of the alveolarcapillary membrane with upregulation in later ARDS. All three principal isoforms (VEGF121, VEGF165 and VEGF189) are expressed in normal human lung with uniform downregulation of all three in early ARDS, which normalises with increasing time following injury. I have not found any evidence of VEGF isoform switching. I have also demonstrated human ATII cells are both a significant cellular source of and a target for VEGF (via VEGF receptor expression) confirming autocrine VEGF activity in the lung. VEGF is an ATII cell survival factor. ATII cells differentially respond to pro-inflammatory stimuli by increasing VEGF isoform but not receptor expression, which may serve as a regulatory control mechanism. Finally, I have demonstrated the VEGF 936 T allele increases susceptibility to and the severity of lung injury. The T allele is associated with an increase in plasma VEGF level in ARDS patients but intra-alveolar levels are unaffected.
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Einfluss einer Statin-Therapie auf das Überleben von Patienten mit Sepsis-assoziiertem ARDS / Impact of statin therapy on mortality in patients with sepsis-associated acute respiratory distress syndromeSteinau, Maximilian 29 June 2017 (has links)
No description available.
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Resolving uncertainty in acute respiratory illness using optical molecular imagingCraven, Thomas Henry John January 2017 (has links)
Ventilator associated pneumonia (VAP) and acute respiratory distress syndrome (ARDS) are two respiratory conditions unique to mechanically ventilated patients. The diagnosis of these conditions, and therefore any subsequent treatment, are befuddled by uncertainty. VAP rates vary considerably according to the diagnostic or surveillance criteria used. The pathogenesis of ARDS is well understood but when the internationally agreed consensus criteria are employed, the histological hallmarks are absent about half the time, indicating a disconnection between the clinical diagnosis and what is known about the biology of this condition. It is argued that tests of biological function should be considered in addition to clinical characteristics in order to improve the utility of diagnosis. Given that the pathological sequelae of both VAP and ARDS are driven by an over exuberant host neutrophil response, the activated neutrophil was selected as a potential biological imaging target. Optical molecular imaging uses visible and near visible wavelengths from the electromagnetic spectrum to derive or visualize information based on the optical properties of the target tissue. Optical wavelengths are safe and cheap to work with, producing much higher resolution images than those relying on x-rays or gamma radiation. The imaging modality can be coupled with exogenously applied chemistry to identify specific biological targets or processes. The hypothesis that optical molecular imaging could be used to detect activated neutrophils in real time in the alveolar region of patients was tested. A bespoke optical molecular imaging agent called Neutrophil Activation Probe (NAP), designed in-house, was used to test the hypothesis. NAP is a dendrimeric compound delivered to the alveolar region of a patient in microdoses (≤100 micrograms), becoming fluorescent only on contact with activated neutrophils, and can be detected by optical endomicroscopy. Both the imaging agent and the endomicroscope are delivered to the distal lung via routine bronchoscopy. The agent was tested extensively in the laboratory to demonstrate function, specificity, and safety. Ex vivo testing took place using human and ovine lungs. A regulated dose escalation Phase I clinical trial of investigational medicinal product (CTIMP) in healthy volunteers, patients with bronchiectasis, and mechanically ventilated patients with a pulmonary infiltrate on chest radiography (NCT01532024) was designed and conducted. The aim of the Phase I study was to demonstrate the safety of the technique and to confirm proof of concept. In order to support the requirement for a technique that interrogates alveolar neutrophils two supplementary clinical studies were performed. Firstly, two VAP surveillance techniques (CDC surveillance and HELICS European VAP surveillance) were compared with clinically diagnosed VAP across consecutive admissions in two large tertiary centres for one year. Secondly, the utility of circulating neutrophils to permit discrimination between acute respiratory illnesses was examined. Blood samples from mechanically ventilated patients with and without ARDS underwent flow cytometric assessment using eight clusters of differentiation and internal markers of activation to determine neutrophil phenotype. All clinical studies received the appropriate regulatory, ethical, and/or Caldicott guardian approval prior to commencement. NAP became fluorescent only in the presence of three processes specific to neutrophil activation: active pinocytosis, progressive alkalinization of the phagolysosome, and the activity of human neutrophil elastase. High optical signal was detected following the application of NAP in the alveolar regions of explanted lungs from patients with cystic fibrosis, known to be rich in activated neutrophils. Using an ex vivo ovine lung ventilation and perfusion model optical signal was demonstrated following segmental lung injury. The safety and specificity of the technique in a small cohort of healthy volunteers and mechanically ventilated patients was demonstrated. The technique was tested on a small cohort of patients with bronchiectasis, which provided the first opportunity to obtain broncho-alveolar lavage samples for laboratory correlation. Fluorescent signal was shown in the lavaged neutrophils, labeling that could only have taken place in the alveolar region. The supportive clinical studies found the concordance between actual VAP events was virtually zero even though the reported VAP rates were similar. Furthermore, the rate at which clinicians initiate antibiotics for VAP was approximately five times higher than either surveillance VAP rate. The study of circulating neutrophils from the blood of healthy volunteers and mechanically ventilated patients with and without ARDS indicated circulating neutrophil activation phenotype was not capable of discriminating between clinically diagnosed ARDS and other acute respiratory illnesses. In summary, an ambitious programme of work was completed to develop and support an optical molecular imaging technique that meets the rigorous requirements for human application and can be applied at the bedside to yield immediate visual results. The spatiotemporal relationship of neutrophil activation in real time both in the laboratory and in volunteers and patients was visualized. The visualization of neutrophil activation at such a resolution has never been achieved before in humans, healthy or unhealthy. The Phase I study was not powered to determine utility but recruitment has begun to a Phase II CTIMP (NCT02804854) to investigate the utility, accuracy, and precision of the imaging technique in a large cohort of mechanically ventilated patients. Ultimately, it is proposed that the technique will facilitate diagnosis, stratify patients for treatment and monitor treatment response using this technique.
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Citoadesão na imunopatogênese da síndrome do desconforto respiratório agudo associado à malária. / Cytoadhesion in the immunopathogenesis of malaria-associated acute respiratory distress syndrome.Ortolan, Luana dos Santos 13 December 2017 (has links)
Infecções por Plasmodium sp. podem levar a complicações pulmonares denominadas síndrome do desconforto respiratório agudo (SDRA). O modelo experimental, que utiliza o parasita murino Plasmodium berghei ANKA (PbA) e camundongos da linhagem DBA/2, é empregado no estudo de mediadores imunológicos e fatores que propiciam o estabelecimento das lesões pulmonares. Camundongos DBA/2 infectados com PbA foram classificados de acordo com a causa de morte como SDRA ou HP (hiperparasitemia). In vivo foi analisada a distribuição do parasita e os pulmões foram coletados para análise da capacidade respiratória, histopatologia, permeabilidade vascular, qRT-PCR e imunoistoquímica e efeito anti-inflamatório (Dexametasona - Dexa). In vitro, células endoteliais pulmonares foram submetidas a diversos estímulos. Verificamos que há acúmulo de PbA nos pulmões de DBA/2 com SDRA e que TNF e IFN-γ aumentam a citoadesão, expressão de ICAM-1, VCAM-1 e EPCR. A inibição de TNF diminui a adesão e dexa protege os animais através da diminuição de fatores inflamatórios, EPCR e inibição da abertura de junções interendoteliais. A intervenção da citoaderência e da permeabilidade vascular com o uso de corticosteróides, pode ser um importante alvo para o tratamento e a prevenção da SDRA. / Infections by Plasmodium sp. can lead to pulmonary complications called acute respiratory distress syndrome (ARDS). The experimental model, using the murine parasite Plasmodium berghei ANKA (PbA) and DBA/2 mice, is used no study of immunological mediators and factors that allow the establishment of lung lesions. DBA / 2 mice infected with PbA were classified according to cause of death as ARDS or HP (hyperparasitism). In vivo the parasite distribution was analyzed, and the lungs were collected for respiratory capacity analysis, histopathology, vascular permeability, qRT-PCR, immunohistochemistry and anti-inflammatory effect (Dexamethasone-Dexa). In vitro, pulmonary endothelial cells were submitted to various stimuli. We found that there is accumulation of PbA in the lungs of DBA/2 with ARDS and TNF and IFN-γ increase cytoadhesion, expression of ICAM-1, VCAM-1 and EPCR. Inhibition of TNF decreases adhesion and dexa protects animals by decreasing inflammatory factors, EPCR and inhibiting the opening of interendothelial junctions. The intervention of cytoadherence and vascular permeability with the use of corticosteroids may be an important target for the treatment and prevention of ARDS.
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Regulation of Innate Immune CellsMaharjan, Anu 05 September 2012 (has links)
Immune cells such as neutrophils and monocytes enter tissues after tissue damage and clear cell debris to allow repair cells such as fibroblasts to close the wound. Monocytes also differentiate into fibroblast-like cells called fibrocytes to mediate wound healing, similar to fibroblasts. However, in abnormal wound healing such as acute respiratory distress syndrome (ARDS) and fibrosing diseases, the accumulation of immune cells such as neutrophils or fibrocytes become detrimental to health. In ARDS, neutrophils accumulate in the lungs and causes additional damage by producing reactive oxygen species (ROS). In fibrosing diseases, increased fibrocyte differentiation is one of the causes that increase extracellular matrix deposition, which leads to severe scar tissue build up. Since there are no effective treatments for ARDS or fibrosing diseases, understanding the regulation of neutrophil activation or fibrocyte differentiation could be helpful to develop new effective therapies.
The Gomer lab has found several factors that either promote or inhibit fibrocyte differentiation. The pro-fibrotic cytokines such as IL-4 and IL-13 potentiate fibrocyte differentiation while the plasma protein serum amyloid P (SAP), crosslinked IgG, and the pro-inflammatory cytokines IFN-γ and IL-12 inhibit fibrocyte differentiation. In this thesis, I have now shown that additional factors such as toll-like receptor 2 (TLR2) agonists and low molecular weight hyaluronic acid (LMWHA) inhibit fibrocyte differentiation, while high molecular weight hyaluronic acid (HMWHA) potentiate fibrocyte differentiation.
The accumulation of neutrophils in the lungs is one of the major factors that debilitate the health of a patient in ARDS. Since neutrophils have Fc receptors, I examined the effect of SAP on neutrophil spreading, adherence, activation, and accumulation. SAP inhibits neutrophil spreading induced by cell debris and TNF-α induced adhesion, but SAP is unable to have any effect on classic neutrophil adhesion molecules or the production of hydrogen peroxide. SAP inhibits neutrophil accumulation in the lungs of bleomycin-injured mice. There is an exciting possibility of using SAP as a therapeutic agent to treat ARDS.
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