John Laffey | University of Toronto (original) (raw)

Papers by John Laffey

Intensive care medicine experimental, 2016

Hypercapnia, with its associated acidosis (HCA), is a consequence of respiratory failure and is a... more Hypercapnia, with its associated acidosis (HCA), is a consequence of respiratory failure and is also seen in critically ill patients managed with conventional "protective" ventilation strategies. Nuclear factor kappa-B (NF-κB), a pivotal transcription factor, is activated in the setting of injury and repair and is central to innate immunity. We have previously established that HCA protects against ventilation-induced lung injury in vivo, potentially via a mechanism involving inhibition of NF-κB signaling. We wished to further elucidate the role and mechanism of HCA-mediated inhibition of the NF-κB pathway in attenuating stretch-induced injury in vitro. Initial experiments examined the effect of HCA on cyclic stretch-induced inflammation and injury in human bronchial and alveolar epithelial cells. Subsequent experiments examined the role of the canonical NF-κB pathway in mediating stretch-induced injury and the mechanism of action of HCA. The contribution of pH versus CO2 i...

F1000 - Post-publication peer review of the biomedical literature, 2011

F1000 - Post-publication peer review of the biomedical literature, 2000

Abstract Presented here is a Dynamic Bayesian Network approach to predict glycaemia levels in int... more Abstract Presented here is a Dynamic Bayesian Network approach to predict glycaemia levels in intensive care patients. Hyperglycaemia in the ICU is associated with increased morbidity and mortality. Patients are therefore administered intravenous insulin to prevent hyperglycaemia. By providing physicians with more accurate real-time estimates of glycaemia levels, the optimal insulin dosage for a given patient can be determined by modelling the most likely effects of planned dosages.

Lecture Notes in Computer Science, 2011

Journal of Critical Care, 2012

Journal of Critical Care, Volume 27, Issue 3, Pages e1-e2, June 2012, Authors:Catherine G. Enrigh... more Journal of Critical Care, Volume 27, Issue 3, Pages e1-e2, June 2012, Authors:Catherine G. Enright; Michael G. Madden; Niall Madden; John G. Laffey.

European Journal of Anaesthesiology, 2002

Ischaemia reperfusion injury is a common and important phenomenon that occurs predictably in pati... more Ischaemia reperfusion injury is a common and important phenomenon that occurs predictably in patients undergoing such procedures as cardiopulmonary bypass, thrombolysis, surgery under tourniquet, organ transplantation or embolectomy. Oxidative stress and the resulting lipid peroxidation play a major role in reperfusion injury. Membrane and cellular dysfunction result and, subsequently, organ injury or failure may ensue. Traditional methods of quantifying ischaemia reperfusion injury, including measurement of malondialdehyde, lack specificity and sensitivity. It was reported in 1990 that isoprostanes, a series of prostaglandin-like compounds, are produced by the free radical-catalyzed peroxidation of arachidonic acid. Measurement of the isoprostane concentration in urine or plasma provides the most reliable, non-invasive method currently available to assess oxidative stress in vivo. Serial measurement of isoprostanes in biological fluids has enhanced our understanding of the mechanisms underlying ischaemia reperfusion injury itself and its role in certain diseases. Furthermore, measurement of the isoprostane concentration provides a means to assess the effects of prophylactic and therapeutic interventions. In the future, the development of rapid, simple assays for isoprostanes offers the potential to assess prognosis during and after ischaemia reperfusion events.

College of Engineering & Informatics

Presented here is a Dynamic Bayesian Network approach to predict glycaemia levels in intensive ca... more Presented here is a Dynamic Bayesian Network approach to predict glycaemia levels in intensive care patients. Hyperglycaemia in the ICU is associated with increased morbidity and mortality. Patients are therefore administered intravenous insulin to prevent hyperglycaemia. By providing physicians with more accurate real-time estimates of glycaemia levels, the optimal insulin dosage for a given patient can be determined by modelling the most likely effects of planned dosages.

Anaesthesia, 2008

Page 1. Correspondence Outreach critical care is not the solution I read with interest the editor... more Page 1. Correspondence Outreach critical care is not the solution I read with interest the editorial on the Acute Pain Service as a model for outreach critical care (Counsel. Anaes-thesia 2001; 56: 925±6). In our hospital, the Acute ...

A66. MECHANISMS OF ACUTE LUNG INJURY FROM CELLS TO ANIMAL MODELS, 2011

Page 1. / Thematic Poster Session / Sunday, May A66 MECHANISMS OF ACUTE LUNG INJURY FROM CELLS TO... more Page 1. / Thematic Poster Session / Sunday, May A66 MECHANISMS OF ACUTE LUNG INJURY FROM CELLS TO ANIMAL MODELS 15/8:15 AM-4:30 PM / Area F, Hall B (Upper Level), Colorado Convention Center Hypercapnic ...

American journal of respiratory and critical care medicine, Jan 6, 2015

Lung protective ventilatory strategies have been widely used in patients with acute respiratory d... more Lung protective ventilatory strategies have been widely used in patients with acute respiratory distress syndrome (ARDS), but ARDS mortality rate remains unacceptably high and there is no proven pharmacological therapy. Mechanical ventilation can induce oxidative stress and lung fibrosis, which may contribute to high dependency on ventilator support and increased ARDS mortality. We hypothesized that the novel cytokine, midkine (MK), that can be upregulated in oxidative stress, plays a key role in the pathogenesis of ARDS-associated lung fibrosis. Blood samples were collected from 17 ARDS patients and 10 healthy donors. Human lung epithelial cells were challenged with HCl followed by mechanical stretch for 72 h. Wild type and MK gene deficient (MK-/-) mice received two-hit injury of acid aspiration and mechanical ventilation, and were monitored for 14 days. Plasma concentrations of MK were higher in ARDS patients than in healthy volunteers. Exposure to mechanical stretch of lung epit...