A5004819829- Immune Response and Inflammation
- Appendicitis Diagnosis and Management
- Sepsis Diagnosis and Treatment
- Cardiac, Anesthesia and Surgical Outcomes
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- Organ Transplantation Techniques and Outcomes
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Ion Transport and Channel Regulation
- Cell Adhesion Molecules Research
- ATP Synthase and ATPases Research
- Abdominal Surgery and Complications
- Cardiac Ischemia and Reperfusion
- Bacterial Identification and Susceptibility Testing
- Trauma and Emergency Care Studies
- Ion channel regulation and function
- Lipid Membrane Structure and Behavior
- Colorectal Cancer Surgical Treatments
- Gallbladder and Bile Duct Disorders
- Neonatal Respiratory Health Research
- Aortic aneurysm repair treatments
- Platelet Disorders and Treatments
- Cell death mechanisms and regulation
- Cardiac Arrest and Resuscitation
- Liver Disease and Transplantation
- Blood Coagulation and Thrombosis Mechanisms
University of Toronto
2016-2025
St. Michael's Hospital
2016-2025
St Michael’s Hospital
2006-2025
Unity Health Toronto
2021-2025
Toronto General Hospital
1996-2024
Brigham and Women's Hospital
2024
Ontario Genomics
2024
Toronto Public Health
2004-2023
Li Ka Shing Foundation
2022
University Hospital Leipzig
2022
The successful treatment of intraabdominal infection requires a combination anatomical source control and antibiotics. appropriate duration antimicrobial therapy remains unclear.We randomly assigned 518 patients with complicated adequate to receive antibiotics until 2 days after the resolution fever, leukocytosis, ileus, maximum 10 (control group), or fixed course (experimental group) for 4±1 calendar days. primary outcome was composite surgical-site infection, recurrent death within 30...
Pre–B cell colony-enhancing factor (PBEF) is a highly conserved 52-kDa protein, originally identified as growth for early stage B cells. We show here that PBEF also upregulated in neutrophils by IL-1β and functions novel inhibitor of apoptosis response to variety inflammatory stimuli. Induction occurs 5–10 hours after LPS exposure. Prevention translation with an antisense oligonucleotide completely abrogates the inhibitory effects LPS, IL-1, GM-CSF, IL-8, TNF-α on neutrophil apoptosis....
Background Thoracic endovascular aortic repair (TEVAR) and complex aneurysm (EVAR) are procedures that carry a significant risk of complications. While prediction tools can aid in clinical decision making, they remain limited. We developed machine learning algorithms to predict outcomes following TEVAR EVAR. Methods The Vascular Quality Initiative database was used identify patients who underwent elective EVAR for noninfrarenal aneurysms between 2012 2023. extracted 172 features from the...
Abstract Ribavirin, a synthetic guanosine analogue, possesses broad spectrum of activity against DNA and RNA viruses. It has been previously shown to attenuate the course fulminant hepatitis in mice produced by murine virus strain 3. We therefore studied effects ribavirin on 3 replication, macrophage production proinflammatory mediators including TNF, IL-1, procoagulant (PCA), fgl2 prothrombinase; Th1/Th2 cytokine production. Although had inhibitory viral replication (<1 log), even at...
New research suggests that, during tubulointerstitial fibrosis, α-smooth muscle actin (SMA)-expressing mesenchymal cells might derive from the tubular epithelium via epithelial-mesenchymal transition (EMT). Although transforming growth factor-β 1 (TGF-β ) plays a key role in EMT, underlying cellular mechanisms are not well understood. Here we characterized TGF-β -induced EMT LLC-PK and examined of small GTPase Rho its effector, kinase, (ROK) ensuing cytoskeletal remodeling SMA expression....
Hypertonic resuscitation fluids are known to be effective in restoring circulating volume the hypovolemic trauma patient. Previous studies have suggested that hypertonicity might exert effects on immune cells leading an altered host response. The present evaluated effect of hypertonic development lung injury a hemorrhagic shock model which antecedent primes for increased neutrophil sequestration response intratracheal LPS. Resuscitation with saline significantly reduced albumin leak,...
The mechanism underlying phagosomal acidification was studied in thioglycolate-elicited murine macrophages. pH of the compartment (pHp) measured fluorimetrically macrophage suspensions following ingestion fluorescein isothiocyanate-labeled Staphylococcus aureus. At 37 degrees C, pHp decreased rapidly, reaching a steady state value 5.8-6.1, while cytoplasmic remained near neutrality, 7.1. phagosome to cytosol gradient could be collapsed by addition nigericin, monensin, or weak bases....
The resolution of neutrophil (PMN)-mediated inflammation occurs through the apoptosis, or programmed cell death, neutrophil. PMN apoptosis is inhibited by a variety inflammatory stimuli; moreover, from critically ill septic patients show profoundly delayed rates in vitro. Since effected activity intracellular cysteine proteases (caspases), we evaluated caspase expression and neutrophils compared them with resting lipopolysaccharide-activated healthy volunteers.Prospective observational...
Abstract Termination of a neutrophil-mediated inflammatory response occurs through the activation endogenous cell death program, apoptosis. Neutrophil apoptosis is constitutive process that can be accelerated or delayed by signals from microenvironment. Since cellular localization at site an challenge critical first step in neutrophil response, we investigated effects transendothelial transmigration on kinetic expression Neutrophils isolated rat lung following with LPS demonstrated...
The mechanisms underlying the survival of intracellular parasites such as mycobacteria in host macrophages remain poorly understood. In mice, mutations at Nramp1 gene (for natural resistance-associated macrophage protein), cause susceptibility to mycobacterial infections. encodes an integral membrane protein that is recruited phagosome infected macrophages. this study, we used microfluorescence ratio imaging from wild-type and mutant mice analyze effect loss function on properties phagosomes...
To investigate the potential immunologic and anti-inflammatory effects of hypertonic saline plus dextran (HSD) in hemorrhagic trauma patients.Unbalanced inflammation triggered by shock has been linked to multiorgan dysfunction (MOD) death. In animal cellular models, HSD alters inflammatory response shock, attenuating MOD improving outcome. It remains untested whether similar humans.A single 250-mL dose either (7.5% NaCl, 6% dextran-70) or placebo (0.9% NaCl) was administered adult blunt...
Abstract Recent studies have suggested that hemorrhagic shock followed by resuscitation renders patients more susceptible to lung injury priming for an exaggerated response a second stimulus, the so-called “two-hit” hypothesis. We investigated role of C-X-C chemokines in mediating augmented inflammation LPS following resuscitated shock. In rodent model, animals exposed antecedent exhibited enhanced neutrophil sequestration and transpulmonary albumin flux intratracheal LPS. This effect...
Objective In a randomized, double-blind, multicenter trial, ciprofloxacin/metronidazole was compared with imipenem/cilastatin for treatment of complicated intra-abdominal infections. A secondary objective to demonstrate the ability switch responding patients from intravenous (IV) oral (PO) therapy. Summary Background Data Intra-abdominal infections result in substantial morbidity, mortality, and cost. Antimicrobial therapy often includes 7-to 10-day course. The use antimicrobials is recent...
Oxidative stress generated by ischemia/reperfusion is known to prime inflammatory cells for increased responsiveness subsequent stimuli, such as lipopolysaccharide (LPS). The mechanism(s) underlying this effect remains poorly elucidated. These studies show that alveolar macrophages recovered from rodents subjected hemorrhagic shock/resuscitation expressed surface levels of Toll-like receptor 4 (TLR4), an inhibited adding the antioxidant N-acetylcysteine resuscitation fluid. Consistent with a...
An Na(+)- and HCO3(-)-independent mechanism of cytoplasmic pH (pHi) recovery was previously demonstrated in acid-loaded macrophages (Swallow, C. J., Grinstein, S., Rotstein, O. D. (1988) J. Biol. Chem. 263, 19558-19563). Acid extrusion found to be ATP-dependent sensitive N-ethylmaleimide N,N'-dicyclohexylcarbodiimide, suggesting involvement an H(+)-pumping ATPase. In this report, the properties mode activation putative pump were studied detail. cells, pHi recovery, measured using a...
Epithelial-mesenchymal-myofibroblast transition (EMT), a key feature in organ fibrosis, is regulated by the state of intercellular contacts. Our recent studies have shown that an initial injury cell-cell junctions prerequisite for transforming growth factor-beta1 (TGF-beta1)-induced transdifferentiation kidney tubular cells into alpha-smooth muscle actin (SMA)-expressing myofibroblasts. Here we analyzed underlying contact-dependent mechanisms. Ca(2+) removal-induced disruption provoked...
In Brief Objective: To compare the operative outcomes of early and delayed cholecystectomy for acute cholecystitis. Background: Randomized trials comparing to cholecystitis have limited contemporary external validity. Furthermore, no study date has been large enough assess impact timing on frequency serious rare complications including bile duct injury death. Methods: This is a population-based retrospective cohort patients emergently admitted hospital with managed over period April 1, 2004,...
Background: Enhanced recovery after surgery (ERAS) programs incorporate evidence-based practices to minimize perioperative stress, gut dysfunction, and promote early recovery. However, it is unknown which components have the greatest impact. Objective: This study aims determine of ERAS largest impact on for patients undergoing colorectal surgery. Methods: An iERAS program was implemented in 15 academic hospitals. Data were collected prospectively. Patients considered compliant if >75%...