Biomedical subjects

A J Seely

Publications and source records attributed to A J Seely.

6 recordsLinked to original sources

PubMed2001

Hemorrhagic shock resuscitation with a low molecular weight starch reduces neutrophil-endothelial interactions and vessel leakage in vivo.

BACKGROUND: The polymorphonuclear neutrophil (PMN) has been implicated in the pathogenesis of endothelial cell (EC) damage and organ injury following hemorrhagic shock. Pentastarch (PTS), a low substituted medium molecular weight (MW) colloid, improves hemodynamics in hypovolemic shock and cardiac surgery. No data exist comparing the immunomodulation of PTS and Ringer's lactate (RL) on the activation of PMN in hemorrhagic shock in vivo. METHODS: Using an in vivo murine hemorrhagic shock model (blood withdrawal to maintain 50 mmHg x 45 min), circulating PMN were observed every 15 minutes using intravital microscopy on cremaster muscle. EC-PMN interactions (videorecorded and subsequently analyzed blindly), vessel leakage (live epifluorescence after injection of 50 mg/kg fluorescent albumin) and PMN expression of L-selectin (immunofluorescent monoclonal antibodies and flow cytometry) were evaluated in three resuscitation groups: PTS (7.14 mL/kg 10% pentastarch/0.9% NaCl + shed blood, n = 13), RL (RL [2 x shed blood volume] + shed blood, n = 13) and SHAM (0 hemorrhage, 0 resuscitation, n = 9). Significance was evaluated by ANOVA with Bonferroni correction. RESULTS: PMN rolling was significantly diminished in PTS and SHAM as compared to RL animals at all time points. Similar differences were found in PMN adherence to EC at most time points onwards from 15 minutes following resuscitation. In vivo vessel permeability was lowest in SHAM and PTS animals (mean 0.274 +/- 0.07 and 0.356 +/- 0.15, respectively, p > 0.05) and highest in RL animals (0.667 +/- 0.09, p < 0.001 vs PTS or SHAM). PMN L-selectin expression tended to be higher in the RL group than either SHAM and PTS groups. There were no flow-mechanics differences between groups (vessel diameter, mean red cell velocity, shear stress, shear rate). CONCLUSIONS: 10% pentastarch reduces RL-associated EC-PMN interactions and vessel leakage following hemorrhagic shock. These results support the use of low MW starches to resuscitate hemorrhagic shock, potentially reducing PMN-mediated tissue injury.

Animals↗

PubMed2000

Decreased systemic polymorphonuclear neutrophil (PMN) rolling without increased PMN adhesion in peritonitis at remote sites.

BACKGROUND: Previous in vitro studies have demonstrated that the host response to intra-abdominal infection produces increased generalized polymorphonuclear neutrophil (PMN) adherence to vascular endothelial cells (ECs), which may lead to subsequent endothelial damage, leaky capillaries, and organ dysfunction. There are scant data to demonstrate this enhanced systemic PMN adherence in vivo or the influence of PMN rolling on PMN endothelial adherence. HYPOTHESIS: Systemic PMN adherence in the animal with sepsis is increased. DESIGN: In vivo murine model of a 2-front infection using intravital microscopy of the cremasteric muscle to quantify PMN-EC adherence in a septic response. SETTING: Basic science laboratory and animal surgical facility. PATIENTS OR OTHER PARTICIPANTS: One hundred CD1 male mice. INTERVENTIONS: Animals underwent cecal ligation and puncture peritonitis, cremasteric muscle Escherichia coli infection, both infections, or neither (controls). Eighteen hours later, the mice underwent exteriorization of the cremasteric muscle under an intravital microscope for measurement of PMN-EC interactions. Blood was then drawn for calculation of circulating PMN counts. MAIN OUTCOME MEASURES: Adherence of PMNs, PMN rolling flux, PMN rolling velocity, and circulating PMN counts. RESULTS: Circulatory mechanics did not differ between the groups. Unlike static in vitro systems, we could not detect an increase in PMN adherence after peritonitis with this dynamic in vivo model. A local (cremasteric) infection was associated with marked PMN adherence. Peritonitis was associated with reduced PMN adherence at a local infection site as well as reduced rolling adhesion and PMN rolling velocity. CONCLUSIONS: The data suggest that intra-abdominal infection does not increase remote PMN adherence, and may actually result in reduction of systemic adherence via modulation of PMN rolling.

Abdominal Muscles↗

PubMed2000

Polymorphonuclear neutrophil (PMN) recruitment in a 2-front murine injury model: triage of PMNs to competing stimuli of recruitment.

BACKGROUND: Intensive care unit patients as a group have the highest rate of nosocomial infections, such as pneumonia, urinary tract infections, and wound infections. The triage of polymorphonuclear neutrophils (PMNs) during an acute inflammatory response was investigated to determine if the severity of injury or infection contributes to PMN delivery. METHODS: A murine cecal ligation and puncture-induced peritonitis model with polyvinyl sponge discs were used to collect the PMNs in the abdomen (primary site) and in the subcutaneous tissue of the dorsum (remote site). Eighty CD1 male mice--20 in each of 4 groups--were assigned to the following: cecal ligation and puncture (CLP), sham laparotomy with cecal manipulation (CM), polyvinyl sponge placement in the abdomen and back only (SP), and sponge placement in the back alone (CON [control]). After 24 hours, the sponges were harvested, and the PMNs were collected and counted on a hemocytometer. RESULTS: These data, reported as mean PMN cells x 10(5) +/- SEM, demonstrated that back sponges contained significantly fewer PMNs in the CLP group (3.29 +/- 1.1) than in the CM group (7.77 +/- 1.61, P = .04), the SP group (8.69 +/- 1.67, P = .01), and the CON group (11.04 +/- 1.91, P < .001). CONCLUSIONS: These results demonstrate that PMN delivery to sites of secondary injury are inversely correlated to the severity of the primary injury or peritonitis.

Animals↗

PubMed2000

Multiple organ dysfunction syndrome: exploring the paradigm of complex nonlinear systems.

OBJECTIVES: The objectives of this article are to introduce and explore a novel paradigm based on complex nonlinear systems, and to evaluate its application to critical care research regarding the systemic host response and multiple organ dysfunction syndrome (MODS). DATA SOURCES: Published original work, review articles, scientific abstracts and books, as well as our personal files. STUDY SELECTION: Studies were selected for their relevance to the applications of nonlinear complex systems, to critical care medicine, and to the concepts presented. DATA EXTRACTION: We extracted all applicable data. DATA SYNTHESIS: Following a brief review of MODS, an introduction to complex nonlinear systems is presented, including clear concepts, definitions, and properties. By examining the multiple, nonlinear, interrelated, and variable interactions between the metabolic, neural, endocrine, immune, and inflammatory systems; data regarding interconnected antibody networks; and the redundant, nonlinear, interdependent nature of the inflammatory response, we present the hypothesis that the systemic host response to trauma, shock, or sepsis must be evaluated as a complex nonlinear system. This model provides a new explanation for the failure of trials using various antimediator therapies in the treatment of patients with sepsis and MODS. Understanding the host response as a complex nonlinear system offers innovative means of studying critical care patients, specifically by suggesting a greater focus on systemic properties. We hypothesize that analysis of variability and connectivity of individual variables offer a novel means of evaluating and differentiating the systemic properties of a complex nonlinear system. Current applications of evaluating variability and connectivity are discussed, and insights regarding future research are offered. CONCLUSION: The paradigm offered by the study of complex nonlinear systems suggests new insights to pursue research to evaluate, monitor, and treat patients with MODS.

Critical Care↗

PubMed1999

Do surgical residents rated as better teachers perform better on in-training examinations?

BACKGROUND: There have been no attempts to objectively compare resident teaching ability with resident knowledge level. METHODS: Resident teaching ability, as rated by medical students and junior surgical residents, was compared with resident knowledge level, estimated by in-training examination results, for 18 PGY5 and PGY4 surgical residents at McGill University (September 1996 to July 1997). RESULTS: There was a trend to suggest that greater teaching ability is associated with higher in-training examination scores; this did not achieve statistical significance. PGY4 residents were rated as better teachers than PGY5 residents. Resident self-evaluation revealed a high degree of interest in teaching; inadequate time was the principal deterrent to resident teaching; enjoyment and learning during teaching were found to be the most common incentives. CONCLUSIONS: Our results suggest an association between resident level of knowledge and teaching ability. The principal deterrent to teaching--inadequate time--must be addressed to effectively assist surgical resident teaching.

Achievement↗

PubMed1998

Reduction in neutrophil cell surface expression of tumor necrosis factor receptors but not Fas after transmigration: implications for the regulation of neutrophil apoptosis.

OBJECTIVES: To test the hypothesis that loss of polymorphonuclear neutrophil tumor necrosis factor alpha (TNF-alpha) receptors during transmigration renders the exudate neutrophil refractory to TNF-alpha-mediated stimulation of apoptosis; and to investigate the surface expression of Fas on both circulating and exudate neutrophils. DESIGN: A prospective cohort study. SETTING: Surgical laboratory of a tertiary care hospital. PARTICIPANTS: Twenty-one healthy human volunteers. INTERVENTIONS: All subjects had circulating neutrophils and exudate neutrophils collected by venipuncture and skin window methods, respectively. MAIN OUTCOME MEASURES: Circulating and exudate neutrophils were incubated in culture medium (1.0x10(6) neutrophils per milliliter) alone or with TNF-alpha (100 ng/mL). Apoptosis was evaluated by flow cytometry (annexin V-fluorescein isothiocyanate and propidium iodide). Tumor necrosis factor alpha-phycoerythrin and anti-human Fas-fluorescein isothiocyanate were used to evaluate neutrophil TNF-alpha receptors and surface expression of Fas. RESULTS: Exudate neutrophils had a significant delay in apoptosis rates when compared with circulating neutrophils. The percentage of neutrophils expressing TNF-alpha receptors was significantly diminished after exudation (80%+/-15% vs 33%+/-9%; P<.001), as was the median channel number of TNF-alpha phycoerythrin fluorescence (8.1+/-1.6 vs 5.2+/-0.5; P=.001). However, the expression of Fas was unchanged after transmigration (percentage positive for Fas: 98.7%+/-0.7% vs 92.8%+/-3.4%, P=.89; Fas antibody-fluorescein isothiocyanate median channel fluorescence: 12.2+/-1.1 vs 13.1+/-1.2; P=.80). Exposure of exudate neutrophils to TNF-alpha failed to increase their rate of apoptosis. CONCLUSIONS: Exudate polymorphonuclear neutrophils are confirmed to have delayed apoptosis. Loss of TNF-alpha receptors during transmigration is necessary for neutrophil survival in the extravascular inflammatory milieu.

Apoptosis↗