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Biomedical subjects

P M Walker

Publications and source records attributed to P M Walker.

At least 37 records · Page 2Linked to original sources

Surgeon compensation and motivation.

HYPOTHESIS: Financial incentives are the only form of compensation that will motivate surgeons at an academic health sciences center to perform the tasks outlined in the hospital's mission statement. DESIGN: A questionnaire divided into 5 sections: demographics, compensation, time allocation, benefits and incentives, and motivational factors. SETTING: The Department of Surgery, The Toronto Hospital, Toronto, Ontario. PARTICIPANTS: All academic surgeons (N=64) practicing at The Toronto Hospital in July 1997. RESULTS: Of the 64 eligible mailed surveys, there were responses for 59. Of these 59 surgeons, 48 (81%) receive compensation through a fee-for-service method. However, only 32 (54%) of the surgeons prefer the fee-for-service method, while 18 (31%) prefer salary and 9 (15%) prefer an alternative system. On average, these academic surgeons spend 44% of their time teaching or performing research, for which they receive 14% of their total income. Of the motivational factors assessed, financial bonuses are a positive motivational factor for all "surgeon tasks." In addition, task-specific motivational factors were established for research, teaching, and operating, including research facilities, mentorship and prestige, and interesting case types, respectively. CONCLUSIONS: Surgeons are not appropriately renumerated for time spent on academic activities, and many would prefer an alternative form of compensation to the fee-for-service method. Knowledge that surgeons are receptive to tasks supporting the hospital's mission statement leads us to conclude that appropriate motivation can shape the activity of academic surgeons. Financial rewards ranked the highest as a motivational factor for all surgeon tasks; however, task-specific motivational factors were identified. Overall, multiple factors, specifically targeted to the individual, will serve to motivate. Thus, compensation packages based on individual preferences and personal motivational factors will be the most successful.

Academic Medical Centers↗

Role of TNF-alpha in myocardial dysfunction after hemorrhagic shock and lower-torso ischemia.

Ruptured abdominal aortic aneurysm (RAAA) repair, a combination of hemorrhagic shock and lower-torso ischemia, is associated with a 50-70% mortality. Myocardial dysfunction may contribute to the high rate of mortality after aneurysm repair. We attempted to determine whether RAAA repair results in cardiac dysfunction mediated by tumor necrosis factor-alpha (TNF-alpha). We modeled aortic rupture and repair in the rat by inducing hemorrhagic shock to a mean blood pressure of 50 mmHg for 1 h, followed by supramesenteric clamping of the aorta for 45 min. After 90 min of reperfusion, cardiac contractile function was assessed with a Langendorff preparation. Myocardial TNF-alpha, ATP and creatine phosphate (CP) levels, and markers of oxidant stress (F(2)-isoprostanes) were measured. Cardiac function in the combined shock and clamp rats was significantly depressed compared with sham-operated control rats but was similar to that noted in animals subjected to shock alone. Myocardial TNF-alpha concentrations increased 10-fold in the combined shock and clamp rats compared with sham rats, although there was no difference in myocardial ATP, CP, or F(2)-isoprostanes. TNF-alpha neutralization improved cardiac function by 50% in the combined shock and clamp rats. Hemorrhagic shock is the primary insult inducing cardiac dysfunction in this model of RAAA repair. An improvement in cardiac contractile function after immunoneutralization of TNF-alpha indicates that TNF-alpha mediates a significant portion of the myocardial dysfunction in this model.

Adenosine Triphosphate↗

Lower limb ischemia: phase 1 results of salvage perfusion.

Revascularization of an ischemic lower extremity is associated with high morbidity (20-30%) and perioperative mortality (10-20%) regardless of the mode of intervention, surgical or thrombolytic, considered to be due to polymorphonuclear (PMN) activation and mediator release. In this study, the safety and feasibility of cell-free extracorporeal perfusion of the limb with a solution designed to minimize both local and systemic injury was tested. Methods. Patients with severe limb ischemia (sensory/motor loss, rest pain/gangrene) were studied prospectively by random assignment into the treatment arm (n = 14) or control arm (n = 21). Surgical management consisted of restorative procedure, thrombectomy or embolectomy (n = 21), or reconstruction (n = 14). Reperfusion of the ischemic limb was achieved with hypertonic, hyperoncotic perfusate containing anti-oxidants delivered via the arterial tree (mean volume 1835 +/- 824 ml) with initial venous drainage (mean volume 775 +/- 263 ml) in the restorative group. Means were compared by paired t test. Results. No adverse systemic effects were detected after limb perfusion (electrolytes, coagulation, platelet function, CBC). Rapid lactate wash-out was observed within 30 min of perfusion (preperfusion 3.2 +/- 4.1 mM, 30 min postperfusion 0.7 +/- 0.71 mM, P < 0.01). Blunting of PMN activation was shown by chemiluminescence (CL) analysis (preischemic CL: 0.68 +/- 0.2; 30 min CL: 0.47 +/- 0. 2; P < 0.013). F2-isoprostanes, a marker of free radical-mediated systemic lipid peroxidation, were significantly reduced in patients treated with study perfusion method (70.55 +/- 39.54 versus control 194.38 +/- 25.24, P < 0.005). Mortality with treatment was 0/14 versus 5/21 in the control. Complication frequency: MI 0/14 vs 3/21; renal 0/14 vs 1/21; leg edema 1/14 vs 5/21; amputations 2/14 vs 1/21. Conclusion. Modification of limb perfusion in patients with severe limb ischemia, using our simple and rapid (15-20 min) method provides beneficial systemic effects.

Cohort Studies↗

Ruptured abdominal aortic aneurysm, a "two-hit" ischemia/reperfusion injury: evidence from an analysis of oxidative products.

PURPOSE: Ruptured abdominal aortic aneurysm (RAAA) remains a lethal condition despite improvements in perioperative care. The consequences of RAAA are hypothesized to result from a combination of two ischemia/reperfusion events: hemorrhagic shock and lower torso ischemia. Ischemia/reperfusion results in tissue injury by diverse mechanisms, which include oxygen free radical-mediated injury produced from activated neutrophils, xanthine oxidase, and mitochondria. Oxygen-free radicals attack membrane lipids, resulting in membrane and subsequently cellular dysfunction that contributes to postoperative organ injury/failure. The purpose of this investigation was to quantify the oxidative injury that occurs as a result of the ischemia/reperfusion events in RAAAs and elective AAAs. METHODS: Blood samples were taken from 22 patients for elective AAA repair and from 14 patients for RAAA repair during the perioperative period. Plasma F(2)-isoprostanes were extracted, purified, and measured with an enzyme immunoassay. Aldehydes and acyloins were purified and quantified. Neutrophil oxidative burst was measured in response to a receptor independent stimulus (phorbol 12-myristate 13-acetate) with luminol-based chemiluminescence. RESULTS: Plasma from patients with RAAAs showed significantly elevated F(2)-isoprostane levels on arrival at hospital and were significantly elevated as compared with the levels of patients for elective repair throughout the perioperative period (two-way analysis of variance, P <.0001). Multiple regression showed a significant relationship between the phagocyte oxidative activity and F(2)-isoprostane levels (P <.013). Total acyloin levels were significantly higher in patients with RAAAs as compared with the levels in elective cases. CONCLUSION: The F(2)-isoprostane levels, specific markers of lipid peroxidation, showed that patients with RAAAs had two phases of oxidative injury: before arrival at hospital and after surgery. The significant relationship between the postoperative increases in F(2)-isoprostane levels and the neutrophil oxidant production implicates neutrophils in the oxidative injury that occurs after RAAA. New therapeutic interventions that attenuate neutrophil-mediated oxidant injury during reperfusion may decrease organ failure and ultimately mortality in patients with RAAAs.

Aldehydes↗

Automatic detection of left ventricular contours from cardiac cine magnetic resonance imaging using fuzzy logic.

RATIONALE AND OBJECTIVES: Gated cardiac cine magnetic resonance imaging provides accurate dynamic data of the left ventricular function. However, the manual extraction of important physiologic parameters such as myocardium wall thickness and left ventricular volumes is invariably time consuming and subjective. To reduce the variability and time constraints inherent in observer contour tracing, the authors developed an automatic left ventricle contour-detection method. METHODS: The purpose was to apply fuzzy logic-based automatic contour detection to identification of endocardial and epicardial borders in short-axis magnetic resonance images. The automatic contouring was compared with manual tracing using the calculated ejection fraction as the comparison criterion. RESULTS: A good correlation was found between the two approaches (r2 = 0.98). CONCLUSIONS: The ejection fraction can be obtained using this automatic contouring method.

Adult↗

MR imaging of the heart in patients after myocardial infarction: effect of increasing intersection gap on measurements of left ventricular volume, ejection fraction, and wall thickness.

PURPOSE: To determine the extent to which the number of planes imaged at magnetic resonance (MR) imaging could be reduced without modifying the calculated volume and thickness of the left ventricle. MATERIALS AND METHODS: Sixty-one patients were examined after a myocardial infarction. The whole left ventricle was imaged by using 5-mm contiguous breath-hold cine MR short-axis sections with no gap (SAng) (two-dimensional fast low-angle shot sequence, 9/4.8 [repetition time msec/echo time msec]). The effect of omitting one section in two (short-axis sections with 5-mm gap [SA5 mm]) or two sections in three (short-axis sections with 10-mm gap [SA10 mm]) was studied. RESULTS: In the comparison of SA5 mm or SA10 mm with respect to the reference SAng, the standard error of the estimate (SEE) for the diastolic volume did not exceed the 6.1% interobserver SEE, and the SEE for the ejection fraction remained lower than the 3% interobserver SEE. The measured wall thickness was not affected. In addition, six simple geometric models were compared with SAng and yielded an SEE of 9.5%-28.1% for the diastolic volume and 3.8%-13.3% for the ejection fraction. CONCLUSION: In the study of left ventricles with heterogeneous contractility, short-axis imaging is more accurate than geometric modeling and permits wall thickness measurements when an intersection gap of 5 or 10 mm is used.

Adult↗

A CD18 monoclonal antibody reduces multiple organ injury in a model of ruptured abdominal aortic aneurysm.

The role of CD18 antibody (anti-CD18) in remote and local injury in a model of ruptured abdominal aortic aneurysm repair was investigated. Rats were divided into sham, shock, clamp, and shock + clamp groups. Shock + clamp animals received anti-CD18 or a control monoclonal antibody. One hour of hemorrhagic shock was followed by 45 min of supramesenteric aortic clamping. Intestinal and pulmonary permeability to (125)I-labeled albumin was determined. Myeloperoxidase (MPO) activity, F(2)-isoprostane levels, and transaminases were also measured. Only shock + clamp resulted in statistically significant increases in pulmonary and intestinal permeability, which were associated with significant increases in MPO activity and F(2)-isoprostane levels. Treatment with anti-CD18 significantly decreased intestinal and pulmonary permeability in shock + clamp animals. These reductions were associated with significantly reduced intestinal and hepatic MPO activity and pulmonary F(2)-isoprostane levels and reduced alanine and aspartate aminotransferase levels; however, anti-CD18 had no effect on intestinal or hepatic F(2)-isoprostane levels or on pulmonary MPO activity. These results suggest CD18-dependent and -independent mechanisms of local and remote organ injury in this model of ruptured abdominal aortic aneurysm.

Alanine Transaminase↗

A rapid assay of endotoxin in whole blood using autologous neutrophil dependent chemiluminescence.

A rapid (30 min) whole blood assay for the detection of lipopolysaccharide (LPS) is described. This chemiluminescent (CL) assay utilizes the CR1 and CR3 receptor-induced oxidant production of polymorphonuclear leucocytes as a detection platform. The differential priming of neutrophils in whole blood by LPS-antibody complexes allows the specificity of the assay to be achieved. Oxidant released in response to complement opsonized zymosan results in luminol oxidation and subsequent light emission. This is dependent on heat labile putative complement proteins in the plasma. The assay consists of a control which measures baseline whole blood neutrophil oxidant production. The test assay contains murine monoclonal IgM antibody against the Lipid A epitope of LPS and measures the enhanced chemiluminescent response of the neutrophils in the presence of LPS-antibody complexes. Maximal sensitivity of the CL assay is dependent upon optimal antigen-antibody equivalence and duration of pre-incubation with the whole blood sample. The quantification of LPS is possible by inclusion of a positive control containing a maximally reactive LPS dose (800 pg/ml Escherichia coli 055:B5 LPS at an antibody concentration of 0.8 microg/assay). The CL assay is insensitive to variations in patient neutrophil concentration over a minimum range of 0.5 to 20 x 10(9) cells/l. The CL assay is widely reactive with the LPS of many strains of gram negative bacteria but not with the cell wall products of gram positive bacteria or Candida and Aspergillus. In comparison to acid extraction chromogenic LAL, the CL assay demonstrates superior recovery precision and accuracy in in vitro studies. This was reproducible over a wide range of LPS concentrations (0.017-1.6 EU/ml or 20-2000 pg/ml). This assay may be a clinically useful tool for the diagnosis of infection or endotoxin in patients.

Antibodies, Bacterial↗

The impact of multiple organ dysfunction on mortality following ruptured abdominal aortic aneurysm repair.

The in-hospital mortality for a patient with a ruptured abdominal aortic aneurysm (RAAA) ranges from 30% to 70% and remains unchanged despite aggressive surgical, anesthetic, and intensive-care management. The purpose of this investigation is to determine the relationship between the development of organ dysfunction and mortality in ruptured AAA patients. Eighty-eight consecutive patients admitted to the Toronto Hospital for repair of RAAAs were studied. APACHE II and multiple organ dysfunction (MOD) scores were calculated for all patients. The MOD scoring system measures daily alterations in the function of six key organs, with increased dysfunction indicated by an increasing score. The overall 30-day mortality rate was 40%; 10% of patient deaths occurred intraoperatively. ICU mortality was bimodal; 11.5% deaths occurred within the first 48 hours compared to 18.2% after 48 hours (late deaths). The APACHE II score was significantly higher in those who died within 48 hours of ICU admission (28.5 +/- 6.36) compared to both those who died late (17.2 +/- 5.7, p < 0.0001) and survivors (11.2 +/- 4.2, p < 0.0001). The survivors' daily mean MOD scores did not increase significantly, while the MOD scores for late deaths increased progressively (p < 0.01). The renal and hepatic dysfunction components of the MOD score were significantly lower in the survivors compared to late deaths (p < 0.001), however the respiratory MOD score did not differ between the groups (p > 0.05). The change in MOD (delta MOD) score over the intensive care stay was significantly greater in late deaths compared to survivors (p < 0.01). The rates of infection were similar in both groups and were not responsible for mortality. We conclude that mortality is better predicted following RAAA by the development of renal and hepatic dysfunction rather than by initial physiologic derangement measured by the APACHE II score.

APACHE↗

Nuclear magnetic resonance evidence of different muscular adaptations after resistance training.

OBJECTIVE: To evaluate muscle bioenergetics, muscle cross-sectional area (CSA), and soreness when the gastrocnemius was subjected to concentric and concentric/eccentric resistance training modes. DESIGN: Prospective study, before and after training. The subjects served as their own controls. SETTING: Rehabilitation center and nuclear magnetic resonance spectroscopy unit of a university hospital. PARTICIPANTS: Sixteen healthy young volunteers from the local physiotherapist school. INTERVENTION: Two distinct resistive training programs were evaluated on the gastrocnemius: a protocol consisting of concentric contractions only and a mixed concentric/eccentric program. MAIN OUTCOME MEASURES: Maximal isometric resistance was measured after each training session. Before and after training, muscle CSA was appreciated using magnetic resonance imaging, whereas changes in muscle pH, phosphorus metabolite ratios, maximal oxidative power (Pmax), and oxidative phosphorylation were studied using 31P nuclear magnetic resonance spectroscopy at rest and during an incremental exercise protocol. RESULTS: Magnetic resonance imaging revealed a significant increase (7.1%) in the gastrocnemius CSA in the concentric-eccentric group only. The PCr/Pi (8.3 +/- 0.9 vs 10.4 +/- 1.7) and PCr/ATP (3.68 +/- .36 vs 4.07 +/- .27) resting ratios increased significantly (p = .008) after concentric-eccentric resistance training. Pmax was significantly improved in the concentric-eccentric group (7.0 +/- 2.1W vs 8.4 +/- 1.8W: p < .02). This mixed protocol also reduced the incidence of muscular soreness. CONCLUSION: The data suggest that the improved oxidative mechanical power output could be due mainly to a greater muscle cross-section in the concentric-eccentric group, with circumstantial evidence suggesting a relatively higher type IIa fiber activity.

Adult↗

Epidural bupivacaine-morphine analgesia versus patient-controlled analgesia following abdominal aortic surgery: analgesic, respiratory, and myocardial effects.

BACKGROUND: The efficacy and effects of epidural analgesia compared with patient-controlled analgesia (PCA) have not been reported in patients undergoing major vascular surgery. We compared the effects of epidural bupivacaine-morphine with those of intravenous PCA morphine after elective infrarenal aortic surgery. METHODS: Forty patients classified as American Society of Anesthesiologists physical status 2 or 3 received general anesthesia plus postoperative PCA using morphine sulfate (group PCA; n = 21) or general anesthesia plus perioperative epidural morphine-bupivacaine (group EPI; n = 19) during a period of 48 h. During operation, EPI patients received 0.05 mg/kg epidural morphine and 5 ml 0.25% bupivacaine followed by an infusion of 0.125% bupivacaine with 0.1% morphine (0.1 mg/ ml); group PCA received 0.1 mg/kg intravenous morphine sulfate. Continuous electrocardiographic monitoring (V4 and V5 leads) was performed from the night before surgery until 48 h afterward. Respiratory inductive plethysmographic data were recorded after tracheal extubation. Visual analog pain scores at rest and after movement were performed every 4 h after extubation. RESULTS: Nurse-administered intravenous morphine and time to tracheal extubation were less in group EPI, as were visual analog pain scores at rest and after movement from 20 to 48 h. Complications and the duration of intensive care unit and hospital stay were comparable. There was a similar, low incidence of postoperative apneas, slow respiratory rates, desaturation, and S-T segment depression. CONCLUSIONS: Epidural morphine-bupivacaine is associated with reduced early postoperative intravenous opioid requirements, more rapid tracheal extubation, and superior analgesia after abdominal aortic surgery, with comparable respiratory effects.

Aged↗

Current indications for carotid endarterectomy.

Randomized, prospective trials examining the effectiveness of carotid endarterectomy have given distinct information into the mechanisms and prevention of embolic strokes. The North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the Asymptomatic Carotid Atherosclerosis Study (ACAS) have demonstrated the benefits of carotid endarterectomy for patients who meet the precise selection criteria and are treated according to established study protocols. The existing challenge to clinicians lies in the application of trial results to the individual patient.

Carotid Stenosis↗

Automatic detection of cardiac contours on MR images using fuzzy logic and dynamic programming.

This paper deals with the use of fuzzy logic and dynamic programming in the detection of cardiac contours in MR Images. The definition of two parameters for each pixel allows the construction of the fuzzy set of the cardiac contour points. The first parameter takes into account the grey level, and the second the presence of an edge. A corresponding fuzzy matrix is derived from the initial image. Finally, a dynamic programming with graph searching is performed on this fuzzy matrix. The method has been tested on several MR images and the results of the contouring were validated by an expert in the domain. This preliminary work clearly demonstrates the interest of this method, although a formal evaluation has to be done.

Fuzzy Logic↗

Risk factors for stroke in patients undergoing coronary artery bypass grafting.

OBJECTIVE: To determine predictors of stroke in patients undergoing first-time coronary bypass grafting, we prospectively collected data on 1631 consecutive patients. METHODS: Patients with a history of stroke and/or central nervous system symptoms (n = 134) and/or carotid bruits (n = 95) underwent carotid Doppler evaluation. Stenosis greater than 70% was considered significant. Patients with symptomatic disease or asymptomatic bilateral disease were referred for combined coronary bypass and carotid endarterectomy (n = 21). Patients with neurologic symptoms after the operation were assessed by a neurologist and underwent a computed tomographic scan. Events were classified as reversible transient ischemic attack, reversible ischemic neurologic deficit, or irreversible stroke. RESULTS: There were 19 strokes (1.2%) and 20 deaths (1.2%) in this series. In patients with carotid screening, risk of stroke increased with severity of carotid disease and ranged from 0% in patients without stenosis, to 3.2% (1/31) in those with greater than 70% stenosis, and to 27.3% (6/22) in those with carotid occlusion. By stepwise logistic regression analysis six variables were identified as risk factors for stroke. The most important predictor was carotid occlusion with or without contralateral stenosis (odds ratio = 28, 95% confidence interval (8,105). In this group, four of five strokes occurred on the occluded side. Other risk factors were presence of ascending aortic disease at the time of surgery (odds ratio = 12.8, confidence interval 3,48), perioperative myocardial infarction (odds ratio = 8.2, confidence interval 2,33), poor left ventricular function (odds ratio = 4.6, confidence interval 1,19), peripheral vascular disease (odds ratio = 3.2, confidence interval 1,9), and age > 60 years (odds ratio = 2.9, confidence interval 0.8,11). CONCLUSION: We conclude that risk factors for perioperative stroke in patients undergoing coronary artery bypass grafting are multiple. Carotid scanning in patients with neurologic symptoms or carotid bruits can identify patients at increased risk. Patients with carotid occlusion are at high risk for stroke on the occluded side.

Adult↗

Asymmetric metabolic profile in mesial temporal lobes: localized H-1 MR spectroscopy in healthy right-handed and non-right-handed subjects.

PURPOSE: To determine a possible asymmetric metabolic profile in right- handed and non-right-handed healthy subjects by comparing proton spectra from temporal lobes. MATERIALS AND METHODS: Twenty-eight healthy adults (17 right-handers, 11 non-right-handers) underwent magnetic resonance (MR) imaging and single-voxel MR spectroscopy. N-acetylaspartate (NAA), choline (Cho), and creatine (Cr) peak areas were measured. RESULTS: Volume of hippocampal formations was larger on the right in right-handers (right volume: 4.04 cm3 +/- 0.67 vs left volume: 3.84 cm3 +/- 0.62; P = .00004) and in non-right-handers (right volume: 4.22 cm3 +/- 0.78 vs left volume: 4.05 cm3 +/- 0.80; P = .004). NAA/Cho was significantly higher in the left temporal lobe of right-handers (right lobe: 1.53 +/- 0.18 vs left lobe: 1.89 +/- 0.18; P=.00004) as was NAA/Cr (right lobe: 1.79 +/- 0.36 vs left lobe: 2.45 +/- 0.45; P=.0001). No statistically significant difference was noted for these ratios in non-right-handers: NAA/Cho (right lobe: 1.49 +/- 0.18 vs left lobe: 1.61 +/- 0.35) and NAA/Cr (right lobe: 1.93 +/- 0.45 vs left lobe: 2.40 +/- 0.70). CONCLUSION: A clear metabolic asymmetry observed in right-handers is less clear-cut in non-right-handers. Both tendencies should be considered when assessing the brain metabolism of patients with uni- or bilateral disorders, such as temporal lobe epilepsy.

Adult↗

Sequential ischemia/reperfusion results in contralateral skeletal muscle salvage.

Sequential ischemia/reperfusion in a paired canine gracilis muscle model resulted in significant muscle salvage. In this model, one randomly chosen gracilis muscle was subjected to 5 h of ischemia followed by 48 h of in vivo reperfusion. The contralateral (second) muscle was then made ischemic and reperfused using the same protocol. Muscle necrosis was determined at the end of 48 h of reperfusion. A mean 60% reduction in muscle necrosis was observed in the second group of muscles. Analysis of tissue adenine nucleotides indicated that significant sparing of ATP utilization occurred in the second muscle group during ischemia. Preliminary analysis of tissue heat shock proteins (HSP) showed that the second group of muscles had a different pattern of HSP expression before the onset of ischemia. The results suggest that reduced ATP utilization and altered HSP expression in the second muscle play a role in the tissue salvage observed in this sequential muscle ischemia model.

Adenosine Triphosphate↗