Fikri M. Abu-Zidan

Elevated Protein Carbonyls as Plasma Markers of Oxidative Stress in Acute Pancreatitis

Background: Experimental studies have demonstrated that protein and lipid oxidation is a feature of acute pancreatitis and that antioxidant pretreatment can ameliorate the severity of the disease. Justification for a clinical trial of antioxidant therapy requires stronger evidence for oxidative stress in patients. Aims: To determine if oxidative stress is evident in patients with acute pancreatitis on admission to hospital, if it increases after admission and if it is related to disease severity. Methods: Measurement of plasma concentrations of protein carbonyls and malondialdehyde as markers of protein oxidation and lipid peroxidation, respectively, in a consecutive series of 85 patients with acute pancreatitis 0, 2 and 5 days after admission. Results: Patients with acute pancreatitis had significantly increased concentrations of protein carbonyls in plasma on recruitment (median 27 h after the onset of symptoms) that persisted over 5 days. Protein carbonyls were higher in severe compared with mild disease (median 0.099 and 0.043 nmol/mg protein, respectively, p = 0.0016). They were higher at day 0 in patients recruited with more established pancreatitis than in those presenting early. No increases in malondialdehyde were seen. Receiver operator characteristic curve analysis demonstrated that protein carbonyls at day 0 were comparable with C-reactive protein at predicting pancreatitis severity. Conclusion: Our demonstration of substantial protein oxidation provides further evidence for oxidative stress in patients with severe pancreatitis. Our results suggest that there could be a window for early antioxidant intervention and that protein carbonyls could be a useful plasma marker of oxidative injury.

Effects of prone and supine posture on cardiopulmonary function after experimental chlorine gas lung injury

Background: Chlorine gas may induce severe acute lung injury. Improvement of pulmonary gas exchange in patients and animals with acute lung injury nursed in the prone position was observed in recent years. The purpose of this study was to evaluate the effects of prone and supine positions on pulmonary and cardiovascular functions following experimental chlorine gas lung injury.

Establishment of a teaching animal model for sonographic diagnosis of trauma.

BACKGROUNDnUltrasound is widely accepted as a valuable diagnostic tool for detecting intra-abdominal and intrathoracic bleeding in trauma patients. Nevertheless, many doctors are reluctant to use it because they do not have sufficient training. This study aimed to define intra-abdominal and intrathoracic fluid volumes that can be detected by sonography and their relation to fluid width in pigs to establish a clinically relevant animal model for teaching and training.nnnMETHODSnDifferent volumes of normal saline were infused into the abdomen (50-2,000 mL) and chest (25-250 mL) in five anesthetized pigs. The maximum width of fluid as detected by ultrasound was recorded. The right upper quadrant, left upper quadrant, pelvis, and right paracolic section of the abdomen and right pleural cavity were studied. An experienced radiologist performed the studies. The effects on respiratory and cardiovascular functions were evaluated.nnnRESULTSnThe sonographic findings in the pig were similar to those in humans. Up to 50 mL of intra-abdominal fluid and up to 25 mL of intrathoracic fluid could be detected by ultrasound. There was a significant correlation between the volume infused and the fluid width detected. The respiratory and cardiovascular monitoring of the animals showed that the infused intrathoracic volumes mimicked a survivable hemothorax.nnnCONCLUSIONnThe pig may serve as an excellent clinically relevant model with which to teach surgeons detection of different volumes of intra-abdominal and intrathoracic fluids. The value of this model as an educational tool has yet to be tested.

Role of platelet-activating factor antagonism in posthemorrhage septic shock in pigs.

OBJECTIVESnTo study the role of platelet-activating factor (PAF) antagonism in posthemorrhage septic shock in pigs.nnnDESIGNnExperimental study.nnnMATERIALS AND METHODSnTwelve anesthetized pigs were bled, kept with a mean arterial pressure of 30 mm Hg for 30 minutes, and then resuscitated with 50 mL/kg of isotonic saline. A continuous infusion of Escherichia coli endotoxin 36 micrograms/kg/hour was given intravenously for 3.5 hours starting 30 minutes after resuscitation. The animals were divided into two groups of six each. One group received I mg/kg of BB-882 (a potent specific PAF receptor antagonist) as a bolus during resuscitation, followed by a continuous infusion of BB-882 1 mg/kg/hour. The other group received vehicle alone.nnnMEASUREMENTS AND MAIN RESULTSnThe measured variables were blood temperature, heart rate, intravascular pressures, cardiac output, systemic and pulmonary vascular resistance, lung-thorax compliance, blood gases, hemoglobin oxygen saturation, packed cell volume and blood sugar and serum lactic acid concentrations. The group treated with BB-882 had significantly higher intracardiac pressures and cardiac output, and had less increase in systemic vascular resistance. The BB-882 group had significantly less lactic acidemia than the control group (p < 0.05, analysis of variance appropriate for repeated measurement design). BB-882 had no effect on endotoxin-induced hypoxia or reduced lung-thorax compliance.nnnCONCLUSIONSnPAF antagonism reduced the increase in systemic vascular resistance, improved cardiac output, and reduced lactic acidemia in posthemorrhage septic shock in pigs, but it did not improve hypoxia or reduced lung-thorax compliance.

Role of Platelet-Activating Factor Antagonism in Haemorrhagic Shock in Pigs

This study aimed at evaluating the role of platelet-activating factor (PAF) antagonism in haemorrhagic shock in juvenile pigs. The animals were bled to a mean arterial pressure of 30 mm Hg which was maintained for 30 min, then they were resuscitated using normal saline 50 ml/kg. Seven pigs received BB-882 (a potent novel PAF antagonist) 1 mg/kg as bolus during resuscitation followed by continuous infusion of 1 mg/kg/h. Seven pigs received only vehicle. The group treated with BB-882 had significantly higher central venous pressure, mean pulmonary artery pressure and pulmonary capillary wedge pressure. The mean arterial pressure and cardiac output were similar in the two groups, while the systemic vascular resistance was significantly reduced by the drug. The BB-882 group had significantly more tachycardia and less arterial pH. Oxygen delivery and consumption and lactic acidaemia were similar in the two groups. These effects were not attributed to anaerobic metabolism and may indicate that PAF antagonism protected against ischaemia and improved the microcirculation in the haemorrhagic shock in pigs.

Role of platelet-activating factor on cardiovascular dysfunction in postischemic shock in pigs.

This study aimed at evaluating the role of platelet-activating factor (PAF) on cardiovascular dysfunction in postischemic shock in pigs. Sixteen pigs were randomly allocated to two groups of eight each. Their aorta was clamped above the celiac axis for 45 min and then declamped. The animals were studied for 2 h after declamping. They were given a continuous infusion of Hartmanns solution 6.75 ml/kg/h throughout the experiment. The experimental group was given a potent specific PAF receptor antagonist 15 min before reperfusion (BB-882 1 mg/kg bolus followed by continuous infusion of 1 mg/ kg/h till the end of the experiment). The control group was given vehicle instead. Reperfusion in the control group caused prolonged hypotension (mean arterial pressure (SEM): 29 (1) mm Hg, immediately after declamping, compared with 74 (3) at baseline), an increase in pulmonary vascular resistance (491.6 (51.5) dyn.s.cm-5, 2 h after declamping, compared with 274.2 (19.4) dyn.s.cm-5 at baseline), a reduction in cardiac output (1.75 (0.15) liters/min, 2 h after declamping, compared with 2.8 (0.21) liters/min at baseline), hyperglycemia (13.7 (0.8) mmol/l, immediately after declamping, compared with 6.26 (0.6) mmol/l at baseline), and lactic acidemia (11.28 (0.5) mmol/l, immediately after declamping, compared with 4.55 (0.67) mmol/l at baseline). BB-882 did not improve any of these variables. PAF does not play a major role on cardiovascular dysfunction in postischemic shock in pigs.

Students' evaluation of surgical seminars in a teaching hospital

To evaluate the surgical seminars given for medical students at Auckland University and factors affecting them, so as to define areas for improvement.

Intestinal ischaemia-reperfusion increases plasma amylin concentration in rats.

Intestinal ischaemia-reperfusion and hyperamylinaemia are both associated with severe acute pancreatitis. The aim of this study was to examine the relationship between intestinal-ischaemia reperfusion and plasma amylin in an experimental model. Wistar rats (n = 24, 400–450 g) were divided into three groups: (1) a sham (S)-operated group (n = 7) that underwent laparotomy and isolation (without clamping) of the superior mesenteric artery, (2) an ischaemia-reperfusion (IR) group (n = 7) that had clamping of the superior mesenteric artery for 60 min followed by 15 min reperfusion, and (3) a control (C) group (n = 10) that underwent no surgery. Amylin was significantly elevated in the IR group (median 39 pM, range 30–44) compared with the S group (19 pM, range 15–45; Mann-Whitney U, p < 0.05) and the C group (24 pM, range 15–55; p < 0.01). Insulin was significantly elevated in the IR group (2,060 pM, range 1,000–4,650) compared with the S group (558 pM, range 424–2,020; p < 0.01). There was a significant positive correlation between amylin and insulin (R = 0.82, F = 46.6, p < 0.0001), but not between amylin and glucose or insulin and glucose. Intestinal histology was consistent with an ischaemia-reperfusion injury, whereas pancreatic histology was normal. The unique finding that plasma amylin concentration is increased with intestinal ischaemia-reperfusion injury warrants further investigation.

The International Conference on Problem-based Learning in Higher Education, September 24-27 1995, Linköping, Sweden.

The aim of the International Conference on Problembased Learning (PBL) in Higher Education was to provide an international forum for the discussion of PBL theory and practice, and to bring about an exchange of views across faculty boundaries. It was held at The Congress Building of LinkoÈping which is in the centre of the city. Its main hall, which has a space for more than 1200 participants, was full during almost every keynote speech of the conference. The keynote speakers presented their experiences to the audience over 3 days, covering: the tutorial process; evaluation and quality issues; and visions for the future.

An interactive problem-solving approach to teach traumatology for medical students.

AimWe aimed to evaluate an interactive problem-solving approach for teaching traumatology from perspectives of students and consider its implications on Faculty development.MethodsA two hour problem-solving, interactive tutorial on traumatology was structured to cover main topics in trauma management. The tutorial was based on real cases covering specific topics and objectives. Seven tutorials (5-9 students in each) were given by the same tutor with the same format for fourth and fifth year medical students in Auckland and UAE Universities (n = 50). A 16 item questionnaire, on a 7 point Likert-type scale, focusing on educational tools, tutor-based skills, and student-centered skills were answered by the students followed by open ended comments.ResultsThe tutorials were highly ranked by the students. The mean values of educational tools was the highest followed by tutor-centered skills and finally student-centered skills. There was a significant increase of the rating of studied attributes over time (F = 3.9, p = 0.004, ANOVA). Students open ended comments were highly supportive of the interactive problem-solving approach for teaching traumatology.ConclusionsThe interactive problem-solving approach for tutorials can be an effective enjoyable alternative or supplement to traditional instruction for teaching traumatology to medical students. Training for this approach should be encouraged for Faculty development.