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Biomedical subjects

W J Perkins

Publications and source records attributed to W J Perkins.

At least 19 recordsLinked to original sources
PubMed1991

Pretreatment with U74006F improves neurologic outcome following complete cerebral ischemia in dogs.

We examined the 21-aminosteroid U74006F, a potent inhibitor of lipid peroxidation, for potential neuroprotective effects in a canine model of complete cerebral ischemia. Two 1.5-mg/kg boluses were administered to six dogs, the first bolus 15 minutes prior to a 12-minute episode of complete cerebral ischemia and the second bolus after 11 minutes of ischemia, 1 minute prior to reperfusion. Using this dosage regimen, plasma U74006F levels of greater than 0.3 microgram/ml were maintained for up to an hour postischemia. An additional six animals received equal volumes of the citrate vehicle solution. At 24 and 48 hours postischemia, the dogs were neurologically evaluated by an observer blinded as to treatment selection. All six U74006F-treated animals had a normal neurologic outcome at 48 hours postischemia, while the citrate vehicle-treated animals all suffered moderate to severe neurologic deficits. The difference in outcome was significant at both 24 and 48 hours (p less than 0.005). Although U74006F is a 21-aminosteroid, it is not reported to possess glucocorticoid activity. This is supported by the present finding that no changes in plasma glucose concentration were observed following administration of the drug. The systemic vitamin E levels of citrate vehicle-treated animals decreased significantly (from 4.10 +/- 0.46 micrograms/ml to 2.95 +/- 0.38 micrograms/ml, p less than 0.05), whereas the vitamin E levels in U74006F-treated animals did not decrease significantly. These results suggest that U74006F may be of benefit in improving neurologic outcome when administered prior to an episode of complete cerebral ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

The effects of dizocilpine maleate (MK-801), an antagonist of the N-methyl-D-aspartate receptor, on neurologic recovery and histopathology following complete cerebral ischemia in primates.

The present study was designed to determine if the noncompetitive excitatory amino acid antagonist, dizocilpine maleate, when administered after a 17 min period of complete cerebral ischemia in primates, would improve postischemic neurologic function and hippocampal histopathologic outcome when compared to placebo-treated animals. Ten pigtail monkeys were anesthetized and subjected to complete cerebral ischemia using an established neck tourniquet model. Five minutes postischemia, five monkeys received dizocilpine 300 micrograms/kg i.v. over 5 min, followed by an infusion of 150 micrograms/kg/h for 10 h. This produced plasma levels of the drug in excess of 30 ng/ml for the duration of the infusion. An additional five monkeys were treated with an identical volume of saline placebo. All monkeys received intensive care for the initial 24 to 48 h postischemia. At 96 h postischemia, there was no significant difference in neurologic function between the two groups (p = 0.53, with the placebo group having the numerically better outcome). There also was no significant difference between hippocampal histopathology scores between dizocilpine and placebo-treated monkeys. The authors conclude that dizocilpine is not an efficacious therapy in the treatment of neurologic injury that occurs following complete cerebral ischemia in this primate model.

Animals↗
PubMed1990

Evaluation of a forced-air system for warming hypothermic postoperative patients.

Thirty adult surgical patients admitted to the recovery room with an oral temperature less than or equal to 35.0 degrees C were randomized into two groups. Group 1 patients were covered with cotton blankets warmed to 37.0 degrees C, and group 2 patients were treated with a forced-air warming system. Mean oral temperature on admission to the recovery room was the same in both groups (34.3 degrees C). Oral temperature and the presence or absence of shivering were recorded at 15-min intervals. After application of the selected warming method, patients in group 2 were warmer at all time intervals. Mean temperatures in the forced-air heating group and in group 1 were, respectively, 34.8 degrees C and 34.3 degrees C (P less than 0.05) at 15 min; 35.0 degrees C and 34.2 degrees C (P less than 0.01) at 30 min; 35.2 degrees C and 34.5 degrees C (P less than 0.05) at 45 min; 35.8 degrees C and 34.7 degrees C (P less than 0.001) at 60 min; 36.0 degrees C and 35.0 degrees C (P less than 0.01) at 75 min; and 36.0 degrees C and 35.0 degrees C (P less than 0.01) at 90 min. The incidence of shivering was significantly greater in group 1 at 15 and 45 min. In addition, time spent in the recovery room was significantly greater in group 1 than in group 2, 156.0 min versus 99.7 min (P less than 0.003).

Adult↗
PubMed1989

The effect of the excitatory amino acid receptor antagonist dizocilipine maleate (MK-801) on hemispheric cerebral blood flow and metabolism in dogs: modification by prior complete cerebral ischemia.

The effect of the N-methyl-D-aspartate (NMDA) receptor antagonist dizociplipine maleate (MK-801) on cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO2), intracranial pressure and systemic variables was examined in 6 normal dogs (Group I). In 6 additional dogs (Group II), the effects of a prior 11 min episode of complete cerebral ischemia on the response to dizocilipine was studied. CBF was measured with a sagittal sinus outflow technique and CMRO2 was calculated as the product of CBF and the arterial to sagittal sinus O2 content difference. Dizocilipine was administered as a 150 micrograms/kg i.v. bolus followed by a 75 micrograms.kg-1.h-1 infusion for 90 min. Plasma dizocilipine levels were greater than 25 ng/ml for the duration of the infusion. The CSF levels were approximately half the plasma levels. Five minutes after initiation of dizocilipine treatment, Group I dogs experienced a 63% increase in heart rate (P less than 0.01) and an 8% decrease in the mean arterial blood pressure (P less than 0.05). Over the same time interval. CBF increased by 85% (P less than 0.01) and intracranial pressure nearly doubled (P less than 0.05). In addition, dizocilipine treatment in all Group I animals resulted in EEG quasiperiodic bursts of delta-waves and polyspikes on a background of beta-activity. With the exception of the intracranial pressure, the above changes in systemic and cerebral variables persisted for the duration of the drug infusion. Intracranial pressure was no longer significantly elevated after 80 min of drug infusion. Hemispheric CMRO2 was unchanged by dizocilipine in Group I dogs. There was a decrease in the cortical glucose level at the end of the study, but no significant change in phosphocreatine, ATP, lactate, or energy charge when compared with 6 laboratory normals. An identical dose of dizocilipine administered after an 11 min episode of complete cerebral ischemia resulted in no significant changes in either cerebral or systemic variables. The absence of systemic effects in Group II dogs suggests that dizocilipine administration in normal dogs results in a centrally mediated activation of the peripheral sympathetic nervous system. The uncoupling of CBF and CMRO2 observed following dizocilipine treatment is similar to that reported for two other known NMDA antagonists, ketamine and phencyclidine. If administration of dizocilipine results in improved histopathological and neurological outcome following an episode of complete cerebral ischemia, this improvement is unrelated to changes in postischemic CBF or hemispheric CMRO2.

Animals↗
PubMed1989

Evaluation of the glutamate antagonist dizocilipine maleate (MK-801) on neurologic outcome in a canine model of complete cerebral ischemia: correlation with hippocampal histopathology.

This study was designed to determine if dizocilipine maleate (MK-801), administered following 11 min of complete ischemia in dogs, could favorably alter neurologic outcome and hippocampal damage. Eighteen dogs were anesthetized and subjected to complete cerebral ischemia by temporary occlusion of the ascending aorta and the venae cavae via a thoracotomy. Five min postischemia, 9 dogs were given dizocilipine 150 micrograms/kg, followed by an infusion of 1.25 microgram/kg/min for 8 h. Control dogs were given equal volumes of placebo. Dogs were evaluated neurologically at 24, 48, and 72 h; thereafter, the brains were perfused, fixed and harvested. There was no significant difference in outcome between dizocilipine- and placebo-treated dogs: 5 of 9 given dizocilipine were normal, 1 was mildly injured and 3 were severely injured or dead. In the control animals given placebo, 3 of 9 were normal, 2 were mildly injured and 4 were moderately to severely injured. Histopathologic examination was limited to the hippocampus. CA1 and CA2,3,4 pyramidal neurons were graded according to degree of injury on a 5-point scale. There were no differences in histopathologic grades between the two groups. However, in both groups combined there was a significant correlation between neurologic outcome grade and histopathologic grade. The only notable systemic effect of dizocilipine appeared to be prolonged sedation which extended beyond 24 h postischemia but was not evident at 48 h postischemia. The authors conclude that more outcome studies in more sensitive models are needed.

Animals↗
PubMed1979

A system for the three-dimensional construction, manipulation and display of microbiological models.

A system is described for building up serial sections into a three dimensional structure, incorporating density, that can be displayed and then further manipulated by rotation about three orthogonal axes. The initial application was to produce a computer model of a protein structure and to compare the diverse images obtained from rotation with the two dimensional images observed in related electron micrographs. To obtain sufficient contrast in the electron microscope images of protein structures, the specimens need to be stained and since this can cause some deformation of the observed images, it is also necessary to simulate ths possible effects of stain on the protein model. Because of the need to compare numerous orientations of the combined model, techniques are available either for speeding up the comparison or for obtaining better accuracy. The methods have been applied to the interpretation of electron micrograph images of microbiological specimens, where the three dimensional structure of the specimen is an important aid in understanding its biological function, but the techniques are also applicable to more general serial reconstruction requirements.

Adenoviridae↗
PubMed1979

The transfer of selected image data to a computer using a conductive tablet.

The processing and analysis of images in a computer often requires the selection of particular features of a complex image for more detailed study. Sometimes such decisions are empirical, in which case it would be extremely difficult to describe a rigorous algorithm for detecting these features automatically in a computer. In this situation graphic tablets can be very useful as they allow an operator to use experience in deciding which features are to be transferred into a computer. A tablet is described which uses a conductive glass plate and pencil probe. A number of subroutines are available in a general purpose program for conventional processing, calculation and displays to be effected by simple option selection on the tablet for specific applications in cell growth, modeling and three dimensional reconstruction of serial sections, special programs were developed which could include appropriate subroutines. The categorisation of subsections by an operator was particularly useful in allowing different methods of analysis and display to be applied to each. For example they could be displayed separately or given different dentisy levels by choosing the appropriate option in the program.

Analog-Digital Conversion↗