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Biomedical subjects

P M Walker

Publications and source records attributed to P M Walker.

At least 19 recordsLinked to original sources
PubMed1992

Systemic phospholipase A2 and cachectin levels in adult respiratory distress syndrome and multiple-organ failure.

In this clinical study we have prospectively measured plasma phospholipase A2 (PLA2) activity and tumor necrosis factor (TNF) levels in ventilated intensive care unit (ICU) patients with (n = 9) and without (n = 12) evidence of respiratory distress syndrome (ARDS) and multiple-organ failure (MOF). The median peak TNF concentration in control patients was 40 ng/L (range less than 40-100 ng/L) and in ARDS patients 231 ng/L (range 100-2550 ng/L; p less than 0.001). All of the control patients were discharged alive from the ICU, whereas 6 of 9 ARDS patients died in the ICU. In 6 ARDS patients, it was possible to measure more than 4 consecutive plasma TNF levels. Of these 6 patients, the 3 with persistent elevations in systemic TNF above 230 ng/L succumbed (p less than 0.05, one-tailed). Patients with ARDS also had parallel elevations in plasma PLA2 activity above controls. These elevations were significant for arterial PLA2 activity but not for venous PLA2 activity. Our study suggests that serial measurement of plasma (arterial or venous) TNF levels may have (1) prognostic and (2) etiologic significance in ICU patients with ARDS and MOF.

Critical Care↗
PubMed1992

Quantification of skeletal muscle necrosis in the lower extremities using 99Tcm pyrophosphate with single photon emission computed tomography.

No non-invasive quantitative method is currently available for measuring the amount of regional skeletal muscle necrosis in humans. A threshold method using 99Tcm pyrophosphate (PPi) with single photon emission computed tomography (SPECT) has been reported to quantify muscle necrosis successfully in a canine model. This method has been modified to measure muscle necrosis in the lower extremities of human patients. Modifications include adding background subtraction and using the contralateral unaffected lower extremity as background region. A region of interest was also manually drawn around the affected lower extremity muscle to exclude the tibia. In order to identify the group of patients with no significant necrosis and with diffuse hyperaemia, nine control subjects were studied. The variance of the counts within the pixels of the lower extremities was 132 (S.D. = 27). A variance of greater than 159 was considered as being significant for necrosis. Thirteen patients were studied. Six patients had significant muscle necrosis (462 ml, S.D. = 280 ml). All except one patient (who had a small amount of muscle necrosis) developed foot drop. Seven patients had no significant necrosis. All patients had normal ankle dorsiflexion. It is possible to quantify regional muscle necrosis using PPi with SPECT. Volume of necrosis determined by this method can also predict clinical outcome.

Aged↗
PubMed1992

Nuclear magnetic resonance spectroscopy of excised human hearts.

BACKGROUND: Phosphorus nuclear magnetic resonance spectroscopy has been proposed as a method of studying the metabolism of the myocardium in patients. Little is known about 31P nuclear magnetic resonance spectroscopy of diseased human hearts. METHODS: Two donor hearts meeting the requirements for heart transplantation and 11 diseased hearts were removed during a transplantation procedure and were studied in a horizontal 2.35 T superconducting magnet. Spectra were obtained at 0 degrees C about 30 minutes after the excision. The areas of the inorganic phosphate peak (Pi) and of the phosphocreatine peak (PCr) were summed and expressed as a ratio with respect to the area of the beta ATP peak. RESULTS: The ratio (Pi + PCr)/beta ATP was found to be significantly lower in five hearts with a myocardial infarct (0.77 (0.18)) than in hearts with dilated cardiomyopathy (1.25 (0.29)) and in normal hearts (1.69 (0.11)). The area of the phosphodiester peak was expressed as a ratio with respect to the area of the beta ATP peak: no differences were found between the three groups. CONCLUSIONS: These results suggest that the phosphocreatine concentration is lower in ischaemic heart disease than in dilated cardiomyopathy and that the phosphodiester peak is probably not useful in distinguishing between these two types of heart disease.

Adenosine Triphosphate↗
PubMed1992

Prolonged adenine nucleotide resynthesis and reperfusion injury in postischemic skeletal muscle.

Skeletal muscle ischemia results in energy depletion and intracellular acidosis. Reperfusion is associated with impaired adenine nucleotide resynthesis, edema formation, and myocyte necrosis. The purpose of these studies was to define the time course of cellular injury and adenine nucleotide depletion and resynthesis in postischemic skeletal muscle during prolonged reperfusion in vivo. The isolated canine gracilis muscle model was used. After 5 h of ischemia, muscles were reperfused for either 1 or 48 h. Lactate and creatine phosphokinase (CPK) release during reperfusion was calculated from arteriovenous differences and blood flow. Adenine nucleotides, nucleosides, bases, and creatine phosphate were quantified by high-performance liquid chromatography, and muscle necrosis was assessed by nitroblue tetrazolium staining. Reperfusion resulted in a rapid release of lactate, which paralleled the increase in blood flow, and a delayed but prolonged release of CPK. Edema formation and muscle necrosis increased between 1 and 48 h of reperfusion (P less than 0.05). Recovery of energy stores during reperfusion was related to the extent of postischemic necrosis, which correlated with the extent of nucleotide dephosphorylation during ischemia (r = 0.88, P less than 0.001). These results suggest that both adenine nucleotide resynthesis and myocyte necrosis, which are protracted processes in reperfusing skeletal muscle, are related to the extent of nucleotide dephosphorylation during ischemia.

Adenine Nucleotides↗
PubMed1992

Phospholipid peroxidation deacylation and remodeling in postischemic skeletal muscle.

Reperfusion of ischemic skeletal muscle is associated with white blood cell (WBC) sequestration and hydroperoxy-conjugated diene (HCF) formation, a marker of free radical-mediated phospholipid peroxidation. The purpose of this study was to define the kinetics of phospholipid fatty acyl peroxidation, deacylation, and remodeling in postischemic skeletal muscle during prolonged reperfusion in vivo, and to determine whether reperfusion with WBC and plasma-depleted blood would attenuate postischemic phospholipid peroxidation and myocyte necrosis. The isolated, paired, canine gracilis muscle model was used. After 5 h of ischemia, muscles underwent unaltered reperfusion or initial reperfusion with WBC-deficient blood cells resuspended in hydroxyethyl starch, followed by return to normal circulation (modified reperfusion). The concentration of native fatty acids and HCDs of linoleic acid extracted from muscle phospholipids was quantified by gas chromatography and positively identified by mass spectrometry. Ischemia and reperfusion resulted in phospholipid deacylation and a selective increase in phospholipid stearic acid content, but had no effect on total phospholipid phosphorus. Modified reperfusion decreased 1) early HCD formation (54%) and 2) postischemic skeletal muscle necrosis (49%). These data suggest that reperfusion results in phospholipid deacylation and remodeling, and that the initial oxidant stress during reperfusion may be a significant determinant of ultimate muscle necrosis.

Acylation↗
PubMed1992

Zinc and iron utilization in young women consuming a beef-based diet.

The purpose of this study was to determine the utilization of zinc in young adult women fed diets containing varying amounts of lean ground beef. A secondary objective was to determine the utilization of iron. The 28-day study was divided into one 7-day preexperimental period, during which a vegetarian diet was fed, and three randomly arranged 7-day experimental periods. During the experimental periods, the diets contained 3, 6, or 9 oz of beef, supplying varying levels of zinc and iron. Complete collections of urine and fecal samples were obtained from each subject. All the diets resulted in positive zinc balance; however, mean zinc balances were significantly higher when subjects consumed the experimental diets containing beef. When data for all diets containing beef were combined, mean values for apparent zinc absorption and zinc retention were not significantly higher than values that resulted from the vegetarian diet. Consumption of all diets resulted in a positive iron balance; however, mean iron balances were significantly higher for diets containing beef. As the amount of beef in the diet increased, the bioavailability of iron increased. We found that zinc and iron utilization was enhanced after consumption of a diet including lean ground beef. Results of this study also suggest that little increase in zinc and iron utilization is realized by including more than 3 oz beef per day in the diet.

Adult↗
PubMed1992

Decreased leukocyte adhesion with anti-CD18 monoclonal antibodies is mediated by receptor internalization.

BACKGROUND: Adhesion of polymorphonuclear leukocytes (PMNs) to endothelial cells is mediated partially by CD11/CD18 integrins. The purpose of this study was to define (1) the response of PMNs to anti-CD18 monoclonal antibody binding, and (2) the mechanism responsible for anti-CD18 monoclonal antibody-mediated decreases in PMN adhesion to endothelial cells. METHODS: Canine PMN O2- production, myeloperoxidase, and lysozyme release in response to the anti-CD18 monoclonal antibody IB4 were measured by standard assays. To examine endocytosis of CD18 receptors, PMNs incubated with IB4 and a fluorescein isothiocyanate secondary antibody were analyzed by flow cytometry. RESULTS: Treatment of PMNs with IB4 did not stimulate O2- production or degranulation but decreased adhesion of 51Cr-labeled PMNs to ex vivo canine aorta. Incubation of PMNs at 25 degrees C resulted in a decrease in fluorescence intensity that was not affected by NaN3 or vanadate but was blocked by NaF, 4 degrees C, and bafilomycin, which prevents endosomal acidification. Treatment with an antifluorescein antibody decreased the fluorescence intensity in NaF and 4 degrees C, but not in bafilomycin-treated neutrophils. CONCLUSIONS: IB4 decreases PMN-endothelial cell adhesion but does not stimulate neutrophil oxidative metabolism or degranulation. These data suggest that reduced adhesion may be the result of internalization of the CD18/IB4 complex. Anti-CD18 monoclonal antibodies may be useful in preventing PMN adhesion without the potentially deleterious effects of cell activation.

Animals↗
PubMed1991

Ischemia/reperfusion injury in skeletal muscle.

Ischemia/reperfusion injury to skeletal muscle may be explained by a cascade of cellular and systemic events initiated by an ischemic period followed by reperfusion. During the period of ischemia there is a gradual reduction of intracellular energy stores. Adenosine triphosphate is gradually depleted despite the buffering effect of creatine phosphate which is present in large stores in muscles. As well, glycogen stores are depleted with resultant production of small amounts of energy and large accumulations of lactate. Upon reperfusion there is a reactive hyperemia, resulting in an overall increase in muscle blood flow, despite the fact that areas may continue to be underperfused. Results of this blood flow are mixed with the beneficial effects of removing metabolic by-products and supplying exogenous substrates and oxygen. However, this blood flow also causes harmful effects by washing out necessary precursors for adenine nucleotide resynthesis. Production of oxygen free radicals occurs with resultant membrane lipid peroxidation, and calcium influx occurs upon reoxygenation with resultant disruption of oxidative rephosphorylation in the mitochondria. The sequestration of white blood cells in the muscle due to up regulation of both neutrophil receptors and endothelial leukocyte adhesion molecules results in a prolongation of the reperfusion injury. This subsequently results in damage to remote organs, including lung, heart, and kidneys. The future for therapeutic interventions aimed at reducing this injury lie mostly in the ability to modulate the reperfusion effect.

Adenosine Diphosphate↗
PubMed1991

Signal-to-noise improvement in mid-field MRI surface coils: a degree in plumbing?

From a series of standard SE imaging sequences, performed on a Bruker 0.28 T imaging system, with the assistance of a healthy volunteer, the image signal-to-noise (S/N) ratio obtained from a 23-cm square surface coil has been shown to increase by up to 38% as the tube gauge is increased from 4 to 18 mm. The reason did not lie solely in the much improved Q factor of the unloaded coils. Despite a more than twofold increase in the unloaded Q factor, the loaded coil Q values only increased by 8%. It would appear, however, that the resistive, dielectric and inductive noise components are all reduced, and hence contribute to the observed improved S/N. The reduction in pure ohmic losses accounts for a quarter of the improved S/N, while the reduced inductive and dielectric losses provide the remaining three quarters. No independent quantification of the two latter noise sources was attempted, although a reduced dielectric contribution is confirmed qualitatively by a reduction in the negative frequency shift of the resonance frequency as a function of increasing coil gauge when the coil is loaded.

Humans↗
PubMed1991

A clinically applicable method for long-term salvage of postischemic skeletal muscle.

The clinical significance and applicability of interventions aimed at reducing reperfusion injury in postischemic skeletal muscle remain unproven, since long-term muscle salvage has not been demonstrated by most treatment protocols that attenuate early reperfusion injury. We have shown that reperfusion of ischemic skeletal muscle results in an early and prolonged sequestration of white blood cells and activation of the alternative complement cascade. The purpose of this study was to determine if 40 minutes of reperfusion with blood depleted of white blood cells and complement proteins, followed by 2 days of normal perfusion, would reduce muscle necrosis after 5 hours of ischemia. The isolated paired canine gracilis muscle model was used. The treatment muscle was initially reperfused with arterial blood that had been spun, washed, passed through a leukocyte removal filter, and resuspended in hydroxyethyl starch (greater than 99.9% removal of white blood cells and the complement proteins factor B and C4). The contralateral control muscle was subjected to unaltered reperfusion. Blood flow (ml/min/100 gm) was measured by timed collection of gracilis venous blood. Myeloperoxidase activity (absorbance at 655 nm/min/mg tissue protein) in muscle biopsies was used to monitor white blood cell sequestration. After 48 hours of reperfusion in vivo, necrosis was quantified by nitroblue tetrazolium staining. Initial reperfusion with white blood cell and complement depleted blood significantly reduced muscle necrosis (53% +/- 3% vs 29% +/- 8%, p less than 0.0025, paired t test). Early blood flow was improved, (p = 0.0025, repeated measure-ANOVA), but subsequent white blood cell sequestration was not altered (p = 0.33, repeated measure-ANOVA). This suggests that a significant amount of white blood cell mediated injury occurs during the first 40 minutes of reperfusion. Preventing early complement activation and white blood cell mediated reperfusion injury is an intervention that is feasible during surgery and may result in clinically significant salvage of postischemic skeletal muscle.

Animals↗
PubMed1990

Improved subtraction technique in intravenous digital left ventriculography: comparison with radionuclide studies.

Adequate processing of left ventricular angiograms depends on the visualisation of all segments of the ventricular wall. At the same time, subtraction of different images can enhance different heart segments but commercially available methods do not allow simultaneous viewing of several images masked by different processes. Using our software, for each studied frame, a four quadrant display permits the simultaneous visualisation of a mask mode image, a diastolic-systolic difference image, an image obtained by subtraction of a frame at the same cycle time and a composite mask subtracted image. The composite mask image is obtained by weighting three images according to videodensitometric measurements by reference to previously acquired data. This method facilitates contour delineation and computation of the ejection fraction by area-length method. Correlation with radionuclide estimates of left ventricular ejection fraction is higher (n = 60, r = 0.90, SEE = 8%) than using the classical mask mode display (n = 60, r = 0.82, SEE = 11%). In a subgroup of 30 patients the contrast medium was injected in an antecubital vein and the correlation coefficient remained satisfactory (n = 30, r = 0.89, SEE = 7%) when compared with the classical subtraction technique (n = 30, r = 0.70, SEE = 12%). We therefore conclude that the composite mask method gives comparatively similar values for left ventricular ejection fraction to those acquired by radionuclide angiography.

Angiography, Digital Subtraction↗
PubMed1990

Exogenous magnesium chloride-adenosine triphosphate administration during reperfusion reduces the extent of necrosis in previously ischemic skeletal muscle.

The lower extremity may be exposed to prolonged periods of ischemia, resulting in depletion of intracellular energy stores in the affected skeletal muscle. The role of adenine nucleotide reduction and failure of resynthesis on reperfusion in determining the extent of muscle necrosis was investigated in this study, in addition to the possible beneficial effects of the addition of exogenous adenosine triphosphate-magnesium chloride during early reperfusion. The isolated paired canine gracilis muscle model was used. After 4 hours of normothermic ischemia in group I, a perfusate Krebs-Henseleit solution plus the gradual reintroduction of oxygenated blood flow was compared to standard reperfusion. In group II, a similar infusion protocol was used, with the addition of 2 mmol/L adenosine triphosphate-magnesium chloride and compared to normal reperfusion. Adenosine triphosphate-magnesium chloride resulted in the salvage of skeletal muscle, 57% +/- 12% versus 44% +/- 14% (p less than 0.05, n = 6 pairs). Reperfusion with the solution alone increased the resulting necrosis (42% +/- 13% vs 60% +/- 20%, n = 6 pairs). Adenine nucleotide stores were not increased, but oxygen consumption was increased by magnesium chloride-adenosine triphosphate (p less than 0.05, analysis of variance [ANOVA]). A clear relationship was demonstrated between the fall in energy stores, as measured by a change in energy charge potential from preischemia to end ischemia levels, and the extent of resulting necrosis (p less than 0.01). In summary, the addition of 2 mmol/L to an infusion of Krebs-Henseleit solution during reperfusion results in significant salvage of skeletal muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗
PubMed1990

The effect of ischemia/reperfusion on adenine nucleotide metabolism and xanthine oxidase production in skeletal muscle.

Prolonged ischemia to skeletal muscle as occurs after an acute arterial occlusion results in alterations in adenine nucleotide metabolism. Adenosine triphosphate continues to be used for cellular functions, and an ischemia-induced degradation of phosphorylated adenine nucleotides is initiated. In this experiment we demonstrated the time-dependent aspect of adenine nucleotide depletion during ischemia and the production of large quantities of soluble precursors. In addition, we studied the rate of conversion of xanthine dehydrogenase to xanthine oxidase, a potential source of oxygen-free radicals, after controlled periods of total normothermic ischemia (4 hours and 5 hours) and during the reperfusion phase. During ischemia complete depletion of creatine phosphate occurred in both groups, and adenosine triphosphate fell from 22.1 +/- 1.3 to 10.3 +/- 1.4 mumol/gm dry weight after 4 hours and from 21.6 +/- 0.7 to 3.9 +/- 0.8 mumol/gm dry weight after 5 hours (p less than 0.05). During reperfusion, creatine phosphokinase resynthesis occurred in both groups, but adenosine triphosphate levels were not significantly increased (p greater than 0.05). A washout of lipid soluble products of adenine nucleotide metabolism occurred equally in both groups. The relationship between phosphorylated adenine nucleotides as measured by the energy charge potential fell significantly in both groups (p less than 0.05), but after the shorter period of ischemia (4 hours it returned to normal during early reperfusion but did not after 5 hours of ischemia. There was 21% +/- 4% necrosis after 4 hours and 51% +/- 8% after 5 hours of ischemic stress when assessed at 48 hours. In conclusion, the degree of adenine nucleotide degeneration as determined primarily by the length of the ischemic period, may be the most important determinant of the ultimate extent of skeletal muscle ischemic necrosis that results from an acute interruption of circulation.

Adenine Nucleotides↗
PubMed1990

Quantitation of skeletal muscle necrosis using 99Tcm-pyrophosphate with SPECT in a canine model.

Patients with acute arterial occlusion may suffer from significant muscle necrosis. It is important to determine the amount of regional muscle necrosis for prognostic purposes and evaluation of therapy. We have used technetium-99m-pyrophosphate (PPi) with single photon emission computed tomography (SPECT) to quantitate muscle necrosis. A canine gracilis muscle ischaemia model was used. PPi was injected 1.5 h before the muscle preparation was removed from the dog. SPECT was performed on the muscle preparations. An automatic edge detection program using the threshold technique determined the number of pixels with significant PPi activity in each transaxial section. Volume was calculated by summing the number of pixels with significant PPi activity and multiplying by the voxel size. The results were compared with quantitation using computerized planimetry with nitroblue tetrazolium staining (correlation coefficient = 0.93). PPi with SPECT is an accurate method for quantiating muscle necrosis.

Animals↗
PubMed1990

Complement activation and white cell sequestration in postischemic skeletal muscle.

After skeletal muscle ischemia, tissue damage is augmented during reperfusion. White blood cells (WBCs) and complement proteins may participate in the reperfusion injury. The purpose of this study was to define the kinetics of classical and alternative pathway complement activation and WBC sequestration by postischemic skeletal muscle during the first 48 h of reperfusion in vivo. The isolated canine gracilis muscle model was used. Systemic levels of the complement proteins factor B (alternative pathway) and C4 (classical pathway) were quantitated by hemolytic assay. WBC sequestration was measured by gracilis arterial-venous WBC differences and tissue myeloperoxidase activity. Reperfusion was associated with an 18% decrease in systemic factor B levels but no consistent change in systemic C4 levels. WBCs were sequestered during the first 4 h of reperfusion, and tissue myeloperoxidase activity was elevated 97-fold after 48 h of reperfusion. These results suggest that skeletal muscle ischemia-reperfusion stimulates 1) activation of the alternative but not the classical complement pathway and 2) an immediate and prolonged sequestration of WBCs.

Animals↗
PubMed1989

A test material for tissue characterisation and system calibration in MRI.

A tissue-equivalent test material for MRI has been produced from a polysaccharide gel, agarose, containing gadolinium chloride chelated to EDTA. By varying the amounts of each constituent, the T1 and T2 of the material can be varied independently. As a result, the entire range of in vivo tissue relaxation times can be covered. Through the mathematical modelling of the 1H relaxation theories for both the gel and chelated paramagnetic ion, it has been possible to create a material with relaxation properties and behaviour predictable as functions of both the Larmor frequency and temperature. The similarity of the material to in vivo tissues, in terms of its biological and physical NMR characteristics, makes it an excellent tissue-equivalent substance, in addition to being an accurate calibration standard for routine MRI.

Edetic Acid↗
PubMed1989

Identification of clinically significant skeletal muscle necrosis by single photon emission computed tomography.

Ischemia-reperfusion damage to skeletal muscle may cause serious local as well as systemic complications, its impact predominantly related to the quantity of ischemic muscle in the lower extremity. To date, there has been no noninvasive method of estimating that quantity. The authors used single photon emission computed tomography (SPECT) to quantify the volume of muscle that takes up technetium-99 pyrophosphate above a baseline threshold. Compared with the standard technique of staining slices of the muscle with nitroblue tetrazolium they found a close correlation using SPECT (r = 0.88, p less than 0.01, n = 19) in the canine model. In humans, this clinically applicable noninvasive technique may allow the surgeon to document accurately the extent of muscle necrosis in the lower extremity, to anticipate the impact of an ischemia-reperfusion injury and evaluate methods of reducing the extent of post-ischemic skeletal muscle necrosis.

Animals↗