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Biomedical subjects

D R Bevan

Publications and source records attributed to D R Bevan.

At least 127 records · Page 7Linked to original sources
PubMed1985

Effect of particulates on metabolism and mutagenicity of benzo[a]pyrene.

Mechanisms of co-carcinogenicity of particulates, such as iron oxide and asbestos, and benzo[a]pyrene (B[a]P) are not completely understood. Particulates dramatically alter rates of uptake of B[a]P into membranes, a factor which could account for co-carcinogenicity. However, B[a]P must be activated to reactive forms to be carcinogenic and mutagenic so alterations in metabolism of B[a]P by particulates also could result in co-carcinogenesis. To elucidate mechanisms of particulate-B[a]P co-carcinogenesis, we have correlated rates of uptake of B[a]P into microsomes with metabolism of B[a]P and with mutagenicity of B[a]P in the Ames test. In general, aryl hydrocarbon hydroxylase (AHH) activity paralleled rates of uptake of B[a]P, though some inhibition of AHH activity by particulates which was not attributable to availability of B[a]P was evident. This inhibition was studied further by assaying separately mixed function oxidase and epoxide hydrase activities in the presence of particulates. Both chrysotile and iron oxide inhibited O-deethylation of 7-ethoxyresorufin and hydration of B[a]P-4,5-oxide. To determine effects of this inhibition on activation of B[a]P to reactive forms, we studied profiles of metabolites of B[a]P and mutagenicity of B[a]P. The only alteration in profiles of B[a]P metabolites produced by particulates was that due to effects on rates of uptake. Similarly, mutagenicity of B[a]P was positively correlated with rates of uptake into microsomes. We conclude that the predominant effects of chrysotile and iron oxide are in altering rates of uptake of particle-adsorbed B[a]P. Changes in uptake rates then result in alterations of B[a]P metabolism and mutagenicity.

Adsorption↗
PubMed1985

Fusion of phospholipid vesicles induced by Zn2+, Cd2+, and Hg2+.

The capacity of Zn2+, Cd2+, or Hg2+ to induce fusion of phospholipid vesicles composed of 50%/50%, 60%/40%, or 80%/20% dipalmitoyl phosphatidylcholine (DPPC)/bovine brain phosphatidylserine (PS) was investigated and compared to that of Ca2+ and Mg2+. In vesicles composed of 50%/50% or 60%/40% DPPC/PS, Zn2+ and Cd2+-induced fusion at concentrations considerably lower than were required for Ca2+-induced fusion. Only limited fusion of 80%/20% DPPC/PS vesicles occurred and Zn2+ was more effective than Ca2+ or Cd2+ in inducing fusion of these vesicles. Mg2+ and Hg2+ did not induce fusion in any of the vesicle systems.

Animals↗
PubMed1985

Accelerated onset of pancuronium with divided doses.

To determine the consequences of administering neuromuscular relaxants in divided doses, pancuronium was given either in a single dose, 0.07 mg X kg-1, or in an initial dose of 0.007 mg X kg-1 followed three minutes later with 0.063 mg X kg-1. When the drug was administered in divided dosage the onset time was reduced, the block was more intense and its duration of action was prolonged. It is suggested that such changes may be advantageous in the provision of rapid intense paralysis.

Anesthesia, General↗
PubMed1985

In vitro technique to study elution of benzo[a]pyrene from particulates into biomembranes with application to woodstove particulates.

A method to study elution of benzo[a]pyrene (B[a]P) from carbonaceous particulates into phospholipid vesicles composed of dimyristoyl phosphatidylcholine (DMPC) was developed. Recoveries of B[a]P at each step of the procedure were quantified, with overall recoveries being 81%. Application of the technique to elution of B[a]P from woodstove particulate revealed that 25% of B[a]P associated with the particulate was eluted into DMPC vesicles in 18 h. From data obtained, it also was possible to evaluate elution of another polycyclic aromatic hydrocarbon (PAH), benzo[k]fluoranthene (B[k]F). Of the total B[k]F associated with woodstove particulate, 68% was eluted. This technique provides a convenient method for evaluating the potential bioavailability of PAH associated with other carbonaceous particulates which occur in the environment.

Air Pollutants↗
PubMed1985

Elution of benzo[a]pyrene from carbon blacks into biomembranes in vitro.

Elution of benzo[a]pyrene (BaP) from carbon blacks into phospholipid vesicles composed of dimyristoyl phosphatidylcholine (DMPC) or dipalmitoyl phosphatidylcholine (DPPC) was investigated. Samples of rubber-grade carbon blacks designated N-234, N-339, N-351, and N-375 containing exogenously adsorbed BaP were prepared by solvent extracting endogenous compounds from the carbon blacks and then readsorbing BaP at the desired concentrations. Concentrations of exogenous BaP on the carbon blacks were approximately 100-fold higher than normally occur on commercial carbon blacks, but the higher levels were used to improve the ability to detect elution of BaP into membranes. Elution of BaP from carbon blacks was studied using a fluorescence spectroscopic technique that allowed continuous monitoring of the elution process. Elution from N-234 was below detection limits of our system. Elution of BaP from N-339, N-351, and N-375 into DMPC and DPPC vesicles occurred in a biphasic manner. Elution occurred within 60 min of mixing carbon blacks with vesicles, although not all BaP was eluted from the particles. When the concentration of BaP adsorbed to N-375 was reduced, the rate and extent of elution were lowered. Extent of elution of of BaP in these experiments may be greater than that of endogenous BaP on commercial carbon blacks because of the considerably higher quantities of exogenous BaP present. Furthermore, solvent extraction of endogenous materials prior to readsorption of BaP may alter the adsorption characteristics. However, methods developed in these experiments will facilitate future studies of the bioavailability of endogenous BaP on carbon blacks, especially in terms of determining the experimental conditions under which elution may occur.

Adsorption↗
PubMed1985

Attempted acceleration of the onset of action of pancuronium. Effects of divided doses in infants and children.

The study was designed to determine whether the onset of action of pancuronium in infants and children could be accelerated by its administration in divided doses. Sixty paediatric patients (0-1 yr (n = 20); 1-3 yr (n = 20); 3-10 yr (n = 20)) were studied during nitrous oxide-oxygen-halothane anaesthesia using train-of-four stimulation, and the results were compared with data obtained previously in adults. The time to onset correlated with the patient's age, and an additional, small acceleration was produced following divided doses which did not alter the duration or pattern of neuromuscular blockade. It was concluded that, in children, divided doses of pancuronium are unlikely to offer important clinical advantages.

Anesthesia, Inhalation↗
PubMed1985

The potencies of edrophonium and neostigmine as antagonists of pancuronium.

Dose response curves were constructed for edrophonium and neostigmine when used to antagonise pancuronium, 0.07 mg/kg during thiopentone-nitrous oxide-halothane anaesthesia. The antagonist was given when 10% twitch height had been restored and the effect was measured 10 minutes later. Recoveries to 50% and 90% twitch height were achieved with 167 and 828 micrograms/kg of edrophonium, and 10.5 and 51 micrograms/kg of neostigmine. The dose response curves were parallel and neostigmine was 16 times more potent than edrophonium. Combinations of equipotent doses of edrophonium and neostigmine were also administered and produced additive but not synergistic effects. It is concluded that either edrophonium or neostigmine may be used for the reversal of pancuronium neuromuscular blockade, but the combination of the two offers no advantage.

Adolescent↗
PubMed1985

Partitioning of respiratory mechanics in halothane-anesthetized humans.

In five spontaneously breathing anesthetized subjects [halothane approximately 1 minimal alveolar concentration (MAC), 70% N2O, 30% O2], flow, changes in lung volume, and esophageal and airway opening pressure were measured in order to partition the elastance (Ers) and flow resistance (Rrs) of the total respiratory system into the lung and chest wall components. Ers averaged (+/- SD) 23.0 +/- 4.9 cmH2O X l-1, while the corresponding values of pulmonary (EL) and chest wall (EW) elastance were 14.3 +/- 3.2 and 8.7 +/- 3.0 cmH2O X l-1, respectively. Intrinsic Rrs (upper airways excluded) averaged 2.3 +/- 0.2 cmH2O X l-1 X s, the corresponding values for pulmonary (RL) and chest wall (RW) flow resistance amounting to 0.8 +/- 0.4 and 1.5 +/- 0.5 cmH2O X l-1 X s, respectively. Ers increased relative to normal values in awake state, mainly reflecting increased EL. Rw was higher than previous estimates on awake seated subjects (approximately 1.0 cmH2O X l-1 X s). RL was relatively low, reflecting the fact that the subjects had received atropine (0.3-0.6 mg) and were breathing N2O. This is the first study in which both respiratory elastic and flow-resistive properties have been partitioned into lung and chest wall components in anesthetized humans.

Adult↗
PubMed1985

Elution of polycyclic aromatic hydrocarbons from carbon blacks into biomembranes in vitro.

Elution of endogenous polycyclic aromatic hydrocarbons (PAH) from four carbon blacks into biomembranes was investigated in vitro. Membrane systems employed were phospholipid vesicles composed of dimyristoyl phosphatidylcholine (DMPC), rat lung homogenate, and simulated lung surfactant. Amounts of benzo[a]-pyrene which were eluted from carbon blacks were not dependent on the type of membrane, but elution was dependent on the type of carbon black. Elution of B[a]P was detected from only 2 of the carbon blacks and amounts eluted represented only 0.2% to 0.6% of total B[a]P associated with those carbon blacks. The largest amount of B[a]P was eluted from the carbon black with lowest surface area and highest endogenous B[a]P content. Benzo[ghi]perylene also was eluted from carbon blacks though amounts eluted again represented extremely small fractions (0.1-0.2%) of the total on the particles. From these experiments, it appears that only very small quantities of B[a]P and other PAH on carbon blacks are bioavailable.

Animals↗
PubMed1985

Antagonism of phase II succinylcholine block by neostigmine.

The neuromuscular effect of neostigmine, 1.25 mg/70 kg, was assessed in 40 adult patients 10 min after cessation of a succinylcholine infusion. The patients had received a thiopental-nitrous oxide anesthetic supplemented by halothane or fentanyl during which they were given at least 5 mg/kg succinylcholine over more than 90 min. Train-of-four monitoring was used. Neostigmine accelerated recovery of neuromuscular function in all patients. The degree of recovery was directly related to the train-of-four ratio, and the results in patients who had received halothane were no different from those who had received fentanyl. The findings are compatible with the hypothesis that phase I block depends upon the presence of circulating succinylcholine and decreases as the latter is cleared, whereas phase II block decreases more slowly. Thus succinylcholine block can be antagonized by neostigmine if enough time is allowed for phase I block to disappear and for a pure phase II block to be present.

Adult↗
PubMed1984

Vecuronium in renal failure.

Neuromuscular blockade during surgery was provided with vecuronium in 24 adult patients in end-stage renal failure and in 21 normal patients who served as controls. Dose response curves were constructed which showed that the effective doses required to produce 50, 90 and 95 per cent neuromuscular blockade in patients with renal failure were 27.5, 43 and 49 micrograms X kg-1 respectively. These were not significantly different from the doses of 31, 49 and 57 micrograms X kg-1 in the normal patients. Repeated small doses of 0.01 mg X kg-1 had a significantly longer duration of action and were associated with some cumulation in the renal failure group. Recovery from the block occurred rapidly after neostigmine, was no different in renal failure and was not associated with recurarization. It is concluded that, when given to subjects in renal failure, vecuronium offers advantages over established agents such as shorter duration of action and easy reversibility.

Adult↗
PubMed1984

Role of renin-angiotensin system in cardiopulmonary bypass hypertension.

The role of the renin-angiotensin system in the aetiology of perioperative hypertension was studied in 15 previously normotensive patients undergoing coronary artery surgery and anaesthetized with fentanyl. Measurements of plasma renin activity were made at intervals before and during cardiopulmonary bypass (CPB). In addition, angiotensin II blockade with saralasin was used in an attempt to treat hypertension during CPB. Nine of the patients became hypertensive (increase in systemic pressure of more than 20 per cent) before CPB and although the mean plasma renin activity was higher in this group than in the normotensive patients it was within normal limits for each group. Hypertension during CPB (mean blood pressure greater than 100 mmHg at 1.8 l X m-2 flow), occurred in seven patients but was not associated with increased renin activity and did not respond to saralasin in doses up to 20 micrograms X kg-1 X min-1. It is concluded that cardiopulmonary bypass associated hypertension is not mediated by activation of the renin-angiotensin system.

Angiotensin II↗
PubMed1984

Differential effects of myoneural blocking drugs on neuromuscular transmission in infants.

Equipotent, paralysing doses of pancuronium and tubocurarine were administered to 40 patients, aged from 1 day to 12 months, during nitrous oxide, oxygen and fentanyl anaesthesia. Neuromuscular activity was measured during onset and recovery from paralysis using train-of-four stimulation. At the same depression of the first stimulus of the train, the train-of-four ratio was decreased more during recovery than during onset with each drug and more with tubocurarine than with pancuronium. These results are qualitatively similar to those found in adults, but the decrease in train-of-four ratio was less in infants. Thus, it is concluded that prejunctional neuromuscular activity, recognized as fade in response to train-of-four stimulation, can be detected after administration of pancuronium or tubocurarine to infants, but that it is less marked than in adults.

Anesthesia, General↗
PubMed1984

Muscle electromechanical correlations during succinylcholine infusion.

The study was designed to compare the electromyographic (EMG) and evoked twitch tension (TT) responses in humans to train-of-four stimulation during neuromuscular blockade induced with a continuous succinylcholine infusion. Mean values of TT correlated well with EMG (r greater than 0.97), but several consistent discrepancies were noted. After the infusion was started but before the block was established, TT increased by up to 38%, which was accompanied by changes in the EMG signal indicative of repetitive activity. After stopping the infusion, TT but not EMG recovered to values greater than control, without changes in the shape of the EMG signal during the period of observation. This TT augmentation during recovery is consistent with a change in the contractile properties of muscle. Detection of phase II block was similar with EMG and TT (38.2 vs 41.3 min). Clinically, EMG and TT may be used interchangeably to evaluate neuromuscular blockade. In the research setting, the synchronous recording of both may help in understanding the mechanism of action of muscle relaxant drugs.

Adult↗
PubMed1983

Succinylcholine apnoea: attempted reversal with anticholinesterases.

Anticholinesterases were administered in an attempt to antagonize prolonged neuromuscular blockade following the administration of succinylcholine in a patient later found to be homozygous for atypical plasma cholinesterase. Edrophonium 10 mg, given 74 min after succinylcholine, when train-of-four stimulation was characteristic of phase II block, produced partial antagonism which was not sustained. Repeated doses of edrophonium to 70 mg and neostigmine to 2.5 mg did not antagonize or augment the block. Spontaneous respiration recommenced 200 min after succinylcholine administration. It is concluded that anticholinesterases are only partially effective in restoring neuromuscular function in succinylcholine apnoea despite muscle twitch activity typical of phase II block.

Adult↗
PubMed1983

Neuromuscular blockade in infants following intramuscular succinylcholine in two or five per cent concentration.

This study determined the characteristics of the neuromuscular block which followed intramuscular succinylcholine 4 mg . kg-1 in 20 infants during halothane anaesthesia. The infants were divided into two groups of ten; the first received succinylcholine in two percent solution and the second in five per cent solution. The mean maximum depression of the first twitch of the train-of-four (T1) was 89.7 +/- 5.0 per cent in 4.0 +/- 0.6 min, and the mean full recovery of T1 occurred in 15.6 +/- 0.9 min after injection. The maximum block achieved and the onset and recovery times were not affected by the concentration used. Depolarizing block, with equal depression of all twitches of the train-of-four was observed during the onset of neuromuscular blockade. During recovery, phase II block, as determined by a train-of-four ratio (T4/T1) of 0.5 or less, occurred frequently at T1 recovery of 25-50 per cent, but was not associated with prolonged paralysis. It is concluded that the onset time of 4 min for intramuscular succinylcholine 4 mg . kg-1 may be too long for emergency use in infants, and no improvement is obtained by increasing the concentration of injected succinylcholine from two to five per cent.

Adjuvants, Anesthesia↗