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Biomedical subjects

K W Miller

Publications and source records attributed to K W Miller.

At least 163 records · Page 9Linked to original sources
PubMed1978

The pressure reversal of a variety of anesthetic agents in mice.

The aim of this work was to study in mammals the ability of high pressures to reverse the anesthesia produced by a wide range of general anesthetics. Dose-response curves were obtained using mice at pressures ranging from 1 to 125 atm for five agents, namely alpha-chloralose, ethylcarbamate, phenobarbital and, for comparison, nitrogen and argon. The increase of ED50 was found to be a linear function of pressure in each case, but the proportionate increases in ED50 with pressure were greater for the three non-inhalation agents than for the two gases. Thus, the ratio of ED50 at 100 atm to that at 1 atm was 1.74 for alpha-chloralose, 1.68 for ethylcarbamate, and 1.54 for phenobarbital. On the other hand, the corresponding ratios for argon and nitrogen were only 1.36 and 1.34. The potencies of three short-acting agents (trichloroethanol, ketamine, and alphadione) were shown to increase with decreasing pressure, although ED50 values could not be obtained. It is concluded that pressure reverses the actions of a wide variety of anesthetics in mice. The results of this study are not inconsistent with either the fluidized lipid membrane or the critical volume hypotheses of anesthetic action.

Alfaxalone Alfadolone Mixture↗
PubMed1978

Naloxone has no effect on nitrous oxide anesthesia.

It has been reported that naloxone antagonizes general anesthesia in rats when the tail clamp is used as a painful stimulus to assess anesthesia. The authors' hypothesis is that this antagonism is to the analgesic component of anesthesia only, and that anesthesia assessed by a non-painful stimulus would not be antagonized by naloxone. Therefore, the anesthetic potency of nitrous oxide in mice was measured using loss of the righting reflex as a non-painful stimulus. Naloxone, 2 and 16 mg/kg, intraperitoneally, failed to antagonize nitrous oxide anesthesia measured 14--39 min after injection. Thus, 19 min after injection of naloxone, 2 mg/kg, the nitrous oxide ED50 was 1.25 +/- 0.0600 atm (n = 35), compared with 1.19 +/- 0.059 atm (n = 35) after injection of saline solution (control). Following naloxone, 16 mg/kg, the nitrous oxide ED50 was 1.18 +/- 0.059 atm (n =35), compared with 1.22 +/- 0.059 atm (n = 35) for saline solution. At neither dose of naloxone was the ED50 different from the control ED50, a finding that supports the author's hypothesis.

Anesthesia, Inhalation↗
PubMed1977

Oral aminophylline therapy. Increased dosage requirements in children.

While monitoring oral aminophylline (theophylline ethylenediamine) therapy, larger doses (milligrams per kilogram) were necessary for children than for adults to achieve similar therapeutic serum levels. The mean apparent theophylline clearance (ATC) determined in 59 children was significantly higher (P less than .001) than determined in 114 adults (84.8 versus 51.4 ml/hr/kg). Additionally, the younger children (1 to 9 years) eliminated theophylline more rapidly than the older children (0 to 18 years) (93.8 versus 77.3 ml/hr/kd). When initiating continuous oral aminophylline therapy, dosage guidelines, based on the mean ATC calculated for each group, were predicted, and trough theophylline serum levels of 10mug/ml were obtained. The guidelines for aminophylline were 28.0, 23.2, and 15.6 mg/kg/day administered in four divided doses for the younger children, older children, and adults, respectively. Monitoring of serum levels is suggested to further individualize the patient's aminophyline therapy.

Administration, Oral↗
PubMed1977

The dependence of the lipid bilayer membrane: buffer partition coefficient of pentobarbitone on pH and lipid composition.

1 The membrane/buffer partition coefficient of [14C]-pentobarbitone has been determined as a function of the lipid composition of bilayer membranes. 2 A new technique based on ultrafiltration gave comparable results to conventional techniques but required less time for equilbration. 3 The membrane/buffer coefficient was independent of pentobarbitone concentration in the range studies. 4 The apparent partition coefficient varied with pH and was a linear function of the degree of dissociation of pentobarbition. 5 Both the charged and uncharged forms of pentobarbitone partitioned into the membrane, the latter to a much greater extent than the former. 6 At low pH the highest partition coefficient observed was in egg phosphatidylcholine bilayer membranes. 7 Incorporation of cholesterol or phosphatidic acid into phosphatidylcholine membranes greatly reduced the partition coefficient. 8 High pressures do not greatly change these partition coefficients.

Buffers↗
PubMed1977

The opposing physiological effects of high pressures and inert gases.

The physiological effects on mammals of elevated pressures (approximately 100 atmospheres) must be considered in the context of the inert gases breathed. The most striking effect of pressure per se is a central hyperexcitability manifest at first by trembling of the entremities and finally by convulsions. Paralysis and death occur at higher pressures. The primary effects of the inert gases breathed are inert gas narcosis and general anesthesia. The exciting effects of pressure per se and the depressive effects of the inert gases tend to oppose each other. Thus consciousness may be restored to anesthetized mice by raising the pressure, and conversely the threshold pressure that causes convulsions is elevated in the presence of anesthetics. These mutually antagonistic effects can be rationalized in terms of model which proposes that both anesthetics and pressure non-specifically perturb thelipid bilayer regions of neutral membranes. This model is termed the critical volume hypothesis. Anthesthetics dissolve in and expand these lipid bilayer regions, while pressure causes mechanical compression. Expansion leads to anesthesia and compression to convulsions if a critical degree of change is achieved. At elevated partial pressures of inert gas the gas-induced expansion is opposed by the compression of pressure per se. With very insoluble gases, such as helium, this expansion is so small that net compression results and the effects of helium differ little from those of pressure per se. With more soluble gases, such as nitrogen, net expansion results in inert gas narcosis and anesthesia. The critical volume hypothesis enables "safe" mixtures of "expanding" and "compressing" gases to be defined. These enable higher pressures to be better tolerated by mammals.

Anesthesia↗
PubMed1975

The effect of pressure and the volume of activation on the monovalent cation and glucose permeabilities of liposomes of varying composition.

Measurement of the cation permeability of phospholipid microvesicles as a function of pressure confirmed that a single rate-determining step occurred in each case. The volume of activation was 20 ml-mole minus 1 for Na+ and K+, and about 40 ml-mole minus 1 for valinomycin-mediated K+ permeability. It was virtually independent of membrane composition. The results were explained in terms of Träuble's theory of kink-substrate dissociation at the membrane interface involving possible 2gl and 2g2 kink isomers. The volume of activation for D-glucose was 37 ml-mole minus 1, which was not significantly different from that for any of the valinomycin-mediated K+ permeabilities. However, other data suggest that the rate-limiting steps for the sugar and cation permeabilities are not the same.

Binding Sites↗
PubMed1975

The Bristol Pyelonephritis Registry: 10 years on.

The reasons for the initiation and the basic structure of the Bristol Pyelonephritis Registry have been discussed. The detailed follow-up data on those patients clinically at "renal risk" has been noted, with a demonstrably low incidence of proven bacterial infection, no radiological progression and minimal interference with pregnancy. Satisfactory and reassuring information has thus accrued for the first time in a particular group of patients with often severe recurrent symptoms.

Adolescent↗
PubMed1974

Inert gas narcosis, the high pressure neurological syndrome, and the critical volume hypothesis.

The hypothesis that general anesthesia or pressure-induced convulsions occur when a hydrophobic region is expanded or compressed, respectively, by critical amounts is consistent with recent data obtained with mice. Calculations show that anesthesia occurs at an expansion of 1.1 percent and convulsions at a compression of 0.85 percent, the latter site of action being more compressible.

Anesthesia, General↗