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Biomedical subjects

D M Fisher

Publications and source records attributed to D M Fisher.

At least 127 records · Page 7Linked to original sources
PubMed1984

The pharmacokinetics and pharmacodynamics of atracurium in patients with and without renal failure.

To determine the influence of renal function on the pharmacology of atracurium, 10 patients with normal renal function and 10 with renal failure (scheduled for cadaver kidney transplant) were anesthetized with nitrous oxide and halothane. Atracurium besylate, 0.5 mg . kg-1, was given as an iv bolus and plasma samples were collected over a 4-h period. These samples were assayed for atracurium (all patients) and laudanosine, one of the principal metabolites (eight of the normal group), using an ion-exchange liquid chromatographic assay. The plasma concentrations of atracurium for each patient were fitted to a two-compartment pharmacokinetic model. The onset time, duration of action, and recovery time of atracurium neuromuscular blockade were measured. There were no differences found in the pharmacokinetics or pharmaco-dynamics of atracurium between patients with normal renal function and those with renal failure. There were measurable levels of laudanosine following atracurium administration with peak levels of 199 +/- 31 ng . ml-1 at 2 min. The authors conclude that the pharmacokinetics and pharmacodynamics of atracurium are not altered by renal failure.

Anesthesia, General↗
PubMed1983

Composition of, and [14C]acetate incorporation into, lipids of rat Sertoli cells in culture.

Primary cultures of rat Sertoli cells were used for the determination of their lipid and fatty acid composition and for a demonstration of their ability to incorporate 14C from [14C]acetate into fatty acids esterified in the cellular lipids. Similar fatty acid compositions were observed in 9-day cultures of Sertoli cells of rats aged 3, 4 or 5 weeks. Cultures of Sertoli cells of 5-week-old rats had relatively less palmitic, linoleic and arachidonic acids and more palmitoleic, stearic, oleic and docosatetraenoic acids than non-cultured cells from the same pool. No difference between these was observed in phospholipid concentration, but the cultured cells had a greater concentration of both total cholesterol and triacylglycerols than did the non-cultured cells. 14C from [14C]acetate added to the culture medium on the 7th (48-h incubation) or 8th (24-h incubation) day was incorporated into fatty acids esterified in cellular lipids. Major incorporation was into phospholipids and triacylglycerols, but cholesterol also was labeled. The fatty acids containing most of the 14C were the saturated fatty acids, oleic acid and docosatetraenoic acid (products of both de novo synthesis and elongation reactions).

Acetates↗
PubMed1983

Shifting patterns of bilateral coordination and lateral dominance in the leg movements of young infants.

Patterns of interlimb coordination and lateral preference of spontaneous leg kicks were described for 8 normal human infants observed biweekly from 2 to 26 weeks of age. Newborn infants showed a high percentage of alternating movements, which were often supplanted by unilateral movements between 1 and 4 months. Simultaneous (in-phase) kicks matured later than alternating kicks. No consistent lateral preferences were detected. The developmental course was marked by variability and discontinuities within each infant. We propose that asynchronous and asymmetrical maturation of subcortical tracts and/or muscle strength could account for these behavioral shifts.

Arousal↗
PubMed1983

The organization of spontaneous leg movements in newborn infants.

Spontaneous, supine kicking in newborn (2- and 4-week-old) infants is described in terms of its temporal structure, interjoint coordination, and muscle activation characteristics as measured by surface electromyography. Phasic kick movements shoed a constrained temporal organization in the movement, but not the pause phases. Hip, knee, and ankle joints moved in temporal and spatial synchrony, and all three joints showed a rhythmical or periodic organization over time. EMGs revealed antagonist coactivation at the initiation of the flexor movement, but little or not extensor activity. The dorsal muscles, the gastrocnemius and hamstrings, showed less activity than the ventral pair, tibialis anterior and quadriceps. Burst and onset-to-peak durations were also constrained. As a result of neural mechanisms and biomechanical forces, newborn leg movements are structured muscle synergies. This organization has implications both for newborn functioning and for later development.

Journal Article↗
PubMed1983

Pharmacokinetics and pharmacodynamics of vecuronium (ORG NC45) and pancuronium in anesthetized humans.

The pharmacokinetics and pharmacodynamics of vecuronium (25-50 micrograms/kg) and pancuronium (25-50 micrograms/kg) were determined in nine ASA class I or II patients anesthetized with nitrous oxide and halothane. Force of thumb adduction in response to supramaximal stimulation of the ulnar nerve was quantified and recorded. Serum concentrations of the muscle relaxants were determined for eight hours after their administration using a mass spectrometry assay. Data were analyzed by nonlinear regression and fit to a three-compartment pharmacokinetic model and a four-compartment pharmacodynamic model. Vecuronium had a more rapid clearance (5.2 +/- 0.7 ml X kg-1 X min-1; mean +/- SD) and a shorter elimination half-life (71 +/- 20 min) as compared with pancuronium (1.8 +/- 0.4 ml X kg-1 X min-1; 140 +/- 25 min). No other pharmacokinetic differences were found between the drugs. Pharmacodynamic analysis showed that the plasma concentration at steady state which produced a 50% neuromuscular blockade (Cpss 50) was similar for vecuronium and pancuronium. The authors conclude that the drugs are equivalent in their onset and potency; however, the more rapid clearance and shorter elimination half-life for vecuronium provides a kinetic basis for its shorter duration of neuromuscular blockade as compared with pancuronium.

Adult↗
PubMed1983

Neuromuscular effects of vecuronium (ORG NC45) in infants and children during N2O, halothane anesthesia.

The authors determined the neuromuscular effects of vecuronium (ORG NC45, Norcuron) during anesthesia with nitrous oxide and 0.9 MAC halothane. To determine potency, they administered vecuronium (15, 20, or 25 micrograms/kg) to 18 infants (less than 1 year old) and 18 children (1-8 years old). They then compared these dose-response relationships with values obtained for adults (greater than 18 years old) under comparable anesthetic conditions. The ED50S (dose producing 50% depression of adductor pollicis twitch tension) of 16.5, 19.0, and 15.0 micrograms/kg for infants, children, and adults, respectively, did not differ significantly. To determine the time course of neuromuscular blockade, the authors administered vecuronium, 70 micrograms/kg, to six infants, six children, and six adults. Onset time (time to maximal effect) was shortest for infants (1.5 +/- 0.6 min, mean +/- SD) compared with that for children (2.4 +/- 1.4 min) and adults (2.9 +/- 0.2 min). Duration (time from injection to 90% recovery) was longest for infants (73 +/- 27 min) compared with that for children (35 +/- 6 min) and adults (53 +/- 21 min). The authors conclude that vecuronium can be used in infants and children in doses similar to those recommended for adults. The time interval for supplemental doses will be longest in infants and shortest in children.

Adolescent↗
PubMed1983

Factor VIII inhibitor and raised platelet IgG levels associated with methyldopa therapy.

An inhibitor to the plasma coagulation factor VIII and abnormally high levels of platelet associated IgG (PAIgG) were found in a patient whilst on methyldopa. Both these parameters fell on initial withdrawal, but on rechallenge with the drug only the PAIgG rose to the high presenting levels. No inhibitory activity to factor VIIIc could be detected in a concentrated eluate prepared from the patient's platelets. These results may imply that two distinct antibodies were provoked by the administration of methyldopa, but could also be explained by the action of anti VIIIc alone on the patient's platelets.

Aged↗
PubMed1983

From spontaneous to instrumental behavior: kinematic analysis of movement changes during very early learning.

3-month-old infants who can activate a mobile with their spontaneous leg kicks increase their kick rate over baseline. Kinematic analyses of the temporal and topographic characteristics of reinforced leg kicks were compared with those of infants who saw noncontingent mobile movement. In both experimental and control groups, the flexion and extension movement phases of the kick remained remarkably invariant in duration. Pauses between movements varied inversely with rate. Kick amplitude increased with increasing rate except in the extinction phase, where in some infants, kicks became less frequent but more forceful. Movement duration was unaffected by reinforcement condition. By varying amplitude and frequency domains, infants adjusted movement by neuromuscular mechanisms similar to those of mature humans. The experimental imposition of a voluntary component on spontaneous kicking did not alter the modifiability of the movement control parameters.

Conditioning, Operant↗
PubMed1983

Pharmacokinetics and pharmacodynamics of 4-aminopyridine in anesthetized dogs.

The pharmacokinetics and pharmacodynamics of 4-aminopyridine (4-AP), a drug which antagonizes nondepolarizing neuromuscular blockade, were studied in seven anesthetized dogs. Using a constant infusion of pancuronium, force of the anterior tibialis contraction in response to stimulation of the sciatic nerve was depressed to 10% of the control tension (90% depression of twitch tension). After 20 min of steady state, 4-AP (1.0 mg/kg) was administered i.v. Serum, urine and bile samples were analyzed for 4-AP concentration at several intervals for 10 hr after administration of 4-AP, using a sensitive high-performance liquid chromatographic assay (1 ng/ml). Serum data best fit a three-compartment pharmacokinetic model. The volume of the central compartment was 412 +/- 352 ml/kg (mean +/- S.D.) and the volume of distribution at steady state was 2517 +/- 363 ml/kg. Initial half-lives were 1.1 +/- 0.7 and 25.4 +/- 11 min. The terminal elimination half-life was 125 +/- 23 min and total clearance was 21 +/- 4 ml/kg/min. Of the injected dose, 60 +/- 9% was recovered in the urine and only 0.01 +/- 0.01% of the dose was recovered in the bile in 10 hr. Inasmuch as renal clearance of 4-AP exceeded glomerular filtration rate we conclude that 4-AP undergoes tubular secretion into the urine. The pharmacodynamic results included an onset time of 14 +/- 8 min, peak effect (maximum percentage of antagonism of twitch tension depression) 97 +/- 27% and duration of action 219 +/- 54 min. We conclude that 4-AP has a longer serum elimination half-life and a longer and more variable duration of action than other antagonists (i.e., neostigmine and pyridostigmine) of nondepolarizing neuromuscular blockade.

4-Aminopyridine↗
PubMed1982

Effects of body build and arousal on newborn infant stepping.

Newborn stepping is widely believed to be a "primitive reflex" whose disappearance signals cortical maturation. Observations of normal newborns showed that the number of steps was directly related to generalized behavioral arousal. In less highly distressed infants, those who were relatively heavier for their length stepped less. These results challenge the view that stepping is reflexively released by the upright posture and support the hypothesis that the movements disappear because infants' muscle strength may not be sufficient to lift their increasingly heavy legs.

Anesthesia, Obstetrical↗
PubMed1982

Pharmacokinetics and pharmacodynamics of d-tubocurarine in infants, children, and adults.

The pharmacokinetics and pharmacodynamics of d-tubocurarine (dTc) were determined in neonates (0-2 months, n = 7), infants (2-12 months, n = 7), children (1-12 years, n = 9), and adults (12-30 years, n = 8) during 70% nitrous oxide, 0.58 MAC halothane anesthesia. dTc was administered by infusion, while blood for determination of plasma dTc concentrations was obtained, and the EMG of the adductor pollicis recorded. The plasma dTc concentration at which 50% depression of EMG twitch height occurs (Cpss(50)) was 0.18 +/- 0.09 micrograms/ml in neonates, and 0.27 +/- 0.06 micrograms/ml in infants, both significantly lower than the values of 0.42 +/- 0.14 and 0.53 +/- 0.14 micrograms/ml for children and adults, respectively. The steady-state distribution volume (Vdss) was 0.74 +/- 0.33 l/kg in neonates, significantly greater than the values of 0.52 +/- 0.22, 0.41 +/- 0.12, and 0.30 +/- 0.10 l/kg in infants, children, and adults, respectively. The elimination half-life (t beta 1/2) was 174 +/- 60 min in neonates, significantly longer than the values of 90 +/- 23 and 89 +/- 18 min in children and adults, respectively. Plasma clearance did not differ with age. We also determined D50, the product of Vdss and Cpss(50). D50, the quantity of drug present at steady-state to produce 50% paralysis, did not differ between groups. The authors conclude that during comparable nitrous oxide-halothane anesthesia, neonates and infants have an increased sensitivity to dTc, as determined by CPss(50). However, because of the larger Vdss in younger patients, dose size should not differ with age. In addition, because of the longer t beta 1/2 in neonates, second and subsequent doses should be required at less frequent intervals.

Adolescent↗
PubMed1982

Potency determination for vecuronium (ORG NC45): comparison of cumulative and single-dose techniques.

To compare two methods of estimating the potency of neuromuscular relaxants of medium duration, the authors determined the potency of vecuronium (ORG NC45) using cumulative dose-response (CDR) techniques, and compared these data with published values from our group obtained using the single bolus technique. During 60% N2O-halothane anesthesia, patients received 10 micrograms/kg vecuronium; additional incremental doses of vecuronium, 5 micrograms/kg, were given when no change occurred in the height of three successive twitches. Using these dose-response data, the authors determined least-squares regression lines and ED20, ED50, and ED80. These results were compared to values obtained by the single bolus technique under comparable conditions. The CDR and single bolus technique yielded ED50 values of 19.9 and 15.0 micrograms/kg, respectively. All potency estimates by CDR were larger than those obtained by the single bolus dose technique. It was concluded that, for vecuronium, a medium duration neuromuscular relaxant, CDR yields potency estimates which are larger than those obtained by the traditional single bolus dose technique. Because the single bolus dose technique is the accepted method for construction of dose-response curves, the authors recommended that CDR not be used for potency determination of muscle relaxants of medium and short duration such as vecuronium.

Adult↗