The neuromuscular pharmacology of neostigmine in infants and children.
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Adult↗
Biomedical subjects
R D Miller
Publications and source records attributed to R D Miller.
The effects of hypercarbia and hypocarbia on pancuronium and vecuronium neuromuscular blockades in anesthetized humans.
To determine the effects of hypercarbia and hypocarbia on a pancuronium or vecuronium neuromuscular blockade, 54 patients were anesthetized with halothane and 60% nitrous oxide in oxygen. In 30 patients, end-tidal PCO2 was maintained at either 25 mmHg (3.5 kPa, N = 10), 41 mmHg (5.5 kPa, N = 10), or 56 mmHg (7.5 kPa, N = 10). Five patients in each group then were given pancuronium or vecuronium 0.022 mg/kg iv. Neither maximal depressions of twitch tension nor recovery indexes (time for spontaneous recovery of twitch tension from 25 to 75% of control) were altered by hypercarbia or hypocarbia. The remaining 24 patients were divided into three equal groups. Either pancuronium (N = 8) or vecuronium (N = 8) was administered iv as continuous infusion at a rate sufficient to produce a 50% depression of twitch tension. In the remaining eight patients, no muscle relaxant was given. After twitch tension was stable, half of the patients in each group had hypercarbia induced, which depressed twitch tension in all three groups. The patients who received vecuronium had a significantly larger decrease in twitch tension than those who received pancuronium or no muscle relaxant. Conversely, in the remaining patients, hypocarbia produced a significant increase in twitch tension. There was no difference in the magnitude of the increases in twitch tension among the three groups. The authors conclude that pre-muscle relaxant administration-induced hypercarbia or hypocarbia has no effect on a subsequent neuromuscular blockade from pancuronium or vecuronium.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Liability and the supervisor.
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Administrative Personnel↗
Effects of alpha-amylase on in vitro growth of Legionella pneumophila.
Sterile parotid saliva inhibited growth of Legionella pneumophila on solid media, and the salivary component involved in this inhibition has been shown to be amylase. Disk diffusion and well plate assays were used to study possible mechanisms for this effect. The amylolytic activity of saliva copurified with inhibitory activity, and both activities were sensitive to proteinase K digestion and heat treatment. In addition, purified alpha-amylase from several sources (bacteria, fungi, porcine pancreas, and human saliva) exhibited similar activity. Incorporation of charcoal or bovine serum albumin into media blocked inhibition by amylase. Replacement of Bacto-Agar with Noble agar (both from Difco Laboratories) prevented growth inhibition in the absence of starch. However, when corn starch was present with Noble agar, amylase-induced growth inhibition occurred. Purification of starch by washing with methanol eliminated some toxic component. The toxic component from starch could be recovered from the methanol wash and inhibited growth of L. pneumophila in the absence of amylase activity. The results suggest that toxic substances exist in media components which may be unmasked during salivary amylase digestion of starch. This effect may explain, in part, the difficulty in recovery of the organism from clinical specimens containing amylase.
Amylases↗
Intermediary metabolism in Legionella pneumophila: utilization of amino acids and other compounds as energy sources.
The utilization of amino acids and other compounds as carbon and energy sources by Legionella pneumophila was examined. Based on the stimulation of oxygen consumption in washed-cell suspensions, glutamate, serine, threonine, and tyrosine were the only amino acids which were utilized as energy sources. Other stimulators of oxygen uptake were lactate, pyruvate, acetate, fumarate, and succinate. Citrate was a good stimulator only when the bacteria were grown in the presence of the substrate. Radiolabeling studies showed that [14C]glutamate was rapidly metabolized, with the label distributed evenly in all cell fractions. [14C]pyruvate and [14C]acetate were incorporated into the lipid-containing cell fraction, whereas glucose and glycerol were found in both the lipid- and polysaccharide-containing cell fractions. Radiorespirometry of differentially labeled [14C]glucose indicated that this compound was metabolized primarily by the pentose phosphate and Entner-Doudoroff pathways rather than by the glycolytic pathway.
Acetates↗
Arginine biosynthesis in Legionella pneumophila: absence of N-acetylglutamate synthetase.
Legionella pneumophila was unable to grow in a chemically defined medium without arginine because it could not carry out the first step in the biosynthetic pathway, the conversion of glutamate to N-acetylglutamate. All strains examined could grow when N-acetylglutamate (or other later arginine precursors) were substituted for arginine. No activity corresponding to N-acetylglutamate synthetase could be detected in cell extracts of L. pneumophila.
Acetyltransferases↗
Characteristics of schizophrenic and depressed patients excluded from clinical research.
The process of selecting patients for research studies introduces factors that can bias outcome. The authors compared schizophrenic and depressed patients accepted for studies on their clinical research unit with patients admitted to the hospital with the same diagnoses. They found significant differences between the two groups in age, sex, and legal status. The authors conclude that many research populations may not be representative of general patient populations for a number of reasons and argue that research studies also need to focus on patients who do not meet research ward criteria.
Adult↗
Emergency involuntary commitment: a look at the decision-making process.
Emergency involuntary commitment is provided in a majority of states to allow for rapid response to patients who are acutely violent and must be hospitalized quickly. The authors investigated the use of emergency hospitalization in North Carolina and found that the majority of petitions executed by law-enforcement officers did not provide adequate evidence for the required criteria. In fact, in many cases the authors noted a marked absence of such criteria. The authors discuss these results and possible reasons for the misuse of the emergency commitment provisions. They stress the importance of cooperation between community mental health professionals and law-enforcement officials in the evaluation of disruptive individuals who may be mentally disordered.
Commitment of Persons with Psychiatric Disorders↗
New muscle relaxants.
There are many new neuromuscular blocking drugs now going through the clinical trials required before new drugs can be used clinically on a routine basis. It is safe to say that within the next five years the muscle relaxants now in common use will be replaced by new and more "ideal" muscle relaxants. This review has attempted to define for the practicing anesthesiologist the goals of muscle relaxant research and the drugs that have been developed from that research. It is hoped that some familiarity with these drugs before they become widely available may hasten their extensive use by practitioner in the interest of better anesthetic patient care.
Androstane-3,17-diol↗
The effect of witnesses, attorneys, and judges on civil commitment in North Carolina: a prospective study.
A total of 388 commitment hearings were observed and analyzed for demographic information on patients, name of judge, duration of hearing, identities of those present and those actually testifying, outcome of any procedural challenges, and concurrence of the judges with attorney and physician recommendations. Age, race, and gender of the patient were found to have no significant effect on the outcome of the cases. Disposition of the cases correlated with recommendations by physicians, witnesses, and state attorneys in an overwhelming number of cases. Possible harmful influences of plea-bargaining in commitment hearings are discussed.
Commitment of Persons with Psychiatric Disorders↗
Judicial oversight of release of patients committed after being found not competent to stand trial or not guilty by reason of insanity in violent crimes.
In 1981, North Carolina joined a growing number of states in passing legislation requiring judicial concurrence with discharge decisions for civilly committed patients who had been found either not competent to proceed to trial or not guilty by reason of insanity. The authors studied all such patients at one of North Carolina's four state mental hospitals during the first year of the new law's operation, and found that there were only 16 of them. These patients were compared to a control sample of civilly committed patients without criminal charges; it was found that the forensic patients spent longer in the hospital than the controls, but still significantly less time than reported in studies from other states. The authors discuss possible reasons for these differences and comment on the effectiveness of such legislation.
Adult↗
Neuromuscular and cardiovascular effects of atracurium during nitrous oxide-fentanyl and nitrous oxide-isoflurane anaesthesia.
The neuromuscular and cardiovascular effects of atracurium were compared during nitrous oxide-isoflurane and nitrous oxide-fentanyl anaesthesia in healthy surgical patients. The dose-response curve was shifted significantly to the left during nitrous oxide-isoflurane anaesthesia (ED50 0.068 mg kg-1) as compared with nitrous oxide-fentanyl anaesthesia (ED50 0.083 mg kg-1). For equipotent doses, the time course of neuromuscular effects (onset and duration) was not appreciably different between the nitrous oxide-isoflurane group and the nitrous oxide-fentanyl group. Minimal cardiovascular effects were observed from atracurium in doses up to 0.5 mg kg-1. Using comparisons from earlier studies, atracurium was approximately one-quarter as potent as pancuronium and vecuronium (Org NC 45). The onset time (time from injection to peak effect) for subparalytic doses of atracurium was approximately 6.5 min and is comparable to the onset time for equipotent doses of pancuronium and vecuronium. The duration of neuromuscular effects of atracurium (time from injection to 95% recovery) was approximately 20 min for subparalytic doses and is the same as that of vecuronium and one-third to one-half that of pancuronium. It is concluded that the peak effect of atracurium is enhanced more by nitrous oxide-isoflurane than by nitrous oxide-fentanyl anaesthesia, but for equipotent doses the time-course is the same.
Anesthesia, General↗
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↗
Comparison of thiopental and midazolam on the neuromuscular responses to succinylcholine or pancuronium in humans.
Midazolam (0.3 mg/kg) was compared to thiopental (4.0 mg/kg) for possible interactions with succinylcholine or pancuronium when used for induction of anesthesia. Neuromuscular function was monitored by recording the force of thumb adduction in response to ulnar nerve stimulation. Following induction of anesthesia with either midazolam (N = 10) or thiopental (N = 10), stable muscle-twitch tension was obtained and succinylcholine (1 mg/kg) was given intravenously. The duration of blockade, recovery time, intensity of fasciculations, or adequacy of relaxation for tracheal intubation did not differ between patients receiving midazolam or thiopental. An additional group of patients anesthetized and monitored in the same manner received pancuronium (0.025 mg/kg) in incremental doses until a 99% depression of muscle-twitch tension was obtained. Dose-response curves for pancuronium, duration of blockade, and adequacy of relaxation for tracheal intubation did not differ between patients receiving midazolam (N = 10) or thiopental (N = 10). We conclude that the neuromuscular blockade produced by succinylcholine or pancuronium was no different in patients receiving either midazolam or thiopental for induction of anesthesia.
Anesthesia, Intravenous↗
Changes in North Carolina civil commitment statutes: the impact of attorneys.
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Alcoholism↗
Ion-pair high-performance liquid chromatographic assay of 4-aminopyridine in serum.
An assay for the quantitative estimation of 4-aminopyridine in biological fluids has been developed using 2-aminopyridine as internal standard and ion-pair reversed-phase (C18) high-performance liquid chromatography with detection at 263 nm. A 7.5% solution o acetonitrile in water containing tetrabutylammonium iodide and sodium heptanesulfonate buffered at pH 3.0 provided excellent separation of the analytes from each other and from an interfering peak that was occasionally observed in the outdated human sera used in these studies. Sensitivity, specificity, precision, accuracy and reproducibility all were judged sufficient for the routine use of this assay for pharmacokinetic and pharmacodynamic studies.
4-Aminopyridine↗
Atypical depression.
The term atypical depression generally indicates either depression accompanied by severe anxiety (type A) or by atypical vegetative symptoms, ie, increased appetite, weight, sleep, or libido (type V). Early age at onset, predominance in women, outpatient status, mild intensity, rarity of attempted suicide, nonbipolarity, nonendogenicity, and minimal psychomotor change are common to both types. Some types of bipolar depression may be considered as atypical if accompanied by reversed vegetative change. Monoamine oxidase inhibitors are more effective than placebo in treating atypical depression, but their reported superiority to tricyclic antidepressants awaits confirmation, for which the development of appropriate operational criteria would be helpful. Atypical depression is a term that covers several types of depressive disorder and can, for the most part, be better defined using the standard nomenclature.
Adult↗
Defective excision of pyrimidine dimers and interstrand DNA crosslinks in rad7 and rad23 mutants of Saccharomyces cerevisiae.
Excision of pyrimidine dimers and interstrand DNA crosslinks was examined in the deletion mutants rad7-delta 1, rad23-delta 1, and rad7-delta 1 rad23-delta 1. These mutants remove pyrimidine dimers and crosslinks much less efficiently than the RAD+ strains; only 30-60% of pyrimidine dimers and 25-40% of crosslinks are removed even after prolonged incubation. The rad7 and rad23 mutations may represent defects in protein factors which increase the efficiency of the nicking enzyme complex or make chromatin more accessible to the nicking activity.
Biological Evolution↗