Biomedical subjects
R D Miller
Publications and source records attributed to R D Miller.
Neuromuscular effects of atracurium during halothane-nitrous oxide and enflurane-nitrous oxide anesthesia in humans.
To compare the effect of halothane and enflurane on an atracurium-induced neuromuscular blockade, the authors studied 40 patients during elective surgery. During 1.25 MAC enflurane-nitrous oxide (n = 20) or halothane-nitrous oxide (n = 20) (MAC value includes contribution from 60% nitrous oxide), the doses depressing twitch tension 50% (ED50S) for atracurium were 70 and 77 micrograms/kg, respectively. The difference was not significant. Time from injection to peak effect did not differ between groups. However, the duration of action of atracurium (expressed as duration 50 or the duration of a 50% blockade) was longer during enflurane-nitrous oxide anesthesia (34.2 min) than during halothane-nitrous oxide anesthesia (25.5 min) (P less than 0.05). The authors conclude that the potency of atracurium does not differ during halothane-nitrous oxide and enflurane-nitrous oxide anesthesia. Combining the results of this study with a previous study (atracurium ED50 = 68 micrograms/kg and 83 micrograms/kg during isoflurane-nitrous oxide and fentanyl-nitrous oxide anesthesia respectively), the potency of atracurium does not differ by more than 20% among the four anesthetic techniques studied. The background anesthetic appears to have less effect on an atracurium-induced neuromuscular blockade than on one produced by other longer-acting nondepolarizing muscle relaxants (e.g., pancuronium and d-tubocurarine).
Laudanosine (a metabolite of atracurium) increases the minimum alveolar concentration of halothane in rabbits.
The authors hypothesized that laudanosine, a metabolite of atracurium and a central nervous system stimulant, might increase the minimum alveolar concentration (MAC) of halothane. An initial study in five rabbits anesthetized with halothane used a two-compartment model to produce estimates of pharmacokinetic variables for laudanosine. These estimates were used to determine the rates of infusion that would produce steady state plasma concentrations of laudanosine of approximately 200, 400, and 800 ng . ml-1. Subsequent infusion of laudanosine in eight rabbits produced mean (+/- SD) steady state plasma concentrations of laudanosine of 234 +/- 56, 457 +/- 66, and 873 +/- 105 ng . ml-1. The control value for MAC of halothane was 1.08 +/- 0.28%. At the lowest steady state plasma laudanosine concentration, MAC did not significantly differ from control (MAC = 1.15 +/- 0.23%, P less than 0.1). However, at 457 and 873 ng . ml-1, laudanosine significantly increased the MAC of halothane by 23% and 30%, respectively. Infusion with saline in two additional rabbits did not affect MAC. Therefore, at the plasma concentrations of laudanosine found in humans after administration of atracurium, laudanosine increased the MAC of halothane in rabbits.
Effect of maternal parasitic disease on the neonate.
Parasitic disease is the most common infectious disease complication of pregnancy worldwide, resulting in maternal debilitation and fetal prematurity and low birth weight. The increasing incidence of these diseases in our population led to the present study of 125 patients, 34 of whom were found to be infected with at least one intestinal parasite. In contrast to studies in developing countries, no significant differences in either maternal anemia, or fetal birth weight, or prematurity were found between the infected and non-infected groups. However, there was a three-fold increase in the incidence of significant neonatal hyperbilirubinemia in the parasitized group. Parasitic disease complicating pregnancy in our population does not appear to exert the same adverse effect on mother and fetus as that described in other countries. In view of the limited pathology associated with parasitic disease, treatment, other than with iron and vitamin supplementation, is not routinely indicated in pregnancy in populations similar to ours. However, due to the increased incidence of neonatal jaundice and morbidity we would recommend close observation of the neonates in the immediate postpartum period.
Antibiotic resistance and population structure in Escherichia coli from free-ranging African yellow baboons.
Two collections of Escherichia coli from human hosts and one from free-ranging African yellow baboons were examined for the ability to utilize various sugars (biotype) and for resistance to antibiotics. The frequency of antibiotic resistance in the E. coli flora of baboons that feed regularly in village garbage dumps was found to be no greater than that in baboons not associated with human habitation. The frequency of antibiotic resistance in E. coli isolated from baboons is similar to that in E. coli isolated from humans before the widespread use of antibiotics but significantly lower than that in recent isolates from humans. The biotype data indicate that the amount and distribution of genetic variation in the E. coli among free-ranging baboon troops are similar to those in isolates from humans. However, E. coli isolates from baboons are able to utilize a greater variety of sugars as their sole carbon source, possibly because of a greater variety of sugars in the baboon diet.
Interactions between Naegleria fowleri and Legionella pneumophila.
Using electron microscopy we documented some of the intracellular events that occur in Naegleria fowleri suspended in Page amoeba saline after ingestion of Legionella pneumophila. Photomicrographs showed intracellular vacuoles containing bacteria in the process of binary fission that was accompanied by alignment of mitochondria and ribosome-like structures along the vacuole membrane. Although these intracellular events are remarkably similar to that seen in Legionella replication within human monocytes, we could not demonstrate an increase in the number of bacteria by CFU or dark-field microscopy. However, when the Naegleria cells were allowed to ingest Legionella cells while suspended in amoeba culture medium, the number of bacteria increased, and this was contingent upon the presence of viable amoebae.
Miranda comes to the hospital: the right to remain silent in civil commitment.
One procedural protection that has not generally made the transition from the criminal justice system to involuntary civil commitment is the Fifth Amendment protection against self-incrimination. The authors present the results of a study of the implementation of the right to remain silent, which demonstrate that warning patients that anything they say may be used against them in the commitment hearing has little impact on their willingness to talk to staff or to cooperate with treatment. The authors discuss the possible reasons for their findings.
Commitment to outpatient treatment: a national survey.
State mental health directors and state attorneys general were surveyed on the use of outpatient commitment in their states. The survey found considerable disagreement between the two groups on responses to several of the items, including whether outpatient commitment was even permitted in their states. The responses also indicated that two-thirds of the jurisdictions that permit outpatient commitment use it as an alternative to inpatient commitment in fewer than 5 percent of commitments. The author concludes that unless states obtain more input from both inpatient and outpatient clinicians in devising procedures for outpatient commitment, it will continue to be underutilized and ineffective.
Sites of multiple lesions in recurrent genital herpes.
The location of herpes lesions affects the potential for infection of sexual partners and newborn infants. During a six-month study of more than 100 patients, 60 percent of the women and 55 percent of the men had as many as six different lesion sites, both genital and extragenital. Multiple outbreaks of lesions may occur simultaneously, or lesions may form at different times during the same recurrence. These are often inconspicuous and usually go undetected.
The harassment of forensic psychiatrists outside of court.
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Pharmacokinetic study of moxalactam in patients undergoing gynecologic operations.
Moxalactam was administered prior to operation to patients undergoing operation for a known or suspected gynecologic malignancy. Subsequent plasma and tissue levels demonstrated a prolonged duration of action and rapid concentration in pelvic organs after infusion.
Human breast milk concentration of moxalactam.
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The use of plea bargaining in civil commitment.
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Distribution of DNA insertion element IS5 in natural isolates of Escherichia coli.
DNA from Escherichia coli strains in a reference collection of 72 recent natural isolates (ECOR strains) and 25 natural isolates from the "pre-antibiotic" period 1930-1940 (Murray strains) were studied to determine the genomic abundance of insertion element IS5 and the size of genomic restriction fragments carrying sequences homologous to IS5. Among the ECOR strains, nearly two-thirds lack DNA sequences that hybridize with IS5, and one-half of the remainder have only one copy. Among strains in which IS5 is present, extensive variation in the size of IS5-bearing restriction fragments occurs, in many cases allowing distinction among strains that are judged to be nearly identical in genotype because of the identical electrophoretic mobility of the enzyme coded by each of 11 chromosomal loci. Among the Murray strains in which IS5 is present, the average number of elements per strain is larger, but not markedly so, than among recent isolates. Comparison between duplicate strains in the Murray collection suggests that the rate of accumulation of IS5 elements in prolonged storage in stab tubes corresponds to an apparent probability of transposition of approximately 0.008 +/- 0.002 per IS5 element per year. Because of the extensive genetic variation among strains, insertion elements such as IS5 would seem to be convenient genetic markers with which to detect recent common ancestry among strains.
The possible use of auto-hypnosis as a resistance during hypnotherapy.
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Specific deletion occurring in the directed evolution of 6-phosphogluconate dehydrogenase in Escherichia coli.
A novel genetic change leading to increased activity of 6-phosphogluconate dehydrogenase (6PGD) in E. coli has been observed. The mutation is a deletion of approximately 0.4 kilobase pairs occurring between the structural gene of 6PGD (gnd) and one copy of an insertion element (IS5) found normally in E. coli K12 a few hundred base pairs upstream (counterclockwise) from gnd at 44 minutes on the conventional genetic map. The deletion is associated with a threefold higher activity of 6PGD and a 57% increase in the maximum growth rate when cells are grown in gluconate.
Vecuronium-induced neuromuscular blockade during enflurane, isoflurane, and halothane anesthesia in humans.
To determine the effect of the commonly used volatile anesthetics on a vecuronium-induced neuromuscular blockade, the authors studied 54 patients anesthetized with 1.2 MAC or 2.2 MAC enflurane, isoflurane, or halothane (MAC value includes contribution from 60% nitrous oxide). During 1.2 MAC enflurane, isoflurane, and halothane, the ED50S (the doses depressing twitch tension 50%) for vecuronium were 12.8, 14.7, and 16.9 micrograms/kg, respectively. During 2.2 MAC enflurane, isoflurane, and halothane, the ED50S for vecuronium were 6.3, 9.8, and 13.8 micrograms/kg, respectively (P less than 0.05). Time from injection to peak effect was the same for each anesthetic group (6.5 +/- 0.5 min, mean +/- SD), except for the group given 2.2 MAC enflurane (9.7 +/- 0.6 min) (P less than 0.05). The duration of a 50% block from injection to 90% recovery was the same for each group (mean 20 +/- 4 min), except for the group given 2.2 MAC enflurane (46.5 min) (P less than 0.05). The authors conclude that enflurane is the most potent volatile anesthetic, followed by isoflurane and then halothane, in augmenting a vecuronium-induced neuromuscular blockade. Increasing the concentration of volatile anesthetic has less effect on a neuromuscular blockade produced by vecuronium than on one produced by other nondepolarizing relaxants (e.g., pancuronium and d-tubucurarine).
Pharmacokinetics, placental transfer, and neonatal effects of vecuronium and pancuronium administered during cesarean section.
Vecuronium and pancuronium were compared for placental transfer, pharmacokinetic variables, and neonatal effects during cesarean section under general anesthesia. Eighteen women underwent rapid-sequence intravenous induction using d-tubocurarine, succinylcholine, thiopental, and oxygen. Immediately after tracheal intubation, an intravenous injection of vecuronium (n = 11) or pancuronium (n = 7), 0.04 mg/kg, was given. Maternal venous blood samples were obtained before induction and at frequent intervals for 4 h after administration of vecuronium or pancuronium. Also, maternal venous and umbilical-cord arterial and venous blood samples were obtained at delivery. To describe placental transfer and maternal pharmacokinetics of the drugs, serum drug concentrations were determined using single-ion-monitoring mass spectrometry. The Apgar score and Neurologic and Adaptive Capacity Score (NACS) were used to evaluate neonatal condition. Both drugs crossed the placenta, as demonstrated by low concentrations of vecuronium (8.5-26.4 ng/ml) or pancuronium (12.2-34.2 ng/ml) found in umbilical venous blood. At delivery, the ratio of the drug concentration in umbilical venous blood to that in maternal venous blood was 0.11 +/- 0.02 for vecuronium and 0.19 +/- 0.03 for pancuronium. Vecuronium had a more rapid clearance (6.4 +/- 0.4 ml X kg-1 X min-1, mean +/- SE) and a shorter elimination half-life (36 +/- 1.8 min) than pancuronium (3.0 +/- 0.1 ml X kg-1 X min-1 and 72 +/- 6 min, respectively). No other pharmacokinetic differences were found between the drugs. Neonatal outcome was not affected adversely by either muscle relaxant, as assessed by Apgar scores and NACSs . The short duration of action, the minimal placental transfer, and the apparent lack of clinical neuromuscular effects on the newborn suggest that vecuronium should be a useful muscle relaxant for cesarean section.