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Biomedical subjects

H F Cascorbi

Publications and source records attributed to H F Cascorbi.

At least 19 recordsLinked to original sources

The effect of two genes on anesthetic response in the nematode Caenorhabditis elegans.

The authors studied the wild type strain, N2, and three mutant strains of the nematode, Caenorhabditis elegans, in order to measure genetically produced changes in responses to nine volatile anesthetics. They determined the anesthetic ED50s of N2 for thiomethoxyflurane, methoxyflurane, chloroform, halothane, enflurane, isoflurane, fluroxene, flurothyl, and diethylether. The log-log relationship of the oil-gas partition coefficients (O/G) and the ED50s of these agents for N2 yields a straight line with a slope of -.997 with a R2 of .98 over a range of O/G (at 37 degrees C) from 48 to 7230. When the O/Gs are corrected to 22 degrees C, the slope is -.964 with an R2 of .98. This relationship is similar to that found in other animals. Two mutant strains, unc-79 and unc-80, show altered responses to these anesthetics. These strains are two to three times more sensitive than N2 to anesthetics with an O/G greater than that of halothane (220 at 37 degrees C), yet they differ little from N2 in response to anesthetics with lower O/Gs. unc-79 and unc-80 are about 30% more sensitive than N2 to diethylether. The double mutant unc-79; unc-80 is more sensitive to halothane, isoflurane, and fluroxene than is either mutant alone. The authors believe these data indicate an alteration at the site of action of volatile anesthetics in unc-79 and unc-80. They also postulate that the interaction of unc-79 and unc-80 indicate these genes code for enzymes in a common pathway, and that unc-79 precedes unc-80 in this pathway.

Anesthetics

Effect of anesthetics and a convulsant on normal and mutant Caenorhabditis elegans.

The authors have developed a method for studying the action of volatile anesthetics in Caenorhabditis elegans (C.e.), a free living nematode. C.e. appears to be a useful model for the study of the influence of genetics on susceptibility to anesthetics. This worm has a small, completely defined nervous system, easily manipulated genetics, and a large number of nervous system mutants. Under normal conditions C.e. moves almost constantly. When exposed to anesthetics there is an initial phase of increased locomotion, followed by uncoordinated motion that progresses to immobility. Motion returns quickly when the nematodes are removed from the anesthetic. The authors called loss of locomotion "anesthesia." The ED50S of various anesthetics with C.e. are as follows: methoxyflurane 0.45%, chloroform 1.25%, halothane 2.7%, enflurane 4.2%, isoflurane 5.6%, fluroxene 9.9%. The authors also studied the action of a convulsant, flurothyl, on C.e. Flurothyl has anesthetizing properties in these animals with an ED50 of 8.1%. No convulsant activity was noted. However, mixtures of halothane and flurothyl were antagonistic in their effects, while halothane and enflurane were additive. Furthermore, the authors isolated a mutant strain (HS1) of C.e. that shows altered responses to several anesthetics and a convulsant. HS1 is uncoordinated when not exposed to anesthetics. Like the normal strain (N2) HS1 loses mobility when exposed to anesthetics. The ED50S for various anesthetics in HS1 were as follows: methoxyflurane 0.04%, chloroform 0.52%, halothane 0.85%, isoflurane 4.9%, enflurane 6.0%, fluroxene 10.9%.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics

Effects of fentanyl and morphine on intraoperative somatosensory cortical-evoked potentials.

We compared the effects of morphine and fentanyl in the presence of 60% N2O on somatosensory cortical-evoked potentials (SCEP). Both drugs were administered by intravenous bolus (n = 12) and infusion (n = 20) techniques. SCEPs were recorded preoperatively and intraoperatively in 32 patients undergoing corrective surgery for scoliosis. Records were taken at the contralateral cerebral cortex by individual stimulation of the posterior tibial nerves at the ankle. Both drugs increased the latencies of the N1, P2, and N2 peaks and affected the peak-to-peak amplitudes of the primary complex. Intravenous bolus injections and continuous infusions of equianalgesic doses produced similar effects. The increase in N1 latency was significantly greater (morphine, P less than 0.05; fentanyl, P less than 0.01) with the bolus than with the infusion technique. The doses of morphine and fentanyl given by bolus injections were 1/3 times and 3 1/3 times greater than doses given by infusion. Changes in latency were more consistent than changes in amplitude. Both fentanyl and morphine increase latencies while affecting amplitudes unpredictably. Equianalgesic doses of fentanyl and morphine have similar effects on SCEP latencies. Low-dose continuous infusions of narcotics depress SCEPs less than intermittent bolus injections.

Adolescent

Halothane hepatotoxicity and fluoride production in mice and rats.

Other investigators have demonstrated halothane-induced hepatic injury in rats anesthetized in hypoxic environments. The authors examined this phenomenon in mice and investigated plasma fluoride levels in mice and rats anesthetized with halothane in 40, 21 and 7 per cent oxygen with or without pretreatment with phenobarbital or carbon tetrachloride. They found no hepatic necrosis in mice. Mice produced less fluoride than rats. This difference in halothane metabolism between Sprague-Dawley rats and Swiss-Webster mice may explain the failure to observe hepatic necrosis in mice.

Animals

Biotransformation, sex hormones, and toxicity of two volatile anesthetics in mice.

Male and female DBA 11 mice recovered from 1 hr of anesthesia with chloroform of fluoroxene apparently unharmed. However, many of the animals died within 24-48 hr after anesthesia. Pretreatment with phenobarbital increased, while pretreatment with a small dose of carbon tetrachloride decreased, this toxicity. Relatively more males than females died. Pretreatment with estradiol in males and testosterone in females reversed this ratio. We conclude that the murine toxicity of chloroform and fluoxene is dependent on biotransformation by hepatic microsomal enzymes and that the testosterone enhances postanesthetic toxicity of these agents.

Animals

Sex differences in anaesthetic toxicity: fluroxene and trifluoroethanol in mice.

A sex difference in postanaesthetic mortality after fluroxene anaesthesia was found in Swiss Webster mice. More males succumbed than females. This toxicity was biotransformation-dependent and could be reversed by pretreatment with "opposite" sex hormones. The toxicity of the fluroxene metabolite trifluoroethanol also was more marked in male mice, but was only partially influenced by microsomal enzyme inhibitors or stimulators, or by sex hormones.

Animals

A survey of anesthetic health hazards among dentists.

Measurable concentrations of waste anesthetic gases have been found in hospital dental operating rooms. A mail survey of 4,797 general dental practitioners and 2,642 oral surgeons indicated that 20.2% of the general practitioners and 74.8% of the oral surgeons had anesthetic exposures exceeding three hours per week. In the comparison of the health of individuals exposed or unexposed to inhalation anesthetics, there was a significant increase (78%) of spontaneous abortion in the spouses of exposed dentists and a significant increase (156%) in liver disease for exposed dentists. The implication of these findings and possible solutions are discussed.

Abortion, Spontaneous