Minaxolone and malignant hyperthermia.
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Biomedical subjects
Publications and source records attributed to G G Harrison.
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The activity of delta-aminolaevulinic acid synthetase (E.C. 2.3.1.37) (ALA-S) was measured in rat liver after the simultaneous administration of various anesthetic agents and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) in vivo. Flunitrazepam, Althesin and phenobarbitone caused a significant increase in the activity of the enzyme which was not observed with propanidid, etomidate and minaxolone. It is suggested that DDC-treated rat, which resembles latent human variegate porphyria, may be a more valid method of testing drugs for their ability to elicit acute porphyric phases in susceptible individuals. The anaesthetic agents which induced the activity of hepatic ALA-S in this model are not recommended in patients with genetic hepatic porphyria.
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The effect of acute anaesthetic (1,0 MAC) and chronic subanaesthetic (0,1 MAC) exposure to methoxyflurane and enflurane on the levels of several liver enzymes is reported. Methoxyflurane appears to be an enzyme-inducing agent similar to spironolactone, whereas enflurane does not appear to be an inducing agent for any of the enzymes studied.
Having studied anaesthetic drug interactions in rats, we report the effects of halogenated anaesthetics on the liver glutathione levels and histology, as well as the results of the enhancement of these effects by microsomal enzyme induction. The anaesthetic agents studied included methoxyflurane, halothane, ethrane, chloroform and fluroxene. While exposure of rats to methoxyflurane, helothane and ethrane produced no significant changes in hepatic glutathione levels, or in liver histology, exposure to chloroform and fluroxene produced marked depression of liver glutathione, especially after microsomal enzyme induction. Furthermore, rats exposed to thses agents after enzyme induction developed gross centrilobular necrosis and died. It is suggested that the study of the effects of any new anaesthetic agent on liver glutathione levels could be a valuable screening test of its hepatotoxic potential, before its clinical trial.
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The mortality associated with 240 483 anaesthetics administered over 10 years at Groote Schuur Hospital, Cape Town, is reported. The frequency of death to which anaesthesia contributed was 0.22 per 1000 anaesthetics (compared with 0.33 per 1000 in the previous 10 years). These deaths were responsible for 2.2% of the total mortality from surgery. Two-thirds of the "anaesthetic" deaths were attributable to (in order of frequency): (a) hypovolaemia; (b) respiratory inadequacy following myoneural blockade; (c) complications of tracheal intubation; (d) inadequate postoperative care and supervision.
Archaeological methods were utilized to monitor trends in food purchase and utilization behavior in Tucson, Arizona households through the analysis of household refuse. As a supplement to traditional methods of collecting data on food consumption, the study of household refuse can provide information on short-term trends in behavior and on food discard. Between 1973 and 1975, households studied decreased the amount of food brought into the home and decreased their purchase of selected animal protein foods. Lower-income tracts, in addition, increased their purchase of grain products, substituted cheaper for more expensive food intems, and decreased food discard. While these data do not reflect nutritional status, they provide a unique view of the socioeconomic and behavioral patterns that in large part determine nutritional status.
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Maternal weight and height before pregnancy and weight gain during pregnancy were recorded for each of 109 mothers who were delivered of normal infants after gestations of 37 to 43 weeks. Infant parameters obtained included gestational age, birth weight, bilateral mid-arm circumference, and eight skin fold thickness measurements. The eight skin fold thicknesses were summed (SSFT) for each infant. Infants with SSFTs greater than 40 mm (N = 8) for the group were classified as "fatter" infants. All of the fatter infants were large for gestational age (LGA), but accounted for only one third of the LGA infants in the study. Birth weight, length, and cross-sectional mid-arm fat area were significantly increased in the fatter LGA group when compared to other LGA infants. Cross-sectional mid-arm muscle area was not significantly different for the fatter LGA infants compared to the other LGA group. Mothers were defined as obese or nonobese according to pregnant weight for height. Obese mothers had infants with significantly increased SSFTs when compared with infants of nonobese mothers. Mulitple regression analysis showed that both prepregnant weight for height and weight gain during pregnancy were associated with increased subcutaneous fat in the neonate. Weight gain during pregnancy was associated with increased neonatal fatness and length, while prepregnant weight for height was associated with neonatal fatness independent of neonatal length.
The oral administration of dantrolene for the prophylaxis of malignant hyperthermia (MH) in susceptible swine has been investigated. Complete protection from MH in pigs exposed to the known MH initiating agents, halothane and suxamethonium, was demonstrated.
From our studies of the rat we report observations on three aspects of the interaction of ethrane and liver. 1. Interaction of ethrane with cytochrome P450 in vitro. 2. The effect of ethrane administration on glutathione levels in vivo. 3. The effects of repeated ethrane administration in the absence and presence of microsomal enzymic induction on liver morphology. We conclude that ethrane has little or no propensity for damaging the liver.
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Experiments are described which demonstrate that dantrolene sodium effectively terminates the syndrome of malignant hyperpyrexia induced in susceptible swine by exposure to halothane. Dantrolene is also shown to block initiation of the syndrome of malignant hyperpyrexia by halothane in MHS swine. Therapeutic use of this drug in patients with anaesthetic-induced malignant hyperpyrexia appears to be indicated.