Biomedical subjects
Publications and source records attributed to N Cohn.
The disposition kinetics of Propofol have been determined in 7 patients (3 men, 4 women) receiving 2.5 mg/kg for induction of anaesthesia. Peripheral venous samples were collected up to 12 hours after injection of the drug. Data analysis indicates a 3 compartment model with a terminal half-life of 480 +/- 141 min, clearance of 0.0352 +/- 0.0014 l/min/kg and volume of distribution of 24.2 +/- 6.2 l/kg.
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Brain protection during ischemia by barbiturates has been clearly demonstrated in many different experiments. Only recently the therapeutic value of large doses of thiopental administered early after cerebral circulatory arrest has been demonstrated experimentally in monkey. Noncontrolled studies in humans also indicate beneficial effect, however the treatment is not without potential complication. Controlled randomized studies in humans are needed to document its beneficial effect. Such studies have several unique medico-legal and ethical implications since the treatment has to be started in an unconscious patient and as early as possible after a totally unexpected cardiac arrest. Informed consent, ethical and medicolegal consideration of randomized controlled clinical trials is discussed and a modified approach to clinical trials in humans is suggested. The modification would not alter the scientific value of the studies, but resolve the ethical and medico-legal problems.
A reproducible noninvasive monkey model for global brain ischemia with exact insult (no flow x 16 min) to the brain, with survival and with standardized preischemic, ischemic and postischemic variables is described. This model allowed us to demonstrate for the first time: 1) that a substantial part of brain damage early postischemia is reversible and amenable especially to barbiturate treatment; 2) that the postischemic brain shows increased vulnerability for additional insults. Optimal postischemic intensive monitoring and immobilization for 24-48 hours is important for improved outcome; 3) that immediate postischemic reperfusion pressure (MAP 110-150 mm Hg) significantly improves the outcome; 4) that heparinisation during ischemia has no protective effect and 5) that postischemic heparinisation and intravenous hemodilution does not ameliorate the outcome. The protective effect of trimetaphan against neurogenic pulmonary edema can be explained by the prevention of pulmonary hypertension but its protective effect on the development of secondary cerebral edema has to be elucidated.
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Phospholipids were isolated from mitochondrial, microsomal, and plasma membranes of LM cells and fractionated into individual phospholipid classes on silicic acid columns. The fatty acid composition and the rotational relaxation time of 1,6-diphenyl-1,3,5-hexatriene (DPH) were determined for each phospholipid class. Sphingomyelin was the only phospholipid isolated from LM cell membranes that showed a phase transition within the temperature range investigated, 5-40 degrees C. The rotational relaxation times for DPH were lowest in phosphatidylcholine in all the membrane fractions. Phosphatidylcholine isolated from the three membrane fractions of choline-supplemented cells had similar rotational relaxation times and phosphatidylcholine isolated from microsomal membranes of linoleate-supplemented cells had lower rotational relaxation times. The results indicate that the differences in the rotational relaxation times of DPH between mitochondrial, microsomal, and plasma membrane phospholipids could be explained primarily by differences in the polar head-group composition, while differences in the fatty acid composition had only a minor effect. This provides a basis for understanding how the different lipid components in these cells contribute to membrane fluidity.
Aminoglutethimide (AG), a known adrenal inhibitor, was administered acutely to normal men in order to study its effects on testicular steroidogenesis. Sixteen subjects between the ages of 21--30 yr received either placebo or 1250 mg AG in divided doses during a 24-h period. To reduce the contribution of adrenal steroids, adrenal function was inhibited in both groups of men by the administration of dexamethasone (2 mg) on the night of the experiment. As a result, mean morning plasma cortisol levels fell to less than 2 micrograms/100 ml. AG blunted the normal diurnal rise in testosterone, which was observed in men receiving placebo, and significantly suppressed the levels of this androgen at 0700 and 0900 h. Estradiol concentrations fell to a greater extent than those of testosterone. The differences between the placebo and drug treatment groups were significant at all time points except 1900 h. A pattern similar to that of estradiol was observed for plasma estrone. When the overall effect of AG administration was examined by analysis of variance, the differences in the levels of all three steroids produced by treatment were highly significant (P less than 0.01 to less than 0.001). After the inhibition of testosterone and estradiol levels, LH and FSH concentrations were significantly (P less than 0.01 and P less than 0.001, respectively) higher in men receiving AG than in those given placebo. However, the data exhibited a large variance due to pulsatile gonadotropin secretion. These observations suggested that AG induces an acute inhibition of testicular steroidogenesis and probably also of the aromatization of testosterone to estradiol.
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