Biomedical subjects
Publications and source records attributed to M D Rawlins.
The case of a patient with episodic hypothermia and profuse sweating believed to be due to diencephalic epilepsy is reported. Despite intensive investigations no other manifestations of hypothalamic dysfunction were found. Conventional antiepileptic drugs were without effect but the patient was successfully treated by total sympathectomy.
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1. Elimination rates of phenylbutazone and warfarin after single oral doses in human volunteers, and steady-state plasma concentrations of these drugs in patients have been measured before, during and after administration of allopurinol.2. Allopurinol, in usual clinical doses, had no significant influence on the elimination rate of either drug in the group of volunteers as a whole although in a few individuals an apparent inhibitory effect was observed.3. No significant changes in the steady-state plasma concentrations of either phenylbutazone or warfarin were observed in patients during the administration of allopurinol.4. It is concluded that although allopurinol may have an apparent inhibitory effect on drug elimination in a few individuals, its administration to most patients on anticoagulant therapy is unlikely to alter dose requirements.
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1. Symmetrical, bilateral micro-injections (10 mul.) of 6-30 mug sodium salicylate have been made into various parts of the brains of febrile and afebrile rabbits.2. In rabbits with fever induced by an intravenous infusion of endogenous pyrogen, micro-injections of sodium salicylate produced antipyresis when given into the preoptic hypothalamus and the mid-brain.3. In afebrile rabbits, micro-injections of sodium salicylate into these areas were without effect on temperature.4. The results suggest that at least part of the antipyretic effect of salicylates may be mediated by antagonizing the effects of endogenous pyrogen within these areas of the brain.
1. The imino-dibenzyl drugs, imipramine and desipramine, which inhibit the uptake by neurones of noradrenaline, were injected into the lateral cerebral ventricles of cats and rabbits: changes in body temperature resulted which were different for the two species, but nevertheless closely resembled those following intraventricular injection of relatively large quantities of exogenous noradrenaline.2. The endogenous noradrenaline content of the hypothalamus in both species was reduced by repeated injections into the lateral ventricle of the methyl ester of DL-alpha-methyl-p-tyrosine: in animals so treated the hypothalamic content of 5-hydroxytryptamine was not significantly changed.3. Noradrenaline-depleted animals showed significantly reduced responses to intraventricular imipramine and desipramine. The diminished responses were primarily due to reduction in endogenous noradrenaline.4. These observations indicate that endogenous noradrenaline, present in the hypothalamus, can influence body temperature in cats and rabbits.
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1. Steady state fever has been produced in rabbits with a priming injection followed by a sustaining infusion of homologous plasma containing endogenous pyrogen (EP). This fever appears to last as long as the infusion continues.2. Intravenous salicylate given 1 h after the start of the EP infusion produced only a small antipyretic effect. The same dose of salicylate given 4 h after the start of an EP infusion resulted in rapid and progressive defervescence. Intermediate antipyretic responses were obtained when salicylate was administered intravenously 2 and 3 h after the start of an EP infusion.3. Less than 1% of the systemic dose, when injected into a lateral cerebral ventricle, produced a significantly smaller response at 1 h than at 4 h after the start of an EP infusion. At both these times the fall in temperature following the intraventricular salicylate injection was dose dependent, but the slope of the dose-response line was significantly steeper at 4 h than at 1 hour.4. It is suggested that salicylates produce their antipyretic effects by antagonizing the action of EP within the nervous system, and that the hypothalamic EP concentration falls during the course of an EP infusion.
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