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David F. James and Spencer Braden

smaller but therapeutically effective doses were used, mild toxic reactions were observed in approximately 50 per cent of the cases. Severe toxic reactions were not noted. For a period of at least 60 minutes following the administration of curare, prostigmine and facilities for artificial respiration were kept in readiness for immediate use. This precaution has never been found to be necessary and after 3 weeks' experience with the drug, facilities for artificial respiration were not alerted. At no time was a change in pulse, blood pressure, respiratory rate or force

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Central Nervous System Resistance

III. The Effect of Adrenal Cortical Substances on the Central Nervous System

R. G. Grenell and E. L. McCawley

nature as those seen in the experimental animals) appeared consequent to the intravenous injection of 0.5 cc./kg. of aqueous adrenal cortical extract. The changes, in both animals and man, appeared 5–10 minutes after intravenous injection, and 20–30 minutes after intramuscular injection. The minimal effective dose and time of latency of the recorded reaction remained to be determined. This was done by the intravenous injection of 0.25 cc./kg. doses at 8 minute intervals ( Fig. 7 ). Fig. 5 Fig. 6 Fig. 4 Fig. 3 Fig. 7 With

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Eldon L. Foltz, Fritz L. Jenkner and Arthur A. Ward Jr.

, muscarinic actions of this drug. Whereas the effective dose of atropine sulfate in the animal is 0.5–1.5 mg./kg., the maximal dose used thus far in humans is approximately 0.1 mg./kg. Obviously an anticholinergic drug is needed that will be maximally effective centrally and will have minimal or no peripheral action. It is hoped that future experiments will permit development of such a method of therapy. CONCLUSIONS 1. Acceleration concussion was studied in cats and monkeys with continuous recording of the electrical activity of cortex and certain brain stem

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P. E. Wiklund

to use induced hypotension both at operations under local anesthesia alone and at operations under general anesthesia. We preferred, however, insufflation anesthesia as a routine method, so as to maintain the patient's airway and to ensure full oxygenation. We were able to use local anesthesia with supplementary exadrine without any untoward effects on the hypotension or the postoperative course. By restricted initial administration of the ganglion-blocking agent, it was possible to arrive at the effective dose for each individual patient

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C. B. Sedzimir

direct proportion to the sedative action of Dromoran and observations upon the conscious level of the patient might be hampered by using an effective dose. We have injected on several occasions 4–6 mg. of Dromoran in combination with 1 mg. of levallorphan with safety. In one case, in order to induce a satisfactory hypothermia when shivering was a predominant and exhausting feature, it was considered that a light general anaesthesia, intubation and a gas/O 2 mixture with very short periods of ether and maintained for 24 hours, might be safer than effective sedation

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Basic Studies in Cerebral Edema

Its Control by a Corticosteroid (Solu-Medrol)

Elliott E. Blinderman, Carl J. Graf and Thomas Fitzpatrick

animal dose would be comparable, therefore, to 100 mg./hr. for the human. Whether these dose values can be compared as “effective dose values” because of species differences, we do not know. CONCLUSIONS It has been shown that, in the brain damaged by vegetable oil emboli, a significant increase in the osmolarity of the brain tissue and an increase of water content were found. A technique is described for measuring these parameters as a basis for study of the modification of cerebral “swelling” or edema. It is our belief that in those animals in which cerebral

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R. Lewis Wright and Adelbert Ames III.

was administered as a solution containing 6 mg./ml. at a pH slightly above 8.5 and in a volume sufficient to provide a dose of 12 mg. /kg. of body weight. The Sodium Pentothal was injected at a concentration of 10 mg./ml. in a solution of pH slightly above 10, to give a total dose of 10 mg./kg. of body weight. Because of the higher pH needed to maintain solubility of the Sodium Pentothal, the relative effective dose which could be administered via this route was appreciably less than with pentobarbital. The ethyl alcohol was administered by intraperitoneal

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Burton L. Wise, Jacob L. Mathis and John H. Wright

comparable to that produced by similar doses of intravenous mannitol. 5 In the dog, there is an increased solute and electrolyte excretion concomitant with the increased urine flow. 5 There is no evidence of significant alteration in electrolyte balance following the administration of effective doses given orally. The osmotic effects of oral isosorbide were tested on normal adult male volunteers. 10 The drug was well tolerated and no circulatory, hepatic or renal toxicity was reported. Isosorbide given orally in doses of 1 gm./kg. body weight caused an osmotic

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Charles B. Wilson and Takao Hoshino

the development of routes of administration, and in the prediction of effective dose schedules. An outstanding example of information provided by animal models is experience with L 1210 murine leukemia. This model not only served for the screening of antileukemic agents but also allowed prediction of the effective dose schedule for maintenance therapy in acute leukemia of childhood. 44 A limited number of studies have been conducted using induced mouse gliomas but, because of the heterogeneous tumor cell types and the limitations imposed by a tumor that is more

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Lights in the great darkness

The 1971 Harvey Cushing oration

Wilder Penfield

surgery whenever he called on the latter to operate on one of his patients. But during the war Foerster took up the scalpel and began to operate for himself without further training. * Then, a few years after the war, Foerster began to operate on veterans who had developed post-traumatic epilepsy from gunshot wounds of the brain. This had been done before, but Foerster did it with a difference. The craniotomy was carried out under local novacaine analgesia, to which was added a very effective dose of stern Prussian discipline to keep the patient still. Electrical