Joseph Wortis

The Sugar Tolerance of Alcoholic Patients

Summary and Conclusions The sugar tolerance was studied in a group of 18 alcoholic patients. On admission there was a marked diminution of the sugar tolerance, which improved after one week in the hospital on a normal diet. It is suggested that the diminished tolerance was due to an undernourished state previous to admission.

Availability of Sodium Pyruvate for Human Brain Oxidations.

Summary and Conclusions The availability of sodium pyruvate for brain oxidations in hypoglycemic insulin coma was studied in human patients. In 2 of 14 experiments with various amounts of pyruvate the patients roused slightly from coma, and in the remaining 12 there was no change observed in the clinical state. In 9 patients the oxygen uptake of the brain was observed, and there was a small, though statistically significant, rise. These results are in striking contrast to those observed with glucose, and indicate that the oxidation of pyruvate by the brain is not sufficient to adequately support cerebral functions.

Changes in Cerebral Blood Flow and Arterio-Venous Oxygen Difference During Insulin Hypoglycemia.∗

Previous work has disclosed that the arterio-venous oxygen difference of cerebral blood is diminished during insulin hypogly-cemia. 1 , 2 However, the arterio-venous oxygen difference is determined not only by the metabolic rate of the brain, but also by velocity of blood flow. Therefore, thd possibility exists that the smaller oxygen difference found may be due to a more rapid blood flow during hypoglycemia. Observations by Loman and Myerson 3 on human subjects and Leibel and Hall 4 on rabbits, have failed to demonstrate any marked changes in the rate of cerebral blood flow during insulin hypoglycemia uncomplicated by convulsions. However, for conclusive information regarding changes of brain metabolism, it is necessary to determine, simultaneously, the cerebral blood flow and the arterio-venous oxygen difference. The results of such a study on patients with schizophrenia are presented in this preliminary report. Methods for the collection and analysis of the blood samples have been previously described. 2 The rate of blood flow in the internal jugular vein was estimated by a modification of the Gibbs thermostromuhr. This instrument proved to be at least as sensitive as the original and will be described elsewhere. Observations on the blood flow were made over long periods during which the position of the thermostromuhr in the vein was maintained constant. A special technique was devised which prevented error resulting from the formation of clots on the needle. In 5 cases the blood flow and the arterio-venous differences were determined before injection of insulin as well as throughout the course of the coma and the subsequent administration of glucose. In 3 other instances the observations were begun during coma and continued until after arousal with intravenous glucose.

Availability of Glucose for Human Brain Oxidations.

Summary and Conclusions The availability of glucose for brain oxidations in hypoglycemic insulin coma was studied in human patients. The intravenous administration of 4 g (in 50% solution) invariably aroused the patients and approximately doubled the oxygen uptake of the brain.

A Simple Method for Prolonging Therapeutic Insulin Coma.

In the treatment of psychoses, insulin coma 1 (or the period of unconsciousness) is generally not allowed to persist beyond an hour or an hour and a half. In cases inadvertently allowed to linger in coma beyond that period, an irreversible insulin coma 2 frequently follows that can no longer be relieved by intravenous glucose. This dangerous and sometimes fatal complication has, however, directed the attention of several investigators to the important fact that patients who survive several hours or days of this relatively irreversible coma often show dramatic psychiatric improvement on awakening. Kraulis 3 attempted to utilize this phenomenon for therapeutic ends by prolonging insulin coma with periodic small glucose feedings sufficient to sustain the patient but not sufficient to rouse him. The difficulties in the clinical management of these sporadic feedings, however, and the frequent presence of gastric retention 2 (which Kraulis did not suspect) made this mode of treatment too dangerous for clinical application. It can be assumed that the cerebral injury which ensues in accidentally protracted coma is due to the diminution of brain metabolism (by withdrawal of substrate) below levels adequate for cell maintenance over long periods of time. In our cases (30 experiments on 10 subjects), we have succeeded in prolonging hypoglycemia as long as 21 hours and coma as long as 18 hours, without mishap, by sustaining brain metabolism above this dangerous level, but still below levels which support consciousness and other associated cerebral functions. This has been achieved by administering infusions of 5 % glucose in physiological saline (Sterisol) intravenously at controlled rates. Inasmuch as large doses of insulin exert their hypoglycemic effect for many hours after administration, 4 one need only maintain the blood glucose at a moderately high level (e.g., 35 mg per 100 ml) to prolong coma for many hours. When the insulin effect begins to subside, a fresh intraiiiuscular iiljection of insulin can be administered.

SERUM TOXICITY IN VARIOUS PSYCHIATRIC DISORDERS

The serum of schizophrenic, alcoholic, and mongoloid patients had no inhibiting effect on the respiratory activity of surviving rat brain. The serum of patients treated with chlorpromazine enhanced the respiratory activity. A slight tendency to elevated values found in recently admitted schizophrenic adults who were not taking chlorpromazine may be due to prior medication before admission. Phenylketonuric serum depressed brain oxidations, though a similar effect was induced by racemic phenylalanine in concentrations above 40 mg.% as well as by other essential amino acids. It has been suggested that the depressant action of various amino acids may be due not to a direct effect of the amino acids, but to aldehyde formation. It has also been known for a long time that a number of toxic amines such as tyramine, phenylethylamine, mescalin, indole and skatol, all inhibit brain oxidations. The observed phenomenon may explain the general depression of brain oxidations found in vivo in phenylketonuria by Himwich a...