This section is from the book "Research In Physiopathology As Basis Of Guided Chemotherapy With Special Application To Cancer", by Emanuel Revici. Also available from amazon: Research In Physiopathology
In one of a group of severely burned subjects, who were at that time under our care and had been experiencing several chills a day, an injection of glycerol solution had been given by coincidence just at the moment when a chill was starting. While such a chill always previously had lasted for more than ten minutes in this patient, it stopped almost immediately after the glycerol injection.
An experiment was set up to confirm or negate this correlation. As soon as any patient of this group felt the sensation or premonition of a chill, he was given either an intramuscular injection of 3-5 cc. of a 20% solution of glycerol in saline or 3 cc. of saline alone as placebo. In almost every case, the chill was cut short by the glycerol while the placebo had no effect. Less striking but still interesting effects were obtained when 20 to 30 drops of glycerol were given orally in 50 cc. of water against an oral solution of 1 % sugar in water as a placebo.
Not one of the other substances used at this time, such as adrenalin, quinine, pilocarpine or pantopon, orally or parenterally influenced a chill once it had begun. Later, butanol also was found to have an effect similar to that of glycerol although less manifest.
Since the first experiment with glycerol, we have tried it in many patients subject to repeated chills and have frequently obtained the same results. We have tried to explain glycerol's effect upon chills by considering the role of chills in the defense mechanism. Chill would mark the beginning of the second phase of the diphasic defense phenomenon. (See Chapter 5.) It brings various constituents, especially those which have to replace constituents altered in the first hydrolytic phase. Among them are agents especially able to influence the free fatty acids liberated in the first phase. Apparently, the fact that it takes some time for the anti fatty acid agents to pass into the circulation, most of them coming from the RES cells, makes the chill last so long. The immediate presence in the blood of a sufficient amount of glycerol, which is a relatively efficient anti fatty acid agent, eliminates the need for liberation of body anti fatty acid agents. Thus, with glycerol, the chill would no longer be required to induce liberation of such agents and would stop.
Figure 292 shows the electrocardiogram of a rabbit receiving a solution of 20% glycerol intravenously. Frequent extrasystoles appeared. It was interesting to note that, at the same time, the animal became somnolent.
Fig. 292. Electrocardiogram of a rabbit receiving intraveinous injections of a solution of glycerol 20%, characterized by the appearance of extrasystoles. (a) before treatment, (b) after 30 cc.
Fig. 293. Extrasystoles appear after the intraperitoneal injection of butanol in very high doses, (a) before treatment, (b) after 1.6 gram/1000 gr of animal.
Repeated injections of glycerol in rats were seen to induce convulsions. Using rats weighing 200-2S0 grams, 5 to 10 cc. of the 20% solution of glycerol in saline were injected intraperitoneally. The injections were repeated once or twice a day. After several days of treatment, usually from 3 to 5 days, one of the injections was followed within a few minutes by a severe convulsion, lethal for most of the animals. In the surviving animals, the next injection was always followed by a lethal seizure.
In order to obtain colloidal suspensions, various lipoids were dissolved in alcohol and a certain amount of the alcohol solution mixed with water, saline or isotonic solutions. From the resulting milky suspensions, the alcohol was eliminated by boiling under reduced pressure. To insure almost complete elimination of the solvent, an excess of water was added and the excess was then eliminated through boiling. The use of acetone or ether as solvent gave much less favorable results.
Relatively stable suspensions were obtained by mixing some lipid preparations such as mixtures of unsaturated fatty acids with a 0.5% solution of cellulose gum. Such stable suspensions could not be obtained with preparations of positive lipids.
When relatively larger doses, such as 5 cc. of 2% cholesterol daily, were administered repeatedly to rats of around 250 gr. of weight, convulsions appeared after 4 to 8 days. They were induced earlier in females than males. The first convulsion always was lethal. Convulsions also occurred in humans after repeated injections of cholesterol in doses as high as 20 cc. of the 2% solution in oil. Even small doses, such as 2 or 3 cc. of the same solution, induced convulsions in patients with brain metastases or in those who had had previous convulsions.