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
A group of advanced schizophrenic patients (221) were given 500 cc. of a 6% solution of n butanol in saline intravenously, the entire amount being injected in 30 minutes. The only manifestation which could be considered to parallel the toxic effect in animals was a very short period of somnolence which, in only one or two cases, could be considered as sleep. Usually, even with doses of 500 cc. of a 6% solution administered intravenously in less than 25 minutes, it was not possible to obtain even this transitory somnolence. No toxic effect was noted when the same dose was again administered 24 to 48 hours later, and repeated several times. Except for an inflammation of the vein which appears only if hundreds of cc. of a solution above 6% is injected, no other noticeable effects are observed.
The intravenous administration, in postoperative cases, even of 15 gm. of butanol diluted in about 2-3 liters of saline per day, repeated for four and even five consecutive days, has been entirely free of any toxic effect.
Intramuscular administration was observed to be well tolerated even for higher concentrations of butanol. We obtained concentrated aqueous solutions by dissolving butanol in a 35% solution of sodium benzoate in water. Preparations containing more than 30% butanol seemed to induce necrosis when administered intramuscularly in animals and to induce pain at the site of injection in humans. A 30% solution of butanol, however, was well tolerated. Daily administration of subnarcotic doses for long periods to mice caused no toxic effects. On the other hand, repeated injections with narcotizing doses were toxic and even led to death of the animals after several days.
The administration of butanol in solutions of 6.5% in saline intraper itoneally in rats was seen to induce a hyperleucocytosis. 5 cc. injected at once was seen to double the previous amount of leucocytes. This increase started two hours after the beginning of the injections and continued progressively, to reach the value of 34,000, seven hours after the beginning of the injections. The hyperleucocytosis was seen to persist for more than 24 hours. The number of leucocytes was increased in the animal shown in Fig. 296.
A still more manifest effect was obtained with injections of 1 cc. of the same solution, repeated every hour during the day. It is interesting to note that this effect was manifested almost 6 hours after the injection with butanol. Fig. 297 shows an example of these experiments in which the number of leucocytes arrived at 42,500.
Fig. 296. The administration of 5 cc. of a solution of 6.5% n Butanol intra peri toneally to rats induces an increase in the leucocyte number.
Fig. 297. The administration of 1 cc. of n Butanol, repeated every hour, induces a sizable increase of leucocytes in rats.
In collaboration with R. Ravich and P. Teitelbaum we studied the effect of various agents upon the survival time of mice to which a severe caloric burn was inflicted. Under ether anesthesia, adult white female mice were scalded until the xyphoid, in water maintained at 90°C. When the duration of this treatment was 4 or more seconds, the animals died in a few minutes in superacute shock. With 3 seconds the animals survived the immediate effect of the burning.
They started to die several hours later, in 6 hours 40% of these animals had died, and at the 18th hour, 90% were dead.
The influence exerted by various agents was studied by injecting the respective solutions 2-3 times a day according to the experiment. The effect was judged according to the survival time. As the animals did not eat or drink and especially due to the local burns did not urinate or defecate, we considered the effects obtained during the first 18 hours, after which the animals were sacrified and used for the study of the chemical changes. Fig. 138 shows the results of such an experiment with sodium chloride, isotonic solution—sodium lactate 6 M solution, butanol 6.5% in saline— and butanol 6.5% in the sodium lactate solution. While sodium lactate alone seemed even to increase the mortality, and butanol in saline alone influence little this mortality, the effect of the butanol—sodium lactate solution was manifest. The mortality was reduced from beginning to end of the experiment. At the 18th hour it was of 30% instead of 90% for the controls. And of 95% for the animals treated with sodium lactate alone.
Adult rats and mice were injected subcutaneously in the back with 20 cc. and 3 cc. respectively of nitrogen which had been sterilized by being passed through sterile cotton plugs. Into the pouches so formed, a suspension of living coli bacilli—2 cc. for rats and 1/4cc. for mice—was injected. This suspension was obtained from a 24-hour culture on agar and was diluted to provide 10 million microbes per cc. One group of animals was treated by intraperitoneal injection of 1 cc. (for rats) and 1/4 cc. (for mice) of sterile sesame oil. The other group received injections of similar doses of 2% heptanol in oil. In some experiments, only one injection with heptanol was given, while in others this was repeated daily or every second day. In the controls no special reaction was seen. In the heptanol injected animals an exudate appeared in the infected pouch and led to rapid necrosis of the skin. A characteristic of the exudate was the presence of a small number of leucocytes.