所謂極量的發熱療法ニ關スル研究 : 第1編 發熱療法ノ生體ニ及ス影響ニ關スル實驗的研究

若林 三捷

The curative process of the fever-cure has not as yet been thoroughly explained. Some regarded it as an effect of a depression of the virulence of pathogenic germs or a destruction of pathogenic germs themselves due to the high temperature of the body. Some suspected that the high temperature of the body caused an alteration of organic cells, which highly stimulated the function of the reticuloendothelial cell system, and consequently gave rise to an invigorated defensive force from an increase of anti-body, macrophages, macrophages and strengthened phagocytic action and the like. Others imagined that an active circulation of blood of the focus due to fever acted favourably to the disease. The author was anxious to explain this subject and made an investigation experimentally and clinically with gonococcus, some pyletics and patients suffering from gonorrhoea. The methods of research and the results obtained by the author are as follow: I. Capability of resistance of gonococcus against heat. Sixteen stocks of gonococcus in cystin saccharose blood nutrient medium (cultivated for 24 hours at 37℃) were put individually into an incubator of 39℃, 40℃ and 41℃. After a certain duration they were taken out of the incubator and each loop of gonococcus culture was bred again in a fresh nutrient medium and the development of gonococcus of each stock was observed periodically. i) Each stock of gonococcus was not much affected at 39℃ up to 24 hours, but the greater part of the stocks was destroyed after 24 hours. There were only a few stocks which stood the temperature for over 30 hours. ii) Each stock was not much influenced at 40℃ up to 10 hours, but one third of the stocks died at the 12th hour and the greater part of the stocks became extinct at the 14th hour and the remaining stocks were destroyed at the 18th hour. iii) Each stock was not much affected at 41℃ up to five hours, while one third of the stocks was annihilated at the 6th hour, the larger of the remaining part at the 7th hour and the residue at the 10th hour. II. Capability of resistance of gonococcus bred at high temperature against medicine. Five stocks of gonococcus were cultivated for six hours at 39℃, for three hours at 40℃ and for two hours at 41℃ respectively. Each two loops of the gonococcus culture was put into an ox brain extract nutricient bouillon and 1cc of 0.1-0.003125‰ solution of protargol, 0.025-0.00078125‰ solution of nitrate of silver or 0.0625-0.001953125‰ solution of albargin was added to it individually and was mixed up well. Thirty minutes later two loops of depositing of the bacteria were bred again in fresh nutrient medium respectively and their state of growth was compared with gonococcus of the same stocks cultivated at 37℃ (control). The gonococcus cultivated for six hours at 39℃ showed a slight decrease of resistance against the noted medicines compared with the control, less in the gonococcus cultivated for three hours at 40℃ and least in the gonococcus cultivated for two hours at 41℃. III. Alteration of elementary constituent of blood caused by fever. The author adopted poly-valent gonococcus vaccine, "Dmelcos" vaccine and "Sulfurol" (a sulphur praeparation) as pyletics. Healthy adult male white rabbits of approximately 2kg. were divided into three groups. Each rabbit belonging to the first group was given an intravenous injection of 0.4, 0.8 and 1.5cc of gonococcus vaccine individually on successive alternate days. The rabbits belonging to the second group were given an intravenous injection of 0.4, 0.8 and 1.5cc of "Dmelcos" vaccine respectively every other successive day. The third group received an intramuscular injection of 2.0 3.0 and 4.0cc of "Sulfurol" individually on alternate days successively. Blood was taken from each rabbit at the successive period and the elementary constituent of blood was determined. i) The erythrocytes and thrombocytes did not differ much in amount by the injection of gonococcus vaccine or "Dmelcos" vaccine as usual, while the leucocytes showed clear changes. A plain leucopenia appeared one hour after the injection, but it soon changed into an obvious leucocytosis. The number of leucocytes was largest three to six hours, and slight nine to 24 hours, after the injection. The leucocytosis came chiefly from the increase of pseudoeosinophilous leucocytes. The latter increased more with the injection. ii) The duration of fever arising from an injection of "Sulfuroll" was longer than that of the others, while the changes of number of erythrocytes, thrombocytes and leucocytes was less than that of the others. There was no occurance of a manifest leucocytosis. Even the increase of pseudoeosinophilous leucocytes itself went hardly beyond the physiologic oscillation. IV. Changes of worth of anti-body in blood. i) Rabbits in the condition stated in (3) were divided into three groups. Rabbits belonging to the first group and to the second group received an injection of 0.4, 0.8, 1.5, 3.0 and 6.0cc of gonococcus vaccine or chancre vaccine individually every other successive day. Each rabbit belonging to the third was given an intramuscular injection of 2.0, 3.0, 4.0, 5.0, and 6.0cc of "Sulfuroll" respectively on alternate days successively. Blood was taken from each rabbit periodically and the worth of aggultinine against typhoid-bacillus was determined. The worth of aggultinine of every group reached its first maximum at the 6th hour from the first injection. The worth of aggultinine in the second group was the greatest, less in the first group and least in the third group. On the 5th day after the first injection there came the second maximum of the worth of aggultinine. This time, however, the worth of aggultinine of the first group was the most, less in the second group and least in the third group. After that the worth of aggultinine in both the first and the second group decreased gradually and returned to its normal worth 15 to 20 days after the first injection, while that of the third group went back below its normal worth. ii) Rabbits in the same condition were previously given an injection of 0.5cc of typhoid fever vaccine in their auricular vein. They were in use 21 days after the previous injection and were divided into three groups. Both the first and the second group received an intravenous injection of 0.3cc of gonococcus vaccine or chancre vaccine respectively, while the third group got an intramuscular injection of 2.0cc of "Sulfurol". Blood was taken from each rabbit periodically and the determination of the worth of immune aggultinine against typhoidbacillus, that is, the examination of the anamnestic reaction, was performed. The anamnestic reaction occurred most markedly in the third group during which the temperature of the body went up higher than the other groups. iii) After three days from a previous anti-gen (0.5cc of typhoid fever vaccine) injection as described in (ii), the rabbits were divided in three groups. Both the first and the second group received an injection of 0.4, 0.8, 1.5, 3.0 and 6.0cc of gonococcus vaccine or chancre vaccine respectively on alternate days successively, The third group got an intramuscular injection of 2.0, 3.0, 4.0, 5.0 and 6.0cc of "Sulfurol" individually every other successive day. Blood was taken from each rabbit periodically and the worth of immune aggultinine was determined. The production of aggultinine of the first group was most active, less in that of the second group and least in the third group. The author is of opinion that the reason why the action of "Sulfurol" was inferior to the others in this experiment was partly due to a decrease in the resistance of the organism itself caused by the application of a succession of higher fever. V. Defensive action of blood and blood-serum caused by fever. i) Rabbits in the same condition cited in (3) were divided into three groups. Both the first and the second group were given an intravenous injection of 0.5cc of gonococcus vaccine or chancre vaccine individually. The third group received an intramuscular injection of 2.0cc of "Sulfurol". Blood was taken from each rabbit periodically and the bactericidal power of serum against colibacillus, typhoidbacillus and staphylococcus aureus was compared with each other. By mixing serum of rabbits in fevric condition (that is, serum of the first and the second group at the third hour, and that of the third at the 16th hour from the injection of pyretics) with the microbes it was evident that the number of the microbes at the 3rd hour from the admixture was generally plainly lessened, and the number lessened still more at the 6th hour than that directly after the adulteration. There was not any manifest difference of the bactericidal power among the pyretics. Moreover, it was recognized that the number of the microbes was lessening with time, though little, after the removal of fever. This led the author to believe that an artificial fever brought an alteration of the organic cells and thereby invigoration of bactericidal poper of serum. ii) Rabbits in fevric condition originated in the same way as cited in (5,i) received an intravenous injection of 1.0cc of depositing staphylococcus aureus in a physiologic salt solution (1 loop of pure cultivation of staphyloccus aureus in 2.0cc of physiologic salt solution). 2.0cc of blood were taken from each rabbit periodically by a cardiac puncture and deposited in agar nutricient medium. It was found that the microbes injected in vein disappeared earlier in blood of every rabbit in fevric condition than in blood of rabbits without fever or rabbits without the previous injection (control). iii) Rabbits in fever origicited in the same method as noted in (5,i) were given an injection of 50% depositing of chicken blood-corpuscle (5.0cc per 1kg.) in their auricular vein.

所謂極量的發熱療法ニ關スル研究 : 第1編發熱療法ノ生體ニ及ス影響ニ關スル實驗的研究

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