iii8 CHEMOTHERAPY OF BACTERIAL DISEASES 



average weight (30-40 cc. of a i per cent solution). As a general rule, 20-30 cc. of a 

 I per cent solution has been generally given, and this dose is quite safe, being at least 

 five to ten times less than the maximum tolerated dose for the lower animals. Follow- 

 ing the injection, the skin and mucous membranes become a dusky blue in color, sug- 

 gesting severe cyanosis, but due to the dye, and usually disappearing within a few 

 hours. The breathing and pulse rate may be increased with the slight increase of 

 blood pressure ; occasionally the patient experiences a tingling sensation of the skin 

 with abdominal uneasiness, but I have never observed any other untoward effects. 



Neutral acriflavin and profiavin are generally administered in doses of 0.005- 

 0,010 gm. per kilogram, corresponding to 0.3-0,7 gm. for an adult of average weight; 

 usually the dose is 30-50 cc, of a i per cent solution (0.3-0.5 gm.) by slow intravenous 

 injection. The skin may become flushed and especially the face; both cardiac and 

 respiratory rates may be increased for a few minutes, but in the majority of cases 

 there are no other effects. These doses are at least four to five times less than the 

 maximum tolerated doses for the lower animals and thereby within the range of 

 safety, but it is my practice never to inject more than 20 cc, of a i per cent solution 

 (0,2 gm,) for the first dose when the patient is profoundly toxic, since resistance is 

 materially reduced by severe bacterial infections. 



Methylene blue has been generally administered by ingestion in doses of 0.15 gm, 

 (2I gr.) without untoward effects, 



Rivanol is usually employed by local application to wounds but, according to 

 Morgenroth, may be administered daily intravenously with safety in doses of 30- 

 50 cc. of 1:1,000 solution for adults, corresponding approximately to 0,0005-0.0008 

 gm, per kilogram or about twenty to thirty times less than the maximal tolerated 

 dose. 



By local application in solutions of 1:500 to i: 1,000 strength, the dyes are well 

 borne by wounds and such serous membranes as the pleural, subarachnoid, and 

 joint cavities. All of the dyes appear to be excreted largely in the bile and urine, but 

 the rapidity of elimination varies considerably, 



Acriflavin in toxic doses by intravenous injection is said to kill by paralysis of 

 respiration, and I believe that a combination of cardiac and repiratory paralysis ac- 

 counts for the acute deaths of rabbits and other of the lower animals injected intra- 

 venously, intracisternally, or intrapleurally with toxic amounts of the anilin dyes. 



Of considerable interest in relation to the mechanism of toxic reactions following 

 intravenous injections of the dyes is the question of their hemolyzing and agglutinat- 

 ing effects upon the erythrocytes. In my experiments acriflavin has proved most 

 agglutinative and gentian violet most hemolytic, but both effects are relatively slight 

 in the presence of serum, and I doubt if these reactions are produced in vivo by the 

 amounts ordinarily given or exert any important role in the production of toxic reac- 

 tions similar, for example, to hemolysis and hemagglutination in relation to the acute 

 toxic reaction following the intravenous injection of acid solutions of arsphenamin, 



ANILIN DYES IN THE CHEMOTHERAPY OF EXPERIMENTALLY PRODUCED 

 LOCAL AND GENERAL BACTERIAL INFECTIONS 



But comparatively little work has been done with the anilin dyes in the treatment 

 of experimental bacterial infections of the lower animals except in tuberculosis, al- 



