JOHN A. KOLMER 1119 



though they have been quite widely employed in the treatment of local and systemic 

 infections of human beings. It is true that experimentally produced infections are 

 usually severe and place a heavy strain upon the curative activities of a medicament, 

 but yet the logical procedure is first to apply studies of this kind whenever possible 

 and before clinical application is made in order to avoid the pitfalls of hasty and 

 erroneous conclusions regarding the practical curative activity of any agent under 

 study. 



I have not worked with rivanol, but in so far as gentian violet and acriflavin are 

 concerned, my associates and I have been unable to demonstrate any constant or well- 

 defined curative activities in experimental staphylococcus, streptococcus, and pneu- 

 mococcus infections, and I believe the same applies to other anilin dyes of the tri- 

 phenylmethane series. Mention may also be made that Spencer found acriflavin un- 

 able to check or control pneumococcus infections of mice, and Churchman has never 

 been able to kill organisms circulating in the blood by intravascular injection of 

 gentian violet. 



Naturally a large amount of investigation has been devoted to the subject of the 

 chemotherapy of experimental tuberculosis, infected guinea pigs and rabbits (cornea) 

 being usually employed, but none of the dyes so far tested has shown any definite 

 therapeutic power in experimental tuberculosis in guinea pigs beyond some prolonga- 

 tion of life and some lessening of the severity of the disease, although the penetrating 

 and bactericidal or bacteriostatic powers were sometimes good. It is still possible, 

 however, that some of the easily diffusible dyes may be used as carriers for more 

 eflEicient therapeutic substances, which may reach in this way the tuberculous tissue 

 which they could not otherwise attain. 



Comparatively little work has been reported upon in the chemotherapy of an- 

 thrax, tetanus, gas bacillus, and other infections by gram positive baciUi. Since gen- 

 tian violet and other triphenylmethane dyes show such well marked selective bac-' 

 teriostasis for gram positive spore-bearing bacilli, it may be expected that these dyes 

 may favorably influence infections produced by these organisms. Dr. Harkins and I 

 have, indeed, observed that gentian violet administered intravenously and intra- 

 peritoneally to mice and rabbits infected with virulent anthrax bacilli exerts some 

 degree of curative activity by lessening temporarily the severity of the bacteremia 

 with prolongation of life, but so far we have not been able to cure animals in which the 

 infection was given a twenty-four-hour or longer start. 



The dyes have been used in the treatment of experimental B. tetani infections, but 

 with negative results; I have not been able to find, however, any records of work 

 devoted to the chemotherapy of experimental infections by B. welchii, B. maligni 

 edematis, or other gram positive spore-bearers producing wound infections. This 

 would appear to be, however, a field worthy of investigation. 



In diseases of human beings the dyes have been mostly employed for the disinfec- 

 tion of wounds and localized infections of mucous membranes. Thus malachite green, 

 brilliant green, gentian violet, fuchsin, acriflavin, proflavin, rivanol, etc., have been 

 employed for the treatment of infected wounds and apparently with some success 

 although thorough preliminary cleansing, and especially with alkaline solutions, is re- 

 quired for the best results. 



