574 Tuberculosis. 



as the teuth day) as hanl, firm, painless, distinctly circumscribed tumors the size 

 of small peas or larger (Ostertag). Later on the internal organs are also attacked. 

 The enlarged Ivmph glands may be resected and examined under the microscope, 

 or the inoculated animals which in positive cases gradually emaciate and whose 

 fur becomes rough, may be killed after three or four weeks for post-mortem 

 examination. After intramammary inoculation tubercles appear in the mammary 

 glands as early as the lifth day and the milk contains numerous tubercle bacilli. 



Allergic Tuberculin Reactions. Tuberculous iufection pro- 

 duces certain changes in tlie animal body as a result of which 

 it reacts to a second infection or to the injection of toxins of 

 the tubercle bacillus in a different manner than the body of an 

 animal that has not yet been infected. This condition, referred 

 to by Pirquet as alley gia, i. e., altered power of reaction, mani- 

 fests itself in increased resistance toward the virus in question 

 (see pp. 530-535) and in h^Tpersensitiveness to its toxins (a 

 kind of anaphylaxis). This latter manifests itself in more or 

 less pronounced symptoms of inflammatory reaction following 

 the administration of very small quantities of the toxins which 

 would have no eifect on healthy animals. 



This hypersensitiveness is particularly evident with re- 

 spect to the tuberculin which Koch prepared from glycerin 

 bouillon cultures and which was recommended as a curative 

 agent in tuberculosis. Expectations along this line have, how- 

 ever, been realized only to a limited degree but later experiences 

 and observations have confirmed Koch's declaration that, on 

 account of its specific action on a tuberculous animal, tuberculin 

 is admirably adapted as a diagnostic agent. For j^ears the 

 general febrile reaction which usually follows the subcutaneous 

 administration of tuberculin was exclusively depended upon for 

 this purpose. Eecently however the local ophthalmic and 

 cutaneous reactions also have attained great diagnostic im- 

 portance. 



Tuberculin and Its Preparation. Koch prepared tuberculin by growing 

 tubercle bacilli at 37-38° C. for eight weeks in veal bouillon containing i% pepton 

 and 5% glycerin. The culture was then evaporated on a water bath to one tenth 

 of its original volume, sterilized at 100° C. and then passed through a clay filter. 

 Crude tuberculin thus produced is a clear brownish-yellow oily fluid which, in its 

 concentrated form, will keep unchanged for months but loses its activity in dilute 

 solution (according to Jansen light and heat does not affect the activity of the 

 concentrated tuberculin). By repeated treatment of the solution with 60% alcohol 

 a white powder may be obtained, the so called purified tuberculin, of which 0.1 

 gm. produces the same effect as 0.5 gm. of crude tuberculin. This powder is readily 

 soluble in water but aqueous solutions are not stable. In solution with 50% 

 glycerin and water it keeps a long time and is not destroyed even at a temperature 

 of 160° C. (Brieger and Proskauer). 



Tuberculin adapted for diagnostic purposes may be prepared in other ways 

 also. Thus Helman prepared it from a glycerin and water extract of cultures 

 grown on potatoes treated with alkaline serum-glycerin (this has only one-fourth 

 the strength of Koch's tuberculin but a similar action). Bujwid makes an extract 

 of glycerin agar cultures by repeated treatment with water, sterilizes the fluid 

 at 100° C, filters through clay and then concentrates on water bath (action identical 

 with Koch's tuberculin). Malm prepares tuberculin by the use of an artificial 

 culture medium that is free from albumen (the tuberculin thus prepared nevertheless 

 contains an albumosedike substance). 



In actual practice the tuberculin prepared according to the original method 

 of Koch is generally used. Tuberculin prepared from human tubercle bacilli is 

 effective in animals as well as such that is prepared from cultures of the bovine 

 bacilli. Kanda found however that tuberculin prepared from bovine cultures acts 



