THERAPEUTIC APPLICATIONS OF TUBERCULINS 295 



may be said that the relation of the phenomena of supersensitive- 

 ness to those of the development of immunity is at present 

 very obscure. 



Therapeutic Applications of the Tuberculins. — As has been 

 indicated, the injection of tuberculins into an infected subject 

 may cause necrosis in a focus of infection, and it was originally 

 supposed by Koch (1890-91) that the origination of such a 

 necrosis might free the body of the invading bacilli. It was 

 soon shown, however, that many single bacilli penetrating the 

 tissues around the focus 'were left unaffected, and this method of 

 treatment was therefore abandoned. 



Tuberculin-R was introduced by Koch in 1897 as a toxin 

 having a minimum of necrotic effect, and the object of its use 

 ' was to increase the natural powers of resistance of the tubercular 

 subject. Doses commencing with T J 1T to -g^ mgrm., gradually 

 increased, were given every second day, the rule laid down for 

 the regulation of the dosage being that no amount should be 

 administered which raised the patient's temperature more than 

 "5° F. In such doses profound local and general effects were, 

 however, still produced and these were sometimes of a harmful 

 character. The difficulty of controlling the effects militated 

 against the general use of this tuberculin as a curative agent, and 

 it was thus not until Wright investigated the effects of extremely 

 minute doses of the agent that it again came into prominence for 

 therapeutic purposes. At the present time the tendency is to 

 abandon the attempt to assign to different elements in a tuber- 

 culin the reactive effects on the one hand and the immunising 

 effects on the other ; thus the bacillary emulsion tuberculin is prob- 

 ably as much used as the tuberculin-R, and the object is now to 

 practice such a dosage as shall give the maximum of good effect. 

 For ordinary cases with little or no evidence of constitutional 

 disturbance, an amount of tuberculin corresponding to from a six- 

 hundredth to a one-thousandth of a milligramme of tubercle 

 powder is a sufficient dose ; for more marked cases with little or no 

 fever, from a two-thousandth to a four- thousandth of a milligramme 

 is given. In febrile cases the greatest care must be exercised, and a 

 twenty-thousandth to a fifty- thousandth of a milligramme probably 

 represents the limits of safe dosage. The injections are also now 

 given less frequently, usually at ten-day intervals. The best results 

 are obtained where the tuberculous infection is localised, e.g., in 

 lupus, tubercular joints and glands, genito-urinary tuberculosis, 

 and, generally speaking, the dosage must be regulated by a study 

 of the clinical effects. Under certain circumstances information 

 as to the effect of the treatment is easily available. Thus, if in a 



