all practical purposes. In a healthy man, 0·25 c. c. produces an intense effect. Koch thus describes the symptoms produced by that dose on himself, after it had been injected into his upper arm: "Three to four hours after the injection there came on pain in the limbs, fatigue, inclination to cough, difficulty in breathing, which speedily increased. In the fifth hour an unusually violent attack of shivering followed, which lasted almost an hour. At the same time there were sickness, vomiting, and rise of body temperature up to 39·6 C. (103·3 Fahr.). After twelve hours all these symptoms abated; the temperature fell until next day it was normal, and a feeling of fatigue and pain in the limbs continued for a few days, and for exactly the same period of time the site of injection remained slightly painful and red."
One c. c. of a one-per-cent solution—that is to say, a dose of 0·01 c. c. of the remedy—is the smallest dose which affects healthy adults, and the symptoms, more or less marked, following its administration are, in the majority of cases, slight pain in the limbs and a sense of transient fatigue. Only a few persons after this dose show a rise of temperature up to not more than about 100 Fahr. The word "reaction" is used to indicate the symptoms, mild or severe, which follow upon the use of the remedy. In non-tuberculous adults there is no real reaction consequent upon the administration of any dose of the remedy less in amount than 0·01 c. c.; therefore, the presence of reaction in the adult after a dose of less than 0·01 c. c. of the remedy shows the presence of tubercle in the patient. If in the adult no reaction were obtained by any dose short of 0·01 c. c, then it would be certain that the case in question was not one of tuberculosis. This is a law to which no exception has hitherto been found, and it gives the remedy great diagnostic value, which, it seems likely, will be one of its most useful clinical applications. The law applies to both man and beast, and to all tubercular conditions. Already cases have occurred in which the presence of tuberculosis was not even suspected until the remedy was injected and reaction followed.
The dose of the remedy is regulated in tubercular cases by the age and strength of the patient, and by the conditions of his disease. In children and weak people, and in cases of very extensive disease of the lungs, the treatment should begin with the smallest effective dose, which should be very gradually increased. In fairly strong adults with lupus, joint or gland disease, and also in cases of lung tubercle, where the disease is slight in extent, or where the case is doubtful, a full dose of 0·01 c. c. may be administered with safety. But in lung disease, however slight or otherwise favorable the case may be, it is well to begin with a much lower dose. The difference in the conduct of the treatment of