23

tendency to produce "pain, inflammation, gangrene and even fatal tetanus"
more than counterbalances the advantages of facility of administration and
promptness of effect, and the use of this method of administration should be
restricted to cases in which delay may be dangerous.

     The behaviour of those Quinine salts that are used for hypodermic injec-
tion, in different strengths of solution, when mixed with ox blood-serum, has
already been described. It should be noted also that solutions of Quinine
hydrochloride prepared with the addition of antipyrine, urethane and sodium
chloride, respectively, as recommended by some for hypodermic and intravenous
use, were tested in the same way and showed no greater miscibility with ox
blood-serum than did simple solutions of Quinine hydrochloride itself. The
ordinary Quinine hypodermic injection, as recommended by Squire,32 is not
more dilute than 1 in 6; the strength of Burrough's and Wellcome's Quinine
bi-hydrochloride Vaporoles is 1 in 5; and the strength of extemporaneous
Quinine injections generally borders on 1 in 1½ Solutions of Quinine of such
strengths must of necessity result in a coagulum and precipitation of much
of the Quinine at the seat of injection. It has already been shown that the
addition of a 1 in 20 solution of Quinine hydrochloride to an equal volume
of ox blood-serum throws about half the Quinine, temporarily at least, out of
solution. An examination of Table II strongly suggests that the more con-
centrated the solution of Quinine salt, the more alkaloid will be precipitated in
the mixture with serum; and the more dilute the solution of Quinine salt,
the less alkaloid will be thrown out of solution. One would expect therefore
from these serum experiments that much of the Quinine contained in the
ordinary Quinine hypodermic injection would be thrown out of solution at
the point of injection, but that, if the Quinine injection is sufficiently dilute
(1 in 150), little or no Quinine would be deposited in the tissues.

     It will be remembered that the substance separated by adding dilute
sulphuric acid to the coagulum (formed by adding Quinine hydrochloride 1 in
20 to serum), after the latter had been washed free from all traces of Quinine,
gave a blue colour when treated with chlorine water and ammonia, and that
this blue colour changed to green rapidly on heating, but after a few days if
left at laboratory temperature. This substance is probably an oxidation product
of Quinine, and the ease with which it can be re-converted into Quinine sug-
gests that, although much Quinine is thrown out of solution at the seat of in-
jection apparently as a transformed product in combination with albumen
(compare with Rossbach's33 investigations), Quinine may be gradually liberated
from the coagulum for two or three days after injection. Reference will
again be made to this coagulum in connection with the occurrence of tetanus
after Quinine injections.