Different opinions were held by older writers as to the best time for administering quinin. In intermittent fever Torti gave the bark immediately before, Sydenham immediately after, the paroxysm; in other words, as long as possible before the subsequent one. The French school, especially Brettonneau and Trousseau, adopted Sydenham's method; the Italian and German schools, that of Torti, even though somewhat modified.

If we believe, with Golgi, that the youngest parasites before they enter the red blood corpuscle-in other words, when they are free in the plasma-are most susceptible to quinin, we must allow that the best time for administration (per os) is several hours before the paroxysm. The greatest part of the quinin would then be circulating in the blood at the time of segmentation, ready to act on the newly formed spores.

Supported by long experience and especially recent theoretic developments, we administer the quinin in intermittent fever, about three to five hours before the paroxysm. This dose naturally does not suppress the paroxysm at hand. On the contrary, this paroxysm may manifest the same severity as previous ones, though it is often somewhat retarded. The subsequent paroxysm usually fails entirely or is very considerably modified. After what has been said, these phenomena require no further explanation.

If the paroxysm is very close at hand or has already broken out, the effect of the drug is less evident. Moreover, during a paroxysm patients frequently vomit the drug, making its administration useless. In these cases, then, the paroxysm is allowed to pass and the drug is exhibited during the apyrexia in Sydenham's way. A decided modification or even the entire cessation of further paroxysms may be expected.

What has been said applies to intermittent fevers of all types. In severe remittent and continued fevers, especially when they manifest pernicious symptoms, the remedy is pushed energetically from the time the diagnosis is assured, without attention to temperature.

It is not justifiable to wait for remissions, since valuable time may thus be lost.

In considering the amount to be administered we must bear in mind that we are endeavoring to destroy the parasites in the blood, and that, therefore, a certain concentration of the solution (in this case the blood) is absolutely necessary. Considering, further, that when administered per os the absorption of the remedy demands a certain time, and that almost simultaneously with absorption excretion of the drug begins, we must realize the uselessness of small, and the necessity of massive, doses at short intervals.*

Whether, as many writers (Steudel, Kiichel) contend, small doses of quinin "stimulate" the plasmodia so as to produce an outbreak of latent malaria , when this exists, must be left undecided.

According to the investigations of Kerner and Thau, the excretion of quinin hydrochlorate through the kidneys begins ten to fifteen minutes after its introduction into the stomach. The excretion reaches its acme about the twelfth hour, and after this (up to forty eight hours) only traces are to be found in the urine. The sulphate of quinin appears first in the urine forty five minutes after taking. The excretion is completed only after sixty hours.

Summarizing, we may say that the quickest possible and most satisfactory quininization of the blood is accomplished by intravenous and subcutaneous injections; that solutions are best for administration per os, and that only readily soluble salts in corresponding doses should be employed in powders.

Cinchona bark or its decoction is scarcely ever employed to day. Yet experience teaches that sometimes an obstinate infection which resists quinin will yield to the bark. In this case about 10 to 15 gm. of the bark or its decoction should be given during the apyrexia.

Fedeli has recently lauded as especially effective the mistura anti quartanaria Cotunni. Its formula is as follows:

Cortic. cinchona? pulverisat..................48.0

Radic. zedoariae

Ammon. chlorat.........................aa 4.0

Camphorae............................... 1.5

Div. in dos. x (begin to take twenty four hours before the next paroxysm).**

* Torti expresses this very appropriately: " Sane una tantum libra aquae affatim effusa par est extinguendo ignitorum carbonum cumulo; duae vero librae guttatim, et longiusculis intervallis stillantes tractu temporis difficile idem praes tant" (loc. ext., p. 56).

** Torti's ordinary therapy consisted in the administration of one half dram (circa 1.8 gm.) of the powder on eight successive mornings, then at fourteen days' interval, followed by one scruple every morning for six days.

In severer cases he gave at once 2 drams and says: "Neque enim sex scrupuli v. gr. pulveris, per sex successivos dies assumpti, sequi valent activitati, licet sequivaleant ponderi duarum drachmarum uno hausta assumptarum; quod, ut maxime verum est, ita et maxime , notandum in praxi."