c. It should be given in one large dose immediately before the expected paroxysm. This mode was advocated by Cullen,** and it numbers many respectable advocates. Dr. Harris, Georgia, strongly advises it, in a dose of gr. xv., an hour before the expected paroxysm. Although doubtful of the efficacy of this method as a general rule, I may add, that in one or two instances, I have seen a single dose of gr. xij., given immediately the cold stage commenced, not only check the paroxysm, but effectually prevent even a single recurrence of it afterwards.

* Amer. Jourri. of Med. Sciences, 1847.

Op. cit.

Indian Ann. of Med., Oct. 1853.

§ Ibid.

|| Edin. Med Surg. Journ., Jan. 1855.

¶ Indian Annals, Jan. 1858.

** Mat. Med., vol. ii. p. 97.

Southern Journ. of Med. and Pharmacy, 1842.

d. It may be effectually applied endermically. Although this proposition is denied by Martin-Solon,* it appears certain, from the experiments of Ahrenson. and others, that the salt, when thus applied, is absorbed into the system, and retains its anti-periodic power. Dr. Guastamacchia found it act as efficaciously as if given internally. He dissolved gr. viij. in f ss. of Spirit, and rubbed first one half, and after the interval of a quarter of an hour, the second half, along the spine. when this was done at the commencement of the cold fit, it very often prevented even a single recurrence. Dr. Daunt,§ also, bears testimony to this method in the fevers of South America. Dr. Chasseaud|| found that one or two grains of Quinine in alcoholic solution, injected into the cellular tissue of the arm, are equally if not more efficient in arresting fever than large doses given internally. It produces, thus used, no unpleasant effects. Mr. W. J. Moore.¶ of the Bombay Medical Service, also states that he has treated thirty cases of intermittent fever, and several cases of remittent, with invariable success, by the subcutaneous injection of Quinine. He uses from fl. drm. ss. - fl. drm. j. of the following solution: -

Remarks On The Administration Of Sclphate Of Quini 196QuiniAe Sulph. gr. xxx., Acid. Sulph. Dil. gutt. viij. - x., AquAe fl. oz. ss. The time at which the injection should be made in intermittents is before the expected cold fit. He believes that four or five grains thus used are equal in their effects to five or six times that amount taken into the stomach.

e. It should be given in one ten-grain dose, on a day free from fever. This method was employed by Dr. Pfeufer,** of Heidelberg, in thirty-four cases, and a cure was effected in every case, in a period varying from four to eight days. The dose, he states, is well borne, producing none of the inconveniences which result from the long-continued use of small doses.

f. It should be given at long intervals. Prof. Graves,+t whose proposition this is, objects to the continued use of Quinine, as thus the constitution becomes accustomed to its influence, when the ague fit is absent, and that influence is thus weakened. He therefore proposes to administer Quinine for four successive days, and to intermit it for the following six, thus embracing the interval comprehended in three fits. By this means, he says, the system is kept sufficiently under the curative influence of Quinine, without being rendered too familiar with it, the six-day interval preventing the constitution becoming saturated by the medicine.

* Bull, de Therap., Pec. 1844.

Essay on the Endermic Method.

Ed. Med. Surg. Journ., No. lix. p. 473.

§ Clin. Notes, Med. Times, vol xvii. p. 476.

|| Med. Times and Gaz., Aug. 2, 1862.

¶ Lancet, Aug. 1, 1863. ** Brit. For. Med. Rev., April 1850.

Dub. Quart. Journ., 1846; and Clin. Lect., vol. i. p. 379.

Concluding Observations. From the above statements, it appears that Quinine, in large doses, is an effectual remedy for intermittents; but we require evidence to show that, thus exhibited, it effects a more speedy or uniform cure than when given in small doses during the intermissions of fever. If it fail in small doses, it may be employed in large doses in any of the methods above proposed; but the latter practice is not free from danger; thus, in a discussion at the Medico-Chirurgical Society of London, May 22, 1843, Dr. Sewell, of Washington, stated that, although he had found that large doses, when given in very bad fevers, did not seem to injure the brain, yet that, in fevers of a milder description, they caused deafness, and, in some instances, stertorous breathing, and a dilated pupil. Mr. Stanley added, that he had known cases of Rheumatism, in the treatment of which gr. x. or xij. doses of Quinine had proved fatal. M. Matteucci* mentions the case of a patient who had taken large quantities of Quinine for an Ague, who was attacked with paralysis of the lower extremities. A plan of treatment which in my hands has proved the most effectual, is to administer a brisk purgative or emetic, or both, and then to give Quinine in very small doses (gr. j. to iss.) at very short intervals, every one or two hours, during the period of apyrexia, thus keeping the constitution continuously under the influence of the medicine. Thus given, it appeared to produce a more speedy effect on the system, and to prevent the return of the paroxysm more certainly and rapidly than if given in much larger doses, at longer intervals.

The following facts, relating to relapses after Quinine has been discontinued, merit attention. Dr. Clark, of Dominica, states that if no more of the remedy be taken in the "West Indian Ague than is barely sufficient to stop a fit, and then the medicine be suspended, a relapse may take place on the eighth day, in the case of a quotidian; on the fourteenth or fifteenth, in the case of a tertian, or double tertian; and on the twenty-first or twenty-second, in the case of a quartan, thus making in each type seven periodical revolutions from the time the fit was suppressed, to the next attack; and the fit was found to return on the proper day, at the same hour at which it would have returned, if its course had not been interrupted by the administration of the remedy. Here we have, adds Dr. Watson, a still earlier glimpse of the abiding periodic tendency, noticed by Dr. Gregory and by Dr. Graves, during the long protracted absence of actual paroxysm. It points out clearly the propriety of continuing the remedy for some time after the disease appears to have vanished.

* L'Experience, April 1843.

Quoted by Dr. Watson, Lectures, vol. i. p. 767.