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effected a change in the period of exhibiting the bark. But, whether the merit of first suggesting this improvement be due to Sydenham, or to some contemporary of his, we cannot at present very accurately determine. He is, indeed, the only person who openly lays a claim to it, and asserts that he was led to this alteration after deeply pondering the subject-diù multumque apud se agebat: yet Morton, who published his Pyretologia in 1692, only three years after the death of Sydenham, asserts, somewhat loosely indeed, that, during twenty or five-and-twenty years (Pa. 114, 132), he had been in the habit of giving this antidote, as he calls it, in every season of the year, and to persons of all ages and constitutions; that he had cured every spe

time, usually administered, was in doses of two drachms given twice in the twenty-four hours; and, as already observed, the time selected for the purpose was during the existence of the paroxysm. It is, moreover, highly probable, that it was sometimes considerably adulterated, from the difficulty of obtaining it in any considerable quantity. In 1658, we learn from Sturmius, who warmly patronised its use, that pure bark was so scarce on the continent that twenty doses of the powper were sold at Brussels for sixty florins, for the purpose of being sent to Paris; and that this order so completely exhausted the apothecary's stock, that he himself was incapable of obtaining any even at that price. And hence, for the use of one patient, who was attacked with an obstinate intermittent fever in the month of Febru-cies of intermittent with it quickly and radically, ary of the same year, he was obliged to wait and had found it more expedient to give it in till the June following before he could obtain a the intervals than in the fits. While Lister, supply.-(Febrif. Peruv. Vindiciarum Pars prior, who was contemporary with both Sydenham and p. 84, Antwerp, 1659.) Nor was it less diffi- Morton, and who treats neither of them with cult to be procured at Brussels than in many respect, directly accuses Sydenham, a few years other parts of Europe; for Bartholine, then re- after his death, of having copied his mode of siding at Copenhagan, having received as a great giving the bark from the miserable mountebank rarity a present of three doses, or six drachms, Talbor, who was its inventor, auctoresuo, of the powder from some friends who had brought misero illo, agyrtâ, Talbor.-(Octo Exercitat ioit from Italy, was induced to make a trial of it nes Medicinales de Cort. Peruv. exhibendi tempoon a lady who had a quartan fever. Of this small re.) Talbor, or Tabor, however, is scarcely open portion, the first dose, or two drachms, was re- to the stigma of being a mountebank. He conjected from the patient's stomach; and, in order cealed, indeed, his preparation of the bark, but he to prevent a repetition of this accident, and con- had been regularly initiated into a knowledge of sequently the loss of his entire stock, the admin- medicine by an apprenticeship to an apothecary istrator macerated his two remaining doses in at Cambridge; was the most successful, and, wine for forty hours, and gave the infusion du- therefore, the most popular employer of the bark ring two successive paroxysms. The only effect in his day; acquired a higher reputation in this was, that the fever was changed from a double line of practice than any other individual whatto a single quartan. And here the experimenter ever; was appointed one of the physicians to was obliged to stop, as having no more materi- Charles II., against all the influence of the colals to proceed with.-(Thoma Bartholini Hist. lege; was specially sent for to Paris to take the Anat. et Med., cent. v., hist. 1., Hafniæ, 1661.) Dauphin under his care; succeeded in curing him, But, ever in 1678, when the same pretext for and afterward divulged his arcanum, for a stipusophisticating it no longer existed, Morton com-lated sum, to Louis XIV., by which it was plains that the bark offered for sale was become found to be an infusion of the powder of bark in so inert, corrupt, and adulterated, that it was port wine as a cordial. necessary to increase the proportion from two drachms, to one, two, or even three ounces for a single dose. And, thus given by wholesale, we cannot wonder that still more mischief should result from its abundance than from its scarcity, whatever might be the purity or impurity of its quality.

To guard against all the evils that seemed to accompany its use, Sydenham proposed to himself the following regulations :

First, To be peculiarly cautious in the quality of the bark he employed; and to allow of no intermixture, whether from fraud or a view of increasing its virtue.

Secondly, To administer the bark in the intervals, instead of in the paroxysms of a fever. Thirdly, To give it after the rate of two scruples every four hours, instead of two drachms twice a day, after the Schedula Romana.

Under these regulations, the bark seems to have acquired all the success to which it has at any time pretended; and modern practice has added little to their value.

The best form of administering it used to be considered its powder, "potissima virtus in toto jacet," says Professor Frank. But it is often found that the stomach will not bear it in this form; and hence, modern chymistry has been at work to provide various others, the best of which appear to be those which consist of its essential principle, now sufficiently ascertained to be a peculiar bitter alkali, separated from the woody fibre, and neutralized into a salt by means of sulphuric acid. The French chymists have put us into possession of two distinct salts of this kind-QUININE and CINCHONINE, of which the former is the more powerful, and both appear to have been employed with great success in the removal of intermittent fevers, in cases where the stomach has uniformly rejected both the gross powder and the decoction.-(De Cur. Hom. Morb. Epit., tom. i., p. 64.) The dose of the first, for an adult, may vary from two to five grains and half a scruple, and still more has been given without ill effects of the second, the dose may be from ten grains to half a

:

The most important of them is that which | drachm. The ordinary ill effects from an over

nights, bark cured the ague in the course of a few days. This practice I learned from my friend Dr. David Pitcairn."*

But as, under whatever form, in whatever quantity, and at whatever time the bark is given, it is not found to be a specific, not only in every individual, but in every intermittent, we are again driven to a principle I have already ventured to lay down, that intermittents of all kinds are occasionally influenced in their character by idiosyncrasies, or the temperament of the atmosphere. And it is hence of considerable importance to know what other medicines have the strongest claim to attention, when, from accidental circumstances, the best fails of its common effect.

relapsed. I have now on the hospital books four patients, ill of quartan fevers, who have received no benefit; and I have no hope left, but in a long course of deobstruent bitters, and tinctura sacra, aided by the approaching summer."-(Med. Trans., vol. iii., p. 165.)

Morton's medicine, of one scruple of cham omile flowers, ten grains of salt of wormwood, and the same quantity of calx of antimony, given every sixth hour, is said to have subdued, in the metropolis, an obstinate tertian in two instances. And Dr. Heberden found, that two drachms of the powder of myrrh, taken just before the time of the expected fit, relieved a patient from an ague, which for a long time had resisted the power of the bark, though taken in very large quantities.

haps produced by its containing a larger proportion of resin, that, writing at this very period, Sir George Baker tells us, "I have for some time avoided the use of it." It contains, however, by far the largest proportion of quinine, and is now usually selected for this purpose.

In the east a variety of other astringent and bitter barks are also employed both by native and European practitioners, and apparently with considerable advantage; as that called, in honour of Van Swieten, Swietenia febrifuga, so warmly recommended by Dr. Roxburgh: that of the bead-tea (Melia Azedarach), and the Tellicherry bark. All these have been now tried in Europe, but with a far less success than in India.

This, as we have already had occasion to observe, was the case in the singular intermit- The red-bark was now also tried for the first tents that prevailed both in this metropolis and time it was proved to be of unquestionably in the country in the year 1787, in which the superior virtue to that in common use; but even bark seemed to have no energy whatever, not- a moderate dose of it so often oppressed the withstanding that its genuineness was suffi-stomach and excited nausea and vomiting, perciently tested and proved; in consequence of which the febrifuge powers of various other medicines were attentively studied and appreciated. In some instances other medicines were mixed with bark, and seemed to a certain extent to call forth its proper power; a mixture of bark and alum answered in some cases, but produced disappointment in others. "The crude sal ammoniac," says Dr. Petrie, who was physician to the hospital at Lincoln, "had not a more certain effect. Several women were cured in a hospital by what is called the Dutch remedy for an ague; which is compounded of the bark and cream of tartar, each two ounces, and sixty cloves powdered. A drachm and a half of this powder was taken every third hour. Yet this likewise frequently failed. We at last thought that we had fallen on a specific in the powder of bayleaves, plucked from the tree and dried in the shade. From one to two scruples of it were given in the beginning of the cold fit. This powder was very efficacious in preventing the fits in many cases, where the bark, in the largest quantity, had been unsuccessful. But almost all who used it had a relapse in the space of a fortnight, three weeks, or a month. One patient, just at the time the fit was expected, took sixty drops of thebaic tincture. On this he fell into a profound sleep, sweated profusely, and escaped the fever, not only then, but at two successive periods. Eight quartans in the hospital, and four in private practice, were entirely cured by one drachm of the theriaca andromachi, the same of the root of calamus aromaticus in powder, and fifteen grains of salt of tartar. This mixture was taken in warm ale or wine and water, an hour or two before the fit. Nevertheless I must confess, that I met with several cases where no medicine prevailed; and many patients, despairing of relief, left themselves to nature; some of whom went into a pulmonary consumption, jaundice, or dropsy. Many, whom I thought cured of quartans, lately

• Lect. and Observations on Medicine, by the late Matthew Baillie, M. D., 1825. Unpublished.

Arsenic was also tried, in combination with opium. It is admitted that it often effected a cure; but was frequently productive of violent vomitings, colic, and dysentery. It seems, however, to have been given at this period in a somewhat rude and unscientific form. "Arsenic," says the distinguished writer whom I have just cited, "is mentioned in books as a febrifuge, but it is one of those substances of which we are not as yet so far masters, as to be able, by any art, to render it transferable from the list of poisons to our Materia Medica; and it cannot be deemed to be a proper remedy for an intermittent fever, while an intermittent fever is less formidable than arsenic." But to this substance we shall have to return presently.

The chief BITTERS and ASTRINGENTS that have been called into requisition, independently of those already noticed, are, gentian, cascarilla, willow-bark, nux vomica, and the leaves of the cherrybay, or Prunus lauro-cerasus; the chief ASTRINGENTS, tormentil, galls, and oak-bark; the bark of both species of the swietenia or mahogany-tree; avens or caryophyllata (the Geum urbanum, Linn.), the Lycopus Europaus of the same naturalist, called in Piedmont, where it is supposed to rival the bark, herb China, alum, and several of the metallic oxydes.

To all these a common remark may be applied, that, where they have been of real ser

vice, it has generally, though not in every instance, seemed to arise from their uniting the two qualities of a bitter and an astringent, and that they have rarely answered where there has been only one of these qualities to depend upon. Thus tormentil, one of the most powerful vegetable astringents we possess, and gentian, one of our most powerful vegetable bitters, succeed so rarely alone, that no dependance is to be placed upon them; but when given in combination, they almost rival the virtue of cinchona, and have occasionally succeeded where the latter has failed. 66 Joined," says Dr. Cullen, with galls or tormentil, in equal parts, and given in sufficient quantity, gentian has not failed in any intermittents of this country in which I have tried it."-(Mat. Med., part ii., ch. ii., p. 72.)

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There is, however, a principle, independently of bitterness and astringency, that seems absolutely necessary to enter into conjunction with these, in order to give full efficacy to any medicine employed as a febrifuge in intermittents; and a principle that has hitherto eluded all research; [unless it be analogous to that of quinine, a principle similar to which has been detected in other barks besides the Peruvian.] If the cure depended upon the intensity of a bitter and an astringent quality alone, galls, oak-bark, and mahogany-bark ought to succeed better, not only than a union of tormentil and gentian, or chamomile and alum, which have also been found very serviceable, but than cinchona itself; which every one knows they do not; although, when Peruvian bark cannot be obtained, they become desirable substitutes.

of eight grains in powder every six hours for an adult under palsy, without any mischievous effect except a slight stupor in the head. And much beyond this we cannot proceed with prudence. Hoffmann (Philos. Corp. Hum. Morb, p. ii., cap. viii.) gives the case of a girl of ten years of age, who was killed by taking fifteen grains of it, divided into two doses, for an ob stinate quartan.

The lauro-cerasus was at one time, as we are told by Dr. Brown Langrish, a common medicine in his neighbourhood for the cure of agues (Experiments on Brutes; see also Phal. Trans., No. 418, 420), but he takes no notice of the dose or mode of administering it. Its properties are nearly the same as those of bitter almonds; and Dr. Bergius frequently prescribed an emulsion of bitter almonds with success in intermittents, in the quantity of a pint or two daily during the intermission; and it sometimes cured where the bark failed.-(Mat. Med., p. 412.) This is an authority worth attending to; and as the same medicines are said to have a peculiar power of resolving visceral obstructions, they have an additional claim to a cautious series of experiments. It is known in the present day, that their poisonous property depends upon their containing a portion of native prussic acid [and consequently the latter would now generally be prescribed by those who desire to ascertain its power over ague].

Mercury, as we learn from Sir James Johnson, was tried extensively some years ago at the Bocca Tigris in the east, on the crews of two ships-of-war, the Grampus and Caroline, in consequence of the stock of bark being exhausted. The paroxysms, he tells us, were invariably put a stop to as soon as the system was saturated; but he adds, that three fourths of the patients thus treated, relapsed as soon as the effects of the mercury had worn off; and this after three, and, in a few instances, four successive administrations, so as to excite ptyalism.-(Amer. Med. Repository, July, 1822.)

The only metallic oxyde really worthy of notice is that of arsenic; for although various oxydes of iron, mercury, zinc, and copper, have been tried, and occasionally extolled, none of them have proved so decidedly beneficial as to The nux vomica and Ignatius's bean (Strych-render it worth while to try them over again. nos nux vomica, and Ignatia amara, Linn.) combine, with an intense bitter, a most active narcotic virtue; and how far the last may be peculiarly opposed to a recurrence of that spasm on the extreme vessels which constitutes the cold fit, it is difficult to determine. M. Bourieu (Hist. de la Soc. R. de Méd., 1776, p. 340) from his own practice strongly recommends the latter, and Paullini (Cent. iii., obs. 45), and Aaskow (Ant. Societ. Med. Hafn., tom. ii.) the former. If Dr. Fouquier's remark be well founded, which we shall have occasion to notice more at large when treating of paralysis, that these poisons have a power of augmenting energy in debilitated muscular fibres, while they leave those in health unaffected, we can account for some part of the success which has been so vauntingly ascribed to them in the case of intermittents. But, notwithstanding that they have been for this purpose before the public for upwards of a century, the infrequency of their use is a strong argument that they are not much entitled to commendation. "In a very small dose," says Dr. Cullen (Mat. Med., part ii., ch. ii., p. 76), "the faba Sancti Ignatii has the effect of curing intermittent fevers." But whether he reports this from his own practice, or from that of others, we cannot exactly determine: nor does he tell us what is the small dose he refers I have tried the nux vomica to the extent

to

Iron, though of little value in most of its forms, has been said of late to have succeeded completely in that of its prussiate. Dr. Zol lickoffer has given various instances of this in a foreign journal, and places its powers above those of arsenic or bark. It must be tried, however, upon a much larger scale before it is entitled to an established reputation. The ordinary adult dose is about four grains, two or three times a day, in a little sugar and water.

Arsenic, under various forms, has been employed from a very early period.-(Act. Med. Berol., dec. i., tom. iii.) It is, strictly speaking, an oriental medicine, and has been in vogue immemorially in India, and indeed all over the east, but especially among the Tamul practi tioners, as a most powerful alterant, as we shall have occasion to notice more at large when

treating of syphilis and elephantiasis. It was probably introduced into European practice by the medical students under the brilliant caliphate of Bagdad; and seems to have been first appropriated to the cure of intermittents by the Jewish physicians of Poland.-(Gilbert, Adversar. Pract. Prim.; Slevogt, Pr. de Permissione Prohib. et Prohibitione Permiss., Jen., 1700.) In Sir George Baker's time, we have seen that it was in extensive use, but productive of such very different results, that, however successful it might prove occasionally, this distinguished pathologist thought it a worse evil than any ague whatever. At that period, however, it does not appear to have been tried in its most commodious forms, which are those of an arsenite or arseniate of potash. M. Macquer recommends the latter; Dr. Fowler, many years ago, introduced and gave abundant proof of the utility and general commodiousness of the former; and, under this modification, it has at length found its way into the Pharmacopoeia of the London College, under the name of liquor arsenicalis. Sir Gilbert Blane tells us, that it was used with great success in our unfortunate expedition to Walcheren, where the stomach could not retain the bark: but was combined with opium, and, in most cases, with bitters and aromatics.-(Select Dissertations, &c., p. 105, Lond., 8vo., 1822.)

passed by without notice, that since the establishment of the large copper-works which are now carrying on in Cornwall, the intermitting fevers which used to be almost constantly present in the neighbouring marshes, are now rarely to be met with in any shape. It should hence seem, that the atmosphere is armed with a specific by becoming impregnated with metallic oxydes or carbonates; and that Cornwall should be the spot recommended for change of air in many cases of chronic or other obstinate intermittents.

The result of this general survey is, that the cinchona (including its preparations, quinine and sulphate of quinine) offers by far the best remedy for intermittents of every kind; that arsenic is its best substitute; and that, where these fail, as fail they will occasionally, or if particular circumstances should prohibit their use, we must throw ourselves upon such other medicines as unite intrinsically, or by combination, a bitter and an astringent principle with a certain proportion of aroma or stimulant warmth.*

It is at the same time clear, that a bitter and astringent principle are not the only, nor even the most effectual qualities, for the cure of an intermittent; for the arsenical preparations contain neither of these in any prominent degree; while, as already observed, there are many medicines that possess them in far greater abundance than the bark, which have no claim

* Quinine is given so extensively by American practitioners, that little need be said to recommend it to more general use. When employed with

even in intermittents attended with local determi

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nation. It enjoys a supremacy over every article in the materia medica, and seems entirely free from the objections urged to bark. Dr. Eberle, however, remarks (Pract. of Med., vol. i.), " in cases of ague which from long continuance or from some previous malady, are attended with visceral indurations or enlargements, the quinine or bark course, or in conjunction with mercurial remedies. must be given either after a gentle mercurial The blue mass will in general answer best for this purpose, , as it is mild, and less apt to pass off by the bowels than calomel." Arsenic must be considered as the most valuable of the minerals for the cure

The cases of success from the use of this medicine are so numerous, and its employment is now become so general, as to render it unnecessary to advert to particular authorities in proof of its febrifuge power. With many constitutions there can be no question that it disa-prudence, it rarely produces any bad effects, not grees very considerably; and there are numerous instances of its failure: but it is a medicine of real and inappreciable value in many diseases, and in none more than in intermitting fevers. Dr. Fowler advises it to be taken in doses of from two to twelve drops, according to the age and strength of the patient, once, twice, or oftener, in the course of the day: and the directions are so broad, and at the same time so much within limit, that no actual harm can occur from following them literally. It will, nowever, often be found advantageous to combine a few drops of tincture of opium with each dose, to guard against the vomiting and griping which it is sometimes apt to excite; and the bowels should be kept open by warm aperients during its use. Under the French Directory a similar preparation of arsenic formed a part of Hosack and Francis' Med. and Phil. Register, the political constitution of the day; for an vol. ii., p. 36.) According to Dr. Firth, the sulphate edict was formally published, commanding that of zinc has cured intermittents when the bark and the surgeons of the army of Italy should, with- arsenic have failed.-(New-York Med. Rep., vol. in the course of two or three days, cure the, P. 145.) And Eberle says of it, "I have very rarely failed to arrest the disease as promptly with vast number of soldiers suffering from agues it as with quinine."--(Pract. of Med., vol. i., p. 81.) caught in the marshes of Lombardy, by the use The list of vegetable substances employed by of this medicine, under pain of military punish-American practitioners for the cure of intermittent fever is very great.-See Bigelow's Medical Botany, Barton's Collection towards a Materia Medica, Chapman's Therapeutics, Bigelow's Sequel, &c.

ment *

It is a singular fact, and ought not to be

It is best to begin with two or three drops of the liquor arsenicalis, two or three times a day, and to increase the dose by degrees. As Dr. Elliotson suggests, this medicine should not be given on an empty stomach.-ED.

of intermittents. Dr. Mann observes (Medical Sketches), that it succeeded like a charm; and his remarks might be confirmed by quotations from many other medical writers of repute; but it sometimes leads to anasarcous effusions, and even paralysis has been remarked by Currie and others.

Among the remedies in popular use, the strong decoction of coffee deserves notice; the coffee in powder is highly recommended by some German practitioners.-D.