186 Q U I Q U I been exposed to miasmatic influence without danger after taking a dose or two of five grains of quinine once or twice a day. In the smallest medicinal doses it is purely tonic, in larger ones stimulant ; but it differs from other medicines of the same class in the stimulant action being longer sus- tained. In large doses it acts as a sedative, and in exces- sive doses it is poisonous. In some individuals it pro- duces an erythematous eruption, and it is also known to act as an oxytocic. Large doses also sometimes produce deafness, and act injuriously in all inflammatory states of the mucous membrane. The other alkaloids of cinchona bark quinidine, cincho- nidine, and cinchonine also possess similar properties, quinidine being even more effectual than quinine ; but cinchonine appears to produce nausea and gastric disturb- ance. This is also the case with the cinchona febrifuge prepared from C. succirubra. Until the year 1867 English manufacturers of quinine were entirely dependent upon South America for their supplies of cinchona bark, which were obtained exclusively from uncultivated trees, growing chiefly in Bolivia, Peru, and Ecuador, the prin- cipal species which were used for the purpose being Cinchona Calisaya, Wedd. ; C. officinalis, Hook. ; C. macrocalyx, var. Paltcm, How. ; C. Pitayensis, Wedd. ; C. micrantha, R. and P. ; and C. lancifolia, Mutis. Since the cultivation of cinchona trees was com- menced in Java, India, Ceylon, and Jamaica, several other species, as well as varieties and hybrids cultivated in those countries, have been used. 1 Recently C. lancifolia, var. Calisaya, Wedd., known as the calisaya of Santa Fe, has been strongly recommended for cultivation, because the shoots of felled trees afford bark containing a considerable amount of quinine ; C. Pitayensis has also been lately introduced into the Indian plantations on account of yielding the valuable alkaloid quinidine, as well as quinine, but the last two species have not as yet been grown in sufficient quantities to afford marketable bark. The first importation from India took place in 1867, since which time the cultivated bark has arrived in Europe in constantly increasing quantities, London being the chief market for the Indian barks and Amsterdam for those of Java. The principal sales take place in May. In 1876, when Indian calisaya bark first came into the European market, the imports into London were the following -.Cinchona succirubra, 45,000 lb ; C. officinalis, 20,000 Ib ; C. Calisaya, 1000 lb. During the last few years Cinchona Call- saya has also been cultivated extensively in Bolivia and in Tolima, United States of Colombia, and this bark, which had almost dis- appeared from commerce, is likely in a few years to again become an available source of quinine. In order to obtain the cultivated bark as economically as possible, experiments were made some years ago ..by M'lvor and others which resulted in the discovery that, if the bark were removed from the trunks in alternate strips so as not to injure the cambium, or actively growing zone, a new layer of bark was formed in one year which was richer in quinine than the original bark and equal in thickness to that of two or three years' ordinary growth. This is known in commerce as renewed bark. The process has been found to be most conveniently practised when the trees are eight years old, at which age the bark separates most easily. The yield of quinine has been ascertained to increase annually until the e'leventh year, at which it seems to reach its maximum. The portion of the trunk from which the bark has been removed is sometimes pro- tected by moss, and the new bark which forms is then distin- guished by the name of mossed bark. The species which yield the largest amount of quinine are by no means the easiest to cultivate, ana experiments have consequently been made in cross-fertilization and grafting with the view of giving vigour of growth to delicate trees yielding a large amount of alkaloid or of increasing the yield 1 In Java, C. Calisaya, vara. anglica, javanica, Jfasskar liana, and Ledyeriana ; C. officinalis, var. anyustifolia ; C. lancifolia ; C. caloptera, Miq. ; C. micrantha and C. succirubra, How. In India, C. succirubra, C. officinalis, vars. angustifolia, crispa, Uritusinga, and Bonplandiana, and to a lesser extent C. Calisaya, vars. Boliviana and microcarpa ; C. micrantha, C. Peruviana, How., and C. nitida, R. and P., form only a small proportion of the plantations. Since Mr J. E. Howard, the eminent quinologist, pointed out that C. Pahu- diana, How., and C. Calisaya, vars. javanica, Hasskarliana, and anglica, were likely to lead to disappointment as quinine-yielding species, these have been replaced in the plantations as rapidly as possible by the more valuable species, of which C. Ledgeriana, yield- ing from 5 to 10 per cent, or even more of quinine, C. officinalis, and a hybrid between C. officinalis and C. succirubra which has been named C. robusta, Trinien, are the most important. in strong growing trees affording but little quinine. Grafting, how- ever, has not been found to answer the purpose, since the stock and the graft have been found to retain their respective alkaloids in the natural proportion just as if growing separately. Hybridization also is very uncertain, and is very difficult to carry out effectually; hence the method of propagating the best varieties by cuttings has been adopted except in the case of those which do not strike readily, as in C. Ledgeriana, in which the plants are grown from the shoots of felled trees. A few years ago it was discovered that a bark imported from the United States of Colombia under the name of cuprea bark, and derived from Remijia pcdunculata, Triana, and other species, con- tained quinine to the extent of to 2 per cent., and in 1881 this bark was exported in enormous quantities from Santander, exceed- ing in amount the united importations' of all the other cinchona barks ; and by reason of its cheapness this has since that date been largely used for the manufacture of quinine. The imports of cinchona bark into London in 1884, including cuprea bark, are stated to have been 59,287 bales, into France 9271 bales, and into New York 8150 bales. Cinchona bark as imported is never uniform in quality. The South-American kinds contain a variable admixture of inferior barks, and the cultivated Indian barks comprise, under the respec- tive names of yellow, pale, and red barks, a number of varieties of unequal value. For this reason a sample from every b.ale is analysed before the importations are offered for sale. The alkaloids are contained, according to Howard, chiefly in the cellular tissue next to the liber. No definite knowledge has as yet been attained of the exact steps by which quinine is formed in nature in the tissues of the bark, nor have the numerous endeavours that have been made to build up quinine artificially or to obtain some idea of its constitution by splitting it up into its component parts been more successful. Nearly all that is known at present has resulted from analyses of the leaves, bark, and root. From these it appears that quinine is present only in small quantities in the leaves, in larger quantity in the stem bark, and increasing in proportion as it approaches the root, where quinine appears to decrease and eiuchonine to increase in amount, although the root bark is generally richer in alkaloids than that of the stem. The altitude at which the trees are grown seems to affect the production of quinine, since it has been proved that the yield of quinine in C. officinalis is less when the trees are grown below 6000 feet than above that elevation, and that cinchonidine, quinidine, and resin are at the same time increased in amount. It has also been shown by Broughton that C. pcruviana, which yields cinchonine but no quinine at a height of 6000 feet, when grown at 7800 feet gives nearly as much crystallized sulphate of quinine, and almost as readily, as C. officinalis. Karsten also ascertained by experiments made at Bogota on C. lancifolia that the barks of one district were sometimes devoid of quinine, while those of the same species from a neighbouring locality yielded 3 to 44 per cent, of the sulphate ; moreover, Dr De Vrij found that the bark of C. officinalis cultivated at Utakamand varied in the yield of quinine from 1 to 9 per cent. In these cases the variation may have been due to altitude. Free access of air to the tissues also seems to increase the yield of quinine, for the renewed bark is found to contain more quinine than the original bark. QUINSY. See TONSILITIS. QUINTANA, MANUEL JOSE (1772-1857), Spanish poet and man of letters, was born at Madrid on April 11, 1772, and after completing his studies at Salamanca was called to the bar. In 1-801 he produced an unsuccessful tragedy El Duque de Viseo; his Pelayo (1805), appeal- ing as it did to the spirit of resistance to foreign oppression, was much more successful. The first volume of his some- what rhetorical and superficial Vidas de Espaiioles Celebres, in 1807, containing lives of Spaniards who had success- fully opposed the enemies of their country, was similar in motive, and at the outbreak of the revolution of 1808 Quintana, as journalist (Variedades, and Semanario patriotico), as secretary to the cortes and the regency, and also as "the Spanish Tyrtteus" (Odas d Espaiia libre, 1808), rendered important services to the patriotic cause. On the return of Ferdinand VII. in 1814 he shared the fate of other " liberals " or " constitutionalists," and had to endure six years' imprisonment in Pamplona, obtaining his release only in 1820, when he was named president of the department of public instruction under the new Govern-
