장음표시 사용
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SOME LINES OF CONDUCTI MALARIA THERAPY 75
Auainst tinnitus aurium I recommen pol brom. 1 uram 2 to times a dcty. In severe Domitini frequent in perniciosa Purgenti recommendchloro m. sum ambic. an l0. Sacc. 20 Av. ad emulsionem 200.4
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Medicat inpariment, hartoum Sudan
man artici in the Iourna of Tropica Medicine and Hygine, o Dec. l. 192q. Vol. XXVII. No. 23, p. 321-22 the author pro- poses the folio in Vimprove method os sivin quinine . The amount of quinine to e ahen urin the strat foriniph os
Accordin to the directions sive in the articie, rittent Dr. Manson Bah for the Lance of March 8, 192q. o the reaiment of malaria. 30 gr. are ordered for therars seven day and 20 gr. a d for the secon seven days. In m practice I sive 20ir for the Brstfou days and after three days est rom quinine I sive 20 gr. a dayat the esinnins of the second wee and for three day only. Lamthus sivin i 40 gr. against 350 gr. of the advised reaiment. Now in the great majorit of cases the reaiment is orderedautio directly supervised, and in his connectiones should like to quote the aphorismos an unknown Arab physician as recorded by Professor E. G. Broine in his hird Fitz-Patria lecture V Know that I and thou and thy dis
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would appear asci haVe found it orae, Sual, is no inevitabie. cannot resard it a neceSSarnio sive the drus to this extent. I do notremember it to have been looked a good practice to keep a syphilitici a state of salivation It musti remembered that by the Murth aYthe siqns of the diseas are no evident excepi perhaps for omeenlargement of the spleen and Some anaemia, and et it is ordainedthat, as a routine patient Should swallo these large doses, althoushthe wor tole done is a diminishins factor, hile the drus accumulates in the SyStem.
The later treaiment of malaria patients. HAVins, a state above, sive four days of quinine followed by three days without mos of the quinine ill have been excrete atthe end of this period and it ma be that such malariat organism ashave furvived ill again besin tot active, sod then sive three daYs quinin and folio by four days rest and then, accordin to the caSe, sive three o fou week of 20 gr. on three days three o Murweek of 20 gr. o two days in the week, and finalty three o Murweek of 20 gr. on ne a a week. I always instructi patientsi hesin to take thei quininein the fame da in the weeh. In his way the malariat organis is hept wel unde controi and at the fame time ample opportunit is sive for the resistance of the individuallo have a hance of developins By the system Ι use an advocate about 500 gr. o quinin are sive against about l,050 gr. by the methodirescribe by Dr. Manson Bahr. The treaimenti relaPSeS. The reaiment of relapses depend greatly on circumstance butSpeakin generali I resar a relapse a no requirins Anythins like ct muchis a primar case Iudsins largel by the siete of the spleen. sive a course two-thirdsi one-half or evenies of that sive above, an in orde to assist in the preventionis relapses Ladvis the takinsos quinine lieneve there is an considerable departure rom theordinar habitis life Unde these condition I advis quininein the firSt, Second. eighth, an somelimes the fifteenth aY. The sortifeVent Whic create or appea to create the necessit for this lineis trectiment are ourneys, chanses of climate fatisue Dominny cctuSe, etc.
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78 CONSIDERATIO ORTHE MALARIA REATMENTA CRITICA CONSIDERATION OF THE REATMENTOUTHE MALARIAS
Sectional Editor, Tropica Dise es Bureau London
ONSIDERATION of the reaiment of the malarias ill of
necessit unde present conditions deal first,it the aikaloidalderivatives of cinctiona bark, particulari mith quinine.
Roughi speakins an acid infusion of the bar homi siven species and strat os cinchona containing the aikalolds, ill in the processos manufactureae reate in ne of two ways. I the bark's quinine content be no sufficienti greatrio permit economicali of the commercia extractionis his aikaloid the whole of the aikaloid wil beprecipitate thereiso b causti soda and willi sold a cinchona
varies in alkaloida content and cinchona febrisus has no fixed chemica composition Prain l92qὶ ho ever reporis that the proportionos quinine to the ollier aikaloid os cinctiona in the har of a particular Species grown in an localit where the condition permitis iis cultivation is remarkabi constBnt. Is however the bark's quinin contentis hish the sulphate is separated rom the acid infusio by special means Aster extractionis quinin the infusio ma again by treated in one of two ways. Elther the whole of the residua athalairi may be precipitaled by causti sodaand used for reaiment unde that name or there a b extracted, one by one first the crystalline aikaloids by precipitation cinchonidinea ct Arirnte quinidine As an acid artrate, and cinchonine by virtve of it insolubilit in 80 per cent alcoholi then the non-crystalline Sa ritile or reacly mas throw down by the evaporatio of the spirit in hic the have been dissolved and known as quinoidine oramorphous ahaloici. The veras analysis of Indian and Sumatra cinchona febrifuse
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CONSIDERATIO ORTHE MALARIA REATMENT 79
30 10 Cumine. Confident recommendations of the mos successis method for thetreaiment of the malarias by quinine, in varyinidoses of the aikaloidoris it man salis, at varYin intervat an hourS, re conSpicuous in the page of the Tropica Diseases Bulletin Thei number induces scepticism. In attempis to determine the best methodis quinin administration severat procedures have been or may be followed. l. The means by whic quinine exercise iis beneficent effecis have been investigated Knowledse of these ould enabiecit tot used tothe best advBntnse. Quinine ho ever administered, enter the blood Ramsden Liphino mille 1918 found that after administrationis quinine Serum contain Tori times a much of it a d erythrocytes. Morgenroth
io defibrinate bloo the re celis containe more quinin than theserum. The condition are different and the observation not necessarii contradictory. Returnin to the work of Ramsden Liphin O hithy withini minutes of injectins quinine direct into the rabbit scirculatio 90 per cent has disappeare thence. Ιt ho ever, recty- ars: - . tored Stishil in lymphilands, considerabi in bone marro , an histit in kidneys, spleen and adrenals Aster the intra- peritonea injectio the last containsint east 700 times as much, eight for eight a doesilood. Quinine oratore is destroyed or meta-bolized ' by the tissues Tested by incubatins these Wit known quAntities of quinine, it metabolismis reates in liver intestinat wall, muscies and kidneys. Since quinin contains merely the Same elementSas do hundreds of other oruanichodies iis metabolites can be indentifiedoni by their constitution nothytheir atomic constituents and their con Stitution identity and reactions are unknown Metabolized quinine dis-appear in the bodyMithout trace in Our present knowledse. 2. Quinineis expelle from the ody. notis ali in the faeces unies there bedictrrhoect to a variable extent in the urine Harimann Galla l9l8ὶ hold the percentage so excretestto varydrom lito 35- more generally
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80 CONSIDERATIO ORTHE MALARIA TREATMENT
is ejected unchansed rom heiod by the kidneys the est, va insfrom 35 to 3 per cent. is brohen minio unknown hodies. To,hichmolet is the beneficent actionis quinine due In either case is theaction directi indirect The literatur speah uncertainly. O theone hand lie such conclusion a these: - Durins that minute however before 90 per cent of quinine leaves the circulationJ the physician knows that the quinin is present in the circulation in maximal concentration and that ita fuit destructive effect is heins exertediponsuc parasites as have no reached the fas area' ithin the erythro cytes . O the other han are these facta Basscit 922 find that in the cultivation in vitro os schizosonae form os P. falciparum a 1 in q,000 solutionis quinine cause evident degenerationi intra-corpuScula forms within yhours this quantityiein equivalent to 2 gram- me in the whole blood os a manifes 50 ib. But as has been noted. the rapi disappearance of quinine Dom the blood seem to exclude the possibilit that such a concentration Should ver occur here atali, certainly that it hould persis for sive hours Moroenroth l9l8 .indeed, Stimates the quinin content of blood asini 1 in 20.000 ala minutes after intravenous injectio an in 150.000 tora in 500.000 after ora administration. Mrschbatim l923 found citrated bloo containin P. Divax to e stili infective after incubation athlood temperature for 5 to 2 hours with an equa quantityis ara in 5 000 solutionis quinine. In eleven cases of the great Liverpool series se below the quinin content of the blood was estimated. In thos 3 in hic it was hishest and quinism greatest P. Dioax persisted longestin the periphera blood. In ne of thera talans lar of quinine times a day. 6 day a wee for 3 weeks the parasites neve test theculaneous circulatio at all. In another Ramsden Liphin O Whithy I.c. found the maximum strensili of the quinin to. bera in 100. 0.
The eviden e suggesis then that quinine is not specificatly poisonousto plasmodia but that Lacts by producins directiror indirectly bodies whic are. Ιf. ho ever, quinine ac throus metabolites, then, grante equa dosas an absorption that individua in hom a large percentas of the drus is excretexunchansed in the urine is usin itunsatisfactortly we have ho ever no eviden e that quinin is evercompletet unabsorbe or completet metabolized Accordinsi ita absence rom the urine ma stili re onably be accepte a proos that
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CONSIDERATION ORTHE MALARIA REATMENT 1
non has been ahen, ut the quantit recoVere does no indicate
as the mos reasonable explanation o facts that quinine directi orindirecti destroys a percentas oni os plasmodia, that his dissolution induces, throus the reeins os antisen the formationis immunebody and that the last, o quinine, destroy the remainder of the parasites an disinfest the host- provide theiod has adequalelyreacted Such considerations indicate that the mode factionis quinineis to imperfecti known to affordiuidance a tociis best method of
2. Investigation of quinine resistance. Is quinine fati to cure malaria. and is the conditions under hic suc fallure occurs couldie discovered, the principies underlyin effective reaiment might et be
tigate reputed quinine-fasines in hundred os persons In ne onlyhave malaria parasites persisted in the blood after he satisfied himself personalty that the quinin ordered had been swallo ed Bassil923ὶ.too fatis tofind substantiatio for claims that quinine resistanc existS: an Moaut an collaborator it 917 have disproved iis existence in many cases in hic it ha been accepted. Similarly warrington
io eradicate parasites Dom the culaneo ilood intramuscular injectionhas invariabi produce this result There has been no qui in resist ance. The rus has no been absorbed, possibi not wallo ed. The investigationis quinine resistanc has but atteste the efficacyo quinin in riddin the lood of malaria parasites It has thrown
tere in different ways attempis have been made to discove thebes line of reaiment. in to the impossibilit os determinins whether disinfestation has been attained such cure ' has commonlyimplied Deedom hom clinica an parasiti relapse aster rectiment has ceased OVer a test period of arbitrarii chosen tensili. O in tothe significant but commoni overtooked conclusion independently reached by both two ni of the many recordeesset os experimentS
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82 CONSIDERATIO ORTHE MALARIA REATMENT
to September. 29. or 3 per cent. . relapsed while of 89 realed belween Ianuar an April. 83. or 3 per cent. . relHPSed. The Macedonia experiment a carrie out unde condition of
conclude that nice arm eather i a belle cure for malaria than quinine , ut held that o the eviden e season has a great influenceo the efficac o quinine reaiment of malaria in the classis case concernes an influence difficult to dispute aster the Macedonia confirmation) and that it is at least clea that to attemptrio determine thevaluei a lineis reaiment meret by notin the number of relapses whicli follo it withi a particula time is Seless. his conclusionrender meaninstes mos of the vast massis ork upo whicli therelative values of various quinin treatments are estimated A seasonalem ac of reaiment correlatins itself,ith the recognized seasonaltendencyclo relapse i noti rectSonable. q. The stasse of infection clinicali pathological not biological at hic quinine realmen is instituted requires notice. It has been
ursed by Geneorier l92li that malaria like syphilis has three Stases: i before ametes appear lastin l0-l2 aYs: ii the intermediate condition: iii after viscera lesion estabiisti themselves Thereason- abienes offuch division is combated by Ed Serpenti l 92li. Experienceo the continent of the reaiment of henis tertia malaria deliber atet induce by injectio for the ameliorationis genera paralysis,shows that theserars attach are almost invariabi cured with im.
confirme theserandings in a considerable series of CASes-mOSquito carrie a mellis injected closel folio edisp. They used 64m. in ali, amel 30 grain on three consecutive days, with a relapse percentas of t 6 in injected and 3 in mosquit cases. MoreOVer, number of paralytic have died at various period after reaiment of induce malaria. In non has close search of the organs detectedylasmodia. Semam's experien eo ordinarilyacquired malaria convinces him l92l l 922 that recent infections are essentiali curabie SucheXUeriences in thei marked contrast to thos of Macedonia and East
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CONSIDERATIO ORTHE MALARIA REATMENT 83
Africa in war time indicate another factor Osa vitai nature and et oneueneralty perhaps completely, diSresctrde in comparative statistics. 5. The est route, time, medium an interva o administrationand the est sal have been canVasSed B reason of the million os person involve the Ora rout must ordinarit be emploYed. isessicac is ampi evidenced. e.9. by Collati l 920ὶ but the immense majorit os case are O courSe no publiShed. ne reason o iis apparent fallure Helcher Wor has a noted indicated. t has been suggeste that iis administration in table formis nother. I has. ho ever been hown that properi made tablet os quinin hydrochloride produce at least a much urinar excretion of the base as doesthe fame quantit in solution, Midelin. 9223. There has been a tendency tollam fuga coatins as preventins absorption Lariseron, l922ὶ but suga cannot ut rapidi dissolve in an aqueous fluid. The fauit reali lies in the tablet' menstruum, hich, as Blanchard has hown l922ὶ may resist solubility for monilis and defy the attacho a hammer. Di as useles to expect absorptioni solution of the quinine hic lies in the centre os an impervious luminos concrete asit is unreasonable to condemn the popular Susa coaled rapidlydisintegratin tablet os prove emcacy, and et the qualit of the
menstruum is raret considere in the reporis of the cases a state
the es solubie salts of quinin are absorbed rom the fastro-intestina canalis leas as energeticalinas the more solubie MacGilchrist
this wit a maximum sastri retentioni Mod for Thour after administration, concludes that absorption is mainlydrom the smali intestine, and that quinine, as whateve sali siven, has before absorption been necessarii precipitaled a the aikaloid by the aikaline intestinat uices. Intestina solution and absorption, ne presumes, would accordinGlydependis the nenes of the resultin precipitate. O the relation
observe in experiment on myself that quinin taken justaefore a mea causes tinnitus aurium in about halLan-hour, his provin iis rapi absorption but ahen after a mea it oes no produce hiSeffectis qui kly.
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8 CONSIDERATIO ORTHE MALARIA REATMENT
the paro sinis due Evidence has notieen traced in iis support Onthe contrary Risux 19l8 observes that is quinin administratio bestarte When schizonis are very youns, growt CeaSexand degeneration besins. Is starte&when these are halfirown somerare hillesanddegenerate and some carr on to Sporulation I besu durins spor-ulation his is not checked. In fametes chans is les rapidivi defeneration follows in time. Possibi the inference mentione is an illegitimative offsprins of the belles that quinin is no absorbed by erythrocytes A noted Bassiund that quinin in a concentrationis in .000 produces degeneration os intracorpuscula formS. Thesivin os quinine at a specia phase of the life cycle does not appear, then tote based on scientific observations. For intramuscula injectioni quinin the mali bul os fluid availabi render necessar the se of a solubie sali, the thydrochloridebein commonly used The rue value of this rout remain undetermined. In MacGilchrist s experiments with bihydrochloride l9llinnecrosis followed intramuscula injectio into uineapis S rapidlyas to exclude even thrombosis ascit cause It was widesprea in dilutions as ea asci in 150 and quinin was precipitated in and recoVere from the necroti tissues. The experiment of Dudoeon l9l9ὶ leave no doubtin his matter and Hele l922 reporis the fame find- ins Mariani, to μα . Mund 60 per cent of quinine bihydrochloride in rabbiis musci l hour after iis injection Clinicatly too the sequelae of intramuscular injection can be grave or catastrophic Apartfrom the reappearance in the literatur os deathchom tetanus BoreI