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MALARIA REATMENTAE QUIN INE INIECTIONS 5
It is interestin to kee the patient unde observation for a fair time. In 27 to 300 day after the reaiment 82 of relapses occur- red. It was also Mund that tertia malaria Strongi tend to relapse in the sprin and summer Les S in the winter. Patient With tropica malaria mere sive the Same quantityrus the tertia froup, excepi a couple os cases hic ha two injections perday. Mostly the injections ere sive for I aYs, after hicli one eek' intervat Aster a couple of weeks, ver three days. days injection reaimen and when the loo was Dee rom parasites,
tions cause the disappearance of the tropical formes incorrect hecausea large percenisse relHPSe. The reaiment of the quartan cases Yield the fame resulis. A complications of the intravenous injection the writer mentions, inter alia that repeated injections result in an aseptic thrombo-phlebitis. In l703 injections he found in two cases, an abscess, and in q, disturb- ance of consciousness 20 to 30 secondsi. comparison belween the preventive effecti intravenous injections a compare mitti quinine per os, hows that o the averasel. 28 ramo quinin intravenousi prevente an expected attac in 85 of the cases. hile, per os, illi an averas of 2.32 gram this percentas was 6 V. The writer concludes that intravenous injectio ma be considere where the poin is to ut hortuli attacks a Speedit a possibie. It is indicate in comatos condition an also perhaps in thoSecases in hic administration throush the mouili causes obstinate
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96 CHRONI MALARIA REATE B INIECTIONS INTRAVENOUS INIECTIONS OF QUININE ASTREATMENT FO CHRONIC MALARIA
LES INIECTIONS INTRAVEINEUSES DE QUININE COMME TRAITEMENT DU PALUDISME CHRONIQUE
Medicat Ossice with the Coloniat Troops
centu , medicat ossicer observed form os intense an acute malaria infection, hic necessitate the absorption by the sufferer os large doses of quinin and quinquina. Habituation to these form and doses die away because both in ou distant colonies an in Alseria, malaria contro mensures theimprove hygieni conditions of owns the se of quininem a re ventive, and the early treaiment of everrattactis laver ere factors hicli in conjunction,ith the terminatio of the milita operations it Europea troops in region withis his malaria index. had made cases of malaria more rare an had reduce to a very large extent the densit amons Europeans of the parasiti infection hichchiesi assume the remittent bilious form. Therefore. while there was a gradua fallis in the dose intramuscula administratio at the fame time ecam neceSSA , O in toine bal conditionis the digestive apparatus in his form. The extende provision os medicat id for natives ad at thebesinninu of the XX h centu . esto generat contactietween medicat me in the colonies and in North Africa wit malaria sufferer whohad hom hirth been infested in a very intense form with hematoetoa
durins a reat portionis the ear o in many place even illi ut interruption, and or,hom there couldiem question o a Chanseo habitat. The treaiment of malaria by quinin thereiare vias trending before the war, in the directio os restoration o considerable doses andrene edititisationis quinquina. The war in Morocco in the East an in the Cameroon again place Europea troops in condition comparabie to those of the conques of Algeri or therars coloniat campaisns. an patients
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CHRONI MALARIA REATE B INIECTIONS 97
simila to those of the old expeditions ere observed For heirtreaiment the doctor again had to have recourse to the heau doses of quinine of hic the had lost the habit. The intravenous method. the se of hic mas more recent, but hic had also been ureatly neglected came into Vosue sat wit the frequenc os pernicious
medica men here and there, hecause the alone observe the pernicious formsi malaria, hecam seneralised in the Frenc colonies. amon doctor of the rusti ood areas, to ard 1903, at the timeo translation into French of Manso ibook. The terms: Bacelli injections ' and malaria chili ' remained. to them, almos inseparabie.
In the arm of the East the method was extende to ali recent form o malaria C. Harimann has by a complete stud of the question Shown extensio of the method the objectis inhic is toconoey the lames quantityi quinin as rapidi a possibi to anciheemit ascion a possibi a me place here me parasites and their permanent form are Dunci. Carnot and de Rercire had never in the reaimentis acute malaria by the intravenous method, observe an troubie harae a littiemalais an Domitino Lapinaad atready stated: Mith intravenous injections I have neve observeci I do no say accidenta, ut even
C. Hariman confirme in harmiessnes of the method. atyrecorde the ood resulis obtaine mitti it in the American NavY: Ioh Thomson showed that by this method the larges possibie quantityis active quinin was utilised John Clarchis Memphis and
Charies Riche junior an Grifin Henri Mulie and Iob anci
Opinion are preti mel divide a to the rapidit of elimination. Accordin t Ieanselme anci alimiet iis period of elimination is much Shorte than o the intramuscula method in hic it actioniast 50 ours, ut is no appreciabi quicher than through thedigestive passages, in hic elimination is complete in 30 hours.
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98 CHRONI MALARIA REATE B INIECTIONS
Laveranδ', alonin illi Grai and Marchoux held the vie that the produc inhen injected in to the Dein is rapidi eliminateae so that me actio of the drust thouph rapta is ery briefBut Riouδὲ proved that whateve the mode os introductionis quin ine, the method, elimination remain practicatly the fame Theseare like is the conclusion of Porcthyy An Charies Hariman con cluded that the excretion beared by certain riter. e no extat. It is heyond dispute that the conditio of the digestive passages is osten an absolute hindrance to the administration os quinine internalty.
and ali the urave loca troubles hich havera repeatedly been ursed against it, is always a very ainsul method. Though the applicationos asepsis rutes to the operator and the patient the sterilisationis the injectio apparatus and the Solution alnowledse of the nerve tracis. and a judicious selectio of the potnts of injectio may obviat ali heunfortunate ra backs hich have been describe a sucii reatlensili it cannoti dented that this method produces Severe and verylensthy sufferins and is prolonsed occasions impotence of very lensthyduration.
The intravenous rout requires a doctor for iis se. t need this doctor tot practised and caresul. I demand complete sterilisationo the solution to e injecte and of the injectin apparatus. f the quinine is used in a concentraled solution ita us may induce obstructingphlebitis aut there is nothin whicli render the se of histi concentration Obligato .
Carno an de Ret die used a solutioni 2 per cent. Richei and Gris a more dilute solution Ieanselme and Hanaud dilute thealcaloid ora per centi R. Labon to ter 1000 Gari tori 60 per 1000 Barberyyy per l000 an it is certain a potnted out byBrah machari . that this defre of dilution may be stili further increased illi aduantase B usin a dilute solution ali ardenins of the
veins ill be avoided, but there musti no hesitation is a firsi injectiondisclose peculat susceptibilit of the wal of the ein in followinstheotherinjections by an ample washingos the vein with artificiat serum. This ill prevent an injurious actionis the ein There i nounfavourabie alteration of the blood o b feared Soulie/'investigated. both alone and alon with Gulman the modications of thes bularresistanc after the injectio os quinine. The resistance a notappreciabi altereci Sometimes even it mas increased Duperie and Obrenovitch likewis observed no appreciable actioni fragilit orresistance of the globules Inmettersy vie . quinine reaiment hy
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CHRONI MALARIA REATE B INIECTION, 19
The actioni quinine by intravenous injectio may be injurious toth heari Brah macharly found that the arteria pressure may tali after this injectio and that serious accident may thus e occasioned: collapse syncope and even death Grailδ' Helch*' Mat δὲ Laveran38. Hopera*δ Maxcyy have indicate numerous mishaps of this hind. Other accidenis suchis e thema, have been called attention to by Patrichy after intravenous injections os quinine. Rouche of Saratosfalso potntestio skin troubles in relation with the quinin indiosyncrasy, one case of hic terminated in death immediatet after intravenous injectionis quinine.
'The intravenous method Abramρ' could say. ωhich theoreticalis representa the ideat course, musti dismissed in practice. . . itfrequently induces phenomena of hypothermi hoch, ometimes foliorue bycollapse, hich madeis aban ius use , and Laveran* concluded a discussion at the Societ os Exotic Patholosy by sayins ' Intravenous injections os quinin inere seneralised in me arm of the East in thehope that this mode of actionis quin me mouissetve more rapi andreliable resulta Thisinope inas disamoinieci . GL Brissauci and Abram δ' had indeed atready potnte to thedanser of the injectionis any heterogeneous substanc into the vel S: Death by collapse due t aloidit is a threat me possibilit os reaLisatio of hic should counse extrem prudence in the practice of
Therefore a Porach so et says: The intravenous method isoni essentia in pernicius forins hecatis in his case the washinyof the laod vesset plavs a very important pari and musti ad di me actionis me quinine . In many instances indeed the injectiono artifica serum an serum illi adrenali have sive unexpected resulis in the reaimentis perniciou attackS. Man writer howeve persis in declarin the method os quinine injectioni the intravenous rout the most reliable mode of attachinsacute malaria*', above ali in ali comatose, delirious, hypothermic Syncopi an adynamic forms illi histi densities of the parasiteδ', iththe qualificatio by the majorit of them that his method must, in Accordance illi the indications o Castellani and Chalmera, b re-SerVed for ver serious cases and noti utilised other is than withthe precautions indicated by Brahmachari, the methodieri remain ins a is rightly and with unflassin persistency. potnted ut bySmuin the mos convenient method is sufficientiose are sed fortreatin the ordinar form os acute malaria, hicli is an essentiallycurabie disectSe. Doctor attendin natives in ur distanti Nortii Africa colonies
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100 CHRONI MALARIA REATE B INIECTIONS
See Ome ery peculia malaria subjecta These re patienis holiave been infeste Domihel earlies childhoo with dense masses of hemalogo and who have rom the uise of thei existence agreatly enlarge malaria spleen the infestationis hom has continue throushout their life either intermittenti in hos countries hich have a inter. r. a in certain tropica regions throughout the welve months of the ear thous Wit more rues intensity. An there an e no question o advisins an entire population tochans it count . Hygienisi and preventio specialisis are Already Securins resulis in preventin thi continuous malaria infectionis anentire population, but the practisins doctor resortesto for treaiment, must try to cur it The spleen and liver of theseseopte in particular must be acte upon No quinin administered by the mout sives very litile result wit them. Quinquina from hic more pronouncedSucces may perhap be expected i very lo in operation and cinctionine like is is no rapid in effeci.
It is an exceedinsi difficult oin to determine exacti the quantit os quinine fixe by the live and the splee of man. accordinsto the method os administration. because the conditions os a test in hic the percentas of quinin in the blood of the portat ei and the hepati artery wouldie determine on the one hand, and on theother hand that of the superhepati vein and the spleni arterrandvein, are exceedinsi difficultri combine. The percentas of quinin in the spleen and live is also exceed-inui dissiculi to determine, bove ali for the rst name orsan, hecause the washing of the orsan a remove large quantitie of quinine and o the other hand though the larges rout os excretionis the idney, ali secretions particulari bile an ali the digestive juices participat in his elimination.δ Unti suc time a these difficuli test cani carrie out me Bytake ou stand by the work of Growery and those of Iehn andRosa'' hom hicli it a b concluded that quinin is fixe by allthe vascula flands, an above ali by the endothelia lining of the capillarie and consequently as resard the spleen, by ali the celis of the alpighian corpuscles It therefore seem logical tori , by mectnSo quinine applied intravenousty to combat the chroni form os malaria laver in the tropies, where spleni enlargement i the chctrctcteristic lesion, here hematoetoa bound in the spleen and where, accordin t Lmeryg the ma stillae liuin ima more siussis formo life when the examinations of the blood remat negative. D. Labosse reate cachecti malaria sufferer in his Way and obtaine very good resulis and Storis-Dussonysi is of opinio that
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CHRONI MALARIA REATE B INIECTIONS 10s
the best treaiment in severe cases of chroni malaria consista in intra- venous injectionS.
The digestive passage Seem to conve the quinin above ali tothe liver, here it Stay an apparently becomes fixe in a fairly large quantity. But chroni malaria lesion of the live are generali secondaryto a derangement of the spleen and it is to the alter orsan that alarge dos o quinin musti conveyed.
Impelled by these considerations I methodicatly applied the quininetrealmen o the intravenous method during one ear a Cantho Cochin-China in l922-23. to a large number of chroni malariat patient presentin scierou lesion of the spleen and the liver. iththe assistance of M. Donς-Moc-Diu auxiliar medicat ossice of
the Indo-China Medicat Aid organisation.
Effective intravenous quinine reaiment is very tryins It is there- fore destrabie to prepare the patienis,horare to underso to carefullyan at reat tensili. The ascites, i any musti emptie out Thepatient musti puti a severe die for disintoxication the hyper- troph of the spleen must e reale wit atropine. Per os theywill e subjecte to severe reaiment ith heau doses of quinine and quinquina unti ali hematoeto have disappeare hom the per iphera circuintion. The the willi sive energeti anti-hemoclastic reaiment milhcalcium chloride an lactate of strontium. The stariis quin ine reaiment throush the ein musti made in
0ram perlilogramme is reached It is in no way destrabie torus muchmore tha 500 ubi centimetres of serum for dilutin the quinine. This quantityi solution howeve is necessar in orde nodito injure the tunic of the ein an to allow of a long dra n oui injection,
lastin lyto 25 minutes. The liquid musti hol 38 C in The most
convenient apparatus is a botile it a syphon and rubber iube of sussicient tensili to prevent the needleieinidram by the iube Thecto must e regulate by the eight of the apparatus, o that theentrance of air into the botile and consequently the entrance of the dilute quinin into the eins hould ni take place in malibubbles and by the effect of the thoraci inductionis inSpiration. Thi produces the minimum reaction. In orde to tone the atterdo i0.25 gram o 0. 60iram os cassetne may usefuit be adde to
More dilute solutions the different hyperioni or Soloni Serct
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and weetene sera are excipients hicli in no a reduce thereaction. Adrenali is also without effeci. Nevertheless, it ould e extremel usefulci do way with orreduce his reaction, ascit is the ni dra bach to the method i is however o rea that frequently the patienis, though persuade of the emcac of the treaiment by Strihins examples in theiriwn familY, have preferre t renounc Cure Ather han continue a therapy the applicationis hicli inspire them illi terror. Since so man qualised authors, hom Phave cited sariso it mustbe belleved that quinin injected into the Vein produces no reactioni prima malaria. In chroni malari ho ever illi cirrhosis of thesplanchnic orsans, it is alWay very Violent and excruciatinslysainful.
violent an prolonge Shiverings, in horribi sensations of chili. Distitialty persistent nausea, terribie headaches intolerable curvatures, poisnant Sensationis Syncope an even collapse by algidity. It must in truth e state that at these torments are quite tranS
Subsequent intravenous injections o quinine illae suided by the indications of therars reactio and the successive crisis meae laeshinjection. The patient is cured when an injectio in normal dos of0 025iram to 0 05 ram per hilogramme of eight produces no further
Indeed it has been proposed as a test of the complete destructiono the emalogo in the organism, to effect intravenous injectionis distille water, hich should produce no reactio is the organism Sise of ali malaria parasiteS. Howeve the cas may be in reachinaethis potnt of the reaiment, it illis Mund that the live has resumed iis normal siete, that thespleen is reduced that the proportionis leucocytes has come bach to the normal and that the formula os obulatio of the nuclei of the polynuclear ne has been rectifled. The reaiment, istainsul has produce a result, and suci a resultthat the patient, he cured, neve refret havin submitted himselfio a course whicli inflicted onaim a real but transitory, martyrdom, but hicli, in return, has freed hi Dom lesion against whicli noother method has eve had an comparabie action.
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H. M. Moo och, Notes and comments pon m malaria experiences hile illi
Brahmachari, Minimum curative dos o quinin in treaimenti malaria laver hyintravenous methos Indian Medicti Gazette, October 1920. p. 366 . Danselm and Dalimier Deueliminatio de la quinine par les urines Presse Medicate, o Ausus 19 17 .l Laueran, Bullatin de a Societe cie patho sei exotique, l918, p. 879.l Marce Riou Courbe thermique de paludeens Thesela Alger. 1920. 12 Porah, Sur telimination decla quinine par les urines Societe de biologie. 919, p. t 35 .l Academi cie medecine l5t Ma 19l7. Communicationi M. Havem. 1 Brahmachari, Danser os rapi intravenous injectionis concentraled solutions os quinine thydrochlor. Iourna of Tropica Medicine London, l922. XXV, p. 209 .l Henri Mulle, Trailementis paludisme Societ de pathologie exotique i in
l Duperie anci Obrenouitch, Resistanc globulaire dans e paludisme secondatre Reunion biologique de Bor Aux, o Ma l922 .l Netter Resistance des hematies deplasmatisees Aux Solutions chlorurres hypotoniques dans te paludisme Societe de bio pie l9l8, p. 45ὶ.l Brahmachari, anser de injections intraveineuses rapides des eis de quinine
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10 CHRONI MALARIA REATE B INIECTIONS
36 Roux Trailement du paludisme par les injections intraveineuses de quinine Presse medicate. 1918, p. 333 ' Injections intraveineuses de collobias de quinine. Move es medecine et hygien tropicales 192l, p. 97 .