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Toua les autres axempleires origjnsux sont fiimte en commenpant par la premiere page qui comporte une empreinte d'impresaion ou d'llluatration et en terminant par la derniAre page qui comporte une telle empreinte. Un dee symboles suivants apparaitra sur la damiAre image da cheque microfiche, selon le caa: le symbols — ^ signifie "A SUIVRE ', le symbole V signifie "FIN". Les cartes, pianchea. tabieeux. etc.. peuvent dtre filmte d dee taux de rMuction diffirents. Lorsque le document eet trop grand pour dtre reproduit en un seui clichA. il est film« A partir de I'angle sup^rieur gauche, de gauche h droite. et de haut en baa. en prenant le nombre d'Imegea niceaaaire. Lea diagrammes suivants iilustrent la m^thode. 1 2 3 1 2 3 4 5 6 w Vg vJcXc^-Ci^ . /^ « G ' TYPHOID FEVER WITHOUT INTESTINAL LESIONS- WITH THE REPORT OF A CASE. BY ALBERT G. NICilOLLS, M.A., MD., Assistant Demonstrator of Pathology, McGill University ; Assistant Pathologist to the Royal Victoria Hospital. ANU C. B. KBENAX, M.D., Resident Surgeon, Royal Victoria Hospital, Montreal. {Reprinted from the Montreal Medical Journal, January, 1898.) \.^^^Q. Fa^ TVPHOID FEVEK WITHOUT INTESTINAL LESIONS- WITFI THE IIEI'OIM' (»K A CASE. BY AhBKRT (J. \l( not,!,,, Al.A., .■\r.f)., AsHiHtanl Dcn^onatralor of I'Mholo^v, M,(;i|| Iniversily ; Assistant P,-itl,„loKMM to tin- Koyal N'icloiifi Unsiiiml, AMI C. }{. Ki:i;n.\.\, MA>., Resident Surgeon, Hoyiil Victoria llospilal, Montreal. Formerly typhoid fever could not he diagnosed with certainty in the ahsence of any of the classical syiiipt.)ius or the characteristic intestinal lesions. With the increase of hacteriological knowledge, however, and the improvement in techni.jUc, we an; now (iial.led to include under the cateoory .,f typhoid iimny atypical cases ahout which we must otherwise have remained in d.nxht. To this result the di.scovery of the serum reaction has contrihuted not a little, and we are now enahled to form a more accurate conception of typhoid pro- cesses and to recognise the v.M-y various aspects which the disease may assume. The occurrence of typhoid fever with absence of the usual ulcerative lesions of the intestines is now recognised liy several oh.servers, nottibly Chanteme.sse, Vincent, Vailhird, Sanarelli, Roux an. I others. A number of such ca.ses are on record, but .some are not corroborated by bacteriological investigation, so that they are of no scientific value A careful search of the literature for the past 10 years has revealed the existence of only 9 such cases which have been conttrmed by the discovery of the bacillus of Eberth. The time has gone by when we could r.-gard typhoid as an infective process locali.sed to the intestines, producing the general symptoms by the secondary action of its toxin. Katlier, have recent researches proved that the disease is an infective one, invading the organism through the lymphatics of the intestine and infecting the system as a whole, the intensity of the legions being generally but not'invariably directly proportional to their proxitnity to the point of inoculation : the brunt of the disease, hence, may fall upon lymphoid tissue, parenchy- matous organs, or at times the central n ervous system. From this point ' Read before the Montreal Meriico.rhirurgical Society, October 20, 1897. of view, which is abundantly .sujjpofted by clinical cviiJencf, thf intesti- nal tract nieivly rcpvcsents n, point of lUiparturc lor tlif typhoid ^crni and not the sole |)lacc of local isation for its duvelopnicnt. SMiiurclli is of tin- opinion that the lesions of the intestine' are due to an elective action, not of the bacilli themselves, but their toxitis acting' from a distance, but this hardly coincides wiili wli.it \vt know of tin pres- ence of the yerins in abundance in tli>' inti/.-liuul mueo,s;i. hi anv ease the intestinal lesions shoulil not In' rej^aj'ded as all important, but rather as incidents in the course of a general process. Tlni> it lieeomes conceivable that these lesions may at times be wanting. And this is the fact. The prodromal symptoms ol' tlie disease, tbe In'iulaclic, malaioG, anorexia and fever, ai-e to be i-eferred to the nervous systfin, and the lesions of tlie intestines may be atypical, delayed, or even absent. Our knowledge, then, of the .symptomatology of tlie disease goes to prove that typhoid is not primarily or necessarily a disease of the intestines any more than variola is mei'ely a disease of the skin. And in support of this view wo have the analogous intestinal lesions which are sometimes present in the course of varioln, measles, .scarla- tina, erysipelas and pyaaiiia. Besides this there is the well known fact that the intestinal lesions bear no relation to the severity of the systemic ini'ection, nor do the objective .symptoms referalile to the intestine — meteorismus, diarrhcea and the like — beai- any relation to the local pathological condition. Consei|Uently it would be UKU'e derinite and more accurate to include the typical text-book disease under the tt;rm "Enteric Fever," employ- ing the term "Typhoid" in a \vi(kn- sense to include all pathological processes nm] conditions resulting fi-om the action of the liacilliis typhi or its toxins. 3 For pui'post's of (■(>iii]i;iris()ii thi' follow iiii;' autlieiitiwitod ciises of typhoid with al»s('nce of tlie usual intestinal lesions may lu' tabulated as follows : Case. 1. OnsKin'KK, Ci.rNK Ai, 'I'yi'k, Batiti Oidinaiv type Tliuf SpU'iio l^llllll^s, «. I'ATIIOI.dilllAI. CdNDITIOX. Iiilt^^tiiics normnl. Spleen ninl iiioseti- IcM'ic (i'liliuls swollen. 1!. 'Pvplli in * N|ileeu iinil niesenteiie ;.iliiii(is, |Sli,ulil tninefiietioiiol' IVyer's t;liinds. B. 'i'yiilii in spleiMi and kiiineyN, V'aillard MeiiinKotyplnis. I'cyei's PiitclieM hoiuihI. I). Typhi in lungs, s|)leen, spinal eord. Sireiitoi'oeei in meninges and spleen. Kai'lin'^Ui. I'^nlaraed spleen. 'I'ypi- Xo lesions in intestines or ines.'ntei'le <'al syin[)|niiis want-; glands. U. Typhi in spleen, ("ulturrvs Inir. Ironi other organs and lilood, si ei'ile. Kailinski, . .. Kidarued s|)leiii. Dark InlesI Ines normal. Two area- oT sol'ten- red paiiules on ( runU. inn' on --eptum of rij^hl ventriele. II. Typhi in spleen, li\er, kidnev and h-iurt. I Vincent 'Diarrlnea, pn rpu ru, Peyer's ])iitches normal. c;onK<'>*tion of eoma. small intestines. Sjjlei n and nieseii- lerie j-'lauds not. swollen. Uilateral pulmonary eon^'estirt the ense we ni'c indebted to Prof. James Stewtirt. Case — W. S., a!t. 2"), laliourer, admitted to Dr. Stewart's wards, Royal Victm-ia H()S]iital, on July Stli, 1N97 complaininj^ of heailache, weakness and eonstiptition. Pfvmndt H'ikIotji. — Whoopino--conoh, seaidatiiia tind mam))s in childhood, IXsed alcohol to e.\cess until three years aott. Family li islor;/— Ko iidierited taint. Un Juno 2iSth, patient came to the out-door department, stating that for some indefinite time, (about Uvo ntonths) previously he had lu't'ii surtiii'iiiH t'l'DMi scvfic! lu'iidiiclit', loss 1)1' iijUM'titc, ami ifi'iicnil weakness. \lv had Ikm-d uldij^cil to ^nv*- up work several times. On admission lie was t'oniid to Ih- a powerhii youn^ man, very som- nolrtit and mentally y Dr.s. ,J. 0. Adiinii niid A. G. Nicholls). Uody that of a youiit; adult male with the usual sifiii.« of deatli. Pectorals and recti of fair size and colour. .\o iiitraiiiuscular h.-eTiiorrhasfes or ahscesses. Peritoneal (•a\lty dry. CV«ji./iOH. — Brain, weinht li'.-Hl grains. .Sliulitly hypera'iuic. 7'//o/7(.c. Hilateral .'idliesive pleurisy. Trachea reddened and cuntalniii)/; frothy mucus. KpJKlottis and Mical cords sonu'wiiai u'deTn.itous. I'eri hroiichial jjiJands enlarjred. A'////(/ /((;(//- \ery u'llcmatous. Lower lolic pi'csenlcd condilioii of broM- chopneumoiiia. Ja'J'I /-io(.r/. — (Kdemalous, l.ouci- lolies ; areas of Wioncho pneinnoiii.i. Muco- purulent broncliitis. Iliiirf. Hijflit side contains adherent anie mortem clol . N'alvi'-, norm.il. .Muscles of li'ft \entricle pale, cloudy, fatly and frialile. Double ri.t;lit cor.inary. Hecent millv spot on vv^\\\ ventricle. Abih>meii.—9 iniidc iiIho uh coiitroJM, ho tliiit the cliiilii of fvidciu r >li()iild lie us coiiiplcit" uh |)OHHil)lu. From II study of tliccasrs iilidvc rclVirrd in. it will In' -iiii Unit this atypical typhoid is a vfcy prntfiui discnsc, its toxic pi>uir nt niic time heirif^ t'oncontrat«'d upon the iiit'si'iitcric! ;^lniids, at atiolluT upon the spleen, the liver nnd oall-liladder, thf centrid nrrvmis system n|iiin the kidneys, heart, or hnios, us the ciise may I"' While in typieal typhoid the Tryei's patches suder tin mo->l, yet the relative intonsitv with \vhi(;h tlio other or-^ans are aflected also varies. Thus, vurialtility, while most characteristic in aty|)ical cases, must Im; regarded as a feature common to typhoid as a whole. Clinicians have long recognized that one or more of the text-book symptoms may be absent, or in the background, and that ca,ses, while they coidorm to a broad general type, often jn'csent minor ditt'ereiices. With respect to the intestinal tract alone, we now know that there may be all grades from a normal Peyer's patch to the most se\ere ulceration ; not only so, but the usual intestinal lesions may be delayed. Ciises have \>wn reported recently where as late as the twenty-tirst day the Peyer's patches presented merely slight hyperplasia without necrosis. We must recognise then great variety in the intensity and course of the process. Broadly speaking, typhoid without intestinal lesion.s falls clinically into three main classes. 1. Typical typhoid, minus the ulcerations. 2. Spleno-typhoid. 3. The nervous type, with extreme intoxication. To the first group would appear to belong the cases of Banti, DuCazal and Cheadle. Diarrhcea may lie present in such cases. Cases of this type are very i-are. The second class, spleno-typhoid, presents a more definite clinical entity, and was first described by Eiselt. This form is characterised by an excessively large spleen, often with acute perisplenitis, and fever of a recurrent type. In such cases the plasmodium malariai and Obernieyer's spirillum are absciit. Some of those cases do present ulceration of the intestines, but it is often absent. Thue's case and Karlinski's first case are examples of this. The third class, due to a severe intoxication, are characterised by extreme prostration, delirium, coma, sometimes hyperpyrexia, degenex'a- tive changes in the vascular system leading to purpura, ha^maturia, meltyna. Jaundice is sometimes present. Many of these cases are, no I I I flniilit txiiiii|ilt's ot'sccoiidiiry septic iiirrctinii. To tills c'liiss iipparcntly lii'loii^ tlir ri'iimiiiirij^- ruses oj' the table, iiicluiliii;j mir own. The cnHi> lure reporteil at l< ii^tli pre.seiitcil on Hroba,biHty to exclude an origin through the respiratory tract, f<.)V the pueunioni;i which was present was clinically 8 a tL-niiiiml event, and sections of the luny tlio Gmm- Wcii>Oit method, showed sucii a niassinj,' of the niicrococcns hmceolatus altont tlH> pnounionie areas that we were; forced to conchide that the condition was (hu to a secondary affection witli tliis acilli of the niorj)lioh)fjy of typlioid ^ci'ms massed in th(> deeper ])arts in the characteristic chniil>s. So tiiat tlie lowest Peyer's patches may liave ht'iMi the point of oriu'in in spite of the fact tliat tht\v presented so little divergence fi-oni the normal. A further point in favour of this view was the fact that the mesentei'ic glands were iniiformly swollen soft : some Iteginning to necrose, and others Inemoi'rliagic. How can we tlien vxplain the;-!, facts ? Observation gives us some information U})ou this point. In relapsed ^^-nhoiil the ulcerative lesions aftect those glands wliich escaped in *■' •, attack, and are also never so intense as tlie primary one.s. Troii deed goes so far a,s to say that in the relapse the intestinal lesiwii.^ are not renewed. However this may be, it seems that the intestinal mucosa having once suffered the action of the typhoid viru.s can resist the force of a second attack, and thus a local immunity is acquired. So that in these relapses the systenuc disease mav prcjceed in the graA-est juanner and even lead to death, while the intestinal lesions are absent. In the case we. record, considering that it was an ambulatory typhoid of six weeks' to two months' duration before admission, it is open to assume that the attack we observed was a reinfection, and that at some earlier period of the illness in the previous 'attack the Peyer's patches had ac(piired a local immunity. This primary attack need not necessarily have been a severe one. It is quite probable that in the so-called abortive typhoid the Peyer's patches never get beyond the stage of tumefaction, and yet they will have ac(iuired an immunity for a short time. Casts where a second distinct attack follow shortly after ccmvalescence upon a previous one would, at first sight, appear to negative this view, but we must remember that in experimental animals when this local innnunity is attained, it only lasts for a .short time, and we have no reason to think that it would be otherwise in the human being. This imnuinity affects the epithelial and lymphoid elements of the intestine and also the phagocytes, so that the bacilli are carried ix-yond the first barrier of defence, which i-emains intact, and are dealt with in the more remote parts of the organism. We have an analogy to this in tlic well-known fact that the bacillus of tuberculosis .sometimes passes through the intestinal mucosa with- out affecting th<' lymphoid elements, and may become localized in the mesenteric glands or in the peritoneum. 9 Or v\'(" may assumt' that wi'tain ptoiuniius di rived from the gastro- intestinal traet, either eircuhitint;' in the liloud, or present in the intestinal niu'josn, act so as to neutralise the local action of the typhoid virus and bring about intestinal inununity. Finally, we may assume that toxins derived from germs other than tv|»hoid mny antae thus !!C(iuired. 'l\) deeidi' betw( en these hypotlieses is an im))ossilile task in our present state of knowledge. As yet they are merely hypotheses, based, it is true, upon experiment, but exactly the degree of importance they possess in relation to the cases here referred to it is impossible to say. Still they are very suggestive. The first assumption indeed explains the process as a partial vaccination of the Peyer's glan^ls and conse- quent immunity to a .second attack. But why should rln' glands bi- singleil out :* Po.ssibly the action of the intestinal nuieosa in excret- ing circulating toxins may have .something to do with tliis, the poisim as it were being coiKtentrated upon the ernunetories, .and thus an iMUuunit}' is confen-ed upon the intestinal glands wliili' utlnr organs are not pi'otected. The last two hypotheses iire ii.ts<'d upon the theory of a uuituid antagonism between the toxins of various geiius. This oiiens n]> a vast subject in which we are still gioping in the darkness of ignor- ance. The relations of t,lie 15. Typhi to the colon bacillus ami other memliei's of the colon group, .ind to the bacteria of the intestinnl ti'act generally, are still unknown, although we are- gradually beginning to see the light. Hut indeed the whole sultject is so entangled with the \ariability in the toxic ]»o\ver of the germs concerned and tln' (jues- tion of the resistance of the bodily organiMii. that the ditiienlties assume gigantic proportions. The recent experimental >tudi.'s of Sanarelli llirow eonsi(|ei;\li|e li^ht upon this subject. It mav lie objected that no propiT inbTencrs can be drawn as regards the human organism from a -tudy of e\pei'iinenl;il .niim.ils, I, lit ibis is not so. The character of tie- lesion-^ in the lower animals depend^ ver\- much upon the ;iniounl of the ti>\in ini>enlated and its virulence. When strong toxins are useil, a condilion i^ obtained bearing very close analogii's to that which obtains in the case of human beings, including the intestinal lesi(jns. Sanai-elli took two series of guinea-pigs and administered for live davs 4 cc. of a typhoid (culture in glyeerlnated liouillon ke|it for a month in the incuiiator at 'M'C. and then sterilised at \'20\ In the first lot of animals the \accini' was inti'oduced into the stomach by means of a sound, and in the second inorulatc'd subeutaneoiish . The 10 last scries of miimals wcfi' ns(!(l as CDtitrols to (U'tcnniuc tin- limit of tolemncf of tlii' oi'traiiisni. It wns found tliat when the animals which hfiil rcc'civt^d tlw typhoiil poison thvouiih the stomach up to the limit of tolerance, were inociilatiMJ with cmii small doses of a virulent culture of H. Typhi thoy died in S to -li hours, and presented neit,h<'i- met<'orisni, alidonnnnl pfiin, wn- intfslin.d legions, while animals which had nu( I n \accinated died in liliuiil ilie same tinn', l>nt with the intestines intensely cun_t;vsted and ecidiynintii-, lymphatic glands enlarged, and mucosa desti'oyed. From these ex])eriments it follows that when an orijfanism receives doses of typhoid toxin within the limits of toleration, the intestinal tract acquires a local imnuniity. A sulise(]Uent injection with a \iru- lent orowth thus may pi'oduce death, laryeiy thi'ouoh the nervous svstem. while the intestine remains normal. Sanarelli also discovered the curious fact that suhcutaiieous injec- tions of sterilized products of the })utri(I fermentation of lieef-Wroth also conferred innuunity upon the intestine, thus opening up the ques- tion whether ptomaines derived from almormal cor.ditions of the dio-cstivc! tract in man may not have some heariiin- upon the .piestioii of the innnunir>- of the intestinal tract. This oliserver also noted the fact that in <>uinea-])i<:s sutlerinfJt from t,Vph(;id. ti)e colon hacilli in the intestine inereasi'(l lioth in numhers and in virulence, killing- out all the other germs, and is inclined to attrihute some of the secondary ])rocesses in typhoid fever to the in- vasion of the liody by these germs which have thus become pathogenic. An innnunity of the organism to typhoid also proved to be an ini- nuuiity against the actum of the B. Coli. Klein's work, tof), on the inhibitory action of certain germs, as the Prodigiosus, Komma bacillus, and putrefactive organisms, \ipon the typhoid bacillus is also vt ry important in this connection. Altoo-ether Sanaivdlis work is the most comphiteand suggesti\e one which has yt't appeared, and we may reasonalily hope for important developments along these lines. We fear that this pa])ei' may a)i])ear to .some too tlu'oretical and visionar\-. It wa^^ not our intention, however, to lay down hard and fast prineiph'^, but rather to ressii)n of tlu' ti'Ue nature of the ]ia,tholo,ui- cal proc-'sses in tliis disease. BIBLIOGRAPHY. Banti, Airhiv. lUilie niifs rli' Biol., Dec. ISHV. Time, .lahri'sl)i;riclit iilK.-rdic Fortsclirittf (Biiiiiii-ai Uiii l-sii, p. \\>0. \';ulliiril, ha St'iiiaiiic MtMiiciilc. M;iri;!i, l.Si«l. N'aillanI ami \'iiic('ii(. l)c I'iiili'itioii par Ic liarillc ty|ilii'|iu' >aiis li-sioiis intcs- linalfs. Bull, el Mem. dc la Soc. .\lf(l. >\. Ilcp- '''' ■'■u'i-. I'^'"'- !•• -'"• (."onplaiul, iaiteiic Fcvci- witliiMit nUtMatioii of Ihi' I'ivim'^ ]i;il(lifs. MidillrMN llosi). H^.p. IHrt)!)!, -Ji). Kailinski. Wii'iu-r .Med. Wochensliritt. March M--.il>l, IsVl Eisolt, Gazil t( Hebdomadairc du Med. et Cliir. de ['aii-, .luiu' :;(ii li. ls:)-j. Vincent, .\iiiiales de rinstitiit Pasteur, Felt. ISl'l, DuCazal, l,-- Bulleiin ivri'dical, Paris. April Killi. ISlll. Jieatt.v. W., Biit. Med. -Idiif. Jan. Kilh. isi)7. p. lis. Cheacile, Lancet, 18i)7, ii.. p. :i-',l Sanarelli. Etudes sur le l''ie\ re lyphoide experimental. .\nn. de I'lnslitii I' is tear, 1.S!I4, pp. 1!« and :t."i:!.