infections of the alimentary tract

752 THE BRITISH J0URNA.L O F SURGERY

INFECTIONS OF THE ALIMENTARY TRACT. ]BY W. HEATEAGE OGILVJE, LONDON.

INTRODUCTION.

Scope of the Investigation.-Thc organs of the alimentary tract and their associated glands are subject to a group of diseases, inflammatory in origin, which may be termed the ‘surgical infections’ because, in the present state of our knowledge, thcir treatment is by operation in all except early cases. These so-called surgical inFections are ulcers of the stomach and duodenum, cholecystitis, pancreatitis, and appendicitis. It is proposed in the present paper to review certain factors which appear to be common to the etiology of the diseases of this group, without dwelling upon the special factor which must admittedly also be present in each case, and to discuss the bearing of recent work, including some original experiments, upon the problem. There are several grounds for bringing together these conditions into one group : (1) They appear to be largely modern diseases ; ( 2 ) T h e y are diseases of civilized I q e ; (3) They are due to the action qf pyogenic micro-oqpnisms; ( 4 ) 2 ’ h p cause of the bacterial inca8ion is still in doubt.

MODERN DrsEasEs.-while these infections have probably been with mankind for a considcrable time, they appear only to have become a t all common in the last thirty or forty years. In reading through the Practice of Phys ic , published jn London by William Salmon in 1’716, a work which claims on the title page to contain information “ beyorid whatever was yet published by any author, ancient or modern, since disease first appeared in the world to this day ”, we come across clinical descriptions which suggest that gall-stones, appendicitis, and gaytric ulcer were afflictions of that time. Yet the second edition of Heath’s Dictionary of Practical Surgery. published in 1887, does not mention infections of the stomach, duodenum, or pancreas, and only refers briefly to gall-stones from the point of view of treatment. The tenth edition of Erichsen’s Surge/y, 1895, contains no reference to duodenal ulcer or pancrcatitis ; gastric ulcer arid gall-stones receive only brief mention, arid inflamnia- tions of the appendix and caxuni are grouped together as typhlitis. In treatises on medicine of this period, gastric ulcer and gall-stones are allotted a much smaller proportion of space than in any text-book of the present time. Thus the second edition of Aitken’s Medicine, a work of nearly 2000 pages, published in 1853, contains no mention of gall-stones, pancrcatitis, or appendicitis, arid only two pagcs on gastric ulcer ; the 1910 edition OF Osler’s Mediciue, out of half that number of pages, devotes eight to gall-stones. nine to gastric ulcer, four to pancreatitis, and seven to appendicitis. Rendle Short.] in his article on the causation of appendicitis, states that the disease was rare in

1. THE INFECTIOKS O F THE ALIRIEKTARY TRACT APPEAlL T O BE LARGELY

INFECTIONS O F THE ,ILIXENTARY TR,\CT 753

this and other countries until the end of the nineteenth century, and did not become frequent until after 1895.

It would be unfair to lay too great stress on this argument, for it is certain that once a disease has been accurately described and investigated, cases of that disease arc subsequently reported in larger numbers than could be accounted for by a sudden increase ill its inciclencc. For example, the diagnosis of so common a condition as duoclenal ulcer mas rarely made, either clinically or a t post-mortem, before the picture of the symptoms was outlined aiid brought before the profession by Sir Berkeley Moynihan. In earlier writings, only those cases which gave rise t o h;rniorrhage or perforation were recognized. Similarly cases of pseudo-coxalgia occur to-day in the practice of every surgeon, while five years ago such cases mere classed with tuberculous disease of the hip. It is difficult to believe, however, that such marked catastrophies as acute hmnorrhagic pancrcatitis, suppurative appendicitis, and gall-stone colic would have escaped the attention of the trained clinical observers of tv-o geiierat,ions ago,* if their incidence had been in any way comparable with that of to-day.

2 . THEY ARE DISEASES OF CIVILIZPI> LIm-These diseases have also in common the fact that they appear to be, in some way, the products of civilized life. With Europeans they are commoner in those whose civilization is highly developed, and in t.hese races have a higher incidencc among city dwellers than among the agricultural population. They are found in domestic animals and in wild animals in captivity, but in the primitive races of mankind and among wild animals in their natural surroundings they are almost unknown. I need only refer to the experiences of Colonel JIcCarrison2 in Xorthern India, of Glenfell in Labrador, and of Fouchb3 among the native races of South Africa, for the confirmation of this statement.

3. THEY ARE DUE TO THE ACTIOS O F PYOGEXIC >kCKO-ORG~4KISMS-

The third reason that I would give for grouping these conditions together, that they are alimentary infections whose primary cause is an invasion by pyogenic bacteria-staphylococci, organisms of the coli group, hut most commonly streptococci-is one which may provoke some disagreement, a t any rate with regard to the gall-bladder and pancreas. I am well aware of the biochemical view of gall-stones propounded by Chauffard4 and his collaborators of the French school, and of the mechanical theory of the causation of pancreatitis associated with the nanic of Ar~h iba ld .~ I believe that most surgeons, while admitting the great increase in the cholesterin content of the blood which occurs in pregnaiic.y and in certain fevers, hold that this is only a contributory factor in the pathology of cholelithiasis, and that, except in the presence of an infected gall-bladder, cholesterinaemia rarely leads to stone formation. In a series of cases which ha.\-e been recently examined by Campbell a t Guy's Hospita1,S the amount of cholesterol in the blood was within normal limits in 10 cases of gall-st.oncs where diagnosis was

~ -. - ~~ ~ ~ _ _ ~ ~

* Richard Bright described acute appendicitis in 1889.

t See recently I h L B E Y a.nd MOORO, La~rerf, 1924, i , 589. \'oL. XII.--NO. 48. 50

(Elemeuts of the Practice Of Jfe t l ic ine , BRIGHT and AI)DISOX.)

734 THE BRITlSH JOURNAL O F SURGERY

vcriliccl by operatioii, ailtl iii 12 cases of suspected gall-sloiics and ch01ec~ys- titis. The rec,etlt work of H o ? d7 allows Chauffard‘s figiires dcinoiistrating iiitra-epithelial cdlections in the gall-bladder wall t o be esplaiiied on the vie\$, liot of exccssixc secretion, but of insufficient absorption on the part of a gall- bladder whose 11 all has been tlaiiiagcd by infection. The figures facing page GO in Chauffard’s well-known book arc almost identical ni th Figs. 278 aiid ?S:? in Boyd’s article in the l3itIrrsIr JOC-RNAL op Sr H G E I ~ T . In every one of 52 pall-bladders w h i c s l i containrd these intramural collections of cholesteriii ester, Boyd found eT idence of iiiflamniation. With regavd to paiicreatitis. tlic reperit work of RIaiiii and JirdtlX has rcndered the mechailicd Ticw unteii- ahle, while Deal er has established thc irifcctivc iiatnve of acute anti chroiiicl paiicrratitis on a sound clinical basis. The primary bacterial origin of ap1)endicitis is more qcneral1)- accepted. the older vien which poslulateti a preceding injury by foreign bodies in the lumen being 110 longer held. Whether the infection i s corninonly hmiiatogeiious, a5 Ixlie\-ed by many German workers, or from the lumen, i5 for the prc5cnt ininlaterial.

Perhaps more work has been done on the etiology of gastric. ulcer than on aiir disease of this group, aiid while niaiiy conditions ha1 e proved to be capable of produciiig experimental ulcers, the general coiiclusions at which most observers have arrived have been recently simiined 1113 by Stewart.gJo ‘. It is now generally belie\ ect ”, hc say<, “ oii strong cliiiical aiid pathological ex-ideiicc, that all chronic gastric ulcers ari\e iii arid Doni acute ulcers ”. Aiid later, “ Bacterial infection arid intoxication is undoubtedly the most important direct cause of acute gastric and duodenal ulcer in man, as i t is the method by which somc of the most reinarkable experimental results hare been obtaiiicd ”. It is not my intention to arialyse these results ; but, of receiit experimental work, the most interesting is probably that of Rosenow, referreti t o by Hurst arid Stewart. Rosenow’s experiments, which h a w appeared in a series o€ papers during the last ten years, lead him to tlie 1-ien-to quote the last sentericc of a paper in h i g e y g , Gynecology and Ol/stei?ics, of 1 92I1l--tha, “ the conclusion that streptococci are the chief cau5e of ulrer of the stoniacl,

4. THE C-LCSE O F THIS BICLERIAL I \ V Q S I O N IS STILL I T DotTwr-If we may proviaioiially accept the view that thcsc infertioils of the alimentary tract are in some way bouud iip mith civilized life, and that thcy are essentially due to ail invasion by pyogenic bactcria of which streptococci are the most important, we ncvcrtheless find considerable difTkulty in tracing the source of these bactcria and accounting for their portage to tlie site of disease. The researches of Kose i io~v ,~~ referred to above, appear to point t o a htEmatogeiious infection in each case. Hc protlured experimental gastric xiid duodeiial ulce~s 111 aiiimals by the intravenous iiioculation of streptococci isolated from tlic teeth, tonsils, appendix, ?all-bladder, and from gastric ulcers, in hiiinari subjects. Certain strains of streptococci appeared to s h o ~ a teriderlcy to produce lesions in special organs, a characteristic which Rosenow calls ‘elective localization’. Thus streptococci from a gastric ulcer, 011 ictravcnous injection in animals, produced 68 per cent of lesioiis in the stomach alld duodeniini, 21 per crrit iri thc gall-bladder, only 1 per cent in the appenclir; ; thosc grown from a human gall- bladder produced cholecystitis ili SO per cerlt

of cholecystitis, and probably paiicreatitis, seems justified ”. 1

INFECTIONS OF T H E TRACT 733

of' aiiinials, gastric lesioiis in 111 per cent ; streptococci fro111 the appp11dis lmdiiced lesions in the appciidix in 70 per cent, in the stomach and duodeilunl in 1 1 per cent. in the gall-bladder in 1 per cent. A K ~ interrelation between infective processes in diflerent parts of the aliineiita tract is clearly pointed out 1))- these and other esperiiiients. as nell as by ( iical experinicy ; but i t is difficult t o be certain whether. in tlie case of the hmmaii subject, thcsc TI idel) -separated lcsionr should be regarded in the light of CUIISC and effcct. or v licthcr they are both. siiiiultaiieousl\. or successi\ el>-, infected froin some ot1ic.r soiirw. JVc are still in doubt as to tlic true ~ a ~ s e of the original hc te r ia l iiir-asion of tlie body.

In spite of this lack of k n o ~ ~ l c d g e coiwerning tlic nieaiis by which the priiii:ary focus has become infected. mwli attention has been given of late to traciiig th? paths by which infection may be rarried from oiie portion of the 'iliniciitary tract t o another. aiid tlic route on M hicli siirgeoiis ha\ e largely focwxd theii. attention is that of thc 1)mil)liaticL channels. The n ork of inany authorities, notably BIaugerct. E'ranke. Pfcillrr, and Bartcls, has been cbollected

Dca\-erl3 in his in\*estigatioiis of the lyiiipliatic routc by n liich the pancreas i n n ? beconic infected. his coiiclusion being that " clironic pancreatitis i s a rctloperitoueal infection secondary to the more common forms of abdominal inflanimation of the tluodeiium, the gall-bladder, the pylorus, the appendix, and of other parts of the aliniciitary tract. all of which are coniiccted by a retroperitoneal chain of I~-inphatic\ *'. .Jwld quotes the work of Graharnl4 aiitl Sudler15 on thc connection I,ct\\ eeii the lymphatics of the liver aiid gall- bladder in support of the \ iew that cholecystitis may in sonic instances be secondary t o a hepatitis. Braithn-aite.16 a s the result of the study of the Iyiiipli-flow from the i leocmd angle. has recently suggested that a chronically infected appendix may give rise to ulcers of the stomach aiici duodenum by a retrograde flow along the lpipliatic channels going from tlieae I isccra to the collectjiig glands round the coiniiieiiceiiieiit of the siiperior niesenteric. artery.

While these iiivcstigations are extrcniely suggestil-e. i t is very question- able uliether the majority of then1 have any real bearing U ~ O I I the paths by nliich infection is actually carried from one organ to anothei- iii the body. d i i euamination of thc lymphatic channcl~ in :t living animal brings out two most striking characteristics : first, the great variation in size which the) undergo at different times-the thoracic duct, for instalice, in the cat, is at oiie t h e ; r h o s t invisible, a t another sw-olleii to a dianieter of 4 111111. ; and seroiidly, the cstrenirly lei5urcly character of the lymph-flow. JVc ha\-e no t1irec.t estimation of thc pres\urc in these \ essels, but by comparing the coiitlitioiis present M ith those in the \ eins, wc are forced to tlie conclusion that i t is re ry Ion- indeed. The pressure in the smaller \eilis is from 7' to 15 iiiiii. of m e r c ~ ~ r y . Pressure in a 1 essel dcpcnds lipon three factors : the force of the flow, the peripheral resistance, and thc resistance of the v d s . Conl- 1):ired with tha t iii the 1 eins, the f l o ~ in the lyniphatics is small indced ; thc rate in tlic thoracic duct of the dog is & inin. per second. compared with 85 miii. it1 tlic iiicsenteric 1-ein. The peripheral resistance is aliiiost negligible, owing t o the wide character and great clistensihility of tlir cliaimels into which they flon. The malls rcscnible in structurc tliosc of' T cins, but are cry muc4 more

756 THE BRITISH JOURNAL O F SURGERY

slender. The pressurc in the lyiiipliatic~ rhannels cannot therefore be more than 1 or 2 mm. of mercury.

Now the method by mhirh these connections liavc been traced is the injection under pressure of dye solutions into the lymphatic spaces of the tissues. Braithwaite used indigo-carminc solution a t a prcssure of 6 to S nim. of mercury, “ the pressurc being increased where obstruction to the flow was observed ”. The effect of iiijecting a solution into a systeni of vessels a t a pressure considerably higher than that normally obtainiiig in them will be that the whole system is filled to the limit of its capacity, and the solution follows all paths that are open to it, without any relation to the flow occurring under normal or even possible conditions in the living tissues. If a dyc is injected into the lacteals of the cat, it does not follow the iiornial path of the lymph-flow through the collecting glands to the thoracic tluct, but takes an apparently haphazard path along collateral channels.

Then again, the use of a soluble dye ignores the fundamental fact that bacteria in the lymph-stream are carried, not in suspension in the fluid, but in the substance of the wandering cells, whose movenients are governed by vital and not by mechanical laws.

The evidence, then, by which i t has been sought to prove the carriage of infection from one orgau in the alimentary tract to another by means of lymphatic channels is, except perhaps in the case of the pancreas, inconclu- sive. The arguments which may be adduced from the spread of tuberculous or cancerous lesions are open to cven more obvious objections. Nor is the pathological evidence any more satisfactory. The lymphatics of the alimentary canal occur in two plexuses : one in the submucous coat, and one between the two muscular coats.17 These do riot communicate with each other. but drain independently into it subperitoneal lymphatic plexus. An infection reaching a hollow viscus along the lymphatic channels by retrograde flow should therefore produce its earliest and most marked effects on the peritoneal coat of that organ. This is directly contrary to what wc know of the early stages of alimentary infection.

TO elucidate the paths by which infection is carried to the alimentary tract, our aim should be to approximate the conditions of our experiments as nearly as possible to those actually obtaining in the living body.

INVESTIGATIONS INTO THE PHYSIOLOGY AND BACTERIOLOGY OF THE ALIMENTARY TRACT.

Surgery to-day looks to the study and recognition of disease in its early stages for its abolition to-morrow. Moynihari has coined that invaluablc phrase, ‘the pathology of the living’, to describe the study of morbid conditions in the living subject, which, in his hands and those of other surgeons, has done so much to supplement and advance the knowledge already acquired by post-mortem pathology. In the case of the alimentary tract, this has gone hand-in-hand with a new anatomy and physiology of the living whose incep- tion dates from the pioneer work of Cannon16 and Hurstlg on the position and movements of the viscera in normal animals and men, and of Hyle, Bciinett.aO and others, who have studied the physiology of gastric secretion and digestion

INFEC”TION8 OF THE ALIMEKTAIItY TR,ICT 757

in healthy individuals by the Rehfuss fractional test nieal. Following closely upon this has conie the application by JIeltzerZ1 and LyonZ2 of the Einhorn tube to the s t d y of the condition.; obtaining in thr diiodenuni arid biliary passa,yes in the living.

-It Dr. Hurst‘s suggestion, I commenced early i n 192’2 a series of investi- gatiotil; on the inicroscopical and cultural characters of the duodenal eontcnts and o f the bile in cases of gall-stone disease, using the duodenal tube by Lyon’s incthod. I shall not refer to this work in the present c:omrnunieation, but \-cry early it became evident to nie that in order to appraise the results obtained a t their true value? it was necessary to hare a normal standard with which to compare them. The six dressers with whom I was then working very kindly volunteered as subjects, and in them I investigated the characters of tlic resting gastric juice, and the microscopical, chemical, arid cultural characters of the duodenal contents, and of the bile recovered after irrigating the ampulla of Yater with magnesium sulphate.* The results, in so far as the!- coneen1 the present investigations. are shown in Table I .

Sterile

4.2 I 47 Had dron!; I water (,. T. H. 0 Str. loiigiis Sterile

- . _ _ _ _ ~

Sterile S t r . loiigics Sta. ulbus I t . c‘. C . T.

Hzmolytic

Enterococeus streptocoecus Sterile RIany I.. r3. le‘lcoc~te’

In these sis apparently iiornial individuals, the bile was in each case stcrilc ; but the duodenal contents showed the prcsence of living bacteria in five out of the six, a streptococcus being present in all of the five, and additional organisms in three. In three out of the six, leucocytes could be seen under the microscope in the duodenal contents. Two of the five from whom streptococci were recovered had no free hydrochloric acid in the resting gastric juice.

* The technique employed is described in the Appendix, where also the discrepancy lietween my results and those of Dr. Hurst is discussed.

-- 138 THE BRITISH JOURNAL O F SURGERY

Peeling that these results could be criticized on the grou~ids that the duodenal tube is contaminated during its passage through thc fauces, I endeavoured to check them by direct p i ic ture of the cluodeiiuiii at operation. Cases were chosen in which the operation was for sonic condition chielly mechanical in nature, such as adhesions ; hut, owing to the fact tha t thc healthy duodeiium is usually found empty a t operation, sufficient material for culture was obtained in only sevcii cases. The results are shown I)elo\v.

3 A. H. 44) . . . . ,%a. aEbus 1 I<;. R. 47 . . . . R. coli coviuizciiis 3 A . S . 36 . . . . Sterile (i F. L. 48 . . . . Staphylococcus 7 11. S. (,rrastric ulcer) 13. coli c o ? l L U ~ ? ~ ~ ~ i s

It is notc\vortliy that in these patients-who had all uiidergonc the usual lire-operative starvation--while organisms wcre recovered from the duodeiinni in all csc:cpt one. no streptococci were fouircl. This is in accordance with the

observations of Cushing and Li\%i- g00d,23 that the intestinal tract, ~ v h e i r cnipty, teiicfs to becomc amicroliic., and of l<nott,28 that the streptococciis is inore easily killed by an acid mediuiii than cithcr the staphylococcus or t h e 11. coli.

In ordcr to iiivestigatc the (3011-

tlitions prevailing in the cluodeiiiuii over a. loiigcr period than I co~iltl inf1ict upon a volunteer, I iiiadc invcstigations iqioii myself on two occasions over a pcriod of twenty hours. The tube was smallomed oiic evening, and the nest morning its position was verified, and the cluodenal contents were withdrawn. Fig. -KX) is a reduced sketch from a radiograni taken 011 one of these occasions. Barium was injected down the ciuo- deiial tube with a syringc, and a t the same time half a ;pint of bariuiii

FIG. 4fiO.--l)rawn from a radiograrn talcen during one of tile a l i t lm ’s personal experiments.

INFECTIONS O F THE ALIMENTXRy TRL2, CT 759

was swallowed to show the outline of the stolnacsll. It (ball be see11 that the metal bulb is opposite the lower part of the 211d lumbar vertebra- that is, at the junction of the 2nd and 3rd parts of the duodenum. A meal was then taken, and the contents of the duodenum .ryere mithdra\rn every twenty niinutes aiid examined at once, c~lieniically ancl microscopicaIlp. Slides of the deposit obtained by centrirugalizing the speoimens \\'ere also dried, and stained and examined later. Fig. 461 shows the result t ha t n.as obtained in one of these experiments. (Fuller details are gi\-ell in the iippendix.)

From these investigations the following facts have becolne apparent :- 1. The duodenuiii is empty in the fasting state (in each experiment 1 C.C.

was recovered for examination a t the comrnencernellt wit,h collsiderable difficulty). It iiever contains large amounts of material, a sample of 5 to 10 C.C. being obtainable only when the stomach is enlptying rapidly. Gastric cmiteiits begin to appear i n tlie diiodeiiuni withill half ari hour of a nical entering the stomach, and after H period of two and a half hours the cluodeiiuni is once M,,,,5 :

2. Leucocytes iiiay be found. cf l ls; ;; These were most marked after =,

the fat meal aiid the protein ' meal, aiid were not found after the carbohrydrate meal. (A portion of the slide taken a t tlic 2;:

point marked X on Fig. -4.61 is I

shown in Fig. 462. The majority "'[ of the structures shown are cer- ,I

TJMf

more empty. 2

z i

tainly not leucocytes, but have FIG. -46:.--Cliart slioning the i ~ n l t oi one of tlie rather the a1,pearal1cc of dis- ~ l ~ ~ ~ ( l r i : t ~ l oxperimrnls. Circles u-it21 dots in the centre

~iiean leucocytes ; two circles incan itbimdant lenco- e l l1hk 'd llu('lei. xe\'wtlldess cptes. d dot only iiieans no leucocytes. The quantity t\vo ullc~ouhtec{ l,olymt~rDhs are of bile niaiked on tlie (lotted line is in comparison

\\-it,li a n ax-erape suinple. X Sl~on i ; tho p ~ i i i t a t u-li i( . l i present, and others are scattered throughout the slide.) Sow i t is generally believeti that lcucocytes lea\-e tlic sxlrface of the tonsils a d retiirn again wit11 iligestetl bacteria. c'. .J. Bondz4 has proved that white cells lcave the surface of a graliulatilig \\-ou~id, cngiilf particLles o l indigo on its surface, ;tnd oftell rcturll again illto the circulation. D i ~ b y ~ ~ lias shown the tliapedesis of watlcleriiig cells throiigli tlie epithelial lining of the appendix of the rabbit. It is, tliell, possible that the cniigration and return immigra- tion of leucocytcs lilap take a part in the absorption of a fat meal, since 13radley allti Gasser2j liai-e showi that f a t s may be absorbed without split- tirlg. But i t is ccrtaiuly uiirrise: i i i T-iew o f tlie scaiity eT-idence, to lay any great stress 011 this obser\-ation.

8. The colitellts of tlie nornial duotlcnum arc not often sterile. ~ l l c y 111ay c*olitaill \-arious orglanis1iis, and often tlie streptococcus. These do llot occL1r in aiiythillg like tlie iiuinber found by Hurst in cases of pernicious anzmia: but they arc iie\-erthclcss present.

t!le slitle sl,o\\i, in p i g . 4li2 \\-:is t;li<rr].

760 THE BRITISH JOCRNAL O F SURGERY

The Factors governing the Entrance of Streptococci into the Intestinal Tract.--The bacterial flora of the duodenum is to be looked upon as a sample of the freshly arrived visitors to tlic intestinal tract. Their number and their nature mill depend on three factors : (1) The quantity a i d type of bacteria which are swallowed ; ( 2 ) The antiseptic power of the gastric juice ; (3) The time during which the swallowed bacteria have been exposed to its action.

1. Food contains a great variety of bacteria unless it has been sterilized shortly before ingestion. We are chiefly concerned, however, with streptococci, whose incrimination in a large proportion of alimentary infections appears to be undoubted. Frost and Bachmann’G isolated hzemolytic streptococci from 28 per cent of cultures made from high-grade milk obtained from four different dairies. Biddle, in a personal communication, tells me that of the foodstuffs

Fm. 162.--Smear of duodenal contents, stained t o show the presence of leucocytrs. (Compare mt,li Fig. 461.)

examined a t the Clinical Research Association, milk, ice-cream, flour, shell- fish, vegetables and fruit in the uncooked state, commonly contain streptococci. Entirely apart from foodstuffs, however, streptococci are found in practically every case of pyorrhea alveolaris, and a large number of the adult population of all classes suffer from this. The number of chronically infected tonsils is less, but in these too streptococci are found in nearly every case. In infections of the accessory sinuses, the streptococcus is again the predominant organism. Thus a considerable proportion of the population are continually swallowing streptococci, apart altogether from any question of food contamination. The high inciderice of foci of infection in the mouth among sufferers from alimentary infections is too well known to need comment.

2. The antiseptic action of the gastric juice has long been recognized.

INFECTIONS O F THE ALIMENTARY TRACT 761

111 1783, Spallaiizani27 called attention to the ‘Iion-putrcfaction ’ of gastric juice. I<nott28 has lately made a detailed study of what he calls the ‘gastric germicidal barrier’, and finds that the antiseptic action is due solely to presence of the hydrochloric acid. He has divided the more comnioll organ- iwis into four groups. according to the concentration of free hydrochloric acid which they are able to survi\-e €or twenty minutes.

a. Spore-bearing organisms, such a5 anthrax, easily able to survive

b. Resistant strains of R. coli, killed by 0.3 to 0.4 per cent HCI. c. Bacilli of the typhoid-dy5entery group arid staphylococci, killed by

d. Streptococci, pneumococci, and diphthcria bacilli, killed by 0.02 to 0.03

In connection with these figures, it may be recalled that Ryle arid Rennett, out of 100 normal young men, found 4 with complete absence of HC1 in the gastric juice, even after excluding 3 apparently normal achlor- hydriacs who had some history of indigestion. In a series of persons with symptoms, the numbcr is dktinctly higher. Thus Hurst29 found that in 325 consecutive test meals a t New Lodge Clinic, complete achlorhydria was present ill 10-5 per cent, and free HCI was absent from the one-hour fraction in another 9-2 per cent. Bennett arid Vcnables30 have shown that the cmotioris of fear and nausea may produce temporarily a very marked drop in acid secretion. Campbel131 found that in 62 healthy students the free HC1 was below 0.03 per cent in 6 (in 3 once, and in 3 on more than one occasion) throughout the meal, arid in 10 others it never rose above 0’07 per cent and was below 0.03 per cent through the greater part of the meal. In 25 others it was below 0.15 per cent. Of course these results were obtained under rather unappetizing conditions with a gruel test meal, and in most cases which have been examincd a much higher figure was found after a meal contaiiiiiig meat and bread. Bonar32 showed that 49 per cent of people with gall-stones had achlorhydria, while 55 per cent of the cases of chronic appendicitis had either no free acid or marked hypochlorhydria.

3. Knott’s figures are based upon an exposure of the organism to the action of hydrochloric acid for twenty minutes. However, I have shown that portions of a meal begin to appear in the duodenum within twenty minutes. Canipbell tells me that water taken by the mouth commences to enter the duodenum in thirty seconds : in many people this would contain dental streptococci which had passed the stomach unscathed. According to Cuyhing, a glas? of milk could be recoi ered from a jejunal fistula within a few miiiutes of iiigestion, with it.; bacterial flora remaining practically unchanged.

In an isolated experiment on Feb. 1, 1921, I swallowed a sterilized duodcrial tube, and one hour later verified its position in the third part of the dnodenum bv a skiagram ; 10 C.C. of sterile water were then injected down the tube. of which 4 C.C. were recovered for culture. A glass of milk, bought from :t well-known dairy with branches all over London, mas then swallowed, and thc duodenal contents were withdrawn erery minute for a quarter of an hour. C~lturcs were taken from the I - . 5 - . arid 15-minute specimens. The results of culture are shown in Table I I r .

0.3 per cent IICl or morc.

0-15 per cent HCl.

per cent HC1.


Table III.--KEsuLT OF PE~SOSAT, Esrr;rc~nr~lv.r. -. - -

PFECI3IJ!!S I cvrrviw I___- __---

!

\V:ish-ouit from duodenum . . Sparse colonies of Sir. brcuis

Milk , . . . . . . . Large numbcrs of R. coEi C O ~ E ~ L ~ ~ W ~ S , Slr. long?rs. and

Duodcnum, 1-miii. specimen Large numbers of B. coli cornmu)&*, few Slr. brevis

])itto, 5-miii. specimen

Ditto, $-hr. syecimea

1 Sir . breois

. . 1;arge numbcrs of I?. coli corn)nutris,* few S ~ T . Zongus* and

All in large numbers, about half that in

~ brcuis

i milk I _ _ ___ ..__.__ .___-~__--. .

* Clrgariisins \shirk c d d h a w out3 come from thc milk.

It can be sccii that both R. The next day, iii large numbers.

i 1 I l h i li 7$ 14 2 h r 2 t ?* 21 3 h r . 3 1

7012551

60(11#J

601 182

40h16

3 a ( m 201075

la / o.rs1 f #.OH I ’ : MCr.J

coli and streptococci have come through Dr. Campbell carried owt a gastric analysis

on me by the fractional gruel test meal. My secretory cur\:e, as shown in Fig. -1.63, exhibits a considerable concentration of HC1, being on the border-line between .J. R. Bell’s classes of average nornial and high normal.

It is impossible, then, to avoid the coric:lusion that streptococci of varying degrees of virulence pass through t lie gastric barrier and enter the intestines in a living condition, in most individuals

FIG, 4,iS.--Chart. showing the of gastric oil1 y under exceptional circumstances, in analysis i r i a,uthor’s experiment. JTlalJ>’ at all times.

THE EVIDENCE THAT BACTERIA ARE ABSORBED BY THE NORMAL ALIMENTARY TRACT.

The Question of Absorption of Insoluble Particles.-Having shotv1-1 tlmt, under c o d t.ioris which cannot be regarded as exceptional, pathogenic bacteria may reach the intestines in considerable numbers, it becomes impera- tive to determine what are the defenccs of the intestinal canal against infection, and under what conditions these defences fail. The first question that requires a definite answer is, ‘‘ (‘(ail minute particles of the sizc of bactci-ia transverse thc intact mucous nieuibranc of the alinientary canal, eritirely a p r t fwm any question of pathogenicity ? ” That such particles are carried through the intact epithclium of t.he respiratory passages is a commonplare.

In 1853, Lister33 investigated the flow of the lacteal fluid in the mesentery of the mouse. H e fed ariiinals on brcad arid inilk mixed with indigo, but was unable to detect any indigo granules in the lacteal fluid. 011 the other hand, states that carmine which has heen mixed with the food of an

INFECTIONS O F THE ,\LIMENT,\RY TR,\CT ‘763

animal passes out through the intact wall of the iiitestiiies, btlt gives 110 proof of his statement. The general consensus of opinioll upholds Lister’s vie\v.3;

Unaware of these observations a t the time. I commeliced two years ago a series of feeding experiments, using carmine intimately mixed wit11 the footl. Carmine appeared best to fit all requirements. It is entirely im~ocuous ; before starting the experiments, I swallowed 30 gr. a clay for a week, and fourid that. i t was passed unchanged and produced no perceptible effect. It is insoluble in, and unchanged by. the body fluids, and---almost as important-is not altered by the cvhemicals used in fixing and embedding tissues for section. In size, the carmine particles closely resemble bacteria. Carniilie is take11 111) hy the same channels as, and in similar amounts to, bacteria. If a mixture of carmine and tubercle bacilli is injected into inuscular or subcutaneous tissues, the granules and the bacilli are picked up irtdiscriminatel3iiatel~~ by the same phago- eytic cells and carried to the same des t i~ ia t io i i .~~ Again, in searching for minute quantities, i t is necessary to examine serial sections of the tissues under a high power, and, for satisfactory work, these must be stained with hxmatoxyliii. In such a section even singlc particles of carniinc can be picked out, while considerable accumulations of indigo or indian ink may be missed. Finally, carmine eannot possibly be confused with the granules of extraneous or natural pigment which may be found in the body, especially-as shown Iny Keith3’ --in the alimentary canal.

In the first experiment, a batch of 12 mice was fed on bread-and-milk mixed with carmine. They ate this readily, so that after a few days the food, the straw, the cage, and the noses and tails of the m i c ~ mere scarlet, while the fiwes were a t all times a bright red. When a mouse was killed, the scarlet c*olour of the carmine showed through the transparent wall of the alimentary canal. Mice were killed after feeding for 3 weeks, 8 weeks, 3 months, 4 months, ’i months, and a year. A careful illspection was niadc of all the viscw-a, and pieces of the stomach, small intestine, e;eeuiii~ liver, spleen, I)aiicreas, galI-l)ladder, kidneys, and niesenteric 1 j q h glands were embedded. Serial sections were cut? aiid every tenth section was placed on a slide, so that ~vhen , as was iisually the case, 13 sections nerc examined, this represented :I thickness of 150 sections, or about 14 nini. of tissue. The thyroid gland alid 111ngs were esaniined i i i sonic cases. Altogether sonic 1100 sections were se:lrched in this way under the high power. I was unable in a single instance to Grid any c\-idencc whatsoe\w that cbarnzine granules had been taken up by the alimentary canal and hatl entered the tissues of the animal.

A scco~id series of mice i ras started in which, in addition to the carminc, \-cry finely powlrrecl glass was added to the food. Two mire of this series were killed at the eiid of 3 weeks and 5 months respectively, with csactly the same results. S o carmine liatl been taken up from the alimentary canal, in spite of the enormous quaiitity that hatl p s w d through it. These experi- iiients werc, iunfortunately, brought to a c~onclilsion owing to the death or‘ the mice when the boy ill charge of the aninlals n-cnt on his holiday.

Neat arld carmilie were put together through a mincing machine, so that they were ititinlately mixed. The eats took this mixture without hesitation, and the f;cecs irerc brightly colonred. One cat. was fed on this diet only, two were

The feeding experimeiits n i th cats were conducted on similar lines.


fed 011 carmine with a diet drficicrit in vitamins, one was fed on carmine and poldered glass, and the fifth was given ,.kr gr. of atropine three times a day in milk, with the object of diminishing secretion, and of producing a certain degree of stasis in the alimentary tract. These experiments are described in the Appendix. The results were exactly the same as in the casc of the mice. The cats wcrc killed after six wceks, and sections examined of each portion of the alimentary canal, of the liver, spleen, pancreas, gall-bladder, lymphatics, liings; and the bone-marrow, but in 110 instance was there any eridcnce of carmine having been taken up.

I iiext set out to determine whethcr carmine could under any circumstances be takcn up from the liealthy alimentary canal. Apart from the

powdered-glass experiments, I made no intentional irivestiga tions on the effect of injury, for it is obvious that, where there is gross damage, foreign mattcr can enter the blood- and the lymph-stream, and the fact needs no special proof.

My main object was to ascertain the effect of stasis on the absorption of carmine. For this purpose, various portions of the alimentary canal were isolated by proximal and distal ligatures, and carmine was injected into the isolated loop. The continuity of the alimentary canal was restored by join- ing the portion above and below the isolated loop, either by a lateral anastomosis without division of the gut, or by an

FIG. -XJ.-To show nietliod of isolating a loop of end-to-end suture (Fig. 464). intestine from alimentary canal, with its blood-supply mid 1pmpha.tic drainage intnct. The loop has been a point in technique I fillrd with carmine suspenqion. may mention that end-to-end

suture in these small viscera is quite easy if performed over a stick of macaroni. If the macaroni is not boiled, but sterilized in alcohol, it completely dissolves in six hours a i d leaves a perfect junction. By these means, a condition of localized artificial stasis is produced, lasting as long as the animal is kept alive. I found that if a sufficiently long loop is isolated, if great care is taken not to injure the blood- supply, if the contents of the loop are first emptied, and only a small amount of material is injected so as not to distend the gut, and if the animal is killed within three days, the closed loop remains absolutely normal in appearance, both to the naked eye and on section ; there arc no signs of toxic absorption, and the animal does not appear to suffer. This experience is entirely in accord with Wilkie’s experiments on the closed intestinal l00p.3~

INFECTIONS O F THE ALIMENTARY TRACT T65

The effect upon absorption of carniioe particles of a condition of stasis --lasting in the longest instance four days, but usually forty-eight hours-ivas studied in the case of the stomach, duodenum, sniall intestine, appendix, large intestine, and gall-bladder. In the case of the sinall iritestiiie and gall-bladder, the results were entirely negative. No evidence of absorption of carmine could be fourid in the wall of thc viscus itself, in the adjacent lyniphatics. or in the liver, spleen, and blood. In the stomach some carmine was found in large cells lying in the submucous lymph nodules at tlie pyloric end. 111

the appendix, while no carmine was found in the wall, indirect but equally good cvidence of absorption was provided by finding one carminc-loaded cell in the ileoczcal gland in one expcrinient, and three such cells in another, representing in one case about 250 cells in the whole glaiitl. in thc other about

FIG.- 4(i5.-Froin sinnll intestine of f r w (oil illllnersion). Carlnine particles can he seen free in lumen of intestine, and also in tlie substmce of txvo phnpocytic rells lying a t the base G f the epithelial layer.

1500 cells. In the ease of the colon. phagocytic cclls loaded with carmine were found in the walls of the lymph channels iii the mesentery.

I made further experiments with the preparation of colloidal silver used by Bolt0n3~ and Timbrel1 Fisher40 in their work oil absorption from the peritoneum and from the knee-joint, but could not obtain any evidence, naked-eye or microscopic, that the silver had been taken up from the ileoczcal anglr.

At Professor Keith’s suggestion I next investigated the absorption of carmine from occluded loops in the alimentary canal of the frog. Six decerebrated frogs were used. The middle portion of the intestine was isolated by two ligatures, and the occluded loop filled with carmine suspension. The animals were killed after twenty four hours. In the case of one frog I found

766 THE BRITISH JOURNAL OF SURGERY

conclusive evideiicc that carmine had been takeii through the epithelium of the alimentary canal, by the agency of the ~vandcriiig cells. Fig. 465 shows i i

portion of the alimentary canal of this frog under the oil immersion. Two cells loaded with carmine particles can bc secii lying a t the base of the epithelial layer. and abutting on a large lynipli channel.

There appears t o be a gradual e\ ohition of a defence niechanisrn on the part of the alimentary canal towards foreign particles a s we ascend the scalc of thc animal kingStloni. Uiiiccllular animals, like the ainccba. “ prove all thiiigs. and hold fast that wliidi i i good .’. In hydra, the cells lining the digestix c s ic cinit pwidopodia. and eiigulf solid particles. Profesroi. El ans tells mr that insoluble particles of food material are c*omiiionly fbund insidc the digestive cells of the marille iiiolliiscaii groul). In the sponges, amccboid

cells aiicler into the gastral CRT it-, and rcturu again into the organism, c,ri-rying solid particles. In the case of the frog, wc have secn that under rvccptional circiini\tance% carmirie particlcs may bc takeii up by the wandering cells €rom the lunieii of the gut, and carried into tlie body. That this taking iip of foreign pi-ticles is not entirely eacqtional in the frog is shown by ail examination of the liver (Fig. 466). The waiitlering cell.;, after takinq u1) carmine from the lnnien of the iiitcstine, deposit i t in cells lining the blood spaces of the liver, arid these cells contttin. as \ ~ c l l as carmine, large quantities of brown and black granules which have presumably gained entrance from time to tinir through the ~ ~ a l l s of the alimentary canal. Pickoi41 ha5 shown that these granule.; contain iio iron. I n the mammals, foreign particles in

INFECTIOX3 OF THE ALIMENTARY TRACT 767

thc food are entirely excluded under iioriiial conditions, but ~rhm a state ot stasis occurs they may be takeii up, the agency being probably exactly tlic sariie as in thc lo\rer orders-wandering amcebocytes which come bet\\ eeii the epithelial cells, especially iri the 11-niphoid areas of the aliriiciitary tuhe. arid. aftcr engulfing the foreign particlcr. takc them by lyinphntic channels to the nearest gland.

‘rllcse n.aiidering cells are knon 11 to show a certain cliciiiical iiitelligeiic(x i n tlicil’ dietary. 111 searchilly for some inert and recognizable particbles vhicli yct mould attract them, I tricd filling ail occluded loop in the cat with a n eniulsion o€ tubercle bacilli killed with formalin, and then examined swtioiis of the intestine and the glands stained by the Zielil-Seelscn riiethod. Tlie rcsiilt was riegativc, but t n o things niust bc renienibered : (1) That the l’oriiialin may have rcndered the organisms unj,alatable t o the phagocytcs ; anti (‘1) That dead bacilli are probably destroyed immediately bj the cells that haw engulfcd them.

The Absorption of Bacteria.-Finally I used li\ in2 bacteria. IIxriio- Iytic streptococci were choscii, because of the case with which they call be recqnized in culture. In two evperimeiits, a long ilcocxcd loop mas ex- c.luded. aiid an emu!sioii of tlic cocci irijcctcd iiito it. Tlic animals xe re L i l k d five hours later. O n opening the abdonieii the appcaraiice n as most striLing. In oiic case the ocL*luded gut \\as per- fectly iiorinal in aj,pear- alive. in the second the

This esperinient, then, may be set aside.

Tho ~leocwcnl -?.rim r q E .pcrri.mit 2P ( w e only abnormalit? I\ as ote 1701111 11 ippenrancc of rnteit nc. III crinli 1>t

that tile aI)l’ellclis alltl i n q c patelies in the lyiripli gldnd5.

11 niplioid follicles were pink in colour (Fig. 467). suggesting that they mere the site of aii active prwes\. The peritoneal surface was smooth, the canal not tli>Lerrded, and 1 1 0 lesion, microscopic 01- m:tcroscopics. c~ould be detected in the gut ~vall. But 111 h t h , the nearest group of lyiiipli glands showed bright scarlct patches of‘ sii1)peritoneal hmnorrhagc. Cultures Irere taken from the heart blood, the thoracic duct, the niaiii collcctiiig 1) niphatic chaiincls, and the nieseritcrk glaiids. In the secaoiid animal, all cultures n erc iiegatix e ; iii the first. whilr I)lood and gland tissue were sterile, both the thoracic duct and the collecting tluct furiiishcd a Ii;m?olytic streptococcus aiid no other organism. I interpret tlicse result? as slion-iiig tha t lil-ing streptococci had passed the intact l i r i i n ~ o f tlic alimentary canal, and had entered the lymph glands. n here they hati 1 )rotlnccd tlcstruc*ti\ e changes in the capillarics, caiisiiig the stibperitoiiral Ii,rniorrhage, but liad theniselves been killcd. In onc c~asc, 5ome had pzisscd niiwathcd through the 11 hole chain of lymph barriers. and arrii ctl in a lii iiig colitlitiori iii the collecting vessels aiid the thoracic duct.

’76s THE BRITISH JOURNAL O F SURGERY

In two further experiments, strcptococcai were injected into the lumen of the jejunum in one case, the duodenum in the other, no ligature loeillg applied. The first animal was killed after five hours, and cultures from the thoracic duct and the glands proved sterile, but the same patches of hteinor- rhage were found in the first group of glands. In the second animal, killcd after three and a half hours, streptococci were grown from the ileal, colonic, and ileoczcal groups of glands, but only in the latter in considerable yuanti- ties. These were not proved to be hFmolytic. In the ileoctecal gland stained by Gram’s method, some bacteria were found in the lymph spaces, but no cocci. These bacteria had come from the alimentary canal.

In spite of a general belief to the contrary, the evidencc that bacteria may be absorbed from the intact alimentary canal appears to me incontestable.

Tubercle bacilli are constantly found in the mesentcric glands of children, though there is no history of a preceding enteritis, and though close inspection fails to reveal evidence of a recent or healed lesion anywhere in the intestinal mucous mcmbrane. Sir Armand Ruffer,42 and later N i c h o l l ~ . ~ ~ have demonstrated the constant presence of bacilli in the mescnteric glands of healthy rabbits. Desoubry and l ’~rcher*~ showed that, during the digestion of fats, many bacteria of all sorts are €ound in the blood arid the chyle. Nicolas and Dercas45 fed dogs on fatty soup mixed with tubercle bacilli, and killed them three hours later: the chyle from the thoracic duct was injected into guinca-pigs, and tubercle bacilli were recovered. These experiments hare been repeated on many different animals by Ravcnel,46 von Behring ant1 Roemer, Bisanti and Panisset, Ficker, Oberwarth and R a b i n ~ w i t c h , ~ ~ and bacilli have been obtained in many instances from the blood as well as the chyle, the frequency with which they were found being greater in young animals. Moody and Irons,48 feeding dogs on B. pyocyaneus arid R. prodigi- osus, were unable to recover the organism from the tissues ; but when these two bacilli were injected directly into the duodenum, they were recovered from the thoracic duct in certain cases aller one or two hours. Calmctte, by killing guinea-pigs, goats, arid cattlc a t different periods after an infected meal, found bacilli in the central lacteal of‘ the villi, lying in the substance of leucoclytes.

(It must be mentioned that the absorption of bacteria from the alimentary canal has been denied by Williamson and Brown, working a t the Mayo Clinic.)

THE PATH TAKEN BY BACTERIA AFTER ABSORPTION. It is not unreasonable to suggest, then, that small numbers of bacteria

are continually- being taken up from the alimentary canal, chiefly a t the aggregations of lymphoid tissue. and by the agency of the wandering cell\. The majority are either destroyed a t once or a t the nearest lymph glaiid. This continual destruction of bacteria in the lymphoid tissues probably plays, as urged by D i g b ~ , ~ ~ an important r6le in the normal defensive mechanism of the body. Herring and MacNaughton state that “ the lymph gland is an extremely efficient filter, and only allows solid particles to pass through i t when they arrive in too great numbers a t a time ”, Somc bacteria, however, do pass this filter unwathed, and escape into the thoracic duct, whence they are carried into the general circulation. Especially does this occur after a

INFEC’TIONS O F THE ALIMENTARY TRACT 769

fat meal, not because a greater number of bacteria are taken up, but because so many fat-laden phagocytes are thronging the lymphatic glands that occasional cells slip through these custom-houses of the alimentary canal carrying more sinister luggage. Under conditions of stasis or of injury in the alimentary canal, the number reaching the general circulation is greatl?. increased. These alimentary bacteriatmias have received unconscious recognition for a long time. Poultry breeders starve their birds twenty-four hours before killing them for market, because they find the meat does not decompose so readily. Laboratories only blecd their immunized animals after a fast, to ensure a sterile serum. FordS0 obtained organisms of different kinds from 60 per cent of cultures made under the most stringent conditions from the livers arid kidneys of healthy dogs? cats, rabbits, and guinea-pigs.

A series of further investigations into the fate of foreign particles after they have left the alimentary canal was carried out, carmine again being used as the indicator.

Absorption of Particles from the Peritoneum.-If one part of thc intestinal canal is so acutely affected that the whole thickness of its mall becomcs destroyed, organisms will escape into, arid bc distributed by, the peritoiieum. The absorption of small particles from the peritoneum has been fully investigated by C u r n ~ w ~ ~ in 1879, by in 1897, aiid by Bolto11~~ in 1921-thc last two both giving full referencc to the literature. A series of my own experiments on cats has entirely confirmed their findings-namely? that such particles are taken up almost exclusively by the great omentuni and by the lymphatics of the diaphragm, whence they are carried to the glands i n the anterior mediastinum. It is very striking, after filling the whole abdominal cavity with carmine suspension, t o find ten days later that the cavit!- is clcar of the dye, save for the vivid scarlet curtain of the omentum and the staining of tlie diaphragm, while, on opening the thorax, the anterior nietliastinal glands, normally inconspici~ous, stand out like decp-red cherries. To the naked eye the walls of the visccra and the inesciiteric glands contain no carmine, but niicroscopic sections show that it has been taken UJ! b j 7 largc cells in the peritoneum and the glands to a small extent. In no part of thc alinientary canal, however, is any evidence to be found that the cells penetrate milch beyond tlie peritoneal coat, and I believe i t is quite exceptional for iiifection to be carried from one abdominal organ to another by this means. 111 110 ])art of the intestinal canal was carniine found in the deeper muscular, srtl~iiiucous, or mucous coats, however heavily loaded the peritoncur11 might he. Where tlie amount of carmine put, into the peritoneum is small, i t is all iiicarceratcd by the onientuni arid nicdiastinal glands. Where a large aniount I S used, c~armine-laden cells get into the general circulation by the thoracic: atid right lymphatic ducts: arid are found in the spleen and to a lesser dcgrec in Kupflcr’s cells of the liver.

Absorption of Particles by the Portal Stream.--Where the infection i.; such as to cause local destruction of the mucous membrane, the infecting agent will be carried by the portal blood-stream, as occurs in the case of the typhoid fevers aiid the dysenteries. Carmine entering the portal blood in moderate quantities is entirely caught up in the liver. If a larger amount is put directly into a portal radicle, carminiferous cells will be found grouped

VOL. XI1.--so, 4s. 51


round the periphery of the licpatic lobules, but some have slipped through. and can be detected in the spleen arid lungs. Where a still larger amount is injected. so as to interfere with the circulation of the liver. a considerable proportion will pass thumgh and be distributed by the general circulation, being €ound chiefly iu the spleen. but also in the stomach, intestine, gall- bladder, and kidneys.

Absorption and Carriage of Particles by the Lymph-stream.- The path with which we are ~hiel ly concerned is that taken by those bacteria which cause 110 local ltsion, but which find their way through the intact wall o l the alinicntary c.anal and enter the lymphatic channels. We have seen that they are carried to the lymph glands for destruction, but that they may p a s heyond. An infection by the lymphatic route may be imitated

FIG, 4(%~--Src t ion of driodenui?~ of c:it (oil iiiiniersion). Carmine had been A cell eontaining injected into glands at hase o f nirsentrry two days previoiisly.

wricine jiraniiles can be i e c n lying in a cnpillary IMween two tubules. - by iiijccting carniinc directly into the lacteals and the main collecting group of iiiesenteric glands i n the cat. An iiijectioii of moderate size is entirely taken up in the gland, and fixed locally ; but a largc injection is, in part, carried away by cells into the collecting vessels, from them to the thoracic duct, and so to the general circulation. The point on which I wish to lay the greatest stress is, that 110 evidence can be obtained of direct local carriage of carmine by the lymphatics from one organ to another. Cells, once they have taken up a load, only follow a centripetal path towards the thoracic duc t ; they never tvarider aloiig the collateral lymphatics in a reverse direction to the normal flow. Aftcr a massive injection into thc Collecting glands, carmine can be detwted in the coats of the stomach, duodenum, small and large

ISFECTIOXS O F THE ALIMENTARY TRACT 771

iiite\tiiie, appeiiclix, ant1 gall-bladder, but none of this has been carried there by lymphatic channels. It lies in the bodies of cells, and these have arrived by the blood-stream. To check this, I injected carmine into the jugular 1-ein of three cats, arid discorered that the granules, distributed by the blood-stream, were found in the same situations and in the same relative proportions as the carmine-bearing cells which had, in other esperiment4, started their career in the nicwiiteric glalld5. The carmine i4 caught up almost entirely in the ~~iucous coat<, i - e y little in the peritonesl, hardly .tt all in the muscular coat.;. Fig. 468 is a section from one of these experiments, and illustrates how carmine particles, and therefore bacteria. m a y reach the different organs of the alimentary tract from a source in 91ie 5uch organ. coming by way of the thoracic duct and thc blootl-strea~n.

FIG. 4 l : 9 . - Section oi pancreas of cat. Cnrll-Llllc suspension had been injected Cell3 carryicy carlriine granules have focnd their way along inen the peritoriewii.

the peptn. lretwecn I lie pnoreat ic lo)lu!ez.

To this gencralization there is one exception, the case of the pancreas. Thr pancreas is slung in the mesentery of the stomach and duodenum ; it has 110 proper capsule, no hiluni where its vessels leave and enter, but appears interpolated in the paths of the lymphatics from the upper alimentary organs on their way to the niaiii collecting channels. In the pancreas alone do w r find e\idcnce of direct infection from the lymphatics. That the cells come along the lyniphatics is shonn by a section where the actual process of permeation can be seen (Fig . 460). The lymphatic origin of pancreatic infections has been ~ e r y 17 ell demonstrated in the human being by Deaver. Clurioudy enough, paiicrea tit is is the coninlonest of the group of alimentary infections under diwrissioil anioiiy wild mammals in cap t idy . By the


kindncss of Dr. Lucas, the Pathologist, I havc examined two specimells of acute hremorrl1agic pancreatitis from cercopitheque niorlkeys which died in the Zoological Gardens last year. The primary lesion in each case was an enteritis, t o which captive animals are especially liable.

I may sunirnarize by saying that on each of the routes by which infection from the alimentary canal may be carried, the peritoneum, the portal blood- stream, arid the lymph-stream, there is interpolated a defence mechanism whereby bacteria arc taken up and destroyed. In the case of the pcritoneum, this defence mechanism consists of thc great omentum and the mediastinal lymph glands ; in the portal blood-stream, it is the phagocytic cells of the liver ; in tlie lymph-stream. the iriesenteric glands. Where these mechanisms are overpowered by a niass infection, the orgallisin or particles are in each case distributed by the general circulation. In the case of the lymphatics, the defeiicc mechanism may- also be partly outwitted, even in the absence of a massive infection, by the crowd of cells which pass along its channels during digestion.

CONCLUSIONS. i h v e erideavoured to advancc proof of tlie following statements :- Pathogenic bacteria may reach the intestine in a living condition in man,

under circumstances by no means exceptional. Such bacteria may be carried through the intact wall of the alimentary

canal and may enter the lyni;)h-stream, and of these a certain proportion will reach the general circulation.

111 conditions of stasis in, or of injury to, thc alimentary canal, the riumbcr of bacteria reaching the blood-stream may be considerably increased. Arid bacteria, alimentary in origin, may be carried again by the blood-stream to all portions of thc alimentary tract, arid arc specially liable to lodge in the mucous coats of these organs.

I should likc now to examine the application of these experimental findings concerning the factors governing alirncrrtary infections to the group of diseases we are discussing.

Therc are two circumstances which imrnediately prescrit, theniselves as distiiiguishiirg tlie life of man untlcr primitive from that. under what we are accustomed to call civilized conditi0il:j. One is the question of dietary, the other the factor of the rush and stress of modern life.

The Possible Influence of the Modern Dietary upon the Question of Alimentary Infection.- -Our arcrage dirt to-day differs in two main respects from that of our immediate predecessors, arid still more from that of ancient arid primitive peoples. One is the high degree of preparation to which our cereals are subjected, the other the smaller and still lessening amount of indigestible material, chietly cellulose, which we consume.

The refining processes to which the cereals consumed by the Western nations are subjectcd rob them t o a great extent of the important accessory food fact,ors. The effects of such a dietary on the alimentary canal have been investigated by Colonel M c C a r r i ~ o n ~ ~ in his well-known experiments upon guinea-pigs, pigeons, arid monkeys. They are, in the main, a loss of propulsive power, the muscular coats being thinned, atrophied, often transparent ; a


profound atrophy of the lymphoid tissues in the bowel wall; a.nd multiple lesions of the mucosa. Thus a deficiency in accessory food factors, alone, will produce the two conditions which favour thc entrance of bacteria-stasis and injury-and will damage the mechanism of defence-thc lymphoid system.

The absence of indigestible elements in modern foodstuffs removes that insoluble bulk which is the normal stimulant to peristalsis and the factor which ensures that regular evacuation on the part of the lower colon which is perhaps its chief duty. H ~ r s t , ~ ~ in his book on Const<pat%on and Allied Intestinal Disorders, states that ‘‘ fragments of vegetable food, consisting of indigestible cellulose, together with the starch and protein which have escaped digestion owing to their covering of cellulose, are the most important of the articles of diet which incchanically stimulate the intestinal niovements ”. And later, “ in civilized countries the small quantity of indigestible cellulose which is present in the food is generally softened to such an extent by cooking, that i t lows much of its value as a mechanical stimiilant of intestinal activity.”

England is a highly industrialized island, unable to produce more than a small proportion of the cereals necessary to feed her inhabitants, and largely depending on imported, and therefore highly-concentrated, foodst,uffs. Hence constipation is an affliction particularly prevalent among our inhabitants: while lesscr degrees of alimentary stasis are probably commoner still. It has been shown that forty-eight hours’ experimental stasis will cause the colon of the cat to take up innocuous carmine particles. It seems a t any rate probable that the effect upon the absorption of bacteria will be still greater. Such delay will riot only favour the multiplication of organisms, but will also conceivably increase that passage through the intestinal walls which probably occurs to some extent under absolutely normal conditions.

The Influence of Modern Social Conditions.~--The effect of the stress of modern life is more dificult to analyse, but I am inclined to attribute a morc important place in thc pathogencsis of alimentary infections to this factor than to that of diet. Professor Lowes Dickinson’s hypothetical China- man says of our Western civilization, L L You have liberated forces you cannot control ; you are caught yourselves in your own levers and cogs. You depend on variations of supply and demand which you can neither determine nor anticipate. The failure of a hxrvest, thc modification of a tariff in some remote country, dislocates the industry of millions, thousands of miles away ”. The sense of security which comes with possession is denied to all except the fortiinate few. Education, without the opportunity to apply the power which it confers in the fulfilment of the creative impulse, leads to a sense of caged ambition. A large proportion of thc population are to-day working harder than ever before, dissatisfied with the present, dreading the immediate future.

The possible part played by this continued mental strain, and by the exhaustion which is its logical sequence, in the etiology of the alimentary infections, may be coilsidered under three headings : ( 1 ) The effect on thc mechanical and motor functions of the alinlentary tract ; (2) The effect on secretory functions ; and (3) The diminished resistance to infection of the body as a whole.

,411 ext,renicly able article by Blundcll Rankart55 appeared three ycars ago, in which he applied Sherriiigton’s experimental work on postural tone in

'774 THE BRITISH JOURNAL O F SURGERY

animals to the problcni o l the pathology and treatment of the static deformi- ties of orthopzdics. Especially valuable is his exposition of the dependence of the reflex mechanism, probably sympathetic, by which this tone is regulated, upon impulses coming from the higher centres, especially from the cerebral cortcx. As Bankart says, '' the upright figure and the bent figure reflect two rery different types of mind. The difference between the attitude of a street loafer and of a trained soldier is not merely physical, it is far more mental ". And again, " mental fatigue and inertia leads to deficient postural activity, eren though the muscles are n ~ l l de\-eloped a i d voluntary muscular power is unimpaired .*. The writer is conccrncd with the orthopzdics of the locomotor apparatus, but. his coiiclusioiis apply with equal force to the ortho- pacdics of the alimentary canal. Milch controversy has ceiitred around the part playcd in abdominal disease by the abnormal degree of fixity or mobility of different portions of the alinicntary canal conscquent on variations, bc they congenital or acquired, in their peritoneal attachments. But it is undeniable that X-ray examinations in norinal individuals, and laparotomies performed for other conditions, reveal these so-called abnormalities in a large number of people who have suffered from none of the symptoms which are said to follow in their t,rain. We are forced to t.he conclusion that the position of the viscera depends less on peritoneal ligaments or fascia1 sheaths than upon their retention on the retro-abdominal shelf by the sustained support of the muscles of the abdominal mall, and especially of the obliques. This sustained support depends not on voluntary contraction, but on the continued action of the post.ura1 reflex. When this support is lost, the mobile ascending colon and the portions of the canal which are fixed by accessory peritoneal bands do probably suffer in funct,ioii sooner than t.hose which follow the standard anatomical descriptions. In the presence of a healthy abdominal wall, however, these variations from the average are iniiocuous, while, where this support is lacking: the most orthodox alimentary canal will in time show signs of giving trouble. This support depends to a great extent upon the condition of the cerebral centres.

The influence of th r cerebral ceiit.rcs upon the musculature of the viscera themselves is no less important than that upon the tone of the abdominal wall. Cannon, working with animals, and B a r ~ l a y , ~ ~ in the case of the human stomach, have demonstrated that fear and unpleasant emotions are able to cause a cessation of movements, and, in the case of the stomach, a decrease in tone. It is quite possible that. the prolongation of such a mental state ovcr lengthy periods would bring about a condition of deficient propulsion in the alimentary can:& and a state of delay or stasis in its contents. I am unaware of any prolonged series of observations on tlic position and movements of the viscera in the same individual under different mental conditions, but such work would be of great value. Two years ago, while Resident Surgical Officer, I investigated the effect of a week of fatigue on the tone of the stomach in the case of a surgical team of seven members, including myself. The stomach of all the members was radiographed fasting a t the same hour and under identical conditions on the first and last days of a very strenuous week of duty. For the meek, the average sleep of individuals was between three and four hours per night. The mean position of the pyloric

INFECTIONS OF THE ALIRIENTARY TRACT 773

valvc was plotted on both days, and to my surprise was fourid to be slightly lligller a t the end of the week than a t the beginning. But it is probable that mcntal depression has a more profound cffect upon visceral tone thari bodily fatigue, and in this case the prevalent mood a t the last examination xvas one of elation, owing to the cnd of an interesting week, and the irnmiriencc of hcakfast after a night, spent in the operat.ing theatre,

The recognition of the influence of mental states upon secretion in the Rlinientary canal dates froni Pawlow's observations upon psychic secretion in the stomach. Reference has already been made to the work of Bennett and Vcnablesm on the effects of temporary mciital stress upon gastric secrction. I m s is known concerning the control of the activity of the other digestive organs, but that the co-ordination between one arid the other is not merely an automatic chemical one is proved by the free pancreatic secretion which is found in many cases of complete achlorhytlria. Again, a serics of observations in the same subject, conduc:tcd orer a long period and under different meiital conditions, uwultl be of the greatest value. But the evidence, such as it is, suggests that unpleasant emotions tend to the inhibition of digestive ferments, and therefore to a decrease in the bactericidal substances, and an i ncrease in the supply of undigested foodstuffs to act as culture media.

The effect of mental fatigue and depression upon the resistance t o hactcrial infection is in any case difficult of proof. Such conditions cannot be reproduced in animals, and in man so many sources of error have to be climinated. Clinical evidence appears to suggest that men doing strenuous iiitellectual work over long periods succumb more readily thari their fellows to microbic invasion, while the course of an established infection appears to be modified favourably or adversely by the mental outlook of the patient.

The Alimentary Sub-infections.--There is thus some support for the Iielici that the conditions, both of diet and of social rkgime, under which men cxist in the western nations, have a tendency to decrease the defensive inechariisrns of the body against thc entry of pathogenic bacteria into the alimentary tract, to favour the entry of these organisms from the alimentary tract into the general circulation, arid to decrease the natural immunity which should hinder their power to produce dcstructive lesions in the tissues.

Every medical man must be familiar with a group of cases to which I shall rcfer as the ' alimentary pseudo-infections ', or (begging the pathology, and borrowing Adami's phraseology) the ' alimentary sub-infections '. In these patients the clinical picture of gall-stones, of appendicitis, of gastric or duodenal ulcer, is mimicked with such accuracy that the absence of an organic lesion can often only be A-erified by operation. They have certain points in common. There is some underlying worry-a husband out of work, an unhappy home, perhaps tlie fear of dismissal. There is loss of tone in the ahdominal ud1, a concavity in the epigastrium, arid a sagging forward below the umbilicus. Their gastric analysis shows hy~osecretion.5~ The barium X-ray of their alimentary tract reveals a general laxity and low position of the x-iscera, sometimes more marked in one portion than another, and a delay in tlie passage of contents.

In this group of cases which I have tried to define, we have the combin- ation of factors which allows the entrance of bacteria into the alimentary

Constipation is often obstinate and habitual.

776 THE BRITISH JOURNAL OF SURGBRY

tract and increases their absorption. The cause of the syndrome I believe to be partly mental and partly dietetic, and a course of treatment based on this hypothesis will relieve the symptoms in all except late cases. But I believe that these ' pscudo-infections' are really true infections of a minor degree. The pain in the appendix and gall-bladder, the dyspepsia, and hzmatemesis are due to a greatly increased entry of bacteria from an alimentary tract whose function is deranged, and their carriage as infective emboli t o the mucous membrane of the diIferent organs, just as we have seen carmine to be carried from the mescriteric lymph glands of the cat. Even the teeth, which are so often condemned and executed after scant trial because of their unfortunately accessible position, may in many instances of alimentary infections be the victims and not the criminals. In the majority of cases these emboli produce a t their place of lodgement transitory infections only, which are completely effaced by the rcparativc powers of the tissues where they lodge. Where their virulence or number is greater, or the local conditions more favourable, they cause those destructive and chronic infections which fall into the category of surgical diseases.

If there is any truth in the views advanced, i t follows that no surgery of the alimentary tract can afford to neglect the general question of alimentary infection ; otherwise even the best planned and most skilfully executed surgical treatment of the local condition cannot promise permanent cure. The search for a satisfactory treatment of gastric ulcer has led to the evolve- ment of one operation after another, each appearing for the time to hold out the promise of cure, until aftcr some years the same tale of recurrences and reinfections commences to be heard. Judd5* states that the number of unsatisfactory results is much the same after local excision as after gastro- enterostomy-about 30 per cent in cadi case.59 Partial gastrectomy has not yet been practised long enough to allow a similar comparison to be made ; but if bacteria are still bcing deposited in the mucous membrane, i t is difficult to ensure that they shall not repeat their former destruction.

In looking for a source of infection, I would plead for a consideratioil of the alimentary canal as a whole, its physiology and mechanics, rather thaii a hasty incrimination of a local lesion which, while often to blame, is in some instances collateral rather than primary. There is an age-long battle of the ileocmal bridge, commencing in cvery individual in the first. hours OP life, whcn his sterile alimentary canal first becomes invaded by bacteria. In this battle the appendix is one of a group of lymphoid collections engaged in a similar task of fighting infection, but is more liable than the others to succumb because of the easc with which a sevcre process may occlude its lumen or jeopardize its blood-supply. The appendix becomes tender in the early stages of many intestinal infections, in the first few days of typhoid fever, in many cases of influenza, often after a cold in people who have lost their tonsils. Very often indeed its protcctive powers havc been damaged, and it remains a menace rather than a safeguard ; but an appendix which is merely reddened and turgid is often making a powerful fight. While it is not suggested tha t the removal of an appendix which might have been spared is in itself harmful, it may happen that a deraiigcd condition of the whole alinicntary apparatus, the condition in the appendix being but one symptom, passes unnoticed.

A d a ~ n i ~ ~ describes tlie healthy body as potcnti.rlly, but no t artually. sterile. If this is 50. asepsis. perhaps in abdoniirid surgery more t h a n an>- other, depeiids not oirIy on the prevention of operative contamination, bu t on the determination tha t t he bacteria when they come by the blood-strcam, as come they 17 ill. shall iiieet 11 ith the hostility of' tissues iiiidamaged by rough haiidlirrg or prolo~iqed e~posiire.

APPENDIX. INVESTIGATIONS ON DUODENAL CONTENTS IN NORMAL STUDENTS.

&faTERIALS.-(1) Duodenal tube of Einhorn type : ('2) Rack of labelled test- tubes : ( a ) Ordinary : (6) Containing sterile broth medium ; ( 3 ) 20-C.C. Record syringe ; (4) Flask of sterile saline solution; ( 5 ) Flask of sterile 25 per cent magnesium snlphat e solution.

The tube was boiled and kept in sterile water. During swallowing, and between the aspiration of specimens, the free end was protected by a glove finger or a sterile gauze swab. The syringe was kept in a dish containing a mixture of ethcr and alcohol: and some of this was drawn in and out after each aspiration, the barrel being allowed to dry before use.

METHOD.--NO brcakfast was taken. The tube was swallowed about 11 .0 a m . as far as mark 2 , and a specimen of rest,ing gastric juice withdrawn, which was later examined chemically. The subject then drank a pint of weak tea, arid lay on a bed on his right side, with a pillow under the buttocks. After an hour, aspiration was tried, and when typical duotlenal contents were withdrawn, abont 1 C.C. was put into a st,erile broth tube, the rest into an ordinary test-tube for microscopical snd chemical investigation. The duodenum was then washed out with sterile saline, using the barrel of the syringe as a funnel, till the contents returned clear. Sanrples of the last wash-out were again taken in plain and broth tubes. Sixty C.C. of magnesium sulphate solution was then run in through the barrel of the syringe. The subject's head was brought to the side of the bed, and the free end of the tube allowcd to hang over, a howl being on thc floor. First the inagiiesiuni sulphate was poured out, followed quickly by a flow o€ bile. Whenever there was a changc in the colour of the bile, samples were taken in plain and broth tubes. All tubes were labelled with name, date, and time of sample.

The bacteriological examinations were carried out by Rlr. T. S. Keith, Assistant, Bacteriologist to Giiy's Hospital. The ordinary specimens were examined for reaction, and inicroscopieally for cells and cholestcrin crystals. The results are shown in Tuble 1.

C'holcsterin crystals were found in the bile in the case of Student No. 4 (H. C. C. 'l'.). Recognized by their shape, these crystals also gave a red colonr wit11 H,SO, run under the corerslip.

The results shown in Tirble I are markedly different from those obtained by Ilurst, ~+h states that .i the Slr. 10)igm is not often found in the contents of the duodenum removed during life with an Einliorri tube, except in Addison's anzmia and in subacute combined degeneration of tlie cord ". The discrepancy is accounted for i ~ y the difference in the method nsed, and the results in each case bear a different interpretation. In iny experiments, tlie duodenal tube was sterilized and then s~vallowed, every precaution being taken to avoid contamination of the exposed end of the tube. The outside of the tube would probably carry down some bacteria froin the fauces, but during its sojonrn in the stomach (very rarely less than an hour) it is exposed to the antiseptic action of the gastric juice to a greater extent than the food.

That tiibe-conta.niiiiatioii did not play a part in my results is shown by the sterility trf the bile in each case. In IIurst's series, after a sterilized tube was svdlowed, the stomach was washed out. Any fluid used to wash out the stomach also waslies throiigli the duodenum t o sonie extent. I consider t,hat the bacteria


rerovered in my own cases reprecent those wliicli may he found in a norrual duodenum on their way through to the intestines, while in IIurst's series such bacteria would bcwashed through l o the jejunum before the samplec were taken, and any organisms recovered represent a Rora definitely established in the duodenum of that individual.

INVESTIGATIONS OF DUODENAL CONTENTS OBTAINED AT OPERATION. In this series, a 10-c.c. Record syringe with a. long fine iieedlc was emplo\.cd.

As Soon as the aljtlomen was opened, the duodenum wa? punctnreti either in the wcond part or commencement of the third (according to tlie poGtion of the hepatic flexure). Sonic of the content5 were asuirated. and iniected into a tube of sterile

FIG. 470.-Chsrt giving the resir:t of the second personal experiment.

broth. 111 several cases nothing coiild bc witli- drawn, and tlir amount was always small. The s l i d puncture required no suture.

Some of the punctures were kindly done for me by Rir. K. P. Rowlands and Air. G. I-,. \l'augti. The bacteriological cxaniinations were done hy Mr. F. A. I h o t t , Barteriolo$st to the New Lodge Clinic.

PERSONAL DUODENAL EXPERIMENTS. In these two experiments no cultures were

takcn. The tube was swallowed at 11.0 p.m. as far as nrark 4, and fixed t o the cheek with strapping. I then slept on niy right side, and commenced investigations next morning.

Specimens were withdrawn every twenty minutes where any duodenal contents could be obtained. Reaction was inrestigated bj7 titrating with T;n hTaOH or HCI, the indicator used being phenol red, and the point of neutralit,\- Ph :: 7.4. Bile was estiiiiated by comparison of the specimens in a Dubosq colorinietcr against a standard representing an averane suecimcn. The colour of t,his standard was o k & d by ox bile, the opacity by soap

solution. Specimens were centrifrigalized and the deposit examined at the time under the microscope, a few drops of rnethylene blue being added. Other samples of the deposit were dried on slides, and later stained with Leishmaii's reagent and examined.

The results of one experiment have already been discussed; a chart giving the results of the second is here shown (Fig. 4'70).

ANIMAL EXPERIMENTS. The feeding experiments require no further description. The operative expcri-

nients include various procedures carried out with 1 guinea-pig, 28 catst and 0 frogs. The procedures have already been described in tlie text, and only a hrief summary is appended. The anatsthetic in the case of tlie mammals was chloroform for the ifiductton, followed by open ether. In two cats, nrethane 1.5 grm. per kilo was employed. The frogs were decerebrated.

In the early experiments on cats, it was found extremely difficult t o trace any except massive quantities of carmine in the tissues, arid the search for the path of spread was accordingly a haphazard one. In the loop experiments, therefore, the following procedure was adopted. After killing ttic animal, a careful inspection of all the viscera was made. The whole abdominal contents were then removed en bloc, including t,he diaphragm and posterior abdominal muscles. This mass was treated as a whole, dehydrated in six changes of alcohol a t intervals of a week, then


cleared in xylol, and finally preserved in liquid paraffin. The advantage of this method was that the organs were thereby rendered partially transparent, so that larger amounts of carmine could be seen ; and that all the tissues were preserved, and therefore additional sections could be cut to substantiate or modify the information obtained from the first sections examined. The disadvantage was that the

Frc. 471.-Diagram to illus- trate the lymphatic drainage of the alimentary canal in the cat.

1 , Gland of lesser omentum ; 2 , Pyloric gland; 3, Pancreatic gland (on neck of pancreas, a t formation of portal vein. Pro- jects mostly into lesser sac); 4, Main group of mesenteric glands (closely related to the duodenojejunal flexure and ileocaecal region ; 5, Appendicular gland ; 6, Ileocaecal group ; 7, Upper colonic group ; 8, Lower colonic group; 9, Ileal gland. B.D., Bile-ducts : P, Pancreas : P.V., Portal vein: S, Spleen: C. L, D,, Collecting lymphatic ducts (opening into thoracic duct ).

fixative only reached the deeper parts of the organs after a considerable amount of autolysis had taken place-a fact which did not vitiate the result, but which accounts for the poor staining observed in some of the illustrations. Except in certain cases, all sections were stained with haematoxylin only. (See Fig. 471.)

Table IV.-DETAILS OF 35 CONSECUTIVE EXPERIMENTS ON ANIMALS. The animals used were cats, with the exception of No. 1 (guinea-pig), and Nos. 30-36 (frogs).

780 THE BRITISH JOURNAL OF SURGERY

6 ' 21.6.23 Appendix tied off ant1 filled I with carniinc

7 25.6.23 Loop of jcjununi isolated and filled with carniiiie

5 27.7.23 Loop of large intestine isolated and filled with carmine

9 ~ 27.7.23 Gall-bladdcr isolated and filled with carmine

10 I 30.7.23 Stomach isolated and filled with carmine

11 1 30.7.23 Loop of ileum isolated and filled with carmine

I

I

1')

13

14

1.5

16

17

15

19

2.8.23 Carmine iiijrcted into lymphatic glands a t basc of mesentery. Indian ink into branch of portal vein

2.8.23 Gall-bladder isolated and

0.3 g r i . carmine into peri- filled with carmine

toneum 26.11.23

29.11.23 0.5 grm. carmine into jugular vein

29.11 .23 0.3 grm. carmine into branch of portal vein. Culture from duodenum

10.13.23 4 c.r. carmiric suspension into jugular vciii

10.12.23 Ileoczcal region ticd off, and filled with eniulsion of killed tubercle bacilli

10.12.23 Carmine injccted into lacteals of ilcum, and glands a t root o i mesentery

I

20 , 13.12.23 1 c.c. ramiinc suspension into branch of portal vein I

31

22

13.12.23 1leoc;ecal junction excluded, and lilled carmine

17.12.23 Appendix tied off and filled carmine

I I

Killed 26.7.23. Sections taken of appendix and gland, ileoczcal gland, pancreatic gland, spleen and liver

Killed 1.7.23.

Killed 1.8.23.

Leakage of contents of loop

Section taken of occluded gut, colonic gland, mesenteric gland, liver, and spleen. Smear of blood taken

Killed 1.8.23. Carmine had escaped into peritoneum. Smear of blood taken

Killed 13.23. Sections taken of stomach, splcen, and livcr

Killed 1.8.23. Section of occluded ileum, liver, splrcn, ileal glands. Smear of blood taken

Section taken of liver, spleen, gall-hladder, stomwh, kidney, spinal cord, knee-joint, bone-marrow, upper duodenum, lowcr duodenum and pancreas, ileum, appendix, colon

Killed 3.8.23. Section taken of gall-bladder, livw, spleen, pyloric gland, head of pancreas

Killed 17.12.23. Sections taken of omentum, stomach, uppcr duodenum, lower duodenum, pancreas, upper ileum, lower ileum, large intestine, liver, gall-hladdcr, spleen, mesentcric gland, and mediastinal gland

Died under anzsthetic. Ihodenal cultures taken. Section of stomach, small intestine, appendix, large intestine, livcr, spleen, kidney, lung, meseriteric gl:tnds, and gall- bltiddcr

Killed 1 J2.23. Sections taken of stomach, small intcstinr, largc intestine, appendix, liver, spleen, kidney, and gall-bladder

Killed 20.12.23. Sections taken of lung, liver, spleen, gall-bladder, stomach, duodenum and pancrcas, small intestine, appendix, large intestine, meseiiteric lymph glands, and bone marrow

Killed after 53 hours. Scctions taken of ileum, appendix, ca?cum, and ileoczcal

Sections taken of stomach, duodenum and pancreas, small intestine, appendix and gland, large intestine, gland from lesser omentuni, liver, spleen, gall- b 1 adder

Sections taken of stomach, duodenum and pancreas, small intestine, appendix and gland, large intestine, mesentcric gland, mediastinal gland, colonic gland, liver, spleen, gall-bladder, lung, and bone- marrow

Sections taken of appendix, large intestine, ileocaxal gland, liver, and spleen

Sections taken of appendix, stomach, liver, ,gall-bladder, pyloric gland, main mcsenteric gland, ileoczcal gland, colonic gland, pancreatic gland, and spleen

Killed 4.8.23.

gi:tIla Killcd 20.1 2.23.

Icilled 22.1 2.23.

Killed 14.1223.

Iiillcd 21.12.23.

INFECTIONS OF THE ALIMENTARY TRACT 781

TabZe I V . --DETAILS OF 35 CONSECUTIVE E X I ~ ~ ~ E N T S 0s ASIMALS- - confd. - ~ _ _ ~~~ -~

NO. ' DkTY, orrir ti IO\

__

23 19.32.23 Thoracic duct tied in neck, culture taken of contents. Carmine injected into mescnteric glands

24 19.12.23

25 4.1.24 I I

I ~

26 3.1.21. 1

27 10.1.21

I I

28 I 10.1.24

29 1 31.1.24

, 30-351 12.1.24

I

Failure to find thoracic duct in neck

Ileocacal region tied off, and injected with suspension of hzmolytic strepto-

Ilcocacal region excluded, and 25 min. of 3 per cent protargol in saline injected

2 c.c. of eniulsion of streptococcus injected into ileum, without exclusion

coccus

1lcocrt.cal region tied off, and 1 C.C. streptococcal emulsion injected

Suspension of streptococci itijected into duodenum

Greater part of small intestine tied off, and filled carmine ~- ~~~ -~

Killed 31.12.23. Leakage of carmine from glands into peritorical cavity. Sections taken of stomach, upper duodenum and pancreas, lower duodenum and pancreas, small intestine, appendix and gland, large intestine, liver. gall-bladder, spleen, lung, bone-marrow, glands from lesser omenturn, mediastinurn, head of pancreas, and inguinal region

Cat killed on table

Killed after 5 hours. Culture of pericardial fluid, heart blood, portal vein, thoracic duct, collecting 1) mphatics, and main niesentcric glands

Killed 7.1.24. Sectioiis of appendix and gland examined

Killed after 3% hours. Cultures from lieart (2), thoracic duet ( 2 ) , collecting lymphatics ( 2 ) , ileal gland, cacal gland. Section of appendix and i1eoc;rcal gland examined

Killed after 55 hours. Culture from heart, thoracic duct, collecting ducts, ileocacal gland

Cultures for heart blood, thoracic duct, collecting ducts, ileoczcal glands, colonic glands, ileal glands

3 killed after 24 hours, 1 after 48 hours. Sec- tions examined of gut mall, liver, spleen, kidney, arid film of blood -

REFEREXCES.

Sftom, A. RENDLII, Brit. .7o?u. Surg., viii, No. 30, 171. M ~ A I Z R I S O X , R., Studies i t8 Deficiency Diseccses. Introduction. London, 1921. Focc~r~?., F. P., Brit. Jfed. Jow. , 1923, June 30. CHAUFYARD, La Litliiase biliairr. Paris : Rlassoii et C'ic., ICE2. ARCJ(IBALD, [,'utmd. M e d . A.ssoc. ,lour., 1912, ii, 337. CAMPBELL, J. hl . II., Personal communication. HOYI), U r i t . Jour. Surg., 1928, s, N o . :39, 337. JUDI , , 13:. S., .7our. Amer. M e d . Assoc . , 1921, lxsvii, 197.

!'ST1: , \ \ am, . 11. .T., Brit. Jletl. ,7our., 1923. ii, 933, 1021. 19 BOLTOX, CZrer of the Sfoi imrl~, 1913, Chap. ii. 11 H~SEKOW, E. C., ,Surg. Gynecol. u t ~ l Obst., 1921, xxsiii, 19. l 2 Rosexow, E. (:., Ibid. ; Jour. Amer. X e d . dssoc., 1913, hi, 18~47 ; Jour. Ittfect. Dis.,

191 ti, xix, 333 ; Jbid., 1923, xxxii, 38.4, etc. l3 DEAVER, .T. B., S'urgird Anatomy, I'hiladelphia, 1903, iii, 810 ; Surg. C'lin. of S.

Artier., i , 1. l4 CRarIaar, E. A., Surg. Cytzecol. at id Obst., 1918, s x + 521. l5 SEVLER, RI. T., ,Johii.s f l o p . Iiosp. Dtdl., 1901, xii, 126. lfi RRAITHWAITIC, Brit. Joicr. Surg., si, No. 41, '7. l i l'nmsom, IIuniuri Atiutomy.

*"RYLE, .T. n., and I J E N N m T , T. I., Ibid. , 1921, Isxi, 286.

2 2 L ~ o ~ , Jour. An~er . M e d . Assoc., 1919, 1

CANNON, W. B., Amrr. Jour. Physiol., 1902, v, 257, also subscquent ycars. HKRST, A, F., anti others, Guy's Ilosp. Rep., 1907, Ixi, 389.

MmxzLm, ilmer. Jour. 11Ied. X c i . , 1!)17? cliii, 469. iii, 980 ; Amer. . four. J l e d . Sci., 1920, CIS,

5151.

782 THE BRITISH JOURNAL O F SURGERY 27 CIXIING and Lrvr?;noou, Johns 11011. I Iosp. Rep . , is. 21 BONI), C. J., Brit. M e d . .70Ur., 19l(i, .June 3, Ilec. 23 ; 3917, Feb. 3 , ; 1918, Scpt. 14. 2; RRAI)LEY and GASSER, , 7 0 1 ~ ~ . o j Hiol. <’hem., 1912, xi? 20. 2s FROST, W. I)., and BACIIMAXS, F., Scicnt. Proc. Anher. Racf.. 1922 (quoted by

Dudgeon, I,. S). 2i SPALLAXZAXI, EzpPriences sur I n Digentio)!, 1784 (see also Luciani, Iurnciti Physiology,

London, 1913,.ii, 179, SO.) 23 KNOW, V. A., (AA!J’s I losp . Rep., 1923, lxiii, 429. 2!’ HURW, A. F., L a ~ c e t , 1!)23, i , 111. 50 BENNICTT, T. I., and VENAim.:s, J . I<’., Brit. Metl. Jour., 1920, ii, Oct. 30. 31 CAMPBELL, J . 31. H., Guy’s Ho.77). R c p . , 1924, lxsiv, 23, and personal commiinic!stion. 32 BONAR, T. G. I ) . > Guy’s Hasp. Itep.. 1922, Isxii. n3 LORI) I x T n n . Collcckd Papers, i, 25 . 39 SPENCER, Lancet, 18!37, i, 722. 35 Gor,~)scrrmrt~, S., PhyRiol. Reviews, 1921, i, 421. 3 6 HERRIM;, P. T., and MACNAGCIITOS, F. G., Lancef, 1922, i, 1081. 37 KErni, SIR A., 13rit. Jour. Surg . , 1915, ii, 576. 3 8 WILKIE, D. 1’. U., Lcctrcc/, 1923, i. 1135. 39 BoLrox, C. H., Jour. Pnthol. n?ld Bucteriol., 1921, xxiv, 429. 4 0 F ~ ~ ~ ~ ~ . ~ , A. G. TIMRRELI.: Laitcut, 1923, ii, 541. 41 Prcrcov. F. L., JOUT. of Irtfect. l j i s . , 1923, xssii, 232. 4 2 Rusvi.:~, Sir A., Quart. .lour. Micr . S c i . , s s x , 481. 43 NICHOLLS, quoted by A h m i in Lane’s Opcrutiw Treatme/rt of Intestinal Stusis, 1018,

Chap. viii, 218. 44 I~ESOUBRY and PORCIIKR, Soc. tle Biol., 1893, 1 O i . 45 NIC~LAS and I ~ ~ R C A S , Ibid.. 1902, .July 19. 4 6 RA~I.KEL, Jour. AZetl. Research, 1903, s, 460 ; Ibid., 1908, xviii, 1. 4 7 Quoted by Calmette, L’l i fect ion bncillairc et lu Tubcrculow, 150.

4 s M o ~ ~ ~ , W. B., and IRONS, E. E., .7our. of Infect. Dis.. 1923, ssxii. 4 9 DIGBY, K. H., Im?~hunity i n Ilealth.

j1 CURNOW, Lancet, 1879, ii, 726, 761. 52 DURIIAM, H. E., Medico-Chir. Truns.. 1807, lsxs, 191 ; Jour. Pnthol. and Bucteriol.,

Paris : JI:I\SOII rt Cic., 1920.

Oxf. Med. Pub., 1919. FORD, W. W., Trans. Assoc. Amer. Phystol., 1900, xv, 389.

1597. 33%. 53 MCCARRISOX, Loc. cif., Chaps. is, x, s i . 54 H U R ~ T , A. F., ConstipatioiL and Allit-% Intestinal Disorders, 21, 61, Oxf. Ned. Pub., 1909. “ B A N K A R T , A. s. B L ~ N n m L , Brit. dled. Jour., 3021, i, 587. BARCLA CLAY, A. E., Lancet, 1922, ii, 261. 5 7 Cf. WALTOX, A. J., Lancet, 1023, ii, 1333. “ , Jun~) , l3. S.. Surg. Gynecol. atid Obsf., 1923, Aug. 59 CONYBEARI:. J . J., Gu?l’s Ilosp. Rep., 1922, lxsii, 174. 6o ADAMI, Lane’s Operative Trentrnrnt of Inlesfinal Sfasis, 1918, Chap. viii.

infections of the alimentary tract

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