ittetiical journal for - national institutes of health · 2015. 6. 4. · 2 syphilis and the liver....

SYPHILIS AND THE LIVER.

BT

J. G. ADAMI, M.A., M. D., F. E. S.E.,Professor ofPathology in McGill University, Montreal.

REPRINTED FROM THE

'Ntto Yorft ittetiical Journalfor April 22, 1899.

Reprinted from the New Yorlc Medical Journalfor April 22, 1899.

SYPHILIS AHD THE LITER *

By J. G. ADAMI, M. A., M. D., E. E. S. E.,PROFESSOR OF PATHOLOGY IN MCGILL UNIVERSITY, MONTREAL.

Without doubt the most important fact elucidatedby a study of the hepatic lesions of syphilis is that, froman anatomical and histological point of view, no dis-tinction can be drawn between secondary and tertiarysyphilis.

Clinically, I admit that such a distinction is useful,nor do I wish it to be thought for a moment that Iimagine it can be done away with, although even clin-ically—as seen in connection with the syphilodermiae—

the establishment of a hard-and-fast demarcation be-tween what is secondary and what tertiary leads not in-frequently to confusion. The most that can be laiddown is that when syphilis is acquired in the ordinaryway, by sexual connection, the extension of the diseasein general follows a definite course, the tissues tendingto be affected in definite order. Or perhaps it is morecorrect to say that in syphilis, as in other zymotic dis-

* A contribution to the discussion upon syphilis at the New YorkAcademy of Medicine, March 9, 1899.

Copyright, 1899, by D. Appleton and Company.

2 SYPHILIS AND THE LIVER.

eases—l use the term zymotic in its strict sense—-there is a local or tissue predisposition, so that certaintissues are apt to be more extensively and more mark-edly affected than others, the virus multiplying morereadily; so that in them, as a consequence, there is anearlier and more pronounced reaction.

But while this is the case, the reaction in a given tis-sue is of like order, be the period of local infection earlyor late; at most there may be histological differencescaused by the age of the lesions and by variation in theinteraction between virus and tissue. If the virus bestrong, or the tissue be possessed of feeble reactive pow-ers, the histological appearances differ to a greater or lessextent from what is seen when the virus is weak or thetissue possesses originally or has acquired strong reac-tive power. And as a corollary to this, it may be saidthat where the virus is powerful and there is rapid pro-liferation there, in such diseases as syphilis and tuber-culosis, the effects upon the tissues are modified so thatwe have to deal not solely or not in the main with thelocal disturbances caused by focal growth of the virus(infective granulomata), but see other well-marked ana-tomical changes, brought about by diffusion of the tox-ines. In other words, where the tissues are susceptibleand the virus relatively powerful there may be general-ized tissue disturbances apart from, and in addition to,the granulomatous developments directly caused by thefocal proliferation of the germs. For at the s.tart itmust be laid down that, although as yet we are uncer-tain as to the exact causative germ of the disease, syphi-lis is a disease of microbic origin. The more one stud-ies, the more is one convinced that the analogy betweentuberculosis and syphilis is complete—only in the one

SYPHILIS AXD THE LIVER. 3

we have isolated and studied the germ, in the otherwe have not.

For what do we find with regard to the hepatic mani-festations of syphilis ? Let ns first take those of the con-genital disease. There are many reasons why theseshould be considered first: these were the first specifichepatic manifestations to be studied and clearly recog-nized; they are much more frequent and more extensivethan are hepatic lesions in the disease of postnatal ac-quirement, and, death occurring very frequently withina month or two after birth, there is less uncertainty asto the period of development and duration of the lesionsthan there can be in the disease of adult life.

That the liver should be so frequently affected in thisform of syphilis is easily understood if we rememberthat the specific syphilitic lesions of the newborn arecongenital and not inherited, that the infection isthrough the placenta, and that, as a consequence, theinfected blood coming from the placenta passes throughthe liver before it reaches the heart or any of the othertissues of the foetal organism. Chiari’s well-known ob-servation may here be repeated—namely, that in a hun-dred and forty-four cases of infantile syphilis he foundthe liver affected, and that extensively, in a hundredand twenty-three, or nearly nine tenths. In the adult,on the other hand, both brain and testicle are more fre-quently the seat of extensive lesions, and when it isremembered how relatively common is tertiary syphilisand how relatively uncommon specific disturbances ofany of these three organs the contrast between the fre-quency of congenital and acquired hepatic disturbancesbecome more manifest. At the same time lam not pre-pared to accept Fournier’s statistics as perfectly reli-

SYPHILIS AND THE LIVER.4

able; careful observation of 3,429 cases of tertiary syphi-lis should surely reveal clinical evidence of more thannine cases of hepatic implication.

This is not the place for me to dwell upon the vulgarerror of speaking of inherited instead of congenitalsyphilis; suffice it to say that Gartner’s * reductio adabsurdum of the inheritance, so called, of paternal tu-berculosis must hold equally for syphilis, f Indeed, wereit possible for the bacillus or germ of syphilis to be pres-ent in the ovum at the moment of fertilization, to lielatent during the embryonic period and only to causereaction during foetal life, that is to say, after the dif-ferent organs have assumed the form and structurewhich will pertain to them through postnatal existence,even then such presence of the germ would not be trueinheritance—it would be an epiphenomenon; for trueinheritance demands the carrying over of features pecul-iar to the germ plasm of the parents. The fortuitousinclusion of a microbe in one particular ovum is not amatter of inheritance.

The different forms of lesions due to syphilis to bemet with in the infant’s liver are, I think, included inthe following list:

I. Well-defined gummata.11. Miliary gummata with generalized fibroid change

affecting circumscribed areas of the liver.111. Admixture of miliary gummata and generalized

fibrosis affecting the whole organ, which is in conse-quence enlarged.

* Gartner. Ztschr. f. Hygiene, xiii, 1893, p. 101.

f By this I do not mean to infer that there is no indirect inheritance.Probably the majority of Fournier’s parasyphilitic lesions, if not all, areexamples of such indirect inheritance: stigmata are inherited, not thedisease itself.

SYPHILIS AND THE LIVER. 5

IY. Generalized atrophic cirrhosis without much evi-dence of gummata, but associated with icterus, oedema,etc., the organ being very granular and contracted.

Time forbids that I should quote examples of thesedifferent conditions. Quite the commonest is the secondform, in which there are no well-developed gummata asgenerally understood, but on section through the affectedareas numerous minute focal collections of small roundcells are to be made out, invisible or just visible to thenaked eye, and in their neighborhood extensive peri-cellular fibrosis, so that the organ presents a patchy ap-pearance, paler areas of large size standing out againstthe darker red or liver-colored background of the un-affected tissue. Here we have to deal with a relativelyearly and progressive stage of disease in which there islittle or no necrobiosis and development of gummymatter.

There are, however, fairly frequent cases on recordof the development of true gummata, easily seen by thenaked eye, some as large as an almond, recognized, not,I believe, in children born dead, but in those dying asearly as two weeks after birth (Canton), and at timesshowing signs of contraction.

The relationship between these miliary gummataand the gross gummata of the liver is that between mil-iary tubercles and isolated caseous tubercles of the sameorgan,. We never think of suggesting that the two lat-ter forms of tubercle indicate different periods of thetuberculous process. At most we regard the first as ofmore acute, the second as of more chronic development.We know full well that miliary tuberculosis of the livermay develop at any stage of the disease, either soon afterthe primary infection or only as a terminal event after


long years of slow and, it may be, intermittent extensionof the disease elsewhere. The fact that both gross andmiliary gummata may occnr in the liver of the newlyborn is an absolute proof that the two forms are notcharacteristic of two different stages or periods of thedisease—“absolute/ 5 that is to say, unless we are pre-pared to admit that while certain tissues, such as theskin, present well-marked secondary lesions, others maypresent either secondary or tertiary changes. If we dothis, then the use of the terms becomes almost meaning-less. For it must be kept clearly in mind that while thelivers of these syphilitic infants show extensive fibrosisand indications which usually are recognized as of ter-tiary type, the cutaneous eruptions are of the nature ofsecondary manifestations.

But over and above the granulomatous changes inthe infant’s liver it is most noticeable that a more gen-eralized affection is the characteristic feature—namely,fibrosis affecting either the whole organ or larger orsmaller areas. Such fibrosis might be due to variouscauses; indeed, our knowledge of the astiology of cir-rhotic changes in the liver, as in the kidney, and ourknowledge of fibrosis in general, is not sufficiently ad-vanced to permit us to make positive statements. Andyet, since 1896, when in this very room, although notbefore your society, it was my privilege to deliver theMiddleton-Goldsmith Lectures,* and I discussed thepathology of fibrosis, some little advance has been madein our conception of the process. For, on the one hand,Flexner f has shown that toxic substances (the blood

* Medical Record, 1896.f Flexner. Transactions of the Pathological Society, Philadelphia,

1896.


serum of another animal) may lead to the develop-ment of cirrhosis, and, on the other, Weaver,* of Chi-cago, within the last few weeks, working (I think I maysay) along lines suggested hy certain publications ofmine, has demonstrated that bacteria exist which direct-ly induce hepatic cirrhosis. Thus it would seem thatwhether in the process of excretion of toxic substancesby the liver cells, or by the taking up of certain bacteriaand the influence of their toxines when so taken up, theliver cells may undergo a parenchymatous degenerationso intense that death ensues, and following thereupona replacement fibrosis occurs, more or less pure and un-accompanied by acute inflammatory change accordingas to whether the parenchymatous disturbance is unac-companied by interstitial irritation or no. Where manymiliary gumraata are present much fibroid change iseventually brought about by the tissue changes whichfollow their development.

We are not as yet in a position to state whether thefibroid change of this type in the liver of the syphiliticchild is a consequence of the attempted removal of thesyphilitic germs from the portal circulation by theagency of the endothelium of the hepatic blood-vesselsand by the liver cells, or whether it is purely the circu-lating toxines of the disease that cause the disturbance.To me it would seem that one or other of these causesmust be at work. The pericellular character of the cir-rhosis is against the change being in the main a fibrosisfollowing upon round-celled and miliary gummatousinfiltration, while the fact that the change may affectthe whole organ, as again the very extent of the areaswhen the whole organ is not affected, is quite opposed* Weaver. Philadelphia Medical Journal, February 4, 1899,p. 283.

8 SYPHILIS AND THE LITER.

to the view that we have to deal with primary focalnecroses, such as are to be met with in typhoid and otheracute infective diseases, or in infarctous disturbances.

If Marchand’s * cases of atrophic granular cirrhosisoccurring in foetuses born dead are, as he holds, of syphi-litic origin, they afford evidence of the extreme resultsof such fibrosis following upon generalized syphiliticparenchymatous hepatitis, f

Thus, to sum up the broad features characterizingthe syphilitic manifestations in the infant’s liver:

1. Syphilis may lead either to granulomatous de-posits in the organ or to interstitial fibroid changes.

2. The specific granulomata may be present eitherin the form of minute multiple miliary gummata, or ofisolated larger gummata,- such as in general are regard-ed as being of tertiary nature.

3. It is not possible to regard the one form as sec-ondary, the other as tertiary, for either may exist withcutaneous disturbances of the secondary type.

4. By analogy, the interstitial fibroid change, socommon in infantile syphilis, would appear in the mainto be secondary to a degeneration and necrosis of thehepatic parenchyma, induced by the action of the tox-ines of the syphilitic virus upon the individual livercells. In part it is developed in direct association withthe development of miliary gummata.

Passing now to the hepatic disturbances in syphilisof postnatal acquirement, we find it more difficult to de-

* Marchand, Ctrlbl.f. dig. Pathol., vii, 1896, p. 273.f Dr. Jacobi tells me that he has described one of these cases of

atrophic cirrhosis in the infant; like Marchand, he was forced to con-clude that it must have been of syphilitic origin.


termine the age and duration of the lesions found, adifficulty due to the fact that syphilis is not in itself acause of death during the months which immediatelyfollow infection. I know of no adequate study madeupon the livers of those who, suffering from well-markedsecondary symptoms, have succumbed to intercurrentdisease or accident. A thorough investigation of thevisceral changes occurring in the secondary period re-mains as much a desideratum to-day as it was in the sev-enties, when Jonathan Hutchinson called attention tothis gap in our knowledge. It is, however, probablethat in the vast majority of cases the liver isnot gravely affected during this stage, for otherwiseit is most unlikely that with the vast number of autop-sies made annually a fair number of instances of deathduring this period should not have been investigated;so that any marked departures from the normal in thecondition of the organ should by now have gained recog-nition. It is equally true that there might be a certainamount of disturbance—the existence of miliary gum-mata, or, again, of a moderate extent of parenchyma-tous degeneration—which might easily escape detection,or be ascribed to other causes.

Some few cases are on record of extensive hepatic de-rangement during the secondary state. Thus, HiltonFagge* reports the ease of a femaleof twenty-three yearsin whom there was a history of syphilitic rash with lossof hair and macular syphilides; jaundice supervened andthe patient became drowsy and comatose. At the au-topsy, the liver, which weighed forty-six ounces, wasof an opaque bright yellow color and of dense consist-

* Hilton Fagge. Transactions of the Pathological Society, London,

xviii, 186V.


ence. The surface was mottled, the left lobe resemblingvery closely that of the infantile syphilitic liver. Onsection the organ appeared pale and semipellucid, andmacroscopically the parenchyma was seen to be replacedby connective tissue. Unfortunately, the descriptiongiven does not extend to full details. But clearly hereis a case of generalized cirrhotic change in secondarysyphilis not unlike that found in the infantile disease.

Somewhat similar cases are recorded by Engel-Eeimers,* Kratz,f and Neumann.J In all these casesthere was a condition not unlike subacute yellow atrophy.Engel-Reimers considered the condition due to enlargedlymph glands at the hilus. While these might causeicterus, it is difficult to see how they could bring abouta general atrophic condition of the organ; the explana-tion is clearly inadequate. Neumann’s case is dis-tinctly interesting; it is that of a man of twenty years,ill for about eight months. When seen, in March,1894, there were papules on the external genitalia andbuccal mucosa, and a slight icterus. The jaundice be-came intense, with great abdominal pain and ecchy-moses. The liver diminished, and in nineteen days thepatient died with urgemic symptoms. To me the specialinterest lies in Kolisko’s diagnosis at the autopsy, whichwas that of “catarrhal icterus with chohemia; regen-eration of the hepatic parenchyma in the form of ade-nomatous tumors, following upon acute atrophy of thesame.” Here was evidently acute generalized hepatitis.

* Engel-Reimers. Jahrh. d. Hamburger StaatskranJcheitanstalten,1889.

+ Kratz. 66. Versamml. d. Naturforsch., Vienna, 1894 (Path.-anat.Section).

\ Neumann. Nothnagel’s Specielle Pathologic, xxiii, p. 409. lamindebted to Neumann for the two previous quotations.


According to Neumann, Dittrich collected forty-sixeases of syphilitic hepatitis, and these in the main werefrom the secondary period of the disease. An observa-tion by Bee * would seem to indicate that such hepatitis,even when somewhat chronic, often leading to extensivetrouble, may undergo complete absorption, or, at least,may be followed by no gummatous development.

It will be noticed that in the above cases jaundicemanifested itself. Now jaundice is a not uncommonevent in secondary syphilis. Attention has frequentlybeen called to its existence from the time of Eicord andGubler onward; Lancereaux alone collected twenty-onecases. Within the last two years Neumann, Joseph,and Uhlmann have redirected attention to its preva-lence. I can not but think that this jaundice mustafford another indication of what I have already dweltupon in connection with infantile syphilis—namely,that the liver, being a great excretory organ, may incertain cases be so injured by the action of syphilitictoxines that parenchymatous and, it may be, catarrhalhepatitis is set up and the jaundice be an indication ofthe functional disturbances due to this cause. Thisview appears to be more probable than either of theother suggested explanations, which are that thejaundice is obstructive and due either to specific growthsin the bile ducts, or to the pressure of enlarged lymphglands at the hilus of the liver upon the larger bile pas-sages. f

We thus, even in the early stages of the disease ofpostnatal acquirement, obtain evidence pointing to the

* Bee. Gaz. med. de.s hopit., Iviii, 1885, p. 140.f Neumann (loc. cit.) gives a full and interesting study of specific

icterus.


existence of generalized effects of syphilis npon the or-gan. As I have pointed ont elsewhere,* a fairly ex-tensive fibrosis, apparently independent of the gum-matous developments, is not infrequently to be met within cases where there is active progressive syphilis longyears after primary infection.

Turning now to the more generally recognized evi-dence of syphilis affecting the liver in the tertiary stage—namely, the gummata—and discussing first the largegummata, which are the most characteristic lesions ofacquired syphilis, it must be clearly borne in mind thattwo distinct conditions are popularly confounded to-gether and both regarded as tertiary manifestations—namely, the fibroid pittings and cicatrices which arethe final indications of gummatous deposits in the liver,which remain after complete absorption of the originalgummatous mass. We not infrequently come acrossthese disfigurements and distortions in the liver in thebodies of those who for years have presented no indi-cations of active syphilis, and they must, I hold, be re-garded as obsolete gummata. Indeed, in one case, uponmaking microscopic sections through a most character-istic puckering, I found scarce any fibroid tissue left;that also had undergone absorption. On the other hand,we have to recognize gummata with cheesy or gummycontents surrounded by fibrous tissue, which are latentor obsolescent, and others again presenting like charac-ters, but surrounded by hepatic tissue, which under themicroscope presents infiltration with small round cellsand evidence of progressive syphilis. It is these latentand active gummata which alone are of any importance.

* Adami. Montreal Medical Journal, xxvii, 1898, p. 413.


for both indicate that the disease, to say the least, hasnot been eradicated from the system.

The important point to notice is that in one liverwe at times meet with all the forms above mentioned.I have come across cases at autopsy showing well-marked cicatrices and puckerings of practically obsoletegummata, large, well-defined gummata with necrosedcentres, and, upon studying the sections of the liver fromthe neighborhood of the latter, I have there seen theirregular minute collections of small round cells which,in an infant’s liver, we would have had no hesitation indescribing as miliary gummata. These appearances Ihave seen in the liver of a man dying apparently onlybetween two and three years after primary infection,as again in the liver of another infected fourteen yearsbefore death.

The evidence before us all points to the fact that inthe adult, as in the infant’s liver, gummatous develop-ment may occur at any period after the disease has be-come generalized throughout the body.

From what has already been stated, it follows thatthe same lesions are to be met with in the adult liveras are recognizable in the organ affected by antenataldisease. There may be:

I. Large well-formed gummata.11. Miliary gummata.111. Acute parenchymatous hepatitis (with jaun-

dice) .

IV, Syphilitic cirrhosis.But clearly the element of time introduces frequent-

ly a difference and appearances not seen in the infantileliver. Thus we encounter in addition:

Y. Obsolescent gummata: large gummata under-

SYPHILIS AND THE LIVER.14

going involution and absorption, with surrounding andlimiting fibroid change and contracture. This is thelesion most often met with, and most typical of thesyphilitic liver of the adult.*

VI. Obsolete gummata, represented by puckeringand deformity of the organ, with a relatively smallamount of fibroid growth radiating from the seat of theprevious gummatous formation—and by nothing else.

VII. A further lesion, which must be referred tohere—one not seen in the infant f—is the developmentof tumorlike outgrowths, so sharply defined and so largeas not infrequently to lead to the false diagnosis ofmalignancy. The structure of these masses affordsground for believing them to be the outcome of a slowlyprogressive centrifugal infection of the liver tissue froman original isolated gummatous focus (or small collec-tion of neighboring specific tubercles), with associatedreactive hyperplasia of the liver tissue at the periphery;progressive infiltration of the newly formed parenchymaby miliary gummata and eventual replacement of theselast by fibrous connective tissue; so that microscopicallythese tumorlike outgrowths present an outer layer ofliver tissue, infiltrated by collections of small cells, in-closing a dense mass of fibrous tissue with more or lessu gummy ” degeneration.

Time, therefore, is an element causing difference in* What is the causation of the coarse bands of fibrous tissue radiat-

ing from these obsolescent gummata I must leave an open question. Ithas been suggested that they indicate a tendency for the fibroid changeto be developed along the course of the main lymphatic vessels leadingfrom the gummatous focus.

fln this lam mistaken. I owe to Dr. Jacobi (verbal communica-tion) a reference to a case by Cohn (?) of one of these tumorlike forma-tions in the infant presenting all the features here described.


the appearances of the adult and infantile lesions. Butthis is not the only one. The other, and yet more dis-tinctive, is the predominance of generalized fibrosis incongenital syphilis, of focal granulomatous changes inthe syphilis of adults.

The explanation of this difference would seem to bethat the young liver cell is more susceptible and lessresistant to injuries inflicted by toxic substances; it ismore prone to degenerate; and, if the view here enunci-ated be correct (namely, that the fibrosis is largely ofthe “replacement” type), we have in this feeblenessof the young liver cell a sufficient explanation whyfibrosis here predominates. With the adult cell it is dif-ferent. Inasmuch as a main function of the liver is toeliminate toxic substances from the circulating blood,its cells with advancing life become capable of with-standing toxines to a relatively very considerable extent.It is, indeed, remarkable to observe what extreme degen-erative changes of the cloudy and even of the fatty typemay be observed in the liver cells of an adult rabbit—for example, a few hours after intravenous inoculationof a centimetre of a culture of such a form as the colonbacillus; and yet in the course of a few days (as deter-mined in other rabbits similarly treated) the liver cellsmay have completely recovered and show no signs of theintense disturbance set up by flooding the system whichthe bacilli and their toxines.

Thus in the adult (as distinguished from the senile)there is not the tendency for the extreme fibroid changeto manifest itself under the action of irritants, whichin the young lead to the production of the same.

It may be asked why the liver of the newly born in-fant more than other organs is susceptible to these de-


generative changes. There are, it seems to me, two mainreasons; 1. The liver is especially concerned in elimi-nation of toxic substances, and its cells bear the brunt ofintoxication by the syphilitic virus. 2. Placed, as it is,between the placenta and the general circulation of thefoetus, its cells tend to eliminate toxic materials broughtby the umbilical vein; in this way, again, they bear thebrunt of intoxication, and at the same time reduce theamount of toxic material capable of acting deleterious-ly on the other organs. But it must be remembered thatother foetal organs may also show fibroid changes.

There is one other factor in the production of spe-cific lesions which so far I have not touched upon, onewhich, judging from studies made, more especially uponthe syphilitic heart and brain, may very possibly be ofsignal importance. I refer to arterial change—endar-teritis and periarteritis. We know, however, practicallynothing concerning the part played by this in he-patic lesions. I can therefore mention it and passit by.

Hence, to sum up: While the changes seen in theadult and infantile syphilitic livers are astiologically andanatomically identical, they may present differences duein part to their relative duration, in part to the reactivepowers of the hepatic parenchyma at different lifeperiods.

A PRACTICAL TREATISE ON THESURGICAL DISEASES OF THEGENITOURINARY ORGANS,

INCLUDING SYPHILIS.Designed as a Manual fob Students and Pbactitxonees.

WITH ENGRAVINGS.

E. L. KEYES, A. M., M. D.,Professor of Genito-Urinary Surgery, Sypliilology, and Dermatology in Bellevue

Hospital Medical College.BEING A REVISION OP A TREATISE, BEARING THE SAME

TITLE, BY VAN BUREN AND KEYES.

Second edition, tliorouglily revised and somewhat enlarged.Bvo. 688 pages. Cloth, $5.00; sheep, $6.00.

“The progress made in surgery during the last ten years, the changes of prac-tice hy the best surgeons with regard to several operative procedures, notablylitholapaxy, suprapubic cystotomy, and operations upon the kidney itself, andother mattersas well, renderednecessary a thorough revision of theworkpublishedsome years ago as the joint production ofDrs. Van Buren and Keyes. Much ofthe work has been rewritten entirely. There is a large amount of entirelynewmatter presented in this volume, tomake room for which the reports of cases givenin the former work are all omitted in this. The work in its present form standsfairly abreast of the latest advances in genito-urinary surgery. Dr. Keyes saysof the book that it is an honest exhibitof his views upon all the subjectsconsidered,and, in view of his wide experience and unquestioned skill,we commendhis bookto the notice and study of all who work in this field.”—St. Louis Courier ofMedicine.

“This handsome volumeis notmerely anew edition of the well-knownwork ofVanBuren and Keyes, but a complete revision of that text-book. The originalplan of the older work has been retained, and its scope remains the same ; but ithas been entirely recast, and in a large measure rewritten. This course has beenmadenecessary by the vast progress which has marked the history of surgery dur-ing the last ten years, especially in the field of therapeutics and operative pro-cedures. To bring the book up abreast of the times upon the new device of litho-iapaxy, suprapubic cystotomy, and modern surgery of the kidney, the treatmentnow followed in diseases of the tunica vaginalis, and the many minor changeswhich find expression in the use of new agents, Dr. Keyes was compelled to omitmany things, to add considerable new matter, and largelyto modify much of theremainder. Some chapters are entirely new, and in order to make room for de-sired additions all the cases have been dropped. As it now stands, it is a treatisewhich may safely be consulted, and which fairly and freely speaks of the mostmodemmethods. Dr. Keyes is enthusiastic in his commendations of litholapaxy,and cordially indorses the high operation for stone, while he decides that thetime-honoredand brilliantmethods of reaching the bladder through the perinseumare only applicable in the cases of male children with stones of moderate size.Dr. Keyes says the book ‘is an honest exhibit of my views upon all the subjectsconsidered’; and as his experience has been large, and his skill and prudence areundisputed,we have no hesitation in saying there is no one in this country whosejudgment is more worthy of confidence or whose directions may be more safelyfollowed.”—American Journal of theMedical Sciences.

D. APPLETON AND COMPANY, NEWYORK.

ittetiical journal for - national institutes of health · 2015. 6. 4. · 2 syphilis and the liver....

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