No. 1291.

MAY 27, 1848.

LecturesON

THE CHEMISTRY OF PATHOLOGYAND THERAPEUTICS.

SHOWING THE

Application of the Science of Chemistry to the Dis-covery, Treatment, and Cure of Disease.

DELIVERED BY

ALFRED B. GARROD, M.D. LOND.,ASSISTANT PHYSICIAN TO UNIVERSITY COLLEGE HOSPITAL; LECTURER

ON MATERIA MEDICA AND THERAPEUTICS, ETC.

LECTURE IX.

Cartilages; their composition and properties. Muscular tissueor fleshj structure of; base consists of coagulated fibrin; juiceof flesh. Analyses, by Berzelius and Braconnot, of the com-position if1nuscle. Claevreulfinds Kreatine infleshj Berzeliusfails to discover it. Liebig’s researches on the composition ofthe juices of flesh,* strong acid reaction of; contains albumenand a red colouring matter in solution, which are coagulatedby heat. JJfode adopted by Liebig to obtain the juice, to pre-pare it fm’ analysis, and to separate the va1’ious constituents.Kreatine always present in flesh. Inoscinic acid a constituentof flesh, also lactic acid. Kreatinine an organic base also pre-sent; properties and composition of K reatinej relation to Sugarof Gelatine ; decomposition into Sarsosine and Urea. Amountof Kreatine contained in difo-ent kinds of flesh; contained inmuscles of all am?KC6—faMmKKcc, Birds, Reptiles, andFishes. Uses of Kreatine in the economy. Kreatinine, howprocured ; results from decomposition of Kreatine ; propertiesand composition of ; relation, in composition, to Kreatine andCafeine. Existence of K reatine and Kreatinine in Urine.

Cartilaginous Tissue.-The next subject to which I shall callyour attention is the composition of cartilage, which naturallyfollows that of bones. In the early part of the embryo con-dition of an animal, the skeleton is chiefly cartilaginous;most of this tissue, however, becomes converted into bone,but small portions are still left in the original state; hencethe division of cartilages into temporary and permanent. Inits intimate structure, as seen under the microscope, cartilageconsists of a matrix or solid mass, with corpuscles disseminatedthrough it.When examined chemically, cartilage is found to consist

chiefly of a chondrin-yielding tissue, the properties and com-position of which I have stated to you before. In the freshcondition, it contains about sixty per cent. of water; whenburnt, it yields from two to seven per cent. of an ash whichhas been examined by Fromherz and Gugert, and also byVon Vibra. The following table will give an idea of itsgeneral character:-

(Costal Oartilage of a Man.— Von Tribra.)

You will perceive, by this analysis, that the ash of cartilageis similar in composition to that derived from bones, onlythat the amount of this ash is very small, and it containsalso soluble salts similar to those which we shall find inmost of the animal fluids. The large amount of sulphatesare, no doubt, formed during the combustion, from the oxi-dizing of the sulphur which I told you is always found inchondrin.The spongy or yellow cartilages which are found in the

epiglottis, ear, eyelids, &c., also yield a species of ehondrin.The fibro-cartilages, which in structure resemble a mixture offibrous and cartilaginous tissue, are stated to afford collin inplace of chondrin.This subject, however, has by no means been perfectly

studied; and there is some probability, as I told you in aformer lecture, that there may exist tissues which are inter-mediate between those yielding true gelatine and chondrin.

1B1"" 1M1

When the temporary cartilages ossify, they no longer yieldchondrin, but common gelatine, to the action of boiling water:the same takes place when the permanent cartilages becomeossified by disease.

Muscular Tissue.-This tissue, which is commonly calledflesh, forms in all animals the largest part of the body, andby its means all the movements of the animal are effected.A muscle consists of a collection of bundles of small fibresunited by cellular tissue, called fasciculi ; and the fibresthemselves, when examined microscopically, consist of ex-tremely minute threads named nbrillse, or ultimate mus-cular filaments, which appear to be made up of cells; but forthe detail of this structure I must refer you to works onmicroscopic anatomy. Muscles are supplied with bloodves-sels and nerves. It is only within the last year that the che-mical composition of muscular tissue has acquired high in-terest ; and this importance has been given to it chiefly by thebeautiful researches of Baron Liebig, a short account of whichI will now endeavour to make intelligible to you.

It had long been known that the chief portion of the solidmatter of muscular flesh was composed of a substance havingall the properties of coagulated fibrin. This is’easily demon-strated by taking a piece of flesh, beating it up, and afterwardswashing it repeatedly in water and alcohol-a mass is left,which is the same when derived from any animal, or frombloodland very’much resembles that from the glutinous portionof wheat and other cerealia; it is insoluble in water, alcohol,or ether-soluble in weak alkaline solutions, from which it isprecipitated in the form of protein by neutralization with anacid; it swells up in acetic acid, and gradually dissolves; pos-sesses, in fact, all the properties which I have described toyou as belonging to fibrin. Berzelius had also found that thejuice of flesh possessed an acid reaction; and he asserted theexistence of lactic acid in it, but never absolutely proved it,the properties and composition of this bodv not being wellascertained at the time. Chevreul then found a crystallizablebody in the juice, which he named kreatine, from /CpT/at;, flesh;but Berzelius having failed to detect it, thought it was onlyaccidentally present. The following table gives you the re-sults obtained by Berzelius and Braconnot:

Berzelius also examined the properties of the alcoholic andwatery extracts derived from flesh, describes a substancewhich had the odour and taste of meat when boiled or roasted,which he named zomidin, from Mjmtoy, broth-and found thatwhen flesh was boiled for a long time in water, a small amountof gelatine was yielded to that fluid, arising from the cellulartissue contained in the structure. Analyses by Schlossberger,Schultz, and others, have shown nearly the same results,whether the flesh was derived from mammalia, birds, or fishes.Ultimate analyses of dried muscular flesh have been made

by Playfair and Bockmann, who found that the organic matterhad a composition almost identical with that of dried blood,and which corresponded to the formula C48 Hss N6 015.

Liebig commenced his researches with the amount of £knowledge on the subject which I have just mentioned toyou, and confined his attention to the juices of flesh, or thatfluid contained in the substance of the muscle, and which canbe extracted from it by means of pressure. He first foundthat when kreatine is boiled in an acid solution it becomesincapable of orystallizing; and this at once explained thereason of Berzelius having failed to procure it, as the juiceof the muscle is in itself an acid solution. Liebig adopts thefollowing method to separate the various constituents whichhe has found to exist in muscle: he takes the flesh of re-cently-killed animals, minces it, and extracts with water areddish-coloured fluid, having an odour which varies with theanimal from which it is procured. When heated it coagulates,first throwing down a white precipitate, which consists ofalbumen, the liquid remaining coloured. If it is afterwardsheated to the boiling point, a further precipitate falls-the redcolouring matter; and by filtration a nearly colourless fluidis obtained. The precipitates have an acid reaction, whichwater will not remove, and the filtered solution is alsostrongly acid. To obtain all the fluid from muscular flesh agood press is desirable ; and satisfactorily to procure the prc-

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ducts at least ten pounds of flesh should be employed. Havingthen procured a clear solution, the next step is to neutralizethe free acid contained in it. This is best done with awatery solution of baryta, which should be added until theliquid becomes slightly alkaline, and as long as it causes anyturbidity in a filtered portion. The precipitate which is thuscaused is due to the presence of phosphoric acid, which isthrown down in the form of phosphate of baryta and phos-phate of magnesia. Scarcely a trace of sulphate of baryta isfound, and this trace is no doubt owing to the presence of asmall quantity of blood in the muscle. We must next filter,and evaporate in flat dishes, taking care that the fluid neverboils; and when it acquires a syrupy consistence, it is left toevaporate very slowly in a warm place. Very soon crystalsare observed to form on the surface, and then on cooling thesides of the vessels become covered with them. The crystalsare the same as Chevreul described, and are named kreatine,of the properties and composition of which we shall speakshortly. When the syrupy fluid has entirely deposited thesecrystals, and is removed from them, and concentrated a littlemore, the addition of alcohol causes it to become milky; andif it is then put aside crystals are again formed, which canbe separated by slow filtration, and purified with alcohol.These crystals are always a mixture of several substances,amongst which we find kreatine, sometimes a little phosphateof magnesia, (if the phosphoric acid has not been quite re-moved ;) but the chief ingredient is a salt of an acid namedby Liebig inoscinic acid, united with potash or baryta, orboth, according as the baryta has been added in excess ornot to the original solution.

If to the filtered fluid we again add alcohol in considerablequantities, (about five times its volume,) it separates into twolayers, one of which, a brownish syrup, falls to the bottom,and in it crystals of chloride of potassium form; when thelighter stratum is decanted and mixed with its own volumeof ether, it first becomes milky, and then separates into aheavy, yellow, viscid liquid, which collects at the bottom ofthe vessel, and a lighter etherial layer.The heavy, viscid, fluid consists almost entirely of lactate of

potash; and the lighter one, when the alcohol and ether aredistilled off, and the residue evaporated to the consistence ofa thin syrup, forms a mass of crystals, which can be freed fromadherent mother liquor by washing with alcohol, and arefound to consist of a substance which has been namedkreatinine, mixed with kreatine. The separation of thesebodies can be easily effected by boiling in alcohol. The solu-tion, on cooling, deposits the kreatine, and the mother liquid,by evaporation, afterwards yields the kreatinine in the formof four-sided tables.By these operations, there can be shown to exist in the

juice of flesh at least six organic compounds-viz., albumen,red colouring matter, kreatine, inosinic acid, lactic acid, andkreatinine. Liebig describes less complex processes forseparating the two latter, which I shall state to you soon, butmust first make you acquainted with the properties of thesebodies.

- K’’ea’e.—To obtain it pure, we must first wash the crystalswith a little water, and then with alcohol, to remove all foreignbodies; afterwards, by dissolving in boiling water, and addinga little animal charcoal, the solution will, on evaporatton,give kreatine perfectly pure. It occurs in the form of right-angled prisms, very brilliant and transparent: when heated to212° Fahr., they become dull, and lose water; they dissolvereadily in boiling, but require about seventy-five parts of coldwater for solution; they are nearly insoluble in cold alcohol.Kreatine is a neutral body; its watery solution is decomposedwhen boiled with baryta, ammonia being given off, and car-bonic acid formed, which unites with the baryta; when boiledwith strong acids, as hydrochloric, nitric, sulphuric, or plios-phoric, it is also decomposed, and kreatinine produced, a bodywhich is contained in the muscle. Dry kreatine, or thatwhich has lost its water, at the temperature of 212° Fahr.,yields, when analyzed by combustion, the following percentage of elements:-

Corresponding to the formula Cg Ng 1-1, 04, which may be con-sidered as representing anhydrous kreatine. In its crystallizedstate it contains 12.17 per cent. of water, corresponding to twoequivalents; hence crystallized kreatine has the formula,Cs Ng Hll Os, or Cg Ns Hg 04 + 2 HO.If we examine the formula for kreatine, in conjunction

with those of some other bodies which are either found in theanimal body, or can easily be produced from such, we shallsee some very curious and interesting relations, which are,indeed, so simple, as to leave little or no doubt that they arenot accidental, but depend on a common relation existingbetween these bodies, and show that they all have a similarorigin.

Thus, if we compare kreatine.with sugar of gelatine orglycocoll,—a substance which I have shown you to be pro-duced by the action of acids and alkalies on gelatine, whichcan also be formed from hippuric acid (a constituent of theurine) and from cliolic acid, (which forms so large a portionof the bile,) by the same means,-we find-

Again:, I told you that when kreatine is boiled with barytawater, ammonia is given off, and carbonate of baryta formed;but we find that the kreatine is not completely broken up bythis means, and in the solution a new substance is contained,which possesses all the properties of an organic base, and iscalled sarsosine. To obtain it we have only to add to aboiling solution of kreatine ten times the weight of purecrystallized hydrate of baryta, and continue the boiling untilammonia ceases to be given off. The filtered solution thencontains only sarsosine and baryta, and by passing a streamof carbonic acid gas through it, the baryta is precipitated asthe carbonate, and the liquid filtered and evaporated yieldssarsosine in crystals.

Sarso81’ne, when pure, occurs in right rhombic prisms, witliacuminated ends, very soluble in water, but sparingly so inalcohol, and insoluble in ether. Sarsosine has the power ofneutralizing acids and forming salts: thus, we can crystallizethe hydrochlorate and sulphate of sarsosine, the doublechloride of platinum and sarsosine, &c. When burnt, itgives a per centage of elements corresponding to the formula,C6 N, H7 0.(, which, compared with kreatine, from which itis produced, gives the following relation :-

So that urea is separated when kreatine is boiled with baryt2,and is afterwards resolved into ammonia and carbonic acid.This Liebig has demonstrated to be the case; for if theprocess is arrested when the ammonia is being freely deve-loped, the solution is found to contain urea, which can becrystallized from it, if nitric acid is added, in the form ofnitrate of urea. Thus we see that in muscle is contained asubstance from which urea can be readily formed, and this isinteresting in connexion with the fact, that the amount ofurea eliminated by animals in their urine bears a close rela-tion to the amount of exertion or muscular force employed;for we shall find that the amount of this substance thrownout by very young children is much less than by adults, and inextreme old age it again becomes greatly reduced. Cceterisparibus, the amount of urea eliminated by an animal in agiven time varies with the amount of muscular exertion, andit has been also found that the quantity of kreatine in theflesh of an animal depends much on its habits; and Liebigstates, that from foxes killed in the chase, ten times as muchkreatine could be obtained as from those which had been fedfor a long time on flesh, in confinement.The amount of kreatine contained in different kinds of

flesh varies greatly; it exists in largest quantities in that offowls and the marten, then of the horse, fox, deer, ox, pig,calf, and last, fishes.

The heart being a muscle, and in constant action, is found,as might have been anticipated, to yield a large amount ofkreatine. It is not, however, contained in non-musculartissues, as in the brain, liver, or kidneys, but, as we shall after-wards have to mention, it forms, in conjunction with kreati-nine, a small portion of the solid elements of the urine, a partof that matter which was called extractive.

Schlossberger found kreatine in the flesh of the alligator,and it appears that this substance is a constant product of themetamorphosis of muscular tissue which takes place duringthe performance of its functions, and that it is not produced

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in any other manner. Liebig regards it as acting an impor-tant part in the vital phenomena, and states in favour of thisopinion, that the broth of flesh cannot be replaced by gela-tiue, or any other liquid obtained from other parts than themuscles; but broth contains many other substances, as thephosphate of potash, &c., which are not found in gelatine andother liquids, and which, probably, are much more importantas ingredients of food. It certainly seems to me more pro-’bable that kreatine is a product of the decomposition of fleshwhich is principally, if not entirely, destined for excretion,partly in the state of kreatine or kreatinine, but chiefly whenit has been further broken up into urea, &c.Kreat’ininc.-I have already mentioned this substance to you

as existing in the juice of flesh, and also as being a product ofthe action of acids on kreatine. From flesh it can be ob-tained in the manner I stated to you, but more readily bytaking the mother liquid from which the inoscinates have beendeposited, evaporating to dryness in a water-bath, and thenboiling with alcohol; this readily dissolves the kreatinine, andfrom the solution it can be thrown down by the addition ofchloride of zinc, which forms a very insoluble crystallizedcompound with it. The best processes, however, for procur-ing kreatinine is to act upon kreatine by means of an acid.The vapour of hydrochloric acid, at the temperature of2120 Fahr., converts kreatine into hydrochlorate of krea-tinine. The same takes place when kreatine is evaporated todryness with hydrochloric acid; or if dilute sulphuric acid isemployed, a neutral sulphate of the base is left, and fromthis last kreatinine is obtained by the addition of carbonate ofbaryta, to the boiling aqueous solution. When pure, kreatinineoccurs in colourless four-sided prisms, much more soluble inwater than kreatine, requiring only about eleven parts, at60° Falir.; it is also soluble in alcohol; the solutions have astrong alkaline reaction to test paper, and will neutralize acids.In many respects kreatinine resembles ammonia; it forms crys-tallizable compounds with nitrate of silver, bichloride of mer-cury, chloride of zinc; and with the bichloride of pIa tina, adouble salt, which can be procured in large yellow crystals,By analysis the following results are obtained:-

Which agrees with the formula, Cg Ng H, O2; and that this isits real formula is seen from the composition of its salts. Youwill perceive that between kreatinine and kreatine a veryclose relation exists, for the former is produced by the ab-straction of four equivalents of water from the latter.Thus, 1 cq. of kreatine, CgNHOg — 4 eqs. of water,

II4 04 == 1 eq. of kreatinine, C9 N H, O2.The formula for kreatinine has also a curious relation with

that of theine or caffeine-a body which I told you exists intea. coffee. and several other nlants.

Kreatinine appears to form a constant ingredient of humanurine, and it is probably also contained in the urine of otheranimals.

Lectures

ON VENEREAL AND OTHER DISEASESARISING FROM

SEXUAL INTERCOURSE.Delivered in the Summer of 1847, at the Hôpital du Midi, Paris.

BY M. RICORD.

(Specially Reported for THE LANCET, at the Hôpital du Midi,by VICTOR DE MERIC, M.D., M.R.C.S.E.)

LECTURE XXIV.CONTINUATION OF THE TREATMENT OF SECONDARY SYPHILIS;

TERTIARY SYMPTOMS, SYPHILITIC SARCOCELE.THE different infusions or ptisans which by turns have hada run for the cure of syphilis, contain, almost all of them, sar-saparilla. In Pollini’s we find sulphuret of antimony andsarsaparilla; in Vigarou’s, crude antimony, sarsaparilla, guaia-

cum, bitters, purgatives, &c. &c. The opera dancer’s ptisanis principally made with sarsaparilla; Arnoud’s with the latterand ineze2-eoii; Feltz’s is composed of sarsaparilla, ichthyocolla,and sulphuret of antimony, which latter must be tied up in abag, and all the. substances boiled together. (I need not tellyou that this sulphuret contains arsenic.) As to the far-famedRob de Laffecteur, which is reputed to be a strictly vegetablepreparation, you are, I dare say, aware that it includes bi-chloride of mercury, and, according to circumstances, more orless box-wood, saponaria, treacle, &c. &c. Of course this pre-paration will effect cures wherever a mercurial course is in-dicated. The corrosive sublimate has, by careful analysis,been distinctly found in this quack medicine, and the impu-dence with which it is set forth as a vegetable preparation isbarefaced enough. It has been publicly stated that I recom-mend the Rob of Laffecteur, but I need hardly say that thisassertion is a pure invention of the vendor. The article onthis nostrum in the Dictionnaire de Medecine," has evidently,I am sorry to say, been written by a venal hand. The cureswhich have been boasted of principally related to patientswho were affected with ulcerations, the nature of which wasunknown; and as some years ago everv ailment which wasnot understood was reputed syphilitic, the Rob got credit formore than it deserved. In fact, many cures have been attri-buted to it when a change of diet was the principal agent of reco-very. Zettman’s ptisan is likewise composed of sarsaparilla anddivers other substances, among which are cinnabar and proto-chloride of mercury; this latter preparation, as you see, con-tains mercury enough, but I do not think that the form underwhich the metal is administered is a very advantageous one.There are certain secondary manifestations which may begreatly benefited by topical applications which you should be"pl111,,;nh>r1 wi Thn TQe: the ocnpi-nl frnf.mrt._ which

must always be mercurial, you may apply to mucous papulesalkaline chlorides and powdered calomel. I would, for in-stance, recommend Labarraque’s liquid one part, water threeparts, and the lotion to be used three times a day; the affectedsurfaces to be then wiped dry and powdered with calomel.The sore places should also be isolated by means of lint.Eight or ten days are sufficient for the cure of the local affec-tion. For dry papules it is advisable to use fumigations ofcinnabar; when patients cannot bear them, the papulesshould be covered with Vigo’s plaster. In this manner wecan in eight or ten days remove sores which the patient isvery anxious to conceal from the public eye. The crustswhich form on the scalp and the squamous papules are muchimproved by vapour baths to the part. Pustulo-crustaceous andsuppurating eruptions are greatly benefited by mucilaginousand gelatinous and bran baths, or cataplasms offecula. Whenthe irritation has disappeared, the emollient applications mayadvantageously be replaced by an ointment containing eithercalomel or opium; and compression with strips of Vigo’splaster, with mercury, has also succeeded very well in myhands. When you have to deal with sores situatect onmucous membranes, either in the mouth, nose, throat, vagina,or uterus, &c., you will find the following preparation veryuseful, either as a lotion or an injection; decoction of cicuta,seven ounces, bichloride of mercury, from three to four

grains. It often happens, likewise, that cauterizations withthe nitrate of silver, or the liquid nitrate of mercury, provehighly beneficial. The topical means, which I have justenumerated, very often destroy the local manifestations ina short time, and this lrapidity of cure very often deceivespatients, and induces them to give up the internal medi-cation. You should be prepared for this, and it will some-times be necessary, when you have refractory people to dealwith, to withhold your topical applications, and allow thelocal accidents to get well of themselves, so that the patientmay be induced to go on with the internal use of mercury.Having now, gentlemen, laid before you the leading facts

connected with secondary syphilis, I will, with your permis-sion, close our course with the study of tertiary symptoms.This classification is by no means arbitrary,"and I would nottrouble you with it, if it had not an immediate practicalbearing, and if it were not in some degree a necessary divi-sion, as much with reference to the treatment as to the pro-gnosis.

Tertiary manifestations are mentioned in Thierry’s work,and hinted at by Hunter. They have, like the primary andthe secondary accidents, a peculiar stamp, which distinguishesthem from all others, and never directly follow the chancre

. which is the primary origin of them. They are, in fact,always preceded by some secondary manifestation, except inthose cases where the patient has undergone a treatment. capable of destroying a link in the chain of accidents, making