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No. 1287. APRIL 29, 1848. Lectures ON THE CHEMISTRY OF PATHOLOGY AND 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 0N MATERIA MEDICA AND THERAPEUTICS, ETC. LECTURE V. Ol’ganic and Inorganic constituents of the Animal body; three wel7-niark-ed classes:-Protein or Albuminous class, all yield Protein; methods of preparing Protein ; properties of this sub- stance. Does Protein contain Sulphur (?) How does it exist in the Protein compounds (?) Fibrin exists in two forms in the living body; how prepared. Properties and composition of Albumen; states in which it is found; mode of preparation; properties and composition of. Casein, two conditions of; pre- paration of; properties and composition of. Globulin and Crystalline, both Protein compounds, Binoxide and Tritoxide of Protein; produced during i?flamniato2-y action; composi- tion of. Products 1’esulting frorn the decomposition of Protein compounds by various 1’e-agents; by Alkalies ; by air and moisture ; by the action of different oxidizing agents. Guckel- I berger’s experiments with Sulphur’ic acid and peroxide of Man- ganese ; with Chromic acid. Review of the various opinions as to the constitution of the Albu??-biizo?L3 class of bodies. THE elements which enter into the composition of the animal body do not immediately unite to form the textures, but are first arranged in certain groups, producing compounds which may be called the proximate elements of the animal body. These may be divided into Organic and Inorganic constituents, the latter being identical with those found in the mineral kingdom. The organic constituents may be conveniently sub- divided into- First-The Albuminous or Protein class. Secondly-The Gelatine-yielding class. Thirdly-The Fatty and Amylaceous class. Besides these, we shall meet with many other principles which cannot be arranged under any of these heads, and of the properties of which we shall defer speaking until treating of the individual solids or fluids in which they occur. The study of the proximate constituents of the animal frame is of the utmost importance for the clear comprehension of the subjects which I shall afterwards bring before you, and although, perhaps, it may not be one apparently possessing much interest, yet you will find that any time bestowed upon the study of these principles will not be misemployed. We shall first speak of The Protein or Albuminous class.-In this most important class of compounds we find albumen, fibrin, casein, globulin, (from the blood corpuscles,) and crystalline, (from the crystalline lens.) They all yield, when treated in a certain way, a substance called protein, by its discoverer Mulder, from his supposing it to occupy a first place 7rpWTWW. The method of proceeding is to dissolve the white of an egg, or the albumen or fibrin from blood, or the curd or casein from milk, in a weak solution of potash, at a temperature of 120° Fahrenheit; neutralizing the solution with acetic acid, when sulphuretted hydrogen is evolved, and a greyish white precipitate falls, which, when dry, assumes the form of a yellowish transparent substance-this is called protein. It is insoluble in water, alcohol, or ether; soluble in alkaline solutions; with the acids, as sulphuric and tannic, it unites to form definite.compounds; when heated it decomposes, and gives off an odour similar to burnt meat. Mulder gave the composition, in 100 parts, as follows :- He denied the existence of sulphur in it, and considered that the sulphur and phosphorus contained in the albumen &c. became converted into sulphuret of potassium and phos- phate of potassa, when the substance was acted upon by the weak alkaline solutions. He assigned to this body the formula C40 Hso N 0,s. Liebig has given the formula ! c4s HS6 N6 U,4· Both nearly agree with the analysis in 100 parts. The non-existence of sulphur in protein was asserted by Mulder from the substance not possessing the power of black- ening salts of lead when dissolved in an alkaline solution; but this is by no means a proof, for in taurine, a principle obtained from the bile, we find twenty-six per cent. of sulphur com- bined in such a manner as not to act on the salts of lead. This seems to be the case with protein, which, when prepared with the utmost care, still contains sulphur, and, in the so-called pro- tein compounds, we have a part of the sulphur separated by the action of potash, while another portion, resisting this action, is precipitated with the other elements. Mulder now admits the existence of sulphur in protein, but supposes that in albumen, &c., the sulphur and phosphorus exist as amides, S, N Hs and P, N H2; and that when these substances are treated with potash, hyposulphurous acid is formed, which unites with the protein, and thus he accounts for the presence of sulphur in his precipitated body. The subject is one of great difficulty, and will require much labour to unravel its mysteries; but at present, without admitting or denying the existence of such a body as protein free from sulphur, it will be convenient to group together, under the head of protein compounds, several substances which possess properties in common, all yielding the so-called protein when acted on in the above-mentioned manner, giving a precipitate with ferro- cyanide of potassium when dissolved in acetic acid, and afford- ing a purplish blue colour when boiled for some time in strong hydrochloric acid. I - FM’tM.—In the body we find this substance in two physical conditions-viz., in the fluid and solid states. In the blood when contained in the vessels, and for a short time after its withdrawal, it remains in the first state, but it soon undergoes the process of coagulation or solidification. In the second, or solid condition, it forms the chief portion of the muscles. To obtain it, we should stir the blood as it is received into a vessel with a bundle of wires or twigs; the fibrin will then adhere to them in the form of threads, and can be easily separated from the remainder of the fluid; or a clot of blood may be washed in a filter until colourless, or a piece of muscle may be thoroughly eduleorated, after being first well beaten to destroy the cell texture of the tissue. When moist, fibrin is soft and elastic, without odour or taste; when dry, it becomes brittle and opaque; it is insoluble in water, alcohol or ether. Soluble in dilute acids and alkalies, from the acid solutions it is precipitated by ferrocyanide of potassium; the alkaline solution, when neutralized with acetic acid, throws down protein; when boiled with strong hydrochloric acid, the purplish blue colour is produced: these characters how- ever, are not peculiar to fibrin, but are common to all protein compounds. Fibrin may, however, be distinguished from the other com- pounds of the group, by its possessing the power of decompos- ing the peroxide of hydrogen, causing the evolution of oxygen, and the production of water: this power is not possessed by coagulated albumen, with which it might easily be confounded. Fibrin also forms a jelly-like mass when treated with acetic acid, a property likewise not possessed by the latter substance. Mulder represented fibrin as composed of ten atoms of protein, with one of sulphur, and one of phosphorus, 10 Pr + S z- P. More recently, however, he considers the sulphur and phosphorus as existing in the form of amides, and gives for the composition of the protein, when separated from them, : the following per centage of elements :— When we examine albumen, we shall find that the oxygen exists in smaller proportion in that substance than in fibrin. The amount of sulphur in fibrin appears to be one per cent.; when burnt it leaves a small quantity of ash, composed of phosphates of lime and magnesia. Albumen.-This substance likewise assumes two forms-the uncoagulated and coagulated; in the former state it is found in the white of egg, in the serum of blood, lymph, chylø and in most animal fluids, (not excretions;) uncoagulated al- bumen can be prepared in the dry state by evaporating the white of egg, serum of blood &e. to dryness, at a temperature
Transcript

No. 1287.

APRIL 29, 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

0N MATERIA MEDICA AND THERAPEUTICS, ETC.

LECTURE V.

Ol’ganic and Inorganic constituents of the Animal body; threewel7-niark-ed classes:-Protein or Albuminous class, all yieldProtein; methods of preparing Protein ; properties of this sub-stance. Does Protein contain Sulphur (?) How does it existin the Protein compounds (?) Fibrin exists in two forms inthe living body; how prepared. Properties and composition ofAlbumen; states in which it is found; mode of preparation;properties and composition of. Casein, two conditions of; pre-paration of; properties and composition of. Globulin andCrystalline, both Protein compounds, Binoxide and Tritoxideof Protein; produced during i?flamniato2-y action; composi-tion of. Products 1’esulting frorn the decomposition of Proteincompounds by various 1’e-agents; by Alkalies ; by air andmoisture ; by the action of different oxidizing agents. Guckel- Iberger’s experiments with Sulphur’ic acid and peroxide of Man-ganese ; with Chromic acid. Review of the various opinions asto the constitution of the Albu??-biizo?L3 class of bodies.

THE elements which enter into the composition of the animalbody do not immediately unite to form the textures, but arefirst arranged in certain groups, producing compounds whichmay be called the proximate elements of the animal body.These may be divided into Organic and Inorganic constituents,

the latter being identical with those found in the mineralkingdom. The organic constituents may be conveniently sub-divided into-First-The Albuminous or Protein class.Secondly-The Gelatine-yielding class.Thirdly-The Fatty and Amylaceous class.Besides these, we shall meet with many other principles

which cannot be arranged under any of these heads, and ofthe properties of which we shall defer speaking until treatingof the individual solids or fluids in which they occur. Thestudy of the proximate constituents of the animal frame is ofthe utmost importance for the clear comprehension of thesubjects which I shall afterwards bring before you, andalthough, perhaps, it may not be one apparently possessingmuch interest, yet you will find that any time bestowed uponthe study of these principles will not be misemployed. Weshall first speak ofThe Protein or Albuminous class.-In this most important

class of compounds we find albumen, fibrin, casein, globulin,(from the blood corpuscles,) and crystalline, (from thecrystalline lens.) They all yield, when treated in a certainway, a substance called protein, by its discoverer Mulder, fromhis supposing it to occupy a first place 7rpWTWW. The methodof proceeding is to dissolve the white of an egg, or the albumenor fibrin from blood, or the curd or casein from milk, in aweak solution of potash, at a temperature of 120° Fahrenheit;neutralizing the solution with acetic acid, when sulphurettedhydrogen is evolved, and a greyish white precipitate falls,which, when dry, assumes the form of a yellowish transparentsubstance-this is called protein. It is insoluble in water,alcohol, or ether; soluble in alkaline solutions; with the acids,as sulphuric and tannic, it unites to form definite.compounds;when heated it decomposes, and gives off an odour similar toburnt meat. Mulder gave the composition, in 100 parts, asfollows :-

He denied the existence of sulphur in it, and consideredthat the sulphur and phosphorus contained in the albumen&c. became converted into sulphuret of potassium and phos-phate of potassa, when the substance was acted upon by

the weak alkaline solutions. He assigned to this body theformula C40 Hso N 0,s. Liebig has given the formula

! c4s HS6 N6 U,4· Both nearly agree with the analysis in 100parts.

The non-existence of sulphur in protein was asserted byMulder from the substance not possessing the power of black-ening salts of lead when dissolved in an alkaline solution; butthis is by no means a proof, for in taurine, a principle obtainedfrom the bile, we find twenty-six per cent. of sulphur com-bined in such a manner as not to act on the salts of lead. Thisseems to be the case with protein, which, when prepared withthe utmost care, still contains sulphur, and, in the so-called pro-tein compounds, we have a part of the sulphur separated by theaction of potash, while another portion, resisting this action,is precipitated with the other elements. Mulder now admitsthe existence of sulphur in protein, but supposes that inalbumen, &c., the sulphur and phosphorus exist as amides,S, N Hs and P, N H2; and that when these substances aretreated with potash, hyposulphurous acid is formed, whichunites with the protein, and thus he accounts for the presenceof sulphur in his precipitated body. The subject is one ofgreat difficulty, and will require much labour to unravel itsmysteries; but at present, without admitting or denying theexistence of such a body as protein free from sulphur, it willbe convenient to group together, under the head of proteincompounds, several substances which possess properties incommon, all yielding the so-called protein when acted on inthe above-mentioned manner, giving a precipitate with ferro-cyanide of potassium when dissolved in acetic acid, and afford-ing a purplish blue colour when boiled for some time in stronghydrochloric acid.

I - FM’tM.—In the body we find this substance in two physical

conditions-viz., in the fluid and solid states. In the bloodwhen contained in the vessels, and for a short time after itswithdrawal, it remains in the first state, but it soon undergoesthe process of coagulation or solidification. In the second, orsolid condition, it forms the chief portion of the muscles. Toobtain it, we should stir the blood as it is received into avessel with a bundle of wires or twigs; the fibrin will thenadhere to them in the form of threads, and can be easilyseparated from the remainder of the fluid; or a clot of bloodmay be washed in a filter until colourless, or a piece ofmuscle may be thoroughly eduleorated, after being first wellbeaten to destroy the cell texture of the tissue. When moist,fibrin is soft and elastic, without odour or taste; when dry, itbecomes brittle and opaque; it is insoluble in water, alcoholor ether. Soluble in dilute acids and alkalies, from the acidsolutions it is precipitated by ferrocyanide of potassium; thealkaline solution, when neutralized with acetic acid, throwsdown protein; when boiled with strong hydrochloric acid,the purplish blue colour is produced: these characters how-ever, are not peculiar to fibrin, but are common to all proteincompounds.

Fibrin may, however, be distinguished from the other com-pounds of the group, by its possessing the power of decompos-ing the peroxide of hydrogen, causing the evolution of oxygen,and the production of water: this power is not possessed bycoagulated albumen, with which it might easily be confounded.Fibrin also forms a jelly-like mass when treated with aceticacid, a property likewise not possessed by the latter substance.Mulder represented fibrin as composed of ten atoms of

protein, with one of sulphur, and one of phosphorus, 10 Pr +S z- P. More recently, however, he considers the sulphurand phosphorus as existing in the form of amides, and gives

for the composition of the protein, when separated from them,: the following per centage of elements :—

When we examine albumen, we shall find that the oxygenexists in smaller proportion in that substance than in fibrin.The amount of sulphur in fibrin appears to be one per cent.;when burnt it leaves a small quantity of ash, composed ofphosphates of lime and magnesia.Albumen.-This substance likewise assumes two forms-the

uncoagulated and coagulated; in the former state it is foundin the white of egg, in the serum of blood, lymph, chyløand in most animal fluids, (not excretions;) uncoagulated al-bumen can be prepared in the dry state by evaporating thewhite of egg, serum of blood &e. to dryness, at a temperature

464

not exceeding 120° Fahrenheit, when a yellowish, transparent,brittle mass like gum is produced. This, when powdered andtreated with alcohol and ether to dissolve out the salts andfat, yields this substance nearly pure; when put into water, itswells, dissolves, and forms a mucilaginous fluid possessingthe following re-actions:-Heated to about 160° Fahrenheit,the albumen coagulates and separates in an insoluble form,(which re-action distinguishes it from the other members of thealbuminous class;) it is also thrown down by alcohol, creosote,many metallic solutions, especially by corrosive sublimate, anextremely delicate test of its presence, causing turbidity in asolution containing no more than ’2o1õõth part. It is likewiseprecipitated with strong acids, with the exception of the bi-basic and tri-basic phosphoric, and acetic acids; the compoundsthus thrown down are soluble to some extent in water, andthe acid solutions are precipitated by ferrocyanide of potas-sium.

Coagulated albumen can be obtained nearly pure by stirringan albuminous fluid, while being heated to the boiling point,washing with water, and afterwards treating with alcohol andether, to remove the salts and fat. In this condition it verymuch resembles fibrin, being soluble in weak alkaline solu-tions, yielding protein when neutralized, and giving the dark-blue colour when boiled with hydrochloric acid. It can,however, be distinguished from it by its not possessing thepower of decomposing peroxide of hydrogen. Mulder assignedto albumen the formula, 10 Pr + 82 + P; but he now con-siders the sulphur and phosphorus to exist as amides, andthe protein contained in it to have the following compo-sition :-

LVV.V

On examining the analyses of albumen and fibrin, you willperceive that the latter has an excess of oxygen amountingto more than 1 per cent. About 1.4 per cent. of sulphurexists in albumen derived from blood.Mulder considered the albumen from white of egg to have

the same composition as fibrin, and gives a formula whichseems to show that it contains only half the amount of sulphurcompared with that derived from the serum of blood. Otheranalyses have given a much larger amount of this element.White of egg, however, differ from the serum of blood inbeing coagulated by ether. When incinerated, albumenleaves an ash consisting of phosphate of lime; in its uncoagu-lated state, it has the power of dissolving a considerableamount of this salt.

Ceet’M.—Another protein compound is found in the animalbody, called casein, constituting a large portion of the solidsof the milk, and found also in small quantities in the bloodand some other animal fluids. It also, like albumen, assumestwo conditions-viz., the coagulated and uncoagulated.To prepare pure casein, we should take skimmed milk, and

precipitate it by means of sulphuric acid, which throws downa sulphate of casein. This, washed and digested with carbo-nate of lead, causes the formation of sulphate of lead, and theliberation of the casein, which dissolves in the fluid. Byevaporation, and treating the residue, first with ether, andafterwards with alcohol, we have casein left, which can befurther purified by re-solution in water and precipitation byalcohol. When thus prepared and dried, it assumes the formof a gummy substance, not very soluble in water. The solu-tion possesses the following characters : It is not coagulatedby heat, but all, even the weakest, acids precipitate it, whichproperties distinguish it from albumen. It has the propertyalso of being coagulated byrennet,-the mucous membrane ofthe calf’s stomach,-which we shall speak of more fully whentreating of milk. Coagulated casein is very soluble in weakalkaline solutions, which exhibits the same reactions as thatof any other protein compound; it is also soluble in diluteacetic acid. Mulder represented casein by the formula,10 Pr z- S, differing from those representing fibrin and albumenby the absence of phosphorus. He gave for its compositionin 100 parts-

But recent analyses have shown the amount of sulphur incasein to be about one per cent.When burnt, casein leaves an ash containing phosphate of

lime, and Scherer has found that when soluble casein is em-ployed, the ash has a strong alkaline reaction : he thereforeascribes the solubility of casein to its combination with analkali, and its coagulation to the saturation of that alkali.

I mentioned two other protein compounds as existing-viz.,globulin and crystalline. Of the first we shall have occasionto speak when on the subject of blood; the second, crystalline,exists in the crystalline lenses of animals; it possesses pro-perties analogous to albumen, being coagulated by heat; butit is said to resemble casein in not possessing phosphorus inits constitution. Mulder represents crystalline by the formula,15 Pr z- S, and gives for its composition in 100 parts-

Besides the protein compounds with which I have justendeavoured to make you acquainted, Mulder has describedseveral others, which he has named the oxides of protein.Two of these are better understood than the rest; these arethe binoxide and tritoxide.

Binoxide of Protein.-This body is described as existing inthe buffy coat of inflamed blood, also in hair and horn; it canlikewise be formed by the long-continued action of boilingwater on fibrin in an open vessel. From hair or horn we. canprocure it by dissolving these substances in a solution ofpotash, then neutralizing with an acid, when the protein isfirst precipitated; on the further addition of the reagent tothe solution, so as to render it acid, the binoxide of protein isthrown down.From fibrin, or the buff, it is procured by long boiling, the

binoxide remaining as an insoluble residue.Binoxide of protein is distinguished from protein by its not

being precipitated until excess of acid is added to the alkalinesolution. Mulder gave the formula C40 IIgo Ns 0, as repre-senting this substance, or containing two additional atoms ofoxygen, compared with protein.

Tritoxide of Protein.-This body is also produced duringthe long-continued action of boiling water on fibrin or albu-men, or from the chloride of protein, by the action of ammonia;it also exists, ready formed, in the buffy coat of the blood. iIt is distinguished from the other protein compounds bybeing very soluble in water; not coagulable by heat; precipi-tated from its solutions by various metallic salts, but not byferrocyanide of potassium, or weak acetic acid. The formulagiven by Mulder to represent this body is, C40 H30 N5 0,s.These two last bodies are represented as not containing

sulphur in their composition; but there appears to be greatdoubts as to the correctness of this. Liebig found sulphur ina substance supposed to be the same as the binoxide of pre-tein of Mulder. Mulder supposes these substances to be con-

stantly formed in the blood, from the action of inspiredoxygen. During inflammatory states of the system, theyappear to be produced in increased quantities, the binoxideappearing in the buffy coat which forms on the clot; and thetritoxide appearing both in the buff, and dissolved in theserum. Hence we find, in such cases, that the dried coagu-lated serum, after being treated with alcohol, will yield toboiling water a considerable amount of this matter, which isnot the case when healthy serum is employed in the experi-ment.

Protein, and ’the bodies containing it, when acted on bystrong re-agents, are broken up, and various new productsresult. When boiled with caustic potash, we produce acrystallizable body, leucin, Cl2 H]2 N 04; together with am-monia, N Ha; formic acid, C2 H, 03; carbonic acid, C 0, andtwo other compounds less understood, called protid anderythro-protid. When cheese and meat are placed in dampsituations, it has been found that a large amount of fatty mat-ters have become generated along with a greenish mould-this proves the breaking np of protein compounds into fattybodies, ammonia and carbonic acid; the same phenomenatakes place when adipocere is formed. Late experiments byGuckelberger appear to throw much light upon the composi-tion of these bodies, by showing that under the influence ofoxydizing agents they may be broken up into various sub-stances, many of which, or bodies closely allied to them, areformed in the animal economy.

465

Guckelberger used three protein compounds in his experi-ment-viz., casein, albumen, and fibrin. These he obtainedas pure as possible, and submitted them to the action of sul-phuric acid and peroxide of manganese; also to sulphuric acidand chromate of potash. The substances were first treatedwith the diluted acid, and the mixture was allowed to stand forsome time, until solution took place, and the fluid assumeda brownish, violet colour; the manganese or chromate wasthen added, and the distillation commenced. By the actionof the sulphuric acid and peroxide of manganese on casein,the following products were obtained :-

These various compounds, being volatile, distilled over atdifferent temperature, and separate from each other. In theretort was found sulphate of ammonia; so that the nitrogencontained in the substance appears to have been separated asammonia, and then formed into the sulphate.

If we examine these various products, we shall discovermany points of great interest in this decomposition. Thefirst six are such as can be produced from bodies be-longing to the amylaceous class of compounds; the first three,being less oxidized conditions of the three following, canbe readily converted into them, aldehyde, by exposureto air, becoming converted into acetic acid, &c.. These sixbodies, then, are very closely allied to the starchy or amyla-ceous groups of compounds. Thus alcohol is formed fromsugar, and from alcohol, aldehyde and acetic acid are pro-duced, by oxidation; aldehyde can also be procured from milk-sugar, by direct oxidation, and from the distillation of lacticacid, in the form of the lactate of copper. Again: butyricacid can be formed by the action of an animal ferment, asa piece of casein, in a strong solution of sugar, at a tempera-ture a little above 80Q Fah. It occurs also in butter, whenceit derives its name.Formic acid, the ninth product, is also allied to this series

of compounds; it is found also in the body of the formica rubra,or red ant.Valerianic acid, found in the valeriana officinalis, is also

formed by oxidating the oil of grain-spirits, or potatoes, and ishence allied to alcohol.

Caproic acid, a volatile, fatty acid found in butter.The two remaining compounds-viz., oil of bitter almonds

and benzoic acid, are closely related to each other, the latterbeing formed by oxidating the former, and is also a consti-tuent of the urine of some animals, and readily produced fromhippuric acid, which forms a constant ingredient of humanurine.These results appear to show, that in protein compounds

we have the elements grouped, or they become so under theinfluence of the acid, as to form an amylaceous atom, pro-bably also a fatty one, and that these are united to a highlynitrogenized group. The body leucin, which I told you wasproduced when protein compounds were broken up by theaction of caustic potash, can also be resolved into valerianicacid and ammonia.

It was found that the volatile products I have just spokenof were obtained in larger quantities when the solution ofthe substances in sulphuric acid was allowed to remain forsome length of time previous to the addition of the peroxideof manganese; so that the action of the acid appeared todetermine the arrangement of the atoms into organic groups,and the process is not simply the effect of oxidation.When sulphuric acid and bichromate of potash were used

as the oxidizing agents in such proportions, that the sulphuricacid is nearly neutralized by the potash, the following resultswere obtained :-

1. Aldehyde of metacetonic acid (?) 2. Acetic acid.3. Metacetonic- acid. 4. Butyric acid. 5. Formic acid, (insmall quantity.) 6. Valerianic acid. 7. Benzoic acid, withtraces of caproic. These products are the same as those wefound to be formed in the first experiment; but in additionto these we now have-S. A heavy oil, with the odour of cin-namon. 9. Prussic or hydrocyanic acid, C2 N H. 10. Valerio-

nitrile, C10 N H9; and the fluids remaining in the retort after

distillation give scarcely any trace of ammonia.. It thusappears that in this last experiment the nitrogen of thecasein passes over in the form of two volatile nitrogenizedproducts, which replace, in a great measure, the formic andvalerianic acids, and the ammonia. Prussic acid, so far ascomposition is concerned, may be looked upon as the formiateof ammonia, and the valerionitrile as the valerianate of thesame base.The experiments repeated, with the substitution of albumen

or fibrin, in place of casein, gave qualitatively the sameresults; but the nature of the substance acted upon appearedto alter the relative quantities of the products. Thus theamount of butyric acid yielded by fibrin was very large com-pared with that formed from albumen or casein. Benzoicacid and the oil of almonds were yielded in the followingorder:-casein gave most; then albumen; fibrin the least.Acetic acid and its aldehyde gave in the order, fibrin, albumen,casein. Under other circumstances, as, for example, whenthese protein compounds are exposed to the action of airand moisture within certain ranses of temnerature. a dif-ferent decomposition takes place, called putrefaction; and theelements composing the substance are evolved mostly in theform of inorganic or very simple combinations: thus we haveproduced, carbonic acid, carburetted hydrogen, ammonia,cyanogen, sulphuretted phosphuretted hydrogen, togetherwith certain volatile compounds, more complex in composi-tion, to which-the peculiar odour is due, and others whichhave the power of producing disease when absorbed by theanimal body, constituting septic poisons and malaria, of whichwe shall have to speak at another time.

I have entered thus fully into the subject, from a convictionthat this mode of studying the composition of bodies willsome day throw considerable light on physiology and patho-logy ; and not unfrequentlywe find that anew set of compoundsmay be formed by a diseased action in the system. In thisway we can explain the conversion of muscle into fat whichnow and then takes place, also the production of sugar indiabetes, when no saccharine or starchy matters are takenwith the food, for we have proved that acetic acid and alde-hyde can be artificially produced from protein compounds;likewise, the presence of milk-sugar in the milk of carnivorafed on lean meat can be thus accounted for.

Before I conclude my remarks on this subject, it wouldbe, perhaps, advisable for me to pass shortly in review theprincipal points which we have been examining in this lec-ture.A close relation has for some time been supposed to exist

betwen the various members of the albuminous class of com-pounds ; formerly they’were considered to be almost peculiarto the animal body, and to be contained in the form of glutenin but few vegetables. Gay-Lussac, Thenard, &c., examinedtheir composition quantitatively, and their analyses showedthe close connexion which existed between these bodies, sofar as their ultimate composition was concerned; their ana-lyses, however, indicated a larger amount of nitrogen in fibrin;they were then supposed to consist of carbon, hydrogen,nitrogen, and oxygen only; sulphur was afterwards found tobe one of their constituents. A few years since, Mulder, froma very careful and elaborate examination of these bodies,formed an hypothesis by which they were all represented ascompounds of a kind of radical which he called protein, withvarying amounts of sulphur and phosphorus: this theory be-came very attractive from its great simplicity, for by its meansall the albuminous compounds could be readily represented,their difference depending either on their containing varyingamounts of the two latter elements, or only one of them.Since the time that Mulder proposed this hypothesis, manyfacts have been discovered, which appear to throw consider-able doubt on its correctness-in the first place, it wasessential that a body named protein should exist, free fromsulphur; this, however, does not seem to be the case, and itappears that the sulphur exists in albumen, &c., in two forms,a part of it being removed by the action of an alkali, anotherpart remaining unaffected by that re-agent. We see this occurin cystine and taurine, substances found in the urine and bile;from the former, potash removes the sulphur, but not fromthe latter body. Again, recent analyses of the different

. protein compounds have shown that a much greater amount

. of sulphur exists, than stated to be the case by Mulder, andL the different amounts of the various products of decompositioni of these bodies in Guckelberger’s experiments, appear toLindicate, that although they very much resemble each other. in the per centage of their elements, yet that the arrangement- of these differs considerably in the different members of ther group.

466

Again, casein, according to Mulder, is completely separatedfrom albumen and fibrin, in not containing phosphorus, yetmilk, which contains this protein compound only, appearscapable of supplying the place of albumen and fibrin ; it isalso doubtful whether the existence of phosphorus in the twolatter bodies in an unoxidized state has ever been proved byexperiment. From all these facts taken together, it seemsthat there is every probability that the protein hypothesiswas a hasty generalization, and that at present our knowledgeof the real constitution of the so-called protein compounds Ihas been very little advanced by it. Probably, further experi-ments on the mode of decomposition which these differentbodies undergo under various circumstances, will one daygive us an insight into their true nature. We shall nextspeak of the gelatine-yielding class of compounds.

Lectures

ON PARTURITION,AND THE

PRINCIPLES & PRACTICE OF OBSTETRICY.BY W. TYLER SMITH, M.B. LOND.

LECTURER ON MIDWIFERY, ETC.

LECTURE XI.

Physiological mechanism of A bortio?t.- T7te p1’ophylaxi8 or pre.vention Q{ Abortion.-Preventive measures relating to-1. Mam.mary irritation; 2. Dental irritation ; 3. 17esical irritation>4. Ovarian irritation; 5. Rectal irritation.-Description of theOBSTETRIC CALENDAR; its use in ascertaining, without calcu-lation, the date of labour; the abortive periods; the date o)quickening; of the viability of the faetu8; of the induction o)premature labour and of special danger in placenta prcevia.

THE mechanism by which abortion, or the premature expul-sion of the ovum, is effected, varies considerably, according tothe time between conception and natural parturition, at whichthe accident occurs. When the impregnated ovum is lostimmediately after conception, the phenomena are very similarto the menstrual period; when the abortion occurs in the lattermonths of utero-gestation, it resembles natural parturition.In abortion at various intervals between conception and par-turition, the nearer it is to the time of conception, the moreit appears like menstruation; the nearer it is to parturition,the more closely is it imitative of that process. In the earliestabortions, the motor actions of expulsion are confined to theFallopian tubes; there is little motor action of the uterus,either of dilatation or contraction, the ovum being washedaway by the menstrual fluid. An exception must, however,be made in the case of women who have borne several children,in whom the uterus is sometimes a contractile organ, evenduring menstruation. Usually the uterus does not contractwith any force during the first two or three months, or abor-ting wnnlrl probably be far more frequent than it is. Abortion

at this time is rather a mechanical dislodgment, by theseparation of the ovum from the uterine parietes, than a

distinct motor act of expulsion; the motor action of the uterusbeing so slight. After the ovum, becoming separated fromthe uterus, has entered the vagina, it excites expulsive actionof the abdominal muscles, similar to those of micturition anddefecation. When quickening, or the first peristaltic move- ’,ment of the uterus, has occurred, the uterus dilates and con-tracts as in natural parturition, only less perfectly; and abortionbecomes gradually divisible into the different stages of naturalparturition. There is the dilatation of the os uteri, the con-traction of the uterus at intervals, or in pains, and thebearing-down, or expiratory actions which expel the ovumfrom the vagina. The condition in which the ovum is ex-

pelled, varies also according to the time at which it takesplace; in the early months the ovum is expelled entire, ex-cept when decomposition has taken place, the foetus beinginvolved in the membranes; but as utero-gestation advances,the membranes are ruptured during expulsion, as in naturallabour, and the foetus and secundines are discharged separately.

Careful and minute attention to all the various causes ofabortion is the true basis of preventive measures. In theprophylaxis of abortion, I propose to follow the order havealready observed in treating of its causes; dealing with thepalliation or removal, in the first place, of the ex-centric, inthe second, of the centric, causes of this accident. I use theword abortion in its largest sense, including every variety ofpremature expulsion of the impregnated ovum.

1. With reference to Mammary irritation, it is hardly ne-

cessary to observe that weaning ought always to take place assoon as the occurrence of pregnancy, during lactation, becomesevident. Gestation and lactation ought never to be permittedto go on at the same time in the same individual, or the childin the breast and the child in the womb must mutually suffer,After weaning, mammary irritation is at once removed,and instead of the exhausting and abnormal irritation in thedirection from the breasts to the uterus, there comes intooperation the healthful and physiological stimulus or synergicaction from the uterus to the breasts, which prepares themfor the new lactation when the fcetus in utero has arrived atmaturity.

. 2. With respect to Dental irritation, it is just necessary to

bear in mind that this is occasionally, and in rare instances, asource of uterine disturbance. When the processes of denti-tion (the appearance of the wisdom teeth) and utero-gestationmeet in the same subject, the alveolar irritation should bekept under by leeches or scarification, on just the same prin-ciple as we should lance the gums during excito-motor dis-turbance in the first dentition, to prevent spinal erythismusand convulsions. In the caries so common in pregnancy, andwhich often attacks several teeth at the same time, extractionof the diseased teeth should be avoided as much as possible.In the first place, as the pain involves the nerves of manyteeth, oftentimes the whole of one side of the jaw affectedbeing neuralgic, the extraction of one or two of the offendmgteeth will not afford permanent relief. The uterine irritationremaining, the pain is generally transferred, after extraction,in all its intensity, to the nerves of the neighbouring teeth.In the second place, caries and toothach do not affect thenervous system so much as the sudden violence and the eiiio-tional disturbance of extraction. It is truly distressing to wit.ness the almost continual misery in which some women passthrough the epochs of utero-gestation and lactation from faultyteeth. This is particularly the case with the wealthier classesof patients; and the fact should urge very strongly uponparents the necessity of attention to the permanent dentitionin young girls, for with this process the health of the futuremother is most intimately connected.

3. The preventive measures relating to Vesical irritation arevery simple. In the most formidable irritation of this kind,-the concurrence of calculus with pregnancy,-and which isnecessarily extremely rare, nothing but palliative measurescan be resorted to during gestation. The cure must be left tothe unimpregnated state. Strangury and urinary deposits,attended with pain and irritation, must be treated carefully,but just as in the unimpregnated condition. Distention of thebladder during pregnancy should be avoided, and actual reten-tion relieved regularly by the catheter. Attention to the stateof the bladder is the more necessary in pregnant women, asthe accidental distention of this viscus may, in the earlymonths of pregnancy, cause retroversion of the uterus, and this,in turn, will produce permanent retention of the urine; theconditions of the bladder and uterus thus uniting to occasiondanger of abortion.4. I now come to the preventive measures which relate to

Ovarian irritation. Here our cautionary plans should be chieflyconfined to the catamenial or periodic dates. Patients suffer.ing from severe ovarian irritation during pregnancy, should betreated in the periodic. exacerbations much in the same wayas we should treat dysmemiorrhceal patients during the actualperiods attended by pain and difficulty. Warm hip baths,not exceeding blood-heat ; warm enemata of the same

temperature; the application of a plaster of opium or bella-donna over the sacrum; and most especially the avoidance ofcoitus during the periodic dates of pregnancy, should bedirected. As regards the blind periods of utero-gestation,as they may be called, continence is as proper in all casesat these times, as it is during the actual flow of the cata.menia. It is during the first half of pregnancy, or in thosewomen who have suffered from dysmennorrhoea before im-pregnation, that moral and physical sedatives should be moststrictly enjoined. I may here observe, that in dysmennor-rhoeal cases the times of conception are probably times ofabortion, the impregnated ovum descending at once throughthe Fallopian tubes, uterus, and vagina, with an appa-rent return of the catamenial discharge, instead of tarryingfor development in the uterus, so that women, under thesecircumstances, may never be conscious of having conceived,though they really do so. There can be little question butthat many supposed cases of sterility are of this kind; owingto increased excitability of the motor apparatus of concep.tion, the generative act never goes beyond impregnated ovi-position ; abortion follows so closely upon abortion, thatneither the conception nor the abortion are perceived. Such


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