[661] Zeit. f. physiol. Chemie, xvi., 1892.
Cadaverine is a thick, clear, syrupy liquid, with a peculiar coniine- as well as a semen-like odour. It absorbs eagerly CO2 from the air, and ultimately is converted into a solid crystalline mass. It volatilises with the steam when boiled with water, and may be distilled in the presence even of the caustic alkalies and the alkaline earths without decomposition. It does not give oil of mustard when treated with CS2 and mercuric chloride, nor does it give with chloroform and alcoholic potash, carbylamine (isonitrile). If dehydrated by KHO, it boils at from 115°-120° (Brieger).[662]
[662] Brieger has also given to the pure base a boiling-point of 175°.
When cadaverine is treated with methyl iodide, two atoms of hydrogen may be replaced with methyl, forming the base C5H12(CH3)2N2; the platinochloride of this last base crystallises in long red needles.
Cadaverine forms well-defined crystalline salts as well as compounds with metals.
Cadaverine hydrochloride, C5H14N22HCl, crystallises in needles which are deliquescent, or it may be obtained from an alcoholic solution in plates. The crystals are insoluble in absolute alcohol, but readily soluble in 96 per cent. alcohol. Putrescine hydrochloride, on the other hand, is with difficulty soluble in alcohol of that strength; hence the two hydrochlorides can be separated by taking advantage of their difference in solubility in 96 per cent. alcohol; but the better method for separation is the benzoyl-chloride process (p. 487). On dry distillation, cadaverine hydrochloride decomposes into NH3,HCl and piperidine C5H11N. The compound with mercury chloride—C5H14N22HCl,4HgCl2 (Hg = 63·54 per cent.); melting-point, 214°-216°—is insoluble in alcohol and in cold water; this property is also useful to separate it from putrescine, the mercury compound of which is soluble in cold water. The platinochloride, C5H14N22HCl,PtCl4 (Pt = 38·08 per cent.), crystallises in dirty red needles; but, by repeated crystallisation, it may be obtained in clear chrome yellow, short, octahedral prisms; it is soluble with difficulty in hot water, insoluble in cold water. The salt decomposes at 235°-236°.
The aurochloride—C5H14N22HCl2AuCl (Au = 50·41 per cent.), melting-point 188°—crystallises partly in cubes and partly in needles, and is easily soluble in water.
Other salts are the picrate, C5H14N22C6H2(NO2)3OH, melting-point 221° with decomposition; with difficulty soluble in cold, but dissolving in hot water, and insoluble in absolute alcohol. There are also a neutral oxalate, C5H14N2,H2C2O4 + 2H2O, melting-point 160°; and an acid oxalate, C5H14N22H2C2O4 + H2O, melting-point 143° with decomposition; both these oxalates are insoluble in absolute alcohol.
Cadaverine dibenzoyl—C5H10(NHCOC6H5)2, melting-point 129°-130°—crystallises in needles and plates, soluble in alcohol and slightly soluble in ether, insoluble in water.
It is not acted on by hot dilute acids or alkalis, and when dissolved in concentrated hydrochloric acid and alcohol it is, only after prolonged boiling, decomposed into benzoic acid and the free base. The benzoic acid after getting rid of the alcohol by evaporation, can be removed by shaking up with ether; then the hydrochloride can be decomposed by an alkali and the free base obtained, or the platinum salt of cadaverine may be formed by precipitation with platinum chloride. Should cadaverine and putrescine be in the same liquid, the dibenzoyl compounds may be separated as follows:—the crystalline precipitate is collected on a filter, washed with water until the filtrate runs clear, and then dissolved in warm alcohol; this solution is poured into twenty times its volume of ether and allowed to stand; after a short time crystals form of the putrescine compound, which are far less soluble in alcohol than those of cadaverine dibenzoyl; these crystals are filtered off and repeatedly crystallised from alcohol until the melting-point is about 175°-176°. The filtrate contains the cadaverine compound; this latter is recovered by evaporating off the ether-alcohol.
§ 665. Putrescine—Tetramethylenediamine, C4H12N2=NH2CH2CH2CH2CH2NH2.
The free base is a clear liquid, with a semen-like odour, boiling-point 135°. It is a common base in putrefying animal substances, and also occurs in the urine in cases of cystinuria. It can be obtained synthetically by reducing ethylene cyanide by the action of sodium in absolute alcohol.
The best method of separating putrescine is the benzoyl chloride method already given.
Putrescine forms crystalline salts, of which the following are the most important:—
Putrescine hydrochloride, C4H12N22HCl, forms long colourless needles, insoluble in absolute alcohol, easily soluble in water.
The platinochloride, C4H12N22HCl.PtCl4 (Pt = 39·2 per cent.), is with difficulty soluble in cold water. When pure, the salt is in the form of six-sided plates.
The aurochloride, C4H12N22HCl.2AuCl3 + 2H2O (Au = 51·3 per cent.), is insoluble in cold water, in contradistinction to cadaverine aurochloride, which easily dissolves.
The picrate, C4H12N22C6H2(NO2)3OH, is a salt of difficult solubility. It crystallises in yellow plates. It browns at 230°, and melts with evolution of gas at 250°.
Dibenzoylputrescine, C4H8(NHCOC6H5)2, forms silky plates or long needles, melting-point 175°-176°. By boiling it for twelve hours with alcohol and strong hydrochloric acid the compound may be broken up into hydrochloride of putrescine and free benzoic acid. As stated before, it is less soluble in alcohol than the corresponding compound of cadaverine.
Putrescine is not poisonous. On the other hand, by repeated treatment with methyl iodide, it takes up four methyl radicals, and the tetramethyl compound, C4H8(CH3)4N2, produces symptoms similar to those of muscarine poisoning.
§ 666. Metaphenylenediamine, , is a crystalline substance, melting-point 63°, boiling-point 276°-277°. The crystals are easily soluble in alcohol or ether, with difficulty in water. The least trace of nitrous acid strikes a yellow colour from the formation of triamidobenzol.
§ 667. Paraphenylenediamine, , is in the form of tabular crystals, melting-point 140°, boiling-point 267°. If this substance is oxidised with ferric chloride or manganese binoxide and sulphuric acid, chinone is produced; if treated with SH2 and ferric chloride, a violet sulphur-holding colouring matter, allied to methylene blue, is formed; these reactions are tests for the presence of the para-compound.
Both these diamines are poisonous. Metaphenylenediamine produces, in the dog, the symptoms of an aggravated influenza with continual sneezing and hoarse cough, which, if the dose is large enough, ends in coma and death. Paraphenylenediamine produces exophthalmia, the tissues of the eye undergoing complete alteration.[663]
[663] Comptes Rend., cvii. 533-535.
Both compounds, in doses of 100 mgrms. per kilo., cause more or less salivation, with diarrhœa. The para-compound is more poisonous than the meta-compound. So far as the author is aware, neither of these diamines have been separated with certainty from the urine of sick persons, nor from products of decomposition.
§ 668. Hexamethylenediamine, C6H16N2.—Hexamethylenediamine has been found by A. Garcia[664] in a putrefying mixture of horse-flesh and pancreas.
[664] Zeit. f. physiol. Chemie, xvii. 543-555.
§ 669. Diethylenediamine, C4H10N2, is a crystalline substance, melting-point 104°, boiling-point 145°-146°. After melting, it solidifies on cooling, forming a hard crystalline mass. It is extremely soluble in water, and is deposited from alcohol in large transparent crystals. A technical product called “spermin piperazidin” or “piperazine” has been found by A. W. v. Hoffmann[665] to be identical with diethylenediamine. The hydrochloride crystallises in colourless needles, insoluble in alcohol, readily soluble in water. The platinochloride, C4H10N2H2PtCl6, is in small yellow needles, and is fairly easily soluble in hot water, but dissolves but slightly in hot alcohol. The mercuro-chloride, C4H10N2H2HgCl4, crystallises in concentrically grouped needles, and is readily soluble in hot water, but is reprecipitated on adding alcohol. The picrate, C4H10N2,C6H2(NO2)3OH, crystallises from water in yellow needles, almost insoluble in alcohol.[666]
§ 670. Mydaleine is a poisonous base discovered by Brieger in putrid animal matters. It is probably a diamine, but has not been obtained in sufficient quantity for accurate chemical study. The platinochloride is extremely soluble in water, and only comes down from an absolute alcohol solution. It has been obtained in a crystalline form, giving on analysis 38·74 per cent. of platinum, C. 10·83 per cent., H. 3·23 per cent.
Mydaleine is very poisonous. Small quantities injected into guinea-pigs cause dilatation of the pupil, an abundant secretion from the nose and eyes, and a rise of temperature. Fifty mgrms. cause death. The post-mortem appearances are not distinctive; the heart is arrested in diastole; the intestines and bladder are contracted. In cats it causes profuse diarrhœa and vomiting.
§ 671. Guanidine.—Guanidine may be considered to have a relation to urea; for, if the oxygen of urea is replaced by the imide group NH, guanidine originates thus:—
Hence guanidine from its structural formula is a carbodiamidimide. Guanidine may be formed by the action of oxidising agents, such as potassic chlorate and hydrochloric acid, on guanine; or by heating amide cyanide with ammonium chloride, and so forming guanidine chloride. It is also produced from the oxidation of albumin. When boiled with baryta-water it decomposes into urea and ammonia. It combines with acids to form salts; the gold salt, CH5N3HCl,AuCl3, is in the form of long yellow needles, with difficulty soluble in water. Guanidine nitrate, CH5N3HNO3, is also almost insoluble in cold water and similar to urea nitrate. By dissolving equivalent parts of phenol and guanidine in hot alcohol, triphenylguanidine is formed; on adding picric acid to a solution of triphenylguanidine, phenylguanidine picrate, CH2Ph3N3C6H2(NO2)3OH, is formed, and falls as a precipitate of slender needles, melting-point 208°; this picrate is very slightly soluble, 1 part dissolving in 12,220 parts of water at 15°. Guanidine is poisonous.[667]
[667] O. Prelinger, Monatsb., xiii. 97-100.
A method of separating guanidine from urine has been worked out by Gergers and Baumann.[668] The principle of the method is based upon the fact that guanidine is precipitated by mercurous oxide. The urine is precipitated by hydrate of baryta, the precipitate filtered off, the alkaline filtrate neutralised by hydrochloric acid, and the neutral filtrate evaporated to a syrup on the water-bath; the syrup is exhausted by absolute alcohol, and the alcoholic solution filtered; this filtrate is freed from alcohol by distillation, the alcohol-free residue dissolved in a little water, shaken up with freshly precipitated mercury oxide, and allowed to stand for two days in a warm place; the precipitate formed is collected, acidulated with HCl and treated with SH2; the mercury sulphide thus obtained is separated by filtration, the filtrate evaporated, and the residue dissolved in absolute alcohol. This solution is precipitated by platinum chloride, filtered, separated from any platinum ammonium salt, and evaporated to a small volume. After long standing the guanidine salt crystallises out. The best method to identify it appears to be, to ascertain the absence of ammonia and of urea, and then to gently warm the supposed guanidine with an alkali, which breaks guanidine up into ammonia and urea, according to the following equation:—
NH=C(NH2)2 + H2O = NH3 + CO(NH2)2.
[668] Pflüger’s Archiv, xii. 205.
The physiological effects of guanidine are as follows:—
A centigrm. of guanidine salt injected into the lymph sac in the back of frogs produces, after a few minutes, muscular convulsions: first, there are fibrillar twitchings of the muscles of the back; next, these spread generally so that the whole surface of the frog seems to be in a wave-like motion. Irritation of the limbs produces tetanus. There is, at the same time, increased secretion from the skin. The breathing is irregular. In large doses there is paralysis and death. The heart is found arrested in diastole. The fatal dose for a frog is 50 mgrms.; but 1 mgrm. will produce symptoms of illness. In dogs there is paralysis, convulsions, vomiting, and difficult breathing.
§ 672. Methylguanidine, .—Methylguanidine has been isolated by Brieger from putrefying horse-flesh; it has also been found in impure cultures in beef broth of Finkler and Prior’s Vibrio proteus. Bocklisch isolated it, working with Brieger’s process, from the mercuric chloride precipitate, after removal of the mercury and concentration of the filtrate, by adding a solution of sodium picrate. The precipitate contained the picrates of cadaverine, creatinine, and methylguanidine; cadaverine picrate, insoluble in boiling absolute alcohol, was separated by filtering from a solution of the picrates of the bases in boiling absolute alcohol; the alcohol was evaporated from the filtrate and the residue taken up with water. From this aqueous solution the picric acid was removed and then the solution precipitated with gold chloride; methylguanidine was precipitated, while creatinine remained in solution.
Methylguanidine aurochloride, C2H7N3HCl.AuCl3 (Au = 47·7 per cent.), forms rhombic crystals easily soluble in alcohol and ether; melting-point 198°. The hydrochloride, C2H7N3HCl, crystallises in needles insoluble in alcohol. The picrate, C2H7N3C6H2(NO2)3OH, comes down at first as a resinous mass, but, after boiling in water, is found to be in the form of needles soluble in hot absolute alcohol; melting-point 192°. The symptoms produced by methylguanidine are rapid respiration, dilatation of the pupils, paralysis, and death, preceded by convulsions. The heart is found arrested in diastole.
§ 673. Saprine, C5H14N2.—Saprine is isomeric with cadaverine and neuridine; it was found by Brieger in human livers and spleens after three weeks’ putrefaction. Saprine occurs, in Brieger’s process, in the mercury precipitate. Its reactions are very similar to those of cadaverine; the main difference being that cadaverine hydrochloride gives a crystalline aurochloride, saprine does not; the platinum salt is also more soluble in water than the cadaverine salt. It is not poisonous.
§ 674. The Choline Group.—The choline group consists of choline, neurine, betaine, and muscarine.
All these bodies can be prepared from choline; their relationship to choline can be readily gathered from the following structural formulæ:—
| Choline. | Neurine. | Betaine. | Muscarine. |
Choline is a syrup with an alkaline reaction. On boiling with water, it decomposes into glycol and trimethylamine. It gives, when oxidised, muscarine. It forms salts. The hydrochloride is soluble in water and absolute alcohol; neurine hydrochloride and betaine hydrochloride are but little soluble in absolute alcohol, therefore this property can be utilised for their separation from choline. The platinochloride is insoluble in absolute alcohol; it melts at 225° with effervescence, and contains 31·6 per cent. of platinum. The mercurochloride is soluble with difficulty even in hot water. The aurochloride (Au = 44·5 per cent.) is crystalline, and with difficulty soluble in cold water; but is soluble in hot water and in alcohol; melting-point 264° with decomposition.
Choline is only poisonous in large doses.
§ 675. Neurine (Trimethyl-vinyl-ammonium hydrate), C2H3N(CH3)3OH.—Neurine is one of the products of decomposition of choline. It is poisonous, and has been separated by Brieger and others from decomposing animal matters. In Brieger’s process, neurine, if present, will be for the most part in the mercuric chloride precipitate, and some portion will also be in the filtrate. The mercury precipitate is decomposed by SH2, the mercury sulphide filtered off, and the filtrate, concentrated, treated with absolute alcohol and then precipitated by platinum chloride. It is usually accompanied by choline; the platinochloride of choline is readily soluble in water, neurine platinochloride is soluble with difficulty; this property is taken advantage of, and the platinochloride crystallised from water until pure. Neurine has a strong alkaline reaction.
Neurine chloride, C5H12N.Cl, crystallises in fine needles. The platinochloride, (C5H12NCl)2PtCl4 (Pt = 33·6 per cent.), crystallises in octahedra. The salt is soluble with difficulty in hot water.
The aurochloride, C5H12NClAuCl3 (Au = 46·37 per cent.), forms flat prisms, which, according to Brieger, are soluble with difficulty in hot water.
Neurine is intensely poisonous, the symptoms being similar to those produced by muscarine.
Atropine is an antidote to neurine, relieving in suitable doses the effects, and even rendering animals temporarily immune against the toxic action of neurine.
When a fatal dose of neurine is injected into a frog there is in a short time paralysis of the extremities. The respiration stops first, and afterwards the heart, the latter in diastole.
The symptoms in rabbits are profuse nasal secretion and salivation with paralysis, as in frogs. Applied to the eye, neurine causes contraction of the pupil; to a less degree the same effect is produced by the ingestion of neurine.
Trimethyloxyammonium hydrochloride causes similar symptoms to neurine, but the action is less powerful.—V. Cervello, Arch. Ital. Biol., vii. 232-233.
§ 676. Betaine.—Betaine may be separated from a solution in alcohol as large deliquescent crystals; the reaction of the crystals is neutral. Distilled with potash, trimethylamine and other bases are formed.
Betaine chloride, C5H12NO2Cl, forms plates permanent in the air and insoluble in absolute alcohol. A solution of the chloride in water gives, with potassium mercuric iodide, a light yellow or whitish yellow precipitate, soluble in excess; but, on rubbing the sides of the tube with a glass rod, the oily precipitate crystallises as yellow needles; probably this is characteristic.
The aurochloride (Au = 43·1 percent.) forms fine cholesterine plates, soluble in water; melting-point 209°. Betaine is not poisonous.
§ 677. Peptotoxine.—Brieger submitted to the action of fresh gastric juice moist fibrin for twenty-four hours at blood heat. The liquid was evaporated to a syrup and boiled with ethylic alcohol, the ethylic alcohol was evaporated, the residue digested with amylic alcohol, and the amyl alcohol in its turn evaporated to dryness; the residue was a brown amorphous mass that was poisonous. It was farther purified by treating the extract with neutral lead acetate and then filtered; the filtrate was freed from lead by SH2 and treated with ether, the ethereal extract being then separated and evaporated to dryness; this last residue was taken up with amyl alcohol, the alcohol evaporated to dryness, and the residue finally taken up with water and filtered. The filtrate is poisonous. The poisonous substance, to which Brieger gave the provisional name of peptotoxine, is a very stable substance, resisting the action of a boiling temperature, and even the action of strong alkalies. It gives precipitates with alkaloidal group reagents, and strikes a blue colour with ferric chloride and ferricyanide of potassium. The most characteristic test seems to be its action with Millon’s reagent (a solution of mercury nitrate in nitric acid containing nitrous acid); this gives a white precipitate which, on boiling, becomes intensely red.
It is poisonous, killing rabbits in doses of 0·5 grm. per kilogrm., with symptoms of paralysis and coma. The nature of this substance requires further elucidation.
§ 678. Pyridine Alkaloid from the Cuttle Fish.—O. de Coninck[669] has obtained, by Gautier’s process, an alkaloid from the cuttle fish, of the formula C8H11N, in the form of a yellow, mobile, strongly odorous liquid, very soluble in alcohol, ether, and acetone, boiling-point 202°. It quickly absorbs moisture from the air. It forms two mercuric chlorides, one of which has the formula (C8H11N,HCl)2HgCl2; this compound crystallises in small white needles, slightly soluble in water and dilute alcohol, but insoluble in absolute alcohol, and decomposing when exposed to moist air. The other salt is a sesqui-salt, forming long yellowish needles, insoluble in ordinary solvents, and decomposing when exposed to moist air. The alkaloid also forms deliquescent very soluble salts with hydrochloric and hydrobromic acids. A platinum salt is also formed, (C8H11N)2H2PtCl6; it is of a deep yellow colour, almost insoluble in cold, but soluble in hot water; it is decomposed by boiling water, with the formation of a very insoluble compound in the shape of a brown powder, (C8H11N)2PtCl4. Coninck’s alkaloid, on oxidation with potassic permanganate, yields a gummy acid; this acid, on purifying it by conversion into a potassium salt and then into a cupric salt, was found to be nicotinic acid; so that the alkaloid is undoubtedly a pyridine compound; indeed, the acid, distilled with lime, yields pyridine.
[669] Comptes Rend., cvi. 858, 861; cviii. 58-59, 809-810; cvi. 1604-1605.
§ 679. Poisons connected with Tetanus.—Brieger, in 1887, isolated a base of unknown composition, to which he gave the name of “spasmotoxine.” It was produced in cultures of the tetanus bacillus in beef broth.
Two more definite substances have also been discovered, viz., tetanine and tetanotoxine.
Tetanine, C13H30N2O4, is best isolated by the method of Kitasato and Weyl.[670] Their method of treating broth cultures of the tetanus bacillus is as follows:—
[670] Zeit. f. Hygiene, viii. 404.
The broth is digested with 0·25 per cent. HCl for some hours at 460°, then rendered feebly alkaline, and distilled in a vacuum. The residue in the retort is then worked up for tetanine by Brieger’s method; the distillate contains tetanotoxine, ammonia, indol, hydrogen sulphide, phenol, and butyric acid. On treating the contents of the retort by Brieger’s mercury chloride method, the filtrate contains most of the poison. The mercury is removed by SH2, the filtered solution evaporated and exhausted by absolute alcohol, in which the tetanine dissolves. Any ammonium chloride is thus separated, ammonium chloride being insoluble in absolute alcohol. The alcoholic solution, filtered from any insoluble substance, is next treated with an alcoholic solution of platinum chloride, which precipitates creatinine (and any ammonium salts), but does not precipitate tetanine. The platinum salt of tetanine may, however, be precipitated by the addition of ether to the alcoholic solution. The platinum salt, as obtained by precipitation from ether, is very deliquescent; it has, therefore, to be rapidly filtered off and dried in a vacuum. It can then be recrystallised from hot 96 per cent. alcohol, forming clear yellow plates; these plates, if dried in a vacuum, become with difficulty soluble in water.
Tetanine may be obtained as a free base by treating the hydrochloride with freshly precipitated moist silver oxide. It forms a strongly alkaline yellow syrup, and is easily decomposed in acid solution, but is permanent in alkaline solutions.
The platinochloride, as before observed, is precipitable by ether from alcoholic solution; it contains 28·3 per cent. of platinum, and decomposes at 197°.
The base produces tetanus.
§ 680. Tetanotoxine may be distilled, and be found in the distillate with other matters. It forms an easily soluble gold salt, melting-point 130°. The platinochloride is soluble with difficulty, and decomposes at 240°. The hydrochloride is soluble in alcohol and in water, melting-point about 205°.
Tetanotoxine produces tremor, then paralysis, and lastly, violent convulsions.
§ 681. Mydatoxine, C6H13NO2.—A base obtained by Brieger from horse-flesh in a putrefactive condition and other substances. It is found in the mercury chloride precipitate. The free base is an alkaline syrup, isomeric with the base separated by Brieger from tetanus cultures. The hydrochloride is a deliquescent syrup, not forming any compound with gold chloride, but uniting with phospho-molybdic acid in forming a compound crystallising in cubes. It forms a double salt with gold chloride, sparingly soluble in water. The platinochloride (Pt = 29 per cent.) is very soluble in water, but not soluble in alcohol; melting-point 193° with decomposition.
The base in large doses is poisonous, causing lachrymation, diarrhœa, and convulsions.
§ 682. Mytilotoxine, C6H15NO2.—This is believed to be the poison of mussels. Brieger isolated it as follows:—
The mussels were boiled with water acidified by hydrochloric acid; the liquid was filtered, and the filtrate evaporated to a syrup, and the syrup was repeatedly extracted with alcohol. It was found advisable to exhaust thoroughly with alcohol, otherwise much poison remained behind. The alcoholic solution was treated with an alcoholic solution of lead acetate. The filtrate was evaporated and the residue extracted with alcohol. The lead was removed by SH2, the alcohol distilled off, water added to the remaining syrup, and the solution decolorised by boiling with animal charcoal. The solution was neutralised by sodium carbonate, acidulated with nitric acid, and precipitated with phosphomolybdic acid. The precipitate was then decomposed by warming with a neutral solution of lead acetate, and the filtrate (after the removal of the lead by the action of SH2) was acidulated with HCl and evaporated to dryness. The residue was then extracted with absolute alcohol, filtered from any insoluble chloride, e.g., betaine chloride, and precipitated by mercury chloride in alcohol.
The free base has a most peculiar odour, which disappears on exposure to air; at the same time, the poisonous properties also diminish. The base is destroyed by boiling with sodium carbonate; on the other hand, the hydrochloride may be evaporated to dryness or be boiled without decomposing.
The hydrochloride crystallises in tetrahedra; the aurochloride crystallises in cubes (Au=41·66 per cent.). Its melting-point is 182°.
§ 683. Tyrotoxicon (Diazobenzol, C6H5N2(OH)).—It appears, from the researches of Vaughan and others, that diazobenzol is liable to be formed in milk and milk products, especially in summer time. It is confidently asserted by many that the summer diarrhœa of infants is due to this toxine; however that may be, it is well established that diazobenzol is a violent poison, causing sickness, diarrhœa, and, in large doses, an acute malady scarcely distinguishable from cholera, and which may end fatally. There will always be difficulty in detecting it, because of its instability. The following is the best process of extraction from milk. The milk will probably be acid from decomposition; if so, the whey must be separated by dilution and filtration; without dilution it may be found impracticable to get a clear filtrate. In order to keep the bulk down, 25 c.c. of the milk may be diluted up to 100 c.c., and, having obtained a clear filtrate from this 25 c.c. thus diluted, the filtrate is used to dilute another 25 c.c. of milk and so on. The acid filtrate is neutralised by sodium carbonate, agitated with an equal volume of ether, allowed to stand in a stoppered vessel for twenty-four hours, and the ether then separated and allowed to evaporate spontaneously. The residue is acidified with nitric acid and then treated with a saturated solution of potash, which forms a stable compound with diazobenzol, and the whole concentrated on the water-bath. On cooling, the tyrotoxicon compound forms six-sided plates. Before the whole of this process is undertaken, it is well to make a preliminary test of the milk as follows:—A little of the ether is allowed to evaporate spontaneously. Place on a porcelain slab two or three drops of a mixture of equal parts of sulphuric and carbolic acids, and add a few drops of the aqueous solution; if tyrotoxicon be present, a yellow to orange-red colour is produced. A similar colour is also produced by nitrates or nitrites, which are not likely to be present under the circumstances, milk having mere traces only of nitrates or nitrites; it may also be due to butyric acid, which, in a decomposed milk, may frequently be in solution. Therefore, if a colour occurs, this is not absolutely conclusive; if, however, no colour is produced, then it is certain that no diazobenzol has been separated. That is all that can be said, for the process itself is faulty, and only separates a fractional part of the whole.
§ 684. Toxines of Hog Cholera.—Toxines have been isolated by F. G. Novy[671] from a cultivation of Salmon’s bacillus in pork broth. The fluid possessed a strong alkaline reaction. For the isolation, Brieger’s method was used. The mercury chloride precipitate was amorphous and was converted into a chlorine-free platinum compound, to which was assigned the composition of C8H14N4PtO8. After separation of this compound, the mother liquor still contained a platinum salt crystallising in needles, and from this was obtained the chlorhydrate of a new base, to which was given the name of susotoxine; it had the composition of C10H26N22HCl,PtCl4. Susotoxine gives general alkaloidal reactions, and is very poisonous.
[671] Med. News, September 1890.
§ 685. Other Ptomaines.—Besides the ptomaines which have been already described, there are a number of others; the following may be mentioned: isoamylamine,[672] (CH3)2CH.CH2.CH2NH2; butylamine, CH3CH2CH2CH2NH2; dihydrolutidine,[673] C7H11N; hydrocollidine,[674] C8H13N; C10H15N (a base isolated by Guareschi and Mosso[675] from ox-fibrin in a state of putrefaction by Gautier’s method; it forms a crystalline hydrochloride and an insoluble platinochloride; its action is like that of curare but weaker); aselline,[676] C25H32N4, isolated from cod-liver oil; typhotoxine,[677] C7H17NO2, isolated from cultures of Eberth’s bacillus. So far as the published researches go, it would appear that other crystalline substances have been isolated from the urine, from the tissues, and from the secretions of patients suffering from various diseases; the quantity obtained in each case has, however, been, under the most favourable circumstances, less than a gramme; often only a few milligrms. To specifically declare that a few milligrms. of a substance is a new body, requires immense experience and great skill; and, even where those qualifications are present, this is too often impossible. This being so, the long list of named ptomaines, such as erysipeline, varioline, and others, must have their existence more fully confirmed by more than one observer before they can be accepted as separate entities.
[672] Hesse, Chem. Jahresb., 1857, 403.
[673] Gautier, A., and Morgues, Compt. Rend., 1888.
[674] Gautier et Etard, Bull. Soc. Chim., xxxvii., 1882.
[675] Guareschi et Mosso, Les ptomaines, 1883.
[676] Gautier, A., et Morgues, Compt. Rend., 1888.
[677] Brieger, 1885, Ptomaines, iii.
§ 686. A large number of cases of poisoning by food occur yearly; some are detailed in the daily press; the great majority are neither recorded in any journal, scientific or otherwise; nor, on account of their slight and passing character, is medical aid sought. The greatest portion of these cases are probably due to ptomaines existing in the food before being consumed; others may be due to the action of unhealthy fermentation in the intestinal canal itself; in a third class of cases, it is probable that a true zymotic infection is conveyed and develops in the sufferer; the latter class of cases, as, for instance, the Middlesborough epidemic of pleuro-pneumonia, is outside the scope of this treatise.
Confining the attention to cases of food poisoning in which the symptoms have been closely analysed and described, the reader is referred to thirteen cases of food poisoning, investigated by the medical officers of the Local Government Board between the years 1878 and 1891, as follows:—
1878. A Case of Poisoning at Whitchurch from eating Roast Pork.—Only the leg of pork was poisonous, other parts eaten without injury. Two persons died after about thirty hours’ illness. The pork itself, on a particular Sunday, was innocuous; it became poisonous between the Sunday and the Monday; the toxicity appeared to gradually increase, for those who ate it for dinner on the Monday were not taken ill for periods of from seven to nineteen hours, while two persons who ate of it in the evening were attacked four hours after eating.
1880. The Welbeck Epidemic, due to eating cold boiled ham. Over fifty persons affected. Symptoms commenced in from twelve to forty-eight hours.
1881. A Series of Poisoning from eating Baked Pork, Nottingham.—Probably the gravy was the cause and not the pork itself. Many persons seriously ill. One died.
1881. Tinned American Sausage.—A man in Chester died from eating tinned American sausage. Poison found to be unequally distributed in the sausage.
1882. Poisoning at Oldham by Tinned Pigs’ Tongues.—Two families affected. Symptoms commenced in about four hours. All recovered. After a few days’ keeping it would appear that the poison had been decomposed.
1882. A Family Poisoned by Roast Beef at Bishop Stortford.—Only a particular piece of the ribs seemed to be poisonous, the rest of the carcase being innocuous. Symptoms did not commence until several hours after ingestion.
1882. Ten different Families at Whitchurch Poisoned by eating Brawn.—First symptoms after about four hours.
1884. Tinned Salmon at Wolverhampton.—Five persons, two being children, ate of tinned salmon at Wolverhampton. All suffered more or less. The mother’s symptoms began after twelve hours, and she died in five days; the son died in three days, the symptoms commencing in ten hours. The post-mortem signs were similar to those from phosphorus poisoning, viz., fatty degeneration. Mice fed on the material also suffered, and their organs showed a similar degeneration.
1886. The Carlisle A Case.—At a wedding breakfast in Carlisle twenty-four persons were poisoned by food which had been kept in an ill-ventilated cellar. The articles suspected were an American ham, an open game pie, and certain jellies. The bride died. Symptoms commenced in from six to forty-three hours.
1886. Poisoning by Veal Pie at Iron Bridge.—Twelve out of fifteen ate of the pie; all were taken ill in from six to twelve hours.
1887. Poisoning at Retford of Eighty Persons from eating Pork Pie or Brawn.—Symptoms commenced at various intervals, from eight to thirty-six hours.
1889. The Carlisle B Case.—Poisoning by pork pies or boiled salt pork. Number of persons attacked, about twenty-five.
1891. Poisoning by a Meat Pie at Portsmouth.—Thirteen persons suffered from serious illness. Portions of the pies were poisonous to mice.
The symptoms in all these cases were not precisely alike; but they were so far identical as to show as great a similarity as in cases when a number of persons are poisoned by the same chemical substance. Arsenic, for instance, produces several types of poisoning; so does phosphorus.
Severe gastro-enteric disturbance, with more or less affection of the nervous system, were the main characteristics. These symptoms commenced, as before stated, at various intervals after ingestion of the food; but they came on with extreme suddenness. Rigors, prostration, giddiness, offensive diarrhœa, followed by muscular twitchings, dilatation of the pupil, drowsiness, deepening in bad cases to coma, were commonly observed. The post-mortem appearances were those of enteritis, with inflammatory changes in the kidney and liver. Convalescence was slow; sometimes there was desquamation of the skin.
In many of these cases Dr. Klein found bacteria which, under certain conditions, were capable of becoming pathogenic; but in no case does there seem to have been at the same time an exhaustive chemical inquiry; so that, although there was evidence of a poison passing through the kidney, the nature of the poison still remains obscure.
The deaths in England and Wales from unwholesome food during ten years were as follows:—
DEATHS IN ENGLAND AND WALES FROM UNWHOLESOME FOOD DURING THE TEN YEARS 1883-1892.
| 1883. | 1884. | 1885. | 1886. | 1887. | 1888. | 1889. | 1890. | 1891. | 1892. | Total. | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Diseased meat, | 1 | ... | ... | ... | ... | ... | ... | ... | ... | ... | 1 |
| Poisonous fish, | 2 | 3 | 2 | 1 | 1 | 4 | 3 | 2 | 9 | 6 | 33 |
| Unwholesome brawn, | ... | 1 | ... | ... | ... | ... | ... | ... | ... | ... | 1 |
| Tinned salmon, | ... | 2 | ... | ... | ... | ... | ... | ... | ... | ... | 2 |
| Putrid meat, | ... | 1 | 1 | 1 | ... | ... | 1 | ... | ... | ... | 4 |
| Diseased food, | ... | 1 | ... | ... | ... | ... | ... | ... | ... | ... | 1 |
| Mussels, | ... | 1 | ... | ... | ... | ... | 1 | ... | ... | ... | 2 |
| Tinned foods, | ... | ... | ... | ... | 2 | ... | ... | ... | ... | ... | 2 |
| Whelks, | ... | ... | ... | ... | 1 | ... | ... | ... | ... | ... | 1 |
| Winkles, | ... | ... | ... | ... | ... | ... | ... | 1 | ... | ... | 1 |
| Ptomaines, | ... | ... | ... | ... | ... | ... | ... | ... | 1 | ... | 1 |
| 3 | 9 | 3 | 2 | 4 | 4 | 5 | 3 | 10 | 6 | 49 |
§ 687. German Sausage Poisoning.—A series of cases may be picked out from the accounts of sausage poisoning in Germany, all of which evidently depend upon a poison producing the same symptoms, and the essentially distinctive mark of which is extreme dryness of the skin and mucous membranes, dilatation of the pupil, and paralysis of the upper eyelids (ptosis). In an uncertain time after eating sausages or some form of meat, from one to twenty-four hours, there is a general feeling of uneasiness, a sense of weight about the stomach, nausea, and soon afterwards vomiting, and very often diarrhœa. The diarrhœa is not severe, never assumes a choleraic form, and is unaccompanied by cramps in the muscles. After a considerable interval there is marked dryness of the mucous membrane (a symptom which never fails), the tongue, pharynx, and the mouth generally seem actually destitute of secretion; there is also an absence of perspiration, the nasal mucous membrane participates in this unnatural want of secretion, the very tears are dried up. In a case related by Kraatzer,[678] the patient, losing a son, was much troubled, but wept no tear. This dryness leads to changes in the mucous membrane, it shrivels, and partly desquamates, aphthous swellings may occur, and a diffuse redness and diphtheritic-like patches have been noticed. There is obstinate constipation, probably from a dryness of the mucous lining of the intestines. The breath has an unpleasant odour, there is often a croupy cough, the urinary secretion alone is not decreased but rather augmented. Swallowing may be so difficult as to rise to the grade of aphagia, and the tongue cannot be manipulated properly, so that the speech may be almost unintelligible. At the same time, marked symptoms of the motor nerves of the face are present, the patient’s sight is disturbed, he sees colours or sparks before his eyes; in a few cases there has been transitory blindness, in others diplopia. The pupil in nearly all the cases has been dilated, also in exceptional instances it has been contracted. The levator palpebrae superioris is paralysed, and the resulting ptosis completes the picture. Consciousness remains intact almost to death, there is excessive weakness of the muscles, perhaps from a general paresis. If the patient lives long enough, he gets wretchedly thin, and dies from marasmus. In more rapidly fatal cases, death follows from respiratory paralysis, with or without convulsions.