CHAPTER V
VEGETABLE AND ANIMAL IRRITANTS
=Mode of Action.=--The general effects produced by the somewhat large class of vegetable irritants are--
1. Severe abdominal pain, accompanied with vomiting and purging.
2. Absence in most cases of any cerebral or nervous symptoms.
3. The irritant properties appear to reside in an acrid oil or resin. In colchicum, stavesacre, and some others, the presence of an alkaloid may account for their active properties.
4. In medicinal doses, the vegetable irritants act as safe purgatives.
5. The _post-mortem_ appearances found in the alimentary canal betoken inflammation, the result of irritation.
6. Applied externally, they produce inflammation, pustular eruptions, and sometimes unhealthy callous sores.
SAVIN
The leaves and tops of this plant, _Juniperus Sabina_ (_N.O. Coniferæ_), yield an acrid volatile oil, to the presence of which the poisonous properties are due. The oil is colourless or pale yellow, with a peculiar terebinthinate odour. It is used in medicine both internally and externally, and is supposed to possess emmenagogue properties. The dried powder is less active than the fresh tops. Savin is seldom used as a poison, more frequently to procure abortion. Its use for this purpose is mentioned in the old ballad of “Marie Hamilton”:
“The King has gane to the Abbey garden, And pu‘d the savin tree, To scale the babe from Marie‘s heart; But the thing it wadna be.”
_Symptoms._--Those of irritant poisoning. Violent pain in the abdomen, followed by vomiting, and in some cases salivation and strangury. Purging is not always present. When taken to procure abortion, death often takes place before the object for which it was taken is attained.
_Post-mortem Appearances._--The stomach, gullet, and intestines are found congested and inflamed. The stomach may in places be seen corroded, and a green powder adherent to its coats. The powder washed and dried, and then rubbed, gives off the odour of savin.
_Chemical Analysis._--When an infusion or decoction of the leaves has been taken, chemical analysis is of no assistance. The oil may be separated from the contents of the stomach by subjecting them to distillation, and then shaking the distillate with ether, when the oil is dissolved out. On the evaporation of the ether, the oil is left for examination. When the powder is taken the contents of the stomach are not unlike green pea-soup. If a small portion of the green liquid be taken, and diluted with water, the green chlorophyll, being insoluble, will sink; but if the colour be due to bile, the liquid will remain of a uniform green colour. If a portion of the green matter be collected, dried, and then rubbed in a mortar, the characteristic odour of savin will be given off. The microscope may detect bits of the twigs.
The oil, on the addition of strong sulphuric acid, gives a brown colour. On diluting the coloured liquid with water, a dense white precipitate forms.
CROTON OIL
The oil expressed from the seeds of _Croton tiglium_ (_N.O. Euphorbiaceæ_).
The seeds, when taken, produce violent pains in the stomach and purging. Pereira has described the case of a man who suffered severely from inhaling the dust of the seeds. The dose of the oil is from half a minim to a minim. Dr. Trail mentions the case of a delicate lady patient who took three drops for a dose without inconvenience. Dr. Adam records a case (_Edinburgh Medical Journal_, 1856) of a man who, in mistake, drank three drachms of a liniment containing about fifty drops of croton oil. After the most alarming symptoms, the patient ultimately recovered. Two drachms and a half have caused death (_Journal de Clinic Médicale_, 1839, p. 509). The poisonous properties depend upon the presence of a fatty acid.
A medical friend informed Husband that in Shetland six drops in as many colocynth pills have, in cases there, only produced “a comfortable ‘_aisement_’ of the bowels.” This is attributed to the _dura ilia_, resulting from a constant fish diet.
_Symptoms._--Pain in the abdomen, vomiting, and purging, followed by exhaustion and collapse. In some cases, when the dose is large, the pain is hot and burning, and may be felt from the mouth downward.
_Chemical Analysis._--Separate the oil from the contents of the stomach by means of ether, and then drive off the ether by means of heat. The oil then warmed with nitric acid becomes of a brown colour, and nitrous acid vapours are given off.
COLCHICUM
The poisonous properties of _Colchicum autumnale_, Meadow Saffron (_N.O. Melanthaceæ_) reside in an alkaloid _Colchicine_, chiefly found in the corms, but also present in other parts of the plant. The seeds have caused death.
In June 1875 an epidemic of gastric irritation among the inhabitants of Rione Boego was traced to the use of the milk of goats which had accidentally eaten the leaves of colchicum.
_Symptoms._--Colchicum, in medicinal doses, increases the activity of the liver, and bile is freely secreted. The action of the kidneys and of the skin is also increased. The heart is more or less affected, and its frequency diminished. In large doses, all the symptoms of irritant poisoning are present, and in some cases have been likened to those observed in Asiatic cholera.
_Post-mortem Appearances._--Death may result from its use without leaving any morbid appearances. In other cases, however, the usual signs of inflammation were present. Casper describes the colour and condition of the blood in those poisoned by colchicum as dark cherry-red, with the consistency of treacle. A marked congestion of the vena cava may also be present.
_Chemical Analysis._--Colchicine, obtained by Stas process, added to concentrated nitric acid, becomes of a violet colour, changing to blue and brown. The violet solution changes to yellow on dilution with water, then to red on adding caustic soda. Tincture of iodine precipitates colchicine of a kermes brown colour, platinum bichloride yellow, and tannic acid white, the precipitate being soluble in alcohol, acetic acid, and alkaline carbonates. Strong sulphuric acid gives a yellow colour with colchicine, which changes to green, violet, and reddish-brown on the addition of nitric acid.
_Fatal Dose._--One ounce of the tincture.
_Treatment._--Stimulants and opium should be given to counteract its depressing effects. Tannin is said to be an antidote.
ERGOT
Like savin, ergot is more frequently used to procure abortion than as a poison. When taken in a large dose it causes vomiting, purging, intense thirst, hurried breathing, and irregularity of the heart‘s action. Ergot appears to act powerfully on non-striated muscular fibre wherever it exists in the body; hence the vessels contract powerfully, and the peristaltic action of the intestinal canal is greatly increased. On the pregnant uterus its action is uncertain, as it does not appear to have any marked power in inducing labour, but on the parturient uterus its effects are most marked. A case is recorded in the _Lancet_ (vol. ii. 1882) in which ergot had been taken for some time to procure abortion, but this end not being accomplished, the patient took “two hands full” of the powdered ergot to expedite matters, which caused the following fatal symptoms: There was some amount of jaundice, and the expression of the face was anxious. Occasionally fits of stupor occurred, and the general condition of the patient was maudlin, but there was no smell of alcohol in the breath; but during the course of the case, which ended fatally, a distinct etherish smell could be perceived. The pulse was so quick that it could not be counted, and it had also a peculiar jerky feeling under the finger. Attempts were made to induce labour by passing a _bougie-a-boule_, but the patient died collapsed before delivery could be effected.
Where the drug has been taken for some time in the form of rye-bread made from the diseased grain, the symptoms in some cases are referable to the nervous system; in others, the blood appears to undergo certain changes; and hæmorrhages into the internal organs, as in the case just mentioned, have been frequently noticed. Gangrene of one or more of the extremities has also been known to occur. To chronic poisoning by this drug the term _Ergotism_ has been applied, and may occur under two forms--the spasmodic and the gangrenous; the former marked by convulsions, giddiness, delirium, dimness of vision, and tetanic spasms; the latter, as a rule, by dry gangrene of the nose or extremities.
_Chemical Analysis._--Ergot has a peculiar, slightly fishy odour, which is increased by rubbing up the powder with liquor potassæ and heating the mixture. At the same time it turns a reddish colour. The production of this odour, and the appearance under the microscope, are the only tests yet known for this substance in powder. From organic mixture it may be extracted with hot alcohol acidulated with sulphuric acid. The solution is red in colour, and shows two bands in the spectrum, one in the green, and a second, broader and more marked, in the blue.
_Treatment._--Wash out the stomach, and give inhalations of amyl nitrite.
BLACK HELLEBORE
This plant, _Helleborus niger_--Black Hellebore--(_N.O. Ranunculaceæ_), known as the Christmas rose, is the melampodium of the old pharmacopœias. All parts of the plant are poisonous.
_Symptoms._--Purging, vomiting, pain in the bowels, and cold sweats. Death is generally preceded by convulsions and insensibility.
_Post-mortem Appearances._--Those common to the action of other irritants.
WHITE HELLEBORE
White Hellebore, _Veratrum album_ (_N.O. Melanthaceæ_), acts very much in the same manner as the black hellebore, but is more powerful. The powder causes violent sneezing. The alkaloid _Veratria_ appears to be the active principle. The symptoms and _post-mortem_ appearances are analogous to those produced by black hellebore.
GAMBOGE
Gamboge is the gum resin of _Garcinia Morella_. It is an active ingredient in certain quack “vegetable pills.” One drachm has caused death by its irritant action. Owing to the imperfect pulverisation of gamboge in quack pills, they have caused violent irritation of the bowels, straining at stool, and prolapsus uteri, due to the irritating
## action of small pieces of this substance.
JALAP
Jalap, the powder obtained from the tubers of _Exogonium Purga_. The
## active properties of the drug reside in a resin. It is a drastic
purgative; twelve grains have killed a dog.
SCAMMONY
Scammony is obtained from the dry root of _Convolvulus Scammonia_. Like the last mentioned, it is a powerful purgative, and may cause death if given in large doses to debilitated individuals.
CASTOR-OIL
The oil expressed, with or without the aid of heat, from the seeds of _Ricinus communis_. A girl, eighteen years of age, died in Liverpool in 1837 from eating a few of the castor-oil seeds.
ARUM MACULATUM
Cuckoo-pint, Wake-robin, or Lords and Ladies, is one of the most acrid of indigenous vegetables. The active property of the plant appears to be lost by drying, and by distillation in water. Children have been poisoned by its leaves.
YEW
The twigs and fruit of _Taxus baccata_ act as irritant poisons, producing also symptoms which point to cerebro-spinal mischief. A case is recorded of poisoning by yew leaves, in which only five grains of the leaves were found in the stomach; yet death took place within an hour from the time the symptoms commenced (_British Medical Journal_, 1876, vol. ii. p. 392). In the above-mentioned case, vomiting and other signs of gastric irritation were absent. The chief symptoms present were--pallor of the face, faintness, an almost imperceptible pulse, facial convulsions, foaming at the mouth, stertorous breathing, loss of consciousness, ending in death. The symptoms are due to an alkaloid toxin. Several children have died after eating the fruit. _Post-mortem_ signs of irritation of the alimentary canal.
LABURNUM
_Cytisus Laburnum_, or common Laburnum, the seeds, bark, and wood of which are poisonous. They contain a narcotico-acrid, crystallisable alkaloid--_Cytisine_--producing vomiting, foaming at the mouth, convulsions, and insensibility. Recovery took place in two cases mentioned by Trail, from the use of emetics and ammonia.
FOOL‘S PARSLEY
_Æthusa Cynapium_ has been mistaken for parsley. Nausea, vomiting, giddiness, and severe abdominal pains are among the most common symptoms of poisoning by this plant.
BRYONY
Two plants are included under this name, _Bryonia dioica_, white bryony (_N.O. Cucurbitaceæ_), the only indigenous cucurbitaceous plant, and the _Tamus communis_, black bryony _(N.O. Dioscoreaceæ_). Both the bryonia dioica and the tamus communis possess active irritant properties. They are of importance from the fact of their growing wild, and the possibility of the fruit being eaten by children.
ELATERIUM
Elaterium, the inspissated juice of _Ecballium officinarum_, or Squirting Cucumber. It is a powerful drastic purgative, one grain having given rise to alarming symptoms in man.
ANIMAL IRRITANTS
CANTHARIDES
Cantharides--_Cantharis vesicatoria_ (_N.O. Coleoptera_)--is seldom given as a poison, but is most frequently employed to procure abortion, or for its supposed aphrodisiac properties.
Cantharides is a pure irritant. Applied externally, it produces vesication; and if absorbed, strangury.
Cantharidine--the active principle of Cantharides--is insoluble in water and bisulphide of carbon. It is but slightly soluble in alcohol, but it is dissolved by chloroform, ether, and some oils. Four parts of cantharidine have been procured from a thousand parts of the flies.
_Symptoms_.--An acrid taste is first experienced in the mouth, followed by a burning heat in the throat, stomach, and abdomen. There is constant vomiting of bloody mucus, and the stools also contain blood. The patient complains of intense thirst, pains in the loins, and an incessant desire to void urine, which is frequently mixed with blood. Salivation in some cases is a prominent symptom. Strangury may result from the external application of cantharides as a blister, &c. Priapism is often obstinate and painful, and the fatal termination is generally ushered in by violent convulsions and delirium. In pregnant women, abortion may take place as a result of the general irritation and disturbance of the system, there being no proof that the uterus is particularly affected by the drug. The vomited matters may contain shining green particles, the presence of which indicates the nature of the poison taken. The invasion of the symptoms may in some cases be retarded.
_Post-mortem Appearances_.--Those of powerful irritation. The mucous membrane of the whole alimentary canal, from the mouth to the rectum, has been found in a state of acute inflammation. The uterus, kidneys, and internal organs of generation share also in the general irritation, ulceration of the bladder having been met with in some cases. Portions of the wings and elytra are sometimes found adhering to the coats of the stomach.
_Fatal Dose_.--One ounce of the tincture has caused death in fourteen days. This is perhaps the smallest fatal dose on record. Six ounces have been stated to have produced no dangerous symptoms. The worthlessness of the preparation may account for this result.
_Treatment_.--Vomiting should be promoted and warm mucilaginous drinks given. If vomiting be absent, emetics should be administered. Oil should not be given, as it dissolves out the active principle. Opium may be given with advantage.
_Chemical Analysis_.--The contents of the stomach should be concentrated and then treated with chloroform, filtered, and the filtrate allowed to spontaneously evaporate. A portion of the residue should then be placed on the skin, and the presence or absence of vesication noticed. Examined under the microscope, portions of the wing-cases may be detected. No change of colour is produced in cantharidine by the action of sulphuric or nitric acid, thus distinguishing this substance from any of the vegetable alkaloids.
PUTREFACTIVE OR BACTERIAL ALKALOIDS
The processes by which complex and highly organised substances are broken up into their primary elements are largely synthetical. The putrefactive processes brought about by the action of bacteria result in the formation of special products, some of which combine with certain mineral and vegetable acids to form definite chemical salts; in this respect they correspond with inorganic and organic bases. These products are called ptomaines, a name suggested by an Italian toxicologist, Selmi, and it is derived from the Greek word πτῶμα, a cadaver or corpse.
On account of their basic properties, resembling the vegetable alkaloids, they are called putrefactive or bacterial alkaloids. They have been called animal alkaloids, but some ptomaines may be produced by the action of bacteria upon vegetable proteids; so this term is not strictly applicable, and should be restricted to those basic bodies or “_leucomaines_” that result from metabolism of the tissues in the animal body.
The essential element of their basic nature is nitrogen, and in this they resemble the vegetable alkaloids. Some contain oxygen, like the fixed alkaloids, while others do not, like the volatile alkaloids nicotine and conine. The kind of ptomaine formed depends upon the nature of the bacterium, the material upon which, and the conditions under which, it grows; the amount of oxygen present; the temperature and the period of growth. All ptomaines are not necessarily poisonous. Albumin is the origin from which all alkaloids, vegetable or animal, are derived. The following is a list of the principal ptomaines:
_Methylamine_, CH₃NH₂.--Found in herring brine and decomposing fish--non-poisonous. _Dimethylamine_, (CH₃)₂NH₂.--From putrefying gelatine, yeast, fish, and sausage--non-poisonous. _Trimethylamine_, (CH₃)₃N.--Various decomposing animal and vegetable tissues, ergot--poisonous in large quantities. _Ethylamine_, C₂H₅NH₂.--Beet-sugar, wheat-flour--non-poisonous. _Diethylamine_, (C₂H₅)₂NH₂.--Putrid fish and sausage--non-poisonous. _Triethylamine_, (C₂H₅)₃N.--Putrid fish and sausage--non-poisonous. _Propylamine_, C₃H₇NH₂.--From cultures of bacteria of fæces--non-poisonous. _Butylamine_, C₄H₁₁N.--From cod-liver oil. Diaphoretic and diuretic--in large doses causes vomiting and stupor. _Iso-amylamine_, (CH₃)₂·CH·CH₂CH₂NH₂.--Decomposing yeast and cod-liver oil--active poison, causes convulsions and death. _Caproylamine_, C₆H₁₅N.--Called septicin by Hager. _Collodine_, C₈H₁₁N.--The first ptomaine obtained in a chemically pure condition--from putrid horse flesh, pancreas, gelatine, and mackerel. _Hydrocollodine_, C₈H₁₃N.--Putrefying horse flesh and mackerel--highly poisonous. _Parvoline_, C₉H₁₃N.--Putrid horse flesh and mackerel. _Unnamed base_, C₁₀H₁₅N.--From decomposing fibrin and jelly-fish. Like curare in its action. _Putrescine_, C₄H₁₂N₁₂.--From human corpses--feebly poisonous. _Cadaverine_, C₅H₁₆N₂.--From human corpses--causes suppuration. _Neuridine_, C₅H₁₄N₂.--Common product of putrefaction--quite inert. _Neurine_, C₅H₁₃NO.--From human corpses, intensely poisonous--resembles muscarin in its action. _Choline_, C₅H₁₅NO₂.--From putrefying animal and vegetable substances--feebly poisonous; by giving up one molecule of water it changes to neurine--this may be brought about by bacteria or chemical agencies. _Muscarine_, C₅H₁₃NO₂.--From putrid fish and horse flesh. The active principle of poisonous mushroom. _Gadinine_, C₇H₁₆NO₂.--From putrefying codfish, haddock, and gelatine, in pure cultures of proteus vulgaris--poisonous in large quantities. _A Base_ (_?_), C₇H₁₇NO₂.--From decomposing horse flesh--its action is like curare: causes loss of temperature, rigors, convulsions, and general paralysis: the heart stops in diastole. _Mydaleine._--Composition not determined--from human corpses--actively poisonous.
Even after prolonged periods and with access of air, any putrefactive alkaloids which may form do so in very small quantities, and they are very unstable. In their chemical reactions they respond to many of the group-tests used for alkaloids, but they differ in their reaction to the special tests used for vegetable alkaloids. There is no test that will differentiate between putrefactive and vegetable alkaloids, as a class; at the same time no putrefactive alkaloid will give the same chemical reactions, and have the same physiological properties, as any one of the vegetable alkaloids.
_Neurine_ was first obtained by Liebreich by boiling protagon with concentrated baryta. Since then it has been extracted from putrefying animal tissues. The free base is strongly alkaline, and gives a white cloud with the vapour of hydrochloric acid. It is intensely poisonous, resembling muscarine in its action. Very small quantities cause complete paralysis in frogs. Respiration ceases first, and the heart beats become more and more feeble, until it stops in diastole. If atropine be now injected the heart begins to beat again.
As a defence set up in cases of poisoning, when one or other of the rarer alkaloids has been used, it has been suggested that the poison discovered in the body of the deceased was due to the processes of putrefaction of the tissues themselves. In view of this it is important to know the toxic power of such putrefactive alkaloids as may be found in the human cadaver.
Two only of these are actively poisonous--_neurine_ and _mydaleine_; others are toxic in so small a degree that large amounts would be required to produce lethal effects, far more in proportion to the body weight than any vegetable alkaloid for which it may be alleged they have been mistaken.
_Neurine_ does not appear before the fifth or sixth day after death, _mydaleine_ not until the seventh day, and only in traces; it does not appear in amount sufficient for quantitative analysis until the end of the second or third week.
At the period after death when a medico-legal analysis has generally to be made, _choline_ is the only alkaloid present, and it is but feebly poisonous.
In rabbits _neurine_ causes marked salivation and increased flow of secretion from the eyes and nose. The heart beats more quickly at first, but gradually slows down and stops in diastole. There is increased peristalsis of the intestines with profuse diarrhœa. There is narrowing of the pupil both after injection or local installation. Clonic spasms and violent convulsions occur, and are followed by paralysis first of the hind then of the fore legs, ending in death. The symptoms are prevented or relieved by atropine.
If atropine be injected first the poisonous effects of the _neurine_ do not show themselves.
_Mydaleine_ was discovered by Brieger in putrefying cadaveric organs. Small doses injected into guinea-pigs cause profuse lachrymation and coryza.
The pupils dilate and then become motionless. The temperature rises from 1° to 2° Centigrade. There is somnolence at this stage, with increased intestinal peristalsis. The pulse and respirations are quickened; later these with the temperature return to the normal, and the animal recovers. Large doses cause death with the heart in diastole and the intestines contracted.
Clonic spasms and stupor precede death.
_The Extraction of putrefactive alkaloids_ from organic matters may be carried out by the process for alkaloid extraction (_vide_ p. 335 _et seq._).
Amongst the attempts made to distinguish the putrefactive from vegetable alkaloids by chemical reactions one method was based on the rapid reduction of potassium ferricyanide to the ferrocyanide. After converting the alkaloid to a sulphate, a solution of it is mixed with a drop of potassium ferricyanide and a drop of ferric chloride added: the deep blue colour of Prussian blue is produced if reduction to the ferrocyanide has taken place. However, certain vegetable alkaloids, viz. morphine, aconitine, eserine, and hyoscyamine act rapidly as reducing agents upon the ferricyanide. Emetine, igasurine, nicotine, colchicine act less rapidly. Brieger considers that when the reaction occurs with putrefactive alkaloids it is due to impurities present in them. Brouardel and Boutmy have suggested making use of the action of alkaloids upon photographic silver bromide paper as a means of distinction. The paper is written upon with a solution of the alkaloid and kept light free for half an hour; it is then fixed in a solution of sodium hyposulphite and washed in water. The putrefactive alkaloids are said to reduce and blacken the silver compound, while the vegetable alkaloids do not. Neither of these processes is to be relied upon for medico-legal purposes.
LEUCOMAINES OR ANIMAL ALKALOIDS
_Leucomaines_ or _animal alkaloids_ are basic substances which originate from the metabolic processes taking place in the animal body. They closely resemble the vegetable alkaloids, and some are found in plants as well as animals. It is probable that some of them may have originated primarily from the putrefactive processes in the intestines and been absorbed into the system. The following is a list of the principal leucomaines resulting from the metabolism of the tissues of the animal body:
_Adenin_, C₅H₅N₅.--From thymus gland, from all tissues animal or vegetable which are rich in nucleinic acid--poisonous in large doses. _Sarkine_ or _hypoxanthine_, C₅H₄N₄O.--From urine and flesh--causes increased reflex excitability and convulsive seizures. _Guanine_, C₅H₅N₅O.--From flesh and guano--it is inert.
_Xanthine_, C₅H₅N₄O₂.--From flesh and urine--acts as a muscle stimulant. _Heteroxanthine_, C₆H₆N₄O₃.--From urine. _Methylxanthine_, C₆H₆N₄O₂.--From urine. _Paraxanthine_, C₇H₈N₄O₂.--From urine--destroys spontaneous muscular action, lessens reflex excitability. _Carnine_, C₇H₈N₄O₃.--From fresh meat. _Gerotine_, C₅H₁₄N₂.--From liver and kidneys, an isomer of cadaverine--exerts a paralysing action upon the nerve centres and cardiac ganglia. _Spermin_, C₂H₅N.--From semen, testicles, ovaries, breast, thyroid, pancreas, and spleen, normal bone marrow. Poehl states that it has a tonic effect on the nervous system. _Creatinine_, C₄H₇N₃O.--From urine. _Crusocreatinine_, C₅H₈N₄O.--From fresh meat. _Xanthocreatinine_, C₅H₁₀N₄O.--From fresh meat--causes depression, fatigue, somnolence, defæcation, and vomiting. _Betaine_, C₅H₁₁NO₂.--From urine. _Mytilotoxine_, C₆H₁₅NO₂.--From poisonous mussels.
=The Relation of Leucomaines to Disease=
It will be necessary in considering the relation of leucomaines to disease to give the term a wider significance than that relative to the chemistry of these bodies. Autogenous diseases may be looked upon as having their origin in altered metabolism of the tissue cells, apart from the introduction of foreign cells or poisons. “It is certainly true that if we should drink only chemically pure water, take only that food which is free from all adulteration and infection, and breathe the purest air free from all organic matter living and dead, yet our excretions would contain poisons. It is true that the excretions of all living things, plants, and animals contain substances which are poisonous to the organisms excreting them” (Vaughan). Bouchard estimates that the amount of a certain poison formed in the intestines of a healthy man in twenty-four hours, if absorbed, would prove fatal. Unless free elimination takes place, elevation of temperature may follow.
The products of imperfect digestion, if absorbed, may give rise to serious disturbances. Hildebrandt has shown by his experiments that subcutaneous injection of pepsin into dogs is followed by elevation of body temperature, which he calls “ferment fever.” The fever reaches a maximum within a few hours and may last several days. Rigors are frequent. The animals suffer from trembling in the limbs, uncertainty of gait, vomiting, dyspnœa, and coma followed by death. On _post-mortem_ examination there are found degeneration of the heart, muscles, liver, and kidneys, abundant hæmorrhages into the intestine, Peyer‘s patches, the mesenteric glands, and occasionally into the lungs. The blood is at first lessened in coagulability, afterwards increased, and thrombi formed which have been found in the lungs and kidneys.
Excessive formation of these poisonous substances within the body or insufficient elimination of them produces serious disturbances. Fatigue fever is an example. A considerable rise of temperature may follow excessive and prolonged exercise, the appetite is impaired, and insomnia is present from excitation of the brain and the senses being rendered more acute. There may be rigors simulating malaria. This fatigue fever occurs particularly amongst recruits in armies subjected to prolonged marching. From his observations of this disease in the Italian army, Mosso states that it is due to the absorption of poisonous substances into the blood from the tissues, which, if injected into the circulation of healthy animals, produces symptoms of exhaustion. The fever of prostration or exhaustion is similar but less in degree, it is more likely to be produced by prolonged exertion with insufficient food, it may resemble typhus fever, delirium may be present, and loss of muscular control over the bowels; death may result. In non-fatal cases weeks may elapse before recovery takes place.
Rachford has pointed out that an excess of paraxanthine in the blood is followed by migraine, and it may give rise to epileptic seizures, gastric neurosis, and asthma; and by injecting paraxanthine into the blood of mice and rats he has produced symptoms of certain forms of epilepsy, and others similar to the nervous symptoms of chronic lead poisoning.
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