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die in an atmosphere saturated with ozone usually in about an hour and a quarter, presenting with great exactitude the order of symptoms I have described above. Rabbits live longer than guinea-pigs, exhaling water from the lungs much more freely, and also micturating with greater freedom. Rats die very rapidly. Mice exhibit a greater tolerance. Pigeons resist the effects of ozone much longer than guinea-pigs, and may be readily taken out of the chamber in which they have been confined with guinea-pigs, apparently but little inconvenienced at the period when the guinea-pigs are dead. If when just removed the chest is auscultated the breathing, however, is found to be particularly sharp, dry, and cooing, the action of the heart being amazingly rapid, reaching even two hundred and forty beats in the minute, and the respiration being from ninety to a hundred in the same time. Pigeons removed altogether from the ozone, when in this condition, will frequently exhibit the third stage of obstruction to respiration and die. Frogs seem to have the power of resisting the influence of ozone permanently, if they are allowed free access to water.-Dr. Day, Lancet, No. 2,317, pp. 124-5.

(38.)-In order to prove the truth of his theory he immersed two frogs in solutions of nicotine, which caused complete prostration or paralysis of motion, and the animals died paralysed in twenty-three minutes. Others he placed in solutions of strychnia, which produced tetanic effects of that drug, and caused death in four minutes. He then placed two others in a compound solution of the two poisons; the first frog lived in the compound solution forty-seven minutes, at the end of which time it died; the second frog was kept in the solution ten minutes, and then taken out, but after its removal from the liquid, in thirty minutes, it was seized with the tetanic spasms of strychnia, in the form of emprosthotonos, but ultimately recovered. -Dr. Part, Lancet, No. 1,961, p. 310.

(39.)—" An experimental inquiry into the mode of death produced by aconite," by Dr. E. R. Harvey, was next read. The author's experiments, which were performed on dogs, rabbits, and frogs, went to prove that aconite acts first on the nerves and then on the muscles, killing by its action on the heart.-Dr. Michael Foster, Lancet, No. 1,923, p. 20.

(40.)-Frogs introduced into a weak solution containing aniline died in periods varying from a quarter of an hour to two hours and a half, and death was also caused by the introduction of aniline into the mouth or into a wound in the back. Rabbits were also poisoned by this substance, a small animal being killed by fifty drops in six hours and a quarter, and a larger one by a hundred drops in four hours. In all the animals experimented upon violent clonic and tonic spasms ensued after the application of the aniline, and continued almost uninterruptedly till death.--Lancet, No. 1,994, p. 470.

(41.)-Ausch finds that sensibility is so much impaired in frogs poisoned by strychnia that pinching the animal's toes, or burning the central end of the divided sciatic nerve, may be performed without being followed by a reflex action.-Fournal of Anatomy and Physiology, 1873, p. 399.

(42.)-The four experiments now to be described are, as regards their results, merely confirmatory of those recorded by other investigators; but in their mode of performance some variations have been made from the methods usually followed, so as to show as clearly as possible the total inability of strychnia to act through the nerves. The experiments were performed on frogs, animals which possess the twofold advantage of being very sensitive to the action of strychnia, and of surviving for a considerable time arrestment of the circulation.

Experiment 1.-A ligature was placed round the heart of a frog at the auricles. A solution containing the one fourth part of a grain of strychnia was then injected into the stomach by means of a tube passed down the oesophagus. Thirty-five minutes after the injection the animal was able to leap about vigorously; fifty minutes after the injection it was still able to move its limbs, although feebly; in five minutes more all movements had ceased.

Experiment 4.—A ligature was placed round the heart of a frog at the auricles. One-and-a-half grains extract of nux vomica, mixed with fifteen minims of water, were then injected into the stomach by means of a tube passed down the oesophagus. Half-an-hour afterwards the animal was leaping about quite unaffected by the poison. The cranium was now cut through immediately behind the eyes with a pair of scissors, and a piece of extract of nux vomica was applied to the exposed nervous matter.

Experiment 5.-The apex of the ventricle of a frog's heart was cut away. An opening was then made in the anterior abdominal vein, and a strong solution of extract of nux vomica was injected into the vein in an upward direction, that is towards the liver and heart.

Twenty-six minutes after the injection the animal was able to leap about; forty-three minutes after the injection it was still able to move its limbs. In a few minutes more all movements ceased.

Experiment 6.-The greater part of the ventricle of a frog's heart was cut away. After allowing the blood to be expelled to as great an extent as possible the remains of the heart were excised. The articulation of the lower jaw on each side was then cut through in order to facilitate the next part of the operation, which consisted in cutting through the cranium with a pair of scissors immediately behind the eyes. To the part of the brain thus exposed a piece of extract of nux vomica was applied. In about three minutes afterwards the action of the poison began to manifest itself. The muscles

of the throat were first affected with spasm.

The anterior extremities then became violently tetanised and directed upwards on each side of the head.-Dr. Spence, Edinburgh Medical Fournal, July, 1866, p. 44.

(43) The following inquiry formed part of a gratuation thesis given in by me to the University of Edinburgh, on the 5th of July, 1873, entitled "Exthroxylon Coca, with an experimental inquiry into the physiological actions of cocaine, theine, caffeine, &c." The experimental research was conducted in the Physiological Laboratory of the University, and I have gratefully to acknowledge much kind assistance from Dr. M'Kendrick.

Upwards of one hundred experiments were conducted on different living animals, chiefly frogs, mice, rabbits, and cats.

The gr. of theine, dissolved in twenty minims of water, was injected under the skin over the back of a healthy middle sized frog; almost immediately afterwards the respirations, which normally had been eighty, were increased to one hundred and twenty per minute. Seven minutes afterwards the respiration had diminished to eighty per minute.

The frog was now distinctly sluggish in its movements. It made attempts to leap, but did so feebly. When placed on its back it recovered its normal position with difficulty. When its toes were pinched with a pair of forceps it drew up its leg.

Two minutes after these symptoms were increased, and in three minntes more the limbs were very weak, and the animal lay on its belly without their support. When placed on its back the frog was unable to recover its position, but lay there with its limbs drawn up, and when the skin or toes were pinched the limbs were moved but sluggishly. The respirations had diminished to forty per minute. Five minutes later the frog still lay motionless on its back with its limbs extended. All four legs were completely paralysed, and they remained in whatever position they were placed. The frog

remained in this prostrate condition for eleven minutes, when slight spasmodic movements were observed in the limbs. Four minutes later it made feeble attempts to move its legs, and when its toes were pinched it drew them up. Four minutes afterwards the animal gave a very feeble leap and tried to crawl along the table. Eighteen minutes afterwards the frog jumped readily, especially if it was irritated. It croaked vigorously when touched and in half an hour it was apparently in its natural state with the exception of looking feeble. . . . . If smaller doses be given similar symptoms ensue, but they are less violent and less rapid in proportion to the amount.

Thegr. of theine, dissolved in ten minims of water, was injected under the skin over the back of a white mouse weighing three

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drachms. For fifteen minutes no effects were observed. When its tail was pinched it uttered a cry, which it did before the drug was administered. It could now only crawl along the table, but could not run. Five minutes later the animal lay with its limbs occasionally kicking.. . . . The under surface of its body, the feet, legs, and mouth were much congested. [Duration of experiment about thirty minutes] . . . . . In many instances the animal had tetanic spasms and opisthotonos.

The left femoral artery of a healthy middle-sized frog was tied, and gr. of theine, dissolved in thirty-five minims of water, was injected under the skin over the back. In ten minutes the animal was almost prostrate. It lay on its back, but was still able to contract its limbs when they were pinched, which both did with equal strength, the left leg being perhaps somewhat more sluggish than the right. Fifteen minutes later the frog was apparently dead. The head was amputated; on irritating the upper portion of the cord with the electrodes of a weak Faradic current the two limbs contracted powerfully, and apparently with equal strength.

The heart of a healthy middle sized frog was exposed by carefully dividing the sternum with a pair of scissors, and a ligature passed round its back and tied so as to interrupt the circulation The gr. of theine, dissolved in ten minims of water, was then injected under the skin of the calf of the right leg. In four minutes both of the posterior extremities were partially paralysed.

Six grains of theine, dissolved in two drachms of water, were injected under the skin over the back of a healthy white rabbit weighing 2 lbs. 3 oz. Almost immediately afterwards the ears were observed to become paler than before, then suddenly they appeared of a brignt-red colour, all the vessels being enlarged and congested. After remaining in this condition for half a minute they again became paler and anemic. These sudden changes from extreme pallor to intense congestion alternated for about five minutes, each stage being about a quarter of a minute in length, after which time the ears became permanently red, hot, and congested. The animal then became restless and somewhat excited, but not hyperæsthetic, and it trembled slightly. When its toe or ear was pinched it struggled. The force of the heart's pulsation was stronger, and the rapidity of the beats, as well as the respiratory acts, quicker than before. Pupils were unaffected. Three minutes later the hind legs struggled slightly, and they seemed to have lost power. Two minutes after all four extremities were considerably weaker, and the rabbit was unable to stand upright; but lay flat on its belly with all its limbs stretched out on the table. When its toe was pinched it did not struggle so much as formerly, still it pulled away its leg and

attempted to crawl along, which it did in a shaky and laboured manner. The breathing was laboured and slow, the heart's pulsations were feeble, and the animal trembled. For twenty minutes the animal lay in this prostrate condition, breathing in a laboured manner, when it suddenly took a tetanic spasm, with slight episthotonos, which lasted for about a quarter of a minute.

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For the next seven minutes the animal took tetanic spasms at intervals, occurring spontaneously, and not brought on by pinching or other external irritations.

Evidence of sensibility had disappeared from all parts of the body except the head, where it seemed to be normal.

The eyelids winked when the eyeballs were touched, and even when the hands were clapped before them. When any portion of the face was touched its muscles contracted. The animal, although completely paralysed in its limbs, looked intelligent, as if sensation was unaffected. Ten minutes later the pupils were considerably contracted, the breathing slow and irregular, and the heart-beats not palpable. It died after a tetanic spasm. The animal never seemed to lose its intelligence. It was watchful, followed every motion of the experimenter, although it was unable to make any

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Six grains of theine, dissolved in a drachm and a half of water, were injected under the skin over the back of a healthy cat weighing four pounds one ounce. In ten minutes the animal became very angry and irritable. Fifteen minutes later this excitement had increased; the animal had a watchful, anxious appearance, prowled about, and when touched with a stick bit at it and growled. If any noise or motion was made it put up its back and made a hissing noise. The legs appeared weakened, and although it could still walk about, it preferred sitting in a corner of the room. Its mouth and tongue were very red, and there was an abundant secretion of saliva, which constantly trickled out of its mouth. The cat defæ cated and micturated several times. Forty minutes later it continued in much the same condition. Salivation was profuse. Animal suffered from tenesmus, and it had a constant straining from the bowel of a clear fluid-like mucus. The limbs, especially the posterior ones, were much weakened, but the animal could still run with difficulty. It could not jump, it made attempts to do so over a bench about two feet high, but failed. The breathing was laboured and irregular. The redness of the tongue and mouth as well as the excessive irritability of the animal had disappeared. It was quiet, lay in a corner stupid and drowsy. It drank freely of water. Twenty minutes later it was prostrate and lay on its side, its limbs quite helpless. It paid no attention to a pinch of the toe or a blow on the tail with a stick. It seemed however to be intelligent, as its eyes watched every movement of the observer, and when the hands

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