Kalium bromatum

Volume I — Main text

Kali bromatum.

L Provings, — i, a.

Bromide of potassium, K Br*» In daily doses of 1 gr. gradually increased,

• " One «t of ohaervcrs believe tbat all tlic effects of KBr are tlic feiult ti< rbc potiv^ium action- Thi<i explanation, however, is ao longer tenabir. The ^pectHc action upon the brain and spinal cord, and upon the reflex initabitiry «f the nerTt*o# the paUtc, a^ well as the eruption upon the skin, can now pot&itivpljr be cxpUtoed as

caused increased stools and urine, headache, disgusting eructations, inclination to vomit, oppression of chest, cough, and a long-continued hoarseness. These symptoms were most marked after taking 37 gr. in 9 d.

b. With a hot iron he burnt his arm in two places the size of a shilling, removed the epidermis and sprinkled on the raw surfaces 10 gr., adding a few drops of water. The pain lasted i h. In afternoon the part inflamed^ there occurred a violent drawing burning pain that spread all over the arm, and in the night pain was very great, but declined towards m. Pulse in n. 85 to 90. At 11 am. next d. he had a loose stool, and 3 more during afternoon and n.) when it became watery. Urine much increased, then slight short cough in c. with dazed head ; at 11 p.m. violent headache, especially in occiput ; at 3 a.m., woke with very great nausea and efforts to vomit, vomiting of mucus, salt taste in mouth. Headache increased, but pulse became full and slow, 65 to 70. He fell asleep and awoke after 2 h., with headache and cough. In m. of 3rd d., 2 soft stools; the cough lasted several d.

c. He made a blister with cantharides, and removed the epidermis ; he then sprinkled on the raw surface 10 gr. of brom. of pot. No inflammation occurred. Next m. he had diarrhoea. (Horing, loc. at.)

1. Heimrdinger took fasting \ dr. in ) oz. water. T'his caused increased secretion of saliva and mucus in mouth ; feeling of heat in abdomen ; after some h. great vertigo and confusion of head, dilated pupils, repeated eructations, two slight attacks of colic, discharge of flatus, slight oppression of breathing ; after dinner tiresome stomachache I in afternoon, slight vertigo, weariness, thirst, increased urination. 2 d. after this he took i dr. distributed in 6 doses during the d. Quickened pulse, vertigo, feeling of heat in abdomen, frequent rumbling in bowels^ eructation, discharge of flatus. In afternoon, headache, thirst, two normal stools. Next m. vertigo, stomach remained weak several d. From loth to 26th March he took 4 gr. daily, from 26th March to 8th April, 8 gr. daily. Nothing occurred except increased urinary secretion. {Op. cit.)

2. a. Laborde took in 2 doses at i h. interval 15 grammes (1 oz.) dissolved in a glass of eau sucree; some m. after, sensation of fulness and heat in epigastric region, nausea followed by repeated eructations with adbtinct salt after-taste, excessive secretion of saliva, spitting, followed by dryness of mouth lasting a long time, and requiring him to drink frequently 1 or 2 h. afterwards, otecuration of vision, heavinesn of eyelids, as though the eyes would be forcibly closed, a sort of general stupe&ction irresistibly leading to sleep. This sleep is a sort of heavy somnolence, often interrupted by jumping up, though there are no actual dreams, or the dreams do not take definite shapes, it is rather a nightmare of indefinite character. The sleeping sometimes is indefinitely prolonged and waking is extremely difficult i the will seems lost

cfepending apoo the bromine of the compound. On the other hand, the effect upor circuJatioOy respintton and temperature is almou entirely due to the potaMum ** (NoTBHACEL and Kossbach).

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af ifsdcaa and self-consciousness could not be regained, sf cuh, Uz)r, and docs not get its usual inteJlectuaJ alimenr, j ness came over him, proround indifference and almost dii On attempting to get up and walk^ there is felt a sin| characterised chiefly by a sense of emptiness around and which he is afraid of placing wrongly ; the ground seeme aj^d the sense of its resistance is lost, the walk is staggei^ impossible, at least he is forced to give it up, Xhcre J tuseness of sensibility, especially with regard to reflex ac the foot is not followed by its usual effects, prnching 19^ the sense of touch of the hands is altered^ so that objects ; with firmness, there is a general feeling of chilliness of thej The pulse became slower and compressible as if exdngti duration of this action is 15 or 18 h., and all that happens i in the way of moral and physical impressions is very distic bered. After the chief phenomena have ceased there rema of head.

h. Took 6 grm. in a doses at J h. interval. Salt increase of saliva, eructations without nausea, some pinching if stomach is empty, not if containing food j a feelingi and calm, inviting to sleep, which speedily fallows if lyings excitement generally accompanied by erection and emis^ic after this the sleep becomes profound^ more or less troubled great difficulty of being awakened, when awake musculav bruised feeling in limbs and loins ; on commencing to steps are shaky and undecided but this soon passes off; aIon| increased saliva there is also an increase of the nasal niucus^i snce/Jng, this is transient ; increased urinary secretion of semen does not take place if the bladder be emptied ; th^ movements arc rendered slower than normal, the pulse ic the reflex sensibility of the fauces is abolished, but not its bility. (Gaz. Med,^ 1869, p. 554.)

1. G. P — , :et, 20, medical student, took at 4.30 p.m, 5 1 37'2°, at4.45 p.m. 5 grm. Salty taste, pressure in epigastrii sensation of warmth, eructations. 5p»m,, p. 84, feeling of head and eyelids, the eyes look glazed, 5.15 p.m., p, 80, fee cular fatigue and weakness, weariness, yawning. 5. 30, tcmf thinking power slow. 6 p.m., p. 66, dulness of head, toud causes no reflex actions. 6.30 p.m., p. 70, feeling of prostra plains of fatigue and dulness of head when walking \ tended rhoea and urging to urinate \ in e. several diarrboeic stool 4rch.f. Exp. Phy. u. Pharm.y 1876, vi, 13.)

5, G. h — , medical student, set. 21 J, took at 3.15 p.m. (t 37° and p. 80) 5 grm. Salty taste. 3.25 p.m., feeling o^ stomach, 5 grm. 3.30 p.m., p. 80, flow of saliva. 3 45, p* | eructation, feeling of pressure m head. 4 p.m., temp. 37*^, oi vertigo and prostration, touching velum palati and postc'rd causes no reaction* 4,15 p.m., dryness in mouth. 4.30 complete anesthesia of palate and pharynx. 5 p.m,, tc p. 68, soft I soft stool and copious urination ; rumbling

5.30 p.m., p. 64, feeling of prostration > frequent spitting of viscid saliva, 6 p,cn., p, 68, touching palate causes slight retching movements, muscular weakness, confusion of head, 6.30, p. 72, soft and small j whilst walking is tired and memory weak ; urging to stool and urine. E., several watery stools ; after sleep, on waking next m*, some difficulty of swallowing -, palate and pharyngeal m.m. very red and somewhat swollen, uvula swollen. {Ibid.)

1. a, Krosz, set. 25. At 8,50 a.m. (temp, being 368'^, p. 80) took 5 grm. Salty taste, eructation, 8.55 a.m., 5 grm. 9 a.m., feeling of fulness, pressure, and warmth in epigastrium, dulness of head, salivation 9.15 a.m., p. 72 ; besides dulness there is heaviness and pressure in head ; chinking acateness diminished. 9,30 a.m., p. 68, slight nausea, liquid stool and much urination. 9.45 a.m., p. 64, palate without reaction. 10 a.m., temp. 366°, p. 64, heaviness of eyelids, head hot, general prostration, laziness of movements. 10.30 a.m., p. 58, small, irrcgularj weariness, can only keep off sleep by walking about, 11 a.m., temp. 365'^, p. 60, irregular. 1 1 30 a.m., p. 60, touching palate causes no reaction. Head rather dull. 12.15 p.m., p. 64, retinal vessels rather contracted than enlarged. 1.15 p.m,, temp. 36^6^^, p. 64, nearly regular. 215 p.m., p. 66, palate very slightly sensitive, all symptoms gone except weariness, stupor, and uneasiness in the belly. 2,45 p.m., p. 80. A certain amount of weariness and exhaustion lasts all d. A few d. later an exanthem appeared \ on shoulders and lower part of face are many, on the extremities, forehead, and chest several lentil-sized, red extinguishable spots, in the middle of which is a pustule, filled with matter, surrounding a hair glandule. On 1. clavicle are two, on shoulders and back several elevated hard red lumps the size of a pea, which are not depressed nor yet do they lose their colour when pressed.

A. On another occasion, — 8.25 a.m., temp. 368% p. 80, took 8 grm. 8.30 a.m., 7 grm., salt taste, eructations. 8.45 a.m., p. 76, salivation, pressure and sore feeling in stomach. 9 a.m., p. 72, headache, 9.15 a.m., p. 68, liquid stool, slight nausea, salivation continues, also pressure in epigastric region. 9.30, temp. 366*^, p. 64, small. No reflex nausea on touching palate, pressive pain and confusion in head. General prostration and weariness, thinking power curtailed and speech slow, 10 a.m., p. 60, irregular and small. 10.30 a.m., temp. 364^, p. 57» small and intermitting. 1 1 a.m., p. 52, small and intermitting, intel-d lectual work difficult, i j.30 a.m., temp. 36'2°, p. 50. 12 noon, p. 52, ■ fauces quite anaesthetic. 12.30 p.m., temp, 36-4'^, p. 56, much clearcoloured urine. 2 p.m., temp, 36" 6^, p. 66, small and irregular, some headache remains as also slowness of speech. Difficulty of thinking, feeling of exhaustion. Palate reacts a little when touched, 3.45 p.m. temp, 37'^, p. 80, regular. At 5 p.m. fell asleep from exhaustion and slept I h. Seven d. after this there appeared, besides acne pustules with heads the size of peas on forehead, checks, chin and back, a good number of hard, red lumps (as before), some of which suppurated in the middle. [Ibid,) M

1. A gentleman, anticipating a wakeful n,, took 20 gr. before goingi to bed at 11 p.m. Slept well till 3, when he awoke, and in ^ h., feeling no inclination to sleep further, took 20 gr. more. H^ %\sy^x w^

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more that n., but at 4,30 a.m. was attacked with flatulent colic tn region of duodenum, which passed off in watery diarrhoea during d. Next d. had pain, swelling, and tenderness in K testicle and cord. Was restless for 4 or 5 n. following, being frequently awakened by voluptuous dreams, with severe erections. (Merrill^ Trans, of 4m /«//, ^ Hornby 1870, p. 326.)

8, A patient affected with epilepsy, but otherwise well^ tuoK lO gr. daily, which soon caused cessation of the "lapses^* {pititmal). But in order to make sure, and stop the greater evil also, he went on increas* ing dose till at length he was taking 70 — 80 gr. daily. " The first symptom," he writes, ** of overdoing the thing that I noticed was the profound and yet disturbed sleep into which it seemed to throw me. I always awoke with mental struggle and effort, not knowing at first where I was, or what had become of me ; in fact, as I told Dr. M., I seemed to have gone too far down into the gulf of sleep. Side by side with this, but of course less noticeable to me, was the enfeebling of mental power. A little page in my accounts, which I should usually prepare and balance in \ h,, took me 2 or 3 evenings' weary work. But the worst thing was the tendency to talk * Mrs. Malaprop ' Englishjj« substituting one word ending in ^ tion * for another in a most provoklngl and yet ludicrous way, — * contraction ' instead of 'subscription,* for instance, when I was asking for the latter, even in writing.^ 1 went from home and for a time dropped the medicine. In a week my host said that I looked ten years younger than when 1 first came, The stoop in my figure, the slow uncertain speech, and other bad symptoms^ especially the heaviness in the eyes, were gone, and 1 felt quite myself again." (Lockhart Clarke, Brit, and For. Mid.-Ckir. Rev,^ Octj| i860.)

IL Poisonings, — I. a. When given in large doses, such as 30 and 40 gr. 2 or 3 times a d., bromide of potassium produces very striking symptoms in about 10 or 15 d. The patient at first complains of a dull headache, becomes listless and apathetic, with an expression le$.s gaze and a lustreless eye. His intellect is clouded, his mind ^ J J

and he is unable to concentrate his thoughts. There is slu^ jfl

perception, and questions have to be asked several times before their meaning is understood and an answer can be obtained. If, when these symptoms have begun to show themselves, the medicine be continued, hebetude follows, with inability to think, and a kind of stupor resembling that of the first stage of typhoid fever, together with drowsiness, somno^ lence, and constantly dropping off to sleep. The pupils are dilated, and contract very sluggishly under the influence of a strong light ^ the sensibility of the conjunctiva is so deadened that a finger may be pressed with impunity on the surface of the eyeball without producing winking. Hearing loses its usual acuteness, and it is only by speaking in a very loud voice that the patient can be aroused from his stupor.

t. The sense of taste is probably impaired like those of hearing and

" Voisin cites an interesting case of a patient who maiiifcsecd thi«t divturbance ol memory tor words also in writing i he wrote some words which were mcompreheft!»i1)ta and other words only h;iU finished, in bewildering succc^^sioo.'* (BO£|lll| ZicinsM-itfl Cyclopedia ^ X V i i» 3 1 8 , ) I

of sight. The tongue is moist and red at first, but after a few d. it has a tendency to drying and browning. There is anaesthesia of the velum palati, the uvula and upper portion of the pharynx, so that these parts may be tickled without producing nausea or involuntary movements of deglutition. Swallowing itself, however, is unimpaired, and, strangely enough, the appetite remains very good ; the patient takes his food well, and dozes off immediately after. Digestion seems to be easy, and the bowels, although sluggish in their action, are not confined. There is intense thirst, and a craving for cold drinks. The anaesthesia is not confined to the mucous membranes only, for the sensibility of the skin is diminished also, so that pinching and pricking are scarcely noticed by the patient. From the beginning the sexual aptitude fails ; erections become rare and imperfect, and cease entirely after a few d.

c. Simultaneously with the impairment of sensibility, disorders of motility manifest themselves. Thus the patient is averse to taking exercise, sits and lounges about ; by degrees his gait becomes altered, he rolls and staggers like a drunken man, his limbs shake and bend under him. After a time he is obliged to keep to his bed, and when he uses his hands, as in the act of carrying anything to his mouth, they are seen to tremble, as if he were suffering from delirium tremens. The respiration is calm and tranquil, with occasional sighing. The circulation is considerably slackened ; the pulse at the wrist is weak and slow \ the heart's beat lacking in energy, and its sounds distant and feeble ; in bet, in its effect on the heart, bromide of potassium seems to resemble digitalis. If the drug be withheld, these symptoms diminish and pass off of themselves^ but they leave behind them for some time afterwards great feebleness, both physical and mental. The anaesthesia of the fauces seems to be the last phenomenon to disappear. (Bazire, Trousseau's Clinical Lectures^ N. Syd. Soc, vol. i.)

1. The following are the symptoms of a toxic dose, which are only an increase or an exaggeration of tho^e of a therapeutic one : — The fcetid breath becomes nauseous ; cedema supervenes on congestion of the uvula and fauces ; the whispering voice sinks into aphonia ; sexual weakness degenerates into impotence; muscular weakness becomes complete paralysis ; reflex, general, and special sensibility disappears ; the ears do not hear, nor the eyes see, nor the tongue taste ; the expression of hebetude becomes first that of imbecility, and then that of idiocy ; hallucinations of sight and sound, with or without mania, precede general cerebral indifference, apathy, and paralysis ; the respiration, without the stertor of opium or alcohol, is easy but slow ; the temperature of the body is lowered. As the bromism becomes more profound, the patient lies quietly on his bed, unable to move, or feel, or swallow, or speak, with dilated and uncontractile pupils, and scarcely any change of the colour of the skin or face ; the extremities grow gradually colder and colder ; the action of the heart becomes feebler and slower, till it ceases altogether. (Clarke and Amory, op, cit.)

2. A man affected with ulceration of larynx used K. brom. internally, and by means of a pulveriser. Soon patient's complexion became of a dirty -yellow colour; he had hollow eyes, a strange fixed look, face without expression, considerable emaciation, tottering limbs, trembling

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hands, and a generally cachectic state. Gradually appetite was lost ; intense pains in hairy scalp supervened, especially at n. ; strength win daily diminished, and trembling increased in proportion. As thcM|H symptoms of bromism developed themselves, disease in throat was relieved. In two months they declined, and eventually patient recovered, (Marcq, VUnim Midicale^ June i6th, 1866.) ■

1. In a case of epilepsy affecting a woman of 22, increasingly large doses of K. br. were given for the space of a year* Patient became emaciated, skin was yellowish, and face covered with acne \ she su'' from gastralgia, and was harassed with dry cough and dryness of tl Finally she died, delirious, and oppressed in breathing, with small, frequent pulse, and acute abdominal pains. In several cases reported by Vulpian, medicine occasioned a state of prostration with involuntary faecal discharges, which threatened death. This result was prevented by withdrawal of medicine. (Stille, op, ch.)

2. The following were the symptoms of bromism as observed in an epileptic boy, to whom 31] of K* br. had been administered daily for a month :■ — extreme pallor and anaemia, dilated pupils, acne on face, forehead, and shoulders ; foetid, bromine breath j slow and feeble action of heart ; breathlessness and quickened pulse on slight exertion j cool hands and feet; general subjective sense of coldness ; movements in walking tremulous and uncertain; diminution of tactile sensibility of mucous and cutaneous surfaces j fauces dry, and their reflex actions sluggish ; swallowing somewhat difficult ; anaphrodisia and complete relaxation of genitals ; mind weak, manifested in silly conduct and unmeaning laughter. (Bartholow, op, at.)

3. There are five principal forms of eruption. The first of these is acneiform. It commences by pustules ; appearing by preference about shoulders, forehead, and nose ; first of pin-head size, each surrounded by a red areola, later enlarging and acquiring an indurated base. In thif condition it may persist for weeks. Afterwards pus is discharged, but a small reddish nodule remains for some time. The second form appears on the lower extremities, rarely elsewhere. It consists of rounded or elongated elevations, 2 to 5 cm. in diameter^ of rosy colour, sometimes yellowish, as if due to pus beneath the epidermis. The surface is roughened by minute agminated pustules. In the rounded patches the centre is depressed. It is rare for the same patient to have more than two or three of these at a time. The elevations are painful and senstlive to touch, except the depressed centre, which is anfesthetic. Later a creamy fluid is discharged which forms a thick crust. They sometimes ulcerate, and may co-exist with the form first described. The third form resembles erj'thema nodosum, and affects skin of trunk and extremities, but spares the face. The appearance of the eruption IS preceded by pruritus and pain in the afi^ected limbs, which may become oedematous. The fourth form is furuncular, and the fifth eczematoua in character. (Voisin, Gi7z. dts Hopitaux^ 1868, p. 6o;j.)

4. There appear in certain individuals, according to their specific disposition, independently of sex and previous condition of healthy at different periods during the administration of this drug, and under th€ widest variation as regards dose, various affections of the skin, such as :

(i) The erythematous form. — This was observed by Veiel as the sole symptom produced by the drug, attended with fever, and diffusely spread over the lower extremities. The erythema caused the patient great pain. Brown also describes this eruption as an effect of bromide of potassium. In children he witnessed the occurrence of roseola under the same circumstances.

(2) Acne. — This is by far the most frequent form of bromide of potassium eruption. According to Veiel a thickened skin, having a greasy look from the free secretion of sebaceous matter, as well as the presence of comedones or a pre-existing acne, especially predispose to the occurrence of this eruption. It appears under different modifications which, as regards their seat and their external behaviour, present a complete analogy to ordinary acne. The first step in its formation is usually an erythematous condition of the skin of varying extent attended with pricking and burning. In this disease, also, it is advantageous to distinguish two varieties, acne punctata and acne pustulosa.

a. Acne punctata. — This usually precedes the pustular form. There appear red elevations, of barley-corn to pea size, on a more or less indurated base surrounded by an areola, seated by preference on the face, the eyebrows, the hairy scalp, more rarely on the breast and back, and almost never on the lower extremities. Veiel found that the majority of the nodules were perforated by hairs. After a longer or shorter duration this form may disappear with desijuamation or develop into:

b. Acne pustulosa. — This may be regarded either as the result of disintegration of the papules or as an independent form of eruption. The pustules are at first of pin-head size, of a yellowish -white colour^ and surrounded by an areola. They afterwards increase in size, and in rare cases, according to Voisin, may present the aspect of ecthyma pustules. After a few days or weeks the pustule empties out its contents and a firm nodule or a red spot remains behind. The number of the pustules varies greatly, the whole face being sometimes covered and disfigured by them. They may remain for days or one or more months, and, if the use of the drug be not stopped, even several years ; but they usually disappear in from one to three weeks after the discontinuance of the bromide. Voisin also noticed that the number of the pustules increased or diminished with the increase or diminution of the dose. After healing they often leave depressed, irregularly-rounded scars or spots behind. They form on the same locations as the nodules previously described, and become confluent in some cases, being usually covered with scabs on the scalp. Veiel sought in vain for bromine in the contents of the acne pustules, but could find it only in the urine. Guttmann, in the case of a man who, after using for t year at first 4 grms. (5J) later 12 grms. (jiijj of the bromide of potassium daily, developed a pustular acne, succeeded in demonstrating the presence of bromine in the pustules by the usual method, viz. separating the bromine from the potassium by the addition of chlorine water to the diluted and filtered pus and extracting the bromine by chloroform.

(3) The urticaria-like form was observed a few times by Veiel. Wheal-like elevations, varying in size from \ to ^ an inch, showed

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themselves in erythematous portions of skin. They were exceedingly sensitive to touch and gradually assumed a wart-like appearance and took on suppurative action. The ulcers thus formed became deeper, and had an unhealthy aspect, but disappeared as soon as the bromide was discontinued. This form is without doubt identical with the tumour-like variety described by Voisin^ which consists, according to his description, in the appearance of oblong or rounded tumours of elevations of the skin with hard bases, 2 to 5 centimetres (i^to2 inches) in diameter, and of a rosy-red or cherry colour. They show themselves only on the legs or calves and are covered with small yellowish prominences, which, on careful examination, are seen to be agminated acne-like pustules, which empty their contents in the form of a creamy mass, either spontaneously or when punctured. They arc very painful when touched, and may be transformed, if the use of the drug is continued, into foul atonic ulcers, which last three or tour months ; but if the agent is stopped disappear in a few d. Neumann observxd the same affection. He proved that these tumours arc produced by an inflammation of the glands of the skin, attended with an increase of their cellular elements and consecutive cell-growth in the cutis, with enlargement of the papillae. During this process the hair-foUtcles arc dilated, and appear either as long tubes or globular bodies, containing pus, epithelial cells, and masses of smegma.

(4) Erythema nodosum.^ — In 2 cases out of 96, treated for a long time with bromide of potassium, Voisin witnessed the appearance on the arms and legs, as well as on the body, of patches slightly elevated above the skin, of different forms, sometimes having smooth and sometimes irregular edges. They attained a size of 4 millimetres to 6 centi* metres (^ to 2i inches), were of a pale red colour in the centre and cherry- red in the periphery. They formed and disappeared very quickly and presented the shape, colour, and hard base of erythema nodosum^ but resembled urticaria in reappearing when rubbed. V eiel states that he has seen such an erythema nodosum a few times, but only on the lower extremities* After large doses of bromide of potassium, Smith also saw patches of the size of a half-dollar, somewhat elevated above the surface of the skin, of a bluish-red colour, seated upon both arms. They bled readily, were indolent, and disappeared soon after the drug was discontinued.

(5) The vesicular form. — Voisin saw in a single case, that of a patient who had taken bromide of potassium for more than a year, a moist eczema on the thighs. This observation stands alone in literature,

(6) The furuncular form, — The coincidence of the use of bromide of potassium with the apj^earance of furuncles has been asserted by so many authors that there can be no doubt that the two things may stand in the relation of cause and effect. Voisin, Smith and Neumann saw furuncles occur in widely varying numbers on many different parts of the body. The latter observed them on the hairy portions of the facci and on the forehead and neck. It should be finally mentioned that Vciel witnessed the appearance of numerous warts on the face and legs of a boy, a short time after beginning the use of bromide of potassium.

Various opinions prevail as to the manner in which the above*

described changes in the skin are produced after the internal administration of the bromine salts. Thus Clarke and Amory regard bromineacne as a cropho-neurosis, and not as an efFect of the eliminated bromide of potassium, and Veiel also does not believe that it is due to an irritation of the sebaceous glands produced by the deposition of bromine in them, having failed to find it there. Martin-Damourette and Pelvet, on the other hand, believe the cause of the affection to be the irritation produced upon the skin in consequence of the elimination of the salt by this channel. The demonstration by Guttmann of bromide of potassium in the contents of the pustules elevates into a certainty the tf^r/W already probable hypothesis, that, under certain circumstances, an elimination of the salt by the skin may take place. In this way, on the one hand^ an analogy is established with the similar changes in the skin which are excited by the salts of iodine, and, on the other, the view is supported that it is the bromine in the bromide of potassium which causes the affection, and not the potassium, as has been claimed by various authors. This is rendered more probable by the fact that other bromine combinations exert a similar influence. Thus Gowers showed that similar eruptions appear after the use of bromide of ammonium, and Stark saw acne occur in 75 p'er cent, of all cases of epilepsy treated with bromide of sodium, which lasted longer than that produced by bromide of potassium, and resulted much more frequently in suppuration. He never found affections of the skin after a similar ad* ministration of chlorate of potassium. (Lewin, op, cit,)

1. All the above-mentioned changes in brain and spinal cord, circulation, generative organs, and skin, are also seen as the result of chronic poisoning. In the latter case, however, we have also bronchial catarrh, with dyspnoea and attacks of coughing resembling those of whooping-cough,* disturbances of nutrition (want of appetite, great thirst, and diarrhoea), anaemia, and wasting. Death may set in through the development of a pneumonic process in the lungs, or of an intestinal catarrh with typhoid or choleriform symptoms. (Nothnagel and RossBACH^ op, cit.)

2. From the experiments of Bill and Rabuteau it appears that tissue change is retarded under the influence of bromides. The ibrmer especially noted that the carbonic acid eliminated was decidedly less than normal, and this independently of diminished nerve-power y and not proportionately to the dose, as it is with morphia and its congeners. For some time after ceasing the medicine the excretion of the gas was increased, implying that, for a time, ^' the way through the lungs was barred.^' Rabuteau found that whilst his average daily excretion of urea was 2125 grms., the mean amount passed whilst he took a daily dose of 15 gr. of K. br. was only 1952 grms. j for a fortnight after omitting drug it remained at 20 grms. ; in third week resumed its normal proportion ; and in fourth week exceeded this. (Phillips, op. cit,)

3. Dr. Hammond relates a series of cases in which the use of K. br. has seemed to bring on mania, or melancholia with delusions. [As all

• *• In a few patients Voisin observed dyspnoea and an irritating croupy cough " (BOEHM, he. cH.}.

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ihese patients had disease of the nervous centres, their symptoms are insufficiently pure to be reported in detail j but the observation must be noted as suggesting further inquiry .^ — Eos.] (DIs, of Mtruous System^ 1 88 1, appendix.)

III. Expertmenti on animals, — i. a. In 1867 Drs. Eulenberg and Gutmann performed a series of experiments on rabbits and frogs, by injecting a solution under the skin; from which they concluded that K. br. exercises a powerfully sedative action directly upon the heart, and also upon the cerebro-spinal centres which control sensibility and motility.

h. Soon afterwards a still more complete investigation of the subject was made by MM. Martin-Damourette and Pelvet. They made use of rabbits, birds, and frogs in their experiments, and found the effects of the medicine identical in all, so far as their nature was concerned, but most easily studied in cold-blooded animals. When administered hypodermically to frogs, doses of gr. j^^^ to ^ produce a remarkably placid and slumberous condition, slowing hearths action and contracting capillaries; and doses of gr. i to i may cause death. In the latter case there is sometimes a transient muscular quivering, soon followed by impaired sensibility and muscular power, which is first manifested near point of introduction. Paralysis of motion precedes that of sensation. The nerve supplying a limb does not lose its excitability until after extinction of that function in the skin, nor does that part of the spinal marrow answering to the nerve lose this function so soon as the nerve itself. Voluntary motion appears to be abolished subsequently, and the respiratory movements at a still later period. One of the first effects is a diminution of the capillary circulation. The rate of movement of the blood through the vessels is first diminished, and then the skin grows pale ; the action of the heart becomes more languid, but continues with a steady diminution until death, and indeed may survive the other vital phenomena for several hours. (Stillb, ^p. cit,)

1. The evidence is, I think, sufficient to prove that K. br. affects all parts of the nervous system of the lower animals ; but that the cerebrum, the motor tract of the cord, and the afferent nerves are the last portions to he affected \ that the most sensitive to its action is the receptive portion of the cord, — that which receives and transmits reflex impulses, — and next to this, and perhaps almost equally susceptible with it, are the peripheral ends of the afferent nerves. (H. C. Wood, ttp. cit,)

2. K* br., when given for several weeks together, according to Albertoni greatly diminishes the excitability of the motor centres, so that when dogs are thoroughly under its influence it is almost impossible to produce epileptic convulsions by irritation of the cortical substance. (Brunton, ^p, cit*)

3. Damourette and Saison, as well as Meuriot, Hammond, and Amory, have witnessed narrowing of vessels in the web, the tongue, or the brain of frogs and dogs ; but others have failed to see this, and Dn H C* Wood considers the evidence insufficient j neither does the observation that divided capillaries of a bromised frog bleed less than normal ones seem free from criticism, for he suggests that lowered

heart's action would account for lessened bleeding. But, these observations apart, I think that the surface pallor that follows the use of bromides, and the lessening of secretion and discharge, points strongly in the same direction (narrowing of vessels). (Phillips, op, cit,)

1. Forty gr., in \ oz. water, injected into jugular of strong greyhound. Had tetanic spasm, with tumultuous and irregular action of heart, and discharge of urine and faeces ; 20 m. after appeared well. Eighty gr. were then injected. Sudden cessation of motion of heart and of respiration^ along with opisthotonos, lasting i^ m., with loss of urine. After this, drew two deep inspirations ; universal trembling of muscles for 3 m., and then cessation of every sign of life. Chest was immediately opened ; voluntary muscles contracted on being cut ; lungs collapsed on opening chest ; heart was without motion ; had lost its irritability in less than 2 m. after death. Heart was gorged with clotted blood, red in 1. ventricle, dark coloured in r. Lungs appeared healthy \ tips of rugae of stomach were somewhat redder than natural. (Glover, lo€. cit,)

2. Sixty gr. in \ oz. water injected into jugular of French poodle. Symptoms were stertorous breathing, escape of urine and fxces, tumultuous and irregular action of heart, which suddenly ceased, frothing at mouth, cries, dilated pupil \ death before animal could be untied, in about 2 m. after injection. On being cut, voluntary muscles contracted strongly ; 5 m. after death heart had lost irritability, and was gorged with fluid blood, red in 1. ventricle. Lungs healthy. {Ibid,)

3. Twenty gr. in 5iss water into jugular of bitch. Death in 40 or 50 seconds. Symptoms: sudden stoppage of hearty preceded by stertorous respirations, escape of urine and faeces, and dilated pupil. Heart had lost irritability, and was gorged with blood, fluid in r. ventricle, red and coagulated in 1. {Ibid,)

4. Haemadynamometer was connected with femoral artery of terrier ; 60 gr. in \ oz. water injected into carotid in direction of heart. Previously to this, mercury was raised 2 inches and 8 lines. As solution was introduced, pressure in instrument was augmented till mercury had risen 5 inches. This elevation was only for i m., during which oscillations were also greater, owing perhaps to struggles and hard breathing. After 1 m. mercury suddenly fell below former level, and continued to fall, until in about 2 m. and 20 seconds all pressure in arterial system seemed removed ; death in 2^ m. after injection. Animal voided urine and faeces during experiment, and seemed spasmodically agitated. Appearances much the same, on inspecting chest, as in experiments where injection was made in jugular. Brain healthy. (Ibid,)

5. Forty gr. in 5iij of water injected into femoral artery of terrierbitch in direction of circulation. Spasmodic extension of limb was followed by spasmodic action of muscles of chest, and by extension of other limbs», with excited heart and dilated pupil. This lasted 5 m. and then subsided. {Ibid.)

6. A hundred gr. in 5iij water into stomach of rabbit. 5 m. after fell flat on belly. Loss of power over hind legs ; made ineffectual eflbrts to crawl. Breathing became quicker, embarrassed^ and abdominal. Heart irregular and feeble. This lasted \ h., during which faeces twice

6i8

escaped, and iris seemed paralysed. Eyelids winked j a stroke appeared to excite convulsive strikings-out of the limbs* Towards dose of ^ h. seemed greatly agitated, recovered for short time use of limbs. Head was moved forwards ^nd backwards with great velocity, body beni in crouchiijg torm while on his legs, Had then cmprosihotonoa and opisthotonos. At length fell on his side, and had rapid movements of forelegs for i m. and died after few deep inspirations. Muscles contracted feebly on being cut* Auricles contracted tcebly ; ventricles did not respond to stimulus of knife a m, after death. Peristaltic action continued* Lungs greatly congested toward dependent part, and coataiiicd much frothy scrum. Pericardium contained serum ; blood dark coloured and fluid in both heart^cavities. Stomach contracted towards pylorus, loose at cardiac extremity. On washing stomach, epithelium came off* Mucous membrane over cardiac portion was softened, grey, but dotted with numerous purple ecchymoses. Beneath, muscular tunic greatly congested* Large bloody patch where oesophagus enters stomach, another at lower portion of cardiac sac* Upper part of small intestines exhibited appearances approaching those of stomach. Lower part of liver darker coloured than natural. Mem* branes of spinal cord showed marks* of congestion, and there was some effusion of serum into ventricles of brain. Bladder full. Brom. in blood, liver, and urine, {Ibid,)

Volume IV — Appendix

KALI BROMATUM.

(See vol. i, p. 606.)

1. II. Dr. FiNCKE relates a case of a young surgeon who took 10 er. in one dose ' for excessive sexual excitement after mental overw(^." He immediately had burning in stomach, going on to aching and empty "gone " feeling, relieved by eating, lasting i — 2 d. These maj have been effects of the dose on a sensitive subject ; but we cannot so reckon excessive diuresis, lasting a week ; then " neuralgia of spine" for i — ad. ; then dysuria, followed by ' regular gonorrhoea.*' {Tht OrganoH^ i, 343.)

2. An epileptic woman who during her pregnancy took daily 2 grm. of K. br. was delivered of an apparently healthy child. But the infant, which slept continually, and nursed only twice a day, steadily declined. After 19 d. it was emaciated, wrinkled, and oldlooking} pulse 86; resp. not over 10 per m., accompanied by a whistling glottis-murmur; general anaesthesia. The urine in the

starched diapers showed the reaction of amylum bromatum, The child was weaned, The following d. there was erysipelas of face and neck, and numerous acne pustules on hands, feet, and buttocks. On the 3rd d. the bromine disappeared from the urine ; and the child got well. (Gaz, des Hip., 1881, p. 136.)