and yet I notice that Ringer states that its efficacy has been denied, and I am myself conscious of having read English evidence to that effect, although I cannot now quote it. I do not believe, however, that a patient trial, on a wide enough scale, has yet been given to the chloride, and this it seems to be our bounden duty to do, whatever our expectations may be as to the results. We might also go further, and say, that the failure of KI to produce similar results to KBr does not seem in any way to exclude the possibility that potassium is the real active element in the latter. When we turn to the other side of the question and inquire for the evidence as to the activity of bromine, we are met, first, by the already mentioned comparative weakness and isolation of the statements in favour of the other bromides. The next question suggested by the clinical evidence already given is whether the bromides of sodium and ammonium agree with KBr in their "extra effects," viz. in the production of those toxic effects which sometimes so disagreeably complicate the use of KBr. It has been broadly asserted that they do not, but, I believe, without sufficient grounds. I can, at least, affirm that the acne-like rash, and also the mental confusion and loss of memory which KBr is well known to occasionally produce, have been seen by me, on more than one occasion, as the result of bromide of sodium; and that the mental confusion has been produced within my knowledge by bromide of ammonium. I have certainly never witnessed those more seriously inconvenient results first noticed by Hammond, viz. positive though temporary paralysis of the extremities, except as a result of KBr: but this may well be because I have used the latter in a far greater number of cases and for much longer periods of time. It is of course open to Dr. Binz to observe that it is not the toxic effects as to which we have to inquire, and that it may well be that these indeed are due to the bromine, while the therapeutical effects are altogether due to the potassium. To this idea we may oppose the fact, quantum valeat, that some of the most marked cases of success with KBr in epilepsy have been distinguished by an uncomfortable amount of these toxic symptoms.

When we examine the constructive part of Dr. Binz's paper, we find him suggesting, first (as already said), that potassium is the important element of KBr, and then, that it may produce

its effects in two ways-first, as a restorative having special influence upon cell-life, and particularly the formation of the blood-corpuscles; and secondly, by its depressing action upon the muscular force of the heart. In support of the first of these supposed functions, it may certainly be alleged that KBr, to a degree that is equalled by but few other drugs, requires to be administered with a persistency and in such large quantities as remind us of the properties of a food rather than of a medicine in the ordinary sense of the word. Dr. Binz himself appears to suggest that the large quantity of potassium which is thus taken is directly valuable; that it is in the nature of a useful excess, such as occurs with other well-known remedies with which one must (so to say) flush the organism before one gets any benefit, though theoretically a much smaller quantity should suffice. If that were so, however, I do not see why the bicarbonate should not answer the purpose; but I have several times given that salt to the extent of keeping up alkalinity of urine for as long as was consistent with safety, without producing the least effect on the course of epilepsy.

It is to be remarked that Dr. Reynolds was very clear in the statement of his opinion that the action of KBr is neither that of bromine nor that of potassium, but a specific something produced by the compound of the two. I believe he would now admit that a similar though somewhat weaker influence is exerted by NaBr; and although Dr. Binz has rather severely handled the evidence to the same effect which Dr. Hollis brought forward in this journal, I do not think it will be found possible, in the end, to exclude NaBr from the position of a direct anti-convulsive remedy, acting, so far as its powers extend, on the same lines with KBr. Here, again, as in the case of the potassium-salt, it is absolutely necessary to give large doses to produce decided effects yet we can hardly suppose that large quantities of sodium can produce any useful results in the direction to which Binz's interesting suggestions point. I would mention, as necessarily of high importance, the opinion of Dr. Weir Mitchell: this distinguished neuro-pathologist finds both the potassium and the sodium salt very useful in epilepsy; but he further states that there are some cases in which neither of these is effective, but the bromide of lithium will produce the desired

result.

On the other hand, the bromides of calcium and magnesium, and bromine itself, failed to control the epileptic fits. This is surely a very singular observation, and coming from Dr. Weir Mitchell it assumes an importance which can hardly be exaggerated. For want of space I cannot now indicate the manner in which it appears to me to affect the bromide question. Enough to say that it fully justifies scepticism on that question, in the proper sense of the word; viz., it allows and indeed renders necessary a spirit of doubt and inquiry as free as that of Dr. Binz himself. The question cannot be allowed to rest in its present obscurity: in fact, the very singularity of the nature of the conflict of opinions is almost a guarantee that we shall shortly be enabled to realise Dr. Binz's just aspiration for a scientific basis for the use of KBr.

I cannot close this paper without quoting a remark which may tend to show, better than anything cited above, the strength of conviction with which KBr impresses some English physicians by its effects in epilepsy. I lately asked one of the shrewdest and most experienced of our authorities on nervous diseases, what he thought of the results of the introduction of KBr? He replied: "It has changed the whole prognostic significance of epileptic attacks."

ON THE ANTIPYRETIC ACTION OF QUININE.

BY DR. CLIFFORD ALLBUTT.

THE progress of our knowledge of the nature of fever and of special febrile disorders, is not the least encouraging of the chapters of modern medicine. Beset and obscured by false hypotheses and its discussion impeded by false terms, the subject of fever was one of the most backward parts of our nosology; but since we have found that fever lends itself to direct investigation by physical methods, and even to quantitative estimation, we have been able of late to put it among the most forward parts of our science. We have made it a matter of common knowledge that fever is a disturbed balance, and that, like other disturbances of a moving equilibrium, it tends under favourable circumstances to resolution.

In particular the loss of balance is seen in a disturbed relation between the formation and loss of heat, and the vis medicatrix naturæ consists in the tendency to restoration of the normal balance as it is restored in a spinning top, after a fillip of the finger. We have to estimate the kind and degree of the disturbing force and its mode of application, and we have to estimate the spin or vitality of the system disturbed, and thus, if all the facts can be calculated, the result may be predicted. Many fevers arise from a single interference, which is not repeated, and the initial velocity and the subsequent course of the disturbance depend upon the character of this single interference. Amid much that is obscure we may notice as a rule that disturbances having a high initial velocity are sooner expended than those in which it is lower. Examples of this

are seen in the respective curves of scarlatina, typhus, and enteric fever. In the former two cases, the disturbing cause reaches its maximum almost at once; in the last, as it seems to reach its highest effect by a slower development, so also it recedes more slowly. In other cases of fever we have a constant repetition of the disturbing cause; as in septicemia or in the lesser varieties of that affection known as hectic. In the former instances we have large and probably frequent absorptions into the system, of material in a state of more rapid combustion than the blood: in hectic we have repeated small absorptions; as in phthisis, chronic diseases of bone, and the like. Clearly, then, there can be no universal antipyretic, but antipyretic methods must include modifications for each of these cases, and probably for others also. Our methods must be founded on a careful estimate of the greater initial velocities of some kinds of disturbance and their earlier resolution, of the more prolonged periods of other kinds with slower resolution, and of the repeated accessions of other kinds in obedience to a recurrent cause. A disturbing cause of high initial velocity and short duration may give us less alarm, and need less resistance, than a cause which will set up a period of disturbance of less intensity but of greater duration. Causes, again, which act less by impressing considerable periods of disturbance upon the system in obedience to one interference, and more by a series of repeated disturbances of short duration, will require other kinds of resistance. In the former cases we have to put the organism in the best position to recover its balance after a single disturbance of tolerably definite extent, in the last we have rather to prevent the repetitions of disturbance. In the former cases we have only to aid the vis medicatrix naturæ, that is, to favour the tendency of the moving systems to recover equilibrium and to resolve conflicting forces; in the last case we have less to do with the system and more to do in neutralising the agencies which keep up its oscillations. We must have means at hand, which shall deal with consequences in the former cases and with causes in the latter. The former means would be directly, and the latter indirectly, antipyretic. It seems clear that water baths are remedies of the former class, and that remedies like the sulphocarbolates are credited with virtues of the second class.