complete, by Thomas Layton,* you will find precious indications concerning this loss of weight, in different febrile processes. In typhoid fever the mean loss of weight is 238.672 grms. per day; in pneumonia it is 387.6 grms.; in acute articular rheumatism, 386.8 grms. These averages have only a relative value. What it is important to know is the march of this loss of weight in the course of a continued fever. This is what Thomas Layton has not shown very conclusively, and I must protest against one of his affirmations, that in acute febrile maladies the loss of weight is uniformly descending.

and the mildness or gravity of the fever depends on the greater or less facility with which this elimination goes on. There are even at certain moments periods of discharge, during which the economy eliminates immense quantities of these extractive matters. These are the "crises" which we witness in the course of continued fevers.

But these extractive principles which thus accumulate in the blood, and which result from the disintegration of the organism, are not the only toxic principles which poison the economy in continued fevers. We are obliged to add the ptomaines and the leucomaines, which take their origin, on the one hand, from septic processes which go on in the

Therefore I propose to take up anew this question by instituting daily weighings of my typhoid fever patients, and by comparing the temperature, the urea-production, and the diminution of weight. This is a work of no little magnitude, which will require a long time, but which will enable me, I believe, positively to demonstrate that in typhoid fever the denutrition does not follow, as Monneret and Layton think, a uniformly descending course, and that, on the contrary, it is vastly more pronounced at the decline of the febrile process and in the first period of convalescence.

But this is only one aspect of the question. There is another which presents still greater interest, namely, the ascertainment of what becomes of the products which result from the disintegration of the organism. This point has been particularly well studied recently by our colleague, Albert Robin. This clinical experimenter has shown us that these products of disintegration accumulate in the economy, and to such an extent that you will find, for instance, in the blood of typhoid patients as much as seven and even nine per cent. of extractive matters, while in the normal state the proportion does not exceed four or four and one-half per cent. The extractive matters are eliminated chiefly by the urine, but also by the fæces and perspiration;

* Layton, "Clinical Study on the Influence of Causes which alter the Bodily Weight of the Adult Sick Person." (Thèse de Paris, 1868.)

presence there of micro-organisms or bacilli. Bouchard and Lépine have clearly shown by the examination of the urine of typhoid patients and its toxic effects the presence of these different products. Thus it is that Lépine has demonstrated that in the normal state the organic matters (products of disintegration) compose but fifteen per cent. of the total toxic ingredients of the urine, while in the febrile state the proportion is as high as forty-five per cent.

From all that goes before, it results, then, that in febrile processes, and in particular in typhoid fever, the digestive tube is not in a fit condition, on the one hand, for the absorption of albuminoid matters, and, on the other hand, the products of organic disintegration accumulate in the system and produce toxic phenomena.

What can be the rôle of alimentation in such cases? Dietetics have a very limited rôle, because only substances which are liquid and charged with salts can penetrate the economy, while albuminoids and fats find in the altered state of the lacteals a serious obstacle to their absorption. In the case which we have under supposition, of typhoid fever, the fatty and albuminoid principles will be furnished, not by the food ingested, but by the individual, who will consume his own fat and muscles.

Reduced to this simple question of the penetration of saline and aqueous matters, diet does not the less play a considerable part in the course of febrile maladies, on condition, however, that the food administered shall be of a liquid nature. The milk and broth which we give to typhoid patients allow us to introduce, on the one hand, a large quantity of water, and, on the other hand, salines in considerable amount. In typhoid

fever, as Albert Robin has well shown, there is a veritable mineral inanition, resulting from the daily losses in potassium, in sulphuric acid, in phosphoric acid, and in chloride of sodium,-losses which take place by the urine, and which amount to 3 or 4 gms. of chloride of sodium, 1.50 gms. to 2 gms. of phosphoric acid, 2.967 gms. of sulphuric acid, and 1.730 gms. of potassium. If you will now refer to the analysis of broth which I gave you in one of the first lectures, and which I here repeat, you will see how well this analysis corresponds to the incessant losses of typhoid patients in saline matters:

Can the same be affirmed with regard to milk? Yes, to a certain extent. By the water and the saline substances which it contains, and which strikingly resemble those of serum, milk responds well to the indication for a liquid and saline nourishment in febrile maladies. But milk contains albuminoids and fats besides. What rôle do these ingredients play? Do they act as food, or are they rejected without being absorbed? We are entirely ignorant; and careful experiments, made with the scales, between typhoid patients fed exclusively with broth and such as have been fed exclusively with milk, will alone enable us to solve this question. For myself, I believe that milk does good in febrile maladies only by the water and saline substances which it contains.

If the saline principles which enter into the composition of foods are suitable for repairing the incessant saline losses of fever patients, the water which is a part of these same aliments answers quite another end,namely, that of promoting elimination by the urine of the extractive matters accumulated in the economy. This end will be fulfilled not only by the aqueous foods, such as broth and milk, but also by the ptisans, at the head of which we must place lemonade, and this not only by reason of its agreeable taste, but also because quite special antifebrile properties have been attributed to the lemon.

The Arabian physicians, and in particular Isach-Ibn-Amrem, have since a remote period pointed out the advantageous action of lemon

pulp in fevers; and Maglieri, who has lately made trials of this simple remedy in Italy, affirms that the decoction of lemon is equal, if not superior, to quinine. Without going as far as this, one may admit that lemonade fulfils a useful rôle in fevers by introducing water and certain saline principles. But there is a point which ought to arrest our attention a little longer. I refer to wine and the alcohols.

Wine and alcohol have been for ages utilized in the treatment of acute diseases, and in the works of Hippocrates we find frequent allusions to the employment of wine as a tonic and stimulant. But it must be remembered that it is only within the last twenty-six years -that is to say, since the publication of Robert Bentley Todd's classical work,-that alcohol has been methodically employed as a part of the routine treatment of inflammatory and febrile diseases. Todd, in the propositions which he lays down with reference to acute diseases, maintains that the duty of the physician is to find the best means for supporting the vital forces in acute diseases whose natural evolution is towards cure. According to Todd, there is no means for sustaining the vital forces so efficacious as alcohol.

My regretted master, Behier, was one of the most earnest advocates of Todd's method, and it was soon the fashion in France to treat all acute inflammations, such as pneumonia, by alcoholic stimulants. Jaccoud has given in this regard some statistics borrowed from Bennett, which are very favorable to this kind of treatment, out of one hundred and twenty cases of pneumonia the mortality being but about three per cent. In cases of treatment by pure expectancy, the mortality rose to 7.4 per cent., and this was strikingly contrasted with a death-rate of from sixteen to thirty-four per cent. in pneumonias treated by bloodletting and tartar emetic.

This same method has been applied to the therapy of fevers. Fourrier, of Compiègne, showed us in 1873 the good effects which he had derived from alcoholic stimulants in typhoid fever.* Burdel, moreover, has called our attention to the advantages of wine in malarial fevers, and curious instances have been mentioned of individuals affected with intermittent fever rebellious to all other means of treatment, who were cured by dosing them freely with alcohol. Todd had observed similar cases.

To-day, now that the enthusiasm which was

*Fourrier, Bull. de Thér., t. 85, p. 241.

at first awakened by the publication of Todd's views and the results of his practice has subsided, there is, nevertheless, unanimity in recognizing the great advantages of the alcoholic medication in acute febrile maladies. It is more especially in the adynamic forms of these affections that the alcohols are indi- | cated. They also give excellent results in the two extremes of life, infancy and old age. In infancy, as our colleague, Gingeot, has well shown,* alcohol is remarkably well borne, and gives the best results in the treatment of pneumonia; this is also the case in old age. Add, lastly, that in the case of persons addicted to the free use of alcohol, when they are attacked by acute diseases, grave symptoms are almost sure to supervene if the usage of alcoholic stimulants is abruptly suppressed, and we see the necessity in such patients of maintaining the treatment instituted by Todd.

To sum up, then, it is in fevers of an adynamic kind, in the extreme periods of life, and in patients of intemperate habits, that we find the three great indications for the use of alcohol in febrile maladies.

Others

If everybody is agreed in recognizing the good effects of the tonic medication in these diseases, this unanimity ceases when we endeavor to explain what is the mechanism of this favorable action. Some, as Gubler, see in alcohol only a dynamic or force-giving medicament, which acts in fevers by sustaining and augmenting the vital powers. consider alcohol as an antithermic medicine, which brings down the temperature and opposes hyperthermia. Still others maintain (and among them Albert Robin) that alcohol opposes organic disintegration, while augmenting the quantity of oxygen inhaled; others, lastly, affirm that alcohol acts only as a food.

For my part, I have deeply studied this question of the physiological action of alcohol, and I believe that all these views are to a certain extent true, and that alcohol acts at once as a food, as a tonic, and as an antithermic; and it is this threefold action which explains its utility in the treatment of acute febrile maladies. I believe alcohol to be a food, and claim that it undergoes a more or less complete combustion in the organism; but this combustion takes place at the expense of the oxygen of the blood. On this account alcohol retards the organic combustions and lowers the temperature; in fact, as Marveaud

Gingeot, "Treatment of Pneumonia of Children by Alcohol." (Thèse de Paris.)

has maintained, it is a waste-restraining aliment. But it acts also unchanged on the nerve-centres, to which it communicates elements of strength and tonicity, and is a forceproducer, as Gubler regarded it.

In our hospital practice we are much in the habit of prescribing alcohol, under the form of Todd's potion, which consists of equal parts of rum or cognac and the potio diacode. (The potio diacode may be conveniently replaced by sweetened water.—TR.)

In private practice I think that it is better to discard Todd's potion, and the various modifications thereof, and to substitute certain wines rich in alcohol, such as the Spanish, Portuguese, or Sicilian. These wines are much more agreeable than Todd's mixture. It is desirable to obtain such wines in their purity, which is easier far than to obtain pure brandy, the brandies of commerce being generally an artificial rather than a natural product.

To sum up, gentlemen, diet in febrile maladies, and, in particular, in typhoid fever, ought to consist of liquid substances, containing, besides the water of their composition, certain saline ingredients, tonic principles, and a very small percentage of albuminoid. principles.

But this regimen should be rigorously observed, especially in the terminal periods of typhoid fever, at the moment when, with the subsidence of the fever, the patient enters into convalescence.

The result

To repair the losses which prolonged inanition has inflicted on the organism, the fever patient, during the first period of convalescence, is possessed of an insatiable appetite, which causes him to devour everything offered him with avidity. He bolts his food whole, always craving for more. is, that the digestive tube is soon encumbered with a load of alimentary substances, which, in its weakened state, it is unable to digest; what with the irritation of the food, and the flatus produced by its decomposition, rupture of the intestines, with fatal peritonitis, is very likely to follow. This rupture is easily explained, when you think of the imperfectly cicatrized ulcers which exist in the ileum. Here, then, your earnest watchfulness ought to be exercised in enforcing extreme moderation in eating, and in permitting only such articles of food as are readily digestible, and are in a state which allows their speedy absorption, the daily rations being little by little augmented as the patient advances towards recovery.

Such, gentlemen, are the indications which I desired to present relative to diet in febrile maladies. I have done with this first part of hygienic therapeutics. I hope that this study of alimentary hygiene has proved of some interest, and that continually in your practice you will be enabled to apply the precepts which I have laid down. But only a part of my task is accomplished. In another series of lectures I shall complete this subject of hygienic therapeutics by taking up gymnastics, hydrotherapy, balneotherapy, aërotherapy, and climatotherapy, and we shall find under these different heads topics of great interest, and presenting a real utility.

CRITICAL OBSERVATIONS AND EXPERI MENTAL STUDIES ON THE INFLUENCE OF PHARMACOLOGICAL AGENTS ON PERIPHERAL VESSELS.

BY PROF. R. KOBERT.*

(Continued from page 14.)

PART II.

ANKE† makes the following assertion :

RAN

the

The walls of all vessels excepting the capillaries contain nerves which form a fine net-work under the adventitia. Also ganglionic cells have been discovered in the larger nerve-nets. According to W. Wundt, arteries and veins contain, like the heart, ganglia in their own walls which act as centres of innervation. Besides, they also receive their nervous supply from outside, and consequently depend, as far as their condition is concerned, on both an outward and an inward influence. The smaller arteries, in particular, are subjected to this double source of innervation.

According to Aubert, § the statements of observers vary materially as to the microscopic behavior of the vascular nerves. Ganglia seem to have been observed only by Beale || and Lehmann,¶ and by the latter exclusively in the vena cava of the frog. Arnold** has described and drawn a nerve-plexus, with nuclei and terminal nodes, in the muscular

* Chief of the Pharmacological Laboratory at Dorpat, Russia.

† Lehrbuch der Physiologie, p. 408. Ibid., p. 350. Hermann's Handbuch der Physiologie, Bd. i. p. 403; Comp. Bd. iv. p. 422.

|| Philos. Transact., 1864, p. 562.

¶ Zeitschrift für Wissenschaftliche Zoologie, xiv., 1864,

p. 369.

** Stricker's Gewebelehre, i., 1864, p. 346.

coat of a small artery. Henocque †† described several plexuses on the arterial walls. One

of these, the basic plexus, lies at the outer side of the tunica externa; another plexus, the intermediary one, lies in the tunica externa, is derived from the former, and contains nuclei, nodules, and ganglionic swellings; and, finally, an intramuscular plexus, which is derived from the former in the form of very thin fibres, and terminates in the muscles.

Gonjaew, however, and, following his example, Gscheidlen, §§ found in the arteries only one net situated in the adventitia, and another one, connected with this, and situated in. the muscular coat. Ganglionic cells could not be found by Gscheidlen, though he saw in the vena cava of the frog structures suggestive of ganglionic cells. The terminal reticula of the vaso-motor nerves in the capillaries have been described by Gonjaew and confirmed by Ch. Legros.

Rouget, Goltz, and the majority of the more recent physiologists, explain the dilatation of vessels, whenever it is independent of the blood-pressure, by the presence of a peculiar mechanism in them, which is allied to the inhibitory apparatus of the heart. other words, they claim that there exists in the walls of the vessels a special peripheral ganglionic apparatus which maintains the vessels constantly at a certain level of tension. The nervetracts connected with these ganglia either increase the activity of the former, and thus contract the vessels, or inhibit―i.e., decrease -their energy, and thus produce a dilatation of the vessels. According to B. v. Anrep and N. Cybulski, this latter hypothesis is in perfect accord with all the established facts of an

atomy and physiology.

The above quotations indicate that though the anatomists have not quite settled the question of the existence of these peripheral vascular ganglia, their presence is required from the physiological point of view. Goltz, with whom, when his assistant, I had often spoken of this subject, has somewhat modified his former view, inasmuch as he no longer insists upon the necessity of anatomically visible ganglia. He believes, however, that the walls contain some independent regulatory apparatus endowed with the power to dilate and contract the vascular lumen. And this

view I also hold myself. It cannot, of course, us here whether this regulatory mechanism refers solely to the muscular coat, or whether the tunica elastica and adventitia also participate in it.

It has likewise been a matter of discussion which portions of the circulatory system are subject to this contraction and dilatation of the lumen. Thus Eckhard speaks of an active dilatation of the capillaries. Again, other experimenters who have instituted investigations with digitalis and ergot, speak of a contraction of capillaries terminating in absolute disappearance.

I have never been able to distinguish any appreciable variations in the lumen of capillaries. On the other hand, all observers agree that arteries can contract and dilate, and that these variations of the lumen are particularly distinct in the smaller arteries. In veins a contraction has also been noticed by a few observers. At the exhibition of certain agents, of which I shall speak below, I have invariably seen this contraction, and feel disposed to interpret this phenomenon as an active change.

Speaking of the calibre of vessels, I wish to mention still another appearance which manifested itself in every experiment. As soon as the canules were fastened and the transfusion began, all vessels at first became filled and turgescent, and the organ assumed a highly sanguineous appearance. The vein also carried a copious stream, which was only from time to time interrupted by a larger coagulum, which had to be expelled. In this stage the organ had not yet attained complete vitality. As soon, however, as the temperature of the blood has been reached, a great contraction of all vessels is suddenly seen to set in, pallor takes the place of ruddiness, and the venous flow decreases considerably. This stage of active contraction has to pass off first before a regular flow and the beginning of measurement can be thought of. As to the quantity of the blood flowing off in a unit of time (a minute), I found this to vary materially, according to the nature and the size of the organ. On isolated portions of a rabbit's uterus the quantity, of course, was very small, amounting frequently to less than I c.C. On the hind part of a dog or the kidneys of a horse the quantity was often less than 100 C.C. And on account of these great variations it is of little value to state on the record the absolute figures obtained from minute to minute. This would only render a comparison of the single trials more difficult.

I have, therefore, only stated how many per cent. the off-flowing quantity changed when the height of action of the single agents had been reached. As can be seen by a glance at the accompanying charts, this change was very trifling in some agents, and, again, quite enormous in others. In another column it is stated how many milligrammes of the pharmacological agent had passed altogether. Another column contains the concentration of the latter in the blood, calculated for one litre. Besides, it is also stated how many minutes the poisoning had lasted. All other statements of the charts speak for themselves.

Many readers of this paper will, after inspection of these charts, probably ask why with a number of pharmacological agents I had only instituted one or two experiments, which, of course, must be entirely insufficient to definitely settle the question of the influence of these agents on the blood-vessels. In reply to such queries I would say that experiments of this nature are enormously expensive and laborious, and take up a very great deal of time. The execution of the work embodied by these researches, for example, has occupied no less than three and one-half years. To mention some of its difficulties, I will state that for the transfusion of a single dog's thigh two dogs are always required, one of which, besides, is to be of a rather large size. For the transfusion in a rabbit three animals are likewise always required. Of the bought organs many were found to be cut, and had therefore to be thrown away; others, again, were not fresh enough, and gave no uniform current, while others, again, were insufficiently freed from blood, and consequently gave no current at all. I have not kept any record of the number of experiments which I had to abandon on account of intervening hemorrhages, of deficiency of blood, of stoppage of the current, of bad regulation of temperature, or, finally, on account of access of air, but I know their number is large.

It is known that every alteration of the vascular calibre caused by a pharmacological agent is followed later by a compensatory alteration, however slight it may be. I have not paid sufficient attention to these compensatory alterations to create a special column in my charts for them. At all events these compensatory variations did not prevent me from examining often four various agents on the same organ during two consecutive hours. It is a matter of course that the poisoned blood had to be thrown away in each instance. In experi