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out influence upon the vessels. Apomorphine, which, according to O. Bergmeister and E. Ludwig,* acts upon the cornea like cocaine, i.e., contracts the vessels,-appeared in my experiments just like cocaine, indifferent in regard to peripheral vessels. Emetine and

ergotine proved themselves to be wholly indifferent, which cannot be surprising regarding the latter drug, which my researches† have exposed as generally inert. Ergotinic acid, on the contrary, paralyzes not only the vasomotor centre, but also the peripheral vasomotoric nerves. Arsenic, strychnine, and nicotine were likewise wholly indifferent.

In regard to curare, it has often been said that it does not influence the blood-vessels, and that if a reduction of the pressure is at times observed, this is caused by an adulteration of the drug.

I cannot agree with this view, for I found that curarine obtained from Gehe-possessing a pure and strong curarine action-causes distinct vascular dilatation even in moderate doses. A similar action I obtained from Hofmeister's platinum base and methylhydroxide of caffeine. The former, as is well known, has nearly all the effects of curarine, and the latter, like all hydroxides of methyl, acts curare-like in some respects.

The soluble double salts of metals did not by any means act all alike.

Iron was in small doses indifferent, while it increased the velocity of the current in larger ones. Platinum, bismuth, antimony, and manganese caused, even in small doses, a distinct acceleration of the current, while mercury and copper acted just the reverse. Still, these investigations ought to be made on various organs, and not, as in my experiments, exclusively on the kidney, as the specific action of the metals on this organ possibly interferes with the interpretation of the results obtained. The same holds true of iodide of lithium, bromide of lithium, and carbonate of lithium, which I could likewise only examine on the kidney, where they accelerated the bloodcurrent, while I know nothing of their influence on the circulation in other organs.

Agents which, like carbonate of sodium, increase the alkalescence of the blood, increase the volume of the blood-current, while agents

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like sulphuric acid, which decrease the alkalescence, decrease also the volume of the current. The action of hydrochloric acid has been referred to above. In the action of oxalic acid and its sodium salt the formation of emboli probably causes the decrease of the velocity of the blood.

The ethereal oils, of which I examined oil of turpentine, oil of peppermint, oil of aniseseed, and oil of mustard, all act as accelerators of the blood-current.

Atropine causes an increase of the velocity of the off-flowing liquid, while muscarine and pilocarpine act just in the opposite manner, but not very intensely.

Chloride of barium, physostigmine, veratrine, antiarine, sabadilline, oleandrine, apocynine, scillaine, convallamarine, erythrophleîne, Schmiedeberg's digitaline and helleboreïne acted so intensely and persistently as vascular contractors in various organs that I was forced to conclude that this action of these drugs makes itself likewise manifest upon man. The experience of my own practice in fact teaches me that that exhibition of preparations of digitalis is followed by an intense vascular contraction. I believe, moreover, that this contraction also occurs in the veins. In German therapeutic books I find a remarkable confusion regarding this point. Thus, Cloetta, for example, says, even in the last edition of his text-book on therapeutics (p. 217), "Dilatation of the renal artery is one of the therapeutic effects of digitalis." The text-books published in the English language entertain likewise confused views in this respect. The view that the increase of blood-pressure caused by digitalis refers to a vascular contraction appeared early in pharmacological literature. Thus, we find it in the writing of Blake,¶¶ in 1839; Béranger Férande,** Oulmont†† and Segroux, L. Brunton,§§ Briesemann,|||| in 1867; Fothergill,¶¶¶ Gourvat,*** in 1871;

¶ Edinburgh Med. and Surg. Journ., vol. li., 1839, No. 139, p. 330; Journal of Physiology, iv., 1883, p. 365.

** Bull. de Thirap., lxxiii., 1867, pp. 145 and 202. †† Ibid., lxxii., Avril, 1867, p. 355.

‡‡ Gaz. Hebdom. (II. S.), iv., 1867, Nos. 8, 9, 11. 22 L. Brunton, "On Digitalis," etc., London, 1868; cf. Centr. f. d. Med. Wissen., 1868, p. 688.

C. Briesemann, "Microsc. Untersuch. über d. Wirk. d. Digit., Veratr. und Ergot. auf die Circulation," Inaug. Essay, Rostock, 1869.

¶¶ Brit. Med. Journ., 1871; 1st, 8th, 15th, 29th July, 5th August. No. 39, P.

*** Gaz. Med. de Paris (III. S.), t. xxv., 438, and No. 47, p. 534.

Ackermann,* in 1872; Brunton and A. B. Meyer, in 1873.

But the proofs presented by these authors were so little convincing that Böhnt and Görz§ regarded them justly as unsatisfactory and critically untenable. Herman Köhler, in 1876, confirmed the views of the two latter observers. W. Williams showed later very clearly that the influence of substances belonging to the digitalis group upon the heart was sufficiently intense to bring about an extraordinary increase in blood-pressure by itself.

Quite available are also the researches of Henry H. Donaldson and Lewis T. Stevens¶ in Baltimore, and Sidney Ringer and Harrington Sainsbury** in London. These authors, who examined the influence of the digitalis group on the vessels (without the heart) of cold-blooded animals, did not content themselves with the unreliable microscopic examination of vessels, but resorted to transfusions in turtles. Reliable transfusions on organs of warm-blooded animals with the digitalis group do not appear to have been made as yet, for the researches of S. Talma and A. J. von der Weyde are little convincing.

In the continuation of my paper which I hope soon to publish, the researches of these. authors will again be referred to.

I do not wish to draw from my own experiments the hasty conclusion that all members of the digitalis group cause a contraction of blood-vessels. Still, I must regard it as settled that some members of this group produce a pronounced vascular contraction. In the third part of this paper I shall treat of the members of the digitalis group having a different action.

The same action was manifested by the poison of toads in the transfusion of frogs,tt while in the transfusion of toads no alteration of the blood-volume was observed. Consequently, in the transfusion of toads with chloride of barium, helleboreïne, and digitalis, in

* Tagebl. d. 44, "Naturf. in Rostock," 1871; Deutsche Arch. f. Klin. Med., vol. xi., 1872; Volkmann's Sammlung Klin. Vortr., No. 48.

Journal of Anat. and Physiol. (II. S.), No. II, 1872, November, p. 135.

Dorp. Med. Zeitschr., iv., 1873, p. 64, and Pflüger's Arch., vol. v. p. 189.

Nicolai Görz, "Untersuch. über die Digitalisprepar.," etc., and " Beitrag zur Phys. Wirkung das Digit.," Inaug. Diss., Dorpat, 1873, p. 90.

"Handb. d. Phys. Therap.," p. 182.

Journ. of Physiol., vol. iv., 1883, p. 165.

** Medico-Chirurg. Transactions. London, 1884. tt Transfusions with blood, of course, and not with solutions of chloride of sodium, are here meant.

doses which in frogs cause a very great reduction of the current, no influence upon the vessels could be made out. These animals, as Vulpian has pointed out, are nearly insusceptible against poisoning by substances belonging to the toad-poison group,-i.e., the digitalis group. (Only if the poison is administered in large doses intoxication ensues.) Quite in concord with this is the fact that the poisoning with toad-poison or helleboreïne succeeds as well in the larvæ of toads as in those of frogs,-the larvæ of toads do not yet secrete any poison, and are consequently still unaccustomed to the action of this poison.

I have dwelt upon this difference of behavior between frogs and toads towards the substances of the digitalis group in bloodtransfusions so explicitly because I regard it as the best proof that the reduction of the off-flowing quantity caused by these agents is not the result of mechanical or chemical alterations of the blood or of any other secondary effect, but of an especial physiological action, which of course is only absent in such animals the organs of which are accustomed to poisons of this kind. In the same manner, for example, the organs of morphiophages would not react to small doses of morphine as the organs of other persons, or, in other words, no dilatation of blood-vessels would ensue in the former.

The experiments on cold-blooded animals I have also utilized in order to determine whether in transfusions of the whole animal the systolic cardiac stoppage sets in previous to the vascular contraction. If such be the case the vascular contraction would be a rather secondary phenomenon, would appear only when large doses are given, and would not take place in vita. In the determination of these points the results obtained of course differed according to whether the injection of the fluid (serum of rabbits) was sent in a centripetal (vena cava) or in a centrifugal (aorta) direction. In either case I obtained, however, provided the poison was added in a state of sufficient dilution, a distinct vascular contraction. From this fact I conclude that the vascular contraction caused by the digitalis group is not a post-mortem appearance, but belongs essentially to the physiological action of these drugs.

I need not add that I have often observed this phenomenon not only under the microscope but also with the unaided eye.

There was still to be determined whether the vascular contraction caused by digitalis is to be regarded as a muscular or as a nervous

effect. I have attempted the solution of this difficult problem in many different ways. Thus I tetanized, after the appearance of vascular contraction during transfusion of a curarized hind portion of a dog, the sciatic nerve by means of faradic currents, a procedure which previous to the poisoning with helleboreïne would have caused great vascular dilatation, exactly as in Bernstein's experiments. During the helleboreïne-poisoning, however, this dilatation did not appear, which can only mean that on account of a musculo-vascular spasm the nervous dilatation did not set in. In this connection I beg to recall the action of muscarine on the physostigmine heart, which is likewise negative, although the two drugs are actually not antidotal to each other.

I also transfused cold organs, and found that the agents having a reputed nervous

appears to have obtained similar results with chloride of barium. These differential results, according to the starting-points of the transfusion,-the hepatic artery or the portal vein,-can only be explained by the assumption that the muscular coat is very feebly developed in the portal vein, but strongly so in the hepatic artery. I consequently believe that these experiments can at the same time be regarded as proofs that the digitalis action is as purely of a muscular nature in regard to the blood-vessels as it is in regard to the heart.

(To be continued.)



action, such as atropine, morphine, and hy-NOT long ago, purely as a matter of curi

drate of chloral, did not produce any effects, while helleboreïne in a sufficient concentration acted very distinctly. It is unlikely that this vascular contraction taking place on cold organs is of nervous origin, for the nervous apparatus of warm-blooded animals do not react at a temperature of 15° to 20° C.

osity, I examined a patient, a lady of some 65 years of age, for the patellar reflex. I found it absent. The phenomenon to which this name has been given has received many synonymes, the most common of which are tendon reflex, knee-jerk, knee-phenomena, etc. It consists in an extension of the leg

A muscular action, on the other hand, is following a blow on the patellar tendon. Simwell possible at so low a temperature.

I also transfused a kidney which in midsummer had been exposed to decomposition for fifty hours, smelled rank, and showed a green-blue coloration; the transfusion was effected in the ordinary manner in the heatbox. While the most powerful agents of vascular dilatation produced no alteration in the current, I succeeded in this readily with the aid of convallamarine and helleboreïne. It is scarcely possible that after a decomposition of fifty hours nervous apparatus should still be functionally active, while this can be well presumed in regard to the smooth muscular organs.

Another series of experiments was instituted with the liver. I have inserted in the charts several experiments, which were executed by transfusing the liver from the artery. The organ was then found to react to the poison like any other organ. In transfusions from the portal vein all poisons, with the sole exception of those belonging to the digitalis group, proved rather inert.* Still, I succeeded several times in obtaining a reduction of the velocity of the current by means of helleboreïne and chloride of barium. Boehmt

* Schmiedeberg's Archiv, vol. iii., 1875, p. 216.

† Mosso's results do not agree with those of Boehm.

ilar phenomena occur sometimes following irritation of other tendons. The phenomenon is spoken of by writers in such a way as to lead the reader to suppose that it is always present in health. Indeed, most of them state distinctly that this is the case. Althaus, in a recent admirable work, says that he has never found it absent in a healthy person, "except in the two extremes of life. It is difficult or impossible to elicit it in some children before they have learned to walk, and also in decrepit old persons, where there appears to be no particular form of spinal disease" ("Sclerosis of Spinal Cord," p. 139). A. Charlton Bastian says, "The knee-jerk occurs in health, so that it is its absence which is of principal significance" (Quain's "Dict. of Med.," p. 1458). Gower speaks of the phenomenon as occurring in health, but does not refer to any exception ("Diseases of Nervous System"). Erb, one of the first to describe the phenomenon, refers to no exception to its occurrence in health, although he remarks in a general way, and in another place, that in some cases the reflexes are difficult to obtain (Ziemssen's "Cyclopædia of Practice of Medicine,” vol. xiii., Wood's ed.). Strümpel says that "after a blow on the tendon there occurs, almost without exception in a healthy person, a more

or less active contraction of the quadriceps by which the leg is extended" ("Lehrbuch der Speciellen Pathologie und Therapie," vol. ii. p. 64). The "almost," etc., here is of course a mere saving clause in case of contradiction.

Works on general practice which, without being very accurate or minute, reflect the drift of public opinion in the profession, are very nearly unanimous in the same direction. Loomis, in speaking of locomotor ataxia, says, "The abolition of the patellar tendon reflex is one of the diagnostic signs of the disease." Eichorst, in "Wood's Library," says, "This is one of the earliest symptoms of ataxia. Its appearance indicates the existence of foci of degeneration in the external portions of the posterior columns in the upper lumbar region of its transition to the dorsal region." Such quotations might be multiplied indefinitely. It is plain, therefore, that the presence or absence of this symptom deserves attention.

Observers are not agreed as to the causation of this phenomenon. The prevalent opinion, however, is that of Erb, that it is a true reflex produced by an irritation of the sensitive nerves of the tendon, which is conveyed to the spinal cord through the posterior roots, and to the motor cells of the anterior horns, where a motor impulse arises, which is conveyed to the muscle. "The reflex centre is in the lumbar region of the cord, in the parts corresponding to the second, third, and fourth lumbar nerves" (Bramwell).

The phenomenon occurs quite independently of the brain, and must occur so long as the machinery by which it is produced is in proper order, just as certainly as the pupil responds to light, or any other of the ordinary reflex phenomena, the disturbance which interferes with the production of the phenomena being of course in the large majority of instances some disturbance in the spinal segment. Prominent among these is the sclerosis of the posterior columns, constituting locomotor ataxia on the one hand and degeneration of the motor cells on the other.

But the person mentioned above is healthy in all respects, and especially so as regards the spinal cord. She is an artist, and, in skill of hand and accuracy of eye, few, even among young professionals, are her equal. She is a good walker, and almost as sure of foot as in her younger days. So far as I could learn, she has never had the slightest symptom that could be considered as indicating disease of the cord. The examination, however, is open to criticism. The percussion of the tendon.

was done over the clothing, and it is possible that it was not sharp enough to irritate the nerves of the tendon sufficiently, or possibly there may have been an active contraction of the hamstring muscles sufficient to prevent the reflex, though the percussion was repeated many times when she was not looking. I could hardly ask her to allow an examination thorough enough to remove all these doubts, without some other reason than the gratification of mere curiosity.

Althaus says, "The phenomenon may be obtained when the patient is sitting in a chair, and crosses one leg over the other; but, where the legs are short and stout, it is better to let him sit on the table, with the legs hanging down. Where the patient is examined in bed, the limb should be raised by the observer passing his left hand underneath the thigh just above the knee, and giving the tap with the right hand. In general it is not necessary for the patient to be undressed, but where the result is doubtful it is always best to strike the bare skin over the tendon, and it may be useful, especially where the patient appears nervous and excitable, to have his eyes bandaged, so that any interference on his part with the production of the phenomenon may be prevented" (p. 132).

Strümpel says, "In order to call forth the symptom, it is specially necessary that the person investigated shall avoid all active tension of the muscles of the leg, especially the extensor cruris" (p. 64).

I have seen sometimes, from the hands of persons who would feel hurt if they were called clumsy, so heavy a blow given as to produce a vibration that might be mistaken for the reflex phenomenon. The blow should be sharp and quick, from something not too heavy, so as to give an irritation at some depth without jarring the limb. A vigorous contraction of the muscles of the arms will increase the reflex in doubtful cases.

I have examined a good many healthy persons for this symptom since it was first described by Westphal, and have frequently found it absent. These examinations, however, have usually been deficient in some point necessary for scientific completeness. Either precaution was not taken to be sure that the blow was sharp enough to produce sufficient irritation, or the possibility of an involuntary contraction of the muscle was not provided against beyond the possibility of doubt, or the presence of some slight symptom of tabes was not carefully enough inquired into to prevent the possibility of doubt. In many of these

cases, also, no memoranda were made, so that they could be referred to again, and many of the phenomena have slipped from my memory altogether, or the details have become so obscure as to be valueless. But I have one case in which all these conditions have been fulfilled, and that is myself. I have been repeatedly examined for the tendon reflex during the last ten years under circumstances which will admit of no doubt, and the reflex has always been absent. I have never had a symptom of tabes, or any other spinal trouble, and I am sure that those who know me will agree that I have at least as much endurance of fatigue, and as good control of my muscles, as the average healthy man.

It is possible, then, for the reflex to be absent in health, and probably in a large percentage of cases. The persons in whom I have found the reflex absent are all persons of considerable muscular power and of a high degree of tonicity of the muscles, and especially persons of considerable inhibitory power, persons who do not lose self-control by any sudden shock. I suspect that the majority of those who have the reflex are persons of weak nerves and undisciplined muscles, who would scream if some one jumped out upon them from a dark passage, or would be unnerved by a sudden danger,-such persons would be the ones likely to come under the observation of hospital physicians. I doubt whether a hunter who retained his presence of mind upon seeing a grizzly bear suddenly rushing out upon him from a thicket would have much of the reflex, while another who had buck fever upon sight of a deer probably would have it well marked. It certainly is exaggerated in hysterical and neurasthenic cases in whom the inhibitory power is weak. The absence of the reflex is considered to be one of the very earliest symptoms of locomotor ataxia. Strümpel says, "The loss of the patellar reflex is the most constant of all the known symptoms of tabes; it is, indeed, observable so early that the time of its appearance can scarcely ever be determined" (p. 201). And, again, p. 211, "A symptom almost constant and of the highest diagnostic value is the loss of the tendon reflexes, especially the patellar reflex. As already mentioned, the extinction of this reflex is one of the earliest symptoms of the disease, which is of the very greatest significance," etc. It is often almost the only means of distinguishing between locomotor ataxia and certain conditions occurring in neurasthenia and in other affections which may simulate locomotor ataxia, and its im

portance as a symptom is growing in favor. But if these observations are correct it loses immensely in value. The temptation to theorize is strong, but I will refrain, and only call attention to a recent article by Prof. Hirt in the Berliner Klinische Wochenschrift for March 8, 1886, in which he describes three cases of locomotor ataxia with retained patellar reflex. After some general remarks, he describes the cases as follows:

"On the 25th of April, 1884, Moriz W., a moulder, from Upper Silesia, came under treatment at my polyclinic. The patient stated that he was 57 years old, and that when a soldier, at the age of twenty-one, he had had a chancre, with resulting throat-affection. In early youth, from his tenth to his fifteenth year, he had been an enthusiastic fisherman, and had stood for hours at a time with bare feet in very cold water. His present disease dated from the year 1877, and was characterized, according to his account, by great weakness and pain in the legs, difficulty of breathing, trouble in urination and defecation, impotence. The history of the family was without importance." "On examination it was found that the coarse strength of the muscles was well retained everywhere, and that in no department was atrophy to be discovered. The sensibility was altered in many ways,-first, cutaneous analgesia could be demonstrated over the whole body with the exception of the face and the portion of the head covered by hair. For light pressure the sensibility was, on the contrary, retained, and there were in the neighborhood of both sciatic regions hyperesthetic zones. Distinct girdle feeling, sense of temperature for small differences retained, muscular sense altered. With closed eyes the patient could give no information concerning the position of his legs in bed, and did not know whether the one or the other was carefully raised. Romberg's symptom, ataxic gait. Patellar reflex on both sides easily and plainly produced, also the plantar and abdominal reflex. Cremaster reflex on both sides gone. and affection of demonstrated.

Reflex fixation of the pupil the eye-muscle could not be Patient had never suffered with diplopia. with diplopia. Pupil of moderate size, reacts very slowly but distinctly to light and accommodative impulse. Paresis of the bladder, unconscious passage of the urine by drops by the impulse of coughing, voiding very slowly, not without burning, boring pain in the urethra. No gastric and no laryngeal crises. Appetite and digestion tolerable; tongue normal; no hemiatrophy." "The circum

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