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The American Therapist. A MONTHLY RECORD OF MODERN THERAPEUTICS, WITH PRACTICAL SUGGESTIONS RELATING TO THE CLINICAL APPLICATIONS OF DRUGS.

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VOL. II. NEW YORK, JANUARY 15th, 1894. NO. 7.

Original Articles.

_NOTES ON RECENT THERAPEUTICS._

By OSCAR H. MERRILL, M. D.

Whoever reads the history of Therapeutics will find there records of much faithful work in many directions—records not infrequently of hope deferred. He will find there also a tolerably full account of human credulity, of human weakness and of human cupidity. The same faulty methods of reasoning are followed century after century. _Post hoc ergo propter hoc_, wrecks as many therapeutists to-day as it ever did, notwithstanding its fallacies have been demonstrated so often as to make mention of the subject distressing. It might be expected that half educated physicians, without preliminary, scientific training, would fall into this error; but when some of the brightest men in the profession—men who have presumably travelled the paths of logic and induction all their lives, go the same way, it shows pretty plainly what must be the inherent difficulties of the subject; and that for the proper discussion of therapeutic questions, no caution can be quite great enough and no learning quite profound enough.

The list of dead theories and abandoned remedies grows longer each year, and the experience of the past is as little heeded in the medical as in the financial world.

Acuteness of intellect and extent of education can, it seems, no more keep a man straight in medicine, than they can in religion or politics. Men, who for years have been esteemed well balanced authors and practitioners, become “a little crazy” on some one therapeutic measure and enthusiastically advocate its employment in all sorts of unsuitable cases. Good illustrations of this form of mental activity may be found in the literature of hydrotherapy and of electricity.

Thus, it has been stated that every case of typhoid fever may be made to end in recovery by the proper use of cold baths; and yet this writer knew in how many ways the disease may kill the patient—some of them almost accidental in their nature; he knew that perforation has occurred many days after the disappearance of pyrexia; he knew that in some fatal cases the temperature never exceeded 100°F.

Occasionally such a man after sowing dogmatic statements broad cast for a few years becomes insane enough to be confined in an asylum; sometimes advancing age with its mental deterioration is the evident cause; sometimes these acts are the work of advertising schemers; but generally the explanation is to be found in that mental substratum which permits otherwise sane and well educated persons to entertain monstrous opinions concerning the most ordinary matters.

The best work in Therapeutics is now carried on quietly without brass bands or sensational announcements. A few earnest men in each civilized country are patiently working out the physiological action of drugs, as a basis for a more rational therapy. The significance of much of this work, is not always manifest on superficial examination; but it already forms an important part of our working knowledge, and is gradually crowding out venerable empiricism which has heretofore occupied so prominent a place in medical practice, whether regular or irregular.

MANUFACTURING CHEMISTS.

No one will deny the value of some of the work done by the manufacturing chemists. Some synthetic compounds have been produced by chemical processes which we should not like to give up, and some improved forms of administering the older remedies are due, at least in part, to their ingenuity. Nevertheless, let any one not accustomed to it read patiently for a few months, the current numbers of half a dozen of what have been called “the minor medical journals,” or let a careful inspection of the advertising pages of the major journals be made, and it will be seen that large classes of medical men—perhaps a majority—have been completely deceived by these shrewd fellows. They have reached a refinement and a delicacy in their commercialism which will compare favorably with the court intrigues of oriental countries. Every prejudice, every weakness, every conceit of “the under medical world” is played upon with consummate skill and with amazing success.

Take, for instance, acetanilid, which, on account for its cheapness has been made to enter into numberless compounds, and every known language is ransacked in the search after new compound names which may be trade-marked. It is not alone the laity that is deceived, but graduates of reputable medical schools are prescribing, and, indeed, dispensing tons of this stuff, and often without knowing its composition.

ANIMAL EXTRACTS.

For thousands of years animal substances of various degrees of nastiness have been used as medicines. In fact some of the darkest chapters of human history are those relating to this subject. Sundry cognate superstitions are extant to this day, even among the nobility of civilized countries. In ancient times weird ceremony and occultism lent their charms to keep up interest in the matter; while in these “scientific times” the influence of a great hyphenated name has rekindled a fire which was merely flickering and which seemed to be in danger of going out altogether.

Since Brown-Sequard made himself young again by his well known treatment of senility great attention has been paid to the subject of animal extracts. From every corner of the earth have come workmen—some of them skilled workmen—to cultivate this promising field. One result of their labor is a mass of literature which contains much that is premature, much that is fantastic, much that is commercial; and it is difficult not to believe that some of it is closely connected with unsoundness of mind.

Another result is the new method of treating myxedema by the administration of thyroid glands—raw, cooked, desiccated, or in the form of extracts. Recently this treatment has been used in several cases with marked success, and already the air is full of rumors. One writer said a few months ago: “The success of this treatment is sure to create a ‘_boom_’ in animal extracts for various diseases.” He proved to be a true prophet, and we are in the midst of this _boom_.

It may perhaps be open to question whether there was need of any more “booms.” We have had “booms” in tuberculin, in coal-tar, in ovariotomy, if not in common sense. Some of them are still with us, though not in very good condition. After the boomers and the seekers after notoriety have done their worst with animal extracts, the final accounting will probably show some increase of positive knowledge in physiology as well as in therapeutics.

BACTERIOLOGY.

Bacteriology having now emerged from noisy babyhood into promising youth, it may not be amiss to ask how far therapeutics has been advanced by its discoveries and what the outlook is for the future. It has been alleged by some clinicians that the bacteriologists have been a little dictatorial, and have carried on their propaganda somewhat after the manner of the Salvation army. Be that as it may, the amount of conscientious and unremunerated work which has been devoted to the subject during the past twelve years is probably beyond the power of conception of any one man.

In spite of numerous mistakes, exaggerations and ludicrous attempts to re-organize therapeutics the bacteriologists have made great additions to our knowledge. The question of bacilliary disease is, however, enormously complex, and can not be settled by a few cultures and a few hasty deductions. Points that were supposed to be settled a few years ago are now under discussion again, and with regard to many of the problems it is still impossible to say just where the truth lies. Many thoughtful men have lately been turning their eyes from the microscope toward the bedside, and are asking themselves whether after all the condition of the soil is not fully as important as the germs which grow there, and they are consequently spending less time searching after germicides. One eminent physician predicts that the very language now used will be unintelligible jargon to future generations of germ seekers, and that the whole subject will have to be recast. Whether this be too strong language or not, it is doubtless true that we are, as yet, only on the threshold of this department of science, and that exact truth can be established only by a closer union of clinical medicine with bacteriological studies. The success of modern methods of preventing disease and the comparative failure of antiseptic and germicidal remedies in the treatment of well developed disease show that the human body is more than a test-tube, even though numerous theories have been tested therein to the discomfiture of the testers.

CREOSOTE.

Creosote still refuses to move on into obscurity with the numerous “cures” for consumption which have recently made their exit from the therapeutic stage. On the contrary it is used to a greater extent than ever before, and the testimony as to its value gets stronger each year. It is interesting to note here that a writer who is by many regarded as the leading American authority on therapeutics feels justified in ignoring the whole matter in the last edition of his work recently published. Such is the perversity of the human mind—or at least of his human mind.

In giving creosote, it will be found that most patients take it in the form of sugar-coated pills more readily than in capsules or liquid mixtures. This statement is deliberately made after thoroughly trying every known method of administration in a large number of cases during a period of eight years.

Patients who have sensitive stomachs can frequently take, at first, only one or two minims per day; but by slowly and carefully increasing the dose, they eventually consume twelve to fifteen minims each day without suffering from gastric irritation.

The success of the creosote treatment is seen most plainly in those patients who have taken it uninterruptedly and in full doses for several years. Many of these people improve in health from year to year, without, however, losing all their symptoms.

COAL TAR.

It has sometimes been claimed by metropolitan physicians that the rural brethren are slow to avail themselves of the various discoveries in medicine and surgery, and that they go on very much as their grand mothers did. Here as elsewhere in the universe there are compensations. Your country doctor can now look back a little, and with regard to many of the startling advances of these latter years he can see that the “advance” has been backward; and he is not quite sorry that his bucolic inertia has kept him from doing urban oöphorectomy upon all his hysterical female acquaintances.

On other occasions he accepts the dicta of the medical centers with alacrity, and refuses to be called off when the fashion changes. This was seen in the case of coal tar. No sooner had the chemists, private docents, assistant physicians, and royal and imperial professors of Germany and Austria, announced the mighty powers of antipyrine, than he began to employ it, and a little later its congeners, to drive fever and pain out of the world.

In many a remote country village this policy is still followed so vigorously that fever patients are kept blue and sometimes black by frequent and heroic doses of coal tar; and yet the great majority survive in spite of the disease and the antipyretic.

Very lately a rampant enemy of coal tar wrote: “While in the medical centers the coal tar antipyretics are being reluctantly abandoned, it will be long ere less enlightened rural practitioner will let this comforting drug slip from his fond grasp.”

Here then we have the two extremes; and here again sound practice lies about midway between them.

These antipyretics when used with skill and caution can be made, in many cases, to replace with advantage, morphine on the one hand, and cold baths on the other. Surely, medicines capable of playing such a part in therapeutics, deserve careful consideration.

245 Prospect Ave., Mount Vernon, N. Y.

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EFFECTS OF MORPHINE ON THE FEMALE ORGANS.—In a paper recently read before the Obstetric Society of St. Petersburg, Passower related the history of two cases, which confirms the opinion already supported by the observation of others, that the long continued use of morphine eventually leads to atrophy of the female generative organs. In both cases amenorrhœa was present; intra-uterine measurements taken during a period of two years showed a diminution in the size of its cavity from 5.1 to 1.9 inches.—_Exchange._

_ACTIONS OF DRUGS ON THE INTESTINES._

By W. C. CALDWELL, M.D.,

Professor of Materia Medica, and Director Pharmacological Laboratory, College of Physicians and Surgeons, Chicago.

_Concluded from page 164._

METHODS OF EXPERIMENT TO DETERMINE WHERE A DRUG ACTS TO PRODUCE CATHARSIS.

(_D_) _By introducing a rubber balloon, to which is attached a graduated rubber tube, through a gastric fistula into the small intestine, and measuring rate of descent and force carrying it onward to anus._

_Technique of the experiment._—Dogs are suited for this. Hess in his experiments used the animal immediately after making the fistula; Brandl and Tappeiner waited for the fistula to heal, and used the same dog a number of times, usually waiting two weeks before using him again, so that he would completely recover from the previous experiment. The balloon is introduced into small intestine and then moderately distended with water through the tube. After it has passed some distance below the pylorus, the cathartic is injected through the tube, the instrument being so constructed that the medicine passes into the intestine just above the balloon; ferrocyanide of potassium is added to the solution so as to tell by its reaction with chloride of iron whether the cathartic solution is in the feces. This method causes no shock and is superior to opening the abdomen to determine peristalsis.

By this method can be learned:

(1) _The location of the peristalsis._ This is done by examining the graduated tube and noticing how many feet been drawn in. If after the cathartic has been introduced above the balloon it does not increase the rate of descent till it reaches the colon, it shows that the drug acts on the colon instead of the small intestine; aloes is an example of this. If it increases its descent in the small intestine, it shows that the drug acts on the small intestine. If the drug greatly increases its speed in both small and large intestines, then the drug stimulates peristalsis through the whole length.

(2) _The rate of the peristalsis._ This is learned simply by noticing how fast the graduated tube is drawn in.

(3) _The time of peristalsis._ When the tube is not being drawn in there is no peristalsis, at least where the balloon is; when the drug acts on the small intestine the peristalsis occurs early; and when on the large intestine, late.

(4) _The force of the peristalsis._ This can be measured by pulley and bag of shot attached to the graduated tube. Of course it is necessary to learn first the lifting power of the peristalsis in the same dog without a cathartic.

(5) _By injecting a solution of the cathartic into a ligatured loop of intestine in the living animal._ It is better to use a rabbit or dog that has been starved for several days so that the intestine will be empty. After several hours remove the loop and measure the amount of liquid. If it is increased the drug stimulates secretion. It must not be forgotten that the irritation of the ligature stimulates secretion, so it is better to have a similar loop for comparison.

(6) _By injecting an equal quantity of water in two similar loops of intestine in the living animal, and then injecting the cathartic into one of them._ Use a starved animal. After several hours remove the loops and measure the quantity of water in each, if the one containing the cathartic has not diminished as much as the other, then it diminishes absorption.

We have now learned how to determine when there is increased peristalsis, and where it is; when there is increased secretion, and when there is diminished absorption. We have next to try to learn the exact manner in which these are produced, but this is far more difficult:

(_a_) Because the nervous mechanism of the intestines is very complicated, and at present not very much of its physiology is known.

(_b_) Because instead of the nerves with different functions having a separate course, they are all in the same sheaths, so that one kind of fibres at a time cannot be cut. The vagus contains motor, inhibitory motor, sensory, etc., fibres, so that when one is cut all must be cut. The same is true of the splanchnic.

(_c_) Because if a drug appears in the urine, sweat, or milk, it is no proof that it acts in the circulation; for it may act locally, then afterwards be absorbed, but have no action on the intestinal mechanism.

(_d_) Because if a drug cannot be found in the urine, sweat, or milk, it is not proof that it does not act in the circulation, and then afterwards be entirely excreted by the intestinal mucous membrane and pass out with the feces.

(_e_) Because when a drug, given hypodermatically, purges, it is not proof that the drug acts as a cathartic in the circulation, and that it does not act locally, for it may be inactive till it is excreted by the intestinal mucous membrane, and then act locally.

At present I will speak of peristalsis only. Perhaps as good a way as any to proceed, though unsatisfactory, is, first, to exclude the brain, and then, second, the abdominal ganglia, and then, third, experiment on the excised living intestine.

(1) Exclude the cerebral centres by cutting the vagi and splanchnics. This is shown in the schematic drawing Fig. 5, in which, for simplicity, one circle represents all the centres in that location. It must not be forgotten that cutting splanchnics affects the intestinal vessels. It is evident that after cutting the vagi and splanchnics the cerebral centres can have no influence on the intestines. After cutting these nerves, give the cathartic:

(_a_) If it does not act as a cathartic, this shows that it acts upon the intestines entirely through the cerebral centres, which now have no influence upon the intestines. This action is probably direct and not reflex.

(_b_) If it acts as a cathartic equally as efficient as it does when the nerves are intact, this shows that it does not act as a cathartic through the cerebral centres. The action is either on some of the abdominal ganglia, or on the local intestinal mechanism.

(_c_) If it acts as a cathartic, but much weaker than when the nerves are intact, this shows that it acts both upon the cerebral centres and also on some part of the remaining mechanism. This action on the cerebral centers may be direct, or it may be reflex from irritation of the intestinal mucous membrane. So far as I have read, no experiments have been made to determine when the action is direct and when reflex. It seems probable, though, that something might be learned about it in the following way, which is illustrated by Fig. 6. Select two similar starved animals; open abdomens of both and expose one carotid artery in one of them. Inject a solution of the cathartic in the exposed carotid and an equal solution in the exposed intestinal loop of the other animal. Place animals in salt solution in tin vat so as to observe through incision the intestines.

(1) If the drug acts reflexly by irritation of the intestinal mucous membrane, it will act quicker in the animal in which the drug was injected into the intestinal canal (see Fig. 6), because it is there to begin action at once, while in the other it must first be excreted into the intestinal canal. The intestine can be observed easily in the salt solution.

(2) If the drug acts directly upon the cerebral centres, it will act quicker in the animal in which it was injected into carotid artery, because in the other animal it has to be absorbed and diffused through the general circulation before it reaches the centre. Clamping the aorta would make this more accurate were it not that the intestines are so easily disturbed by changing the circulation.

(3) Exclude the abdominal ganglia. This can be done either by extirpating the ganglia, or by using a piece of excised living intestine. (Fig. 7 represents the abdominal ganglia concerned destroyed.) After extirpating the ganglia, and performing tracheotomy, and injecting the cathartic into the small or large intestine, place the animal in a physiological salt solution in tin vat, and observe the action of the drug. This experiment is not very satisfactory, because the vessels are greatly dilated.

(_a_) If the drug does not excite peristalsis, this shows that it acts through the abdominal or cerebral centres. This action may be direct or reflex.

(_b_) If the drug excites equally as strong peristalsis as are produced when the ganglia are intact, this shows that its action is not on the abdominal ganglia but on the intestine.

(_c_) If the drug excites weaker peristalsis, this shows that it acts at both places. This may be direct or reflex.

If it is decided that the drug acts on some part of the intestine to cause the peristalsis, two methods may be used to determine what part it acts upon:

1st Method.—After performing tracheotomy, opening abdomen and destroying abdominal ganglia, place the animal in a tin vat containing warm physiological solution. The first thing is to find out:—

(1) Whether the cathartic acts reflexly by the irritation of the mucous membrane being transmitted to Auerbach’s plexus, and from there to the muscles, or

(2) Whether it acts upon some structure in the intestinal wall after being absorbed.

_Demonstration._—If it acts reflexly, it will act quicker when injected into intestinal canal than when injected into mesenteric artery. If it does not act reflexly, it will act quicker when injected into the artery.

Next determine where in the intestinal wall the cathartic acts. The points are:

1st. Stimulation of the muscle.

2d. Depression of the inhibitory motor ganglia.

3d. Stimulation of Auerbach’s ganglia, and,

4th. Stimulation of the motor fibres.

_Demonstration._—If the drug in large dose causes tetanic spasm of the intestinal muscles, which is not affected by electrical stimulation of the inhibitory motor nerves, this shows that the drug acts directly on the muscles. In this way it can be shown how physostigmine acts.

If the drug in large dose increases peristalsis, and electrical stimulation of inhibitory motor nerves has no effect upon it, this shows that the drug paralyzes the inhibitory motor nerves. It can be shown that morphine acts in this way. In fifteen or twenty minutes after giving a dog a grain of morphine hypodermatically, it usually has one movement of the bowels. A small dose of morphine constipates, because it stimulates the inhibitory motor nerves. If the drug increases peristalsis and stimulation of the inhibitory motor nerves lessens the peristalsis, this shows that the drug either stimulates Auerbach’s ganglia, or the ends of the motor nerves. By the method above described Jacobi has made some very elaborate experiments with morphine, atropine, muscarine, and physostigmine.