8.

Can they by their presence effect such a result?

9. Can bacilli or bacteria have any relation with diseased action of any kind save as an effect of disease?

IO. What is the cause and mode of action of the poison producing phlebitis and of the poison from a cadaver?

II. Is not organic matter just as stable as respects composition as inorganic?

J2. If changes in the tissue occur only from the action of micro-organisms must we not look for the poisonous substance in the excrementitious products of these agents?

13. Are not all poisons both of animals and plants the products of cell actions?

14. Must not the morbific agents of the specific and contagious diseases be assigned a like origin?

15. Is not the poisonous saliva of rabies canina a product of vital action in living cells?

16. If the living germs of complex organisms produce poisonous products, may not micro-organisms excrete poisonous substances organic and inorganic?

ARTICLE XIII.

SALICYLATE OF AMMONIUM IN THE TREATMENT OF TYPHOID AND SEPTIC FEVERS AND INFLAM

MATIONS.

BY DR. J. R. BARNETT, OF NEENAH.

For some two years I have been employing the salicylate of ammonium in some of the affections in which we have been accusto.ned to place our main reliance upon quinine, and I desire to submit the results of such experiments and my own conclusions.

Before doing so it may not be amiss to speak of the leading motive of such an investigation; its development, step by step, will appear later on.

Briefly, the inadequacy of quinine in typhoid and remittent fevers and other grave affections to which it is commonly addressed, nay, its not infrequent harmfulness, raised the question in my mind years ago whether it were not desirable to supersede it as an antipyretic by some other of at least equal power and free from its disadvantages and dangers. That many physicians have entertained the same question is amply attested by the multitude of substitutes that have been submitted during the last few years, some of them of the cinchona series and closely allied to quinine, as if it were not safe to get far away from the parent tree, others derivatives of coal tar, as if it were better to get entirely away, and still others quite remote from both.

I speak of typhoid and remittent fevers together, not from their pathological but from their clinical relationships. The former would involve questions outside the scope of this paper. Still I may remind you of the spirited discussion of this question by this society three years ago, which settled only one thing clearly, which was that the typhoid of one observer was quite liable to be the remittent of another, and vice versa, the treatment of both, however, displaying

the closest similarity. It seemed to be the general experience that cases of fever possessing all the clinical features of typhoid often occur side by side with those distinctively remittent, and that the two classes shade so insensibly together as to puzzle the most experienced in making a differential diagnosis. It is this clinical relationship of those fevers which renders the name "typho-malarial" convenient if not accurate, and which justifies the rather narrow line of routine treatment addressed to both.

For my purpose it is not necessary to particularize this, but to refer only to the one indispensable agent, quinine; indispensable because few physicians had the hardihood to disregard the canons of the Fathers which required its use, whatever they did with the collateral treatment that might be associated with it. I felt myself so bound for years, an unwilling subject, for it was my fortune to see but few cases where the quinine treatment was of marked benefit, while I saw many in which it did unequivocal harm as long as its use was persisted in. I never knew it to abort the fever, given in any safe quantities and at the earliest moment. It never distinctly shortened it, at whatever stage its administration was begun, in whatever quantity given, and to whatever length of time. Given early it often seemed to hasten the occurrence of delirium and adynamia, and to accentuate the character and degree of each. Dryness of the mouth and sordes, absent before or slight in degree, would promptly follow its use, irrespective of its effect upon temperature, which was by no means uniform, and the more distinctive typhoid phenomena later on would be favorably modified only exceptionally, and then, as it would usually seem, only when these phenomena approached those of a genuine septicemia. I am far from saying that there is no stage or condition of those fevers where quinine can be employed with tolerably uniform advantage, but that is seldom found earlier than the end of the second, or the beginning of the third week and, except in sepsis from intestinal lesions, only in tonic doses.

The antipyretic salicylic acid and its salts, so fortunate in their earlier application, raised the extravagant hope that at last something approaching a specific in fevers had been discovered.

Their experimental use as such became so general as to at least demonstrate the general belief in the inadequacy of former remedies; but, unhappily, it failed to convince the profession that anything

better had come to take their place. Such experiments were generally, if not always, limited to the acid and its salts of soda and potassa. Generally the soda salt was the one used, doubtless because of its superior success in the pyrexia of rheumatism, and because of the general acceptance of the theory that both the acid and its different salts are at once changed in the system into the sodium salicylate. Some still adhere to this as superior to the classical antipyretics, a conclusion which my own experience with it does not sustain.

At the meeting of the American Medical Association in Washington, Dr. Jackson, of Norfolk submitted a paper on the ammonia treatment of typhoid fever remarkable in its record of successful cases, and still more so for the startling theories of the author concerning the pathology of the disease and the rationale of a successful treatment. Forgetting these theories,-vagaries, I had nearly said,— and remembering only their substantial fruits, because in harmony with what I had myself recently observed, I was, and still am convinced that his paper was the most valuable contribution to the therapeutics of typhoid fever that has appeared in recent years.

The ammonium salts he employed were the nitrate, the acetate, the carbonate and the hydrochlorate, each in its appropriate stage of the fever, and is in its well marked indications, and he did not hesitate to affirm that, one and all, they constituted the sole necessary treatment.

The year before this paper appeared I had seen a number of cases of an exceedingly malignant type of the fever in consultation with a medical friend. Five adult members of a family had been stricken in succession; three had died, and the other two seemed in the last extremity. One of these had intercurrent pneumonia and gangrene of the lung. The treatment had been strictly orthodox in all particulars, in one case embracing the cold pack and cold affusion, with free alcoholic stimulation in all. In the remaining two cases it was determined to discard all former remedies with the exception of opiates in moderate quantities, and to rely upon the carbonate of ammonia for stimulation, as advocated by Stokes. These cases recovered.

Two years ago quite an endemic of remittent fever occurred in Neenah, the malady often assuming a distinct typhoid type, attacking several members of a family. Two of my earlier cases died

under the classical treatment. My own son, a lad eight years old, sickened and rapidly grew worse until his condition became grave in the extreme. I dared not depart from the old ways with him, although a trusted colleague and friend was in almost hourly attendance during the worst. I felt bound to them by fear and hope until the last moment. There were suppression of urine and uræmic coma in his case, and I feared to give carbonate of ammonia as a stimulant, for has it not been said that uræmia is not uræmia but ammonæmia? Moreover, as a condition consequent upon this, there was oedema of the lungs,and surely I could give ammonia only at peril of strangulation. At last in desperation I administered it cautiously, two grains every two hours. It did no harm but it seemed to do no good, and the time shortly came when it seemed to my faithful colleague that the boy was dying. His extremities were cold; his finger nails were blue, his lips livid, his face leaden, and the rattle that precedes death was in his throat. Death seemed inevitable and imminent. But he was my only boy, and I had the desperate courage to strangle him, if need were, in the frantic effort to do something for him as long as he should live. I gave him the ammonia every 15 minutes, with what difficulty you can imagine. The boy lived, but had he been any other on the wide globe, and under my care, he would have died.

This is how I came to venture upon the ammonium treatment of typhoid fever. But I also ventured upon a radical departure at the outset. I reasoned that the rational remedy must be the ammonium salicylate, for reasons which need be only alluded to.

Its germicidal properties, possessed in common by all salicylates and its antipyretic and antiseptic powers, would at least give promise of effectiveness in modifying if not aborting the course of a fever. It would certainly avail in hyperpyrexia, it ought to fortify against systemic contamination from intestinal ulcerations, and whether or not it were to be decomposed in the body and thus produce a nascent ammonium carbonate, it should, in common with all ammonium compounds serve as a stimulant, which could be strengthened at will by the addition of ammonia in excess.

I had cases enough for a guarded, and finally a confident trial. In the first one, that of a young man with all the symptoms of commencing remittent fever, I had the good fortune to be called on the first day of high temperature, 104°. A drachm of the ammon