Volume 1 — GENERAL DISEASES. (continued 19)

⁶⁰ Practitioner, xxviii. 393.

It would burden this narrative even to enumerate the instances in which a strict quarantine has protected places to which cholera has been carried by sea. In the United States numerous examples might be given of seaports into which cholera was brought from foreign countries, and within whose quarantine stations it was confined by rigid sanitary regulations; but it is sufficient to cite the case of New York, through whose quarantine at Staten Island nine-tenths of all emigrants to America have passed. Writing in 1867, Dr. Peters said: "There have been fourteen epidemics of cholera at Staten Island, and only four have reached New York." A large number of illustrations has been collected by Dr. Smart, Inspector-General, R. N.,⁶¹ who sums up the matter as follows: "Believing that cholera has frequently been excluded from islands by quarantine, and as often introduced by its non-observance, I regard it as a truly preventive measure; but, recognizing the impracticability of exacting it under many circumstances, I would insist on the most strict isolation of all the first cases or units of disease, whether introduced from without or originating from relationship to introduced cases, or persons or goods imported from infected countries."

⁶¹ Lancet, April, 1873, pp. 555, 659; Times and Gazette, April, 1874, p. 387. Compare also Colin, Brit. and For. Med.-Chir. Rev., July, 1874, pp. 42-44.

While experience demonstrates the efficacy, and therefore the necessity, of quarantine against cholera in seaports, it has also shown that the same agent of prevention need not be invariably and rigidly applied. When quarantine meant literally a detention, and almost an incarceration, for forty days, it often failed through its very rigor at a time when proper methods of disinfecting ships, cargoes, crews, and passengers were either unknown or inefficiently applied. It is now certain that quarantine may be reduced to a fraction of its original duration, and yet possess a much greater degree of efficiency, its length depending upon the number and the sanitary condition of the crew, etc., the nature of the cargo, etc. It is evident that a ship carrying only cabin passengers is less open to suspicion than one crowded with filthy emigrants, although both may have sailed from the same cholera-infected port. A more liberal rule may govern the one than the other; and in the second case a rigid inspection and cleansing of luggage may be imperative which would be superfluous as well as vexatious in the first case. The importance of such a treatment of emigrants' effects has already been illustrated by cases in which they caused an outbreak of cholera after having been carried from a seaport into an interior town many hundreds of miles distant.

In regard to the time during which a vessel that has had cholera on board within a week or ten days should be detained under sanitary inspection and treatment, including a thorough cleansing of the passengers and their effects, no absolute rule can be laid down; but it would appear that if no suspicious cases arise within a week, there need be little apprehension that any will occur.

The sanitary measures which should be undertaken wherever there is reason to fear an invasion of cholera are, in the first place, such as are equally appropriate in anticipation of any infectious and contagious epidemic disease, and relate especially to the removal of all sources of putrid emanations, whether in stagnant ponds, in streets, markets, shambles, sewers, privies, cellars, or inhabited rooms; for these influences, although they do not cause cholera, yet, by lowering the vitality of persons exposed to them, create an abnormal susceptibility to disease. Many instances in Europe might be cited to prove that whole cities, which in the earlier epidemics were devastated by cholera, were either spared entirely in the later ones or suffered in a far less degree. The measures which proved most efficient were an improved water-supply and a better system of sewerage; and this fact strongly corroborates the belief that contaminated water and fecal emanations are the principal agents in propagating this disease. Cleanliness is the best disinfectant, but during epidemics of cholera, as of other diseases, the popular faith is very strong in numerous articles called by that name. The real value of these preparations is commercial rather than sanitary, but, indirectly, they are useful by prompting those who use them to be more diligent in searching out and removing many sources of air-contamination that perhaps invite and intensify attacks of cholera.

The disinfectants in common use comprise chlorine gas, chlorinated soda, chloride of zinc, sulphate of iron, permanganate of potassium, carbolic acid, and the fumes of burning sulphur. Some of them—and especially the chloride of zinc, sulphate of iron, the permanganate of potassium, and carbolic acid—are supposed to be capable of destroying the infectious principle of the vomit and stools. Another method is to receive such matters in vessels containing saw-dust, which, after being dried, is consumed by fire; and still another is to mix them with dry earth and bury them. If they are thrown into water-closets or privies, they should have added to them a portion of sulphate of iron. Whatever has been used by cholera patients should be destroyed, unless of value, and in that case it should be thoroughly purified by hot air or boiling water and long exposure to the sun. The importance of having large and well-ventilated rooms for cholera patients is very great, but less, perhaps, for the patients themselves than for their medical attendants and nurses. All persons should be excluded from them who are not required by the duties of the sick chamber, and in case of death funeral assemblages ought not to be allowed; nor, during a cholera epidemic, ought crowded assemblies for any purpose to be permitted.

During epidemics of cholera, as of some other diseases, the liability to be attacked is greatest when the vital powers are depressed by mental or by physical causes. Hence it is desirable that one's courage and confidence should repose upon a consciousness of having done whatever is recognized as proper to ward off the disease—not by a minute, watchful, and anxious attention to rules at every step, but by such a general care of the health as good sense and experience enjoin. Undoubtedly, other things being equal, the weak, sickly, careless, and imprudent are more liable to suffer than the strong and cautious, and therefore it is incumbent upon all to maintain as high a degree of health as possible, avoiding not only all probable sources of contagion, direct or indirect, but excessive fatigue, catching cold, depressing emotions, sexual excesses, etc. During the first cholera epidemics in this country it was considered so dangerous to eat fruit and fresh vegetables that many persons lived entirely upon meat, rice, and bread. Such a regimen intensified choleraphobia, and was also an unsuitable midsummer diet. There is no reason to believe that any intrinsically wholesome food need be prohibited during the prevalence of cholera.

The one article of diet about which the greatest and most peculiar care should be taken is water. It is the first duty of towns supplied with water from a common source to be sure that it is, and continues to be, uncontaminated. Well-water should be used as little as possible after the disease has made its appearance, and, as an additional precaution, no water should be drunken that has not previously been boiled. Where ice can be procured it may be used to restore the boiled water to an agreeable temperature for drinking. Filtered water, provided that it be properly filtered, may likewise be regarded as innocuous.

TREATMENT.—If regard be had to the various methods and particular medicines which have been used in the treatment of cholera, it will appear that in hardly any other acute disease has a greater number or variety been employed. If, on the other hand, we endeavor to learn what measures have been really and generally curative in cholera, and what are they to which, on the occurrence of an epidemic of the disease, we may turn with confidence in their power to cure, the result of the investigation is disheartening, and adds to the accumulated proofs that the power of medical art is exceedingly restricted. To this conclusion we must assent at whatever cost to a faith which is strong in proportion to the ignorance out of which it grows. Nor, if we consider the matter rationally, ought we to be surprised or humiliated on account of the comparative helplessness of medicine in this disease, since, if we reflect upon it, the case is by no means peculiar or exceptional. Every disease that may become mortal occurs more or less frequently with phenomena which place it beyond the resources of therapeutics as completely as cholera is in its most malignant forms; and yet no one lays it to the charge of medicine that the various fevers, for example, are at times utterly uninfluenced by the most rational and judicious treatment. Nor does any one bring a railing accusation against medicine when accident fatally damages a part essential to life.

One accident of frequent occurrence presents a certain analogy to cholera in its effects, and that is a burn or scald involving a very large portion of the skin. In cases of this sort experience assures us that death is almost inevitable, and that the duty of the physician is to avoid officious and meddlesome treatment, and address himself to soothe the patient's suffering and maintain his strength, if haply the powers of nature may triumph over the effects of the injury. This, too, is the lesson, substantially, which experience has taught respecting cholera. It is certain that in this disease the function of the whole gastro-intestinal mucous membrane is reversed, and that it is no longer a secreting and absorbing organ, but one almost exclusively exhaling, and that through it the liquid which is essential to carrying on the functions is rapidly running away. If the lesion on which this symptom depends is complete, if the gastro-intestinal mucous membrane has entirely lost its natural function, evidently it is quite futile to address any treatment to this organ. But if, as probably happens in a great majority of the cases, the disorganization takes place gradually, it is evident that there is more to hope from remedies when the disease is gradually developed than when it reaches its acme at a single bound and leaves no time for medical intervention. The one unmistakable lesson that experience teaches respecting the treatment of cholera is, that its success depends upon its prompt and early application. Almost as distinctly does observation teach that subsequently to the first (or diarrhoeal) stage the comparative value of different methods and individual medicines is very uncertain. And, finally, it would seem that in this, as in other acute diseases, intelligent and careful nursing and regimen are quite as important as any medicinal treatment whatever. However a false notion of the power of medicine may blind us to the fact, it is none the less a fact, that if different methods of treatment are compared, that method gives the best results which is least perturbative. For example, in England, on board of a hospital ship, were 85 cases, of which 19 treated by quinine gave 12 deaths, 12 by calomel gave 2 deaths, 12 by carbolic acid gave 3 deaths, and 37 by "Nil" gave 1 death.⁶² Or, again, in 1865, at the London Hospital, 159 patients were treated—48 with a mixture containing logwood, ether, aromatic sulphuric acid, camphor, and capsicum, of whom 31 died; 56 with sweetened water, of whom 28 died; 21 with castor oil, of whom 14 died; and 20 with "saline lemonade," of whom 6 died.⁶³ In the last example the deaths during the use of the astringent mixture were twice as great as under sugar and water, and under castor oil twice as great as under "saline lemonade."

⁶² Times and Gaz., Dec., 1866, p. 590.

⁶³ London Hosp. Reports, iii. 444.

We shall first give an account of the management of cholera in general, and then consider some of the particular medicines used in its treatment.

The essential elements of all plans of treatment for this disease, as for so many others, are rest and abstinence. Whatever else may be done, nothing avails without them. This remark applies emphatically to the premonitory diarrhoea; if it is neglected it may readily be converted into the full-formed disease. It is therefore essential, during the prevalence of cholera, that whoever is attacked with diarrhoea should at once give up all active occupation, and confine himself to a recumbent posture and to the use of food of the blandest quality, such as mucilages and similar preparations, especially of rice, which, less than any other vegetable food, is liable to fermentation during digestion. It is prudent to drink no water that has not been boiled. If there is reason to believe that the bowels retain feces from before the attack, it is generally thought advisable to administer a laxative dose of castor oil, to procure the discharge of matters which would act as irritants. Except for this purpose purgatives are neither indicated nor expedient. In a large number of cases nothing more is necessary than the use of means to check the action of the bowels, and which should consist of absorbents or antacids, astringents, and opiates as they are contained in the officinal chalk mixture, with the addition of tincture of kino or catechu and a small proportion of laudanum. This medicine should be given in dessertspoonful doses at intervals of not more than an hour.

If, instead of a diarrhoea which differs from ordinary dyspeptic diarrhoea chiefly by its watery character, there should also be colic and profuse discharges, it is proper to add to the medicines just suggested some which are of a decidedly stimulant character, such as the essential oils of cajeput, cloves, cinnamon, peppermint, etc., with which chloroform, ether, or Hoffman's anodyne may be associated. At the same time rubefacient embrocations may be applied to the abdomen, which should also be compressed slightly with a broad flannel bandage. Instead of these stimulants, and perhaps more efficiently, may be used a simple epithem made by dipping a large towel several times folded in cold or cool water, applying it so as to cover the whole abdomen, and then enveloping it and the body with a dry towel. This application is more soothing than any liniment and its action is more constant. Instead of any of these agents dry heat may be used, obtained from bags of hot salt or sand, or moist heat from thick poultices of flaxseed meal or Indian corn meal or similar substances enclosed in flannel bags and applied to the abdomen while they are as hot as can be borne. It is difficult to determine which of these applications is the most useful. But, on the whole, heat is preferable to rubefacients, and moist to dry heat. The cold-water dressing is probably best suited to young and robust persons.

It must be remembered that between choleraic diarrhoea and cholera in its complete form there are several grades, in one of the most common of which a tendency to vomit, and even a certain amount of vomiting, accompanies the diarrhoea. Anti-emetic remedies are then indicated. They may consist externally of rubefacient and aromatic applications to the epigastrium (especially the spice poultice); and it is claimed that a hypodermic injection of morphia in this part is very efficient. Internally, the best remedies are ice swallowed in small pieces and small but frequent draughts of iced carbonated water or iced champagne. Where these liquids cannot be procured, effervescing powders used in the same way form a very good substitute for them. If, notwithstanding such remedies, the diarrhoea continues or if it tends to increase, astringent and absorbent medicines may be substituted for them; for example, bismuth may be given instead of chalk, and if this also fails acetate of lead may be prescribed. The last may be used by the rectum as well as by the mouth, but with very questionable advantage. Meanwhile, especial care should be taken to avoid giving so much of any opiate as will induce sopor or excite nausea.

Whoever has had the care of cholera patients has probably, at first, felt sanguine of success in their treatment, even after the characteristic discharges and the symptoms of collapse had set in; but a little more experience has proved their hope to be deceptive, and revealed the reason of it in the absolute suspension of the sensibility and absorbent function of the digestive canal. Hence the dismal unanimity of all medical authors, who from actual observation of cholera have declared that no treatment avails to arrest the fully-developed disease. And yet there is some encouragement in the fact that recoveries sometimes occur from even the most desperate state of collapse and under the most dissimilar methods of treatment; so that the physician is warranted in not yielding to discouragement and in cheering his patients with hope even to the end of life. The popular dread of this, and indeed of all epidemics, is sure to be exaggerated, and it therefore behooves the physician to combat the fears of his patients, and by a cheerful manner as well as encouraging words administer the cordial of hope, which often proves stronger than pharmaceutic elixirs.

It may be well to enumerate, as many do, the indications of treatment in the active stage of cholera, but they really need no such specification. It is evident that they consist in combating the symptoms—the vomiting, the purging, the debility, the cyanosis, the cramps, etc.; and the only means by which the carrying out of such indications can even be attempted are neither more nor less than would be used to relieve the same symptoms in other affections. If the evacuations could be controlled, evidently the cramps and the collapse would not occur; but this essential and preliminary step cannot be secured. The medicines introduced into the stomach or rectum are not absorbed, but are speedily rejected; those which are administered subcutaneously are not taken up by the stagnant blood as freely as in other diseases; the nervous system gives little or no response to the mechanical and physiological stimulants applied to the skin. Yet, in spite of these obstacles, the physician must persist in the use of rational methods, in the hope, however faint it may be, that he may succeed in restraining, and possibly in arresting, the fatal course of the attack. For this end he has hardly any means at command except those, or such as those, which were recommended in the first stage of the disease—the anti-emetic and anti-diarrhoeal medicines, which he is only too likely to see rejected as soon as administered. Yet he must not cease to allay the thirst by the repeated administration of small quantities of carbonated and cold liquids, water, or champagne wine, or morsels of ice swallowed whole. The application of pounded ice in a bladder to the epigastrium is a measure of an analogous sort, and is sometimes as efficient as generally it is soothing. In other cases the aromatic poultice seems to answer better. Of irritants little can be said that is favorable, but the combined irritant and anæsthetic action of chloroform is useful, and morphia should be applied to the epigastrium as well as given hypodermically.

If the vomiting tends to become less frequent, acetate of lead may be prescribed, in the hope that it will exert some constringing action upon the gastro-intestinal mucous membrane. The distressing symptom, hiccough, cannot with any certainty be controlled by medicine, but perhaps the inhalation of chloroform is more efficient than any other remedy, as it also is for the cramps in the limbs. For the latter purpose it is preferable to the frictions with flannel or with stimulating liniments which are generally employed. If such liniments are used, care should be taken that they do not contain ingredients that may disorganize the skin either immediately or subsequently. A dangerous compound of the latter sort introduced during the first epidemic of cholera in this country became officinal under the name of liniment of cantharides.

The loss of the water and of the salts it holds in solution in the blood is, as has now been frequently repeated, the chief pathological element of the disease, next after the conjectural cause which injures the mucous membrane of the stomach and bowels. It was rationally indicated, and therefore a method was early practised, to supply this loss by injecting into the veins a solution of sodium salts. The method was seductive as well as rational, for its primary effects were extremely encouraging; it nevertheless failed, and probably for the very reason that suggested its use. Indeed, there is no more reason, if there is as much, to suppose that a liquid artificially introduced into the blood-vessels will be retained when the natural liquor sanguinis cannot be so. Necessarily, the one will escape where the other has escaped.

Certain systematic writers prescribe a method intended, on the one hand, for reviving the animal heat, and on the other for restoring the movement of the circulation. It need hardly be remarked that the two form essentially but one and the same indication. If the circulation is restored the animal heat will revive, but not otherwise. The same treatment leads to both ends, and it consists partly, as already stated, in the use of stimulants, such as alcohol, camphor, coffee, ether, etc.; but their efficacy depends upon their being taken into the blood, and with it reaching the various nervous centres upon which the renewal of functional activity depends. Little, therefore, can be expected from them at the height of the disease—that is, in the stage of collapse—but as soon as any signs of reaction are manifested they tend to promote it, and hence may enable the functions to revive. For this reason they are adapted to persons who are feeble by reason of their tender or their advanced age, or who have previously suffered from ill-health. But if they act at all, and the more they tend to act, they must be employed with circumspection, lest they outrun the purpose of their administration and produce a violent or excessive reaction. Instead of, or in conjunction with, these internal remedies the local stimulants of the skin, already enumerated, may be used with the due precautions, and, in addition, baths at a temperature of 105° F. of water alone or with the addition of salt or mustard; but all such remedies are of little avail until reaction has commenced. Before that event there is reason to believe that the cold bath is preferable, or, still better, frictions of the whole body with cold water, or even with ice, after which the patient should be wrapped in dry and warm blankets. Yet the efficacy of this powerful agency is by no means comparable to that which it produces in the algid forms of malarial fever. The two conditions, although apparently analogous, are, in reality, very different. In the cold stage of fever the mechanism is indeed paralyzed, but none of its mechanical elements are wanting; but in algid cholera there is an actual subtraction of water from the blood, that turns it from a liquid capable of circulating through the narrowest channels into one that stagnates even in the largest vessels. In the one case force is wanting to circulate the blood; in the other there is no normal blood to circulate.

The treatment of the stage of reaction when it does not exceed a moderate degree, consists simply in strictly enforcing the rules for the patient's repose; that is to say, in intelligent nursing. Mental excitement must be forbidden, and neither medicine nor food allowed that is likely to interfere with the gradual and steady progress of convalescence. Of all articles of food, cool water is not only the most urgently desired, but is the most imperatively necessary for replenishing the emptied blood-vessels and restoring the normal functions. But unless great caution is observed it will be taken too freely and provoke a renewal of the discharges. If any food besides water is allowed, it should be of the simplest sort—of whey first, and then of milk in small quantities at a time, with lime-water if it provokes nausea or retching. Afterward thin broths may be given, also in great moderation, and by degrees farinacea in milk and in animal broths. Only when the strength is much improved should even the most digestible meats be permitted. In proportion as convalescence is marked or interrupted by symptoms of undue reaction is it necessary to prolong and render stringent this regimen; and if those symptoms unfortunately arise which oftener, perhaps, depend upon an over-zealous stimulant treatment than upon the natural reaction of the system, they must be combated by measures which will lessen the local congestions, especially of the brain and the lungs, and also by such as will tend to prevent the system from falling into a typhoid state. For the former dry cups applied to the back of the neck, and cold lotions and affusions upon the scalp, are to be recommended, and for the latter dry cups and warm stimulating poultices upon the chest near the affected region. It is probable that the general warm bath, with cold affusion upon the head at the same time, would prove as efficient as it does in analogous states of typhoid affections. If the urinary secretion is suspended or remains scanty, there is not usually an urgent need of using means for its restoration; for that will generally occur when the blood-vessels become replenished. It should, however, be mentioned that, according to Macnamara, if the patient does not pass any urine within thirty-six hours of reaction coming on, ten minims of the tincture of cantharides in an ounce of water should be given every half hour until six doses have been taken, and the patient encouraged to drink freely of water. If this treatment does not cause urine to pass, we must, after the sixth dose, discontinue the medicine for twelve hours, and then repeat it in precisely the same way. The dose here referred to is of the British preparation, and if the use of it were not recommended by so competent an authority its propriety might very properly be challenged.

After the cholera patient has become convalescent his restoration is very apt to be retarded by dyspeptic disorders, for which, perhaps, the best remedy is a judicious use of condiments with the food and of bitter tonics, especially quinine, colombo, quassia, etc., before meals. If there is constipation, it should be corrected by the cautious use of fruits, and, if these prove insufficient, of mild saline laxatives or small doses of castor oil or rhubarb. On the other hand, if there is a tendency to diarrhoea, it should be met by the use of a mild laxative, such as castor oil, magnesia, or rhubarb, followed by chalk or bismuth, and the use for a time of simpler food and in less than the usual quantities.

Having thus furnished a sketch of the plan of treatment of cholera which we regard as dictated by experience, it may be not without some interest to consider certain elements of the method a little more fully, and criticise, in passing, some other remedies which have from time to time been proposed. The first of these is venesection. There was a time when certain physicians, carried away by conceptions of the disease evolved from their inner consciousness, maintained that it consisted essentially of a spasm of the blood-vessels, and that the natural and legitimate cure for it was to be found in bleeding. No theory is so gratuitous or absurd but cases may be found which appear to justify it, and in this instance also examples were not wanting to illustrate at once the truth of the theory and its successful application. Longer experience, however, and a more correct conception of the disease, have long since condemned this method, which was almost as dangerous as it was irrational. If any additional argument against it were required, it would be found in the condition of the lungs after death. These organs, we have seen, are not only not engorged, but they are empty of blood, and death is due not to asphyxia, but to apnoea, when it takes place in collapse.

If ever there existed any reason for the administration of an emetic—and ipecacuanha has generally been used at the commencement of an attack of cholera—it must be looked for, not in any clinical experience of its virtues, but simply in the deplorable routine that required the administration of an emetic at the commencement of nearly all acute diseases, so that, whatever else was prescribed, the lancet and an emetic seldom failed to be so. In this case also the proofs of the successful administration of ipecacuanha were not wanting, and one might be tempted to suppose, in view of the alleged facts in its favor, that it was useful by causing an evacuation of the material cause of the disease. Physicians were even to be found, of high station and character, who contended that cholera is a species of fever, and to be treated by an emeto-cathartic composed of tartar emetic and epsom salts. If the treatment had been efficient, the absurdity of the reasons for it might have been overlooked; but the one was as disastrous as the other was false. But, as usual, the facts had been misstated or misinterpreted, and emetics ceased to form a part of the systematic treatment of cholera. The idea which possessed those who advocated the use of evacuants was that there was either a poison to be eliminated from the blood or one to be expelled from the bowels. Apparently, the method was not efficacious, for the latest phase of it, the use of castor oil in acute stage of cholera, was of short duration.

When cholera first appeared in Europe the tendency naturally arose to follow in its treatment the example of the British practitioners in India. It then appeared that one of the most eminent among them, Annesley, gave a scruple of calomel, with two grains of opium, at the commencement of the attack, and repeated the dose in six or eight hours, and again upon the following day. In the decline of the disease he ordered scruple doses of calomel for the removal of a "cream-colored, thick, viscid, and tenacious matter exactly like old cream cheese, which glues the gut together and obstructs its passage." Three, four, and even five, scruples of calomel were usually taken before this effect was produced. When it is added that this practitioner held depletion to be the capital element of the treatment, and that he was equally lavish of his patient's blood and of his own drugs, we can only wonder that any subjects of his heroic method survived. It is now conceded by all enlightened physicians that mercurials in large or in ordinary doses are worse than worthless in epidemic cholera. In 1832, Dr. Ayre of Hull, Eng., proposed another method of using calomel, to which he adhered in treating this disease. It consisted in the administration of very small doses of calomel at short intervals, and with each of the first doses a few drops of laudanum. Such a method, if not carried too far, certainly has the merit of sparing the patient a great deal of the perturbative treatment against which we have, in the preceding pages, protested. But that was not at all the notion of its proposer. He claimed for it positive and active virtues. He stated, as the fundamental ground of his plan, that "the primary and leading object of the treatment must be to restore the secretion of the liver." He did not in the least doubt that he was able to do this by the administration of mercury—not, indeed, by a direct action upon the liver itself, but indirectly and sympathetically through the stomach, and by the healthy and specific stimulus imparted to it, by which the due secretion of the bile is promoted. It is, indeed, difficult to conceive of any stimulus that calomel could impart to the stomach that would not be equally given by any other non-irritant and insoluble powder—subnitrate of bismuth, for example. Indeed, Ayre himself relates the case of a man who in an attack of cholera took during three days no less than five hundred and eighty grains of calomel, and recovered without any soreness of the mouth. But the plan which he finally elaborated was different. It was to give small doses of calomel repeatedly—in the premonitory stage one grain every half hour or hour for six or eight successive times, or, if this failed, every five or ten minutes—and in the stage of collapse one grain and a half every five minutes. In a few cases of extreme severity two grains of calomel were given every five minutes for an hour or two, and then the ordinary dose of one grain was resumed. But this was not all: with every dose of calomel was associated one, two, or three drops of laudanum, so that if these doses were repeated frequently the patient received a very efficient amount of the narcotic during the attack. Indeed, Ayre attributed to it the virtue of sustaining the vital powers under the depressing influence of the disease, and of removing or abating the cramps, as well as of detaining the calomel in the stomach.⁶⁴ From the preceding account it follows that the treatment of cholera by small doses of calomel with laudanum is founded on an erroneous assumption of the mode of action of calomel, and that whatever efficacy the plan of treatment may possess may with more justice be attributed to the opium, whose effects we know, than to the calomel, whose action, so far as it is known at all, has no conceivable relation to the disease for which it was given. However this may be, if the results of Ayre's treatment are compared with those of other plans, it exhibits very little if any superiority. In the report of the cholera committee of the College of Physicians, London, made in 1853, we find the statement that in 725 unequivocal cases treated on Ayre's plan the deaths were 365, or about 50 per cent., and also the following commentary: "In general, no appreciable effects followed the administration of calomel, even after a large amount in small and frequently-repeated doses had been administered. For the most part, it was quickly evacuated by vomiting or purging, or, when retained for a longer period, was passed from the bowels unchanged. Salivation but very rarely occurred, and then only in the milder cases. We conclude that calomel was inert when administered in collapse, and that the cases of recovery following its employment at this period were due to the natural course of the disease, as they did not surpass the ordinary average obtained when the treatment consisted in the use of cold water only."⁶⁵ It is of interest to compare the mortality of 50 per cent. above stated to have occurred under this sort of calomel treatment with the mortality noted at the London Hospital under various kinds of treatment, including the administration of calomel in doses varying "from five to ten and twenty grains every quarter, half, one hour, two, four, etc." Out of 509 cases, 281 were fatal, or 54.9 per cent.⁶⁶

⁶⁴ A Report on the Treatment of the Malignant Cholera, Lond., 1833.

⁶⁵ Dr. Gull's Report, p. 177.

⁶⁶ Lond. Hosp. Reports, iii. 437, 441.

Every disease in which exhaustion and coldness occur is sure to be treated more or less actively with alcohol, but in the collapse of cholera, as in the cold stage of fevers, it is generally useless, and sometimes hurtful. We believe that the following protest of Macnamara is sustained by almost universal experience: "I would here enter an earnest protest against the use of brandy or any alcoholic stimulant in this [the second] stage of cholera. I believe these, both theoretically and practically, to be the cause of unmitigated evil. I simply, therefore, mention brandy, champagne, and the like in order to condemn their use most emphatically in cholera; according to my ideas and experience, it is almost impossible to hit on a more detrimental plan of treatment than that usually known as 'the stimulant' in this form of disease."⁶⁷ It is true that apparent dissidents from this judgment may be found, like Playfair, a deputy inspector of hospitals in Bengal, who even circulated printed directions for the treatment of the first stage of the disease by means of brandy or strong rum, cayenne pepper, and laudanum, and had entire confidence in the efficacy of the method.⁶⁸ Dr. Macpherson, inspector-general of hospitals, also, after comparing the results of a stimulant treatment with those of other methods, reaches the conclusion that the mortality-rate of cholera is affected neither by the moderate nor by the excessive use of alcohol.⁶⁹

⁶⁷ Op. cit., p. 456.

⁶⁸ Edinburgh Med. Jour., xix. 471.

⁶⁹ Med. Times and Gaz., Jan., 1870, p. 62.

Upon no other point in the treatment of cholera is the agreement of physicians more complete than upon the use of opiates in the early stage of the disease. The premonitory diarrhoea has always been treated by opiates alone or associated with astringents. Probably the best rule is to give from twenty to thirty drops of laudanum, or an equivalent dose of some other liquid preparation of opium, in a little brandy and water, and repeat the dose as often as a stool is voided. Opiates have also been generally employed to mitigate the symptoms of the fully-developed disease. But, like all other medicines introduced into the stomach or rectum, they are apt to be rejected, and even if they are not, their absorption is very doubtful, so that at the height of the attack they must be considered as nearly if not quite useless. When the vomiting and purging begin to subside and reaction is about to commence, small and repeated doses of opiates undoubtedly tend to lessen the evacuations; but great caution must be observed not to exceed the due degree of stimulation, lest a dangerous state of narcotism or collapse be induced. It might be supposed that the hypodermic use of morphia would be less open to objection than its administration by the stomach; but it is to be remembered that the suspension of gastric absorption is only a part of the similar condition affecting the whole circulatory system, and that the stagnation of the blood in the systemic veins prevents the absorption of medicines administered subcutaneously perhaps as completely as the state of the gastric blood-vessels interferes with their absorption from the stomach itself. In point of fact, the utility of opiates at any stage of cholera after the first is not easily determined, for nearly always they are associated with other medicines, and especially with astringents. In this disease, as in others that involve life, we are seldom at liberty to test the powers of individual medicines, but are bound to endeavor to save life by associating those which seem to be required for the purpose. Opiates, then, are nearly always given in conjunction with astringents or stimulants during the first (or diarrhoeal) stage of the attack, but after vomiting is added to diarrhoea and a tendency to collapse is manifested they are at least useless.

The patient, it has already been said, should be disturbed as little as possible, and hence, if he becomes restless, and especially if he is rendered so by pain, he should be tranquilized by means of anæsthetics. Chloroform has generally been employed, and is best administered on the first accession of cramps. Much pain, with muscular fatigue and depression, is thus saved, and the inhalation of the medicine may be repeated as often as the pain threatens to return. No doubt other anæsthetics, and especially ether, would answer the same purpose.

Camphor has been claimed to be a valuable medicine in cholera, but there is no clinical evidence that it is so. Indeed, the only series of cases in which it was mainly depended upon gave a large mortality.

Acids have been employed in cholera, but chiefly on theoretical grounds, "in the hope of destroying the specific cholera process going on in the intestinal canal" (Macnamara). It is hardly necessary to discuss so vague a reason. What specific process is going on? What relation to it has the administration of acids? And, after all, only the hope is held out of destroying the hypothetical morbid process. The reaction of normal stools is usually acid, but sometimes it is neutral or even alkaline. In other acute bowel complaints with profuse diarrhoea they are acid, as in cholera infantum, but in epidemic cholera they are alkaline, because they consist chiefly of the water of the blood. It is far from proven that mineral acids can be useful merely by reversing the reaction of the stools. Far more probable is it that, in so far as they are of use, it is because they act as astringents upon the digestive mucous membrane. This may be inferred from the fact that, according to the advocates of these medicines, it is always difficult, and is often impossible, to acidify the stools in cholera. Moreover, it must be remembered that, like other medicines, the greater part of them are rejected by vomiting. If, then, mineral acids tend to lessen the diarrhoea of cholera, they act by their astringency and not by their acidity. Diluted or aromatic sulphuric acid may be given in the dose of from two to thirty minims, at intervals of an hour, in acid water or carbonated water, or diluted nitric acid, in doses of from twenty to fifty minims, at the same or somewhat longer intervals.

Intravenous injections were used in England during the first epidemic of cholera in 1832-33, but their results were regarded as unfavorable; subsequently, in 1849, they were tried with somewhat better success, and in 1867 the effects were still more encouraging. The liquid employed on the last-mentioned trial consisted of chloride of sodium 60 gr., chloride of potassium 6 gr., phosphate of sodium 3 gr., carbonate of sodium 20 gr., alcohol 2 drachms, and distilled water 20 ounces. The alcohol was added only when the liquid was about to be used, and the temperature of the latter was not allowed to exceed 110° F. or fall below 100° F. The liquid was contained in a zinc vessel holding about eighty ounces, with a lamp underneath, a thermometer hanging within, and a tap near the bottom, from which proceeded an india-rubber tube four feet long, with a silver nozzle at its end. The fluid was allowed to enter the vein by the force of gravity. If difficulty was experienced in introducing the nozzle, the vein was freely exposed, supported on a probe, and incised longitudinally. It was found that the success of the operation depended greatly upon having an ample supply of the solution prepared, so as to repeat the injection as often as might be found necessary. Mr. Little, who practised this method in numerous cases, stated as follows: "When a patient has been long pulseless clots form in the heart, and, as I have seen, extend into the larger veins. In one case the fluid would not flow in, and only distended the veins of the arm injected. After death clots were found extending from the heart into the axillary vein."⁷⁰ Five out of twenty apparently hopeless cases recovered under this treatment. The first effect of the injection was to revive the pulse, which had ceased to be felt; the voice also was restored, the color and expression improved, the cramps were relieved, the temperature rose, and the patients became convinced that their recovery was assured. A profuse perspiration and a severe rigor accompanied these symptoms. The rigor was evidently a nervous phenomenon, and not a chill, for it occurred when the temperature was rising. Other cases might be cited which unquestionably owed their recovery to this mode of treatment. It is true, however, that much more frequently it failed of success; and probably not only because the injection could not reach the heart, but because, having permeated the blood-vessels of the whole body, it escaped, as the serum of the blood had done, from the damaged intestine. Nevertheless, it would seem that an expedient which in a certain proportion of cases has been quite successful might yet be rendered more certain in its results if the operative procedure were perfected.

⁷⁰ London Hosp. Reports, iii. 470.

Cramps in the limbs may be lessened by active friction and shampooing, but there is no clinical reason for believing that these measures tend to restore the circulation. Equally ineffectual are other means used for communicating heat to the algid body and thereby reviving its functions. It is true that some physicians found that warm baths, at from 90° to 104° F., gave relief to the cramps and restored the failing pulse. In most cases the calming influence of the bath was noted, but it does not seem to have been curative or to have diminished the mortality-rate.⁷¹ It should not be forgotten that the patient has no perception of his coldness. In all analogous conditions, as has already been remarked, such as frostbite and the cold stage of periodical fevers, cold, and not heat, promotes reaction. Still more injurious, if possible, than hot applications are irritants and stimulants after the stage of collapse has set in. Not only are they absolutely futile for restoring the animal temperature, but they are liable, unless very cautiously used, to produce intractable sores upon the skin if recovery ensues. It should also be remembered that the cholera patient's exhaustion is exceptionally great, and is apt to be increased by the officiousness implied in the use of many stimulating agents.

⁷¹ Ibid., iii. 445; St. Bartholomew's Reports, iii. 190.

As early as 1832 a marked advantage was ascribed to the use of cold affusions in cholera.⁷² One of the physicians of the cholera hospital of Berlin said: "In these living corpses which are struck with asphyxia, lying cold and powerless, external and internal medicines cease to stimulate; no steam apparatus, no warm bathing, no friction, no irritant, avails." The condition is comparable to that in approaching death by cold, in which friction with snow is well known to be the proper remedy. Cold affusions were employed in the second stage of the disease. If the pulse revived, the affusions were continued in a tepid bath, after which the patient was put to bed and gently rubbed with cold flannels. Internally, ice-water was freely administered. Labadie-Lagrave⁷³ refers to forty cases treated in this manner, with only seven deaths. Yet the cold-water treatment does not appear to have commended itself to physicians generally. Evidently it does not meet the prime indication, which is to restore the wasted waters of the blood and retain it in the blood-vessels.

⁷² Ainsworth, Pestilential Cholera, 1832.

⁷³ Du Froid en Thérapeutique, 1878.

Cold water ought to be given as freely as possible to assuage the thirst that exists in every stage of cholera, and especially in collapse. Nor should it be withheld because it will presently be rejected, for not only does it produce a grateful sensation in the mouth and throat, but it renders the act of vomiting easier. Yet, to some extent at least, the thirst may be allayed by rinsing the mouth and throat with cold water. Iced water is preferable to ice used for the same purpose, for the latter, by its relatively intense coldness, irritates and dries the mouth. Fragments of ice swallowed whole allay the burning heat in the stomach.

On the hypothesis that the cholera poison consists of organic germs various antiseptics have been employed in this disease. Permanganate of potassium was fortunately excluded from the list, on account of its corrosive action, but, unfortunately, carbolic acid was conceived to possess virtues that rendered it an eminently suitable remedy, and creasote, which resembles it very closely, was presumed to possess corresponding virtues. Then sulphurous acid and the sulphites, which for a time were warranted to destroy every species of germ, were confidently appealed to to stay the progress of cholera, and it was at one time even a matter of dispute whether sulphite of sodium or sulphite of potassium was the more efficacious. In truth, all of these medicines were useless, even when they were not mischievous.

Cholera has never prevailed in any country without giving rise to extraordinary theoretical and practical divagations. One physician in the earliest American epidemic gravely proposed, as the best mode of checking the diarrhoea, to plug the anus with a soft velvet cork. Another, in England, suggested that the "blood may be kept circulating by putting the patient on his back on a board and keeping up a rocking, see-saw, to-and-fro movement from eighty to one hundred times a minute." Another had the revelation that the disease is essentially a "paralysis of the sympathetic nerve and want of performance of the organic functions, with deficient vitality of the mucous membranes," and that its proper remedies are "bleeding, turpentine, and cool drinks, without heat and stimulants;" and to this remarkable doctrine a well-known physician gives his adhesion, thus: "The cause, I firmly believe, is an union of the poison with the sympathetic."⁷⁴ Still another discovered that the disease is a spinal disorder, and is to be treated by the application of ice-bags to the spine. Were not the evidence so palpable, it would hardly be believed that such irrational ideas should have been published concerning a disease which had then been under observation by the whole medical profession in Europe and America for more than thirty years, and in Asia for a much longer period.

⁷⁴ Times and Gazette, Aug., 1866, p. 209; ibid., Nov., 1866, p. 555.

The most important lesson to be drawn from this history of the treatment of epidemic cholera is, that the arrest of the disease in the diarrhoeal stage is comparatively easy, and that in the stage of collapse its cure by any means whatever is altogether an exceptional occurrence.

THE PLAGUE.

BY JAMES C. WILSON, M.D.

DEFINITION.—An acute specific fever of short duration and very fatal, endemic in certain Oriental countries, and frequently epidemic; it is characterized by buboes, carbuncles, and petechiæ.

SYNONYMS.—([Greek: plêgê], plaga, a stroke); the Pest; Pestilence; the Bubonic, Glandular, Inguinal Plague; the Oriental, Levantine, Levant Plague; the Indian, Pali Plague; Máhámari; Septic or Glandular Pestilence; Pestilential Fever, Adeno-nervous Fever; Typhus Pestilentialis, Gravissimus, Bubonicus, Anthracicus, etc. Gr. [Greek: ho loimos]; Lat. Pestis; Fr. La Peste; Ger. die Pest, Beulenpest.

CLASSIFICATION.—The plague, pest, pestilence, and their equivalents in various tongues, are terms that have been used from the earliest historical times to designate every epidemic disease attended by great mortality. As knowledge of diseases becomes clearer the terms by which they are designated become more definite; those which did service for a class are restricted to particular groups, and new names are found for other maladies only allied to such groups by superficial resemblances. Hence by degrees the term plague has become more restricted in its use. To-day it is understood as designating exclusively the specific affection defined above, the bubo plague.

The student of medical history meets with insurmountable difficulties in attempting to classify the recorded epidemics which have been described under this term. Even when used in its more restricted signification, difficulties as to the propriety of its application to certain epidemics arise. Thus, nosologists are not in agreement as to whether the great plague—the black death—which swept over Europe in the fourteenth century and destroyed in three years twenty-five millions of inhabitants, was a modification of the bubo plague or an essentially different disease. A like difference of opinion exists in regard to the relationship between the Indian or Pali plague which has from time to time prevailed in North-western India during the present century and the true plague.

The black death of the fourteenth century and the Pali plague, though presenting many of the characteristics of bubo plague, differ from it, while they resemble each other, in one important particular. Among the earlier and more common symptoms of note are those dependent upon gangrenous inflammation of the lungs, a lesion, according to Hirsch,¹ extremely rare in bubo plague. This author informs us that recent observations have fully confirmed the early opinion that the Pali plague differs from that of the Levant chiefly in this modification, and cites Pearson and Francis as saying of the former disease that "the collective symptoms are more like those of plague than of any other known disease.... We believe it to be in all essential particulars identical with the plague of Egypt."

¹ Handbuch der historisch-geographischen Pathologie, Dr. August Hirsch, 1860.

The three forms of plague—(a) the grave (or ordinary), (b) the fulminant (pestis siderans), and (c) the larval or abortive, observed in epidemics and hereafter to be described—do not represent distinct varieties of the disease, but are merely expressions of differences in the intensity of the action of the infecting principle upon different groups of individuals in given communities—differences to be explained here, as in the other infectious diseases, in part by variations in the activity of the poison itself, in part by the individual peculiarities and susceptibilities of those exposed to it.

HISTORICAL SKETCH.—Upon the authority of Rufus of Ephesus, quoted by Oribasius,² it is stated that the bubo plague prevailed as an endemic, and at times as an epidemic disease, in Libya, Egypt, and Syria prior to the beginning of the Christian era.

² Medicinalia Collecta.

In the year 542 A.D., according to Procopius,³ the plague appeared in Egypt, at Pelusium; extended westward to Alexandria; eastward to Palestine, Syria, and Persia; passed from Asia Minor to Europe, where it first invaded Constantinople, whence it spread in all directions with such fury that before the close of the sixth century one-half the inhabitants of the Eastern empire had perished, either of the plague itself or of the universal destitution that followed in its train.

³ See Hirsch.

With this epidemic, known in history as the Justinian plague, this disease established itself for the first time in Europe, where it maintained foothold for more than a thousand years.

About the middle of the seventeenth century the wide prevalence of the plague in Europe began to draw to an end. In Spain it was epidemic for the last time from 1677 to 1681; in Italy the last general epidemic came to a close in 1656, although local outbreaks continued to occur till the beginning of the following century. In France it still prevailed in several provinces in 1668, although it had for the most part disappeared some years before. In Switzerland we encounter it for the last time in 1667-68; in the Netherlands in 1677; from England the plague disappeared with the great outbreak of 1665. In the early part of the eighteenth century two important epidemics occurred within the boundaries of Europe. The first spread from Turkey, through Hungary and Poland, to Russia, thence to Norway and Sweden, and along the shores of the Baltic Sea to the Low Countries. This epidemic came to an end in 1714. Six years later the last great outbreak of the plague on European soil took place. It prevailed with great fury in Marseilles in 1720-21, and overran the whole of Provence. From this date till the close of the century Europe remained free from the plague, with the exception of Turkey and the contiguous countries. During the second and third decades of the present century repeated epidemics occurred in the Balkan Peninsula and the regions bordering on the Lower Danube and the Black Sea. The plague appeared also in Malta in 1813, and prevailed till 1815, and in 1816 it reached certain of the Ionian Islands. Only twice has this pest shown itself during the present century in Western Europe—once, during the epidemic at Malta in 1815, at Noja, a town of the Neapolitan province of Bari; the second time, in 1820, at Majorca, whither it was carried over from the coast of Barbary.

Between 1552 and 1784 the plague prevailed twenty-six times in Tunis and Algiers. Some idea of the importance assumed by this scourge in the countries of North-western Africa may be found from the fact that many of these epidemics lasted continuously for years, that which came in 1784 not ceasing for fifteen years. Between 1816 and 1821 the plague again prevailed in Tunis and Algiers, and again in 1836-37.

During the first half of the present century a change took place in the prevalence of the disease elsewhere. Shortly before its complete disappearance from Europe it ceased to prevail in Western Africa (with the exception of the Nile countries), in Mesopotamia, and in Persia. It disappeared from Asia Minor, Syria, and Palestine in 1843, from Egypt in 1844.

For a short period the plague seemed to have disappeared altogether. Those who cherished this hope were, however, destined to disappointment. In 1853 an outbreak occurred in the Assyr country, Western Arabia; and from that time till the present unmistakable local epidemics of the bubo plague have occurred in isolated regions of Africa and Asia; thus, in 1858 at Benghazi in Tripoli; in 1857 in Mesopotamia; in 1863 in the district of Maku, Persian Kurdistan; in 1867 in the marsh district on the right bank of the Euphrates; in 1870 in Persian Kurdistan; in 1871-73 in the Yunnan province, Western China; in 1873 in the marsh district on the left bank of the Euphrates. During four years following the outbreak of 1873 the disease continued to prevail over an extensive area in the countries bordering on the northern banks of the Persian Gulf. In 1874 it reappeared also in the Assyr district, Western Arabia, and in Benghazi, Northern Africa. In 1876, whilst still infesting the regions about the Lower Euphrates, the plague appeared in South-eastern Persia, and during this and the following years it appeared at several isolated points on the borders of the Caspian Sea. Early in 1878 the disease was reported as prevailing in the district of Souj-Bulak, Persian Kurdistan, and it appeared in October of the same year at the Cossack village Vetlanka, on the Lower Volga, district of Astrakhan, Russia, after an absence from Europe of thirty-seven years. It has more recently prevailed in the Assyr district, Western Arabia, and there have been rumors of its reappearances in Persian Kurdistan.

The Indian or Pali plague (Máhámari) has prevailed in local epidemics of great severity on several occasions during the present century in the North-western provinces of India. This fever was first recognized in Kutch in May, 1815, after a season of great scarcity of food. It spread rapidly over an extensive territory, and appeared in the spring of the following year at various points in Guzerat, next in Merawi, later in Rhadenpur, spreading thence westward to Sindh. Not until the following year (1817) did the pest reach the British possessions. This epidemic continued to prevail until 1821. The disease did not reappear until July 6, 1836, when it broke out in Pali, the principal dépôt of traffic between the coast and North-western India. It spread with great rapidity to the adjoining provinces. Toward the close of the year 1837 the disease broke out anew in Pali, and raged until the spring of the following year. In 1834-35, again in 1837, there were outbreaks of this pest in Gurwal, and in 1846 and 1847 in Karmoun, provinces of the southern slopes of the Himalayas. This destructive pest has raged at an altitude of 10,300 feet, and we learn from Hirsch that it has never wholly disappeared from the mountain-districts of the Himalayas since 1823, and that its ravages in these regions have been so great that certain settlements have been wholly destroyed.

The fever was remittent in type, with a great tendency to become continued; it was characterized by rapidly developing extreme prostration, and was very fatal. In most cases there were glandular swellings in the groins, armpits, and neck. Carbuncles and petechiæ are not mentioned as having been observed. Dyspnoea, cough, and bloody expectoration were frequent symptoms. Vomiting, at first of bilious matter, later of dark, coffee-colored fluid, was likewise common.

The plague has never appeared in the western hemisphere.

ETIOLOGY.—1. Predisposing Influences.—Whilst the present views as to the causation of the specific diseases compel us to assume a specific infecting principle as the real cause of every outbreak of the plague, there are certain circumstances which are recognized as so favoring the development and action of that principle that they have come to be looked upon as indirect or auxiliary causes of particular epidemics. It is more in accordance with the facts to speak of them as predisposing influences. Chief among these circumstances is that combination of physical and social wretchedness which goes hand in hand with poverty and overcrowding. The plague has been termed by a recent observer (Cabiadis) miseriæ morbus, and he has thus reproduced in 1878 a name applied to the great plague of London in 1665—the poor's plague. All observers of recent epidemics unite in ascribing to poverty the foremost rank among the predisposing influences of plague epidemics. It is only necessary to enumerate the evils which form the train of poverty, whether in cities or in villages, to complete the list.

With poverty come ignorance and neglect of all sanitary laws; overcrowding and ill ventilation; personal filthiness; improper as well as insufficient diet; indifference as to the location of dwellings and their surroundings. The condition of the villages which have been the scene of some of the recent epidemics beggars description. All observers unite in testifying to such accumulations of filth in and around the houses as requires to be seen to be believed. In these communities latrines are unknown, and no such thing as organized scavenging has ever existed.

The accumulation of unburied or imperfectly buried corpses has been looked upon as the real cause of the plague, and some of the recent epidemics have followed the prevalence of distinctive epizoötics. Whilst it is not difficult to disprove that under ordinary circumstances the effluvia from exposed and rotting carcasses can give rise to outbreaks of the plague, it is more than probable that an atmosphere charged with such emanations (together with other causes) can so unfavorably influence a community as to increase its susceptibility to the specific cause of this or any other infective disease. There can be but little doubt that the dead bodies of the victims of the plague are capable of disseminating the disease, and that the reopening of graves containing such bodies, even after a long period of time, has given rise to fresh outbreaks of the disease.

The season of the year does not appear to exert any very marked influence upon the development of epidemics, if we base our deductions upon observations made in different countries. In northern countries the disease has prevailed as severely in mid-winter as in summer. The epidemics of London showed a rise during July and August, their furious prevalence in September, and a gradual decline during October and November. In Constantinople the disease has commonly remained dormant during the winter months, and become active as the weather grew hotter. In Egypt, on the contrary, the activity of the outbreaks has developed in winter, increased with the advance of spring, and suddenly abated upon the advent of the summer. Such also has been the case with the three general epidemics in Mesopotamia studied by Tholozan.⁴ "Their beginning took place in winter, their development during the spring, their decline and their extinction in summer. Their recrudescences obeyed the same laws: after an incubation during the summer season ... revivification took place in winter and in spring." It is added in this writer's account that the exceptional hot weather of summer in that country, and especially that of the shores of the Persian Gulf, has always moderated or directed the course of epidemics of this pest. In Cairo the epidemics have usually ceased upon the recurrence of intense summer heat in June. Dampness, and particularly a thoroughly wet soil, are favorable to the development and spread of the disease. The marshy regions of the Lower Euphrates, the shores of the Caspian and the Black Seas, the valley of the Nile, have been the scenes of repeated visitations. On the other hand, the plague has maintained its foothold in the mountainous districts of Western Arabia, in Yunnan, on the slopes of the Himalayas at a great elevation, and upon a dry, non-alluvial soil even more firmly than in the low and humid plains of Mesopotamia.⁵

⁴ Histoire de la Peste Bubonique en Mesopotamie, 2d Mémoire, Paris, 1874.

⁵ Tholozan, Histoire de la Peste Bubonique en Perse, 1st Mémoire, Paris, 1874.

Individual predisposition to contract the disease seems to be increased by all depressing influences, among which may be mentioned excessive bodily or mental exertion, intense and prolonged anxiety, fear, and the like. Previous debilitating disease also increases the liability to the attack. Neither sex nor age exerts an influence in this respect, save that after the age of fifty few contract the disease. Occupation confers no immunity. Physicians, nurses, and others occupied in the care of the sick, and those who bury the dead, have especially suffered in recent⁶ as well as in the older outbreaks. Oil-carriers and dealers in oils and fats, and to a less degree water-carriers and the attendants at baths, are said to enjoy a comparative immunity from attack. Those who have suffered from the disease and recovered also enjoy a relative immunity. Second attacks are usually of less intensity than the first.

⁶ See summary of a report addressed by Dr. G. Cabiadis to the Constantinople Board of Health on the outbreak in Astrakhan in Russia, 1878-79, by E. D. Dickson, M.D., Medical Times and Gazette, 1881, vol. i. pp. 4, 32, 119.

2. The Exciting Cause.—The exciting cause of the plague must, in the present state of our knowledge, be assumed to be a specific infecting principle. Upon no other hypothesis can the continued existence of a disease so specific in its characters, unchanged through the course of centuries, disappearing when the influences favorable to its presence cease, reappearing in certain regions when they again arise, be explained. Capable of being transmitted by the vehicles of commercial intercourse, of control by quarantine and cordons sanitaires, of spreading from limited foci of contagion into overwhelming epidemics, the plague is the very type of the infective diseases. The nature of this infecting principle is wholly unknown. It is probably a microphyte capable of development within the human organism—capable also of a prolonged independent existence under favorable circumstances outside of the body, and of again giving rise to the disease. The plague is properly to be classed as a contagious-miasmatic disease (Liebermeister) with cholera, dysentery, and enteric fever. It continues to exist by the continuous propagation of its cause, and it spreads by the transportation of that cause.

It is conceded on all hands that the plague has never arisen autochthonously in Europe, but has in every instance been conveyed thither. Those who regard its reappearance after long intervals of time in those countries where it still occasionally prevails as spontaneous are compelled to ignore difficulties in reasoning far greater than the supposition of an equally prolonged condition of quiescence or an inexplicable or unsuspected reintroduction of the cause.

As to the disputed question of the contagiousness of the plague, to set forth the arguments and examples adduced in favor of either view would far exceed the limits of the present article. All the facts are to be explained upon the theory that the exciting cause of the plague, like that of cholera and enteric fever, consists of a miasm that must undergo certain changes outside the body before acquiring its virulent properties, and that the time required for these changes is exceedingly brief. But what the physical properties of this miasm are, or how it finds access to the body, or how it is eliminated, are alike utterly unknown to us.

It is certain, however, that it is incapable of being freely transmitted to great distances in the air. Whether or not it is conveyed or retained by the discharges from the bowel is not known. The history of recently observed outbreaks, from which alone definite and trustworthy facts are to be obtained, goes to show that the exciting cause of the plague clings closely to the patients and their immediate belongings. The closer the relation between those sick and the healthy, the greater the risk that the latter will contract the disease. Those in the house with the patients are more liable to fall sick than those in the adjoining houses—those who are constantly in their presence than those who occasionally see them. Thus, nurses much more frequently contract the plague than doctors, though the latter have in all epidemics been largely numbered among the victims. Among 357 deaths in the outbreak in Vetlanka, already referred to, were a priest, his wife and mother, three doctors, six assistant medical officers, and two Sisters of Mercy. Dr. Cabiadis remarks that the information obtained "shows that the malady propagated itself, in the first instance, from the sick to their relatives and to those who lived with them or who assisted them during their illness. If, on the one hand, these facts showed its contagious character, on the other hand evidence is still wanting to prove whether this transmission of the malady was caused by contact with the sick and their clothing, or by breathing an atmosphere impregnated with the deleterious particles emanating from their morbid bodies."

The period of incubation is from two to seven days. In the report of the commission of the French Academy of Medicine, drawn up by Prus in 1844, the statement appears that the plague has never shown itself among compromised persons after an isolation of eight days. The recent outbreaks tend to confirm this conclusion. L. Arnaud concluded from observations made at Benghazi in 1874 that the mean duration of this period was five or six days, and that the maximum did not exceed eight days. Cabiadis sets this stage down as three days as the rule, but as occasionally not exceeding twenty-four hours. He found no data, however, to show the longest period to which it could extend. Hirsch, from information collected in his investigation of the same epidemic (that of Astrakhan), concluded that the minimum period of incubation observed was from two to three days, the maximum more than eight, and that the average was five days. He states that very short or very long periods were seldom observed.

SYMPTOMATOLOGY.—Individual cases of the plague, as of other epidemic diseases, differ in their onset and progress under different circumstances and at different periods of particular outbreaks. Besides the ordinary form, to which as a type the greater number of the cases more or less closely conform, there are, on the one hand, others so severe that death takes place before the characteristic manifestations have time to appear, and, on the other hand, cases so light that such manifestations are but partly developed, and the nature of the malady is only to be recognized in the light of the prevalent epidemic influence.

Hence among the cases three forms are recognized: (a) The grave or ordinary form; (b) the fulminant form; and (c) the larval or abortive form.

(a) Grave or Ordinary Form.—The plague in typical cases is a febrile malady of the most acute kind, with localizations in the form of buboes or carbuncles.

The course of the attack may, for convenience of description, be divided into four stages: 1, the stage of invasion; 2, the stage of intense fever; 3, the stage of fully-developed localizations; and 4, the stage of convalescence.⁷

⁷ This formal division of the description is suggested in some of the older accounts. (See "Loimologia; or, An Historical Account of the Plague in London in 1665, by Nathan Hodges, M.D., and Fellow of the College of Physicians, who resided in the City all that Time, Lond., 1721.")

The appearance of the plague in France in 1720 was the occasion of a great number of curious and interesting publications on this subject.

1. The stage of invasion is marked by a feeling of lassitude, by pains in the loins and extremities. There is extreme bodily and mental weakness, headache, fulness and throbbing of the head, dizziness. The patient's expression is dull, stupid; he replies to questions slowly or awkwardly, his face is pale, his eyes languid, his gait feeble and staggering. The appearance in this stage has been compared by several observers to that of a drunken man. Shivering occurs, but if fever be present it is slight. Nausea, vomiting, and diarrhoea are symptoms sometimes observed. This stage begins suddenly. It is often imperfectly developed, and it may last only a few hours or a day or two.

2. The second stage is characterized by fever of the most intense kind. It is ushered in by a chill, sometimes slight, commonly severe. The lassitude continues, the headache increases, the dulness deepens to stupor or gives way to delirium. The temperature rises to 102°-104° F., or even to 107.6° F. The pulse quickly mounts to 120 or 130. The skin is hot and dry; the patient complains of burning inward heat and of great, sometimes unbearable, thirst. The eyes are sunken and injected; the tongue moist, pale, and thickly covered with a chalk-white or grayish pasty coating; the vomiting often continues. The delirium is commonly active or noisy, and accompanied by great restlessness; it may, however, be mild, tending to sopor or coma. The progress of the disease now rapidly advances. The patient falls into the so-called typhoid state. His tongue becomes dry, hard, and fissured; sordes collect upon the teeth and lips, bloody crusts about the nostrils. At this time the evidences of failure of the forces of the circulation become conspicuous. The pulse grows feeble, small, often irregular—sometimes it can scarcely be felt; the lips become bluish, the extremities cold. There is tendency to collapse. During the course of this stage buboes begin to make their appearance. Sometimes the enlargement of the superficial lymphatics is preceded by tenderness or pain of more or less intensity; often the glands are found to be enlarged only upon search.

The termination of this stage is marked by a sudden fall of the temperature to subnormal ranges (93.2° F. has been observed); at the same time copious strong-smelling sweat not infrequently occurs. The pulse grows feebler, and falls to 100 or below it, and the mind becomes clearer.

3. These changes lead up to the stage of fully-developed local manifestations. The enlarged lymphatics are most commonly situated in the groins or on the upper part of the thighs at a point below that commonly the seat of venereal buboes; less often they are to be found in the armpits or the region of the angle of the jaw; as a rule, they occupy only one or two of these positions in the same patient. They vary in size from a little mass or kernel, only to be discovered after careful search, to the bulk of a hen's egg or a mandarin orange. The swelling of the gland takes place at times with great rapidity. Suppuration is followed by the discharge of an ichorous pus, and not rarely by ulcerative destruction of the surrounding tissues. Suppuration occurs more frequently than resolution, but is comparatively rare in fatal cases. Hence it has come to be popularly regarded as a favorable prognostic sign, whilst the early subsidence of the swelling has been looked upon as an omen of grave import.

The time of the appearance of the buboes varies greatly. In the greater number of cases they have shown themselves on the second, third, or fourth day of the attack, occasionally within six or eight hours of the beginning of the attack, and occasionally they have been observed to precede the general manifestation of the disease; rarely they have appeared as late as the fifth day. In many cases they are absent altogether.

Carbuncles demand attention as being among the characteristic local manifestations of this stage. They are less common than buboes. Their usual position is upon the lower extremities, the buttocks, or the back of the neck. In favorable cases the gangrene after a few days becomes limited and the slough separates. Boils also occasionally appear.

Petechiæ occur in the worst cases, and often at an early period in the course of the disease. Their appearance usually indicates a fatal issue. They occupy at times extensive areas of the body or the greater part of its surface; at times they appear only in the neighborhood of the buboes. They vary in size from a mere speck to spots several lines in diameter. When very numerous they give a livid hue to the skin, and that appearance to the cadaver to which, together with the high mortality, was doubtless due the term black death by which severe epidemics were known in the Middle Ages.

Vibices and extensive ecchymoses sometimes appear shortly before death.

4. The stage of convalescence sets in between the sixth and tenth days. It is often protracted by prolonged suppuration of the bubonic enlargements. Both relapses and distinct second attacks have been noted by recent as well as the older observers.

In addition to the foregoing sketch of the course of the disease in its ordinary form it is necessary to describe certain other symptoms.

The attack has sometimes begun with a convulsive tremor, at other times with a prolonged shaking, which has lasted from six hours to three days, the patient remaining free from fever and not complaining of cold. This condition has terminated in coma, followed speedily by death.

Sometimes the attack has come upon the patient with great confusion of mind, so that he appears dazed, or else a curious distraction has befallen him in the midst of his ordinary avocations. If absent from home, such patients commonly at once set out to return, either trembling and staggering as though tipsy, or else rushing wildly through the streets with frantic gestures and outcries.

The vomited matters are usually at first gastric mucus with bile, afterward dark coffee-colored fluid; in certain cases blood is vomited. Bleeding from the nose, lungs, bowels, vagina, and urethra have also been observed. Cases attended by hemorrhages have in almost all instances terminated fatally.

Constipation has been, as a rule, present during the acute stages; later in the attack diarrhoea has occasionally occurred. It has been looked upon as a favorable symptom.

The urine has been diminished and suppressed in grave cases. Trustworthy observations, both as to its quantity and its chemical composition, are wanting. It has been observed to contain blood.

As has been already pointed out, the Máhámari of North-western India has been especially characterized by lung symptoms. Other regions also have been visited by epidemics in which acute pulmonary lesions formed a prominent part of the morbid complexus.

(b) The Fulminant Form.—Chiefly in the early days or weeks of epidemics, but to some extent also later, cases occur in which the intensity of the sickness is so great that the patient dies before its usual manifestations have time to develop. The duration of the whole attack, which ends fatally, is often not more than a few hours; its symptoms, which differ but little if at all from those of similar cases of other epidemic diseases—such, for example, as epidemic cerebro-spinal fever in its fulminant form—are of the most aggravated character, and the patient perishes overwhelmed by the infection as though struck by a thunderbolt. Profound disturbance of the nervous centres, convulsions, coma, the rapid formation of vibices and petechiæ, collapse, are the speedy forerunners of the fatal issue.

(c) The Larval or Abortive Form.—Toward the close of an epidemic the character of the disease usually undergoes a change. It becomes less malignant. The cases present the essential symptoms, but in diminished intensity. Some cases terminate in an early defervescence with rapid subsidence of beginning local manifestations; others present merely the evidences of a slight disturbance of the general health, without any characteristic symptoms of the prevalent disorder; others, again, are characterized by the appearance of buboes without pain or fever. These swellings undergo resolution in fourteen days or thereabout. Exceptionally they suppurate.

The duration of the plague is from six to ten days in typical cases running a favorable course; those of fatal cases from one to twenty days. Clot Bey⁸ found the duration of the worst cases two or three days, of those next in point of severity five or six days, whilst in milder cases death did not occur until the second or third week. Of 534 fatal cases noted by W. H. Colvill, 126 occurred one day after the attack, 80 two days after it, 105 three days, 76 four days, 60 five days, 26 six days after the attack. After six days the number of deaths rapidly declined; on the nineteenth day 1 death, and on the twentieth day after the attack 11 deaths, occurred. It is said that death after the seventh day is commonly not in consequence of the disease itself, but of sequels. Of 16 fatal cases in the village Prischib in Astrakhan, noted in the report of Dr. Cabiadis, and of whom the names, as well as the day of their exposure, their falling sick, and their death are given, 1 died in one day, 4 in two days, 6 in three days, 3 in four days, and 2 in six days.

⁸ De la Peste observée en Égypte, Paris, 1840.

The mortality of the plague is greater than that of any other epidemic disease. In all epidemics a large majority of those who contract the disease die. This is especially true of epidemics at their beginning, when it has often happened that for a time all the cases have perished. Of this, as of other epidemic diseases, it is true that the death-rate has varied in different outbreaks and at different periods of the same outbreak. Colvill states that in the epidemic of 1874 in Mesopotamia the mortality of stricken villages during the first half of the time was 93 to 95 per cent. of those attacked, but that afterward the majority of those attacked recovered. The same authority states that in Bagdad in 1876 the mortality was 55.7 per cent. of persons attacked. Arnauld gives the mortality at Benghazi in 1874 as 39 per cent. of attacks. The death-rate at Vetlanka was 82 per cent. of those attacked. In Toulon in 1721, of a population of about 26,000 human beings, about 20,000 were attacked, and of these 16,000 died. It has been by no means of rare occurrence that nearly half the population of towns have perished in an epidemic, or that small villages have been completely depopulated by this scourge.

COMPLICATIONS AND SEQUELS.—The appalling mortality of the plague on its approach, the rapidity of its spread, the popular commotion upon its appearance, its brief course, and the fact that its recent outbreaks have taken place in regions where trained European physicians have been, with a few exceptions, beyond reach, all unite in maintaining the gloom that has since the Middle Ages enveloped the clinical facts of this disease.

Of its clinical course, beyond the brief outline already given, little is accurately known, of its complications still less. In some of the recent epidemics, and particularly in the outbreaks of plague in India, the evidences of pulmonary lesions have been so conspicuous that they deserve to be classed among the essential manifestations of the disease rather than as complications; in others pulmonary congestion, hæmoptysis, the evidences of croupous or catarrhal pneumonia, have occurred in a small proportion of the cases. Aside from this, there is nothing to be said as to the complications.

Among the known sequels are protracted ulceration of the enlarged lymphatics, boils, superficial or deep abscesses, catarrhal pneumonia, pertussis, mental troubles, and the like. Extensive and deep cicatrices are not infrequently found in the site of the ulcerating local manifestations.

MORBID ANATOMY.—The existing knowledge of the morbid anatomy of the plague is but scanty. The observers of the early outbreaks contributed nothing; the recent outbreaks have taken place under circumstances in which anatomical investigations were impracticable. The knowledge which we possess is almost wholly due to the investigations conducted by the French in Egypt at the close of the last and the beginning of the present century, and again during the years 1833 to 1838.

The descriptions of Bulant,⁹ Clot Bey, and others point to gross lesions, such as are found after death in the acute stages of the infectious diseases in general. The viscera were engorged with dark fluid blood; ecchymoses were often found in the mucous and the serous membranes, in the substance of the different organs, and into the connective tissue. The spleen was in almost all cases enlarged, softened, and of a dark color. Not rarely the kidneys were deeply engorged, and extravasations of blood into their substance, their pelves, and into the surrounding connective tissues were often encountered.

⁹ De la peste oriental d'apres les matérnaux recuillés à Alexandrie, à Smyrne, etc., pendant les Années 1833 à 1838, Paris, 1839.

The only constant and characteristic changes relate to the lymphatic system. The lymphatic glands were, as a rule, enlarged and deeply injected with blood. Where no buboes existed the glands of the various cavities of the body showed evidences of acute inflammatory processes. In some instances the affection of the glands appeared to be general; less frequently it was most conspicuous in, or apparently limited to, one or more great groups. Thus, the bronchial, the mediastinal, the mesenteric, the lumbar, etc. were severally the seat of marked changes with or without enlargement of superficial groups, or several of these groups were at the same time implicated.

In no instance were symmetrical enlargements of the inguinal regions, the axillæ, or the throat met with.

According to Runnel,¹⁰ in 2700 cases there were inguinal buboes in 1841, axillary in 569, maxillary in 231; inguinal buboes occurred 175 times on both sides, 729 times on the right only, 589 times on the left only; the axillary buboes were double 9 times, right only 185, left only 163. Buboes of the neck only occurred 130 times, and of them 67 cases were children.

¹⁰ A Treatise on the Plague, London, 1791.

The connective tissue surrounding the affected glands was the seat of an infiltration sometimes serous, sometimes cellular; it also very commonly contained more or less extensive extravasations of blood. Even where no buboes appeared on the surface of the body the glands were enlarged to twice their usual size or more. The substance of the glands in the larger swellings was at times uniformly red or violet, again whitish or marbled or pulpy or denser, or of the consistence of fat. It was also sometimes soft like jelly, and rarely it contained minute collections of pus. Some observers speak of dilatation of the lymph-vessels in the neighborhood of the enlarged glands.

DIAGNOSIS.—The difficulties attending the recognition of the plague at the beginning of an outbreak speedily subside. The rapid spread of the disease, its frightful mortality, the overwhelming intensity of the symptoms, the prompt occurrence of cases characterized by buboes, carbuncles, or petechiæ, are collectively considered diagnostic of this, and of no other disease whatever. In regions subject to the repeated visitations of this pest there exists a universal unwillingness to mention even the name of a disease whose suspected presence alone is followed by consequences of the most serious nature to the freedom of personal and commercial intercourse. To this unwillingness, rather than to any real likeness between the plague and other diseases with which it has been compared, are to be traced most of the difficulties as to the differential diagnosis that have been raised, especially in the regions bordering on the Mediterranean Sea.

It is not, therefore, necessary in this place to discuss the diagnosis between the plague and malarial and other pernicious fevers, malignant typhus, epidemic dysentery, lymphadenitis, syphilitic buboes, parotitis, and so forth.

TREATMENT.—Preventive.—The efficient treatment consists in prophylaxis. The history of this disease indicates with singular clearness the measures which, properly carried out, are capable of controlling the spread of the epidemic diseases. These measures arrange themselves into two groups, of which the first has to do with the removal of the conditions familiar to the development of the disease, the predisposing influences; and the second with the restriction of the disease to the locality in which it shows itself—isolation, quarantine.

The conditions favorable to the development of the plague have already been set forth under the heading Etiology. They relate to poverty and ignorance, and their attendant evils, in communities. They are those conditions which tend to disappear under the influences of civilization, and in truth it may be said that at the present time the plague occurs only in half-civilized countries.

Preventive medicine has achieved no other work comparing in magnitude and importance with the extinction of the plague in Europe. This was, to use the words of Hirsch, "a gradual process, and kept pace in great measure with the development and perfection of the quarantine system with reference to the Orient and the different countries of Europe." This author continues: "I cannot, in fact, understand how any one criticising the facts without prejudice, and having regard to the state of the plague in the East, can for a moment hesitate to attribute the chief cause of the disappearance of the plague from European soil to a well-regulated quarantine system." The European has by no means lost his susceptibility to the disease. He is liable to attack in the East. His protection at home lies in the restriction of the exciting cause of the disease to its present haunts.

Any extended notice of quarantine and quarantine laws is beyond the scope of this article. It may be said, however, that with reference to the plague measures quite unnecessary under ordinary circumstances assume the greatest importance when this disease makes its appearance in countries bordering upon Europe, and that no amount of hardship to individuals necessary to avert so great a calamity as a plague epidemic could be looked upon as excessive. Indeed, we can with difficulty realize the severity with which measures of isolation have been carried into effect at times when the devastation produced by the plague was still vividly remembered. Violation of the orders issued during an epidemic has been punished with no less a penalty than death. It is related that upon the appearance of the plague in the little town of Noja in Lower Italy in 1815, troops were despatched immediately to surround the place with a cordon. The town was encircled by two deep ditches, and opposite the gates three ditches were spanned by drawbridges, which served as a means for the introduction of provisions, but no other communication was allowed. Only letters were allowed to leave the city, and these were first dipped in vinegar. Cannons were posted at the city gates. The ditches were occupied by sentinels, who were ordered to shoot down any one who approached and failed to stand still the moment he was hailed. A plague patient who escaped while delirious and attempted to pass the lines was, in fact, shot dead. Outside this cordon two others were established. Those who disobeyed the orders were treated with the greatest severity. An inhabitant of Noja, who had thrown a pack of cards to the soldiers, together with the soldier who picked it up, was tried by court-martial and shot.¹¹

¹¹ Ueber die Pest zu Noja, Nürnberg, 1818, quoted by Liebermeister in Ziemssen's Encyclopedia, article "Plague."

Lower Italy, possibly Europe also, owed its escape to the rigorous measures carried out in this instance; nor can it be doubted that the measures of isolation practised during the outbreak on the Volga 1878-79 restricted the disease to the district in which it appeared and brought it to a speedy end. On this occasion three efficient cordons were established to isolate the infected places. The first cordon was put around every place where plague prevailed, to prevent persons from entering or quitting that locality until forty-two days had elapsed after the last attack of the malady there. The second cordon was formed around the infected area, encircling all the infected localities. Its circumference extended 800 kilometres, and was guarded by pickets of soldiers stationed at intervals of five kilometres. This cordon had four quarantine stations. The third and outermost cordon was established round the whole province of Astrakhan. It served to control the functions of the inner cordons, inasmuch as all persons coming from within its area, who could not prove that they had undergone quarantine at the stations of the middle cordon, were stopped.

The complete disinfection of all clothing and other articles used in the service of the sick is to be included among measures of prophylaxis. It is no uncommon thing to destroy by fire the houses in which cases have occurred, along with their contents.

No efficient means of protection are known for those who during an outbreak cannot escape from the infected neighborhood. It would be without purpose other than to amuse the reader to reproduce the quaint fancies of the older physicians in this matter, or to dwell upon the amulets and incantations, the absurd costumes, the protective power of tobacco, according to Diemerhoeck, or the disbelief in its virtues on the part of Hodges, who preferred "canary, of the best sort, of which he frequently drank while he attended the sick."

Clinical.—"The treatment of individual cases must in the present state of knowledge be expectant and symptomatic. Notwithstanding our acquaintance with the symptoms that characterize plague, we are utterly ignorant of the treatment best suited to its cases" (Cabiadis).

Physicians who have written from personal observation unite in advising a treatment of the simplest kind. Ventilation, cleanliness, a liquid diet, abundant cool drinks, are to be ordered. The initial collapse and the evidences of failure of the circulation call for the use of stimulants, and especially of alcohol. Cold or tepid sponging, in accordance with the sensations of the patient, may be resorted to. If there be high fever an energetic antipyretic treatment might be carried out. Cold effusion is said to have been of use in many instances.

Purging, bloodletting, mercurials, blistering, emetics, have proved either positively injurious or altogether without effect upon the course of the disease.

Of drugs, ammonium chloride, salicylic acid, carbolic acid, quinine, have been administered without positive effect.

It is stated that the free inunction of oil from the very beginning of the attack was affirmed to exert a favorable influence.¹²

¹² See Griesinger, Virchow's Handbuch der Speciellen Pathologie und Therapie, ii. 2, s. 316.

In early times the buboes were often incised, or even excised, as soon as they began to swell. More recently they have been treated with leeches or inunctions of mercurial ointment. The treatment by poultices and the evacuation of pus as soon as it can be detected is at present regarded with greater favor. Carbuncles are likewise to be treated in accordance with accepted surgical procedures.