quinine for a long time, really suffer from quinine poisoning, and especially is it inadvisable to give very large doses in chronic malaria. They would rely on arsenic in chronic malaria.

This difference of opinion from different parts of the world may represent different types of the disease. There is no question that we must recognize that the constant taking of a protoplasmic poison as is quinine cannot be to the advantage of the individual. It is an appetizer and a stimulant, but at the same time it may inhibit many cellular and glandular activities. It also is a habit-forming drug; the patient soon misses the stimulation when the drug is stopped. At times it has been noted in tropical regions that if hemoglobinuric fever develops, those who have taken considerable quinine previously have the disease more severely. We must, however, come to the conclusion that for short periods at least, a prophylactic dose of 3 to 5 grains of quinine aids in preventing malarial infection.

The treatment of estivo-autumnal fever combines so much more than the administration of quinine that it belongs to a book on therapeutics. The relation of hemoglobinuric fever to malaria and the treatment with quinine is also too broad a subject to here discuss. Suffice it to say that in some cases the administration of quinine may increase the danger from hemoglobinuria, however, it seems still to be the best treatment for this form of fever. The germs of hemoglobinuric fever can undoubtedly, without any action of quinine, cause hemoglobinuria. Also this infection may produce a nephritis.

Pernicious malarial fever, so called congestive chills, is recognized as of great danger to the patient; therefore intensive treatment with quinine is necessary. If there is not time before the expected next chill for the absorption of a large dose of quinine, perhaps 40 to 50 grains, it has been advised to give the drug either subcutaneously, intramuscularly, or intravenously. It seems that intramuscular or subcutaneous injections of quinine are hardly safe, even in the form of the quinine and urea hydrochloride, as serious destruction of tissue may be caused. Also intravenous injections may cause serious symptoms, especially if the blood-pressure is low.

In so-called chronic malarial poisoning, often associated with

an enlargement of the spleen, various treatments have been suggested, all with quinine as a basis. Hydrotherapeutic measures, sweating treatments, and the administration of iron, arsenic and quinine represent the best treatment.

For patients who cannot take quinine and who have malarial fever, arsenic and methylene blue are the best, but poor, substitutes.

Other Uses.-Quinine in small doses has long been used as a tonic. It increases the appetite and tends to raise the bloodpressure.

The dihydrobromide of quinine is many times very successful in the tachycardia of Graves' disease. The dose must be large, at least 0.30 Gm. (5 grains) three times a day, and it must be given for some time. The disagreeable cinchonism at first caused is soon not in evidence, and the drug is generally well tolerated.

The anesthetic properties of quinine and urea hydrochloride have been much lauded, especially to cause desired necrosis. It would seem hardly safe to inject this drug into the thyroid gland in Graves' disease, although it has been advocated. The use of the drug to destroy tissue has been well described by Babcock. The first sensation caused by this drug, when injected, is intense burning, which is soon dulled by the anesthetic action. When injected under the skin Babcock states that the tissue becomes at first anemic, then necrotic, and a few days later there is a black eschar. When injected into mucous membrane, the black eschar does not occur. There is likely to be a good deal of edema develop in the region of the injection, and there also is considerable danger of a patient having an idiosyncrasy against quinine and developing unpleasant symptoms. An idiosyncrasy could probably be readily determined by the skin antigen tests, as above suggested. Babcock believes this anesthetic destroyer of tissue may be valuable to use in port wine stains or birth marks, for some growths on the skin, and to destroy warts and moles.

This drug may be obtained in ampules, from a few drops to 2 mils of which may be injected, depending upon the area it is 1 New York Med. Journ., March 3, 1917, p. 385.

desired to destroy. It would seem that other methods of cauterization and destruction of tissue would be safer.

SERUMS AS SPECIFICS IN HEMORRHAGE

The drugs used to stop external bleeding have been termed styptics. The best for local use are peroxide of hydrogen solutions; ferric salts; suprarenal extracts; ice; and, perhaps, cauterization. It should not be forgotten that the most effective means of stopping external bleeding is by pressure, either at the point of bleeding or on the artery above.

The method used to stop internal bleeding depends somewhat upon the location of the bleeding part, but anything that lowers blood-pressure and quiets the heart's action tends to stop hemorrhage; hence rest, quiet, and at times, in nervous excitement, small doses of morphine, if the hemorrhage has not been too great in amount, are of great benefit in causing the bleeding to cease.

Nitroglycerin is valuable in lowering blood-pressure and in stopping internal hemorrhage, especially in hemoptysis. It is a mistake to give drugs that raise the blood-pressure during hemorrhage unless that hemorrhage is venous and is due to insufficiency of the heart. Venous bleeding is likely to be from the nostrils, or it may be from the lungs In such a case digitalis will be of benefit, although it does not act until some hours after it has been administered. In most internal hemorrhage, strychnine, suprarenal, atropine, caffeine, ergot, tyramine, etc., are contraindicated. Ergot is of value in uterine hemorrhage when the uterus is dilated, as it contracts that organ, and therefore closes the bleeding vessels.

Bleeding from the nose may be checked by cotton tampons, dry or soaked in peroxide of hydrogen solution or in some more active styptic, or by post-nasal packing. Applications of an epinephrine solution may stop the hemorrhage, but it is likely later to cause local congestion.

Hemoptysis may be checked by rest, nitroglycerin, and morphine in a small dose if needed. Repeated bleeding may require calcium, digitalis, or some serum injection, and possibly the injection of gas or air into the pleural cavity. Hematemesis

may be stopped by a suprarenal solution taken into the stomach, or by swallowing ice, and by rest.

Intestinal hemorrhage may be combated by some tannic acid preparation, as protan ("tannin nucleo-proteid"), by gelatin, by calcium, and by rest. Morphine may be necessary to cause peristaltic rest. Kidney hemorrhage perhaps is well treated by gallic acid. It is doubtful if cotarnine salts, as cotarnine hydrochloride or cotarnine phthalate (styptol) are of any value.

Of course it is understood that in every case of internal bleeding, the exact cause must, if possible, be determined, and often surgery must be invoked to cure the condition of which hemorrhage is a symptom. If the blood does not normally coagulate, calcium must be administered in the form of lime water or as calcium lactate, and plenty of milk must be given.

Thromboplastic substances and fibrin ferments, brain extract and so-called kephalin and coagulin are described on pages 371, and 509 but the serum from blood seems to be the most active coagulant that we can administer.

The blood serums used are from the human, from the horse, and from the rabbit. The serum of the rabbit is perhaps more similar to human serum than that of the horse, but horse serum is always available, as it can be obtained in sterile ampules or in the form of diphtheria antitoxin, and when other serum cannot be obtained, the contents of an ordinary tube of diphtheria antitoxin, representing the fewest units, may be injected. Subcutaneous injection of course is a slower therapeutic method than the intravenous injection. It must be known whether the patient is susceptible to the emanations of the horse, i.e., whether he has any hay fever or asthma when in the region of a horse or a stable, else serious poisoning, serum sickness, may be caused.

Theoretically when it can be obtained, normal human serum from a person who is known not to be diseased, and in whom the Wassermann test is negative, is the best serum to use. From 10 to 20 mils of the serum may be given to hemophiliac patients daily for a short time, until the bleeding stops. While human blood should not be administered intravenously to a patient

unless the tests have been made to show that the donor's blood is not destructive to the recipient's blood, serum from a donor may be injected without such an examination. At the present time transfusion has become so successful that, when possible, it should be the treatment for a hemophiliac or for one who has a serious hemorrhage, unless more simple treatments are quickly successful.

At times profuse bleedings occur on account of endocrine gland disturbances, and sometimes the administration of thyroid extract is successful in stopping such bleedings, and at other times suprarenal extract is successful.

Coagulose, which is a dried product prepared from horse serum, comes in ampules, ready for use. It may be placed dry on a bleeding surface, or it may be dissolved in sterile water and injected subcutaneously. The whole contents of the ampule, representing about 10 mils of the fresh serum, may be injected and repeated, every few hours if deemed advisable.

Gelatin may be dissolved and given for hemorrhage from the stomach and intestines, and may be of some value, when absorbed, for other forms of internal hemorrhage; but to inject preparations into the muscle tissues, even if sterile, is inadvisable. If gelatine is used for injection purposes it must be thoroughly sterilized, as it may contain the germs of tetanus.

Thromboplastin solutions for injection come in sealed vials containing 20 to 25 mils of the solution. These preparations are likely to deteriorate, and therefore should be kept where they are cool, like other serum products, and should be dated.

CLASS VIII

DRUGS USED AS SPECIFICS

COLCHICUM IN THE TREATMENT OF GOUT

The cause of gout is unknown, but it is of interest to note that as arthritis deformans, which is due to some focal infection, is more and more frequently recognized, gout is becoming less frequent. However, there is a disease or a condition of gout, and the tendency to gout is inherited.