are absorbed parenterally, i.e., outside of the intestine, poisoning may occur and sensitization and anaphylaxis result.

Novy and de Kruif1 state that anaphylatoxin is produced by the circulation of the matrix of the poison in the blood. This matrix circulating in the blood becomes a poison when any alien substance is added to the serum, and many of the simplest substances may cause this transformation of the matrix into a poison. The sudden development of this anaphylatoxin or "taraxin" as these investigators state may bring on the explosive symptoms seen in eclampsia and surgical shock, or may be the cause of some of the sudden symptoms in autointoxications, and many of the symptoms of infectious diseases are probably caused by the formation of anaphylatoxin. In other words, infection leads to "taraxy," as they term it. They urge the importance of the consideration that perfectly harmless substances in the blood may suddenly, under certain conditions, develop this anaphylatoxin and taraxy, and serious symptoms may immediately result.

It has been shown that surgical shock may be caused by absorption of muscle juices from the destruction of muscle tissue, and hence the condition is one of protein poisoning.

Typically anaphylaxis is a fever reaction, with rapid heart, with flushings of the skin, frequently eruptions on the skin of erythema, urticaria, or patches of angioneurotic edema, and possibly cerebral excitation. Sometimes in susceptible individuals very dangerous reactions occur from injections of serum, with swelling of the mucous membranes, especially of the bronchial tubes, with the development of asthma and dyspnea even to the point of suffocation. Such a reaction may be immediate, and has occurred when an antitoxin made of horse serum was injected into individuals who were susceptible to protein poisoning from emanations from the horse. Consequently, it is unjustifiable to inject a serum prepared from the horse into any individual without the knowledge that he is not subject to asthma or hay fever from contact with the horse. Also any asthmatic patient should be given protein injections only with the greatest of care. In such cases, at least, it is Journal A. M. A., May 26, 1917, p. 1524.

wise to give an intradermal drop test before the larger injection is made to determine the presence or absence of hypersensitiveness to the particular vaccine or serum to be used.

Some protein poisons cause an increased temperature and some a lowered temperature. Those that cause a lowering of the temperature are supposed to do so by their ability to dilate the peripheral blood-vessels and the blood-vessels of the abdomen and to cause congestion of the liver. Consequently, with this subnormal temperature there is also a subnormal blood-pressure and more or less shock, sometimes termed anaphylactic shock. Prevention of Anaphylactic Reaction.-A careful study of every patient should be made before injections of horse serums or other proteins are given. In all acute conditions the necessity for carbohydrate food and alkali should be recognized, and toxic reactions during serious illness will frequently not occur if the development of acidosis is prevented.

The relation of the endocrine glands to protein poisoning should also be considered. An insufficiency of the thyroid and parathyroids (both the thyroid and parathyroids may be seriously affected by infection) should be considered. At times thyroid extract in small doses, or small doses of an iodide should be given in both acute and chronic diseases. Also, if there are symptoms of muscle, nerve and cerebral irritability, alkalies, especially calcium and sodium preparations, should be given to counteract the irritability caused by a possible insufficiency of the parathyroid glands.

Non-specific protein therapy is now advocated for many conditions. The protein reaction seems to aid in the production of antibodies or antitoxins for the disease that is present. Protein injections have been given in chronic infections as well as in some acute infections, but their value is still a subject for future investigation, and such treatment is not without danger. Before injecting vaccines or proteins the possibility of lighting up a latent infection must be considered.

Sensitization. This is a condition caused by previous injection of some protein, and generally does not occur for at least a week and perhaps ten days or more after the first injection. Consequently, secondary injections of an antitoxic serum after

the lapse of a week or more may cause a serious anaphylactic reaction when injections previous to that one have caused no such symptoms.

PROTEIN POISONING-ANAPHYLAXIS

Allergy, an increased sensitiveness to certain foods may be hereditary or acquired, and Schloss1 summarizes the forms which this idiosyncrasy or hypersensitiveness may take as urticaria, asthma, shock, angioneurotic edema, erythema multiforme, eczema, acute dermatitis, and gastroenteric disturbances (vomiting and diarrhea). He also notes, as is occasionally seen, cyclic disturbances of a susceptible individual, with the development at intervals of from two weeks to three months of one or more of the above signs of poisoning. When there is idiosyncrasy against a certain food the patient may be so sensitive to it that if that food is added, even in a small amount, to any nutriment poisoning will occur. This is particularly true of milk and eggs. Sometimes the susceptibility to poisoning from a particular food is outgrown, especially, Schloss says, in the congenital type.

To desensitize a patient to a protein poison hypodermics of the substance may be given. This method is satisfactory in desensitizing to pollen; but the food proteins are difficult to sterilize in solutions that are tolerated by the tissues.

Schloss has attempted to immunize by feeding, i.e., an exceedingly small dose of the offending food is given, even as little as 0.002 to 0.005 Gm., in capsule, three times a day, either of egg, milk, or other protein. Every day one more capsule is given (avoiding a reaction), then, after one week, larger doses, in capsules, are given, up to 15 to 30 Gm. a day, until finally the particular food is given in normal amount. This method takes from three to six months to cause desensitization, and after such immunity has been caused the individual must take the food daily to keep up his immunity, else it is lost, although it is not difficult to again desensitize him.

Schloss says that while the intracutaneous test for protein idiosyncrasy is more sensitive, he believes it often misleading,

1 American Journal of Diseases of Children, June, 1920, p. 433.

and that the cutaneous test is better. The cutaneous test as outlined in the American Journal of the Diseases of Children, May, 1920, p. 402, is as follows: "A cut one-eighth of an inch long and not deep enough to draw blood is made in the skin through a drop of decinormal sodium hydrate solution. A small amount of blood is not of consequence. A small quantity of dry powdered protein is then mixed with a drop of alkali and this in solution comes in contact with the serum of the patient.

Schloss finds that protein tests are not satisfactory in patients who are suffering acute symptoms of urticaria and asthma. He applies a control test near the bend of the elbow on the inner surface, which is a very tender region and readily reacts to a trauma, and, consequently, makes a valuable comparison with the protein test incision. A positive test is evidenced by an urticarial wheal surrounded by a zone of erythema, and Schloss states that the wheal is always irregular in outline, and that five millimeters or more in size represents a strong reaction. A negative reaction does not positively show immunity to the protein used, as there may be temporary desensitization.

To sum up the practical understanding of susceptibility to protein poisoning, it may be stated that it is congenital (handed down from parent to child) or acquired, and patients who have a reaction to such food will also have a cutaneous reaction, if the substance is rubbed on an abraded surface. It should, however, be noted that a reaction to a skin test with a certain protein does not prove that that is the protein or substance that is causing the diseased condition either of the skin or other part of the · body, any more than because a patient has an infected tooth it necessarily is the cause of the disturbance from which he is suffering. Some patients have an acute eczema when certain foods are eaten; others have a chronic eczema due to certain foods. Consequently, individuals who do not readily recover from eczema should be studied from the standpoint of the skin susceptibility to the protein cutaneous test, and any food to which they are susceptible should be removed from the diet.

Treatment. The treatment of protein poisoning is to withhold the food or drug that caused the condition, to give saline purgatives, to insist that large amounts of water be drunk, and

to give alkaline medication. The best alkaline drugs for this purpose are sodium bicarbonate and sodium citrate, given in sufficient doses and frequently enough repeated to render the urine alkaline. Bicarbonate of sodium should be given in a dose of 2 Gm. three times a day, and sodium citrate in a dose of I Gm. every two hours. Larger doses may be given if symptoms of acidosis are present, such as headache, cerebral excitation or delirium. Such a condition may also call for the administration of bromides.

If the offending substance is probably still, in part at least, in the stomach, an emetic should be given and if there is much intestinal disturbance castor oil may be the best cathartic. If the fever is high and the heart action good, one or two doses of acetanilid may be advisable. In conditions of shock, besides eliminating the poison from the gastrointestinal tract, the patient should be surrounded with dry heat and given cardiac stimulants, such as atropine, caffeine, and suprarenal or pituitary extracts.

VACCINES

Vaccines, which are prepared from killed bacteria, when injected hypodermatically cause the production of antibodies for the particular germs. It is self-evident that an autogenous vaccine is of the greatest value. Even autogenous vaccines may not cause the antagonistic properties of the blood to act upon the bacteria that are causing a superficial infection unless the blood supply to that part is sufficient. For this reason hyperemic methods applied to surface infections are often of value.

Theoretically it cannot be good judgement or wise to inject bacteria to stimulate the production of antibodies or antitoxins when the system is already overwhelmed with the infection. If, however, the condition is chronic or subacute such stimulant bacterial injections may be advisable and therapeutically valuable, as in tuberculosis and chronic gonorrhea. In streptococcic infection vaccines are sometimes curative, but more frequently they fail. As there are various strains and types of streptococci and staphylococci, stock vaccines which represent many organ