highly toxic and locally destructive on account of the trypsin they all incorporate. Suprarenal diabetes is an altogether different matter. The injection hypodermically, intravenously or intraperitoneally of adrenalin into the circulation produces a transitory glycosuria, that can be reproduced for a time with each renewed injection. Administration of adrenalin by mouth is without effect. The hypothesis has been advanced that adrenalin stimulates the liver to pour out its glycogen and that the hyperglycemia or glycemia are produced in this way. In other words its effect would be exactly opposite and antagonistic to that of the pancreas, the former acting, as one author puts it, as a whip the latter as a brake upon the liquidation of glycogen in the liver. That there is an antagonism between the action of the two glands seems quite plausible from all the evidence (not proof) so far at hand; the injection of a pancreas extract for instance as a preliminary to an adrenalin injection preventing the development of glycosuria. Therapeutically nothing has so far developed from the study of adrenalin diabetes. That the thyroid and parathyroid glands are concerned in the sugar metabolism is apparent from the following observations: Thyroidectomy is followed by an increased tolerance for carbohydrates and in myxedema the boundary of assimilation is always high. Hyperthyroidism, on the other hand, is frequently accompanied by a low tolerance for carbohydrates and alimentary glycosuria; feeding thyroids producing a similar effect. Removal of the parathyroids produces the same effect as thyroid feeding; one is justified, therefore, in attributing to the parathyroids, an antagonistic, regulatory action upon the thyroid. The various ductless glands in so far as their effect upon the carbohydrate metabolism is concerned either accelerates the latter or retards it, i.e., stimulate or inhibit. To the former category belong the pancreas, the suprarenals (chromaffine system) and the hypophysis to the latter the pancreas and the parathyroids. Their interrelated action can best be illustrated by the following triangle scheme by Eppinger-Falta.

The elimination of any one of these three ductless glands either experimentally or clinically by spontaneous degeneration would therefore exercise a two-fold effect, viz., first a direct effect resulting from the elimination of its specific secretion; second, an indirect effect the result of the disturbed action on the other two glands. All this is very theoretical, but so many of the experimental results fit into this scheme that it

THERAPEUTIC CONSIDERATIONS.

Therapeutically very little that is new has developed. The main progress has been along dietetic lines, i.e., a more strict individualization and less routine, a more accurate classification of types, and a more careful gradation of severity, some refinement in tolerance determinations, all as a preliminary to more appropriate diet regulation. The value of single carbohydratefeeding, with the oatmeal cure as a prototype, has become fully recognized chiefly as a method prophylactic against acidosis and coma. Much has been taught in regard to the best method of preparing and administering the oatmeal diet, and the dangers of the oatmeal treatment, as well as of any one-sided diet have become fully recognized. Alcohol has come into its own as a valuable remedy in threatened coma. kalies maintain their old place. Organotherapy, as we have seen, so far offers nothing of therapeutic value. Of drugs we can expect nothing other than a relief of symptoms. Opium remains our best remedy for reducing the symptom glycosuria. Of course diabetic remedies to cure the disease are nevertheless extensively advocated.

All in all the life expectancy of diabetics, even those afflicted with the more severe grades of the disorder is better, provided proper feeding is instituted under frequent and accurate control. Where an individual metabolic study is permitted a great deal is usually accomplished. Watering-places and resort "cures" still enjoy deserved esteem in the treating of diabetic patients, especially in the milder forms; the rest, the attention to diet, the respite from daily worries, possibly the alkaline waters, are of value, provided the patients do not consider, as most of them do, the one careful resort month as absolution for eleven careless

months at home; and provided that they do not fall into the hands of a certain abounding type of resort doctor who, by dint of rigorous dieting and abundant water drinking, temporarily rids the urine of sugar, dismisses the patient as "cured" and thus lulls them into a false and dangerous sense of security. Most of the severe cases of adult diabetes that it has been my misfortune to see had been thus in their early milder stages dismissed as "cured."

32 North State Street.

LOCAL FOCI OF INFECTION CAUSING GENERAL SYSTEMIC DISTURBANCES.* CHARLES H. MAYO, M. D., Rochester, Minn. The life of multicellular organisms, which includes both the animal and vegetable world, may be destroyed by intent, accident or disease. By disease would be included old age in which so-called natural changes have led to an exhaustion of the organs of defense and nutrition. It is only to unicellular organisms that death does not come as a natural end. These organisms live on and multiply by division. At times, lacking proper conditions necessary for continuation, they rest for varying periods, thus developing spore conditions to again take up active life under proper environment. While death is the natural end of all living things, in the human world the event is frequently looked upon as unncessary, unfortunate, unnatural and preventable, the physician often being blamed. From the time of birth, life is maintained by the organisms only through a continued battle for existence against varying destroying agents of which the bacteria and protozoa form the greatest causative factors. Our real knowledge of the specific organisms which cause the great majority of diseases covers a period of but few decades. The fact that there were such was assumed long ago as evidenced by preventive medicine and vaccination against smallpox. These measures were placed upon an exact basis by that remarkable scientist, Pasteur, who did so much to protect mankind and animal life by developing and standardizing various vaccines in the prevention of disease. Due credit must be given also to that most able surgeon, Sir Joseph Lister, who applied Pasteur's methcds in controlling the growth of or destroying the pus-producing bacteria, thus per

*Oration in Surgery before the Medical Society of the Missouri Valley, Omaha, September 18th, 1913.

mitting the development of modern surgery.

Protozoa or intestinal parasites play their part in the exhaustion of the vital forces by the development of toxins which are the cause of many chronic diseases. Formerly these conditions were considered quite generally as tropical diseases and in Northern climates were found only in the mixed populace of seaports. It has been shown, however, that they are very common in the interior. From an examination of the intes tinal secretions of 1000 patients made during 1912, Sanford found protozoa in addition to the usual intestinal bacterial flora in 10 per cent of the cases. However, of these but one-half were of a nature to cause disease and produce symptoms.

There are three methods of bacterial invasion: First, by continuity of tissues, as in the eye, ear and sinuses; second, by ingestion; and third, by direct entrance of tissues and lymph channels.

From birth until death, micro-organisms are constantly found in the intestinal tract. Metchnikoff1, possibly the best known scientist of the present day, as a result of extended investigation, states that the toxins produced by the intestinal flora of the large bowel are the cause of much of the vascular and degenerative changes of old age. It is along these lines that Sir Arbuthnot Lane has developed the surgery of intestinal elimination.

The total number of instances in which infection takes place by way of the skin is small, as compared with that of the alimentary canal. It has been shown that bacteria and bacilli can pass the intestinal mucosa and be absorbed by the lac teals or enter the portal circulation. The liver has an enormously important duty to perform in destroying such organisms to prevent their passing into the blood. Some attenuated yet living bacteria do pass and are thrown into the bile stream, thus fre quently producing acute and chronic inflam mation of the gall-bladder and ducts or the development of gall-stones, while the organisms which pass into the lymphatics and lymph glands are delivered with more or less attenuation into the blood stream. In children the large amount of lymphoid tissue of the nasopharynx with various crypts, pockets and neighboring sinuses for harboring germ life renders the child most susceptible to the various preventable diseases which are frequently manifest, first in the throat and mouth as local symptoms. The mouth naturally harbors the greatest variety of bacteria of any region of the body, from a few to sixty varieties being reported by various observers. Due to known and un

known causes, the teeth in various individuals are often surrounded by large areas of ulcerating surfaces. If these areas be measured, as pointed out by Hartzell, they would represent from one-half square inch to nearly four square inches of septic surface.

Hale White, Osler, Billings, and many other noted internists have written on the subject of systemic diseases arising from infections of the mouth. Looked at from every point of view, the mouth may be said to be the greatest portal of entry for pyogenic organisms.

That scourge of the human race, pyorrhea, is responsible for the entrance of many infections of youth, and as age advances it becomes a most serious menace. In appreciation of Dr. Riggs' efforts to overcome pyorrhea and reveal to the dental profession the possibilities of doing so, the condition is often termed Riggs' disease. Extensive investigations have been made by Black, Talbot, and various other observers. Hartzell has given the profession advanced ideas on the subject.

Greves and Baer report 100 cases of diseases of joints in which alveolar abscesses of varying size were apparently the source of the infection. Murphy states that every type of non-traumatic inflammation of a joint is the metastatic manifestation of a primary infection in some other part of the body. The genital tract is also a wellknown field of infection which causes many disorders other than specific joint and nerve lesions. There is probably no area of equal size which is a greater menace to the health of children than the tonsil, an open lymph gland in the greatest septic cavity of the body, the mouth, the drainage of which passes into lymphatic channels which open into the venous system. As long ago as 1887, Mantel stated that rheumatism came from diseased tonsils, and since then many observers have proved the truth of this statement. Schichold reports 70 cases of rheumatism in which pus was found in the tonsil. Kelynack has called attention to the association of tonsillitis with appendicitis. Poynton and Paine report a case of appendicitis which, upon removal of the appendix, gave pure culture of the same strain of bacteria as that cultivated from a diseased tonsil removed at the same time. These streptodiplococci were injected into rabbits causing arthritis, and the fluid removed from the arthritis again gave a pure culture. Acute tonsillitis frequently precedes an attack of acute osteomyelitis. About 70 per cent of the cases of hyperthyroidism have tonsillitis. It may be noted here that

chronic diseases of the tonsils may cause few or no local symptoms.

Smithies of our clinic made a routine examination of the mouth, teeth, tonsils and saliva of 318 patients who presented themselves for test-meal examination because of gastric disturbance. Similar examinations were made, as controls, of the mouths of 16 other persons selected from laboratory assistants, nurses and physicians. Out of the 334 individuals examined but one-fourth of the number were found to have good teeth, half of them having inferior or diseased teeth, while 201 (60 per cent) showed erosions of the teeth, gummargins, or a definite pyorrhea alveolaris. Twenty-seven per cent of the cases showed enlargement of the tonsils and nasopharnyx, and exudate on erosion of the tonsils, 19 per cent gave evidences of nasal pharyngeal inflammation and in 3 per cent there were ulcerative conditions of the oral mucosa apart from adenoid hypertrophy or pyorrhea. The chemical examination of the saliva showed the presence of enzyme similar to that found in the stomach which causes the cleavage of the dipeptid glycyltryptophan in a large majority of the gastric specimens. It was noted, however, that the amount of this enzyme seemed to be greatest in those individuals having the most in. fection in the mouth. It was also shown that cultures of bacteria grown from saliva, when added to salivas in which the enzyme had been destroyed by heating to 100 C., rendered such saliva again capable of splitting the dipeptids. These experiments seem to furnish evidence first that a large proportion of patients complaining of gastric symptoms have infected oral cavities, and second, that this infection is in direct relation to the formation of a peptid splitting enzyme in the saliva.

It has been generally believed that bacteria which pass into the stomach would, under normal conditions, be destroyed by the acids and digestive activity. Microscopic examination of the gastric contents in 2,406 different individuals with "stomach complaint" (dyspepsia, indigestion and the like) showed that irrespective of the degree of acidity of such gastric extract, bacteria were present in 87 per cent. Morphologically cocci and diplococci were present in 83 per cent, short and long rods (often of the colon group) in 58 per cent.

Within a comparatively recent period it has been shown by the internists that disorders of the body occurring with various diseases are not alone due to toxins produced by bacteria and their fermentation, but that the actual living micro-organisms

causing these diseases exist in the blood. This condition is a true bacteremia, which formerly was considered to be associated only with pyemia and septicemia, conditions in which the blood is overwhelmed with living organisms. Such conditions, for example, tetanus, which arises from the most minute injuries, are caused commonly by punctured wounds. Frequently such diseases may be combatted by a serum which, if used early, undoubtedly prevents the activity of the great majority of such infections; when used later, the serum may aid resistance. Therefore the size of the infective area or focus has nothing to do with the amount of systemic disturbance, and this is certainly true of a tonsillar abscess or pyorrhea pocket.

We speak of typhoid fever as a disease of the intestines caused by a specific organism, of measles or small-pox as diseases showing lesions of the skin or specific organisms. These are practically all diseases of the blood due to infection which gains an entrance by way of the mouth. Each has its specific way of affecting either the mucosa of the skin, secondary, however, to the bacteremia of the blood.

In typhoid fever the blood stream contains more or less of the typhoid bacilli; the liver is constantly destroying and throwing them out through the bile, the kidneys perform the same function through the urine, while there are enormous numbers passing from the intestine in the stools. Secondary diseases often occur, especially of the gall-bladder, and, persisting, may produce the unknown typhoid carriers, a pure culture of typhoid bacilli occasionally being found at long periods following the disease.

The valves of the heart may become diseased, i.e., ulcerated and sclerotic from contraction caused by the many hemorrhages of embolic bacterial origin. Endocarditis then is an infectious disease in which the vegetations and ulcerations on the valves of the heart and injury of some of the larger vessels occur from local bacterial growth. Such diseases are more common in children than in adults, the increased susceptibility in youth being due to the presence of capillary vessels in the valves of the heart. The relatively avascular condition of these areas protects the bacterial groups from the destroying effects of the leucocytes which cannot approach them. Later attacks in children and in older individuals may lead to ulcerative malignant endocarditis.

Rosenow has shown that the bacteria are of a low grade of virulence but tena

cious of life. After repeated passage from animal to animal these cocci resemble pneumococci. By using strains cultured from the blood of such cases and also from tonsils in the same group, and inoculating into the veins of rabbits' ears, he could, within forty-eight hours, show lesions of the valves of the heart in more than one-half the cases, while others showed lesions from infected emboli in the lungs, kidneys, etc. The appearance of bacteria is undoubted. ly often changed by environment or variation in culture.

Wadsworth made a valuable suggestion when he found that in order to produce pneumonia in rabbits with pneumococci it was necessary to have a properly balanced relation between their virulence and the resistance of the host. This is true of the human variety also, since pneumococci may be found in the mouths of about one-third of individuals. Rosenow secured blood cultures of pneumococcus in 132 of 145 cases of pneumonia, blood smears being successful in 47 of these cases in three of which the blood cultures had failed.

The kidneys are frequently involved in their efforts to remove bacteria from the blood. Hale White reports finding in the urine of patients bacillus coli communis, streptococci, staphylococci, gonococci, pneumonococci, bacilli of typhoid, etc., the more common variety being the coli communis, especially in the urine of pregnant women. Children, as we know, are frequently found to have bacteria of intestinal origin in the urine with but few symptoms. Their discovery is relatively infrequent since they are seldom looked for microscopically. A high temperature in a child without known cause is an indication for microscopic examination of the urine. In some instances one kidney in a child may be destroyed by the colon bacillus. We have seen such in young children. Should this destruction be confined to one kidney it might appear late in life that the individual was born with but one kidney. Such infections may occur through the genital tract or through the blood stream, but rarely by direct penetration of the kidney itself. About seven female children are affected to one male, and this probably indicates that infection takes place more frequently by way of the urethra. It is also reported that staphy lococci found in pyorrhea were found in the urine. The staphylococcus aureus has been found in the gums and in the urine. The finding of such bacteria is often unaccompanied by pus, blood or albumin.

Libman and Zeiler report the finding of pneumococcus, streptococcus and strepto

coccus mucosae in middle-ear infection, while Kobrak found bacteremia to be a significant diagnostic point in sinus thrombosis from middle ear and mastoid disease. These bacteria may be found in the blood for many days before positive local indications demand operation and they may rapidly disappear after a successful operation.

While it has been shown that a lowered resistance of the body may be a factor in permitting the entrance of micro-organisms, the cure of disease requires that the resistance be raised and that bacteria in the blood be destroyed by the forming of opsonin which prepares the bacteria as a food for the phagocytes. This resistance may be accomplished by vaccination, as in small pox and in typhoid fever, by the injection of special serum, as in diphtheria and tetanus, and by the injection of dead bacteria which raises the resistance of the fluids of the body against the living bacteria of the same type.

Wright's vaccines prepared from bacterial cultures taken from the patient himself (autogenous vaccines) have become of universal application in raising the resistance of the individual against the bacteria from which he suffers. Many bacteria grow well in mixed cultures while some are only thus rendered virulent. Vaccines in such cases must be made from combined organisms and not from pure cultures. Repeated doses of irritants and bacterial toxins may break down resistance and even create in the individual an anaphylactic condition which renders him more than commonly susceptible to certain diseases, such as hay fever, asthma, erysipelas, urticaria, etc.

A great gain has come to mankind through the treatment of diseases of which the specific germ-cause is known, both by vaccines and the injection of the specially prepared sera made from the blood of animals with a natural immunity to special organisms. The years added to human life by diphtheria antitoxin alone are almost incalculable.

In obscure maladies and cases of puzzling diagnosis, the immediate or past presence of these agents in the system, however remote, can be determined in most cases by the reactions of the skin or of the blood in the presence of proper sera.

From the foregoing it might appear that

the treatment and cure of diseases caused by infection would be rather a simple matter by the use of serum and vaccines in the development of proper antibodies to aid the body to resist disease. While this is true in a few diseases (sufficient to show that the principle is correct) in many diseases of both man and animal the practical work has not been sufficiently developed as yet to have obtained more than an average degree of success.

For convenience of description and treatment, infections are commonly divided into periods according to their activity:

First, the early infective period, ordinarily of 24 to 48 hours duration, when pus infections are still local. In this period com plete surgical ablation, if possible, is indicated.

Second, an indeterminate period of pus development, during which Nature's chemic-biologic laboratory is at work. In this stage surgery requires the best judgment, as it may spread disease, delay healing and add to Nature's troubles by interfering with the developing opsonins and leucocytes which are necessary to a cure in any mode of treatment.

The third period is a safe one for surgical interference, since Nature's work is nearly complete, the exudate being absorbed or sterile (the laudable pus of the old school) and the condition subacute chronic.

or

Within the past ten years it has been found that a rather large group of diseases are carried by insects and directly implanted by their bites.

The greatest benefit to mankind still lies in preventive medicine and the professions must pause for a time that the laity may be properly educated concerning diseases. and their cure, and especially their prevention. Much of this work is now being done through the Medical Lecture Bureau of the American Medical Association. There should be a few dentists, oral surgeons and members of the Triological Association added to this corps of lecturers. Probably no greater field can be found for the education of the masses, as well as for the immediate good of the child, than the work done in the medical inspection of school, but since this is comparatively new work the results will be more apparent in the next generation.