introduction to his second volume, now in its ninth edition, were solved. Any one of these discoveries would qualify him to earn the gratitude of posterity. Thus he was able to offer a ready solution to the experimental results of a multitude of investigators which thus fell into line, as it were, of their own accord. Pulmonary and tissue respiration, absorption and nutrition, the circulation of the nervous system (Harvey having discovered that of the larger vessels and Malphighi that of the capillaries), the nature of organic function and the manner in which it is awakened by vasodilator nerves, the composition of ferments, the physiologic and morbid production of sleep, etc., are but a few of the many problems which physiologists had admittedly failed to solve. This is well illustrated by Osler's remark that while we know little concerning the action of drugs, "we put them into bodies, the action of which we know less."

Recently Sajous showed in this connection, in his presidential address before the American Therapeutic Society, that such a state of things need no longer prevail. As far back as 1903 he had demonstrated that the ductless glands as a group constituted the mechanism thru which the body defended itself against disease, and that those of our remedies which were positively curative (other than those such as quinine and anthelmintics, which directly kill a parasite or germ) did so thru the agency of the ductless glands which combine to supply the immunizing substances. Experience has, in many respects, so directly confirmed. Sajous' views that the London Lancet, editorially recommends in a recent issue that they should form the basis of teaching of therapeutics in that great center of learning.

How does all this bear upon the subject of dental physiology and pathology? The significance of this fact is great, that in order to understand calcium metabolism it is necessary to know the functions of the ductless glands as Dr. Sajous interprets them. I specify his views because, unlike those of many other workers in the same line, they have withstood the test of time and have been confirmed independently by manifold other workers both in research and in practice. These regulative glands prove of particular interest in the present connection. They consist of the adrenals, two small organs overlying the kidneys, the thyroid, overlying the thyroid cartilage in the neck, and the thymus, immediately below the thyroid, between the sternum and the trachea.

ADRENALS.

Sajous found that these organs supply a secretion which passes to the lungs and takes up therein the oxygen of the air. This solves the cardinal problem of human functions, namely, that of pulmonary respiration. Physiologists had also heretofore failed to discover the identity of 94 per cent. of the hemoglobin molecule. This, likewise, proved to be the oxygenized adrenal secretion. The nature and the source of an oxidizing substance found in the blood, viz., oxidase, had also remained undetermined. Sajous found that this substance, the (albuminous) 94 per cent. of hemoglobin, and the oxygenized adrenal secretion were one and the same; that all tissues contain it; also that it was this substance which supplies the tissues with oxyThis contention has since been abundantly confirmed.

gen.

Briefly we now know, thru Sajous' discovery, how the venous blood becomes converted into arterial blood.

THYROID GLAND.

As is now well known to all physicians, thyroid extract given to a cretin or an idiotic child in whom the functions of the thyroid gland are deficient, brings about wonderful changes for the better. body soon begins to grow, all the functions are remarkably stimulated, and the brain, practically inactive before, assumes its

The

investigator, G. A. MacCallum, i. e., calcium assimilation. Thus a local disorder of the parathyroids which alters their structure, such as fibrosis, is known to produce a bone disease, osteomalacia, for instance. It is further determined that removal of the parathyroids tends to check repair of disease in bones. Yet we know that calcium is combined with a phosphorus com

What amounts then to a mere "human plant" becomes finally transformed into a normal child, and remains such, but only so long as thyroid extract is administered to it, since it cannot secrete enough for its own needs. Now, thyroid extract has long been known to enhance actively the body's metabolism, the complex modalities of biochemical processes..

The thyroid gland was also found by Sajous to be the source of a substance which has been receiving considerable attention of late-Wright's "opsonin," known to sensitize bacteria and render them vulnerable to the attacks of phagocytes-those white cells or leucocytes of the blood and lymph which act as the body's scavengers and do so much to protect it against infectious diseases.

This connection between the thyroid and immunity has been confirmed twice at the Pasteur Institute of Paris and likewise in Belgium and Italy.

THE PARATHYROIDS.

Closely associated functionally with the thyroid, and forming part of their structure, are found pea-like glandules, the parathyroids. Not only are these small organs participants in the defensive functions just described, but they also take part in a function of direct importance in the present connection, also discovered by an American

THE THYMUS GLAND.

From Sajous' viewpoint, also confirmed in various ways since he formulated his opinion in 1903, phosphorus supply is the function of another organ, the thymus, also classed among the endocrines, but the fact is, it is not a secreting gland. The thymus produces small, white cells which he termed "thymocytes," whose function is to supply nucleins, which are known to contain 4 per cent. of phosphorus in organic combination, so constituted as to be appropriated in particular by the osseous and nervous systems, and in combination with calcium brings about the formation of bone. As the thymus is most active up to the sixteenth year, when it begins to atrophy, it is essentially an organ doing duty thruout the period of development, during infancy, childhood and adolescence. If from any cause local lesions arise during an active febrile process, such as the many infections to which children are so liable, or as in precocious involution, a part or all of its functional efficiency is impaired, then we have deficiencies or defects of development of the bones, deformities suggesting rickets, retardations in growth or stature or muscle competence with often mental backwardness, all associated with poorly developed dentures or anomalies of the teeth.

In considering calcium metabolism, therefore, three fundamental organs must be taken into account: (1) The adrenals, which govern oxygenation; (2) the thyroid, which acting in combination with the adrenals materially influences metabolism; (3) the parathyroids, which glands form part of the thyroid mechanism and influence calcium metabolism, particularly that of all osseous tissues; (4) the thymus, which supplies the phosphorus which with calcium forms the calcium phosphates of these osseous structures.

How may we recognize inadequacies of these various organs, to ascertain the origin perhaps of dental defects or disorders? Summarized, they may be classified as follows:

ADRENAL DEFICIENCY.

As we are dealing here with defective oxygenation we observe (1) muscular weakness and emaciation, pallor, deficient hair growth, sensitiveness to cold, subnormal temperature, all due to deficient tissue oxidation and recession of the blood mass into the splanchnic area; (2) weak action and pulse, low blood pressure, and constipation due to deficient peristalsis, the result in turn of torpor of the intestinal muscular layer; (3) pigmentation, sometimes limited to bronze colored areas on the face and back of the hands, and also large freckles; (4) mental torpor, slow intellection, or even idiocy where the adrenal deficiency is initiated in utero. The outstanding phenomenon of old age, especially of premature senility, is hypoadrenia.

THYROID DEFICIENCY.

Here slowed metabolism produces subnormal temperature, cold extremities due to defective oxidation and metabolism, the

thyroid in health collaborating actively with the adrenals and thymus-before puberty only as to the thymus-in sustaining this process, showing also a tendency to obesity; (2) a doughy, dry skin, with at times cervical or axillary fat, pads due to local plasmatic infiltration and circulatory torpor; also in very marked cases, a scaly skin and dry, brittle hair and nails due to deficient nutrition of these structures; (3) mental torpor or deficiency is present where true thyroid stigmata are discernible. For complete development of the brain there is required perfect coordination of the thyroid, adrenal and thymic functions.

PARATHYROID DEFICIENCY.

The parathyroid being merged in with. the thyroid, deficiency of these organs is manifested by deficient metabolism. But since this thyroparathyroid inadequacy bears mainly upon calcium metabolism and thus affects the nervous system and muscles, there is a tendency to twitching, hyperexcitability and, in severe diseases or where destructive changes occur in these small organs, or when the entire thyroid, which contains them is removed, there ensues tetany.

THYMUS DEFICIENCY.

The thymus supplying, as it does, the phosphorus necessary for the development of bone it must function adequately. If there is deficient development of the osseous system and of the epiphyses, there result deformations suggesting rickets or osteomalacia. This is due to inadequate assimilation of calcium owing to the deficiency of thymic nucleins which plays a major part in the building up of calcium. phosphate, and the termination is undersized or asymmetrical stature; (2) deficient

mental development due chiefly to the insufficient production of thymic nucleins to supply the neurons of the central nervous system during its developmental phases; (3) a low relative lymphocyte count is an evidence of the inadequate formation of these cells by the thymus.

A peculiarity of those individuals in whom deficiency of any of the ductless glands is pronounced is their vulnerability to infection of any sort. This again emphasizes Sajous' dictum that while these organs sustain the life process they also serve to protect life. 1504 Pine St.

THE ORBITAL CARDIAC MURMUR.

BY

A. E. VIPOND, M. D.,

Senior Physician to the Children's Hospital, Montreal, Canada.

Some time ago I was consulted by the mother of a young girl of 14 years of age, who suffered from very marked type of Graves' disease. All of the cardiac signs. and symptoms were present. There were murmurs all over the cardiac area as well as in the carotid arteries; a marked murmur was also heard in the abdominal aorta and in the femoral arteries. Exophthalmos was well marked and on placing my stethoscope over the closed eye I detected the same systolic murmur which was met with in the other areas. I then decided to try this orbital test in other heart conditions and I have arrived at certain conclusions which are of some interest.

I have found this systolic murmur in the orbit of advanced heart disease, in mild. cases of mitral regurgitation, in aortic cases

and in congenital cardiac conditions; also in dextrocardia complicated with mitral disease, etc. This applies more particularly to children than to adults. In many cases of advanced heart disease with murmurs all over the chest and in many mild cases of mitral regurgitation, this murmur is not heard, particularly in the adult. Why this murmur is heard in many of these conditions and why it is not heard in others where I fully expected to find it, I cannot tell at the present time. I will leave this problem for MacKenzie and Lewis, of England, or for any of our great American cardiologists to work out.

The ophthalmic artery being a terminal vessel I can conceive that the murmur could be carried up from the aorta thru the internal carotid and then end in the ophthalmic branch.

I have notes on a number of cases in which I detected this systolic orbital murmur and a few may be of interest:

Case I. Congenital heart: B. N., aged 31⁄2 years. There is a loud systolic murmur over the whole of the cardiac area, also well heard over the back of the lungs. This congenital deformity appears to be some abnormality of the mitral orifice; there is no cyanosis and no clubbing of the tips of the fingers. However, there is marked dyspnea on exertion or even when the slightest extra strain is put upon the heart. The systolic orbital murmur is well heard in this case.

Case II. Acute myocarditis, endocarditis and chorea of an aggravated type, occurring simultaneously: G. T., aged 51⁄2 years, a well-marked case of rheumatic endo- and myocarditis. A loud systolic murmur is heard at the apex transmitted round to the left of the scapula; a systolic murmur is heard over the aortic area, the apex of which is one inch external to the nipple line. The systolic orbital murmur is clear and well marked.

Case III. Rheumatic mitral myocardial insufficiency: J. C., aged 5 years. Left ventricle slightly hypertrophied; second sound at base accentuated and a soft systolic myocardial murmur is heard at the apex, transmitted slightly to the left. The systolic murmur is well marked in the orbit.

Case IV. Rheumatic peri- and endocarditis (I do not mention myocarditis, as I fully believe that we can take it for granted that when

we have an endocarditis that myocardial trouble is present in every instance.) Mrs. W., aged about 46. This patient also presented erythema nodosum. On examination, a pericardial friction is well heard and a systolic murmur is heard up and down the sternum. There is slight hypertrophy of the left ventricle and the orbital murmur is distinct.

Case V. Another case of interest is that of B. J., a young girl of 16 years of age, who has suffered from a chronic endocarditis for about eight years. She has had many attacks of rheumatism with progressive endocardial sclerosis involving the auriculoventricular bundle. There is considerable hypertrophy of the heart, the apex being two to three fingers breadth external to the nipple line. There is a double murmur at the apex; in fact, murmurs are to be heard all over the cardiac area. The pulse was weak and rapid. I placed her upon soda salicylate and tincture of digitalis, but she came rapidly under the cumulative effect of the digitalis and there was marked pulsation in the neck vessels, in the epigastric region and over the cardiac area; in fact, the pulsation was marked over the whole of the arterial system, she had to sit up in bed and the pulsation caused great distress; the pulse was reduced in frequency and the blood pressure much increased. I have never seen digitalis produce such a marked effect on the cardiac muscle and vessel walls as it did in this instance. I stopped the digitalis and my patient improved rapidly. The systolic murmur was well marked in the eyeballs.

Case VI. Rheumatic myocarditis: B. W., aged 31⁄2 years. This little girl was sent to me by Dr. McGoveran. Her mother states that a few weeks ago the child had a very sore throat, followed by pains in the legs. On examining the heart I found that the apex was barely external to the nipple line. On exertion a soft systolic murmur was heard at the apex and there was a flapping second sound at the base. A systolic murmur was quite distinct over the eyeball.

Case VII. The next case is a condition of peri- and endocarditis in J. E., aged 4 years. The mother brought him to the hospital to consult me about his condition a month ago.

to the nipple line, the heart irregular, loud, rasping, systolic, mitral and aortic murmurs are to be heard. Here the orbital murmur was also heard.

Case IX. Mitral regurgitation: R. P., aged 9 years, suffers from a mitral regurgitation; a loud, sharp, systolic murmur is heard at the apex and is transmitted around the axilla and to the back; the second aortic sound at the base is accentuated. The apex is one-half inch external to the nipple line. This little girl came to my clinic in June, 1920, and at that time I examined her for the orbital murmur and found it quite distinct.

A short review of the above cases will be of interest: It will be seen that I have found this orbital murmur to be present in several different types of cardiac trouble. I have found it to be present in Graves' disease, in endocarditis, involving most of the valves, in aortic and mitral valvular disease and in mitral disease alone, in mitral disease complicated with pericarditis, in dextrocardia complicated with mitral disease and in congenital heart disease. It will be seen that in four of the cases the children were under six years of age and four of the others were sixteen and under; one was in a woman of forty-six. I believe that for this murmur to be heard distinctly in the orbit, the heart muscle must be in a fair tonic condition; in other words, the systolic blood pressure must be fairly high. We all know that the heart muscle of the child has great reserve force and that sclerotic changes are not so prone to take

of the left ventricle and a well-marked mitral systolic murmur. I advised absolute rest and large doses of sodium salicylate with sodium bicarb. The mother would not or could not keep the little lad in bed and in a couple of weeks' time he developed a general endocarditis with a marked pericarditis. The pericardial friction was to be heard all over the

cardiac area. The systolic murmur was loud and distinct in the eyeballs, but the loud pericardial murmur was not to be heard at this site.

Case VIII. General endocarditis: C. F., aged 12 years, has had rheumatism frequently during the past four years. I saw him for the first time at my clinic on August 28, and on examination I found the apex one inch external

as in the adult. Again, how often do we feel that a child who suffers from an acute endocarditis will never be able to carry on, and yet we are often deceived and the little sufferer frequently recovers sufficiently to enjoy life again. I have many instances of this kind on my list. Again, at times I have looked for this murmur in some severe cases of endocarditis and have been unable to find it; here the muscle is so weak that it has been unable to carry this mur