epinephrin, nicotin, lead, diphtheria toxin and pure cultures of different species of bacteria, he obtained no effect, while in a second series of experiments with these same substances, when administered orally, he obtained positive effects.

L. F. Bishop' states that heart disease and hardening of the arteries are nine times out of ten due to disturbance in the chemistry of the body (of the adrenals, the thyroid, toxemias, etc.), particularly in relation to the intestines and the liver. According to this authority the most important cause of arteriosclerosis is amino-acid poisoning, by acids to which the individual tissues are sensitive. Intestinal putrefaction has a very important bearing. He believes that idiosyncrasy accounts for the susceptibility in certain individuals as compared with others.

The amino-acids, which are responsible for these conditions, are, in all probability, derived from the breaking down in the intestinal tract of nitrogenous foods derived from milk, eggs, fish, meat and soups. And here he expressed the view already published by Rudolph2 who quotes Huchard by saying, that the second most important factor in the production of arteriosclerosis is the continued excretion of toxins by the kidney, these toxins coming from abnormal proteid metabolism in the digestive tract and also in the liver.

INCIDENCE OF ARTERIOSCLEROSIS

While this disease usually is looked upon as one of the second half of life and is encountered usually during de

1 Jour. A. M. A., Mar. 15, 1913, lx, No. 11.

2 Brit. Med. Jour., Nov. 26, 1910.

clining years, it should not be forgotten that well-marked cases are often met before the age of thirty and an occasional apoplexy has been reported in the early twenties.

The development of arterial disease and its complications are attracting more and more attention, because reports show the condition to be on the increase. Insurance statistics, particularly, point to the fact that both the age and incidence (development of symptoms) and the percentage of cases encountered are advancing, the disease being met in earlier life and more frequently than even a decade ago.

This unfortunate prevalence seems attributable to the increased tension and the greater artificiality of the life led by the average business and professional man to-day. Statistics show that men are more frequently victims of arteriosclerosis than women.

ETIOLOGY OF ARTERIOSCLEROSIS

Having discussed the "exciting agents" of arteriosclerosis, we now come to a consideration of what may be conveniently called the "productive or provocative causes." By this is meant those conditions which clinically are looked upon as entering actively into the etiology of the disease and which are found pathologically to be favorable to the development of this disease by contributing to the production or liberation of the "exciting agents" which are themselves directly responsible for the arterial changes found in arteriosclerosis (see page 246) and which are characteristic of the disease.

In reviewing the relation of these "provocative agents"

FIG. 49.-Female. Aged sixty-seven. Diagnosis: Chronic myocarditis and arteriosclerosis. Previous history one of hard work. Family history one of cardiovascular disease. First symptom dated four years previously and included loss of weight, dimness of vision, constant dyspnea with occasional orthopnea, palpitation, dizziness, headaches, edema of the ankles, physical weakness and abdominal pain. Examination shows moderate edema of legs up to knee, no ascites, a large and tender liver, transverse enlargement of the heart, chiefly to the left, apex not palpable, a slight systolic murmur at the apex, very irregular cardiac rhythm, including variations in strength of the impulses with intermissions and extra-systoles. Difference in 26 beats between radial count and apex count. Arteries slightly thickened, slight general cyanosis, urine shows large amount of albumen, normal specific gravity with hyaline casts not always present.

Morphine, rest and elimination resulted in reduction in pressure chiefly systolic from (A) to (B) accompanied by some relief from all symptoms. The dyspnea has been held in control by the intermittent alternating use of digitalis and strychnin.

The response to this treatment is gradually becoming lessened, while the tendency to an elevated systolic pressure becomes more persistent.

The case is one very difficult to manage and is working her own distruction by failure to adhere to restrictions particularly in regard to physical exertion.

Note. Since the preparation of this chart the patient has shown a systolic pressure persistently in the neighborhood of 200 with almost continuous orthopnea, nocturnal cardiac asthma and several attacks very suggestive of angina which are relieved by the use of heroin.

two difficulties are met in attempting to place formally the responsibility. First the indisputable fact that arteriosclerosis does not invariably follow in the wake of these causes, even when they appear to be very active and when their influence has persisted for a great length of time. Second, the almost universal existence of multiple "provocative causes" in the history of any given case, and the nearly utter impossibility of indicating definitely the single cause, if indeed any single cause be found to exist (see Fig. 49).

Accepting the existence of at times unsurmountable obstacles, in the way of isolating the cause of the disease in any particular case, we are now in a position to review the statistics available and to understand the apparent discrepancies found. Finally, to form our own conclusions, which can be adopted to our individual needs and employed as diagnostic leads in the course of practice.

One of the earliest statistical reports is that of Huchard1 who reported the causative factor in 2680 cases of arteriosclerosis found in 15,000 patients seen in the course of private practice. In their relative frequency these were as follows: gout, uricemia, food, syphilis, tobacco poisoning, worry, mental over-exertion and alcohol.

Herz's2 more extensive study covered the tabulation of reports of the most frequent cause furnished him by 822 different observers. This composite report gives as follows the relative frequency of causes as met by each contributor:

1 Med. klin. Berlin, v, No. 35.
1 Wien. klin. Wochen., xxiv, No. 44.

Thayer1 tabulates his study of 3894 cases in their order of frequency as follows: heavy work (62.2 per cent.), alcohol, rheumatism, diphtheria, scarlet fever, malaria and pneumonia.

Brooks2 studied 400 cases and heads the list with occupational lead poisoning, severe manual labor, alcohol, nephritis, syphilis and tuberculosis.

Thayer and Brush admit that the majority of cases give a history of multiple factors which they do not attempt to separate but which they divide into four groups:

First.-Manual labor, 57.6 per cent.
Second.-Alcohol, 46.8 per cent.
Third.-Acute infections.

(a) Rheumatism, 34.6 per cent.
(b) Typhoid fever, 26.3 per cent.

Fourth.-Those having acute infections alone (variety not stated), 24.3 per cent.

Rodger I. Lee3 reports the following causes present in the percentages given below which in the majority of instances were multiple.

1 N. Y. Med. Jour., June 18, 1904.

2 A. M. A. Jour. Med. Sci., May, 1906.

3 Jour. A. M. A., Oct. 7, 1911, lvii, No. 15.