Sixty-four with blood sugars of 70 mgm. or less per 100 cc. of blood. Of these 64:

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34 had blood sugars of 70 mgm. or less per 100 cc. of blood.

22 had blood sugars of 60 mgm. or less per 100 cc. of blood.

6 had blood sugars of 50 mgm. or less per 100 cc. of blood.

2 had blood sugars of 40 mgm. or less per 100 cc. of blood.

Of the 431 only 10 were above 120, the upper limit usually given for normal.

In diabetics whose blood sugars were high, that is above 300 mgm., symptoms of insulin shock frequently have been observed when their blood sugars were rapidly reduced to within usual normal range. One carefully observed case showed unmistakable signs of insulin collapse with a blood sugar of 160 mgm. which had been reduced by insulin from 440 mgm. just three hours before.

The causes of this hypoglycemic reaction has not been determined. Low blood sugars due to extreme undernutrition and fasting as well as the occasional hypoglycemia of normal persons indicate that the symptoms follow the rapid lowering of the glucose in the blood. Quoting Professor MacLeod,

"This does not mean to say that the violent symptoms are directly due to the disappearance of glucose as such from the blood; that would be a rather unscientific conclusion to draw. One must imagine that the immediate cause of the symptoms is the development of some toxic condition in the nerve cells, the prevention of which in the normal animal is dependent upon a certain percentage of glucose in the tissue juices."

Insulin causes a vacuum for sugar in the tissue cells and juices, thus causing a reduction of the sugar in the blood. Banting and MacLeod give three possibilities as the cause of the development of a vacuum in the tissues: (1) That it is due to an increased combustion of sugar; (2) that it is due to a condensation of sugar into glycogen; and (3) that it is due to a reduction of sugar into some other substance, possibly related to fatty acid.

The diagnosis is not difficult for the physical findings are definite and the subjective symptoms-nervousness, weakness, extreme hunger—are as a rule noted several minutes before unconsciousness appears. In the nervous and imaginative patient the objective findings must be our chief guide.

Those occurring most frequently are extreme weakness, hunger, sweating, tremor and localized or general twitching of muscles. Most cases are drowsy, cannot think clearly and drawl out their words in a do not care disinterested sort of a way characteristic of those who are slightly under the influence of liquor. The time of occurrence is usually two to four hours after insulin is administered. Mild cases usually recover if given a cup of hot coffee or tea, the more severe cases requiring a few grams of carbohydrates by mouth in the form of orange juice, sugar, syrup or candy, while those who are unconscious should be given a hypodermic of epinephrin 1 mil of a 1:1000 solution followed by sugar, syrup or other concentrated carbohydrates by mouth when the ability to swallow is restored by the epinephrin injection. If the epinephrin does not restore the func

tion of deglutition within a few minutes then 15 or 20 grams of glucose should be administered intravenously. This promptly restores the patient.

The necessity of hypodermic injection and the insulin reaction which is liable to occur in the poorly nourished, especially in the beginning of treatment, are the two points emphasized by those who oppose insulin therapy in diabetes. Hypodermic injection, as stated earlier in our paper, is necessary because insulin is rarely effective by mouth. The hypoglycemia can usually be avoided if the dose and time of administration is arranged to suit the individual case and in those who are emaciated we arrange insulin dosage and diet so their urine will be sugar free and blood sugar not below 150 mgm. per 100 cc., thus giving a larger margin for variations in the intake or absorption of carbohydrate. We have seen no case of unconsciousness in hypoglycemia which could not quickly be differentiated from diabetic coma and rapidly restored to normal. Should it be impossible to make such a differentiation procure blood at once for a glucose estimation by veni-puncture and immediately administer 10 grams of glucose. Within thirty minutes the blood sugar estimation should be completed giving definite data for the administration of either glucose or insulin.

We have summarized the records of 31 reactions during insulin administration. This summary is as follows:

The 31 collapses in our first 172 diabetics requiring insulin were distributed among 16 different patients, the greatest number of collapses experienced by one patient being 6.

This patient was sixty-five years of age, weighed 70 pounds her ideal weight was 130 pounds-and had a gangrenous infected right foot and leg which was later amputated above the knee. During the time of the collapses she was receiving from 105 to 115 units of U insulin during twentyfour hours divided into four doses.

WEIGHT

The heaviest patient weighed 150 pounds but was not obese and the lightest one was 57 pounds—her ideal being 120 pounds. The average of the entire group was 100 pounds. All of these cases were adults except two, one a boy aged thirteen years weighing 98 pounds, and the other a girl aged thirteen years weighing 87 pounds. Every case was under its ideal weight. This seems to suggest a definite relationship between the body weight and the occurrence of hypoglycemia.

TIME OF COLLAPSE

The meals were served at 9:00 a.m., 1:30 p.m., and 6:15 p.m. and no special distribution of carbohydrates was carried out other than attempting to approach the average arrangement of meals of the patient when at home. The dosage of insulin was arranged in general as follows: (1) largest dose preceding breakfast; (2) smallest dose noon; and (3) intermediate dose in the evening, and, if necessary, a small dose at midnight. The insulin was administered from ten to thirty minutes preceding the meal. Eighteen or 58 per cent of the collapses occurred between 2:50 and 6:50 p.m.; 12 or 39 per cent of the collapses occurred between 7:00 and 9:30 p.m.;

a commercial firm especially for intravenous administration.

Twelve cases or 40 per cent received no carbohydrate. Their symptoms were of such a mild nature that no treatment other than a cup of hot coffee or absolute rest in bed was necessary to relieve their symptoms.

Seventeen cases or 55 per cent received carbohydrate by mouth. The largest amount given was 60 grams, the smallest was 5 grams, the average given was 14 grams.

27

Two cases or 5 per cent received carbohydrate both intravenously and by mouth. They averaged grams of glucose intravenously and 20 grams by mouth. Both of these cases were unconscious with the loss of the swallowing reflex when first seen by the resident physician. They were both given the above-mentioned amounts of glucose immediately over a period of 3 minutes when they had sufficiently reacted to swallow, after which the remainder of the glucose was given by mouth. We accounted for one of these cases through failure to have his evening meal consumed at the proper time after the insulin had been administered. The other case was a man that had an infected gangrenous foot amputated three days previously, and, as has been frequently observed in diabetics following the cleaning up of an infection, this patient's tolerance suddenly increased, or his insulin requirement decreased and he went into collapse following his evening insulin and meal.

SYMPTOMS

1. Perspiration-every patient observed had this symptom. The skin was cold and clammy and the perspira

tion was general, the degree of which varied directly with the depth of the collapse.

2. Deep reflexes-the patellar reflex was appreciably increased in 50 per cent of the cases.

3. Pulse and respiration-there was no marked or definite variation of the patient's pulse and respirations during any of the collapses.

4. Mentality-2 of the cases were unconscious. One case, a boy aged thirteen years was loquacious, threw himself about the bed as would a severe case of chorea and his face was flushed. The remainder of the cases displayed a very typical dulled or clouded mentality. They had a dazed or vacant expression, could not answer questions quickly, slightly confused as to orientation, drawled their speech and had some difficulty in enunciating their words distinctly.

5. Sensations-practically every patient complained of feeling weak,

very hungry and partial loss of coordination of the voluntary musculature.

6. Diplopia-2 cases, both children, complained of double vision.

RESPONSE TO TREATMENT

Every case to whom carbohydrate was administered obtained complete relief in from five to ten minutes. Those cases that received no medication except a cup of coffee and rest were a little slower in recovering but recovered none the less completely.

In conclusion we have had no insulin reactions in cases of coma. Only 2 cases, or 5 per cent, required glucose intravenously. These were in ward patients and occurred during the changing period of the nursing staff. All of the patients experiencing reactions were severe diabetics and very poorly nourished. Two of them were skeletons.

E

| XTRASYSTOLES have such a serious aspect in the minds of the laity and many of the medical profession that I have decided to review 100 cases in which this abnormality has been found. While this is not a large number, each patient has been carefully studied with the idea in mind of determining whether this abnormality is a manifestation of a pathologic condition or not.

Extrasystoles are premature contractions which are the result of generating and discharging stimuli in any part of the myocardium outside the sino-auricular node.

This study of 100 patients, each of whom has been examined by me in my office several times, might be termed that of an ambulatory class. It covers a period from 1916 to 1924, few of these, however, being seen in 1916. The longest history of extrasystole being known before examination was twenty-five years and this patient was a physician who had watched this type of arrhythmia appear whenever he smoked and disappear when he did not indulge in this pastime. The shortest period was of a few days when the extrasystole appeared during an acute influenza. Many did not know of the presence of this abnormality but it was discovered

during the routine examination of the heart.

I will not review the lengthy literature on this subject but will attempt to discuss my own findings and give my own conclusions. The extrasystole, besides being of especial clinical interest, is also of great prognostic importance to me as a medical director of an insurance company, and I confess in the beginning it was hard for me to decide what was the best thing to do with an applicant with an arrhythmia of this type.

MECHANISM AND CLASSIFICATION

The normal cardiac stimuli arise in the sino-auricular node and spreading throughout both auricles result in the auricular contraction. Some of these stimuli are transmitted through the auriculo-ventricular node and bundle to the ventricles which contract shortly after the auricle. The ventricular systole normally follows the auricular systole in less than 0.20 second.

Of the five properties of the myocardium all may be affected by extrasystoles, but irritability is the one which is chiefly involved. Tonicity may be depressed during extrasystoles of rapid rate, the predominating rhythm may be changed, conduction