Angina Pectoris *

Angina Pectoris *

AN GINA PECTORIS· G. K. FENN, M.D.t HISTORICAL BACKGROUND EIGHT years before the Declaration of Independence was signed in Philadelphia, the Illinois...

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EIGHT years before the Declaration of Independence was signed in Philadelphia, the Illinois country, which included Chicago, had recently been transferred from French to British control. Captain Thomas Sterling, on behalf of the British, took possession of Fort Chartres and the Illinois country in 1765. In 1768 the command passed to Colonel John Reed of the British Army. This historical reminiscence will serve to sketch in the local background of the year 1768, in which an English physician named William Heberden published a paper in the Medical Transactions of the College of Physicians. The title of this paper was "Pectoris Dolor" and in the course of it Heberden says, "But there is a disorder of the breast marked with strong and peculiar symptoms, considerable for the kind of danger belonging to it, and not extremely rare, which deserves to be mentioned more at length. The seat of it and the sense of strangling and anxiety with which it is attended, may make it not improperly be called angina pectoris." Thus was the label attached to the subject of our discussion this morning. The pain of angina pectoris had been known before Heberden's time and had been previously described. Indeed, some of the best descriptions had been from the pen of lay persons. Seneca, whose life spanned the birth of Christ, and who wrote very bad tragedies in very good Latin, described his own anginal pain with great clarity. The Earl of Clarendon, in the seventeenth century, described the pain in the left arm suffered by his father, Lord Clarendon. He says, " ... he was seized on by so sharp a pain in the left arm for half a quarter of an hour, or near so much, that the torment made him as pale (whereas he • From the Medical Departments of Northwestern University Medical School and St. Luke's Hospital. t Associate Professor of Medicine, Northwestern University Medical School; Senior Attending Physician, St. Luke's Hospital. 16



was otherwise of a very sanguine complexion) as if he were dead; and he used to say, 'that he had passed the pangs of death, and he should die in one of those fits!' " He did. It was Heberden, however, who placed this disorder before the medical profession as a distinct clinical entity and who gave it the name it bears today. Now then, Heberden and his colleagues, among whom were Jenner, Hunter and Fothergill, thought that this disorder had something to do with the coronary circulation. It is popularly reported that Heberden did not mention the coronary circulation in his original report because he did not wish to worry his friend John Hunter, who suffered from anginal attacks. Hunter, however, seemed to be under no misapprehension about his trouble. He stated at one time that "my life is in the hands of any rascal who wishes to worry and tease me." He demonstrated the truth of this observation by dying suddenly at St. George's Hospital just after a rather acrimonious session with some of his colleagues. This rather ill-defined relationship to the coronary circulation was not made clearer by Heberden's paper in which he said, "On opening the body of one who died suddenly with this disease, a very skillful anatomist could discover no fault in the heart, in the valves, in the arteries or in the neighboring veins ... " The ill-understood relationship between the coronary circulation and anginal pain caused all breast pain of this type to be called angina pectoris, and it was not until 1912 that our fellowtownsman, James B. Herrick, taught us how to distinguish the pain caused by coronary occlusion and to make a diagnosis of coronary occlusion under the proper circumstances. In his article, Herrick removed a large number of patients from the general collection of those suffering from breast pain and placed them in a special group. Henceforth this group shall be known to suffer from coronary occlusion. In the present discussion the term angina pectoris will not be applied to those patients suffering from coronary occlusion. THE ORIGIN OF ANGINAL PAIN

. It seems obvious that anginal pain is related to the coronary circulation. It seems equally obvious that all anginal pain is not due to the same sort of coronary artery disorder. For instance, it is quite possible to have anginal pain with a relatively normal



coronary circulation. In view of the fact that most anginal pain occurs after the age of forty-five years, it goes without saying that most anginal pain is associated with some coronary artery change. However, in many cases the anginal pain must be predicated upon things other than the changes in the structure of the coronary arteries. In the days when we saw very low red cell counts and low hemoglobin percentages in pernicious anemia, anginal pain was a common symptom of this disease. Nowadays when the red cell count and the hemoglobin are usually maintained at normal or near normal levels, anginal pain is much less frequently observed. It still occurs occasionally as a symptom of severe anemia. Here, of course, the coronary vessels are not entirely at fault. The impoverished blood is an important factor. Likewise, one may encounter a diabetic in whom anginal pain occurs as the result of hypoglycemia. The usual story is that the patient seems to be well controlled by insulin. No sugar appears in the urine. Upon questioning it develops that anginal pain is relieved by food. The patient feels fine following meals. Further investigation reveals low fasting blood sugar levels. Here again, it is not the structure of the coronary vessels that is primarily responsible for the pain. It is the quality of the medium that is passing through them. Anginal pain may sometimes occur in association with marked hypotension. One must remember that the coronary flow is a function of the mean blood pressure. It is entirely conceivable that the blood pressure may at times be so low that a sufficient coronary flow is not available. These represent a few examples of the occurrence of an inadequate coronary flow with a normal or relatively normal coronary vascular system. A rather unique situation lying somewhere between the foregoing and the frank coronary artery disorders is encountered in some cases of hypertension with left ventricular hypertrophy. Anginal pain is usually a rather late manifestation in hypertension. Its occurrence ordinarily signifies the appearance of structural changes in the coronary vessels. This, however, is not always true. In certain instances the muscle mass of the left ventricle increases rather rapidly to compensate for the additional load interposed by the hypertension. The coronary circulation increases with the blood pressure up to a certain point and thus the increasing pressure carries its own compensatory increase in coronary flow. At certain levels of cephalic pressure



the coronary flow becomes reflexly inhibited. We are then confronted with a situation in which an increased muscle mass cannot receive an adequate blood supply even though the coronary vessels are relatively normal. The coronary circulation cannot increase in the number of vessels. In addition, the coronary capillaries, which lie between the muscle fibers, have been stretched out by the muscle hypertrophy and dilation and this stretching tends to reduce the lumen of the capillary. Thus we have a normal, or relatively normal', coronary circulation which is unable for at least two reasons to meet the demand placed upon it by an increased cardiac muscle mass. And so it is that anginal pain may occur in such cases without the necessity of seriously damaged coronary vessels. Mention of the cephalic inhibition of the coronary flow opens the question of reflex inhibition of the coronary flow in general. F or a long time it was not admitted that the coronary vessels might undergo active constriction, or dilatation either as far as that is concerned. This is no place to enter upon a discussion of whether or not the coronary flow may be influenced by things other than blood pressure and cardiac work. That discussion has already filled many, many pages in the medical literature. Those of us, however, who have insisted that active coronary vasoconstriction and reflex vasoconstriction was a fact believe that a great weight of evidence is piling up to support us. Evidence has been brought forward to show that stimuli in at least . three different places are capable of producing reflex coronary constriction. It is altogethe1; likely that other sources for this reflex constriction exist. A few years ago Hall in Toronto and LeRoy in our own laboratory showed the presence of reflex coronary artery constriction resulting from acute coronary occlusion. This work seemed quite conclusive and has modified our treatment of acute coronary occlusion. At about the same time, de T akats, Beck and I published some work that showed the occurrence of reflex coronary constriction associated with pulmonary embolism. Sometime later Gilbert, LeRoy and I demonstrated experimen~ally that the coronary flow may be greatly reduced by distention of the stomach. This work was carried over to the human where it was shown that anginal pain came on much more rapidly and easily when the stomach was distended and that this phenomenon might be prevented by breaking up certain re-



flexes. All of this has been published at considerable length and need not be discussed now, but it convinces us that stimuli arising in various parts of the body are capable of producing reflex coronary constriction and that these reflexes added to an already impaired coronary flow may be responsible for anginal pain. In addition to those stimuli mentioned here there are doubtless many others that produce constriction of the coronary vessels in one way or another. Emotional stress is notorious in this regard. There is no doubt that the smoking of tobacco produces appreciable coronary constriction in some persons. Altogether there are many things apart from structural change that may produce a reduction of the coronary flow in a susceptible individual. Now then, I distinctly do not want to leave you with the impression that I believe that most anginal pain occurs without structural change in the coronary circulation. It is true that most persons suffering from anginal pain have a disorder of the coronary arteries. The coronary artery disease itself many times produces the anginal pain but the other factors that I have mentioned often enter into the picture. The anginal pain caused by obstructive changes in the coronaries has certain distinctive characteristics that I shall discuss in a moment. At this point I wish to call your attention to certain cardiovascular disorders that produce a pain that is often confused with the pain of angina pectoris. Aortitis produces substernal pain that is very similar to that produced by coronary artery disorders. It is a burning pain that may have the same location and radiation as the pain that we have been discussing. Yet for purposes of this discussion, at least, aortic pain must not be confused with true anginal pain. It was not so long ago that most anginal pain was attributed to aortic causes, and Sir Thomas Clifford Albutt rather scornfully called the adherents of the coronary artery theory the "coronarians." In this category comes also the pain of aortic insufficiency. The rupture of a dissecting aneury sm may cause pain that is very difficult, if not impossible, to differentiate from pain of coronary origin. This event is more likely to be confused with a coronary occlusion than an attack of angina pectoris but the pain element is the same. Pericarditis may for a time be confused with anginal pain. T~ere are, of course, a host of pains of noncardiac origin that



may be confused with anginal pain but there is no time to discuss that phase of the subject here. It is well to reme.mber, however, that all chest pain does not have its origin in the coronary circulation. CLI NICAL PICTU RE

Angina Pectoris

Now that we have dealt with the origin of anginal pain it might be well to discuss the pain itself. It would seem almost unnecessary to describe the pain of angina pectoris when it has been done so many times but we must try to differentiate the several varieties of anginal pain as well as we can in order to have a logical approach to the management of each case. For the purpose of this discussion let us say that the term angina pectoris is applied only to a certain variety of anginal pain. That variety is the sudden attack of breast pain that comes on without much warning and is very severe indeed. The patient is seized with an attack of pain that is located beneath the sternum usually at the junction of the lower and middle third. The pain comes on suddenly and reaches its full development almost immediately. The patient has no time to do anything but stop where he is and seize upon the nearest object for support. The pain may be and usually is referred to the left shoulder and down the left arm. It goes down the inner aspect of the arm and may extend into the middle and ring fingers or it may terminate abruptly at the inner aspect of the elbow. Rather frequently the pain is referred to both shoulders and arms, and sometimes it may go to the right side only. It is not infrequently referred upward to the neck and the jaws and it may cause a sensation resembling toothache. Much less frequently it is referred into the back at the base of the neck. Very rarely it may be felt between the scapulae. It may also be referred downward but with much less frequency. When the pain is referred downward toward the abdomen it is sometimes difficult to differentiate the entire episode from an attack of upper abdominal pain. It seems to me that this variety of angina is particularly important because it is so likely to be overlooked and attributed to an abdominal disorder. Together with the pain there is a sense of constriction in the chest. This has been described as a viselike pressure or a sense of fullness that resembled a pressure from within. There is also



a certain feeling of apprehension that does not accompany other varieties of pain. This sense of apprehension has received a number of titles among which "the icy hand of death clutching the heart" and "a sense of impending dissolution" are perhaps the most descriptive. The pain with its attendant phenomena comes on as described, lasts a varying period of time usually not exceeding fifteen minutes. and then subsideS! as quickly as it came. During the attack the patient remains perfectly quiet. He seldom makes a sound. His breathing is slow and shallow. Dyspnea is no part of this attack. It seems that the patient voluntarily inhibits his movements from fear of greater pain as a result of movement, even breathing. During the attack the patient's face is gray, a mixture of pallor and cyanosis. His lips appear blue and he looks very ill indeed, as he is. With the subsidence of the attack the patient takes a long breath, slumps back relaxed in his chair, perhaps smiles and apologizes and except for a great exhaustion he seems to feel quite well. This is a typical attack of angina pectoris. It is a burning, chest-filling pain, with a sensation that the ribs are being pressed into the chest and a sensation that every breath may be the last. With the subsidence of the attack, no signs are left behind. There is no change in the blood pressure or pulse; no physical signs that would indicate that a serious crisis had just been passed. It is important to remember this, since often the aftermath produces the only evidence to differentiate such an anginal attack from an occlusion of a coronary artery.- It is my opinion that the attack just described is always precipitated by an active constriction of the coronary circulation. This is not to say that sU,ch attacks frequently occur in the absence of coronary artery disease. Not at all. A pathologic change in the coronary artery is usually present but still the determining factor in the attack is that of active constriction of the coronary vessels. Angina of Effort

When marked coronary artery disease is present, one is likely to see a different type of anginal pain. This is the pain that be-gins almost exclusively' with exercise and builds up rather slowly. The patient notes the pain as he walks .along the street and he knows if he goes too far it will become quite severe. BUT, he is able to go along until the pain slowly reaches a cer-



rain point in severity and then he may stop and rest for a time and the pain slowly subsides. Thus by exercising and resting alternately, he may carry on fairly well. In-other words, he has the pain more or less under control and he is able to escape severe attacks: by watching his behavior. This type of pain is the result of an insufficient coronary circulation, either functional or organic, and is quite different from the attack of angina pectoris that was previously described. Atypical Anginal Pains

We must also consider the somewhat atypical pains that point toward a coronary origin. Lord Clarendon spoke of his father's pain which was confined to the left arm-only. As a matter of fact, the pain may be confined to any of the areas of reference and may be of any degree of severity. We must therefore carefully investigate all of the pains in this locality that occur in individuals of a certain age group and determine whether or not these pains may be of coronary origin. Pain any place in the chest or anns that has this peculiar squeezing character and that is pre~ic.ated upon exercise must be investigated for a coronary orIgIn. Illustrative Cases

It is difficult to present before the clinic an example of angina pectoris, for it is seldom that the patient times his attack to coincide with the hour of the clinic. Only once in many years of teaching has the attack occurred at the proper time. I have one or two records that I exhibit rather frequently to demonstrate some of the things that we have talked about. A. P., a gentleman aged sixty-six years, first came to me because of pain in the left .shoulder and arm. He operated a small machine shop where he specialized in the repair of automobile carburetors and generators. His office was situated on -a balcony above the work floor and he noted that when he went up and down the stairs to his office too frequently he developed a pain in the left shoulder and arm. He had assumed that this pain was due to a local disturbance in the shoulder and he had discovered that if he immersed his arm in hot water the pain usually subsided..He confessed, however, that if he merely sat down and waited the pain disappeared in a few minutes anyway. He also had attacks of the same sort when he was d;riving his car in heavy traffic and became irri-



tated by his inability to move along rapidly. When the attack came on under these circumstances he stopped his car at the earliest opportunity and waited for the pain to pass. I was very curious about the relief he obtained from immersion of the arm in hot water but he insisted that there could be no mistake about it and that he kept a pan of water heated in his shop exclusively for this purpose. I was quite convinced from the history and from the location of the pain that I was dealing with an anginal affair. I could not see, however, how the local application of heat could be effective in stopping the pain. It occurred to me, however, that this immersion of the arm in hot water might provoke a general vasodilatation and thus relieve the anginal pain. I suggested that next time he immerse his right arm in the water and observe the effect on the pain in the left arm. He saw no point in this procedure but he agreed to undertake it just to humor me. To his great surprise it worked just as well as the immersion of the left arm. This then was a case of moderately severe anginal seizure that was relieved by rest and by heat. Later under appropriate management these attacks were reduced materially in number and severity. . About a year after this gentleman came under my observation he had an unusually severe attack of pain one afternoon at the shop. Immersion of the arm in water, nitroglycerin under the tongue and other measures failed to have any effect on the pain. Intsead of subsiding in ten or fifteen minutes it lasted for three hours in such a severe form that he was unable to get home. When he did arrive at home some three or four hours after the onset of the pain he became nauseated and vomited. His pain still continued but was less severe. He stated that the pain was almost identical with that from which he had suffered for the past months. It extended slighly more into the chest and was more violent than most of his previous attacks. I sent him to the hospital, of course, as soon as my attention was called, and subsequent examinations proved thart he had suffered a coronary occlusion. }Iere then was a man who had suffered numerous attacks of anginal pain without anything more than temporary disability. The same sort of pain with certain modifications and sequelae proved to be the principal symptom of a coronary occlusion. R. H., a man of fifty-eight and an executive in a highly competitive insurance business, began having attacks of substernal distress that were brought on by rather moderate exercise. He noted that he could no longer walk from the station to his office, a thing



that he had done for years without trouble. He has never had .3 crushing anginal attack but very uncomfortable anginal pain followed upon every attempt to get actively about. After this had been going on for about a year he took a six-months' holiday and went abroad to visit his daughter. Very soon he found himself doing things that he would not dream of attempting at home. Soon his anginal pain had virtually disappeared and it took a great deal of exercise to cause him to feel it at all. Naturally, he was delighted, only to be greatly disappointed when his symptoms promptly reappeared when he returned home and resumed his work. This seems to me to demonstrate the effect of emotional stress in promoting painful episode of this sort. I could go on indefinitely presenting case records to show the variable nature of this disorder and the different forms under which it appears, but perhaps we should now approach the discussion of what to do about it. MANAGEMENT

Nothing in the field of medicine requires a more careful individual study than does the case of angina pectoris. First, we must be sure of the diagnosis. Almost everyone nowadays realizes the seriousness of a diagnosis of angina pectoris and we must be careful not to subject our patient to the mental burden of this diagnosis unless we are sure of our ground. Secondly, the general management and the specific treatment are greatly influenced by the correctness of the diagnosis. General Measures

When the diagnosis seems to be definitely established it becomes the duty of the physician to determine, if possible, what sort of anginal pain he is dealing with. Is it effort alone that produces the distress or is it the pressure of business or emotional stress? Or is it a combination of several contributing factors? It is necessary, of course, to greatly modify the habits of the patient in many instances and a study of the immediate causes of his anginal pain is the most important guide to the modification. Unless the patient is engaged in an occupation that requires hard manual labor, it is surprising how frequently he can carry on his usual occupation with certain modifications. Perhaps it will be necessary to shorten his working hours; frequently short vacations not too far apart will work very well.



Avoidance of controversial subjects and avoidance of any activity or occupation that causes emotional stress must be insisted upon. In other words, the patient may play golf if he does not take his game too seriously. The same applies to bridge or to attending football or baseball games or even to listening to the radio under certain circumstances. A careful study of the entire situation will often show how the attacks may be greatly reduced. A patient may be able to do a certain amount of exercise in the summer that is impossible in the winter. It is well known that many attacks are precipitated by breathing cold air. The same is true of exercise before and after meals. This brings me to a discussion of the relationship of the gastro-intestinal tract to the occurrence of anginal pain. It is well known that anginal attacks occur more frequently following meals and in the presence of gastro-intestinal disorders. It has now been shown that distention of the stomach. and bowel, either by food or by gas, causes a sharp reduction in the coronary flow and causes anginal pain to come on with less provocation. Therefore, as a general proposition, the gastro-intestinal tract should be kept in good order. Any tendency toward constipation should be overcome. A study of the patient's peculiarities will show what foods he does not tolerate well. The known gas-formers should be avoided. And above all the patient should avoid any provocative activity after meals. Indeed, he should avoid large meals. Mental tranquillity is of great importance in dealing with anginal pain. We are all familiar with the greater prevalence of anginal attacks during periods of financial crisis or during an election year or even in wartime. Of course it is not always possible to achieve mental tranquillity. We cannot, apparently, avoid having financial depressions occasionally and we do not want to avoid election years. We can attempt to keep our patients out of many emotional crises and we can teach the patient to avoid too much mental excitement. It is surprising how much a bit of self-control will accomplish. When the patient is taught that he cannot afford to get angry or that he cannot afford to argue about trivial subjects, his life becomes very much more tranquil. The patient must realize that violent argument accomplishes very little anyway except to precipitate anginal attacks in susceptible individuals.



Treatment of the Attack

After we have studied the patient carefully to determine what general management to apply to his case we come to the matter of administering drugs. For the treatment of the attack, nitroglycerin under the tongue has no serious competitor. We still find most sufferers of this disorder carrying the small vial of hypodermic tablets of nitroglycerin, grain ){oo, in his pocket. One of these placed beneath the tongue will ward off most attacks or at least shorten the duration. This dosage may be repeated frequently without apparent danger, but to assume that unlimited amomits of nitroglycerin are quite innocuous is a mistake. It does lower the blood pressure to a considerable degree and when this effect is pushed unduly, ill effects may result. Inhalation of amyl nitrite from the well known amyl nitrite pearl is almost as effective as nitroglycerin but it is perhaps slightly more dangerous. These remedies are so well known that I need not talk further about them here. As a general rule, narcotics are in the class of bad treatment for attacks of angina. The attacks occur too frequently and in any event if the pain persists long enough for the physician to arrive and prepare and give a narcotic one should doubt the diagnosis. Drug Prophylaxis

The next task is to attempt to forestall the attacks. As already pointed out, prevention is first a matter of management rather than drug treatment, but unfortunately it is impossible to "manage" away most attacks of 'angina. We therefore prescribe one of the drugs that has the effect of dilating the coronary vessels. The most trustworthy of these are the theobromine and theophylline compounds. In our own clinic we use specifically alkaloidal theobromine, 5 grains four times a day; theocalcin, which is theobromine calcium salicylate, 7 Y2 grains four times a day; aminophylline, which is theophylline with ethylenediamine, 3 grains three or four times daily. The latter may be given parenterally but this is rarely if ever necessary in the treatment of angina pectoris. Under certain conditions in which it is impossible to have medication retained in the stomach the intramuscular administration of aIninophylline is indicated. Parenteral administration is usually limited to the treatment of coronary occlusion.



I feel that I should offer a few words about the theobromine and theophylline compounds, because there seems to be doubt in certain quarters concerning their efficacy. This is a question that the physician must answer from his own experience. Those of us who have done experimental work with these drugs cannot fail to be impressed by the effect on the coronary flow in the animal, and their efficacy in clinical usage seems equally plain to me. A high percentage of my own patients are greatly benefited by the proper administration of these drugs. It is true that one must again study the individual case. A routine handling is not satisfactory. Some patients will not tolerate one form of medication that may be given with impunity to another patient. I cannot see how careful administration of adequate doses of these purine base preparations will fail to benefit a large number of patients. It is, of course, obvious that in those patients whose vessels are rigid and sclerotic, dilatation by any means is almost impossible. A striking testimonial to the efficacy of theobromine and theophylline is obtained when one attempts to persuade patients, particularly physicians, to get along without either drug after they have been rendered reasonably comfortable by its use. One obstacle to their use formerly lay in the gastric distress that accompanied their administration. This has been largely obviated by the newer preparations, and if the medication be given together with the meal, difficulty is seldom encountered. Other drugs that are used for the dilatation of the coronaries are the nitrites, apart, of course, from those nitrites already mentioned. In my hands the effect has been too transient to be dependable. Furthermore, I believe the purine bases to be superior in effect. The administration of a small dose of a barbiturate often seems to be effective in reducing the number or severity of anginal attacks, but I do not favor the combination of barbiturate and purine base in a single tablet. I prefer to be able to vary the dose of one or the other drug at will. The parenteral administration of certain tissue extracts has been effective in some patients. This material is surely worth a trial if difficulty is encountered in controlling attacks by other means. In some cases, indeed, it seems to be superior to any other medication. Unfortunately its administration is time-consuming and this fact has had something to do with its less widespread



popularity. When this material is used it must be given in adequate doses. This means a daily injection for a time, with a longer time interval later as indicated. The patient may be taught to give his own injection but this always seems to me to be throwing too much responsibility upon the patient. The administration of male sex hormone (androgen) has been recommended. Androgen has not been particularly efficacious in the relatively few cases in which I have used it. Perhaps I have not been sufficiently persistent because in a few of my cases the results have been rather striking. Drugs That Should Not Be U sed.-There are a few contraindications in the use of drugs that probably should be mentioned. Any drug that increases cardiac work should be avoided or given with great care. The most common of these are thyroid, epinephrine, ephedrine and benzedrine. As you may know, digitalis is one of my pet abominations. I am already on record with my belief that digitalis may sometimes produce anginal pain. To my mind the only indication for digitalis, apart from auricular fibrillation, is congestive heart failure, and congestive heart failure and angina pectoris seldom coexist. I cannot see how digitalis can be of any benefit in angina pectoris and I feel sure that it may at times be harmful. Surgical Measures

Some years ago cervical sympathectomy or injection ot the nerve trunks was practiced as a means of interfering with the pain. Either may be justified in certain instances but is not recommended for widespread adoption. Likewise, thyroidectomy has been effective in controlling anginal attacks but the cases must be selected with great care and this surgical procedure is not to be considered as a general routine treatment of angina pectoris. The surgical operations pioneered by Beck and O'Shaughnessy have been interrupted for the present. Perhaps this work will be resumed later and result in a means of creating an auxilliary coronary flow. PROGNOSIS

I know of no situation in which it is more difficult to make an accurate prognosis. The patient may die in his next attack and he may live for years. Because of this uncertainty it is well that some member of his family be told of the possibilities. As a



general rule, it is unwise to tell the patient all of the possibilities, since few of us are able to face immediate extinction with mental tranquillity. To those of you who may suffer from this disease, let me say that you travel in distinguished company. Some of the most famous men of history have suffered from the disease and even died from it.