Cardiovascular Eponymic Signs: Diagnostic Skills Applied During the Physical Examination

© Springer Nature Switzerland AG 2021

S. H. Yale et al.Cardiovascular Eponymic Signshttps://doi.org/10.1007/978-3-030-67596-7_1

1. Aneurysm

Steven H. Yale¹  , Halil Tekiner², Joseph J. Mazza³  , Eileen S. Yale⁴   and Ryan C. Yale⁵

(1)

Department of Internal Medicine, University of Central Florida College of Medicine, Orlando, FL, USA

(2)

Department of the History of Medicine and Ethics, Erciyes University School of Medicine, Melikgazi, Kayseri, Turkey

(3)

Clinical Research Center, Marshfield Clinic Research Institute, Marshfield, WI, USA

(4)

Division of General Internal Medicine, University of Florida, Gainesville, FL, USA

(5)

The Cooper Union for the Advancement of Science and Art, New York, NY, USA

Joseph J. Mazza

Email: [email protected]

Eileen S. Yale

Email: [email protected]

Keywords

AneurysmAortic dissectionSignsEponymsCollateral

Introduction

Prior to the advent of advanced imaging methods, physicians relied on the physical examination and their bedside skills to diagnose aortic aneurysms, dissection, and to test the integrity of the collateral vessels to verify if there is adequate blood supply being delivered to the peripheral tissues prior to ligation of an aneurysm. The techniques used and recognized as signs have been eponymously named to honor these physicians’ contributions to medicine. We begin our review of signs of aneurysms, aortic dissection, and the collateral circulation by first providing a brief overview of key historical features leading to the recognition of these diseases.

Historical Background

The word aneurysm originated from the Greek term widening. The earliest known description of aneurysms dates back to the Egyptians as written in the Ebers Papyrus in 1550 BC:

When thou meetest a tumour of the vessels in any part of the body of a person and thou findest it round in form, growing under thy finger, and spread out against the flesh; it is not big and does not protrude; then say thou: ‘It is a tumour of the met [vessel]. I will treat the disease. The metu [injury] causes it and it then becomes a pricking of the met [vessel]’. Treat it with the knife and burn it with fire so that it bleeds not too much. Heal it like the cautery heals [1, p. 148].

Galen of Pergamon (130–c.200 CE) was believed to be the first to describe and define traumatic aneurysm, presumably those caused by punctures inflicted by swords from gladiator wounds, of the false (pseudoaneurysm) type involving the outer layers of the arterial wall:

When an artery is opened, the disease that occurs is called second an aneurism. It happens in consequence of the skin in the neighbourhood of a wounded artery cicatrizing, whilst an ulcer remains in the vessel, which neither becomes agglutinated nor cicatrized, nor filled up with flesh. Diseases of this description are known by their pulsating, and by their disappearing entirely when pressed upon; the contents of the tumour, which we have elsewhere shown to be a thin and bright blood mixed with much subtle spirit, warmer than that contained in the veins, passing back into the artery [2, p. 3].

Oribasius (c.325–403 CE), in the Iatrikai Synagogai (Medical Collections), wrote about Galen’s and Antyllus’s views on the classification of aneurysm types (true and false). They were transcribed by Oribasius as much of Antyllus’s works were lost in antiquity:

Galen and Antyllus both distinguish two kinds of aneurisms; only it is not certain that the classes of these two authors exactly correspond. The identity of the second class of Galen and Antyllus (aneurysm by wound and aneurism by rupture of an artery) seems scarcely doubtful; but the first species (aneurysm anastomosis in Galen and dilatation aneurysm in Antyllus) presents more difficulties. (…) After these preliminaries, we believe we can express the opinion that these small lateral holes were, in Galen’s opinion, the seat of the aneurysms by anastomosis, and that, consequently, these tumors corresponded to the true aneurisms of the moderns, it is that is to say, those which really stand at the break of the clean tunic of the arteries. On the other hand, modern surgeons agree that there is no real dilatation aneurysm, except in the nearest parts of the aorta of his anatomy origin, and that it is impossible to admit that in speaking of aneurysms by dilatation, Antyllus had in view these aneurysms alone, one is naturally led to think that Antyllus dilatation aneurysms are still the same as the True aneurysms of the moderns. As a result, the first class of aneurysms, according to Galen, does not differ from the first class of Antyllus, having regard to the tumors which constituted these two classes; only the two doctors explained in a completely different, way the formation of the tumors in question [3, p. 660].

The location and characteristics of aneurysms were first described by Aëtius of Amida (mid-fifth century to mid-sixth century CE):

A dilatation of the vessels, which the Greeks call an aneurism, may occur in any part of the body. (…) The signs of an aneurism are a tumour, which may be large or small, without discoloration of the skin or pain, soft to the touch, having a loose spongy feel, and yielding in such a way to the pressure of the fingers that it almost disappears, but returning again on the fingers being removed, which is very evident in those aneurisms that have arisen without a wound; but when it has been preceded by a wound of the artery, and the skin then uniting, a dilatation of the vessels has occurred, the tumour is not equally soft: for the blood being in larger quantity than the spirits, coagulates, and thus distends the tumour [4, p. 4].

Achilles Pirmin Gasser (1505–1577), an Augsburg physician, sent a consilium to Andreas Vesalius (1514–1564) about the autopsy findings of Leonard Welser, a patient for whom Vesalius was referred by Gasser to provide medical consultation. Vesalius diagnosed Leonard Welser with a thoracic aortic aneurysm. Vesalius’s correspondence to Gasser, written on July 18, 1557 at Brussels, reaffirmed his ability to clinically diagnose thoracic and abdominal aortic aneurysms:

I am very grateful to you for this, since I am well aware of how we are compelled to deduce the ailments of our patients from various conjectures. It is truly remarkable how the enlargement of an artery of this sort is chiefly distinguished by the closely packed matter contained in the blood, and that which in our patient resembled lard I have found in others to be somewhat similar to the vitreous humor of the eyes; (…). If we frequently discover [an aneurysm] lying concealed in the body of the living, how often may it be hidden from us in the brain, in the thoracic cavity, and around the pelvic region. May I perish if, after Master Leonard was seen by me, I did not meet with at least six ailments of this sort, but located in different regions. This condition was first seen by me, as I also informed you in the thoracic cavity near the root of the neck, and it shaped the upper ribs of the chest just as you write that the ribs and transverse processes of the vertebrae were gradually shaped in Master Leonard rather than attacked by caries and putrefaction [5, p. 395–396].

Ambroise Paré (1510–1590) in 1582 acknowledged Galen’s observations regarding the formation of atherosclerotic changes within an aneurysm, recognized that not all aneurysms are pulsatile, and postulated the mechanism for the formation of atherosclerotic lesions and thrombosis within the aneurysm:

[t]his hardness is owing to the cold and repercussing applications constantly made to such tumours, which may harden and thicken them. (…) Besides, in very large aneurisms there is frequently no pulsation; and on pressing upon them, the blood cannot be forced back into the artery, both because it is in too large quantity, and because it concretes into a thrombus [6].

It was Richard Wiseman (1622–1676) who was the first to believe that aneurysms arise from rupture of all the layers (coats) of the vessel wall with blood extravasating into the surrounding tissues:

[b]ut not having been able by my practice to discover one aneurisma made by dilatation or relaxation of the outward coat, I am apt to believe that there is no such thing, but that it takes its rise from the blood bursting quite through the artery into the interstices of the muscles, where it raiseth a tumour suitable to the cavity it findeth, growing bigger or less, of this or that shape, as the muscles give way. (…) Those which I have met with did all come from downright eruption through both the coats; and those that come from external punctures must of necessity begin with a breach of the external coats first, it being next the lancet or other weapon that made the division [7, p. 70–71].

Later, Donald Monro (1727–1802) in 1760 described the case of John Parker, a 40-year-old man with multiple aneurysm where all three layers of the vessel wall were identified on macroscopic dissection within the aneurysmal sac reaffirming Wiseman’s impression:

For in the three smaller ones of the right side, the circular fibres, and all the other coats, were traced distinctly over the whole circumference of the tumours: In the one in the left ham they were seen on the fore side; and, although they could not be traced on the back part, nor be at all observed in the large sac of the right ham, it is most probable that these two aneurisms were originally formed in the same manner as the others; though the violent stretching, and the mixture of other substances with the coats of the sac, confounded all the parts so much, as to make such a demonstration impracticable. And we may presume, that so many good anatomists, who have given us histories of what they call true aneurisms, were not deceived in the nature of the disease, although they have not described minutely the texture of the aneurismal sacs, corresponding to that of the arteries in a natural sound state [8, p. 239–240].

Giovanni Maria Lancisi (1654–1720), in De Motu Cordis et Aneurysmatibus published posthumously in 1728, proposed a general definition of aneurism, recognized that weakness of the arterial wall occurs prior to its dilation and the congenital nature of some aneurysms:

In the first place, then, I will divide aneurysms into the genuine and the spurious: I call genuine those that arise from causes close at hand when they weaken the tissue and powers of resistance of the arteries and heart; I mean those that in a short time destroy or at least enfeeble the firm strong web of the villi; and moreover there are some that belong to this class which arise from external causes, wounds, for instance, or contusions; others again, from internal causes, that is now from a natural deficiency and slackness of the villi [9, p. 15].

Jean-Louis Petit (1674–1750) in 1736 was the first to recognize the tendency for aneurysm to undergo recurrent episodes of rupture and bleeding [10].

We conclude our discussion by acknowledging the contributions by Pierre Bourdelot (1610–1685) and Giovanni Battista Morgagni (1682–1771) who were the first to recognize and describe arteriovenous and dissecting aneurysm, respectively. Bourdelot in his description of arteriovenous aneurysm wrote, He will see sufficiently large pulsating arteries pouring all their blood into veins that do not pulsate. The veins and arteries of which he speaks as opening into other veins and arteries have the same orifice, and one often performs the functions of the other (…). [11, p. 212]. Morgagni described the autopsy findings in a 60-year-old man with a dissecting aneurysm:

The pericardium was distended with a large quantity of blood. (…) On the internal surface of the great artery, not far from the heart, a foramen large enough to admit the finger originated, and passing between the coasts in an oblique direction, for about the space of three digits, it opened on the external surface of the artery, within the pericardium [12, p. 362].

Great strides in understanding the pathogenesis, diagnosis and surgical management of aneurysms continued into the nineteenth century to the present. These advanced can be attributed to the development of the microscope and radiography. A variety of signs have been identified as mechanisms to diagnose aneurysms and dissection particularly during the nineteenth and early twentieth century. Our goal in this chapter is to provide a brief historical background of the person who described signs of aneurysms, dissection, and the collateral circulation and to record their original description. The lack of studies evaluating sensitivity, specificity, and predictive value limits the ability to draw meaningful conclusions regarding their utility in clinical practice. The signs are described chronologically from the date they were first reported.

Signs

Corrigan Sign

Sir Dominic John Corrigan (1802–1880) was born in Dublin, Ireland, and graduated from medical school from University of Edinburgh, Scotland, in 1825 [13–16]. After graduation, he served as a medical assistant in the dispensary on Meath-street, Dublin, followed by appointments at Fever Hospital and House of Recovery, Cork-Street, and Jervis Street Charitable Infirmary , Dublin [14]. He was appointed consulting physician to the Whiteworth and Harwicke Hospitals (House of Industry Hospitals) in Dublin from 1840 to 1856 [14, 17]. The title baronet of Cappagh and Inniscorrig in Dublin was granted to Corrigan in 1866 [16, 18]. Corrigan was Fellow of the Royal College of Physician, Ireland in 1856, President of the King and Queen’s College of Physicians from 1859 to 1864 and President of the Royal Zoological Society, Ireland [16]. He served as Member of Parliament from 1868 to 1874, Physician-in-Ordinary to her Majesty the Queen in Ireland, Senate and Vice-Chancellor of Queen’s University in 1871 and corresponding member of the Academy of Medicine [13, 14, 16, 18].

He is best recognized for his work titled Permanent patency of the aortic valve published in the Edinburgh Medical and Surgical Journal in 1832, which he provided the most thorough description of the clinical and pathological features of aortic insufficiency, a name referred to by Armand Trousseau (1801–1867) as Maladie de Corrigan [14, 19, 20]. In a description of his character as described in a memoriam:

He was a man of great physical energy; his feats of activity and strength in his youthful days were most surprising; his powerful frame is well preserved in the grand statue of him by Foley which was presented by numerous friends and admirers to the College of Physicians-no doubt the most appropriate place for it to rest [17, p. 271].

Corrigan identified a visible pulsation of the arteries of the upper extremities in three cases of aneurysm of the ascending aorta or its arch [21, p. 589]. Regarding the significance of this finding, he stated that:

The arteries are empty, and, of course not at their full caliber, as in the living body. If the eye be kept on the situation of even comparatively minute branches at the moment when the injection is sent in, these vessels are seen thrown out in strong relief, presenting precisely the same appearance which the larger trunks present in a case of aneurism. (…) Whether this singular pulsation of the arteries be a constant accompaniment of aneurism of the ascending aorta, it will remain for further observation to ascertain but from what I have seen, were a patient to be presented to me with this symptoms with constant bruit de soufflet and frémissement cataire in the larger trunks, I would not hesitate to pronounce on the case [21, p. 590].

Thus, Corrigan sign refers to the visible pulsation of the arteries of the upper extremity in patients with an aneurysm of the ascending aorta or aortic arch (Table 1.1).

Table 1.1

Aneurysm signs

Hope Sign

James Hope (1801–1841) was born in Stockfort, Cheshire, England, and received his medical degree from the University of Edinburgh, Scotland in 1825 [22, 23]. He studied surgery at St. Bartholomew’s Hospital, London in 1826 qualifying for the diploma from the Royal College of Surgeons [23, 24]. In 1827, he was a clinical clerk to Auguste-François Chomel (1788–1858) and also studied under Gabriel Andral (1797–1876), Pierre Charles Alexandre Louis (1787–1872), and Alexis Boyer (1757–1853) at the Charité, Paris followed by additional studies in Switzerland, Rome and Florence [23, 25, 26]. He returned to London to practice medicine in 1828 and from 1829 to 1831 operated a private dispensary. After a brief appointment as a physician at Marylebone Infirmary, he became a student and governor at St. George’s Hospital, London in order to enhance his future station and appointment in the English University [25]. In 1831, he completed his book Diseases of the Heart and Great Vessels and in 1832 was elected Fellow of the Royal Society of Medicine [27]. He was appointed assistant physician in 1834 and full physician in 1839 at St. George’s Hospital [22, 25]. In a letter to Mrs. Hope, Dr. George Julius spoke of her husband’s character:

Having once made up his mind to do a thing, however arduous, however remote the accomplishment, nothing could check, or interrupt his course. Every energy was bent towards that one object; he never lost sight of it; every daily task had a direct reference to it; every occupation bore upon it; every attainment was regarded but as a step towards the honourable prize he held in view. It was this loftiness of aim that gave a largeness to his design: he rejected all competition for mediocrity: nothing short of success, and eminent success in the highest sphere, would satisfy his desires [28, p. 325–326].

Hope described the auscultatory double beat which he believed to be a pathognomonic sign for detecting aortic aneurysm and explained how this sound can be distinguished from the normal heart beat:

1st: The first aneurismal sound, coinciding with the pulse, is invariably louder than the healthy ventricular sound, and generally than the most considerable bellows-murmurs of the ventricles. 2nd: On exploring the aneurismal sound from its source towards the region of the heart, it is found to decrease progressively, until it either becomes totally inaudible, or is lost in the predominance of the ventricular sound. Now, if the sound emanated from the heart alone, instead of decreasing, it would increase on approximating towards the precordial region.

3rd: The second sound actually does sustain this progressive augmentation on advancing towards the heart; and as its nature and rhythm are found to be precisely similar to those of the ventricular diastole heard in the precordial region, it is distinctly identified as the diastolic sound. The second sound, therefore, corroborates, rather than invalidates the evidence of aneurism afforded by the first; for, if both sounds proceeded from the heart, both would, on approximating towards it or receding from, it , sustain the same progressive changes of intensity.

4th: Another distinctive characteristic of the aneurismal pulsation is, the peculiar nature of its sound. It is a deep, hoarse tone, of short duration, with an abrupt commencement and termination, and generally louder than the most considerable bellows-murmurs of the heart. It accurately resembles the rasping of a sounding-board heard from a distance; whereas, the sound occasioned by valvular disease of the heart has more analogy to the bellows-murmur, being somewhat soft and prolonged, with a gradual swell and fall [29, p. 425–426].

Thus, Hope sign refers to the presence of the double sound heard on auscultation of the thorax in patients with aortic aneurysms (Table 1.1).

Jaccoud Sign

François Sigismond Jaccoud (1830–1913) was born in Geneva, Switzerland, and received his medical degree from the University of Paris in 1860 [30, 31]. He was appointed physician to the Central Bureau in 1862 and agregé in 1863. Jaccoud served as hospital physician at Lourcine, Cochin, Saint Antoine (1867), La Maison Municipale de Santé (1868) and Lariboisière (1870), Paris [30, 31]. He was appointed Professor of Internal (Medical) Pathology in 1877 and later appointed Professor of Clinical Medicine at Faculty of Medicine in Paris at the Pitié-Salpêtrière Hospital in 1883 [31, 32]. Jaccoud was a member of the French Académie de Médecine (Academy of Medicine), section of medical pathology in 1877, served as its President in 1898 and life secretary from 1901 [31, 33, 34]. He was honorary professor in 1901 and honorary doctor of the hospital in 1902 [30]. He was the recipient of the Order of Saint James of the Sword of Portugal, Knight of the Légion d'honneur and the Royal Crown of Prussia [35]. Among his best known works he published Traité de Pathologie Interne in 1871, Leçons de Clinique Médicale (1867 to 1888), and served as editor of a 40-volume set titled Nouveau Dictionnaire de Médecine et de Chirurgie Pratique (1864 to 1886), collegially referred to as Jaccoud’s Dictionary [31, 32, 36].

In his book titled Traité de Pathologie Interne, under the discussion on cancer, he stated:

I have shown in several examples in my Leçons de Clinique, that the diagnosis of aneurysms compared with other thoracic tumors can be confirmed based on physical signs. I have dwelt with this question at length and studied aortic aneurysm in order to avoid having to return to it at this moment. I recalled that voluminous cancers that exceed the ordinary limits of the lung are found by the beating of the great vessels on which they extend and by compression may cause systolic murmur sounds (the case of Graves and Stokes). These beats as well as the murmurs are always simple and there is never any sound of closure of the cardiac valves as to giving the impression of a second cardiac sound [37, p. 126].

In his discussion on aortic aneurysm in his book titled Leçons de Clinique Médicale, Jaccoud wrote:

Suppose a hard mass, a tumor, situated in front of the aorta is raised by it so as to project isochronously with the arterial beats. Its soft parts are found at a limited point at the second intercostal space. You hear two normal aortic clicks which are transmitted and exaggerated by an interposed mass acting as if it were pushing with support. You have a sudden and direct uplift without expansion or undulation with the second pulsation being completely absent. It would be similar to a thrill or vibrating tremor but which in this case would be absent. A solid tumor situated more deeply behind the aorta and pushing this vessel forward may cause a vibrating tremor with a single pulsation. Moreover, there would be a murmur as a result of a membranous cleft caused by the posterior-anterior compression of the artery and the diminution of its caliber. Finally, in either of these varieties because of their anatomical relations there would be signs of compression either on the side of the superior vena cava or right bronchus [38, p. 235].

Thus, Jaccoud sign refers to displacement of a solid tumor by aortic pulsation for tumors located anterior to aorta. For tumor located posterior to the aorta, a vibrating tremor with a single pulsation is present (Table 1.1). Other authors refer to this sign as a prominence of the aortic arch in the suprasternal notch or fullness of the sternal notch in patients with leukemia [39–41]. We were unable to identify the passage where he described such a phenomenon although a chloroma, or a solid mass of leukemic cells within the superior mediastinum, could be displaced by an aneurysm involving the aortic arch in the suprasternal notch.

Cardarelli Sign

Antonio Cardarelli (1831–1927) was born in Civitanova del Sannio, Italy, and completed his medical studies at the Collegio Medico di Sannio Aniello, University of Naples, Italy, in 1853 [42]. After graduation, he served as an assistant, achieving the rank of physician at Ospedale degli Incurabli, Naples. At the University of Naples, he was appointed Professor of Medical Pathology in 1890, and Professor of Clinical Medicine and Director of the First Medical Clinic [42]. He also served as Senator of the Kingdom of Italy. A description of his character:

From the story of his pupils, Cardarelli had to be a man with a strong and decisive character, confident, but not vain, unwilling to rethink and to be contradicted. (…) However, he was much loved by his students because the activity to which he devoted himself with the greatest passion was precisely teaching . In fact, all his experiences that were gradually obtained were transmitted to his students (as opposed to many university students today). His classroom was always packed with a considerable number of students who had chosen him as their teacher… [42].

Cardarelli published in 1879 in Movimento Medico-Chirurgico (Medical-Surgical Movement) his observation and palpatory finding involving the posterior portion of an aortic arch aneurysm (Fig. 1.1):

[I] have above all recognized a throbbing pulse of the trachea which is felt by applying the finger tips to the right side especially if one presses with some force. The pulsation is less obvious when the same observation is made on the left side of the trachea. In this case, it seemed to me that the aneurysm is located far left to the arch, at a point where the aorta crosses the left bronchus. Alteration of the left chest wall is felt due to pressure exerted on the left bronchus and at the same time the impulse emanating from the left side is felt, using the other hand, to the right of trachea as well as observing the neck [43, p. 488].

Fig. 1.1

Cardarelli sign (by Ryan Yale)

He accounted for the pathogenesis of the condition:

When the anatomical relationship is present, in which the trachea is adjacent to the aortic arch, it is easy to understand that an aneurysm particularly in its posterior aspect causes compression against the trachea. It is all the more valid as it is easily seen that the aneurysmal sac contractions are caused by more or less dense adhesions extending to the trachea. In conditions other than stenosis, the tracheal tube can in part undergo a more or less remarkable displacement and receive the aneurysm impulse . This deviation and impulse of the endothoracic portion of the trachea can be observed and therefore serves as an important sign of aortic aneurysm. Since this fact is true, as in our case, even for a very small aneurysmal sac it must have important diagnostic value since no other objective signs are present [43, p. 489].

Thus, Cardarelli sign refers to the palpable pulsation felt to the right of the trachea in patients with aneurysm of the aortic arch (Table 1.1). A variation of this sign was also described by General William Silver Oliver in 1878, Pietro Francesco Castellino in 1896, and William Henry Porter in 1899.

Oliver Sign

General William Silver Oliver (1836–1908) was born in Kilfinane, Ireland, received his medical degree from Halifax, Nova Scotia, and ascended to the ranks from an assistant surgeon in 1857 to Brigade Surgeon in 1882 [44, 45]. On his retirement in 1883, he was named Honorary Deputy Surgeon-General [44]. As Deputy Surgeon in Halifax, he designed and patented the Canadian army accoutrement, designed to redistribute the load weight in order to avoid spinal injuries [46]. Oliver described the diagnostic method for detecting a thoracic aneurysm as follows (Fig. 1.2):

Place the patient in the erect position, and direct him to close his mouth and elevate his chin to the fullest extent, then grasp the cricoid cartilage between the finger and thumb, and use gently upward pressure on it, when, if dilation or aneurism exist, the pulsation of the aorta will be distinctly felt transmitted through the trachea to the hand. The act of examination will increase laryngeal distress should this accompany the disease [47].

Fig. 1.2

Oliver sign (by Ryan Yale)

Howard noted that in addition to aortic aneurysm, the tracheal tug has also be reported to occur in certain cases of indurative mediastinitis where the trachea and aorta are firmly bound together [48, p. 143]. A variation of this sign was described by Antonio Cardarelli in 1878, Pietro Francesco Castellino in 1896, and William Henry Porter in 1899 (Table 1.1). The presence of this sign in other disease states suggests that it lacks sufficient specificity to confirm a diagnosis of aortic aneurysm.

Drummond Sign

Sir David Drummond (1852–1932) was born in Dublin, Ireland, and received his Bachelor of Medicine and Bachelor of Surgery degrees from Trinity College, Dublin. He continued his studies in Prague, Vienna and Strasbourg prior to receiving his medical degree [49]. Drummond was subsequently appointed assistant physician to the Children’s Hospital in Newcastle-on-Tyne and next as pathologists and assistant physician to the Royal Victoria Infirmary from 1878 to 1912 [49]. At the University of Durham College of Medicine Newcastle, he served as a Lecturer in Physiology, Pathology, and Therapeutics, Professor of the Principles and Practice of Medicine (1911–1924), and Vice-Chancellor of the University and President of the College of Medicine [49]. In 1920, he received the title Commander of the Order of the British Empire for his services as a physician at the Northumberland War Hospital and knighted in 1923 [49, 50]. He was the recipient of honorary degrees from the University of Durham College of Medicine (DCL), Ireland and University of Glasgow (LLD), Scotland. He was appointed Fellow of the Royal Academy of Medicine, Ireland. He served as President within the British Medical Association (1921–1922) as well as the Association of Physicians of Great Britain and Ireland [49]. As a pathologist, his name is also recognized in association with the identification of the marginal artery of the colon (artery of Drummond), the anastomotic branch connecting the superior mesenteric with the inferior mesenteric artery [51]. A description of his character:

No appreciation of Physician Drummond, as he was known throughout the North, would be adequate without a reference to his invariable and unstudied courtesy, his consideration for others, his genuine sympathy, and generous help to all in need of it. Apart from the justified confidence in his professional attainments, these qualities won for him the respect and love of many friends. No man consistently held to higher ideals of the duty of a consulting physician in relation to medical ethics none had greater pride in his profession [49, p. 865].

As described by Professor Grey Turner:

Sir David Drummond will always be gratefully remembered by a numerous succession of men, now scattered all over the world, who came under his influence either as students or house-physicians or young practitioners, and each will remember him for his sound teaching, genial personality, and kindly influence and timely help rendered in one way or another. Drummond was a great clinician and clinical teacher, who constantly taught and urged the importance of actual contact with patients. (…) In dealing with patients he was habitually courteous and kindly, but on occasion he could be-to say the least of it unmistakably emphatic, and by observing his methods of handling difficult situations young practitioners gained a great insight into the conduct of their work [49, p. 866].

Drummond in a paper read before the Northumberland and Durham Medical Society in 1880 and British Medical Association in 1882 [52], and published in the British Medical Journal that same year, described a sign found in patients with aortic aneurysm:

Briefly, the oral whiff, which I may call the sign I am now referring to, can be detected in the following manner in cases of aortic aneurysm. The patient is directed, whilst lying on his back, to breathe as quietly as possible through the widely open mouth; the oval piece of the binaural stethoscope is then introduced into the mouth to receive the expired air. Should, then, the sign be present, the expiration will appear to be interrupted at each beat of the heart by a whiff, which, in some cases, is very loud, whilst, in others, it is only detected at the end of expiration, an indication that it is but feebly marked. In certain cases, especially if the aneurysm be large, a diastolic whiff can be heard as well as a systolic. In cases in which the sign is well marked, it can be plainly heard in the trachea during quiet expirations, or when the patient is holding his breath, with the mouth open and the tongue depressed, so as to allow the gaping glottis to communicate freely with the buccal cavity. In very well marked cases, the whiff is audible in the trachea with the mouth closed, but it at once disappears when the nostrils are compressed by the fingers. In seeking for the sign, it is most important to avoid cardiac excitement; hence it should only be sought for after the patient has lain in the recumbent position for a short while, and after the reasons for inserting such a formidable looking instrument as the binaural stethoscope into the mouth have been fully explained. It is well , indeed, to school the patient accurately before commencing the examination, for nervous, interrupted respiration on the one hand, and forcible or nasal breathing on the other, will defeat the object of the examination [53, p. 773].

Drummond in his assessment of 24 patients with thoracic aneurysm (23 involving the aorta and 1 of the innominate artery) found:

Of the 23 aortic aneurysms , the whiff was present in 17; in some of which it was well marked, and in others but feebly so; it was entirely absent in 3; in 1 it was not sought for; and in 2 stridor and ráles were so loud as to interfere with its development. The sign was altogether absent in the case of innominate aneurysm. In 3 cases, the whiff only developed after the patients had been observed in hospital from six to eight weeks [53, p. 773].

Thus, Drummond sign refers to the soft interrupted whiff heard during expiration when the mouth is open in patients with an aortic aneurysm (Table 1.1).

Bozzolo Sign

Camillo Bozzolo (1845–1920) was born in Milan, Italy, and received his medical degree from the University of Pavia in 1868. After graduation in 1871, he furthered his studies in Vienna, Austria under the auspices of Johann Ritter Oppolzer (1808–1871), Salomon Stricker (1834–1898) and Carol von Rokitansky (1804–1878), and in Berlin under Rudolf Virchow (1821–1902) and Ludwig Traube (1818–1876). After returning to Milan in 1871, he was appointed Assistant to the Office of Pathological Anatomy at the Ospedale Maggiore under Achille Visconti (1836–1911) [54]. In 1872, he worked in the branch of Pathological Anatomy with Giulio Bizzozero (1846–1901) in Torino [54, 55]. He returned to Milan and served as an Assistant Physician at Maggiore Hospital and Prosecutor of Anatomy and Pathology from 1873 to 1876 [55]. Bozzolo served as Senator of the Kingdom beginning in 1910 [56]. In 1877, he directed the Medical Clinic at the University of Torino, was chair of the newly formed Propaedeutic Medical Clinic from 1878 to 1883, and appointed ordinary Professor and Chair of the new General Medical Clinic in Torino in 1833, a position which he held for 37 years. His noteworthy honors include Knight, Commander, and Grand Officer of the Order of the Crown of Italy [56]. He was one of the first physicians in Italy to apply radiology as diagnostic and therapeutic tools used as radiotherapy for leukemia [57]. In addition to the sign which bears his name, other notable accomplishments include the discovery that the parasite ancyclostoma duodenale was the cause of anemia in workers at the St. Gothhard railway and recognized thymol as a treatment for this condition [58].

A description of his character as described by Sen Prof. E. Maragliano, Camillo Bozzolo was a character that never broke in the face of difficulties; tenacious in defending his own convictions; inflexible, who never capitulated to everything that did not persuade him: but he was always honest, always correct, always right [1, p. 234]. As described by G. Satta:

Subtlety and sharpness of observation and genius of views were the main qualities of his teachings. His objective and conscientious lessons devoid of any form of courage and any display of eloquence, were not always rightly appreciated by the novices, but for the student and the attentive doctor, it was the sources of precious lessons [54, p. 234].

Bozzolo building on the studies of Giulio Ceradini (1844–1894) and Angelo Mosso (1846–1910), regarding the movements which the column of air in the cavities of the nostrils undergoes in relation to the cardiac moments, applied this phenomenon to the diagnosis of intrathoracic aneurysms:

This is based on the following four facts: 1. The positive pulse of the open glottis nostrils. 2. The nostrils pulse is positive when the glottis is open, but is preceded by a slight negative pulse corresponding to systole. A more or less strong positive nostril pulse follows this towards the end of systole. 3. When the pulse of the heart in the chest is negative, the pulse of the open glottis nostrils is positive. 4. The pulse of the nostrils remains negative during the systole.

Here are the conclusions: 1. The presence of an endothoracic aneurysm can be suspected by changes occurring in the pulse of the nostrils. 2. The pulse of the nostrils can become positive when the glottis is open due to an aneurysm. 3. The negative open glottis pulse in thoracic aortic aneurysms, when not due to an extended elevation of the ribs, may signify filling of the aneurysmal sac with clot and therefore a greater tendency to heal. 4. From the examination of the pulse of the nostrils you can draw important conclusions regarding the pathological mechanisms of the heart [59, p. 962].

Thus, Bozzolo sign refers to the visible pulsation of arteries within the nasal mucosa (Table 1.1).

Delbet Sign

Pierre Louis Ernest Delbet (1861–1925) was born in La Ferté-Gaucher, Seine-et-Marne, France, and received his medical degree from the University of Paris in 1899. He served as agrégé at the University of Paris in 1892, surgeon at des Hôpitaux de Paris in 1893, and Full Professor of the Surgical Clinic at the faculty of Medicine of Paris in 1909 [60, 61]. He was a member of the Academy of Medicine (Operative Medicine Section) from 1921 to 1957 and founding member, along with Dr. Charles Jacques Bouchard (1837–1915) and Henri de Rothschild (1872–1947), of the French Association for the Study of Cancer (currently Société Française du Cancer or French Society of Cancer) [61].

He is perhaps best recognized for his work on the use of magnesium chloride as an antiseptic and for identifying the relationship between low magnesium levels and the development of cancer [62]. He is also credited for establishing that magnesium halide salts enhance phagocytosis of white blood cells and was the first to use rubber as a hip prosthesis in the finger joint and as an abdominal-like mesh [62–64]. Arrou in his description of the management of absent pulsation in a popliteal aneurysm stated:

When the useless malleable piece of the sac is removed, the arterial circulation continues to function as it has been doing so by way of the collaterals. This point is not new and was established exactly twenty years ago by our colleague Delbet. I have been able to appreciate its value in the six observations I have already published and here is a seventh, of recent date, which seems to me rather suggestive. (…) In closing, I will repeat my opening sentence: look for the pulse of the posterior tibial artery, and remain confident as it signifies that the circulation is not affected by the aneurysm . On the contrary, the dilated collateral circulation is providing blood flow to the leg and foot [65, p. 868].

Delbet further discussed the role of mechanical and elastic compression:

Indeed, indirect compression that acts as an incomplete and temporary ligature prepares for the development of the collateral circulation by dilating the vessels which must take part in opening the way beyond the ligature. On the other hand, elastic compression flattens all of the arterioles and thus cannot in any case favor the collateral circulation [66, p. 557–558].

Delbet sign describes the method for determining the integrity of the collateral circulation in patients without pulsation of a popliteal aneurysm (Table 1.1). There is sufficient collateral circulation to the distal lower extremity if the posterior tibial arterial pulse is palpable in patients with absent pulsation of a popliteal artery aneurysm.

Cheesman Sign

Williams Sanderson Cheesman (1853–1912) received his medical degree from the College of Physicians and Surgeons, New York in 1879 [67]. He served at Bellevue Hospital in New York City from 1879 to 1884 and practiced in Auburn New York in 1881 [68]. Cheesman served as President of the Central New York Medical Association, Fellow of the New York Academy of Medicine and Member of the Committee on Experimental Medicine, New York Medical Society [67]. A description of his character:

It may readily be seen, therefore, that Dr. Cheesman’s preparation for the life work he had chosen was thorough and complete. His constitution was not strong, however, while his ambition to work and achieve was almost without limit. Thus he labored against a grievous hindrance, yet, he made notable progress in his profession and gained a reputation that was state wide. (…) As a physician, surgeon and friend, Dr. Cheesman won a place in the community and in the state that will remain on record during the years to come. (…) As a citizen of Auburn, Dr. Cheesman had the confidence and honor of everybody. He was interested in good works and gave time and money to further the causes [68, p. 259–260].

Cheesman reported the auscultatory finding of respiratory puff or whiff in five patients, thoroughly describing the symptoms conveyed by a 33-year-old man who:

[o]bserved that the sound of his breathing, particularly in expiration, was intermittent, giving a puff at each beat of the heart. The expired air, instead of leaving the mouth in an even, prolonged current, came in a series of whiffs which may be represented quite accurately by the sounds huh, huh, huh, huh. These were loudest at the commencement of expiration, and became fainter toward its close. Inspiration was similarly broken, but the interruptions were less marked. As the heart’s action quieted down, this pulsation of the breath became less and less noticeable, till it finally ceased. A second run, however, reproduced it exactly as before [69, p. 235].

When he examined the chest, the puff was absent at rest but when he asked the patient to run up and down the stairs several times:

The sound was then plainly heard by the ear held about a foot distant from the patient’s open mouth. I listened with the stethoscope over the chest, but could not distinguish it there at all. When the instrument was applied along the trachea, however, it came out loudly, and had the characters already described. Drummond’s oral whiff as a sign of thoracic aneurism came to my mind, and therefore, though there were neither symptoms nor physical signs of this disease, I re-examined for it carefully and repeatedly, but with an entirely negative result [69, p. 235].

Based on his observations in these patients, he concluded:

The only account which I can find is in descriptions of Drummond’s oral whiff, where it seems to be looked upon as a familiar fact. But, considering the sort of men who have professed to me their ignorance, it certainly cannot be an every-day matter. To them, as well as to myself, it was a puzzle—which is my reason for describing it here. Why it occurs in so few subjects and not in others I cannot explain . In my small experience it has usually been associated with a distinctly neurotic constitution [69, p. 236].

He proposed two mechanisms for the pathogenesis of this finding:

Two explanations have occurred to me. When one listens to the sound along the trachea, it seems as if it must certainly be due to interruptions of the column of in-going and out-going air by the intermitting pressure of some part of the circulatory apparatus; the entering current being simply retarded at each systole, the emerging current being alternately obstructed, and then liberated under accumulated pressure. This is the explanation sometimes given of the whiff in cases of thoracic aneurism. No such compression of the air-passages could take place, however, without dyspnoea. Both in health and in aneurismal disease it seems more likely that the sign described is due to the fact that each rise of intra-thoracic pressure attending the aortic expansion so increases the expulsive force of expiration that the sound of the air rushing through the narrow rima glottidis is momentarily intensified into a puff [69, p. 236].

Cheesman clarified the significance of the whiff sign in intrathoracic aneurysms:

The value of this whiff as a sign of intrathoracic aneurysms must depend on its association with other physical signs of that disease. It would certainly seem that any physician accepting the usual statement that the oral whiff occurring during physical mental quietude is of itself evidence of aneurism (see Pepper’s System of Medicine, vol. iii, p. 811) would inflict needless alarm his patient [69, p. 236].

Thus, Cheesman sign refers to the presence of an interruption of expiration or whiff sound. He clarified its presence in conditions other than aneurysm such as in otherwise healthy persons or those with neurosis (Table 1.1).

Potain Sign

Pierre Carle Édouard Potain (1825–1901) was born in Paris, France, and received his medical degree from the University of Paris in 1853. Following graduation, he served in the Ivry Insane Asylum until 1856 when was named chef de Clinique under Jean-Baptist Bouillaud (1796–1881) in 1856 [70]. He was appointed Physician to the Bureau Central and staff physician at Hospice des Ménages, Hôpital Saint Antoine , and Hôpital Necker, Paris [70, 71]. In 1861, he qualified with the title Professeur agrégé (adjunct professor) and was appointed Physician to the Hospital of Paris [71]. Potain served briefly as Professor of Medical Pathology followed by an appointment as chair of Clinical Medicine at Necker Hospital in 1887, and from 1886 to 1900 was chief of Bouillad’s clinic at la Charité [70, 72, 73]. He received numerous honors including being elected Member of the National Academy of Medicine in 1883, National Academy of Science in 1893, Member of the Institute of France and Commander of the Légion d'honneur [70, 73, 74].

In addition to the sign which bears his namesake, Potain made a number of important contributions to the field of medicine. These included among others refinements in Marey’s sphygmograph, a device used to measure the pulse, collapsotherapy for the treatment of pulmonary tuberculosis, thoracentesis device for removable of pleural fluid, further description of the gallop rhythm and distinguished a split first heart sound (S1) from a presystolic sound (S4 gallop), and a hemocytometer, a device to count red blood cells [74–76]. A description of his character as described in his obituaries:

In his devotion to his profession, to his pupils, and to those who sought counsel of him, in his scorn of everything savouring of advertisement or self-seeking in his constant effort to relieve suffering and do good. Professor Potain was the model of a true physician. The history of his life may be summed up in the words, Pertransiit benefaciendo [70, p. 121]. (…) His kindness to the pupils, his gentleness to his poor patients, his justice in the examination of students, which was always tempered with kindness, made him one of the most beloved of all the teachers in the faculty of medicine. (…) In the death of Professor Potain France has lost one of her noblest sons, the medical profession one of its most illustrious members, the world a good and noble man [72].

Potain described three patients with severe aortitis and dullness on percussion of the thorax:

[t]here is an increase in the extent of dullness to the right of the sternum. The precise limits of this deep dullness must be carefully traced and great care should be taken to strike the chest wall hard, because if the lung is slightly emphysematous superficial percussion provides no information. To conduct a good examination, it is necessary to strike around the region of proposed dullness starting peripherally and moving in a medial direction. If we suddenly find a low pitch tone, when percussing under the clavicle in person with a normal lung, this signifies the presence of a tumor of the mediastinum whose nature remains to