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7.2.9 Gilbert Sign
7.2.9.1 Augstin Nicolas Gilbert
Augustin Nicolas Gilbert (1858–1927) was born in Buzancy (Ardennes), France,
and was appointed extern in 1878 and intern at Hôtel-Dieu under the tutelage of
Hippolyte Hérard (1819–1913), Victor Charles Hanot (1837–1915), Paul Camille
Hippolyte Brouardel (1837–1906), Jacques-Joseph Grancher (1843–1907), George
Hayem (1841–1933), Jean Alfred Fournier (1832–1914), and Charles-Jacques
(Joseph) Bouchard (1837–1915) [56]. He received his medical degree in 1886 with
a gold medal distinction [56–59].
Gilbert was a physician of the Central Hospital Ofce in 1888 and agrégé of the
Faculty of Medicine, Paris, in 1889 [56]. He was appointed to the Tenon Hospital in
1893 and Broussais Hospital in 1894 and served as head of the laboratories of Georges
Hayem and Louis Théophile Joseph Landouzy (1845–1917) [56]. Gilbert was a pro-
fessor of therapeutics in 1902 and a professor of clinical medicine at the Hôtel-Dieu,
Paris, in 1905. He was chair of the medical clinic of the Hôtel-Dieu in 1910 [56–59].
With Paul Brouardel (1837–1906) and J.Girode, he co-edited Traité de Médecine
et de Thérapeutique (Treatise on Medicine and Therapeutics) in 1895 and 1902
[56]. Among his awards and accolades, Gilbert was elected member of the National
Academy of Medicine, Therapeutic Section in 1905 and recipient of the Commander
of the Legion of Honor in 1913 [56, 58].
7.2.9.2 Pierre Émile Auguste Lereboullet
Pierre Émile Auguste Lereboullet (1874–1944) was born in Paris, France, and was
an intern under the aegis of Paul Jules Tillaux (1834–1904) and Henri Barth
(1853–1945) at Charité, Hôtel-Dieu with Édouard Brissaud (1852–1909), Gilbert at
the Broussais Hospital in 1900, and interim-laureate of Hutinel at Hospice des
enfants assistés (Assisted Children’s Hospice) [59, 60]. He was appointed Doctor of
Hospitals in 1907, associate professor of infant medicine in 1920, and professor of
hygiene and the clinic of early childhood and director of the Childcare Institute,
Paris, in 1928 [59, 60]. Lereboullet returned to Hospice des Enfants-assistés where
he remained through retirement. He was elected president of the Ofce for Maternal
and Infant Protection of the Department of Seine, National Committee for
Childhood, and member of the Academy of Medicine in 1925 [59, 61].
As described by Carnot:
Our notice of the life of Pierre Lereboullet would be incomplete and disloyal if we did not
state here the great discreet, active, benevolent, and charitable piety that guided him all his
life. He was largely open-minded, and one could easily remain his friend provided one
strives to be like him, a “good man” [60, p.32].
As to his character as described by Girons:
We would omit an essential part of the pediatric work of M.Lereboullet if we did not recall,
if only in a few words, what he was for his patients and pupils. He welcomed the former,
7 Liver andBiliary Signs
249
whether at his hospital or family consultations, with an affectionate gentleness that doubled
the value of his advice. He knew how, even to the parents of the incurable, to lavish the
encouragement which allows hope, even if the improvement is slow or nonexistent. All
those he healed now realize what they have lost through his death. His pupils, students,
doctors, and nurses maintain a profound recognition of his teaching. He opened up to them
the various elds of pediatrics and frequently inspired their vocation. They will piously
keep his memory by seeking inspiration from his example [61, p.166].
Gilbert and Lereboullet described a phenomenon at the Biological Society in 1901,
occurring in patients with cirrhosis (Table7.1):
Examining the urine in the morning on an empty stomach or during the day after meals
shows that in the physiological state, the urine is much more abundant after the meal. In
cirrhosis, we observe an opposite phenomenon. The urine becomes scarce after a meal and
is more abundant after fasting. This phenomenon is what M.Gilbert and Lereboullet refer
to it as the inversion of the normal rhythm of aqueous elimination. This disorder in urinary
secretion is an early sign of portal hypertension as it may precede ascites and is an extremely
important prognostic sign. This sign is found not only in cirrhosis but also in congestions of
the liver of cardiac origin and even in jaundice. Gilbert and Lereboullet explain that this
symptom is caused by obstruction of the portal circulation, leading to a delay in aqueous
absorption in the intestine [62, p.400–401].
Thus, Gilbert (and Lereboullet) sign refers to the nding in hepatic cirrhosis of
increased excretion of urine occurringduring fasting than after a full meal (opisura).
7.2.10 Kayser–Fleischer Sign (Ring)
7.2.10.1 Bernhard Kayser
Bernhard Kayser (1869–1954) was born in Bremen, Germany, and received his
medical degree from the University of Berlin in 1893 [63]. He was an intern in
Tübingen and an assistant at the University Eye Clinic in Freiburg. Kayser traveled
overseas and worked as a physician at the North German Lloyd Shipping Company
and general practitioner in Brazil [63]. On his return to Germany, he was a general
practitioner in Brandenburg and Bremen, followed by a specialty in ophthalmology
in Stuttgart [63].
Kayser at the University Eye Clinic in Tübingen in 1902 described the case of a
23-year-old male with multiple sclerosis and congenital greenish discoloration of
the cornea:
Even on external inspection in ordinary daylight, it is immediately noticeable in both com-
pletely non-irritated eyes that the cornea, which is clear and transparent in its central parts,
shows a ring-shaped opacity in the periphery, resembling gerontoxon in form and extent.
The cornea appears opaque here and has a dark green-brown color. This ring of opacity is
widest above, less wide below, and very narrow outside and inside so that the area of the
clear cornea is lying oval. The opacity begins immediately at the limbus and has no sharp
border extending to the clear center of the cornea [64, p.22–23].
On binocular microscopic examination:
[i]n the peripheral ring zone described above, there is a signicant accumulation of ne yel-
low spots in the deeper layer close to the posterior wall so that the underlying iris and chamber
7.2 Liver andBiliary Eponymous Signs
250
angle cannot be seen. The yellow spots are apparently in an area parallel to the corneal sur-
face. (…) This accumulation of yellow spots begins in the periphery, where their arrangement
is densest, and the individual spots are the largest. In general, they are smaller and less dense
in the middle portion of the ring and ne in the portion nearer the corneal center so that their
turbidity no longer appears patchy but diffuse, allowing more light to reach the underlying
surface of the iris. While the above dense patches of turbidity give a yellow appearance at the
center of the cornea, the color is different: the yellow hue gradually changes into a yellowish-
green, proceeding gradually into the black of the pupil. The arrangement of the spots is
entirely random. The individual spots appear under the binocular microscope as at bodies,
without sharp boundaries, that are quite irregular shaped, at least the coarser ones in the
periphery. The corneal tissue does not reveal any abnormal abnormalities. There is no sign of
vascular formation. The central parts of the cornea are completely normal [64, p.23].
7.2.10.2 Bruno Fleischer
Bruno Otto Fleischer (1874–1965) was born in Stuttgart, Germany, received his
medical training at the Universities of Tübingen, Geneva, and Berlin, and earned a
medical degree from the University of Tübingen in 1898 [65]. He was an assistant
at the University of Tübingen Eye Clinic, habilitating in ophthalmology in 1904. He
was appointed chair of ophthalmology at the University of Erlangen, Germany,
from 1920 to 1951 [65].
Fleischer identied, in two cases, ocular ndings similar to that reported by
Kayser. His rst case involved a 29-year-old photographer with tremors and on
ocular examination:
The greenish discoloration of the cornea is ring-shaped in the periphery, approx. 1mm wide
and consists of small brownish-greenish dots and spots merging into one another, becoming
ner towards the center of the cornea and gradually merging into the clear cornea. Fine,
lighter stripes run through the discolored area irregularly. The supercial layers of the cor-
nea are clear. The discoloration resides in the deepest layers, in an area concentric to the
surface, and is quite similar in both eyes [66, p.490].
Thus, Kayser-Fleischer sign refers to the greenish-yellow ring surrounding the cor-
nea at the lumbus, which was later found to be caused by excessive copper deposi-
tion (Table7.1).
7.2.11 Murphy Sign
John Benjamin Murphy (1857–1916) was born in Appleton, Wisconsin, USA, and
received his medical degree from Rush Medical College in 1879. He completed an
internship at Cook County Hospital, Chicago, in 1881. Murphy then traveled abroad
to the Wiener Allgemeine Krankenhaus (Vienna General Hospital), continuing his
medical studies under Theodor Billroth (1829–1894) in 1882 and at the University
of Berlin and Heidelberg, Germany [67, 68]. Upon his return to Chicago in 1884, he
served as a lecturer in surgery at Rush Medical College and an attending surgeon at
Cook County Hospital and Alexian Brothers Hospital [67–70]. He was appointed
professor of clinical surgery at Chicago Post-Graduate Medical School, College of
7 Liver andBiliary Signs
251
Physicians and Surgeons (later renamed the University of Illinois College of
Medicine) in 1892 [70]. He was a chief surgeon and chief of staff at Mercy Hospital,
Northwestern’s rst teaching hospital in Chicago, from 1895 to 1916 [69, 70].
Murphy later accepted a position as professor of surgery at Northwestern University
Medical School from 1901 to 1905 [67, 69], returned to Rush Medical College, and
was appointed co-chairman of surgery department from 1905 to 1907, and later
again at Northwestern where he accepted an appointment as chairman of surgery
department from 1908 to 1916 [71].
Murphy was the founder and editor of The Clinics of John B.Murphy at Mercy
Hospital, Surgical Clinics of John B.Murphy at Mercy Hospital (later renamed
Surgical Clinics of Chicago, Surgical Clinics of North America) and “Volume of
Surgery” in the American Year-book [67, 68]. He also served as president of the
Chicago Surgical Society in 1904, the Chicago Medical Society from 1904 to 1905,
the American Medical Association from 1911 to 1912, and the Clinical Congress of
Surgeons from 1914 to 1915 [67, 69]. He was the founder of the American College
of Surgeons. Murphy received an honorary degree of DSc from the University of
Shefeld, an LLD from the University of Illinois and Catholic University, and the
Laetare Medal from the University of Notre Dame for his service to humanity and
science [67, 68]. He also received the Collar and Cross of Saint Gregory the Great
from the Pope in 1916 [68].
His work spanned multiple therapeutic areas, including abdominal surgery, neu-
rology, and orthopedics. His many discoveries and contributions included end-to-
end arterial anastomoses, grafting cartilage and bone, restoration of ankylosed
joints, and rectal saline infusion in the treatment of peritonitis. His name is epony-
mously associated with the Murphy button, Murphy punch, Murphy–Lane bone
skid, and Murphy drip [67–69].
As to his character as described in a memoriam by Dr. John B.Deaver:
He was a man of unusual personal charm, striking originality, and exceptional skill [68,
p.994]. (…) [h]e was sure of himself and unafraid; abiding by his statements, radical and
unusual though they may have appeared, because they were based on accurate, painstaking
research, experimentation and observation [68, p.995]. (…) He was a powerful, vigorous
public speaker, full of enthusiasm and earnestness, which, coupled with an attractive per-
sonality and delightful humor, at once gained for him the attention of his hearers, young and
old alike [68, p.996].
Murphy described a maneuver for identifying patients with acute cholecystitis sec-
ondary to gallstone and infection of the gallbladder (Fig.7.2):
Hypersensitiveness of the gall-bladder is present in all varieties of infection and calculous
obstruction, but not in the neoplastic, torsion, exion, cicatricial or valvular obstructions.
The hypersensitiveness is elicited by deep palpation just below the right ninth costal carti-
lage, or in a line from that point to the middle of Poupart’s ligament, as this is the common
track of gallbladder enlargement. Deep percussion along the same line, with patient in
forced inspiration gives pronounced pain. The most characteristic and constant sign of gall-
bladder hypersensitiveness is the inability of the patient to take a full, deep inspiration,
when the physician’s ngers are hooked up deep beneath the right costal arch below the
hepatic margin. The diaphragm forces the liver down until the sensitive gall-bladder reaches
the examining ngers, when the inspiration suddenly ceases as though it had been shut off.
I have never found, this sign absent in a calculous or infectious case of gall-bladder, or duct
disease [72, p.827–828].
7.2 Liver andBiliary Eponymous Signs
252
Fig. 7.2 Murphy sign I (by Ryan Yale)
Murphy discussed another technique for examining the gallbladder during a sympo-
sium on the gallbladder, gall ducts, and liver at the Chicago Medical Society on
April 20, 1910. During this maneuver, the middle nger of the left hand is exed
perpendicularly at the tip of the ninth costal cartilage, and “[t]he nger struck with
the right hand when the patient is in deep inspiration. This causes great pain if the
gallbladder is distended or inamed” [73, p.278] (Fig. 7.3). Thus, Murphy sign
refers to the palpable technique in which the patient is unable to take a deep inspira-
tory breath secondary to pain when the examiner hooks their ngers below the right
costal margin and deeply beneath the hepatic margin in patients with acute chole-
cystitis (Tab le7.1).
7 Liver andBiliary Signs
253
Fig. 7.3 Murphy sign II (by Ryan Yale)
7.2 Liver andBiliary Eponymous Signs
254
7.2.12 Abrahams Sign
Robert Abrahams (1861–1935) was born in Russia and immigrated to the USA in
1880. He received his medical degree from the College of Physicians and Surgeons,
Columbia University (currently Columbia University Vagelos College of Physicians
and Surgeons), and after graduation, was a private practitioner [74]. He was a mem-
ber of the Board of the NewYork Manhattan State Hospital, Ward’s Island, begin-
ning in 1913, and served as president of the Board of Managers [75]. He was also
an adjunct professor of medicine at Postgraduate School and Hospital and attending
physician at the Home of the Daughters of Jacob, NewYork [74].
Abrahams described a pathognomonic sign to assist in the bedside diagnosis of
cholelithiasis (Table7.1) (Fig.7.4):
The sign consists in a painful point midway between the umbilicus and the costal cartilage
of the ninth rib in the right hypochondriac. The method of eliciting it is as follows: Place the
patient in the recumbent position with the arms and legs extended. Ascertain a point mid-
way between the umbilicus and ninth costal cartilage, then with a sudden thrust press the
index and middle ngers of the right hand into that point. The effect on the patient is like an
electric shock, there is either a grimace on the face denoting suffering or a quick involuntary
jump of the abdomen as if it were struck with a pointed instrument. (…) In an acute attack
with a diffuse area of hyper asthenia, the midway point mentioned is the point of maximum
pain. In chronic cases the painful point is present at all times while the whole area around
it may enjoy freedom from sensitiveness [76, p.74].
Abrahams believed this painful point corresponds to the location on the fundus of
the inamed gallbladder. Although he did not expressly state, this location corre-
sponds to the region where the inamed distended fundus of the gallbladder con-
tacts the parietal peritoneum causing a somatosensory reex. Thus, Abraham sign
refers to pain occurring when palpable pressure is applied midway between the
ninth right costal cartilage and the umbilicus.
Fig. 7.4 Abraham sign (by Ryan Yale)
7 Liver andBiliary Signs
255
7.2.13 Finsterer Sign
Hans Finsterer (1877–1955) was born in Weng, Austria, and received his medical
degree from the University of Vienna in 1902 [77–79]. He was a surgeon at the
University of Vienna Surgical Clinic under the aegis of Julius von Hochenegg
(1859–1940) in 1906 and assistant to Viktor Ritter von Hacker (1852–1933) from
1907 to 1909in Graz, Austria [78, 79].
He returned to the University of Vienna Hochenegg Surgical Clinic, where he
was appointed assistant in 1910 and received venia legendi (authorization to teach)
in 1913. During World War I, he was a surgeon in the Russian Front’s Deutsch-
Ordensspital (German Order Hospital) and served in the Garrison Hospital from
1915 to 1918 [77, 79]. He was appointed associate professor in 1919 and headed the
Kaiser-Franz-Joseph-Ambulatorium Outpatient Clinic, followed by Krankenhaus
der Barmherzigen Brüder (Brothers of Charity Hospital) Surgical Department,
returning to the Kaiser-Franz-Joseph-Ambulatorium Outpatient Clinic from 1924 to
1935 [77, 79].
Finsterer was awarded the titles of extraordinary professor in 1919, ordinary
professor in 1940, and full professor of surgery in 1948 at the University of Vienna
[79]. He was chief physician in the surgical department of the Vienna General
Hospital in 1935 and head of the surgical department at the University of Vienna
from 1935 until 1951. His name is eponymously associated with a sign and two
surgical procedures: Finsterer–Drüner operation and Hoffmeister–Finsterer opera-
tion [77, 79].
Finsterer described the case of a 27-year-old man who sustained a self-inicted
gunshot wound and tissue injury involving the left lobe of the liver. He found that:
[t]he patient presents with a symptom that I believed had never previously been mentioned
or appreciated in abdominal injuries-bradycardia in acute anemia. I observed that the pulse
in our patient had dropped to 52, and signicant bleeding was found at laparotomy. (…)
Review of the literature shows that my observation is not unique in that a striking slowing
of the pulse has been found in twelve other cases [80, p.1751].
Finsterer believed that bradycardia in patients with injury to the liver has prognostic
importance in that a high pulse rate and pallor are more likely to be found in cases
of severe hemorrhage compared to patients with a lower pulse (Table7.1).
7.2.14 Milkó Sign
Vilmos Milkó (1878–1956) was born in Óbecse, Serbia, and received his medical
degree from the University of Budapest in 1900 [81]. He was a physician in the
Pathology Institute and Surgical Clinic in 1901 and surgery department at Szent
Rókus Hospital in Budapest in 1903 [81].
He was appointed chief surgeon at the Park Sanatorium, Orsz, Budapest, in 1908,
Németvölgy út State Pulmonary Hospital and Hospital for Disabled People from
7.2 Liver andBiliary Eponymous Signs
256
1920 to 1928, Madarász út Children’s Hospital in 1929, and Maglódi út Hospital
from 1933 to 1943 [81]. He maintained an appointment since 1928 as a surgical
expert for the Social Insurance Institute and Social Insurance Center of the Trade
Unions. His last appointment was as a Capital City Council’s Disability Assessment
Committee member [81].
Milkó was co-editor of Orvosi Hetilap (Medical Weekly) and editor-in-chief of
Magyar Sebészet (Hungarian Surgery). Among his appointments, he was president
of the Surgical Group of the Medical Trade Union. The focus of his research was on
general, military, and pediatric surgery [81].
Finsterer, in his paper “Zur Diagnose der Leberverletzungen,” spoke of a com-
munication by Milkó that he could only access in a report. Milkó found that:
In the early diagnosis of abdominal injuries, reex tension in the abdominal wall is the most
important symptom. The behavior of the pulse, even in the most severe abdominal injuries
and in general peritonitis, may remain normal longer than expected. In several cases of
severe intestinal injury, Milkó found marked bradycardia lasting 8 to 10hours [82, p.378].
Thus, Milkó sign refers to bradycardia occurring in abdominal injuries (Table7.1).
7.2.15 Grocco Sign
Pietro Grocco (1856–1916) was born in Albanese, Piemonte, Province of Pavia,
Italy. He studied medicine at the Faculty of Medicine and Surgery at the University
of Pavia, receiving his medical degree in 1879 [83]. He was assistant to Francesco
Orsi (1828–1899), followed by a teaching appointment in clinical propedeutics at
the Faculty of Medicine in Pavia [83]. He continued his training with Jean-Martin
Charcot (1825–1893) at the Salpêtrière, Paris, and with Hermann Nothnagel
(1841–1905) and Moritz Rosenthal (1833–1889), Vienna, in 1882 [83–86].
Grocco was appointed chair of special medical pathology at the University of
Perugia in 1884, chair of the medical clinic at the University of Pisa from 1887 to
1889, and nally director of clinical medicine at the Istituto di Studi Superiori
(Institute of Higher Studies), Florence, Italy, in 1892 [83, 85, 86]. He founded the
Instituto Antirrabico and Montecatini thermal baths used to treat rheumatism [83,
84, 86]. He was appointed Senator of the Kingdom in 1905. Among his many acco-
lades, he was Knight of the Order of the Crown of Italy [84]. He also described
another sign that eponymously bears his name, the paravertebral or “Grocco trian-
gle,” a triangular-shaped area of dullness occurring in patients with pleural effusion.
As to his character and teacher:
Anyone fortunate to know Grocco as a clinical teacher could learn a good amount about
him by scrolling through his book of clinical lessons. A book without vain documentation
or useless information that contained historical comparisons and elegance of style, and not
philosophical digressions. A simple, practical, honest book written by a great doctor for his
students to make them physicians in his form based on comparable experience. The style of
this book is the mirror of his spirit: in those pages, you see him, you hear him speak; short,
7 Liver andBiliary Signs
257
jerky, nervous, clear, intelligent, very eloquent, all the more so as stripped of any artice
[83, p.11]. (…) The best reward for his long labor as Master was his gift to Tuscany and
Italy, educating a whole generation of physicians who were aware of their duties and rigidly
trained based on his honest, objective, simple and practical method [83, p.13].
Grocco emphasized that percussion should extend from the last dorsal vertebral and
left paravertebral zone to determine whether there is an enlargement of the left lobe
of the liver. He reported a systematic method of percussion of the liver (Table7.1):
In order to detect this nding, percussion must be applied with sufcient force. Practice is
required before it can be easily and condently detected. Percussion is performed in a
methodical manner moving from the top to bottom, rst along the right paravertebral line a,
then along the spine b and to the left of it, corresponding to lines c, d, e, etc., so that each
time where the thoracic sound ends and liver dullness begins is marked. In this way, one
nally arrives at line f, which delimits the almost horizontal section of liver dullness to the
left of the spinal column. Once line f is reached, it is advisable to percuss from left to right,
along the horizontal line i-g, in the direction of arrow 1, in order to pinpoint point g, the
outer limit of the left portion of the hepatic dullness [87, p.668].
Thus, Grocco sign refers to a percussion dullness technique to detect enlargement
of the left lobe of the liver. Percussion begins to the right of the last dorsal vertebral
and right paravertebral zones, extends from the top to bottom, moves from right to
left and nally left to right.
7.2.16 Lesieur Sign
Charles Lesieur (1876–1919) was born in Cousance, Jura, France, in 1876, received
his medical training in Lyon, and served as an extern in 1894, intern in 1897, and in
the Laboratory of Experimental and Comparative Medicine of Saturnin Arloing
(1846–1911) in 1897 [88]. He served in the Hygiene Laboratory of Jules Courmont
(1865–1917) from 1900 to 1909. During this period, he was chief of the anti-rabies
services at the Bacteriological Institute of Lyons and a physician at the anti-
tuberculosis dispensaries [88].
Lesieur was agrégé beginning in 1907 and was chair of the medical clinic from
1908 to 1910, the position previously held by Raphaël Lépine (1840–1919) [88]. He
was director of the ofce of hygiene in Lyon in 1909 and succeeded Gabriel Roux
as chair of pathology and general therapeutics in 1912 [88]. During World War I, he
organized the Municipal Hospital and Joffe School for the Disabled in Lyon [88].
He was also stationed in Verda, Bar-le-Duc, and Bouges, France, the latter where he
was director of the health service of the eighth region [88]. Lesieur was awarded the
Vernois Prize from the Academy of Medicine in 1904, was the recipient of the cross
of the Legion of Honor, and was appointed chair of hygiene, the position occupied
by his former mentor Jules Courmont in 1918 [88].
Lesieur’s work involved multiple therapeutic areas, including infectious dis-
eases. (e.g., diphtheria, typhoid fever, tuberculosis, pneumococcus, rabies), poison-
ings (e.g., alcoholism), neurology, and gastrointestinal [88]. At the time of the
7.2 Liver andBiliary Eponymous Signs