Dear Friends,

It saddens me to present the last full edition of the Historical Grand Rounds. We've had a good run, but thankfully the labors of coursework are behind us and there is less of a need for distraction. However, to keep myself occupied I will still post a case now and then during third year, perhaps one per month, so I encourage you to check the website once in a while. As those around us embrace the doldrums and despondency of board examinations, I hope you friends of mine maintain the spirit for learning that sets you apart.

-Michael


Pulmonology

 

1. Named after the Greek word meaning "unextinguishable," this material has been wreaking havoc on the lungs of mediterranean people for over 4000 years. Its first documented use was making fire-proof tablecloths (The Emperor Charlemagne used his to amaze party guests), and in the mid 1800s it was incorporated into a whole host of other industrial products. One notable epidemic was that of Greek women who would mix the material with white paint for their houses, making them resistant to fire and giving them a nice clean look. Unfortunately, many of these women started getting specific types of pulmonary malignancies in the 1960s and 70s. What histological finding would you expect to see in the most common tumor-type associated with this material?

a. psammoma bodies wrong, mesothelioma less common
b. atypical epithelial cells within the bronchial mucosa correct, bronchogenic carcinoma
c. keratin pearls and intracellular bridges
d. pleomorphic giant cells
e. nests of neuroendocrine cells

(The correct answer will have "correct" written in white font next to it. Highlight to see.)

2. George Orwell's life was a chronicle of pulmonic misfortunes. Born in India in 1903, he spent his early years suffering from numerous bouts of bronchitis and non-descript lung infections. After later episodes of dengue fever, tuberculosis, and years of heavy smoking, he finally retired to Northern Scotland where he would write his greatest work. Some say the torture scenes in 1984 were even inspired by a procedure he went through to collapse the cavitary lesions from his TB. Soon after completing the book, he died of a  condition characterized by copious amounts of purulent sputum, hemoptysis, dilated airways, and recurrent infections. What was the most likely causative factor in his final illness?

a. chronic allergies
b. defective ion transport wrong, no GI symptoms
c. lung scarring and fibrosis
d. poor ciliary motility correct, bronchiectasis as a consequence of smoking
e. viral URI


Eric Arthur Blair (aka George Orwell), 1903-1950


3. Baruch Spinoza was a Portuguese Jew who became one of the greatest philosophical minds of the 17th century. After being excommunicated from the Jewish community for his rationalist thinking, he lived a simple life as a lens grinder, spending hours each day inhaling fine glass dust. He died at the age of 44, allegedly of a serious lung illness purported to be tuberculosis. Which of the following describes the condition that made him more susceptible to this infection?

a. calcification of the hilar lymph nodes correct, silicosis
b. macrophages laden with carbon
c. calcified pleural plaques
d. pneumoconiosis affecting primarily the lower lobes
e. noncaseating granulomas


4. The now famous King George VI, father to Queen Elizabeth II, had a lifelong stammer that he dealt with by smoking (with some additional help from his Australian speech therapist). Somewhat ironically, he later developed lung cancer and was forced to undergo a pneumonectomy of his left lung, leaving him unable to speak more than a couple sentences at a time. His last few broadcast speeches had to be recorded in sections and edited together. What is the best physiological description of his lung function after the surgery?

a. increase V/Q ratio
b. decreased FEV1/FVC ratio   
c. decreased FiO2
d. increased FEV1/FCV ratio
e. decreased V/Q ratio correct, same air volume, twice the blood flow




Albert Windsor (George VI), 1895-1952


5. The story of Patrick Bouvier Kennedy is not well known, since his death was overshadowed a few months later by his father's assassination. Born at 29 weeks gestation to First Lady Jacqueline Kennedy in 1963, he developed infant respiratory distress syndrome soon after birth, and died two days later following treatment in a hyperbaric chamber. At that time no other treatments were in place, but his death sparked a push in research on prematurity that lead to several important innovations. What modern day treatment would have been most likely to help Patrick?

a. inhaled glucocorticoids
b. i.v. glucocorticoids
c. maternal steroids before birth correct
d. albuterol
e. bosentan




Nephrology

Not the most fruitful topic when it comes to Historical cases... However, one clever case appears in the work of Charles Dickens. Tiny Tim, the son of Ebenezer Scrooge's clerk Mr. Cratchit, suffered from a short stature, asymmetric crippling, and episodes of weakness that would have lead to his death had Scrooge not dreamt of his tombstone and decided to pay for his medical treatment. The most plausible explanation for his symptoms is renal tubular acidosis type I, which, left untreated, leads to osteomalacia, paralysis, and death by renal failure. What treatment would have been most effective for Tiny Tim?

a. spironolactone
b. acetazolamide
c. ammonium nitrate plus calcium
d. vitamin supplements
e. sodium bicarbonate plus calcitriol correct, to neutralize the acid in his blood

Board Review Edition

Here is the first ever Board Review Edition of the historical grand rounds. I took a fair bit of poetic license (most of the details are made-up), but everyone featured really had the disease in question. The correct answer will have "correct" written in white font next to it. Highlight to see.

1. One of the world's greatest ever Opera divas spent her last months locked in her Parisian apartment. On a home visit her doctor notice that she had an erythematous periorbital rash, red patches overlying her knuckles, and diffuse muscle pain. He warned her that this condition carries an increased risk of occult malignancy. Which antibody is her condition associated with?

a. anti-dsDNA
b. anti-microsomal
c. anti-Ro/SSA
d. anti-Jo correct, dermatomyositis
e. anti-Smith
f. anti-scl-70
g. pANCA

a. Leontyne Price
b. Renee Fleming
c. Birgit Nilsson
d. Maria Callas  correct

2. In 1911, an Austrian composer presented to Mt. Sinai Hospital complaining of a fever that he had for 2 weeks. He reported no other symptoms but on physical exam they noticed tender raised lesions on his palms, pale mucus membranes, splinter hemorrhages on his nails, and a low frequency murmur heard best at the lower left sternal border. How is the most likely pathogen identified when it's cultured?

a. Gram positive, catalase positive, coagulase positive cocci correct, staph aureus 
b. Gram positive, catalase positive, novobiocin resistant cocci
c. Gram positive, catalase negative, optochin resistant cocci
d. Gram positive, catalase negative, optochin sensitive cocci
e. Gram positive, catalase positive, novobiocin sensitive cocci

a. Franz Liszt
b. Gustav Mahler correct
c. Johannes Brahms
d.  Franz Schubert

3. This preeminent physicist, who became famous for his 1905 paper "On the Electrodynamics of Moving Bodies", died suddenly after an episode of intense chest pain. He had multiple cardiac risk factors included hyperlipidemia, hypertension, and smoking. An autopsy was not performed, but months prior his physician noted a large pulsating mass in his abdomen. Which of the following is not a possible cause of this event?

a. medial calcific sclerosis correct
b. Treponema Pallidum infection
c. mutation in the gene coding for collagen type III
d. defect in the fibrillin 1 gene
e. Takayasu's arteritis

a. Robert Oppenheimer
b. Richard Feynman
c. Paul Dirac
d. Albert Einstein correct

4.  The founder of the New York City Ballet and one of the greatest choreographers of the 20th century presented to NYU hospital with ataxia and new-onset dementia. Soon after he was admitted his attending physician performed a physical exam and found the patient delirious with hyperreflexia and startle myoclonus. He died four weeks later and a tissue biopsy was performed, which to the pathologist's surprise, was negative for alpha synuclein. What is the most likely cause/etiology of his disease?

a. tau protein aggregates
b. amyloid precursor protein
c. Infectious cause correct, creutzfeldt-jacob disease
d. Vitamin deficiency
e. Copper accumulation

a. Mikhail Baryshnikov
b. Rudolf Nureyev
c. George Balanchine correct
d. Vaslav Nijinski

5. This monarch of the British Empire underwent an infamous mental decline in their final years due to a series of severe psychological disturbances. However, their personal physicians noticed a constellation of other symptoms including episodes of abdominal pain, polyneuropathy, and dark red urine. There was never any documented photosensitivity or exposure to environmental toxins. This disease is characterized by an accumulation of which of the following subsrates:

a. porphobilinogen correct, acute intermittent porphyria
b. uroporphyrin
c. vWF multimers
d. protoporphyrin
e. glycine

a. King George III correct
b. King Edward VIII
c. Queen Elizabeth II
d. Diana, Princess of Wales

6. This composer, Michael's personal favorite, had a unique talent for presenting intense romanticism through a veil of elaborate civility. He suffered from chronic bronchitis and steatorrhea, and was always a very frail, delicate man. When he died at the age of 39, his autopsy report said he had TB, but the doctor admitted that the enlarged heart and abnormal lung findings pointed to a different pathology that was "unknown to medicine" at the time. He also had a sister who died of unknown causes at a young age, and he never had children despite having a female partner for over 10 years. What is the mechanism of the exotoxin produced by the most likely cause of his recurrent pulmonary infections?

a. protease that cleaves SNARE
b. activates T cells
c. over activates adenylate cyclase
d. Inactivation of 60S ribosome
e. inactivation of elongation factor EF-2 correct, pseudomonas in cystic fibrosis

a. Mozart
b. Bach
c. Chopin correct
d. Schubert 

Endocrinology and Reproductive Medicine
(Ancient Rome Edition)



Roman Mosaic from Centocelle

1. Since the beginning of civilization couples have searched for ways to prevent conception while still being able to enjoy the pleasure of each other's company. One ancient method involved a certain species of plant that grew on the shores of North Africa called silphium. It was first noted by the Egyptians and Phoenicians, who discovered that a small dose of the resin that came from its roots had the power to both prevent and terminate pregnancy. Unfortunately the plant could not be cultivated, so there were only small amounts available to those wealthy enough to obtain it. Roman aristocrats, who were renowned for their debauchery and numerous mistresses, became enamored with the power of this plant, and its value became such that they started minting coins depicting its seeds. It is even mentioned by Pliny the Elder, who attested to its ability to "promote the menstrual discharge". Silphium went extinct sometime around 100AD due to over-harvesting, and the last specimen on record was presented to Emperor Nero "as a curiosity". Based on modern day contraceptives, how do you think the medicine worked?


A coin depicting the silphium seed. Many scholars cite this plant as a possible origin of the heart symbol.
 
More coins, uncovered at Cyrene, 6-5th century BC. Several ancient sources make the connection between silphium, sexuality, and love.


2. By the time Emperor Maximinus I came to power in 235AD, Rome was already crumbling under the pressure of invasions, civil war, plague, economic depression, military revolts, and religious upheaval. It was termed The Crisis of the Third Age, and sowed the seeds for what would inevitably become medieval Europe. However, Emperor Maximinus had his own problems to worry about. Roman historians write about his "colossal" size and "frightening appearance", and it is clear from the statue of him below that he had some abnormal facial features. His hands were said to be so large that he was able to wear his wife's bracelet as a thumb ring. He also suffered from severe bouts of sweating and headaches, as well as a specific type of congestive heart failure. He was assassinated by his own soldiers in 238AD. What disease did he likely have?


Maximinus I, 173-238AD


3. Some of our greatest insight into the Roman world come from polymath-type writers such as Strabo and Pliny the Elder, who sought knowledge from across the empire and compiled it into enormous volumes containing history, geography, philosophy, medicine, botany, etc. One interesting anecdote found in both their writings is an account of several small villages hidden away in the Alps whose inhabitants all suffered from a strange series of physical misfortunes. They were all "short, strangely behaved creatures" who had what they called a "bronchocele" tumor. These towns lasted up until the 1700s, when mountain travelers would still encounter them and sometimes draw their findings (see below). Roman writers had a theory that drinking snow-water was responsible, and they came up with the rather clever treatment of eating burnt seaweed (Galen suggested burnt sponge). What did these villagers have and what was the treatment?

 
A French print depicting villagers in the Swiss Alps.


4. Julia Domna was the daughter of a Syrian high-priest who rose up to become one the most powerful women in history. As the wife of Emperor Severus, she became the de facto ruler of the Roman empire through her intelligence and shrewd political scheming, and her husband was so reliant on her wisdom that she was frequently brought along on military campaigns and political dealings. She also gave birth to and influenced future emperor Caracalla, famous for building one hell of a bath house (See Baths of Caracalla). When her son was assassinated by a rival in 217AD, she reportedly struck herself on the breast hard enough to inflame a "dormant cancer", which from that point on remained as an irregular mass until her death soon after. Historians are uncertain whether she died of breast cancer or self-inflicted starvation because of the loss of her son, but luckily we may be able to settle this debate. What is one likely breast pathology that Roman doctors may have mistaken for cancer?

 
Julia Domna, 170-217AD


5. A celebration of the classics would not be complete without a little archaeology. In 2010, the skeletal remains of a 30-40 year old woman were uncovered in the ruins of a Roman town in Catalonia. Overall she seemed pretty healthy, apart from a few ordinary bone spurs in her spine and arthritic lesions in her joints. However, there was a peculiar large calcified mass found in her pelvis. Researchers weren't able to identify it so they sent it off for some fancy scans and chemical analysis. All this was quite unnecessary because once they broke open the mass it became clear what it was. From the picture below can you identify it? This is the only example of this pathology ever found among ancient remains.

 
Contents of the archaeological specimen


6. CHALLENGE CASE!

While not himself a Roman, the British historian and member of parliament Edward Gibbon is perhaps the man most responsible for our current understanding of Ancient Rome. Born in 1737 in a small town in Surrey, Gibbon was "a puny child, neglected by his Mother, starved by his nurse". As was customary he was sent away to boarding school at the age of 9, and underwent a semi-religious education that was interrupted by his poor health, which included episodes of severe muscle and joint pain, fever, and flailing arm movements all consistent with Rheumatic fever. Further, at the age of 24 he began noticing some scrotal swelling that would one day lead to his death, and unfortunately prevent any exploits with the opposite sex.

Though perhaps Gibbon's amorous misfortunes were necessary for his success, for no man caught up in petty romantic pursuits could ever find the time to produce such a work as The History of the Decline and Fall of the Roman Empire. This six-volume series is among the best and most stylistically inspiring works of history ever written, and it gives a complete account of the years between the rule of the Caesars and the middle-ages. However, soon after its completion Gibbon's bothersome scrotal mass suddenly swelled to "the size of a small child", and in 1793 his physicians began tapping the fluid, collected upwards of 6 quarts of clear liquid each time. His death soon followed, likely from peritonitis, and on his autopsy doctors found his scrotum hanging below his knees and filled with fluid as well as large portions of his large and small bowel, to the point that it was dragging his stomach down to the pubic bone. Apart from his childhood maladies his past medical history also included lifelong obesity, gout, and frequent alcohol consumption (he'd have several glasses of madeira every night after writing), as well as increasingly severe leg edema, poor skin, and a non-existent libido. Given this description, see if you can explain the source of the massive swelling, as well as the anatomic anomaly that must have been present from a young age.


“The ascent to greatness, however steep and dangerous, may entertain an active spirit with the consciousness and exercise of its own power: but the possession of a throne could never yet afford a lasting satisfaction to an ambitious mind.”   -Edward Gibbon, The History of the Decline and Fall of the Roman Empire


ANSWERS: (highlight to see)
1. High dose of estrogen prevents ovulation. Even emergency contraception works via this mechanism.
2. Gigantism, Acromegaly
3. Congenital hypothyroidism, treated with iodine
4. Fat necrosis following trauma
5. Teratoma
6. The swelling likely started as an indirect inguinal hernia, and began filling with fluid as a result of ascites secondary to alcoholic liver disease. For the scrotum to fill with fluid he would need to have had a patent processus vaginalis.

GI/Liver 


Napoleon abdicating in Fontainebleau, by Paul Delaroche 

1. Napoleon's death on the Island of St. Helena has been the subject of many medical debates. Elaborate theories about arsenic poisoning and potential foul play by his British captors have been around for centuries, though few fully consider the circumstances of his death. Let's walk through the available evidence and see if we can't put this matter to rest. During the first two years of his captivity his health was relatively stable, but in January 1819 he started complaining of severe epigastric pain radiating towards his right shoulder blade. The physician's log book reported emesis, diarrhea alternating with constipation, recurrent fevers, chills, and headaches. A note from December 1820 stated "The illness of the Emperor has definitively worsened. His pulse is weak, his gums, lips and nails are colorless." In the following months he began losing weight and experiencing such severe night sweats that he had to change his clothing several times each night.

In April 1821 there was noted hematemesis, melena, and tachycardia (112 bpm). The emperor died about a month later. According to the autopsy report filed by an esteemed Italian anatomist, his stomach was filled with dark "coffee ground" like material, and there was an ulcerated lesion with raised, hardened, and irregular borders extending from the cardia to the pyloric region. There were also hardened and enlarged lymph nodes around the stomach and mediastinum. In addition to all of this, he spent his life eating a large amount salt-preserved foods and smoked meats during military campaigns. There is even speculation that an episode of GI bleeding interrupted his command duties at the battle of Waterloo, and contributed to the infamous French defeat. Seems like a classic case, what did he die of? What are two other pathologies present in this description?

 
Some say this famous pose originated from Napoleon's chronic epigastric pain.

2. Theodor Billroth was one of the greatest surgeons of the 19th century, and is best known today for developing procedures that treat refractory peptic ulcer disease. However, he was also an avid violinist, and was a dear friend to the composer Johannes Brahms. Together they were at the center of the Viennese music scene. Brahms frequently used Billroth's opinion to influence his compositions, and Brahms helped Billroth with his research on cognition and musical perception, the first of its kind. Unfortunately, Billroth died in 1894, two years before Brahms developed an illness that he potentially could have helped with (as the father of modern abdominal surgery). Less than a year before Brahms' his death an observer wrote, "He looked terribly miserable. The thin white beard, the withered face, the yellow eyes, the flabby thin body, his clothes hanging like on a hanger." His doctor also noted "considerable swelling of the liver with complete obstruction of the biliary ducts," perhaps related to his lifelong alcohol consumption or heavy smoking. Before jumping to any conclusions, it is important to note that his health was very good up until his illness began at age 73, and his decline was very rapid. Of the several possible causes of his death, which is the most likely?

 
Theodor Billroth Operating, A.G. Seligmann

3. Hollywood icon Audrey Hepburn was born in Belgium in 1929 to semi-aristocratic parents, both of whom were members of the British Union of Fascists. Luckily her father, who was a real nazi sympathizer, left the family when Audrey was six years old, and didn't have any lasting impact on her sensibilities. Though what she experienced during the war in Holland impacted her for life, and by all accounts she conducted herself quite nobly. Despite suffering from malnutrition, anemia, respiratory problems and edema, she insisted on helping with the war effort. She gave secret dance recitals to collect money for the Dutch resistance, acted as one of their underground couriers, and baked cakes out of tulip bulbs during the Dutch famine of 1944. Later in her life she became heavily involved with UNICEF, and was very dedicate to fighting child hunger around the world.

Like many who survived the war, Audrey was left with lifelong psychiatric problems, and struggled with depression and an eating disorder throughout her career. She said the one thing that helped most was gardening, which she was very passionate about. In 1993 she made an emmy-winning program called "Gardens of the World," which aimed to transmit the serenity and catharsis she found in them. However, soon after she finished filming she began having sudden, terrible abdominal pain. She checked herself into Cedars Sinai in Los Angeles and the doctors performed laparoscopic surgery. Surgeons found a tumor of the appendix that had metastasized to the small intestine, and they removed a large portion of ilium. After that she received 5-Fluorouracil and leucovorin therapy, which was largely ineffective. She died several months later at the age of 63. What she had was an extremely rare cancer of the appendix called pseudomyxoma peritonei. Based on gut physiology, can you think of what made her tumor present with sharp pain so suddenly without preceding symptoms? The answer is not appendicitis. 

 
Audrey Hepburn, 1929-1993

A clip from her excellent documentary on gardens: http://www.youtube.com/watch?v=t6ArElsvCUA

4. Dr. Frederick Treves was a British physician who had one of the most extraordinary careers in the history of medicine. He became famous for his relationship with Joseph Merrick, aka "The Elephant Man", which turned both of them into Victorian celebrities. He was also a renowned surgeon and was named honorary surgeon to the royal family. In 1902, Prince Albert of Wales (Soon to be King Edward the VII), who had waited 62 for his mother Queen Victoria to die, was finally going to assume the throne in a lavish coronation ceremony. Unfortunately, days before the event he fell ill with sharp lower right quadrant pain. Treves was called and explained that the king likely had an appendicitis, and would probably die if he did not operate. Appendectomies were not well received at the time, but Treves was adamant and finally convinced him. With the personal assistance of Lord Joseph Lister his operation was a success, the monarchy was saved, and from that point on surgery became the standard treatment for appendicitis. Dr. Treves retired having completed over 1000 appendectomies, and spent his final years traveling the world. He wound up in a Swiss nursing home, and in 1923 died from an abdominal infection. There was no autopsy, but it was noted that he suffered from peritonitis during his last few days. I searched and searched but there are no more details on this great doctor's illness. Had his pain started in the lower right it is likely he succumbed to an appendicitis of his own, but what would be the most likely diagnosis had it started on the left?

 
Dr. Frederick Treves, played by Sir Anthony Hopkins in The Elephant Man

 
A British newspaper clipping from 1902

5. There's not much history here, but I want to finish with another music clip. Pavarotti, despite his dalliances with the pop music world, was one of the most beloved singers of the 20th century. His powerful, golden voice was recognized the world over, and his death in 2007 sparked national mourning in his native Italy. A year earlier, he came to New York to have an tumor removed that appeared very suddenly and probably had something to do with his lifelong obesity. Despite complete resection and five rounds of chemotherapy, he was never able to recover. He will be missed.

  
Luciano Pavarotti, 1935-2007

 
My favorite aria, from Puccini's Tosca

 

ANSWERS (highlight to see):
1. Gastric adenocarcinoma, likely from an H. pylori infection. Cholecystitis (right shoulder blade pain), Iron deficiency anemia.
2. Pancreatic cancer (at the head of the pancreas)
3. Bowel obstruction. Ilius and intussesception often occur near the ileocecal valve and as a result of neoplasms in adults.
4. Diverticulitis
5. Pancreatic cancer

Finally, I would like to dispel a malicious rumor that our well-meaning but grossly misinformed lecturers propagated throughout the course. As brilliant as the ancient Greeks were, there is in fact no evidence that they knew about the regenerative capacities of the liver. Prometheus's liver did indeed grow back each day after being devoured by an eagle, but then, there are a whole host of other mythologies whose anatomic claims did not pan out with the coming of modern medicine. Manipulating history to reinforce our current beliefs is a slippery slope, and should not be indulged regardless of the stakes!

 
Tityus, by Titian. A lecturer used this painting to tell the story of Prometheus, unfortunately it portrays an entirely different legend concerning the god Tityus who had his liver eaten by two vultures. It's been a carnival of errors this year in terms of historical accuracy.

Hematology

 
The Latona Fountain in the gardens of Versailles

1. We will begin by revisiting a criminal investigation that took place in France in 1668. Jean-Baptiste Denis was the son of the chief hydraulics engineer to Louis the XIV, and was famous for creating an elaborate system of pumps that transported water from the Seine to the great fountains of Versailles. Rather than become an engineer himself, Jean-Baptiste decided to combine the family craft with the field of medicine. During his time as a lecturer in physics, mathematics, and medicine, he came across the work of William Harvey, and became fascinated with the possibility of blood transfusions. On June 15th 1667, he conducted the first ever animal to human transfusion using 13 ounces of lamb's blood and a series of goose quills as an I.V. line. His work made him a Parisian celebrity, but also earned him a fair number of enemies within the French Medical Academy. They were vehemently against the procedure and jealous of his position as personal physician to the king.

After a couple more "successful" trials, he performed his fourth animal-human transfusion on a madman named Antoine Mauroy, who died soon after the procedure. However, the case was wrought with suspicious behavior, especially from the man's wife who buried her husband herself to avoid the inevitable autopsy. At Denis' trial there was a witness who described Mauroy's death. Apparently he became very pale and started having seizures and may have shown evidence of GI irritation and discoloration of his nails (leukonychia striata). There was no jaundice, splenomegaly, hematuria, or fever. The judge was smart enough to know that these were the signs of overdose from a type of syphilis treatment common in those days. Denis was set free, and the wife was convicted of murder. Unfortunately the case left such a stain on Denis' reputation that he quit medicine, and the idea of transfusing blood disappeared for 150 years. Can you name the substance that killed Mauroy? What would be the cause of death from xenotransfusions?


A diagram of Denis' method

2. Most people know Pythagoras of Samos for his work on the triangle, but he was also one of the first documented polymaths. He was said to have studied medicine in Egypt, he wrote music, made extensive contributions to philosophy, and even started a kind of mystic mathematical cult called Pythagoreanism. In 529 BC he established a school near the southern Italian town of Crotone with a small group of his followers. They lived an aesthetic lifestyle, spent their free time practicing music and math, and ate an exclusively plant-based diet (interestingly, before the 1800s vegetarianism was known as The Pythagorean Diet). There was however a very strict rule against eating beans, which was likely the result of Pythagoras witnessing episodes of severe hemolytic anemia among some of his male followers. Today, the same area around Crotone is known to have the highest incidence of a certain Mediterranean genetic defect linked to this phenomenon. What is it? What is the genetic term we use to describe what happened with the Pythagoreans?


Pythagoreans celebrate sunrise by Fyodor Bronnikov


We've been here before. Pythagoras teaching music in Raphael's School of Athens

3. In 1932 two men excavated a temple in England from the 4th century AD. The temple was dedicated to the god Mars and it was written that any of his followers suffering from weakness could come drink from the temple waters and acquire some of the god's strength. Also of note was that the temple waters were frequently discolored on account of the high mineral content of the nearby soil. They even appeared red at times (hence the Mars-red connection). The two archeologists uncovered an interesting statue at the site, displaying one of the typical symptoms one might find among these weak followers. What did people come to the temple to treat? What is name of the symptom shown below?


Hand uncovered at Lydney, Gloucestershire

4. Now time for some political intrigue. In 1974 the Shah of Iran noticed a swollen lymph node in his neck, and was secretly treated by two French physicians for the next five years. He kept it a secret even from his wife until 1979, when he became severely ill at his villa in Mexico. He suddenly developed jaundice, nausea, chills, and a fever. Local doctors confused his symptoms with malaria, so an American doctor was brought in from Cornell to consult. Unfortunately he also made an incorrect diagnosis, thinking it was gallstones. But when the Shah began rapidly deteriorating his French doctors finally spoke up, and President Jimmy Carter made the very controversial decision to allow the Shah into the U.S. for treatment at Sloan-Kettering. In the hospital he received a full workup, and they discovered that he had a very unusual type of cancer characterized by an increased blood viscosity without lytic bone lesions, as well as other features typical of lymphoma. When news got out that the Shah was in the U.S. for treatment, the Ayatolla Khomeni became furious, and pro-revolutionary student groups began protesting outside of the U.S. embassy in Tehran. A quite well-known hostage crisis ensued, decades of political strife followed, and an overrated movie was made. What was the specific disease that set all of this off?


The Pahlavi Family

5. One of the greatest pianists of the 20th century is also one of the least well known. Dinu Lipatti was praised in his own lifetime by some of the most famous musicians of his age. Francis Poulenc called him "an artist of divine spirituality", and Herbert von Karajan described his playing as "no longer the sound of the piano, but music in its purest form." Though sadly, at the age of 29 he began suffering from a mysterious illness that started as a persistent fever and weight loss. After a number of incorrect diagnoses and random treatments, his doctors began administering x-ray therapy, which he said helped immensely. He also went through a trial of mustard gas injections, which caused swelling and disfigurement in his left arm. At 31 he began requiring weekly blood transfusions, and stopped chemotherapy after it destroyed one of his lungs. He remained positive and calm throughout, saying his swollen left arm gave "such formidable sonorities in the bass," and he continued touring, captivating audiences with "a different kind of expression." Based on his age and treatment, which disease was he suffering from?

 
Dinu Lipatti, Romanian classical pianist and composer (1917-1950)

In the midst of his final decline, and against the advice of his doctors, Lipatti decided to give one last recital in the French city of Besançon. Barely able to walk onstage, he gave a performance that has entered into legend, displaying an artistry that epitomized his musical purity. Towards the end of the concert, he found himself too weak to finish a series of Chopin waltzes, and ended with a simple Bach Chorale instead. The audience knew this was a final prayer from a man at the end of his life, and were moved to tears by the performance. Lipatti died ten weeks later at his home in Geneva, at the age of 33.

Listen to Dinu Lipatti's performance of J.S. Bach's Chorale, Jesu Joy of Man's Desiring:

ANSWERS (highlight to see):
1. Arsenic, autoimmune hemolytic anemia. Rumor has it members of the Paris Faculty of Medicine supplied the wife with arsenic in an attempt to frame Denis.
2. Glucose-6-phosphate dehydrogenase deficiency (G6PD), founder effect
3. Iron deficiency anemia, koilonychia. Mythology states that Iron was a gift from Mars to mankind.
4. Waldenstrom's macroglobulinemia
5. Hodgkin's Lymphoma

Psychiatry

This week's grand rounds will focus on the world of art! Some of history's greatest artistic achievements came at the price of terrible psychiatric illnesses, and in our reverence for these works we tend to romanticize the plight of the artists. However, there was little romance in it for them, so let's take this opportunity to examine the personal hardships they went through. As psychiatric diseases are fairly simple to identify on paper, see if you can name the artist along with the disease.

1. In the world of ballet, the names Mikhail Baryshnikov and Rudolf Nureyev are ubiquitous, but there was one male dancer who is said to have towered above both as the greatest of all time. In the early 1900s he toured the world with the Ballet Russes, and became a worldwide phenomenon owing to his gravity-defying leaps, inspired technique, and intense eroticism. However, problems arose due to "sexual and moral issues," and only a few years after his debut he disappeared from the stage and spent the rest of his life in and out of mental institutions. His psychiatrist noted his "marked lack of social interest... wholly disillusioned and hopeless" and his "irrational imagination." He would also sit silent and motionless for long stretches of time, occasionally "breaking off into a friendly laugh." He died in 1950, and is buried in the famous Montmartre Cemetery in Paris.

2. Known as a introverted, impersonal man throughout his life, this artist became more and more troubled as he grew older. He became so unsatisfied with his work that he began burning his drawings and attacking his own statues. His neighbors said he would wake up in the middle of the night, go down to his workshop and stare at unfinished works for hours with a candle stuck in his hat, unable to finish them because of his disgust at their mistakes. Before he died he said he regretted ever becoming an artist. In one of his pantings he included a figure that encapsulated what he felt throughout his life:

An artist who was a contemporary of his included a "psychiatric" portrait of him in one of his larger paintings (also note the severe gout):

3. This musician, if he were diagnosed today, would probably qualify for three or four different disorders. He experienced repeated episodes of hypomania, waking up at 6am and composing nonstop until 2am, and wrote letters that seemed incoherent and inappropriate, but there were other periods where he would procrastinate endlessly and waste his time with billiards or other solitary activities. In the final years of his life, he was reported to have felt a "pervasive sadness" and disinterest in composing, which included a loss of energy and excessive feelings of guilt. His personality was also quite strange. He had a constant need for attention and nurturing even as an adult, a lingering emptiness, a tendency to throw away money, and a constantly fluctuating and impulsive mood. Many fellow composers including Tchaikovsky, Chopin, Wager, Schubert, and Brahms considered this man the greatest musical genius of all time.

 

He was also easily distracted, and did little doodles while composing


4. In her lifetime she was best known for her volatile affaire with French sculptor Auguste Rodin, but she is now regarded as an inspired sculptor in her own right. Part of the reason she is not so well recognized is that she ended up destroying many of her statues. At the age of 41 she began showing signs of mental illness, she had intense paranoia, violent outbursts, and accused Rodin of leading a conspiracy to kill her and steal her ideas. Eight years later she was involuntarily committed to a psychiatric hospital in the outskirts of Paris. Despite reports from doctors that her condition improved when she resumed her work, her family insisted that she remain in treatment. She died in 1943, having lived 30 years in an asylum. 

 

The Mature Age, Musee d'Orsay

5. This painter's work is divided into two categories, the first "is characterized by joy and light, the second by horror and ghosts." It is believed that a strange illness took place between the two. In 1792 he became extremely ill and suffered severe depression together with hallucinations, delirium, and weight loss. He also had a wide range of physical symptoms including tinnitus, headaches, dizziness, right arm paresis, and hearing loss. While a wide range of pathologies have been proposed, including Meniere's disease, lead poisoning, syphilis, and mercurial encephalopathy, none can explain the full extent of his symptomatology. What is one thing we have learned about that may have contributed to his physical symptoms?

Yard with Lunatics, painted during the onset of his illness




ANSWERS (highlight to see):
1. Vaslav Nijinski, schizophrenia with "negative symptoms" and automatisms (catatonic)
2. Michelangelo, major depressive disorder. Paintings: Sistine Chapel and The School of Athens (by Raphael)
3. http://www.youtube.com/watch?v=k1-TrAvp_xs bipolar/cyclothymia, major depressive disorder, or borderline personality disorder
4. Camille Claudel, schizophrenia
5. Francisco De Goya, Conversion Disorder?

Have a nice winter break everybody! Hope to see you next semester for some compelling historical cases of leukemia, asthma, diabetes, hypogonadism, bowel issues, etc.

-Michael 

Cardiology (Ancient Egypt Edition)

Hello friends. Early humans saw that all life depended on the continuous pulsing of the heart, and therefore assigned the most fundamental elements of life to this organ. To the Egyptians, the heart was the seat of all love, thought, and emotion, and was necessary to keep the body and soul together after death, which is why the heart is the only organ we find intact in ancient mummies. Yet the Egyptians were far more than a bunch of ancient mystics. The Ebers Papyrus, a compendium of Egyptian medical knowledge from 1500BC, spends a great deal of time explaining some very real diseases of the heart, so let's take a look and see what we can decipher...


The Weighing of the Heart: A measure of worth in the afterlife

1. There is a warning in the papyrus: "If thou examinest a man for illness in his cardia and he has pains in his left arm, and in his breast and in one side of his cardia, it is death threatening him." The phenomenon of angina leading to left arm pain was well known, and it inspired them to name the left fourth finger the "heart finger" (Romans later had the idea to wear rings on it to symbolize marriage). Since atherosclerosis was a lot less common back then, can you name a cause of angina pectoris that is not due to coronary artery plaques?


A page from the Ebers Papyrus

2. They also described certain disorders of the cardiac conduction system: "When the heart is diseased, its work is imperfectly performed: the vessels proceeding from the heart become inactive, so that you cannot feel them … if the heart trembles, has little power and sinks, the disease is advanced and death is near." What do you think they are describing?

3. The scroll includes descriptions of over 700 medications. Most sound like nonsense, but perhaps a few of them had some benefit. If the heart was "weak due to old age" or suffered from "heart dancing", they would prescribe the bulb of the squill plant, which we now know contains a kind of natural glycoside. What variant of this chemical do we use today for these same problems and what does it do?


Squill Plant

4. The Egyptians were also familiar with aneurisms (for which it was advised "to treat it with a knife and burn it with a fire so that it bleeds not too much") as well as other anomalies of the great vessels. However, one modern study identified a mummy with a finding that the Egyptians likely did not diagnose (they never conducted autopsies). A scan showed its ribs having irregular notches along their edges. Which vessel abnormality would explain this?


Interdisciplinary Research

5. One last excerpt: A "Debility that has arisen in the heart... its arching out as far as the borders of the lung and liver. It happens there from to him that his vessels become deaf, having fallen down as a result of their heat.” Which chronic problem could they be describing? Hint: Egyptians were not foreign to alcohol consumption.


ANSWERS (highlight to see):
1. Coronary vessel spasm (Prinzmetal's angina or Cardiac syndrome X)
2. Likely ventricular tachycardia (no pulse, heart trembles)
3. Digitalis, it slows the beats per minute (gets rid of the dancing) and increases the force of each beat (reduces the weakness)
4. Coarctation of the aorta
5. Dilated cardiomyopathy (for one)

Dermatology (Guest Contributions Edition)

Dear friends,

It gives me great pleasure to present a very special "Guest Contributions Edition" of the Historical Grand Rounds. There is no higher mark of friendship than lending time and enthusiasm to another's interests, and I'd like to sincerely thank those who took part. I hope you find each other's cases as interesting and inspiring as I did.

1. George Washington, by Jason

We start at the beginning. Our beloved American patriarch, George Washington, is best known as the first United States President, the president of Constitutional Convention in 1787, and the commander-in-chief of the Continental Army during the American Revolution. Unfortunately, all of the time he spent outdoors fighting the British would have made for a dermatologist’s nightmare, especially given Washington’s pale complexion. Check out the following portrait by William Joseph Williams for the Alexandria Masonic Lodge number 22. The portrait was completed in 1794, during Washington’s second term as President. Do you notice anything on his right cheek? How about next to his right ear?



Fortunately, Washington had access to the best medical care 18th Century America had to offer. Washington wrote a testimonial letter on behalf of Dr. James Tate on February 25, 1795 in which he might have been referring to this lesion:“I have, myself, experienced the fruits of his skill, in this art; being cured by him of an irritable spot on my right cheek which had for years been increasing in pricking and disagreeable sensations; and in June last assumed the decided character of a Cancer; of which I was perfectly relieved by Doctor. Tate in about two months by an easy course, under the operation of which I felt no confinement, or other inconvenience at that time, nor any injury to my constitution since.” Further sources indicate that Washington was treated with the repeated application of a cream or paste. Based on these clues, what is the most likely diagnosis?

2. Rembrandt van Rijn, by Ruyan

Rembrandt van Rijn is considered one of the greatest painters and etchers in Dutch history and well known for his masterful contributions to European Art. His work paved the way for the Dutch Golden Age with innovative and creative pieces that moved away from the Baroque style of the past. Rembrandt achieved great success as a young painter and was respected and popular throughout his life. His ability to portray the human condition with empathy and sincerity marked him as “one of the great prophets of civilization.” His self-portraits are considered to be among his greatest artistic triumphs, offering raw and unadulterated insight into his life. He portrayed himself without vanity, including features such as an enlarged nose, visible blood vessels, and pimples in many areas of his face. In some paintings he depicted several papular lesions, a telangiectatic lesion under his right eye, and a bulbous nose. These signs indicate the presence of an inflammatory dermatosis – which one?


Rembrandt van Rijn (1606-1669)

3. Viktor Yushchenko, by Abraham (old friend of Michael's)

 The political situation of Ukraine in the past decade has created a deeply divided society. One particular incident was the illness of presidential candidate Viktor Yushchenko. After having a rowdy night eating sushi and drinking plenty during a political meeting, Yushchenko's face began to grow a very serious amounts of acne and pockmarks.  Skin colour turned a gluey, greenish-yellow. One eye was partly paralyzed and everything in his face looks swollen. His back ached, his stomach hurt. After a few days of these symptoms he checked himself in to a prestigious clinic in Austria where doctors suggested his symptoms were due to severe pancreatitis due to viral infection. A few doctors worldwide suspected a very different illness that reminded them of patients in a few isolated incidents in italy, and victims and veterans of the vietnam war. What is the likely cause of Yushchenko's deformity?


He's since mostly recovered from the Kafkaesque appearance and illness but his face remains largely scarred.

4. Remus Lupin, by Roberta

Professor Remus John Lupin of the Hogwarts School of Witchcraft and Wizardry secretly sought treatment from Professor Severus Snape for a medical condition. The primary manifestation of Professor Lupin’s disease was hypertrichosis. In addition, Professor Lupin demonstrated a biphasic anagen phase with his hair growing at the normal rate of half an inch each month until the last day of the month when his hair growth rate skyrocketed and his main symptom of hypertrichosis was most apparent. This acceleration in hair growth rate was followed by an accelerated telogen phase, so Professor Lupin’s symptom of hypertrichosis resolved by the first day of the month each month.  What disease did Professor Lupin suffer from, and what mythological creature was he mistaken for in the Harry Potter series?

 
Professor Snape made a potion to treat Professor Lupin from the pictured flower, aconitum (wolfsbane).

5. Paul Klee, by Monica (Michael's mom)

Paul Klee (December 18, 1879-June 29, 1940) was a painter born in Switzerland. The son of a music teacher, he was a talented violinist growing up. As a teenager, his attention turned from music to the visual arts. His style was influenced by expressionism, cubism, surrealism and orientalism, and his signature technique including drawing with a needle on a blackened pane of glass. Klee also experimented with and eventually got deep into color theory. Ad Parnassum is widely considered to be his masterpiece.

Klee was plagued by stomach problems and suffered from weight loss and hardening of the skin, as well as difficulty swallowing and incontinence. His doctors failed to diagnose his true condition, and he was misdiagnosed in 1935 with bronchitis and measles. He was bedridden until 1936, when he resumed painting on a limited basis. He died in June 1940 from cardiac paralysis. He once wrote, “Everything vanishes around me, and works are born as if out of the void. Ripe, graphic fruits fall off. My hand has become the obedient instrument of a remote will.” What was his diagnosis?


Ad Parnassum, by Paul Klee

6. Madame X, by Marissa

Painted in 1884, John Singer Sargent's portrait of Madame X caused a great stir when it was first displayed in a Paris Salon. The portrait is of Virginie Amélie Avegno Gautreau, a socialite born in New Orleans who moved to Paris with her mother and sister after her father died in the Civil War. Her revealing dress and prominent décolletage were perhaps the most provocative features of the painting. Her pale translucent almost bluish-purple tinged skin was considered the epitome of a beautiful complexion in that day.  It is rumored that she ingested small wafers containing this substance (let's  call it substance X) in order to achieve her fair complexion. Exposure to substance X can cause Mee's Lines in the nails. Exposure to substance X can also cause Basal Cell Carcinoma. Other common etiologies of Basal Cell Carcnioma include UV exposure, X rays and scars/chronic inflammation.


Madame X, by John Singer Sargent

7. Salif Keita, by Alex

Salif Keita is a world-famous musician who is said to be a descendant of the founder of the Malian empire, Sundiata Keita, who lived in the 13th century. Although he was born into wealth and status, he was disowned by his family because of this instantly noticeable skin disorder, which is said to be an omen of bad luck in Madinke culture. He eventually fled Mali, taking his group Les Ambassadeurs with him, and eventually moved to Paris. He went on to work with musicians from all over the world, including renowned jazz saxophonist Wayne Shorter and Carlos Santana. Who knows what would have become of Keita if he had not been disowned, though, as one Wikipedia editor pointed out, because of the Malian caste system, “he should never have become a singer, which was deemed to be a griot’s role.” In 2009, he dedicated his album La difference to fellow sufferers of this condition. What kind of deficiency most likely caused his skin disorder?



8. Jean-Paul Marat, by Michael

When Napoleon said "vanity made the revolution; liberty was only a pretext," perhaps he was referring to the man featured in our final case. Jean-Paul Marat was a Swiss physician who in 1789, set his sights to the world of political journalism in favor of France's new revolutionary government. With his self-stylized title of "Friend of the People", he became one of the most vocal supporters of the bloodshed that came to define Robespierre's Reign of Terror, and his daily newspaper columns encapsulted the odd combination of savagery, fraternity, and enlightenment that defined the revolution. Interestingly, most of his political musings were written as he lay in an oatmeal bath, which he used for three years to help treat a severe and debilitating skin condition. The condition started in his late 40s and originated in the anogenital area. It was extremely itchy and at times purulent and blistering, and was sometimes accompanied by headaches, insomnia, polydipsia, and "paranoia". It spread to his entire body, and certainly did not do any favors for a man already considered to be ferociously ugly. Some doctors thought syphilis, other eczema, but a more recent diagnosis based on the late-onset and chronicity lead to speculation that Marat may have also had a certain gastrointestinal disease. What could it be? 

As you would expect, Marat's fiery public persona earned him a few enemies, and in 1793 a young woman named Charlotte Corday stabbed him as he lay in his bath. The event would be immortalized by Marat's friend and fellow revolutionary Jacques-Louis David in one of the most famous propaganda paintings of all time:


The Death of Marat, by Jacques-Louis David


Answers (highlight to see):
1. Actinic Keratosis that underwent acute solar degeneration, possibly to squamous cell carcinoma in situ (Bowen’s disease).
2. Rosacea
3. Chloracne from digoxin poisoning
4. Porphyria, Werewolf
5. Scleroderma
6. Arsenic
7. tyrosinase (albinism)
8. Dermatitis herpetiformis (goes with celiac disease)