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.