The Great Pellagra Epidemic of 1915

You're thinking, "What? Pellagra Epidemic?" Yea, I did too, but apparently, this epidemic is what lead to the discovery and identification of pellagra as a disease caused by vitamin deficiency, specifically Vitamin B3. Pellagra was found to be a vitamin deficiency by Dr. Joseph Goldberger:

The puzzle of pellagra was solved by Dr. Joseph Goldberger. Dr. Goldberger was assigned in 1914 by the US Public Health Service to the South to deal with pellagra. After inspecting Southern orphanages, mental hospitals and prisons, Goldberger made the pivotal observation that the malnourished inmates of those institutions often developed pellagra while the better-fed staff did not. Pellagra, he deduced, did not arise from germs, as was commonly believed, but rather from a nutritional deficiency. To prove this, Dr. Goldberger, his assistants and even his wife engaged in experiments called "filth parties." They injected themselves with blood or ingested the scabs, feces and body fluids of patients. None developed pellagra. He also did decisive experiments with Mississippi prison inmates (who "volunteered" in return for a full pardon). Dr. Goldberger fed them a poor diet that he believed caused pellagra and within months, many developed the disease. He then added meat, fresh vegetables and milk to their diet and reversed all of the signs and symptoms of pellagra. Dr. Goldberger never identified the dietary principle that had this extraordinary effect. He died in 1929 (of kidney cancer). Eight years later, the factor was found to be niacin. This discovery was made in 1937 at the University of Wisconsin. Niacin is abundant in red meat, fish, poultry, and green leafy vegetables. Niacin can prevent pellagra (and can cure it).

Another point of interest: the name "pellagra" comes from the Italian "pelle", skin + "agra", rough = rough skin, referring to the skin problems in pellagra.

Want to read more? Italians also were involved with atropine, as well as pretty women.

8 Phun Pharmacology Phacts

Here are some random drug facts/trivia/history I picked up while studying pharmacology. Some of them are well-known; some, perhaps not so much. Anyway, here are 8 "phun pharmacology phacts":

Q: Why do diuretics trigger sulfa allergies?

A: The observation that patients treated with sulfonamides developed a hyperchloremic metabolic acidosis led to the development of acetazolamide and subsequently the thiazide diuretics. (Note: loop diuretics also trigger sulfa allergies, but I am not sure why)



Q: Which drug used to treat hypertension was noted to have a side effect that some middle aged men might find beneficial?

A: Minoxidil was found to cause hypertrichosis (increased hair growth), so a less potent form was marketed as the anti-balding agent Rogaine.



Q: A patient presents with hypotension, weakness, disorientation, psychosis, and a breath that smells like bitter almonds. Which antihypertensive drug might the patient have been on?

A: The bitter almond breath is due to cyanide toxicity, a side effect of nitroprusside. The metabolism of nitroprusside releases cyanide.



Q: Why should people on Viagra not take nitrates?

A: Sildenafil (Viagra) and nitrates act synergistically. Nitrates activate guanylate cyclase to increase cyclic GMP; sildenafil inhibits phosphodiesterase V to inhibit break down of cGMP. Together, the drugs markedly increase cGMP which leads to massive vasodilation and hypotension. Not exactly the best way to rekindle one's marriage, huh?

Quick note: One of the side effects of Viagra is difficulty with blue-green color discrimination, just like the color of the pills.



Q: What are "poppers"?

A: Per PharmCards, poppers are "street forms of amyl nitrates used to produce giddiness and enhance sexual perfomance via release of NO in the corpora cavernosa." The drug is related to nitroglycerin.



Q: What drug was initially discovered by William Wuthering as a treatment for dropsy, an old term for edema?

A: Digoxin is a purified extract of the foxglove plant, also known as digitalis.

Another quick note: One of digoxin's side effects is blurry yellow vision (think Van Gogh).









Q: Why are tricyclic antidepressants sedating?

A: They were first developed as antihistamines.



Q: How was penicillin discovered?

A: Penicillin was included in this list of 10 notable accidental inventions. As the story goes:

Everybody knows the story – or at least, should – the brilliant yet notoriously absent-minded biologist Sir Alexander Fleming was researching a strain of bacteria called staphylococci. Upon returning from holiday one time in 1928, he noticed that one of the glass culture dishes he had accidentally left out had become contaminated with a fungus, and so threw it away. It wasn’t until later that he noticed that the staphylococcus bacteria seemed unable to grow in the area surrounding the fungal mould.
Fleming didn’t even hold out much hope for his discovery: it wasn’t given much attention when he published his findings the following year, it was difficult to cultivate, and it was slow-acting – it wasn’t until 1945 after further research by several other scientists that penicillin was able to be produced on an industrial scale, changing the way doctors treated bacterial infections forever.

Can't get enough? Check out why Italian women love atropine, or the top 5 medical urban legends.

Who Was Typhoid Mary?

Since I'm studying infectious diseases, salmonella has been on my mind. Specifically, the "First Lady" of Salmonella, Typhoid Mary. Who exactly was Typhoid Mary?

Mary Mallon (September 23, 1869 – November 11, 1938), also known as Typhoid Mary, was the first person in the United States to be identified as a healthy carrier of typhoid fever. Over the course of her career as a cook, she infected 47 people, three of whom died from the disease. Her fame is in part due to her vehement denial of her own role in causing the disease, together with her refusal to cease working as a cook. She was forcibly quarantined twice by public health authorities and died in quarantine. It was also possible she was born with the disease, as her mother had typhoid fever during her pregnancy.

However, my research also uncovered another Typhoid Mary:

Typhoid Mary (Mary Walker), also known as Typhoid and Bloody Mary, is a fictional mutant character in the Marvel Comics universe, most commonly associated with Daredevil as a supervillainess. She first appeared in Daredevil #254, and was created by Ann Nocenti and John Romita, Jr.

Typhoid Mary is an enemy and former lover of Daredevil with low level psionic powers, including telekinesis. She has been employed by organized crime syndicates as an assassin in the past. She is also truly and gravely mentally ill.

I love how the comic Typhoid Mary does not even come close to sharing the actual disease, which is decidedly much less glamorous. Can you imagine a comic book with the real Typhoid Mary? "Oh no, Superman is ill. All he did was eat at the local cafet... oh no! Typhoid Mary strikes again!"

Anyway, back to the real Typhoid Mary. Salmonella causes enteric fever, which presents with fever (duh), abdominal pain, liver or spleen enlargement and "salmon"/rose colored spots on the abdomen. Salmonella can also cause gastroenteritis, sepsis, and osteomyelitis especially in sickle cell patients. Some individuals enter a carrier state, such as Typhoid Mary:

People catch typhoid fever after ingesting water or food which has been contaminated during handling by a human carrier. The human carrier is usually a healthy person who has survived a previous episode of typhoid fever but in whom the typhoid bacteria have been able to survive without causing further symptoms. Carriers continue to excrete the bacteria in their feces and urine and poor hygiene can lead to its introduction into food and water.

However, it fails to mention how exactly Mary achieved this. Was she a mutant, as the comic book world would like you to believe? Sadly, no. The reality is salmonella can live in the gallbladder for years, and carriers secrete the bacteria in their stool. The best part of the story to me is how Mallon continued to work as a cook even after she was quarantined! She was eventually quarantined again and died in quarantine. You've gotta love the level of denial some people have.


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Why Monica Bellucci Might Take Atropine

Q: Why might some Italian women be crazy?

A: Atropine makes them that way! Atropine is an anti-muscarinic agent that acts on M1 receptors in the CNS, M2 receptors in the heart, and M3 receptors in smooth muscle tissue and various glands. The drug can be used to treat bradycardia, cholinesterase inhibitor overdose, and mild cramping and urgent bladder in mild cystitis. The side effects of atropine can be remembered by the mnemonic:

• Red as a beet - Dilation of superficial vessels leads to flushing
• Blind as a bat - Cycloplegia and mydriasis
• Dry as a bone - Decreased lacrimation and salivation
• Hot as a hare - Atropine fever due to decreased perspiration
• Mad as a hatter - Delirium and hallucinations

It was first isolated from the plant Atropa belladonna (right), so named because extracts from the plant were allegedly used by Italian women to dilate their pupils. However, my un-PC hunch is that some of the women OD'ed on the atropine causing them to be "mad as a hatter." Then again, Italy gave us Monica Bellucci, so perhaps that's an acceptable trade-off.

More anecdotes? Find out why the French are a little too familiar with a certain STD and with a certain might-as-well-be an STD.

Extraocular Muscle Movements - Function Explained

Usually, anatomists and clinicians share the same base of knowledge regarding how the body functions. However, as I was doing Step I practice questions today, I came across a question that referred to the functions of the extra-ocular muscles. As I flipped through First Aid for the USMLE Step 1, I noticed that the section on extra-ocular muscles had been visited by me before:

Abduction:
Inferior oblique
Superior rectus
Inferior oblique
...

Apparently, I had reviewed this topic at various times and found varying results from different sources. I decided to end this once and for all with the med student's almost authoritative resource: Wikipedia. The page that came up was helpful, but Wikipedia posed more questions than it answered. Apparently, clinicians in the past believed that the obliques adducted, while anatomists begged to differ. Luckily, a reference to a British Medical Journal article resolved the issue: the anatomists won, the obliques abduct.

It is interesting to see how someone's mistake if inculcated enough can become dogma. Simply by looking at the muscles, as was pointed out to me, the actions are apparent. As the obliques attach on the temporal aspect of the orbit, when they contract, the orbit will rotate against the force around its axis. In other words, the eye will abduct. How clinicians missed this for apparently a long time is beyond me. However, the British have a theory:

Our final conclusions, and what is now our policy for instruction on this muscle, is as follows. The superior oblique, acting in isolation, turns the eye down and out. However, if it was tested clinically by the patient being asked to look down and out, its action could be mimicked by the combined action of inferior and lateral recti. This is particularly so as the inferior rectus acts most effectively when the eye is abducted (looking laterally). Thus if the patient is asked to look down and in, these muscles are excluded and the problem is solved. Essentially we are testing the ability of the superior oblique to look downwards.
The confusion, which I hope the above clarifies, is compounded by some ophthalmologists being so used to testing the muscle by asking the patient to look down and in that they have forgotten that the isolated action is down and out.

Ah ha! So it was the ophthalmologists' fault! Well, well. Mystery solved!

Updated 2015-12-08

Of Phimosis and France

I was reading a random Top 10 list about movies that were saved by historical inaccuracies, when I came across a little tidibt about King Louis XVI (the monarch who immediately preceded the French Revolution):

One of the conflicts in the film centers around Marie and Louis' (Jason Schwartzman) difficulty in producing an heir. In the movie, Louis is afraid of sex. In reality, Louis had phimosis, a condition in which the foreskin of the penis cannot be fully retracted. This was later fixed with an operation, and the couple did in fact conceive.

Ah, phimosis. One of those conditions that causes people of sound mind sadly to snicker just a little (hello, priapism). Having read a little history and been in a med school for a few years but never having heard of this, I decided to do a little investigating. However, being the lazy guy that I am, I entrusted my research to the good folks at Wikipedia. I thought the phimosis theory was strange enough, but the Wikipedia posits an even more outlandish theory:

The true cause of the couple's infertility is revealed in a letter written by Marie-Antoinette's brother, Joseph II, to another brother, Leopold II. Joseph in April 1777 visited Louis and Marie-Antoinette in France, and had a frank talk with both of them regarding sexual matters; from this, he discovered that the King slept with his wife for duty rather than pleasure. There was no problem with the King's sexual organs: Joseph wrote, "he has strong perfectly satisfactory erections", and "he sometimes has night-time emissions"; the problem was that when the King and Queen slept together, "he introduces the member, stays there without moving for about two minutes, withdraws without ejaculating but still erect, and bids goodnight...when he is inside and going at it...[ejaculation] never happens." In the Emperor's opinion, the pair were "two complete blunderers", who had nothing wrong with them aside from lack of sexual knowledge and desire (Lassonne had already opined in 1773 that the lack of consummation was down to "clumsiness and ignorance").^[11]

Joseph, it would appear, remedied the couple's ignorance during his 'talks' with the pair; by August, the marriage was finally consummated, and the pair had thanked him for his advice, to which they attributed the consummation.^[12]

So, Wikipedia, you're telling me this guy... not just any guy, but the KING OF FRANCE... had n idea how to use his... um... "royal sceptre" for over 5 years??? I couldn't believe it, so I decided to go to another source, the all-knowing PubMed. But, again, being lazy, I am just going to link to the first abstract I found. But, yea, this does not really answer anything, as I did not have access to the article, and the article is in French. Since I am too lazy to continue this investigation further, I will simply conclude that King Louis XVI had phimosis *AND* had no idea what to do with his phimotic (?) phallus. Mystery solved.

A brief history of French mothers and STDs

Here's a little story I heard from a friend that I found both interesting and educational. I cannot vouch for its veracity, but like Stephen Colbert, my gut says it's true.

Back in 18th century France, French mothers were very concerned about who their daughters consorted with. In order to save them from men of suspect character who may be intent upon sowing their wild oats, the mothers would warn their daughters to avoid men with bobbing heads. The question for modern day medical students is, why?

The answer? The bobbing head, also known as De Musset's sign, is a sign of severe aortic regurgitation caused by syphilitic aortitis. Had the daughters flaunted their mother's warnings and flirted with these loathsome Lotharios and perhaps gone in for the proverbial French kiss, they may have also noted a bobbing uvula, also known as Muller's sign.