Recently in Medical history Category
The "JC" in JC virus stands for John Cunningham, and like the previously anonymous Henrietta Lacks of the immortal HeLa cells, this John Cunningham remains largely unknown. The virus itself is ubiquitous and harmless in most people (40%-60% of the general population are seropositive), but it creates a potentially devastating and often fatal white matter disease in immunocompromised persons.
A cursory search leads to a Google-available (or really, partially available) book entitled Human Polyomavirus, which was edited by Kamil Khalili and Gerald Stoner and published in 2001. The first 3 chapters concern the search for the cause of PML, which was first described or recognized in 1958 (first published paper by Astrom et al..."a hitherto unrecognized complication of chronic lymphatic leukaemia and Hodgkin's disease"). Chapter 2, written by Dr. Gabriele M. Zu Rhein, a codiscover of JC virus, reveals that John F. Cunningham was a patient at the VA Hospital in Wood, Wisconsin, in the summer of 1970. Cunningham had Hodgkin's disease and "rather rapidly progressing neurologic deficits." He was given a diagnosis of PML during life on the basis of a brain biopsy and thereafter "expressed the wish that his brain should aid research into this fatal disease." A "new human polyoma virus" was subsequently detected by Rhein and her colleagues in Cunningham's postmortem brain tissue, and the virus was named JC virus in honor of the patient.
A Wisconsin death record reveals that John F. Cunningham was 36 (born August 30, 1933) when he died on July 12, 1970, in Milwaukee. As a military veteran, his likely service would have been in the Korean or Vietnam War.
01/26/12 follow-up: The 1971 Lancet article by Padgett et al indicates that Cunningham was 38 in 1970 (although his death certificate indicates that he was about 6 weeks shy of his 37th birthday at the time of his death). Cunningham had been diagnosed with Hodgkin's disease for 8 years before he developed a "progressive left central facial palsy, left hypoglossal palsy, and palsy of the left upper extremity" in the Spring of 1970. (His cancer had been treated with nitrogren-mustard derivatives since 1968.) These neurologic deficits were attributed to PML, a diagnoses confirmed by brain biopsy (which showed "pathognomonic oligodendrocytes along the periphery of demyelinating lesions") during life. He reportedly granted permission for the postmortem examination of his brain only (examination occurred 10½ hours after death). Gross and microscopic study confirmed the diagnosis of PML, and extracts of his brain were used to grow and identify the newly recognized intracellular virions in culture—which were dubbed JC virus.
The commission's official report will reportedly be available in early September (tomorrow?), but a few highly disturbing details of the investigation were made available to the AP this week. Among them:
- 1300 Guatemalan soldiers, prisoners, prostitutes, or mental patients were intentionally exposed to the microbes that cause syphilis or gonorrhea
- Only about 700 (53%) of the exposed individuals received some sort of treatment (presumably penicillin*)
- 83 people in the study died, although it's not clear if death was due to intentional infection
- The research provided "no useful medical information"
- 7 women with epilepsy, residents of Guatemala's Asilo de Alienados (Asylum for the Insane), were injected with Treponema pallidum at the base of the skull, as a hopeful cure; all developed bacterial meningitis, probably as a result of unsterile technique
- A female patient with syphilis and an unknown terminal illness received an inoculation of gonococci in the eyes "and elsewhere"; she died 6 months later
Notorious US physician John C. Cutler, MD (right), who oversaw the PHS's Tuskegee syphilis experiment, led the American-funded
human experimentation in Guatemala.Guatemalan authorities are evidently conducting their own fact-finding investigation of the matter, but official reports have been delayed on more than one occasion. According to the AP, the Guatemalan report should be completed by November. (It should be remembered that Guatemalan authorities were complicit in the PHS experiments, according to Reverby.)
* The described rationale for the program was to determine the preventive benefit of penicillin.
Portrait of PHS physician John C. Cutler, MD, August 25, 1942, from the National Library of Medicine.
Saturday marked the beginning of the 2011 Iditarod Trail Sled Dog Race, spanning more than 1150 miles from Anchorage to Nome. The trail was first raised in the American consciousness in 1925, as 20 mushers and 150 sled dogs relayed life-saving diphtheria antitoxin through blizzard conditions from Nenana, where the antitoxin had been shipped by train, to epidemic-stricken Nome.
A brief account of the historic event is provided by Stanley Scheindlin in the August 2008 issue of Molecular Interventions. A much more comprehensive record is available from Salisbury and Salisbury: The Cruelest Miles: The Heroic Story of Dogs and Men in a Race Against an Epidemic.
From Alaska's Digital Archives: Image of sledder Gunnar Kaason with Balto, who traversed the last 78 miles to Nome during the 1925 "Great Race of Mercy."
HT: Terry Glauser.
By drawing mostly from cited data at Dr. Zebra, a list of presidential ailments is compiled in honor of our nation's all-too-mortal Commanders-in-Chief.
1. George Washington: poor dentition, possibly due to mercury oxide treatments for various infectious diseases
2. John Adams: depression; hypochondria
3. Thomas Jefferson: recurrent, persistent headaches; chronic back pain
4. James Madison: psychogenic epilepsy; chronic biliousness
5. James Monroe: recurrent malaria; possible pulmonary tuberculosis
6. John Quincy Adams: cerebrovascular disease
7. Andrew Jackson: smallpox; malaria; heart failure
8. Martin Van Buren: alcoholism; obesity; gout
9. William Henry Harrison: generally healthy; died of pneumonia
10. John Tyler: transient, generalized paralysis—possibly Guillain Barre syndrome; cerebrovascular disease (TIAs, stroke)
11. James K. Polk: generally healthy; died of cholera
12. Zachary Taylor: yellow fever; recurrent malaria
13. Millard Fillmore: generally healthy (medical history as boring as his Presidency)
14. Franklin Pierce: chronic depression; alcoholism; tuberculosis
15. James Buchanan: blepharospasm?; alcoholism
16. Abraham Lincoln: malaria; depression; smallpox
17. Andrew Johnson: typhoid fever
18. Ulysses S. Grant: alcoholism; tobacco abuse
19. Rutherford B. Hayes: generally healthy (see Millard Fillmore)
20. James Garfield: malaria
21. Chester Arthur: alcoholism; Bright’s disease; hypertension
22. Grover Cleveland: obesity; alcoholism; tobacco abuse; cancer of the jaw
23. Benjamin Harrison: recurrent “breakdowns” or “nervous collapse”
25. William McKinley: generally healthy; possible bout of influenza (“grippe”)
26. Theodore Roosevelt: severe myopia; unilateral deafness; overweight (if not obese)
27. William H. Taft: morbid obesity; gout; sleep apnea
28. Woodrow Wilson: possible dyslexia; cerebrovascular disease
29. Warren G. Harding: recurrent mental illness; tobacco abuse; cardiovascular and cerebrovascular disease
30. Calvin Coolidge: chronic depression
31. Herbert Hoover: cholecystitis; intestinal cancer
32. Franklin D. Roosevelt: polio; hypertension; cerebral hemorrhage; possible melanoma
33. Harry S. Truman: paralytic diphtheria as child; presbyopia; cardiac failure
34. Dwight D. Eisenhower: history of tobacco abuse; Crohn disease; coronary artery disease; cerebrovascular disease
35. John F. Kennedy: chronic back pain; possible autoimmune endocrine deficiency (hypothyroidism, Addison disease)
36. Lyndon B. Johnson: coronary artery disease; cholecystitis and/or cholelithiasis
37. Richard M. Nixon: venous thromboembolism; possible blepharospasm; cerebrovascular disease
38. Gerald Ford: tobacco abuse; tongue abscess due to Actinomycetes; coronary artery disease
39. James Carter: hemorrhoids
40. Ronald Reagan: myopia; chronic prostate problems; colon cancer; Alzheimer disease
41. George H. W. Bush: history of “bleeding ulcers”; atrial fibrillation; Graves disease
42. William J. Clinton: gastroesophageal reflux disease; coronary artery disease
43. George W. Bush: hemorrhoids; alcoholism; substance abuse; syncope; colonic polyps
44. Barack Obama: tobacco abuse
Today is the 115th anniversary of the first production of x-rays (thank you, Google, for the reminder) and the approximately 27th anniversary that Dr. David C. Sabiston, Jr, pimped yours truly about their discoverer, Wilhelm Roentgen (RENT-gun). No commemoration of historic medical events seems complete without traumatic personal memories of formal education, which also include being presented on rounds with a radiograph of a buckshot shoulder (something like this, if not this) and the ever-popular ruse of showing a chest x-ray of situs inversus...backwards.Google eases or heightens the retentive pain (depending on how jazzed you get by primary sources) by providing, in its ever-expanding Books section, access to Roentgen's original paper, "Eine neue Art von Strahlen." For those who don't read German, a translation ("On a new kind of x-rays") is provided here by the Indian Academy of Sciences.
Radiograph taken by Wilhelm Roentgen on December 22, 1895, of the hand of his wife.
A lot more obscure than the "seven-fourteen" slang for Quaalude, "420," as a code for Mary Jane, is exhaustively mined by Ryan Grim of the HuffPo. (And God help me, I'm linking to the HuffPo).
HT: KPB, my (what else) college roommate.
Photo of growing marijuana plant from the Department of Justice.
King Tut was buried in his condo made of stone-a after succumbing to the severest form of malaria, malaria tropica, say preeminent medical archaeologists in this week's JAMA. The boy king also had a form of osteochondrosis—namely, avascular necrosis of the second and third metatarsal bones (in the foot). The bone disease, which probably caused limping, explains the afterlife canes placed in Tut's tomb.
The conclusions about Tut's medical problems were made on the basis of an unprecedented combination of anthropologic, genetic, and radiologic studies and free access to the mummified remains of Tut and those of other Egyptian royalty. The researchers propose that the immediate cause of Tut's death was likely a leg fracture (possibly from a fall), which precipitated a series of life-threatening events in the already medically compromised teenager.
Crashing the curiosity party, U Michigan's Howard Markel raises the sticky issue of ethics when conducting medical examinations on historical subjects in an accompanying JAMA editorial. "Are major historical figures entitled to the same privacy rules that private citizens enjoy even after death?" he asks. While Markel acknowledges, "All historians are guilty of enjoying reading the mail and personal materials of others," he advises,
[B]efore disturbing the dead with the penetrating wonders of 21st-century medical science, it is essential to follow the lead of these authors by pondering all the ethical implications of such inquiries to avoid opening a historical Pandora's box.
Steve Martin, who wrote that Tut "gave his life for tourism," would probably concur.
Photo of banner advertising the 2008 tour of Tut's tomb artifacts from http://www.atlantaga.gov/media/citynewsbytes_040808.aspx.
While film director Roman Polanski fights extradition to the United States, time is taken here to remember Quaalude—the drug that a 43-year-old Polanski allegedly gave to a 13-year-old girl before he had sex with her in 1977.*
Quaalude is the trade name for methaqualone, a chemical developed in the 1950s in India as an antimalarial compound. Contemporaneous data also indicated that the drug provided "good hypnotic activity" and had "low toxicity" when compared with widely used barbiturate sedatives. Consequently, during the 1960s, the drug became a popular prescription alternative to potentially addictive agents like secobarbital (Seconal; Eli Lilly) for the treatment of insomnia.
In the United States, the drug was first sold by Pennsylvania-based William H. Rorer, Inc, which applied the trademark Quaalude to its tablets in 1965. The company incorporated the double-a into the brand name as a way of capitalizing on the success of its antiacid product, Maalox (which is now owned by Novartis Consumer Health). The recommended therapeutic dosage for Quaalude was 150 or 300 mg.
Reports of physiologic addiction to and overdose of methaqualone were published repeatedly in the medical literature, beginning in the late 1960s (for example, here and here). Among Americans, abuse of Quaalude exploded during the 1970s, especially among young adults and teens—who often combined the drug with alcohol for a really soporific buzz. The activity was known as "luding out." The drug also gained a word-of-mouth reputation as an aphrodisiac and enhancer of sexual pleasure (eg, "The Love Drug" or "Heroin for Lovers"); although these effects were overstated, if not outrightly made up. As one young user described her Quaalude experience to the Washington Post in 1978: "I fell asleep."
With the rise of its legitimate and recreational popularity, the unpatented methaqualone was also legally manufactured in the United States by Anar-Stone Laboratories, which called its capsule Sopor (in 75-, 150-, and 300-mg doses). Other American manufacturers of methaqualone compounds included Parke-Davis (Parest) and Wallace (Optimil).
A 1972 Chicago Tribune report ("A Sedative Gains in Drug Culture") indicated that the street cost of methaqualone was 25 or 50 cents per pill. Slang names for the drug included "Rorers" and "seven-fourteens." These terms were derived from the stamp on the branded Quaalude tablet, "Rorer 714." In her grand jury testimony, Polanski's 13-year-old victim reported that the director gave her part of a tablet (dose unknown) that had "Rorer 714" on it.**
According to a 2006 "Frontline" report, high methaqualone demand in the United States was supplied not only by drug firms, but through rogue domestic labs and counterfeit South American operations. In 1981, recreational use of methaqualone was so widespread that it ranked second to marijuana in popularity. The DEA estimated that 80%-90% of the world's methaqualone production was diverted to the illegal drug business. (The DoJ cites the emergence of "stress clinics" in New York, New Jersey, and Florida—essentially B&M equivalents of today's dubious online pharmacies—for the boost of methaqualone abuse in the early 1980s.)
"Frontline" credits the DEA's Gene Haislip with shutting down the illicit methaqualone business in the United States. Haislip successfully convinced foreign manufacturers of the methaqualone powder and their resident countries to stop production. And without the powder, South American producers, like those in Colombia, could no longer pound out pills for export. Simultaneously US physicians began prescribing other hypnotics as sleep aids, and law enforcement shut down the stress clinics. Then in 1984, federal legislation banned the domestic production and sale of methaqualone; in other words, the compound was designated a Schedule I drug.
South Africa is the current hotbed of methaqualone abuse. There the drug is consumed in the form of Mandrax (which combines 250 mg of methaqualone with 25 mg of diphenhydramine). The tablet is typically crushed and snorted or smoked with cannibis.
* Polanski also allegedly plied the girl with champagne. For relevant court records, including Polanski's contemporaneous guilty plea to having sex with a minor, start at thesmokinggun.com.
** Rorer 714 t-shirts were a popular counterculture item.
Image of methaqualone pills attributed to Indiana Prevention Resource Center.
While drugmakers create a vaccine against the currently pandemic swine-flu virus (H1N1 S-OIV 2009), neurologists are advised to monitor the safety of such inoculations, should they be implemented. The caution is founded on a higher-than-expected rate of Guillain-Barre syndrome (GBS) in vaccine recipients during the 1976 immunization campaign against swine flu, reports Neurology Today.
More than 30 years ago, soldiers at Fort Dix, New Jersey, experienced an outbreak of swine flu. Fearing a recurrence of the 1918 influenza epidemic, US government officials implemented a widespread vaccine campaign in which more than 40 million Americans were immunized. However, the drive was aborted after 3 months when reports of GBS in vaccinated individuals emerged. Although GBS surveillance data for the time period are sketchy, evidence suggests that vaccine recipients were significantly more likely to develop the condition within several weeks after inoculation.*
At present, leading neurologists do not anticipate a government-led vaccine campaign against H1N1 S-OIV 2009, given the low mortality rate (0.5%) of the current swine-flu pandemic and the historical risk of GBS with inoculation.
* The typical background rate of GBS is about 1.5 per 100,000 individuals.
[Beat.] How old is it?
Human remains in Rajasthan, India (24°43'N 73°59'E) provide the oldest known evidence of infection with leprosy. Anthropologists from North Carolina and India describe tell-tale signs of bone pathology, consistent with the infection, in a 4000-year-old male skeleton uncovered about 40 km northeast of Udaipur. Findings unearthed at the site of the large Copper Age settlement are described in the latest issue of PLoS One.
The investigators describe widespread evidence for leprosy throughout the bones, including changes in the remarkably intact skull. Findings there are consistent with the characteristic rhinomaxillary syndrome (or leonine facies) of lepromatous leprosy (for an example, see Fig. 1 at link). Other possible infectious causes, like syphilis, leishmaniasis, and TB, were ruled out by the investigators, but additional data to support the conclusion of leprosy will be obtained from any recovered Mycobacterium DNA in the skeleton and geographically related bone collections. The oldest archeological evidence of leprosy, previous to this discovery, dated to the 1st millennium BC in Uzbekistan.
The authors claim that their skeletal remains support contemporaneous Sanskrit text in the Atharva Veda,* which described a plant treatment for leprosy.
Born by night art thou, O plant, dark, black, sable. Do thou, that art rich in colour, stain this leprosy, and the grey spots!...The leprosy which has originated in the bones, and that which has originated in the body and upon the skin, the white mark begotten of corruption, I have destroyed with my charm.
*Dating to the end of the 2nd millennium BC, according to Wikipedia.
Photograph of 4000-year-old skull shows various findings of bony erosion, remodeling, resorption, and necrosis, consistent with lepromatous leprosy.
