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Sources are now implicating propofol (Diprivan; sanofi-aventis) in Michael Jackson's death. TMZ reports that police recovered the anesthesia inducer at Jackson's rented home. And ABC News interviewed Jackson's nutritionist, Cherilyn Lee, who stated that the singer asked her for Diprivan, by trade name, 3 months ago. Jackson's alleged intention, bizarre as it may sound, was to be put to sleep at home under the guidance of an anesthesiologist.
In use for more than 2 decades, Diprivan is a rapidly acting (within 40 seconds) IV sedative-hypnotic that is FDA approved for the induction and maintenance of anesthesia and for sedation in an intensive care unit (in both cases, patients are mechanically ventilated). According to the prescribing information, the induction dosage for ICU sedation begins at 5 microg/kg/min and should be titrated (by increments of 5-10 microg/kg/min) to the desired clinical effect. Maintenance rates are generally 5-50 microg/kg/min or higher for adults.*
For anesthesia induction, the typical dosage is 40 mg every 10 seconds in healthy adults younger than 55 years of age; maintenance of anesthesia can be achieved by intermittent boluses of 20-50 mg. However, slow infusion or injection techniques are recommended to avoid apnea and hypotension. Diprivan dosages should be reduced in patients who have received large doses of narcotics.
Common adverse events with Diprivan use include bradycardia or other arrhythmias, hypotension, and apnea. Burning pain or stinging at the injection site, which is also common, may be reduced by preinjecting the vein with a 1% lidocaine solution (1 mL).
Subanesthetic doses of Diprivan may have the potential for abuse by inducing euphoria. Diprivan's abuse potential is particularly high among physicians who have access to the drug—namely, anesthesiologists. An e-mail survey in 2007 indicated that Diprivan abuse has increased substantially in academic anesthesia departments during the last 10 years. Among the 25 reported abusers in the survey, 16 (64%) were resident physicians. Seven (28%) abusers died; 6 of the deceased were resident physicians. In academic centers where abuse occurred, none had established pharmacy protocols to account for the drug (as is done routinely with opiate medications).
In 2008, an anesthesia nurse was convicted of killing a University of Florida student, with whom he was infatuated, by injecting her with propofol in her home. The victim's propofol blood level was 4.3 microg/mL. The expected propofol concentration after a bolus induction dose of 2.5 mg/kg (175 mg for a 70-kg man) is 1.3-6.8 microg/mL.
If a vial or vials of Diprivan were indeed recovered from Jackson's home, it seems almost certain that the medication was palmed by someone who had access, rather than formally prescribed.
Addendum: It also appears that Diprivan can be purchased through online pharmacies. For instance, drugdelivery.ca offers a 50-mL prefilled syringe for $122.99 USD. The completion of a patient questionnaire is necessary (along with payment); it is not clear that a valid prescription is required.
* So for a 70-kg man (~154 lbs), 0.35 mg/min would be administered for induction, and the maintenance dosage ranges from 0.35 to 3.5 mg/min. Vials of Diprivan contain 10 mg/mL and come in 20-, 50-, and 100-mL vials.
Image of Diprivan formulations from APP.
07/04/09 update: Yesterday the AP, citing an anonymous law enforcement official, confirmed that Diprivan was found in Jackson's rented home. CNN also reported that Neil Ratner, an anesthesiologist, traveled with Jackson during his HIStory tour in the mid-90s. Ratner's NY medical license was suspended in 2002 after being convicted of insurance fraud.
In late October 1937, gossip columnist Louella Parsons revealed that both Warner Brothers and film executive B. P. Schulberg were in preproduction stages for 2 separate films that would dramatize the "shocking elixir deaths" [1].
Warner Brothers had bought the rights to the muckracking novel of investigative journalist Samuel Hopkins Adams, The Clarion. The book, published in 1914, was an expose of the fraudulent advertising of patent medicines. Screenwriters would incorporate the recent elixir-related deaths into the film, Parsons reported, which was to star Dick Foran (The Petrified Forest) and newcomer Ann Sheridan as the "romantic leads." The working title for Schulberg's production was Permit to Kill, with Edward Arnold (Diamond Jim) in a starring role.
Although the New York Times reported later that the Warner Brothers film title was changed to One Hundred Million Suckers, with a screenplay by Larry Kimble and Ring Lardner, Jr., neither film appears to have made it to production [2].
The elixir-related deaths were conveyed in nonprint media through NBC's radio broadcast of The National Farm and Home Hour, which was produced by the US Department of Agriculture, and William Randolph Hearst's "News of the Day"* newsreel, which was shown contemporaneously in movie theaters [3,4]. While attending the cinema in Flushing, New York, a pleasantly surprised FDA chemist praised the well-conceived "dramatic presentation" and the "clear and distinct voice" of FDA chief Walter G. Campbell in a letter to the FDA's New York station. The chemist described the production's scenes from memory:
I. S. E. Massengill's plant.
II. Dr. Calhoun [of Mt. Olive, Mississippi] (?) one of the physicians that had prescribed the Elixir, and a nurse who had taken some of the Elixir but was still alive.
III. The laboratory of the American Medical Association at Chicago, showing a chemist working on a distillation apparatus and then holding in a graduate some of the distillate which was described as being the deadly ingredient.
IV. The same A.M.A. laboratory protraying[sic] a chemist using a Spectrographic apparatus.
V. Mr. Campbell's office door.
VI. Scene showing Mr. Campbell picking up a phone, and instructing all agents to immediately stop all other work and to concentrate on location the Elixir, to be seized wherever found. In this scene Mr. Campbell did the talking rather than the commentator.
* Released by Metro-Goldwyn-Mayer.
1. Parsons L. Ford will direct Haycox in new film for Sam Goldwyn. Modesto Bee and News-Herald. October 31, 1937.
2. Screen news here and in Hollywood. New York Times. March 18, 1938; p 23.
3. FDA correspondence. Letter from W. G. Campbell to Chief, Central District. January 31, 1938.
4. FDA correspondence. Letter from D. M. Walsh to Chief, New York Station. October 29, 1937.
Public domain screenshot of Ann Sheridan from Wikipedia.
Pathophilia's Top 10 Medical Stories of 2008: A Recap
10. Gunvalson v. PTC Therapeutics
9. California v. Roozrokh and Cardiac-Death Organ Donation
8. Hand, Foot, and Mouth Disease in China
7. Continuing Backlash Against Pharma
6. Media Obsession With Delayed Results of ENHANCE Trial
5. Investigational Drugs for Alzheimer's Disease Disappoint
4. Milder Rotavirus Season Coincides With Vaccine Uptake
3. USAMRIID Scientist Identified as Sole Perpetrator of "Anthrax Letter Attacks"
1. Intentional Drug and Food Tampering in China
Other notable stories of 2008 that didn't make Pathophilia's totally arbitrary list:
- More cases of progressive multifocal leukoencephalopathy (PML) with Tysabri (natalizumab) use
- Pig-slaughter neuropathy
- US government compensates Poling family for vaccine-related autism
- Ted Kennedy diagnosed with glioblastoma multiforme
If anyone doubted the intellectual limits of Jenny McCarthy, the Weiners actress, here's unmitigated proof.
In response to Amanda Peet's characterization of antivax parents as "parasites" (which is not a far-off description), McCarthy—a supporting actress in Larry the Cable Guy's Witless Protection—tells Spectrum magazine, "I am so proud to be a parasite."
In all mustered graciousness, maybe McCarthy, featured in the straight-to-video Python, got "parasite" confused with "paragon"? Paralegal? Pair of shoes?
In any case, the same smarts that led McCarthy to accept a starring role in Dirty Love has evidently resulted in an embarrassingly limited vocabulary. Perhaps Jim Carrey will pull aside his girlfriend, who bumped boobs with Pam Anderson in Scary Movie 3, and whisper something corrective in her ear. Or maybe not. After all, he delivered that tin-ear you're-getting-on-my-nerves-like-Robin-Williams performance in Horton Hears a Who!
Peet evidently apologized for using the word "parasites" to describe antivax parents. But why is an apology necessary to someone like McCarthy, a cast member of the Untitled Patricia Heaton Project, when she views the characterization as favorable? Or maybe McCarthy (aka Yvette Denslow in BASEketball) is confused about the meaning of "proud."
Autism's False Prophets: Bad Science, Risky Medicine, and the Search for a Cure
By Paul A. Offit
328 pages
If anybody thinks Paul Offit, infectious-disease specialist at one of the nation's best pediatric hospitals, overstates the physical threats he gets from antivaccinationists, here's a sobering rebuttal: There will be no book tour for Autism's False Prophets, Offit's plain-speaking chronicle of how vaccinations have been erroneously implicated in the rise of autism. The security risk is just too high says the book's publisher, Columbia University Press.
Paul Offit has become the medical equivalent of Salman Rushdie (who went into hiding after the publication of The Satanic Verses, which prompted a fatwa from the Ayatollah Khomeini). And it's not a bad analogy, given the blind faith practiced by those who thoughtlessly adhere to and profit from, against all credible scientific evidence, the idea that vaccines are somehow responsible for a neuropsychiatric condition that is so poorly understood.
In the book's prologue, Offit—who holds a patent on a rotavirus vaccine and who vocally advocates for vaccinations in general—reveals that he gets a lot of hate mail, some of it with religious overtones. One correspondent asked, "Why did you sell your soul to the devil?" and another prays "that the love of Christ will one day flood [his] darkened heart." Offit has also received gruesome death threats ("I will hang you by your neck until you are dead!") and non-too-subtle threats toward his children. But Offit's book, most importantly, is not about Offit.
Autism's False Prophets is a systematic unpacking of the relatively short history of autism, its identification 70 years ago, its rise in frequency (which is primarily, if not exclusively, due to increased recognition), and its broad manifestations, which have driven some parents of severely affected children to the unthinkable. Other parents, desperate for treatment, have been sucked into trying one or more bogus therapies (for instance, facilitated communication), which have been hawked by one or more charlatans willing to fill the therapeutic void in allopathic medicine.
As Offit writes, some of these false prophets are credentialed; some have no medical training whatsoever. Many have been either implicitly or outrightly endorsed by the media and political figures, with no consequences for those who sow the unfounded and dangerous idea that vaccines cause autism. One of the most prominent false prophets, according to Offit, is English gastroenterologist Andrew Wakefield, who attempted to implicate the MMR vaccine as a cause of autism in the late 1990s. Wakefield's work, which received tremendous media attention, was largely funded by a personal-injury lawyer, reveals Offit, and was later discredited on charges of fraud. However, Wakefield's ideas on the dangers of the MMR vaccine contributed to England's recent measles epidemic, and astoundingly, the doctor still has his rabid supporters.
There is also the father-son duo of Mark and David Geier, who (along with others) implicate the vaccine preservative thimerosal as a cause of autism through work performed in their home-basement laboratory in Maryland. The Geiers, in particular, have migrated into shocking territory by advocating dangerous chelation therapy and chemical castration with leuprolide (Lupron; TAP) for autistic children. Offit writes how librarian and tenacious blogger Kathleen Seidel, whose child was diagnosed with a form of autism, has nearly single-handedly revealed the highly questionable nature of the Geiers' work.
Parents of autistic children, like Seidel, who refuse to neglect science or waste their time, energy, and money on unproven and far-fetched treatments, are the poorly credited heroes of the autism story. Offit reveals that he wrote Autism's False Prophets for them. However, the noise from opportunists has been cranked up by ignorant, but highly influential (and arguably financially conflicted), political figures—specifically US Congressman Dan Burton, whose grandchild was diagnosed with autism, and tort lawyer Robert F. Kennedy, Jr., a vocal proponent of the idea that thimerosal causes autism. Public figures like Burton and Kennedy have essentially ignored the series of epidemiologic studies that have exonerated vaccines as the cause of autism, mindlessly asserting that the issue should be settled in the public, instead of scientific, arena. Consequently they divert attention and funding away from credible research into the causes of autism and its treatment.
At play in this mess, Offit soundly argues, is the media's undying hunger for controversy. The idea that vaccines don't cause autism, although true and of vital public interest, isn't particularly provocative. The story's would-be title would mimic a banal headline from the parody newspaper The Onion. Moreover, science itself, which many consumers find terribly dry, isn't easily conveyed in sound bites. Case in point is the appearance of IOM president Harvey Fineberg on "Meet the Press," when he found himself contending on air (in a show of journalistic "balance") with media-savvy writer David Kirby, author of the vaccine-maligning Evidence of Harm. And if "Meet the Press" can't be counted on to provide sound information, little can be expected of Oprah.
For readers who don't believe that science is a yelling contest, the events in Autism's False Prophets—events in which self-interested figures ride roughshod all over medical evidence—will anger. Nevertheless, it is this justifiable anger that can mobilize investigations away from life-saving vaccines and onto the very elusive causes of autism.
Asked on behalf of mothers everywhere, given Michael Phelps's crazy calorie consumption.
HT: NY Post by way of the WSJ Health Blog and every other conceivable media outlet.
The longstanding answer to inactivity in the city kid is now an official, judged sport in NYC schools, writes the AP.
A video segment of the 2006 Double Dutch Holiday Classic at the Apollo Theater: The Harlem crowd reacts with lovable honesty to a Japan team's Best in Show win.
This may be merely an example of water seeking its own level, but World Wrestling Entertainment and Jenny McCarthy will be getting together next month on prime-time network TV* to support Generation Rescue, an organization which promotes the unfounded (and dangerous) idea that "toxins" in vaccines produce autism and other neuropsychiatric disorders in children.
I suspect between choreographed body slams, there will be no discussion of the hazards of anabolic steroids.
* NBC, to be exact.
