October 2011 Archives
A Halloween KBF by guest blogger KTG:Buried in the pile (some might say steaming pile) of campy horror flicks from the 1950s are a few lumpy gems—which, when compared with the rest of the genre, smell positively April fresh. Night of the Demon (1957), a British production, is one such notable exception: a psychological, supernatural thriller, redolent with genuinely creepy atmosphere.
Eminent American psychologist, Dr. John Holden (played by a seemingly unflappable Dana Andrews*), is summoned to a British conference, the intent of which is to debunk a local stanic cult. The coven's distinguished, goateed leader (real-life surgeon Niall MacGuinnis) spends his afternoons performing magic shows for underprivileged children while dressed as a clown**; but the devilish character has a few real tricks up his sleeve, one of which marks Dr. Holden for death in 72 hours at the hands of a hideous hell-beast—an unholy cross between South Park's ManBearPig, the Statue of Liberty, and a flying monkey. Admittedly that description sounds like an unintentional comic misstep, and there are a few in Night of the Demon; but the movie generally prevails with several great frights (one of which features a truly disturbing defenestration), a satisfyingly grisly death, and a chilling final shot.
Boo.
* Despite a role that screams, "DOWNWARD CAREER SPIRAL."
** Confirming once again: Clowns are scary.
Title shot from Night of the Demon, with some kind of creepy font.
From this week's issue of Neurology.Using MR venography and ultrasound* in 40 patients with MS, German investigators failed to replicate the 100% prevalence of chronic cerebrospinal venous insufficiency (CCSVI) defined famously (and notoriously) by Zamboni et al in 2009 (for background, start here or search Pathophilia for "Zamboni"). This newly published study, by the authors' account, is at least the 13th study** that has failed to validate Zamboni's theory of venous insufficiency in MS and his follow-up idea that the stenting of cerebral veins (ostensibly to improve the egress of iron) could be somehow objectively clinically beneficial.
Here's the parade of negative studies cited by the German authors (Doepp et al); 11 of these studies have been published in English-language peer-reviewed journals (all of which are reasonably well regarded).
Ultrasound studies
- Doepp F, Paul F, Valdueza JM, Schmierer K, Schreiber SJ. No cerebrocervical venous congestion in patients with multiple sclerosis. Ann Neurol. 2010;68:173-183.
- Baracchini C, Perini P, Calabrese M, Causin F, Rinaldi F, Gallo P. No evidence of chronic cerebrospinal venous insufficiency at multiple sclerosis onset. Ann Neurol. 2011;69:90-99.
- Krogias C, Schroeder A, Wiendl H, Hohlfeld R, Gold R. "Chronic cerebrospinal venous insufficiency" and multiple sclerosis: critical analysis and first observation in an unselected cohort of MS patients. Nervenarzt.
- 2010;81:740-746. (article in German)
- Mayer CA, Pfeilschifter W, Lorenz MW, et al. The perfect crime? CCSVI not leaving a trace in MS. J Neurol Neurosurg Psychiatry. 2011;82:436-440.
- Centonze D, Floris R, Stefanini M, et al. Proposed CCSVI criteria do not predict MS risk nor MS severity. Ann Neurol. 2011;70:52-59.
- Sundstroem P, Wåhlin A, Ambarki K, Birgander R, Eklund A, Malm J. Venous and cerebrospinal fluid flow in multiple sclerosis: a case control study. Ann Neurol. 2010;68:255-259.
- Wattjes M, van Oosten BW, de Graaf WL, et al. No association of abnormal cranial venous drainage with multiple sclerosis: a magnetic resonance venography and flow-quantification study. J Neurol Neurosurg Psychiatry. 2011;82:429-435.
- Zivadinov R, Lopez-Soriano A, Weinstock-Guttman B, et al. Use of MR venography for characterization of the extracranial venous system in patients with multiple sclerosis and healthy control subjects. Radiology. 2011;258-562-570.
Measurement of intraocular venous pressure
Measurement of CSF ferritin levels
* Specifically dynamic extracranial color-coded duplex sonography (ECCS).
** The cited studies do not include the essentially negative ultrasound study from the University of Buffalo, which was recently published in April in Neurology. Consequently the peer-reviewed tally comes to 14 negative studies.
Image of neck veins from Gray's Anatomy (1918).
From a number of sources on Abbott's announcement yesterday to split off its brand-name pharmaceutical business:The Chicago Sun-Times swallows the PR version.
Forbes's Matthew Herper rationalizes the company split in relatively comprehensive fashion (for a blog, anyway).
Derek Lowe appears on target (as usual) about what biz folks think of the biz of brand-name drugs (not much).
And the In Vivo blog asks what the name of the currently unnamed split-off should be (most online wags favor "Costello").
The fact that the Abbott name stays with the medical-device/baby-formula/generic-drug company, and that eternal CEO Miles White stays with "Abbott" speaks volumes about whatever confidence, or lack thereof, folks at Abbott (or anywhere else, for that matter) have in the future of prescription brand-name pharmaceuticals.
Abbott's (or Costello's?) far-and-away leading revenue generator has been Humira, a TNF inhibitor for rheumatoid arthritis and Crohn's disease with $6.5 billion in annual sales. But Humira's got growing competition, and Abbott doesn't have a particularly robust product list or pipeline (despite what Abbott would like potential buyers to believe). That said, any shoppers interested in diversifying their brand-name portfolio (Merck, Roche, or Bayer AG, according to Bloomberg) will essentially be buying the right to profit off of Humira sales...for as long as they last.
For whatever reason, The Street really dug yesterday's announcement.
By way of Pharmalot:Cheng Yi Liang, 57, pleaded guilty yesterday to securities fraud and "making a false statement," after the SEC charged the former FDA chemist in March with insider trading (for background, go here). The maximum sentence for the first count is a 20-year prison term followed by a 5-year supervised release and a fine of $5 million. For count two, Liang could be imprisoned for 5 years and fined $250,000. An alternative fine could also be ordered for Liang, the plea agreement indicates: twice his gross gain or loss—or about $7.5 million by my calculation. A guilty plea also may endanger his immigration status (it is not stated in the agreement what Liang's immigration status is, however).
The plea agreement also argues that Liang's offenses are especially egregious because of the amount of money he earned through insider knowledge, the "sophisticated means" by which he earned it, and the fact that he was in a "position of public trust" as an FDA employee. Liang has evidently agreed to forfeit his $3,776,152 in gains through his TDAmeritrade and other accounts, as well as some vital real estate (eg, his residence in Gaithersburg, Maryland, and the home of his son, "A. L.").
Pharmalot also reports that Cheng Yi Liang's son, Andrew Liang, pleaded guilty last month to one count of possessing child pornography (yeesh), which was discovered in the government's investigation.
It's still not clear what tipped off the feds to the elder Liang's trading activities, but Derek Lowe's original thought about the profits Liang realized from the surprise approval of the antipsychotic iloperidone (Fanapt; Vanda Pharmaceuticals) remains highly plausible.
Lolita (1962): The Kubrick-directed version of Nabokov's creepy, absurd, and supremely sad first-person account of the fictional Humbert Humbert—a comically caustic and acutely observant pedophile. Contemporary promotion for the movie asked, "How did they ever make a movie of Lolita?" and the answer is with a lot of innuendo (thank God). A related question is, "How did they make an enduring movie of Lolita?" and the answer here lies in Kubrick's relatively understated directorial hand, coupled with Nabokov's deft screenplay and bull's-eye casting. I can hardly imagine any other actors—James Mason (Humbert), Sue Lyon (Dolores Haze, aka Lolita), and Shelley Winters (Charlotte Haze, Lolita's mother)—as the three primary leads. (And nobody has a harder lock than Winters on the whining, emotionally needy woman.) The only conspicuous, and therefore detracting, performance is that of Peter Sellers. Riffing on his farcical skills, Sellers here plays Humbert's nemesis, the hip-kinky Clare Quilty, with an incongruous tone.
There are journalistic programs in which we (I) place more credit than others—possibly owing to their style, possibly owing to their length and supposed care with a subject, and possibly owing to the fact that they air on the Public Broadcasting System. "Frontline" is one such show. However, credit afforded to news programs can be easily and permanently eroded when they showcase a subject of which we (I) know something about—like medicine—and present a terribly biased or outrightly incorrect view of an issue. This is presumably done for the sake of generating controversy and attention (irresponsibly) or, I can only guess, because the show's producers are lazy or stupid or both.
Last evening, "Frontline" aired a documentary of the FBI's investigation of the so-called anthrax attacks of 2001, a subject of which I know something about, at least on an amateur basis. The program, "The Anthrax Files," was heavily informed, it appears, by input from ProPublica, an amorphous collection of "independent" journalists, that partners with all sorts of more tangible news organizations like "60 Minutes"* and NPR. And from ProPublica, the format and theme of the program—that being, that USAMRIID scientist Bruce Ivins was not the perpetrator of the anthrax attacks—were heavily informed by ProPublica's curiously perpetually suited managing editor Stephen Engelberg.
As a recurrent talking head, Engelberg heavily insinuates in his program (and it really does appear to be his program) that Bruce Ivins was not the anthrax killer by first laying out the case of Steven Hatfill. Hatfill, an American physician and virologist, was the FBI's prime initial suspect as the anthrax killer, circa 2002, and the agency basically hounded the guy (for a number of reasons that are not explained in the "Frontline" program) to no success. Engelberg's prelude on Hatfill provides the basis for later suggesting that the FBI pushed another hapless suspect, Bruce Ivins, who was much more mentally brittle than Hatfill, to suicide when the agency pursued the USAMRIID scientist in the same harassing way as it did Hatfill. In other words, according to Engelberg, Ivins didn't commit suicide out of guilt of being the anthrax killer or fear of rightful criminal prosecution, but because the FBI drove him to it.
But here Engelberg's journalistic transgression is one of serious omission. Namely Engelberg utterly fails (and I can only conclude that he intentionally utterly fails) to include essential information from a 2009 court-authorized psychological review of Bruce Ivins. From this review, a 9-member panel concluded in March that "Dr. Ivins was psychologically disposed to undertake the mailings; his behavioral history demonstrated his potential for carrying them out; and he had the motivation and the means." So why wouldn't Engelberg include this important psychological review of Ivins in the "Frontline" program? The answer: Because it gets in the way of his controversy- and attention-generating themes—namely that Ivins wasn't the anthrax killer, and the FBI is an incompetent and/or pernicious government institution.
Engelberg also attempts to undermine the FBI's scientific evidence pointing to the "smoking gun" RMR-1029 flask at USAMRIID (for background on this flask, start here), over which Ivins had control. To my understanding, there were 16 domestic labs that had the RMR-1029 strain before the 2001 anthrax attacks; however, only one of these labs was located where the "federal eagle" envelopes (which were used in the attacks) were distributed and sold (in Maryland and Virginia). And this was the USAMRIID RMR-1029 flask over which Ivins had control. Engelberg completely fails (and again, I can only conclude that he intentionally fails) to provide the information about the envelopes in his "Frontline" program. The fact that the scientific evidence (meaning the genetic evidence implicating RMR-1029) does not solely support the fingering of Ivins is nothing new. It is the confluence of the 2 vital pieces of information—the genetic identification of RMR-1029 and the location of the envelope purchase that points to Ivins.
Engelberg also attempts to erode the FBI's allegations that 1) Ivins worked alone in lengthy late-night shifts during September 14-16, 2001, and from September 28 to October 5, 2001, before the rounds of the NY Post/Brokow and Leahy/Daschle letters were respectively mailed, and 2) Ivins, in highly disingenuous fashion, submitted "unusable" and false B. anthracis spores to the FBI for testing. Engelberg's attempted correction of the FBI's graph of Ivins's late-night hours during the fall of 2001, although less impressive than the FBI's original graph, still reveals a spike in Ivins's work hours during the time in question. And Engelberg doesn't negate the fact that Ivins submitted an unusable sample of B. anthracis to the FBI, but that Ivins also submitted at least 2 workable samples to the agency at some point during their investigation.** Last Engelberg fails to include any information about the 2002 contamination of Ivins's laboratory with B. anthracis spores, outside of the proper containment facility, and Ivins's failure to report the incident.
Whatever easy agenda Engelberg is pushing to some receptive sector of the American population in "The Anthrax Files" (the FBI is a terrible organization—?), it is, in the case of the anthrax attacks and Bruce Ivins, nothing other than irresponsible and, in my view, only serves to undermine the credibility of ProPublica and "Frontline."
* Speaking of a news program in which we (I) have no confidence.
** Apparently because he had no choice but to do so.
Public domain photograph of Daschle "anthrax" letter from Wikipedia.
This week's NEJM provides a useful barometer article, including a neato graphic timeline, on the litigation status of [PP]ACA ("Not So Fast—Jusisdictional Barriers to the ACA Litigation"). Thanks, Mssrs Jost and Hall.
Their salient points:
ACA = Affordable Care Act.
* Haven't heard that one yet.
** For scorekeepers: 1, it's constitutional; 1, it's unconstitutional; 4, no jurisdiction; 1, decision pending.
Their salient points:
- So far, ~30 lawsuits have been filed against the ACA.
- A Supremes' decision in June 2012 is likely, given the admin's petition for their review on September 28.
- The jurisdictional issues generally, which are somewhat intertwined, rest on one of the following:
- Whether Congress exceeded its constitutional authority when imposing the individual mandate to purchase insurance.
- Whether state or individual plaintiffs have standing when challenging the ACA—particularly, in the latter case, before the "meat" of the ACA (eg, the individual mandate) goes into effect in 2014.
- Whether grievances are sufficiently ripe—meaning whether cases have been filed prematurely (before the "meat" of the ACA goes into effect in 2014).
- Whether the fine for not purchasing insurance is a penalty or tax or something else altogether (eg, an "exaction"*) and whether the label really makes any difference (the answer: it seems to; in fact, maybe big time).
ACA = Affordable Care Act.
* Haven't heard that one yet.
** For scorekeepers: 1, it's constitutional; 1, it's unconstitutional; 4, no jurisdiction; 1, decision pending.
As demonstrated by grad student Abbie Smith at her ERV blog.
Smith's post heard 'round the Web—which is a major, career-devasting bust to researcher Judy Mikovits—shows how Mikovits clearly used the same Western blot data to describe two different experiments, both of which made the now highly dubious link between XMRV and chronic fatigue syndrome.
Although Smith acknowledges that she was not the first to recognize the identical nature of Mikovits's Western blot images (one of which was published in Science in 2009 and the other of which was presented at a recent conference in Ottawa), she should get credit for the worldwide disclosure.
Snap.
Smith's post heard 'round the Web—which is a major, career-devasting bust to researcher Judy Mikovits—shows how Mikovits clearly used the same Western blot data to describe two different experiments, both of which made the now highly dubious link between XMRV and chronic fatigue syndrome.
Although Smith acknowledges that she was not the first to recognize the identical nature of Mikovits's Western blot images (one of which was published in Science in 2009 and the other of which was presented at a recent conference in Ottawa), she should get credit for the worldwide disclosure.
Snap.
