August 2011 Archives
A Presidential commission, charged with investigating the US-funded VD experiments on Guatemalan prisoners and mental patients in the mid-1940s, revealed some of its shocking findings this week to the press (for background on this story, start here). The experiments, performed without subjects' consent, were discovered and reported by a Wellesley medical historian, Susan Reverby, last fall, and President Obama shortly thereafter apologized to the Guatemalan government for the unethical studies and ordered a commission to investigate them.
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:
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.
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.
However, I urge closed captioning or subtitles (which are not available through my Netflix streaming device) if you want any chance of understanding Poldark's interminably drunken servant, Jud Paynter, or of catching any dialog when an actor turns away from an overhead mic.
* Series 1.
A peculiar kind of living agony must be had by those who are diagnosed with psyche-robbing disorders, like Alzheimer's disease, while they remain aware that they're being robbed of whatever makes them them. A recent case in point is that of Pat Summitt, legendary coach of the UT women's basketball team, who was recently diagnosed with early-onset AD.In this Washington Post clip (along with a funny and moving write-up by the coach's friend and the coauthor of Summitt's 1999 autobiography), there are subtle, but definite, halts in Summitt's speech that hint at her early, mental disability—which troubled family (primarily her incredibly stalwart son), friends, and UT colleagues early on and ultimately brought Summitt to the attention of physicians at the Mayo Clinic—where she received her diagnosis 3 months ago.
Photo of Summitt on one of many of her days of basketball victory; from the UT website.
What goes around certainly comes around on the web (or Facebook [same difference]). The latest, at least in my web-based microcosm, is a 1-year-old reference to a 2010 article from Neurosurgery, in which a couple of eggheads from Johns Hopkins argued their case for hidden neuroanatomy in Michaelangelo's Sistine Chapel paintings.
What the JH authors* are receiving implied credit for, though, in online posts and forums (see here, for example) is a compelling proposal that a sagittal view of the brain, complete with brainstem and vertebral artery, surrounds God in the Creation of Adam (above). But that argument was originally made (and the JH authors did acknowledge this in their 2010 Neurosurgery article) by Meshberger way back in 1990 (An interpretation of Michelangelo's Creation of Adam based on neuroanatomy. JAMA. 1990;264:1837-1841).
What the JH authors proposed last year, riffing on the hidden-anatomy-in-Michelangelo's-painting theme, was a much more complex, ventral view of the brainstem in God's neck in The Separation of Light From Darkness (below). It's a less compelling argument, IMO, but one that remains plausible. Even less convincing, however, was their proposal that the artist embedded an image of the optic nerves in God's robe (read the free article to make your own judgment).
A popular, diverting hobby seems to be the hunt for hidden anatomic elements in Michelangelo's Sistine Chapel works (which is somewhat more highbrow than the hunt for horsies in clouds...but just somewhat). Eknoyan, a nephrologist at Baylor, argued in 2000 that the artist, who suffered with renal stones, surrounded God with a big kidney (not a brain) in the panel Separating Light From Darkness. (It may well be that God's environment is dependent on the medical specialty of the viewer.) And two Brazilian physicians, Barreto and Oliveira, have written an entire book (but in Portuguese) on hidden anatomy in Michelangelo''s work.
* One of whom has a joint appointment in the Department of Neurosurgery and the Department of Art as Applied to Medicine. (There's a department for that?)
What the JH authors* are receiving implied credit for, though, in online posts and forums (see here, for example) is a compelling proposal that a sagittal view of the brain, complete with brainstem and vertebral artery, surrounds God in the Creation of Adam (above). But that argument was originally made (and the JH authors did acknowledge this in their 2010 Neurosurgery article) by Meshberger way back in 1990 (An interpretation of Michelangelo's Creation of Adam based on neuroanatomy. JAMA. 1990;264:1837-1841). What the JH authors proposed last year, riffing on the hidden-anatomy-in-Michelangelo's-painting theme, was a much more complex, ventral view of the brainstem in God's neck in The Separation of Light From Darkness (below). It's a less compelling argument, IMO, but one that remains plausible. Even less convincing, however, was their proposal that the artist embedded an image of the optic nerves in God's robe (read the free article to make your own judgment).
A popular, diverting hobby seems to be the hunt for hidden anatomic elements in Michelangelo's Sistine Chapel works (which is somewhat more highbrow than the hunt for horsies in clouds...but just somewhat). Eknoyan, a nephrologist at Baylor, argued in 2000 that the artist, who suffered with renal stones, surrounded God with a big kidney (not a brain) in the panel Separating Light From Darkness. (It may well be that God's environment is dependent on the medical specialty of the viewer.) And two Brazilian physicians, Barreto and Oliveira, have written an entire book (but in Portuguese) on hidden anatomy in Michelangelo''s work.* One of whom has a joint appointment in the Department of Neurosurgery and the Department of Art as Applied to Medicine. (There's a department for that?)
Random Harvest (1942): A prime example of cinematic melodrama, with Greer Garson (Is there a lovelier star?) and Ronald Colman (Is there one more debonair?). As a shell-shocked WWI soldier, Colman loses, sort of regains, but then reloses major chunks of two highly disparate lives through traumatic amnesia. And while his brain remains broken and his existence is stubbornly compartmentalized, Garson is the common thread—attempting to mend the wounded veteran through tireless, selfless love. Aw, gee [sigh].
Most US physicians will be sued at some point during their medical career, says a newly published malpractice-claims study in the NEJM. And for those clinicians in high-risk specialties,* the chance of being sued by the age of 50 approaches 100%. That's sobering news for every physician, who already knew that the odds of a malpractice suit—whether frivolous or no—were high, but who maybe didn't know that they were THAT high.
The study results also, perhaps ironically, support a nihilistic attitude among practitioners, who maybe (maybe) would have been enthusiastic about measures to reduce the risk of a malpractice suit. But given the reported odds now, they might think Why bother?
The happier news from the study (at least from the physicians' and insurer's perspectives): A minority (22%) of malpractice claims lead to a payment.
The quasi-perplexing news: Higher payments aren't necessarily from more frequently sued docs. The average payout from neurosurgeons, $344,811, was substantially less than that from pediatricians, $520,924—despite the fact that a neurosurgeon is about 6 times more likely to be sued in a given year than a pediatrician.
* Surgical specialties, gastroenterology[?], ob-gyn.
The study results also, perhaps ironically, support a nihilistic attitude among practitioners, who maybe (maybe) would have been enthusiastic about measures to reduce the risk of a malpractice suit. But given the reported odds now, they might think Why bother?
The happier news from the study (at least from the physicians' and insurer's perspectives): A minority (22%) of malpractice claims lead to a payment.
The quasi-perplexing news: Higher payments aren't necessarily from more frequently sued docs. The average payout from neurosurgeons, $344,811, was substantially less than that from pediatricians, $520,924—despite the fact that a neurosurgeon is about 6 times more likely to be sued in a given year than a pediatrician.
* Surgical specialties, gastroenterology[?], ob-gyn.
Eight months after buying King Pharmaceuticals, in Bristol, Tennessee, for $3.6 billion, Pfizer announced on Wednesday that it's cutting 130 manufacturing and 16 logistics positions at its latest acquisition. The most recent job cuts, added to 117 job losses so far at the Bristol plant since Pfizer took over, may not seem like much on a national scale. But in a city of about 24,000, King was a significant and reliable employer. Pfizer says that 166 positions will remain "in place," which means that the uber drug firm plans to wipe out 60% of the Bristol plant's workforce.Pfizer's acquisition of King was intended to expand the former company's pain-med portfolio. Among two other analgesics (Avinza and the Flector Patch), King had launched Embeda in 2009. The drug was promoted as "the first approved opioid pain drug designed to discourage abuse"; although claims to this effect were questionable. In March, Pfizer recalled the drug because of "stability" problems.
Local TV news coverage on Wednesday,* which reported on the Pfizer job losses, also provided a cheery feature, in which the history of the Bristol plant was showcased. It was the original site of the S. E. Massengill Company, which was acquired by Beecham in 1971, which became SmithKline Beecham in 1989. King Pharmaceuticals began operations there in 1993.
The coda to the lighthearted TV coverage: "Dr. Samuel Massengill used to sit in his office at
night and smoke a big cigar. Some say you can still smell the smoke late
at night." There was absolutely no mention of the Elixir of Sulfanilamide tragedy of 1937—which understandably might have been off point, but was nevertheless a glaring omission.* I just so happened to be in the area on the day of Pfizer's announcement.
Photo of Pfizer's Bristol plant, taken August 10, 2011. (c) Barbara J. Martin.
Photo of Massengill's dilapidated mansion in Bristol, TN, taken August 10, 2011. (c) Barbara J. Martin.
08/15/11 update: According to the Bristol Historical Association, the current owner of the Massengill house has (evidently) not maintained the property but also refuses to sell it. The city has responded by issuing an ultimatum in which the house will be auctioned or demolished, and the house sits in a kind of realty limbo as of last week. The building is reportedly "sound and could be restored," so the city is interested in responsible buyers. I can attest that the historic hilltop neighborhood is lovely; the house, from the exterior anyway, looks like a money-pit mess. No, thank you. (Although friends suggest that, as an owner, I could thoroughly comb the house for old bottles of Elixir of Sulfanilamide.)
According to George Stone's Bristol (p 65), the "stately home" was constructed in 1910, and its foundation is made up of 2000-pound blocks (of what, I don't know). Zillow (for what that source is worth) estimates the property value at $282,700.
Today the WSJ provides a very high-level overview of the currently prevailing idea for meaningful Alzheimer's treatment: attack earlier. The conclusion is largely based on increasingly disappointing results of anti-amyloid drugs in development (from Pfizer/JNJ, Lilly, and BMS), which have been tested in established disease.
Some scientists speculate (and it's all speculation) that amyloid deposition in the brain may be most toxic before symptoms of clinical dementia appear, the WSJ notes. Others imply that follow-up tau-related deposits are the major instigator of brain damage. The WSJ cites one study, presented at the recent ICAD conference, in which there was little change in amyloid deposits among patients "progressing toward Alzheimer's" but "substantial changes in tau and brain volumes."
The quoted industry cheerleaders, who (understandably) remain tireless in their efforts to find uses for their companies' investigational anti-amyloid agents:
Howard Feldman, MD, BMS's vice president of global clinical research for neuroscience ("Earlier intervention will allow us to treat patients when they have much less disability and when it could still be possible to prevent or delay such [memory] losses");
Rachel Schindler, MD, Pfizer's executive director for Alzheimer's disease ("The growing evidence from biomarkers has led to a greater acceptance in the field of looking towards earlier treatment"); and
Eric Siemers, MD (right), senior medical director for Alzheimer's disease ("There's not quite a template,but there's a broad acknowledgment of how important [linking biomarkers to disease progression] is"). The Midwesterner—to his credit—has a very accessible, almost mild-mannered way of speaking, which is probably keeping some Lilly shareholders from running for the hills.
Some scientists speculate (and it's all speculation) that amyloid deposition in the brain may be most toxic before symptoms of clinical dementia appear, the WSJ notes. Others imply that follow-up tau-related deposits are the major instigator of brain damage. The WSJ cites one study, presented at the recent ICAD conference, in which there was little change in amyloid deposits among patients "progressing toward Alzheimer's" but "substantial changes in tau and brain volumes."
The quoted industry cheerleaders, who (understandably) remain tireless in their efforts to find uses for their companies' investigational anti-amyloid agents:
Howard Feldman, MD, BMS's vice president of global clinical research for neuroscience ("Earlier intervention will allow us to treat patients when they have much less disability and when it could still be possible to prevent or delay such [memory] losses");
Rachel Schindler, MD, Pfizer's executive director for Alzheimer's disease ("The growing evidence from biomarkers has led to a greater acceptance in the field of looking towards earlier treatment"); and
Eric Siemers, MD (right), senior medical director for Alzheimer's disease ("There's not quite a template,but there's a broad acknowledgment of how important [linking biomarkers to disease progression] is"). The Midwesterner—to his credit—has a very accessible, almost mild-mannered way of speaking, which is probably keeping some Lilly shareholders from running for the hills.
Laquinimod, Teva's investigational pill for multiple sclerosis, was no better than placebo for reducing relapses in a 2-year phase 3 study (BRAVO) of patients with relapsing-remitting disease. These initial trial results were provided yesterday by Teva in a press release, which also reported that laquinimod-treated patients had a greater burden of disease at baseline, as demonstrated by MR images. When this "imbalance" was corrected, hedged the company, significant reductions in the annualized relapse rate, disability progression, and loss of brain volume were realized.*
But no matter. Company share value dropped precipitously on the news, from about $46.50 to less than $42.50 (~9%), as of this post.
And despite this dismal outcome for the maker of Copaxone (the number-1-selling and most expensive self-injected MS drug in the world), Tevas says that it still plans to submit laquininod for FDA approval at some unspecified time. Claimed Teva's Group VP of Global Branded Products, Yitzhak Peterburg, somewhat disingenuously but expectedly, "We are encouraged by the overall outcomes achieved in the laquinimod Phase III clinical development program...Teva remains committed to the clinical development of laquinimod and is confident that the drug could provide a unique option for the treatment of multiple sclerosis."
Unlike fingolimod (Gilenya; Novartis), the only FDA-approved disease-modifying pill for the treatment of MS, laquinimod appears to exert its anti-inflammatory effects less specifically, through a variety of possible mechanisms. Maybe that fact has something to do with the phase 3 outcome. Who knows?
Other possible oral options for MS in late-phase development include teriflunomide (sanofi-aventis) and BG-12 (dimethyl fumarate; Biogen Idec). In June, Merck KGaA announced that it would cease development of its oral contender, cladribine.
* A separate arm evaluated once-weekly IM interferon beta (Avonex); however, the study was not powered to compare laquinimod with the injectable disease-modifying agent.
But no matter. Company share value dropped precipitously on the news, from about $46.50 to less than $42.50 (~9%), as of this post.
And despite this dismal outcome for the maker of Copaxone (the number-1-selling and most expensive self-injected MS drug in the world), Tevas says that it still plans to submit laquininod for FDA approval at some unspecified time. Claimed Teva's Group VP of Global Branded Products, Yitzhak Peterburg, somewhat disingenuously but expectedly, "We are encouraged by the overall outcomes achieved in the laquinimod Phase III clinical development program...Teva remains committed to the clinical development of laquinimod and is confident that the drug could provide a unique option for the treatment of multiple sclerosis."Unlike fingolimod (Gilenya; Novartis), the only FDA-approved disease-modifying pill for the treatment of MS, laquinimod appears to exert its anti-inflammatory effects less specifically, through a variety of possible mechanisms. Maybe that fact has something to do with the phase 3 outcome. Who knows?
Other possible oral options for MS in late-phase development include teriflunomide (sanofi-aventis) and BG-12 (dimethyl fumarate; Biogen Idec). In June, Merck KGaA announced that it would cease development of its oral contender, cladribine.
* A separate arm evaluated once-weekly IM interferon beta (Avonex); however, the study was not powered to compare laquinimod with the injectable disease-modifying agent.
