Sunday, June 18, 2006


Please note that Terra Sigillata has moved to (as of 9 June 2006) to Wordpress (as of 21 July 2010) to CENtral Science (as of 24 August 2010). Kindly update your bookmarks to the following URL:


This site will remain live for archival purposes but some classic posts will migrate over to the new site.

Thank you for your support of our mission to provide objective information on herbal dietary supplements and other therapeutic natural products.

Please continue to read us at:

Friday, June 09, 2006

The move to is live!

Well, dear readers, the time has come to close up this shop and move over to The new site went live today at noon EDT (1700 GMT) along with a snazzy new homepage and, count 'em, 25 new bloggers!

I am deeply indebted to all of your who have supported me here over the last six months and I'll close sometime over the weekend with a (hopefully) thoughtful thank-you post. So many of you have been instrumental in the success of our little blog that I want to give this last post some serious thought.

Until then, saunter over to the new and improved Terra Sigillata.

For those of you on your PDAs, the new URL is:

For those of you getting our RSS feed, the new feed is at: http://scienceblogs.terrasig/index.xml

This site will remain up indefinitely although I will slowly transfer some of the more classic and timeless posts over to the new blog at Sb. C'mon over, grab a beer or glass of wine, and kick the tires. I launched with an essay entitled, "A Sort of Homecoming."

Thursday, June 08, 2006

The 36th Skeptics' Circle is up

Mosey on over to The Examining Room of Dr Charles for The 36th Skeptics' Circle, the biweekly compendium of the best of debunking and deboning of the critical thinking-challenged.

Wednesday, June 07, 2006

The loss of Dr Anita Roberts

Cancer research and the cause of women in science and medicine lost a true leader and shining example last week with the passing of Dr. Anita Roberts to gastric cancer. She was only 64.

From her Washington Post obituary:
Dr. Roberts, the 49th most-cited scientist in the world and the third most-cited female scientist, was chief of the Laboratory of Cell Regulation and Carcinogenesis at the National Cancer Institute, where she created a nurturing culture, a colleague said.

She and her research partner, Dr Michael Sporn of Dartmouth Medical School, won the 2005 Komen Foundation Brinker Award for Scientific Distinction for their work on molecules that can turn a healthy cell cancerous. She also won the Federation of American Societies for Experimental Biology's 2005 Award for Excellence in Science.

I did not have the pleasure of knowing Dr Roberts, but the following passage makes me wish I had been privy to her wisdom:
Dr Roberts was described as a warm, enthusiastic and consistently upbeat supervisor who figured out how to balance work and family not just for herself, but for her colleagues as well, said Dr Lalage Wakefield, who worked with her for 25 years. She kept the 17 people in her lab happy "through the force of her personality," Wakefield said, describing a clear-eyed and supportive scientist.

Her work on TGF-beta with Dr Sporn shed considerable light on how cancer develops and wounds heal. She left us with this reflection on the complex nature of trying to "cure" cancer:
"Research takes a long, long time," she said. "I know the public is always looking for a magic bullet. They want you to say, 'This does that.' But our own biology is incredibly complex, so 'this' doesn't always do 'that.' As basic scientists, we're all driven by our excitement in finding answers. We hope it ends up as something that becomes therapy. But that doesn't happen unless you have a basic understanding of the process. And that's what my work is all about."

Moreover, I only learned this morning in the NCI Cancer Bulletin that Dr. Roberts had kept a blog diary of her struggle with cancer.

Her son and daughter-in-law wrote a beautiful on-line children's book, BellaDonna: A Story of Hope, to explain to their own children what was happening to their grandmother. The love and creativity illustrated in this work is touching and it works for me as a father of a 4-year-old. The book tells me that Dr. Roberts was an overwhelming success as a parent to her son, Greg, the book's co-author.

I highly recommend the book to anyone trying to explain cancer and cancer treatment to young children.

NOTE ADDED IN PROOF: Dr Bill Hooker over at Open Reading Frame wrote a small personal tribute to Dr Roberts and his personal experience with her selflessness and kindness.

(Hat tip to Ms.PhD at YoungFemaleScientist for reminding me of Dr Roberts' passing.)

Monday, June 05, 2006

On becoming friends with other author-functions

More later on this beautiful post by Bitch Ph.D....

Okay, so I've only been around for six months after commenting on the blogs of others for about another six. Yet I am amazed at how many truly good friends I have made via these online discussions and conversations. I've only met a couple of you in real-life and look forward to meeting more, especially with the pending move to

Today, the much-revered Bitch Ph.D. posts on how deeply we often develop relationships with other "author-functions" and share in their joys and pains.

Go there and if after reading you are so inclined, pray for her dear friend:
"I'm thirty-three.

They told me I had cancer.

Then they told me I had another cancer.

That's when I knew I needed a new blog."

Sunday, June 04, 2006

Exclusive Michael Pollan interview with Ewen Callaway at Complex Medium

Here a belated plug to my Colorado compatriot, hard-working microbiologist, and real-life journalist, Ewen, at his microbiology/infectious diseases blog, Complex Medium.

If you're a fan of Michael Pollan from reading The Botany of Desire or have been thinking about buying his new book, The Omnivore's Dilemma, take 28 minutes and listen to Ewen's interview with Pollan on one of nation's best public radio stations, KGNU of Boulder, Colorado. (Go to Ewen's post to access the interview from the KNGU archives.)

Michael Pollan has a tremendously engaging talent for examining the relationships between science, particularly food science and agriculture, and everything from anthropology to big business. The guy can make watching paint dry seem like a life-changing experience. I had read some of the content of the interview from a Pollan excerpt in Mother Jones and it's interesting to hear him discuss in his own voice his working and living on a true organic farm in Virginia.

In The Botany of Desire, Pollan explores four plants (apple trees, tulips, potatoes, and marijuana) to discuss whether we have manipulated the plants or vice versa. In The Omnivore's Dilemma, he takes the same approach to four meals and interrogates the big business of industrial agriculture and the dichotomy of "industrial organic" commerce.

I have yet to read the complete new book, but listening to Ewen's interview with Pollan gives one a good flavor for the stories and the author's approach. Ewen takes the approach of letting Pollan tell the stories, rather than jump in evey minute as does Terry Gross. (Addendum: Ewen notes below in the comments that his reserve had more to do with using a single field mic.)

This coming Fall, Ewen is hanging up his pipetmen and heading to UC-Santa Cruz to enter their science writing program. But we all hope that he keeps Complex Medium rolling along. We launched our blogs within two weeks of one another and I really appreciate the perspective he brings to the sci/medblogging world.

When you're reading the Wall Street Journal Health Journal section or listening to a national NPR program in a couple of years, remember the name: Ewen Callaway.

Thursday, June 01, 2006

American Society of Clinical Oncology (ASCO) frenzy on tap

Before I turned in for the evening, I got my feed from Derek Lowe's In the Pipeline for his take on the media frenzy that will accompany the kickoff of the ASCO meeting in Atlanta this weekend.

Dr Lowe is a great chemist and fabulous source for all sorts of pharmaceutical news and information. In fact, coverage of his blog in the 1 August 2005 edition of The Scientist is what originally got me a-thinking about launching a blog of my own.

Derek makes a great point of not reading too much into the ASCO frenzy for cancer drug development trends since what we'll be reading about the next few days are things conceived by Pharma six to ten years ago.

I did, however, comment on his blog that I just saw on this afternoon a report from Jennifer Corbett Dooren that BMS's potent but non-selective Src/Abl kinase inhibitor, dasatinib (formerly BMS-354825), will be recommended by the FDA Oncologic Drugs Advisory Committee (ODAC) tomorrow for approval in Gleevec-refractory CML. A recent study is suggestive that dasatinib will also share imatinib's activity against c-kit in gastrointestinal stromal tumors. Truly a great win for my esteemed BMS chemistry and pharmacology colleagues - congratulations to all involved in the development of this new agent.

Anyway, this approval recommendation makes interesting news for those of us that get killed on NIH grant applications for being cancer phenotype-directed instead of molecular target-directed. Dasatinib was an almost thrown-away kinase inhibitor that had just enough promiscuity to have potent inhibitory activity on imatinib-resistant Bcr-Abl kinase. But, never fear, we pharmacologists have already generated dasatinib-resistant mutations to make way for the next, even less-targeted inhibitor.

We've already gotten the ASCO abstract book at home but I'll be staying tuned to In the Pipeline and the Wall Street Journal for the real stories!

Justification of public science funding and update

Thank you readers and blog-lleagues for the best wishes and congrats - my promised thank you posts have gotten tied up in communications online and off, as well as the June 1 NIH grant deadline. Again, the move to wouldn't have been possible without your support, links, and advice.

However, the news from SEED Media Group is that the launch of the second waves of their stable of science bloggers and new homepage will be delayed. My e-mail from the Mother Ship indicates that the launch date, scheduled for tomorrow, is indefinite. However, Bora has posted at Science & Politics that the launch is likely for Monday, June 5. (Addendum: Well, uh, maybe Monday, June 12.).

As Bora points out astutely,
"...the new blogs (including mine) will have a debut some time later, hopefully on Monday, which is good as traffic drops precipitously between Friday noon and Monday morning - thus Friday is not a good time to make an impressive start of a new blog."
Incidentally, this is the exact reason that the Bush administration likes to drop controversial bombshells on Friday afternoons: the European and Asian press is already into the weekend and most of the White House reporters are closing up shop, so there's minimal risk of counterspin being put on things until Monday.

No surprise to any of us that Bora is the best informed of us newbie SBers as he has been setting the standard for science blogging since the early days. Add to that his recent trip to SEED's offices in NYC. He notes that meeting the SEED staff, editors, writers, and IT people should improve his online communications with them since the human interactions, or "skin" as I've heard it called by the hipsters, serve to reinforce online interactions.

I noted in his comment thread that I feel this is the reason that virtual meetings, especially in science and medicine, will never completely replace conventional scientific conferences and annual society meetings. So many other interactions occur over beer and wine or dinners that serve to complement and reinforce interactions that scientists have from just reading each others' names in author lines. Real conferences, especially the small ones like Gordon Conferences, Keystone Symposia, and Cold Spring Harbor Symposia also provide great networking opportunities for graduate students and postdoctoral fellows, the mechanism by which most of my lab folks have made contacts for their next positions.

I mention the value of scientific conferences in light of this week's 'Ask a ScienceBlogger' question:

"Since they're funded by taxpayer dollars (through the NIH, NSF, and so on), should scientists have to justify their research agendas to the public, rather than just grant-making bodies?"

The responses from bloggers and their commentors make for great reading.

However, I wanted to draw your attention to two superb articles that appeared in yesterday's (31 May 2006) issue of The Scientist (subscription req'd but available at most academic institutions) on the future of scientific conferences.

In the first article. Keith O'Brien speaks of the partnership that is growing amongst the three aforementioned small meeting purveyors in light of meeting saturation and their own problems getting conferences underwritten by grants, such as the NIH R13 mechanism. This article also has a useful sidebar of "Six Tips for Getting the Most from Your Next Conference" that includes my favorite recommendation to my trainees:
"4. Break away: People tend to attend conferences with colleagues, co-workers, and friends - people they already know. But during talks and at meal times, try and sit with people you don't know. You are bound to learn something new, whether it is about work in your field, how other institutions function, or how different people approach questions relevant to your work."

The second article, written by Keystone Symposia CEO James W. Aiken, details the results of a survey of just over 1,000 meeting attendees on the quantifying the monetary value of the meetings in response to a "return on investment" query in his application for funds form the Bill and Melinda Gates Foundation.
"I had to propose a method for quantitative assessment of the impact of our conferences. Our stated goals are to connect the scientific community for the benefit of society as well as catalyze scientific progress by having the highest quality programs - all well and good, but how to measure this?"
A free version of the survey results and quantitative methodology is available at the Keystone Symposia website.

The amazing, but not surprising, conclusion drawn by Aiken was that each annual series of Keystone meetings saves $20-30 million (US) in terms of making connections for collaborations and the sharing of time-saving reagents and protocols.

Scientists generally despise being pushed to make these calculations for the beancounters. But I think we are all being asked to justify ourselves and our activities more and more, regardless of our research setting or position in the scientific hierarchy.

Tuesday, May 30, 2006

Terra Sigillata to move to

I'm quite happy to announce formally that Terra Sigillata will be one of the new blogs in the new wave of additions to, the "global, digital science salon." is a division of Seed Media Group in New York City and publishers of Seed Magazine. The proposed move and launch date is June 2nd.

I have to admit that the invitation to join came as a bit of a surprise. I started this blog a little over five months ago as an experimental instrument to gain experience writing on health issues for a more general audience. I didn't even tell my family about the blog until about six weeks ago.

Spurred on by my medical journalism colleagues (i.e., real career writers and publishers) and several bloggers who have grown to be good friends, I learned there was a void in the blogosphere for objective information on herbal medicines, dietary supplements, and single-chemical-entity pharmaceuticals derived from nautral sources. I also started with the intention of publicizing my chosen field, Pharmacology, one of the original interdisciplinary sciences and the forerunner to what academics are now calling Chemical Biology.

Reading over my old posts this weekend, I realize that I've gotten a bit distracted at times from my primary goal. There have been a few very popular posts on that relate to herbal medicines and natural products but, as in my professional life, I have been easily distracted by many other things that excite me: music, civil rights, gender inequality in science and medicine, the politics of science, and helping British readers solve their crossword puzzles. I've also moved some of my more local interest posts to another blog as I have always been a booster of every town or city where I've trained or been a prof.

So, I'll be spending this week expressing my gratitude to those who inspired me, gave me advice, encouraged me, and gave me shots at hosting carnivals. You hear me talk about these people all the time.

But the greatest thanks go to those of you who are frequent readers, without whose support I would've never gotten Seed's attention in the first place. A few of you are commentors and fellow bloggers, but the majority of you are faithful lurkers whose IP domains frequent my Site Meter logs. You are the unsung heroes of my success to date. I hope to continue to earn your confidence and continued readership as we move on to our higher profile gig at

Monday, May 29, 2006

Spam control apologies

Dear Readers, if you've ever corresponded with me via e-mail you may have just received a verification e-mail from SpamArrest. I mistakenly activated the control before importing my address book into the application.

Rest assured that spam control e-mail is not itself spam. I have now entered all of you into the application and you should not have to respond to the e-mail in order to correspond with me.

Please accept my sincerest apologies for this intrusion and many thanks to Joe for alerting me to the issue.

Saturday, May 27, 2006 co-founder on NPR

It took a quiet Saturday morning for me to catch up on the fact that the co-founder of, Dr William (Bill) Obermeyer, was featured on NPR earlier this week. Allison Aubrey of NPR's Morning Edition produced a thoughtful four-and-a-half minute segment on the seven-year mission of Dr Obermeyer and colleagues to provide consumers with independent laboratory testing of specific brands of herbal medicines and dietary supplements.

Readers of Terra Sigillata will know that I have long recommended as one of the top subscription services to learn about herbal medicines. (See my lengthy post on the best objective herbal medicine information sources for under $100 per year).

Of course, there are limits to what can do as they do not conduct clinical trials with specific supplements nor do they determine whether recommended doses produce blood levels of active constituents consistent with biological effects observed in vitro.

But their services are an admirable good start: they assess specific supplement formulations for content of purported active constituents and assure purity by testing for heavy metal contamination. The latter point is critical since many plants will sequester metals from the soil they are grown in and the Eastern herbal medicine cultures often intentionally add heavy metals like mercury and arsenic to their supplements.

You may be asking how this can happen in the US where a major pharmaceutical company is currently being decimated by lawsuits as to whether their anti-inflammatory drug did or didn't create cardiovascular risks. Well, a regulatory double-standard exists here for "drugs" vs. "supplements", where the latter are classified under the food side of the Food and Drug Administration.

The most interesting part of Dr Obermeyer's story is that he worked for the US FDA prior to starting In fact, it was he, pharmacognosy colleague Dr Joseph Betz, and their team who published a 1998 New England Journal of Medicine report on the mistaken adulteration of a herbal laxative supplement with Digitalis lanata, the plant source of useful but potentially toxic cardiac glycosides. Dr Obermeyer observed first-hand how limited the power of the FDA was in preventing such incidents from occurring in the first place.

In defense of the FDA, they can only enforce laws that are legislated by the US Congress. In the past, any proposals for stricter regulation of the dietary supplement industry has been met with strong opposition, usually funded by a natural foods industry whose monetary and political influence rivals that of medium-sized pharmaceutical companies.

There remain some concerns of potential conflicts of interest in that outlicenses for a fee their seal of approval. In addition, companies can pay a fee to submit their products for comparative testing if they were not selected originally by But frankly, it is impossible to keep up with the dozens or hundreds of supplements that contain a certain herb, say, like valerian (Valerian officinale) as discussed in the NPR story, for the organization to test all on the support of $27/year subscriptions.

As you might suspect, is not terribly popular among those in the herbal industry. In fact, a defamation suit was brought against them by a trade-group calling themselves the Council for Responsible Nutrition (CRN). Last week, the suit was wisely struck down by the New York State Supreme Court. CRN was also playing some nasty games:
"CRN distributed a press release in January 2005 publicizing a letter that it simultaneously sent to the FTC alleging that violated the FTC Act. CRN entitled its letter "Enforcement Action against," creating the false impression that the FTC was involved in an action, which was never the case. The news release and letter were rife with false and misleading information about The FTC refused to take action with respect to CRN complaint, issuing a "no action" letter."

This is the same Council for Responsible Nutrition cited last week at Respectful Insolence for objecting to the reliance on evidence-based studies by a NIH-convened scientific panel to assess the utility of vitamin and mineral supplements:
The dietary supplement industry criticized the panel for not considering less scientifically rigorous studies that point to multiple benefits from multivitamin and mineral use.

"They have done exactly what they set out to do, which is a review based solely on randomized controlled trial data, which results in a misleading picture," said Annette Dickinson, past president of the Council for Responsible Nutrition, an industry trade association.
Hmmm...I'd be a wee bit embarrassed to be a paying member of CRN.

Terra Sig applauds Dr Obermeyer and colleagues for doing what our government refuses to do - protect the consumer (and his/her money) from unsafe or substandard supplements.

Friday, May 26, 2006

Reform of US National Institutes of Health research grant review process

Funny that I should receive an e-mail from the US NIH today on this topic, the same day that Seed Magazine's posts a question on whether there should be public input on the federally-funded, research grant review process. For those of you outside the US, NIH is our national health agency whose funds are designated by the US Congress for the general good of public human health.

Dr. Toni Scarpa is NIH's relatively new director of CSR (Center for Scientific Review), the entity that assigns applications and oversees the review activities of over 100 peer-review panels. He recently wrote a highly-discussed "policy forum" article in Science on attempts to improve the peer-review process, particularly the agonizing 9-month turnaround from grant submission to funding notification (or not). The e-mail from NIH today links to a compilation of some of the 700 comments Dr Scarpa received in response (note: PDF format).

Those of us in academic or otherwise non-profit research environments rely on NIH support for anywhere from 25% to 100% of our salaries and generally 100% of the salary support for our personnel in our missions to solve research problems that impact human health. A standard investigator-initiated research grant proposal (termed a 'R01' in NIH jargon) is comprised of 25 single-spaced pages of research background, preliminary studies and restults, and the persuasive planning of new studies over a three- to five-year period.

There is also a sometimes equal amount of paperwork and bewildering array of institutional approvals associated with a R01 submission, a rather rude surprise to the newly-hired assistant professor who thought that being a good scientist was all that mattered in submitting a grant.

I have many stories to share on being reviewer and reviewee, but one thing struck me most among the comments Dr Scarpa received. US universities, private and public, are increasingly expecting professors to bring in a greater percentage of their salary on NIH grants. This is done to leverage NIH salary support to save state dollars or other salary savings to hire additional professors who are then also expected to bring in substantial salary support to the point that NIH is now subsidizing US higher education. I won't even get into a discussion of how colleges and universities use the overhead funds on grants (those additional funds intended for use in "facilities & administration"). Students and their parents then wonder why they are paying such high tuition and complain that the professors spend too much time on research and leave much of the teaching to less experienced teaching assistants.

As NIH funding rates are declining, with paylines for some institutes around 11 percentile (compared with the high 20s or even low 30s several years ago), the consequences of this leveraging are going to come home to roost. State higher-education institutions are in for a rude shock and state legislators are going to be forced to be creative in maintaining their higher-ed systems with such a sharp decline in the NIH subsidy. I fear most for fate of non-tenured junior faculty, those who are the future of science and medical education.

Tuesday, May 23, 2006

Grand Rounds vol. 2, no. 35

A well-organized and aesthically-pleasing edition of Grand Rounds is up from half a world away in the Philippines at Parallel Universes.

Thanks to Dr. Emer for selecting our post by way of my blog bud, Bora at Science & Politics.

Alternative medicine in conventional medicine

The expansion of offering so-called complementary and alternative medicine services in the context of "conventional" medical centers and private medical practices has been on my mind of late. Orac just recently posted an encore discussion of the topic that makes for good reading. Serendiptously, a number of British scientists issued yesterday a scathing indictment of the British National Health Service (NHS) Trusts for their financial support of alternative therapies in the UK while access to known, beneficial conventional medicines is often denied. Among those signing the letter to the NHS is Sir James Black, the 1988 Nobel laureate whose team brought us histamine-H2-selective antagonists for gastric ulcers and beta1-selective adrenergic antagonists for heart disease.

The British have had a very open and sober discourse on alternative medicine for a number of years. Part of the problem with discussing this issue in a scientific context is that alternative medicine ranges from conceptually-accessible plant-based herbal medicines to homeopathy and crystal healing. Dismissing all of alternative medicines is like making that converse statements that drugs are dangerous. The British are different, however, since the NHS will pay for some alternative therapy services. Hence, the issue is of greater public concern since all citizens ultimately pay for alternative medicine whether they agree with it or not.

In the US, the issue is more straightforward because very few managed care companies reimburse the insured for alternative therapies and services. Hence, a number of academic medical centers have jumped onto the alternative medicine bandwagon because most of those seeking services have the financial capacity to pay for services out of pocket. As a result, alternative therapies in the US are becoming the medicine of the rich and famous.

A bigger issue, worthy of further discussion after upcoming grant deadlines, is that US academic medical centers are promoting these services under the guise of "integrative medicine." In some institutions, these efforts are rigorously overseen, led by MDs well-trained in internal medicine and an appropriate sub-specialty, and only offered where evidenced-based medicine supports their use. In other institutions, integrative medicine programs operate as programs on the fringe, aggressively promoted to the community but often not even known to researchers and clinicians and within the very same institution.

A commentor at Respectful Insolence recently raised my awareness of the Consortium of Academic Medical Centers for Integrative Medicine, programs within academic medical centers in North America offering some sort of alternative medicine services. Those that I know of personally vary considerably in the quality and scientific rigor of their programs; even more interesting is the glaring omission of outstanding integrative medicine centers who are not part of this collaborative group. Were they not invited to join? Or, did they choose not to participate?

As a PhD researcher whose training and career has always been associated with US medical schools, I firmly believe that it should be safer and wiser for a patient to pursue alternative medicine approaches in academic medical centers than in the community. Contingent to this belief is that academic medical centers will be committed to providing the highest-quality, most rigorously supported therapies and services based in scientific fact and evidence-based medicine.

The biggest challenge to this notion, though, is how well these integrative medicine programs are themselves integrated within the medical center/health system to which they belong.

Moreover, if academic medical centers get into this business, should there be integrative medicine services specific to each medical specialty as opposed to one large overriding integrative medicine service? Compare everyone's hot-button target NCCAM who tries to fund research for all types of alternative modalities across all types of diseases to the quietly and highly-successful OCCAM that operates under the roof of the US National Cancer Institute, researching those modalities most likely to benefit the cancer patient and cancer survivor.

Some of my colleagues contend that there should be no need for integrative medicine. Test alternative therapies, keep what works and incorporate it into conventional medicine, and discard the rest.

Sunday, May 21, 2006

Sure, but will you be awake to notice the difference???

David Douglas of Reuters Health reported last Friday on the publication of a clinical trial revealing that a one-week trial of Benadryl (diphenhydramine HCl) was superior to Clarinex (desloratadine) in managing symptoms of moderate-to-severe allergic rhinitis, or hay fever. The article was published in the April 2006 issue of Annals of Allergy, Asthma & Immunology (2006;96:606-614)

You can read the results here but Douglas misprinted the Benadryl dose as 500 mg! three times daily. The actual dose, 50 mg, t.i.d., is already high enough to make one so drowsy as to not really care about one's hay fever. (Somnolence was reported in 22.1% of pts on Benadryl as compared with 4.5% for Claritin, and 3.4% for placebo).

At 500 mg (twenty, 25 mg tabs or capsules) even taken once a day will cause disturbing hallucinations due to the central anticholinergic effects of this drug. I fear that some readers of the Reuters story who are really suffering with allergies might try to take the misprinted dose. (Disclaimer: DO NOT attempt taking high doses of Benadryl/diphenhydramine for the purpose of recreational hallucinations; it can be fatal, particularly when taken with other CNS depressants. Diphenhydramine alone can cause paradoxical CNS stimulation, seizures, and death in infants and should not be used in children under age two).

I wrote in to Reuters on Sunday but have yet to get a response or a correction to the article.

As a seasonal allergic rhinitis patient, I can say that diphenhydramine HCl at 25 mg twice daily can manage my symptoms. However, even me at 215 lbs. has to work up to the tolerance of drowsiness that invariably occurs with this old OTC drug. In fact, this is how the non-sedating antihistamines (loratadine, desloratadine) are designed to produce less drowsiness: their physicochemical characteristics make it difficult for the drug to cross the blood-brain barrier whereas diphenhydramine HCl does it much better. However, I also think that since the non-sedating antihistamines cross tissues generally more poorly than diphenhydramine, I tough it out with a little bit of the latter drug instead of the more-expensive, less-effective desloratadine. Frankly, I'm surprised that somnolence was as low as 22.1% in the 50 mg, t.i.d. group - I'd wager that participants self-titrated to a lower dose to avoid drowsiness.

From the abstract:
"Results: The mean reduction from baseline in 24-hour reflective TNSSs [total nasal symptom score] relative to the placebo response was 77.6% for the diphenhydramine group (P < .001) and 21.0% for the desloratadine group (P = .12). A TNSS between-treatment difference of −1.81 (46.7%; P < .001) was observed when comparing diphenhydramine with desloratadine. A similar between-treatment difference was observed for the 24-hour reflective total symptom score comparing diphenhydramine to desloratadine (−3.35; 45.5%; P < .001). Diphenhydramine provided clinically and statistically significant reductions vs placebo and desloratadine in all individual symptoms, including nasal congestion. Desloratadine had a tendency toward improvement compared with placebo for most individual symptom scores. However, a statistically significant result was reached only for sneezing (−0.27; 33.9%; P = .04)."

Oh, by the way, the trial was financed and conducted by the makers of Benadryl. The timing of the publication, April, was also nicely coincidental with the peak of allergy season on the US East Coast.

Friday, May 19, 2006

How to appreciate your oncologist

I just saw this link posted yesterday by Bora at Science & Politics. It's a truly heart-warming story about the kind of things that go on at Duke University 99.9% of the time:

Patient's Family Says 'Thank You' For Saving Life

DURHAM, N.C. -- For three years, Ara Everett has been treated for Stage 4 breast cancer and a brain tumor. But she has survived longer than she and her family ever expected.

They give the credit to Dr. Heather Shaw, an oncologist at Duke University Medical Center.

Everett's daughter, Erica Green, wrote to NBC17 to ask Triangle Wishes to honor Shaw and the medical staff that have provided such personal care for her mother.

"How do you say thank you to doctors, the people that save your life?" Green wrote in her e-mail. "We hear all of the bad stuff about doctors these days. It's time to thank them for the awesome work they do to benefit so many."

Triangle Wishes arranged for Piper's Tavern to provide a luncheon for Shaw and the Oncology Department staff at the Duke Medical Center.

"We just wanted to say, from the appointment coordinators who greet her and see her standing, struggling and say, 'Sit down, Ms. Everett, we got it,' to the nurses that whisk her back and take care of her and bring her crackers and soda if they see she's jittery to Dr. Shaw and all the surgeons, we just really wanted to say thank you to everybody in a big way," Green said.

The video of the story can be accessed here.

I post this for a number of reasons, not the least of which is that PharmMom is a 23-year breast cancer survivor - had such a mechanism existed back then, I would have been beating down the doors of my local TV station to do a story about my Mom's miraculous oncologist in northern New Jersey. I applaud the marvelous Everett family and daughter Erica Green for going the extra mile to find a way to thank their medical oncologist and her entire team.

The other reason is that, like my blog bud Orac, this oncologist (and all of her colleagues) does this kind of work every day, week after week, year after year. And while doctors do get compensated reasonably most academic physicians, even in the best teaching hospitals, make little more than a first-year MBA grad.

Moreover, they are expected to balance the provision of top-quality, cutting-edge medical care with grant-writing, research (basic and clinical), teaching med students, fellows, and mid-level colleagues, as well as fighting with university and hospital administrators about funds and the basic resources to do their jobs. All the while, the fat cats at health insurers are living quite high on the hog, often off the blood, sweat, and tears of oncologists like Orac and Dr. Shaw (not to mention the vomit, urine, and feces). In fact, "declining reimbursement and rising overhead" has been cited in the recent decision by Medpundit to hang up her keyboard from medblogging because her medical practice leaves little time for even a family life.

I'm a cancer researcher and I hope that one day my discoveries help real people fight their real cancer. In the meantime, I hope that the academic medical system can remain sustainable over the long-term to retain such great docs as Orac and the aforementioned Dr. Shaw so such discoveries can be brought to cancer patients in such a loving and compassionate manner.

If you're going to see you doctor this week or next, any kind of doctor, take a few minutes to say 'thank you.' Say 'thank you' to the nurses, the receptionists..anyone who looks like they are involved in your care.

They are all fighting a battle to keep us healthy that many of us never see.

Monday, May 15, 2006

Stetson Kennedy revisited, literally

I've been dabbling on this post for 3 months or so, partly because I was unsure of my goal or message. I'm still not sure but I know that I just want to tell a story. Learning of journalist Anton Zuiker's StoryBlogging effort helped me commit to finishing it.

Let it suffice to say that I have been blessed to meet a number of prominent people as of late, mostly outside of my scientific discipline. I'm trying to make sense of their coming into my life as I recognize that I have truly settled back into Southern culture, tradition, and lifestyle. So much of my introduction to the South took place as a graduate student in North Florida, an area more like southern Georgia than the flashy coastal cities further south. I'm a Yankee by birth, but my relationships and experiences in Florida and North Carolina have now come full circle. I've not only married into a long-time Southern family, but my daughter is a native of the South. The South is now home.

Standing Up For Stetson
You may recall my fondness for the book, Freakonomics, and one of the key case subjects, the folklorist, author, civil rights activist, and general hellraiser, Stetson Kennedy. I already had an strong affinity for Mr Kennedy ever since I learned he went to the University of Florida at age 21 in 1937 - he then signed on to one of FDR's New Deal projects, the Works Progress Administration (WPA), to catalog Southern folklore together with the venerated author, Zora Neale Hurston. Their travels are detailed in his first book, Palmetto Country, published in 1942.

In stark contrast, when a certain other 21-year-old was a UF student in the mid 1980s, his primary goal was to keep track of which nights each bar had the best beer, maragarita, buffalo wing, and oyster specials.

Well, as detailed in my previous post, ol' Stet moved on to infiltrating the Ku Klux Klan and revealing their secrets in radio and other media so as to subvert their influence and embarrass racist politicians and law officers. In detailing how Stetson defused the 'information asymmetry' used by the Klan to intimidate and evoke fear, Dubner and Levitt remarked in Freakonomics that, "Had the Internet been around when Kennedy infiltrated the Klan, he probably would've rushed home and blogged his brains out."

But, recently, Stetson's firsthand accounts of Klan infiltration in The Klan Unmasked have come under attack and he now acknowledges, as detailed in this objective reassessment, that some accounts were compiled from other undercover colleagues. Nothing to be ashamed of since others didn't have the courage to have their revelations attributed to them and, all the while, Stetson was expatriated in Europe unable to have his book accepted for publication by any American house and separated from his wife and then-teenage son due to a $1,000-a-pound bounty placed on his head by the Klan.

Making Friends
Well, my vocal defense of Mr Kennedy caught the eye of his personal secretary and keeper of the flame, Jill Bowen, a self-described "God's own brat" for her luck in falling into being Stetson's caretaker and gofer. Miss Jill wrote to tell me that Mon Jan 30 was to be the inaugural fundraising event for the new Stetson Kennedy Foundation at the University of North Florida in Jacksonville. Dedicated to human rights, environmental protection, and folklore preservation, the SKF pretty much stands for everything I believe in. Jill elaborated further that she was the recipient of a second $500 'Inner Circle' ticket and that her dear husband Bobby was not particularly fond of dressing up and comingling with large crowds. Hence, the fine young lady invited me to come down to Florida to accompany her to a preceding reception to meet such luminaries as Arlo Guthrie, Bob Edwards (formerly of NPR's Morning Edition), Dr Anna Lomax (the daughter of the late folklorist, Alan Lomax, and amazing scholar in her own right), Dr Peggy Bulger (director of the American Folklife Center at the US Library of Congress) and, of course, Stetson Kennedy himself. Perhaps, Jill suggested, I could even stop by Stetson's house beforehand and help her organize a few things before heading over to the event.

I'm certainly not one to be so spontaneous to blow off NIH grantwriting responsibilities and readers know that I was pretty scarce in these parts around the Feb 1 deadline. But, my wife and daughter both recognized the once-in-a-lifetime opportunity and pushed me out the door to go press the flesh of history. Like a deer blinded by the headlights, I was off to north Florida to the Kennedy home and his estate and state park of Beluthahatchee, on the Florida peninsula south of Jacksonville, between the St. John's River and the Atlantic Ocean.

Touching History
I arrived at the small but cozy Lindal cedar home and writer's den of Stetson Kennedy. His two decks overlook a live oak hammock and 20 acre wetland that had been a lake before Hurricane Frances blew out the dam that Stetson had built with his father. The home is a national historic literary landmark in that Woody Guthrie spent several spans of time with Stet writing over 80 songs and completing his autobiography, The Seeds of Man. In fact, if you're a Woody Guthrie fan and have either of the Billy Bragg/Wilco Mermaid Avenue collaborations, the image on the disc of Woody playing a guitar on a felled log was taken in 1953 by Stetson at Beluthahatchee. Here's the image again on the cover of a collection of Mr Guthrie's Beluthahatchee works that sits on the coffee table as you enter the house.

I enjoyed a lovely afternoon with Jill showing me all of Stetson's memorabilia, feeding raw catfish to "Blue Boy," the resident blue heron, and speaking with Dr Lomax who had awoken from a respite for a cold she was fighting. Bob Edwards had been by in the morning and Stetson was already gone with him for some interviews and pre-production work at the UNF auditorium.

I got a real tangible impression that Beluthahatchee was a crossroads for all thoughtful, progessive people who had ever been part of Stetson's work and legacy. I'm not a writer, but the sense I got of Beluthahatchee was much like others have written about the late Hunter S Thompson's Owl Farm kitchen in Woody Creek, Colorado (minus the acid and ammunition) - a community gathering place for whatever influential folk were coming through town, where ideas were exchanged and debated and plots hatched. Relaxing and pristine in its beauty of a Spanish moss-draped Florida hammock, it also seemed very much a nerve center. Sitting on the back porch overlooking the wetlands, I could understand how such a natural setting could inspire great idealistic thoughts and actions.

But the real world crept back in and Jill was frantic on the cell phone upon learning that Arlo Guthrie had not yet made it to the UNF auditorium - he was supposed to sing another of his Dad's songs about Stetson called "Beluthahatchee Bill" at the reception (Stetson's given name is William Stetson Kennedy). It was a hoot to watch Jill go through her address book (no newfangled Palm Pilot for this Florida gal) and sift through all of the entries for "Guthrie" until she was able to locate a relative who had a cell phone number for Abe, Arlo's son and band member. I'm an amateur guitarist myself and had made an effort to learn the Billy Bragg/Wilco version of "Stetson Kennedy" from Mermaid Avenue vol. II just in case I was needed. It was amazing to actually see the lyrics in Woody's handwriting that Messers. Bragg and Tweedy had used to write and record the song, composed originally by Woody to commemorate Stetson's 1950 write-in campaign for the US Senate battle between Claude Pepper and George Smathers. In fact, Woody had written "Mathers" instead of "Smathers" in his indictment of the former Florida senator and the comfortable business relationship enjoyed with the executors of the DuPont estate.

Off To The Show
So, then, off to the reception with Jill and Anna Lomax in my rented Caddy, a fitting vehicle to transport Stetson's assistant and the president of the Association for Cultural Equity to the University of North Florida. I had a good laugh driving Dr Lomax, knowing that she is the same "little 22-month-old Annie Lomax" referred to by Woody Guthrie in the liner notes of his album, Songs to Grow On for Mother and Child, that I routinely play in the car for my own daughter.

I am not famous, nor do I normally keep company with people who are. I've always wanted to meet famous people who I admire: Springsteen, Branford Marsalis, Elvis Costello, Bill Clinton - but more as dinner guests to discuss their views and how they got to where they are. I had one brush with fame, standing at a urinal next to Nobel laureate, Dr George Palade, at a 1986 Johns Hopkins memorial symposium for Dr Albert Lehninger - kind of awkward in that I didn't want to shake his hand at the time, nor say something like, "Dr Palade, you are a great man."

Well, the Stetson Kennedy event had me tongue-tied and awe-struck...times ten. I had no idea where to even start talking with Anna Lomax. When we got to the reception, Jill immediately introduced me to Arlo Guthrie who had just arrived. I got to shake Arlo Guthrie's hand, all I could blurt out was, "Uhhh...I'm a big fan of you and your Daddy's music," rather than relate that my daughter loves to sing Woody's "Ridin' in My Car" with me, especially when we get to the part about the horn sound. Woody wrote these songs for his kids and I'm sure that Arlo would have been touched.

Instead, I took a few pictures and walked around, talking with Arlo's wife, Jackie, and meeting some of Stetson's family, even having my own picture taken with them for the society page of The Jacksonville Weekly ("Uh, yes, that's 'PharmBoy' spelled with a 'Ph'.") Turns out that although Arlo was there, even he hadn't ever learned his Dad's song. But local folksinger, Alvah Allen, had - dang, there went my chance to play 'Stetson Kennedy' for the admiring crowd. That's okay, I would've stumbled over my words and Alvah has a far more beautiful voice anyway.

The program was a spectacular tribute to the life and times of Stetson Kennedy. Set up like a talk show with a video screen overhead and an African musician (Ajamu Mutima) providing drum segues between pieces, it was as professional a function I had ever seen. Stetson was interviewed first by folklorist Dr Peggy Bulger and then by Bob Edwards,

now with his own show on XM Radio. Arlo provided some commentary about his Dad and his relationship with Stetson that he had only really learned about in the last decade or so. Dave Isay, founder and executive director of StoryCorps sent a heartfelt video piece honoring Stetson's work. Isay's message was particularly poignant since StoryCorps is designed after the WPA folklore projects Kennedy worked on in the 1930s. The whole program is downloadable in this pdf and I'm still trying to find out who will be marketing the DVD of the event.

I mentioned Bob Edwards and also got to meet the NPR legend afterwards (I'm almost 6'2" and he towered over me). Despite my long-time subscription to Sirius, he fetched his producer to get me to switch to XM and sent me home with a promotional CD of his interviews with a special discount coupon if I subscribed. Edwards was a key player in the early days of NPR and seems rejuvenated by the chance to do the same in satellite radio.

My admiration for Arlo Guthrie notwithstanding, the musical highlight of the night was the Steve Blackwell/Dan Leach duet of "Beluthahatchee on my Mind," a song Steve wrote but has yet to record. Steve and Dan are stalwarts in the Florida folk music community and students of Florida folk legend, Frank Thomas, who also performed. Steve and Dan offered to meet with me on a subsequent trip to Florida to learn the song, but my schedule didn't permit. Such is the kindness and openness of folk musicians.

Back to Beluthahatchee
After all of the festivities, we retired to Stet's place. Jill had me pick an orange off one of Stetson's trees to eat and gave me a snail shell from the swamp to share with my daughter. We went back inside to set for awhile with The Man himself and his dear friend, Anna Lomax. So, here I was, sitting with two of the most important people in American folklore - just settin' for a spell like typical visitors to any home, eating quiche that Stet had warmed in the microwave and drinking Korbel to celebrate the evening. [This article tells a little more about what Stet has been doing in recent days and has a beautiful picture of him at the very table where we shared champagne and goodies.]

Again, billions of questions for them flooded my mind but I was still so stunned as to just listen to their conversation. A real journalist would have been far more prepared, but I was content to be mindful, present, and in the moment. Anna really challenged Stet on what the goal of the foundation was beyond preserving his estate and continuing environmental education programs. Dr Lomax is still deeply tied to the challenges of youth in New York City and around the world, so we all talked for awhile on what the foundation could do to improve the promise of young inner-city kids who need only for adults to believe in their desires and dreams. I have not since been in touch with Anna, but her vision for improving society seems so clear.

Nearing midnight, I took leave and wished Jill, Anna, and Stetson a good night. The Man was so gracious about me coming down to share in his honor. But all I could do is tell him that the rest of my life would be unlikely to equal what he has done to eradicate human injustice.

The next morning I woke to a magnificent sunrise over the St. John's River. My wife, ever the Internet travel wizard, had found me a great hotel room with a free breakfast. I enjoyed the most spectacular Eggs Benedict over lump crabmeat that I had ever tasted. Mentioning this to the hotel manager at checkout, she sounded surprised because I was the second person that day to comment on that dish.

As I drove to the airport, I heard on the radio the Coretta Scott King had died. The night before, Jill had tried to find me the letter from Dr King to Stetson that she had recently archived. I consider myself quite fortunate to have met a major civil rights figure of our time while he was still here to receive the accolades of admirers across several generations.


Returning home, I made an effort to catch up with Stetson's son, Loren, a major force behind-the-scenes in urban redevelopment in my community (again, another amazing coincidence). Over lunch I shared with Loren my story about meeting his Dad and how moved I was by the experience. Loren smiled knowingly and asked me what I was going to do with my new-found excitement about everything from combatting human injustice to playing folk-rock music. I didn't have a good answer; in fact, my delay in posting this story is largely because I still don't have a good answer.

I live a modestly comfortable life just miles away from some pretty serious poverty, drug dealing, and gang violence. I've always tried to use my good fortune as a laboratory director and educator to help kids and adults from underrepresented minorities get experience to make a better life for themselves. But should I be doing more? I'm extended pretty far between work and helping my wife raise our daughter, but people much more busy still find time for substantial community service. Is my community service the use of my lab and teaching skills to help those less fortunate to make a better life for themselves?

I don't know - sounds pretty weak to me. When you meet people like Stetson Kennedy, people who have literally put their life on the line to stop the persecution and terrorizing of the black community, anything else you do pales in comparison.

But perhaps the lesson is that we don't have to be a Stetson Kennedy - every step one makes to aspire to be a Stetson Kennedy is a step that, when combined collectively across a community, makes the world a better and more compassionate place.

I can't wait to bring my family back to Beluthahatchee to meet Stet for his 90th birthday celebration later this year.

[This post is dedicated to my new friend, Jill Bowen, personal assistant to the author and civil rights legend, Stetson Kennedy. Everyone should be so fortunate to have a Jill Bowen in their life.]

Thursday, May 11, 2006

Civility and dialogue in the sci/med blogosphere

Okay, so this is turning into Bora Zivkovic week at Terra Sigillata. I can't help myself because he is one of the most influential bloggers in my short career.

Today's is Bora's 40th birthday - go on over and wish him a happy birthday.

Bill Hooker's lead in the shout-out for assistance to Bora and his family has resulted in some very nice posts and contributions. Bora, being who he is, is now asking to spread the wealth since he'll now be able to make the family's electricity payment this month.

But the title of this post came from a comment I had to post in response to an exchange between Bora and Kim of Emergiblog. Kim also tops my list of nursing bloggers (if I ever get around to revising and categorizing my blogroll). The show of mutual respect here and here between these two religiously- and politically-opposed bloggers led me to leave Bora the following comment early this morning:

I, too, share a deep respect for Kim's skills as a blogger and humanitarian for reasons somewhat similar to you: because PharmMom started her 30-year nursing career in the ER and her influence led me to a career in research (although she would have been happier had a become a "real" doctor). Kim has an incredible gift for bringing us there.

But, Bora, you point to a larger issue that is ever so refreshing in our little part of the blogosphere - civility and mutual respect. At a time when anyone who holds views different from you is labeled a traitor, nutcase, terrorist-lover, etc., I find that many of us sci/med bloggers who hold different political and religious viewpoints can still respect each other for the ideas and experiences to further our discussions. Perhaps it is because in science and medicine, we are forced to interact with (and even care for) people of other beliefs and cultures, whereas many other bloggers (and pundits) can safely write from the confines inside the Beltway or in a NYC highrise without ever having to interact with people different from themselves.

Locally, the Duke lacrosse rape case is one that has polarized our community and, in some cases, taken civility out of discussion of real problems that deserve so much more attention than namecalling can give. I was very impressed by the efforts of The Center for Dialogue, a group in Brevard, NC, whose framework for community dialogue was published this past Sunday in a part of the Raleigh News & Observer's Q (opinion) section. It appears that these rules are also promoted by a Durham-based leadership development organization called Wildacres Leadership Initiative. Their bottom line is, "Dialogue is about inquiry and learning, sharing our perspectives and beliefs, and broadening our understanding of the different perspectives and beliefs among us. The result of dialogue is shared meaning, not influence to a certain outcome."

Anyway, my own bottom line is to thank you and Kim for being great examples of mutual respect in the sci/med blogosphere and illustrating the goodness that can come from blogging.

Yeah, yeah, Pharmboy, let's hold hands around the campfire and sing "Kumbaya." (Well, actually, it wouldn't hurt because it might serve as an educational moment about African and Gullah culture.)

No, what I'm saying is that while namecalling and labeling those with opposing or dissenting views might increase votes, site traffic, or fill college auditoriums, it does little to advance discussion in a way that solves the critical problems facing our society. For example, I would love to have a civil discussion with a supporter of the current US presidential administration who won't call me a traitor, heathen, or tell me I'm aiding the terrorists. I just want to understand why an intelligent person would hold such a view to find out if there's a way to bridge the divisiveness facing this country.

Of course, I am not so naive to think that compromise on every issue will solve every problem of poverty, crime, racial and gender inequality, health disparities, immigration, etc. But I do have faith that mutual respect and and an attempt at true understanding will move us further than we are today.

Tuesday, May 09, 2006

Bora could use a hand

For those of you who are regular readers or are coming over from Tara's Grand Rounds at Aetiology, you are probably familiar with our colleague, Bora Zivkovic (aka Coturnix), known best for his blog, Science & Politics. He's trying to finish his thesis while supporting his family and has hit a bit of a financial rut; I know it took a lot of humility for him to put out a call for assistance.

My Northwest coast blog bud, Bill Hooker of Open Reading Frame, has put together a lovely justification for sending a few dubloons Bora's way:
"More to my point, Bora's a member of my community: inter alia, a researcher and a science blogger. And if you happen to be a blogger, teacher and/or researcher, consider this: Bora is the sort of person we want in our community. It will not take much reading of his main site, or his associated teaching and research blogs (Magic School Bus and Circadiana, respectively), to convince you that he has talent for science and for science teaching; nor will it take more than a glance at the support he has given various blogging carnivals to demonstrate that he understands and values community; nor is it necessary to look beyond his writing about science blogging itself to see that he has a forward-looking, can-do way of thinking about science and community and what the two can do for each other."

I'm lucky to know Bora personally but I know that folks all around the world are grateful for his knowledge and insights. So, I encourage my readers to roll on over to Bora's main site and click on the PayPal and Amazon icons on his right sidebar. Let him know how much you value his contributions to our community, local and international. Others with their own blogs may care to do the same.

While you're at it, let Hooker know he's a good egg for getting this ball rolling.

Monday, May 08, 2006

The best objective herbal medicine information for less than $100 per year

For several years, various media outlets have asked my opinion about herbal medicine and dietary supplement issues. I've generally written several pages of responses only to find a few key quotes mined from my paragraphs of wisdom (in my mind). No problem at all; I just have trouble with churning out sound bites. So, I'd like to share with you stuff that never makes it to the so-called mainstream media.

Recently, I was asked by a US television network to comment on the value of the release of Consumer Reports' Natural Medicines Ratings Database (follow link then click on "Browse Index"). In filing my response, I composed the following diatribe that concluded with my 'best of' final recommendations for sources in which I have no financial or scholarly interest (except for Terra Sig, of course) but find to be quite valuable to the general public.

What do consumers/patients want to know about "natural medicines?"
My interactions with patients are mostly through giving public education programs and talking with BS/PharmD-level pharmacists and my MD colleagues at academic medical centers. The first question patients have is, Will taking this supplement interfere with my prescription drug(s)?” This question is undoubtedly the most common and the most serious challenge since 95% of patients who use alternative therapies do so together with conventional medicine (conversely, only 5% of patients who use alternative medicines do so exclusively of conventional medicine).

The second question is usually, Is this herb/supplement really good for disease/disorder X?” This is a difficult question to answer since supplements in the US are not required to undergo efficacy testing although they can be advertised for thinly-veiled indications like “supports a healthy cholesterol level” rather than “reduces cholesterol” as the latter would be a drug claim requiring clinical trials. Support claims or “structure-function” claims are acceptable for foods and supplements under the 1994 US Dietary Supplement Health and Education Act (DSHEA; pronounced duh-SHAY).

Hence, most of what we know clinically about herbs/supplements comes from companies, usually European, who support clinical trials of their product to gain a market advantage. In such cases, like the 1997 JAMA paper showing that Ginkgo extract slows the progression of Alzheimer’s disease, that conclusion can only be made for that Ginkgo product and not the 20 others that are on the health food store shelves. Other companies rushed to advertise that their Ginkgo products were standardized to the same composition of active compounds, but a consumer could not be certain this was the case. In fact, the sponsor of the JAMA study, Dr Willmar Schwabe (pronounced VIL-mar SCHVAB-uh) Pharmaceuticals (Karlsruhe, Germany) had a US process patent for this product, rare in the herbal industry, and threatened to bring suit against any company who was trying to sell their products under this patent.

This brings me to the third related question, “Where can I buy an herbal product that has shown efficacy in a placebo-controlled, randomized trial that has been published in a major peer-reviewed journal?” Let’s take the Ginkgo example above. If you go to the JAMA paper, you’ll find that the product used was called EGb 761 and is sold as Tebonin. Well, great, but Tebonin is not available in the US. You would have to know that Utah’s Nature’s Way imports EGb 761 and sells it here under the brand name Ginkgold. However, you will pay a premium of about 4-fold to buy Ginkgold over Nature’s Way’s regular brand of Ginkgo extract.

Where does the consumer find this information? First, the American Botanical Council (also abbreviated ABC) of Austin, TX is a non-profit educational organization that publishes a journal called HerbalGram, kind of like the Scientific American of the herbal field. Periodically, they will publish a table of clinically-proven herbs and the name of the formulation as sold in the US. For example, an extract of saw palmetto has been shown to reduce prostate swelling in men with BPH (benign prostatic hypertrophy) but the product, Permixon, does not yet appear to be for sale in the US. ABC founder and director Mark Blumenthal also included this table in the latest English translation of the German Commission E monographs, the equivalent of an FDA sanctioned guidebook if the FDA had any power to make prospective pronouncements on herbs.

Based on what we know about Consumer Reports, how might the new CR database be useful?
Related to the third question above, most patients now understand that all herbs of the same name are not created equal. Several scientists, and Consumer Reports itself, demonstrated as early as the late 80s and early 90s that composition of active constituents in a given herb can vary by 20-fold or more across manufacturers. In fact, I have a copy of my original 1995 lecture I gave on the topic to my pharmacy students and the handout contains a table from an issue of Consumer Reports on active components from ginseng products – I still use this table in my professional and public lectures.

Hence, I view the Consumer Reports Natural Medicine Ratings Database with great enthusiasm. The organization has really only been off-base once in the past with their "12 Supplements to Avoid” in May 2004. At least two of their “dangerous” recommendations were based on hearsay (i.e., unpublished reports) that had been medically discounted well before 1994 (such as skullcap-mediated liver damage which is now well-known to be due to one report of one wholesale batch of herb that was contaminated with germander, a herb that really is hepatotoxic).

Other than that, Consumer Reports has a excellent brand recognition, a history of impartiality that extends back at least 60 or 70 years, with its only agenda being to protect the consumer. The fact that they are often remembered in the estates of subscribers yet frequently attacked by industries they criticize speaks to their impartiality and the high level of confidence that they generate among the public.

The database is outstanding and the few entries on herbs I know about are comprehensive and up-to-date. I attribute this to their partnership with the Pharmacist’s Letter and Natural Medicines Comprehensive Database director/founder, Jeff Jellin, PharmD. Jeff is held in the highest regard by a great many of us in herbal medicine research and pharmacy education (and, no, I do not get any free subscriptions from his organization. However, many hospitals and academic medical centers subscribe to one or more these databases).

Another great feature is the drug-herb interaction search engine that errs on the side of caution. However, I fear that patients may use this feature rather than tell their physician about their herbal use. An additional concern for the health care provider is that the original literature citations for the interactions are not provided on this site and one must subscribe to the professional version of Jellin’s Natural Medicines Comprehensive Database (a clever marketing tactic).

Technically, I don’t really like the drop-down menus that only show one section at a time – I’d like a choice to “expand all.”

What are other credible sources, outside of physicians, currently on the internet or elsewhere that can help guide patients on natural medicine choices?
First, the internet is largely a horrible place for information on natural medicine choices. Misinformation outweighs objective truth 99 times out of 100 (no exaggeration). Most internet sites are written to sell you a product and make you think you are getting “scientific” information.

The one thing missing from the CR site is a rating of products based upon labeled content matching actual, independently-analyzed content of active components, something CR has done previously for select herbal products. does fill this void and it would be great if CR could work out a deal to partner with was founded by an MD and a former FDA natural products chemist to serve as a sort of Consumer Reports for herb and dietary supplement content and issues of contamination and safety. For example, they were the first to bring to widespread knowledge that some herbal products can contain toxic levels of cadmium, mercury, and even uranium depending on where the plant is grown. (Full disclosure, they gave me a free $24.95 annual subscription two years ago (now $27.00) – however, I had paid for my own subscription previously and now continue to do so since the freebie expired).

I am also partial to HerbalGram and the American Botanical Council because they have a long history of working hand-in-hand with researchers in the field and in pharmacy education. (I get nothing free from them and, in fact, donate at least $250/year to them to support their mission.).

I also think very highly of Joe and Terry Graedon of The People’s Pharmacy enterprise and their very recently updated and well-constructed website. As mentioned above, they have a syndicated weekly NPR radio show on drug, natural medicine, and health issues, maintain herb and home remedy information on their website, have published over a half-dozen books, and have a syndicated weekly column in over 500 papers across the US. They are pioneers in self-care, with Joe’s first book, The People’s Pharmacy, released in 1976 when it reached #1 on the NY Times bestseller list. I have recommended them for over 15 years but have come to know them personally over the last 5 years or so. Joe holds a master’s in pharmacology but has done enough work in this field for several PhDs; his wife Terry holds a PhD in medical anthropology and has been a professor in the nursing school at Duke University. They sell CDs of each radio show for $16 and almost 400 well-researched in-depth guides on drugs and natural medicines for $3 or $4 each. (Disclosure: I have been a guest on their radio show but have not received any compensation from them in either money or services).

(I also disclosed the truth about the following to the media outlet who consulted me). There is also a blogger that I know personally who writes at Terra Sigillata and covers issues of natural medicines and even solicits and answers questions from readers. He has very similar training to me (PhD in pharmacology with experience in herbal medicine research and pharmacy/medical education) but his current employment situation requires that he writes under a pseudonym.

Several well-known scientists and clinicians, including some from the US National Institutes of Health, have authored an ever-expanding book called, The Encyclopedia of Dietary Supplements, from Dekker. It is written at a higher level than for the average consumer but is approachable by the internet-savvy consumer. Its original price was quite high but I know they are addressing this as their website no longer lists an official price and directs the consumer to call for pricing. I know many of the chapter authors and editors and find this to be a top-notch reference for upper-level consumers through PhDs and MDs.

Finally, there is a two-volume book series that addresses clinical trials issues and the mystery of US marketed names of supplements tested in clinical trials called The Handbook of Clinically Tested Herbal Remedies. It is written by an independent pharmacognosy consultant named Marilyn Barrett, PhD. It is superb but not regularly updated (no web mirror) and goes for about $160 for both volumes.

I’m afraid that the consumer won’t have much luck turning to their conventional medical provider. I think there is a slightly higher probability that a pharmacist will know more about herbal products and drug interactions than the average physician. Frankly though, the overall percentage isn’t that high in either profession and can be quite spotty geographically. A survey in 1998 of US pharmacy schools on alternative medicine course offerings revealed that the problem is due in part to the fact that some schools devote entire semesters to the topic while others have 2 or 4 lectures in the entire curriculum. Also, I have found that some unscrupulous physicians and pharmacists sometimes sell supplements regardless of the scientific basis for their use.

I would encourage consumers to BEWARE of herb counseling advice they might receive in a health food store or supplement store. There are several reports in the scientific literature of incorrect or dangerous advice given to patients by health food or vitamin store clerks when asked about products for diseases as serious as cancer or HIV/AIDs.

Final recommendations
My advice, for what it's worth, is to get a subscription to this new Consumer Reports Natural Medicine Ratings ($19), ($27), and HerbalGram of the American Botanical Council (starts at $50/year for a superb print journal and web access to it and other added info). For less than $100 per year, you’d be set up pretty well and be able to stay current.

For free on the web, the two objective sources I recommend are The People’s Pharmacy and, of course, the Terra Sigillata blog. Take a look at The People’s Pharmacy once a week, especially if your newspaper or NPR station doesn’t get them and check out their store. As a supplement, dial-up Terra Sigillata twice a week as [he] often links to other content that he has reviewed for accuracy and objectivity.

Hope this helps - I'm happy to add useful links that readers might find.

Friday, May 05, 2006

The pharmacology of Rep Kennedy's nighttime crash

Seems like there is a good deal of interest today in Rep Patrick Kennedy's one-car accident last evening that he has attributed to taking a combination of the prescription sleep aid, Ambien (zolpidem tartrate), and Phenergan (promethazine), an old phenothiazine antipsychotic drug most often used now to treat nausea and gastrointestinal upset.

Fortunately, Rep Kennedy emerged from the accident unharmed. However, many questions have arisen today as to whether the accident was the result of alcohol impairment. Here at Terra Sigillata we will use this case instead as a pharmacology teaching moment to note that motor coordination and consciousness can be adversely affected by combinations of other depressants of the central nervous system (CNS).

Ambien alone is a very rapid acting sleep aid and its rapid onset of action is primary reason for its popularity among those with sleep disorders. Some of my MD colleagues stress strongly to their patients with insomnia that they immediately go to bed after taking the drug because its effects are so precipitous.

From the Sanofi-Aventis prescribing information [bold is my emphasis]:

"Ambien, like other sedative/hypnotic drugs, has CNS-depressant effects. Due to the rapid onset of action, Ambien should only be ingested immediately prior to going to bed. Patients should be cautioned against engaging in hazardous occupations requiring complete mental alertness or motor coordination such as operating machinery or driving a motor vehicle after ingesting the drug, including potential impairment of the performance of such activities that may occur the day following ingestion of Ambien. Ambien showed additive effects when combined with alcohol and should not be taken with alcohol. Patients should also be cautioned about possible combined effects with other CNS-depressant drugs. Dosage adjustments may be necessary when Ambien is administered with such agents because of the potentially additive effects."

For those who care about specifics, Ambien/zolpidem is a non-benzodiazepine (non-Valium-like) enhancer of GABA(A) chloride channel function. But like Valium, it depresses the CNS by enhancing GABA-dependent chloride influx, making it more difficult for excitatory neurons to fire. Like other CNS depressants, it should not be combined with other CNS depressants, even something as seemingly innocuous as the over-the-counter antihistamine, Benadryl (diphenhydramine).

Phenergan (promethazine) is a dopamine D2-antagonist developed originally as an antipsychotic drug (i.e., used to treat schizophrenia). It is a member of the chemical class of drugs called phenothiazines. Thorazine (chlorpromazine) is the founder of this drug class, introduced in the early 1960s. People today, and even doctors, underappreciate how Thorazine revolutionized the treatment of mental illness. Despite Thorazine's side effects, institutionalization in "insane asylums" as they were known then decreased dramatically as Thorazine allowed psychotic patients to regain a degree of normal functioning in society.

Today, a number of other "cleaner" and more selective-acting drugs are available for the treatment of psychosis and schizophrenia. Therefore, Phenergan is used today instead to primarily treat nausea simply because it is a "dirty" or non-selective drug: its dopamine D2-blocking effects combine with its antihistaminic (H1) and anticholinergic effects. However, all of these effects together also it a very sedating drug, even when taken alone. (Addendum: The last sentence of this AP article notes that Kennedy has a history of bipolar disorder. However, it is seriously doubtful that he'd be taking Phenergan for that indication as far more superior and selective drugs are now available.)

Combine Ambien with Phenergan and you've got a formula for a situation consistent with the circumstances of Rep Kennedy's accident.

For whatever reason, (oh, I don't know, Chappaquiddick perhaps?) some accounts are trying to link alcohol use to this accident:

For example, The Smoking Gun cites the police report noting that Mr Kennedy's eyes were red and watery at the time of the accident. The "watery" description might not initially seem consistent with the use of Phenergan (promethazine), whose antihistaminic and anticholinergic effects would cause eye dryness. However, the eyes might appear red and irritated due to initial dryness and, depending on the Phenergan dose, might ultimately lead to watery eyes as a physiologic compensatory mechanism.

Only time will tell as to whether Rep Kennedy was impaired by alcohol as well.

However, this should be a lesson to all who take Ambien that they should 1) go immediately to bed after taking the drug, 2) do not combine it with any other CNS depressant, including OTC antihistamines or alcohol, and 3) certainly do not drive an automobile after taking such a drug combination.

Alcohol is not necessary to explain this case... unless one is trying to make a tabloid story out of this unfortunate incident.

[Please note that the author is a PhD pharmacologist with a teaching background in CNS pharmacology. He is not a practicing physician and is not qualified to treat patients or give individual prescription drug counseling or advice. All questions regarding the reader's prescription drug use should be referred to one's doctor and pharmacist.]

Medical wiki revisited - via Respectful Insolence

As we've discussed the promise and danger of open collaboration wikis for medical information over the last week or so, many have raised concerns about who might be providing information for such sources. Several of us have expressed concern that zealots or others with a particular agenda, usually not supported by science, might hijack entries on more controversial or polarizing issues.

My ever-thorough blogging colleague, Orac, has found one example that takes this concern to an extreme: an entire wiki that is not only supported by, but where authorship is exclusive to, the faction who does not accept that the science that supports HIV infection as the cause of AIDS. Orac's post is enlightening because many of my colleagues don't really think that the HIV deniers are all that significant in the public discourse these days.

Actually, I have been quite shocked at just how influential and pervasive groups have become on the Web who, I believe, have the right intentions initially but refuse to budge on their hypotheses when proven wrong by the body of accumulating data. What do I mean? I mean the people for whom hypotheses become beliefs in the face of numerous studies that refute their position. I mean the HIV deniers that have trolled Tara at Aetiology, the mercury/vaccination/autism movement that comes to visit Orac, and the anti-evolution folks who plague PZ and others.

Many of us in biomedical research often just blow off these "believers" as a fringe element. But most of my colleagues would be shocked by how rabid and pervasive this fringe element has become. I am all for open discourse but the scientific method should carry the day.

Freedom of speech most certainly defines the web. But thinking that is not supported by data has no place in medical reference material. More than misleading, it can be downright dangerous. This is a very serious issue that must continue to be considered by my colleagues and visionaries like Peter Frishauf and Larry Sanger as they move forward with their respective projects.

Tuesday, May 02, 2006

Required reading from Dr Larry Sanger

An extremely valuable link on academic/medical wikipedias has emerged from the comment thread, this time from Wikipedia co-founder/chief organizer, Dr Larry Sanger.

Larry's essay at Digital Revolution entitled, "Text and Collaboration," takes a lengthy but clear and highly worthwhile look at many of the issues of a wikipedia (or whatever) for medicine and the academy at-large.

As I commented there,
"Your post here is fascinating and truly begins to discuss the issues that might keep academics and journalists from buying into the concept. The post is well-worth reading and re-reading, with its length reflecting that there are many issues that require contemplation and discussion."

"I’ll write more later on the idea that while academics are expected to be independent and develop a track record of individual, peer-reviewed attribution, there is also a strong movement to encourage and demonstrate collaboration. In fact, I’d argue that research problems in the life and biomedical sciences have grown so complicated and require such diverse and specialized expertise, that one can rarely succeed without [strong] collaboration."

"I’m always inspired by people who continue to move beyond, “no, it won’t work,” and find a way to make it work because of the great benefits for all."

Between hosting last week's Tar Heel Tavern and current research demands, I haven't developed much original content as of late and really do promise to address some of the topics raised by e-mail contributors. But until I can dig out, Larry's essay makes for great reading and further discussion amongst all of us stakeholders in both the blogosphere and traditional academic publishing.

Monday, May 01, 2006

Medical wikipedia - Peter Frishauf responds

Medscape visionary, Peter Frishauf, took the time to respond to my earlier post and our discussion on the virtues of a medical wikipedia:


Thanks for all the kind words. I want to emphasize that in my editorial I said some variant of Wikipedia for medicine would be welcome. Larry Sanger, PhD, a Wikipedia co-founder, is working on just such a venture, to be run by the Digital Universe Foundation.

I want to emphasize that one huge advantage of the Wiki format is that you can read one article enhanced by the wisdom of many, as opposed to having to wade through multiple articles containing the wisdom of a few authors and the people they chose to site. There is no reason we can't marry scientifically-rigourous peer review to the wiki!

Finally, peer review is just one form of a reputation system, and there are many that could be used to assure good science. I will post more about this in the future."

Stay tuned for more discussion from Peter. It's a pleasure to have this dialogue here.