"Islands -- I don't get them.
Surrounded by water, poor things."

Patrizia, in Antonioni's L'Adventura

Have been dutifully working through the manuscript worksheet for 'Fatigue' this morning.

Funny how one's perception about something changes with proximity. This subject for the ies was not developed by either Catherine Whitney or me, but rather by our editor, and I was always a bit leery about the concept, since it is not a proper disease per se, but rather a common component of a tremendous number of other, more specific, diseases.

Yet now that I work on it, I am beginning to believe that there is an important contribution here.

One thing I had forgotten about was the large body of work that I had done on the subject back in the late 1980's, most of which has never seen the printed page. Things like second-messenger (cAMP) enhancement, Schwartzman's endotoxin phenomenon,and the cortisol- 11 beta-hydroxysteroid dehydrogenase axis.

Now I just have to decipher all the cryptic doodlings in my notebooks, which could be a problem since I am one of those people who cannot read their own handwriting.

The quote above is from the delightful Waterfront by Phillip Lopate. The book is literary tour around Manhattan island, from the perspective of a social historian. I am a sucker for architectural history, especially of my beloved borough of Brooklyn ('Fourth Largest City in America'). About a year ago, I embarked on a project to determine the exact whereabouts of original Dutch settlement of New Utrecht, a neighborhood of Brooklyn close to where I grew up, and probably most famous for supplying the high school shots at the opening of 'Welcome Back Kotter.'

From old landholding maps I found on the internet, I could superimpose the old street drawings of New Utrecht as layers in Photoshop over the Mapquest diagrams of the modern area. To my surprise, the town center of New Utrecht lay within the parking lot of a ramshackle discount store where as a child I would get my school supplies, and whose owner in 1969 once tried to convince several very sceptical kids that a chunk of sidewalk in the display case under the checkout counter was actually a moon rock from Apollo 11.

To understand the apparent lack of purpose for that interaction, you must read some of Arthur Miller's remembrances of his childhood in Brooklyn .

I believe our 'Blood Relations' columnist Cocky Van Hesteren hails from 'Old Utrecht' --the real one in the Netherlands.

My brother recently gave me An Architectural Guidebook to Brooklyn by Francis Morrone and James Iska which is a tad on the boring side. However I am sure it will serve much better purposes with the buildings directly in front of me.

If you are interested in NYC architectural history, you'd probably enjoy surfing Kevin Walsh's Forgotten NY website.

Spent yesterday's austere training session working on something called a 'jump spin back kick,' a strange gyration that involves spinning in the air as you jump, ultimately kicking into a direction that you cannot actually see.

Interesting how easy something like this appears to a twelve year old, versus, say, a forty-eight year old. A kid just jumps, much like a cat, knowing that he is springy enough to get up and around, and flexible enough to not be troubled by the thought of a posterior landing. By the time you get to my age, you start to ponder the osseous consequences of this sort an action, which is why you hesitate and fail.

Napoleon once said that it was amazing what you could get an eighteen year old to do for a piece of ribbon.

The immortality thing.

The forty-eight year old is more likely to say 'Uh, no thanks. I have enough ribbon right now.'

Last night my sister in law Rita, an nurse with an extensive background in research, sent me an abstract from the Journal of Clinical Oncology, titled 'Herbal Remedies in the United States: Potential Adverse Interactions With Anticancer Agents' (J Clin Oncol 2004;22 2489-2503). The crux of the article being the potential threat to chemotherapy drug effectiveness posed by such botanicals as garlic and echinacea, which may influence the body's ability to metabolize chemotherapy drugs, and compromise their effectiveness. She asked me what I thought about the article.

When I finally got a full version, two things stuck out immediately. One, this was a review article, meaning that there was no proof of any such activity being presented, but rather a tenuous connection between the known, but rather modest, effects of certain herbs on the cytochrome p450 system (drug detoxification) and the p-glycoprotein levels (drug delivery).

More accurately an editorial, it provided absolutely no evidence to back up any of its assertions. C'mon guys, talking about garlic interfering with p-glycoprotein and blocking a drug like taxol is like saying that a paper bag containing your lunch has the 'hidden potential' to derail an Amtrak train. Hey, if garlic or herbal antioxidants and p-450 modulators were all that effective at blocking cell damage (chemically programmed or not), there wouldn't be any need for oncologists and oncology journals in the first place.

Amazingly, the article then goes on to advise physicians to look into herbal use in non-responding cancer patients as a rationale for treatment failure, a rather cruel balm to the fact that greater than 99% of those non-responders are simply not going to be cured by chemotherapy, herbal medicine or no herbal medicine.

An article published in the Archives of Internal Medicine (Archive Int Med; 1998;20: 2187-2191) may help explain why medical academics spend their time worrying about garlic blocking chemotherapy. It looked at conventional attitudes toward supplementation. Their conclusions: Throughout 20th century American academic medicine has resisted the concept that supplementation with micronutrients might have health benefits.

According to the authors, this resistance is evident in several ways:

(1) by the uncritical acceptance of news of toxicity, such as the belief that vitamin C supplements cause kidney stones;

(2) by the angry, scornful tone used in discussions of micronutrient supplementation in the leading textbooks of medicine; and

(3) by ignoring evidence for possible efficacy of a micronutrient supplement, such as the use of vitamin E for intermittent claudication.

Part of the resistance stems from the fact that the potential benefits of micronutrients were advanced by outsiders, who took their message directly to the public, and part from the fact that the concept of a deficiency disease did not fit in well with prevailing biomedical paradigms, particularly the germ theory. Similar factors might be expected to color the response of academic medicine to any alternative treatment.

I boldfaced the line about 'outsiders' as I can relate to that one personally, since I am a naturopathic physician (strike one!) posit a diet theory that does not fit in well with the prevailing paradigm (strike two!) and wrote a book on the subject for the public (yer out!)

Instead of wasting time looking for herbal inactivators of chemotherapy these folks should look at ABO polymorphism to help explain cancer treatment variation. Type A individuals may have as much as seven fold higher levels of p-glycoprotein, 30% higher levels of von Willebrand Factor and significantly higher levels of e-selectin and ICAM --all know modifiers of metastasis, drug delivery or resistance.

There is a certain lack of candor in a medical community that rebukes supplements as weak and ineffective medicines, yet warns that these same supplements are dangerously blocking chemotherapy drugs.

Reminds me of the joke about the two oldtimers at the early bird special:

The first one turns to the other and says 'The food here is terrible.'

The second oldtimer turns to the first and says 'Yeah, and the portions are small, too.'