The Trouble With Ginger

By |April 29th, 2011

A short post for Friday:

The Times published a short piece on ginger this Tuesday, on whether or not it relieves morning sickness. The conclusion is that it’s less effective for nausea in pregnancy than in seasickness and chemotherapy treatment.

When I was getting chemo, I received a gift of ginger tea. It didn’t help at all. Now, if I even sniff that stuff, I want to throw up.

Curiously, I have no problems with ginger in food. I use the fresh ingredient all the time.

No explanation -

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Some Articles I Authored A While Ago

By |April 28th, 2011

This post, on my research in cancer immunology, is strangely personal.

At one level, what follows is nothing more than a list, a narrative if you will, a sketch of a formative chunk of my career and personal history. I’ve wanted to put this out there (here) for quite a while, but couldn’t: It’s been hard for me, harder in some ways than was the breast cancer and spine surgery and all the other unpleasant illnesses I haven’t mentioned yet, to come to grips with my near-hit academic medial research career that stopped, which until today has been for the most part disconnected from this blog and my new on-line life.

So here goes, a partial list of my publications, selected from ~30:

On a novel mechanism for B-cell death, my first first-author article based on my research in lymphoma immunology, in The Journal of Experimental Medicine, 1995:

CD40 ligation induces Apo-1/Fas expression on human B lymphocytes and facilitates apoptosis through the Apo-1/Fas pathway

On how “helper” T cells can kill some forms of malignant B cells, in Blood, 1996:

CD4+ T-cell induction of Fas-mediated apoptosis in Burkitt’s lymphoma B cells

A solicited review of my early labwork, completed with my research mentor, in Immunologic Research, 1996:

Fas expression and apoptosis in human B cells

My first paper on CD40L and autoimmunity, in CLL, in Blood, 1998:

Chronic Lymphocytic Leukemia B Cells Can Express CD40 Ligand and Demonstrate T-Cell Type Costimulatory Capacity

A case report (as my lab and non-physical stature grew I became senior author), in the British Journal of Haemotology, 1998:

Novel association of haemophagocytic syndrome with Kaposi’s sarcoma-associated herpesvirus-related primary effusion lymphoma

On some experiments with mantle cell lymphoma cells, in Leukemia, 2000:

Proliferative response of mantle cell lymphoma cells stimulated by CD40 ligation and IL-4

Work accomplished with colleagues-now-friends, in Blood, 2000:

Inhibition of NF-kB induces apoptosis of KSHV-infected primary effusion lymphoma cells

The first major paper from my NIH-funded lab, in The Journal of Immunology, 2000:

Modulation of NF-kB Activity and Apoptosis in Chronic Lymphocytic Leukemia B Cells

We sent this one to Science. They declined. So did a bunch of other journals. Eventually it came out in Blood, 2001:

Survival of leukemic B cells promoted by engagement of the antigen receptor

A nearly life-eating chapter that took up way too much of my time but was probably worthwhile nonetheless, on immunology, for a Neoplastic Hematopathology textbook, in 2001:

Immune System: Structure and Function

An interesting story, we thought, in Autoimmunity, 2002:

Inhibition of Fas-mediated apoptosis by antigen: implications for lymphomagenesis

A monograph I wrote around the time I got sick, on how malignant lymphocytes die, somewhat theoretical, in Cancer Investigation, 2002:

Apoptosis in Lymphocytic Leukemias and Lymphomas

For there record, there’s earlier and later stuff too, by me alone and with others, and (sadly) reams of unpublished data, mainly from 1997 – 2002. These are the published papers I consider most my own.

Looking back, I’m pretty sure we were right, at least on most of these findings.

(Is there an opposite-of-decline effect?)

I’ve often wondered how differently things might have turned out if there’d been blogs and open-access journals with real-time comments when we in my lab were trying to get our work published in top, grant-renewing, tenure-securing journals.

Didn’t happen…

Well, now that this is done, I can keep moving forward!

With gratitude to my colleagues who collaborated, and especially to those who worked with me in the lab,

ES

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New Findings on Leprosy and Armadillos

By |April 27th, 2011

A surprise lesson arrived in my snail mailbox today: the April 28 issue of NEJM includes a fascinating research paper on a probable cause of leprosy in the southern U.S. New, detailed genetic studies show that armadillos, long-known to harbor the disease, carry the same strain as occurs in some patients; they’re a likely culprit in some cases.

Dr. Gerhard Henrik Armauer Hansen, who identified the bacteria causing leprosy

Dr. Gerhard Henrik Armauer Hansen, who identified the bacteria causing leprosy

For those who didn’t go to med school: Leprosy is a chronic, infectious disease cause by Mycobacterium leprae. In my second year we were told to refer to the illness as Hansen’s disease. We learned that some people are more susceptible to it than others, possibly due to inherited immunological differences, a point that is reiterated in the current article.

The World Health Organization reports there are under 250,000 cases worldwide every year. Here in the U.S., Hansen’s disease is quite rare, with about 150 new cases reported annually according to the study authors. The condition wasn’t evident in the Americas before Columbus’ travels, but by the mid-18th Century it was affecting some settlers near New Orleans. Today, most cases in the U.S. arise in travelers and others who’ve lived or worked abroad in regions where leprosy is endemic. About a third crop up in people who’ve never left the country, and these cases tend to cluster in the southeastern U.S.

Leprosy tends to affect the skin, and what the NEJM investigators first did was examine skin biopsy specimens from patients who live in the U.S. and hadn’t traveled. It’s been known for decades that armadillos can carry these bacteria, and so the researchers took specimens from wild armadillos in five southern states, and analyzed the M. leprae bacterial genomes. They matched. Then they looked at more patients’ samples, and also analyzed M. leprae sequences from patients in other parts of the world.

The conclusion is that wild armadillos and some leprosy patients in the southern U.S. are infected with an identical strain of the bacteria that causes leprosy. From this information, the authors infer that armadillos are a reservoir for this stigmatizing germ, and that they may be the source of some patients’ infections.

So the news is that leprosy may be a zoonosis.

A personal note –

Only once I saw a patient with Hansen’s disease, at the Bellevue dermatology clinic, when I was a fourth-year student. She was an elderly woman from China. Her face, which I can picture now, had classic leonine features. The resident caring for her,  an intern with a plan to become a dermatologist, prescribed antibiotics.

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A Trans-Cultural Time-Crossing Take on Long Words, and Medical Jargon

By |April 26th, 2011

Today Scientific American shared this bit from its 50-year archive, by the mathematician Sherman K. Stein, recounting an interview with the composer George Perle on a theory of rhythm developed in India over 1000 years ago:

While reading about this theory,’ he said, ‘I learned my one and only Sanskrit word: yamátárájabhánasalagám.’ I asked him what it meant. ‘It’s just a nonsense word invented as a memory aid for Indian drummers…. As you pronounce the word you sweep out all possible triplets of short and long beats.’

Sounds like onomatopoeia, or something similar in ancient Indian music parlance. But I’m no drummer, and I don’t know Sanskrit.

It’s got me wondering about the thousands of ancient, hard-to-spell-or-say terms, not rooted in Greek or Latin, for complex medical conditions doctors use today, about which we have so little knowledge.

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Who Was Nurse Mary Jane Seacole?

By |April 25th, 2011

(and, on bias in education)

On the bus last week I was reading the latest New Yorker and came upon a short, front-end piece by Ian Frazier on Mary Jane Seacole, a Jamaican nurse who tended wounded soldiers in the Crimean War. As best as I can recall, I’d never heard before of Florence Nightingale’s colleague.

Wiki Commons image

From Two Nurses:

Florence Nightingale strongly disapproved of Mary Jane Seacole, but that did not stop either of them. The former invented the profession of nursing and became famous for her work on the battlefields of the Crimean War. The latter grew up in Jamaica, knew native remedies learned from her Jamaican mother…supported herself by selling jams, pickles, and spices after her husband’s death, travelled widely, and offered to nurse soldiers in the Crimean War with Nightingale. Turned down, Mary Seacole went to the Crimea anyway. She paid her own expenses, tended the wounded on both sides, constructed a hotel-clinic from scrap, and handed out wine and hot tea to the soldiers. They loved her…

Moving beyond the certainly fact-checked details on the legend of Mary Seacole, I learned that there is a Society for the Advancement of the Caribbean Diaspora, based in Brooklyn, a borough in the city where I live. And confirmed that March was Woman’s History Month.

Seacole’s autobiography, Wonderful Adventures of Mrs. Seacole in Many Lands, was an 1857 best-seller, Frazier wrote. According to the University of Pennsylvania’s Digital Library, James Blackwood, a 19th Century London publisher based at Paternoster Row, put forth her story.

So much to learn here. I wonder if anyone’s written a Seacole biography other than her own?

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Blogging Addiction Disorder

By |April 21st, 2011

The author has been concerned for a while that she might be addicted to blogging. Symptoms include wanting to post instead of working on a book proposal and other, likely more important projects. She was thinking of crowd-sourcing how best to describe this disposition, but it turns out the Internet already provides a diagnostic term:

Blogging Addiction Disorder, a.k.a. BAD, a possible variant of Internet Addiction Disorder.

That’s enough for today. (NTW, I’ll get back to work now.)

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Dr. Greenfield is Human

By |April 20th, 2011

A few days ago I read that Dr. Lazar Greenfield, Professor Emeritus at the University of Michigan, resigned as the president-elect of the American College of Surgeons over flak for authoring a Valentine’s Day-pegged, tacky, tasteless and sexist piece in Surgery News. The February issue is mysteriously absent in the pdf-ied archives. According to the Times coverage: “The editorial cited research that found that female college students who had had unprotected sex were less depressed than those whose partners used condoms.

From Pauline Chen, also in the Times:

It begins with a reference to the mating behaviors of fruit flies, then goes on to discuss studies on the menstrual cycles of heterosexual and lesbian women who live together. Citing the research of evolutionary psychologists at the State University of New York, it describes how female college students who had been exposed to semen were less depressed than their peers who had not, concluding: “So there’s a deeper bond between men and women than St. Valentine would have suspected, and now we know there’s a better gift for that day than chocolates.”

Not that I’m OK with any of this, as I’ve known the ickiness of older male physicians who don’t even realize when they’re being inappropriate.

But this morning I learned from Orac that Dr. Greenfield is the Dr. Greenfield, the one that invented the Greenfield filter. This threw me a bit, because I admire Dr. Greenfield for his work. He’s saved a lot of lives, perhaps tens of thousands. (I’m guessing on this number; it could be more, the point is – a Tsunami’s worth of lives.)

Doctors, including non-surgeons like me, would sometimes advise insertion of Greenfield filters in patients with blood clots and a contraindication to blood thinning. One example of countless I recall in my own experience as an oncologist: an elderly patient with pancreatic cancer and limited mobility who had a DVT in the leg and a brain met. We wouldn’t want to give the patient a standard blood thinner, like heparin or coumadin, because the tumor in the brain might bleed with catastrophic effect.

The common teaching was that a Greenfield filter, inserted through a large thigh vein up to the inferior vena cava, would prevent a blood clot from spreading from a patient’s leg up to the heart’s right chamber and into the lung’s circulation, where it might lodge in the form of a pulmonary embolus, a serious and sometimes lethal condition.

As a patient, I once had a newer-model Greenfield placed on a temporary basis. Because I’d had a major DVT while immobilized after spine surgery for scoliosis as a teenager, and then I had breast cancer – another risk factor for DVT – when I needed spinal repair as an adult in 2003, my orthopedist and hematologist were concerned that my risk for developing another major clot was great. Because they couldn’t put me on an anticoagulant for days after such a big operation, they advised prophylactic insertion of a temporary Greenfield device. I accepted the plan, hesitatingly, as reasonable.

So from both my professional doctor’s and my patient’s perspective, I’ve perceived value in Dr. Greenfield’s contribution and possibly benefited from his work. Then again, a 2000 review in Blood suggests more evidence is needed to support the filters’ widespread use. I agree.

The clearest take, maybe, is that some powerfully driven, innovative and brilliant people make personal mistakes.

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Passover Preparations, and Good Housekeeping

By |April 18th, 2011

There’s so much medical stuff I’d like to write on today. The thing is, it’s almost Passover. I’ve just got a few hours to finish readying our home for the holiday.

And so this will be the topic for today’s ML, on home-making:

Part of the Passover preparation is, in my mind, like spring cleaning: we scrub surfaces in the kitchen, pantry and elsewhere; we shake out all the rugs and vacuum or sweep extra carefully; we go through old foods and decide what’s worth keeping or should be discarded. We remove all bits of bread, and then set a minor flame (I use a match) to, symbolically and really, burn the last crumb.

I’m reminded of the spring of 1987, when I spent the second half of Passover in a small apartment in Cochabamba, Bolivia, where I followed an endocrinologist in his rounds and learned about so-called tropical diseases: malaria, Chagas, amoeba and other parasites I hadn’t seen first-hand before. There was running water for only 4 hours early each day in the place where I stayed; I learned to gather, boil it and apply iodine to sterilize it before washing my few dishes. There I ate matzah I’d stashed in my suitcase. (Later on in my journey, its well-known constipating effects proved beneficial.)

The main public hospital in Cochabamba held patients in old-fashioned, long rectangular rooms with 15 or 20 beds along each side. Ventilation came by breezes through the open windows, and patients’ families were responsible for giving them food. Nurses – nuns, really – kept the place clean; they swept under each bed daily. No blankets or sheets touched the floor; it was immaculate.

I know there are people out there who think a sterile home breeds diseases – like asthma and peanut allergies and maybe even Hodgkin’s; the notion is that somehow it’s good to get our immune systems exposed at an early age to lots of bacteria and other organisms, so they won’t respond too vigorously to nature’s tiniest offerings. While there may be a germ of truth in some of these arguments (for the record, I don’t agree with most, and am fearful of the harmful bugs and parasites that can be lethal if ingested), I do think that for the most part, we could do a better job on the hygiene front.

At the AHCJ meeting I attended a session on food safety. There was a lot of discussion of how the FDA, USDA and other agencies are and aren’t tracing sources of contamination in the food supply, from large and small (excluded from some regulations) growers and manufacturers, and what to do about imported foods, which are screened now for radioactivity as well as for unwanted germs.

The way I see it is this: We’re responsible for our health to the extent that our behavior can reduce our risk of illness. Keeping a clean home, and washing food thoroughly, and cooking it carefully, are things we can do to reduce the odds of getting sick. Nothing’s full-proof, and I don’t mean to suggest that if someone develops hemolytic uremic syndrome from eating contaminated spinach or bad ground beef that it’s their fault.

But maybe we’ve become lazy as a culture, or just too rushed: we buy prepared food and pre-”washed” salad. We grow accustomed to the dust behind a bed-board or bookcase that’s hard to move; we don’t flip the couch cushions periodically and clean what’s under there, as perhaps our grandmothers would have, should they have been sufficiently fortunate to have upholstered furniture.

I admit that I’m very imperfect in all of this, that my home is far from absolutely clean, and that I sometimes eat salad in restaurants where I doubt it’s been quite so-well washed as I’d like or want to know. There is surely some dust on this laptop, and I fear now there may be a crumb of bread that’s escaped the feather’s final sweep.

But I’ll do my best, and sign off now, and enjoy the holiday with my family.

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The Medical Word of the Week is Theranostic

By |April 17th, 2011

The author learned a new word this weekend while attending the annual meeting of the Association of Health Care Journalists in Philadelphia.

In a richly-informative session on ethics of clinical trials, one of the speakers, Dr. Jason Karlawish – a bioethicist, geriatrician and Alzheimer’s researcher at the University of Pennsylvania, taught me a new term: theranostic (alt. spelling: theragnostic).

The neologism calculatingly brings together the concepts of medical therapy and diagnosis. This goes beyond biomarkers, he explained; theranostics are novel tests or diagnostic markers that would identify patients who, as defined, benefit from a particular therapy.

The first international conference on theranostics will be held in June, he told the audience.

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Internet-Based Medical Information May Prove More Trustworthy Than Printed Texts

By |April 12th, 2011

Today Ed Silverman of Pharmalot considers the case of a ghost-written medical text’s mysterious disappearance. The 1999 book, “Recognition and Treatment of Psychiatric Disorders: A Psychopharmacology Handbook for Primary Care,” (reviewed in a psychiatry journal here) came under scrutiny last fall when it became evident that the physician “authors” didn’t just receive money from a relevant drug maker, SmithKline Beecham; they received an outline and text for the book from pharmaceutical company-hired writers.

poster for the X-Files

The book is no longer evident at the website for STI (Scientific Therapeutic Information), the company that provided authorship “help.” I tried to get a copy on Amazon.com, where it’s said to be temporarily out-of-stock. The work remains listed in the Library of Congress on-line catalog: #99015420.

I’m reminded of clinical handbooks I used all the time when I was practicing hematology and oncology. At the hospital, I’d get freebie, small-sized chemo regimen primers that conveniently fit into my white coat pocket. In retrospect, perhaps I didn’t adequately check the authors’ credentials on those mini-book sources. It was too easy to take that information and keep it at hand, literally, especially in the times before we had constant Web access.

And I’m struck by how the Internet – that infinite bucket of once-lowly or at-best mixed-quality information doctors disparaged for years – may prove a better information source than printed books.

It’s a minor paradox, or a twist in trust -

Now, with a few clicks if you know where to look, you can get recommendations for chemo dosing from reliable sources, like the NIH or peer-reviewed journal articles. Although transparency about physicians’ ties to industry is not nearly yet where it should be, you can find out about more about an author’s connections and potential conflicts of interest than at any time in medical publishing history.

What we write here can’t be discarded, burned, or go out of print.

(And it may be corrected, readily, before the next edition.)

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