a change of place

By |September 7th, 2014

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(what follows here at ML will be old posts, rotated occasionally):

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By |September 7th, 2014|Categories: Blogs, from the author, journalism||Comments Off on a change of place

Looking Back on ‘The Normal Heart,’ and Patients’ Activisim

By |June 24th, 2011

A few weeks ago I saw The Normal Heart, a play about the early, unfolding AIDS epidemic in NYC and founding of the Gay Men’s Health Crisis. The semi-autobiographical and now essentially historical work by Larry Kramer first opened at the Public Theater in 1985.

Cover of the paperback, published by “Plume,” from Wikipedia

The story takes on the perspective of a young man who’s seeing the death of too many of his friends and neighbors from a strange and previously-unknown disease. As much as the situation is disturbing, and frightening, and shattering of the gay men’s barely decade-old freedom to behave as they choose, most of the protagonist’s associates just can’t deal with it. Nor can other, potentially sympathetic officials like Mayor Koch, health officials at the CDC and NIH.

Among the men who form GMHC, in this drama, there’s a mixed crew. Some say they’re  embarrassed by the attention the illness drew to some gay men’s behavior. Many stay fully or half-closeted, understandably insecure in their jobs. They worry about discrimination and rejection by families, landlords and even doctors, some who were reluctant to take on patients with this disease. Some of the affected men and their friends, straightforwardly, fear death; others are in plain denial about what’s going on in their community.

The scenes unfold between 1981 and 1984, more or less the time when I moved to Manhattan, lived downtown, applied and matriculated at NYU’s medical school. Many of the first clinical cases, i.e. patients, I saw, were young men with HIV and Kaposi’s sarcoma, one of the first conditions associated with the outbreak and that’s featured in the play – the appearance of maroon or violet-colored, usually but not always flat, often elongate, spots on the skin. The AIDS patients tended to have anemia, either from immune blood disorders or, more often, infection in the bone marrow. As a hematologist-to-be, I was intrigued.

Then and now, looking back, it’s hard not to respect those men’s activism, especially those who, with Kramer, created the AIDS Coalition to Unleash Power (ACT UP). They were impatient with the pace of research and physicians’ protocols, and spoke out so emphatically about their needs: for more research; for prevention and treatment; for easier access to new drugs; and, simply, for good medical care.

The play closes soon in New York;  its producers are said to be planning a tour and a London production of the work. Patients and their advocates, of all backgrounds and particular concerns, might take notes.

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Radiologists’ Experience Matters in Mammography Outcomes

By |February 24th, 2011

There’s a new study out on mammography with important implications for breast cancer screening. The main result is that when radiologists review more mammograms per year, the rate of false positives declines.

The stated purpose of the research,* published in the journal Radiology, was to see how radiologists’ interpretive volume – essentially the number of mammograms read per year – affects their performance in breast cancer screening.  The investigators collected data from six registries participating in the NCI’s Breast Cancer Surveillance Consortium, involving 120 radiologists who interpreted 783,965 screening mammograms from 2002 to 2006. So it was a big study, at least in terms of the number of images and outcomes assessed.

First – and before reaching any conclusions – the variance among seasoned radiologists’ everyday experience reading mammograms is striking. From the paper:

…We studied 120 radiologists with a median age of 54 years (range, 37–74 years); most worked full time (75%), had 20 or more years of experience (53%), and had no fellowship training in breast imaging (92%). Time spent in breast imaging varied, with 26% of radiologists working less than 20% and 33% working 80%–100% of their time in breast imaging. Most (61%) interpreted 1000–2999 mammograms annually, with 9% interpreting 5000 or more mammograms.

So they’re looking at a diverse bunch of radiologists reading mammograms, as young as 37 and as old as 74, most with no extra training in the subspecialty. The fraction of work effort spent on breast imaging –presumably mammography, sonos and MRIs – ranged from a quarter of the group (26%) who spend less than a fifth of their time on it and a third (33%) who spend almost all of their time on breast imaging studies.

The investigators summarize their findings in the abstract:

The mean false-positive rate was 9.1% (95% CI: 8.1%, 10.1%), with rates significantly higher for radiologists who had the lowest total (P = .008) and screening (P = .015) volumes. Radiologists with low diagnostic volume (P = .004 and P = .008) and a greater screening focus (P = .003 and P = .002) had significantly lower false-positive and cancer detection rates, respectively. Median invasive tumor size and proportion of cancers detected at early stages did not vary by volume.

This means is that radiologists who review more mammograms are better at reading them correctly. The main difference is that they are less likely to call a false positive. Their work is otherwise comparable, mainly in terms of cancers identified.**

Why this matters is because the costs of false positives – emotional (which I have argued shouldn’t matter so much), physical (surgery, complications of surgery, scars) and financial (costs of biopsies and surgery) are said to be the main problem with breast cancer screening by mammography. If we can reduce the false positive rate, BC screening becomes more efficient and safer.

Time provides the only major press coverage I found on this study, and suggests the findings may be counter-intuitive. I guess the notion is that radiologists might tire of reading so many films, or that a higher volume of work is inherently detrimental.

But I wasn’t at all surprised, nor do I find the results counter-intuitive: the more time a medical specialist spends doing the same sort of work – say examining blood cells under the microscope, as I used to do, routinely – the more likely that doctor will know the difference between a benign variant and a likely sign of malignancy.

Finally, the authors point to the potential problem of inaccessibility of specialized radiologists – an argument against greater requirements, in terms of the number of mammograms a radiologist needs to read per year to be deemed qualified by the FDA and MQSA. The point is that in some rural areas, women wouldn’t have access to mammography if there’s more stringency on radiologists’ volume. But I don’t see this accessibility problem as a valid issue. If the images were all digital, the doctor’s location shouldn’t matter at all.


*The work, put forth by the Group Health Research Institute and involving a broad range or investigators including biostatisticians, public health specialists, radiologists from institutions across the U.S., received significant funding from the ACS,  the Longaberger Company’s Horizon of Hope Campaign, the Breast Cancer Stamp Fund, the Agency for Healthcare Research and Quality (AHRQ) and the NCI.

**I recommend a read of the full paper and in particular the discussion section, if you can access it through a library or elsewhere. It’s fairly long, and includes some nuanced findings I could not fully cover here.

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A Play About the Life and Work of Dr. Rosalind Franklin

By |November 11th, 2010

Last weekend I snagged a last-minute ticket to see Photograph 51, a new play about the work and life of Rosalind Franklin. Her data, possibly stolen, enabled Francis Crick and James Watson to decipher and model the double-helix structure of DNA.

The intimate production, enacted by the small Ensemble Studio Theatre on the second floor of a nondescript building on West 52nd Street, affords a fresh look, albeit partly fictionalized, into important moments in the history of science. Most of the scenes take place in a research lab in post-War London, at King’s College, where Franklin took on a faculty appointment.

Franklin’s story starts like this: She was born in 1920 to a Jewish family in London. She excelled in math and science. She studied physical chemistry at Cambridge, where she received her undergraduate degree in 1941. After performing research in photochemistry in the following year on scholarship, she joined the British Coal Utilisation Research Association (BCURA) and carried out basic investigations on the micro-structure of coal and carbon compounds, and so earned a Ph.D. from Cambridge University. She was a polyglot, and next found herself in Paris at the Laboratoire Central des Services Chimique de l’Etat, where she picked up some fine skills in x-ray crystallography.

You get the picture: she was smart, well-educated and totally immersed in physical chemistry before, during and after WWII. Single-minded and focused, you might say –

Franklin in Photograph 51 wears a simple brown dress with large black buttons straight down the middle of her lithe frame. Her lipstick and haircut seem right, but her three inch heels, even after a few years of experiencing the joie de vivre in Paris, or just being holed up in a research institute there, seem a tad too high for such a pragmatic soul. The lab set is perfect with its double-distilling glassware, wooden pegs on racks, tall metal stools with small, flat circular seats, light microscopes, heavy metal desks with file drawers and a contentious cast of characters.

As this narrative goes, Franklin spurns socializing with most of her colleagues. They find her difficult. She spends nearly all of her time and late hours using x-rays to generate crystallographic images of DNA and making detailed notes and related calculations. Eventually a lab assistant gives her key data, Photograph 51, to her colleague, Maurice Wilkins, who is inexpert in crystallography and cannot independently interpret the structure. While Franklin continues working at a measured pace, refusing to rush into publishing a model until she’s sure of her findings and the implications, Wilkins shares the image with Watson and Crick. They move quickly, publish first in Nature and, later, win the Nobel Prize for the discovery. Meanwhile Franklin leaves Wilkins’ lab and starts a new project on the structure of tobacco mosaic virus. She dies at the age of 37 of ovarian cancer, likely caused or effectuated by the radiation to which she exposed herself at work.

It’s a sad story, but instructive, engaging and very well-done, so much that it’s haunted me for days. Hard to know what’s real –

According to a program note from Anna Ziegler, the playwright: “this play is a work of fiction, though it is based on the story of the race to the double helix in England in the years between 1951 and 1953.” Ziegler refers to several books from which she drew material: The Dark Lady of DNA (by Brenda Maddox), The Double Helix (by James Watson) and The Third Man of the Double Helix (by Maurice Wilkins).

My favorite part is Franklin’s statement at the beginning: “We made the visible, visible.”

For a (depressing) counterpoint to this play’s version of events, you can take a look at Nobel Laureate James Watson’s 2007 TED lecture on YouTube. “She was a crystallographer,” he says of Franklin, and other things, before delving into his late-life happiness and current ventures in cancer genetics and autism studies.

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