the Natural Condition

An important study was released in Nature today that described alarming findings concerning Diet Coke. Researchers discovered that drinking as little as 9 cans of Diet Coke each day can induce hyper-metastatic hyperplasia of the lateral incisors: tooth cancer. Even more disturbing than the fact that this common American beverage causes cancer is the speed of its onset. Certain subjects in their phase IV, double-blind, covariate-adapted, randomized, placebo-controlled trial reported symptoms within seconds of consumption, and many subjects regrettably succumbed to the disease after only a few hours.

The sweetener aspartame is the suspected cause of the tooth cancer, although researchers are continuing to investigate the dubious additive dihydrogen oxide as a possible agent. This rigorous, NIH study found conclusive evidence that aspartame causes cancer in rats. Although the source is yet to be verified in a phase V randomized, controlled trial, scientists have preemptively decided to name the Diet Coke illness “Sweetener-Induced Dental Syndrome,” or “SIDS” for short (although the Samui International Diving School contests their use of the acronym).

The following video shows one man, Rick Astley, shortly before his untimely demise. Mr. Astley had imbibed only 10 cans of Diet Coke in one hour, but he quickly became symptomatic for SIDS. His convulsions in the video demonstrate the relentless cruelty of the disease. The song is a requiem for his ambivalent love of Diet Coke. “Never gonna give you up, never gonna let you down…” were Mr. Astley’s dying words.

Well I think that will suffice for this April Fool’s Day. See, isn’t medicine fun?!

Cancer. The very word evokes an uneasiness in our health-obsessed culture … and, unfortunately, for good reason: malignant neoplasms (cancers) are responsible for more than 1 in every 5 deaths in the United States.¹

First, a little background on cancer (skip to next paragraph for the news). Cancer is basically the proliferation of cells that shouldn’t proliferate. However, a ‘malignant’ neoplasm is additionally defined by proliferating cells that invade the surrounding tissue, causing an indistinct margin between normal cells and the neoplasm. Malignant tumors are contrasted by their benign counterparts, called ‘in situ’ tumors. In situ literally means ‘in place,’ and indicates a well-behaved neoplasm that sticks to itself. In situ tumors can, however, be precursors to malignant behavior. Malignant cancer cells, in addition to encroaching on the immediate surrounding tissue, may enter the blood vessels and lymphatics of the tissue and travel to other parts of the body like the liver, lungs and bone, where they will implant and seed a new colony of cancer cells (however, the colony is made up of the same tissue type as the primary tumor). This event is named metastasis.

The diagram on the right illustrates the accepted progression of healthy cells into cancer. A most interesting aspect to the process is that, while we understand how cancer cells arise — inactivation of tumor suppressor genes, DNA repair mechanisms going haywire, etc. — there is little consensus on why they arise. Many scientists believe that genetic mutations occur at random in some tumor cells, which then father a line of more “rare variant clones,”² leading to observable metastases. Everyone agrees that genetic mutation is the root, but the reason for the genetic mutation is the subject of much debate and extensive research.

Fortunately, new findings help to shed a little light on possible sources of the genetic anomalies. This week’s Nature journal hosted an article that identifies the nuclear protein SATB1, a genomic organizer, as one likely cause of the upregulation of oncogenes and the downregulation of tumor suppressor genes in breast carcinoma. Likely, as in P<0.0001 for prognostic ability, likely.

[The SATB1 protein works] by recruiting chromatin remodelling/modifying enzymes and transcription factors13, 14 to genomic DNA, which it tethers via specialized DNA sequences highly potentiated for unpairing (base unpairing regions, or BURs). … In breast cancer cells, we find that once SATB1 is expressed, it coordinates expression of a large number of genes to induce metastasis.²

The SATB1 protein affects the regulation of over 1000 genes, making it a major player in the pathway to metastatic disease. The researchers also discovered that removing SATB1, “not only reverses metastatic phenotypes but also inhibits tumour growth”² in aggressive breast cancers. The study comprised tests for the presence of SATB1 in human breast carcinoma, among other in vivo trials in mice and in vitro assays.

This discovery is novel because most cancer therapies attempt to combat the disease by minimizing the proliferation of the cancer cells. If a drug were made that targets the SATB1 protein for destruction, it could prevent the cells from developing into cancer at all. Of course, those are BIG “ifs,” and the next obvious question is, what leads to expression of SATB1? And down the carcinogenic rabbit hole we will continue.³

References:
(1) Final Draft of National Vital Statistics Report for 2004. CDC. 2007.
(2) SATB1 reprogrammes gene expression to promote breast tumour growth and metastasis. Nature. 2008.
(3) The proverbial ‘rabbit hole’ is not, itself, a carcinogen; that wouldn’t make any sense. It was just a metaphor for the limitless depth of cancer understanding that we will pursue for the sake of saving lives. Ok, you know what, just forget I mentioned the rabbit hole.

“Count something.”

This keen piece of advice comes from Dr. Atul Gawande, as espoused in his most recent book, Better: A Surgeon’s Notes on Performance. Gawande is a general and endocrine surgeon at the Brigham and Women’s Hospital in Boston, MA. Although he is a surgical fledgling, completing his residency in 2003, Dr. Gawande’s insights blossom from his experience in public health issues, at one point serving as a senior health policy adviser for the Clinton administration.¹

The thesis of Better is that, while advances in medical technology, new drugs, and the like can lead to an overall healthier humanity, the most effective — and commonly overlooked — way to improve well-being is to make better use of what we already have. When he proposes that everyone in the healthcare community ‘count something,’ he means that evaluation and reevaluation of current methodology and practice are the true keys to success. We must measure ourselves, and then use those measurements to understand where shortcomings occur. He also makes it gravely clear that all doctors are not created equal in their ability to treat patients.
… (Read the rest of this article »)

The situation: you are by yourself, and you begin to have severe chest pain, followed by acute vertigo. You are having a heart attack, and moments later you feel like you are about to faint. With a few seconds left before you lose consciousness, what do you do?

In truth, you should dial 911 on your cell phone. But after that… cough, deeply and forecefully, about once every 1 to 3 seconds. Long derailed as a hype product of the devious “world-wide web,” improvised ‘cough CPR’ may actually have some merit, according to some cardiovascular researchers. The idea of coughing to sustain arterial pressure and to induce blood flow first appeared in the Journal of the American Medical Association in 1976¹. Therein, the authors purported that coughing during ventricular fibrillation not only kept several patients conscious for up to 39 seconds after the onset of VF, but that coughing maintained arterial pressure at almost 140mmHg, compared to only 60mmHg for traditional chest compressions. That is, they indicated that ‘cough-CPR’ could have advantages over normal CPR.

And while the American Heart Association, formally and adamantly, does not endorse the maneuver², scientists continue to demonstrate that coughing during a heart attack can actually help blood circulate. The picture below shows the EKG … (Read the rest of this article »)

Today I attended a forum on genetic testing for the Massachusetts General Hospital’s weekly Breast Rounds (I do research in breast oncology at the MGH). This week’s lecture, presented by Joseph D. McInerney, the Director of the National Coalition for Health Professional Education in Genetics, considered various aspects of the new wave of direct-to-consumer genetic testing. Genetic testing for specific gene markers¹ has been available for many years, and the results are primarily used by doctors and genetic counselors to determine the relative risks of disease onset and/or recurrence. This information allows the healthcare team to plan a course of treatment or preventative measures for a patient under supervised, knowledgeable care.

However, unlike “traditional” genetic testing, the professional health world does not filter this new era of direct-to-consumer genetic testing before it reaches the “consumers” (read: patients). Sites such as 23andMe.com and Navigenics.com advertise that anyone can obtain a complete genetic profile for as little as $999, which will outline propensity for certain diseases, among other recreational identifiers, like food preference. A most important note about these sorts of health-related tests: the FDA … (Read the rest of this article »)

I was at an interview for medical school a few weeks ago, and was asked the question:

What do you think is the greatest problem facing healthcare today?

In the following paragraphs I outline the gist of my response, and some embellishments on the topic.

While I was in college, I can remember attending a lecture by the former United States Surgeon General Dr. C. Everett Koop. While Dr. Koop is best known for his monumental work in enhancing public awareness about the dangers of cigarette smoking (indeed, he is the one responsible for the warning labels prominently displayed on all packs of smokes), he actually spent most of his career pioneering the field of pediatric surgery at the Children’s Hospital of Philadelphia. He is a most distinguished graduate of Dartmouth College (class of 1937), and, more interestingly for the non-Dartmouth readers, he was interviewed on the Ali-G show, so clearly he merits profound respect.

At the time of this lecture, Dr. Koop was almost 90 years old. I was expecting to hear a speech from a elderly man whose wisdom would be sadly muffled by his frailty. It turned out that he still spoke with a loud and penetrating voice … (Read the rest of this article »)