Judy Foreman

Nationally Sindicated Fitness, Health, and Medicine Columnist

A New Heart Disease Test That Could Save Your Life

by

A new test called high sensitivity CRP, catapulted into the headlines last week by a study in the New England Journal of Medicine, appears to be better than cholesterol at predicting the risk of heart attack and stroke. The test measures levels of an inflammatory substance, C-reactive protein that plays a role in cardiovascular disease.

So, to cut to the chase, should you ask for the CRP test? Yes. It’s cheap (about $16).  It’s already on the market. It could save your life, especially if it a worrisome result gets you to exercise more and eat less. Besides, if it’s good enough for President George W. Bush, who has passed the test with flying colors, it’s good enough for the rest of us.

To be sure, an editorial last week in the New England Journal took a more cautious view, arguing that “it may be premature” to adopt widespread screening for C-reactive protein.

And there are legitimate caveats. No one -yet – is recommending that the test be done routinely for all adults. The experts – a committee of specialists from the Centers for Disease Control and Prevention and the American Heart Association – are still hashing out who should get it. Chances are their recommendations, due out soon, will initially recommend the test, if at all, only for people whose risk is unclear or moderate based on other tests. In any event, CRP will not replace cholesterol testing, but will be an add-on.

There’s also the concern, present with any screening test, that worrisome results could set you on a path of intervention that could do harm as well as good. For instance, if your CRP test is high, do you just exercise more and eat less? Or do you start taking statins, which can lower CRP as well as cholesterol? The evidence that statins lower CRP is growing, but it’s not conclusive, and statins do carry some risk.

Moreover, CRP testing might not pan out once it’s used widely, not just in research. After all, cholesterol hasn’t been such a great predictor – half of people who have heart attacks have normal cholesterol.

Finally, just for the record, much of the work on CRP, including the latest study, has been done by researchers at Brigham and Women’s Hospital, which owns the patents on inflammatory markers for cardiovascular disease. This does not taint the research. But CRP testing is a potentially lucrative business.

That said, the new study, which confirms a considerable body of previous work, is paradigm-shaking, poised to change the way doctors screen for heart disease.

Led by Dr. Paul Ridker, director of cardiovascular disease prevention at Brigham and Women’s, the new study followed 27,939 healthy middle-aged women for eight years to assess their risk of having a first heart attack, stroke, cardiac bypass surgery or death from cardiovascular causes.

The researchers found, as expected, that women with high levels of  both CRP and LDL cholesterol were at high risk of cardiovascular problems, and that women with low levels on both tests were at low risk. The surprise was the women in the middle.

In the study, women with high CRP but low cholesterol were actually at higher risk than those with high cholesterol and low CRP, even though the former group is usually deemed low risk by current screening.

“The study provides overwhelming evidence that inflammation is at least as important as LDL cholesterol in predicting vascular risk,” notes Ridker. In fact,25 percent of the US population has elevated CRP levels but normal to low levels of LDL, suggesting that millions of Americans may be at increased risk despite normal or low cholesterol.

 “The CRP story gets more interesting every day,” says Dr. Sidney Smith, chief scientific officer for the American Heart Association and professor of medicine at the University of North Carolina at Chapel Hill. “The evidence for its value is compelling, but not as a replacement for cholesterol. It will be useful for some patients in combination with other measures of risk.”

For years, doctors have known that cholesterol-filled plaques in artery walls pose a significant danger. If these plaques completely block an artery, the heart can be deprived – sometimes fatally – of adequate blood flow.

But doctors also know that even if plaques don’t completely block an artery, they can trigger heart attacks if they rupture, releasing blood clots that themselves can block an artery to the heart or brain.

Indeed, most heart attacks are actually caused by smaller, “vulnerable” plaques at risk of rupture, says Massachusetts General Hospital cardiologist Dr. James Muller, co-director of the vulnerable plaque program of CIMIT, the hospital’s center for integration of medicine and innovative technology.

So far, vulnerable plaques, which are filled with inflammatory cells from the immune system, cannot be detected with standard imaging techniques such as coronary angiograms or CT scans.

Enter C-reactive protein, a substance made in the liver and released during infections. Standard CRP tests are routinely used to gauge the degree of inflammatory response in everything from pneumonia to rheumatoid arthritis.

But the new, high sensitive cardiac CRP tests, sublicensed through Dade Behring in Deerfield, Ill., measure tiny fluctuations at the low end of the range. (A worrisome score on the new test could indicate nothing worse than a common cold; but if a repeat test several weeks later is still high, it may indicate a persistent inflammation in the body, including fragile, inflamed plaques.)

Moreover, CRP is not just a marker of inflammation, but a bad actor directly involved in the in process of inflammation in plaques, notes Dr. Richard  Pasternak, director of preventive cardiology at MGH.

That suggests that lowering CRP may directly lower the risk of cardiovascular disease. Indeed, with statin drugs (Lipitor, Pravachol, Lescol, Zocor and Mevacor), already used to lower cholesterol may be prescribed to lower CRP as well.

There’s already “an overwhelming abundance of data that statin drugs lower CRP levels,” says Dr. Karol Watson, co-director of the preventive cardiology program at the University of California, Los Angeles. In fact, one study, published in August in  the Circulation, the journal of the American  Heart Association, showed that such drug, simvastatin, lowers CRP levels very quickly – in just two weeks.

Still, not everyone believes CRP testing is ready for prime time, or that, even if it is,  doctors should begin prescribing statins for this reason, as Ridker is the first to note.

Compelling as the new data may be, it does not address whether treating people on the basis of high CRP test results is justified, notes Dr. Christopher O’Donnell, associate director of the Framingham Heart Study, a research effort sponsored by the National Heart Lung and Blood Institute..

Indeed, statins, though generally safe, can cause liver and muscle damage. One statin,  Baycol (cerivastatin), was voluntarily taken off the market last year because it was associated with 31 fatal cases of a kind of muscle damage called rhabdomyolysis.

In other words, key  questions remain, including whether the humble aspirin, an anti-inflammatory as well as anti-clotting drug, might also be used to lower CRP levels.

 Still, CRP is the most promising advance in a long time in detecting cardiovascular risk. At the very least, it makes sense to ask your doctor about it.

No Drug Cure in Sight for Obesity

by

Three very fat Turkish people, all cousins, got very lucky this year, when they spent a few months in Los Angeles getting injections of leptin, the “satiety” hormone discovered in 1994 and immediately hailed as the long-awaited magic bullet to cure obesity.

The three, a 27-year old man who weighed 312 pounds, a 35-year old woman who weight 253 pounds and a 40 year old woman who weighed 194 pounds, were all miserable.

The man was so fat, he said through an interpreter, that he couldn’t get a job, or a girlfriend. One woman had to work at home as a seamstress because people made fun of her if she went out. The other had given up her dreams of marriage, devoting herself to taking care of her parents.

By the time they headed back to Turkey in July after their treatments, they had each lost roughly half of their body weight, says the researcher who treated them, Dr. Julio Licinio, professor of psychiatry and medicine at the David Geffen School of Medicine at UCLA.

A pair of obese Pakistani cousins living in England, both born, like the Turkish family, with defective genes for leptin, also lost significant amounts of weight with leptin injections.

And that’s pretty much it, folks. That’s the good news: A handful of obese people who get better with leptin, and  – let’s be generous here- maybe several thousand  more helped modestly and temporarily by other drugs.

After all the hoopla, all the hype, all the hope and all the research, anti-obesity drugs, at least so far, have largely been a bust. And barring some secret miracle concoction now in development, there will simply not be a pharmaceutical fix for fatness in the near future.

It’s all rather depressing.

Two-thirds of Americans are now overweight, the latest government figures show, and one in every three is obese. Obesity is defined as having a Body Mass Index (BMI) of 30 or more and being overweight, by having a BMI of 25 to 30. (To calculate your BMI, multiple your weight in pounds by 703; then divide that number by your height in inches squared.)

Yet, aside from repeating the old mantra of diet and exercise, and maybe a mention of gastric bypass surgery, there’s still very little that doctors have to offer the millions of Americans stuck in weight loss hell.

“There is certainly nothing on the horizon in terms of a drug that will solve obesity,” says Dr. Eric Colman, medical team leader for the metabolic and endocrine division at the US Food and Drug Administration.

“It would be wonderful if there were something that was highly effective and without side effects. But nobody should be waiting for that pill to arrive,” adds Dr. Walter Willett, chairman of the department of nutrition at the Harvard School of Public Health.

The more researchers try to find a magic bullet for weight loss, the more they are discovering that the biochemical pathways in the brain that control appetite and weight maintenance are devilishly complicated. 

At the moment, for instance, there are only two prescription weight-loss drugs on the market that are approved for long term use – Meridia (sibutramine) and Xenical (orlistat).

Meridia works promotes a feeling of satiety by increasing levels of serotoninn, norepinephrine and dopamine, chemical messengers in the brain. But, as the Harvard Heart Letter of March, 2002, notes, the drug only works as long as you take it, and even then, only modestly, resulting in a 5 to 10 percent weight loss. This amount of weight loss can help lower blood pressure and cholesterol but may not make a huge dent in what you see in the mirror.

Nor is Xenical a magic answer. It acts in the digestive tract to stop absorption of fat from foods by blocking enzymes called lipases. Like Meridia, it can result in a 5 to 10 percent weight loss, but all that unabsorbed fat can cause uncontrollable bowel movements, messy underwear and frequent passing of fatty gas.

There used to be more choices, but they weren’t terrific either. In 1997, the US Food and Drug Administration asked manufacturers to remove two highly popular anti-obesity drugs from the market, fenfluramine (part of the combination called “fen-phen”) and dexfenfluramine (Redux) because of an apparent increase in the risk of heart disease and serious lung problems.

There still are a few other weight-loss drugs on the market, including those containing phentermine (the “phen” of the old fen-phen combo). But these aren’t approved for long term use (which obese people need) and many are stimulants that can cause nervousness, rapid heartbeat and similar symptoms. These drugs can trigger brief spurts of minor weight loss, but they often lose their effectiveness over time.

So where does this leave the millions of Americans who are either overweight or obese? Still fat and still desperate.

Some people resort to gastic bypass operations – surgery to reduce the size of the stomach, which limits the amount of food a person can take in.  In 2000, 40,000 Americans underwent this procedure, almost double the number performed five years earlier, reports Ellen Ruppel Shell, co-director of the Knight Center for Science Journalism at Boston University, in her highly-readable new book “The Hungry Gene.”

But the costs are high. “Gastric bypass surgery kills one out of every hundred patients on the operating table, and not everyone recovers from the complications,” notes Shell.

On the other hand, gastric surgery may work not just by limiting stomach volume – but biochemically as well, according to a recent paper in the New England Journal of Medicine.

Cells in the stomach produce a chemical called ghrelin that has been shown to stimulate feeding and obesity in animals. Unlike the weight loss induced by dieting, weight loss induced by gastric bypass may lead to longer term maintenance of  weight loss because of  reduced ghrelin levels, note Drs. Jeffrey Flier, an endocrinologist and chief academic officer at Beth Israel Deaconess Medical Center and Eleftheria Maratos-Flier, director of the obesity section at the Joslin Diabetes Center in Boston in an editorial accompanying the research. This suggests that a grehlin-blocking drug might work where others have failed.

And someday, there may be other pharmaceutical options.

Some scientists are hopeful that a drug now in clinical trials called CNTF, for ciliary neurotrophic factor, may work out.

Others are looking at a compound called MLN 4760, made by Millenium Pharmaceuticals in Cambridge, MA, which has been working on obesity drugs for years. So far, says Lou Tartaglia, vice president of metabolic diseases, none of the drugs in the works are yet ready for marketing, but MLN 4760 is now in early human safety trials. The company will not say exactly how it works except that it block an enzyme called carboxypeptidase.

Farther back in the Millenium pipeline is a drug that would activate a receptor molecule called MC4 that seems to act in the brain, at least in mice,  to decrease body weig

Tartaglia thanks that the reason that drugs marketed so far have failed is that they are crude and act essentially “by hitting the brain with a hammer.” New drugs could work better because they are targeted to more specific molecules in the brain.

But even then, there are no guarantees. Take leptin, for exaple, a highly specific drug. 

Amgen, a company based in Thousand Oaks, Calif., has been trying for years to develop a leptin-based drug, with no success. Company spokeswoman Barbara Bronson Gray says Amgen researchers have conducted several trials but the drug “did not achieve clinical or commercial hurdles needed for an obesity drug in this population.”

Why? For one thing, obese people often turn out to have perfectly normal or even higher than normal levels of leptin, which is made in fat cells and travels to the brain to deliver “satiety” or “I’m full, stop eating” signals.

The Turkish cousins were genuinely – and genetically – leptin-deficient, so giving leptin to them worked. But most obese people are not leptin deficient, perhaps in part because of the sheer number of their fat cells. These fat cells, which never go away, even when a person loses weight, keep cranking out leptin but, obese people, one current theory goes, may become resistant to their own leptin, much as people susceptible to diabetes can become insensitive to their own insulin.

Maybe, some day, the growing understanding of all the biochemistry involved in appetite and weight regulation will result in a magic pill.

Until then? It’s same old, same old: Diet and exercise. Turn off the TV and take a walk instead. Don’t adopt a “low fat” diet that allows you to eat endless carbohydrates. Eat more veggies and less processed junk. At the very least, if you are already overweight, don’t give up and let the problem get even worse.

Oral Cancer Poses Growing Threat

by

Patrice Di Carlo’s ordeal with oral cancer just might be enough to scare anyone who still chews tobacco or smokes and drinks heavily out of denial forever.Di Carlo, 49, a former smoker who lives in Malden and works as a legal secretary at the Boston lawfirm, Ropes and Gray, discovered what she thought was a harmless canker sore on her tongue eight years ago. Her dentist thought it was nothing, too, which is not terribly surprising: Every year, thousands of people get funny little spots in their mouths that appear benign to the naked eye – even the naked eye of a trained dentist, though two new detection tests are beginning to make things easier.

But as month after month ticked by and Di Carlo’s spot did not go away, she decided to see another dentist. He immediately sent her to an oral surgeon who removed a sizable chunk of her tongue – a squamous cell cancer –  five days later.

Five and a half years later, Di Carlo developed a new primary tumor, as happens to one of every five people with oral cancer. 

So doctors removed more of her tongue, plus her salivary glands and, through an incision from her earlobe to her Adam’s apple, dozens of lymph nodes. Then came radiation therapy, which left her with mouth sores that felt like “being burnt with blisters,” she says. The sores made eating so painful that Di Carlo lost 75 pounds. Last summer: Yet another tumor, more surgery. This summer, same story.

Cancer of the oral cavity – the tongue, mouth, insides of the cheeks and pharynx (back of the throat) – kills more people every year than melanoma, cancer of the cervix, cancer of the uterus or certain subtypes of leukemia, including chronic lymphocytic leukemia, acute myeloid leukemia, chronic myeloid leukemia and others.

It’s a “very serious cancer because the oral cavity is where we eat, breathe and speak,” says Dr. Robert Haddad, an oral cancer specialist at Boston’s Dana-Farber Cancer Institute. Aggressive tumors “can grow within weeks – they can become symptomatic, meaning speech and swallowing are affected. I have patients who can’t swallow at all.”

Yet so few people even know about oral cancer – much less know when to worry about mouth lesions – that the American Dental Association and coalitions of dental schools in a handful of cities, including Boston, San Francisco, Kansas City and others, have all launched campaigns in the last year or so to raise public awareness.

Their message, and mine, is simple: Roughly 29,000 Americans, including 19,000 men, are diagnosed with oral cancer every year, according to American Cancer Society figures. About 7,400 die. The 5-year survival rate is only 54 percent, though it’s improving at major cancer centers.

The implications are clear: Don’t become one of these statistics. Which means ,don’t smoke, don’t chew tobacco and don’t drink heavily. Do see your dentist regularly.  If he or she doesn’t routinely feel the lymph nodes in your neck, move your tongue from side to side to look for lesions in your mouth and look at the back of your throat carefully, get a new dentist.

You can also monitor yourself, but early cancers can be hard to see. More advances lesions may appear as sores that bleed easily or do not heal; changes in the color of oral tissue; lumps or rough spots, or areas that are painful or numb anywhere in the mouth or lips. Suspicious lesions can be either red or white.

But, unfortunately, there’s more to it than that. As many as 25 percent of oral cancers seem to be caused by something other than smoking and drinking, and researchers aren’t sure what it is. The chief suspect is HPV-16, the same strain of human papilloma virus that causes cervical cancer.

So far, there is no proof that oral sex with an HPV-infected person causes oral cancer. But that is an obvious theoretical possibility and it might explain another worrisome observation: The growing numbers of young people with oral cancer. 

Some published data suggest there is “an increased incidence in young adults, patients between 20 and 39,” says Haddad of Dana-Farber. “Many of these people have never drunk except socially and they are not smokers.”

Indeed, even if people this young “smoked like fiends, they wouldn’t have enough time to make a cancer of the tongue,” agrees Dr. Barbara Conley, a head and neck cancer specialist and chief of the diagnostics research branch in the cancer diagnosis program at the National Cancer Institute.

Whatever the cause, the death rate from oral cancer has budged little in 40 years because many people “are being detected too late,” says Dr. Thomas Kilgore, professor of oral and maxillofacial surgery at the Boston University School of Dental Medicine.

When oral cancer is detected early, “it has an 80 percent cure rate,” Dr. Michael C. Alfano, dean of the New York University College of Dentistry, explains in an email interview. “Late diagnosis has a survival rate of only 20 percent.” 

“When a lesion is small,” Alfano adds, “it often looks like any benign minor irritation of the soft tissues of the mouth. Dentists are reluctant to biopsy these lesions since a conventional biopsy is invasive and requires both anesthesia and sutures, and because the lesions are usually benign.”

Recently, two new tests (and a third on the way) are beginning to help dentists sort out which patients need to have a surgical biopsy and which do not.

One test, a “brush biopsy” kit called OralCDx, appears to have helped identify more than 2,500 precancerous or cancerous lesions since it went on the market in January, 2000.  

In the brush biopsy, a dentist twirls a little stick with small brushes on top of the lesion to get a sample of cells. The cells are then sent to a lab where a computer scans them, picks out atypical cells and projects them onto a TV screen for a pathologist to read. If the pathologist confirms that the cells are abnormal, he or she tells the dentist, who orders a surgical biopsy. (A surgical biopsy is also needed if the cells are judged normal but the lesion persists for several weeks anyway.)

In a study published in October, 1999 in the Journal of the American Dental Association, the brush biopsy test was tried on 945 patients. It detected all the lesions that were subsequently identified as cancerous or precancerous by surgical biopsy; it also had few false positives – lesions incorrectly deemed to be dangerous. 

“This test is not a substitute for traditional surgical biopsy. It allows dentists to test harmless looking lesions that might not have been tested otherwise, and if the test comes back abnormal, to send that patient traditional biopsy,” says Dr. Drore Eisen, medical director of the company that analyzes the brush biopsy specimens, CDx Laboratories in Suffern, N.Y.

In another study of the brush biopsy kit published in March, 2002 in the same journal, nearly 1,000 dentists and dental hygienists were screened by the naked eye; nearly 10 percent, 93 people,  had lesions, which were then tested with brush biopsy. Three precancers were found. Without the brush biopsy test, all 93 might have been referred for traditional biopsy.

Another test called Vizilite, also approved by the US Food and Drug Administration, is a  chemiluminscent light that is shined in the mouth. A dentist can spot potentially dangerous lesions because, under this light, abnormal tissue glows differently from normal tissue, says Dr. Sol Silverman, professor of oral medicine at the University of California, San Francisco. The light makes lesions more visible, though can’t necessarily tell if they are potentially cancerous. The company that makes Vizilite, Zila, Inc. in Phoenix, AZ. is also working on a noninvasive dye (toluidine blue) that stains abnormal tissues.

Like diagnostics, treatments are getting better, too. Historically, side effects from surgery to remove all or parts of the tongue have proved so difficult for patients to live with that some “say they might have made other decisions, like not being treated,” if they had known, says Silverman.

Without a whole tongue, some patients can’t swallow, which means they must eat through a feeding tube. If the base of the tongue, which extends down to the voice box, must be removed, patients can’t speak either, except through an artificial larynx, nor can they breathe, except through a permanent tracheotomy.

But at major centers like Dana-Farber, which now claims a 5-year survival rate of 65 percent, the focus is not just on survival but on “organ preservation,” specifically, postponing tongue surgery until after chemotherapy and radiation to minimize the amount of tongue tissue to be removed. The emerging protocol is first chemotherapy, then chemotherapy plus radiation, then surgery of the tongue and, if necessary, the lymph nodes. Organ preservation is also improving because of better radiation techniques, including IMRT (intensity modulated radiation therapy), in which external beam therapy is precisely targeted only to the areas needed to spare surrounding tissues.

For Patrice Di Carlo, all this is promising, but sobering as well. Her latest surgery, in August, removed much of the base of her tongue and part of the back of her throat. The cancer now appears to be spreading. She can still swallow and speak. “Where I go from now ,I don’t know. How much can one person take. I am a fighter. But this time, I am having a very difficult time.” But it may be in her blood vessels. Her advice? If you have any spots in your mother that lasts longer than several weeks, she says, “get it checked out.”

Women and Stress

by

Do men and women handle stress differently? Or, to put it more provocatively, do women have a built-in hormonal advantage when it comes to dealing with chronic stress?

That’s the (highly loaded) question at the heart of a fascinating body of research that’s got the Net humming, with enthusiastic emails flying from woman to woman.

The case for this feminist theory of stress management is circumstantial  – built largely on inferences from animal studies and, at some points, frank leaps of faith. Still, the hypothesis has intuitive appeal, at least to women, so it’s worth exploring.

For decades, scientists who study the body’s physiological response to stress have focused on the “fight or flight” model. This view says that when an animal perceives danger, a number of hormones kick into action (among them, cortisol, ACTH, CRH, vasopressin and others). These hormones rev up heart rate and blood pressure, get sugar to the muscles and generally speed things up, the better to fight predators or get out of harm’s way, fast.

And there is absolutely no question that both males and females have – and need – this system.

But this view of stress is both male-biased and incomplete, say a number of researchers, most notably Shelley E. Taylor, a professor of psychology at the University of California at Los Angeles.

Taylor’s theory, based on more than 200 studies by other people, mostly biologists and psychologists, is that women have a powerful system for fighting stress that’s based in part on a hormone called oxytocin.

Granted, there’s no clear evidence that women on average actually have more oxytocin in their bloodstreams than men. But they do have more of another hormone, estrogen, which does boost the effectiveness of whatever oxytocin is around.

Oxytocin, which some dub the “cuddling” or social attachment hormone, is best known as the hormone produced during childbirth and lactation and during orgasm, in both sexes. But it’s also secreted during other forms of pleasant touch, such as massage, and has been shown to stimulate bonding in animals, most notably prairie voles and sheep.

Even more intriguing, there’s evidence from the laboratory of Kerstin Uvnas-Moberg at the Karolinska Institute in Stockholm and elsewhere that oxytocin may act as a genuine “antistress” hormone.

For instance, the Karolinska group reported in 1998 that daily oxytocin injections, into both male and female rats, decreased blood pressure and the stress hormone, cortisol, and promoted weight gain and wound healing. The group has also shown that injections of oxytocin in rats enhanced sedation and relaxation and reduced fearfulness.

To Taylor and her colleagues, the thrust of this evidence suggests that women may be programmed by evolution to deal with stress, not just in the “male” way, by fighting aggressors or running away, but also by “tending and befriending,” that is, turning to each other for moral support and nurturing the young.

In other words, “there appears to be a counter-regulatory system that may operate more strongly in females than males, that leads to engagement of oxytocin and social contact,” which in turn may reduce stress, says Taylor, author of the book, “The Tending Instinct.”

“If we want to get a complete picture of how people manage stress, we need to look at both men and women,” she adds. “Historically, researchers have looked mostly at men.” Indeed, prior to 1995, women constituted only 17 percent of studies of the hormonal responses to stress. Things have gotten somewhat better since then, she says, but of nearly 15,000 people in 200 stress studies between 1985 and 2000, only 34 percent were female.

What, then, is really known about oxytocin? Quite a bit.

First, it’s a tiny molecule of only nine amino acids that is made in a part of the brain called the hypothalamus. It works closely with a related molecule, vasopressin, which is carried on the same chromosome as oxytocin and is so similar that the two chemicals fit into each other’s receptors in the brain, notes Sue Carter, a behavioral neuroendocrinologist at the University of Illinois in Chicago.

But while oxytocin, which acts in tandem with estrogen, often has calming effects, vasopressin, which acts in tandem with the male hormone, testosterone, can act as a stress response enhancer, among other things, raising blood pressure.

In most species, says Carter, male brains contain more vasopressin than female brains, especially in an area called the amygdala, a fear processing center. Vasopressin has also been linked to increased aggression and male territoriality.

Put another way, oxytocin “is associated with typically female behaviors, such as childbirth and nurturing the young, whereas vasopressin is associated with male behaviors, such as territorial aggression,” writes Dr. Norman Rosenthal, clinical professor of psychiatry at Georgetown University in his new book, “The Emotional Revolution.”

The most intriguing feature of oxytocin is that it seems to act as both a cause of bonding between animals and a result of it, suggesting that perhaps through bonding behavior, it can be a stress reducer.

For instance, a number of studies have shown that oxytocin promotes bonding in animals: between mothers and babies, and between adults. In prairie voles, Carter’s studies show, injections of oxytocin lead to increased bonding. And when stressed, Carter has found, both male and female voles choose to bond – with females.

 “Many things stimulate production of oxytocin, including breast stimulation, orgasm or even contact with a friendly companion,” says Carter. “All these are  known to release oxytocin, which may help damp down the body’s reactions to stressful experiences, in men as well as women.”

Several studies, for instance, have suggested that women who nurse their babies have lower anxiety compared to bottle-feeding mothers and that lactating rats exhibit less fear.

In one 1995 study, for instance, Carter and Dr. Margaret Altemus, a psychiatrist at Weill Medical College, Cornell University, asked about 20 new mothers to undergo an exercise stress test – running on a treadmill. About half the women were nursing and half were bottle-feeding. The women who were bottle-feeding showed steeper increases in stress hormones than the nursing mothers. Other studies, notes Altemus, have suggested that panic disorder is relieved during pregnancy and lactation.

In other words,  “there may be something going on in a woman’s nervous system that may protect her against stress, at least transiently,” says Carter. And because any kind of positive social experience has the potential to trigger release of oxytocin in both men and women, she adds, men as well as women can  benefit from positive emotional contact with other people.

Beyond oxytocin, there are other chemical clues to differences in the ways in which women and men may handle stress.

At Ohio State University, Janice Kiecolt-Glaser, professor of psychiatry at Ohio State University  and her husband, Ronald Glaser, an immunologist, have studied hormonal and immunological responses to stress and found some striking gender differences.

In one experiment, the Ohio team asked 90 young, happy, newly-wed couples to spend 24 hours, including a night’s sleep, in the hospital lab. “They were in absolutely pristine mental and physical health,” says Kiecolt-Glaser. The researchers placed a catheter in each subject’s arm so that blood could be drawn every hour to test for hormone levels and various aspects of immune function.

Early in the stay, each couple was asked to spend 30 minutes discussing an area of disagreement. This conflict was recorded on videotapes that were later scored by trained observers, both male and female, for evidence of negative behavior such as hostility, sarcasm, put downs, etc.

The results were stunning:  Marital strife was much tougher on women than men. The women showed a faster and more enduring response to hostility, says Kiecolt-Glaser, noting that women’s stress hormones (particularly epinephrine, norepinephrine and ACTH) rose more sharply and stayed up longer than men’s. Women also showed a lowering of certain aspects of immune function.

In a follow-up study, the Ohio team found that women whose stress hormones had risen the highest during the earlier phase of the study were the most likely to get divorced.

 “Women show greater sensitivity to negative marital interactions than men,” says Kiecolt-Glaser. And this can’t be chalked up to over-reacting, or to some female hypersensitivity to stress in general because in other situations designed to induce stress in the lab, such as being asked to perform mental arithmetic, men show larger increases in stress than women.  

In other words, in a marriage, Kiecolt-Glaser says, women are actually more accurate judges of what’s going on emotionally. Indeed, when the outside reviewers rated the videotapes of the couples’ interactions, their assessment of hostility and negative behavior correlated with the women’s. Women simply experience a bigger stress response to men’s sarcasm and hostility than men do to women’s, she says.

The bottom line? If you feel stress in an interpersonal relationship, you’re probably right that the stressors are truly there. If you do feel stressed out, call a friend. If you don’t have a friend, make one, or more. And if all else fails, snuggle up with a prairie vole.

Judy Foreman is  Lecturer on Medicine at Harvard Medical School and an affiliated  scholar  at the Women’s Studies Research Center  at Brandeis University.. Her column appears every other week. Past columns are available on www.myhealthsense.com.

SIDEBAR

Do Women Have More Stress than Men?

At least in terms of behavior and feelings – as opposed to physiological measures of oxytocin and other hormones – there are clear differences in the ways men and women experience stress.

For one thing, women seem to have more of it, even though they outlive men, says Ronald Kessler, a sociologist and health care policy professor at Harvard Medical School.  

In one 1998 study done with colleagues at the University of Arizona, Kessler had men and women keep daily mood diaries for a week. “There were large sex differences,” he says. Men and women were equally good at getting rid of minor “spells of depression,” says Kessler, but “women have more bad stuff going on.”

“What really gets to people is the little crap,” says Kessler, “the daily hassles,” which women may have more of because they are often the ones who take responsibility for coordinating family and work schedules. “It’s the coordination that kills you, and when something gives, it’s the woman who fills in the gap.”

And while women often do relieve their own stress by turning to each other, the fact that women also often have more people in their lives to care -and worry – about may actually increase stress, says Kessler. “Men and women have the same emotional reactions” when something bad happens to people close to them, he says, but women often have more people in those networks, a phenomenon he calls the “cost of caring.”

Psychologist Alice Domar at the Mind/Body Medical  Institute at Beth Israel Deaconess Medical Center in Boston agrees that data clearly show that women are more stressed day to day than men, and it’s not, as was once thought, because they ruminate more.

“Men worry about three things: their immediate family, their job and money,” she says. “Women worry on a daily basis about up to 12 things – their immediate family, their job, money, their extended family, their friends, their kids’ friends, the way the house looks, their weight, the dog, etc.”

That same gender breakdown seems to occur in one of life’s most stressful situations, being diagnosed with cancer, says Barrie Cassileth, a psychologist and medical sociologist who runs the integrative medicine service at Memorial Sloan-Kettering Cancer Center in New York.

When first diagnosed with cancer, “men and women do respond very differently,” she says. “Women always talk…and women gain as much from giving as from receiving support from others. Women have such a nurturing instinct that even when facing harsh realities, they do reach out to others.”  

When Drinking Too Much Water Means Disaster

by

Kelly Hall, 34, was in fantastic shape, routinely biking 100 to 200 miles a week in preparation for last year’s AIDS Ride from Boston to New York. Usually, she trained with other riders, who made it a point to take food and hydration breaks. But one day last June, Hall, a strategic planner at Partners Community Health Care in Needham, decided to ride alone, despite the 95 degree heat.

The first 50 miles, around Concord, were a breeze. “I thought I’d do another 25,” she recalls. She drank a little Gatorade, the sports drink designed to restore normal blood levels of electrolytes, but relied mostly on water, constantly sipping from the 70-ounce Camelbak water supply on her back.

 Halfway through the last loop, hyponatremia, a relatively rare but potentially fatal condition in which blood levels of sodium sink dangerously low, “hit like a ton of bricks,” says Hall. She finished her ride “really, really slowly,” got back to her car, threw up, drove home and threw up again. She made it to Brigham and Women’s Hospital, where she had a grand mal seizure.

Nearly the same thing happened to Sarah Snyder, 45, a Globe editor, who was training with friends for another long, benefit ride.  She, too, was in good condition, and she too,  dutifully sipped water for 56 miles. “What a good doobie I’m being,” she remembers thinking.

But after her ride, she threw up violently and was rushed to the hospital, where she drifted in and out of consciousness for 18 hours. “You drank too much water. You screwed up your sodium,” the doctors told her. When asked to say her name, “It came out like Swahili.”

Full-blown cases of hyponatremia (sometimes called water intoxication) are relatively rare, roughly 0.1 to 4 percent of people who sweat steadily for hours in grueling, long distance events, says Scott Montain, a research physiologist at the US Army Research Institute of Environmental Medicine in Natick. The incidence of hyponatremia appears to be highest in events lasting more than four hours, especially at high temperatures.

But the prevalence of warning symptoms is much higher – up to 27 percent of athletes who seek attention in a medical tent during a long race – and appears to be rising.

In the 1996 New Zealand Ironman Triathlon (3.8 kilometer swim, 180 kilometer bike and 42 kilometer run), researchers found that 9 percent of athletes who showed abnormalities on medical tests had hyponatremia.

Typically, conscientious athletes get in trouble because they adhere too diligently to one recommendation  (drink lots of fluids) but ignore another (keep electrolytes up). (Electrolytes are charged particles such as sodium, potassium, calcium and bicarbonate that must be kept in near-perfect balance) Indeed, for most marathoners, Montain notes, the real problem is drinking too much water, not failing to take in enough sodium.

Women in particular, may be at risk, some researchers believe, in part because they may too dutiful about drinking water.

Some studies suggest that certain drugs may also increase risk, among them ibuprofen and other NSAIDS (non-steroidal anti-inflammatory medications), acetaminophen, some cancer drugs, nicotine, diuretics, narcotics and some antidepressants and anti-psychotic drugs. On the other hand, data presented recently at the American College of Sports Medicine meeting suggest that ibuprofen and other NSAIDS may not increase risk after all.

“When you sweat, you lose both water and salt,” says Dr. Soheyla Gharib, medical director of the women’s health center at Brigham and Women’s Hospital. “If you replace only water, the salt level in the blood gets diluted.”

And that can be disastrous. Normally, the body tries to keep positively and negatively charged electrolytes in balance to keep cells electrically neutral, says Dr. Ronenn Roubenoff, associate professor of medicine and nutrition and director of human studies at the Jean Mayer USDA Human Nutrition Research Center at Tufts University. Though sodium is probably the most important electrolyte for endurance athletes to worry about, he says, “an imbalance of any one of the electrolytes can be harmful.”

Normally, sodium is plentiful in the blood and relative low inside cells. But when the concentration in the blood gets too low compared to the amount inside cells – either because a person drank too much water, took in too little sodium, or both – water rushes into cells. “Water follows sodium as day follows night,” Roubenoff says.

The result is dangerous swelling, particularly in the brain, that can lead to brain damage, coma and death.

Curiously, hyponatremia can occur whether a person is dehydrated, normally hydrated or overhydrated because any of those conditions can happen while blood levels of sodium are too low, adds Roubenoff.

Further complicating things is that the symptoms of  hyponatremia can be easily confused with those of heat stroke and heat exhaustion. With heat exhaustion (also called exertional heat injury), people feel ill, get nauseous, have muscle cramps and may feel dizzy standing up quickly.

With heat stroke, people have all those symptoms plus another one: mental status changes, that is, confusion about who and where they are and what day it is. People with genuine heat stroke also typically have extremely high body temperatures

With hyponatremia, people also feel very ill and may have mental status changes, but don’t have the high temperatures of heat stroke. They also vomit forcefully and repeatedly and, unlike those with heat exhaustion, do not feel better by resting and cooling off.

Treatment of hyponatremia may involve restricting fluid intake and promoting urine production, but some people also need intravenous (IV) salt water (saline) with a high concentration of salt, until blood electrolytes return to normal. Re-setting the water-salt balance “must be done carefully and slowly,” cautions Dr. Gabriel Danovitch, professor of medicine at the University of California , Los Angeles, School of Medicine because overly-rapid correction of electrolyte imbalance can cause further problems.

To protect yourself against hyponatremia, start by paying attention to how much you sweat. In general, women sweat less than men and their ability to regulate core body temperature (and sweating) may also vary with different phases of the menstrual cycle.

Individuals also vary considerably in how much sodium they lose in sweat. You may be a heavy sodium loser if your sweat burns your eyes, tastes salty or leaves a cakey-white residue on your skin. 

Sweat contains between 1 to 2 grams of sodium per liter – and since it’s easy to lose a liter of perspiration in a long race, that means you’re losing this much sodium, too. You can replace 2 grams of  sodium with about a half-teaspoon of salt.

You can also make sure you’re getting enough sodium by drinking sports drinks like Accelerade, Cytomax, Gpush, Gatorade and the like instead of plain water during long events. (Check the labels for sodium content; some brands have twice the sodium of others.) Sports drinks also typically contain carbohydrates as well, which provides energy and helps with water and sodium absorption.). These sports drinks are similar to Pedialyte and other oral rehydration solutions used to treat children who become dangerously dehydrated.

If you don’t like sports drinks, you could take salt tablets, but they may make you nauseous.  At the very least, you can eat salty foods prior to and during a big event.

You can gauge how much fluid you’re losing by weighing yourself before and after half an hour of exercise. (Don’t drink anything between weigh-ins.) If  you lose a pound in half an hour, your sweat rate is two pounds per hour, which means you need to replace that much fluid. (Two pounds of fluid is 32 ounces.)

As a practical matter, you’re probably not in any danger from dehydration unless you lose more than  2 to 3 percent of your body weight during exercise, but you can’t rely on thirst to guide you because by the time you’re thirsty, you may already be dehydrated. So the goal is to adjust your fluid intake to how much you sweat.

In fact, for ordinary mortals who work out for less than an hour, sports drinks are unnecessary and plain old water (along with the salt you normally get in food) will do just fine, says Roger Fielding, an exercise physiologist and associate professor of health sciences at Boston University.

For endurance athletes doing events longer than an hour and sweating profusely, it’s probably wise to drink 6 to 8 ounces of fluid every 20 minutes to prevent both excessive dehydration and hyponatremia, says Montain of the US Army lab. For events lasting longer than two hours, you’re probably better off with a carbohydrate-electrolyte sports drink than plain water. But don’t drink more than 40 ounces (1 and

SOME Sun is Good For You

by

Remember how good it used to feel, hanging out in the sun, letting your face acquire that nice, ruddy glow?

Then came all those depressing public health messages telling us that the sun was dangerous, that we should feel guilty about even the slightest tan.

Well, fellow sun worshipers, the sad truth is that as a general rule, we should still practice “safe sun” – including hats and sunscreen, especially for little kids – much of the time.

But there’s a new ray of hope – dare we say “sunshine?” – in the form of a modest but significant shift in medical thinking toward the view that SOME unprotected sun exposure may actually be a good thing, like 15 minutes or so a day in the summer for adult Bostonians who tan well, less for those burn easily.

“In my opinion,” says Dr. Robert Stern, chief of dermatology at Boston’s Beth Israel Deaconess Medical Center, “it’s probably true that for people over 40, even people who have had a non-melanoma skin cancer, we have oversold the idea of having to be sun-phobic. For them, modest exposure has little risk.”  For kids, cautions Stern, it’s another matter – excessive childhood exposure to sunlight has been linked to later basal and squamous cell skin cancers, as well as to melanoma, a more serious form of skin cancer.

The rationale for the some-sun-is-good point of view, supported by a number of recent articles in medical journals, is that the vitamin D made in the skin in response to ultraviolet B radiation may protect against certain diseases, including cancer of the breast, colon and prostate.

Other diseases, most notably MS (multiple sclerosis), also show a “latitude effect,” that is, they are less prevalent among people in sunnier climes, though, as with cancer, whether this is truly due to vitamin D or to some other factor that varies by region such as diet, behavior or genetics is unclear.  In rodents, high doses of vitamin D can actually prevent MS.

Sunlight may even be an effective treatment for some diseases. In a recent study published in the journal Lancet, Dr. Michael F. Holick, an endocrinologist and leading vitamin D researcher at Boston University School of Medicine and others showed that exposing people with mildly high blood pressure to UV-B can lower blood pressure, perhaps by correcting an underlying vitamin D deficiency.

Before we get in too deep here, let’s be clear. It’s vitamin D that has the real benefit, not sunlight per se, which means you can take vitamin D supplements, especially during the winter if you live at higher latitudes and especially if you have dark skin (which makes less vitamin D). By contrast, people in Florida typically make plenty of vitamin D all year in their skin. It’s very tough to get enough vitamin D from your diet unless you consume lots of fish liver oil, the flesh of fatty fish like salmon and fortified milk and cereals.

Actually, vitamin D is not a vitamin at all in the normal sense, but is really a steroid-like hormone made, after exposure to the UV-B rays from sunlight,  from a precursor of cholesterol in the skin. After an inactive form of vitamin D is made in the skin, it is transformed in the liver and kidney to the active or hormonal form called 1,25 dihydroxy vitamin D. Indeed, several teams of researchers have recently found that the organs such as the breast, prostate and colon in which vitamin D seems to reduce cancer risk can also make their own stores of the vitamin’s active form, an important finding.

Like other hormones, vitamin D works by fitting into specialized receptors on cells in many organs of the body and has numerous biological effects, the most important one being to aid in the absorption of dietary calcium. When a person has enough vitamin D in his system, the intestines can absorb 30 percent of the calcium available in the diet; without enough vitamin D, this drops to 10 percent, notes Holick.

The consequences of insufficient vitamin D can be serious. When the body can’t absorb enough calcium from the diet, it steals calcium from the bones to restore proper levels in the blood, a process that weakens bones, often leading to osteoporosis. Low levels of vitamin D can also lead to weak and achy muscles, as well as generalized bone pain, symptoms often misdiagnosed as fibromyalgia.

Just as important as its effects on calcium and bone is the fact that  vitamin D helps regulate many basic cell processes, notes Dr. David Feldman, an endocrinologist and vitamin D researcher at Stanford University School of Medicine. By acting on specific regions of DNA called vitamin D response elements, it helps control the biochemical signals that tell cells when to divide, when to stop dividing and when to die – all processes that are crucial in both normal and malignant cells.

In the early 1990s, for instance, researchers showed that adding the active form of vitamin D to cancer cells in the test tube inhibits their growth, a finding that has now been shown in breast, prostate and colon cancer cells as well as leukemic cells.

Currently, researchers at several labs around the country are testing whether a high dose, prescription form of vitamin D called calcitriol can slow the progression of prostate cancer in men with the disease. This treatment could increase the risk of kidney stones, says Feldman, but it’s promising enough that numerous drug companies are pursuing closely-related versions (or analogues) of active vitamin D that would be active against cancer without triggering kidney stones.

Vitamin D as a supplement has also been shown to be extremely effective at preventing Type I diabetes. A study by Finnish researchers published in Lancet last fall shows that vitamin D (2000 International Units a day) in infancy can reduce by 80 percent the risk of Type I diabetes 30 years later, perhaps because vitamin D slows the body’s immune attack on its own insulin-producing cells. This fits with data from mice showing that high doses of activated vitamin D will markedly reduce the risk of Type I diabetes.

But perhaps the most intriguing evidence of vitamin D’s importance comes from studies of sun exposure and cancer.

In the March 15 issue of Cancer, William Grant, by day an atmospheric scientist at NASA’s Langley Research Center in Hampton, VA and by night, an independent researcher, published a study showing that the geographic distribution of many cancers varies with UV-B exposure. 

Since the early 1980s, Grant notes, scientists have been gathering evidence that some types of cancer – most notably, cancer of the breast, colon, ovary and prostate, as well as non-Hodgkin’s lymphoma – are higher in Americans who live in the least sunny regions.

“What I did was basically take two maps and put them together,” says Grant of his latest study. This showed that in addition to the cancers already known to vary with UV-B exposure, there appear to be many others (bladder, esophagus, kidney, rectum, stomach and uterus) that also increase as sunlight decreases. 

In fact, more than 30,000 Americans die prematurely every year from cancer that may be attributed to low levels of UV-B exposure, Grant estimates.

Other researchers, too, have found links between sun exposure and cancer.  In 1999, a team led by epidemiologist Esther M. John of the Northern California Cancer Center in Union City reported on a study of more than 5000 white women, 190 of whom developed breast between the time they were first interviewed by government researchers in the early 1970s and 1992.

The team correlated various measures of sun exposure and found that the women with the highest levels of sun exposure were the least likely to get breast cancer.

This March, researchers from the National Cancer Institute led by Dr. Michal Freedman, an epidemiologist, found that Americans living in sunny areas were significantly less like to die from (not just get) cancers of the breast, ovary, prostate and colon. Not surprisingly, her team found, high levels of sun exposure were also linked to the milder (non-melanoma) types of skin cancer, too.

The bottom line ? If you’re white, all it takes for your skin to make enough vitamin D is about 15 minutes a day in the sun, without sunscreen, at noon, says Holick.  If you’re black, it may take considerably more than that. How much sun you should get depends on your skin type and sensitivity to sun – if you burn readily, you may only be able to tolerate five minutes in the sun, and that would be enough.

And if you’d rather just take vitamin D supplements? That’s fine – the general guidelines are 200 IUs a day if you’re 50 or under, 400 if you’re between 50 and 70, and 600 IUs if you’re over 70, says Tufts University epidemiologist Susan Harris. Some researchers even recommend 800 to 1000 IUs a day. (Since there’s almost no vitamin D in breast milk, Harris notes, breast fed babies living in less sunny regions of the country should probably take baby vitamins.

The risks of overdosing are small, adds Reinhold Vieth, a biochemist and vitamin D researcher at Mount Sinai Hospital in Toronto, who believes it would take tens of thousands of IU s for long periods to become a problem.. Still, to be on the safe side, many researchers suggest limiting vitamin D intake to 2000 IUs a day.

Judy Foreman is  Lecturer on Medicine at Harvard Medical School and an affiliated  scholar  at the Women’s Studies Research Center  at Brandeis University.. Her column appears every other week. Past columns are available onwww.myhealthsense.com.

SIDEBAR

Vitamin D and the Evolution of Skin Colors

  • Vitamin D is part of one theory for the evolution of different skin colors among humans.

  • Human beings arose with black skins in Africa and then migrated outwards from there. Black skin is rich in melanin, a pigment that acts as a natural sunscreen, protecting against sunburn.

  • But, just like sunscreen of SPF 8 or higher, melanin reduces the amount of vitamin D the skin can make. That’s fine for someone in Africa who spends lots of time in the sun. Farther from the equator, however, people with light skin gain an evolutionary advantage. With less available UV-B, light skin probably evolved so that humans migrating northward would still be able to make enough vitamin D.

  • Indeed, people who failed to make this adaptation would have had a difficult time reproducing. Insufficient vitamin D can lead to rickets, which causes defective bone growth. In women, this can mean such poor pelvic development that babies could not be borne – and the mother’s genes would not be passed on.

Coated Stents Show Huge Promise

by

Vice President Dick Cheney made the problem famous, but thousands of  Americans each year need a new round of treatment to fix a heart problem they thought was already solved. 

The setback generally goes something like this: Having experienced a chest pain or heart attack, the patient undergoes a procedure to open up the clogged artery, and to install a tiny mesh-like device called a stent to keep the artery propped open. But in many cases, this foreign object causes the body to react with scar tissue and the artery narrows again.

To combat this re-clogging process – which is called restenosis and affects roughly 30 to 50 percent of patients, like Cheney, who have stents – scientists are aggressively testing a variety of drug-coated stents that would release inflammation-reducing medications. These drug-coated stents, which are available in Europe, are expected to radically alter the treatment of cardiovascular disease.

“The anticipation is extraordinary,” said Dr. Campbell Rogers, director of the cardiac catheterization laboratory at Brigham and Women’s Hospital. “The impact of having a new, less-invasive and more effective treament for coronary heart disease is vast.” Coated stents will probably be on the US market in the next year or so, with several major companies in various stages of clinical trials.

The leaders are Cordis (a Johnson & Johnson company), Boston Scientific and a joint effort by Guidant Corporation and Cook Inc. Some preliminary data show an almost unheard-of 100 percent success rate (meaning zero restenosis) for the drug-delivery stents after two years of follow up. These results are particularly impressive given that patients who receive regular stents often get a diagnosis of restenosis within a year.

Coated stents are expected to replace substantially coronary artery bypass surgery, an expensive, highly invasive operation now performed on more than 350,000 Americans a year. The bypass surgery will probably still be needed for some heart patients who also have diabetes and for those whose arteries are completely blocked.But the new stents will likely become the preferred option not just for the 1 million or so Americans a year who now get regular stents, but for hundreds of thousands of others currently deemed ineligible because they have too many bad arteries. They may also be used for hundreds of thousands of others with “vulnerable plaques,” that is, arteries with fatty deposits that have not yet ruptured (a process that can cause an instant heart attack).

Coated stents are nothing less than a “revolution,” says Dr. James  Muller, director of clinical research in cardiology at Massachusetts General Hospital and co-director of the CIMIT Vulnerable Plaque Program. “They are wonderful.”

Dr. Jesse Currier, associate director of the adult cardiac catheterization  lab at the UCLA Medical Center, puts it even more emphatically: “This is Neil Armstrong, one giant leap for interventional cardiology…this is a huge, huge quantum leap.”

Commonplace as they now are, regular stents have actually been on the US market for only a few years, after two major trials showed that simply placing an uncoated stent into an artery was better than angioplasty alone in reducing the risk of restenosis. (In angioplasty, doctors thread a tube called a catheter up through an artery in the groin to the coronary arteries, then push a button to inflate a balloon to compress the plaque against the artery wall.)Even though uncoated stents do just fine at keeping artery walls from collapsing, their sheer presence can create new problems, notes Dr. Elazer Edelman, director of the Harvard-MIT Biomedical Engineering Center, professor of Health Sciences and Technology at MIT and a cardiologist at Brigham and Women’s Hospital.

The worst possibility is that, immediately after insertion, the stent can trigger blood clots, a process that doctors guard against by giving patients anti-clotting drugs such as aspirin and Plavix. Some researchers have also tried coating stents with heparin, a blood thinner. But heparin-coated stents have not proved ideal, in part because heparin dissolves instantly in water – or blood – which means that it disappears rapidly from the area where it’s needed.

But there’s another danger, too, after insertion of a stent. “You’re leaving a foreign body behind. Now, as opposed to a single injury from inflating a balloon, you have a rigid, metal object that can trigger a slow, chronic inflammatory process, ” says Edelman.

Indeed, inflammation is now believed to be a root cause of both atherosclerosis, the initial formation of plaques, and of restenosis, the re-clogging of arteries during the healing process after angioplasty and stent insertion. Cholesterol, specifically LDL (the “bad” cholesterol) is still a major culprit in atherosclerosis. But its effects include stimulation of the body’s natural inflammatory response to injury – sending immune cells to clean up the area .To fight this inflammatory process in people with regular stents, doctors have tried local application of radiation, including radioactive stents and pellets placed temporarily within the stent. This approach has not been shown to prevent restenosis – and may actually impair normal healing of the artery – but can help combat restenosis that has already occurred.A potentially better solution, Edelman and other researchers reasoned, might be to coat stents with drugs that could stop proliferation of inflammatory cells. One idea was to coat a stent directly with a medication, the approach taken by Guidant/Cook. Another was to create polymers (chains of identical chemicals) that could act as a glue to hold drugs on and inside a stent in such a way as to release the drugs slowly, over a matter of days or even weeks.

Working with others at MIT, Edelman began years ago to search for ways to accomplish this slow release. Most drugs, he says, cannot move through sheets of polymer materials. But if the polymer sheet is melted and mixed with a drug, when it’s recast, it looks like a sponge with drug-filled channels supported by walls of the polymer materials.Once implanted in the body, fluid enters the channels and dissolves the drug so that it can then leave the polymer sponge. The more curvy (or “tortuous”) the channels, the longer it takes for the drug to be released. A number of teams have worked to adapt the polymer technology to stents.Yet another hurdle was figuring out which drugs to use. One early choice was an antibiotic called actinomycin-D. But to researchers’ surprise, it proved no better than a bare stent at reducing restenosis.Another was a coating with paclitaxel, the active form of Taxol, a drug used to treat cancers of the breast and other tissues. The drug works by slowing cell proliferation. At moderate doses, says Rogers at Brigham and Women’s Hospital, paclitaxel holds “tremendous promise, essentially wiping out restenosis.” But at the considerably higher doses used in one early trial, paclitaxel-coated stents triggered clots and heart attacks, Rogers notes.Still, researchers knew they were fundamentally on the right track and a compelling series of studies recently made public shows just how effective coated stents – using drugs, such as paclitaxel or sirolimus – can be.Two years ago, a pilot study involving 45 patients in the Netherlands and another 30 in Brazil suggested that the Cordis stent coated with a drug called sirolimus (also known as rapamycin) could help prevent restenosis.But it was the 2-year follow up on these patients, presented this spring at the meeting of the American College of Cardiology in Atlanta, that blew other scientists away: a restenosis rate of zero.

Another study called RAVEL was also presented at the Atlanta meeting. Like the pilot study, the stents in this research were coated with sirolimus, and the results on 238 patients in Europe and Latin America were “astonishing,” says Currier of UCLA. Several hundred patients were followed for up to one year “with no major adverse cardiac events, no restenosis.”

Currently, the sirolimus-coated stent is being tracked in an even bigger study of 1,100 patients (SIRIUS) at Lenox Hill Hospital in New York City and other centers. The 6-month follow up data are not yet public, but the initial data is being submitted to the US Food and Drug Administration for approval of this stent product. The sirolimus-coated stent, called Cypher, has already received regulatory approval for marketing in Europe.

The other main approach is coating stents with paclitaxel. Boston Scientific Corp., based in Natick, uses a polymer to stick paclitaxel onto its stent. In the pilot study of 61 patients, researchers found zero restenosis after six months of follow up.

A larger study of about 500 patients “provided further support for the safety of paclitaxel,” says company spokesman Paul Donovan. The paclitaxel stent also seems to prevent restenosis, a third study shows, as a stent placed inside a stent already in the artery – a kind of stent sandwich.

Boston Scientific’s most important study, TAXUS IV, which involves more than 1,000 patients at 80 medical centers, is still underway, but the company is optimistic: “We plan to launch a drug-coated stent in Europe this year and in the US next year,” says Donovan.

The third main contender for bringing a drug-coated stent to the US market is Guidant/Cook. Like Boston Scientific, Guidant/Cook uses paclitaxel to coat its stents. But therein lies a problem. Boston Scientific and Guidant/Cook are expected to square off in court in early June over distribution rights for stents coated with paclitaxel, which is made by a company called Angiotech Pharmaceuticals in Vancouver, Canada.

Guidant is currently conducting a trial of its paclitaxel stent in more than 1,000 patients in a study called DELIVER, which is now in its follow-up phase.There will certainly be bumps in the road to developing future generations of coated stents. But to a degree unusual in medical circles, cardiologists believe that even the first coated stents to reach the US market will bring vast improvements to America’s heart patients.

Granted, there is still a lot to learn about the use of stents, particularly in people who have already had bypass surgery. “Who knows? ” adds Edelman of MIT, “New delivery strategies may bring us to the day when we not only do not need coatings on stents, and we may not need the stents, either.”

New Drug for Narcolepsy

by

Mary Rourke, a 55-year old teacher from Salem, N.H., used to nod off all the time as a child, but people just shrugged and said, “Oh, she must be very tired,” she recalls.

Then, as an adult, she began having attacks in which her muscles would lose tone and she’d fall- every time she laughed or felt any strong emotion. “I was constantly falling,” she says. “If you told me a joke, I’d flip. I couldn’t be around people.”

In Massachusetts, a 49-year old nurse from Norwood who asked that her name not be published also used to crash helplessly to the floor whenever she laughed or got angry, a fact her children quickly learned to exploit. “I couldn’t yell at my kids when they were younger because if I got too mad, I couldn’t stand up,” she says.

Things were even worse for Bob Cloud, a 58-year old lawyer from Cincinnati, Ohio. It was bad enough falling asleep talking to judges, he says, but one day he went limp while swimming and had to be rescued.

At least, he says, that provided a “great educational opportunity” to tell stunned onlookers what was really wrong: A brain disorder called narcolepsy, characterized by extreme daytime sleepiness and caused by low levels of a brain chemical called hypocretin. In many cases, low hypocretin levels also cause cataplexy, sudden loss of muscle tone due to the intrusion of dreaming (REM) sleep in the waking state.

Though the true numbers are probably higher because many people go undiagnosed for years, narcolepsy is believed to affect at least 140,000 Americans and 3 million people worldwide – more than are affected by some better-known diseases like cystic fibrosis and muscular dystrophy.

Yet stunning brain research in the last three years, along with the hoped-for approval this spring of a controversial new cataplexy drug called Xyrem – known on the street as the date-rape drug, GHB – are catapulting this once-hidden condition into the limelight.

With luck, the research on narcolepsy and cataplexy – essentially, disruptions in the body’s normal sleep-wake cycles – may lead to novel treatments for insomnia and depression as well.

And there’s another reason for the limelight: A remarkable degree of cooperation on the Xyrem/GHB issue by Congress, the US Food and Drug Administration and law enforcement officials that shows that it is possible to treat the same substance as both legitimately needed by desperate patients and subject to criminal penalties when abused.  

In the illicit street form, GHB (gamma hydroxybutyrate), has been blamed for dozens of deaths and countless sexual assaults. The colorless, odorless liquid can be slipped into someone’s drink. It is so simple to concoct at home that “a 9-year old can make it,” says Bob Gagne, a public affairs consultant for Orphan Medical. “I stumbled upon a crockpot recipe” for one form of the drug on the Internet, he notes. Some people also drink industrial chemicals such as GBL (gamma butyrolactone) for their GHB-like effects.

Because GHB is also believed to promote the body’s production of growth hormone, some body builders take illicit forms of the drug to increase muscle bulk.

All in all, a dicey substance for a pharmaceutical company to pursue. But in the early 1990s, Congress, concerned that big, profit-minded pharmaceutical companies were showing little interest in making drugs for so-called “orphan diseases” passed legislation encouraging companies to make such drugs. (Orphan diseases are those that affect 200,000 or fewer people – a small market.)

So Orphan Medical, Inc. of Minnetonka, Minn. began researching Xyrem. It’s still not quite clear how it works, though it may act through a brain chemical called dopamine. It is clear that Xyrem seems to reduce cataplexy attacks, and restore restful sleep for narcoleptics, who, despite overpowering sleepiness during the day, wake up frequently at night. Indeed, Mary Rourke, Bob Cloud and the Massachusetts nurse have all taken Xyrem under research protocols – and all say it has significantly improved their lives.

Though GHB was classified in March, 2000 as a Schedule I (most restricted) controlled substance, its potential as the prescription drug Xyrem for cataplexy (but not narcolepsy) meant that it was recommended as “approvable” last summer by an advisory committee to the FDA. The agency usually follows the recommendations of such committees. To make sure it does not get into the wrong hands, Orphan Medical is setting up a special distribution system so that all prescriptions will be filled by one central pharmacy.

To be sure, there are skeptics. Dr. John Winkelman, medical director of the sleep health center at Boston’s Brigham and Women’s Hospital, says, “I think the jury is still out on Xyrem because of concerns about potential abuse.”

But other doctors are as positive as patients. “Many people are transformed by it,” says Dr. Emmanuel Mignot, a professor of psychiatry and behavioral science at Stanford University Medical School.

Some people with cataplexy have as many as 15 to 20 falls a day, says Dr. Michael Biber, medical director of Neurocare, Inc. in Newton. “People are unbelievably disabled.” Yet on Xyrem, which he has tried on three patients so far,  people can become “almost completely free of symptoms.”

But just as important as the advent of Xyrem is the remarkable confluence of brain research on the triggers for narcolepsy, notes Dr. Jerome Siegel, professor of psychiatry and behavioral sciences at UCLA and chief of neurobiology research at the Sepulveda VA Medical Center in Los Angeles.

“What is extraordinary is that everything has been done in the last three years,” adds Mignot, the Stanford narcolepsy researcher.

In 1998, while looking for brain chemicals believed to control appetite,  two independent teams – one in San Diego, one in Dallas – discovered a neurotransmitter in a part of the brain called the hypothalamus. It quickly acquired two names – hypocretin and orexin – and it is made by only by a few cells in the hypothalamus. Significantly, hypocretin-producing cells in the hypothalamus connect to other parts of the brain and brainstem that control arousal and muscle tone.

Curious, the Texas team went on to see what would happen if they deleted, or “knocked out,” the gene for hypocretin in mice. To their surprise, mice with the missing hypocretin gene seemed to wander around normally, then suddenly drop in their tracks, just like narcoleptics with cataplexy. Also like narcoleptics, the knock-out mice began their night’s sleep abnormally – with REM, instead of non-REM sleep.

Meanwhile, unaware of this work, Mignot’s team at Stanford University was trying to figure out the genetic causes of narcolepsy in dogs.

Within weeks of each other in 1999, the Stanford and Texas teams reported work that dovetailed perfectly. The Stanford team found that dogs with narcolepsy have a mutation in the gene for the hypocretin receptor. The Texas team found that mice missing the gene for hypocretin itself showed behavior remarkably similar to narcolepsy.

“It was quite amazing and convincing,” says Siegel of UCLA. The cause of narcolepsy suddenly seemed obvious: lack of hypocretin, or its receptor.

In early January, 2000, Mignot’s team reported that human narcolepsy patients had low levels of hypocretin in the fluid that bathes the brain and spinal cord. Another key clue.

But an important step remained. So both Mignot’s group at Stanford and Siegel’s at UCLA obtained brain tissue from narcoleptics who had died and they, too, published their findings in the fall of 2000 within weeks of each other. Both teams found that almost all of the hypocretin-producing cells in the hypothalamus of people with narcolepsy were missing.

Moreover, Siegel’s group found that there was scar tissue where hypocretin-producing cells should have been, a clue that (unlike dogs, in whom narcolepsy is often hereditary) people who develop narcolepsy are born normal and subsequently suffer damage to these cells, most likely because of a misguided attack on these cells by the immune system.

It’s still not clear why many people with narcolepsy also have cataplexy while others don’t. But a number of companies are now scrambling to make narcolepsy drugs that mimic hypocretin to restore normal levels.

In the meantime, prescription stimulants such as Provigil, Ritalin and Dexedrine often help people with narcolepsy stay awake during the day. And anti-depressants such as Tofranil and Prozac can partially control cataplexy. If Xyrem is approved, it may prove a valuable addition to the medical arsenal.

Longterm sufferers like Mary Rourke are crossing their fingers. Because she participated in a research study on Xyrem, Rouke has been allowed to take the drug, even though her participation in the study is over. She says it has changed her life.

Recently, she was standing in her classroom when a student snuck up behind her and said, “Boo!”

“If I hadn’t been taking this drug,” she says, “I would have gone right down.” 

Sentinel Node Biopsy – Ready for Prime Time?

by

Anna Coppinger, 61, a school cafeteria worker from Hingham, lies waiting outside the operating room at South Shore Hospital in Weymouth, chatting with her husband and daughters –  and wincing whenever she jostled the needle that had been placed in her left breast several hours earlier to guide surgeons to the exact spot where her tumor lay.

As she liese there, a radioactive substance called technetium-99m sulfur colloid, injected earlier, is seeping through the lymph ducts in her breast toward lymph nodes in her armpit.

Like a growing number of people with cancer, Coppinger was about to undergo a relatively new – and still-controversial – procedure called sentinel node biopsy.

Instead of removing 10 to 20 lymph nodes in the armpit to check for signs of cancer, Coppinger’s surgeon, Dr. Suniti Nimbkar, is planning to remove just the first, or “sentinel,” node into which cancer cells were most likely to have spread. If that node turns out to contain cancer, Coppinger will have another operation to remove the rest of her armpit lymph nodes. But if it’s clean, she’ll get no further node surgery.

Ever since doctors began experimenting with sentinel node surgery in melanoma patients a decade ago, the technique has “caught on like wildfire with most surgical oncologists,” says Dr. Kenneth Tanabe, chief of surgical oncology at Massachusetts General Hospital.

Today, this state-of-the-art technique is well-accepted for melanoma, and is being studied for a number of other malignancies, including colon cancer. But perhaps its most controversial application is in women with breast cancer. The National Cancer Institute insists the procedure should be considered “investigational” until the results of two major studies, now underway, are available.

But around the country, surgeons like Nimbkar are already switching to the new procedure, convinced that there is no need to wait.

The argument in favor is clearcut. Many solid tumors have been shown to “drain,” or shed cancer cells, in an organized pattern, first to the nearest lymphatic ducts and nodes, then to more distant ones, although cancers sometimes  “skip” directly to distant ones. (The lymphatic system is part of the body’s immune defense system. Cancer can also spread directly through blood vessels.)

This means that taking out only the sentinel node could be just as reliable a way to tell if cancer has spread as more drastic node surgery. Indeed, two reviews published in 1999 and 2000 suggest that in breast cancer patients, if  the sentinel is negative, the other armpit nodes will also be negative 95 percent of the time.  If the sentinel node is positive, there’s a 25 to 50 percent chance that the other armpit nodes will be positive.

Sentinel node biopsy clearly causes less pain. And it avoids many of the complications of the full nodal surgery, which more than 80 percent of women suffer. These range from temporary discomfort to numbness, persistent burning sensations, infections, limited shoulder mobility and more rarely, lymphedema, in which the arm can become chronically swollen and prone to infection.

But a key question looms: Does taking out all the armpit lymph nodes make a difference in long-term survival, or is the outcome be the same if only the sentinel nodes are removed?

Historically, one of the main reasons that surgeons removed all the lymph nodes in the armpit of a woman with breast cancer was to get rid of any possible traces of cancer, says Dr. David Krag, the lead researcher for NCI’s study in Vermont and professor of surgery at the University of Vermont Cancer Center in Burlington.

But a government-sponsored study nearly 20 years ago began to challenge that notion. It looked at women with breast cancer who had all their armpit nodes removed and those who didn’t and could not find any  “survival difference,” says Dr. Jeffrey Abrams, senior investigator in the division of cancer treatment and diagnosis at the NCI.

 Indeed, “there is no firm evidence that removing involved lymph nodes improves survival, even though it is standard practice,” the NCI notes on its website (http://cancer.gov) “Randomized studies suggest that lymph node removal may not improve survival, although it is valuable in determining the stage of the cancer. Sentinel node biopsy can be used to determine stage, so that may be all that is necessary, even in node-positive women.”

On the other hand, the 20-year old American study that showed no survival difference did not have enough patients to detect differences of less than 10 percent in survival. Moreover, when data from this American study are lumped together with data from five studies from outside the US, the overall picture suggests that women who have full lymph node dissection do have a five percent survival advantage over those who don’t.

In other words, leaving cancerous nodes in the body does appear to be “dangerous for survival,” Krag says.

In Krag’s own study, 5,400 women will be randomized to get sentinel node biopsy plus a full armpit node dissection, or to sentinel node biopsy only. Those who get the full dissection then go on to get whatever subsequent treatment – chemotherapy or radiation – doctors deem best.

Among those who get only sentinel node biopsy, if there is no sign of spreading cancer, there is no further no surgery, although, like the first group, they get whatever chemotherapy or radiation they need. If there are signs of spreading cancer, those women get a full armpit node dissection, as well as appropriate further therapy.

 “Until you prove the ultimate survival is the same, you haven’t proved that sentinel node biopsy can replace complete removal of all the underarm lymph nodes,” says Abrams of NCI.

Krag’s study will also try to determine whether full armpit node dissection decreases the odds of recurrence of cancer in the armpit, and will compare the value of sentinel node biopsy versus full dissection as a way of staging patients, or classifying them into categories to determine their subsequent treatment.

The other major study is being led by Dr. Armando Giuliano, chief of surgical oncology at the John Wayne Cancer Institute in Santa Monica, CA.

In his study, which is designed to include 7,600 women with breast cancer, Giuliano’s team will give all the women a sentinel node biopsy. Women with negative sentinel nodes will receive whatever further therapy doctors think best.

Women with positive sentinel nodes – expected to number about 1900 –  will then be randomized to full armpit node dissection or no further node surgery or radiation. The idea is to see whether there is any therapeutic value to removing all the lymph nodes. But the prospect of leaving cancerous nodes in place is proving a tough sell, Giuliano says, because many women do not want to take a chance on leaving lymph nodes in if there are any signs of cancer. 

Both Giuliano and Krag will also use a new test to try to determine whether women whose sentinel nodes are negative may nonetheless have “micrometastases”- tiny traces of usually-undetectable cancer.

Normally, scientists examine lymph nodes with a simple test dubbed “H&E,” for hematoxylin and eosin, colored stains that make all cells visible and allow pathologists to see which cells might be cancerous.

The new technique uses IHC, or immunohistochemistry, which involves antibodies that stain only epithelial cells. A healthy lymph node usually contains no epithelial cells. But cancer cells are epithelial cells, so a node that contains even a few cancerous cells will stain positive.  The IHC technique, only done currently if there is ambiguity on the H and E test, can detect even one or two cancer cells.

At South Shore Hospital, Coppinger’s sentinel lymph node surgery takes less than an hour.

With Coppinger under general anesthesia, Nimbkar slips a sterile covering over a special wand hooked to a geiger counter on a table.

By now, the radioactive substance (technitium sulfur colloid)  that was injected into Coppinger’s breast earlier has migrated to her lymph nodes. Sure enough, as Nimbkar slides the wand over Coppinger’s armpit, the geiger counter squawks as Nimbkar finds a “hot spot.”

“This is just what you hope for,” says Nimbkar, as she makes a 1-inch incision just above the hot spot. Slowly, she dissects away the top layers of fat, probing with her finger until she locates the first node. Carefully, Nimbkar cuts out the node, then slips the wand back into Coppinger’s armpit. The geiger counter now registers almost nothing, a strong sign that there are no other nodes in the area.

“I think we’re good,” she says, beginning to sew up the small armpit incision before moving on to do a lumpectomy to remove the tumor in Coppinger’s breast.

A week later, Coppinger says she’s “doing terrific – I’m going to play baseball.”

Her lab results turned out fine, too. Her node was negative, which means it’s very unlikely that cancer has spread to any other nodes.

Better Ways to Scan the Colon

by

“We Cater to Cowards,” proclaims the cheery little sign at Mount Auburn Hospital in Cambridge, where countless cowards (including this one) go for what may well be everyone’s least favorite test: colon cancer screening.It’s no secret why people stay away in droves from such things. To detect cancer, or the small growths called polyps that might someday turn cancerous, a doctor must pass a tube containing a tiny video camera up through the patient’s rectum into the large intestine, or colon – not exactly most people’s idea of a good time.

If the doctor looks at only the lower third of the colon, the procedure is called a flexible sigmoidoscopy, though this test is so limited that some doctors are abandoning it, arguing it’s like doing a mammogram on only one breast. If the doctor inspects the whole colon up to the small intestine, that’s a full colonoscopy  – psychologically, a bit more daunting, perhaps, though the patient does get sedation, and the whole day off from work.

With either a colonoscopy or “flex sig,” the bowel must be pumped full of air to keep the walls from closing together and obscuring the view. And with either test, the patient must “prep,” that is, spend a few lovely hours cleaning out the colon, either by drinking a gallon of a  nonabsorbable liquid such as Golytely, taking strong laxatives like Fleet phosphosoda  that flush stool from the entire system, or (for flexible sigmoidoscopies) by using enemas such as Fleet.

At the moment, only 20 percent of people who should get regular colon cancer screening – in other words, everybody over age 50 –  actually do so, even though such screening can save lives.  But take heart, fellow cowards.

A number of new techniques now being tested, including a noninvasive test called “virtual colonoscopy,” should make screening more appealing. And if these new tests can be refined to match the accuracy of current colonoscopy, the death rate from colorectal cancer, which has been declining for the last 20 years, could decline further.

Currently, colorectal cancer is the second leading cause of cancer deaths, according to the American Cancer Society. Last year, more than 135,000 people were expected to be diagnosed with it, and nearly 57,000 to die.

Yet it is “one of the most preventable of cancers,” says Dr. J. Randolph Hecht, a gastroenterologist and oncologist at the UCLA Jonsson Comprehensive Cancer Center in Los Angeles. The average person – someone with no family history of the disease –  has 1-in-20 lifetime chance of getting colon cancer. Early detection, by eliminating the polyps and early cancers, can reduce this risk even further.

“Some people say they’d rather die than have a colonoscopy,” says Hecht.  “But I have lots of people who are dying because they didn’t have a colonoscopy.”

That’s a shame, because standard colonoscopy, which at $1000 or more is relatively expensive, is still the best way to find polyps and cancers in the colon. Medicare and many other insurers now pay for routine colonoscopy, though if  all the millions of people who should get a colonoscopy did, the financial squeeze would be enormous.

The big advantage of colonoscopy is its accuracy. It has a “miss rate” of only 2 percent, says Dr. Douglas Pleskow, director of the colon cancer center at Beth Israel Deaconess Medical Center in Boston.

And if the doctor finds a polyp, he or she can take it right away. If the patient does have polyps, the recommendation is for a repeat colonoscopy in three years. If no polyps are found, you don’t need another for 10 years because polyps turn into cancer do so slowly.  

“The procedure is not entirely risk free. There’s the risk of perforation of the intestine, which leads to infection or bleeding in one of every 500 to 1000 procedures”, says Dr. Seth Glick, clinical professor of radiology at the University of Pennsylvania.

With flexible sigmoidoscopy, a big advantage is that no sedation is required. But it’s being phased out in many hospitals, including Beth Israel Deaconess and Massachusetts General Hospital in Boston, because it does not catch enough potential cancers. In a major study published in August in the New England Journal of Medicine, researchers found that “flex sig,” even when combined with a low-tech test called FOBT, failed to detect cancer and high risk polyps in 24 percent of patients.

(FOBT stands for fecal occult blood test. Doctors analyze a tiny stool specimen for traces of blood. The test is not very reliable, because many cancers or polyps bleed only intermittently and some things that bleed do not indicate cancer.)

Of the emerging alternatives, virtual colonoscopy is the furthest along. In fact, it’s already used for patients who cannot tolerate colonoscopy – either because they have intestinal obstructions or because they refuse to have the invasive test.

In virtual colonoscopy, which insurers do not yet pay for, the patient still has to clean out the bowel beforehand, and the bowel must still be pumped full of air. But instead of having a video camera inserted through the rectum, the patient gets a CT scan – a series of X-rays – that are reconstructed by a computer into a two- or three-dimensional image.

The downside is that this involves considerable radiation – much more “than a mammogram because you expose the entire abdomen,” says Dr. William Brugge, director of gastrointestinal endoscopy at Massachusetts General Hospital in Boston. And if the doctor discovers polyps, the patient has to go on to have a full colonoscopy anyway, so the doctor can take them out. 

On the other hand, virtual colonoscopy carries no risk of perforation. Because the X-rays scan the whole lower abdomen, doctors can also pick up cancers in the liver, spleen, kidneys and stomach that might otherwise be missed. Moreover, virtual colonoscopy requires no sedation and it takes under one minute of the patient’s time, though it can take an hour to analyze the results, says Dr. Judy Yee, chief of CT and gastrointestinal radiology at the San Francisco Veterans Affairs Medical Center and a pioneer in the technique.

In a study of 300 patients published in Radiology in June, 2001, Yee’s team found that virtual colonoscopy was great at picking up polyps that measure 10 millimeters or more, the ones that are most likely to turn into cancers. But because the quality of the CT images are not as good as in standard colonoscopy, the virtual technique didn’t catch many smaller polyps.  A 1999 study at the Boston University School of Medicine came to similar conclusions.

For that reason, among others, no one is – yet- recommending that virtual colonoscopy replace standard colonoscopy for routine screening.

But virtual colonoscopy could take off in the next year or two if scientists succeed at making it “prep-less,” that is, if patients don’t have to clean out the colon beforehand. One idea is to have patients swallow a substance such as barium that would act as a positive contrast agent to “tag” residual fluid and stool in the colon so that it shows up as a different color or density in the computerized image. Doctors could then “electronically subtract” this part of the image and, “see” any true polyps or cancers lying underneath.  

Researchers are also pursuing a different kind of fecal tagging to help diagnose colon cancer. First, the patient supplies a whole stool specimen. (This involves a special “bucket” that fits onto the toilet seat; the patient defecates into the bucket.) The sample is then tested for human DNA mutations known to be involved in colon cancer.

In this non-invasive approach, reported in late January in the New England Journal of Medicine, researchers at Johns Hopkins University, M. D. Anderson Cancer Center, a team in Sweden, and the Lahey Clinic and Exact Sciences Corp. in Massachusetts, reported they were able to find fragments of human DNA in stool (which contains mostly bacterial DNA). They were then able to isolate the colon cancer-causing APC gene in about 60 percent of early-stage cancer patients tested. The test could become a noninvasive method of detecting colon cancer

The bottom line, fellow cowards?

  • If a radiologist touts the plusses of virtual colonosopy (which radiologists do), ask for an opinion from a gastroenterologist, who does colonoscopies. These two groups of specialists will be competing ever more aggressively for the privilege of looking inside your guts. Don’t assume that if you get a fancy “total body scan” for $1000 or so that you’ve taken care of colon cancer screening. You haven’t. since those scans involve no “prep” beforehand, the intestine is too full of stool for the scan to detect anything else.

  • So, be a savvy consumer. But one way or another, get screened for colon cancer at regular intervals after age 50. 

    For more information, you may contact:

    The American Cancer Society, 1 800 ACS-2345 begin_of_the_skype_highlighting              1 800 ACS-2345      end_of_the_skype_highlighting (1 800 227 2345 begin_of_the_skype_highlighting              1 800 227 2345      end_of_the_skype_highlighting) or www.cancer.org.

    The National Cancer Institute’s information line, 1-800-4-CANCER begin_of_the_skype_highlighting              1-800-4-CANCER      end_of_the_skype_highlighting; also, www.cancernet.nci.nih.gov