Judy Foreman

Nationally Sindicated Fitness, Health, and Medicine Columnist

Fatty Acid Imbalance Hurts our Health

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Throughout most of human history, our ancestors ate a diet that was nearly perfect in its balance between two essential fatty acids, omega-3s and omega-6s, which have crucial, though opposite, roles to play in metabolism.

In the last few decades, however, this delicate balance has been thrown out of whack, with most of us eating too many omega-6s, which come chiefly from corn and safflower oils, and far too few omega-3s, found in fatty, cold-water fish such as salmon and tuna as well as walnuts, canola, soy and flax seed oil. This nutrient imbalance is believed to contribute to arthritis, cystic fibrosis, heart attacks and other diseases.

“We are drowning in omega-6 relative to omega-3’s,” says Dr. George L. Blackburn, associate director of nutrition in the Division of Nutrition at Harvard Medical School.  Throughout evolution, the ratio of omega-6 to omega-3 was two 6’s to one 3, he says. “Now it’s about 20 to one. We have wiped out a lot of sources of omega-3 and have a huge intake of omega-6-heavy products like corn and safflower oils.”

“We need some of both,” adds Dr. Walter Willett, chair of the department of nutrition at the Harvard School of Public Health. The goal is to bring back a balance “by increasing omega-3s, not by decreasing omega-6s.”

Omega-6 fatty acids get converted in the body to substances that rev up the immune system and inflammatory response – a good thing for fighting infections, but detrimental in people prone to auto-immune problems such as arthritis. Omega-6s also boost clotting – a benefit if you’re bleeding to death, but potentially harmful in terms of increasing clots that can lead to heart attacks or strokes.

“We have doubled omega-6s in our food supply in the last 40 years” says Willett. “That’s one of the most important reasons that heart disease mortality has declined by 50 percent since the 1950s…Omega-6 lowers cholesterol and has some benefits on platelets and anti-arrhythmic effects as well….We need the 6s. We don’t want to reduce those.”

Omega-3s, by contrast, get converted in the body to substances that decrease the immune response, a benefit for people with auto-immune problems, and increase the time it takes for blood to clot, a benefit for people at risk of heart disease. Omega-3’s also decrease potentially fatal cardiac arrhythmias and are crucial to the healthy development of the spinal cord, brain and retina in infants and to healthy brain functioning in older people as well. 

Because Americans are relatively deficient in omega-3s, doctors and scientists are now scrambling to find ways to increase omega-3s in our diet.

Last week, researchers at Massachusetts General Hospital announced that they had genetically altered mice to produce omega-3 fatty acids. Scientists from Beth Israel Deaconess Medical Center and UMass Memorial Medical Center in Worcester also reported on research that suggests that people with cystic fibrosis may be helped by increasing omega-3s.

Later this month, the Institute of Medicine, an arm of the National Academy of Sciences, is expected to issue a report evaluating the methods used to assess the safety of additives to infant formula, including DHA, an omega-3 fatty acid, and AA, an omega-6. European countries have long added DHA and AA to baby formulas; American manufacturers began doing so two years ago to bring formulas closer to the composition of breast milk.

Because there are now so many products, particularly dietary supplements, out there in health food stores, supermarkets and pharmacies, it’s worth taking a moment to understand the terminology on product labels and ads.

There are many kinds of omega-6 fatty acids, and the one people need to consume in the diet – that is, the “essential” fatty acid – is linoleic acid. This gets converted in the body to arachidonic acid (AA) (which cannot be obtained from the diet) and which boosts the immune system and clotting by increasing a hormone called prostaglandin E2.

There are also many kinds of omega-3 fatty acids, the most important of which are DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid), both of which are found in fish. DHA can also be made by the body from its precursor, an omega-3 called linolenic acid, which comes from soy, canola, walnut and flaxseed. EPA can also be made from linolenic acid. The body’s biochemical machinery uses these acids to make prostaglandin E1, which slows down the immune system and increases the time it takes for blood to clot.

Omega-6 and omega-3 are both in the family of “PUFAS,” or polyunsaturated fatty acids. Fatty acids are long chains of carbon atoms hooked to each other and linked hydrogen bonds. If there are no “double bonds” between carbons, the fat is said to be saturated.  If there is a “double bond” anywhere in this chain, the fat is unsaturated. If there are lots of double bonds, the fat is polyunsaturated.

Polyunsaturated fats are considered  “good” because every double bond causes a 37 degree kink in the chain, which makes the fat more fluid. That in turn makes it easier for the fat to do one of its major jobs, slink into the fatty membrane around cells.

Because omega-3 fatty acid suppresses immune function and increases the time it takes for blood to clot, one might think that an excess could lead to an increase in infections and bleeding problems. This does not appear to be the case. “We’re not even close to those dangers – maybe the Eskimos are,” says Dr. Ernst Schaefer, chief of the lipid metabolism laboratory at the Human Nutrition Research Center at Tufts University.

The bottom line? Don’t stop eating omega-6 oils, but increase omega-3 however you can. This means eating more fish – yes, even salmon despite the risk of pollutants such as mercury, dioxin or PCBs. It also means breastfeeding if you can, or choosing formulas containing DHA and AA if you can’t.

If you hate fish, try taking 1 gram a day of fish oil supplements containing omega-3 fatty acids. But beware: Fish oil capsules vary greatly in quality. To reduce the chance that the supplements have the same pollutants as in fish, it may be wise to stick with well-known national brands. 

Keeping Your Nose Clean

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Okay. So your daily attempt at perfection already includes brushing and flossing, exercising, meditating, eating fruits and veggies, and overall clean, healthy living. Here’s one more health habit you might consider. (Or not.)

In lay terms, it’s called keeping your nose clean. In fancier language, it’s nasal lavage – also known as nasal irrigation or sinus rinsing.It’s a simple, low tech way to wash out the viruses, bacteria, mold, allergens, dust, mucus and general crud that lands inside the nose and sinus passages, thereby contributing to colds, chronic nasal congestion, post nasal drip, frequent sinus infections, asthma and other respiratory ills.

The basic idea, unappealing as it sounds, is to squirt a slightly salty water solution up your nose, let it drip out, blow your nose gently, then repeat. The mechanical action of flushing out thickened mucus cleanses the nasal passages, making it easier for tiny hair-like cilia that line the nose to push the remaining mucus out.

Before we get to the bewildering array of products out there for the nasally challenged, take it from a reluctant connoisseur of this somewhat arcane practice: No matter what product you use, technique matters.

Squirt the solution up your nose with too much force and it hurts. Squirt too gently and you’re not accomplishing a thing.  If the solution is too salty, it stings. Ditto, if it’s not salty enough.

That said, here’s the case for indulging in this weirdness. For one thing, it’s been around in many cultures for centuries. For another, ear, nose and throat specialists swear by it for anyone with chronic sinus problems – even kids.

“Many patients that have sinus disease, allergies or chronic infections are improved tremendously by lavaging their nose out once or twice a day,” says Dr. Gerald Berke, chief of head and neck surgery at the University of California, Los Angeles. And for those who have had surgery to open up narrowed sinuses, regular lavage is a must. “The main improvement they experience is the ability to lavage out the cavity,” says Berke.

Even if antibacterial medications are added to the lavage solution, “most of the benefit is from the mechanical rinsing of the nasal cavity,” says Dr. Eric Holbrook, an otolaryngologist at the Massachusetts Eye and Ear Infirmary. Among other things, the gunk you rinse out in mucus includes natural chemicals called cytokines, which promote inflammation. “If you remove the mucus, you can actually reduce the inflammation,” Holbrook says.

“I am a strong believer in nasal lavage,” adds Dr. Ralph Metson, another sinus specialist at Mass Eye and Ear. But people need to do it with salty water “to wash out mucus.”

While large, controlled studies of nasal lavage for treating and preventing colds and sinus infections are hard to come by, the little data that does exist seems to support the practice.

One study of more than 200 patients published in 2000 in the journal Laryngoscope found that after three to six weeks of nasal irrigation, patients reported statistically fewer nasal symptoms. A 1997 study of 21 volunteers in the same journal found that lavage improved the speed with which nasal cilia were able to move mucus along.  A 1998 study in children published in the Journal of Allergy and Clinical Immunology showed that lavage is “tolerable, inexpensive and effective.”

So, how to do it. First, the recipe.  To make an isotonic solution (the same saltiness as body fluids), add to eight ounces of water one-quarter teaspoon of salt and one-quarter teaspoon of baking soda. (The baking soda keeps it from stinging.) To make a hypertonic solution, use more salt. 

The simplest, albeit messiest, way to get the solution up your nose is to cup it in your hand and sniff, although this lacks a certain elegance. Ceramic Neti pots, popular among the yoga set, work better, although you may not get the water up high enough.

Those blue bulb syringes for cleaning out babies’ ears and noses work, too, though, again, it can be hard to get the solution up high enough. Turkey basters and flower pots with nostril-sized spouts are also said to work, although this could not be confirmed. (Well, it could have been, but it wasn’t.)

Small, 3-ounce squeeze bottles of pre-packaged saline nasal spray available at most drugstores don’t really flush out the sinuses; they just moisten the inside of the nostrils.

Nebulizers also deliver a spray, not a real jet of water , but they work well for kids, says Dr. Sandra Lin, an otolaryngologist at Johns Hopkins School of Medicine, who says she has “seen patients really turn around” on nasal lavage.

Larger squeeze bottles such as the 14-ounce ones made by SaltAire Sinus Relief get the cleaning solution higher up into the sinuses. This system, developed by Drs. Robert Pincus and Scott Gold, co-directors of the New York Sinus Center, is indeed, just as they claim, easy to use and the buffered hypertonic solution does not sting. (Buffering means the acidity of the solution is adjusted so that it is close to that of the body.) The SaltAire product costs $12.50.  

Dr. Ketan Mehta, a pulmonologist and intensive care specialist based in Santa Rosa, CA, has developed a different lavage system called “Sinus Rinse,” made by his company, NeilMed Products, Inc.

For $10.95, you get an 8-ounce squeeze bottle with a gently-pointed tip and 50 packets of pre-mixed solution to which you add eight ounces of water. The NeilMed product can also be hooked up to a Waterpik or similar system that is electrically powered and delivers pulses of solution.

The  Waterpik Technologies folks, who make oral irrigation devices that squirt water around the teeth under the gums, also have their own attachment called Gentle Sinus Rinse. The Waterpik irrigators cost from $35 to $50 depending on the model, with an extra $10 to $15 for the sinus adapter.

Other nasal hygiene products are becoming increasingly available on the Net and in stores. Yeah, it sounds weird. But you just might end up with one of the true blessings in life – clear sinuses.

The Science of Pain (This is the second of a two part column on pain)

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Dr. Darlyne Johnson, 46, an obstetrician-gynecologist at South Shore Hospital in S. Weymouth, MA. is no stranger to pain – and not just the pain of other women having babies.

Over the years, Johnson has had surgery, and each time, wound up with such terrible nausea and vomiting from painkillers that she had to stay in the hospital overnight.

Not surprisingly, when she found out three years ago that she needed hernia surgery, she balked. “I knew what was going to happen – I’d get sick.” Then she heard about a device called ON-Q. It consists of a tiny tube, placed in the incision and connected to a small container of local anesthetic worn outside the body. Like water through a soaker hose, the medication, usually lidocaine, oozes into the wound for several days. The idea is that by blocking pain at the site of injury, patients should need smaller doses of opioid painkillers, which act on the whole body, often making people sick and spacey.

“Basically, I was pain-free,” says a delighted Johnson, who immediately began offering ON-Q to her patients undergoing C-sections.

And that is just the beginning of doctors’ increasingly successful efforts to manage pain.

Chronic pain, which can be caused by damage to nerves (as in shingles or diabetes), inflammation (as in arthritis) and diseases (such as cancer), is a fact of life for 50 million Americans, according to some estimates, and as many as 75 million Americans, according to the American Pain Foundation, a consumer group. Another 25 million more suffer every year from acute pain after surgery or injury.

At its essence, pain “is an unpleasant and emotional experience associated with tissue injury,” says anesthesiologist Dr. Daniel Carr, professor of pain research at Tufts-New England Medical Center in Boston. People can also feel pain when there is no obvious tissue damage, as in fibromyalgia, or after a limb has been amputated.

Pain, obviously, is an intensely subjective phenomenon. But there is growing objective evidence of how pain is registered in the brain, too.

In one recent report, Wake Forest University School of Medicine researchers subjected volunteers to pain (heat) on their skin and had them rate it on a scale of 0 to 10. They also scanned the subjects’ brains with fMRI (functional magnetic resonance imaging) and found that in those reporting the most intense pain, several regions of the outer layer of the brain (the cortex) were activated more often and more intensely.

Dr. Catherine Bushnell, a professor of anesthesiology at McGill University, also uses brain scans to study pain. When people are distracted from pain, she has found, the scans reflect a dampened experience of pain, suggesting that a person’s psychological state can  change the way pain is processed in the brain. 

On a more technical level, pain comes in several forms.

Nociceptive pain is triggered by tissue injury, including strong, noxious stimuli from the outside world such as a pin prick, heat or cold, as well as internal threats such as a kidney stone, obstructed bowe or infection. Neuropathic pain is caused by damaged nerves. Inflammatory pain is caused when joints or other tissues become swollen and release a cascade of natural, but harmful, chemicals.

During transmission of pain signals from, say, a cut finger, to the brain, a slew of chemical signals is produced by injured tissues and nerves, including substance P, bradykinin and glutamate, which Dr. Clifford Woolf, a professor of anesthesiology research at Massachusetts General Hospital, calls “the star of the show.”

At normal levels, glutamate is essential to the functioning of the nervous system; in excess, it can be devastating.

When excess glutamate over-stimulates certain receptors on spinal cord neurons (called NMDA receptors), acute pain can be transformed into chronic pain. Some drugs already on the market such as ketamine and dextromethorphan can block this process.

Researchers now know that not only do all cells, including nerve cells, have ion channels through which substances like sodium and calcium move in and out, but that particular subtypes of sodium channels govern the transmission of pain. “Some sodium channels are specific to pain fibers,” says Woolf. This means that drugs targeted at only these channels could block pain without affecting other cells.

The growing understanding of pain is the way pain is treated, says Dr. James Rathmell, chairman of the committee on pain medicine for the American Society of Anesthesiologists and a professor of anesthesiology at the University of Vermont Medical College in Burlington.

One example is sensitization, or “wind up” pain. When you injure nerves in your finger, nerves in the spinal cord “reorganize to amplify pain and remember it,” says Carr of Tufts. In other words, acute pain becomes transformed into chronic pain.

To prevent this in surgical patients, some doctors now give patients COX-2 inhibitors like Vioxx or Celebrex before surgery. These drugs block an enzyme called cyclooxygenase-2, a key player in pain transmission.

For women in labor, low doses of morphine injected into the intrathecal space around the spinal cord provides “tremendous pain relief,” Rathmell says.

For cancer pain, doctors also implant a permanent catheter (tiny tube) into the intrathecal space and attach the tube to a morphine pump placed in the abdomen. A major Johns Hopkins study showed that this technique not only provides dramatic pain relief, but increased longevity by a month or two.

For people with neuropathic pain, anti-epileptic drugs such as Neurontin (gabapentin) are showing promise. The rationale is that the body produces the same cascade of harmful chemicals during both the  “electrical storm” of partial seizures and in neuropathic pain.

Two 1998 studies showed that gabapentin can reduce nerve pain in both diabetes and shingles. Other gabapentin-type drugs are now in clinical trials for pain.

For people with back pain, microsurgery to remove damaged disks in the spine can improve pain control significantly, says Dr. Michael Ferrante, director of the UCLA Pain Management Center and co-director of the UCLA Spine Center. So can non-surgical techniques such as heated coils to destroy nerves in damaged disks.

Directly addressing the link between chronic pain and depression can also help, says Dr. Alan F. Schatzberg, chairman of the department of psychiatry and behavioral sciences at Stanford University Medical School. An epidemiological survey of 19,000 people in Europe shows that there is a huge overlap between pain and depression.

Anti-depressants that boost both serotonin and nor-epinephrine, neurotransmitters in the brain, seem to help with both pain and depression.

Non-drug approaches to pain control, most notably  acupuncture, can also be effective for some kinds of pain.

As for Dr. Darlyne Johnson and the ON-Q story?  One study by University of Vermont researchers on this method of post-surgical pain control following knee surgery found it had no effect. But the company that makes ON-Q, the I-Flow corporation, says studies of patients undergoing hysterectomies or colorectal surgery found that many patients using it needed less then the usual level of opioids after surgery.

At the Johns Hopkins Hospital, anesthesiologists Dr. Lee Fleisher and Dr. Christopher Wu are studying ON-Q in prostate surgery patients. “We are very interested in seeing if there is a benefit to blocking pain up front and never getting ‘wind up’ pain,” says Fleisher.

There’s no need to convince Dr. Darlyne Johnson of that. After her surgery, she went home quickly and needed only over-the-counter pain relievers: “It was a whole different experience.”

A Conversation with Kathleen Foley

Dr. Kathleen M. Foley, 59, spends most of her waking hours dealing with two subjects that make many people cringe: pain, and death.

As an attending neurologist at Memorial Sloan-Kettering Cancer Center, she treats the pain of cancer patients, including many who are dying.

As director for the last nine years of the Project on Death in America, an effort by George Soros’ Open Society Institute to change the culture of death in this country, she’s been a prominant voice for helping Americans get what polls show they want: a dignified death, in many cases at home, with good pain control and emotional support, for both patient and family.

As chair of three World Health Organization expert panels over the last 27 years, she helped create  guidelines for doctors on managing cancer pain, setting up palliative care services and controlling pain in children.

A New Yorker through and through, Dr. Foley was born and raised, with her four sisters and two brothers, in Queens by her homemaker mother and banker father. Though her mother died when Dr. Foley was 13, she chugged straight through a Catholic girls’ school, St. John’s University for a B.S. in biology, Cornell University Medical College (now Weill Medical College of Cornell University) for her M.D., and New York Hospital for her internship and neurology residency. She has been at Sloan-Kettering ever since.

Q. How did you get interested in the subject of death and dying?

A. I was dragged into it. I was being interviewed for a position at Sloan-Kettering to focus on pain in cancer. I told the interviewer I knew nothing about pain. He said, ‘That’s okay. Nobody else does, either.’ This was 1974. Researchers had just discovered that there were receptors in the brain for painkillers, or opiates.

We knew how to give morphine for acute pain, but we didn’t know how to use it for chronic pain. It’s quite shocking to remember. Six years after I got to Sloan-Kettering, we set up the first pain service in the country for cancer patients.

Q. In the last five years, three major reports from the Institute of Medicine (part of the National Academy of Sciences) have shown that pain control is woefully inadequate. A 1995 study by the Robert Wood Johnson Foundation showed that 50 percent of adults die in pain. If we know so much about pain these days, why aren’t we more aggressive about controlling it?

A.  A big part of the problem is that our efforts to treat pain aggressively have run into the war on drugs, as the furor over opioids (or narcotics) like oxycodone [OxyContin] shows. Opioids are safe and effective medications and patients can function very well on them. But the increase in abuse of prescription opioids is impacting the use of these drugs for legitimate medical problems. Some drug stores won’t stock opioids. In some states, Medicaid makes doctors get prior authorization before prescribing them. Some doctors in New York – 30 percent in one survey – report they are reluctant to prescribe them because of strict regulations.

Q. So, what’s the solution?

A. We need to balance our concerns about the risk of prescription drug abuse with the needs of pain patients. There are certain pain syndromes like neuropathic pain –  pain resulting from injury to a nerve – for which current therapies work for less than half of the patients less than half of the time. We need to make pain research a national priority.

Q. Why don’t medical schools do a better job on all this? According to a 2000-2001 survey of 125 medical schools compiled by the Association of American Medical Colleges, only three percent had a separate, required course on pain management and only four percent had one in end-of-life care. The 2003 survey, which asked questions differently, still shows only a few schools teaching pain and palliative care as a separate course, though most do include these issues to some extent in the curriculum. 

A. The three Institute of Medicine reports identified lack of professional education in pain and palliative care as the major barrier to advancing these areas of expertise.

Q. Hospice care, usually in the patient’s home but also in nursing homes, assisted living facilities and hospitals, is growing. According to the National Hospice and Palliative Care Organization, 11 percent of all deaths in 1993 took place in hospice; by 2002, it was 28 percent. Yet polls show about 75 percent of Americans want to die at home. Why hasn’t the hospice movement grown more?

A. It’s complicated. To qualify for hospice benefits, a patient has to have about six months to live. But doctors have trouble prognosticating like that, especially for diseases other than cancer, such as Alzheimer’s disease and congestive heart failure. So people get to hospice late – when they have only a week or two to live. But the biggest issue is that in our culture, we don’t want to address death until it happens.

Q. If more people were in hospice or palliative care, wouldn’t that save money? It must be cheaper to take care of someone at home than in a hospital.

A. It’s probably at least cost-neutral. If we expand hospice to non-cancer populations, we may shift costs from acute, inappropriate care to appropriate, quality care.

Q. In many ways, palliative care seems like an ideal form of medicine. Why do you have to be dying to get that kind of pain control and emotional support?

A. Actually, we argue that palliative care should be an integrating principle for both those at risk of imminent death and those with chronic diseases.  The World Health Organization has it right – palliative care is an approach to care for patients with life-threatening illnesses that focuses on their quality of life.

Q. If we really had that, would we need physician-assisted suicide?

A. Probably not. Since Oregon passed its law in 1997, there have been 129 cases of physician-assisted suicide, although requests for a doctor’s aid in dying have increased. The real issue is providing palliative care for all Americans. At the present time, we have not provided the education to health care professionals and to the public about their real choices.

Q. A Canadian study three years ago showed that terminally ill cancer patients who denied that they were dying were three times more likely to be depressed than those who exhibited understanding of their imminent deaths. Do you think talking about death helps?

A. There is a distinction between people knowing they are going to die soon and their being willing to talk about it. Many people know, but don’t wish to articulate it. Some don’t need to talk about it. But you don’t have to force someone to talk about it to be helpful. I am most humbled by all of this. What you can ask is ‘What do you know about your situation? What are you worried about? And how can we help.’

Q. So what is your definition of a “good death?”

A . It’s a good death is if the patient has what he or she wanted – having the family there, if that’s what they wanted, or not, if it’s not. It’s not suffering in the last days or hours or minutes. It’s having an opportunity to say goodbye, if that was something they valued. And it’s being recognized as the person they have been.

The Politics of Pain (This is the first of a two part column on pain)

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America is seriously schizophrenic about controlling chronic pain, which afflicts more than 50 million people and costs the country $100 billion a year.

So, on the one hand, we grossly under-treat it: Management of chronic pain and the pain of dying patients is arguably the most egregiously neglected field of medicine.

On the other hand, as a society, we have become obsessed with the war on drugs — and the fear of addiction to opioids (narcotics).

Pain patients who were functioning well on morphine-like drugs such as oxycodone (OxyContin) are now fearful of them — or just plain can’t get them.

Some drug stores, wary of robberies of OxyContin, are afraid to stock it. Some unscrupulous doctors have written excessive prescriptions for it. Some patients, like talk show host Rush Limbaugh, abuse it as well. And in some states, Medicaid regulations require doctors to get prior authorization before prescribing the drug.

The basic problem is obvious: Some of the drugs that most effectively treat pain are the same ones that are commonly abused. In one survey of New York doctors, 30 percent said they were prescribing fewer opioids or were switching patients to less-effective pain medications for fear that the Drug Enforcement Agency (DEA) might investigate them.

At the root of our national ambivalence is what June L. Dahl, professor of pharmacology at the University of Wisconsin-Madison Medical School, calls “opiophobia” — the fear of addiction to opioids. That phobia has led to serious undertreatment of pain — particularlychronic pain.

“Every bit of evidence suggests that we have been under-treating pain,” said Dr. Kathleen Foley, an attending neurologist at the Memorial Sloan-Kettering Cancer Center and director of the Project on Death in America of the Open Society Institute, an operating foundation supported by George Soros.

In the last five years alone, three major reports from the Institute of Medicine, an arm of the National Academy of Sciences, have concluded that pain control in this country is woefully inadequate. These pronouncements follow a 1995 study by the Robert Wood Johnson Foundation that found that 50 percent of people had moderate to severe pain in the last three days of life.

A separate study found similar rates of untreated pain in dying children. Even the US Supreme Court, in deciding in 1997 against a constitutional right to physician-assisted suicide, highlighted the need for better pain control and palliative care. Though the fear of addiction is great, in reality, the risk is small, when patients take drugs in the doses prescribed by physicians.

“Addiction,” to be sure, is a loaded word. Researchers prefer to speak of physical dependence, which does occur in patients taking opioids, and psychological dependence, which typically does not. It is psychological dependence — a compulsion to seek more and more of the drug, despite the harm it causes — that lay people usually mean by “addiction.” One 1982 study on patients in 93 burn facilities found no evidence that any patients became addicted to opioids. More recent data from pain clinics suggest the addiction rate might be around 10 percent, but people who attend pain clinics are not typical of all pain patients. 

Moreover, though opioids can cloud the mind, they don’t damage vital organs such as the liver, stomach and kidneys, notes Foley of Sloan-Kettering. And once doses are adjusted correctly and monitored by a doctor, patients on opioids for chronic pain often function “at high levels,” including taking care of families and even driving, she said.

Dr. James Rathmell, chairman of the committee on pain medicine for the American Society of Anesthesiologists and professor of anesthesia at the University of Vermont College of Medicine in Burlington, puts it even more forcefully.

Fears of addiction? “Forget it,” he said. “If you have intractable cancer pain, addiction should be the farthest worry from your mind. Addiction is very unlikely. There are wonderful medications that provide continuous relief over time.” That is true for non-cancer pain as well, although aggressive control of pain for non-lethal diseases is even more controversial. 

Arthritis, both rheumatoid and osteoarthritis, affect an estimated 70 million Americans, said Dr. John Klippel, medical director of the Arthritis Foundation. Yet many suffer daily because their pain is inadequately controlled.

With rheumatoid arthritis, one way of controlling the pain is by treating the underlying inflammatory disease itself, with drugs called DMARDS, disease-modifying anti-rheumatic drugs such as methotrexate. In addition,non-steroidal anti-inflammatory drugs such as ibuprofin (Motrin) and COX -2 inhibitors (like Vioxx and Celebrex) can help.

And despite America’s conflicted views, there are signs that we’re overcoming our collective phobia. Last month, the American Academy of Pain Medicine and leading doctors announced a new initiative called Top Med which will provide a web-based “virtual textbook” available free to all medical students across the country.It is sorely needed.

At the moment, only 3 percent of medical schools have a separate, required course on pain management and only 4 percent require a course in end-of-life care, according to a 2000-2001 survey of 125 medical schools by the Association of American Medical Colleges. A new survey (2003) shows that most medical schools now cover these topics as part of existing required courses.

There’s other good news, too. In 2001, the Joint Commission for the Accreditation of Healthcare Organizations (JCAHO), the group that accredits the vast majority of the nation’s hospitals, mandated that hospitals must assess and manage pain for all patients, something that, astonishingly enough, had not been done routinely until then.

On a more grass roots level, almost all states (including Massachusetts, California and Maryland) have launched pain initiatives to reduce legislative barriers to effective pain control.

Many states are also establishing electronic systems to monitor prescribing and dispensing of controlled substances — a tricky business because the idea is to protect against abuse while not restricting access for people who need opioids. Nationally, there is a controversial bill pending in Congress dubbed NASPER (National All Schedules Prescription Electronic Reporting Act) that would do much the same thing. Klippel of the Arthritis Foundation said what pain control — for arthritis sufferers and others in chronic pain — should ultimately come  down to is quality of life.

Patients should realize, he said, that, when taken properly, “the potential for addiction is really minimal.”

The Impact of Obesity on Hospitals

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The patient was so obese – more than 700 pounds – that it took seven nurses to turn him over. Three nurses at the New England hospital where he was in intensive care went out on workman’s compensation after injuring their shoulders and backs trying to move him.  

Because it was so hard to turn him over, he developed bedsores that got so large “you could see his colon – you could have put a basketball in there,” recalls a nurse. During one admission, when the man needed a CT scan, he had to be taken to a nearby aquarium.

“Toiletting,” in the discreet phrase of medical professionals, became horrific. A urinary catheter solved one problem, but the man couldn’t be moved onto a bedpan, so doctors put in a rectal tube to withdraw his bowel movements. Taking his blood pressure was hard, too  – he needed extra-large cuffs around his lower arms or legs or a catheter placed into an artery in his arm.

 America’s obesity epidemic is creating a nightmare for hospitals, both medically and economically. It’s no day at the beach for patients, either. Lynn McAfee, a spokeswoman for the Council on Size and Weight Discrimination in Mount Marion, N.Y., says obese patients often face hostility and discrimination from health professionals.  “No matter why we are fat,” she says, “right now we exist. And we deserve the best possible medical care, just as anyone else is who is another size.”

According to the federal Centers for Disease Control, 64 percent of adult Americans, or 135 million people, are overweight or obese. One third of all Americans – 68 million – are obese.  (Overweight is defined as having a body mass index, or BMI, of 25.0 to 29.9. Obesity is defined as having a BMI of 30 or more. BMI is calculated by taking weight in pounds and multiplying by 703; this number is then divided by height in inches squared.)

People with a BMI of 40 or more are now called severely or extremely obese, a category that includes  12.3 million people, says Dr. George Blackburn, director of the center for the study of nutrition medicine at Beth Israel Deaconess Medical Center in Boston. “Super morbid” obesity is defined as a BMI of 50 or more, a category that includes 5.9 million Americans, and “mega obesity” as a BMI of 70 or more, which includes 1 million Americans.

The burden that “people of size,” the politically correct term for obese people, is putting on hospitals is huge. It takes special expertise to get an intravenous tube in a place “where you can feel the vein,” Blackburn says. “You can’t feel the liver. Bowel sounds are distant. Detection and treatment of pneumonia are more challenging because you can’t hear breath sounds as well. You can’t see subtleties on X-rays because the thickness of the fat creates a haze on the image.”

Regular beds are nowhere near big or strong enough, either. Nor are operating tables. Or chairs. Or walkers, or ventilators, or hypodermic needles. Nurses need stools to to reach an obese person’s chest.

But capitalism being capitalism, adaptation to the needs of obese patients has become a growth industry.

In the last six years, the instruments needed for bariatric surgery (in which most of the stomach is stapled off and the remaining 5 percent is connected to the small intestine) have gotten larger as patients get heavier, says Dr. Michael Schweitzer, assistant professor of surgery at Johns Hopkins University.  Surgeons have needed ever- larger instruments for laparoscopic surgery – done through several small incisions rather than one large one – and “companies have responded.”

Bariatric surgery itself is booming, too. According to the American Society for Bariatric Surgery, there are now more than 100,000 such operations a year. Five years ago, it was 25,800, and five years before that, 16,800.

Just as dramatic, the industry that supplies over-sized beds, wheelchairs, operating tables and the like to hospitals is growing, by about 20 percent a year, says Lynne Sly, vice president for marketing for Kinetic Concepts, Inc., based in San Antonio, Texas.

Demand is growing for bari-beds with “pressure relief” air mattresses – the mattress inflates and deflates section by section to relieve pressure sores. Gore-Tex sheets allow a patient’s skin to “breathe,” which helps prevent skin breakdown. There’s even a device called “AirPal” that helps heavy patients slide from one bed to another.

Susan Ross, clinical manager of the medical Intensive Care Unit at Rhode Island Hospital, says caring for  obese patients is “a challenge, let me tell you.”  One woman had so much fat hanging down her legs she developed a fungal infection in the skin folds. Just feeding obese patients – often through intravenous lines or naso-gastric tubes- is a major task because “these people require thousands of calories a day,”  she adds.

All of this gets expensive. The cost just for the extra-large bed needed for the 700-pound New England man was $5,568, for less than a month.

Renting an extra-large bed runs an extra $650 a day, says Dawn Arthur, a nursing director at the Santa Monica-UCLA Medical Center in Santa Monica, CA.  Normal wheelchairs cost $750, she says; super-sized ones cost $1200.

But the demand for such products is clearly growing. Since the Stryker Corp. in Kalamazoo, Mich. introduced its 650-pound capacity cot for ambulances last year, it has become a top-seller, says Dean Bergy, chief financial officer for the company.

Despite such accommodations to obesity, some hospitals may still not be doing enough, says McAfee of the size and weight council.  McAfee, who weighs 416, says hospitals “should look in their hearts and ask, “If that were me, would I really think the hospital was doing enough?”

The ramifications seem endless. Well, not quite. As the New York Times reported recently, even the funeral industry is  having to adapt to obese bodies – with extra-large coffins, and super-sized burial plots.

Parents Fight for Experimental Drugs

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Two and a half years ago, several months before she died, Abigail Burroughs, a 21-year old senior at the University of Virginia, sat with her father as chemotherapy dripped, once again, into her body. Together, they mapped out a plan they hoped would save Abigail’s life, and the lives of other desperately-ill people.Burroughs, who was diagnosed with head and neck cancer at 19, had taken every medication her doctors could think of, to no avail. Her last chance, she believed, might be two experimental drugs, Erbitux (still not approved by the US Food and Drug Administration) and Iressa, approved in May.

The Burroughs begged the manufacturers, ImClone and AstraZeneca, respectively, to give her the drugs on a “compassionate use” basis, but  ImClone said did not have such a program at that  time. (It does now.) And  AstraZeneca, which was giving Iressa free to 22,000 people with lung cancer, said no because Abigail had the wrong kind of cancer.

These drugs might not have helped Abigail. But she and her father, Frank, became convinced that seriously ill people should be allowed to get- and even pay manufacturers for – experimental drugs once they have passed preliminary (Phase I) safety trials in humans, even if the drugs might turn out to be dangerous, or useless.  In their view, the currently-available ways to get experimental drugs  – through clinical trials,  “compassionate use” or “expanded access” programs – are tragically inadequate.

So this summer, Frank Burroughs, who now heads the Abigail Alliance for Better Access to Developmental Drugs, teamed up with the Washington Legal Foundation and sued the FDA to loosen its rules.

They want the FDA to create a new level of review called Tier 1 Initial Approval. Under this plan, patients would be able to get an experimental drug if it drug has passed Phase I trials, if the patient has been rejected from clinical trials of the drug, and if nothing else has worked. Perhaps most controversially, they also want to allow patients to be allowed to pay manufacturers for these minimally-tested medications.

Despite its powerful emotional appeal, the Tier 1 plan is creating a firestorm of opposition, including from other patient advocacy groups.

 Fran Visco, president of the National Breast Cancer Coalition based in Washington, D.C., says, “We have a system in place to prove the safety and efficacy of therapies. We can’t afford to undermine that system. The system is premised on [the idea that] drugs should not be available until they are proven safe and effective. ”

Visco points to two notorious instances in which medical interventions became widely used without adequate testing and later proved to be harmful or ineffective: bone marrow transplantation for breast cancer and hormone replacement therapy for menopause. Asked whether an individual should nonetheless be free to choose his or her own risks, she is emphatic. “When you start talking public policy, decisions have to be made. It’s not on the individual autonomy level.”

Nancy Roach, a director of the Marti Nelson Cancer Foundation based in Vacaville, CA, also opposes the Tier 1 idea, saying “it would rip the heart out of clinical research,” adding “these drugs are not candy, they are not harmless.”

At the end of a Phase I (safety trial), a drug may have been tested in only a few dozen people, she notes. (It is not until larger Phase II and Phase III trials that a drug is tested in more people and researchers study dosages and efficacy.)  “You don’t give drugs to people unless there’s a good reason to, you know how to give them, and the person has some chance of benefiting,” argues Roach.

Medical ethicist Dr. Marcia Angell, the former editor of the New England Journal of Medicine and senior lecturer on social medicine at Harvard Medical School, is also opposes to the Tier 1 idea. “New drugs are far more likely to fail than to succeed, so the chances are that a patient will be hurt by a drug rather than helped,” she says. She also rejects the idea that manufacturers need financial incentives to release them. Drug companies already “are profitable beyond any industry,” she says. “They are protected by the government. They have monopoly rights, patents, tremendous tax breaks.”

The pharmaceutical industry also vehemently opposes the Tier 1 idea. Alan Goldhammer, associate vice president for regulatory affairs for the Pharmaceutical Research and Manufacturers of America, says it would be “potentially reckless” to release drugs after only Phase I trials because at that point there is “no proof of efficacy at all.” There could also, he adds, “be potential product liability issues.”

At the FDA, Terry Toigo, director of the office of special health issues, says the agency has no comment on the lawsuit but adds, “We’re always looking to hear from people about ideas on where our system doesn’t work.”

For seriously ill patients like Abigail Burroughs, there are many parts of the system that don’t work.

It takes at least 10 years (and $800 million) for the average drug to pass through Phase I, II and III clinical trials en route to full market approval. Many patients can’t wait that long, and four out of five drugs fail along the way.

In addition to joining a clinical trial  (which can be hard to get into for medical or geographic reasons), there are a few ways to cut the waiting time, but they involve navigating a complex, bureaucratic maze. Under  “compassionate use,” also called a single patient IND (for investigational new drug), a doctor can write the manufacturer asking for a specific drug for a specific patient. The FDA reviews this request and usually approves. The company may then – but does not have to – give the drug to the patient.

Another route is the expanded access” program, in which a drug maker develops a protocol for giving the drug to an entire group of patients who meet medical criteria. If the FDA approves, the company then enrolls patients, but often there are more patients than drug available, in which case the company may set up a lottery. Drug makers can charge for “cost recovery” but usually don’t.

Companies can also try to rush drugs through the FDA under the “accelerated approval” program, as occurred with AstraZeneca’s Iressa.  In this scenario, the company gets approval on the basis of “surrogate markers,” such as regression of a tumor, rather than demonstrated clinical benefit, such as increased survival.

Companies can also ask for a “priority review” if a new drug would be a significant improvement over drugs already on the market. And they can “fast track” a drug by submitting data on a rolling timetable, as the research marches along, not just at the end of the process.

For many patients, this system works well enough. For others, including Ruth-Ann Santino of Arlington, it doesn’t. Two years ago, Santino “wrote the world” to put pressure on ImClone to give her Erbitux, says her husband, Fred Santino. The Santinos even heard of  another patient who appeared to have gotten the drug from ImClone.

 But Ruth-Ann Santino never did. She died in May, 2001.

Joy of Fitness

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There we stood in our color-coded bathing caps, 1336 women — nervous, excited and all lined up in “waves” on a recent summer Sunday morning on the shores of (I kid you not) Lake Chargoggagoggmanchauggauggagoggchaubunagungamaugg in Webster, MA.

For each of us – we ranged in age from 27 teenagers to five hardy souls in their early 60s – the goal was at least to finish this Danskin triathlon, a mere “sprint,” or short, triathlon in the world of more or less extreme sports, but a daunting enough challenge for many participants who, like me, had never done such a thing before. We were about to wade into the 77 degree, beautifully clear water of the lake, trying not to drown as sleeker, faster bodies swarmed over us, to swim a half-mile course around a series of orange buoys.

Dashing out of the water at the finish, we were then supposed to step quickly over the mats that would record our individual times for the swim from the little electronic “chips” fastened around our ankles. From there, we were to run or walk fast to the “transition area,” where our 1336 bikes were lined up by number on racks. This first transition, which the winner of the overall event (in her early 20’s) managed in two minutes and thirty-four seconds, took me six minutes and five seconds – including a quick wash of the sandy feet, donning of the bike helmet and sneakers, and pushing the bike to the start line.

We would then bike 12 miles around the lake, uphill steeply in the beginning (uphill enough that some people had to get off and push and at least one, not me thankfully, stopped to throw up). Then it was downhill as fast as one’s courage would allow, with faster bikers yelling encouragement – “You go, girl!” – as they whizzed past. At the bike finish, the mats again recorded our times electronically, bikes were stowed, helmets removed, “Hammer gel” or other so-called food gulped with a sip of water, then we were off on the truly hellish bit, the 3.1 mile run. Then back, mercifully, to the finish.

It was glorious, a total high, just to be part of this mob of slightly-crazy women with gorgeous legs, pretty, muscular arms and energetic, delighted faces. There was a sense of unrestrained exuberance in the air, and a feeling of immense gratitude, at least on my part, to have the good health to even contemplate such an event.

Which made me wonder. Why do so many people hate exercise? And why do doctors’ urgings about the medical benefits of exercise fall on so many deaf ears?

My new theory is that we’ve been misguidedly selling exercise as a medical duty, a “should,” when it’s really a form of constructive selfishness, a short cut to joy and self-affirmation in lives that have too many “shoulds” already.

Granted, the medical reasons to exercise are endless. Exercise physiologist Bill Evans of the University of Arkansas for Medical Sciences estimates that regular exercise can prolong life by two and a half years, if you start at age 35, and by six months even if you start at 75.  A Harvard study that has followed 17,000 men for decades has found that vigorous exercise (expending 1,500 calories a week or more in physical activity,  including brisk walking) reduces the risk of mortality in any given year by 25 percent.

“Physical activity is the closest thing that we have to a magic bullet for health,” says Dr. I-Min Lee, associate professor of medicine at Harvard Medical School. “There is no single drug that can give the same overall benefit to health that physical activity does. Everything that gets worse as we get older gets better with exercise. Even moderate intensity exercise such as brisk walking, 30 minutes a day, is sufficient to lower the risk of stroke, heart disease and diabetes, in both men and women.”

The medical benefits go on and on. Studies at the Cooper Institute in Dallas, TX.  show that the death rate from all causes is about 50 percent less in moderately fit men and women than in the non-fit at any given point in time.

Indeed, an article in the New England Journal of Medicine last year concluded that “poor physical fitness is a better predictor of death than many other factors, including smoking, hypertension and heart disease.” Other studies show that exercise dramatically improves the quality, and well as the duration, of life, not just be reducing the risk of physical diseases but by reducing depression, stress and anxiety as well.

And yet, many Americans don’t do it.  Figures released earlier this year by the National Center for Health Statistics show that while one in five Americans do engage in a high level of regular physical activity, an astounding one in 4 “engage in little or no regular physical activity.” The data come from 32,000 interviews conducted in 2000.

That’s appalling, given that it doesn’t take all that much exercise to meet the government’s recommendations, which say, among other things, that a person should engage in physical activity, at work or at leisure, that causes light sweating or a slight to moderate increase in breathing or heart rate five times or more a week for at least 30 minutes each time.

The excuses people offer for not doing this minimum are legion. Too busy with kids, work and housework. Too fat to look decent in exercise clothes. No place to walk in dangerous neighborhoods. Too tired. Too impatient to build up stamina slowly. Etc, etc.

So take it from a newly minted triathlete who, like all but eight women in the Danskin triathlon, finished the course, with glee (and great admiration for the winner, who finished in an hour and five minutes, 29 seconds).

Don’t think of exercise as one more “should” in your life. Think of it as a treat, a break from the kids and the computer. A time to get away by yourself, or to socialize with fellow walkers. It’s not just for your body. It’s for your soul.

Sorting out the Hype and Hope of Targeted Therapies

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Dean Gordanier is a tax lawyer, fitness buff, father of three and, at age 54, a veteran of the roller-coaster ride of hope and despair that is becoming a way of life for growing numbers of people with cancer, thanks to the promise, and the heartbreak, of a new generation of cancer drugs.Many of these drugs, which oncologists call “targeted therapies,” are breathtaking scientifically. With names like Gleevec, Avastin, Iressa, Rituxan, Herceptin, even the still-nameless drug known as SU11248, these drugs are the closest scientists have come yet to the holy grail of cancer treatment – knocking out cancer cells with great specificity without wreaking too much havoc on the rest of the body.

Some of these drugs target specific enzymes called kinases that act as switches that control cell functions; in some cancer cells, kinases are locked in the “on” position. Others are monoclonal antibodies that attack  markers on the surface of cancer cells. And some starve tumors of blood supply by attacking proteins that make blood vessels grow.

“I am so unbelievably excited about the science because it is like standing on the Nina, the Pinta or the Santa Maria. You can see the New World coming,” says Dr. George Demetri, director of the Center for Sarcoma and Bone Oncology at the Dana-Farber Cancer Institute in Boston.

Gordanier is excited, too, as well he might be, since these drugs have saved his life – twice. But he is wary as well. Like any seeming miracle treatment, targeted therapies are fabulous if, and while, they work. But because cancer cells are wily and can mutate to escape a drug’s action, even the most promising drug may stop working after a while. 

In the fall of 1999, Gordanier went to his doctor complaining of acid indigestion. Two days after Christmas, he had tests that showed a grapefruit-sized lump in his belly. It turned out to be a potentially deadly kind of stomach cancer called GIST (gastrointestinal stromal tumor).

In early January, 2000, Gordanier signed a consent form “acknowledging that life is uncertain and evisceration has its risks,” as he wryly put it in his diary, and underwent a drastic form of surgery called a “Whipple” in which doctors removed the tumor, 90 percent of his stomach, his spleen, 70 percent of his pancreas and his transverse colon.

But by September, his pain- and his cancer – were back. Doctors tried chemoembolization, or squirting chemotherapy drugs directly into the blood supply of his tumors, which had now spread to his liver. It didn’t work. In late February and early March of 2001, he simply “waited to die,” as he wrote in his diary.

Then he got lucky, joining a clinical trial of Gleevec for GIST. (In May, 2001, the US Food and Drug Administration approved Gleevec for chronic myeloid leukemia. The FDA went on to approve Gleevec for GIST in February, 2002.)

“I have been saved by the bell,” Gordanier wrote in his journal. “It looks like Gleevec will allow me to struggle on with a good possibility of a successful outcome, if you define success (as I do) as being able to live and work without pain and to enjoy each day as it comes and for what it brings.”

But 18 months later, by December, 2002, Gleevec had stopped working, as it does in about 75 percent of people after two years.

Once again, death loomed perilously close until Gordanier’s doctor referred him to Demetri. Demetri suggested  SU11248, an experimental new drug also called Sugen, for the company that developed it. (It is now made by Pfizer.) Since mid-January, Gordanier has been taking SU11248. So far, it’s working.

“It’s a holding action,” says Gordanier. “The cancers will mutate. But I will be alive as long as the doctors can keep one step ahead of the tumors.”

As Gordanier and others with life-threatening illnesses have learned the hard way, it’s crucial to ask questions about any new drug, even an apparent wonder drug that sounds like the best, or only, option.

“With any kind of experimental drug, you want to know two things: how likely is it to help, and what kind of harm can it cause?” says Gordanier. “If the likelihood of buying more time is low and severe side effects are a real possibility, it’s hard to decide whether to risk whatever good weeks or months you have left- no matter how desperate you are.”

For instance, even when a new drug is successful by statistical standards, the impact in real life may be minimal. Avastin, for instance, garnered big headlines at the recent meeting of the American Society of Clinical Oncology because it proved an important principle: That blocking a tumor’s blood supply can slow tumor growth.

But the drug only prolongs life for an average of five months in colon cancer patients. Whether that is a lot or a little “depends on what the five months are like. Is the five months likely to be spent in the intensive care unit of a hospital or at home?” asks medical ethicist Dr. Walter Robinson, a pediatric pulmonologist Boston’s Children’s Hospital.

Patients should also ask doctors to explain carefully the figures they quote from studies. Usually, such figures are averages, which means that if a drug prolongs life by five months on average, some people may get 10 months or more, some barely any.

And if you’re basing your decision on results of a few specific studies, ask exactly what those studies measured, cautions Dr. Sidney Wolfe, director of Public Citizen’s Health Research Group, an advocacy group in Washington, D.C.

“You really want to know whether the drug is effective for treating the condition you have, not some surrogate end point. Lowering blood pressure doesn’t count unless it decreases stroke,” he says. It may not be compelling for a drug “just to shrink tumor size temporarily if it’s not accompanied by increased survival.”

Ask about side effects, too, though with very new, experimental drugs, doctors may not know much. Rita Raj, a women’s health advisor to the United Nations in New York, has taken Gleevec for stomach cancer, like Gordanier. Her tumor appears to have disappeared, she says, but she has had side effects, chiefly fluid retention and kidney failure.

“Be extremely proactive,” adds Cyndie Mc Lachlan, 63, a philanthropist from Lopez Island, Wash., who was given one to three months live when she was diagnosed with advanced lung cancer nearly two years ago. She has been taking Iressa and seen the  tumors in her lungs and brain shrink dramatically.

The bottom line for patients like these is that these new drugs, imperfect as they still are, can buy time – time in which still newer, and possibly better drugs, may be found.

“I’m feeling good each day, and new drugs are in the research pipeline, but nothing is certain,” says Gordanier. “I’m still doing my best to live my life one day at a time.”

“Chemo Brain” Leaves Patients at a Loss

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She had been, she says, “a smart cookie,” a university grad who had built up a successful business in Toronto as a marketing consultant.

But several years ago, when she was 38, she had chemotherapy for breast cancer and wound up with a bad case of “chemo brain” — cognitive problems such as trouble with thinking and memory that many cancer patients, and a growing number of doctors, believe may be related to chemotherapy.

Starting with her third round of chemotherapy, says this woman, who asked not to be identified, “I lost my sharpness. Memory became a huge issue. It was like being drunk without being drunk.”

Since she had never heard of “chemo brain,” she adds, she was terrified.

After years of being dismissed as a figment of patients’ imaginations or as a result of anxiety or depression, “chemo brain” is beginning to be taken seriously by cancer doctors and researchers.

Indeed, it appears to be fairly common, affecting as many as 16 to 40 percent of women undergoing chemotherapy for breast cancer, says Dr. Ian Tannock, the Daniel E. Bergsagel professor of medical oncology at Princess Margaret Hospital and professor of medicine and medical biophysics at the University of Toronto.

So far, most studies of “chemo brain” have been in women with breast cancer, but “chemo brain” can affect both men and women.

In one study by Tannock and others, women who had undergone chemotherapy for breast cancer fared worse, as a group, on certain cognitive tests than a similar group of women without cancer. The differences in cognitive functioning could not be explained by differences in age, education, menopausal status or mood.

Luckily, says Tannock, the problem is usually mild to moderate: “These women are not demented. It’s a subtle thing.” The problems usually improve after chemotherapy but in some cases may persist for years.

At the Netherlands Cancer Institute, researchers have conducted a number of studies suggesting that chemotherapy is linked to cognitive deficits. In one study published in 1998, they found cognitive impairment in 32 percent of women with breast cancer given high dose chemotherapy and in 17 percent of patients getting standard dose chemotherapy.

On average, the women were studied two years after treatment. Another Dutch study in 1999 also found that breast cancer patients who got chemotherapy had significantly more cognitive impairment than those who did not.

At Dartmouth-Hitchcock Medical School, psychologist Tim Ahles and his team studied 71 men and women who had had chemotherapy for breast cancer or lymphoma and 57 similar people who had received only surgery and localized radiation for those cancers. Five years after treatment, all were cancer-free, but those treated with chemotherapy fared worse on paper-and-pencil cognitive tests than those who did not get chemotherapy.

Still, “chemo brain” is tough to explain. At least until recently, it’s been thought that most drugs used in chemotherapy do not cross the blood-brain barrier, the protective membrane that acts a filter between substances in the circulating blood and the brain. (One notable exception is methotrexate when given in very high doses.)

Indeed, many chemotherapy drugs are too big or have chemical properties that prevent them from crossing the blood-brain barrier, says Dr. Lawrence Shulman, chief medical officer at Boston’s Dana-Farber Cancer Institute. In fact, this is a major reason why most chemotherapy drugs are ineffective at treating cancers that have spread to the brain.

But “chemo brain” could be caused by chemotherapy drugs indirectly. Even though most chemotherapy drugs do not cross the blood brain barrier, they can cause the body to pump out natural chemicals called cytokines that do enter the brain and may trigger significant decreases in cognitive function.

Cancer cells themselves also pump out cytokines, notes Christina Meyers, a professor of neuropsychology at the M.D. Anderson Cancer Center in Houston, TX.

That might explain why some cases of “chemo brain” seem to set in even before treatment starts, she says.

And some cognitive problems experienced by cancer patients might be caused by drugs given along with chemotherapy, like anti-nausea medications, steroids, sedatives and antihistamines.

Rachel Morello-Frosch, 37, an assistant professor of environmental studies at Brown University who had chemotherapy for breast cancer 10 years ago while she was in graduate school, never could figure out what caused her “chemo brain.” Yet for three or four days after every treatment, she would “have a conversation with someone and completely forget what they said.” she says.

Part of the problem understanding “chemo brain” is that definitive, longterm tests – on the same patients before, during and after chemotherapy – have not been done, says Cheri Geckler, a neuropsychologist at Tufts-New England Medical Center.

Another part is that it’s proven hard to tease apart, at least in women with breast cancer, whether “chemo brain” comes from chemotherapy per se or from the fact that chemotherapy plunges some women into abrupt menopause, which can cause hormonal, mood and sleep disturbances that can affect cognitive performance..

And “none of these studies has been done in large enough numbers or with good enough controls for us to be certain of what’s going on,” cautions Dr. John Glaspy, an oncologist at the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles.

Potential treatments for “chemo brain” are at an even earlier stage. Researchers are considering drugs used to treat Alzheimer’s, stimulants, drugs used to treat anemia and the related fatigue that can lead to some cognitive impairment..

As for the Toronto marketing consultant, memorization exercises, and the sheer passage of time since chemotherapy, have helped.

“My brain is different,” she says. She now has to use notes to deliver presentations that she wrote herself and used to know by heart. “My brain is about 90 percent back. But the rest has not come back.

Brain Scanning and OCD

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The sophisticated science of brain scanning may be on the brink of revolutionizing the intuitive art of psychiatry, one of the few domains left in medicine in which a doctor’s educated guess is still the most common way to figure out what’s wrong

To be sure, brain scanning is still too young a science to be used for routine diagnosis of the most common psychiatric ills. But it is already proving invaluable in understanding the underlying abnormalities in a wide range of psychiatric disorders including obsessive compulsive disorder (OCD), schizophrenia, anxiety and depression.

Obsessive-compulsive disorder, for instance, which strikes roughly 8 million Americans, is a potentially disabling condition in which recurrent fears, images or impulses cause severe anxiety and drive people to repetitive behaviors such as compulsive hand-washing, arranging, checking or hoarding.

At the University of California, Los Angeles, doctors are experimenting with PET (positron emission tomography) scanning to predict which patients with OCD or major depression will respond to the anti-depressant drug, Paxil, and which won’t.  (In PET scans, patients are given a radioactive form of the sugar, glucose; the color-coded images show, in real time, which areas of the brain are using the most glucose and are working hardest.)

One patient in the UCLA study, Marc Pincus, is a 41-year old office manager who used to wake up at night and feel he had to turn his head toward the clock exactly 19 times (once for each family member) within one minute to protect them from disaster. “If, by chance, the clock changed, I had to start again. So I didn’t get a lot of sleep,” recalls Pincus, who knew this was not protecting anyone but felt he had to do it anyway.

Just as Pincus’ initial PET scan predicted, he had a good response to Paxil. A second PET scan after several months on the drug showed the characteristic changes of a good response to the drug.

The lead researcher, Dr. Sanjaya Saxena, an associate professor at the UCLA Neuropsychiatric Institute, says that PET scans have “the potential to be used for identifying patterns of brain activity that predict response” to therapy for both OCD and depression, even though the scans confirmed that the underlying brain abnormalities in OCD and depression are different.

At Massachusetts General Hospital in Boston, Dr. Scott Rauch, director of psychiatric neuroimaging, has long been using PET and other scans in psychiatric illnesses. In OCD, he and his colleagues scan patients first, while they are resting, then they touch them with feared objects that induce obsessions.

 “You see the circuitry light up,” says Rauch, noting that the abnormal brain circuits involve nerve pathways from the orbitofrontal cortex (behind the eyes) to the caudate nucleus (part of the basal ganglia) and thalamus, which lie deep within the brain.

Rauch and his colleagues have also shown that abnormal neural activity in the anterior cingulate portion of the OCD pathway can predict how well people with severe, intractable OCD respond to surgery in which doctors interrupt the pathways through tiny cuts.

Armed with patients’ scans, brain surgeons are now  trying a potentially better approach – implanting permanent electrodes (brain pacemakers) into the abnormal brain tissue to modulate the abnormal electrical activity, a technique, called deep brain stimulation, already being used to treat Parkinson’s disease.

More than 15 patients with severe OCD have received the implants from doctors in a multi-center study based at the Cleveland Clinic in Ohio, Butler Hospital in Providence, R.I. and the University of Leuven in Belgium.  The electrodes, made by Medtronic, Inc., can be turned up or down by the doctor, making the procedure is reversible – unlike traditional neurosurgery.

Dr. Ali Rezai, director of functional neurosurgery at the Cleveland Clinic, says patients who have had the electrodes implanted show an average 35.7 percent improvement in OCD symptoms.  At Butler Hospital, Dr. Benjamin Greenberg, who heads the brain stimulation work in OCD, says that while longer follow up is needed, initial results seem “promising.” The researchers are also trying deep brain stimulation for intractable depression.

Elsewhere, researchers are using other types of scans to probe other psychiatric afflictions. At the National Institute of Mental Health, researchers have used MRI, or magnetic resonance imaging, to study ADHD, or attention deficit hyperactivity disorder in children. (In MRI, a magnet induces chemicals in the body to emit characteristic radio signals. These signals are converted into 3-D images that show the anatomical structure of the brain. No radioactive drugs are needed.)  They found their brains to be 3 to 4 percent smaller than those of normal children.

Other researchers are using a variant of MRI called fMRI, or functional MRI, to study brain abnormalities in schizophrenia and other disorders. (Functional MRI provides a real-time image of the brain’s functions, not just structure, by tracking blood flow.) 

At Johns Hopkins University, Dr. Rudolf Hoehn-Saric, a professor emeritus of psychiatry, is using fMRI to compare the brains of normal and anxious people. In tests involving listening to recordings of personal worries, people with generalized anxiety disorder, his research shows, have increases in activation in parts of the prefrontal cortex (the thinking part of the brain) and in parts of the emotional brain, or limbic system, including the hippocampus.  But after seven weeks on the medication Celexa, an anti-depressant, the patients’ scans improved considerably, says Hoehn-Saric.

In fact, many of the drugs, like Celexa, that were originally designed to combat depression also seem to work for anxiety, which raises a question the imaging scientists haven’t quite answered yet.

 “We know that anxiety and depression, while distinct syndromes, have certain common clinical features and both respond to similar drugs,” says Dr. Helen Mayberg, chair of neuropsychiatry at the Rotman Research Institute at the University of Toronto. “Interestingly, when we get to scanning, we can see at the brain level what might account for some of these similarities and differences.”

In other words, brain scans may never substitute for intuitive guesswork by a good psychiatrist. Nor should they.  But they will undoubtedly be increasingly useful in helping doctors figure out which patients with severe psychiatric illnesses are most likely to respond to treatments.