Judy Foreman

Nationally Sindicated Fitness, Health, and Medicine Columnist

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Drugs could eradicate a fatal cancer

May 17, 1999 by Judy Foreman

For years now, the incidence of some types of lymphoma – the cancer that killed former US Sen. Paul Tsongas, Jackie Onassis and Jordan’s King Hussein – has been among the fastest rising of all cancers, and no one is quite sure why.

The death rate has been increasing, too. This year, 64,000 Americans will get lymphoma and 27,000 will die from it.Yet lymphoma, which springs up in the core of the immune system – in B and T cells in the blood, lymph nodes, and lymph vessels – may be the cancer with the brightest hopes for treatment, and even cure.

There’s good reason for this. In solid tumors such as breast cancer, cancer cells are packed together with normal cells; in the liquid cancers – leukemia and lymphoma – some cancerous cells float freely in the blood.

This makes them “easier to capture,” says Dr. David Rosenthal, head of the Harvard University Health Services and immediate past president of the American Cancer Society.

Over the years, the ability to study these cells has yielded a detailed knowledge of markers on the cell surface, against which promising new drugs called monoclonal antibodies are being targeted.

Lymphoma comes in two basic types – Hodgkin’s disease, which has four subtypes, and non-Hodgkin’s, which has 30 subtypes “and more as we get smarter,” says Dr. Morton Coleman, director of the center for lymphoma and myeloma at New York Presbyterian Hospital-Cornell Medical Center.

Chemotherapy and radiation work well for Hodgkin’s, which unlike non-Hodgkin’s, has been declining in incidence. Ten years after diagnosis, 77 percent of Hodgkin’s patients are alive, according to the American Cancer Society.

With the most common form of the aggressive non-Hodgkin’s lymphoma, chemotherapy can cure about 50 percent of patients. Of those who aren’t cured initially, 50 percent can be cured with high dose chemotherapy and bone marrow transplants.

“These data are really quite convincing,” says Dr. Lawrence Shulman, vice-chairman for clinical services for adult oncology at the Dana-Farber Cancer Institute.

Paradoxically, it’s the less aggressive forms of non-Hodgkin’s lymphoma that have been incurable. However, some of these do respond to monoclonal antibodies and to relatively new chemotherapy drugs like Fludara, Leustatin and Nipent.

The work that led to the development of monoclonal antibodies against lymphoma began years ago, when researchers discovered that all B cells carry a marker called CD20 on their surface, notes Dr. Andrew Zelenetz, chief of the lymphoma service at Memorial Sloan-Kettering Cancer Center in New York.

A year and a half ago, Rituxan, made by Genentech, Inc. and IDEC Pharmaceuticals, was approved by the Food and Drug Administration for a cancer called follicular lymphoma.

Rituxan works by finding and destroying all cells, normal and malignant, that carry the CD20 marker. Afterwards, stem cells in the bone marrow create a new crop of B cells. In some patients, the new crop is cancer-free. In others, it contains both healthy and malignant cells. But because Rituxan has few side effects, treatment can be repeated.

Rituxan has now been used in 15,000 patients, many of whom had relapsed after other therapy. So far, half have responded favorably, and six percent of those get a complete remission, meaning that cancer is undetectable. The benefits last about a year.

Just behind Rituxan in the pipeline is Bexxar, made by the Coulter Pharmaceutical Co. and expected to be approved later this year. It’s like Rituxan, but has a radioactive compound (I-131) attached. In trials with patients who have relapsed after other treatment, it produces a favorable response in 70 percent; of those, 30 percent had a complete remission for three years.

In patients who have not had prior treatment, Bexxar seems to produce a whopping 100 percent response rate – with 70 percent in complete remission. But Dr. Bruce Cheson, head of the medicine section in the division of cancer treatment and diagnosis at the National Cancer Institute, is cautious: “Patients relapse – no one is cured.”

Because it makes a patient’s body radioactive for a few days, Bexxar will probably have to be given in a hospital in some states, says Dr. James Levine, a lymphoma specialist at Beth Israel Deaconess.

But other states, including Massachusetts, have recently redrafted their regulations to comply with new requirements of the federal Nuclear Regulatory Commission. The NRC has concluded that at the doses suggested, such drugs drugs do not present a danger to people in close proximity to patients and therefore can be given on an outpatient basis.

Also in the pipeline is another radioactive monoclonal antibody called Y2B8, which contains yttirum and has some of the advantages of both Rituxan and Bexxar. The manufacturer, IDEC, says it will probably seek FDA approval in mid-2000.

Yet another drug, Oncolym, is aimed at a different cellular marker, HLAdr. It’s being developed by Techniclone Corp. and will be marketed by Schering AG of Germany; it could be on the market within a year and a half. Still another, LymphoCide, by Immunomedics Inc., is aimed at a different marker, CD22.

Beyond the new antibodies, scientists are trying to find other ways to treat lymphoma, including so-called antisense RNA compounds to block a gene called Bcl2 that often goes awry in lymphoma, customized vaccines to prevent relapse, and new variations on bone marrow transplants.

The bottom line is that lymphoma “is the area where there has been the most progress” in basic science, much of which is already being translated to new therapies says Dr. Jerome Groopman, chief of experimental medicine at Beth Israel Deaconess Medical Center.

Indeed, there are “more exciting treatments currently being explored for patients with lymphoma than probably for any other tumor,” says Cheson of NCI.

“Given the rapid pace of development,” adds Coleman of New York, “I fully anticipate that the overwhelming majority of patients will be cured within the next decade.”

Concern over rare tumor

A year and a half ago, Zenar Ambrozik thought he’d had a stroke – he became incontinent and began stumbling badly.

Ambrozik, now 81, was rushed from his Wakefield home to Melrose-Wakefield Hospital, where he had a brain scan. “They said, ‘Oh, boy. There’s something in your brain,’ ” he says.

There certainly was. At Massachusetts General Hospital, where he was later seen, doctors found a kind of brain tumor that is rare – it strikes 3,000 Americans a year – but it is increasing so fast some experts fear it could become the most common brain tumor.

It’s called brain lymphoma, or primary central nervous system lymphoma, and it’s a strange cancer indeed. It also appears highly sensitive to a therapy pioneered at MGH.

Between 1973 and 1991, brain lymphoma increased 10-fold nationwide; researchers initially thought it might be linked to better diagnosis or perhaps to AIDS.

But neither of those would completely explain the increase, says Dr. Tracy Batchelor, director of neuro-oncology at MGH.

Brain lymphoma appears to be a subtype of non-Hodgkin’s lymphoma, a systemic cancer that affects B cells of the immune system. But brain lymphoma is confined to the nervous system and the tumors are “biologically very distinct,” says Dr. Michael Grossbard, an MGH lymphoma specialist. They “don’t get out into the rest of the body.”

In other words, people with brain lymphomas don’t usually have systemic lymphoma, even though the latter can spread to the brain. “Even when systemic lymphomas do spread to the brain, they look very different from primary brain lymphomas,” says Dr. John W. Henson, executive director of the MGH brain tumor center.

Nobody knows where brain lymphomas arise, but it’s probably some “cryptic location elsewhere,” says Dr. Fred Hochberg, an MGH neuro-oncologist. What is clear is that brain lymphomas are highly lethal. “This kills people within four months if it’s not treated,” he says.

Historically, doctors used whole-brain radiation, which temporarily eradicated tumors, but caused memory loss and did not have a long-term survival benefit. The new treatment – high dose methotrexate – does seem to work, MGH doctors say. In fact, Zenar Ambrozik is back to playing golf and says his progress has been “fantastic.”

Over the last three years, MGH has treated 30 patients and 80 percent went into remission. Half relapse after two years, but half of those can achieve remission again with re-treatment.

“This is very unusual for brain tumors,” says Batchelor. “This is a uniquely sensitive tumor.” The team is now working with nine other medical centers to broaden their research.

More information

For more information, you may contact:

  • Cure for Lymphoma Foundation, 212-213-9595 begin_of_the_skype_highlighting              212-213-9595      end_of_the_skype_highlighting; on the Web it’s www.clf.org.

  • Lymphoma Foundation of America, 800-500-9976 begin_of_the_skype_highlighting              800-500-9976      end_of_the_skype_highlighting or 310-204-7040 begin_of_the_skype_highlighting              310-204-7040      end_of_the_skype_highlighting; on the Web, it’s www.lymphoma.org.

Is there a doctor in the hospital

May 10, 1999 by Judy Foreman

Several months ago, when Lloyd A. Coombs, 61, a retired machinist from Springfield, was rushed to the hospital with congestive heart failure, he was surprised to find the person in charge of his care would not be his primary doctor but one he’d never heard of with a title he’d never come across: hospitalist.

Actually, he says “it was fine.” The hospitalist, Dr. Winthrop F. Whitcomb, director of inpatient medical service at Mercy Hospital in Springfield, kept his regular doctor informed, and best of all, was on the scene whenever Coombs needed him.’

“I liked it because I could see him every day, sometimes twice, three times a day. He corresponded with my family and everything,” says an enthusiastic Coombs, who now feels well.

In the old days, when care wasn’t so “managed” and patients stayed in the hospital longer, a primary care physician would often stop by to see his hospitalized patients early in the morning and maybe later as well. In between, he’d try to coordinate things as best he could from his office.

The plus was the continuity of the bond between patient and doctor. The negatives were the hours wasted as the primary doctor and hospital specialists chased each other by phone, not to mention the primary doctor’s disgruntled patients waiting to be seen in the office.

Now, hospital stays are so short that a doctor who might once have had 10 hospitalized patients a day may now have only two or three, sometimes even at different locations, making it less efficient to drive all over town to visit them while trying to take care of office patients as well.

In theory, the answer to that dilemma is hospitalists – a term coined in 1996 to refer to internists who, instead of seeing private patients of their own, spend all day in the hospital overseeing the care of other doctors’ patients.

There are now 3,500 such physicians in American hospitals, say Whitcomb and Dr. John Nelson, a hospitalist at the North Florida Regional Medical Center in Gainsville, who co-founded the National Association of Inpatient Physicians in 1997. The group now has 800 members and is gaining 100 new ones a month.

Though the hospitalist movement is growing fastest in California and the Southeast, hospitalists now practice in many Massachusetts hospitals, adds Whitcomb.

There’s not enough evidence yet to say how well hospitalist programs are working, but there is some:

  • A 1998 study of nearly 10,000 Pennsylvania patients published in the Annals of Internal Medicine found that costs were about 15 percent less for patients seen by hospitalists compared to those whose hospital care was managed by their primary care doctors. Although length of stay decreased in all comparison groups, the decline was greatest in the hospitalist model. Hospitalists’ patients also needed fewer readmissions.
  • A 1998 study of 1,623 California patients published in the Journal of the American Medical Association showed that a hospitalist model reduced length of stay and did not affect mortality or readmission rates or patient satisfaction.
  • Hospitalists also cut length of stay and costs at the Park Nicollet Clinic in St. Louis Park, Minn., according to an observational analysis in the February 16, 1999 issue of Annals.
  • On the other hand, an analysis of 16 Kaiser Permanente hospitals in California, also published in the February 16 Annals, found that although length of stay decreased, costs increased with hospitalist care. Researchers couldn’t explain this trend but speculate that patients may have been sicker.

Still, some observers say the advantages are many.

At Brigham and Women’s Hospital in Boston, for instance, a survey showed that patient satisfaction with hospitalists is as good or better as with traditional care, says Dr. Andrew Halpert, who runs one of the Brigham’s two hospitalist programs and heads inpatient care for Harvard Vanguard Medical Associates, a group practice in Boston.

And 30-day readmission rates dropped about 25 percent among patients seen by Harvard Vanguard hospitalists, he says.

Because patients in the hospital are sicker than those seen in office settings, hospitalists may be better at managing complex cases, proponents say.

“You get good at what you do all the time, and a hospitalist does inpatient care all the time,” says Nelson. “Last year, I cared for nearly 1,000 hospitalized patients. A doctor with my same training who practices mostly in the office and a little in the hospital has done hospital care a lot less.”

Still, there’s so little data that “we’re flying blind,” cautions Dr. John Eisenberg, administrator of the Agency for Health Care Policy and Research, the lead government agency for researching medical cost and quality issues.

“I like the idea of voluntary hospitalists – if I’m a doctor and I need to have someone [ else] care for a patient in the hospital and the patient agrees,” he says. “What I don’t like is mandatory hospitalists, if I think I could provide better care and I’m not allowed to.”

Dr. Harold Sox, chairman of the department of medicine at Dartmouth-Hitchcock Medical Center, agrees, noting in an Annals article that mandatory “hand-offs” of patients to hospitalists “threatens the internist’s identity as the physician who can care for the sickest patients in any venue. . .”

In Texas and Florida, the issue of mandatory versus voluntary hospitalists is becoming a legislative battle; managed care companies are urging laws to mandate the practice and doctors are generally opposed to it. The hospitalists’ association sides with primary care doctors, saying that the hospitalist system should be voluntary.

“I’m not sure this model is for everybody,” concedes Whitcomb of Springfield. “Some patients really want to see their doctor when they’re in the hospital, and some physicians want to retain their hospital responsibilities.”

But so far, “patients are telling us it’s okay,” says Nelson of Florida. “They’re willing to trade a familiar doctor and in turn get a more available doctor.”

The idea may increasingly appeal to more primary care doctors. So long as a doctor is kept in the loop, having someone else in the hospital all day to chat with patients and make sure lab tests get read is a boon, adds Nelson.

“And it eliminates the need to practice telephone medicine.”

Information

For more information on hospitalists, contact:

  • The National Association of Inpatient Physicians at 1-800-843-3360 or on the Web at www.naiponline.org
  • You can also read the February 16, 1999 supplement to the journal, “Annals of Internal Medicine.”

Beating anger

May 3, 1999 by Judy Foreman

Blame it on Aristotle, who believed that watching tragic plays led to a healthy catharsis of emotions like pity and fear.

Or on Freud, who, at least in his early days, also took the hydraulic view — that pent-up feelings, like steam in a pressure cooker, need release lest they cause hysteria or phobia.

Or on self-help gurus urging that anger be vented by yelling, pounding pillows or bopping people with hollow, plastic bats.

Wherever its provenance, the idea that vigorously expressing anger — even getting carried away with it — is both helpful and healthy has persisted for centuries, despite a stunning lack of evidence that it is.

Now, there’s a series of elegant studies that “ought to be a stake through the heart of the notion that every time you are angry, it’s better to let it all out,” says Dr. Redford Williams, director of the behavioral medicine research center at Duke University.

The research, published recently in the Journal of Personality and Social Psychology, shows that catharsis — verbal or physical venting — is “worse than useless,” says the lead author, Iowa State University psychologist Brad J. Bushman. “Expressing anger produces harmful effects — it increases aggression.”

Now, before you slam down the paper and mutter unprintable things about the mental health profession, take a deep breath. There’s also solid research showing that anger should be expressed, but in ways that are constructive — not destructive. Take a look, for instance, at the following:

– Road rage. One 30-year old New York lawyer, a patient of Raymond Chip Tafrate, a Connecticut psychologist, was a chronic tailgating, fist-shaking, horn-beeping driver. He’d leap out at lights and get into fist fights with other drivers. In therapy, he learned not to act on his anger by changing his thinking and understanding that most drivers who enraged him had not done so intentionally, and that he shouldn’t take it personally.

– Workplace wrath: A verbally abusive businessman with his own company went to Colorado psychologist Jerry Deffenbacher in distress. He was a big, loud man — intimidating by his presence but even more so by his outbursts. Two of his most senior people told him they were thinking of leaving because of his behavior.

In therapy, he learned to rate his rising anger on a scale of zero to 100, and when it hit 60, to tell whoever he was about to blow up at that he didn’t want to say things he shouldn’t and that he needed a “time out.” He then went into his office for 10 minutes, not just to cool down, but to rehearse mentally how to get his message across without being abusive.

He also invented an unusual trick that helped. An arch-conservative, he hated Bill Clinton. He promised himself that whenever he lost his temper, he’d wear a Clinton button for 30 minutes. Amazingly enough, it helped keep his anger from running away with him.

The new studies nail down the case against indulging anger.

In the first, psychologist Bushman used 360 male and female college students. Half were chosen randomly to read a fake newspaper article touting the benefits of catharsis; the other half read an anti-catharsis article. All were then asked to write an essay on abortion — pro or con, depending on their beliefs.

Students were then selected randomly to receive either a positive response to their essays, with comments such as “No suggestions, great essay!” or negative ones like “This is one of the worst essays I have ever read.” The negative responses were geared to making the students angry.

Finally, all the students were asked to rank a list of 10 activities, including hitting a punching bag, that they would like to do later. (In this part of the experiment, they didn’t get a chance to.)

The results were stunning: If people were not angered, they didn’t want to hit the punching bag, regardless of whether they were primed to believe in catharsis or not. If they were angered, those who had read the pro-catharsis article were twice as likely as those who’d read the anti-catharsis article to want to hit the bag, suggesting that “media messages can persuade people to vent anger,” Bushman says.

In the second study, Bushman’s team randomly assigned 600 college students, male and female, to read a pro-catharsis article, an anti-catharsis one or a neutral story. All were angered with negative comments about their essays and then given the chance to hit a punching bag.

Seven women declined, but all the others hit it. Each subject was then paired with an “opponent” (an experimenter) for a competitive task that offered the opportunity for aggression — blasting the opponent with a loud, unpleasant noise.

The students who read the pro-catharsis article were twice as aggressive as the others “and the more they liked hitting the bag, the more aggressive they were,” says Bushman. This is the opposite of what catharsis theory predicts — that venting should dissipate anger.

“People expect catharsis to work, they expect relief,” says Bushman. “But it never happens. In fact, people lash out more and more as if trying to get that relief.”

In yet another twist, the psychologists then took 100 students, primed them all to believe in catharsis and made them all angry. But this time, they were told to sit quietly for two minutes, instead of hitting the bag, before getting the chance to be aggressive in the competitive task. With just this two-minute time out, they ended up being much less aggressive than students in the previous experiment who had had the chance to hit the bag.

So what do these studies prove?

Just what many researchers, including social psychologist Carol Tavris, author of “Anger: The Misunderstood Emotion,” has been saying for years: Venting doesn’t work.

“The biggest, fattest cultural myth, the elephant in our living room . . .is that catharsis is good for you,” she says. “All you have to do is go to another country and realize that the kind of excess we take for granted is considered loss of face in Japan, childish in France and rude and selfish in England.”

What yelling and punching pillows does is let a person “rehearse” anger, she says, which only encourages more anger. It’s not much of a stretch, in other words, to imagine that rehearsing anger — like writing violent threats on a Web site — could contribute to the murders that tore apart Columbine High School in Colorado recently.

And mere venting means you never get to the bottom of things. Anger is often a “defense against feelings of helplessness and depression,” says psychologist Anne Alonso, clinical professor of psychiatry at Harvard Medical School. “So when you encourage the defense, you put a greater distance between the real problem and the patient’s ability to deal with it.”

Furthermore, indulging your anger can be bad for your health, especially if you’re male, notes Williams of Duke. While some data suggest that women who hold their anger in may be at higher risk of death from all causes, other data show that men who express it outwardly have higher death rates, he says.

Growing evidence, in fact, shows that anger, like other strong emotions, can directly trigger heart attacks, says Dr. Murray Mittleman, director of cardiovascular epidemiology at the Institute for the Prevention of Cardiovascular Disease at Beth Israel Deaconess Medical Center in Boston.

In 1995, Mittleman’s study of more than 1,600 heart attack survivors, male and female, showed that in the two-hour period after someone feels intense anger, heart attack risk more than doubles. Admittedly, this is a small effect because the baseline risk of a heart attack in a healthy 50-year old man is one in a million in any given hour; anger raises this to two in a million.

Another study of more than 1,300 male veterans showed that the most hostile had a three-fold higher risk of heart attacks than mellower men.

The bottom line, says psychologist Bushman, is to cool it. “Counting to 10 is good advice. If you are really angry, count to 100.”

Venting, in other words, “does not reduce the buildup of anger. Expressing anger only leads to further anger.”

SIDEBAR:

Coming to grips with taming anger:

People often think there are only two ways to deal with anger: venting or bottling it up. Neither works long term.

But there are things that do, says clinical psychologist Raymond Chip Tafrate of Central Connecticut State University, who has pooled and analyzed data on 18 studies of anger treatment, and by summer, will have analyzed data on 50.

The research clearly shows, he says, that catharsis not only doesn’t work but “may actually be harmful.”

“There is a kernel of truth in the expressive school,” says Jerry Deffenbacher, a Colorado State University psychologist. Some inhibited, overcontrolled people may be helped by learning to be “more noisily expressive,” especially in therapy, and to learn that their anger will not make the world crumble. But then they must move on and deal with their anger constructively.

For that, several methods — notably relaxation and cognitive-behavioral therapy — have been proven effective in studies.

Some relaxation approaches are modelled on treatments for anxiety, says Deffenbacher. The idea is to practice relaxation, then imagine an angering situation with increasing intensity until you can counteract your arousal with relaxation.

In the heat of an angry moment, he adds, the tried and true remedies of counting to 10, taking deep breaths and simply relaxing your muscles can also help.

In cognitive therapy, you learn to defuse anger “by thinking about your thinking,” says psychologist Albert Ellis, head of the Albert Ellis Institute for Rational Emotive Behavior Therapy in New York, and co-author, with Tafrate, of the 1997 book, “How to Control Your Anger Before it Controls You.”

Say that a co-worker frustrates you. If you think, “I don’t like this. She really frustrates me,” you’ll feel mildly angry. But if you keep fuming, “She is screwing up my entire life,” you’ll fan the flames and make anger last longer.

The problem really, Ellis believes, is an irrational belief that the world owes you something and that the other guy is “no good as a human being” because he’s not doing “what I consider the right thing.”

While many people who are chronically angry may have shaky self-esteem, that’s not always the case. Some research, in fact, suggests it’s grandiosity — inflated self-esteem and sensitivity to criticism — that causes chronic anger.

And what of anger that once had a concrete trigger — like childhood sex abuse — but becomes a crippling way of life? The trick here, psychologists say, is to acknowledge the anger, but to move on with your life and not get stuck in the anger forever. Still mad at your parents after 40 years? The tough-to-accept reality is that you may well have reason to be, but you’re only keeping your own life on hold if you focus on that, not forward motion.

Sometimes, of course, anger “is a signal that you need to act,” notes Dr. Redford Williams, director of the behavior medical research center at Duke University and author, with his wife, Virginia Williams, of the 1997 book, “Life Skills.”

If she hadn’t acted appropriately on her anger, he says, “Rosa Parks would still be riding in the back of the bus.”

Lyme disease vaccine is only part of answer

April 26, 1999 by Judy Foreman

With summer — and tick season — fast approaching, there’s a new weapon available to reduce your chances of catching Lyme disease: a vaccine called LYMErix, approved by the Food and Drug Administration late last year.

Now, the bad news. The vaccine isn’t approved for kids under 15 or people over 70. It protects about 80 percent of the people who get it, and that’s if you get three shots, which, according to current FDA licensing, must be taken over 12 months. If you get only two shots, a month apart, there’s only a 50 percent chance you’ll be protected. And no one knows how long the protection will last.

Moreover, even if the vaccine were 100 percent effective, you’d still have to take the usual precautions — wearing long sleeves and pants and using tick repellents and removing attached ticks — if you live, work or play in woodsy or marshy areas. That’s because ticks that carry Lyme can also infect you with babesiosis and erlichiosis, other tick-borne infections for which there are no vaccines.

But there’s a promising new wrinkle in all this. Last fall, the vaccine manufacturer, SmithKline Beecham, reported that it’s possible to compress the timetable for the three immunizations into six months or even two and still get the same degree of protection as with the year-long schedule.

The company is not pushing this timetable — yet — because it’s still in the process of seeking FDA approval for it. But since there’s justification for accelerating the shots, it’s worth talking to your doctor about it if you’re at high risk.

Lyme disease is a nasty, though rarely fatal, illness that is both often-missed and overreported. It strikes about 12,000 to 16,000 Americans a year, mostly in the Northeast, but also in the upper Midwest, Pacific Northwest and elsewhere.

It starts with a bite from the deer tick, Ixodes scapularis. If you get the ticks off your skin within 36 to 48 hours, you’re probably safe because it takes this long for the disease to be transmitted, says David Weld, executive director of the American Lyme Disease Foundation in Somers, N.Y.

The bite causes a rash that often looks like a “bull’s eye” and flu-like symptoms — fever, chills, headache and fatigue — as well as occasional facial weakness and heart disturbances. Some people may have chronic arthritis or neurologic problems even months or years later.

In fact, scientists from Boston reported this month at an international conference that they have found a neurotoxin made by the Lyme bacterium.

The toxin “may explain memory problems and why nerves get stimulated so that they fire off and you get pain, numbness or tingling,” says Dr. Sam Donta, the lead researcher and a Lyme disease specialist at Boston Medical Center and the Boston VA Medical Center.

‘The evidence is accumulating,” he says, “that this is a subtle, chronic infection, but we have a long way to go.”

If you catch Lyme disease quickly — while you still have the rash — antibiotics often work. But not always. New evidence also presented at the conference showed that even after receiving antibiotics, some dogs with Lyme disease still harbored the bacteria that causes it, Borrelia burdorferi.

Complicating the decision about whether to get vaccinated this year (other vaccines are in the pipeline for future seasons) is the fact that scientists are unsure as to whether this tick season will be worse than usual. Some say it will be, but much of this is guesswork is based on the complicated life cycle of ticks.

Adult ticks mate in the fall on the bodies of large mammals, chiefly deer.

No disease is transmitted at this point, but after feeding on deer blood, pregnant female ticks drop off and bury themselves in leaves. Each female lays about 3,000 eggs, which then hatch — as larvae — the following summer.

The larvae are harmless at first. But they feed on mice or other rodents, and if those animals carry the Lyme bacteria, the larvae become infected, too. After feeding on mice, the larvae huddle in the ground for the winter, then emerge the following spring as nymphs that can potentially infect humans.

But a number of things can affect how many ticks there are in any given area in any year. A mild winter and a wet spring, for instance, can boost the tick population — and may this year.

So can a bumper crop of acorns two years before the ticks appear, says Rick Ostfeld, an ecologist at the Institute of Ecosystem Studies, a private nonprofit research organization in Millbrook, N.Y.

“There are two pathways by which acorns have an effect,” he says. Deer love acorns, so when there’s a bumper crop of acorns, it lures deer deep into oak forests. Mice love acorns, too.

So lots of acorns means lots of mice survive the winter, which means that “two summers after a good acorn fall you have lots of infected nymphs,” he says. Since there were bumper acorn crops in 1997 and in 1998, Ostfeld predicts “a pretty bad summer for Lyme disease in 1999 and worse in 2000.”

Dr. Ned Hayes, an epidemiologist at the Centers for Disease Control and Prevention who specializes in bacterial diseases transmitted from animals to humans, is less convinced about this year’s forecast: “I wouldn’t make any predictions.”

But he and other Lyme specialists, among them, Dr. Bela Matyas, medical director of epidemiology at the Massachusetts Department of Public Health, say that if you’re at risk for Lyme disease, you should talk to your doctor soon about getting the vaccine.

The vaccine works by stimulating the immune system to make antibodies to a protein called OspA, which is found on the surface of the bacteria in the tick’s gut. The vaccine does not attack the tick itself. But when the tick sips a person’s blood, it sucks in the antibodies, which then kill the bacteria.

This process is not foolproof, however. If bacteria enter the body despite vaccination, they quickly stick a different protein called OspC on the surface. The vaccine doesn’t work against this protein, which means that if the first line of defense fails, you may still get infected.

Next month, the Advisory Committee on Immunization Practices, a group of experts that advises the CDC on vaccine issues, is expected to recommend that anyone at high risk of Lyme disease because of frequent or prolonged exposure to tick-infested habitats should consider being vaccinated.

For people with less frequent or less prolonged exposure, it’s unclear how much added benefit a vaccine provides over standard anti-tick precautions.

People with minimal exposure to tick-infested areas need not get the vaccine.

People who have uncomplicated arthritis from a prior Lyme disease infection and are at high risk should consider getting the vaccine, the committee is expected to say. But those who have Lyme disease that has not responded to treatment should not, because the vaccine could make things worse. In healthy people, however, initial data indicate that there are no serious side effects.

The bottom line is to discuss vaccination with your doctor and remember that it takes a while for the vaccine to kick in, it doesn’t work for everyone, and even when it does, it doesn’t protect against other tick-borne illnesses. This means you still have to take precautions to avoid ticks — forever.

  • Look for the deer tick on your skin or clothing after walking in fields or woods. The tick – a dark speck the size of a poppy seed – is most likely to bite in the nymph stage.
  • If you can’t avoid areas where ticks thrive – woods, marshy areas, high grass and bush – wear long-sleeved shirts, long pants tucked into socks, and closed-toe shoes. Light colors make it easier to spot ticks on your clothes.
  • Use insect repellants. Permethrin kills ticks on contact, but it can be irritating, so spray it on your clothes, not your skin. You can use DEET (diethyltoluamide) on your skin and clothes. State guidelines vary, but in Massachusetts and some other states, health officials say you should not use DEET on infants, and don’t use products with more than 15 percent DEET on children. Adults should use products with no more than 30 to 35 percent DEET. High concentrations of DEET may cause severe allergic reactions and seizures.
  • When you get home from a tick-infested area, shower or bathe and remove any ticks with tweezers within 24-48 hours.
  • If pets have been in tick-infested areas, check them, too, as well as areas where they sit or lie.
  • If you become infected – you should notice a rash and flu-like symptoms – call your doctor; antibiotics are often effective if given early, but not always.

For more information, contact:

  • The Lyme Disease Foundation, 1-800-886-LYME (or 1-800-886-5963) or on the Web, www.lyme.org.
  • American Lyme Disease Foundation, 914-277-6970 or on the Web, www.aldf.com.

Lyme disease in Massachusetts

The original column in the Boston Globe contained a photo and a chart. The Photo Caption read:

  • With summer — and tick season — fast approaching, there’s a new weapon available to reduce your chances of catching Lyme disease: a vaccine called LYMErix, approved by the Food and Drug Administration late last year. Now, the bad news. The vaccine isn’t approved for kids under 15 or people over 70. It protects about 80 percent of the people who get it, and that’s if you get three shots, which, according to current FDA licensing, must be taken over 12 months. If you get only two shots, a month apart, there’s only a 50 percent chance you’ll be protected. And no one knows how long the protection will last.

The chart data is available at the Boston Globe on Microfilm.

Skin ailment leaves people red-faced

April 19, 1999 by Judy Foreman

What Allison Taylor hates most about rosacea, the skin problem that turns faces red and makes people look like they’ve had a few too many, is the chronic embarrassment.

“I wear a lot of makeup because I’m so self-conscious,” says Taylor, 35, who manages a medical practice in Boston. “I always look sunburned. People ask me if I don’t feel well.”

For others, like a 44-year old Cape Cod psychologist who asked that her name not be used, it’s the complications of rosacea, like eye irritation, that are unattractive and make wearing contact lenses impossible. “It’s not like I won’t go out of my house,” she says. But it’s a “major pain in the neck.”

Rosacea is an unglamorous problem. It won’t kill you. It won’t even really make you sick. But emotionally, it can make life miserable for the 13 million Americans who have it. Some hate to go to work; others, like Taylor, dread parties because some foods and alcohol make you “get redder and redder.”

Rosacea is a chronic condition that first strikes in one’s 30s and 40s, though many people suffer for years before they’re properly diagnosed. Famous faces with rosacea have included Rembrandt, W.C. Fields, and Princess Diana. President Clinton also suffers from the ailment.

Initially, rosacea is just excessive flushing and blushing caused by dilation of blood vessels on the cheeks, nose, chin or forehead, says Dr. Arthur Sober, associate chief of dermatology at Massachusetts General Hospital.

Nobody is sure why this happens, but it may be an abnormal response to temperature changes. In fact, researchers have shown it’s the heat in hot coffee or tea, not the caffeine, that triggers flushes. Other triggers include stress – notably anger and embarrassment – sun, wind, hot showers, coughing, spices, chocolate, tomatoes, and even exercise.

When a healthy person exercises hard, he may get red, “but this usually calms down in about 15 minutes,” says Dr. Mark V. Dahl, chairman of dermatology at the University of Minnesota Medical School. When someone with rosacea exercises, his face may stay red for an hour or two.

Chronic flushing leads to the appearance of broken blood vessels, or telangiectasia. “If you have a constantly increased blood flow to the skin, it creates new blood vessels. They may look broken but they’re not,” says Dr. Steven J. Ugent, a dermatologist at Boston Medical Center. But these vessels are treatable with lasers – “perhaps the most gratifying cosmetic procedure one can perform because it works so well and there’s so little risk,” says Dr. Robert Stern, a Beth Israel Deaconess Medical Center dermatologist.

In many people, though, rosacea doesn’t end with flushing and blushing but progresses to inflammation, in which the face breaks out with papules (little red bumps) and pustules (pus-filled pimples) that may look like acne.

Some think this may be caused by skin mites called Demodex folliculorum, though it’s unclear which comes first, the mites or the rosacea. The mites may trigger inflammation, but they may also flock to sites of rosacea and take up residence.

Others blame Helicobacter pylori, the bacteria that causes stomach ulcers. One recent study of more than 200 people, however, found that the prevalence of H. pylori is no higher in people with rosacea than in those without it, says Dr. Kenneth Arndt, chief of dermatology at Beth Israel Deaconess. And treatment of H. pylori doesn’t seem to get rid of rosacea.

What does work for inflammatory rosacea is the antibiotic metronidazole (Flagyl), applied as a cream or gel, with or without tetracycline, another antibiotic taken in pill form.

“Antibiotics work tremendously well,” says Dahl of Minnesota, though researchers still aren’t sure whether it’s because the drugs – often taken for months or longer, at low doses – actually kill microbes or simply quell inflammation.

In some cases, rosacea progresses to a third phase, called rhinophyma – or W.C. Fields nose – in which the nose becomes bulbous as oil glands become enlarged and the layer of skin called the dermis becomes thicker.

“This is women’s greatest fear,” says Dr. Joseph Bikowski, clinical associate professor of dermatology at the University of Pittsburgh. In reality, women “rarely, if ever” get rhinophyma, he adds, though men often do.

If the nose gets so big it interferes with vision, surgery is necessary to resculpt tissues. In cases where rhinophyma is caught early, a drug called Accutane may work, though it can’t be taken by women who are pregnant or who might become pregnant because it causes birth defects.

In some people, like the Cape Cod psychologist, rosacea can attack the eyes. She’s been taking low dose antibiotics for years, which helps, though she still can’t wear eye makeup.

But for most people with rosacea, it’s the embarrassment, not the medical problems, that hurts most, especially the assumption that rosy faces are a sign of alcoholism.

“People assume that people with rosacea are drinkers, when that is not the case,” says Ugent of Boston Medical Center. “You can have rosacea and never touch alcohol.”

“People tend to trivialize it because it’s a skin disease,” adds Dahl of Minnesota. But “for some people, it’s life-destroying.”

Triggers of rosacea

A number of foods, drinks, skin care products and other factors can cause flare-ups of rosacea, including these:

Foods:

  • Certain cheeses, chocolate, soy sauce, vinegar, citrus fruits, spicy and thermally hot foods.
  • Beverages: Alcohol, especially red wine, beer, bourbon, gin, vodka or champagne. Any thermally hot drink.
  • Emotional factors:
  • Stress, anxiety, embarassment, anger.
  • Skin Care Products and Medications:
  • Cosmetics and hair sprays, especially those containing alcohol, acetone, witch hazel or fragrances.
  • Topical steroid creams.
  • Any product that causes redness or stinging.
  • Vasodilators (used to lower blood pressure).

Thermal factors: 

  • Saunas, hot baths, excessively warm environments.

Weather:

  • Sun, strong wind, cold, humidity.

Exercise:

  • Any workout that raises body temperature and increases blood flow to the face, such as aerobic exercise.

Medical conditions and behavioral factors:

  • Menopause, chronic cough, caffeine withdrawal, smoking.

For more information, contact the National Rosacea Society on the web at www.rosacea.org/ or by telephone, 1-888-NO-BLUSH.

Alcohol’s insidious grip

April 5, 1999 by Judy Foreman

Barbara Raymond, now in her mid-50’s, started drinking hard as a 15-year-old in Abington. At the time, she had no idea why, though she later linked it to depression.

She made her first suicide attempt at 16. At 18, in the throes of alcoholic amnesia, she married a man she’d known for two weeks. He turned out to be an alcoholic and a batterer who broke her arm and gave her “a bunch of bruises” over the years. She rarely sought care, she says: “I was too ashamed.”

By 24, she’d had six kids and several more suicide attempts. After the last, she ended up “dead on arrival” at a local hospital, where doctors revived her and someone suggested Al-Anon, a program for people affected by other people’s drinking.

Nobody asked whether she had a problem herself. But she knew she did. “I detoxed at AA [Alcoholics Anonymous]. I had the DTs (delerium tremens, severe withdrawal symptoms). No one treated me. I did it by myself, at home . . .At the time I got sober, there was not as much help as there is today.”

Today, there are new medications, better understanding of male-female differences in alcohol metabolism, and research into genes that may trigger alcoholism. Most important, there’s the recognition that, as Raymond says, “you don’t have to hit bottom like I did. If you’re worried about drinking, get help. Sooner rather than later.”

This Thursday, you can get free alcohol screening at any of 2,000 sites nationwide, including 450 colleges. You just show up, fill out an anonymous questionnaire, then meet confidentially with a clinician for 10 minutes. If he or she thinks you have a problem, you’ll get a referral for help.

Modelled on the 9-year-old depression screening day (held each October), the alcohol screening is run by Dr. Shelly Greenfield, medical director of the alcohol and drug abuse outpatient program at McLean Hospital. It is sponsored by the National Institute on Alcohol Abuse and Alcoholism, a government agency, and dozens of professional organizations.

Depression screening has proved that offering a chance to drop in and talk privately with a counsellor turns up a “big, undiagnosed, untreated population who can be helped,” Greenfield says. It is hoped the same will hold for people with alcohol problems, she says. And there are many of them.

By government estimates, nearly 14 million Americans have an alcohol use disorder, which includes abuse (impairment but not physical dependence) and dependence (alcoholism), which is characterized by uncontrolled drinking, tolerance for high doses and withdrawal symptoms when drinking stops, among other things.

Granted, moderate alcohol use — one drink a day for women, two for men (with a “drink” defined as 5 ounces of wine, 1.5 oz. of spirits or 12 oz. of beer) — lowers the risk of heart disease.

This is because alcohol raises HDL, or “good cholesterol,” and lowers LDL, or “bad cholesterol.” It also makes it harder for platelets to form clots that can block arteries. And some alcohol, notably red wine, contains anti-oxidants that keep LDL from oxidizing; in oxidized form, LDL leads to arterial plaques.

Heavy drinking, on the other hand, can adversely affect not just the drinker — raising the risk for hypertension, stroke, heart disease, some cancers, violence and suicide — but family and friends as well. And half of all US adults have or have had a close relative with a drinking problem, government data show.

But researchers are getting an increasingly good grip on how alcohol problems develop and how best to treat them.

The drug Antabuse, for instance, has long been known to help people quit by making them sick if they drink, says Dr. Enoch Gordis, director of the National Institute on Alcohol Abuse and Alcoholism. But the drinker has to be motivated to take it.

A newer approach, using naltrexone (marketed as Revia or Trexan) may help more. In 1992 studies at the University of Pennsylvania and Yale, researchers found it reduced craving and increased abstinence. The drug is now FDA-approved for this use.

Yet another drug, acamprosate, also helps, perhaps by reducing craving.

In addition, anti-depressant drugs such as Zoloft have been shown to reduce drinking in people who have both depression and alcohol problems, though not in those who aren’t depressed.

Non-drug treatments work, too. The most famous is the 12-step AA model. But an NIAAA study of 1,726 alcoholics in 1997 found that several types of group therapy are also effective ways to quit and stay abstinent.

For true alcoholics, abstinence is still the only longterm solution. For alcohol abusers, cutting back may work.

Ultimately, scientists hope to find a genetic trigger — or several — for alcoholism. The idea that genes play a role is supported by indications that alcoholism, often, though not always, runs in families. If either parent is an alcoholic, you have three to five times the normal risk of becoming one yourself.

More support for the genetic hypothesis comes from the fact that half of Asians who drink experience unpleasant side effects such as flushing, almost “as if they had Antabuse built in” to their genes, says Gordis. Just like the drug, this genetic factor seems to protect against alcohol abuse.

But so far, scientists haven’t found a single gene related to any alcohol-related behavior, even in animals.

What is clear is that alcohol affects men and women differently. In men and women of equal size who consume equal amounts of alcohol, blood levels of alcohol are higher in women, because women’s bodies have less water and more fat, which means alcohol is not diluted as much as it in men. Women also produce lower amounts of a stomach enzyme called alcohol dehydrogenase, which helps digest alcohol.

Women’s livers also are more vulnerable to alcohol. Some data suggest it takes five drinks a day to cause cirrhosis, or scarring, in men, but only a glass and a half or so in women.

Breast cancer is another worry for women who drink. A study published last year of pooled data on more than 322,000 women found that the risk of invasive breast cancer is 41 percent higher for women who have two to five drinks a day than for nondrinkers. This is considered a modest increase in risk.

Women are also less likely to seek treatment for alcohol problems and more likely to say their drinking is related to depression or family problems, which means the drinking itself may not get addressed.

Whether you’re male or female, if you’re worried about your drinking, get screened and get help. Take it from Barbara Raymond, who now counsels alcoholics at McLean.

She’s been happily remarried for 12 years. She’s earned her bachelor’s degree from Bridgewater State and is about to get a master’s in social work. And she’s been sober — for 27 years.

SIDEBAR 1:

Some questions you might be asked in alcohol screening

  • How often do you have a drink containing alcohol?
  • How many alcoholic drinks do you have on a typical day when you are drinking?
  • How often do you have four or more drinks on one occasion?
  • How often during the last year have you found that you were not able to stop drinking once you started?
  • How often during the last year have you failed to do what was normally expected from you because of drinking?
  • How often during the last year have you needed a first drink in the morning after a heavy drinking session?
  • How often during the last year have you had a feeling of guilt or remorse after drinking?
  • How often during the last year have you been unable to remember what happened the night before because you had been drinking?
  • Have you or someone else been injured as a result of your drinking?
  • Has a relative or friend or doctor or other health worker been concerned about your drinking or suggested you cut down?
  • SIDEBAR 2:

    Bottom line on bottoms up, who has an Alcohol Problem?

    • Nearly 14 million Americans meet diagnostic criteria for alcohol use disorders.
    • Half of US adults have or have had a close relative with a drinking problem.
    • About 74 percent of male drinkers and 71 percent of female drinkers exceed moderate drinking guidelines at least once a year.

    Harmful Effects of Alcohol

    • Heavy drinking raises the risk for high blood pressure, stroke, heart disease, certain cancers, accidents, violence, suicides, birth defects and overall mortality.
    • Economic costs to society are $167 billion annually.
    • Harmful drinking is involved in one-third of child abuse cases and many unintentional deaths from falls, burns, and drownings.

    Drinking Among Teens and College Students

    • Young persons who begin drinking before age 15 are four times more likely to develop alcohol dependence and twice as likely to develop alcohol abuse as those who begin drinking at age 21.
    • More than one-third of high school seniors perceive no great risk in consuming four to five drinks a day.
    • Alcohol is a factor in about one-half of fatal traffic crashes among persons 18-24 years of age. Among fraternity and sorority residents, 81% report binge-drinking.
    • Two to three times as many teenagers and young adults die in alcohol-related crashes as die from illegal drug use.

    SOURCE: National Institute on Alcohol Abuse and Alcoholism and Dr. Shelly Greenfield.

    Hopes dim for controversial breast cancer treatment

    March 29, 1999 by Judy Foreman

    Convinced by doctors that bone marrow transplantation offered the best chance at survival, thousands of women with breast cancer have agreed to the controversial procedure — despite the lack of proof that it could save, or even prolong, their lives more than standard therapy.

    Indeed, so many women — about 5,000 women a year — now undergo the treatment, arguably the most devastating procedure in modern medicine, that breast cancer has become the most common reason for transplants, edging out leukemia and lymphoma, for which there is considerably more evidence of efficacy.

    Now, it appears that this faith in transplants for breast cancer — and advocates’ demand that insurers pay for it — may have been misplaced, or at least premature.

    Pressured by patients and doctors, researchers have agreed to take the unusual step of posting abstracts of two US and three foreign studies on transplants and breast cancer on the Internet next month. They will give more details in May at the American Society of Clinical Oncology meeting in Atlanta.

    That decision stems from a meeting of researchers and patient advocates in February at the National Cancer Institute, which sponsored the two American studies.

    Susan Braun, a patient advocate and president of the Susan G. Komen Breast Cancer Foundation in Dallas who was at that meeting, says the group was concerned about not releasing findings before the data were fully analyzed, but didn’t want to “hold on [to the findings] waiting for the meeting in May.

    Until they’ve fully analyzed their data, the lead researchers aren’t talking, even to collaborators, including some in Massachusetts, where insurance companies have been forced to pay for the transplant treatment.

    That silence is fueling speculation that at least one study found no benefit for transplant in women with Stage IV (metastatic) cancer and another is inconclusive for women with Stage II or III cancer and 10 or more lymph nodes containing cancer.

    Concern is also growing that insurers may stop paying for the $50,000 to $100,000 procedure, though Karen Ignagni, president of the American Association of Health Plans, a managed care group, denies it. “It would be wrong to suggest a conclusion that would make patients concerned about access to these procedures until we know what the research says,” she says.

    But patients are nevertheless bracing for bad news. Amid the confusion, two things seem clear. One is that, in general, when studies show an obvious benefit of one treatment over another, they are stopped early, as happened when the drug tamoxifen was found to reduce the risk of breast cancer in high risk women.

    These studies are “clearly not a homerun . . . or they would have met the stopping criteria,” says Dr. Steven Come, director of hematology/oncology at Beth Israel Deaconess Medical Center and a contributor to one of the American studies.

    The other is that the studies have not gone on long enough to be truly informative. The American study called CALGB followed 874 patients for an average of 37 months; one called ECOG followed 553 patients for an average of 31 months. Usually, longterm survival is given after five years, not three or less.

    Furthermore, even if the studies show no clear benefit for transplantation — in which patients are given near-lethal doses of chemotherapy, then “rescued” by infusion of stored immune cells — subgroups of women might still benefit, says Dr. John Durant, executive vice president of the oncology society.

    “It’s a horrible situation for women,” says Fran Visco, president of the National Breast Cancer Coalition, an advocacy group. “If the studies are ambiguous, women should not have a transplant, except in a clinical trial. If more women had been told by their doctors to do that, we’d have better answers by now. Insurers should also be compelled to fund the trials like these that can provide better answers.”

    But “in the absence of data, it’s mutual self-deception,” for women and their doctors to assume a transplant is better than standard therapy, says medical ethicist George Annas, professor of health law at the Boston University School of Medicine. Transplants are “heroic.” To put women through them without more evidence is mere “faith healing.”

    Indeed, Memorial Sloan-Kettering Cancer Center in New York does not offer the procedure for breast cancer patients and in the past, only offered it in research settings.

    If the findings do turn out to be ambiguous, says Braun of Dallas, it “will leave women very much where we are now. We would like to have seen more people in the clinical trials.”

    “No kidding,” says Dr. Mary Horowitz, scientific director of the International Bone Marrow Transplant Registry and the Autologous Blood and Marrow Transplant Registry in Milwaukee.

    Recruiting was a nightmare, she says, “because everyone thought they knew the answers,” and because mortality from the transplant procedure itself has dropped from about 15 percent to 3 to 5 percent for women with Stage II or III breast cancer. “I can see why women decided to take the chance.”

    But what is “particularly wrenching is there was such a lot of hype around this procedure for women with breast cancer when it first came out,” in the early 1990s, says Grace Powers Monaco, a lawyer and head of the Bethesda, Md.-based Medical Care Ombudsman Program, which evaluates recommendations for transplants for HMOs and patients.

    Some of those early studies found that as many as 20 to 30 percent of women with advanced breast cancer survived at least a few years after transplant, says Come of Beth Israel.

    But that, as Monaco sees it, prompted women to feel, “ `I should get this treatment and I will not be randomized.’ Because of that, the data was delayed many years because people did not fill up the clinical trials.”

    Indeed, faced with mounting pressure, including lawsuits, many insurers agreed to pay for the procedure, and some states, including Massachusetts, now even mandate coverage by law.

    The bottom line, sadly, is that there will be no bottom line in the near future, although four other randomized studies on transplants for breast cancer are underway through the National Cancer Institute.

    For the moment, though, the expected results from the current studies are simply “not sufficiently mature to analyze,” says Dr. Thomas Spitzer, director of the bone marrow transplant program at Massachusetts General Hospital and a contributor to the American study called ECOG, run by the Eastern Cooperative Oncology Group.

    Come of Beth Israel, who participated in the CALGB trial, agrees. “While awaiting further analysis and follow up from these trials, women contemplating a transplant owe it to themselves to seek a variety of perspectives before making a final decision.”

    “Personally, I can’t make up my mind” about the data, muses ASCO vice president Durant, who lost his wife to breast cancer. But he’s guardedly optimistic. Because these studies were so short-term, there’s “lots of time for benefits to appear.”

    SIDEBAR:

    How to learn more

    To read more about the emerging data from studies of bone marrow transplantation for breast cancer, you can visit the website of Cancer Letter, www.cancerletter.com. The letter is privately published by journalists Paul and Kirsten Boyd Goldberg.

    For the National Cancer Institute’s position on the issue, visit http://cancertrials.nci.nih.gov. Beginning April 15, you can read preliminary results of the studies and suggested interpretations of them at www.asco.org, the site of the American Society of Clinical Oncology.

    Chronic pain often goes untreated because some doctors don’t believe their patients

    March 22, 1999 by Judy Foreman

    James Murphy is only 26, but some days, he can hardly get out of bed.

    Three years ago, Murphy, a North Easton man who used to fix power tools for a living, damaged a disc in his back lifting a steel workbench. The injury allowed the jelly-like material that cushions vertebrae to ooze out and press on a nerve. Pain raged through his lower back and shot down his right leg.

    Despite surgery, cortisone injections, pills and numerous visits to a major Boston pain clinic, where, he says, he was told it was all in his head, Murphy’s pain is worse.

    Murphy became so disgusted at what he feels is the medical establishment’s disregard of chronic pain that a year ago he started a web site (http://come.to/painsupport). It now gets 400 hits a week from people, some suicidal, whose lives are ruined by pain.

    Chronic pain, defined as pain lasting more than three months, affects 35 to 40 million Americans, says Dr. Russell Portenoy, head of the American Pain Society and of pain medicine and palliative care at Beth Israel Medical Center in New York.

    And researchers now know that, far from being all in one’s head, it is an all-too-real physiological phenomenon, though the specifics vary depending on whether it’s caused by damage to nerves, as in shingles or diabetes; by inflammation, as in arthritis; or by other things, like spreading cancer.

    With a nerve injury, for instance, chronic pain may be the body’s way of learning to avoid future injuries. When you injure nerves in your finger, nerves in the spinal cord “reorganize to amplify pain and remember it,” says Dr. Daniel Carr, a professor of anesthesia at New England Medical Center. This reaction is so ancient — it’s been in the genetic structure of animals for 600 million years — it must be crucial to survival.

    But despite this new understanding and an explosion of treatments — including non-drug remedies — millions suffer “because doctors don’t believe patients’ reports,” says Dr. Kathleen Foley, a cancer pain specialist at Memorial Sloan-Kettering Cancer Center in New York.

    Chronic pain is also undertreated because of the fear that patients — even those who are dying — might become addicted to high doses of powerful painkillers like morphine. And doctors fear running afoul of drug enforcement officials.

    In reality, such abuse is rare. One study of 12,000 patients showed only four became addicted. Another found that not one of 10,000 burn patients became addicted. In yet another study of 2,000 patients, only three became addicted.

    What does happen is that people don’t get enough medication. A major 1995 by the Robert Wood Johnson Foundation showed that 50 percent of dying patients had pain in the last three days of life.

    Another found that only 12 percent of cancer patients in nursing homes got basic pain care recommended by the World Health Organization. And a New England Journal of Medicine study of 1,000 cancer doctors showed half their patients had bad pain — and the doctors didn’t know what to do about it.

    And it’s not just dying patients whose pain is inadequately addressed, it’s people without terminal illnesses as well.

    In a recent Roper survey of 805 people without cancer and with moderate to severe chronic pain, 40 percent said their pain was out of control. The survey, which was sponsored by a drug company that develops pain relief medication, found that half of the respondents had switched doctors at least once, and half had been in pain for more than five years.

    Much of that suffering can be avoided, and the first step is to get an evaluation to see exactly what type of pain you have.

    If it’s arthritis pain, for instance, traditional NSAIDS (nonsteroidal anti-inflammatory drugs) and newer ones called COX-2 inhibitors may help. If your pain is from spreading cancer, opioids such as morphine, hydromorphone, oxycodone, codeine, methadone or fentanyl often help. These drugs all work through a special type of opioid receptor in the brain called mu.

    On the other hand, if you have nerve pain, opioids may not be the answer. But other drugs that work through a different receptor, called NMDA, may be, including dextromethorphan and ketamine. Another drug, d-methadone, also shows promise.

    Chronic pain also makes many people depressed and anti-depressants often help. But these medications actually do more than simply elevate mood — they fight pain directly.

    Older anti-depressants like Elavil work through brain chemicals such as norepinephrine both to reduce transmission of pain signals up the spinal cord and to rev up transmission of pain-killing signals down it. Newer antidepressants like Paxil work by boosting another neurotransmitter, serotonin, which helps control pain just as it elevates mood.

    Other drugs besides anti-depressants have this dual use. Anti-convulsants such as Neurontin are now known to block the firing of nerves that have grown new sprouts in response to injury. Anti-anxiety medications such as Valium, Ativan and Klonopin also block transmission of signals along pain nerves.

    Researchers are also finding better ways to deliver painkillers in patients who can’t swallow or don’t want injections. Fentanyl, for instance, comes in patches that deliver a steady dose over several days. Some patches now come with buttons that a patient pushes when relief is needed. There’s even a lozenge of fentanyl on a stick, so the drug can be absorbed directly through mucus membranes in the mouth.

    If pain is intractable, doctors can implant pumps in the spinal cord to supply morphine or even “snail slime” (a substance called SNX-111 that mimics a chemical put out by ocean snails).

    At a few clinics, including the Advanced Pain Management Center in Stoneham, doctors are trying to shrink damaged spinal discs with heat. A wire is inserted into the disc through a tube and then heated to 194 degrees Fahrenheit. This seems to shrink collagen in the disc and reduce pain, says Dr. Anil Kumar, who has performed the procedure on a dozen patients so far.

    In other patients with back pain, steroids injected near the spinal cord sometimes work, as can injections of local anesthetics into nerve ganglia in the neck or lower back.

    In some cases, doctors put electrical devices in the brain or spinal cord to activate the descending pain pathways that block pain. They can also destroy pain nerves surgically or chemically. For tic douloureux, for instance, the trigeminal nerve in the face can be cut by radiofrequency waves; a similar technique is used in the neck in cancer patients.

    But nerve destruction is usually done only if patients have a short life expectancy because new pain nerves can sprout, notes Dr. Douglas Merrill, chairman of the committee on pain management for the American Society of Anesthesiologists.

    The bottom line is that there is help available. But, as James Murphy have discovered, you may have to fight to get your doctor to take you seriously or to get your insurer to pay.

    You may also have to fight your own tendency to let pain become “a way of life,” says Merrill. You may not want to hear that you should get off the couch and onto the treadmill. But the ultimate solution may be to “find something to do with your life other than watch TV and wait for six hours to go around to take your pills again.”

    SIDEBAR

    Other treatments for chronic pain

    Whether you treat chronic pain with mainstream medications, nondrug therapies, or alternative remedies like acupuncture, it pays to match the type of pain to the remedy.

    Cognitive behavioral therapy, for instance, in which you learn ways to control your response to pain is effective for many people, For others, the answer may be biofeedback, relaxation, meditation or plain, old distraction.

    For many people, exercise helps with the deconditioning that accompanies chronic pain. Acupuncture, the ancient Chinese technique of inserting needles through specific sites on the skin, may help, too, says the National Institutes of Health.

    Some researchers, among them Dr. Paul White, an anesthesiologist at the University of Texas Southwest Medical Center at Dallas, use acupuncture needles plus electrical stimulation (a technique called PENS, for percutaneous electrical nerve stimulation) to treat back pain. A similar technique called TENS sends electrical signals through skin without needles.

    Some also swear by magnet therapy. In one small study at Baylor College of Medicine in Houston, researchers found that attaching a magnet to muscles or joints provided relief to some post-polio patients. Other data suggest magnet therapy may help people with nerve damage from diabetes.

    Overall, however, there’s “little scientific evidence that magnet therapy works,” says Jim Livingston, an MIT physicist who studies magnets.

    Whatever your particular type of chronic pain, the real key, pain specialists say, is to be assertive: Don’t allow your primary physician to focus solely on the underlying disease. Insist on addressing the pain, too.

    If your regular physician can’t help, see a pain specialist, which is often an anesthesiologist, neurologist or psychologist. Or go to a special pain clinic, which many hospitals now have.

    And don’t avoid psychological treatments. If something like cognitive-behavioral therapy helps, it doesn’t mean your pain was all in your head — it means you’ve learn how to cope with the pain better.

    For more information on chronic pain on the Web:

    American Pain Society (www.ampainsoc.org)

    American Academy of Pain Medicine (www.painmed.org)

    American Academy of Pain Management (aapainmanage.org)

    American Society of Anesthesiologists (www.asahq.org)

    International Association for the Study of Pain www.halcyon.com/iasp)

    Chronic Pain Forum (come.to/painsupport).

    American Chronic Pain Association (theacpa.org)

    National Foundation for the Treatment of Pain (www.paincare.org)

    After April 1, you may also try: American Pain Foundation (www.painfoundation.org)

    Anxiety over antidepressants

    March 15, 1999 by Judy Foreman

    Modern anti-depressants, for which Americans spent more than $5.6 billion last year, have been a huge boon, partly because they have few disastrous side effects, even in overdose.

    With older, “tricyclic” anti-depressants like Elavil, for instance, “a 10-day supply could kill you,” says Dr. Michael Jenike, associate chief of psychiatry at Massachusetts General Hospital. The newer drugs, called SSRIs, or selective serotonin reuptake inhibitors, are rarely fatal.

    The leading SSRIs — Prozac, Zoloft and Paxil — also sidestep a hazard of older anti-depressants: MAO inhibitors like Nardil and Parnate can cause a fatal rise in blood pressure when taken with red wine, aged cheese and other foods.

    But for all their magic against both depression and anxiety, the SSRIs do have drawbacks. Like the older drugs, they can take weeks to kick in. They can also cause sexual dysfunction (lack of orgasm) and, initially, agitation. (A fourth SSRI, Luvox, which combats depression but is approved for obessessive compulsive disorder, may be somewhat less likely to cause sexual dysfunction.)

    Worse yet, the SSRIs don’t work for nearly a third of the people who try them.

    This is frustrating for the 18 million Americans who are depressed and 23 million more who are anxious, but it’s strong motivation for drug companies racing to find better drugs.

    And they are, including new classes of anti-depressants designed to act through entirely different pathways in the brain — drugs that block a brain chemical called substance P and others that block CRH, corticotropin releasing hormone.

    Spurring this effort is an explosion of basic knowledge about the brain, some of which will be presented this week in Washington by the Dana Alliance for Brain Initiatives, a nonprofit organization involving more than 185 neuroscientists.

    “For four decades, we have been increasingly perfecting anti-depressant drugs,” says Dr. Steven Hyman, director of the National Institute of Mental Health. “Now, for the first time. . .we are beginning to see the possibility of real alternatives.”

    Much of the excitement comes from the growing recognition that an almond-sized brain structure called the amygdala plays a central role in the processing of fear and almost certainly in depression and chronic anxiety as well.

    The amygdala is rich in receptors for substance P, a brain chemical originally thought to transmit pain signals but now believed to be more important for depression and anxiety. The amygdala is also rich in receptors for CRH, the stress hormone.

    At the same time that drug makers are scrambling to find drugs to block CRH and substance P, they are scurrying to improve the current SSRIs, which combat depression and anxiety by increasing levels of a brain chemical called serotonin in the synapse, or space, between nerve cells.

    Scientists have never proven that depression is caused by a deficiency of serotonin, but they have found low serotonin levels in studies of people who are aggressive or suicidal, says Dr. Peter Whybrow, director of the neuropsychiatric institute at UCLA. Increasing serotonin, he adds, is a “fulcrum where one can intervene,” but there may be even deeper root causes of depression yet to be found.

    In recent years, scientists have discovered that there are at least 15 subtypes of serotonin receptors on brain cells, as well as subtypes for two other neurotranmitters, norepinephrine and dopamine, that are also involved in depression.

    This is crucial information: It means scientists should be able to tailor a drug so it acts on some receptors and not others, keeping anti-depressant activity high while minimizing side effects like time lag to efficacy and sexual dysfunction.

    Here’s how it works: An electrical signal travels down one brain cell, telling it to release serotonin into the synapse. The serotonin lands on “post-synaptic” receptors across the synapse in the next cell, triggering new signals in that cell.

    Serotonin then floats back toward the first, or presynaptic, cell, which sucks some of it in through a “re-uptake pump” to be recycled for further use. It is this re-uptake system that the current SSRI drugs block.

    But brain cells also have “autoreceptors” that interact with serotonin in another way — by telling the cell when there’s enough serotonin in the synapse that no more needs to be made, in essence, a negative feedback loop.

    Scientists now think that one reason it takes so long for SSRIs to kick in is that it takes weeks for the cell to learn to “ignore” this feedback and start making more serotonin, says Dr. Scott Ewing, director of the depression and anxiety service at McLean Hospital in Belmont. By tinkering with drugs aimed at these autoreceptors, he says, it should be possible to make drugs that work faster, though none are available yet.

    Similarly, better knowledge of receptors has led to drugs like Serzone and Remeron, which have fewer sexual side effects because they block certain post-synaptic serotonin receptors.

    A new SSRI, Celexa, approved last fall, avoids still other pitfalls than standard SSRIs by triggering fewer interactions with other drugs.

    Researchers are also discovering other ways to help people who don’t respond to standard drugs. For instance, some data suggest that taking a blood pressure drug called pindolol with an SSRI makes the SSRI act sooner by acting on the presynaptic autoreceptors to stop the negative feedback loop.

    SSRIs can also be made more effective by taking them with other drugs like lithium (normally used for manic-depression), a synthetic thyroid hormone called T3, an anti-anxiety medication called Buspar or tricyclic anti-depressants, says Ewing.

    Sometimes, combining two “atypical” anti-depressants like Wellbutrin, Effexor, Serzone or Remeron, also helps people who have not responded to other drugs.

    The bottom line is that “if you’re doing well on your current anti-depressant and can stand the side effects, stay on it,” says Ewing. After all, anything you switch to may bring new side effects. “It’s a mistake to go off a drug you’re responding to.”

    But if you’re not responding well, don’t give up. Psychotherapy, the talking treatment, can be very effective, even without medications, for many people. The herbal antidepressant St. John’s Wort seems to help many people, too.

    And if you do want to switch to a different prescription anti-depressant, talk to you doctor. If he or she can’t provide an answer, see a psychiatrist or psychopharmacologist. Remember: Depression and anxiety are highly treatable problems.

    SIDEBAR

    Some of the new anti-depressants in the pipeline

    Substance P blockers: In terms of published data, Merck Research Laboratories is the leader. Six months ago, it reported in Science that its drug MK-869, worked as well as Paxil in depressed people. Since then, the company says it has finished an unpublished study with less clear results and is now pursuing an unnamed substance P blocker it feels is more potent.

    A number of other companies, including Pfizer Inc. and Eli Lilly & Co. are also working on substance P blockers.

    Corticotropin releasing hormone (CRH) blockers: Published data are scanty, but informal reports “look promising,” says Dr. Steven Hyman, director of the National Institute of Mental Health. A 1998 study in Munich showed that mice missing a receptor for CRH exhibited reduced anxiety and stress, suggesting that CRH blockers might be effective in humans.

    Improvements to SSRIs, or selective serotonin reuptake inhibitors. Many companies are working on this. Lilly and Sepracor are working on R-fluoxetine, a Prozac variant with fewer side effects. Celexa, already on the market by Forest Laboratories, Inc., causes less agitation than standard SSRIs.

    Other serotonin-based drugs. Solvay Pharmaceuticals is working on flesinoxan, which boosts serotonin by increasing the activity of a particular receptor called 5-HT1A.

    Norepinephrine reuptake inhibitors. This is a new class of drugs that would boost a different neurotransmitter, norepinephrine. So far, Pharmacia & Upjohn’s drug, reboxetine, appears closest to getting approval for marketing.

    RIMAS, or reversible inhibitors of monoamine oxidase. The idea is to tinker with MAO inhibitors so a patient doesn’t have to follow a special diet. A drug called moclobemide is already on the market in Great Britain, Canada and Europe to do this. It’s not clear whether any company will bring it to market in the US.

    Glutamate drugs. Some scientists think this important neurotransmitter may play a role in depression, as it does in Alzheimer’s disease and schizophrenia. Lilly is exploring this.

    Herbal antidepressants. The leader is St. John’s Wort, already shown to be effective in European studies. McLean Hospital is studying a sustained release form of the drug. There’s another study at 12 centers nationwide. If you want to participate, call 617 855 2862 for the first study, or 919 668 8991 for the second. (On the web, you can find out more about the second study at http://hypericum.rti.org.)

    New drugs fight sores from cancer treatment

    March 8, 1999 by Judy Foreman

    The worst part of Colleen Combes’ breast cancer treatment three years ago, besides losing her hair, was the awful mouth sores caused by chemotherapy.

    These ulcers “were like canker sores that had broken open, only much worse. They were everywhere – on my tongue, the inside of my lips, my cheeks. It was very painful. I couldn’t eat. It was difficult to talk,” says Combes, a 41-year old Rockland woman currently on leave from her job in a law firm.But in January, when Combes’ cancer had spread and she needed a stem cell transplant (a major procedure akin to a bone marrow transplant), things were different. She had no mouth sores despite the even higher doses required in the second round of chemotherapy.

    Just before the transplant, Combes agreed to participate in a test of a new drug to prevent mouth sores. She still doesn’t know for sure whether she got the drug or a placebo, but she had “no mouth sores, nothing. I was ecstatic.” Perhaps because of this, she says, she also went home sooner than most patients.

    Until recently, the main reason doctors had to limit or stop chemotherapy in many patients was damage to the bone marrow or immune system – the body’s infection-fighting equipment.

    Now, that problem has become more manageable, thanks to drugs that protect the marrow, and mouth sores and other oral complications are becoming the number-one treatment-limiting issue, says Dr. Stephen Sonis, chief of oral medicine, oral maxillofacial surgery and dentistry at Brigham and Women’s Hospital in Boston.

    “It’s a major, major problem,” agrees Dr. Jerome Groopman, chief of experimental medicine at Beth Israel Deaconess Medical Center.

    This year alone, 1.2 million new cases of cancer will be diagnosed among Americans. About 400,000 patients will develop oral complications from their treatment, many to the point where they’ll need morphine or will have to stop treatment altogether, which can affect survival.

    Those like Combes who have stem cell or bone marrow transplants, which involve high-dose chemotherapy, are at special risk: 75 to 80 percent get severe oral complications, says Dr. Philip Fox, former clinical director of the National Institute of Dental and Craniofacial Research at NIH and now research and development director at Amarillo Biosciences Inc. in Amarillo, Tex.

    Indeed, oral complications from cancer treatment are emerging as such a major problem that the National Institutes of Health recently launched a public education campaign to raise consciousness of the issue among patients, doctors and dentists.

    Like cancer cells, cells that constitute the mucosal lining of the mouth have a quick turnover rate. This means that, like cancer cells, they are easily killed by chemotherapeutic agents.

    As cells in the mouth die, they release molecules called cytokines, which cause inflammation that further damages mouth tissue. The resulting breaks and ulcers then make it easy for germs from the mouth to enter the bloodstream and cause systemic infection, particularly since the immune defenses are also hurt by chemotherapy.

    In other words, once the lining of the mouth is damaged, patients lose a key “physical barrier” to infection, says Groopman. On top of that, patients often have so much pain from mouth sores that they can’t eat or absorb much-needed nutrients.

    With head and neck cancers, which will be diagnosed in about 30,000 Americans this year, the main problem is the radiation that patients get after surgery. Radiation can destroy saliva glands, as well as blood vessels and bones in the mouth and jaw.

    Saliva is essential, not just because it lubricates the mouth but because it contains proteins that fight viruses, yeast and bacteria. Without saliva, patients have difficulty swallowing, chewing, speaking and fighting infection, which means tooth decay can become rampant.

    In addition, radiation can damage blood vessels and the jawbone to such a degree that if a person later needs a tooth extracted, the bone may never heal. Taken together, this means that patients with head and neck cancer should get major dental work done before radiation.

    But it’s chemotherapy, because it affects more people, that’s an even larger concern, specialists say, and some drugs, especially fluorouracil (5-FU), cytarabine, methotrexate, and some combinations of drugs, are particularly damaging.

    On the plus side, scientists have “learned more about mucositis, or mouth sores, in the last two years than in the prior 50,” notes Sonis. As a result, a number of new drugs to prevent or treat mucositis are now in testing.

    At the University of Connecticut Health Center in Farmington, Dr. Douglas Peterson, head of oral diagnosis, has completed a study in stem cell transplant patients of a drug called misoprostol, already on the market for stomach ulcers. Taken in mouthwash form within two hours of the start of chemotherapy, he says, the drug may reduce oral tissue injury. Other data, however, suggests that in tablet form, the drug can make mucositis worse.

    At the Fred Hutchinson Cancer Research Center in Seattle, Dr. Mark Schubert, director of oral medicine, along with Sonis and others, is testing a new antimicrobial drug, IB367. The idea, says Schubert, is to see if by killing oral bacteria and yeast, the drug can reduce the severity of mucositis. This is the drug Colleen Combes, the breast cancer patient, thinks she had.

    Elsewhere, researchers are testing growth factors called KGF-1 and KGF-2, designed to stimulate oral mucosal cells called keratinocytes. Others are testing TGF-beta3, a drug that stops cells from dividing and hence might help cells in the mouth escape the damage from chemotherapy drugs.

    Still others are testing an amino acid called glutamine that, when swished in the mouth, might help mucosal tissue to regrow. Also under study is benzydamine, a drug that may block inflammation of mouth tissue, and Il-11, a drug that may block mucositis in multiple ways.

    For patients like Combes, these and other drugs in the works hold the promise not only of increasing quality of life during and after cancer treatment but, because they may enable more people to complete treatment, may boost the chances of survival.

    It’s not easy to get yourself to the dentist when you’ve just been told you have a life-threatening disease. “People with cancer have a gazillion things to think about,” says Sonis of the Brigham. “It’s like sitting under a dump truck and getting unloaded on. But to the extent that they can be proactive and get to the dentist, it’s a huge help.”

    Treat the mouth before therapy

    If you’re facing chemotherapy for any kind of cancer or radiation for head and neck cancer, it’s important to get major dental work done before you start treatment, according to the National Institutes of Health.

    With radiation in particular, treatment can damage oral tissues so severely that dental work later, including tooth extractions and gum surgery, may be difficult or impossible.

    During cancer treatment, mouth care is also crucial, which means you should:

    • Brush teeth gently with an extra-soft toothbrush or foam sponges. Brush after every meal and at bedtime.

    • Floss once a day to remove plaque, unless your oncologist says your blood platelet levels are so low that the risk of bleeding is too great.

    • Rinse your mouth often with water or salt water and ask your oncologist or dentist if you should use a fluoride gel or rinse as well.

    • Don’t use mouthwashes that contain alcohol, as most commercial mouthwashes do.

    • Use a saliva substitute such as Biotene to help keep your mouth moist.

    • Eat soft, easy-to-chew foods.

    • Don’t eat spicy, sour or crunchy foods.

    • Eat foods that are warm but not too hot or cold.

    • Avoid alcoholic drinks.

    • If you smoke or chew tobacco, quit and ask your oncology team for help if you need it.

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