Judy Foreman

Nationally Sindicated Fitness, Health, and Medicine Columnist

Skin cancer hits many, but it can be very curable

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Sally Loring, 70, a retired volunteer for the historical society in Manchester-by-the-Sea, is one lucky lady.

Seven years ago, while on vacation in Australia and New Zealand, Loring knocked the head off a mole that she’d had for decades but that hadn’t been checked by a doctor for four years. The headless mole wouldn’t heal.When she got home, she saw a doctor, who gave her the grim news on Good Friday: Stage 4 melanoma, “as bad as it can get. . .” That night, she says, “I was in a choral group singing the Mozart Requiem. I couldn’t even croak it.”

She had surgery and other treatments, but the melanoma spread to her breast. Finally, in 1992, she tried interleukin-2, a then-experimental treatment, which helps significantly in about 20 percent of patients with advanced melanoma. Loring was one of them, and now has “almost forgotten it happened to me.”

Skin cancer – which includes melanoma and the far less aggressive basal and squamous cell carcinomas – is one of the most common and curable of all cancers – but only if it’s caught early.

Even melanoma, which will account for 7,300 of the 9,200 skin cancer deaths among Americans this year, is highly curable – more than 90 percent survival after five years – if detected while the tumor is still thin and localized.

The message is obvious: Have your skin checked regularly by a health care professional, preferably a dermatologist. It’s especially important if you have fair skin, lots of moles or a family history of skin cancer. If you call 1-800-227-2345 begin_of_the_skype_highlighting              1-800-227-2345      end_of_the_skype_highlighting this week, you can get a free skin check, thanks to a combined effort of the American Cancer Society and the American Academy of Dermatology.

You can keep a watchful eye on your own skin, too. Basal and squamous cell cancers, which together will strike 1 million Americans this year, usually start out looking like pale, waxlike, pearly nodules or red, scaly, sharply outlined patches.

Melanomas often start out as small, mole-like growths that grow in size and may change color. They can be hard to see yourself because they often appear on the back – and sometimes pop up even on areas of the body never touched by sunlight.

In fact, dangerous moles, or atypical nevi, can fool all but the most trained eyes, says Dr. Richard J. Sharpe, a dermatologist in private practice in Gloucester and Hamilton.

Last fall, Dottie Lucas, a Gloucester woman in her mid-50s, asked her nurse practitioner to look at a “pimple-like thing” on her calf. The nurse thought it was nothing.

Last month, when Lucas went to see Sharpe for something else, he offered a skin check. The “pimple-like thing” was melanoma.

If you do get diagnosed with skin cancer, don’t panic.

If it’s basal cell, remember that “basal cells are not lethal,” says Dr. Arthur Sober, associate chief of dermatology at Massachusetts General Hospital. Over the last 70 years, a mere 400 people have died from basal cell cancer worldwide. Even so, it pays to get basal cell cancers treated quickly – usually with surgery – because they can destroy tissues such as eyelids, parts of the nose and ears, he says.

Squamous cell cancers are less common than basal cell cancers, but more lethal, causing 1,500 deaths a year in the US. Like basal cell cancers, they are usually treated with surgery. For both basal and squamous cell cancers, cure is “highly likely if detected and treated early,” says the cancer society.

But the biggest payoff from regular skin checks is catching melanoma when it, too, is early and curable. Its incidence has been rising sharply, by about 4 percent a year since 1973.

If a melanoma is thin (less than 1/16th of an inch deep) and hasn’t spread, it’s Stage I and the chances of surviving at least five years are more than 90 percent. If it’s Stage II (thicker but still localized), five year survival is 65 percent.

If the melanoma has spread to nearby lymph nodes (Stage III), the survival rate is 25 to 50 percent at five years, though treatment involves not just surgery to remove the tumor but often high doses of a drug called alpha interferon. In 1996, a major study showed that interferon clearly boosts survival for Stage III patients, says Dr. Robert Soiffer, a medical oncologist at Boston’s Dana-Farber Cancer Institute.

Even if you, like Sally Loring, are diagnosed with Stage IV melanoma, there are new options. Typically, these melanomas have caused lumps in the skin and have spread to distant lymph nodes or organs like the brain, bone, lungs or liver.

In January, interleukin-2, the treatment Loring had, was approved for Stage IV melanoma. Unlike chemotherapy, which directly poisons cancer cells, this drug seems to activate the immune system, making the body better able to recognize and fight tumor cells, says Dr. Michael Atkins, director of melanoma program at Beth Israel Deaconess Medical Center.

Chemotherapy – a drug called DTIC – also helps 20 percent of patients with advanced melanoma. Some patients may be helped by a combination of chemotherapy, interleukin-2 and interferon, which probably acts chiefly by boosting the immune system.

But most exciting, researchers say, are the new, experimental melanoma vaccines. Unlike regular vaccines that prevent disease, these vaccines, under intense study for the last five years, are designed to boost immunity in people who are already sick.

Several of these vaccines use small bits of protein from melanoma cells – sometimes from the patient himself, sometimes from other patients – to boost immune response. Another vaccine, under study at MGH and Dana-Farber, contains a gene for a natural immune-booster called GM-CSF as well. Still other vaccines in combination with interferon and interleukin-2 are being tested at the National Cancer Institute and Beth Israel.

So far, says Soiffer, a number of these vaccines have been shown to boost immune function considerably. But it remains to be seen whether this truly shrinks tumors or prolongs survival.

What is clear is that prevention is the key for skin cancer. Between 85 and 95 percent of basal and squamous cell cancers are linked to sun exposure, says Dr. Howard Koh, the Massachusetts public health commissioner, who is also a dermatologist and a medical oncologist.

That means you should limit sun exposure and use sunscreens with SPF, or sun protection factor, of 15 or higher. Sunscreens with an SPF of 15 block 92.5 percent of ultraviolet B light (the wavelength that causes sunburns); an SPF of 30 increases this slightly, to 96.3 percent. Scientists now think ultraviolet A light may also trigger cancer, and some sunscreens now protect against UV-A as well.

Sunlight may be less tightly linked to melanoma, though it is still thought to cause about 70 percent of cases. Scientists disagree on how well sunscreens protect against melanoma.

In February, researchers at a meeting of the American Association for the Advancement of Science reported that ten studies have looked at sunscreens and melanoma. Three studies found no link, two found sunscreens may be protective and five suggested melanoma risk may be increased among sunscreen users.

But if that’s true, it may be because people who rely most on sunscreens are those who are fair-skinned or are genetically at higher risk. Fair-skinned people who burn easily are two to three times more likely than darker people to get melanoma. People with many moles are at 6-to-10 times higher risk.

And since stronger sunscreens – with an SPF of 15 or higher – have only been available since the mid-1980s and melanoma can take years to develop, the protective value of sunscreens may simply have not shown up yet in epidemiological studies.

So dermatologists recommend “safe sun,” that is, wearing protective clothing, minimizing sun exposure between 10 a.m .and 3 p.m., using sunscreens and avoiding excess exposure, even with sunscreens. And this may be especially true for kids. Although studies are mixed, some research suggests that bad childhood sunburns are linked to melanoma later in life.

The bottom line, as Koh puts it, is simple: “Melanoma is unique among cancers in that it is visible. This is a cancer where literally everybody can participate in early detection.”

THE ABCD’s OF CHECKING MOLES FOR MELANOMA

PLEASE SEE MICROFILM FOR CHART DATA GLOBE STAFF CHART

Screenings

To learn where you can get a free skin cancer screening, call 800-227-2345 begin_of_the_skype_highlighting              800-227-2345      end_of_the_skype_highlighting, through May 8. If you are told that a screening is not available in your state, call your state dermatological society or 1-847-330-0101 begin_of_the_skype_highlighting              1-847-330-0101      end_of_the_skype_highlighting X394. The free screenings are a joint effort by the American Cancer Society and the American Academy of Dermatology.

When the cure is a killer, Extra vigilance is the key to avoiding adverse reactions to valuable drugs

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Betty Moody, a 40-year-old partially disabled veteran from Sidney, Maine, had been taking little blue pills for her arthritis for five years and expected no problems when she asked for a refill in March from the Togus veterans’ hospital.

She noticed the new pills – a drug called Piroxicam – were green. In fact, she says, she called the Veterans Affairs pharmacy because she is allergic to yellow dyes – just as it says in her medical chart – and she knew yellow dyes are used to make green. She says she was told not to worry.

A week later, she broke out in hives and her face swelled so badly that her husband, Dennis, a totally disabled vet, had to get friends to rush her to the hospital.

Moody survived her adverse drug reaction, though she’s sobered by it. So is the Togus VA Medical and Regional Office Center, which plans to “pay more attention on specific issues like this” from now on. In fact, Dr. Arnold Brown, the chief of staff, says he’s “happy this issue of adverse drug reactions is on the front burner.”

It certainly is, and about time.

Two weeks ago, Canadian researchers stunned the medical world – and everybody else – with a study estimating that in one year alone (1994), somewhere between 76,000 and 137,000 Americans died from adverse reactions to prescription drugs. More than 2 million had reactions serious enough to land them in the hospital or complicate hospital care they were getting.

That’s enough fatalities to rank adverse reactions as the sixth leading cause of death, and possibly as high as fourth.

What makes the study by University of Toronto researchers even more compelling is that they didn’t count errors in drug administration, overdoses, abuse, or minor or merely possible adverse reactions.

There is absolutely no question that overall, medications “have enormous benefits,” says Dr. Bruce Pomeranz, a co-author of the study. But what the new study makes clear is that bad reactions have been vastly under-reported. In 1994, the year his team found roughly 106,000 deaths, the FDA tallied only 3,500 such deaths, and data from death certificates showed only 156.

Even at 100,000 deaths a year, the adverse reaction rate is relatively low, given the 2.5 billion prescriptions written every year, says Dr. John SiegfriedCQ, speaking for the Pharmaceutical Research and Manufacturers Association.

In fact, “drugs are remarkably nontoxic,” insists Dr. Hershel JickCQ, a Boston University researcher whose work is funded by drug companies. “No reasonable person could really expect drugs to be any less toxic than they are.”

Maybe so. But even if that’s true, there are ways for reasonable people – and hospitals – to at least minimize the chance of bad reactions.

For instance, hospitals could scan their own computerized laboratory and pharmacy data for orders for antidotes used to combat bad reactions, says Dr. David Bates, an internist at Brigham and Women’s Hospital. These red flags could help spot trends early, says Bates, who has studied adverse reactions and wrote an editorial accompanying the Canadian research in the Journal of the American Medical Association.

Hospitals could also monitor their patients’ kidney function more closely – and some are. If kidney function slips, patients need less medication temporarily because they excrete drugs more slowly.

In fact, hospitals may have to do more monitoring for adverse drug reactions, if pending new federal regulations are approved. If re-written properly, Bates contends, these regulations could “provide a major impetus for quality.”

And there’s lots you can do yourself, outside the hospital.

Most important, tell your doctor – and pharmacist – what other drugs, prescription and non-prescription, you are taking every time you get a new prescription, and be sure to mention if you’ve ever had an allergic reaction to a drug. (One quarter of the deaths in the study were from allergic reactions.)

You should also ask your doctor and pharmacist to be specific about the risks and benefits of your new prescription, and to tell you whether the drug is likely to interact with your current medications.

Pharmacists, of course, should be alert to possible interactions whether you ask or not. But at least one study shows that when someone shows up with two prescriptions for drugs that should not be taken together, a third of pharmacists fill both without issuing a warning, says pharmacist Larry SasichCQ of the Public Citizen Health Research Group, a Washington advocacy group.

Ask the pharmacist to give you the FDA-approved package insert, not just the pharmacy’s own summary. “If the pharmacy says it’s not allowed to give out the FDA-approved insert, that’s not true,” says Sasich, “and you should get a new pharmacist.

When you get the package insert, read it. If you can’t read the fine print – and microscopic type is an issue the FDA is trying to rectify – get a magnifying glass. If you can’t read at all – many adults are illiterate or have poor eyesight – ask someone to read it to you, because it’s important to know what side effects to look for.

You may also want to ask about the so-called “therapeutic range,” that is, how far a toxic dose is from the safe, effective dose. The bigger the range, the better. While you should never exceed the dose prescribed by your doctor, this is especially important to know when the safe and toxic doses are close.

It’s also a good idea to ask whether there are any special precautions you should take while on the drug – like avoiding certain foods or staying out of the sun.

And it’s worth knowing if the drug has FDA approval for your diagnosis. Doctors can prescribe for one use a drug that’s been approved for another, but chances are there’s less data on the safety and efficacy for the nonapproved use.

If your medical problem is chronic, as most conditions are, ask your doctor whether you can “taper up” on medication, that is, try small doses first, then increase if you have no bad reactions. This won’t work in emergencies, though, and may not be wise with some drugs, like antibiotics, because low doses may increase the chances that the microbes will develop resistance.

Be especially alert with new drugs – including free samples and drugs advertised on TV – unless they have documented advantages over older ones. New drugs can be great, but by definition, doctors have less experience with them. Side effects that did not show up in relatively small, pre-marketing studies often become apparent when more people begin taking a drug.

Generic drugs, by the way, should have the same risks and benefits as their brand name equivalents, but if you’re worried, ask your pharmacist.

Finally, if you experience any worsening in your health, the first thing to suspect is the last drug you added. And the first thing to do is tell your doctor, then the drug company. You can also call the FDA directly, 1-800-332-1088.CQ

Doctors aren’t required to report serious adverse reactions to the FDA, but manufacturers are. It may not help you directly to make sure the government hears about serious adverse drug reactions, but there’s a good chance it will help someone else.

To learn more about drugs

  1. Remind your doctor and your pharmacist – about other drugs you’re taking whenever you get a new prescription.
  2. Ask about possible interactions among the drugs you take.
  3. Ask about risks and benefits of the new drug – how likely you are to have side effects and how likely it is to help.
  4. Ask what side effects to watch for.
  5. Ask the pharmacist for a copy of the FDA-approved package insert that comes with your medication.
  6. Read it.
  7. Ask whether there are any special precautions to observe while taking this drug – like avoiding certain foods or staying out of the sun.
  8. Ask if you can “taper up” your dose – start with low doses and then, if side effects are tolerable, increase slowly.
  9. Be especially attentive to new drugs because doctors have less experience with them. Be especially alert to side effects.
  10. Tell your doctor immediately if you have side effects.

LEADING CAUSES OF DEATH

A new study estimates that adverse drug reactions are so common that are one of the nations biggest killers.  PLEASE SEE MICROFILM FOR CHART DATA GLOBE STAFF CHART

 

Treating impotence getting easier

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Not long ago, when researchers were testing a new heart drug in men, they noticed something weird. The drug did little to offset chest pain, but the guys wouldn’t give it back.

It turned out the drug, now called Viagra, had an unanticipated side effect: it enhanced erections.

Just approved last month by the FDA, Viagra is already so hot – $ 78 million worth of presciptions in its first 48 hours on the market – that it could fast become the leading treatment for impotence. At $ 7 per pill.

Technically called erectile dysfunction, impotence is the consistent inability for six months to maintain an erection sufficient for satisfactory intercourse.

That’s distinct from other types of sexual dysfunction. Low libido, or, desire is often caused by depression or low testosterone levels. Inability to reach orgasm is often a neurological problem. Failure to ejaculate sperm can be caused by antidepressant drugs like Prozac.

By contrast, impotence is a matter of sheer hydraulics: There’s not enough blood getting into or staying in the penis to make and keep it erect – a troubling problem for 20 million American men, few of whom seek treatment.

But all that could change if Viagra and other effective treatments, some still emerging, induce more men to seek help.

Impotence can have many causes. In younger men, it’s often due to athletic injuries to blood vessels, which can be fixed surgically. In older men, it’s often due to atherosclerosis, the buildup of plaque inside blood vessel walls. In fact, impotence, not coronary disease, can be the first sign of atherosclerosis.

In other cases, impotence is caused by the very drugs used to treat heart disease. Smoking contributes, too, because it makes atherosclerosis worse. (One study showed that when smokers quit, blood flow to the penis increased significantly.)

Surgery or radiation for prostate cancer also cause impotence, and diabetes has always been a problem because it damages blood vessels and interferes with production of a neurochemical called nitric oxide, the first step in the biochemical cascade that leads to erections.

In terms that are unromantic at best, that cascade goes like this, says Dr. Irwin Goldstein, a Boston University urologist:

The brain tells penile nerves to secrete nitric oxide, which triggers release of another chemical, cyclic GMP, which causes blood vessels in the penis to relax, allowing blood to rush in. As long as cGMP is being made, the penis stays erect. As soon as cGMP production begins to fall, another chemical, PDE-5, destroys the remaining cGMP.

The reason Viagra helps – it worked in 70 percent of men tested – is that it blocks PDE-5. But Viagra only works if there’s cGMP around, that is, if a man is already aroused.

Sorting out the causes of impotence can sometimes be tricky.

Men normally have three to five erections a night, says Dr. Paul Church, a urologist at Beth Israel Deaconess Medical Center. If tests show that you have erections during sleep but have trouble during sex, the problem may be psychological.

In some cases, tests made be needed, including a duplex Dopper ultrasound to “listen” to blow food in penile arteries.

Some men turn to specialized medical practices like Diagnostic Centers for Men, a national chain with 28 outlets – including one in Woburn. The chain disputes it, but critics say some for-profit outfits may do excessive testing.

Regardless of the cause of impotence, psychotherapy can often help. Though most impotence is now believed to have physical roots, it can be so upsetting that men, and couples, need emotional help. And sometimes, emotional problems really are the cause, including childhood sexual abuse, power struggles in a relationship or “performance anxiety,” says Kathleen Logan-Prince, a sex therapist and social worker in Weston.

While Viagra and psychotherapy may be the most obvious solutions, other options can also help, including vacuum pumps, which cost several hundred dollars. These devices slip over the penis and create a vacuum to draw blood in. Blood is then trapped with a band placed around the base of the penis.

Hormone supplements may also be appropriate. A simple blood test can show whether your testosterone is low, though this often shows up as low libido, not impotence. If testosterone is low, hormone patches or injections are a solution, though they can promote prostate cancer and make men more aggressive.

“If a man has a tendency to argue, he’ll argue more. If he honks the horn, he’ll honk more,” says Dr. Gregory Broderick, director of the Center for the Study of Male Sexual Dysfunction at the University of Pennsylvania.

If none of these first-line treatments work, you can turn to less user-friendly options, including injections into the base of the penis of drugs like Caverject or Edex. Unlike Viagra, these drugs, which cost $ 20 per treatment, can inititate an erection, an advantage for men who can’t get aroused, such as those who have nerve damage in the pelvis.

Another option in this category is MUSE, a pellet containing prostaglandin E-1, the same medication as the injections. The pellet is inserted into the urethra, costs $ 20 per use, and also can initiate erections in the absence of sexual stimulation.

For most men, surgery, including implants, is a last resort. With a semi-rigid implant, the man can bend the penis up or down at will. With inflatable devices, he pushes a button under the skin that triggers release of saline solution into the penis from a pouch implanted in the abdomen.

And some men try herbal remedies before they seek mainstream help. One popular option is yohimbine, a tree bark derivative available by prescription (Yocon)and as a dietary supplement (Yohimbe).

Some doctors, like Beth Israel urologist Church think yohimbine helps. Others, like Dr. Drogo Montague, a Cleveland Clinic urologist who chaired a panel on impotence treatments for the American Urological Association, say it doesn’t.

If you do try yohimbine, a word of caution. It has never been approved by the FDA. Nor is it recommended by the German commission that reviews herbal treatments, because there’s no proof it works and its side effects – agitation, tremors, anxiety and hypertension – can be serious.

Among other herbal options is NuMan, a combination of Chinese herbs. Dr. Thomas Kingston, a Salem Hospital urologist, has tried it in 20 patients and feels it’s “more effective than yohimbine.” One of his patients, a 46-year old North Shore real estate agent, has tried it and claims it’s “fabulous.”

So what should you do with so many options out there and more on the way, including a topical gel called Topiglan and a pill called Vasomax.

Given the strong evidence for Viagra and other mainstream remedies – and the weak evidence for herbals – the choice seems clear. Stick with mainstream medicine on this one, and talk things over with your partner – and your doctor.

  1. Medications that can cause impotence Type of Medication: Examples:
  • Heart/blood pressure medications: Beta-blocker propranolol (Inderal) * * Calcium channel blocker* diltiazem (Cardizem) * * Nitrate* isosorbide dinitrate (Isordil) * * Diuretics: chlorthiazide (Diuril)
  • spironolactone (Aldactone) * * Alpha-blockers:* prazosin (Minipress) * * ACE inhibitors:* catopril (Capoten) * * Cholesterol-lowering drugs:* niacin, lovastatin (Mevacor) * Anti-arrhythmia drug: Digoxin * * Other: Anti-ulcer drugs: cimetidine (Tagamet) * Antidepressants: amitriptyline (Elavil)
  • fluoxetine (Prozac) * * Tranquilizers: diazepam (Valium)
  • thioridazine (Mellaril) * * Antifungal: ketoconazole (Nizoral) Miscellaneous: finasteride (Proscar)
  • estrogens, antiandrogens
  • antihistamines
  • anticholinergics
  • anticancer drugs * Less likely to cause impotence * And others * *

And many others SOURCE: Harvard Men’s Health Watch, Sept., 1997 and Dr. Irwin Goldstein, Boston University Globe staff chart

 

2.  To learn more

For more information on impotence and treatments:

  • call: 800-242-2383, the American Foundation For Urological Disease.
  • On the Net, you can try these sites:
    • www.iiem.org
    • International Impotence Education Month www.auanet.org
    • American Urological Association

 

Frustrating skin disease begins to yield it’s secrets

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Gloria E. Grubbs, a Vietnam Vet from Dorchester, is 50 now, has “raised two kids up” and made a life for herself, despite a 19-year struggle with scleroderma, the disfiguring disease that can turn the body into a mass of stiff, scar-like tissue, inside and out.

It started with a tightening and thickening in her skin, then moved on to her joints and internal organs. Her heart is now so rigidly encased that she needs an operation, and fibrous tissue is threatening her lungs and kidneys, too.

Grubbs keeps her spirits up by getting out of bed as often as she can to “mess with my plants” and do the washing, ironing and babysitting she must do to supplement her disability check.

She wouldn’t wish scleroderma “on my worst enemy,” she says. “It’s a very depressing disease.”

It’s also “the most frustrating disease in rheumatology,” says Dr. Don Goldenberg, chief of rheumatology at Newton-Wellesley Hospital. “That’s because of the lack of effective treatment, the difficult lifestyle and cosmetic issues people face, and the fact that we still don’t know why it happens.”

There’s no cure in sight for Grubbs or 300,000 other Americans with scleroderma, a disease that chiefly strikes women of childbearing age. In its virulent form, it kills half its victims within five years. But researchers are finally on the trail of its causes – and of new treatments.

Acting on a tip about the high rate of scleroderma among Choctaw Indians in Oklahoma, for instance, researchers at the University of Texas-Houston Medical School have discovered a region on chromosome 15 that may contain a scleroderma gene.

Back in 1830, the US government seized the land of the Choctaw, who then lived in Mississippi, giving them a cruel choice: stay behind on small plots or migrate to Oklahoma.

Roughly 20,000 trudged to Oklahoma in what became known as the “trail of tears.” There, they became a kind of genetic laboratory – a small, intermarrying population in which any mutation that popped up would spread through the group.

The fact that researchers are closing in on just such a mutation means they can now look for similar genes in others with scleroderma – and perhaps understand its origins.

In Seattle, researchers from the Fred Hutchinson Cancer Research Center and the Virginia Mason Research Center are chasing another theory. They’ve found that women with scleroderma have higher levels of fetal cells from past pregnancies in their blood than other women, even decades later.

Since a fetus has genetic material from its father and mother, says rheumatologist Dr. J. Lee Nelson, any fetal cells that get into the mother’s bloodstream may be seen by her immune system as “non-self,” triggering an immune disruption that can lead to scleroderma.

Still other researchers, are trying to sort out the physiological steps that lead to scleroderma.

The initial problem, some think, is microscopic damage to small blood vessels, usually in the extremities, causing periods of reduced blood flow, followed by a restoration of normal flow.

This cycle causes normal proteins in the blood and tissues to break apart, says Dr. Frederick Wigley, director of the scleroderma research center at Johns Hopkins School of Medicine.

The newly-exposed protein fragments, or antigens, are then spotted by the immune system, which treats them as foreign and begins making antibodies against them.

A second wave of the immune response is then thought to cause cells called fibroblasts to start pumping out excessive amounts of collagen, a fibrous protein that helps hold body tissues together. At the same time, the cells begin making too little collagenase, the enzyme that destroys excess collagen.

Other researchers believe immune problems come first – perhaps from a genetic mutation, renegade fetal cells or some other stimulus – and that the blood vessel damage comes second.

Whatever the sequence, researchers agree that a key warning sign is Reynaud’s phenomenon, in which blood vessels in the fingers bcome severely constricted in response to cold or stress. About 95 percent of people with scleroderma have Reynaud’s, though half of those with Reynaud’s never get scleroderma.

Until recently, treating the underlying process of scleroderma has proved difficult. “There are no proven efficacious therapies,” says Dr. James Siebold of the Robert Wood Johnson Medical School in New Brunswick, N.J.

But doctors are getting better at treating the damage it does, organ-by-organ. The cancer drugs Cytoxan and methotrexate, for instance, often combat scarring in the lungs.

Drugs called ACE inhibitors can reverse kidney damage. The once-reviled sedative thalidomide, expected to be approved soon for limited use in the United States, may retard scarring.  And some researchers are trying photopheresis – pumping blood out of the body and exposing it to ultraviolet light to destroy immune cells.

Some approaches have proved disappointing. Prednisone, a powerful steroid, helps with joint pain but can make high blood pressure and kidney problems worse. Another once-promising drug, d-pencillamine, has also been a letdown.

On the other hand, some treatments in the pipeline show considerable promise, notably a drug called Relaxin, made by the Connetics Corp. in Palo Alto, Calif.

A genetically engineered version of a hormone secreted in pregnancy that allows a woman’s skin to stretch, Relaxin works by boosting collagenase and decreasing collagen.

In studies, 70 percent of patients taking low doses have shown improvement, including a 30 percent softening of the skin. Other symptoms improved, too, like patients’ ability to open their mouths wider and stretch their hands. Curiously, though, higher doses did not work.

Another ray of hope comes from stem cell transplants, a variant of bone marrow transplants. The idea is to remove stem cells (immature immune cells from which other immune cells grow), then blast the patient with drugs and radiation to destroy the immune system, including “memory” cells that contribute to auto-immune problems.

Then, the stem cells are infused back into the body to regenerate a new immune system that, hopefully, has lost the memory of its auto-immune attacks, says Dr. Daniel Furst, a Seattle rheumatologist who is spearheading this effort.

Furst has transplanted three patients with early aggressive scleroderma and says the results look promising, which suggests that stem cell transplants might help with other auto-immune diseases such as lupus, multiple sclerosis and arthritis.

In research to be presented at a conference next month, Dr. David Trentham, a rheumatologist at Beth Israel Deaconess Medical Center, has gotten encouraging results using an antibiotic called minocycline in 11 people with scleroderma.

As of now, none of these options appears miraculous. But they do represent the kind of progress Gloria Grubbs is rooting for.

“I really want them to find a cure,” she says. In the meantime, she tries to “dwell on positive things. And when you think you hit the lowest point, remember there is somebody out there worse than you that you can help.”

Where to learn more

For more information, call The Scleroderma Foundation: 800-722-HOPE (or 4673). On the Web, it’s www.scleroderma.com

 

Women do have more pain, but they cope

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Jean Cummings, a 38-year-old urban policy analyst from Cambridge, lives in almost constant pain.

Diagnosed with rheumatoid arthritis 10 years ago, she’s had two hip replacements and will have both knees replaced in June, right after her wedding.

She’s tried every medication in the book — and some in the pipeline. “There’s almost nothing left for me to take,” she says. She can barely stand or walk without crutches. There are times her body hurts so much she can’t roll over in bed.

Yet she copes, “with humor, mostly,” and sheer grit. “There’s a temptation to stop everything and stay in bed. But that doesn’t work for me. It makes the pain more apparent and makes you stiffer. And it’s so boring.”

Both her problems with pain and her fortitude in dealing with it are impressive. And both may be enhanced, a growing body of research suggests, by one basic fact: Cummings is female.

Not only are there some painful afflictions — migraines, arthritis, lupus, problems with jaw joints — that are more common in females, there may be gender differences in the perception of and response to other types of pain as well.

Furthermore, many differences show up not just in human beings — who are clearly subject to cultural teachings about how men and women should deal with pain — but in lab animals, too.

Not long ago, the question of gender differences in pain might have been hooted off the research agenda. But tomorrow, researchers from around the country will gather at the National Institutes of Health in Bethesda, Md., for a first-of-its-kind conference to discuss just that.

“Women do report more pain. . .and that’s likely related to varied mechanisms, physiological and cultural,” says M.A. Ruda, a neuroscientist at the National Institute of Dental Research and the conference organizer.

There will, of course, be a few skeptics, among them psychologist Dennis Turk from the University of Washington. He studied about 400 men and women at a pain clinic and found few differences, except the women were more depressed.

But since other data show women in general are more depressed than men, this doesn’t prove much, he says. And when he studied cancer patients, men and women had equally severe pain and were equally depressed, probably because a life-threatening illness is upsetting for anyone, male or female.

But other researchers have uncovered provocative evidence that there are gender-specific responses to pain. For instance:

– Men get more upset about pain, at least when it lingers. In a study of 48 men and women having surgery for dental implants, McGill University dentist Jocelyne S. Feine found that in the 10 days afterwards, they rated pain equally. But as pain ebbed, men got more impatient.

– Some medications work differently in men and women. Christine A. Miaskowski, a nurse and physiologist at the University of California in San Francisco, has studied people having wisdom teeth extracted. Morphine, a painkiller that works through one type of receptor (called mu) in the brain and spinal cord, works equally well in men and women. But other morphine-like drugs that work through a different receptor (called kappa) work better in women, suggesting the biology of pain control is gender-specific.

– In mice, too, pain control differs by gender, at least for stress-induced analgesia — the phenomenon that occurs when overwhelming stress, like childbirth or running from a predator, temporarily blocks awareness of pain. In mice, says neuroscientist Jeffrey S. Mogil of the University of Illinois/Urbana-Champaign, a drug called MK-801 reverses stress-induced analgesia, but only in males. He believes females have a separate system for some types of pain control, and he’s found a region on chromosome 8 that may carry the gene for it.

– Though studies are somewhat mixed, women seem to be more sensitive to experimentally-induced pain than men, and some research suggests female sensitivity to pain may fluctuate with the menstrual cycle, indicating hormones may play a role.

In fact, researchers recently identified receptors for the hormone estrogen “in the portion of the spinal cord through which pain signals pass,” says Dr. Daniel Carr, medical director of pain management at New England Medical Center.

Another clue that hormones may affect pain sensitivity is that pregnant women who have surgery need less anesthesia than nonpregnant women, probably because progesterone, secreted during pregnancy, blocks some pain.

The data on gender differences have important implications for treatment, especially the growing evidence that doctors tend to ignore or undertreat pain in women.

In a study of 550 AIDS patients, for instance, Dr. William Breitbart, chief of psychiatry at Memorial Sloan-Kettering Cancer Center in New York, found women’s pain was twice as likely to be undertreated.

It’s not that women are more reluctant to tell doctors about pain, he says. It’s how doctors respond. “I didn’t want to believe it, but it all boils down to the stereotypes about women being hypochondriacal. . .exaggerating symptoms.”

But ignoring any patient’s report of pain can be costly, because it can be the first signal of serious disease.

Several studies, for instance, show that doctors take chest pain more seriously in men, says Dr. C. Noel Bairey Merz, director of the prevention and rehabilitation medicine center at Cedars-Sinai Medical Center in Los Angeles.

One shows doctors are less likely to refer for further evaluation patients who talk about chest pain in “histrionic” terms, versus those who are “more businesslike.” Another shows doctors are simply less likely to refer women with chest pains.

And two studies presented last week at a meeting of the American College of Cardiology showed that women are 13 percent more likely than men to die of their heart attacks. One reason is that women take longer to get to the hospital because instead of the crushing chest pain that men often have, women often have more ambiguous symptoms such as shortness of breath, an ache in the neck or jaw or something that feels like gas pains.

Merz and others are now studying whether chest pain in women correlates to estrogen levels, on the hunch that higher estrogen levels — as in younger women — lead to more awareness of pain.

Even among children, pain can manifest itself differently in boys and girls. At Children’s Hospital, Drs. Charles Berde and Christine Greco are studying a disorder called reflex sympathetic dystrophy, in which one arm or leg becomes painful and gets cold, turns blue, or becomes sweaty while the other doesn’t, suggesting a neurological abnormality.

For mysterious reasons, the condition is six times more common in girls than in boys, says Berde.

Despite inequities in the incidence of pain, research suggests that women and men believe that women cope better, perhaps because nature has somehow endowed them to withstand the pain of childbirth.

Part of women’s skill is an ability to control their emotions during intense pain, says Francis Keefe, an Ohio University psychologist. Even though arthritis caused more intense pain in women than in men in his study, women were better able to maintain a positive mood.

Cummings can buy that, especially when guys approaching 40 complain to her about minor injuries cramping their athletic style. “It’s stunning to me,” she says. Stacked against the pain she copes with every day, “there is no comparison.”

Sneezing early? It’s el Nino’s fault

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Just when you thought there was nothing left to blame on El Nino comes this: We’re in for an unusually early – and perhaps long and nasty – allergy season this year.

Granted, everybody always thinks whatever allergy season they’re suffering through is the worst ever, but this year, it really will be bad – and in some places, already is – because El Nino created perfect growing conditions for trees and molds – a mild winter in the Northeast, rains in the South and North.”We’re in for a mega-season,” says Dr. Donald Pulver, an allergist in Rochester, N.Y., echoing a warning from the National Allergy Bureau, a program of the American Academy of Allergy Asthma & Immunology. And this is on top of a winter that – because there was no killing frost in many places – provided no respite for those allergic to molds.

“We’re seeing tree pollen in the air already, three to four weeks early,” says Dr. Julian Melamed of Allergy and Asthma Specialists in Chelmsford.

Because of the “priming effect” – once airways are inflamed by allergy-causing substances, it takes less and less exposure to cause further misery – the key is to begin taking medications now, before things get too far ahead of you, adds Dr. Frank Twarog, a Harvard allergist.

Allergies – also known as hay fever and allergic rhinitis – mean the body is making an excessive immune response to specific triggers, or allergens, in the environment.

About 50 million of us are allergic to something – either seasonal, outdoor things like trees and grasses, or year-round indoor things like mold, dust or cats. Or both.

In the spring, the big culprit is pollen – a packet of sperm that trees and grasses release into the air to be carried to female organs in the same plant or one nearby to form a seed.

Depending on your genetic makeup, pollen from a particular kind of tree, say a birch, may cause an immune reaction – release of a type of antibody called IgE. This antibody sits on the surface of mast cells – immune system cells that line the nose, throat, gastrointestinal tract, and skin.

The next time this pollen enters your system, it combines with these antibodies, causing the mast cells to release histamine and 44 other chemicals that can trigger an allergic reaction. These chemicals make blood vessels dilate and leak proteins into tissues, causing swelling – the stuffy noses of allergy sufferers – or hives on the skin.

Usually, this is just annoying. But allergies also can cause asthma, an inflammation of the bronchial tubes, and sinusitis, an inflammation of the sinus cavities around the eyes and nose.

If the sinuses are blocked, mucus cannot drain properly, which means that viruses or bacteria lurking there can thrive. Infected mucus then drips into the lower respiratory tract, triggering bronchitis and asthma.

So what can you do? Plenty.

Basic preventive measures include staying indoors when pollen counts – and air pollutants – are high. Close the windows and turn on air conditioners at home and in the car. If you exercise outdoors, do it at dawn when plants are covered with dew, after a rain, or at dusk, when pollen has fallen to the ground.

You can also use a HEPA (high-efficiency particulate arrestor) air cleaning filter – roughly $ 200. A dehumidifier may help combat mold allergies, too. The goal, says Pulver, is to keep indoor humidity at between 35 and 45 percent, which means you also have to get rid of any carpeting that’s been wet for more than 48 hours.

A growing array of medications can help, too, especially if you start using them now.

If your allergies are mild, over-the-counter antihistamines like Benadryl or Chlor-trimeton (or their cheaper, generic equivalents) may do the trick, though they can make you groggy. Newer antihistamines, like the nasal spray Astelin and pills like Allegra, Claritin or Zyrtec, don’t cause grogginess, except possibly for Zyrtec. But you can only get them by prescription.

A better solution, many allergists say, is one of the anti-inflammatory nasal sprays that act by a different mechanism.

Nasalcrom, now available over the counter, is a nonsteroidal drug that helps some people. Another nonsteroidal spray, which works by decreasing nasal mucus, is Atrovent, available by prescription. A different formulation of the drug is used to control asthma.

But often, allergy sufferers need the stronger stuff – prescription steroid sprays like Nasonex, Flonase, Nasacort, Nasacort AQ, Rhinocort, Nasarel or Vancenase AQ/DS. It may take 24 hours to a week for the steroid drugs to kick in, but once they do, they control allergies well if you use them faithfully.

If you have asthma, it’s especially important to treat allergies so smaller problems don’t become bigger ones, says Dr. Marshall Plaut, chief of the allergic mechanisms section at the National Institute of Allergy and Infectious Diseases.

For asthma, which kills 5,000 people a year, the mainstays of prevention and treatment are inhaled steroids such as Vanceril DS, Flovent, Aerobid, Azmacort, and the just-approved Pulmicort to dampen down the inflammatory response in airways.

These drugs must be taken regularly – not just during an attack – to allow delicate airways in the lungs to heal. Non-steroid inhaled drugs such as Intal and Tilade also help, by incapacitating mast cells.

And for some people with asthma, bronchodilators may help.

Short-acting “rescue” bronchodilators, such as Proventil, Ventolin, Alupent, Maxair, and Tornalate work by boosting the stress hormone adrenalin, which opens airways.

These are available only by prescription and should not be used regularly because they raise the risk of cardiac arrhythmias and stroke. If you use them more than three times a week, it’s a sign your asthma may be out of control and you should see your doctor again.

And be especially careful with Primatene Mist, a short-acting bronchodilator available over the counter. It provides relief fast – in little as 15 seconds – but is often overused.

A long-acting bronchodilator called Serevent can control nighttime and exercise-induced asthma by keeping muscles around airways relaxed, but it’s best used with inhaled steroids.

Increasingly, allergists are also prescribing a new class of drugs called anti-leukotrienes – Accolate, Zyflo and Singulair. These drugs block leukotrienes, substances that, like histamines, are released during inflammation.

If all this seems a bit overwhelming, take heart. It’s well worth the trip to the doctor and the pharmacy to keep allergies and asthma under control. Whatever El Nino may do out there, there’s no point in suffering if you don’t have to. Judy Foreman is a member of the Globe staff. Her E-mail address, via the Internet is: foreman, (AT SIGN SYMBOL)globe.com

1.  For pollen data

For more information on pollen counts nationwide and tips for dealing with allergies, you can try:

  • 1-800-9-POLLEN begin_of_the_skype_highlighting              1-800-9-POLLEN      end_of_the_skype_highlighting (765536).

  • On the web, try www.aaaai.org (the American Academy of Allergy Asthma and Immunology)

2.  Telling symptoms

It can be hard to determine if you’ve got a cold, allergies or sinusitis. Colds get better by themselves, but allergies and sinusitis persist and often need medical treatment. Here are the distinguishing symptoms. Symptom Sinusitis Allergy Cold Facial pressure/pain Yes Sometimes Sometimes

  • Duration of illness More than 10-14 days Varies Less than 10 days

  • Nasal discharge Thick, yellow-green Clear, thin, watery Thick and whitish or thin and watery

  • Fever Sometimes No Sometimes

  • Headache Yes Sometimes Sometimes

  • Pain in upper teeth Sometimes No No Bad breath Sometimes No No

  • Coughing Yes Sometimes Yes

  • Nasal congestion Yes Sometimes Yes

Sneezing No Sometimes Yes SOURCE: American Academy of Otolaryngology.  Globe staff chart

Treatment options are growing for women with bleeding disorders

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Teresa Menz, a 34-year-old teacher from Sidney, N.Y., tried almost everything for her fibroids — benign uterine tumors that cause pain and bleeding in millions of women.

With more than 100 fibroids, Menz’s belly was as big as that of a woman 26 weeks pregnant and she hemorrhaged during every menstrual period. She tried hormone treatment for a year and had four major operations. Nothing worked.

Until last fall, when she became one of a few hundred women worldwide — and the first at North Shore Medical Center in Salem — to undergo a procedure called uterine artery embolization. Her fibroids are still growing and the treatment may have left her infertile. But at least her periods are normal now.

For years, Leslie Magier, 36, a Framingham interior decorator with a hereditary bleeding disorder called von Willebrand disease, also had such heavy periods she “couldn’t walk into someone’s house because of the fear I would bleed onto their couch,” she says.

Magier, too, took a chance on a then-experimental treatment — uterine balloon therapy — two years ago at Brigham and Women’s Hospital. She’s has been fine since, the balloon device was approved by the US Food and Drug Administration in December and the procedure is becoming available at many hospitals.

As many as one-fifth of women are believed to have excessive menstrual bleeding — bleeding that lasts more than seven days or necessitates more than 10 pads a day. But until recently, both women and their doctors often ignored it.

In fact, many women never mention it, either because they’ve gotten used to becoming shut-ins every month or because they fear they’ll be told to have a hysterctomy.

In the past, those fears were often justified. Hysterectomies — done 600,000 times a year — are the second-most common operation, after Caesarean sections. And many hysterectomies — 25 percent, according to a 1993 Rand study; more than 90 percent, say some women’s advocates — may be unnecessary.

But a growing recognition of bleeding problems in women and new treatment options may soon change this mindset, starting with a research conference this weekend in Philadelphia.

The first step in treating excessive menstrual bleeding, specialists say, is to figure out exactly what’s causing it.

Often, the cause is a hormonal disturbance in which the ovary does not release an egg, which triggers irregular bleeding — light one month, heavy the next, says Dr. Brian Walsh, chief of surgical gynecology at the Brigham.

Other times, it’s fibroids, which affect one-third of women and can cause heavy bleeding during and between periods.

Occasionally, it’s that the lining of the uterus (the endometrium) grows into the uterine wall. And sometimes, as in Magier’s case, the cause is von Willebrand disease, a genetic defect that’s less well-known, but more common than hemophilia.

Von Willebrand disease affects at least 3 million men and women — versus 20,000 (mostly men) for hemophilia, according to figures from the Centers for Disease Control and Prevention to be presented at this weekend’s conference.

And while both men and women with von Willebrand have severe nosebleeds and bruise easily, women have an extra problem — heavy menstrual periods, says Dr. Jeanne Lusher, a Wayne State University hematologist and co-organizer of the conference, which is being sponsored by the National Hemophilia Foundation.

Once the cause of heavy bleeding is identified, the next step is to choose among the growing treatment possibilities.

If the problem is hormonal disturbance, for instance, the solution is hormonal — birth control pills to regulate periods if you’re young and don’t smoke, progesterone pills for two weeks a month if you’re older or smoke.

If the problem is von Willebrand disease, injections — or a relatively new nasal spray — of DDAVP (1-deamino-8-D-arginine-vasopressin) often help, as do transfusions in some cases.

Surgery, of course, is the right solution for some women, but that doesn’t have to mean a traditional hysterectomy, which takes four to six weeks to recover from. Today, many hysterectomies can be done vaginally and recovery takes two to four weeks. Some women also take a hormone called Depo-Lupron before surgery to shrink the uterus to allow vaginal removal.

Another alternative is ablation, or destruction, of the lining of the uterus. This is a deeper procedure than a D & C (dilation and curettage), which removes only the surface of the lining and reduces excessive bleeding for only a few cycles.

Ablation, which usually stops excessive bleeding or at least makes it lighter, is often done with a “rollerball,” a kind of electrified paint brush passed repeatedly over the endometrium.

“If you don’t want a hysterectomy and want normal bleeding,” this may be an answer, says Dr. Alan Penzias, a gynecologist at Beth Israel Deaconess Medical Center.

But the fluid (glycine) used to inflate the uterus during this procedure can cause electrolyte imblances, warns Dr. John Petrozza , a reproductive endocrinologist at the New England Medical Center. Ablation is also likely to cause infertility.

And because the rollerball demands considerable skill, some surgeons are now turning to a new, easier technique that utilizes a balloon device made by Gynecare, Inc.

In this procedure, which Magier had, a balloon is inserted into the uterus and filled with water that is then heated to 188 degrees Farenheit for eight minutes.

So far, more than 125 women have had balloon therapy, says Walsh of the Brigham, who ran part of the study that led to FDA approval of the device. It takes 28 minutes, he says, versus 45 for the rollerball, and can be done under local anesthesia plus intravenous sedation.

Like any ablation technique, though, balloon therapy “destroys the endometrium by scarring it,” warns Nora Coffey , director of the HERS (Hysterectomy Educational Resources and Services) Foundation in Pennsylvania.

And because ablation is chiefly for women whose bleeding is not caused by fibroids, those who have fibroids must consider other options, like Depo-Lupron to temporarily shrink fibroids.

If surgery does seem to be the best solution for fibroids, there’s still an option to hysterectomy. Called myomectomy, it involves removing just the fibroids that protrude into the uterus, not the uterus itself. This can preserve fertility.

If the fibroids are big or numerous, the myomectomy must be done through an abdominal incision. But if they’re small or few in number, they can be removed with an instrument called a hysteroscope that is inserted vaginally. Some researchers are experimenting with freezing and thawing to remove fibroids.

The option Terera Menz chose — embolization — is still another option for fibroids. So far, it’s still rare, but “very exciting,” says Dr. Robert Mals, the interventional radiologist at North Shore Medical Center who treated her, with gynecologist Mitchell Rein.

In the procedure, a catheter is inserted into the groin and threaded up to the uterine arteries under X-ray guidance. When it reaches the blood vessels supplying the uterus, tiny particles of polyvinyl alcohol are released. This triggers a kind of heart attack in the uterus; the resulting blockage of blood flow then causes the fibroids to shrivel.

Dr. Robert L. Worthington-Kirsch, an interventional radiologist in Bala Cynwyd, Pa., who has done 186 such embolizations, says that while fibroids shrink, the uterus itself survives because of collateral blood flow. Even so, the procedure should be assumed to cause infertility.

The procedure, long used to treat hemorrhaging after childbirth, is 90 percent successful for fibroids, he says, in that women get at least some reduction in bleeding. But so far, there are few published reports and many are skeptical, including Coffey of the HERS Foundation.

“I don’t think embolization is conservative,” she says. “We are still doing these destructive things to women in the name of its being an alternative, it not being a hysterectomy.”

But Teresa Menz doesn’t see it that way at all. “I would totally recommend this over hysterectomy to women who definitely are done having children.”

SIDEBAR:

Where to learn more

Talk to your doctor about a possible bleeding disorder and tests for von Willebrand disease if:

  • Your menstrual periods get progressively heavier or longer or last more than seven days, you need more than 10 pads a day or more than a super-tampon an hour, or if you pass large clots.
  • You bleed heavily after surgery, including dental work.
  • You have a family history of heavy bleeding.
  • You get nosebleeds that demand emergency treatment.
  • You bruise easily.

If you have excessive menstrual bleeding, ask about:

  • Tests for anemia, and iron supplements.
  • A drug called DDAVP if you have von Willebrand disease.
  • Hormonal treatment, including birth control pills, to restore menstrual regularity.
  • Ultrasound and other tests to see if you have fibroids. If you do, consider medications, including GnRH agonists like Depo-Lupron (a monthly injection), Synarel (a daily nasal spray) and Zoladex, capsules injected under the skin. The drugs are expensive — $300 a month or more — and bring on menopausal symptoms such as hot flashes, vaginal dryness, and bone loss.

If your doctor suggests a hysterectomy, ask about other options:

  • If you choose to have your uterus removed, ask if this can be done vaginally, which can shorten recovery time.
  • If the problem is fibroids, ask about a myomectomy — surgery to remove fibroids, not the uterus. This can be done vaginally or through an abdominal incision. You might also ask about uterine artery embolization.
  • If bleeding is not due to fibroids, ask about endometrial ablation, including the new balloon therapy device.
  • Get a second opinion or call a women’s health group such as the HERS Foundation, 610-667-7757, for more information.

Dancing to siren song of pheromones

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In the late 1960s, Martha McClintock, then a Wellesley College student, was captivated by the dormitory buzz: Women who hung out together got their menstrual periods at the same time.

It wasn’t the first time women had noticed this, but McClintock was intrigued. And it only made her more so when male researchers with whom she studied one summer at Jackson Laboratory in Bar Harbor, Maine, pooh-poohed the whole thing.

So when she got back to school in the fall, she recruited 135 women and kept track of their cycles and friendships. Within four months, women who were friends began to cycle together. The degree of synchronization increased over time, as if they were communicating via an undetectable chemical signal.

They were. Last week, after decades of work in rodents, McClintock proved it in a study in Nature that has scientists buzzing.

McClintock, a psychology professor at the University of Chicago, showed — in research others describe as “elegant” and “carefully controlled” — that odorless underarm secretions taken from some women then wiped under the noses of others can shorten or lengthen the recipients’ cycles, depending on where in their own cycles the donors were when the secretions were taken.

This is the first solid evidence that pheromones — chemicals emitted by one animal that exert a behavioral or physiological response in another — can influence physiological responses among humans, though human pheromones per se have not been isolated.

Pheromones are fascinating.

By synchronizing ovulation, for instance, they may increase genetic diversity. Since males often mate according to size or dominance, if only one female is in heat at a time, chances are the dominant male will inseminate her. If many are in heat, more males have a chance to pass on their genes.

And if females give birth together, they nurse and care for each other’s young, which has been shown to increase survival of the infants, says Julie Mennella , a former student of McClintock’s and now a biopsychologist at the Monell Chemical Senses Center, a nonprofit research group in Philadelphia.

Pheromones also help animals mark territory and tell friend from foe. In some species, bedding from the cages of strange males can cause miscarriages if placed in the cages of pregnant females, says Charles Wysocki, a neuroscientist at Monell.

Other studies suggest that human mothers can identify their own newborns by the smell in T-shirts worn by the child and that infants prefer breast or armpit pads worn by their own mothers, says Israeli psychologist Aron Weller in a commentary accompanying McClintock’s paper in Nature.

And pheromones clearly play a role in mating behavior.

When sexual attractant pheromones are put in traps, beetles can’t help themselves; they flock to the stuff (and get stuck in the trap). When female pigs in heat get a whiff of a pheromone called androstenone from the saliva of males, they assume the mating position, whether a male is around or not.

When female hamsters are anesthetized and rubbed on the rear end with vaginal secretions, males mate with them even though they’re out cold.

Nobody knows yet how pheromones affect human mating, if they do, though this has hardly cooled the ardor of hypesters — check the Net — touting products supposedly laced with pheromones. (One product is described as a “perfectly legal sexual stimulant cleverly masked in a men’s cologne that when unknowingly inhaled by any adult woman unblocks all restraints and fires up the raw animal sex drive in every woman.”)

Even if all that were true, the most interesting word in that purple prose is “unknowingly,” because pheromones can indeed act outside of conscious awareness, perhaps because of the specific nerve pathways through which pheromone signals travel.

In many species, the olfactory system consists of two parts. The main system, for the conscious detection of smells, involves a patch of nerve tissue high up in the nose. This tissue contains receptors that catch airborne molecules.

The neurons connect to the olfactory bulb, a lightbulb-shaped structure in the front of the brain that processes chemical signals. The bulb then passes the signals to higher centers in the cortex, or thinking part of the brain, where information is further processed and the animal becomes conscious of the scent, or at least acts as if it does.

But in many animals, there’s also an accessory olfactory system, called the VNO, or vomeronasal organ, located lower in the nose closer to the mouth.

The intriguing thing about this organ is that its nerve fibers run to a different part of the olfactory bulb and from there go not to higher centers in the brain but to the amygala and hypothalamus, which can process signals without the animal’s awareness. From the hypothalamus, signals then go to the pituitary gland, which controls ovulation and reproduction.

Because these signals don’t wind up in the cortex, they may remain outside conscious awareness, says John Vandenbergh, a zoologist at North Carolina State University.

The big question is whether humans have something similar. Until recently, scientists thought not, or that if there is one, it is vestigial and disappears during fetal development.

But now, says Linda Buck, a neurobiologist at Harvard Medical School, the consensus is that there seems to be a structure that might be the human counterpart of the VNO, “but no one has been able to demonstrate that it’s connected to the brain.”

Buck and others have found genes in human DNA for two families of receptors that would respond to pheromones in a VNO system, but the genes are mutated and can’t make functional receptors, she says.

With or without functioning VNO receptors, it’s clear from McClintock’s study of 29 women that humans can react to phermones somehow, “either by using an unidentified part of the main olfactory system, or perhaps with a sixth sense with its own unique pathway,” as McClintock puts it.

Armpit secretions obtained when the donors were in the first half of the menstrual cycle shortened recipients’ cycles, by as much as 14 days. When secretions were taken when donors were ovulating, the recipients’ ovulation was delayed and their cycles were lengthened, by as much as 12 days.

“It was like eau d’ovulation,” says McClintock, and what makes the study “quite elegant,” adds Wysocki, is that “not only did the McClintock group show they could alter the cycle, they showed they could advance and retard it in the same women.”

Weller, in the Nature commentary, calls the finding “ground-breaking,” not least because pheromone-based drugs might be developed to help regulate menstrual cycles in infertile women. And “we may yet discover that other aspects of our behavior and physiology are affected by covert olfactory messages from other people during social interactions,” he says.

Napoleon I certainly seemed to believe something like that, according to a famous message he is said to have sent to Josephine, the empress of France. “I return in three days,” he wrote. “Don’t bathe.”

Granted, the effect of pheromones may be muted in modern society, where daily showers and deodorants are a mark of civilization. But the McClintock study shows we are more like other animals in our ability to process hidden chemical signals than some might like to think.

“It’s like the Titanic in the sense that we can only see the tip of this iceberg,” says Wysocki. “We have only begun to realize how susceptible we may be to chemical communication among ourselves.”

Tinnitus: It’s not just in your ears

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Until four years ago, Dr. Stephen Nagler, 49, was a busy breast and colon cancer surgeon in Atlanta.

Suddenly, he began suffering from tinnitus, which most people describe as a ringing in the ears, but for him was “a cross between the sound of a teakettle and a jet turbine.”

“It was incredibly loud. It was there all the time. Every waking moment my head was screaming,” he says.

An estimated 50 million Americans have some form of tinnitus, according to the American Tinnitus Association, and it’s often triggered by exposure to loud noise and accompanied by some degree of hearing loss. For 12 million sufferers, tinnitus is bad enough to affect everyday life.

And for 2 million, like Nagler, tinnitus (pronounced “TIN-nit-us” or “tin-NITE-us”) becomes disabling. “It can drive to you distraction and utter despair,” he says.

In rare cases, it can drive people to suicide.

In Nagler’s case, probably triggered by medications, things got so bad that he had to stop working. “I was bedridden,” he says. “I couldn’t concentrate. I couldn’t make decisions. I stayed home and held my head most of the day.”

Like similar sufferers, Nagler went on a “tinnitus odyssey,” eventually seeing 15 doctors. He started with his internist, then saw an ear, nose and throat specialist, then an ear specialist, then a neurologist, and a psychiatrist.

He tried herbs, histamine medications, acupuncture and “masking” devices, small gadgets that are worn like hearing aids and flood the ear with noise to drown out the tinnitus.

Nothing helped – until he consulted neuroscientist Pawel J. Jastreboff of the University of Maryland, whose theories got a boost in January when researchers at the State University of New York in Buffalo published a tiny but provocative study in the journal Neurology.

Just as Jastreboff had predicted 15 years ago, they showed that tinnitus – a kind of phantom noise that does not come from the outside world – involves not just the auditory cortex in the brain, but the limbic, or emotional, system as well. That’s a possible clue as to why tinnitus create so much anxiety and distress.

“This was a surprise,” says experimental psychologist Richard Salvi, who, with colleague Alan H. Lockwood, studied four tinnitus patients who had an unusual ability. They could turn their tinnitus on and off with various tricks, like moving their jaws, clenching their teeth or pressing on the face.

As they turned their tinnitus up and down, Salvi and Lockwood studied the patients’ brains with PET ( positron emission tomography) scans that can monitor the level of activity in all parts of the brain. When the tinnitus was turned up, the auditory cortex and the limbic systems of their brains “lit up” on the scans; when it was quiet, their brains were, too.

This was music to Jastreboff’s ears, more evidence, he says, that he has long been on the right track. Unlike some theorists, Jastreboff believes tinnitus is not only an inner ear problem but involves abnormal electrical activity in higher brain centers as well.

This fits, others say, with the observation that although surgery to cut the auditory nerve that runs from the ear to the brain can sometimes make tinnitus better, it often makes it worse – almost as if, with no sensory input coming in from the outside world, the brain’s sound system tries to stimulate itself.

If tinnitus does involve higher brain function, Jastreboff’s theory goes, then it should be possible to retrain the brain to filter out annoying signals and be unaware of them.

Jastreboff’s program, which helped surgeon Nagler so much he opened his own center, the Southeastern Comprehensive Tinnitus Clinic in Atlanta, has two parts: a counselling component that teaches people about tinnitus and helps them dissociate feelings of panic from the auditory sensations, and an old Pavlovian technique called “passive extinction.”

To accomplish this, Jastreboff has patients wear a device that looks like a hearing aid all day long for several months. It provides a constant, broadband sound (a kind of “white noise”) that does not mask tinnitus but allows the brain to pair this benign sound with tinnitus and to filter both out. The brain does the work of “habituation,” he says, adding that 80 percent of his patients get “significant improvement.”

Nagler puts it this way. With masking, he says, if you rate your tinnitus at 10 on a 10-point scale, then add another noise that’s also a 10, you won’t hear the tinnitus because it’s drowned out. But because you don’t hear it, you cannot “habituate it.” By using a softer, constant sound, you learn to become unaware of tinnitus.

Today, Nagler says he can still hear his tinnitus “if I listen for it and occasionally, it can distract me, even if I don’t listen for it. It still keeps me from surgery. But it’s no longer annoying or distressing, and most of the time, I don’t hear it at all.”

The treatment can be costly – $ 1,500 to $ 3,800, he says, and insurers may not pay. But the retraining techniques are available now at dozens of centers nationwide, though, none, apparently, in Boston.

The fact that the technique hasn’t penetrated the Boston medical establishment doesn’t surprise Dr. David Vernick, an ear, nose and throat specialist at Beth Israel Deaconess Medical Center and Brigham and Women’s Hospital.

Though the electronics Jastreboff uses may be more accurate than older masking devices, he says, in general, tinnitus treatments have “a huge placebo effect. If I give you a pill and treat you well and make you feel good, that will work 60 to 70 percent of the time. And that’s true of almost every treatment.”

But try telling that to Nagler. “The beauty of tinnitus retraining therapy,” he says, is that it “cleaves the bond between the limbic system and the tinnitus signal.”

To skeptics, that might translate into little more than simply learning to ignore or live with tinnitus. But to desperate sufferers like Nagler, it’s nothing less than salvation. 

Coping with tinnitus

See an ear, nose and throat specialist to rule out problems like impacted ear wax, Meniere’s disease, otosclerosis (hardening of the bones in the middle ear) or an acoustic tumor.

  • Avoid extremes of sound. Loud noises can damage hearing and may cause tinnitus or make it worse. Tinnitus does not cause hearing loss, but hearing loss can cause tinnitus. But silence is bad, too, because it can make tinnitus seem worse.
  • If tinnitus starts or gets worse with aspirin, caffeine, cigarettes, quinine or alcohol, stop using these substances. More than 200 drugs, including some antibiotics, may also make tinnitus worse, so check with your doctor.
  • If an ear, nose and throat specialist cannot help you, consider biofeedback, relaxation training, yoga, acupuncture, self-hypnosis or other stress reduction techniques to offset the anxiety that is often associated with tinnitus.
  • Anti-convulsant, anti-depressant, anti-anxiety and antihistame drugs also help some tinnitus patients.
  • Some people use herbal remedies like ginkgo baloba, though there is almost no solid data on this.

For more information on tinnitus, call:

The American Tinnitus Association, 1-800-634-8978. On the web, it’s www.ata.org.

 

The caffeine brouhaha is percolating again

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Malcolm Noriega, 35, a consulting engineer from Manchester, used to wake up on weekend mornings with wicked headaches, complete with nausea and a light-sensitivity so intense he had to wear sunglasses indoors.

“The damned things were Tylenol-and ibuprofen-resistant,” he says. “Maybe by afternoon I’d be able to function.”

Finally, friends suggested his problem might be caffeine withdrawal, though he drank only a cup and a half of coffee on workdays. So he started drinking coffee on the weekends and, “presto! My headaches went away. . .it’s like a necessary evil to do this.”

Caffeine is the only drug that’s widely added to food. But whether it should be – and if so, in what amounts and with what labels – is an old battle that’s heating up again.

Last summer, the Center for Science in the Public Interest, a nonprofit advocacy group in Washington, petitioned the US Food and Drug Administration to take another look at the safety of caffeine and to require that products that contain it – including heavily-hyped soft drinks kids love to guzzle – be labelled to reveal how much caffeine they contain.

The amount of caffeine in various products might surprise you. A cup of Starbuck’s coffee ice cream has as much caffeine as half a cup of instant coffee, the public interest group says, while other brands have almost none. A cup of Dannon coffee yogurt has as much as a 12-ounce Coke, while Dannon light cappucino yogurt has none.

The FDA is now mulling it over, but hints its long-time view will prevail: Pregnant women should avoid caffeine or drink it in moderation, but overall “there’s no reason to suspect the status of caffeine should be changed.”

Not surprisingly, that’s what the National Soft Drink Association thinks, and the National Coffee Association as well.

Even caffeine researcher Roland R. Griffiths, a psychopharmacologist at Johns Hopkins School of Medicine, says there’s “no life-threatening health risk associated with daily consumption” – a good thing, given that 85 percent of the population consumes at least 200 milligrams of the stuff a day.

Though lay people often use the word “addicted” to describe their love-hate relationship with the stimulant, caffeine is “very unlike our classic drugs of abuse,” he adds, though it can produce dependence – and withdrawal symptoms like Noriega’s – at doses as low as 100 mg a day. That’s just one 5-ounce cup of coffee or a couple of Diet Cokes.

But if caffeine won’t kill you, neither is it harmless. At 100 to 200 mg a day, your mood may be mildly enhanced, says Dr. Andrea Seek, a Lahey Clinic psychiatrist. But at 300 mg – two small cups of coffee – you may feel anxious. At 1,000 mg – that’s ten cups – your speech may ramble and you may get heart palpitations. At 10,000 mg, you may get seizures.

And because caffeine stays in the body up to 10 hours, it can cause insomnia, unless you’re tolerant to its effects.

So this part is easy: If you’re prone to anxiety, panic attacks or insomnia, you may want to eschew the brew, because caffeine can make things worse. Ditto if caffeine makes your heart beat crazily, though a recent review of data showed that even five to six cups of coffee a day did not increase the frequency or severity of arrhythmias.

But what of the stickier wickets like cancer, fibrocystic breast disease, cardiovascular disease, osteoporosis, and reproductive problems?

So far, the research “has identified no significant health hazard from normal caffeine consumption,” says the International Food Information Council, an industry group, in a brochure approved by American Academy of Family Physicians.

But some folks – and Science in the Public Interest – aren’t convinced. A point by point analysis is in order:

– Cancer. More than a decade ago, a New England Journal of Medicine study suggested a link between coffee and pancreatic cancer. That has since been shown to be “not true,” says the FDA.

Several years ago, an analysis in the British medical journal Lancet of data pooled from 35 studies examined the putative link with bladder cancer – and found none. Two large studies in Norway and Hawaii also found no link between coffee and cancer. The bottom line? There’s no known link between cancer and caffeine.

– Fibrocystic disease (benign breast lumps). Anecdotes to the contrary, researchers have found no link with caffeine. (They’ve found no link with breast cancer, either.)

– Cardiovascular disease. Years ago, some data suggested that coffee could raise blood pressure and cholesterol, but this was in Scandinavia, where coffee is made by boiling. In studies with coffee that is filtered – as it usually is in America – there was no such effect, probably because filtering removes the bad stuff (cafestol and kahweol) from the oils in ground coffee.

Coffee can produce a transient boost in blood pressure in people with normal pressure, notes Dr. Barry Woods, a Lahey Clinic cardiovascular specialist. But a review of 17 studies found no persistent increase.

And considerable data – including two Harvard studies of nurses and other health professionals – found no link to heart disease even among people who drank as much as five cups of coffee a day. “It’s a dead issue,” says Dr. Meir Stampfer, a Harvard epidemiologist.

– Osteoporosis. While data are mixed, some studies suggest caffeine leads to loss of calcium from bones and an increased risk of fractures. This can be offset by drinking milk.

– Infertility. Studies are mixed here, too. A 1990 study of nearly 3,000 women by researchers at Harvard Medical School and the federal Centers for Disease Control found no link between caffeine and fertility. But a 1995 Johns Hopkins study of 2,500 women suggested that drinking more than 300 mg a day of caffeine reduced the odds of conception by 17 percent per cycle.

– Miscarriage. There are four studies on this, in which pregnant women who drank coffee were followed to see if problems turned up later. Two found no effect of caffeine and two found a somewhat higher miscarriage rate at 150 to 300 mg of caffeine a day.

– Birth defects. Three studies involving more than 15,000 women have found no effect. Even the Science in the Public Interest folks concede there’s little evidence linking caffeine to birth defects.

However, three studies found consumption of more than 300 mg a day of caffeine can lead to lower birth weight.

Taken together, all this means that caffeine doesn’t exactly rank as a leading health problem. But it can feel that way, especially when you try – and fail – to quit. It may help to realize that the DSM-IV, the psychiatrists’ bible, lists caffeine withdrawal as a genuine disorder. (Caffeine intoxication is, too.)

Often, caffeine researchers say, the real problem is that people think they have a handle on everything that contains caffeine and they don’t.

That’s because it’s not just in foods, as a natural ingredient or additive, but in medications, too, from over-the-counter wake-up remedies like Vivarin (200 mg per tablet) and painkillers like Excedrin (130 mg per two tablets) to prescription headache pills like Fiorinal and Esgic.

People also underestimate how much caffeine they take in, especially with mugs of coffee, which may contain twice the caffeine of a cup, says Dr. Fred Sheftell head of the New England Center for Headache in Stamford, Conn.

Some people, especially those who have headaches, including migraines, may also get caught in a vicious cycle because some caffeine is a double-edged sword. It boosts the effectiveness of pain medications, but withdrawal can also trigger headaches.

For Malcolm Noriega, the solution to the withdrawal problem is to increase intake so it’s constant every day. If you want to quit instead, you have to do it slowly – by 100 to 160 mg – roughly a cup of coffee – every two or three days. If you’re not drinking that much to start with yet still have withdrawal because you’re highly sensitive, decrease by a half cup every four or five days.

If your energy sags along with your intake, the answer is not caffeine, says Sheftell. It’s exercise: “Get those endorphins going.”