Medicine Discovers A New Ally: The Clock

If asthma attacks are most likely to occur in the middle of the night, doesn't it stand to reason that medication administered before bedtime would be most effective? And if the risk of stroke is greatest between 6 a.m. and 10 a.m., shouldn't hypertensive individuals take blood-pressure drugs in doses that would prevent early-morning surges?

For chronobiologists, who study biological functions in relation to time, the answers to such questions have long been apparent. To them, the human body is a symphony of rhythms in which rising and falling blood pressure, heart rate, hormone levels, and temperature are part of a highly integrated and time-sensitive interplay.

Applied clinically, chronobiology uses what is known about the body's cyclical processes to recognize and treat disease. Michael Smolensky, director of Hermann Hospital's Center of Chronobiology & Chronotherapeutics in Houston, says health is a "synchrony of all the biological rhythms within the human body." Thus, any cycle--sleep/wake, menstrual, hormonal--that demonstrates rhythmic abnormalities indicates biological discord, better known as illness.

OFFBEAT RHYTHMS. Thanks to technology, mapping the body's rhythms and discovering any aberrant beats is easier and less expensive today. Ten years ago, the 24-hour monitoring crucial to clinical chronobiology would have meant constant surveillance and repeated pokes and prods by a team in lab coats. But several new computerized devices, including wristwatch-size motion sensors and pocket blood-pressure and heart monitors, make it possible to determine patients' cyclical fluctuations without disrupting their daily routines.

"Technology has been the single most important factor in the growth of clinical chronobiology over the past five years," says Dr. Franz Halberg, a researcher at the University of Minnesota Chronobiology Laboratory. Halberg coined the term chronobiology in 1969. Nowadays, he says, mainstream doctors can continuously track their patients' biological activities over extended periods and not rely on single, point-in-time measurements--which amounts to taking "snapshots of a roller coaster."

This has implications for treatment as well as diagnosis because, as with biological rhythms, illnesses also undulate. Studies show that rheumatoid arthritis flares up at night, heart attacks typically occur in the morning, and cancer cells vary in their activity according to season and time of day. As a result, chronobiologists pay as much attention to timing of therapeutic intervention as to choice of therapy. "Before now, we've always asked how to treat. Today, we must also ask when to treat," Smolensky says.

SURGE PROTECTION. For example, blood pressure naturally revs up in the early morning as the body readies itself to tackle the day. But this increases the risk of heart attack and stroke for people with heart problems or high blood pressure. Thus, Dr. Ronald Portman, a kidney specialist and researcher at the Hermann Center, says hypertensive patients can often get better results and even take lower doses of medication if they target its administration to prevent dangerous, morning pressure surges.

Clinical trials have also proved that anti-inflammatory drugs to combat asthma and rheumatoid arthritis are more effective if given at night, when levels of the body's inherent anti-inflammatory agents, such as the hormone cortisol, fall. Such strategic dosing dramatically reduces the likelihood of nighttime asthma attacks and diminishes the swelling of joints and stiffness that arthritics notice upon awakening.

Also asking "when to treat" is Dr. William Hrushesky, senior attending oncologist at the Samuel Stratton Veteran's Administration Medical Center in Albany, N.Y. Hrushesky has been caring for cancer patients chronobiologically since 1979. "The importance of timing in the screening and treatment of cancer cannot be overemphasized," he says.

Several international population studies indicate that cancer growth rates vary seasonally. Breast-cancer cells tend to be most active in spring and less in fall. Premalignant and malignant changes on the surface cells of the cervix occur more frequently in the summer months. And of the two most common types of testicular cancer, the growth of one peaks in December-January, the other in August-September. Hrushesky says these rhythms suggest false negatives would be less likely if cancer screenings were done "in-season."

Furthermore, biological rhythms can help determine when to schedule therapies once cancers are discovered. Hrushesky has published a study that indicates women's breast-cancer surgeries are far more likely to be curative if performed in the middle of their menstrual cycles (the week following ovulation). His ongoing investigations show that patients respond better to chemotherapy and radiation administered at certain times of the day or week. The actual schedule varies, depending on the type of cancer as well as the therapeutic agent.

"The toxicity of cancer drugs varies rhythmically," explains Smolensky. "The goal is to administer them during those windows of time when they will do the most harm to the cancer but the least harm to the patient." And with the advent of pumps that deliver intravenous drugs at preprogrammed times, he says, such timed treatments are now possible without hospitalization.

Chronobiology also has applications in the management of sleep and mood disorders. "In these situations, bright light is often of great benefit," says Dr. Daniel Kripke, professor of psychiatry at the University of California at San Diego. He "resets body clocks" by exposing his patients to bright light at specified times during the day. Such light therapy seems to regulate the hormonal cycles that strongly affect sleeping and emotions. There is also early evidence that precisely timed light therapy reduces confusion in the elderly and regulates menstrual cycles.

While proponents claim chronobiology is a field that is limitless in its breadth, it also is a field with few players. Only a handful of chronobiology clinics are operating in the U.S. and Europe, and many deal exclusively with sleep disorders. But more mainstream doctors are incorporating chronobiology into their practices, and big medical centers, such as Brigham & Women's Hospital in Boston and the University of Pittsburgh School of Medicine, are using its techniques. The National Institutes of Health has funded several studies on the subject. Also, chronobiology conferences are drawing hundreds of health-care professionals rather than the sprinkling of erudite researchers who showed up in years past. "Chronobiology is taking off in the world of medicine," Smolensky says. Time, after all, is on its side.

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