This month, Dr. Sydney Spiesel discusses SIDS and pacifiers, a vaccine for cervical cancer, a new treatment for kidney stones, and a surprising explanation for the rise of a killer germ. (Click here and here for the last two roundups.)
Pacifiers: Do they prevent SIDS?
The mystery: For a long time, Sudden Infant Death Syndrome has been—and to some extent remains—a horrible epidemiological mystery. Babies die unpredictably and for no apparent reason, and medical science can almost never identify a cause. Yet it is tantalizingly obvious that SIDS is caused by something in a baby's environment, because the deaths are not randomly distributed. The rate varies with the seasons, is increased by parental smoking, and at times has been greater in some countries than in others.
Clue No. 1: The turning point in our understanding of SIDS came in 1986 with the publication of the first of several papers by S.M. Beal. Based on research done in South Australia, Beal established—not for the first time, but definitively—that it is dangerous for babies to sleep face-down. The rate of SIDS was unusually high in Australia, almost certainly because babies customarily slept face down on a sheepskin thrown atop a crib mattress. Soft surfaces, especially deep furry ones like sheepskins, magnify the dangers of face-down infant sleeping. The risk isn't that the baby will suffocate (as any TV crime-show watcher can tell you, suffocation causes changes that an autopsy can detect, which isn't true of SIDS). Instead, the most plausible explanation is that babies who die of SIDS in some way re-breathe exhaled air, and with it excess carbon dioxide.
Bonus mystery: Understanding the role of face-down sleeping in SIDS helped explain related epidemiological mysteries. Why, for instance, did the Netherlands experience a sudden and sustained tripling in the rate of SIDS beginning in about 1973? At the time, doctors suspected a mysterious virus or a change in a vaccine or medication. But the correct explanation, which came to light after sleeping-position studies like Beal's were conducted, was that in 1972 the Dutch government began supplying parents with a new edition of a baby-care pamphlet that instructed parents to put their babies to sleep face-down. (The idea was that this would diminish the risk of choking, which in fact is minuscule.)
Clue No. 2: Holland has, of course, stopped advocating face-down sleeping. There (and everywhere else) the rate of SIDS has dropped a lot since the "back to sleep" campaign was started. But SIDS has not disappeared and doctors continue to look for ways to further decrease it. De-Kun Li and colleagues, writing in a recent issue of the British Medical Journal, compared the sleeping habits of 185 California children who died of SIDS with the sleeping habits of a cohort of randomly chosen infants matched for age and maternal ethnicity. They focused on whether the babies went to bed with a pacifier—and found that those who did were at a reduced risk of SIDS of more than 90 percent.
Resolution: Since we know so little about the underlying mechanism of SIDS, it is foolish to speculate about why this is so or even whether pacifiers themselves (as opposed to something associated with their use) cause the reduction in risk. But I must say that Li's study reinforces my long-standing support for pacifiers. I've never believed that they interfere with breast feeding, and I generally favor any practice that makes a child happy. It's nice to have my indulgent instincts acquire authoritative support, however irrationally.
A vaccine for human papilloma virus: Will kids get it?
The disease: Cervical cancer almost always starts as a young person's disease. It isn't cancer early on, just a virus infection transmitted sexually or through skin-to-skin contact. Usually, the virus fades away over time and does no harm. Which is fortunate, since over time about three out of four sexually active women catch this virus—the human papilloma virus —most in the first five years after they become sexually active. HPV will be transmitted 5.5 million times in the United States this year, with younger people at greater risk. But it will result in only about 10,000 cases of invasive cervical cancer, 40,000 cases of noninvasive cervical cancer, and fewer than 4,000 deaths. If you become infected with HPV, your risk of cancer will depend largely on which strain you have. Other factors include age, genetics, whether your immune system is suppressed as a result of infection or medication, and luck.
Vaccine: Because cervical cancer is a viral disease like measles, mumps, and smallpox, it seems plausible that a vaccine could prevent it. And that now appears to be true. Two candidate vaccines, one (Gardasil) made by Merck and the other (Cervarix) made by GlaxoSmithKline, are being evaluated for FDA licensing or will be soon. Final testing of the Merck product was described at the recent annual meeting of the Infectious Disease Society of America and sounded impressive, indeed. More than 12,000 women from 13 countries were enrolled in Merck's clinical trial. Half were immunized with Gardasil and half were treated with a placebo. There were no cases of cervical cancer or precancerous conditions in the immunized group, compared with 21 cases in the placebo group.
Controversy?: If these vaccines live up to their promise, then what? My hope is that they will be reasonably priced and will become part of the standard pediatric vaccine set given to all children in the United States. A cheaper version, tailored to local HPV strains, could be released for use in developing countries—where it would be even more valuable because the Pap smears needed to diagnosis cervical cancer are often unavailable and treatment is often out of reach. But according to the Washington Post, some conservative groups oppose making the HPV vaccine mandatory. Their fear is that any treatment that makes sex safer for teenagers will undermine the message that abstinence is best. Who can guess now how this will turn out?
Kidney stones: New relief.
The condition: Kidney stones cause excruciating pain, predispose sufferers to infection, and can lead to severe kidney damage. They form when the concentration of solids in the urine becomes too great. Remember high-school chemistry? First a solution becomes saturated, then supersaturated, then precipitation occurs. If it occurs slowly, the precipitating solids form crystals or accrete into hard stones. If these stones, which are often sharp, form inside a small confined place like the inside of the kidney, imagine how much damage they can do as they grow. Kidney stones are surprisingly common, sooner or later afflicting between 8 percent and 20 percent of the U.S. population. Some people are genetically predisposed to the condition, though for almost everyone the risk decreases if daily fluid intake is good.
Standard treatment: Often, small stones pass spontaneously and the patient is symptom free. The problems usually begin when the stones change location or become large enough to block the passage of urine. The resulting pain is usually so excruciating that the need for treatment is urgent. The oldest method, surgery, was developed in the 18th century for stones located in the bladder. It's now a method of last resort. Stones are commonly treated by passing a tiny fiber-optic instrument through the body wall that is used to break up the stone. If the stones are trapped in the lower end of the ureter near the bladder, the fiber-optic instrument can go up through the urethra, through the bladder, and then into the ureter, where the stone can be broken up or snagged for removal. Another method is lithotripsy: Focused high-energy shock waves are passed through the body wall onto the stone, causing it to explode into tiny fragments.
New treatment: An extremely successful alternate method for dealing with stones trapped in the lower ureter has been developed by a team headed by Marco Dellabella, a urologist on the faculty of the School of Medicine in Ancona, Italy. Dellabella and his colleagues realized that stones trapped in the ureter were held in place by a tightening of the smooth muscle in the walls of the ureter. They reasoned that a muscle relaxant might permit the wall of the ureter to loosen its grip on the stone, which would then wash its way out. After comparing several medications, they settled on tamsulosin (the trade name is Flomax), a medication often used to relieve the symptoms of prostate enlargement. Their results were remarkable: 68 of 70 patients experimentally treated with this drug, given orally at home, expelled their stones. Compared with patients treated in other ways, patients treated with tamsulosin lost fewer days of work, had less pain, and had virtually no need for hospitalization. For patients with stones in the lower ureter, then, at-home low-tech treatment with tamsulosin is likely to largely replace all other methods.
Caveat: Tamsulosin makes the iris floppy and hard to handle in the operating room, complicating cataract and other eye operations. Patients taking this medication must make their ophthalmologists aware well in advance of surgery. One more reminder of the unexpected connections within the body—who would have thought that the inside of the eye and the pipes that carry urine were so deeply intertwined?
Gray goo and heartburn tablets: A bad match?
The disease: Soon after doctors began to use wide-spectrum antibiotics to treat infections, some patients began to develop diarrhea shortly after treatment was started. Usually the diarrhea was unpleasant but mild; occasionally it was uncontrollable and lethal. When the lining of the inflamed colon of terribly sick patients was examined, in life or after death, it was often found to be covered with patches of gray goo that looked like a membrane but didn't have enough structural integrity to be properly called one. So, the patients' condition was called "pseudomembraneous colitis"—an inflamed colon with a false membrane.
Culprit: In the mid-1970s, doctors began to suspect that an unusual and then-little-known bacterium played a role in this disease. Clostridium difficile—"C diff" to its friends and enemies—is a germ with four important properties from a physician's standpoint: 1) it doesn't grow in the presence of oxygen, so it is likely to be found deep in the bowel; 2) it forms spores, which are resistant to heat and many disinfectants; 3) it produces two toxins that cause the characteristic diarrhea and intestinal-wall damage; and 4) it is resistant to most antibiotics. The germ also has odd and unexplained properties. About half of newborn infants quickly get C diff but usually remain well, even when large amounts of both toxins that the germ produces are present. And while we know that broad-spectrum antibiotics dramatically alter the balance of bacteria in the bowel, we have no idea why this should favor the development of the disease that C diff causes.
Causes: In England, the annual incidence of disease caused by C diff has gone up 22 times over the past 10 years, with 44,000 cases and about 1,000 deaths among the elderly last year. Why has the disease become much more common, especially in hospital and nursing-home settings? Widespread use of broad-spectrum antibiotics probably plays a role. And it wouldn't surprise me if staffing cuts for nurses and housekeepers has lowered cleanliness standards and thus increased the probability of transmission. The use of alcohol hand sanitizers by hospital staff has also increased the risk of C diff. Such sanitizers have helped tremendously to control most hospital infections. But the spores formed by C diff resist alcohol's lethal effect on bacteria. Which means that even doctors and nurses who compulsively wash their hands with alcohol gel can easily become vectors of C diff transmission. To stop this germ, nothing beats old-fashioned soap and water.
New finding: Now research reported by a McGill University group led by Sandra Dial has revealed another reason for the march of this disease. One of the main protectors against infection from most dangerous ingested bacteria is the intense acidity of the stomach, which kills most germs. But that acidity causes heartburn if it splashes up from the stomach into the esophagus, and painful ulcers if it leaks into the upper part of the small intestine. To treat these problems, two classes of powerful and widely available drugs—histamine blockers (Pepcid is an example) and proton pump inhibitors (like Prilosec)—decrease the stomach's acid production. These medications do their jobs well, sometimes too well. By inhibiting acid production, they decrease the stomach's ability to block bacteria like C diff. That's Dial's important finding: In her large study of nonhospitalized British patients infected with C diff (compared with uninfected patients from the same population), she found a markedly increased risk that a patient taking a stomach-acid reducing drug would be infected with C diff.
Caveat: This is all guilt by association, of course. But the connection between stomach acid reduction and C diff is biologically plausible. It raises some concern that these over-the-counter drugs, which are among the most frequently prescribed medications, may have an unanticipated and sometimes dangerous side-effect.
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