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Unformatted text preview: MEDICAL NEWS & PERSPECTIVES drops to 20% for patients who take the drugs. Still, Dworkin said, this is not enough. "I'm over 50, and if I woke up tomorrow morning with shingles and I started taking an antiviral, I'd still have in the back of my mind that there's as much as a 1 out of 5 chance that I'm still going to be in pain 6 months from now," he said. Dworkin has high hopes for his prediction that aggressive treatment of acute shingles pain might prevent postherpetic neuralgia, but he admits that the best way to accomplish this remains in question. Opioid analgesics, given in conjunction with antivirals, are likely candidates to decrease the incidence of postherpetic neuralgia even further (Dworkin and Schmader. Clin Infect Dis. 2003;36:877-882). Dworkin is conducting a study in which all patients with shingles receive antivirals, and then individuals are randomized to receive one of various analgesics or a placebo. Preliminary results from this 90-patient phase 2 trial, called the Shingles Trial of Oral Medications to Prevent Postherpetic Neuralgia (STOMP-PHN), suggest that opioid analgesics are more effective than placebo in treating the acute pain of shingles. Dworkin acknowledged that the finding is not a surprise, but he added that this marks the first study of oral medications designed to relieve acute pain in patients with shingles. "Even though we primarily did it because the prize our eye is on is postherpetic neuralgia, it turned out to be the first time that anyone's tried to treat, in a placebo-controlled fashion, shingles pain," he said. Now that Dworkin has data indicating that opioid analgesics are relatively well-tolerated in elderly patients and can help alleviate acute pain, he plans to embark on a larger 750-patient study to look at the effect of opioid analgesics on preventing postherpetic neuralgia.
SURGE OF SHINGLES? enpox, which will likely translate to fewer cases of shingles in the future. But experts worry that vaccination might actually cause a rise in the incidence of shingles in the near future. Adults who had chickenpox as children may benefit from reexposure to the varicella-zoster virus, as this appears to cause a boost in the immune response that keeps the host virus latent. Interestingly, studies have shown that adults who live with children or who come into contact with them through their work have a lower risk of developing shingles than adults who are in infrequent contact with children (Solomon et al. J Am Acad Dermatol. 1998;38(5pt1):763765; Thomas et al. Lancet. 2002;360: 678-682). Today, noted Dworkin, the number of cases of chickenpox is a quarter of what it was in 1995 and the decrease in viral exposure for adults could mean a surge in shingles. "That prediction, I think, is not well known and is really a fascinating one," said Dworkin. He added that the Centers for Disease Control and Prevention are conducting surveillance studies of shingles to see whether the incidence is rising, although he noted that an increase might not be evident "for another 5 years or so." Researchers are hopeful, however, that an ongoing shingles prevention study (a joint effort of the Department of Veterans Affairs, the National Institute of Allergy and Infectious Diseases, and Merck & Company) might indicate a way to reduce the incidence of shingles and thwart this potential future surge. The multicenter study, which includes more than 38 000 volunteers at 22 study sites around the United States, is testing the effectiveness of an experimental shingles vaccine. Results are anticipated to be released later this year. Even if the shingles vaccine is successful, Dworkin is not worried about finding patients for his shingles pain research. "At least for my lifetime, there's going to be plenty of shingles around to study," he said. Environmental Neurotoxin May Pose Health Threat
Bridget M. Kuehn
BEYOND GUAM? T HE LATEST TWIST IN A MORE THAN Ten years ago, the chickenpox vaccine became available for the immunization of children. The vaccine has done wonders for reducing the incidence of chick-
60-year-old medical mystery suggests a brain toxin once thought to be a threat only to a handful of western Pacific populations may be a ubiquitous environmental hazard. The provocative finding suggests that -N-methylamino-L-alanine (BMAA), a neurotoxin produced by blue-green algae and implicated in the development of severe neurodegenerative disease in a few populations, might play a broader role in the development of Alzheimer disease, amyotrophic lateral sclerosis (ALS), and Parkinson disease (Cox et al. Proc Natl Acad Sci U S A. 2005;102:5074-5078). BMAA has been associated with an unusually high number of cases of ALS/ parkinsonism-dementia complex (ALS-PDC) in three distinct western Pacific populations, most notably the Chamorro people of Guam. Prior to the newly published report, scientists believed that the toxin was produced only by blue-green algae, also called cyanobacteria, that live symbiotically in the roots of a cycad trees native to tropical and subtropical regions. It was thought to be a threat only to those few populations whose diet and medicines rely heavily on cycad seeds and/or animals that feed on them. However, the discovery by an international team of researchers that 2460 JAMA, May 25, 2005--Vol 293, No. 20 (Reprinted) 2005 American Medical Association. All rights reserved. Downloaded from www.jama.com at Cal Poly - San Luis Obispo, on November 26, 2007 MEDICAL NEWS & PERSPECTIVES The cycad tree (left), native to Guam and other tropical and subtropical regions, has a coral-like root (right) that contains symbiotic blue-green algae, or cyanobacteria (inset) that produces a neurotoxin. The toxin has been linked to neurologic disease in some populations. cyanobacteria from diverse terrestrial, freshwater, and saltwater ecosystems around the world produce the toxin is requiring a reassessment of whether it poses a larger health threat. "We don't know if this has implications for illness elsewhere, but we do believe humans far from Guam could be exposed to this neurotoxin," said ethnobotanist Paul Alan Cox, PhD, of the National Tropical Botanical Garden, Kalaheo, Hawaii. Neurotoxins produced by bluegreen algae are a growing public concern worldwide, particularly in the developing world, according to Hans W. Paerl, PhD, a cyanobacteria expert and the Kenan Professor of Marine and Environmental Science at North Carolina State University, based at the Institute of Marine Science in Morehead City. As population growth and development around waterways contribute large amounts of pollutants into the water--from fertilizers, sewage treatment plants, or other sources--it stimulates the development of blue-green algae blooms. The toxins produced by these blooms might be deadly to humans or animals that drink contaminated water. Swimming in contaminated water has also been associated with other conditions, such as contact dermatitis. The toxins can also accumulate in the tissues of fish, shellfish, or other ani- mals. On Guam, Cox et al found the concentration of BMAA increases 100fold as it moves up the food chain (Proc Natl Acad Sci U S A. 2003;100:1338013383). Chamorros who eat flying foxes--bats that feed on cycad seeds and accumulate BMAA in their tissue-- are exposed to high doses of the toxin. The blue-green algae blooms can occur in both freshwater and saltwater environments, but are most commonly found in stagnant bodies of water enriched by runoff, Paerl said. Public health officials in the southeastern United States are beginning to monitor water supplies for some of the toxins.
WATER MONITORING Although it has yet to be proved that BMAA causes neurodegenerative disease, monitoring BMAA levels in cyanobacteria-contaminated water supplies "might be prudent," Cox said. He and colleagues recently identified BMAA in the brain tissues of several individuals with neurodegenerative disease. In one blinded study aimed at determining whether BMAA crossed the blood-brain barrier, researchers identified BMAA in tissues taken from the brains of 6 deceased individuals from Guam with ALSPDC and one asymptomatic individual from Guam; another asymptomatic individual had no BMAA. They also made an unexpected dis- covery: BMAA in the tissues of 2 deceased individuals from Canada who were part of the 15-person control group and who (further investigation revealed) had Alzheimer disease (Murch. Proc Natl Acad Sci U S A 2004;101:12228-12231). Since then, he and colleagues have conducted a second blinded study of brain tissue samples from deceased individuals (also from Canada), 7 of whom had Alzheimer disease and one control who did not. BMAA was found in tissue from 6 of those who had Alzheimer disease. Cox said that the small number of individuals makes it difficult to draw conclusions from these findings. In addition, noted Peter Spencer, PhD, director of the Center for Research on Occupational and Environmental Toxicology at Oregon Health and Science University in Portland, independent confirmation of these findings is needed to ensure that a mimic of BMAA is not causing these results. But other scientists say the idea that BMAA may play a wider role in neurodegenerative disease than previously suspected is a plausible one. The preliminary research by Cox suggests the toxin could be a major environmental factor in neurodegenerative disease, said Walter Bradley, DM, chairman of the department of neurology at the University of Miami School of Medicine. "We've always thought there were environmental factors." He and another University of Miami researcher, Deborah Mash, PhD, are currently examining brain tissue samples from deceased patients with ALS for traces of BMAA; preliminary findings have been promising, he said. If BMAA is indeed a causative factor in some cases of neurodegenerative disease, it could help to explain some notable clusters of the disorder. For example, Bradley hypothesized, a recently identified cluster of ALS cases in professional soccer players in Italy might be caused by toxins produced by terrestrial cyanobacteria living on the soccer fields.
2461 Paul Cox, Sandra Banack, and Patty Stewart 2005 American Medical Association. All rights reserved. Inset: Paul Cox (Reprinted) JAMA, May 25, 2005--Vol 293, No. 20 Downloaded from www.jama.com at Cal Poly - San Luis Obispo, on November 26, 2007 MEDICAL NEWS & PERSPECTIVES 83 W 33 N 82 W 81 W 80 W 79 W 78 W 77 W 33 N National Academy of Sciences; Satellite image courtesy of NASA 32 N GEORGIA AT L A N T I C OCEAN 32 N 31 N 31 N Jacksonville
30 N 30 N FLORIDA
29 N 29 N Trichodesmium Orlando
28 N Tampa
BAHAMAS 28 N 27 N 83 W 82 W 81 W 80 W 79 W 78 W 77 W 27 N A new study has raised concerns that toxins produced by blooms of cyanobacteria, or blue-green algae (such as this Trichodesmium bloom in Florida, as seen from satellite), might be deadly to humans or animals that drink contaminated water. Cox et al. Proc Natl Acad Sci U S A. 2005;102:5074-5078. But while research on the ALS-PDC cases on Guam suggests that environmental factors play an important role in at least some cases of neurodegenerative disease, clear-cut answers have been elusive. Although decades of study and even the folklore of the Chamorro point to the role of the cycad seed in the development of this disease, the precise chemical or chemicals from the seed that cause disease have been debated. More work is needed to conclusively determine whether BMAA causes neurodegeneration in animal models and at what dosages it is toxic. Spencer, whose work in the mid-1980s linked BMAA to the development of ALS-PDC on Guam, is also investigating the potential role of a chemical produced by the cycad tree, cycasin. With so many unanswered questions, said Bradley, it is too soon to declare that BMAA poses immediate public health concerns. "But if this turns out to be right," he added, "it gives us new pathways for treatment and prevention of neurodegenerative disease." FDA Warns Antipsychotic Drugs May Be Risky for Elderly
Bridget M. Kuehn T REATMENT WITH ATYPICAL ANTIpsychotic drugs may cause a nearly 2-fold increase in the rate of death in elderly dementia patients, warned the Food and Drug Administration (FDA) in a recent advisory. Analyses of 17 placebo-controlled studies of four drugs--olanzapine, aripiprazole, risperidone, and quetiapine-- have revealed a 4.5% mortality rate among elderly patients with dementia who had been treated for behavioral symptoms with these second-generation antipsychotics compared with a 2.6% mortality rate among patients treated with a placebo, according to the agency. The studies were, on average, 10 weeks in duration and enrolled a combined 5106 patients with dementia. The causes of death varied, although most were related to cardiovas- cular problems, including heart failure and sudden death or infections such as pneumonia. The advisory applies to these four drugs, plus two other atypical antipsychotics (clozapine and ziprasidone), which the FDA has approved for the treatment of schizophrenia and mania. A formulation that combines olanzapine and fluoxetine, FDA-approved for the treatment of depressive episodes associated with bipolar disorder, also is included in the advisory. The FDA is advising physicians who are currently prescribing these drugs for elderly patients with dementia to review their treatment plans. The agency is also requesting that drug companies add a black box warning to the labeling of these drugs describing these risks and noting that the drugs are not approved for use in elderly patients with dementia. The FDA is extending the warning to all atypical antipsychotics, not just those 4 that have been studied in patients with dementia and associated with increased risk, because the agency has concluded that the risk is related to common effects of this class of drugs. The exact mechanism for the increased risk has not been identified, said Christine Parker, a spokeswoman for the agency. Additionally, the agency has recently begun reviewing the safety of using typical antipsychotic drugs in this population and is considering adding a warning to the labels of those drugs, based on preliminary data that suggest they may also pose a risk. When asked for further information about the review, Parker said the FDA could not yet discuss the details because it was too early in the process. 2462 JAMA, May 25, 2005--Vol 293, No. 20 (Reprinted) 2005 American Medical Association. All rights reserved. Downloaded from www.jama.com at Cal Poly - San Luis Obispo, on November 26, 2007 ...
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This note was uploaded on 04/15/2008 for the course BIO 213 taught by Professor Lee during the Fall '08 term at Cal Poly.
- Fall '08