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A federal ban on two insecticides is benefiting newborn babies, according to a study by the Columbia Center for Children's Environmental Health in the Mailman School. The results of the study – the first to demonstrate the benefits of the ban during pregnancy in human subjects – will be published in Environmental Health Perspectives.

The study looked at the impact on fetal growth of chlorpyrifos and diazinon – two insecticides whose use in households was banned by the federal government starting in 2000. The two insecticides had been among the most commonly used for residential pest control (available in numerous household sprays). Chlorpyrifos, for instance, was the most frequently used residential insecticide in New York City prior to the ban. Both are still widely used in agriculture and continue to be found in the food supply.

The research involved 314 infants of African-American and Dominican women in Washington Heights, central Harlem, and the South Bronx. The researchers measured the levels of the two insecticides in blood drawn from the umbilical cords at birth, both before and after the ban, and correlated those levels with the babies' birth weight and length.

Before Jan. 1, 2001, newborns with combined insecticide exposures in the highest 26th percentile had birth weights averaging almost 200 grams (almost half a pound) less than infants with no detectable levels. There was also a highly significant inverse association between the sum of the two insecticides and birth length. After Jan. 1, 2001, the combined insecticide exposure levels had been reduced substantially, and impact on fetal growth was no longer apparent.

"This human study confirms the developmental impact, shown previously in animal studies, of these insecticides," says Dr. Robin M. Whyatt, assistant professor at the Mailman School and principal author of the study. "It also demonstrates the positive effect of the federal ban, which has substantially reduced exposures and benefited human health. The differences in fetal growth seen here are comparable to the differences between babies whose mothers smoke during pregnancy and babies whose mothers don't. The fact that the ban was associated with such an immediate change in birth weight and length provides considerable evidence of cause and effect."

The research is part of a broader, multi-year research project, "The Mothers & Children Study In New York City," started in 1998, which examines the health effects of exposure of pregnant women and babies to air pollutants from vehicle exhaust, the commercial burning of fuels, and tobacco smoking, as well as from residential use of pesticides and allergens.

This study was made possible by grants from the National Institute of Environmental Health Sciences and the U.S. Environmental Protection Agency, as well as a number of private foundations. Other co-authors of this study are Dr. Virginia Rauh from the center, Dr. Dana Barr from the Centers for Disease Control and Prevention and David Camann from Southwest Research Institute.

Antibacterial household cleaning products have no detectable effect on infectious disease symptoms, according to a new study by Columbia University Medical Center researchers.

In what may be the first double-blind, randomized trials of antibacterial soap use in the home, Dr. Elaine Larson, professor of pharmaceutical and therapeutic research at Columbia's School of Nursing and professor of epidemiology at the Mailman School, and colleagues tracked 228 northern Manhattan households of generally healthy people for infectious disease symptoms during one year.

The households were randomly assigned to use antibacterial household cleaning products or identically packaged products without antibacterial ingredients. The researchers gave households liquid kitchen spray, "all-purpose" hard-surface cleaner, liquid dishwashing detergent, bar soap, and laundry detergent. The researchers conducted weekly telephone interviews and monthly visits, which included weighing the remaining cleaning products to measure how much was used. Every three months, the researchers assessed infectious disease symptoms in each household member.

"We found no difference in the two groups in episodes of infectious disease symptoms such as vomiting, diarrhea, sore throat, and runny nose, which are symptoms of primarily viral infections," Dr. Larson says.

Antibacterial products may be beneficial for reducing bacteria-related symptoms such as those from skin or gastrointestinal infections or for households with someone whose immune system is compromised, such as someone with HIV or who is undergoing chemotherapy, Dr. Larson says. Cleaning product manufacturers and health-care providers need to teach consumers about the best use and limitations of household antibacterial products, she says. The study was published in the March 2 issue of Annals of Internal Medicine.

The research was supported by a grant from the National Institute of Nursing Research.

—Matthew Dougherty

Two ostensibly unrelated medical problems, panic disorder and a bladder condition called interstitial cystitis, appear to be part of a genetic syndrome, according to studies by Columbia University Medical Center researchers.

In a collaboration of Columbia's psychiatry and urology departments with the New York State Psychiatric Institute, the researchers found that patients with interstitial cystitis were four times more likely to have panic disorder and twice as likely to have thyroid, mitral valve, and chronic headache conditions – which make up the proposed syndrome, says Dr. Myrna Weissman, first author of the study and professor of epidemiology in psychiatry and chief of the Division of Clinical and Genetic Epidemiology at NYSPI.

First-degree relatives of interstitial cystitis patients were twice as likely to have panic disorder, thyroid disorder, urologic problems, and the syndrome disorder whether panic disorder was included in the syndrome definition. The researchers looked at 67 people with interstitial cystitis and 79 with other urologic problems and 815 first-degree relatives of the patients.

Dr. Weissman's colleagues on the study, published in the March issue of the Archives of General Psychiatry, include Dr. Abby Fyer, professor of clinical psychiatry and co-director of the Anxiety Disorders Clinic at NYSPI, and Dr. Steven Kaplan, Given Foundation Professor of Urology.

Their findings support evidence of a syndrome Drs. Weissman and Fyer identified last year when working with Dr. Steven Hamilton, a former resident and research fellow in psychiatry, Dr. Susan Hodge, professor of clinical biostatistics, and Dr. James Knowles, associate professor of clinical psychiatry, on a genetic linkage study, published in the Proceedings of the National Academy of Sciences.

There is no generally accepted treatment of interstitial cystitis, which mainly affects women. "Our new findings, if replicated, could lead to new treatments for interstitial cystitis," Dr. Weissman says.

The research was supported by a National Alliance for Research on Schizophrenia and Depression Senior Investigator Award and grants from the National Institute of Mental Health.

—Matthew Dougherty

As many as one-third of heart transplant recipients break bones in their spines during the first year after transplantation because of the bone loss caused by drugs used to prevent rejection.

Now, CUMC researchers have found that two different drugs can prevent much of the bone loss that contributes to fractures in these patients. The study appeared in the Feb. 19 issue of the New England Journal of Medicine.

The study compared two drugs, alendronate and calcitriol, in 149 patients who received a heart transplant at CUMC or Newark-Beth Israel Medical Center between 1999 and June 2001. Another 27 patients refused to take part in the study but agreed to have their bone density monitored and serve in a reference group. The study did not include a true control group because the investigators judged that giving placebos to participants with a high potential for bone fracture was unethical.

The researchers found that both drugs prevented bone loss. After one year, the alendronate and calcitriol groups lost between 0.7 percent and 2.1 percent of bone mineral density, while the reference group lost between 3.2 percent and 6.2 percent. Dr. Elizabeth Shane, professor of clinical medicine and the paper's lead author, says a loss of 2.5 to 3.0 percent is generally considered clinically relevant.

The researchers also found that the fracture rate in the reference group was 14 percent, lower than the 35 percent rate they found in the early 1990s. The reduction is likely due to changes in anti-rejection medications, particularly a lower dose of steroids.

The fracture rates in both treated groups were lower than in the reference group. However, because of the lower rate of fracture in the reference group, the study did not have the power to determine whether the difference in fracture between the reference and treated groups was statistically significant.

Dr. Shane says all heart transplant recipients receive rather high doses of prednisone, a drug that is well-known to cause rapid bone loss and fractures. She believes that all should be placed on a medication that prevents bone loss, just as they are given drugs to prevent other complications that commonly develop after heart transplantation.

"Even though fracture is less common now than in the 1990s, we still see patients who haven't received preventative therapy and who develop painful fractures," she says. "Physicians need to be aware that bone loss is still a problem in heart transplant patients and also in recipients of other organs, such as kidneys, livers and lungs."

This research was supported by grants from NIH and Merck. Drugs and placebos were supplied by Merck, Hoffmann-LaRoche Pharmaceuticals, and Mission-Pharmacal.

—Susan Conova

The prevalence of asthma among homeless children in New York City is approximately 40 percent, six times the national rate for children, according to researchers at Columbia University Medical Center and colleagues at the Children's Health Fund.

"High levels of exposure to adverse psycho-social factors – such as stress, trauma, maternal depression, and mental health issues – may play a critical role in determining the high levels of severity and under-treatment found among homeless children," said Dr. Irwin Redlener, associate dean at Columbia University's Mailman School of Public Health and senior author of the article published in the March issue of the Archives of Pediatrics & Adolescent Medicine.

The researchers, led by Dr. Diane McLean, postdoctoral residency fellow in psychiatry at Columbia University and the New York State Psychiatric Institute, investigated the prevalence of asthma among 740 children whose families entered three city family shelters between June 30, 1998, and Sept. 18, 1999. Of the children, 26.9 percent had a prior physician diagnosis of asthma. In addition, 12.9 percent of those without a prior physician diagnosis of asthma reported symptoms consistent with moderate or severe persistent asthma. The researchers also found that few of the children with persistent asthma received appropriate anti-inflammatory treatment, even those in contact with the medical care system.

The research was supported by the Children's Health Fund and an unrestricted educational grant from Schering-Plough.

The discovery of unexpected "flickers" of dopamine release from neurons has changed the way scientists view one of the most fundamental brain processes, according to a new study by CUMC and New York State Psychiatric Institute researchers. They speculate that flickering may have important, but as yet unknown, roles in memory formation as well as in brain diseases such as schizophrenia. The research, to be published in Nature Neuroscience, went on the journal's Web site Feb. 29.

Neurons communicate by releasing neurotransmitters, such as dopamine, into synapses. For decades, scientists believed that each vesicle that delivers neurotransmitters to the synapse releases its entire cargo at once. Thus, it was thought that the only way to control the amount of neurotransmitter released is by controlling the number of vesicles that fuse.

Instead, the researchers found that vesicles in dopamine neurons can flicker open and shut rapidly, releasing only a portion of their neurotransmitter at a time. The rapid flickering had never been seen before because previous techniques were too slow to capture the action. Each flicker lasts only 1/10,000th of a second.

Neurons can also regulate the number of times each vesicle flickers, the researchers found. Three- to- five flickers in a row release nearly all the dopamine into the synapse, but the neurons can also limit the number to a single flicker, which releases 25 percent to 30 percent of the neurotransmitter.

The discovery of neuronal flickering illustrates that neurotransmitter release is far more variable than expected, say the study's authors, Dr. David Sulzer, professor of neurology and psychiatry at CUMC and neuroscience at NYSPI, and Drs. Roland Staal and Eugene Mosharov, associate research scientists at CUMC.

The researchers have also found a means to regulate flickering, likely by the protein kinase C, and suspect that as they learn more about its regulatory molecules they will learn how flickers are involved in memory and brain diseases.

The research was supported by the National Alliance for Research on Schizophrenia and Depression, the Lowenstein Foundation, the Parkinson's Disease Foundation, NIDA, and NINDS.

—Susan Conova

Cells and cell phones share more than a similar name. Cell phone calls are restricted to broadcasting from the antenna nearest your phone. Similarly, cellular signals are frequently active in just one region. Biologists, unlike communication engineers, had little idea how this worked until recently.

CUMC researchers have now found that lipid rafts – recently discovered specialized regions of a cell's membrane – are integral to localizing signals in migrating fibroblasts. The discovery may be applicable to other migrating cells, including inflammatory or metastasized cancer cells, say the two senior authors, Dr. Gregg Gundersen, professor of anatomy & cell biology and pathology, and Dr. Eugene Marcantonio, associate professor of pathology and anatomy & cell biology. The research was published in the Feb. 6 issue of Science.

In the study, the researchers investigated how migrating fibroblasts, which are involved in wound healing, limit microtubule stabilization to the leading edge of the cell. In order to move, migrating cells stabilize microtubules, which are usually dynamic structures. The researchers had previously discovered a signaling pathway for microtubule stabilization. Since the pathway's molecules are distributed throughout the entire cell, however, the mechanism for specific stabilization at the leading edge was unknown.

The answer proved to lie in a second pathway that was stimulated at the cell's leading edge. Here, adhesion between the cell's integrin receptors and their extracellular matrix ligands results in the localization of lipid rafts. It's the first time integrins have been shown to control lipid raft distribution.

Lipid rafts then send signals to the microtubule pathway to turn on stabilization, thereby restricting stable microtubules to the front of the cell.

"Combining two different signals is an elegant way to get a localized effect," Dr. Marcantonio says, and may be a general mechanism to generate cell polarity.

The research was funded by the NIH and pre-doctoral fellowships from Fonds de Recherche en Santé Du Québec and Howard Hughes Medical Institute.

—Susan Conova


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