Alumni Discuss Attitudes on Insurance
In a pilot study conducted by Dr. Donald S. Kornfeld, professor of psychiatry, and Dr. Nicole L. Dubbs, assistant professor of health policy and management at the Mailman School of Public Health, 981 P&S graduates were surveyed to see whether their attitudes about managed care had changed since the early 1990s.
“In 1992,” says Dr. Kornfeld, “Bill Clinton was elected president with a campaign pledge to provide affordable health insurance for all Americans. Soon after his inauguration he assigned the task of crafting the needed legislation to his wife, Hillary Rodham Clinton. She and her associate, Ira Magaziner, after a series of meetings with a wide range of health care constituencies, presented a plan, which they called Managed Competition.”
The plan never became legislation, and patients and physicians have continued participating in the health care system using a mixture of managed care commercial insurance, Medicare, Medicaid, and fee-for-service plans. “In the past 10 years,” says Dr. Kornfeld, “physicians have had considerable experience utilizing managed care and Medicare for most of their patients. We wanted to know whether this experience had any effect on the preferences of physicians.”
Drs. Kornfeld and Dubbs decided to survey alumni who graduated from P&S before 1987 and who had e-mail addresses on file with the alumni office. “Doctors who graduated before 1987 would be the ones most likely to have been in clinical practice in 1993 when the managed competition legislation was considered,” says Dr. Dubbs.
The survey was conducted via e-mail in the spring of 2002. E-mail messages asked alumni to go online to complete a questionnaire that contained 14 questions and space for comments. Responses were entered directly into a database. Of the 981 alumni contacted, 310 responded (a 36 percent response rate). Male respondents made up 78 percent of the total, and the mean age was 60. Most of the respondents (63 percent) were doctors in single specialty practice; 51 percent were physicians at an academic medical center.
Alumni were asked to recall their health care insurance program preference in 1993: commercial managed care or a single payer system such as Medicare. They reported being significantly less in favor of managed care than of single payer at that time.
Alumni were then asked if their preferences had changed during the past 10 years. They reported being significantly less in favor of commercial managed care in 2002 than they were in 1993 and significantly more in favor of single payer today.
The strongest factors driving attitude shifts were increased administrative burdens — paper work and the pre-approval process required by managed care. Income considerations were noted less frequently.
“The results are derived from data collected from a relatively small selected sample,” says Dr. Dubbs. “The findings are therefore limited in their generalizability. Obviously, we do not know the preferences of the non-participants (64 percent of the sample). We do not know how alumni who registered e-mail addresses differ from those who did not.”
“We also do not know how Columbia alumni may differ from other medical school graduates,” adds Dr. Kornfeld. “However, if these findings are supported by additional research with a larger broader sample, there would be significant policy implications.”
The researchers recommend that similar studies of more representative samples be done. “The issue of how best to deliver adequate health care is high on the agenda of government. It should be useful for policy-makers to know how the physicians of America, in various specialties and practice settings, feel about this critical matter,” say Drs. Dubbs and Kornfeld.

Hormone and Stomach Stretching Reduce Food Intake
The combination of a natural appetite-suppressing hormone with stomach distension reduces eating more than either factor alone, according to new research from Columbia and the New York Obesity Research Center at St. Luke’s-Roosevelt Hospital Center. The results suggest that potential weight-loss drugs based on the hormone, cholecystokinin, could be more effective in promoting weight loss if combined with something that activates stretch receptors in the stomach. The research was published in the November 2003 issue of the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology.
Cholecystokinin is an appetite-suppressing hormone produced by the intestine after eating protein or fat-rich food. Dr. Harry Kissileff, professor of clinical psychiatry, and his colleagues found that a combination of a small dose of the hormone and a water-filled rubber bag that stretched the stomach reduced appetite as measured by food intake in men, but neither treatment reduced appetite alone. The researchers hypothesize that the hormone enhances the activity of nerves from the stomach that send appetite-suppressing messages to the brain.
However, in women, the researchers found the hormone alone worked as well as the hormone/water bag combination. The researchers are investigating the disparity, which may be due to the smaller women in the study receiving an effectively higher dose of cholecystokinin than the men or due to underlying sex differences.

Birth Rates and Global Warming
A steady decline in birth rates in Western societies has been blamed on an array of factors, such as growing career pressures, contraception, and social changes. But a group of Columbia researchers suggests a possible new explanation: global warming. In a study published in the June 2003 issue of the journal Medical Hypotheses, the researchers find a statistically significant relationship between fertility and temperature change. The authors found that rising temperatures and falling birth rates went hand in hand throughout the 1900s, except, tellingly, during the baby boom from 1946 to 1964.
The researchers examined mean global air temperature and birth rate data for 19 industrialized nations through the century, using NASA and UN statistics. The lead author was Dr. Harry Fisch, associate clinical professor of urology.

Parkinson’s Disease: Two Studies
Research by P&S neurologists suggests that COX-2 inhibitors like Celebrex and Vioxx may help Parkinson’s disease patients by preventing the neuronal death that characterizes the disease. Dr. Serge Przedborski, professor of neurology and of pathology, and Dr. Peter Teismann, a postdoctoral researcher, found excessive amounts of the COX-2 enzyme in the dopamine neurons of Parkinson’s patients and in mice with a similar disease. In the mice, they found that a COX-2 inhibitor doubled the number of surviving neurons: 88 percent survived with the drug, while only 41 percent survived without it. The research was published in the April 29, 2003, issue of the Proceedings of the National Academy of Sciences.
In the other study, neurologists show that the death of many neurons in mice with Parkinson’s symptoms can be prevented by injecting the mice with a molecule already found in our bodies. The molecule, called D-b-hydroxybutyrate (DbHB), is normally used as a source of energy in the brain when glucose is unavailable. Writing in the September 2003 issue of the Journal of Clinical Investigation, the researchers report that DbHB-treated mice had twice as many neurons as untreated mice.
The molecule saves neurons by helping the cells produce more energy, say the study’s authors, Dr. Przedborski and Dr. Kim Tieu, a postdoctoral research scientist. Deficits in energy production, commonly found in Parkinson’s patients, may be a major cause of neuronal death during the disease. Though the researchers saw no side effects in the mice from the short-term use of DbHB, they also say it metabolizes too quickly to be used in people. Alterations to the molecule may produce a longer-lasting form.

Genetic Mutations Linked to Exercise-Induced Cardiac Arrhythmias
Researchers have found that a genetic defect may make some people with otherwise structurally normal hearts more susceptible to exercise-induced cardiac arrhythmias. Their findings, which were reported in the June 27, 2003, issue of Cell, show that a deficiency of FKBP12.6, a protein that binds to the intracellular cardiac calcium channel (ryanodine receptor or “RyR2”) may result in abnormal calcium release and be linked to exercise-induced cardiac death.
Dr. Andrew Marks, chairman of physiology and cellular biophysics and director of the Center for Molecular Cardiology at Columbia, and colleagues studied genetically modified mice deficient in the FKBP12.6 gene to observe heart function at rest and during exercise. “The research showed that the FKBP12.6-deficient mice consistently exhibited exercise-induced ventricular arrhythmias that cause sudden cardiac death — suggesting that ‘leaky’ RyR2 channels can trigger fatal cardiac arrhythmias,” Dr. Marks says.

Prozac’s Effects Tied to Creation of New Neurons
Columbia neuroscientists have shown for the first time that antidepressants work by stimulating the birth of new neurons in the brain, according to a study’s senior author, Dr. Rene Hen, associate professor of pharmacology. The study appeared in the Aug. 8, 2003, issue of Science.
Because antidepressants take three to four weeks before mood begins to improve, many researchers hypothesize that the drugs work because they promote neuronal growth, a process that may take weeks. Though the drugs have been shown to increase the number of neurons in the hippocampus, until now no one had demonstrated a link between the new neurons and depression-related behavior. In the study, the researchers show that preventing neurogenesis blocks the antidepressant’s behavioral effects in mice. The results suggest that new neurons may also be necessary for the drug’s mood-altering effects in people.

Caught on Tape: DNA Repair
For the first time, Columbia researchers have caught the repair process of double-strand DNA on video, a feat that will enable researchers to better understand the cell’s ability to fix DNA breaks, the inefficient repair of which can leave individuals prone to cancer and other diseases. Though the researchers filmed yeast, the repair would be similar in humans. The research was published in the June 2003 issue of Nature Cell Biology.

The video shows that DNA double-strand breaks are repaired in only one or a few repair centers inside the nucleus of yeast cells. In cells that had nearly 80 breaks, only two centers formed. Paper authors Dr. Rodney Rothstein, professor of genetics & development, and postdoctoral fellow Dr. Michael Lisby say the limited number of repair sites potentially benefits the cell. First, the sites concentrate the molecules needed for repair in a small region, which may increase the rate of repair. Second, because cells don’t divide until repair is complete, a limited number of sites could reduce the workload of the checkpoint molecules that determine when it’s safe to replicate. Finally, the centers may provide scaffolding for the broken ends of DNA to assure proper alignment during the repair.

Tic-Tac-Toe: Computer vs. Humans
Researchers have built a device out of DNA molecules that beats all human challengers at tic-tac-toe. Dr. Milan Stojanovic, assistant professor of medicine, and colleague Darko Stefanovic from the University of New Mexico developed MAYA, an intricate assembly of DNA enzymes, and programmed it to play tic-tac-toe against human opponents. The DNA is arranged into logic circuits similar to those used in today’s computers, thereby eliminating the need for hands-on human computing. MAYA remains undefeated after more than 100 games and represents the most advanced implementation of biological “digital logic circuits” yet described and the first use of biological molecules to play an interactive game. The research was described in the September 2003 issue of Nature Biotechnology.
MAYA consists of nine wells that are arranged in the 3x3 pattern of a tic-tac-toe board and contain various combinations of DNA enzymes. MAYA signals a move by glowing fluorescently in one of the nine wells, whereas the human player indicates a move by adding a short DNA strand to the wells. The DNA strand is keyed to one of the nine wells but is added to all the wells. MAYA can “analyze” the DNA strand selected by the human player and make its own move by cutting this DNA in the appropriate well, which triggers the fluorescence. Whatever move the human chooses, MAYA is programmed to respond with the optimal counter-move.
Using biologically available cofactors, it takes MAYA about 15 minutes to process a move. “It seems far-fetched now, but in the long run we hope that an eventual outcome of this research would be diagnosis of disease or delivery of drugs,” says Dr. Stojanovic.

HIV-1 Tricks Cells to Gain Entry
Researchers at Columbia and Rockefeller have found that HIV-1 escapes a human viral defense system by using one of the defense’s own proteins against itself. The research, published in the September 2003 issue of Nature Medicine, could potentially lead to therapies that prevent HIV-1 from co-opting the protein and allow defense systems to attack the virus.

The protein, called cyclophilin, attaches to HIV-1 inside the cell. The new research shows that in monkeys, which are resistant to the virus, cyclophilin is part of a successful defense against HIV-1. In humans, HIV-1 has turned cyclophilin into an ally that protects the virus from the same antiviral system. Infection was thwarted by human cells only when the virus could not bind to cyclophilin, says one of the study’s authors, Dr. Jeremy Luban, the Richard J. Stock Associate Professor of Medicine and associate professor of microbiology. “The results may suggest new ways to block HIV-1 replication and treat HIV-infected people.”

Low-Calorie Diet Slows Age-Related Changes in Rat Retina
Decades of research on lab animals have shown that restricting caloric intake can extend lifespan and protect against some cancers and neurodegenerative disorders. Now a new study indicates a low-calorie diet retards age-related damage in the retinas of rats.
Dr. Keyang Wang, associate research scientist in ophthalmology, and colleagues found that rats on restricted diets had significantly higher levels of some protective factors — including amino acids and antioxidant levels — in the neural retina. They also retained more retinal cells as they aged. The low-calorie regimen appears to limit harm caused by free radicals, possibly by maintaining the protective factor levels, says Dr. Wang. The findings suggest a low-calorie diet may benefit human vision as well, but more research is needed. The study was published in the Sept. 19, 2003, issue of Biochemical and Biophysical Research Communications.

Ethnic Differences in Breast Cancer Survival
A Columbia study has found that African-American women may have lower breast cancer survival rates than their Caucasian counterparts because of lower baseline white blood cell counts that can delay treatment or alter chemotherapy dosing. The study was published as a communications brief in the Oct. 15, 2003, edition of the Journal of the National Cancer Institute.
Using data from the medical center’s tumor registry, Dr. Dawn Hershman, assistant professor of medicine, and colleagues compared white blood counts and courses of treatment for a select number of African-American and Caucasian women with early-stage breast cancer. They found that the African-American women in the study had significantly lower white blood cell counts both before and after treatment and required a longer time to complete chemotherapy than their Caucasian counterparts. According to the researchers, these findings suggest that doctors might be delaying treatment or prescribing lower doses of chemotherapy for African-American breast cancer patients — possibly compromising the effectiveness of chemotherapy in this population.
“If African-American women are more susceptible to treatment delays or dose reductions due to differences in white blood count values, we have the ability to intervene,” says Dr. Hershman. “Unlike some other contributing factors, this may be something we can fix.”

Common Antibiotic Helps Cystic Fibrosis Patients
An antibiotic given by mouth and commonly used to treat children’s ear infections can also dramatically improve the lung function in people with cystic fibrosis, according to a new study published in the Oct. 1, 2003, issue of JAMA. The drug, azithromycin, could potentially lengthen the lives of patients, who usually succumb to chronic lung infections by their early 30s.
The lung function of patients with cystic fibrosis usually deteriorates over time. Mortality in people with cystic fibrosis is due in large part to lung infections with the Pseudomonas aeruginosa bacteria. By age 18, 80 percent of patients are chronically infected with this pathogen, which leads to destruction of lung tissue. This deterioration is the major cause of morbidity and mortality in the disease.
“This therapy could be a great benefit,” says Dr. Lisa Saiman, professor of clinical pediatrics and the study’s lead author and co-principal investigator. “There are no magic bullets in cystic fibrosis, but to improve or stabilize lung function is wonderful.”
The study compared 87 patients who took the oral antibiotic three days a week with 98 patients who received a placebo. All had chronic Pseudomonas infections and were on a regular regimen of aerosol medications, such as TOBI and Pulmozyme. Though patients typically lose about 2 percent of lung function every year, the addition of azithromycin to the medications caused a 6.2 percent improvement after 24 weeks. It also improved the weight of patients, halved the number of days spent in the hospital, and reduced the total amount of antibiotics (both intravenously and orally) the patients needed. Dr. Saiman cautions, though, that they don’t know the long-term effectiveness beyond the six months of the study or safety of the antibiotic for people with cystic fibrosis. She is planning longer-term efficacy and safety studies, as well as research into how the drug works.

ILLUSTRATIONS: CLAUDIA BRANDENBURG

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