New Drug Combos Help AIDS Patients

Cocktails of anti-AIDS drugs have dramatically increased survival of individuals infected with HIV. But the virus often develops resistance to the drugs in people who previously have taken multiple combinations of the medications. Now a multi- center, randomized, placebo-controlled trial of 481 people infected with HIV, co-chaired by Dr. Scott Hammer, the Harold C. Neu Professor of Infectious Diseases at P&S and professor of epidemiology at the Mailman School of Public Health, shows that giving patients a new combination of drugs, which includes two protease inhibitors rather than one, can reduce the viral load (as measured by plasma HIV RNA concentration) in a substantial proportion of patients who already had taken several anti-HIV drugs. In addition, patients with the best responses were those who also received a non-nucleoside reverse transcriptase inhibitor (another potent class of anti-HIV drugs) for the first time as part of the study.

The study results imply that doctors treating HIV-infected individuals should try to reserve at least one potent class of drugs during the first- and second-line treatments rather than use all of them early on. The results of the study, supported by the NIAID-sponsored Adult AIDS Clinical Trials Group, were published in the July 10, 2002, issue of JAMA.

Form of Heart Failure May Benefit From New Measurement

Standard heart failure diagnosis relies on assessing the ejection fraction, a measure of how much blood the heart pumps vs. how much blood the heart holds. An abnormal heart pumps out less than half the heart’s blood volume with each beat and has an ejection fraction of 45 percent or lower. But more than 2.5 million people with heart failure symptoms have a normal ejection fraction, a condition called diastolic heart failure, yet no diagnostic test exists to identify their problem.

Now Columbia investigators led by Dr. Mathew Maurer, the Warner Lambert Assistant Professor of Medicine and director of the Clinical Cardiovascular Research Laboratory at the Allen Pavilion, have developed a new, non-invasive way to confirm diastolic heart failure. Their findings about the method, called myocardial contraction fraction, were published in the July 17, 2002, Journal of the American College of Cardiology.

Embryonic Stem Cells and Motor Neurons

During normal nervous system development, the location of a cell in the embryo and its exposure to growth factors from nearby cells determine the type of nerve cell it will become. Columbia researchers have used their unique understanding of the temporal, spatial, and signaling processes involved in the normal steps of neuronal development in the spinal cord to convert mouse embryonic stem cells into viable motor neurons.

The research, led by postdoctoral fellow Dr. Hynek Wichterle in the laboratory of Dr. Thomas Jessell, professor of biochemistry and molecular biophysics and Howard Hughes Medical Institute investigator, was published in the Aug. 9, 2002, issue of Cell. Dr. Wichterle’s findings show that motor neurons derived from embryonic stem cells behave normally in a living embryonic system, opening the way for studies to test the potential efficacy of embryonic stem cell-derived motor neurons in the adult mouse model of ALS and in spinal cord injury.

Making the Right Connections in the Urinary Tract

Urinary tract abnormalities occur in almost 1 percent of all infants, and a newborn often will have multiple irregularities, such as having both a small kidney and an abnormal connection between the bladder and ureter. Reasons for atypical linkages between the ureter and the bladder have remained unclear.

Now, P&S researchers have the first visual and genetic evidence of how the ureter connects to the bladder during mouse development, providing clues as to how similar birth defects occur alone and in conjunction with other urinary tract abnormalities in humans. The results of the study, led by Dr. Cathy Mendelsohn, assistant professor of urological sciences in urology, pathology, and the Institute of Human Nutrition, were published in the September 2002 issue of Nature Genetics. A better understanding of urinary tract genetics and development could lead someday to better prevention and detection of these abnormalities.

Headache Patients and Use of Alternative Treatments

Patients are increasingly turning to alternative treatments for headaches. To better understand what kinds of alternative treatments patients seek on their own, researchers from the Department of Neurology and the Center for Facial and Head Pain asked 73 headache sufferers to answer questions about their knowledge and use of complementary and alternative medicine and their beliefs about its effectiveness.

Eighty-five percent of the surveyed patients used alternative therapies for head pain relief, and 60 percent of them believed the therapies helped. Almost 100 percent of the patients surveyed were familiar with one or more alternative treatments, and 88 percent of the surveyed patients considered at least one of the complementary treatments—including massage, acupuncture/acupressure, and meditation— to be an effective remedy for headaches. The research, led by Dr. Casilda Balmaceda, assistant professor of clinical neurology, was published in the June 2002 issue of the journal Cephalalgia.

SSRI Safety Tested for Heart Patients

About 20 percent of Americans who suffer a heart attack will also develop depression that triples their risk of dying. Yet most of these patients are not treated with antidepressants because older antidepressants are known to be cardiotoxic and the effects of the newer ones are unknown. New research findings show the drug sertraline is safe and effective for depressed patients recently hospitalized for a heart attack.

The results of the study, led by Dr. Alexander Glassman, professor of clinical psychiatry, and Dr. Christopher O’Connor, associate professor of cardiology at Duke, found fewer life-threatening cardiac events in patients taking sertraline compared with those on placebo, although the difference was not statistically significant. The study was published in the Aug. 14, 2002, issue of JAMA. The trial paves the way for a larger study to determine if sertraline treatment reduces death and recurrent heart attack.

Novel Gene Blocks Retrovirus Gene Expression

Physicians have fewer drugs to kill viruses than they do to destroy bacteria. But scientists have had some success in developing antiviral medications based on the body’s defenses against viruses. Physicians, for example, now prescribe a certain interferon, a human immune protein, to treat hepatitis C.

To find other hidden antivirals in our genes, Dr. Stephen P. Goff, the Higgins Professor of Biochemistry and Molecular Biophysics and professor of microbiology at P&S, and colleagues went on a hunting expedition in a library of the complete set of mammalian genes. In the Sept. 6, 2002, issue of Science, Dr. Goff reports he found a new gene that codes for a protein called ZAP, which stopped the replication of a mouse retrovirus in a completely novel way. ZAP somehow blocks the virus’s ability to reproduce by preventing the formation of viral messenger RNAs inside the cytoplasm of infected cells. Further research will attempt to elucidate ZAP’s mechanism of action. Drugs designed to activate a human ZAP gene might someday be used as antivirals.

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