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Vital Signs:
Focus on Recent Research

This section includes brief accounts of selected Dartmouth research projects on biomedical and health-policy issues.

Revealing patterns

Magnetic resonance imagining (MRI) may one day play a key role in the early diagnosis and treatment of Alzheimer's disease. Using repeat MRI scans to track changes in the brains of 90 older adults, DMS researchers, led by Andrew Saykin, Psy.D., found a strikingly similar pattern of brain activity and gray-matter loss in patients who have only perceived cognitive deficits and in those diagnosed with mild cognitive impairment, a precursor condition to Alzheimer's. Saykin presented the findings at the International Conference on Alzheimer's Disease and Related Disorders.

Structural insight

Dartmouth computer scientist Bruce Donald, Ph.D., and his students are working to make structural genomics—the study of proteins' three-dimensional, geometric structures—less onerous. In the Journal of Biomolecular NMR (nuclear magnetic resonance), his team presented new algorithms that require less data and deliver more accurate results. Most NMR experiments measure a protein and report the distances between molecules and the angles of chemical bonds, but can't indicate which atoms or bonds the measurements correspond to. "It's a little like taking all the heights and weights of everyone at a cocktail party, but you don't know which height goes with which person," says Donald. The new techniques assign the measurements to the correct nuclei, unveiling the architecture of proteins more accurately.

Calcium does a colon good "Previous studies have demonstrated an association between calcium intake and moderate decreases in the risk of precancerous colorectal tumors, but this is the first randomized trial to evaluate the effect of calcium on different types of colorectal lesions," says DMS epidemiologist John Baron, M.D., about his recent study with DMS graduate student Kristin Wallace. The researchers analyzed data from 913 patients and found that supplemental calcium slightly decreased the risk of all types of colorectal polyps; the effect was greatest for the most advanced lesions. The results were published in the June 16 issue of the Journal of the National Cancer Institute.

Same relief, lower dose

Tacrolimus, a topical, steroid-free ointment often used to treat eczema, is effective in a lower concentration than is commonly prescribed, according to a DMS study. The ointment, which also goes by the brand name Protopic, proved successful in adults and children ages two and older at only a 0.03-percent concentration. The results were presented at the annual meeting of the American Academy of Dermatology. In a report on the study in Dermatology Times, DMS's Shane Chapman, M.D., the study's principal investigator, said that in his own practice he used to prescribe 0.1- percent ointment to his patients regardless of their age or the severity of their condition. "I suspect a lot of other dermatologists also favor the higher-strength product," he said, noting that these findings will allow dermatologists to prescribe the lower dose with confidence.

A matter of some sensitivity

A Phase I clinical trial at Dartmouth's Norris Cotton Cancer Center is testing a new drug, gefitinib (also known by the brand name Iressa), to see if it can restore sensitivity to tamoxifen in breast-cancer patients who have become resistant to the popular antiestrogen therapy. For more than 20 years, tamoxifen has been a staple treatment for the two-thirds of women with breast tumors that express estrogen receptors. But the vast majority of metastatic tumors eventually become resistant to tamoxifen and other endocrine therapies, explains Gary Schwartz, M.D., the principal investigator of the trial. The results of the study are due out in early 2006.

Unlocking metabolic mysteries

Thanks to a recent DMS study, energy regulation in mammalian cells has become less mysterious. DMS endocrinologist Lee Witters, M.D., and colleagues at Harvard have shown that a gene known as LKB1 is responsible for the activation of an important cell-energy mediator, AMP-activated protein kinase (AMPK). AMPK regulates cellular metabolism and proliferation and protects against cellular death. It has been known that LKB1 is a tumor suppressant, yet cells lacking LKB1 are more likely to die. Witters' team proposed a model to explain this paradox and a way that strategic manipulation of LKB1 and AMPK may help combat certain cancers and type 2 diabetes. The work was published in the Proceedings of the National Academy of Sciences.

Helping to stub out smoking

Parents, take note: a new DMS study, led by pediatrician James Sargent, M.D., shows that children whose parents restrict them from viewing R-rated movies are much less likely to try smoking than their peers. In the study, only 3% of adolescents who were never allowed to watch R-rated movies had lit up, compared to 14% of those whose parents let them view such flicks sometimes or all of the time. For a list of actors who light up and films that glamorize tobacco use, visit www.scenesmoking.org/whyitsimportant.cfm, an American Lung Association site that mentions Sargent's ongoing research. His new study, which received a lot of press, appeared in the July issue of Pediatrics.

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