Faculty Bibliography

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging threat worldwide. CA-MRSA strains differ from hospital-acquired MRSA strains in their antibiotic susceptibilities and genetic backgrounds. Using several genotyping methods, we clearly define CA-MRSA at the genetic level and demonstrate that the prototypic CA-MRSA strain, MW2, has spread as a homogeneous clonal strain family that is distinct from other CA-MRSA strains. The Panton-Valentine leucocidin (PVL)-encoding genes, lukF and lukS, are prevalent among CA-MRSA strains and have previously been associated with CA-MRSA infections. To better elucidate the role of PVL in the pathogenesis of CA-MRSA, we first analyzed the distribution and expression of PVL among different CA-MRSA strains. Our data demonstrate that PVL genes are differentially distributed among CA-MRSA strains and, when they are present, are always transcribed, albeit with strain-to-strain variability of transcript levels. To directly test whether PVL is critical for the pathogenesis of CA-MRSA, we evaluated the lysis of human polymorphonuclear leukocytes (PMNs) during phagocytic interaction with PVL-positive and PVL-negative CA-MRSA strains. Unexpectedly, there was no correlation between PVL expression and PMN lysis, suggesting that additional virulence factors underlie leukotoxicity and, thus, the pathogenesis of CA-MRSA

BACKGROUND: Previous studies have shown that alcohol consumption is associated with decreased medication adherence, but this association may be confounded by characteristics common among those who drink heavily and those who fail to adhere (e.g., illicit drug use). Our objective was to determine whether there are temporal and dose-response relationships between alcohol consumption and poor adherence. METHODS: We administered telephone interview surveys to participants in the Veterans Aging Cohort Study, an eight-site observational study of HIV+ and matched HIV- veterans in care, to determine whether alcohol consumption on a particular day was associated with nonadherence to prescribed medications on that same day. We used the Time Line Follow Back to measure alcohol consumption and the Time Line Follow Back Modified for Adherence to measure adherence. Individuals were categorized as abstainers (no alcohol in past 30 days), nonbinge drinkers (alcohol in past 30 days but < or =four standard drinks on each day), or binge drinkers (> or =five standard drinks on at least one day). RESULTS: Among 2702 respondents, 1582 (56.6%) were abstainers, 931 (34.5%) were nonbinge drinkers, and 239 (8.9%) were binge drinkers. Abstainers missed medication doses on 2.4% of surveyed days. Nonbinge drinkers missed doses on 3.5% of drinking days, 3.1% of postdrinking days, and 2.1% of nondrinking days (p < 0.001 for trend), and this trend was more pronounced among HIV+ individuals than HIV- individuals. Binge drinkers missed doses on 11.0% of drinking days, 7.0% of postdrinking days, and 4.1% of nondrinking days (p < 0.001 for trend), and this trend was comparably strong for HIV+ and HIV- individuals. CONCLUSIONS: Among veterans in care, self-reported alcohol consumption demonstrates a temporal and dose-response relationship to poor adherence. HIV+ individuals may be particularly sensitive to alcohol consumption

[Jeanna Giese] told her pediatrician, Dr. Howard Dhonau, about the bat shortly before she left Fond du Lac, Dr. [Rodney E. Willoughby Jr.] said. Dr. Dhonau passed on the information to Children's Hospital, where Dr. Willoughby initially was skeptical about the possibility that she had rabies, a viral disease, largely because it is so rare in the United States. From his search of scientific articles and telephone discussions with the diseases centers, Dr. Willoughby said he learned that only five patients had recovered from rabies and that all had received rabies shots. No one who had not been immunized, as was Jeanna's case, had survived. Dr. Willoughby learned that laboratory researchers at the Pasteur Institute in Paris had shown that an anesthetic, ketamine, was active against the bullet-shaped rabies virus. So Dr. Willoughby proposed giving Jeanna ketamine to induce a deep coma and midazolam, a sedative, to prevent hallucinations

Early detection centers focus on women who may be at high genetic risk for ovarian cancer -- women like Cara Kealy, a 36-year-old mother of two from Mount Vernon, N.Y. After Kealy developed breast cancer at age 30, she was found to have a BRCA-1 gene mutation, which is associated with a high risk of ovarian cancer. [David Fishman] was thus able to tell her, based on established pathological testing of ovaries removed from other patients, that her ovaries have a 20 percent chance of having premalignant changes. This was enough to make Kealy decide to have her ovaries removed once she no longer wants the option of becoming pregnant again. 'I know I'll have them out. It won't be this year, but it will be soon,' she said. The spirit of international cooperation that Fishman envisions for the acceptance of his protein test doesn't yet exist. Critics of his spectrometric blood analysis haven't been able to reproduce his findings of almost 100 percent specificity, which were published in 2000. Fishman says improvements in technology -- he can now look at millions of protein fragments at once -- make his results far more reliable and reproducible. But a group of researchers at Yale remain unconvinced. They also say the state-of-the-art computer required for Fishman's method is too costly to be practical for broad use in a clinical setting. Led by Gil Mor and David Ward, the Yale group published a study in the May 10 issue of the Proceedings of the National Academy of Sciences, identifying four proteins -- leptin, prolactin, osteopontin and insulin-like growth factor-II -- that all tend to be abnormal in ovarian cancer more than 95 percent of the time. True, the abnormalities aren't unique to ovarian cancer, acknowledges Mor, director of the Reproductive Immunology Unit at Yale University School of Medicine, but identifying abnormalities in four complete proteins -- not just protein fragments -- is 'a good start,' he says; he intends to end up with 12 or more in an assay, or blood analysis, that will cost $10 to $20 to run -- instead of thousands of dollars

Remarkably, I found that she was also much less confused. A lung doctor who had treated Pearl for many years for occasional bronchitis came to visit her in the hospital, and she cheerfully complimented the doctor on her new hairstyle. The lung doctor remarked to me that she thought Pearl was very observant -- and grumbled that her own husband hadn't noticed her hairstyle change. At first, the neurologist didn't agree. Ultimately, when Pearl resumed doing crossword puzzles and knowing the details of others' lives, even the neurologist -- though still not convinced -- admitted that the sodium aberration had been the more likely culprit. Because 4 million Americans suffer from Alzheimer's disease, including almost half of people older than 85 (Pearl was close at 83), it was understandable that the neurologist had considered this disease. Alzheimer's has a devastating outcome attached, and because there are many other conditions that can cause similar memory loss and confusion (depression, infection, metabolic disturbances of all kinds), rushing to give a stigmatizing diagnosis such as Alzheimer's is unwise unless a doctor is almost certain. Without absolute tests at this point, and because Alzheimer's disease evolves, diagnosing it properly means observing a trend, not making a pronouncement on one day's observations

Last September, the giant drug company Merck announced that it was pulling its popular arthritis drug, Vioxx, off the market, even though it racked up $2.5 billion a year in sales. This happened on the heels of the publication of three separate books dealing with drugs and health care

In March 2004, a U.S.-born boy aged 15 months in New York City (NYC) died of peritoneal tuberculosis (TB) caused by Mycobacterium bovis infection. M. bovis, a bacterial species of the M. tuberculosis complex, is a pathogen that primarily infects cattle. However, humans also can become infected, most commonly through consumption of unpasteurized milk products from infected cows. In industrialized nations, human TB caused by M. bovis is rare because of milk pasteurization and culling of infected cattle herds. This report summarizes an ongoing, multiagency investigation that has identified 35 cases of human M. bovis infection in NYC. Preliminary findings indicate that fresh cheese (e.g., queso fresco) brought to NYC from Mexico was a likely source of infection. No evidence of human-to-human transmission has been found. Products from unpasteurized cow's milk have been associated with certain infectious diseases and carry the risk of transmitting M. bovis if imported from countries where the bacterium is common in cattle. All persons should avoid consuming products from unpasteurized cow's milk.