Faculty Bibliography

Methicillin-resistant Staphylococcus aureus (MRSA) remains a major problem in hospitals, and it is now spreading in the community. A single toxin, Panton-Valentine leukocidin (PVL), has been linked by epidemiological studies to community-associated MRSA (CA-MRSA) disease. However, the role that PVL plays in the pathogenesis of CA-MRSA has not been tested directly. To that end, we used mouse infection models to compare the virulence of PVL-positive with that of PVL-negative CA-MRSA representing the leading disease-causing strains. Unexpectedly, strains lacking PVL were as virulent in mouse sepsis and abscess models as those containing the leukotoxin. Isogenic PVL-negative (lukS/F-PV knockout) strains of USA300 and USA400 were as lethal as wild-type strains in a sepsis model, and they caused comparable skin disease. Moreover, lysis of human neutrophils and pathogen survival after phagocytosis were similar between wild-type and mutant strains. Although the toxin may be a highly linked epidemiological marker for CA-MRSA strains, we conclude that PVL is not the major virulence determinant of CA-MRSA

Precisely when and where grand rounds began is not known. There are many types of rounds where doctors learn from patients. For example, there are the daily working rounds as doctors walk through a hospital to visit and examine patients. In teaching rounds, more senior doctors supervise the work of residents, or house officers, at a patient's bedside or in a clinic. Yet attendance at grand rounds has reportedly declined in recent years. Many subspecialists prefer to attend rounds in their narrower field, and doctors who go to national and international meetings can hear much of the same information that may be later presented in lectures at grand rounds. So Dr. [Francis D. Moore] asked Dr. [Roy Y. Calne], now Sir Roy, to present his findings at a grand rounds session. In his college days, Dr. Moore had been president of The Harvard Lampoon humor magazine. (For full disclosure, years later I was an officer of The Lampoon.) So after Dr. Calne summarized the case, and with Dr. Moore's approval, he invited the patient to join grand rounds

BACKGROUND: The highly homologous PE_PGRS (Proline-glutamic acid_polymorphic GC-rich repetitive sequence) genes are members of the PE multigene family which is found only in mycobacteria. PE genes are particularly abundant within the genomes of pathogenic mycobacteria where they seem to have expanded as a result of gene duplication events. PE_PGRS genes are characterized by their high GC content and extensive repetitive sequences, making them prone to recombination events and genetic variability. RESULTS: Comparative sequence analysis of Mycobacterium tuberculosis genes PE_PGRS17 (Rv0978c) and PE_PGRS18 (Rv0980c) revealed a striking genetic variation associated with this typical tandem duplicate. In comparison to the M. tuberculosis reference strain H37Rv, the variation (named the 12/40 polymorphism) consists of an in-frame 12-bp insertion invariably accompanied by a set of 40 single nucleotide polymorphisms (SNPs) that occurs either in PE_PGRS17 or in both genes. Sequence analysis of the paralogous genes in a representative set of worldwide distributed tubercle bacilli isolates revealed data which supported previously proposed evolutionary scenarios for the M. tuberculosis complex (MTBC) and confirmed the very ancient origin of 'M. canettii' and other smooth tubercle bacilli. Strikingly, the identified polymorphism appears to be coincident with the emergence of the post-bottleneck successful clone from which the MTBC expanded. Furthermore, the findings provide direct and clear evidence for the natural occurrence of gene conversion in mycobacteria, which appears to be restricted to modern M. tuberculosis strains. CONCLUSION: This study provides a new perspective to explore the molecular events that accompanied the evolution, clonal expansion, and recent diversification of tubercle bacilli

Food-borne illness is a serious problem in this country, but E.coli 0157 is a very small part of that problem. The National Center for Health Statistics estimates more than 9,000 Americans die yearly from food-borne illnesses, and more than 75 million people get sick. But the Centers for Disease Control estimates that just 73,000 of these illnesses are from the kind of bacteria (E. coli 0157:H7) that has been found at Taco Bell, with 60 deaths yearly. Most victims get diarrhea, but few develop the kind of kidney failure that has currently affected at least three people. Of course, this hardly lets Taco Bell off the hook. The chain's response to the outbreak is hardly reminiscent of that for the spinach outbreak of the same toxigenic E. coli in September. Then the government had easy access to evidence. Now it must work through the Taco Bell bureaucracy. The Food and Drug Administration and the CDC have been trying to track the cause of the outbreak to a certain vegetable, believed to be green onions

About 36,000 Americans die each year from the flu, and 200,000 are hospitalized. Though a relatively small number of the deaths -- 100 -- are children 5 or younger, 20,000 hospitalizations include children in this age group. Inoculating children won't end this annual misery, but if more kids receive the vaccine, the impact of the flu virus could be softened considerably. *Efficacy. In addition, the flu shot's effectiveness in children has been questioned. Indeed, recent studies have indicated that the shot might be less effective in children younger than 2 because of weaker immune reactions. Two shots appear to be necessary to achieve comparable results. Does this mean these children shouldn't receive the shot -- or shots? No, it means parents and the children's doctors need to be vigilant in ensuring that these infants build up the required immunity. As for older children, the flu vaccine has proved highly effective. A 2001 study in the Journal of Pediatric Infectious Diseases showed a 77%-91% effectiveness against influenza in inoculated children ages 1-15. *Myths. The National Foundation of Infectious Diseases found that nearly half of the people surveyed this year believed erroneously that the flu vaccine, which uses a dead virus, can cause influenza. Another myth: A shot must be administered by November for it to be effective during the flu season, which generally runs from October through May. Because it takes less than a month for most patients to develop antibodies, and because flu season tends to peak in most parts of the USA in January, December is still a reasonable time to get the shot

The premise: ER resident Dr. Abby Lockhart (Maura Tierney) accompanies the crew of a medical evacuation helicopter to a local community hospital, where an 88-year-old woman is having a heart attack. Abby's hospital is a Level One Trauma Center with a cardiac catheterization lab, which the other hospital lacks. But when Abby and the emergency response team arrive, they find that the woman is already in cardiogenic shock (extreme heart failure) and intubated (has had a breathing tube inserted in her trachea). The woman has a blood pressure of 74/38, a heart rate of 144, and she is receiving the vasopressor drug dopamine to keep her blood pressure from dropping further. A clot-dissolving drug has been given without any effect. Abby also discovers severe EKG changes -- known as 'tombstoning' (giant abnormal waves) -- indicating much heart damage. Seeing the patient's condition, Abby states, 'She's not coming back from this.' She favors leaving her in the community hospital, but the paramedics disagree. They tell the patient's family: 'It's your mom's only chance.' The paramedics prevail, and the patient is transported. But the woman develops a lethal arrhythmia en route (ventricular fibrillation) and dies

David Oshinsky reviews "Tunney: Boxing's Brainiest Champ and His Upset of the Great Jack Dempsey," a biography by Jack Cavanaugh

BACKGROUND: Medical schools must address the fact that students embarking on careers in medicine are idealistic but have a vague understanding of the values and characteristics that define medical professionalism. Traditionally, we have relied primarily on unsystematic role modeling and lectures or seminars on related topics to teach professionalism. METHODS: A committee of students and a faculty advisor created a curriculum, based on a needs assessment of the targeted learners, to raise students' awareness of professional tenets and provide them with the skills to recognize and analyze conflicts between the values of professionalism and the daily pressures of medical school training. The student-run professionalism curriculum begins during medical school orientation and is followed by three student-facilitated case-based workshops over the next two years. All of the workshops involve small group discussions led by trained upperclass student facilitators. The workshops address the application of professional values to both the preclinical and clinical situations and prepare students for self-reflection, self-assessment and peer evaluation. We evaluated students' satisfaction following each workshop and pre/post attitudes for the first workshop. RESULTS: Twenty five upper-class student facilitators were trained in the first year. Student attendance ranged from 80-100% of the class (N=160), the proportion of students who agreed or strongly agreed that the workshops were educationally useful ranged from 60-75% for each workshop. Certain student attitudes improved immediately after the first workshop. These workshops continue annually. CONCLUSIONS: Students have been a driving force behind this curriculum, which is a model for professionalism education. It was accepted by students and, although somewhat controversial, created a level of awareness and discussion regarding professional behavior in medical school that had previously been absent.

Molecular typing based on 12 loci containing variable numbers of tandem repeats of mycobacterial interspersed repetitive units (MIRU-VNTRs) has been adopted in combination with spoligotyping as the basis for large-scale, high-throughput genotyping of Mycobacterium tuberculosis. However, even the combination of these two methods is still less discriminatory than IS6110 fingerprinting. Here, we define an optimized set of MIRU-VNTR loci with a significantly higher discriminatory power. The resolution and the stability/robustness of 29 loci were analyzed, using a total of 824 tubercle bacillus isolates, including representatives of the main lineages identified worldwide so far. Five loci were excluded for lack of robustness and/or stability in serial isolates or isolates from epidemiologically linked patients. The use of the 24 remaining loci increased the number of types by 40%--and by 23% in combination with spoligotyping--among isolates from cosmopolitan origins, compared to those obtained with the original set of 12 loci. Consequently, the clustering rate was decreased by fourfold--by threefold in combination with spoligotyping--under the same conditions. A discriminatory subset of 15 loci with the highest evolutionary rates was then defined that concentrated 96% of the total resolution obtained with the full 24-locus set. Its predictive value for evaluating M. tuberculosis transmission was found to be equal to that of IS6110 restriction fragment length polymorphism typing, as shown in a companion population-based study. This 15-locus system is therefore proposed as the new standard for routine epidemiological discrimination of M. tuberculosis isolates and the 24-locus system as a high-resolution tool for phylogenetic studies