Recent Publications by CFE Educators

Of the carcinogens to which humans are most frequently exposed, the polycyclic aromatic hydrocarbon benzo[a]pyrene (BP) is one of the most ubiquitous. BP is a byproduct of grilled foods and tobacco and fuel combustion and has long been linked to various human cancers, particularly lung and skin. BP is metabolized to diol epoxides that covalently modify DNA bases to form bulky adducts that block DNA synthesis by replicative or high fidelity DNA polymerases. Here we present the structure of a high fidelity polymerase from a thermostable strain of Bacillus stearothermophilus (Bacillus fragment) bound to the most common BP-derived N2-guanine adduct base-paired with cytosine. The BP adduct adopts a conformation that places the polycyclic BP moiety in the nascent DNA minor groove and is the first structure of a minor groove adduct bound to a polymerase. Orientation of the BP moiety into the nascent DNA minor groove results in extensive disruption to the interactions between the adducted DNA duplex and the polymerase. The disruptions revealed by the structure of Bacillus fragment bound to a BP adduct provide a molecular basis for rationalizing the potent blocking effect on replication exerted by BP adducts.

An emotionally-distressed, elderly Caucasian woman presented with chest pain and hypertension. Electrocardiogram showed inferior ST-segment elevation, and an urgent cardiac catheterization was performed. Coronary angiography revealed normal appearing coronary arteries; however, left ventriculography showed extensive left ventricular apical akinesis. The patient had a mild rise in cardiac enzyme levels indicative of myocardial injury. She was discharged after an uncomplicated in-hospital course. One month later, the left ventricular wall motion abnormality had improved. In this report, the authors discuss this compilation of findings known as tako-tsubo-like left ventricular dysfunction.

Workers employed in 15 utilities that generate nuclear power in the United States have been followed for up to 18 years between 1979 and 1997. Their cumulative dose from whole body ionizing radiation has been determined from the dose records maintained by the facilities themselves and the REIRS and REMS systems maintained by the Nuclear Regulatory Commission and the Department of Energy, respectively. Mortality in the cohort from a number of causes has been analyzed with respect to individual radiation doses. The cohort displays a very substantial healthy worker effect, i.e. considerably lower cancer and noncancer mortality than the general population. Based on 26 and 368 deaths, respectively, positive though statistically nonsignificant associations were seen for mortality from leukemia (excluding chronic lymphocytic leukemia) and all solid cancers combined, with excess relative risks per sievert of 5.67 [95% confidence interval (CI) -2.56, 30.4] and 0.506 (95% CI -2.01, 4.64), respectively. These estimates are very similar to those from the atomic bomb survivors study, though the wide confidence intervals are also consistent with lower or higher risk estimates. A strong positive and statistically significant association between radiation dose and deaths from arteriosclerotic heart disease including coronary heart disease was also observed in the cohort, with an ERR of 8.78 (95% CI 2.10, 20.0). While associations with heart disease have been reported in some other occupational studies, the magnitude of the present association is not consistent with them and therefore needs cautious interpretation and merits further attention. At present, the relatively small number of deaths and the young age of the cohort (mean age at end of follow-up is 45 years) limit the power of the study, but further follow-up and the inclusion of the present data in an ongoing IARC combined analysis of nuclear workers from 15 countries will have greater power for testing the main hypotheses of interest.

The objective of this study was to describe the relationship between attendance at conferences during residency training and residents' performance on the In-Training Examination (ITE) in Internal Medicine. Nineteen house officers participated in the study. Conference attendance records were retrospectively reviewed for the one-year period preceding the ITE (pre-ITE), and in the three-month period after house officers received their ITE scores (post-ITE). After receiving their scores, participants completed a questionnaire asking about study habits and opinions about conferences. Attendance was taken at 126/165 (76.4%) conferences pre-ITE and 32/42 (76.2%) conferences post-ITE. House officers attended a mean of 35% (range, 10-59) of the conferences pre-ITE and 32% (range, 9-75) post-ITE (p = 0.365). There was no correlation between prior conference attendance and ITE scores (Spearman correlation coefficient -0.230, p = 0.34), and no correlation between score and conference attendance post-ITE (Spearman correlation coefficient 0.174, p = 0.48). Participation in clinical rotations also failed to influence ITE scores in that content area (all p > 0.05). The findings of this study suggest conference attendance does not influence ITE scores. Medical educators may need to rethink and study how best to impart medical knowledge.

In term neonatal encephalopathy, little is known about the relationship between early inflammatory markers, neonatal brain injury, and long-term neurodevelopmental outcome. Our goal was to determine whether neonatal serum cytokine levels are associated with cerebral metabolism assessed by proton magnetic resonance spectroscopy (MRS), with magnetic resonance imaging (MRI) abnormalities, and with neurodevelopmental outcome at 30 mo of age. Levels of seven cytokines [IL-1 beta, IL-6, IL-8, IL-9, IL-12, IL-13, and tumor necrosis factor (TNF)-alpha] were measured in dried neonatal blood by immunoaffinity chromatography in a prospective cohort of 62 term newborns at risk of neonatal encephalopathy. MR images (n = 61) were scored and lactate/choline and N-acetyl-aspartate (NAA)/choline were measured by MRS (n = 42) on median day of life 6 in the deep gray nuclei (DGN) and in the watershed/cortical zone (WS). Neurodevelopmental outcome (n = 54) was considered abnormal if the infant died or if cognitive delay and/or functional motor deficit were detected at 30 mo. IL-1 beta, IL-6, IL-8 and TNF-alpha were significantly associated with lactate/choline in the DGN (p = 0.03, 0.02, 0.03, and 0.01 respectively), but not in the WS (all p > 0.1). Cytokines were not associated with NAA/choline in any region or with MRI scores. Children with abnormal neurodevelopmental outcome had higher neonatal levels of IL-1 beta, IL-6, IL-8, and lower levels of IL-12 (p = 0.04, 0.03, 0.01, 0.03 respectively). Elevated inflammatory cytokines were associated with impaired cerebral oxidative metabolism, but not with detectable MRI changes in the neonatal period. Understanding the link between elevated cytokines and outcome would inform novel strategies of cerebral protection.

Although the lesions of psoriasis might be "skin deep," the disease has dramatic physical,mental, social and financial ramifications for those it afflicts. Clinicians should be able to assess the impact of psoriasis on quality of life (QOL) to measure disease severity,monitor improvement, and ensure equitable funding for research and reimbursement. The development of various clinical tools to assess health-related QOL has led to increasing awareness of the extent of patient morbidity. The fact that psoriasis causes disability comparable to that seen in other major systemic diseases has important implications for how it should be viewed and treated.

OBJECTIVE

To examine how the association between excessive weight gain and cesarean birth is modified by infant birth weight in nondiabetic women.

METHODS

We designed a retrospective cohort study of singleton, term, nulliparous women with cephalic presentations delivering at a single university hospital. Subjects with diabetes were excluded. Bivariate and multivariate analyses were performed. Regression models controlled for maternal age, maternal prepregnancy body mass index, gestational age, ethnicity, smoking, birth weight, and date of delivery.

RESULTS

Women gaining above Institute of Medicine guidelines were more likely to have a cesarean birth, even if birth weight was less than 4,000 g. In the multivariate analysis, women with excessive weight gain had an odds ratio of 1.40 (95% confidence interval 1.22-1.59) for cesarean birth. When absolute weight gain (total pregnancy weight gain minus birth weight and placental weight) was used in the multivariate analysis, excessive weight gain was still an independent predictor of cesarean delivery. Although macrosomia was a stronger predictor of cesarean than weight gain alone, excessive weight gain was much more common than macrosomia in our cohort.

CONCLUSION

Excessive weight gain during pregnancy is an independent risk factor for cesarean birth, even when birth weight is not excessive. Other mechanisms besides macrosomia may be involved in the association between high weight gain and cesarean birth. We estimate that of the approximately 288,000 primary cesarean deliveries performed in nulliparas annually in the United States, 64,000 would be prevented if no women gained above Institute of Medicine recommendations.

LEVEL OF EVIDENCE

II-2

Over the past seven years, educational innovations and scholarship have flourished at the University of California, San Francisco, (UCSF) School of Medicine. Prior to 1998, there was no infrastructure to support educational research and yet a few faculty members published in medical education journals and were active in national professional associations. With the initiation of curriculum reform in 1998, a great deal of excitement about education was generated and innovative new educational programs were envisioned. These changes became opportunities for educational scholarship. With the development of an Office of Medical Education in 1997 and the Haile T. Debas Academy of Medical Educators in 2001, the infrastructure was in place to expand educational research and the scholarship of teaching. The components of this support include educational leadership, faculty development, the Teaching Scholars Program, the Office of Educational Research and Development, the Academy, a Fellowship in Medical Education Research, collaborative research, and extramural grants. As a result of these investments, the number of UCSF faculty members who are involved in educational research has increased significantly. There has been a four-fold increase in peer-reviewed articles published in medical education journals and a greater increase in the publication of educational abstracts, editorials, chapters, and books, plus presentations at U.S. professional association meetings. In this article, the authors describe the changes that have occurred at UCSF to achieve these results.