Recent Publications by CFE Educators

Longitudinal population studies have confirmed plasma levels of high-density lipoprotein (HDL) cholesterol to be an important inverse coronary risk factor. Although environmental influences are known to regulate HDL cholesterol levels, genetic factors are also known to be important, and over 25 candidate genes have been proposed to be associated with variation in HDL cholesterol levels. A variety of monogenic conditions of extremely low or high HDL cholesterol has helped to delineate the physiology of HDL cholesterol metabolism in humans, which has led to the development of new therapeutic approaches to HDL cholesterol. However, most causes of genetic variation in HDL cholesterol in the general population are likely oligogenic or polygenic. We review the monogenic disorders associated with both high and low HDL cholesterol and the relevance of mutations and polymorphisms in these genes to variation in HDL cholesterol levels in the general population.

Interns are expected to teach medical students, yet there is little formal training in medical school to prepare them for this role. To enhance the teaching skills of our graduating students we initiated a 4-hour "teaching to teach" course as part of the end of the fourth-year curriculum. Course evaluations demonstrate that students strongly support this program (overall ratings 2000 to 2005: mean=4.4 [scale 1 to 5], n=224). When 2004 course participants were surveyed during the last month of their internship, 84%"agree" or "strongly agree" with the statement: "The teaching to teach course helped prepare me for my role as a teacher during internship" (2005: mean 4.2 [scale 1 to 5], n=45, response rate 60%). A course preparing fourth-year students to teach during internship is both feasible and reproducible, with a minimal commitment of faculty and resident time. Participants identify it as an important addition to their education and as useful during internship.

AIM

The Primary Medical Education (PRIME) program is an outpatient-based, internal medicine residency track nested within the University of California, San Francisco (UCSF) categorical medicine program. Primary Medical Education is based at the San Francisco Veteran's Affairs Medical Center (VAMC), 1 of 3 teaching hospitals at UCSF. The program accepts 8 UCSF medicine residents annually, who differentiate into PRIME after internship. In 2000, we implemented a novel research methods curriculum with the dual purposes of teaching basic epidemiology skills and providing mentored opportunities for clinical research projects during residency.

SETTING

Single academic internal medicine program.

PROGRAM DESCRIPTION

The PRIME curriculum utilizes didactic lecture, frequent journal clubs, work-in-progress sessions, and active mentoring to enable residents to "try out" a clinical research project during residency.

PROGRAM EVALUATION

Among 32 residents in 4 years, 22 residents have produced 20 papers in peer-reviewed journals, 1 paper under review, and 2 book chapters. Their clinical evaluations are equivalent to other UCSF medicine residents.

DISCUSSION

While learning skills in evidence-based medicine, residents can conduct high-quality research. Utilizing a collaboration of General Internal Medicine researchers and educators, our curriculum affords residents the opportunity to "try-out" clinical research as a potential future career choice.

Millions of persons around the world are exposed to low doses of arsenic through drinking water. However, estimates of health effects associated with low-dose arsenic exposure have been extrapolated from high-dose studies. In Bangladesh, many persons have been exposed to a wide range of doses of arsenic from drinking water over a significant period of time. The authors evaluated dose-response relations between arsenic exposure from drinking water and premalignant skin lesions by using baseline data on 11,746 participants recruited in 2000-2002 for the Health Effects of Arsenic Longitudinal Study in Araihazar, Bangladesh. Several measures of arsenic exposure were estimated for each participant based on well-water arsenic concentration and usage pattern of the wells and on urinary arsenic concentration. In different regression models, consistent dose-response effects were observed for all arsenic exposure measures. Compared with drinking water containing 8.1 microg/liter of arsenic, drinking water containing 8.1-40.0, 40.1-91.0, 91.1-175.0, and 175.1-864.0 microg/liter of arsenic was associated with adjusted prevalence odds ratios of skin lesions of 1.91 (95% confidence interval (CI): 1.26, 2.89), 3.03 (95% CI: 2.05, 4.50), 3.71 (95% CI: 2.53, 5.44), and 5.39 (95% CI: 3.69, 7.86), respectively. The effect seemed to be influenced by gender, age, and body mass index. These findings provide information that should be considered in future research and policy decisions.

Prodynorphin-derived peptides elicit various pathological effects including neurological dysfunction and cell death. These actions are reduced by N-methyl-d-aspartate receptor (NMDAR) but not opioid receptor antagonists suggesting NMDAR-mediation. Here, we show that a conserved epitope (KVNSEEEEEDA) of the NR1 subunit of the NMDAR binds dynorphin peptides (DYNp) noncovalently. Synthetic peptides containing this epitope form stable complexes with DYNp and prevent the potentiation of NMDAR-gated currents produced by DYNp. They attenuate DYNp-evoked cell death in spinal cord and prevent, as well as reverse, DYNp-induced paralysis and allodynia. The data reveal a novel mechanism whereby prodynorphin-derived peptides facilitate NMDAR function and produce neurotoxicity. Furthermore, they suggest that synthetic peptides that bind DYNp, thus preventing their interaction with NMDAR, may be novel therapeutic agents for the treatment of spinal cord injury.

OBJECTIVES

To determine whether the failure of the orexigenic hormone ghrelin to increase as it normally does with weight loss contributes to impaired weight recovery in older persons.

DESIGN

Prospective diet intervention study.

SETTING

University of Washington Medical Center from 2001 through 2005.

PARTICIPANTS

Twenty-one younger (18-35) and 18 older (> or =70) men and women.

INTERVENTION

Two weeks of a weight-maintaining diet were followed in sequence by 2 weeks of 30% calorie restriction, then 4 weeks of ad libitum food intake.

MEASUREMENTS

Twenty-four-hour plasma ghrelin levels, dual x-ray absorptiometry scan for body composition, resting energy expenditure, and calorie intakes were measured.

RESULTS

Both younger and older subjects lost weight with calorie restriction and failed to fully regain their baseline weight. The older adults trended toward increasing their calorie intake above their baseline level during the ad libitum period (111+/-66 kcal, P=.11), whereas the younger individuals did not (-236+/-95 kcal, P=.02). There was no statistically significant difference between the two cohorts in 24-hour ghrelin levels before or after calorie restriction. Ghrelin levels in the two cohorts increased equivalently after calorie restriction and decreased after ad libitum food consumption resumed.

CONCLUSION

Ghrelin levels in healthy older individuals respond appropriately in a compensatory manner to changes in body weight and calorie intake.

PURPOSE

To investigate whether gadolinium (Gd)-based contrast enhancement (CE) affects high-resolution magnetic resonance imaging (MRI) measurements of carotid arterial wall volume.

MATERIALS AND METHODS

The common carotid artery (CCA), bifurcation, and internal carotid artery (ICA) of 50 consecutive patients were imaged using 1.5T MRI. T1-weighted (T1W) images were obtained before and after Gd administration. Pre- and post-CE measurements were compared among different arterial locations of the CCA, bifurcation, and ICA, and among different atherosclerotic lesion types.

RESULTS

In comparison to pre-CE T1W images, post-CE images showed an increase in the apparent wall volume measurement of 28.2% (108.7 mm3 vs. 84.7 mm3, P 0.001). The post-CE measurement increases in wall volume for the CCA, bifurcation, and ICA were 26.7%, 29.2%, and 28.0%, respectively.

CONCLUSION

Gd CE causes a significant increase in the apparent volume of the carotid wall throughout multiple carotid artery locations, which may be associated with improved visibility or neovascularization.