Recent Publications by CFE Educators

The Academy of Medical Educators at the University of California, San Francisco (UCSF), was established in 2000 to (1) foster excellence in teaching, (2) support teachers of medicine, and (3) promote curricular innovation. A membership organization, it recognizes five categories of educational activity: direct teaching, curriculum development and assessment of learner performance, advising and mentoring, educational administration and leadership, and educational research. Excellent medical student teaching and outstanding accomplishment in one or more areas of educational activity qualify a teacher for membership. Candidates prepare a portfolio that is reviewed internally and by national experts in medical education. Currently 37 faculty members, 3% of the entire school of medicine faculty, belong to the academy. The academy's innovations funding program disburses one-year grants to support curricular development and comparisons of pedagogical approaches; through this mechanism, the academy has funded 20 projects at a total cost of $442,300. Three fourths of expended funds support faculty release time. Faculty development efforts include promotion of the use of an educator's portfolio and the establishment of a mentoring program for junior faculty members built around observation of teaching. The Academy of Medical Educators vigorously supports expanded scholarship in education; the academy-sponsored Education Day is an opportunity for educators to present their work locally. Recipients of innovations-funding program grants are expected to present their work in an appropriate national forum and are assisted in doing this through quarterly scholarship clinics. The Academy of Medical Educators has been well received at UCSF and is enhancing the status of medical education and teachers.

Human immunodeficiency virus (HIV)-specific CD8(+) T-lymphocyte pressure can lead to the development of viral escape mutants, with consequent loss of immune control. Antiretroviral drugs also exert selection pressures on HIV, leading to the emergence of drug resistance mutations and increased levels of viral replication. We have determined a minimal epitope of HIV protease, amino acids 76 to 84, towards which a CD8(+) T-lymphocyte response is directed. This epitope, which is HLA-A2 restricted, includes two amino acids that commonly mutate (V82A and I84V) in the face of protease inhibitor therapy. Among 29 HIV-infected patients who were treated with protease inhibitors and who had developed resistance to these drugs, we show that the wild-type PR82V(76-84) epitope is commonly recognized by cytotoxic T lymphocytes (CTL) in HLA-A2-positive patients and that the CTL directed to this epitope are of high avidity. In contrast, the mutant PR82A(76-84) epitope is generally not recognized by wild-type-specific CTL, or when recognized it is of low to moderate avidity, suggesting that the protease inhibitor-selected V82A mutation acts both as a CTL and protease inhibitor escape mutant. Paradoxically, the absence of a mutation at position 82 was associated with the presence of a high-avidity CD8(+) T-cell response to the wild-type virus sequence. Our results indicate that both HIV type 1-specific CD8(+) T cells and antiretroviral drugs provide complex pressures on the same amino acid sequence of the HIV protease gene and, thus, can influence viral sequence evolution.

There is significant heterogeneity in survival time among patients with idiopathic pulmonary fibrosis. Studies of baseline clinical and physiologic variables as predictors of survival time have reported inconsistent results. We evaluated the predictive value of changes in clinical and physiologic variables over time for survival time in 81 patients with biopsy-proven idiopathic pulmonary fibrosis. Six-month changes in dyspnea score, total lung capacity, thoracic gas volume, FVC, FEV1, diffusing capacity of carbon monoxide, partial pressure of arterial oxygen, oxygen saturation, and alveolar-arterial oxygen gradient were predictive of survival time even after adjustment for baseline values. Analyses were repeated on 51 patients with 12-month change data. Twelve-month changes in dyspnea score, total lung capacity, FVC, partial pressure of arterial oxygen, oxygen saturation, and alveolar-arterial oxygen gradient were predictive of survival time after adjustment for baseline values. Evaluation of changes in clinical and physiological variables over 6 and 12 months may provide clinicians with more accurate prognostic information than baseline values alone.

Anemia presents a challenge both in determination of cause and appropriate management. Careful history taking and appropriate screening in keeping with AAP recommendations will aid in identifying cases of anemia. Judicious use of laboratory testing will assist in achieving accurate diagnosis. Finally, appropriately timed and monitored treatment strategies will offer the most optimal outcome.

BACKGROUND

Few studies have examined the relationship between subject-reported allergy and results of allergy skin testing in large unselected or unbiased cohorts. The objective of this study was to compare the results of self-reported allergy via verbal questioning with the results of allergy skin testing by the puncture method in 237 healthy adult subjects enrolled in a common cold study.

METHODS

On enrollment, all subjects were verbally asked if they had a history of allergy and then underwent puncture skin testing to 19 relevant aeroallergens, as well as appropriate positive and negative controls. A skin test was considered positive if its wheal diameter was at least 3 mm larger than that obtained with the negative control.

RESULTS

Forty-eight (20%) subjects reported a history of allergy and 124 (52%) subjects had at least one positive skin test response. A history of allergy was reported in 40 (32%) of the skin test-positive subjects and 8 (7%) of the skin test-negative subjects. At least one positive skin test response was found in 40 (83%) of those subjects reporting a history of allergy and 84 (44%) of those subjects denying a history of allergy.

CONCLUSION

These data indicate that there is a relatively poor correlation between self-reported history of allergy and skin test results in subjects enrolled in a common cold study. These results have implications in both clinical practice and research settings.

Impaired lung function in severe acute pancreatitis is the primary cause of morbidity and mortality in this condition. Preprotachykinin-A (PPT-A) gene products substance P and neurokinin (NK)-A have been shown to play important roles in neurogenic inflammation. Substance P acts primarily (but not exclusively) via the NK1 receptor. NKA acts primarily via the NK2 receptor. Earlier work has shown that knockout mice deficient in NK1 receptors are protected against acute pancreatitis and associated lung injury. NK1 receptors, however, bind other peptides in addition to substance P, not all of which are derived from the PPT-A gene. To examine the role of PPT-A gene products in acute pancreatitis, the effect of PPT-A gene deletion on the severity of acute pancreatitis and the associated lung injury was investigated. Deletion of PPT-A almost completely protected against acute pancreatitis-associated lung injury, with a partial protection against local pancreatic damage. These results show that PPT-A gene products are critical proinflammatory mediators in acute pancreatitis and the associated lung injury.