Faculty Bibliography

OBJECTIVE:The introduction of ablation technology has simplified surgical intervention for atrial fibrillation. However, most ablation devices cannot create focal transmural lesions on the beating heart and have difficulty ablating specific regions of the atria, such as the atrioventricular isthmus, coronary sinus, and ganglionated plexus. The purpose of this study was to examine the efficacy of a pen-type bipolar radiofrequency ablation device on both arrested and beating hearts. METHODS:Endocardial and epicardial atrial tissues in the free wall, left atrial roof, atrioventricular annuli, and coronary sinus were ablated for varying time intervals (2.5-15 seconds) in porcine cardioplegically arrested (n = 6) and beating (n = 9) hearts. The hearts were stained with 1% 2,3,5-triphenyl-tetrazolium chloride solution and sectioned to determine lesion depth and width. In 5 animals epicardial fat pads containing ganglionated plexus were stimulated and ablated. RESULTS:Lesion depth increased with ablation time similarly in both arrested and beating hearts. Transmurality was fully achieved in the thin atrial tissue (<4 mm) at 10 seconds in the beating and arrested hearts. The device had a maximal penetration depth of 6.1 mm. Epicardial ablation of the coronary sinus showed complete penetration through the left posterior atrium only in the arrested heart. Seven of 17 fat pads demonstrated a vagal response. All vagal responses were eliminated after ablation. CONCLUSION/CONCLUSIONS:The bipolar pen effectively ablated atrial tissue in both arrested and beating hearts. This device might allow the surgeon to ablate tissue in regions not accessible to other devices during atrial fibrillation surgery.

PURPOSE: To assess 23 years of Health Resources and Services Administration (HRSA) Title VII Training in Primary Care Medicine and Dentistry funding to the New York University School of Medicine/Bellevue Primary Care Internal Medicine Residency Program. The program, begun in 1983 within a traditional, inner-city, subspecialty-oriented internal medicine program, evolved into a crucible of systematic innovation, catalyzed and made feasible by initiatives funded by the HRSA. The curriculum stressed three pillars of generalism: psychosocial medicine, clinical epidemiology, and health policy. It developed tight, objectives-driven, effective, nonmedical specialty blocks and five weekly primary care activities that created a paradigm-driven, community-based, role-modeling matrix. Innovation was built in. Every block and activity was evaluated immediately and in an annual, program-wide retreat. Evaluation evolved from behavioral checklists of taped interviews to performance-based, systematic, annual objective structured clinical examinations. METHOD: The authors reviewed eight grant proposals, project reports, and curriculum and program evaluations. They also quantitatively and qualitatively surveyed the 122 reachable graduates from the first 20 graduating classes of the program. RESULTS: Analysis of program documents revealed recurring emphases on the use of proven educational models, strategic innovation, and assessment and evaluation to design and refine the program. There were 104 respondents (85%) to the survey. A total of 87% of the graduates practice as primary care physicians, 83% teach, and 90% work with the underserved; 54% do research, 36% actively advocate on health issues for their patients, programs, and other constituencies, and 30% publish. Graduates cited work in the community and faculty excitement and energy as essential elements of the program's impact; overall, graduates reported high personal and career satisfaction and low burnout. CONCLUSIONS: With HRSA support, a focused, innovative program evolved which has already met each of the six recommendations for future innovation of the Alliance for Academic Internal Medicine Education Redesign Task Force. This article is part of a theme issue of Academic Medicine on the Title VII health professions training programs

Recent preclinical and epidemiologic studies have suggested that certain Mycobacterium tuberculosis genotypes (in particular, Beijing lineage strains) may be resistant to Mycobacterium bovis BCG vaccine-induced antituberculosis protective immunity. To investigate the strain specificity of BCG-induced protective responses in a murine model of pulmonary tuberculosis, C57BL/6 mice were vaccinated with BCG vaccine and then challenged 2 months later with one of nine M. tuberculosis isolates. Four of these strains were from the W-Beijing lineage (HN878, N4, NHN5, and ChS) while four were non-Beijing-type isolates (C913, CDC1551, NY669, and NY920). As a control, the WHO standard M. tuberculosis Erdman strain was evaluated in these vaccination/challenge experiments. To assess the protective responses evoked by BCG immunization, organ bacterial burdens and lung pathology were assessed in vaccinated and naive mice at 4, 12, and 20 weeks postchallenge as well as during the day of infection. At 4 weeks after the aerosol challenge with each of these strains, significantly reduced bacterial growth in the lungs and spleens and significantly improved lung pathology were seen in all vaccinated animals compared to naive controls. After 12 weeks, reduced organ bacterial burdens were detected in vaccinated animals infected with six of nine challenge strains. Although lung CFU values were lower in vaccinated mice for only three of nine groups at 20 weeks postchallenge, significantly decreased lung inflammation was seen in all immunized animals relative to controls at 20 weeks postchallenge. Taken together, these data demonstrate that BCG vaccination protects against infection with diverse M. tuberculosis strains in the mouse model of pulmonary tuberculosis and suggest that strain-specific resistance to BCG-induced protective immunity may be uncommon

The objective of this study was to describe the cultural domain of ethical behaviours in clinical practice as defined by health care providers in Mexico. Structured interviews were carried out with 500 health professionals employed at the Mexican Institute of Social Security in Mexico City. The Smith Salience Index was used to evaluate the relevance of concepts gathered from the free listings of the interviewees. Cluster analysis and factor analysis facilitated construction of the conceptual categories, which the authors refer to as ;dimensions of ethical practice'. Six dimensions emerged from the analysis to define the qualities that comprise ethical clinical practice for Mexican health care providers: overall quality of clinical performance; working conditions that favour quality of care; use of ethical considerations as prerequisites for any health care intervention; values favouring teamwork in the health professional-patient relationship; patient satisfaction scores; and communication between health care providers and patients. The findings suggest that improved working conditions and management practices that promote the values identified by the study's participants would help to improve quality of care.

OBJECTIVE:The effects of the Cox maze procedure on atrial function remain poorly defined. The purpose of this study was to investigate the effects of a modified Cox maze procedure on left and right atrial function in a porcine model. METHODS:After cardiac magnetic resonance imaging, 6 pigs underwent pericardiotomy (sham group), and 6 pigs underwent a modified Cox maze procedure (maze group) with bipolar radiofrequency ablation. The maze group had preablation and immediate postablation left and right atrial pressure-volume relations measured with conductance catheters. All pigs survived for 30 days. Magnetic resonance imaging was then repeated for both groups, and conductance catheter measurements were repeated for the right atrium in the maze group. RESULTS:Both groups had significantly higher left atrial volumes postoperatively. Magnetic resonance imaging-derived reservoir and booster pump functional parameters were reduced postoperatively for both groups, but there was no difference in these parameters between the groups. The maze group had significantly higher reduction in the medial and lateral left atrial wall contraction postoperatively. There was no change in immediate left atrial elastance or in the early and 30-day right atrial elastance after the Cox maze procedure. Although the initial left atrial stiffness increased after ablation, right atrial diastolic stiffness did not change initially or at 30 days. CONCLUSIONS:Performing a pericardiotomy alone had a significant effect on atrial function that can be quantified by means of magnetic resonance imaging. The effects of the Cox maze procedure on left atrial function could only be detected by analyzing segmental wall motion. Understanding the precise physiologic effects of the Cox maze procedure on atrial function will help in developing less-damaging lesion sets for the surgical treatment of atrial fibrillation.

Meiosis is coupled to gamete development and must be well regulated to prevent aneuploidy. During meiotic maturation, Drosophila oocytes progress from prophase I to metaphase I. The molecular factors controlling meiotic maturation timing, however, are poorly understood. We show that Drosophila alpha-endosulfine (endos) plays a key role in this process. endos mutant oocytes have a prolonged prophase I and fail to progress to metaphase I. This phenotype is similar to that of mutants of cdc2 (synonymous with cdk1) and of twine, the meiotic homolog of cdc25, which is required for Cdk1 activation. We found that Twine and Polo kinase levels are reduced in endos mutants, and identified Early girl (Elgi), a predicted E3 ubiquitin ligase, as a strong Endos-binding protein. In elgi mutant oocytes, the transition into metaphase I occurs prematurely, but Polo and Twine levels are unaffected. These results suggest that Endos controls meiotic maturation by regulating Twine and Polo levels, and, independently, by antagonizing Elgi. Finally, germline-specific expression of the human alpha-endosulfine ENSA rescues the endos mutant meiotic defects and infertility, and alpha-endosulfine is expressed in mouse oocytes, suggesting potential conservation of its meiotic function.

Loss-of-function mutations in the Arabidopsis (Arabidopsis thaliana) ENHANCED DISEASE RESISTANCE1 (EDR1) gene confer enhanced resistance to infection by powdery mildew (Golovinomyces cichoracearum). EDR1 encodes a protein kinase, but its substrates and the pathways regulated by EDR1 are unknown. To identify components of the EDR1 signal transduction pathway(s), we conducted a forward genetic screen for mutations that suppressed edr1-mediated disease resistance. Genetic mapping and cloning of one of these suppressor mutations revealed a recessive missense mutation in the KEEP ON GOING gene (KEG; At5g13530), which we designated keg-4. KEG encodes a multidomain protein that includes a RING E3 ligase domain, a kinase domain, ankyrin repeats, and HERC2-like repeats. The KEG protein has previously been shown to have ubiquitin ligase activity and to negatively regulate protein levels of the transcription factor ABCISIC ACID INSENSITIVE5. KEG mRNA levels were found to be 3-fold higher in edr1 mutant plants compared to wild type. Loss-of-function mutations in KEG are seedling lethal and are hypersensitive to glucose and abscisic acid (ABA). The keg-4 mutation, in contrast, conferred resistance to 6% glucose and suppressed edr1-mediated hypersensitivity to ABA, suggesting that the keg-4 mutation suppresses ABA signaling by altering KEG function. Several ABA-responsive genes were found to be further up-regulated in the edr1 mutant following ABA treatment, and this up-regulation was suppressed by the keg-4 mutation. We conclude that edr1-mediated resistance to powdery mildew is mediated, in part, by enhanced ABA signaling.