Page S. Morahan

Kinetics of changes in peritoneal cell populations following acute inflammation

The kinetics of macrophage (M phi) recruitment to the peritoneum following the induction of acute inflammation by thioglycollate broth (TG) was evaluated after prelabeling resident M phi with the fluorescent cell tracking dye, PKH-1. Most of the PKH-1-labeled resident M phi disappeared from the recoverable peritoneal cell population within the first hour after injection of TG. This disappearance coincided with the inflammatory influx of neutrophils (PMNs) and was sustained for at least 5 days after administration of TG, although the PMN number had returned to resident levels by this time. PKH-1-labeled peritoneal M phi were observed again in most animals at 7 days after injection of TG. The number of labeled M phi recovered at 7 days was approximately twice the number of resident peritoneal M phi in control animals which did not receive the TG broth. These additional M phi may include progeny of either the resident M phi or other local M phi precursors, such as omental M phi, which were labeled by the PKH-1 injection.

Effective faculty preceptoring and mentoring during reorganization of an academic medical center

The experience and lessons learned in the design, implementation and initial evaluation of a demonstration faculty-to-faculty mentoring program, during a time of major institutional reorganization, are described. The question addressed was: Can a voluntary mentoring program be established with minimal resources and be effective in the context of major organizational change? Key design elements included two-tiered programs (one year preceptoring and multi-year mentoring), voluntary participation, and selection of senior faculty members by the junior faculty members. A total of 20% of junior faculty and 30% of senior faculty participated. Faculty indicated the program was worth the time invested, had a positive impact on their professional life and increased productivity. There was high satisfaction with the mentoring relationship, especially the psychosocial mentoring functions, and a trend toward increased retention of minority faculty. Within two years, the program was institutionalized into the Office for Faculty Affairs, and faculty approved a mentoring policy. It is concluded that voluntary mentoring programs can have a positive impact on junior and senior faculty satisfaction, reinvigorate the collegial culture, and improve productivity and retention even during a time of reorganization and minimal resources.

Review of the macrophage disappearance reaction.

Macrophages (Mφs) undergo a physiological response known as the macrophage disappearance reaction (MDR) in response to certain stimuli in the peritoneal compartment. The types of stimuli that can cause the MDR, the relationship of the MDR to the host immunological response, and the possible role of the MDR in Mφ activation are reviewed. The data indicate that the MDR occurs in response to both acute nonspecific inflammatory and specific immune delayed hypersensitivity processes and that the MDR may play an important role in Mφ activation. J. Leukoc. Biol. 57: 361–367; 1995.

Innovative mentoring programs to promote gender equity in academic medicine.

The authors describe the history, characteristics, and goals of four innovative programs, each in a medical school, that were established in 1998 to help faculty members of both sexes obtain mentors and thereby facilitate their career advancement. The programs were established as the result of an initiative by the Office on Womens Health (OWH) within the U.S. Department of Health and Human Services. Specifically, the OWH convened the National Task Force on Mentoring for Health Professionals, which determined that two principles are paramount to the success of any mentoring relationship or program: institutional commitment and institutional rewards and recognition to mentors. In accordance with the task force findings, the OWH created the National Centers of Leadership in Academic Medicine, one at each of four medical schools: MCP Hahnemann School of Medicine; the University of California, San Diego, School of Medicine; East Carolina University School of Medicine; and Meharry Medical College School of Medicine. The authors give highlights of each programs goals and progress, and note that, ideally, these programs will eventually serve as models for similar programs at other schools. Programs such as these foster the advancement of a diverse faculty, a more supportive academic environemnt, and the education of providers who are sensitive to the needs of all their patients, staff, and colleagues.

Selective depletion of liver and splenic macrophages using liposomes encapsulating the drug dichloromethylene diphosphonate: effects on antimicrobial resistance.

The current results provide direct evidence for a role of tissue macrophages (Mφ) in natural immunity and support the use of immunomodulators to enhance antiviral resistance in immunocompromised individuals. In this study, macrophages (Mφ) in the spleen and liver were eliminated by intravenous (i.v.) injection of the drug dichloromethylene diphosphonate (DMDP) encapsulated in liposomes. The effect of this depletion system on peritoneal Mφ, peripheral blood leukocytes, splenic natural killer (NK) activity, and natural and immunomodulator‐induced host resistance was then assessed. Barrier‐maintained CD‐1 female mice were inoculated i.v. either with DMDP liposomes, free liposomes (containing no DMDP), or saline on day ‐2 or on days ‐3 and ‐1 before cell population analysis or infection. Single or double treatment with DMDP liposomes had no effect on peritoneal Mφ as indicated by no changes in total number, differential counts, or ectoenzyme patterns. Double treatment with DMDP liposomes caused a marked leukocytosis in blood, primarily of lymphocytes and polymorphonuclear leukocytes (PMN), and a transient depression of spontaneous and interferon‐inducible splenic NK activity. The effects on host resistance to i.v. infection with Listeria monocytogenes or herpes simplex virus type 2 (HSV‐2) indicated that i.v. treatment with DMDP liposomes significantly reduced natural resistance to these microorganisms as evidenced by increased mortality and decreased median survival time. When DMDP liposomes‐treated mice were given the immunomodulator maleic anhydride divinyl ether copolymer (MVE‐2) intraperitoneally the day before infection with HSV‐2, the immunosuppressive effect of DMDP liposome treatment was significantly reversed.

Maintenance of peritoneal macrophages in the steady state

Resident peritoneal macrophages (Mø) were labeled in situ by intraperitoneal (i.p.) injection of the green fluorescent cell tracking dye PKH‐1. After immunofluorescence staining with Mø specific monoclonal antibodies (Mabs) and phycoerythrin (PE) second antibody, the resident Mø were labeled with both the green dye and red Mab label, while recruited Mø were labeled only with the red Mab tag. These populations were distinguished by two‐color flow cytometry.

Ensuring the success of women faculty at AMCs: lessons learned from the National Centers of Excellence in Women's Health.

Since the early 1970s, the numbers of women entering medical school and, subsequently, academic medicine have increased substantially. However, women faculty have not advanced at the expected rate to senior academic ranks or positions of leadership. In 1996, to counter this trend, the U.S. Department of Health and Human Services (DHHS) Office on Womens Health included womens leadership as a required component of the nationally funded Centers of Excellence in Womens Health to identify effective strategies and initiate model programs to advance women faculty in academic medicine. The authors describe the experience of Centers at seven U.S. medical schools in initiating and sustaining leadership programs for women. The processes used for program formation, the current programmatic content, and program evaluation approaches are explained. Areas of success (e.g., obtaining support from the institutions leaders) and difficulties faced in maintaining an established program (such as institutional fiscal constraints and the diminishing time available to women to participate in mentoring and leadership activities) are reviewed. Strategies to overcome these and other difficulties (e.g., prioritize and tightly focus the program with the help of an advisory group) are proposed. The authors conclude by reviewing issues that programs for women in academic medicine will increasingly need to focus on (e.g., development of new kinds of skills; issues of recruitment and retention of faculty; and increasing faculty diversity).

Slowing the brain drain: FAIMER education programs.

Migration of physicians has produced serious shortages in many developing countries. The Foundation for Advancement of International Medical Education and Research (FAIMER) is attempting to show this international brain drain through creation of faculty development programs for medical school faculty from developing countries in order to strengthen medical education and help build a sustainable discipline of medical education. The goals of these programs are to allow Fellows to acquire basic skills in medical education, skills in leadership and management, and build a strong community of practice. Acquisition of these skills will improve medical education in their home country, stimulate growth of the field of medical education, and improve opportunities for professional advancement. Three programs currently exist: the FAIMER Institute, a two year fellowship with residential and distance learning components; International Fellowships in Medical Education, which funds selected Institute alumni to obtain masters degrees in medical education; and FAIMER regional institutes, which use the principles and structure embedded in the FAIMER Institute to build faculty development programs overseas. Evaluation of FAIMER programs indicates approximately one-third of Fellows have been promoted, and that a community of medical educators is being created in many developing countries which may promote retention of these physicians. Practice points•Slowing out-migration of medical educators from resource-poor countries will require development of field of medical education and pathway for professional advancement in that field.•Enhancement of faculty skills in medical education methods should be presented in conjunction with leadership and management skills required for implementation of those methods.•Active development of a community of practice in medical education will lead to enhanced support and productivity.•Program evaluation of a faculty medical education leadership program requires a variety of quantitative and qualitative data sources.

Evaluating a leadership program: a comparative, longitudinal study to assess the impact of the Executive Leadership in Academic Medicine (ELAM) Program for Women.

Purpose The Hedwig van Ameringen Executive Leadership in Academic Medicine (ELAM) program provides an external yearlong development program for senior women faculty in U.S. and Canadian medical schools. This study aims to determine the extent to which program participants, compared with women from two comparison groups, aspire to leadership, demonstrate mastery of leadership competencies, and attain leadership positions. Method A pre-/posttest methodology and longitudinal structure were used to evaluate the impact of ELAM participation. Participants from two ELAM cohorts were compared with women who applied but were not accepted into the ELAM program (NON) and women from the Association of American Medical Colleges (AAMC) Faculty Roster. The AAMC group was a baseline for midcareer faculty; the NON group allowed comparison for leadership aspiration. Baseline data were collected in 2002, with follow-up data collected in 2006. Sixteen leadership indicators were considered: administrative leadership attainment (four indicators), full professor academic rank (one), leadership competencies and readiness (eight), and leadership aspirations and education (three). Results For 15 of the indicators, ELAM participants scored higher than AAMC and NON groups, and for one indicator they scored higher than only the AAMC group (aspiration to leadership outside academic health centers). The differences were statistically significant for 12 indicators and were distributed across the categories. These included seven of the leadership competencies, three of the administrative leadership attainment indicators, and two of the leadership aspirations and education indicators. Conclusions These findings support the hypothesis that the ELAM program has a beneficial impact on ELAM fellows in terms of leadership behaviors and career progression.

Decreases in macrophage mediated antitumor activity with aging

We have demonstrated that immunotherapy of young (6-10 weeks old), and aged, (greater than 24 months old), tumor bearing mice with biological response modifiers enhanced survival and inhibited tumor growth, while treatment of aged mice had little or no effect. We hypothesized that the antitumor activity in young mice was principally mediated by activated macrophages (M phi) and predicted that the change in aged mice was caused by an intrinsic M phi defect which develops with advancing age. To directly test our hypothesis, we examined the antitumor activity of resident peritoneal M phi, purified and activated in vitro with IFN gamma plus LPS. Paralleling the results seen in vivo, M phi from aged mice exhibited reduced antitumor activity in comparison with M phi from younger mice. Moreover, there was reduced capacity of in vitro activated M phi from aged mice to produce TNF, IL-1 and nitric oxide, which are critical monokines and effector molecules that have been established to either directly inhibit tumor growth or cause tumor cell destruction. These studies establish that peritoneal M phi from aged mice have an intrinsic defect which prevents them from fully expressing their antitumor potential.