The difficulty of sustaining curricular reforms: a study of "drift" at one school.

In 1997, five years after a major curricular reform at the University of Michigan Medical School, the authors revisited the Goals for Medical Education (written by faculty to guide the reform process) to identify factors that had facilitated or hindered their achievement. By reviewing responses to identical questionnaires circulated to faculty in 1993 and again in 1997, they learned that considerably more lectures were being used to deliver curricular content in the first-year curriculum than the faculty thought was ideal, and that less social science, humanities, and ethics material was being presented in the first year than the faculty thought was ideal. The authors also learned that consensus between faculty basic scientists and faculty clinicians about the content that would make up an ideal first-year curriculum had diverged since adoption of the new curriculum. Movement toward decreasing the amounts of social sciences, humanities, and ethics in the first year of medical school was particularly pronounced among the basic scientists, who felt this material was being taught prematurely and at the expense of essential basic science content. In contrast, by 1997 much closer agreement had developed between the two groups regarding time they would allocate for lectures; this agreement unfortunately reflected a stagnation in the adoption of active learning methods. Movement toward increasing the amount of time for lectures in the first-year curriculum was particularly pronounced among the clinicians, who reported feeling more and more pressured to bring in clinical revenues. Based on faculty comments and the school's experience with centralized governance and centralized funding, the authors propose a direct linkage between institutional funding to departments and the teaching effort of faculty in the departments, and sufficient, centralized funding to relieve pressure on faculty and to foster educational creativity. They maintain that this may be the most effective way to guarantee ongoing innovation, support interdisciplinary teaching, and subsequently move the curriculum and teachers completely away from content that is isolated within traditional department structures. At the same time they acknowledge that changing faculty attitudes presents a challenge.

Compostela Valley: a new endemic focus for Capillariasis philippinensis.

A 20 year old female from Compostela Valley Province in the Philippines, presenting with chronic diarrhea, borborygmi, bipedal edema, anorexia and weight loss was seen at Davao Regional Hospital. Her stool specimen, suspected by a local medical technologist to have Capillaria philippinensis ova, was forwarded to the Diagnostic Parasitology Laboratory of the College of Public Health, University of the Philippines Manila. It was examined and found to contain Capillaria philippinensis adults, larvae and eggs. Twelve deaths among people coming from the same barangay, affected by a similar illness with no definite diagnosis except "gastroenteritis" were also reported. These prompted health officials to send a team that would investigate the etiology of the disease outbreak labeled as a "Mystery Disease". Seventy-two stool samples from symptomatic patients were examined. Fifty-three (73.6%) individuals were proven to harbor at least one parasite with 16 (22.2%) individuals positive for Capillaria philippinensis infection. Ocular inspection, interviews and focus group discussions revealed that the people's eating habits are not much different from the habits of those from the Ilocos provinces where capillariasis was initially described. In both areas, people are fond of eating kinilaw or raw fish. They also eat raw shrimps, crabs and snails. Furthermore, the people defecate in the field or in the same body of water where they get the fishes, shrimps, crabs and snails that they eat, thus completing the life cycle of Capillaria philippinensis. Fish-eating birds were likely to have spread this parasite to the area. This is the first report of a capillariasis outbreak in Compostela Valley Province, and this should alert health authorities to consider embarking on serious efforts for developing proficiency of laboratory and clinical diagnosis especially in government health facilities where the poor and marginalized sectors of society are likely to consult.

In vivo regulation of replicative Legionella pneumophila lung infection by endogenous interleukin-12.

The in vivo role of endogenous interleukin 12 (IL-12) in modulating intrapulmonary growth of Legionella pneumophila was assessed by using a murine model of replicative L. pneumophila lung infection. Intratracheal inoculation of A/J mice with virulent bacteria (10(6) L. pneumophila cells per mouse) resulted in induction of IL-12, which preceded clearance of the bacteria from the lung. Inhibition of endogenous IL-12 activity, via administration of IL-12 neutralizing antiserum, resulted in enhanced intrapulmonary growth of the bacteria within 5 days postinfection (compared to untreated L. pneumophila-infected mice). Because IL-12 has previously been shown to modulate the expression of cytokines, including gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and IL-10, which regulate L. pneumophila growth, immunomodulatory effects of endogenous IL-12 on intrapulmonary levels of these cytokines during replicative L. pneumophila lung infection were subsequently assessed. Results of these experiments demonstrated that TNF-alpha activity was significantly lower, while protein levels of IFN-gamma and IL-10 in the lung were similar, in L. pneumophila-infected mice administered IL-12 antiserum, compared to similarly infected untreated mice. Together, these results demonstrate that IL-12 is critical for resolution of replicative L. pneumophila lung infection and suggest that regulation of intrapulmonary growth of L. pneumophila by endogenous IL-12 is mediated, at least in part, by TNF-alpha.

Development and evaluation of an instrument to assess medical students' cultural attitudes.

This paper describes the development and psychometric evaluation of an instrument designed to assess medical students' comfort with a range of sociocultural issues and intercultural experiences. Each survey item obliged students to reflect on their own sociocultural identities and academic status in relation to others', and to judge how comfortable they would be interacting across perceived boundaries based on sociocultural identity and academic status. More than 90% of University of Michigan first-year medical students (n=153) completed the survey just before classes began. Principal components analysis of the survey's 26 items identified 7 interpretable factors or subscales; the Cronbach alpha reliability coefficients for the 7 subscales and the total scale ranged from .73 to .92. T-tests were used to investigate differences in average ratings among student subgroups (based on gender and ethnicity). To assess the magnitude of the effect of the differences between groups, effect size was computed for each of the means comparisons. Psychometric analyses indicated that this survey was both reliable and valid for assessing students' cultural attitudes. Further, analyses by gender and ethnic subgroup identified meaningful ratings differences in men's and women's reported comfort levels. Our findings suggest that this instrument is useful for assessing students' openness to developing cultural awareness and competence. Educators at other medical schools may find this instrument useful as a needs assessment tool for planning educational programs designed to increase students' cultural competence.

The role of Legionella pneumophila-infected Hartmannella vermiformis as an infectious particle in a murine model of Legionnaire's disease.

Legionella pneumophila is a bacterial parasite of many species of freshwater protozoa and occasionally an intracellular pathogen of humans. While protozoa are known to play a key role in the persistence of L. pneumophila in the environment, there has been limited research addressing the potential role of L. pneumophila-infected protozoa in the pathogenesis of human infection. In this report, the potential role of an L. pneumophila-infected amoeba as an infectious particle in replicative L. pneumophila lung infection was investigated in vivo with the amoeba Hartmannella vermiformis, a natural reservoir of L. pneumophila in the environment. L. pneumophila-infected H. vermiformis organisms were prepared by coculture of the amoebae and virulent L. pneumophila cells in vitro. A/J mice, which are susceptible to replicative L. pneumophila lung infection, were subsequently inoculated intratracheally with L. pneumophila-infected H. vermiformis organisms (10(6) amoebae containing 10(5) bacteria), and intrapulmonary growth of the bacteria was assessed. A/J mice inoculated intratracheally with L. pneumophila-infected H. vermiformis organisms developed replicative L. pneumophila lung infections. Furthermore, L. pneumophila-infected H. vermiformis organisms were more pathogenic than an equivalent number of bacteria or a coinoculum of L. pneumophila cells and uninfected amoebae. These results demonstrate that L. pneumophila-infected amoebae are infectious particles in replicative L. pneumophila infections in vivo and support the hypothesis that inhaled protozoa may serve as cofactors in the pathogenesis of pulmonary disease induced by inhaled respiratory pathogens.

L-selectin stimulation of canine neutrophil initiates calcium signal secondary to tyrosine kinase activation.

Neutrophils play an important role in myocardial ischemia-reperfusion injury. Neutrophil adhesion to the vascular endothelium is one of the important early mechanisms that lead to reperfusion injury. The leukocyte adhesion molecule, L-selectin, plays a major role in the initial interaction between neutrophils and endothelial cells. Intervention aimed at blocking selectins or their associated ligands can exert cardioprotective effects. The purpose of this study was to examine the role of L-selectin in the initiation of transmembrane signaling and regulation of canine neutrophil responses. Cross-linking of canine neutrophil L-selectin using anti-L-selectin antibody induced a rapid and transient increase in intracellular Ca2+ levels and superoxide anion generation that were dependent on the extent of L-selectin cross-linking. The responses were significantly inhibited by the protein tyrosine kinase inhibitor, genistein. The results demonstrate that ligation of canine neutrophil L-selectin is coupled to intracellular signal transduction pathways and the generation of second messengers, which may independently play important regulatory roles in modulating neutrophil-endothelial cell interactions.

A predictive model of student satisfaction with the medical school learning environment.

PURPOSE: To examine differences in attitudes toward the medical school learning environment among student subgroups based on gender and race-ethnicity, to identify the most influential predictors of student satisfaction with the learning environment, and to create a model of student satisfaction with the learning environment. METHOD: Three years of survey data (1992-93 to 1994-95) from first-year students at the University of Michigan Medical School were combined. The total sample consisted of 430 respondents, broken into two sets of subgroups: women (n = 171) and men (n = 259), and whites (n = 239) and underrepresented minorities (n = 74). Asian students were removed from analyses when comparisons were made by race-ethnicity, but were included in the analyses for all students and those comparing men and women. Student's t-tests were used to identify differences between gender and racial-ethnic groups in mean responses to seven survey items, and effect sizes were used to characterize the magnitudes and practical significances of the differences. Forward stepwise regression was conducted to determine the best predictive models for each student subgroup and for the total sample; the subgroup models were compared with each other as well as with the total-sample model. RESULTS: Cross-validation of the gender and race-ethnicity models showed that the men's satisfaction and the women's satisfaction were predicted equally well using either subgroup's model, and that the white students' satisfaction and the underrepresented-minority students' satisfaction were predicted equally well using either subgroup's model. Furthermore, the total-sample model, employing a subset of five predictors, was similar in its predictive power to the subgroup models. CONCLUSION: The study's findings suggest that curriculum structure (timely feedback and the promotion of critical thinking) and students' perceptions of the priority faculty place on students' education are prominent predictors of student satisfaction (across all subgroups) with the learning environment. In contrast, students' perceptions of the learning environment as a comfortable place for all gender and racial-ethnic groups, although less prominent predictors of satisfaction, will discriminate among the subgroups.

Effector mechanisms responsible for gamma interferon-mediated host resistance to Legionella pneumophila lung infection: the role of endogenous nitric oxide differs in susceptible and resistant murine hosts.

To facilitate identification of the effector mechanism(s) responsible for gamma interferon (IFN-gamma)-mediated host resistance to Legionella pneumophila, a murine model of legionellosis in BALB/c mice with a targeted disruption in the IFN-gamma gene (gamma knockout [GKO] mice) was developed. Immunocompetent BALB/c mice and GKO mice were inoculated intratracheally with virulent L. pneumophila (10(6) bacteria per mouse), and bacterial clearance and the pulmonary inflammatory response were assessed. L. pneumophila did not replicate in, and was rapidly cleared from, the lungs of immunocompetent BALB/c mice, demonstrating that immunocompetent BALB/c mice are resistant to replicative L. pneumophila pulmonary infections. In contrast, similarly infected GKO mice developed persistent, replicative intrapulmonary L. pneumophila infections with extrapulmonary dissemination of the bacteria to the spleen. Histopathologic and flow cytometric analysis of L. pneumophila-infected lung tissue demonstrated that while immunocompetent BALB/c mice develop multifocal pneumonitis which resolves, similarly infected GKO mice develop diffuse pneumonitis with persistent neutrophil recruitment into the lung. Intratracheal administration of exogenous IFN-gamma to L. pneumophila-infected GKO mice facilitated intrapulmonary clearance of the bacteria, confirming the pivotal role of IFN-gamma in innate host defenses to L. pneumophila lung infection in this murine host. The potential role of endogenous reactive nitrogen intermediates, including nitric oxide (NO), in IFN-gamma-mediated resistance to L. pneumophila pulmonary infections in immunocompetent BALB/c mice was subsequently assessed. Macrophage inducible nitric oxide synthetase (an enzyme responsible for the production of NO) was induced in alveolar cells from L. pneumophila-infected immunocompetent BALB/c mice (with maximal expression at 48 h postinfection) but was not induced in similarly infected GKO mice. However, administration of the NO synthetase inhibitor N-monomethyl-L-arginine did not significantly inhibit clearance of L. pneumophila from the lung of immunocompetent BALB/c mice (compared with that in similarly infected mice not administered N-monomethyl-L-arginine). In contrast, we have previously demonstrated that IFN-gamma-induced host resistance to replicative L. pneumophila lung infections in a susceptible murine host (A/J mice) is mediated, in part, by endogenous NO. Taken together, these studies identify a differing role of endogenous NO in IFN-gamma-mediated resistance to L. pneumophila pulmonary infection in susceptible and resistant murine hosts.

Humoral immunity and regulation of intrapulmonary growth of Legionella pneumophila in the immunocompetent host.

The potential role of humoral immunity in regulating intrapulmonary growth of Legionella pneumophila in the immunocompetent host was investigated using a murine model of Legionnaires' disease. Intratracheal inoculation of A/J mice with a virulent strain of L. pneumophila (10(6) bacteria per mouse) resulted in the recruitment of B lymphocytes into the lung and the development of anti-L. pneumophila Ab. Opsonization of L. pneumophila in vitro with anti-L. pneumophila-specific mAb resulted in a significant decrease in intrapulmonary growth of the bacteria at 24 to 72 h postinfection. Transmission electron microscopic analysis of lung tissue from L. pneumophila- infected mice demonstrated that while there was no significant difference between phagocytosis of the unopsonized and opsonized L. pneumophila by alveolar macrophages at 24 h postinfection, phagocytosis of opsonized bacteria by alveolar mononuclear phagocytic cells was significantly enhanced at 48 h postinfection. Depletion of A/J mice of complement before intratracheal inoculation of opsonized L. pneumophila (10(6) bacteria per mouse) did not significantly alter intrapulmonary growth of L. pneumophila. These results suggest that anti-L. pneumophila Ab, produced during replicative L. pneumophila lung infections, may regulate intrapulmonary growth of L. pneumophila in the immunocompetent host by decreasing the viability of extracellular L. pneumophila and by enhancing phagocytosis of the bacteria by alveolar mononuclear phagocytic cells by a complement-independent mechanism.

Coinoculation with Hartmannella vermiformis enhances replicative Legionella pneumophila lung infection in a murine model of Legionnaires' disease.

The effect of inhaled amoebae on the pathogenesis of Legionnaires' disease was investigated in vivo. A/J mice, which are susceptible to replicative Legionella pneumophila infections, were inoculated intratracheally with L. pneumophila (10(6) bacteria per mouse) or were coinoculated with L. pneumophila (10(6) bacteria per mouse) and Hartmannella vermiformis (10(6) amoebae per mouse). The effect of coinoculation with H. vermiformis on bacterial clearance, histopathology, cellular recruitment into the lung, and intrapulmonary levels of cytokines including gamma interferon and tumor necrosis factor alpha was subsequently assessed. Coinoculation with H. vermiformis significantly enhanced intrapulmonary growth of L. pneumophila in A/J mice. Histopathologic and flow cytometric analysis of lung tissue demonstrated that while A/J mice inoculated with L. pneumophila alone develop multifocal pneumonitis which resolves with minimal mortality, mice coinoculated with H. vermiformis develop diffuse pneumonitis which is associated with diminished intrapulmonary recruitment of lymphocytes and mononuclear phagocytic cells and significant mortality. Furthermore, coinoculation of mice with H. vermiformis resulted in a fourfold enhancement in intrapulmonary levels of gamma interferon and tumor necrosis factor alpha compared with mice infected with L. pneumophila alone. The effect of H. vermiformis on intrapulmonary growth of L. pneumophila in a resistant host (i.e., BALB/c mice) was subsequently evaluated. While BALB/c mice do not develop replicative L. pneumophila infections following inoculation with L. pneumophila alone, there was an eightfold increase in intrapulmonary L. pneumophila in BALB/c mice coinoculated with H. vermiformis. These studies, demonstrating that intrapulmonary amoebae potentiate replicative L. pneumophila lung infection in both a susceptible and a resistant host, have significant implications with regard to the potential role of protozoa in the pathogenesis of pulmonary diseases due to inhaled pathogens and in the design of strategies to prevent and/or control legionellosis.

In vivo regulation of replicative Legionella pneumophila lung infection by endogenous tumor necrosis factor alpha and nitric oxide.

The in vivo role of endogenous tumor necrosis factor alpha (TNF-alpha) and reactive nitrogen intermediates (RNIs) in modulation of growth of Legionella pneumophila in the lung was assessed using a murine model of replicative L. pneumophila lung infection. Intratracheal inoculation of mice with L. pneumophila resulted in induction of endogenous TNF-alpha, which preceded clearance of L. pneumophila from the lung. Inhibition of endogenous TNF-alpha activity, via in vivo administration of TNF-alpha neutralizing antibody, or inhibition of endogenous RNIs, via administration of the nitric oxide (NO) synthetase inhibitor N-monomethyl-L-arginine (NMMA), resulted in enhanced growth of L. pneumophila in the lung at > or = 3 days postinfection (when compared with untreated L. pneumophila-infected mice). Because of the similar kinetics of enhanced pulmonary growth of L. pneumophila in mice treated in vivo with either anti-TNF-alpha antibody or NMMA, the immunomodulatory effect of NO on endogenous TNF-alpha activity in the lung was assessed. Administration of NMMA to L. pneumophila-infected mice resulted in a significant decrease in endogenous TNF-alpha activity in the lung during replicative L. pneumophila infections in vivo. However, administration of exogenous TNF-alpha to NMMA-treated mice failed to significantly enhance clearance of L. pneumophila from the lung. Results of these studies indicate that both endogenous NO and TNF-alpha facilitate resolution of replicative L. pneumophila lung infections and that regulation of L. pneumophila replication by TNF-alpha is mediated, at least in part, by NO.

The effect of pass/fail grading and weekly quizzes on first-year students' performances and satisfaction.

BACKGROUND: In 1992-93 the University of Michigan Medical School revised its first-year curriculum. An evaluation system using honors, high-pass, pass, and fail grading and only two examinations (a midterm and a final) was replaced with a system using pass/fail grading and weekly quizzes in addition to the two examinations. The objective was to increase students' satisfaction while maintaining a high level of achievement. METHOD: Students' performance scores and survey data from the final year of the former system (1991-92, 222 students) and the first year of the new system (1992-93, 195 students) were used to investigate whether overall performance decreased and whether the students liked the new approach to grading. Statistical methods used were one-sample t-tests, Student's t-test, and Fisher's Z-test. RESULTS: Under the new system, the average scores for courses remained well above passing, and no evidence was found that the students achieved at lower levels than had their predecessors with the former, more traditional grading system. Also, higher cumulative pre-final scores (i.e., scores on the weekly quizzes as well as the midterm) did not predict lower, "just passing" achievement on final examinations. The students' responses to the surveys included comments that pass/fail grading eased anxiety and reduced competition while encouraging the students' co-operation. CONCLUSION: Despite concerns that implementing pass/fail grading for all first-year courses would result in lower overall performance and decreased motivation among students, during the first year of implementation these fears proved to be unfounded as the students continued to perform well and reported greater satisfaction with the new system.

Activation of human neutrophils through L-selectin and Mac-1 molecules.

The effect of selective cell activation through L-selectin and Mac-1 molecules cross-linking on neutrophil superoxide anion (O2-) generation and changes in intracellular calcium [Ca2+]i was investigated. Cross-linking of L-selectin using different mAbs induced a rapid and transient increase in [Ca2+]i and O2- generation by neutrophils that were dependent on the extent of L-selectin cross-linking and mAb epitope binding. In addition, cross-linking of L-selectin induced an up-regulation of surface Mac-1 expression on neutrophils. Cross-linking of Mac-1 molecules with mAb also induced significant changes in [Ca2+]i levels and O2- generation by neutrophils, which was also dependent on the epitope binding by mAb. Pretreatment of neutrophils with LPS caused a marked decrease in the expression of L-selectin molecules and significant inhibition (i.e., 59 +/- 4%) of anti-L-selectin mAb-dependent O2- generation and [Ca2+]i signal. In contrast, LPS pretreatment caused a significant up-regulation of Mac-1 molecules on neutrophil and enhanced O2- generation by neutrophils. The data indicate that cross-linking of L-selectin and Mac-1 initiates changes in [Ca2+]i and O2- production in neutrophils and suggest that these distinct adhesion molecules independently may play important regulatory roles in modulating neutrophil-endothelial cell interactions, transmigration, and neutrophil function at sites of tissue injury.

Regulation of monocyte chemoattractant protein-1 gene expression and secretion in rat pulmonary alveolar macrophages by lipopolysaccharide, tumor necrosis factor-alpha, and interleukin-1 beta.

Chemotactic cytokines coordinate the recruitment of leukocytes into the lung during pulmonary inflammation. In a previous study, we determined that rat pulmonary alveolar macrophages (PAMs) facilitate monocyte recruitment and activation in the lung during acute inflammatory lung injury, in part, through the inducible expression of monocyte chemoattractant protein-1 (MCP-1). MCP-1 is an 11 to 15 kD basic peptide that specifically mediates monocyte chemotaxis and activation. Inflammatory mediators that regulate the expression and secretion of MCP-1 by rat PAMs have not been identified. We determined that stimulation of resident rat PAMs with bacterial lipopolysaccharide (LPS), murine tumor necrosis factor-alpha, or human interleukin-1 beta resulted in the inducible expression of MCP-1 mRNA and the secretion of biologically active MCP-1. In contrast, phorbol myristate acetate, a nonphysiologic leukocyte activator, was significantly less effective in stimulating either enhanced MCP-1 mRNA expression or secretion of MCP-1. These results indicate that the expression of MCP-1 mRNA and the secretion of MCP-1 by rat PAMs are regulated by bacterial products (LPS) and inflammatory cytokines. Further, these results suggest PAMs are regulated by bacterial products (LPS) and inflammatory cytokines. Further, these results suggest that resident PAMs, through elaboration of MCP-1, may play a pivotal role in regulating recruitment and activation of monocytes in the lung during acute inflammatory lung injury.

The selectins: insights into selectin-induced intracellular signaling in leukocytes.

Characteristic features of the inflammatory and immune responses involve the recruitment of leukocytes to sites of tissue injury and the recirculation of lymphocytes through hematopoietic and lymphoid tissues. Recent studies indicate that the regulated cell surface expression of a family of protein adhesion molecules known as selectins and their counterreceptors on both leukocytes and endothelium play critical roles in both biologic processes. Initially, the function of these molecules was thought to be restricted to regulating cell-cell adhesive interactions. Selectin-dependent cell-cell binding has been shown to be essential in localizing leukocytes within tissues by promoting cell rolling along endothelium prior to the development of tight adhesion and subsequent cell migration. However, recent studies suggest that these molecules also play an active role in regulating additional leukocyte functions. This article will review the emerging evidence that indicates a broader and significant role of selectin molecules and their counterreceptors in the initiation of intracellular signaling pathways and regulation of other leukocyte functional responses including degranulation, cytokine expression, activation of the respiratory burst, and T lymphocyte activation.

Replicative Legionella pneumophila lung infection in intratracheally inoculated A/J mice. A murine model of human Legionnaires' disease.

The role of host immune responses in the pathogenesis of Legionnaires' disease is incompletely understood, due in part to the current lack of an animal model that is both susceptible to replicative Legionella pneumophila-induced lung infection and for which species-specific immunological reagents are available. We have developed a model of replicative L. pneumophila lung infection in intratracheally inoculated A/J mice. L. pneumophila was obtained in the exponential growth phase and inoculated into the trachea of 6- to 8-week-old female A/J mice. Microbiological and histopathological evidence of infection was demonstrated in mice inoculated with 10(6) colony-forming units. Development of an acute pneumonia that resembled human Legionnaires' disease coincided with exponential growth of the bacteria in the lung 24 to 48 hours after intratracheal inoculation of L. pneumophila. This was associated with increased plasma levels of interferon-gamma at 24 hours after inoculation. After 48 hours, the bacteria were gradually eliminated from the lung over the next 5 days, corresponding with resolution of the inflammatory response in the lung, thereby mimicking the outcome frequently seen in the immunocompetent human host. Treatment of animals with anti-interferon-gamma antibody enhanced bacterial replication and disease progression, indicating an important role of host immune response in resolution of the infection. Because of the availability of murine-specific reagents, this model of replicative L. pneumophila lung infection in A/J mice after intrapulmonary inoculation of L. pneumophila potentially provides an important tool for future studies investigating the role of host immune responses in the pathogenesis of Legionnaires' disease in the immunocompetent host.