Inhibition of vascular permeability changes in rats by captopril.

Systemic treatment of rats with captopril (50 mg/kg body wt per os), a specific competitive inhibitor of angiotensin l-converting enzyme, significantly inhibits vascular permeability changes induced by the intradermal injection of the vasoactive mediators histamine, bradykinin, serotonin, and compound 48/80. This effect of captopril is both dose- and time-dependent with approximately 60% inhibition of edema formation observed 7 h after captopril treatment (100 mg/kg body wt per os). The inhibitory effect of captopril on edema formation is temporally unrelated to the inhibition of serum angiotensin l-converting enzyme activity or serum prostaglandin E2 levels and is not inhibited by systemic treatment of rats with indomethacin. The data suggest that captopril may have potent antiinflammatory activity through as yet undefined mechanisms.

In vivo damage of rat lungs by oxygen metabolites.

The intrapulmonary instillation into rat lung of enzymes that generate oxygen metabolites results in acute lung injury. The injection of xanthine oxidase and xanthine produces acute lung injury that, in the presence of superoxide dismutase, but not in the presence of catalase, can be significantly diminished, suggesting that O2- has the capacity to injure the lung. Instillation of a generator of H2O2, namely glucose oxidase, will, in sufficient quantities, produce acute injury that is not neutrophil-dependent. When either a low dose of glucose oxidase alone or lactoperoxidase alone is employed, little lung injury occurs. However, instilling the combination of the two enzymes produces severe, acute injury that can be blocked in a dose-dependent manner by catalase, but not by superoxide dismutase. Purified human leukocytic myeloperoxidase, but not horseradish peroxidase, will substitute for lactoperoxidase in the model of lung injury. The lung damaging effects of these enzymes cannot be attributed to the presence of contaminating proteases. Acute lung injury produced by the instillation of glucose oxidase and lactoperioxidase progresses to interstitial fibrosis. These studies represent a direct application of generators of oxygen metabolites to the in vivo induction of lung injury. The data suggest that rat lung is susceptible to injury by a variety of oxygen metabolites, including O2-, H2O2 and its lactoperoxidase or myeloperoxidase-produced derivatives. The studies also indicate that lung injury produced by oxygen metabolites can result in interstitial pulmonary fibrosis.

Oxygen radical scavengers selectively inhibit interleukin 8 production in human whole blood.

The hydroxyl radical (OH.) scavenger dimethyl sulfoxide (DMSO) was found to dose-dependently inhibit interleukin 8 (IL-8) production in LPS-stimulated human whole blood. At a concentration of 1% (vol/vol), DMSO blocked IL-8 release by approximately 90% in the presence of 1 microgram/ml LPS at a 24-h time point, but did not affect cell viability or reduce the production of tumor necrosis factor (TNF), interleukin 6, or interleukin-1 beta (IL-1 beta). DMSO was found to directly inhibit IL-8 expression at the level of transcription. Furthermore, this effect was not LPS-specific, in that IL-8 production was reduced by DMSO to a similar extent upon stimulation of blood with phytohemagglutinin, aggregated immune complexes, TNF, or IL-1 beta. Other oxygen radical scavengers that have been shown to inhibit OH.-dependent reactions (dimethyl thiourea, thiourea, mannitol, and ethanol) also inhibited IL-8 production. Conversely, addition of H2O2 caused a dose-dependent stimulation of IL-8 release. These results provide evidence that reactive oxygen metabolites play an important role in the regulation of IL-8 production and suggest that reduction of IL-8 release may contribute to the beneficial effects of antioxidants in experimental models of inflammation and ischemia/reperfusion injury.

Reduction of experimental canine myocardial reperfusion injury by a monoclonal antibody (anti-Mo1, anti-CD11b) that inhibits leukocyte adhesion.

A monoclonal antibody (904) that binds to a leukocyte cell adhesion-promoting glycoprotein, (Mo1; CD11b/CD18) was administered (1 mg/kg, iv.) to open chest anesthetized dogs 45 min after the induction of regional myocardial ischemia. Ischemia was produced by occluding the left circumflex coronary artery (LCX) for 90 min and then reperfusing for 6 h. There was no difference between control and antibody treated groups with respect to arterial blood pressure, heart rate, or LCX blood flow. Administration of antibody produced no observable effect on circulating neutrophil counts, suggesting that antibody-bound neutrophils were not cleared from the circulation. The mean size of myocardial infarct expressed as percentage of the area at risk of infarction that resulted was reduced by 46% with anti-Mo1 treatment (25.8 +/- 4.7%, n = 8) compared to control (47.6 +/- 5.7%, n = 8; P less than 0.01). The area at risk of infarction was similar between groups. Circulating (serum) antibody excess was confirmed in all 8 anti-Mo1 treated dogs by immunofluorescence analysis. Analysis of ST segment elevation on the electrocardiogram as an indicator of the severity of ischemia suggests that the anti-Mo1 reduces infarct size independent of the severity of ischemia. An additional group of dogs (n = 5) was tested with a control monoclonal antibody of the same subtype (murine IgG1) and was found to produce no significant reduction in myocardial infarct size. Accumulation of neutrophils within the myocardium was significantly attenuated with 904 treatment when analyzed by histological methods. These data demonstrate that administration of anti-Mo1 monoclonal antibody after the induction of regional myocardial ischemia results in reduced myocardial reperfusion injury as measured by ultimate infarct size.

Phorbol myristate acetate-induced adherence of Walker 256 carcinosarcoma cells.

Treatment of nonadherent Walker 256 carcinosarcoma cells with phorbol myristate acetate (PMA) causes these cells to become adherent to noncellular foreign surfaces such as nylon fibers and plastic culture dishes and to monolayers of endothelial cells. Increased adherence is first observed after a short lag period (5 to 15 min) and is transient. Other tumor-promoting analogs of PMA also induce this response, while inactive analogs of PMA do not. Simultaneous treatment of the cells with 2-deoxyglucose, colchicine, cytochalasin B, and cycloheximide indicates that the adherence response of the cells is an energy-dependent process that requires an intact cytoskeleton but does not require protein synthesis. Inhibitors of phospholipids and arachidonic acid metabolism including indomethacin, nordihydroguaiaretic acid, and p-bromophenacyl bromide greatly inhibit PMA-induced adherence, but acetylsalicylic acid is much less effective. PMA also increases the rate of attachment to plastic dishes of cells which would normally attach, although slowly, and grow as substrate-attached cells. However, PMA treatment has no effect on the subsequent degree of susceptibility of these cells to release from plastic dishes mediated by proteolytic enzymes. These findings suggest (a) that PMA may be useful in delineating the initial events involved in the adherence of cells to cellular and noncellular surfaces and (b) that PMA may stimulate tumor cell adherence in a manner similar to that of chemotactic peptides may be useful in delineating the events associated with chemotactic factor stimulation of these cells.

Human platelets mediate iron release from transferrin by adenine nucleotide-dependent and -independent mechanisms.

We assessed the ability of platelet sonicates and mediators secreted by unstimulated and thrombin-stimulated platelets to facilitate the release of iron from transferrin. Platelet sonicates and platelet conditioned media potentiated the release of iron from transferrin. The rate of release of iron was dependent on the pH of the reaction and amount of platelet sample added. Conditioned media from thrombin-stimulated platelets was more effective in mediating the release of iron from transferrin than was conditioned media from unstimulated cells. The rate of iron released from transferrin following addition of ATP and ADP in amounts equivalent to that present in platelet conditioned media was significantly less than the rate of iron released following the addition of conditioned media from platelets. Depletion of ATP and ADP in platelet conditioned media by incubation with apyrase only partially inhibited their ability to enhance the rate of iron release from transferrin. These observations indicate that platelets enhance the release of iron from transferrin by adenine nucleotide-dependent and -independent mechanisms. These observations are consistent with the hypothesis that platelets promote oxidant-induced tissue injury at sights of inflammation secondary to their ability to enhance the local release of iron from transferrin.

Prostaglandin modulation of N-formylmethionylleucylphenylalanine-induced transmembrane potential changes in rat neutrophils.

Prostaglandins of the E-series (PGEs) and PGI2 will inhibit formylmethionylleucylphenylalanine-(f-Met-Leu-Phe) induced lysosomal enzyme release and superoxide-anion (O2-) production by neutrophils. The inhibitory effects of PGEs and PGI2 on neutrophil functional responses have been correlated with their ability to increase intracellular cAMP. In this study we have examined the effects of PGEs and PGI2 on f-Met-Leu-Phe- and phorbol-myristate-acetate-induced rat neutrophil membrane potential changes using an optical probe of membrane potential 3,3-dipropylthiodicarbocyanine iodide. 15-(S)-15-methyl-PGE1 (15-methyl-PGE1), a stable analogue of PGE1 and PGI2 inhibited f-Met-Leu-Phe-induced transmembrane potential changes in a dose-dependent manner. This inhibition was correlated with the ability of these agents to increase intracellular cAMP levels and inhibit O2- production and degranulation. In contrast, 15-methyl-PGE1 and PGI2, did not inhibit phorbol-myristate-acetate-induced transmembrane potential changes and O2- production. These results suggest independent mechanisms of activation of neutrophils by phorbol myristate acetate and f-Met-Leu-Phe, and they also suggest that the inhibitory effects of prostaglandins and cAMP on f-Met-Leu-Phe-stimulated cells is at a step or steps prior to activation of those processes involved in effecting changes in transmembrane potential, which are common to both stimuli.

High dose intravenous aspirin, not low dose intravenous or oral aspirin, inhibits thrombus formation and stabilizes blood flow in experimental coronary vascular injury.

OBJECTIVES: The purpose of this study was to assess the anti-thrombotic potential of various forms of aspirin administration. BACKGROUND: Platelet activation in response to endothelial injury has been implicated in acute coronary syndromes. METHODS: Delivering 100-microA anodal direct current to the intima of the left circumflex coronary artery in dogs at a site of moderate external stenosis provides a thrombogenic model of vascular injury. Animals were treated with aspirin (Group I, 20 mg/kg intravenously [n = 11]; Group II, 4.6 mg/kg intravenously [n = 6]; Group III, 4.6 mg/kg orally 18 h before the experiment [n = 7]) or vehicle (Group IV, control [n = 11]). RESULTS: The time required for thrombotic occlusion to occur was longer and the incidence of thrombosis was lower in Group I (Group I, 238 +/- 7 min [n = 2]; Group II, 127 +/- 25 min [n = 3]; Group III, 156 +/- 35 min [n = 6]; Group IV, 90 +/- 11 min [n = 11]) (p < 0.05). Thrombus mass was smaller in Group I (Group I, 5.0 +/- 0.8 mg; Group II, 12.2 +/- 2.6 mg; Group III, 11.6 +/- 3.9 mg; Group IV, 9.1 +/- 1.6 mg) (p < 0.05). Initial hemodynamic variables did not differ among groups. An increase in mean arterial pressure was noted for several hours after intravenous aspirin administration in Group I (99 +/- 5 to 110 +/- 4 mm Hg) (p < 0.05). Left circumflex coronary artery blood flow was stable for 5 h in Group I (Group I, 31 +/- 2 to 26 +/- 4 ml/min) but decreased in all the other groups (Group II, 26 +/- 4 to 10 +/- 5 ml/min; Group III, 27 +/- 5 to 7 +/- 7 ml/min; Group IV, 29 +/- 4 to 0 ml/min) (p < or = 0.05). The in vivo area of left ventricle perfused by the left circumflex coronary artery was not different among groups. Platelet counts were similar and did not change over the course of the protocol. Ex vivo arachidonic acid-induced platelet aggregation decreased in all groups after aspirin (p < or = 0.001). Indium-111-labeled platelet adherence to the coronary vasculature was decreased in distal vessel segments after all doses of aspirin (p < 0.05). Platelet deposition in thrombi was similar for all treatment groups. CONCLUSIONS: High dose intravenous aspirin has salutary effects. It stabilizes left circumflex coronary artery blood flow, prolongs the time to thrombosis, reduces the incidence of thrombotic occlusion, reduces thrombus mass and limits platelet adherence to sites of arterial injury. Low dose aspirin given intravenously or orally was ineffective. When persistent intracoronary thrombi precipitate unstable coronary syndromes, high dose intravenous aspirin may be useful in the acute period even though platelets continue to interact with injured vascular segments through aspirin-insensitive mechanisms.

3-deaza-adenosine inhibition of stimulus-response coupling in human polymorphonuclear leukocytes.

In an effort to define better the functional role of S-adenosyl-methionine-mediated methylation reactions in modulating polymorphonuclear (PMN) functional responses to chemotactic stimuli, we investigated the effects of 3-deaza-adenosine (3-DZA), a known inhibitor of methylation reactions in phagocytic cells, on formyl methionyl-leucyl-phenylalanine (FMLP)-induced responses in human PMN leukocytes. Using the fluorescent cyanine dye 3,3'-dipropylthiocarbocyanine (di-S-C3-(5)) as an optical probe of membrane potential we observed that 3-DZA at concentrations that inhibit FMLP-induced O2- production does not significantly alter FMLP-induced changes in transmembrane potential. Additional studies showed an inhibitory effect of 3-DZA on FMLP-induced PMN pinocytosis and to a lesser degree on FMLP-induced degranulation. However, pretreatment of PMNs with 3-DZA did not alter FMLP-induced changes in Quin-2 fluorescence, an indicator of changes in intracellular calcium levels. These findings demonstrate a dissociation between chemotactic factor-induced cell membrane depolarization, changes in intracellular calcium, and specific neutrophil functional responses and suggest that chemotactic factor-induced changes in transmembrane potential and intracellular calcium are independent of chemotactic factor-induced methylation reactions. Furthermore, 3-DZA did not alter phorbol myristate acetate induced O2- production or fluid pinocytosis indicating a stimulus specificity for the inhibitory effects of this agent on O2- production.

Oxygen metabolite detoxifying enzyme levels in bleomycin-induced fibrotic lungs.

The activities of three enzymes cytosolic superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSHP), and malonyldialdehyde (MDA), a by-product of lipid peroxidation, were determined in whole lungs of normal and bleomycin-treated rats. Two days after bleomycin treatment total lung SOD, CAT, and GSHP activities were significantly (p less than .025) depressed between 15 and 25%. The activities of all three enzymes increased 4 days after bleomycin treatment with only SOD significantly increased at days 4 and 7. Total lung CAT activity remained near normal levels while GSHP activity increased only at day 28 (160.5%, p less than .01) indicating a specificity of the response of lung SOD and GSHP levels. Total lung MDA levels were increased by 17% at 2 and 4 days (p less than .05) after bleomycin treatment, and returned to normal levels at 7 and 28 days. These data suggest that impairment of the lung's ability to detoxify O2 metabolites may play an important role in the development of bleomycin-induced pulmonary fibrosis.

Inhibition of hypochlorous acid-mediated reactions by desferrioxamine. Implications for the mechanism of cellular injury by neutrophils.

Inhibition of free radical mechanisms by desferrioxamine, an iron chelator, is often thought to be a good indicator of iron-catalyzed hydroxyl radical (OH.) production. The specificity of desferrioxamine is critical for such identification. This study was undertaken to determine whether desferrioxamine could prevent the in vitro cytotoxic reactions of hypochlorous acid (HOCl), a major neutrophil-derived oxidant. Red blood cells were used as a target for HOCl, and cell lysis and haemoglobin oxidation were measured. Desferrioxamine, and its iron-chelated form, ferrioxamine, were shown to prevent both effects of HOCl. However, desferrioxamine was 6 to 8 times more efficient than either ferrioxamine or taurine, another amine which prevents HOCl-mediated cell lysis, in preventing both lysis and Hb oxidation. After reaction with HOCl, ferrioxamine and taurine retained almost all the oxidizing equivalents as long-lived chloramine. However, with desferrioxamine less than half the oxidizing equivalents were recovered as chloramines indicating that sites other than the terminal amine reacted with HOCl. The chloramines formed were able to oxidize molecules in solution, but being hydrophilic they were confined to the extracellular medium and cell lysis did not occur. The results indicate that scavenging of HOCl could be a factor in the inhibition by desferrioxamine of neutrophil-mediated cell lysis in vitro.

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.

Rapid purification of human peripheral blood monocytes by centrifugation through Ficoll-Hypaque and Sepracell-MN.

We have developed a rapid and simple method for isolating human peripheral blood monocytes in suspension. The procedure combines two separation media and involves isolation of the mononuclear cells by centrifugation through Ficoll-Hypaque followed by purification of the monocytes using Sepracell-MN, a colloidal silica-based medium. The final cell population contained approximately 90% monocytes with good functional ability. The contaminating cells were lymphocytes. Viability was always greater than or equal to 99% with 90% recovery of the monocytes from the mononuclear cells.

Noncaseating pulmonary granulomas associated with small cell carcinoma of the lung.

Noncaseating pulmonary granulomas are rarely associated with primary carcinoma of the lung. The patient described herein presented with constitutional symptoms and nodular pulmonary infiltrates associated with noncaseating granulomas without evident neoplasm in both transbronchial and open lung biopsy specimens. Despite corticosteroid therapy for presumed sarcoidosis, chest roentgenographic findings worsened and repeated transbronchial biopsy 12 months after the onset of initial symptoms revealed small cell carcinoma of the lung. Twenty-two months after initiation of chemotherapy, the patient is well with no evidence for carcinoma.

Inhibition of neutrophil activation by p-bromophenacyl bromide and its effects on phospholipase A2.

In an effort to elucidate the nature of the inhibitory effects of p-bromophenacyl bromide (pBPB) on neutrophil stimulation, we have examined its effects on several stages of stimulus-response coupling. Pretreatment of rat neutrophils with pBPB resulted in a dose- and time-dependent irreversible inhibition of both N-formylmethionyl-leucylphenylalanine (fMet-Leu-Phe)-induced lysosomal enzyme release and change in transmembrane potential. Inhibition of the biological responses to the chemotactic peptide fMet-Leu-Phe was not due to receptor inactivation since fMet-Leu-[3H]-Phe binding to the formyl peptide receptor was not significantly altered by pBPB pretreatment. Inhibition by pBPB of phorbol myristate acetate (PMA)-induced changes in transmembrane potential and the generation of superoxide (0-2) was also observed. pBPB treatment appeared to inhibit activation of the NADPH oxidase without a direct effect on the oxidase itself. This inhibitory effect was not accompanied by cell death or decrease in cellular titratable sulphydryl groups (at least at doses less than 20 microM). There was, however, significant inhibition of a membranous fraction of fMet-Leu-Phe-induced phospholipase A2 activity by pretreatment with 10 microM pBPB, although total cellular phospholipase A2 was only minimally (less than 20% inhibition) affected. These data would indicate that pBPB inhibits an early event associated with stimulus-response coupling in rat polymorphonuclear leukocytes (i.e. change in transmembrane potential). The inhibitory effects of pBPB may be secondary to the inhibition of a critical membranous fraction of cell bound phospholipase A2 activity or its activation, necessary for the initiation of cell activation.

Polymorphonuclear leukocyte-mediated cell and tissue injury: oxygen metabolites and their relations to human disease.

Reactive oxygen metabolic products derived from an activated NADPH oxidase present in the cell membrane of PMNs and mononuclear phagocytic cells play a critical role in the host's defense against bacterial infection. Recent studies have also demonstrated the ability of these toxic products to initiate eukaryotic cell injury and promote the development of the acute inflammatory responses. Experimental studies suggest that neutrophil-derived oxygen metabolites contribute to the development of the tissue injury associated with a variety of disease states, including emphysema, myocardial infarction, adult respiratory distress syndrome, immune complex-mediated vasculitis, and rheumatoid arthritis. Future studies to define further the mechanisms by which reactive oxygen-derived metabolic products mediate tissue injury will provide insight into the development of new therapeutic strategies for the modulation of disease states that are mediated by the recruitment and activation of PMNs.

Parosteal osteogenic sarcoma. Ultrastructural observations in three cases.

Ultrastructural study of three parosteal osteogenic sarcomas showed this type of tumor to contain numerous myofibroblasts. These cells were admixed with occasional cells resembling osteoblasts and fibroblasts. Cartilaginous areas showed the typical arrangement of cartilage cells embedded in a dense collagen matrix. Ultrastructural examination of a recurrent lesion revealed the presence of numerous undifferentiated cells as well as the types of cells just described. In addition, desmosomes were evident between the more undifferentiated cells. The ultrastructural study of these tumors shows that parosteal osteogenic sarcomas are ultrastructurally a distinctive type of osteogenic sarcoma.

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.

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.

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.