A monoclonal antibody (904) that binds to a leukocyte cell adhesion-promoting glycoprotein, (Mol; 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-Mol treatment (25.8±4.7%, n = 8) compared to control (47.6±5.7%, n = 8; P < 0.01). The area at risk of infarction was similar between groups. Circulating (serum) antibody excess was confirmed in all 8 anti-Mol 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-Mol 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 IgGI) 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-Mol monoclonal antibody after the induction of regional myocardial ischemia results in reduced myocardial reperfusion injury as measured by ultimate infarct size.

A novel H1N1 influenza A virus emerged in April 2009, and rapidly reached pandemic proportions. We report a retrospective observational case study of pathologic findings in 8 patients with fatal novel H1N1 infection at the University of Michigan Health Systems (Ann Arbor) compared with 8 age-, sex-, body mass index-, and treatment-matched control subjects. Diffuse alveolar damage (DAD) in acute and organizing phases affected all patients with influenza and was accompanied by acute bronchopneumonia in 6 patients. Organizing DAD with established fibrosis was present in 1 patient with preexisting granulomatous lung disease. Only 50% of control subjects had DAD. Peripheral pulmonary vascular thrombosis occurred in 5 of 8 patients with influenza and 3 of 8 control subjects. Cytophagocytosis was seen in all influenza-related cases. The autopsy findings in our patients with novel H1N1 influenza resemble other influenza virus infections with the exception of prominent thrombosis and hemophagocytosis. The possibility of hemophagocytic syndrome should be investigated in severely ill patients with H1N1 infection.

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 90% in the presence of 1 ,ug/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-1fi ). 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-1ft.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 H202 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 ofantioxidants in experimental models of inflammation and ischemia/reperfusion injury.

A B S T R A C T 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°2 has the capacity to injure the lung. Instillation of a generator of H202, 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 ofthese 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 O°, H202 and its lactoperoxidase or myeloperoxidase-produced derivatives. The studies also indicate that lung injury produced by oxygen metabolites can result in interstitial pulmonary fibrosis.

Students revealed that their conflict was connected to feelings of powerlessness, along with exacerbating factors including limited time, concerns about expectations for their behavior, and pessimism about change. Role modeling had a significant influence on consequences related to students' patient-centered values.