Adhesion of monocytes to arterial endothelium and initiation of atherosclerosis are critically dependent on vascular cell adhesion molecule-1 gene dosage.

- Vascular cell adhesion molecule-1 (VCAM-1/Vcam1) is a cytokine-inducible member of the immunoglobulin gene superfamily that is expressed by arterial endothelial cells in regions predisposed to atherosclerosis and at borders of atherosclerotic plaques. To determine whether VCAM-1 expression regulates atherosclerotic lesion formation, we crossed Vcam1 domain 4-deficient (D4D) mice, which partially circumvent the embryonic lethality of Vcam1 null mice, with apolipoprotein E null (Apoe(-/-)) mice, which spontaneously develop hypercholesterolemia and atherosclerosis. In the Apoe(-/-) background, mice homozygous for the Vcam1 D4D allele had markedly reduced arterial VCAM-1 expression, monocyte adherence in the aortic root, and fatty streak formation. Heterozygous Vcam1 D4D mice revealed a Vcam1 gene-dosage effect and had intermediate, yet significant, reductions in these parameters. Our data demonstrate that VCAM-1 plays a pivotal role in the initiation of atherosclerosis in Apoe(-/-) mice.

Apo A-I inhibits foam cell formation in Apo E-deficient mice after monocyte adherence to endothelium.

We have previously shown that expression of the human apo A-I transgene on the apo E-deficient background increases HDL cholesterol and greatly diminishes fatty streak lesion formation. To examine the mechanism, prelesional events in atherosclerotic plaque development were examined in 6- to 8-week-old apo E-deficient and apo E-deficient/human apo A-I transgenic mice. A quantitative assessment of subendothelial lipid deposition by freeze-fracture and deep-etch electron microscopy indicated that elevated apo A-I did not affect the distribution or amount of aortic arch subendothelial lipid deposits. Immunohistochemical staining for VCAM-1 demonstrated similar expression on endothelial cells at prelesional aortic branch sites from both apo E-deficient and apo E-deficient/human apo A-I transgenic mice. Transmission electron microscopy revealed monocytes bound to the aortic arch in mice of both genotypes, and immunohistochemical staining demonstrated that the area occupied by bound mononuclear cells was unchanged. Serum paraoxonase and aryl esterase activity did not differ between apo E-deficient and apo E-deficient/human apo A-I transgenic mice. These data suggest that increases in apo A-I and HDL cholesterol inhibit foam cell formation in apo E-deficient/human apo A-I transgenic mice at a stage following lipid deposition, endothelial activation, and monocyte adherence, without increases in HDL-associated paraoxonase.

Violence against surgical residents.

Violence against hospital personnel is underreported (less than one in five assaults), and accurate statistics as to the rate of violence against hospital personnel are thus difficult to establish. In the psychiatric discipline, an abundance of information has been published regarding violence in the health care setting, but few studies have examined violence outside psychiatric hospitals or by patients not diagnosed with psychiatric ailments. Using a survey that elicits information about workplace violence, we sought to gauge the prevalence of violent acts affecting general hospital workers who treat victims of violence on a daily basis. The survey was completed by a cohort of surgical staff nationwide (475 responses from 57 residency programs). Two hundred and eighty residents reported having witnessed one or more physical attacks, and 179 reported having been attacked. Violent acts were more likely to be committed in a public hospital than a private institution (P = 0.05). As shown in previous research, most attacks occurred in the emergency room (P = 0.01); the wards and parking lot were next in frequency. Women residents were more likely than men to call hospital security to intervene in a potentially violent situation (P = 0.04), and junior residents (postgraduate years 1-4) were more likely to be attacked than senior residents (> or = 5 years) (P = 0.04). The attacker was most likely to be a young black male between ages 19 and 30 (P = 0.01). We found no statistical relationship between the attacker and the victim regarding sex or race. Of the 475 respondents, 470 reported that they carry a gun themselves or know someone in the hospital environment who carries a gun.