Elevated levels of leukocyte- and blood-MPO are associated with the presence of CAD. These findings support a potential role for MPO as an inflammatory marker in CAD and may have implications for atherosclerosis diagnosis and risk assessment.

A single initial measurement of plasma myeloperoxidase independently predicts the early risk of myocardial infarction, as well as the risk of major adverse cardiac events in the ensuing 30-day and 6-month periods. Myeloperoxidase levels, in contrast to troponin T, creatine kinase MB isoform, and C-reactive protein levels, identified patients at risk for cardiac events in the absence of myocardial necrosis, highlighting its potential usefulness for risk stratification among patients who present with chest pain.

In recent studies we demonstrated that systemic levels of protein-bound nitrotyrosine (NO(2)Tyr) and myeloperoxidase (MPO), a protein that catalyzes generation of nitrating oxidants, serve as independent predictors of atherosclerotic risk, burden, and incident cardiac events. We now show both that apolipoprotein A-I (apoA-I), the primary protein constituent of HDL, is a selective target for MPO-catalyzed nitration and chlorination in vivo and that MPO-catalyzed oxidation of HDL and apoA-I results in selective inhibition in ABCA1-dependent cholesterol efflux from macrophages. Dramatic selective enrichment in NO(2)Tyr and chlorotyrosine (ClTyr) content within apoA-I recovered from serum and human atherosclerotic lesions is noted, and analysis of serum from sequential subjects demonstrates that the NO(2)Tyr and ClTyr contents of apoA-I are markedly higher in individuals with cardiovascular disease (CVD). Analysis of circulating HDL further reveals that higher NO(2)Tyr and ClTyr contents of the lipoprotein are each significantly associated with diminished ABCA1-dependent cholesterol efflux capacity of the lipoprotein. MPO as a likely mechanism for oxidative modification of apoA-I in vivo is apparently facilitated by MPO binding to apoA-I, as revealed by cross-immunoprecipitation studies in plasma, recovery of MPO within HDL-like particles isolated from human atheroma, and identification of a probable contact site between the apoA-I moiety of HDL and MPO. To our knowledge, the present results provide the first direct evidence for apoA-I as a selective target for MPO-catalyzed oxidative modification in human atheroma. They also suggest a potential mechanism for MPO-dependent generation of a proatherogenic dysfunctional form of HDL in vivo.

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To study the risk factors for febrile morbidity associated with hysterectomy, the authors reviewed the medical records of women who underwent hysterectomy at their institution between January and September 1997. Only women with benign conditions were included. Possible risk factors for postoperative febrile morbidity, including demographic, reproductive, clinical, and operative characteristics of patients, were identified and subjected to multivariate logistic regression analysis. Sixty percent (n ϭ 408) of the procedures were abdominal hysterectomy, 13% (n ϭ 90) were laparoscopic-assisted vaginal hysterectomy, and 27% (n ϭ 188) were vaginal hysterectomy. The women who had abdominal procedures were more likely to have private health insurance, to be nulliparous, and to have a body mass index above 30 kg/m 2 than those who had vaginal hysterectomy. Also, more women who had abdominal or laparoscopically assisted vaginal hysterectomy were less than 50 years of age. Differences in clinical characteristics included higher rates of estimated blood loss in the abdominal and laparoscopic-assisted vaginal hysterectomy groups and longer operative times in the laparoscopic-assisted vaginal hysterectomy procedures. In all, 14% (n ϭ 96) of the 686 patients developed a postoperative fever. The incidence was significantly higher in the abdominal group compared with the vaginal and laparoscopically assisted vaginal hysterectomy (18% vs. 9% and 8%, respectively). Fifty percent of all patients were given no preoperative antibiotics. Forty-five percent of the women who underwent abdominal hysterectomy received preoperative antibiotics compared with 53% and 59% of those who had vaginal or laparoscopically assisted vaginal hysterectomy, respectively. Nineteen percent of all patients received no prophylactic antibiotic therapy. Multivariate logistic regression analysis of possible risk factors for febrile morbidity, after adjustment for age, insurance, parity, and body mass index, found that surgical approach and estimated blood loss were predictive of postoperative febrile morbidity. Abdominal hysterectomy had an odds ratio for development of postoperative fever of 2.5 (95% confidence interval, 1.3-4.9) compared with vaginal hysterectomy. The comparable odds ratio for blood loss greater than 750 mL was 3.7 (95% confidence interval, 1.9-7.2). ABSTRACTThe authors used a running mass technique using looped N. 1 polydioxanone suture to close the abdominal wall in a series of 149 high-risk gynecologic surgery patients who were either obese or had a diagnosis of gynecologic cancer. A midline vertical incision was used in 146 cases and transverse incision in 3. The first bite was draw through the loop. ABSTRACTDanish women who were scheduled to undergo hysterectomy for benign disease were invited to participate in a randomized, controlled trial of total versus subtotal hysterectomy. Outcome measures included urinary incontinence, postoperative complications, quality of life, constipation, prolapse of the vaginal top/cervical stump, satisfac...

Background-Inflammation after myocardial infarction (MI) heralds worse left ventricular (LV) function and clinicaloutcomes. However, whether inflammation affects LV function by extending myonecrosis and/or altering LV remodeling remains unknown. We hypothesized that cytotoxic aldehydes generated during oxidative stress may adversely affect remodeling and infarct size. One theoretical source of reactive aldehydes is oxidation of common ␣-amino acids by myeloperoxidase (MPO) released by leukocytes. However, a role for MPO in formation of aldehydes in vivo and the functional consequences of MPO-generated oxidants in ischemia/reperfusion models of MI have not been established. Methods and Results-In studies with cell types found in vascular tissue, MPO-oxidation products of glycine (formaldehyde) and threonine (acrolein) were the most cytotoxic. Mass spectrometry studies of myocardial tissue from murine models of acute MI (both chronic left anterior descending coronary artery ligation and ischemia/reperfusion injury) confirmed that MPO serves as a major enzymatic source in the generation of these cytotoxic aldehydes. Interestingly, although MPO-null mice experienced 35.1% (PϽ0.001) less LV dilation and a 52.2% (PϽ0.0001) improvement in LV function compared with wild-type mice 24 days after ischemia/reperfusion injury, no difference in infarct size between wild-type and MPO-null mice was noted. Conclusions-The present data separate inflammatory effects on infarct size and LV remodeling and demonstrate that MPO-generated oxidants do not significantly affect tissue necrosis after MI but rather have a profound adverse effect on LV remodeling and function. (Circulation. 2005;112:2812-2820.)