Right ventricular cardiomyocyte apoptosis in patients with acute myocardial infarction of the left ventricular wall.

Cardiac remodeling after acute myocardial infarction (AMI) is characterized by molecular and cellular mechanisms involving both the left (LV) and right ventricular (RV) walls. Cardiomyoycte apoptosis in the peri-infarct and remote LV myocardium has a central role in cardiac remodeling. Whether apoptosis also occurs in the right ventricle of patients with ischemic heart disease has not been investigated. The aim of the present study was to investigate the presence of cardiomyocyte apoptosis in the right ventricle in patients with AMI. We assessed the number of apoptotic cardiomyocytes using multiple samplings in the LV and RV walls of 12 patients selected at autopsy who died 4 to 42 days after AMI. Five patients without cardiac disease were also selected at autopsy as controls. Apoptotic rates were calculated from the number of cardiomyocytes showing double positive staining for in situ end-labeling of DNA fragmentation (TUNEL) and for activated caspase-3. Potentially false-positive results (DNA synthesis and RNA splicing) were excluded from cell counts. The apoptotic rate in the right ventricle in patients with AMI was significantly higher than in control hearts (median 0.8%, interquartile range 0.3 to 1.0 vs median 0.01%, interquartile range 0.01 to 0.03, p <0.001). RV apoptosis significantly correlated with such parameters of global adverse remodeling as cardiac diameter to LV free wall thickness (R = +0.57, p = 0.050). RV apoptosis was significantly higher in five cases (42%) with infarct involving the ventricular septum and an adjacent small area of the RV walls (median 1.0%, interquartile range 0.8 to 2.2 vs median 0.5%, interquartile range 0.2 to 1.0, p = 0.048, p <0.001 vs controls). The association between apoptotic rate in the right ventricle and cardiac remodeling was apparent even after exclusion of cases with RV AMI involvement (R = +0.82, p = 0.023 for diameter to LV wall thickness ratio and R = -0.91, p = 0.002 for RV free wall thickness). In conclusion, patients with cardiac remodeling after AMI had a significant increase in RV apoptosis even when ischemic involvement of the RV wall was not apparent.

Left ventricular diastolic filling pattern at Doppler echocardiography and apoptotic rate in fatal acute myocardial infarction.

Heart failure is a complex syndrome characterized by impaired emptying and/or impaired filling of the heart chambers. The use of parameters of diastolic function has provided novel tools for risk stratification and management of patients with heart failure. This study evaluated the potential correlation between apoptosis at time of death and left ventricular (LV) diastolic function after acute myocardial infarction. We selected, at routine postmortem examination, 14 subjects who died 10 to 62 days after an acute myocardial infarction and had an available echocardiographic report from the most recent hospital admission. The apoptotic rate was calculated at the region bordering the infarct, using co-localization of in situ end-labeling for deoxyribonucleic acid fragmentation and immunohistochemistry for caspase-3. Transthoracic echocardiographic studies were retrospectively reevaluated and pulse-wave Doppler spectra of mitral inflow were analyzed. LV diastolic function was assessed by measuring the ratio of E peak velocity to A peak velocity and E-wave deceleration time; a ratio of E peak velocity to A peak velocity >or=2 and deceleration time <115 ms were considered a restrictive filling pattern. A restrictive pattern was found in 4 cases (29%). All subjects with a restrictive pattern were symptomatic for New York Heart Association class IV heart failure (100% vs 20%, p = 0.015) and had larger transverse heart diameters at pathology (p = 0.014). The apoptotic rate in the peri-infarct region was significantly higher in patients with a restrictive versus nonrestrictive diastolic pattern (13%, 10 to 14, vs 3%, 1 to 6, p = 0.014). At multivariable analysis that included the restrictive pattern, class IV heart failure, and cardiac diameters, the restrictive pattern remained an independent predictor of increased apoptosis (p = 0.030). In conclusion, patients with severe postinfarction LV diastolic dysfunction had significantly higher rates of cardiomyocyte loss by apoptosis, which may partly explain their unfavorable outcome.

BUBR1 expression in oral squamous cell carcinoma and its relationship to tumor stage and survival.

BACKGROUND: Defects in the mitotic spindle checkpoint have been proposed to contribute to the chromosomal instability observed in human cancers, including oral squamous cell carcinoma (OSCC). BUBR1 is a key component of the spindle checkpoint, whose role in oral carcinogenesis still needs to be clarified. METHODS: We have analyzed the expression of BUBR1 in 49 cases of OSCC by immunohistochemistry and compared the findings with clinicopathologic parameters, proliferative activity, and DNA ploidy. RESULTS: BUBR1 was overexpressed in 11 cases (22.4%). Tumors with overexpression of BUBR1 were associated with a less advanced pathologic stage (p = .05) and showed longer survival periods (p = .38) but shorter recurrence-free survival periods (p = .13) than those without it. CONCLUSIONS: Our data imply the possibility that BUBR1 may be involved in the progression of OSCC, and suggest that BUBR1 may be a promising prognostic marker in patients with OSCC.

Primary pericardial mesothelioma in an asbestos-exposed patient with previous heart surgery.

We present a case of primary pericardial mesothelioma occurring in an asbestos-exposed 67-year-old man who underwent four aortocoronary bypass grafting seven years prior to the onset of the mesothelioma. Primary pericardial mesothelioma is a rare tumor whose association with asbestos is more infrequent than that of the much more common pleural form. Factors other than asbestos that may play a role include genetic predisposition, immune impairment, infections, radiation, dietary factors, and recurrent serosal inflammation. We consider that, in the presented case, inflammation and healing resulting from pericardiotomy might have had a synergistic effect with asbestos in the pathogenesis of the tumor. To our knowledge, this is the first reported case of primary pericardial mesothelioma arising in a patient exposed to asbestos who previously underwent cardiac surgery.