[Redo Aortic and Mitral Valve Replacement by Manouguian's Procedure for Active Prosthetic Valve Infection].

The damage to the intervalvular fibrous trigone (IVFT) by infective endocarditis makes combined aortic and mitral valve replacement difficult. We performed Manouguian's double valve replacement for such a case and obtained a good result. A 81-year-old male underwent emergency operation due to active prosthetic valve endocarditis. He had a history of receiving combined aortic and mitral valve replacement because of active infective endocarditis at the age of 74 and redo aortic valve replacement 3 years after that. The infectious lesion extended from the mitral annulus to the IVFT and the aortic annulus, and it caused the prosthetic valve detachment from the aortic annulus. Manouguian's double valve replacement was required for radical resection and reconstruction of the IVFT. No recurrent infection or paravalvular leakage was observed during 49months follow up period. Manouguian's procedure is useful for complete resection of the infected IVFT and makes combined aortic and mitral valve replacement safer.

[Second use of preserved aortic cusps for bentall procedure after aortic valve replacement with intravalvular implantation technique in aortitis syndrome].

A 44-year-old woman who had undergone aortic valve replacement with intravalvular implantation technique due to aortitis syndrome 13 years before, required Bentall procedure and hemiarch replacement because of the tissue valve dysfunction and the root and ascending aortic aneurysms. The exposed native aortic cusps sandwiched between the felt pledgets and the tissue valve seemed to be useful in reinforcing the proximal anastomosis of the composite graft. A combination of an intravalvular implantation technique and a skirted composite graft technique was applied, and her postoperative course has been uneventful for more than 2 and a half years.

Perivascular adipose tissue-secreted angiopoietin-like protein 2 (Angptl2) accelerates neointimal hyperplasia after endovascular injury.

Much attention is currently focused on the role of perivascular adipose tissue in development of cardiovascular disease (CVD). Some researchers view it as promoting CVD through secretion of cytokines and growth factors called adipokines, while recent reports reveal that perivascular adipose tissue can exert a protective effect on CVD development. Furthermore, adiponectin, an anti-inflammatory adipokine, reportedly suppresses neointimal hyperplasia after endovascular injury, whereas such vascular remodeling is enhanced by pro-inflammatory adipokines secreted by perivascular adipose, such as tumor necrosis factor-α (TNF-α). These findings suggest that extent of vascular remodeling, a pathological process associated with CVD development, depends on the balance between pro- and anti-inflammatory adipokines secreted from perivascular adipose tissue. We previously demonstrated that angiopoietin-like protein 2 (Angptl2), a pro-inflammatory factor secreted by adipose tissue, promotes adipose tissue inflammation and subsequent systemic insulin resistance in obesity. Here, we examined whether Angptl2 secreted by perivascular adipose tissue contributes to vascular remodeling after endovascular injury in studies of transgenic mice expressing Angptl2 in adipose tissue (aP2-Angptl2 transgenic mice) and Angptl2 knockout mice (Angptl2(-/-) mice). To assess the role of Angptl2 secreted by perivascular adipose tissue on vascular remodeling after endovascular injury, we performed adipose tissue transplantation experiments using these mice. Wild-type mice with perivascular adipose tissue derived from aP2-Angptl2 mice exhibited accelerated neointimal hyperplasia after endovascular injury compared to wild-type mice transplanted with wild-type tissue. Conversely, vascular inflammation and neointimal hyperplasia after endovascular injury were significantly attenuated in wild-type mice transplanted with Angptl2(-/-) mouse-derived perivascular adipose tissue compared to wild-type mice transplanted with wild-type tissue. RT-PCR analysis revealed that mouse Angptl2 expression in perivascular adipose tissue was significantly increased by aging, hypercholesterolemia, and endovascular injury, all risk factors for coronary heart disease (CHD). Immunohistochemical and RT-PCR analysis of tissues from patients with CHD and from non-CHD patients indicated that ANGPTL2 expression in epicardial adipose tissue was unchanged. Interestingly, that analysis also revealed a positive correlation in ANGPTL2 and ADIPONECTIN expression in epicardial adipose tissue of non-CHD patients, a correlation not seen in CHD patients. However, in epicardial adipose tissue from CHD patients, ANGPTL2 expression was positively correlated with that of TNF-α, a correlation was not seen in non-CHD patients. These findings suggest that pro-inflammatory adipokines cooperatively accelerate CHD development and that maintaining a balance between pro- and anti-inflammatory adipokines likely protects non-CHD patients from developing CHD. Overall, our studies demonstrate that perivascular adipose tissue-secreted Angptl2 accelerates vascular inflammation and the subsequent CVD development.

Macrophage-derived angiopoietin-like protein 2 accelerates development of abdominal aortic aneurysm.

OBJECTIVE: Recently, we reported that angiopoietin-like protein 2 (Angptl2) functions in various chronic inflammatory diseases. In the present study, we asked whether Angptl2 and its associated chronic inflammation contribute to abdominal aortic aneurysm (AAA). METHODS AND RESULTS: Immunohistochemistry revealed that Angptl2 is abundantly expressed in infiltrating macrophages within the vessel wall of patients with AAA and in a CaCl(2)-induced AAA mouse model. When Angptl2-deficient mice were used in the mouse model, they showed decreased AAA development compared with wild-type mice, as evidenced by reduction in aneurysmal size, less severe destruction of vessel structure, and lower expression of proinflammatory cytokines and matrix metalloproteinase-9. However, no difference in the number of infiltrating macrophages within the aortic aneurysmal vessel wall was observed between genotypes. AAA development was also significantly suppressed in wild-type mice that underwent Angptl2-deficient bone marrow transplantation. Expression levels of proinflammatory cytokines and metalloproteinase-9 in Angptl2-deficient macrophages were significantly decreased, and those decreases were rescued by treatment of Angptl2 deficient macrophages with exogenous Angptl2. CONCLUSIONS: Macrophage-derived Angptl2 contributes to AAA development by inducing inflammation and degradation of extracellular matrix in the vessel wall, suggesting that targeting the Angptl2-induced inflammatory axis in macrophages could represent a new strategy for AAA therapy.

Clinical evidence versus patients' perception of coronary revascularization.

Coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) have been developed as revascularization techniques for coronary artery disease. CABG offers a survival advantage over medical therapy, especially for high-risk coronary patients, whereas PCI is the most frequent initial procedure to treat multi-vessel coronary artery disease, because it is less invasive. However, PCI has been found to confer no additional benefit with respect to myocardial infarction (MI) or death. The SYNTAX trial compared the outcomes of patients with left main and/or three-vessel coronary artery disease treated with CABG versus PCI using drug-eluting stents. The 4-year results showed that all-cause mortality and cardiac death were both significantly higher in the PCI group than in the CABG group. Despite extensive evidence of the advantages of CABG over PCI with respect to death or MI, PCI is recommended more often and CABG less often than indicated in the guidelines. Patients with coronary artery disease should receive unbiased information about the risks and benefits of each procedure and the alternatives. A multidisciplinary approach, referred to as "the Heart Team", could help to improve the informed consent process when recommending revascularization treatment for coronary artery disease.

Debate over patient-centered care: percutaneous coronary intervention or coronary artery bypass grafting?

Coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) have developed as effective therapies to treat coronary artery disease. Initial CABG is associated with lower mortality than initial medical management, especially among high- and intermediate-risk patients with coronary artery disease. However, PCI is currently the most frequent initial treatment delivered by interventional cardiologists to treat multivessel coronary artery disease, despite substantial evidence from meta-analyses of randomized trials and registry data favoring CABG. Recent advancements in PCI did not result in detectable improvements in death or myocardial infarction compared with medical therapy, although significant reductions in target lesions or vessel revascularization were identified after implantation of a drug-eluting stent (DES) rather than a bare-metal stent. The SYNTAX trial compared patients with left main and/or three-vessel coronary artery disease treated with DES or CABG. The results of the trial demonstrated the 1-year inferiority of PCI compared with CABG with respect to major adverse cardiac and cerebrovascular events. Nevertheless, patients with coronary artery disease continue to receive more recommendations for PCI and fewer for CABG than are indicated in the guidelines. A multidisciplinary team approach should be the standard of care when recommending interventions for treating complex coronary artery disease among patients for whom CABG is superior in terms of survival and freedom from reintervention.

Intravascular papillary endothelial hyperplasia in an aneurysm of the superficial temporal artery: Report of a case.

We herein report a rare case of an intravascular papillary endothelial hyperplasia in an aneurysm of the superficial temporal artery. The patient was a 67-year old Japanese woman. She noticed a throbbing swelling in her left forehead, which had gradually been increasing in size. She had no previous history of head trauma. Ultrasonography and three-dimensional computed tomographic angiography revealed an aneurysm with a mural thrombus measuring 10 mm in diameter fed by the frontal branch of the left superficial temporal artery. The aneurysm of the superficial temporal artery was dissected from the surrounding tissues, and was resected after ligation of feeding vessels. A microscopic examination revealed papillary endothelial hyperplasia in a true aneurysm. Nontraumatic aneurysms of the superficial temporal artery are rare. In the previous English literature, there have only been a few reports of papillary endothelial hyperplasia in an artery, and none in an aneurysm of the superficial temporal artery.

Different roles of Foxo1 and Foxo3 in the control of endothelial cell morphology.

Foxo1, a member of the Foxo subfamily of forkhead box transcription factors, is known to be essential for progression of normal vascular development in the mouse embryos. In the cultures of endothelial cells derived from embryonic stem cells, Foxo1-deficient endothelial cells exhibit an abnormal morphological response to vascular endothelial growth factor-A (VEGF-A), which is characterized by a lack of cell elongation, yet the molecular mechanisms governing endothelial cell morphology under angiogenic stimulation remain unknown. Here, we report that transforming growth actor-beta also induces endothelial cell elongation in collaboration with Foxo1 and VEGF-A. Furthermore, tetracycline-regulated induction of Foxo3, another member of the Foxo subfamily, into Foxo1-null endothelial cells failed to restore abnormal morphological response to VEGF-A at an early differentiation stage. In contrast, Foxo1 and Foxo3 exerted the same function at a late differentiation stage, i.e. enhancement of VEGF responsiveness and promotion of cell elongation. Our results provide evidence that endothelial cell morphology is regulated by several mechanisms in which Foxo1 and Foxo3 express distinct functional properties depending on differentiation stages.

Prognostic factors of curatively resected esophageal carcinoma associated with multiple metastatic lymph nodes.

BACKGROUND/AIMS: Prognosis of esophageal carcinoma with multiple metastatic lymph nodes is dismal despite radical operation and adjuvant therapy. We investigated prognostic factors for curatively resected esophageal carcinoma with multiple positive nodes. METHODOLOGY: From January 1983 to December 2002, 343 patients with thoracic esophageal carcinoma underwent an esophagectomy with curative intent. Of these patients, 82 patients were associated with 4 or more histopathologically positive nodes. Of these patients, 59 patients underwent a curative resection. Of these 59 patients, 7 patients who died of postoperative complications during the hospital stay were excluded. Therefore, 52 patients were enrolled in this study. Survival curves were compared after stratifications according to 14 clinicopathologic variables. Independent prognostic factors were detected using a multivariate Cox proportional hazard model. RESULTS: The cumulative 5-year survival rate for the subjects was 10.6%. The factors affecting cumulative survival rate by a univariate analysis were intramural metastasis (absence vs. presence) (p=0.03), and postoperative therapy (performed vs. not performed) (p=0.02). A multivariate analysis detected the performance of postoperative therapy (Hazard Ratio= 0.390, p= 0.002) and the absence of intramural metastasis (Hazard ratio=0.429, p=0.01) as positive prognostic factors. CONCLUSIONS: The positive prognostic factors for esophageal carcinoma with multiple lymph node metastases were the absence of intramural metastasis and the performance of adjuvant therapy.

Tumor suppressor WARTS ensures genomic integrity by regulating both mitotic progression and G1 tetraploidy checkpoint function.

Defects in chromosomes or mitotic spindles activate the spindle checkpoint, resulting in cell cycle arrest at prometaphase. The prolonged activation of spindle checkpoint generally leads to mitotic exit without segregation after a transient mitotic arrest and the consequent formation of tetraploid G(1) cells. These tetraploid cells are usually blocked to enter the subsequent S phase by the activation of p53/pRb pathway, which is referred to as the G(1) tetraploidy checkpoint. A human homologue of the Drosophila warts tumor suppressor, WARTS, is an evolutionarily conserved serine-threonine kinase and implicated in development of human tumors. We previously showed that WARTS plays a crucial role in controlling mitotic progression by forming a regulatory complex with zyxin, a regulator of actin filament assembly, on mitotic apparatus. However, when WARTS is activated during cell cycle and how the loss of WARTS function leads to tumorigenesis have not been elucidated. Here we show that WARTS is activated during mitosis in mammalian cells, and that overexpression of a kinase-inactive WARTS in Rat1 fibroblasts significantly induced mitotic delay. This delay resulted from prolonged activation of the spindle assembly checkpoint and was frequently followed by mitotic slippage and the development of tetraploidy. The resulting tetraploid cells then abrogated the G(1) tetraploidy checkpoint and entered S phase to achieve a DNA content of 8N. This impairment of G(1) tetraploidy checkpoint was caused as a consequence of failure to induce p53 expression by expressing a kinase-inactive WARTS. WARTS thus plays a critical role in maintenance of ploidy through its actions in both mitotic progression and the G(1) tetraploidy checkpoint.

Defining the roles of beta-catenin and plakoglobin in cell-cell adhesion: isolation of beta-catenin/plakoglobin-deficient F9 cells.

F9 teratocarcinoma cells in which beta-catenin and/or plakoglobin genes are knocked-out were generated and investigated in an effort to define the role of beta-catenin and plakoglobin in cell adhesion. Loss of beta-catenin expression only did not affect cadherin-mediated cell adhesion activity. Loss of both beta-catenin and plakoglobin expression, however, severely affected the strong cell adhesion activity of cadherin. In beta-catenin-deficient cells, the amount of plakoglobin associated with E-cadherin dramatically increased. In beta-catenin/plakoglobin-deficient cells, the level of E-cadherin and alpha-catenin markedly decreased. In these cells, E-cadherin formed large aggregates in cytoplasm and membrane localization of alpha-catenin was barely detected. These data confirmed that beta-catenin or plakoglobin is required for alpha-catenin to form complex with E-cadherin. It was also demonstrated that plakoglobin can compensate for the absence of beta-catenin. Moreover it was suggested that beta-catenin or plakoglobin is required not only for the cell adhesion activity but also for the stable expression and cell surface localization of E-cadherin.

Monocyte chemotactic S19 ribosomal protein dimer in atherosclerotic vascular lesion.

To elucidate the molecular mechanism inducing monocyte/macrophage infiltration in the atherosclerotic lesion, we measured the monocyte chemotactic capacity in the extracts of aortic lesions. Five out of seven extracts exhibited significant chemotactic activities. Immunohistochemical examination with an anti-CD68 monoclonal antibody demonstrated that the five positive lesions possessed obvious monocyte/macrophage infiltrations at the intima, whereas the two negative lesions did so at significantly lower intensities. We subjected the chemotactic extracts to immunological analyses to identify the monocyte chemoattractant in them. The monocyte chemotactic capacities of all positive extracts were removed with anti-S19 ribosomal protein (RP S19) antibody beads and antimonocyte chemoattractant protein-1 (MCP-1) antibody beads. In three of the five extracts, the anti-RP S19 antibody beads were more effective than the anti-MCP-1 antibody beads for removal, while in the remaining two extracts, the opposite was observed. A combined immunoabsorption with these beads depleted the monocyte chemotactic capacity of a representative sample of each group. Consistently, the chemotactic capacity of an apparently RP S19 dimer-predominant extract was strongly inhibited by the presence of a C5a receptor antagonist. These results suggest that the RP S19 dimer and MCP-1 play a major role in the monocyte/macrophage infiltration of the atherosclerotic vascular lesion.

Protective effect of melatonin on human peripheral blood hematopoeitic stem cells against doxorubicin cytotoxicity.

BACKGROUND: The dose-limiting toxicity of doxorubicin on hematopoietic stem cells reduces the maximum benefit from this powerful drug. Melatonin may play a role in reducing this toxicity. MATERIALS AND METHODS: Melatonin at 10 microM was used while challenging human peripheral blood stem cells (PBSC) with doxorubicin (0.6 microM and 1 microM), and colony formation was used to evaluate the protective effect of melatonin. RESULTS: Melatonin was protective for the myeloid and erythroid series when given during or 1 hour after, but not before, doxorubicin, as measured by colony assay. This protection was independent from its antioxidant function as measured by 2', 7'-dichlodihydro-fluorescein diacetate and was selective for PBSC when compared to the MCF-7 cancer cell line. CONCLUSION: The results suggest the importance of the time sequence for melatonin administration to exert its protective effect in relation to doxorubicin treatment, as well as its protective effect on both erythroid and myeloid elements independent from its antioxidant function.

Electrocardiographic gated (99m)Tc-MIBI SPECT for functional assessment of patients after coronary artery bypass surgery: comparison of wall thickening and wall motion analysis.

UNLABELLED: Abnormal septal motion after coronary artery bypass graft surgery (CABG) is a common finding. This study was undertaken to investigate the change in various global and regional ventricular function parameters measured by gated myocardial perfusion SPECT after surgery and to determine which quantitative parameter of WT and WM is more appropriate for the evaluation of regional cardiac function, especially in the septum of patients with CABG. METHODS: Before and 3 to 5 wk after CABG (all patients underwent at least 1 bypass grafting to the left anterior descending coronary artery), 35 patients (28 men, 7 women) underwent gated SPECT using (99m)Tc-methoxyisobutylisonitrile. Quantitative global and regional ventricular functional analysis was performed using quantitative gated SPECT software. RESULTS: Global ejection fraction did not change (59.3% +/- 16.0% to 60.5% +/- 14.5%, P = 0.24). However, end-diastolic and end-systolic volumes lessened significantly after CABG (81.4 +/- 37.3 mL to 68.9 +/- 28.9 mL, P < 0.0001, and 38.1 +/- 33.1 mL to 30.4 +/- 23.0 mL, P < 0.005, respectively). As global function parameters, the changes in both total WM (r = 0.88) and WT (r = 0.86) correlated well with the change in ejection fraction after surgery. Segmental analysis showed a significant postoperative increase in relative tracer uptake in the anterior, anteroseptal, inferoseptal, and inferior walls and in the apex. Segmental wall motion (WM) deteriorated in the anteroseptal, inferoseptal, and mid anterior walls. On the other hand, anterolateral, inferolateral, and inferior WM increased. As a whole, these WM changes showed a reduction in septal motion associated with a concomitant increase in lateral motion after surgery. Segmental wall thickening, however, did not decrease in septal areas and did not increase in the lateral wall and correlated with percentage tracer uptake (r = 0.69) better than WM did (r = 0.30) after CABG. CONCLUSION: In patients with CABG, postoperative WM analysis by gated SPECT underestimated septal motion and overestimated lateral motion because of exaggerated systolic anteromedial cardiac translation. Therefore, wall thickening analysis would be recommended for the evaluation of postoperative cardiac function.

The width of a gastric tube has no impact on outcome after esophagectomy.

BACKGROUND: We evaluated the impact of the size of gastric tubes on tissue blood flow of the anastomotic site, the frequency of leakage and the postoperative nutritional status. METHODS: Forty-four patients were randomly allocated to either reconstruction using subtotal stomach (n = 22) or to reconstruction using slender gastric tube (n = 22) after esophagectomy. The tissue blood flow at the anastomotic site was measured. The postoperative nutritional status of 17 patients without recurrence was examined. Possible correlations between the type of esophageal substitute and the tendency to leakage as well as postoperative nutritional status were examined. RESULTS: There was no significant difference in the tissue blood and the frequency of leakage between the types of gastric tubes. There was no significant difference noted between the two in the postoperative nutritional status at 6 and 12 months after operation. CONCLUSIONS: The width of gastric tube has no impact on tissue blood flow, the frequency of leakage, and the postoperative nutritional status after esophagectomy.

Three-field dissection or two-field dissection?--A proposal of new algorithm for lymphadenectomy.

BACKGROUND/AIMS: There are no systematic criteria for cervical lymphadenectomy in esophageal carcinoma. We provide a new algorithm for deciding whether to use three-field dissection or two-field dissection. METHODOLOGY: Ninety-eight patients underwent curative esophagectomies with three-field lymph node dissections for squamous cell carcinoma of the thoracic esophagus. We examined the outcomes and predictors for survival of these patients. Therefore, we devised a new decision tree for deciding whether to use three-field dissection or two-field dissection. RESULTS: The overall 5-year survival rate for the 98 patients was 41.3%. The number of positive nodes was the only significant predictor for survival in the multivariate Cox proportional hazard model. The outcomes of patients with positive supraclavicular/internal jugular nodes were poor. On the other hand, positive cervical paraesophageal nodes do not worsen prognosis. We provided a new algorithm for selecting procedure of lymphadenectomy based on the presence of lymph node metastases. This algorithm is decided by the number of positive nodes, the presence of cervical node metastasis and recurrent nerve node metastasis. According to this decision tree, there were a few patients who needed absolutely three-field dissections. CONCLUSIONS: The new algorithm may be helpful for deciding three-field dissection or two-field dissection for thoracic esophageal carcinoma.

Predictive factors for platelet number after cardiopulmonary bypass and postoperative blood loss.

We retrospectively searched for factors that can predict the circulating platelet count after cardiopulmonary bypass (CPB) and postoperative blood loss. Correlations between the circulating platelet count after CPB and several other perioperative variables were investigated in 42 patients who underwent cardiac surgery using the same type of oxygenator. Correlations between perioperative variables and 24 hour postoperative blood loss were also investigated. A multiple stepwise regression analysis showed that the preoperative platelet count, age, and intraoperative blood transfusion values were independent predictors of the circulating platelet count after CPB (R2 = 0.661, p < 0.0001). Gender, operation type, and priority (elective or urgent) were not associated with the platelet count after CPB or postoperative blood loss. Independent predictive factors for postoperative blood loss consisted of age and intraoperative blood loss (R2 = 0.231, p = 0.006). In addition to preoperative platelet count, age and amount of intraoperative blood transfusion are predictive factors for circulating platelet count after CPB. The association of postoperative blood loss with age and intraoperative blood loss may suggest friability of the tissues, including blood vessels, in elderly patients.

Cardiac displacement with a congenital complete left-sided pericardial defect in a patient with exertional angina pectoris--a case report.

A 71-year-old man with exertional chest pain was admitted to the hospital. A chest roentgenogram exhibited levoposition of the heart. An electrocardiogram showed clockwise rotation in the precordial leads and ST depression in V6, V7, V8, and V9 as well as in II, III, aVF leads associated with chest pain in a treadmill exercise test. The congenital complete left-sided pericardial defect could not be diagnosed preoperatively, but it was confirmed by thoracotomy.

Changes in respiratory condition after thymectomy for patients with myasthenia gravis.

BACKGROUND: Anesthesia without muscle relaxants has been reported to be effective for early extubation after thymectomy, but postoperative respiratory status of the patients has not been studied intensively. METHODS: Fifty-two consecutive patients undergoing thymectomies for myasthenia gravis (MG) were evaluated. RESULTS: Forty-two (81%) of the 52 patients were extubated in the operating room, and 49 (94%) patients were extubated within 24 hours. However, 6 (12%) patients required subsequent reintubation for respiratory support. There was a sudden increase in the respiratory rate (RR) and PaCO(2). The mean value of the increase in PaCO(2) at the time of reintubation was 23 mmHg (12-58 mmHg). The mean value of the increase in RR above the preoperative level at the time of reintubation was 16/min (7-30/min). In univariate analysis, vital capacity (VC), %VC, the preoperative pyridostigmine dose and the duration of surgery correlated with reintubation, but with multivariate analyses, the pyridostigmine dose was the only significant factor related to reintubation. CONCLUSION: The patients who received at least or more than 240 mg of pyridostigmine should be monitored carefully after tracheal extubation.