Oral OPC-8212 for the treatment of congestive heart failure: Hemodynamic improvement and increased exercise capacity

Summary The chronic effects of the oral administration of OPC-8212 (3,4-DIHYDRO-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-quinolinone) on resting hemodynamics and exercise capacity were assessed in 15 patients with congestive heart failure (NYHA II–IV). Doses of 30 or 60 mg per day were given per os over 3.0 weeks on average (range 2–6 weeks). Multigated radionuclide ventriculography and multistage exercise testing were performed before and during OPC-8212 therapy to assess the changes in left ventricular volume and exercise capacity respectively. Systolic blood pressure showed a slight increase (from 123±3 to 129±4 mmHg) during OPC-8212 therapy, while heart rate was unchanged (69±3 vs 67±3 beats/min). The left ventricular end-diastolic volume index decreased from 127±9 to 107±7 ml/m², and ejection fraction and the P/V index (the ratio of peak systolic pressure to left ventricular end-systolic volume index) increased during OPC-8212 therapy (from 27%±3% to 30%±4% and from 1.5±0.2 to 2.0±0.3 mmHg/ml/m² respectively). NYHA functional class was improved in 9 of 15 patients, and the average peak work load achieved during exercise testing increased from 27±6 to 47±7 W. No significant adverse effect was observed in any patient. These results indicate that OPC-8212 enhances the inotropic state and, hence, reduces heart size with no change in heart rate. Moreover, it increases exercise capacity. Thus, OPC-8212 is an inotropic agent with promise for application in the long-term treatment of congestive heart failure.     

Early postoperative heparinization reduce hemolysis in patients with HeartMate II devices

Journal of Artificial Organs - Hemolysis is closely related with pump thrombosis and thromboembolic events in patients with continuous flow left ventricular assist devices. We retrospectively...     

Congenital generalized lipodystrophy with insulin-resistant diabetes

Hyperglycemia, glucose intolerance, hyperinsulinemia and resistance to exogenous insulin were found in a 10-year-old Japanese boy diagnosed as having congenital generalized lipodystrophy.Studies on insulin receptors of circulating mononuclear leucocytes indicated that insulin-resistant diabetes combined with congenital generalized lipodystrophy may be due to disturbance of insulin binding to membrane receptors. No insulin-binding antibody or antibody that impairs insulin-receptor binding was found.Plasma glucagon showed an exaggerated response to L-arginine before treatment. After treatment with a controlled diet and an oral sulfonylurea (500 mg/day) for 4 weeks, there was improvement in the plasma glucagon response to L-arginine. Improvement in the hyperglycemia, hyperinsulinemia and acanthosis nigricans was also observed.On the other hand, on completion of a 7-day high-fat diet, a marked increase in serum free fatty acids, triglycerides and -lipoproteins was observed. The total plasma post-heparin lipolytic activity during the high fat diet was within the normal range. However, the level of protamine-inactivated activity was 3 times that of the control.     

Cytopathological and immunocytochemical findings of pancreatic anaplastic carcinoma with ZEB1 expression by means of touch imprint cytology

Pancreatic anaplastic carcinoma (PAC) is rare and has an aggressive clinical course. We report an autopsy case of PAC focusing on the cytopathological characteristics of the tumor and immunocytochemical staining for vimentin, E‐cadherin, and zinc finger E‐box binding homeobox 1 (ZEB1), which markers are associated with epithelial markers of epithelial‐mesenchymal transition (EMT). A 50‐year‐old woman presented to our hospital with a chief complaint of jaundice. A pancreatic head tumor and multiple liver nodules were detected on abdominal computed tomography. Biliary cytology under endoscopic retrograde cholangiopancreatography suggested ductal adenocarcinoma. Three months after admission, she died of multiorgan failure. At autopsy, touch imprint cytology using squash preparation of the pancreatic tumor identified two different cell types; numerous isolated malignant cells with large and pleomorphic nuclei and a few clusters showing irregularly overlapped nuclei and irregular contours within the necrotic background. Immunocytochemically, isolated cells were positive for vimentin and ZEB1, and negative for E‐cadherin. Conversely, clusters were negative for vimentin and ZEB1, and positive for E‐cadherin. Histologically, the tumor was composed of sarcomatous cells with small foci of adenocarcinoma, which were consistent with a diagnosis of PAC. Immunohistochemical staining of the adenocarcinoma and sarcomatous cells corresponded to those of the clusters and isolated malignant cells, respectively. Immunostaining of these EMT markers is useful to distinguish sarcomatous cells from adenocarcinoma and can contribute to the accurate diagnosis of pancreatic tumors with EMT.     

Increased plasma levels of the soluble form of Fas ligand in patients with acute myocardial infarction and unstable angina pectoris

OBJECTIVES: To examine whether the Fas/Fas ligand system is involved in the pathogenesis of acute myocardial infarction (AMI), we measured the levels of the soluble form of the Fas ligand (sFasL) in the plasma of patients with AMI and stable or unstable angina pectoris (AP). BACKGROUND: The Fas ligand (FasL) is rapidly cleaved off by a metalloproteinase from the cell membrane to become a soluble form as a cytokine. Fas is expressed in most cells, including cardiomyocytes, whereas FasL is mainly expressed in inflammatory cells such as macrophages, which are greatly accumulated in unstable plaque. METHODS: Thirty patients with AMI, 10 patients with unstable AP, 10 patients with stable AP and 30 control subjects were enrolled in the present study. RESULTS: Plasma sFasL levels were significantly elevated on hospital admission in patients with AMI and unstable AP, compared with control subjects. Time-course studies revealed that plasma sFasL levels rapidly decreased within 3 h and then increased again after percutaneous transluminal coronary angioplasty in patients with AMI, but not in patients with stable AP. Importantly, the sFasL levels were higher in the coronary sinus than in the circulation. In addition, in vitro studies showed that the expression of FasL messenger ribonucleic acid was upregulated in mononuclear cells isolated from patients with AMI and that hypoxia stimulated the release of sFasL from isolated mononuclear cells. CONCLUSIONS: This demonstration of elevated levels of sFasL in patients with AMI and unstable AP suggests that activation of the Fas/FasL system may play a pathogenic role in AMI and acute coronary syndromes.     

Crimes in New York and Tokyo: Sociocultural perspectives

Patterns of major crimes in Tokyo and New York City, based on officiai reports, are compared. Among other findings, the rate of infanticides among the total of murder cases was strikingly higher in Tokyo than in New York City. Intruders in New York City, on the other hand, were found to seek confrontation with victims more actively than their counterparts in Tokyo. Social and cultural factors underlying or contributing to the causes of major crimes are discussed.