Effects of DPI 201-106, a novel cardiotonic agent,on hemodynamics,cardiac electrophysiology and arrhythmias induced by programmed ventricular stimulation in dogs with subacute myocardial infarction: A comparative study with dobutamine

Summary DPI 201-106 (DPI), a novel and potent cardiotonic agent, exhibits its effects by prolonging the open state of Na⁺ channels, resulting in an increase in action potential duration, and thus, is supposed to share the class III antiarrhythmic activity. The effects of DPI on the hemodynamics, intraventricular conduction and refractoriness of heart, and the incidence of arrhythmias induced by programmed electrical ventricular stimulation (PES) were compared with (±)-dobutamine. Dogs which survived for 5 to 7 days after the induction of myocardial infarction were used as the model. The presence of sub-acute myocardial infarction caused by occluding the left anterior descending coronary artery elicited a mild left ventricular dysfunction represented by a significant decrease in peak LV dp/dt by about 20%.Both i.v. bolus injection of DPI (1, 3 and 5 mg/kg) and i. v. continuous infusion of dobutamine (3, 5 and 10 g/kg/min), which were administered in a cumulative manner, dose-dependently improved the hemodynamic parameters. At the higher doses of both DPI (3 and 5 mg/kg) and dobutamine (5 and 10 g/kg/min) the control values were reached or even exceeded. DPI dose-dependently increased the effective refractory period (ERP) of both non-infarcted and infarcted ventricular myocardia to a similar degree, but the conduction time showed a frequency-dependent increase in the infarcted myocardium to a greater degree than in the non-infarcted myocardium after DPI. In contrast, dobutamine decreased the ERP in both non-infarcted and infarcted myocardia, and slightly increased the difference of refractoriness between the non-infarcted and infarcted zones with no effect on the intraventricular conduction. In the PES study, DPI (3 and 5 mg/kg) produced a significant decrease in the incidence of ventricular tachycardia, whereas dobutamine (5 and 10 g/kg/min) tended to worsen the arrhythmias. These findings suggest that cardiotonic agents with a class III antiarrhythmic property such as DPI may be potentially useful for the management of heart failure accompanied by ischemic heart disease.Abbreviations DPI, DPI 201-106; PES programmed electrical ventricular stimulation - LV dp/dt the rate of rise of left ventricular pressure - ERP effective refractory period - RVOT right ventricular outflow tract - VT ventricular tachycardia - LAD left anterior discending coronary artery Send offprint requests to T. Uematsu at the above address     

Investigations on physiological values of blood in industrial workers. Report 3. Serum colloid reaction and enzyme activity values

The purpose of this study is establish the physiological values of serum colloid reaction and serum enzyme activities representing the liver function. 1,732 industrial workers (1,035 males aged 35-65 yr, and 697 females aged 35-60 yr) were examined by the serum zinc sulfate turbidity test (ZTT) and serum thymol turbidity test (TTT) according to the standard method of "The Japanese society of gastroenterology," serum alkaline phosphatase (ALP) by Kind-King method, serum gamma-glutamyl transpeptidase (gamma-GTP) by the modified Orlowski method, and serum glutamic oxaloacetic transaminase (GOT) and serum glutamic pyruvic transaminase (GPT) by UV method. Then frequency distributions, geometric means, several percentile values of these six laboratory data and correlations among the values were determined. The results are as follows: 1) Frequency distributions of serum ZTT, TTT, ALP, gamma-GTP, GOT, and GPT almost fitted to the log-normal distribution. 2) Geometric means and 0-95th percentile or 5-95th percentile values in bracket were 6.6 (3.7-11.7) Kunkel unit for ZTT in male, 8.2 (5.1-13.0) Kunkel unit for ZTT in female, 0.6 (0-2.8) Kunkel unit for TTT in male, 0.8 (0-2.8) Kunkel unit for TTT in female, 6.6 (4.1-10.4) King-Armstrong unit for ALP in male, 5.5 (3.2-8.9 for 49 year or less, 4.6-10.3 for 50 yr or more) King-Armstrong unit for ALP in female, 15.8 (0-45) mU/ml for gamma-GTP in male, 8.4 (0-17 for 44 yr or less, and 0-20 for 45 yr or more) mU/ml for gamma-GTP in female, 21.4 (0-39) Karmen unit for GOT in male, 20.8 (0-35) Karmen unit for GOT in female, 13.9 (0-29) Karmen unit for GPT in male, and 12.7 (0-32) Karmen unit for GPT in female. 3) Serum ZTT and TTT levels were higher in female than in male. Both ALP and gamma-GTP levels were higher in male than in female, and have become high according to aging in female. Serum level of GPT was higher in male than in female. 4) There were significant positive correlations between serum ZTT and serum TTT levels, and also between serum GOT and serum GPT levels.     

Myoepithelial hamartoma of the ileum causing intussusception in an infant

Intussusception is a relatively common pediatric gastrointestinal emergency, although the etiology in most cases remains unknown. In a small number of cases the lead point is a tumor or tumor-like lesion of the small bowel. We report an unusual case of a myoepithelial hamartoma of the ileum causing an intussusception in a 4-month-old boy. This is the second such report in the literature.     

Infantile hemangioendothelioma of the thymus with massive pleural effusion and Kasabach-Merritt syndrome: Histopathological, flow cytometrical analysis of the tumor

Infantile hemangioendothelioma of the thymus is a rare disease. We describe a patient who developed a large anterior mediastinal mass, severe thrombocytopenia and massive pleural effusion at 1 month of age. Glucocorticosteroid and irradiation therapy had no effect on either the tumor size or clinical symptoms and the tumor was resected subtotally. Three months after the subtotal resection, the remaining tumor had almost disappeared and the symptoms had resolved. The patient has now been well for 1 year after surgery without evidence of recurrence. The tumor tissue was characterized by prominent vascular endothelial proliferation intermixed with a normal thymic structure, producing a picture consistent with that of an infantile hemangioendothelioma in the thymus, lmmunohistochemically, the tumor cells showed positive staining for vimentin, factor VIII and CD34. The DNA stemline and proliferative activity were examined by flow cytometry, which revealed a diploid stemline with a low growth fraction. DNA content and cell cycle analyses of the tumor tissue may be useful for predicting the biological behavior of the tumor.     

Yolk sac tumor with a unique uniform hepatoid pattern histology

Abstract Background: Yolk sac tumors (YST) exhibit several different histological subtypes and the mechanisms of cellular differentiation and prognosis of each subtype remain unknown.
Results: We report two infants with sacrococcygeal YST; one represented a typical histological subtype and the other showed a hepatoid subtype with uniform histology. The isoform of alpha-fetoprotein (AFP) in the patient with the hepatoid pattern was examined by lectin-affinity Immunoelectrophoresis and represented as a YST. but not hepatocellular, subtype. The patient with typical YST responded well to VAB-6 combination chemotherapy. However, this regimen was only partially effective to the patient with the pure hepatoid histological subtype, and an etoposide with ifosfamide and cisplatin (VIP) regimen as a salvage chemotherapy combined with complete tumor resection was useful to achieve complete remission (CR). Both of the patients have been in CR for more than four years.     

Effects of Interleukin-12 on the Induction of Cytotoxic T Lymphocytes from the Regional Lymph Node Lymphocytes of Patients with Lung Adenocarcinoma

Lung cancer-specific cytotoxic T lymphocytes (CTL) were induced by repeated stimulations of regional lymph node lymphocytes (RLNL) in lung cancer patients with either autologous or HLA-A-locus-matched tumor cells. To investigate the effect of interleukin-12 (IL-12), IL-12 was added during the stimulation of RLNL from HLA A24 / adenocarcinoma patients with either autologous tumor cells or HLA A24-positive adenocarcinoma cells (PC-9) in combination with, or instead of interleukin-2 (IL-2), and then the cytotoxic activity, cytokine production and populations of the lymphocyte subsets were examined. The addition of IL-12, or the substitution of IL-2 by IL-12 was found to enhance the cytotoxic activity and the cytokine production (IFN-γ, GM-CSF) of the CTL as compared with IL-2 alone. The cytotoxic activity and cytokine production were both partially inhibited by anti-MHC-class I monoclonal antibody. The CTL thus induced by IL-12 had a higher proportion of CD3⁺/CD56⁺ cells than the CTL induced with IL-2 alone. The positively selected CD8⁺/CD56^– lymphocytes showed PC-9-specific cytotoxic activity, because the population did not show any cytotoxicity to K562 or A549 (HLA-A26/A30). However, the CD3⁺/CD56⁺ lymphocytes were cytotoxic to both PC-9 and K562. In conclusion, IL-12 is considered to be a useful cytokine for both the induction of lung-cancer specific CTL and the augmentation of non-MHC-restricted cytotoxicity against tumor cells, and may be applicable for adoptive immunotherapy using CTL.     

Angiomyolipoma arising in the thigh

A 41-year-old man presented with an asymptomatic mass in the right medial thigh. Magnetic resonance imaging (MRI) revealed a well-demarcated, 10-cm mass in the right adductor muscles. The margins of the mass exhibited high signal intensity and the rest showed low or iso signal intensity on T1-weighted MR images. However, the high signal intensity was decreased on T2-weighted images with fat suppression. The central part of the tumor was of inhomogeneous high signal intensity on T2-weighted images; after Gd-DTPA injection it enhanced inhomogeneously on T1-weighted images with fat suppression. On dynamic computed tomography (CT) in the arterial phase, there were strongly enhancing spotty areas in the tumor. At surgery, a yellow-whitish tumor was resected and a pathological diagnosis of angiomyolipoma (AML) in the thigh was made. Received: 21 June 1999 Revision requested: 28 July 1999 Revision received: 13 December 1999 Accepted: 15 December 1999     

Depression of long term potentiation in gerbil hippocampus following postischemic hypothermia

To investigate the mechanism of chronic cell death following postischemic hypothermia, the change of N-methyl- -aspartate receptor (NMDAR) were examined by immunohistochemistry of NMDAR1 and long-term potentiation (LTP) in the CA1 subfield of the gerbil hippocampus. At 1 week following postischemic hypothermia (32°C×4 h), all CA1 neurons survived; however, immunoreactivity of NMDAR1 increased in neuronal perikarya whereas decreased in dendrites in the CA1 neurons. The abnormality was still observed in remaining CA1 neurons at 1 month after hypothermia. LTP was also significantly depressed at 1 week after hypothermia. These results suggest that some abnormalities in the glutamate receptor may be caused by ischemia; such abnormality would persist in spite of hypothermia treatment, resulting in the depression of LTP.     

Movement of the side hole occurring in a port‐catheter system percutaneously implanted for hepatic arterial infusion chemotherapy

The authors report a case in which catheter‐related difficulties occurred with a port‐catheter system implanted to perform repeated hepatic arterial infusion chemotherapy for advanced hepatocellular carcinomas. The port‐catheter system had been percutaneously implanted with the catheter tip fixation method, and a side hole had been created in the indwelling catheter for placement in the common hepatic artery. Four months after port‐catheter placement, however, the indwelling catheter became bent at the location of the side hole in the proper hepatic artery. Subsequently, the side hole moved into the left hepatic artery, resulting in a lack of distribution of chemotherapeutic agents to the tumours in the segments of the liver supplied by the right hepatic artery. This situation was easily corrected with a simple interventional radiological method so that hepatic arterial infusion chemotherapy could be resumed with sufficient distribution over the entire liver. To our knowledge, such a problem involving a port‐catheter system implanted with the catheter tip fixation method and its management thereafter has not been reported in the published literature.