Use of a Paracorporeal Pneumatic Ventricular Assist Device for Postoperative Cardiogenic Shock in Two Children with Complex Cardiac Lesions

Pneumatic ventricular assist device (VAD) was utilized for cardiogenic shock after intracardiac operation in two children with complex cardiac anomalies based with single ventricle. In the first case (a 10-year-old), after a modified Fontan operation, VAD was placed between the functional left atrium and ascending aorta, serving as a "artificial single ventricle" with neither pumping chamber nor artificial support in the right side of the heart. The systemic circulation was maintained by keeping relatively high central venous pressure. In another child (a 3-year-old) who underwent repair of incompetent atrioventricular valve leaving intracardiac lesions, VAD was placed between the common atrium and ascending aorta, serving as a pump for both pulmonary and systemic circulation with regulation of pulmonary blood flow through an aortopulmonary Gore-Tex shunt. The circulatory assist with VAD was utilized for 5 and 6 days, respectively. Although weaning from the device was not feasible in both patients because of the pulmonary dysfunction, these experience showed the possible use of VAD for cardiogenic shock after surgery in patients with complex cardiac anomalies.     

Reduced Inhomogeneity of Angelica acutiloba Plants Propagated Clonally Through Somatic Embryoids

Clonal plants propagated from a single plant of a commercial variety of ANGELICA ACUTILOBA (Umbelliferae) through somatic embryoids induced in cell suspension cultures proved to be significantly more uniform with respect to the contents of medicinally important chemical constituents (ligustilide and choline) of the root when compared with seed-propagated plants.     

The future of 5-HT1A receptor agonists. (arylpiperazine derivatives)

Mitsukuni Murasaki and Sadanori Miura: The Future of 5-HT_1A Receptor Agonists. (Aryl-Piperazine Derivatives) Prog. Neuro- Psychopharmacol-& Biol Psychiat, 1992, 16(6): 833–845.

1. 1. At present the dominant position among anti-anxiety medications has changed from meprobamate to the benzodiazepine derivatives.

2. 2. In order to avoid benzodiazepine's (BZ) undesirable side effects such as impairment of psycho-motor function, memory impairment, low dose dependence and withdrawal symptoms, a third generation anxiolytic agent, buspirone, the focus of the aryl-piperazine group of anti-anxiety agents, has been introduced recently.

3. 3. Aryl-piperazine derivatives work as 5-HT_1A receptor partial agonists and are known as serotonin normalizers.

4. 4. Therefore, they are expected to have not only an anxiolytic function but also an anti-depressant effect as well.

5. 5. A characteristic of the aryl-piperazine derivatives is that they have no sedative and muscle relaxant effects, and they do not have BZ's undesirable side-effects, especially in regard to withdrawal symptoms. However they have a rather weak anxiolytic action and a slow onset of action.

6. 6. Aryl-piperazine derivatives will not take the place of BZ, but the use of BZ and buspirone as bridge medications, making the most of the strong points of both, can be proposed as a way to compensate for their respective disadvantages.

Long-term effect of urokinase therapy in IgA nephropathy

Effects of urokinase (UK) therapy in patients with moderate to advanced degrees of IgA nephropathy (IgAN) were examined. Twenty-seven patients were treated by "two weeks" UK administration, 14 patients were treated by "consecutive" UK administration and 16 patients were treated by antiplatelet drugs. There were marked improvements in urinary protein concentration, serum creatinine and blood urea nitrogen after UK therapy, especially in patients treated by "consecutive" UK administration which was performed by "single shot" UK injection. Clinical prognosis was favorable in patients treated by UK administration compared with those given antiplatelet treatment. It was concluded that "consecutive" UK administration might be useful for treatment of IgAN with moderate to advanced renal injuries.     

The development of health risk appraisal for Japanese as a new health educational tool

Health risk appraisal (HRA) is a new health educational tool widely-used in the United States, which informs clients about how their health habits and lifestyles affect their probability of dying from potentially preventable causes and helps to motivate them to reduce their personal health risks. It personalizes mortality statistics and epidemiologic data by combining these data with a person's risk factors. We have got started the development of HRA for Japanese with reference to a new version of HRA named "Healthier People" revised by the Carter Center of Emory University and the Centers for Disease Control in the United States.     

Reversal of multidrug resistance by new dihydropyridines with lower calcium antagonistic activity

Summary BS compounds, a series of new dihydropyridines, successfully overcame multidrug resistance in P388/ADR cells in vitro. These agents synergistically potentiated the cytotoxicity of Adriamycin to P388/ADR cells at a concentration of 1–2 M, whereas they showed hardly any synergistic effect in the parental cell line (P388/S) at the same concentration. They inhibited the active drug efflux in P388/ADR cells as well as the binding of [G-³H]-vinblastine to membrane vesicles from P388/ADR, which was increased in resistant P388 cells as compared with parental cells. Besides, unlike the activity of clinically used calcium antagonists, the calcium antagonistic activity associated with BS compounds was very weak: their arterial relaxation activity was <21% of that of verapamil. These data suggest that BS compounds specifically overcome multidrug resistance without the serious hypotensive side effects that accompany the use of verapamil orother calcium antagonists.     

Pharmacokinetic study of iminodibenzyl antipsychotic drugs,clocapramine and Y-516 in dog and man

The pharmacokinetic properties of the iminodibenzyl antipsychotic drugs clocapramine (CCP, 3-chloro-5-[3-(4-carbamoyl-4-piperidino piperidino) propyl]-10, 11-dihydro-5H-dibenzo[b, f]azepine) and Y-516 (3-chloro-5-[3-(2-oxo-1, 2, 3, 5, 6, 7, 8, 8a-octahydroimidazo [1,2-a] pyridine-3-spiro-4-piperidino) propyl]-10, 11-dihydro-5H-dibenzo[b, f]azepine) were investigated in dog and man. Dogs were administered CCP and Y-516 intravenously, intraperitoneally, and orally, and the concentrations of the parent drugs and their metabolites in the plasma and urine were determined. Half-life (t1/2) was approximately the same by all three administration routes, being approximately 5 h for CCP and 3 h for Y-516. Bioavailability following oral administration was 0.16±0.01 (mean ± SD, n=3) for CCP and 0.29±0.07 for Y-516. The fractions of dose absorbed following oral administration were 0.43±0.07 and 0.79±0.24, and the fractions of dose metabolized in the liver due to the first-pass effect were 0.63±0.05 and 0.63±0.04 for CCP and Y-516, respectively. Y-516 was detected in the plasma after intraperitoneal and oral administration of CCP. The ratio of the AUC of Y-516 to that of CCP was 0.06 following intraperitoneal administration and 0.40 following oral administration. This indicated that while the metabolism of CCP into Y-516 may occur partly in the liver due to the first-pass effect, it occurs mostly within the gastrointestinal tract itself or its mucosa. When CCP and Y-516 were given orally to man, the plasma concentrations of both parent drugs increased in a dose-dependent manner. The t1/2 of CCP at a dose of 50 mg was 46±6 h (n=3) while that of Y-516 at a dose of 25 mg was 15±2 h (n=5), so that elimination from the circulation was slower than in the dog in both cases. As in the dog, Y-516 was detected in the plasma following administration of CCP, but its concentration was approximately one fifth that of CCP and lower than that found in the dog. From the ratios of Y-516 produced upon oral administration of CCP in dog and man, we concluded that Y-516 is involved to a considerable degree in the pharmacological action of CCP in the dog and, though to a lesser degree, in man as well.     

Recent Trends in the Treatment and Prognosis of Adult Leukemia with Characteristics of Patients in Japan: Transition during the Fifteen Years from 1971 to 1985

Patients with acute (2,569) and chronic (957) leukemia diagnosedat 19 institutes took part in the study on the "MultidisciplinaryTreatment of Leukemia" between 1971 and 1985 and were investigatedretrospectively. By dividing the 15 years into three five-yearperiods, we were able to compare patient ratios in the differentperiods. The proportions of acute to chronic leukemia casesshowed no obvious change; however, the proportions of casesdiagnosed as acute lymphocytic leukemia in acute leukemia showeda significant increase. The main chemotherapeutic drugs usedduring the three time periods were cytarabine or its analogues,the anthracyclines, 6-mercaputopurine and prednisolone, againstacute myelogenous leukemia, and the vinca alkaloids, prednisoloneand the anthracyclines against acute lymphocytic leukemia. Therate of complete remission from acute myelogenous leukemia mademarked progress, from 45.1% during 1971–1975 to 62.3%during 1981–1985, but that of acute lymphocytic leukemiashowed no significant progress, being 65% during 1971–1975and 69.7% during 1981–1985. The durations of remission,however, and the survival times for patients with acute lymphocyticleukemia, as well as for those with acute myelogenous leukemia,became significantly longer over the three periods. Median survivaltimes from chronic myelocytic leukemia were 37–40 mo inall three periods, showing no progress. There was a better prognosisin cases of chronic myelocytic leukemia with, than without,Philadelphia chromosome. Except for a low incidence of chroniclymphocytic leukemia in Japan, adult leukemia patients' characteristicsand prognoses seem to be almost the same in Japan as in theU.S.A. and Europe.     

Detection of polymeric IgA in glomeruli from patients with IgA nephropathy.

A study on the detection of polymeric IgA in glomeruli from renal biopsy specimens in patients with IgA nephropathy is described. Renal biopsy specimens were obtained from patients with IgA nephropathy. These specimens were stained with FITC-labelled anti-human J chain antisera and then examined with a fluorescent microscope. The J chain was observed in the glomerular mesangium by immunofluorescent staining. In parallel studies, renal biopsy specimens were treated with citrate buffer (pH 3.2) and the 'eluate' was neutralized by sodium hydroxide. The eluate was labelled with iodine-125, and the radiolabelled 'eluate' was fractionated by sucrose density-gradient ultracentrifugation. Polymerized IgA in the 'eluate' obtained from patients with IgA nephropathy was found to sediment predominantly as 9S to 11S using a sucrose density gradient analysis. Polymeric IgA in the fractions of the density gradient analysis was determined by anti-human IgA and anti-human J chain antisera. It was demonstrated that IgA and J chain were eluted from the glomeruli in some patients with IgA nephropathy. It is concluded that IgA deposited in the glomeruli is composed of dimers and/or larger polymers of circulating IgA in some patients with IgA nephropathy.     

Fine structure of the mouse portal vein in relation to its peristaltic movement

The hepatic portal vein has been known to make a spontaneous peristaltic movement in some mammals, including the mouse and rat. To investigate the fine structure of the portal vein in relation to its physiological characteristics, we observed the mouse portal vein by using various histological techniques including conventional light microscopy, videomicroscopy, transmission and scanning electron microscopy, and real-time confocal laser scanning microscopy. The mouse hepatic portal vein was provided with a spiral fold which was produced by the inner layer, i.e. the endothelium and smooth muscles of the wall protruding into the lumen. Longitudinal smooth muscle cells spanned the interval of the fold, like a spirally arranged palisade around the vessel wall. The longitudinal muscle fibers ended at the spiral fold, being partly connected with a network of irregularly shaped smooth muscle cells. This network, hitherto unknown, was recognized to be restricted to the fold in distribution and characterized by numerous gap junctions connecting the muscle cells. Real-time confocal laser scanning microscopy using a Ca2+ sensitive fluorescent dye revealed that a transient and periodic increase in Ca2+ concentration occurred in the longitudinal smooth muscle cells and was transmitted spirally from the intestinal to the hepatic side. These findings indicate that, during the peristaltic movement, the contraction of smooth muscle cells is transmitted along the longitudinal smooth muscles of the portal vein wall toward the liver, presumably controlled by the network of the irregularly-shaped smooth muscle cells in the fold of the portal vein. Light microscopic observation in some specimens indicated an occurrence of cardiac muscle cells outside the smooth muscle layer. Restricted to the site of the porta hepatis in distribution, their involvement in the peristaltic contraction of the portal vein seemed unlikely.