[The effects of amrinone on hemodynamics and myocardial oxygen balance in anesthetized dogs with experimental left ventricular failure by ventricular fibrillation].
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Biomedical subjects
Publications and source records attributed to Y Gotoh.
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Myocardial contractile responses to halothane, enflurane, and isoflurane were studied in papillary muscles isolated from streptozotocin-induced diabetic rats and in those from age-matched control rats. The developed tension in diabetic papillary muscles electrically paced at a constant rate was not different from that in control muscles, but both the time to peak tension and the relaxation time of the isometric contraction were significantly prolonged in diabetic muscles. Halothane, enflurane, and isoflurane all produced negative inotropic effects in both diabetic and control muscles. However, the negative inotropic effects were significantly less in the muscles from diabetic rats than in the muscles from control rats throughout the range of concentrations. In muscles from both the diabetic and control rats, the negative inotropic effects of these anesthetics were accompanied by decreases in the time to peak tension and in relaxation time. The results suggest that the myocardium from the diabetic rat is less sensitive to the negative inotropic action of volatile anesthetics than is the myocardium of normal hearts.
The direct correlation analyses between the distribution of chlorpromazine (pharmacokinetics) and the biochemical effects of the drug on monoamine metabolisms (pharmacodynamics) are reported. Both samples for quantitative determination of CPZ and of monoamine transmitters and metabolites were obtained by organic extraction procedures from the same sample. The determinations were carried out by high performance liquid chromatography with electrochemical detection. CPZ affected the concentrations of metabolites of noradrenaline, dopamine and 5-hydroxytryptamine, but not those of the monoamine transmitters themselves. However, simultaneous assay demonstrated differences in effects of the drug on the transmitter systems. The concentrations of HVA and DOPAC were increased over a wide range of intracerebral concentrations of the drug, but those of MOPEG, in the range of higher concentrations. On the other hand, CPZ did not reveal any correlations between the intracerebral concentrations of the drug and 5-HIAA. These results suggest that CPZ affected primarily the dopaminergic system rather than the serotonergic one in the early stage of its biochemical actions. The proposed procedure is demonstrated to be simple and useful as a new approach in biochemical pharmacology. The same procedure can be applicable for other centrally acting drugs.
Neuron-specific enolase (NSE) in sera of 3 patients with neuroblastoma (Stage IV) were measured by radioimmunoassay, as compared with urinary catecholamine metabolites (vanillyl-mandelic acid (VMA) and homovanillic acid (HVA] during the course of chemotherapy, radiation, and second look operation. In Case 1 (Stage IV B) and Case 3 (Stage IV A), NSE-level on admission was found to be elevated to 51.0 ng/ml and 25.5 ng/ml, respectively. VMA and HVA were also elevated. In Case 2 (Stage IV A), NSE on admission was elevated to 128.0 ng/ml., HVA was high, but VMA was within normal range. From 1 to 3 weeks after chemotherapy and radiation, high levels of urinary VMA and/or HVA in patients promptly decreased within normal range. The size of primary tumor masses either showed no marked change or slightly decreased by radiological examinations. After intensive chemotherapy, high levels of serum NSE decreased within normal range. At that time, second look operations were carried out. The size of primary tumors was reduced (3.6 X 2.7 X 2.1 cm in average) and almost all masses had scarred over. These data suggest that serum NSE levels correlate very well with residual tumor burdens.
Urine levels of neuron-specific enolase (NSE) were determined in 6 patients with neuroblastoma, in 72 controls and in 5 infants with hematuria by means of a double-antibody inhibition radioimmunoassay method. Urine levels (NSE ng/creatinine mg) in 2 patients with advanced neuroblastoma were elevated (3.03 +/- 0.28 (S.D.)), when compared with those of 4 patients with neuroblastoma in remission (0.65 +/- 0.26 (S.D.], 10 healthy neonates (1.26 +/- 0.42 (S.D.)), 25 healthy infants (0.51 +/- 0.26 (S.D.)), and 37 healthy adults (0.37 +/- 0.17 (S.D.)). Urine levels in 4 infants with microhematuria and an infant with macrohematuria were 1.62 +/- 0.10 (S.D.) and 33.83, respectively. Serial measurements in 3 patients with neuroblastoma receiving various therapies have revealed that there was a good correlation between urine NSE level and the response to therapy. These results indicate that NSE in urine may be a valuable marker for monitoring the effectiveness of therapy in patients with neuroblastoma.
The first case of successful bone marrow transplantation (BMT) in a patient with I-cell disease is reported. A 8-month-old girl with I-cell disease (N-acetylglucosaminylphosphotransferase deficiency) has had successful reconstitution with bone marrow from her HLA-MLC-matched brother who has heterozygous level of the transferase activity. The following biochemical and clinical improvements have occurred: the transferase in peripheral lymphocytes increased to donor's level, and lymphocytic alpha-neuraminidase, beta-galactosidase and alpha-mannosidase increased to normal levels. Plasma acid hydrolase activities, which had been 10 to 60 times higher in the patient than normal control levels, have slowly but steadily decreased from one month after the graft. Such decreases were observed in the activities of alpha-mannosidase, N-acetyl-beta-glucosaminidase, alpha-fucosidase, arylsulfatase A and acidic beta-galactosidase. There was also a marked decrease of vacuolated peripheral lymphocyte after the BMT. Three-months after the engraftment, hepatomegaly gradually decreased in size, corneal clouding has not progressed, and tight skin seems to have improved.
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The administration (i.v., 20, 40 and 60 mg/kg) of the thiol protease inhibitor bis[ethyl(2R, 3R)-3-[(S)-methyl-1-[4-(2,3,4-trimethoxyphenyl-methyl) piperazin-1-ylcarbonyl] butyl-carbonyl] oxiran-2-carboxylate]sulfate (NCO-700), before and/or after the coronary ligation significantly reduced the necrotic mass in the rabbit left ventricle and also prevented the creatine phosphokinase loss in the ischemic myocardium up to 3 h and not at 6 h after the ligation. The activities of both calcium-activated neutral protease and cathepsin B in the subendo- and subepicardial layers of the ischemic, marginal or control myocardium of dog were inhibited by the NCO-700 administration (20 mg/kg i.v.) after the coronary ligation. A hemodynamic study using heart-lung preparation of the dog demonstrated a dose-dependent coronary dilatation with weak and transient negative ino- and chronotropic effects. These data suggested that NCO-700 sensitive protease(s) is(are) included in the step of myocardial cell degradation and that NCO-700 temporarily salvages it, as is important for the recent PTCR (percutaneous transluminal coronary reperfusion) therapy.
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Out of 12 cases of bilateral stenosis of the internal carotid (IC) system underwent unilateral STA-MCA anastomosis on the symptomatic side, no ischemic signs recurred in 8 cases, while, in the remaining 4, symptoms appeared postoperatively, requiring the anastomosis of the contralateral side. Preoperative findings of CT scan, CAG and r-CBF were reviewed and compared. It has, consequently, become evident that, in the latter 4 cases, angiography showed stenotic lesion of over 50% of the ICA lumen, between the mastoid-mandibular line (MML) and the circle of Willis, on the initially asymptomatic side. Furthermore, in the same 4 cases, multiple thrombotic foci were more liable to be demonstrated on the CT scans and r-CBF was lowered in both hemispheres without significant difference in laterality. In additional 7 cases presenting such characteristics as stated above, one-stage bilateral STA-MCA anastomosis was carried out with a successful result.
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The localization and distribution of peroxidase (PPO) activity were studied ultracytochemically in thrombocytes from lampreys, carps, frogs, snakes, tortoises, rabbits, sheep, dogs, and monkeys. PPO activity was not detectable in the thrombocytes of lampreys, carps, frogs, and snakes. However, this enzyme activity was demonstrated in the nuclear envelope and endoplasmic reticulum of tortoise thrombocytes. Dog and monkey thrombocytes (blood platelets) exhibited PPO activity in the dense tubular system, but this enzyme activity was not detectable in rabbit and sheep thrombocytes. Our observations are interpreted to suggest that thrombocytes from animals lower than amphibia are peroxidase negative. Furthermore, it can be said that thrombocytes from animals higher than reptiles are generally positive, although there are exceptions. PPO activity was localized in the endoplasmic-reticulum system, but not in the cytoplasmic granules of thrombocytes common to submammals and mammals. In this study, we also compared the distribution of peroxidase activity in thrombocytes, neutrophils, and eosinophils and conclude that these are significant differences in the distribution of PPO and myeloperoxidase.
Urine levels of neuron-specific enolase were determined in 3 neuroblastoma patients (1 in an advanced state and 2 in remission), 25 control children, 37 control adults and 4 children with hematuria by means of the double-antibody inhibition radioimmunoassay specific to the gamma subunit of enolase isozymes. The levels of neuron-specific enolase mean +/- S.D. ng/creatinine mg in an advanced neuroblastoma patient were elevated (1.25 +/- 0.29 before or after treatment and range 1.61-74.2 during treatment) when compared with those of control subjects (0.51 +/- 0.26 in children and 0.36 +/- 0.17 in adults). The levels in 2 neuroblastoma patients in remission were within normal range. Urine samples with hematuria were not used for the assay.