Biomedical subjects
Publications and source records attributed to J Okamoto.
Infective endocarditis is extremely rare in early pregnancy. We report an emergency mitral valve replacement performed successfully on a 16 week pregnant woman for infective endocarditis without preexisting heart disease. On admission, the patient was in acute heart failure, and the fetus had been already dead. Induced abortion was performed uneventfully 6 days after the cardiac operation.
Dynamic susceptibility contrast MRI has been performed using the gradient echo sequence on conventional MR imagers. On echo planar imaging (EPI) devices, not only gradient-echo EPI but also spin-echo EPI allow for the monitoring of contrast agent-induced changes in susceptibility. The purpose of this study was to evaluate the contribution of each EPI pulse sequence to susceptibility-induced delta R2(*) through the first pass of a bolus of Gd-DTPA. Thirty healthy volunteers were examined with a 1.0T superconducting MRI unit (IMPACT, Siemens) using EPI. For dynamic susceptibility contrast MRI, we used gradient echo EPI (TE = 60), spin echo EPI (TE = 60) and asymmetric spin echo EPI (TE = 88). Regional relative CBV (rrCBV) maps were generated. On the rrCBV map generated with gradient echo EPI, the high-intensity area of the brain surface was more conspicuous than that generated with spin echo EPI. The rrCBV map generated with asymmetric spin echo EPI represented the contrast between those generated with spin echo EPI and gradient echo EPI. The rrCBV rate between gray matter and white matter with gradient echo EPI was significantly higher than that with spin echo EPI. We suggest that the rrCBV map calculated with spin echo EPI tends to reflect capillary blood volume and the rrCBV map calculated with gradient echo EPI tends to reflect total blood volume.
Between August 1980 and December 1995, 29 patients have undergone valve replacement for active infective endocarditis (IE) at our institute. Twenty five patients had native valve endocarditis (NVE) and 4 had prosthetic valve endocarditis (PVE). The indication for surgery in 29 patients was congestive heart failure, septicemia or systemic embolization. Twenty six patients had vegetation. Eleven patients had AVRs, including one modified Bentall operation, 10 had MVRs and four had DVRs with mechanical prosthetic valve. There were eleven early death (38%) and one late death. Operative mortality rate has reduced to 24% after 1991. We conclude that early surgical intervention should be taken according to the hemodynamic state of the patients irrespective of the presence of septicemia.
In eight hundred and sixteen consecutive patients undergoing coronary artery bypass grafting (CABG) within the past 19 years (1974 to 1993), repeated CABG were performed on 12 patients (1.47%). The main reasons for repeated CABG were graft failure (GF), progression of native disease (NP) and incomplete revascularization (IR). The incidence of GF only and GF combined NP were high either within a half year or around 5 years after CABG. When the recurrence of angina is noted after CABG, the catheter intervention should be chosen at first but the reoperation should be done not so late. Although all patients survived from reoperation, three patients continued to have mild angina pectories. If a reoperation is inevitable, maximum utilization of arterial graft and accomplishment of complete revascularization are emphasized.
A capillary gas chromatographic method for the determination of a newly developed thromboxane A2 antagonist, S-1452, and its metabolites in human plasma has been developed. This nitrogenous compound was detected as the free acid (+)-S-145 using a nitrogen-phosphorus detector. The two metabolites bisnor-(+)-S-145 and tetranor-(+)-145 were also assayed. The three compounds, which all possess carboxylic acid group, were converted into their hexafluoro-2-propyl esters with hexafluoropropan-2-ol-pentafluoropropionic anhydride as reagent. The esterification resulted in a decreased background response from the detector, and hence higher sensitivity and better precision. The glucuronides of the three compounds were also assayed after alkaline hydrolysis. The plasma concentration of the glucuronide of I was more than twice that of the free acid. This method allows determination of the three compounds at more than 2 ng/ml with a precision of 2-6% and an accuracy variation of less than +/- 5%. The analysis was performed within 2 min after injection to assay the sample rapidly from the Phase I test. The method is suitable for pharmacokinetic studies.
A capillary gas chromatographic method using a sulphur-specific detector (Hall's electrolytic conductivity detector) was established to determine the thromboxane A2 antagonist S-1452 and its metabolites in human urine. The target species were the free acid (+)-S-145 of the drug and its nine metabolites: the three hydroxyl forms of (+)-S-145 (I, II and III), bis-nor-(+)-S-145 (IV) the hydroxylated forms of IV (V and VI), tetranor-(+)-S-145 (VII) and the hydroxylated forms of VII (VIII and IX). These ten compounds, which have the same sulphur-containing functional group in common, were determined simultaneously. Their conjugated forms, which were assumed to be glucuronides, were also assayed after hydrolysis. The first derivatization was esterification with diazomethane. The second, for the hydroxylated compounds, was trimethylsilylation with bis(trimethylsilyl)trifluoroacetamide. The ten analytes appeared as separate peaks without mutual interference during 5 min. Hall's detector distinguished the ten analytes selectively from the other urinary components, which removed the need for complex clean-up procedures and led to higher sensitivity with a lower noise level. The method is sensitive enough for the assay of substances present at more than 0.1 micrograms/ml of urine. All the compounds could be determined with a high level of precision and accuracy, with 2-5% relative standard deviation and within +/- 5% deviation from the actual value. Day-to-day measurements verified the reproducibility of the method. Recovered substances were quantified by following the time course, and the analytical data together with previously obtained plasma data clarified the metabolism pharmacokinetically.
Internal thoracic artery (ITA) grafts for coronary artery bypass grafting (CABG) are superior to SVG in the long-term patency and survival. In spite of our effort to utilize ITA whenever possible, we still have some cases which have to receive only vein grafts. Among the consecutive 201 patients undergoing CABG in the past three years, 32 patients (16%) received only vein grafts. We compared these patients (SVG group) with those who received ITA grafts (ITA group). The SVG group consisted of all emergency cases and many cases with single and double vessel disease. In the SVG group, perioperative use of IABP was more frequent and operative mortality was higher, although the number of grafts was fewer (2.66 vs 3.61) and aortic cross clamping time was shorter in this group. Main reasons for selecting only vein grafts were emergency surgery, inadvertent injury of ITA, inadequate ITA free flow etc. Technical refinement in the preparation of ITA is important to make possible wider application of arterial grafts for CABG.
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The development of the inner ear vessels of guinea pigs were studied by SEM. Employing 32- to 55-gestational-day-old guinea pig embryos, corrosion casts of inner ear blood vessels were prepared using Mercox resin and then observed by scanning electron microscopy. Between the 35th and 40th gestational days, the vascular structure of the vestibule was sufficiently developed, but the capillary network in the wall of the cochlea remained immature. Thus, in the guinea pig, the development of the vestibular structure precedes the development of the cochlear vessels. Moreover, at both sites, the density of the embryonic blood vessels was high, and the vessels were believed to transport a large blood flow. From about the 40th day of gestation, the coiled vessels and the capillary network in the lateral wall of the cochlea underwent rapid development, and the vascular structure in both the vestibule and cochlea was nearly complete by the time of birth.
Under scanning electron microscopy we measured the vessel diameters of every part of the inner ear in rats and guinea pigs with casting method using Mercox resin. There were only few errors in measurement values in the same part of the same vessel with this method. The vessels of the stria vascularis were much larger in diameter than any other capillaries in the lateral wall of the cochlea in the rat and especially in the guinea pig. It is suggested that the velocity of the blood flow in the stria vascularis is slow and that the stria vascularis can retain much blood. The anterior vestibular artery (AVA) was larger in diameter than the posterior vestibular artery (PVA). The AVA supplies the large area in the vestibule whereas the PVA supplies the small area.
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The present study was designed to elucidate whether naftidrofuryl oxalate (LS-121) may exert a beneficial effect on survival time and cerebral energy metabolism of bilateral carotid artery (BCA)-ligated mice. Survival time of BCA-ligated mice ranged from 100 to 308 sec. Administration of 15, 45 and 100 mg/kg, i.p. and 100 mg/kg, p.o. LS-121 significantly prolonged the survival time. Cerebral adenosine triphosphate (ATP), creatine phosphate (CP) and glucose contents were markedly reduced at 2 min after BCA-ligation. Cerebral lactate content was increased by the ligation, whereas the pyruvate content was not altered. Pretreatment of mice with 15, 45 mg/kg, i.p. and 100 mg/kg, p.o. LS-121 suppressed BCA-ligation induced decrease in high-energy phosphates of the mouse brain. Ligation-induced decrease in glucose and increase in lactate content tended to be attenuated by the treatment with 45 mg/kg, i.p. LS-121. Time course of changes in metabolic variables altered by BCA-ligation with and without the pretreatment with 45 mg/kg, i.p. LS-121 showed a significant suppression of ligation-induced decrease in cerebral high-energy phosphates. The results suggest that LS-121 is beneficial for ischemic mouse brain energy metabolism, which may be related to the prolongation of the survival time.
The disulfiram-like effect of various beta-lactam antibiotics containing N-methyltetrazolethiol (NMTT) on the alcohol-metabolizing system was studied using rats. Their administration caused decreased activities in low Km aldehyde dehydrogenase (ALDH) and acetaldehyde oxidation in the liver, with marked depression from several hours to 2 days after the treatment. Blood acetaldehyde level increased markedly when ethanol was administered 18-24 hr after pretreatment with antibiotics. A similar time course change in the effect was obtained when disulfiram was administered. The following results obtained in the present study indicate that the disulfiram-like effect associated with these antibiotics was not mediated by the whole molecular structures of these drugs: Firstly, the antibiotics were eliminated rapidly from the plasma and liver, and the disulfiram-like effect was followed by a disappearance of the drugs. Secondly, the concentration of antibiotics required to inhibit mitochondrial low Km ALDH activity in vitro was very high compared with their liver concentration. Thirdly, rapid onset of disulfiram-like effects occurred after administration of NMTT itself, and a pronounced elevation of blood acetaldehyde level was observed when ethanol was administered 3-5 hr after the NMTT injection. Fourthly, almost the same amounts of NMTT were released in the body after the intravenous administration of various NMTT-containing antibiotics, as judged by the urinary excretion. These results suggest that the disulfiram-like effect of beta-lactam antibiotics is mediated by NMTT released from them.
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A distinct difference in the 3-methylhistidine (3-MeHis) content and the pH-dependency curve for calcium-activated adenosine triphosphatase (Ca-ATPase) activity was observed between chicken and mammalian cardiac ventricular myosins. The 3-MeHis content and pH dependency of the Ca-ATPase activity of myosins from adult and embryonic chicken cardiac ventricular muscles and chicken fast white and slow red muscles were almost the same.
Several beta-lactam antibiotics, especially those containing N-methyltetrazolylthiomethyl groups at the 3-position of the cephalosporin nucleus, affect the alcohol-metabolizing system in rats. These effects were compared those with disulfiram, well-known as a potent inhibitor of aldehyde dehydrogenase (ALDH). Both disulfiram and antibiotics containing the N-methyltetrazolylthiomethyl group inhibited both mitochondrial low Km ALDH and acetaldehyde oxidation in rat livers. The high Km ALDH and alcohol dehydrogenase activities in livers were not affected by these treatments. When ethanol was given to rats pretreated with disulfiram or these antibiotics, the blood acetaldehyde concentration increased markedly concomitant with a decrease in activity of the low Km ALDH. Administration of N-methyltetrazolethiol alone suppressed the low Km enzyme activity and also increased the blood acetaldehyde level; both effects were pronounced and observed several hours after administration. beta-Lactam antibiotics without N-methyltetrazolethiol in their molecule did not affect the liver mitochondrial enzyme activity or the blood acetaldehyde level.
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