Biomedical subjects
Publications and source records attributed to A Takao.
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The blood level of PH-FU following oral administration to rabbits and tumor-bearing mice was considerably lower than that of Tegafur, HCFU or 5'DFUR, and decreased more rapidly. The t1/2 beta was 0.48 h (rabbits) and 1.74-1.91 h (mice). The blood level of 5-FU derived from PH-FU was higher at an earlier time after administration than that derived from other 5-FU derivatives, but it disappeared more rapidly. The tissue level of PH-FU in S-180-and Lewis lung carcinoma-bearing mice was detected at a low level in various tissues of mice, except for a higher level in the digestive tract and a lower level in the brain and muscle. The tissue level of 5-FU in both types of mice was high in the digestive tract and kidney. The 5-FU level in the 2 kinds of tumor tissues was relatively high and persisted for several hours. After incubating PH-FU and tissue homogenates from humans and mice at 37 degrees C for 2 h, PH-FU was converted to 5-FU very strongly in the liver and kidney, and considerably strongly in the muscle, heart, tongue and testis. In conclusion, PH-FU seems to be characterized by a low blood and tissue level of unchanged drug, a high production of 5-FU and a short duration of the level.
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To preserve right ventricular function after intracardiac repair of tetralogy of Fallot, we developed a standardized patch infundibuloplasty with minimum ventriculotomy and myocardial resection. An experimental study suggested that short and medium-length patch infundibuloplasty, less than 50% of the right ventricular length, did not reduce the right ventricular function. A morphologic study showed that the ratio of the infundibular septal and the right ventricular lengths ranged from 0% to 34% with an average of 14% in 100 cases of tetralogy of Fallot. The optimal infundibuloplasty patch length was determined to be between 30% and 45% of the right ventricular length. The standard formulas for determining minimum (30%) and maximum (45%) patch infundibuloplasty lengths were as follows: 1.28 X body surface area (m2) + 1.10 cm (minimum) and 1.93 X body surface area (m2) + 1.65 cm (maximum). In clinical experience, a patch infundibuloplasty length shorter than 45% of the right ventricular length resulted in an intraoperative right ventricular to systemic arterial pressure ratio of 55% +/- 15% (n = 90).
Pharmacokinetic studies of 5-FU in normal and Sarcoma 180-bearing mice were performed, and the following results obtained: When the administered dose of 5-FU was increased, it was found that there was an increase in the half-life and AUC (area under the concentration curve) and a lower rate of plasma clearance. When the drug was administered at equal doses of 40 mg/kg, the rate of clearance was high in the order of p.o. greater than continuous infusion greater than i.v. bolus. When Sarcoma 180-bearing mice were injected with CCl4 to induce liver dysfunction and subsequently administered 5-FU, the AUCs of 5-FU in the plasma and tumor tissue were increased by 2 and 1.3 times, respectively, as compared with non-treated mice. The Vmax (nmol/mg protein/min) of DHU (dihydrouracil dehydrogenase) in the liver homogenate from normal mice was 1.18 and found to be 0.70 in CCl4-treated mice. In conclusion, the pharmacokinetics of 5-FU were found to be dependent on the dose, infusion time, administration route and liver function, which seem to be correlated with the capacity of the catabolic enzyme, DHU.
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Displacement of the infundibular septum and coronary anatomy was studied in 40 patients with variable transposition of the great arteries who underwent the Jatene operation between August, 1982, and May, The perioperative mortality was 12.5%. Fourteen of the 16 patients (87.5%) with intact ventricular septum (Group I), eight of the 12 patients (67%) with aligned infundibular septum and perimembranous trabecular defect (Group II-A), and four of the 12 patients (33%) with anteriorly displaced infundibular septum, malaligned defect, overriding of the pulmonary valve, and severe pulmonary hypertension (Group hypertension (Group II-B) has Shaher type 1 coronary anatomy. In this type of coronary anatomy, the left coronary artery courses in front of the pulmonary artery. However, two patients (12.5%) from Group I, four (33%) from Group II-A, and eight (67%) from Group II-B had various unusual coronary patterns, such as Shaher types 2,3,4,7, and 9. All patients had a left or circumflex coronary artery coursing behind the pulmonary artery. These data suggest that the displacement of the infundibular septum not only determines the type of the defect and hemodynamics, but also often relates to the coronary anatomy Removal of a whole, scallop-shaped sinus of Valsalva and minimal dissection of the coronary artery are preferable, particularly for translocation of such unusual coronary anatomy.
A case of a 20-year-old man with superoinferior ventricular heart complicating situs inversus, levo-loop and dextro-malposition (I,L,D), and double-outlet right ventricle is described. The associated anomalies were hypoplastic right ventricle, ventricular septal defect, atrial septal defect secundum, infundibular and valvular pulmonary stenosis, and mitral regurgitation. Intraventricular conduit repair was successfully performed.
Clinical, hemodynamic and angiographic features of coronary obstructive disease (greater than or equal to 90% diameter reduction) in Kawasaki disease were evaluated in 30 patients. The mean age at the onset of Kawasaki disease was 2.9 +/- 1.9 years and that at cardiac catheterization was 6.3 +/- 2.8 years. Obstructive lesions were observed in the right coronary artery in 12 patients (group 1), in the left anterior descending coronary artery (LAD) in 6 (group 2), in both right coronary artery and LAD in 10 (group 3) and in the left main coronary artery in 4 (group 4). Twenty-two patients (73%) had cardiac symptoms, including myocardial infarction in 10 (33%). Cardiac symptoms were observed in 41% in group 1, 100% in group 2, 80% in group 3 and 100% in group 4. Left ventricular (LV) end-diastolic pressure, end-diastolic volume and ejection fraction were abnormal in 32% of the patients in group 1, a frequency less than that in other groups (83% in group 2, 78% in group 3 and 100% in group 4). Fifty percent had mitral regurgitation and 73% had left ventricular wall motion abnormalities. No patient in groups 1 or 2 has died, but 8 of 14 patients in groups 3 and 4 have died. These observations indicate that coronary obstruction owing to Kawasaki disease can cause depressed LV function, mitral regurgitation and LV wall motion abnormalities in children.(ABSTRACT TRUNCATED AT 250 WORDS)
Postoperative right (RV) and left ventricular (LV) volume characteristics in patients with complete transposition of the great arteries were studied to compare ventricular function after Senning and Jatene procedures and to analyze RV dimensional change during systole in patients after the Senning procedures. RV end-diastolic volume (EDV) was 181 +/- 74% of normal (mean +/- standard deviation) and RV ejection fraction (EF) was 0.48 +/- 0.09 in 15 patients who underwent the Senning procedure. In 9 patients who underwent the Jatene procedure, LVEDV was 152 +/- 27% of normal and LVEF was 0.61 +/- 0.09. One patient with aortic regurgitation, 1 with aortic regurgitation and residual ventricular septal defect, and 1 with aortic regurgitation and generalized LV wall hypokinesia of unknown cause had large LVEDVs. Pulmonary ventricular EDV and EF were within normal ranges except in the patients with persistent pulmonary hypertension, who had large EDVs and low EFs regardless of the anatomic type of ventricle, either the left or right. The study of RV dimensional change in the Senning group showed a reduced systolic shortening of the anteroposterior diameter compared with the preoperative transposition of the great arteries and normal. This reduced shortening may be related to postoperative adhesion of the RV free wall to the anterior chest wall and fixation of the atrium secondary to the intraatrial repair. In conclusion, systemic ventricular function after intraatrial repair for complete transposition of the great arteries is depressed by unavoidable residua and sequelae: persistent RV hypertension, anatomy of the right ventricle and, possibly, postoperative adhesions.(ABSTRACT TRUNCATED AT 250 WORDS)
A two-dimensional echocardiographic (2-DE) method of segmental approach for diagnosis of congenital heart disease is presented. Firstly, the visceroatrial situs is determined, i.e., whether it is solitus, inversus, or ambiguous, by identifying the inferior vena cava to right atrium junction. Secondly, it is ascertained whether the ventricular loop is D-loop or L-loop. The ventricular loop is determined by identifying the internal structure of the right and left ventricles by 2-DE. Thirdly, the spatial relationships of the great arteries are determined by identifying the pulmonary artery and aorta. The pulmonary artery is identified by its branches, and the other artery is the aorta. Fourthly, the atrioventricular connection is determined as follows: (1) usual alignment, (2) criss-crossing, (3) straddling, (4) double inlet, and (5) unilateral atrioventricular valve atresia, by using an apical four-chamber echo view. Finally, the ventriculo-great arterial relationship is determined from the apical four-chamber echo view with a tilting maneuver or by echocardiographic recognition of the existence of the fibrous continuities. Following this echocardiographic "five-step approach," hemodynamic considerations should be included, and by integrating all the information the diagnosis of congenital heart disease is completed.
In a case with tricuspid atresia, a coronary sinus septal defect was found and closed following Fontan's operation. This defect should be found, at latest, during surgery, otherwise Fontan's operation cannot produce functional repair.
We report a case of absence of the right superior vena cava. Hitherto, the findings in this condition have only been obtained using invasive methods; this report is the first in which the diagnosis was made by means of echocardiography. The findings include a markedly enlarged coronary sinus draining into the right atrium and a specific finding of contrast echocardiography in which contrast material injected into the right antecubital vein can be seen in the enlarged coronary sinus. The contrast echo flows into the right atrium from the coronary sinus only. The size of the coronary sinus was far beyond the range (91 +/- 38 mm2/m2) in patients with persistent left superior vena cava with the presence of the right superior vena cava.
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Effects of respiratory and metabolic acidosis (pH approximately 6.8) on myocardial function were studied in the newborn and adult rabbits. Mechanical function was studied in the isolated arterially perfused heart preparation. Acidosis was induced either by increase of the perfusate PCO2 or by decrease of the bicarbonate content. During respiratory acidosis, developed tension (DT) decreased to 43 +/- 3% of control (n = 18) in the adult and this depression was significantly greater than in the newborn (DT = 92 +/- 4%, n = 6). Depression of DT by respiratory acidosis was observed even at high extracellular Ca. During metabolic acidosis, mechanical function decreased gradually and DT at 30 min into acidosis in the adult was 78 +/- 3% of control (n = 6). This depression of DT in the adult was significantly greater than in the newborn (DT at 30 min = 96 +/- 1% of control, n = 6). Statistical analysis using paired t test showed that respiratory acidosis, but not metabolic acidosis, caused significant negative inotropism in the newborn. Myofibrils were isolated and the ATPase was measured at 10(-8) to 10(-4) M Ca and at pH of 7.1 (control), 6.5, and 6.0. Reducing pH depressed the ATPase activity similarly in the newborn and adult. Intracellular buffer capacity was determined by titrating muscle homogenate with HCI. Although the initial pH was not different, addition of HCl to the homogenate caused less decrease in pH in the newborn. These data indicate that contractile function in the newborn heart is more resistant to acidosis and this may be due partly to the greater intracellular buffer capacity.
In 1983, 290 patients with congenital heart disease (CHD) underwent surgery at our institute. Among them, 36 (12%) had no preoperative catheterization or angiography. These 36 patients were categorized as group I consisting of 12 patients less than two months of age and group II consisting of 18 patients more than one year of age. The diagnosis was accurate in 34 of the 36 patients (94%). Assessment by two-dimensional echocardiography (2-DE) was incomplete for two patients. A secundum atrial septal defect in one patient diagnosed by 2-DE, proved at surgery to be a sinus venosus type atrial septal defect with partial anomalous pulmonary venous drainage. Another patient was diagnosed as having tetralogy of Fallot with the absent pulmonary valve by 2-DE, but anomalous origin of the right pulmonary artery from the ascending aorta was also found at surgery. There were 25 operations in patients less than two months of age, and 12 (48%) of them had surgery without catheterization (Group I). Most patients in Group I were less than two weeks of age (nine patients) and six of these were operated without catheterization (pure pulmonary atresia: 2, total anomalous pulmonary venous drainage: 2, interruption of the aorta: 1, tetralogy of Fallot with absent pulmonary valve: 1). Another two cases had surgery after only radial artery retrograde aortic arch visualization, then, preoperative intracardiac catheterization was avoided in eight (89%) of the nine patients. Atrial septal defect (ASD) and patent ductus arteriosus (PDA) patients, 25% and 69% of the cases, respectively, were operated on without catheterization. In conclusion, we can better maintain the general condition of critically-ill neonates and infants in surgery, when prompt and accurate 2-DE diagnoses are made for typical cases without catheterization and angiography. In older children of uncomplicated ASD or PDA with typical physical findings, we can avoid catheterization before surgery. If, however, information is insufficient for deciding surgery, we should carry out invasive examinations without hesitation.