[Oral glucose loading test].
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Biomedical subjects
Publications and source records attributed to K Inoue.
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Non-invasive assessment of ischemic heart disease requires information of both LV function and myocardial perfusion. Recently, ECG-gated myocardial SPECT with technetium-labeled radiopharma-ceuticals can provide both of them. Gated myocardial SPECT were performed in thirty-three patients with cardiac disease using a two-headed rotating gamma camera system (ADAC; VERTEX), 30-60 minutes after resting injection of 555-740 MBq of 99mTc-Tetrofosmin. Then, the SPECT data were used to determine the LV epi- and endocardial surface, and LV volume for measurement of LVEF was calculated automatically. This entire computational process required only 210 seconds per 16 frame study. Interobserver agreement of EF values obtained from gated SPECT was excellent (r = 0.996, n = 10, p < 0.01). LVEFs obtained from gated SPECT showed good correlation to those calculated from radionuclide ventriculography (MUGA) (r = 0.91, p < 0.01). In conclusion, this automatic method using gated myocardial SPECT data was considered to be useful for assessment of LV function with reproducibility.
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Factor VII coagulant activity (FVIIc) and fibrinogen (Fbg) levels have been investigated as cardiovascular risk factors. We studied these two factors with stratification for age, sex and blood pressure, and the relation with other atherosclerotic risk factors in a Japanese general population. The subjects were 3,139 Japanese (1,315 males and 1,824 females) aged 30 to 89 in 1992 and 1993. A linear increase with age was observed in the levels of Fbg in both men and women, but no differences were observed between men and women in each age group. A linear increase with age was also seen in the levels of FVIIc in women, but the levels of FVIIc in men were significantly higher for the age group 40-49 years than for any other age group. The levels of FVIIc in women were significantly higher than in men at age > or = 60 years. As concerning the effect of alcohol intake status, Fbg had a tendency to decrease with alcohol intake. Fbg and FVIIc levels were associated with an increase in smoking status in men, but no association was seen in women in either Fbg or FVIIc. FVIIc was positively correlated with age, body mass index, total cholesterol, triglycerides and fasting insulin level. Fbg was positively correlated with age, systolic blood pressure, diastolic blood pressure, total cholesterol, LDL-cholesterol and triglycerides in women, but Fbg had few positive correlations with risk factors in men. A comparison with previous Western studies showed that the Fbg levels of our Japanese population were lower than those of the Caucasians studied, but the present FVIIc levels were nearly the same level or slightly higher than theirs. The association of Fbg and FVIIc and with other cardiovascular risk factors in Japanese was similar to those observed in Caucasians.
The forms of cytochrome P450 involved in the stereoselective S-oxidation of flosequinan [(+/-)-7-fluoro-1-methyl-3-methylsulfinyl-4-quinolone] were investigated in vitro using liver microsomes from rats and humans. Rat liver microsomes supplemented with NADPH catalyzed the four different S-oxidations, which were from flosequinan sulfide (FS; 7-fluoro-1-methyl-3-methylthio-4-quinolone) to R(+)- and S(-)-flosequinan (R-FSO and S-FSO, respectively) and from R-FSO and S-FSO to flosequinan sulfone (FSO2; 7-fluoro-1-methyl-3-methylsulfonyl-4-quinolone). The activities of all the S-oxidases in liver microsomes from male rats were higher than those from female rats. The activities of the S-oxidases measured at a high substrate concentration (1 mM) were induced by treatment of rats with phenobarbital and dexamethasone. Treatment of rats with 3-methylcholanthrene also induced the activities, but only at a low substrate concentration (50 microM), except for the S-oxidase catalyzing the reaction from FS to R-FSO. Enzymes induced by clofibrate and ethanol were not involved in the oxidations at a low substrate concentration. The activities of S-oxidases were correlated with the contents of cytochrome P450 (CYP)3A enzymes. Anti-CYP3A2 antisera inhibited the activities of the S-oxidases catalyzing the reactions from FS to R-FSO (40%) and to S-FSO (60%) at the high substrate concentration and inhibited the activities of the S-oxidases, thus catalyzing reactions from R-FSO and S-FSO to FSO2 (70%) at both high and low substrate concentrations. These results suggest that CYP3A is the major enzyme involved in all S-oxidation pathways in flosequinan metabolism in rats. On the other hand, except for the S-oxidation of FS to R-FSO, the rates of the other three S-oxidations by liver microsomes from 30 individual humans correlated highly with each other, suggesting that the same enzyme would be involved in the three S-oxidations. Anti-CYP3A2 antisera inhibited the activities of all the S-oxidases in human liver microsomes ranging from 40 to 80%, suggesting that CYP3A is also involved in all of the S-oxidations of flosequinan in humans.
We investigated activation of the globus pallidus using conventional gradient echo sequence with a 1.5 tesla equipment. In accordance with complex finger tapping in the left hand, an increase in signal intensity from bilateral globus pallidus was attained, being grossly predominated on right side. On the other hand, activations in primary motor cortex were elicited mainly on right side, thereby being correctly accorded in attitude of on-off changes in signal intensity. fMRI in basal ganglia faces severer condition in detecting real activation, owing to influences to signal recording by ventricular pulsation, accumulation of iron by age, and differences in activation by the tasks applied. This study, however, suggests that fMRI of basal ganglia is a promising technique for mapping brain function in regard to correlations between cerebral cortex and deep structures.
Since 1991, 27 consecutive patients with aortic dissection (Stanford A) have been operated on using deep hypothermic retrograde cerebral perfusion (RCP). There were no differences in ECC time (247 +/- 15 vs 307 +/- 22 min), and RCP time (47 +/- 2 vs 47 +/- 3 min) between the aged (> or = 70 y.o., n = 11) and non-aged (< 70 y.o., n = 16) group. Although the aged group showed the higher incidences of postoperative neurological complications of prolonged emergence (2 cases) and delirium (3 cases), respiratory disorder (3 cases), and renal dysfunction (3 cases), there was no significant difference in hospital mortality (18% in the aged vs 13% in the non-aged). We concluded that RCP is well acceptable procedure for surgical treatment of the aged patients with aortic dissection.
Transurethral electrovaporization of prostate (TVP) is a new minimally invasive procedure to treat enlargement of prostate. From April 1996 to the end of October, TVP was carried out in 37 cases (mean age, 71.0) with symptoms of urethral obstruction. Standard transurethral resection equipment was utilized. This included a Stortz 26F resectoscope with a Conmed SABRE 2400 electrical current generator. A Stortz 3 mm Spike Electrode was used as the vaporization electrode. The average setting was 250 W for cutting and 80 to 100 W for coagulation. Efficacy parameters evaluated included International Prostate Symptom Score, peak uroflow and postvoid residual volume. By the end of January 1997, 28 cases could be followed up for more than three months after surgery and evaluated. Postvoid residual volume decreased from 68 to 10 and 17 ml at 1 and 3 months. Peak uroflow increased from 8.5 to 15.1 and 17.9 ml/sec at 1 and 3 months. All 28 cases were categorized as effectively treated cases at 1 and 3 months postoperatively. TVP was found to have several advantages, particularly minimal bleeding and the low incidence of postoperative morbidity. The technique is simple and symptoms improve at an early stage following surgery. We intend to continue longer follow up with larger numbers of patients.
Preoperative histological diagnosis of lung cancer is usually based on findings from a transbronchial biopsy specimen of the tumor obtained through a fiberoptic bronchoscope. However, peripheral pulmonary tumors can be difficult to diagnose in this way. We report two patients with lung cancer invading the chest wall for whom histological diagnoses were not possible by transbronchial biopsy. Treatment for lung cancer is different from that for chest-wall tumors, so preoperative differential diagnosis of these conditions is important. Other organs should be searched to exclude metastatic chest-wall tumors. Percutaneous needle biopsy done under ultrasonic guidance made the histological diagnosis of lung cancer possible in both cases.
In a familial amyotrophic lateral sclerosis (FALS) with SOD-1 mutation (Asn 86-Ser), there were intra-familial clinical diversities. The proband, a daughter patient, shows a mild clinical course of 16 years. Her father died of respiratory failure in 3 years. His initial symptom was weakness of upper extremity. The daughter's first symptom was that of lower extremities. Her respiratory-assist started after 9 years from the onset. She is alive under whole-day respiratory assist while she had been taking nutrients per os for 15 years. Her abilities of swallowing remain, even more dependent of tube-feeding (15 years after the onset). The fact of the presence of intra-familial clinical varieties with SOD-1 mutation in FALS suggests that the mutation is not an exclusive factor to determine the clinical phenotype, age of the onset and rapidity of illness of FALS associated with SOD-1 mutation. We collect reports of FALS with SOD-1 mutation which have similar diversities of intra-familial clinical manifestations as our family. Varieties of intra-familial clinical manifestations of motor neuron disease are shown in 9 families with SOD-1 mutation. The genetic error appears to have a limit, and is not a exclusive cause of FALS. However, we should not underestimate the significance of the discovery of a gene, since it might offer a clue to still unanswered riddle of ALS pathogenesis.
In liver surgery, postoperative liver failure has been a serious problem of concern. Recently, the advances in the imaging diagnosis and in the operative procedures have contributed to reduce the operative mortality to less than 1%. Between October 1994 and December 1996, a total of 159 patients, including 39 with chronic hepatitis and 66 with cirrhosis, underwent liver resection for hepatocellular carcinomas (n = 103), metastatic tumors (n = 24) and others (n = 32). Although about 20% of patients had some postoperative complications, no patient died of postoperative liver failure. Preoperatively, the liver function was estimated by ICG R15 and CT volume metry, and portal vein embolization and the splenectomy, if necessary, was performed. Blood loss was replaced by plasma as far as possible. Postoperatively, it is most important to maintain the optimal water balance and electrolyte levels using fresh plasma and diuretics. Even in patients with cirrhosis, no operative mortality can be achieved with optimal hepatectomy and careful perioperative management.
Chylothorax, a rare complication after pulmonary resection, has no single established treatment. Generally, conservative therapy is tried first, but surgery should be done without delay if chyle leakage is severe. A 73-year-old woman underwent upper left lobectomy for lung cancer. Two days later, chylothorax was diagnosed, and because chyle leakage was great, emergency re-thoracotomy was done on day 4 after the first operation. With the preoperative ingestion of 200 ml of milk and 20 g of margarine, chyle leakage from the injured thoracic duct was readily located in the upper mediastinum. Closure of the trunk of the thoracic duct may be undertaken, but a direct approach to the site of injury is more preferable, because the trunk may have collateral.
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Nine hundred and seventy-three consecutive patients were referred to our hospital for thoracotomy to treat chest diseases between January 1, 1981, and December 31, 1995. Of these patients, 20 males were readmitted within a mean of 20 months with a diagnosis of contralateral pneumothorax. Sixteen of the patients with a mean age of 28.5 years (range 16-76 years of age) had been operated on for bullous lung disease. The remaining four, with a mean age of 60.8 years (range 54-71), had been operated on for lung cancer. All of the 20 patients had received unilateral thoracotomy for lung resection. One patient had undergone pneumonectomy for lung cancer; three had undergone lobectomy; and 16 had been treated by partial lung resection. The patient who had undergone pneumonectomy was found to have contralateral pulmonary metastasis of lung cancer. In the other 19 patients, emphysematous bulla was the origin of the contralateral pneumothorax. The mean value of body mass index (BMI) of the group was 18.4 as compared to 21.7 in the patients who did not go on to develop contralateral pneumothorax, a significant difference (p < 0.05). In conclusion, postoperative contralateral pneumothorax was correlated to the existence of emphysematous changes of the lung and a significantly lower BMI. We conclude that patients with BMIs less than 20 may be at increased risk of developing postoperative contralateral pneumothorax.
Omeprazole 5-hydroxylation and sulfoxidation activities were determined in liver microsomes of different humans whose levels of individual forms of cytochrome P450 (P450 or CYP) varied. Correlation coefficients between omeprazole 5-hydroxylation activities (when determined at a substrate concentration of 10 microM) and S-mephenytoin 4'-hydroxylation and testosterone 6beta-hydroxylation activities were found to be 0.64 and 0.67, respectively, in liver microsomes of 84 human samples examined. Omeprazole sulfoxidation activities in these human samples were correlated with testosterone 6beta-hydroxylation activities (r = 0. 86). Omeprazole 5-hydroxylation by liver microsomes of a human sample that contained relatively high levels of CYP3A4 and low levels of CYP2C19 were inhibited very significantly by ketoconazole and anti-CYP3A4 antibodies, although a human sample having high in CYP2C19 and low in CYP3A4 was found to be sensitive toward fluvoxamine and anti-CYP2C9 antibodies. Sulfaphenazole (at 100 microM) did not affect the omeprazole 5-hydroxylation and sulfoxidation catalyzed by human liver microsomes. Both recombinant human CYP2C19 and CYP3A4 enzymes had activities for omeprazole 5-hydroxylation, with low Km and high Vmax values for the former enzyme and high Km and low Vmax values for the CYP3A4. These results suggest that contributions of CYP2C19 and CYP3A4 in the omeprazole 5-hydroxylation depend upon the ratio of these two P450 levels in human liver microsomes. Omeprazole 5-hydroxylation activities of different human samples were found to be related to predicted values calculated from the kinetic parameters of recombinant enzymes and the levels of liver microsomal CYP2C19 and CYP3A4 enzymes. Finally, when recombinant human CYP2C19 and CYP3A4 were mixed at levels found in different human samples, relatively similar profiles of omeprazole oxidation by the recombinant and microsomal enzyme systems were determined by analysis of high-performance liquid chromatography. These results suggest that both CYP2C19 and CYP3A4 are involved in the 5-oxidation of omeprazole (at a substrate concentration of 10 microM) in human liver microsomes and that contributions of these P450 enzymes depend on the compositions of CYP2C19 and CYP3A4 in liver.
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A 33-year-old man who had been treated for chronic prostatitis was diagnosed to have urachal cysts by transabdominal ultrasonography. Cystoscopy revealed protuberance at the dome of the bladder. Computerized tomography scan and magnetic resonance imaging showed the mass to be mostly cystic but partly solid. Resection of the urachal cysts and partial cystectomy were performed. Histopathologically, most cysts had a normal cylindrical epithelium with retention of mucinous substance. However, several small cysts contained epithelial cells resembling tubulo-villous adenoma and showing mitotic figures. This case was concluded as urachal carcinoma detected in its very early stage.