Search PubMed⌕ Search

Biomedical subjects

M Ohkubo

Publications and source records attributed to M Ohkubo.

At least 55 records · Page 3Linked to original sources

[A limitation of the split-dose method for evaluating rCBF changes using 99mTc-ECD and SPECT].

The purpose of the study is to validate the split-dose method corrected with dose ratio of 99mTc-ECD for brain perfusion scan. A dose of 600 MBq of 99mTc-ECD was divided into two with various dose ratios from 1:1 to 1:4, and injected to eleven patients with various cerebral diseases. A lesser dose of 99mTc-ECD was injected under a control state for the first SPECT scan, and 15 min SPECT scan was performed 10 min after injection with a triple-head high resolution gamma camera. After the scan, the other dose of 99mTc-ECD was injected under the same control state and the second SPECT scan was performed as same as above. A ratio of the activity of the first scan to the net activity of the second scan corrected by dose ratio, defined as K, was measured in brain regions of each subject. Expected value of K was 1, but the value was distributed with large variations in each subject. The mean % error of the K value was 10.4 +/- 4.9%. Hence it is considered that activity changes by more than 20% from the control values should be required to detect a significant rCBF change in an activation SPECT study. Then, we proposed a new method in which the activity of both two SPECT scans was normalized by cerebellar or occipital activity and compared. The ratio obtained by the proposed method came closer to 1 with less variations and with less mean % error in comparison with those of K value obtained by the dose-correction method. Although the proposed method has a limitation in the use of an activation study loaded with Diamox, it may be useful to evaluate an alteration of rCBF in the study such as postural testing or finger-moving test.

Brain↗

Quantification of cerebral blood flow and partition coefficient using iodine-123-iodoamphetamine.

UNLABELLED: The aim of this study was to develop a simple, noninvasive method for quantifying both regional cerebral blood flow (rCBF) and the partition coefficient (lambda) using N-isopropyl-p[123I]iodoamphetamine and SPECT. METHODS: By employing a two-compartment model (influx, K1: outflux, k2), a new method was introduced that requires two serial SPECT scans at 30 min and 60 min, and a single arterial sample 5 min after tracer injection. The integral of the arterial input function is inferred from the sample by using the correlation obtained from 25 subjects. Two original mathematical functions, phi for K1 and gamma for lambda (= K1/k2), were obtained from the input functions of 12 subjects. The values of K1 and lambda are determined from the two scans and the single arterial sample by using these functions. The values obtained for K1 (= rCBF) and lambda were compared with those obtained by nonlinear least-squares fitting analysis and the 133Xe inhalation SPECT method. RESULTS: K1 and lambda were in good agreement with the values obtained by nonlinear least-squares fitting analysis (r = 0.873 in K1 and r = 0.825 in lambda), and rCBF values were closely correlated with those obtained by the 133Xe method (r = 0.843). CONCLUSION: The proposed method has three advantages: (a) accurate, simultaneous quantification of both rCBF and the partition coefficient; (b) simplicity and noninvasiveness; and (c) a relatively short period (approximately 70 min) for the study.

Amphetamines↗

[Mid-term follow-up results of coil embolization for patent ductus arteriosus].

Mid-term follow-up results of coil embolization for patent ductus arteriosus (PDA) were evaluated in 19 patients aged from 2 years 9 months to 13 years (median: 5 years and 10 months) who underwent coil embolization for PDA. The minimum diameter of PDA ranged from 1.0 to 3.5 mm (mean 2.3 +/- 0.8 mm). Coil embolization was performed by the retrograde approach in 16 patients and the anterograde approach in 3, using a Gianturco coil in 11 and a Jackson detachable coil system in 8. Sixteen patients underwent single coil embolization and three patients received two coils simultaneously with detachable coil systems. Follow-up evaluation was performed with color flow mapping and pulsed Doppler echo to identify residual shunt or acquired left pulmonary artery stenosis after embolization at 1 day, 1 week, 1, 3, 6 and 12 months, and every 6 months thereafter. In two patients, a coil had migrated into the distal left pulmonary artery immediately after implantation, and could be safely retrieved. Minimum residual shunt was found in six patients (32%) on the day after the procedure. Spontaneous closure was noted in all patients within 6 months. Recanalization of completely occluded PDA was observed in one patient at 1 month after embolization. However, spontaneous closure of the residual shunt was found at 1 year and 6 months of follow-up. There was no evidence of acquired left pulmonary artery stenosis during the follow-up period (14.5 +/- 5.8 months). Coil embolization is an effective and safe therapy for PDA. Small residual shunt may be observed immediately after the coil embolization, but will close spontaneously during the follow-up. Recanalization occurred after complete coil occlusion, so careful follow-up with color flow mapping is mandatory.

Adolescent↗

[Quantification of cerebral blood flow with 99mTc-ECD SPECT by a single arterial or venous blood sample].

The purpose of the study is to develop a simple and less invasive method for quantifying regional cerebral blood flow (rCBF) using 99mTc-ECD and SPECT. By employing a microsphere model, a new method to measure rCBF was developed, which required a single arterial or venous sample instead of continuous withdrawal of arterial blood. Using a regression line, the integral of input function of arterial blood from 0 to 30 min was inferred by activity of arterial blood sampled at time t; A(t), by activity multiplied by its octanol extraction rate; AN(t), by activity of venous blood at time t; V(t), and by activity multiplied by its octanol extraction rate; VN(t). The optimum sampling time of arterial or venous blood was examined when mean % error for inference became minimum. Consequently, minimum error of AN(6 min) was 5.5%, A(3 min) was 8.9%, VN(6 min) was 5.9%, and V(20 min) was 10.0%. Quantitative measurement of rCBF using the value of VN(6 min) was performed on other 6 subjects with dementia etc. To validate the method, 133Xe inhalation SPECT studies were also performed on the same subjects. We found a good agreement between them (r = 0.851). The presented one-point sampling methods were simple and less invasive for quantifying rCBF.

Adult↗

Application of percutaneous transluminal coronary angioplasty to coronary arterial stenosis in Kawasaki disease.

BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) has rarely been performed on patients with coronary lesions that result from Kawasaki disease. In this study, we retrospectively evaluated the effectiveness of PTCA in five patients with coronary arterial stenosis that resulted from Kawasaki disease and reviewed previous reports for possible indicators of PTCA effectiveness. METHODS AND RESULTS: Five patients, ranging in age from 2 to 16 years (median 8 years) underwent conventional PTCA for localized stenosis. The lesion targeted for PTCA was located in the middle right coronary artery of three patients and in the left anterior descending artery in two patients. In four of the five patients, PTCA was angiographically effective, with stenosis rates improving from 84 +/- 10% to 33 +/- 11% (P<.05). When the previously reported cases of six similar patients were taken into consideration, the only predictor of successful PTCA seemed to be the time elapsed between the onset of Kawasaki disease and performance of this procedure. CONCLUSIONS: In cases in which patients show significant localized stenosis as a result of Kawasaki disease, PTCA should be attempted within 6 to 8 years of the onset of the disease. Additionally, intravascular ultrasound imaging was found to be a useful tool for evaluating internal morphology before and after PTCA. In older patients with coronary calcification, other alternatives to PTCA, such as the use of a rotablator or an atherectomy catheter, should be considered.

Adolescent↗

Improved tumor detection by anti-CEA chimeric Fab oligomers with disulfide linkages in a pancreatic-carcinoma-xenograft model.

We have investigated the effect of Fab oligomerization on imaging efficacy in a pancreatic-carcinoma xenograft model in mice. Recombinant mouse/human chimeric Fab of the anticarcinoembryonic antigen (CEA) monoclonal antibody A10, which has been shown to react specifically with gastrointestinal cancers, was used in this study. Fab homo-oligomers (dimers and trimers) were prepared by linkage of chimeric Fab with N-succinimidyl-3-(2-pyridyldithio)-propionate. Oligomers with S-S bonds showed 10-fold higher binding activity against human CEA than Fab, while the binding activity of oligomers was similar to that of F(ab')2. In mice bearing pancreatic-carcinoma xenografts, tumor uptake of S-S oligomers was significantly greater than that of monomeric Fab, while there was no difference in tumor uptake between S-S Fab trimers and F(ab')2. S-S oligomers showed more rapid clearance rates and uniform percolation in the tumor nodules than F(ab')2. At 18 hr after injection, clear scintigraphic detection of the pancreatic-carcinoma tumors was obtained with 123I-labeled S-S Fab dimers. At 24hr, improved tumor imaging was shown for 123I-labeled S-S Fab oligomers with slightly visible uptake in normal tissues, similar to that of F(ab')2. S-S oligomers of chimeric A10 Fab may be useful as rapid diagnostic tools of pancreatic carcinomas.

Animals↗

Decrease in benzodiazepine receptor binding in a patient with Angelman syndrome detected by iodine-123 iomazenil and single-photon emission tomography.

A receptor mapping technique using iodine-123 iomazenil and single-photon emission tomography (SPET) was employed to examine benzodiazepine receptor binding in a patient with Angelman syndrome (AS). AS is characterized by developmental delay, seizures, inappropriate laughter and ataxic movement. In this entity there is a cytogenic deletion of the proximal long arm of chromosome 15q11-q13, where the gene encoding the GABAA receptor beta3 subunit (GABRB3) is located. Since the benzodiazepine receptor is constructed as a receptor-ionophore complex that contains the GABAA receptor, it is a suitable marker for GABA-ergic synapsis. To determine whether benzodiazepine receptor density, which indirectly indicates changes in GABAA receptor density, is altered in the brain in patients with AS, we investigated a 27-year-old woman with AS using 123I-iomazenil and SPET. Receptor density was quantitatively assessed by measuring the binding potential using a simplified method. Regional cerebral blood flow was also measured with N-isopropyl-p-[123I]iodoamphetamine. We demonstrated that benzodiazepine receptor density is severely decreased in the cerebellum, and mildly decreased in the frontal and temporal cortices and basal ganglia, a result which is considered to indicate decreased GABAA receptor density in these regions. Although the deletion of GABRB3 was not observed in the present study, we indirectly demonstrated the disturbance of inhibitory neurotransmission mediated by the GABAA receptor in the investigated patient. 123I-iomazenil with SPET was useful to map benzodiazepine receptors, which indicate GABAA receptor distribution and their density.

Adult↗

A multicenter validation of regional cerebral blood flow quantitation using [123I]iodoamphetamine and single photon emission computed tomography.

Recently, two methods have been proposed for regional cerebral blood flow (rCBF) quantitation using [123I]iodoamphetamine (IMP) and single-photon emission computed tomography (SPECT). The table look-up (TLU) method has been shown to provide both rCBF and volume of distribution, Vd, images from two SPECT scans, while a single-scan autoradiographic (ARG) technique provided rCBF using a fixed and assumed Vd. In both methods, a single blood sample was referred to calibrate the previously determined standard input function. The present multicenter project was designed to evaluate the accuracy of both methods for use as clinical investigative tools. Ten independent institutions performed [123I]IMP-SPECT studies according to both methods in 76 subjects (10 normal volunteers, 32 patients with cerebrovascular disease, and 34 patients with other diseases). Calculated rCBF values were compared with those obtained by the following reference methods available in the participating institutions; [15O] H2O positron emission tomography (PET) (five institutions), [133Xe]SPECT (four institutions), and the [123I]IMP microsphere method (three institutions). Both ARG and TLU methods provided rCBF values that were significantly correlated with those measured by the [15O] H2O PET technique (p < 0.001 for all subjects; overall regression equation, y = 15.14 + 0.54x) and those measured by the [123I]IMP-microsphere method (p < 0.001 for all subjects: y = 2.0 + 0.80x). Significant correlation (p < 0.05) was observed in 18 of 24 subjects studied with the [133Xe] SPECT reference technique (overall regression equation, y = 15.0 + 0.55x). Mean cortical gray matter rCBF in a group of normal subject was 43.9 +/- 3.3 and 43.4 +/- 2.0 ml/min/100 g for the ARG and TLU methods, respectively. Regional Vd of [123I]IMP estimated by the TLU method was 45 ml/ml +/- 20% in the normal cortical region. Close agreement between ARG and TLU rCBF values was observed (y = -3.21 + 1.07x, r = 0.97), confirming the validity of assuming a fixed Vd in the ARG method. Results of this study demonstrate that both the ARG and TLU methods accurately and reliably estimate rCBF in a variety of clinical settings.

Adolescent↗

Elevation of cerebral lactate detected by localized 1H-magnetic resonance spectroscopy in migraine during the interictal period.

We used localized 1H-magnetic resonance spectroscopy (MRS) to study the metabolic changes in the brains of patients with migraine during the interictal period. Measurement of metabolite levels in the occipital visual cortex in six normal subjects and six patients disclosed high lactate levels in the five patients who had experienced a migraine attack within the previous 2 months. One patient who had not experienced a migraine attack in the previous 4 years did not show a lactate peak. We speculate that anaerobic glycolysis occurs in the brains of patients with migraine during the interictal period, and a long attack-free period may normalize the subclinical metabolic disturbance.

Adolescent↗

Studies on cerebral protective agents. X. Synthesis and evaluation of anticonvulsant activities for novel 4,5,6,7-tetrahydrothieno[3,3-c]pyridines and related compounds.

Novel 4,5,6,7-tetrahydrothieno[3,2-c]pyridines, 1-thienyl-1,2,3,4-tetrahydroisoquinolines and related compounds, in which the benzene rings of (+)-1 (FR115427) were replaced with heteroaromatic rings such as thiophene, furan, benzothiophene and indole, were synthesized and evaluated for anticonvulsant activity against i.c.v. N-methyl-D-aspartate (NMDA)-induced seizures in mice. Among these compounds, (+)-4-methyl-4-phenyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine hydrochloride ((+)-2a), (+)-4-methyl-4-(2-thienyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine hydrochloride ((+)-2g), and (-)1-methyl-2-(2-thienyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride ((-)-3a) showed significant anticonvulsant activity. The structure-activity relationships with regard to the anticonvulsant activity of this series of compounds are discussed.

Animals↗

Studies on cerebral protective agents. IX. Synthesis of novel 1,2,3,4-tetrahydroisoquinolines as N-methyl-D-aspartate antagonists.

A series of 1,2,3,4-tetrahydroisoquinoline derivatives were synthesized and evaluated for anticonvulsant activity against intracerebro-ventriculas (i.c.v.) N-methyl-D-aspartate (NMDA)-induced seizures in mice. Among these compounds, (+)-1-methyl-1-phenyl-1,2,3,4-tetrahydroisoquinoline hydrochloride ((+)-1a, FR115427) was the most effective anticonvulsant, and also protected CA1 hippocampal neurons from ischemia-induced neuronal degeneration in rats at 32 mg/kg i.p. In addition, (+)-1a showed anti-hypoxic activity in mice at 3.2-32 mg/kg i.p. The absolute configuration at the C-1 position of the isoquinoline ring was determined to be S by a single-crystal X-ray analysis of (+)-1a (+)-di-p-toluoyl-D-tartrate. Structure-activity relationships with regard to the anticonvulsant activity of this series of compounds are discussed, and the three-dimensional structures of (S)-(+)-1a and MK801 are compared.

Animals↗

Angiographic assessment of the stretch-recoil-gain relation after balloon coarctation angioplasty and its relation to late restenosis.

The effects of stretch and immediate recoil after balloon angioplasty were evaluated in 21 patients with coarctation of the aorta who underwent balloon coarctation angioplasty. A total of 28 procedures were performed in these patients, who ranged in age from 1 month to 17 years with a mean of 4.3 years. The systolic pressure gradient and coarcted diameter changed significantly from 42 +/- 22 to 14 +/- 9 mmHg (P < 0.0001) and from 4.0 +/- 1.7 to 6.1 +/- 2.0 mm (P < 0.001), respectively. Immediate recoil was responsible for the loss of 33% of the potentially achievable coarcted dimension. Recoil was determined mainly by the degree of arterial stretch. Gain increased exponentially with an increase in stretch. There was a narrow range of % stretch (60-80%) within which an effective diameter gain could be obtained. Both gain and stretch were the best predictors for late restenosis: patients with a larger immediate gain and stretch developed more restenosis. These results suggest that the stretch-recoil-gain relationship may be clinically important for evaluating the best predictor of late restenosis after balloon coarctation angioplasty.

Adolescent↗

[A new method for measurement of both regional cerebral blood flow and distribution volume using N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) and SPECT].

We developed a new method (functional IMP SPECT) to quantitate both regional cerebral blood flow (rCBF) and distribution volume (Vd) using 123I-IMP and SPECT based on a 2- compartment model (influx; K1 =rCBF and outflux; k2). This method requires one arterial blood sampling at 5 min after injection of the tracer and two SPECT scans at 30 min and 60 min. It takes approximately 60 min for total measurements. The integration of arterial input function is estimated by one blood sample taken at 5 min after injection of the tracer without octanol treatment, by using the correlation between one blood sample and the integration, which was obtained from studies on 25 subjects. With the value of integration, K1 and Vd are calculated from the data of two SPECT scans by using the mathematical functions based on the 2-compartment model, which were obtained from studies on 12 subjects. In the practical range of K1 (0.3-0.7 ml/g/min) and Vd (15-35 ml/g) given in the 2-compartment model, statistical errors of K1 and Vd obtained by the functional IMP SPECT were evaluated at approximately 14.0% and 17.2%, respectively. In clinical studies for eight subjects including two healthy volunteers, three patients with cerebral infarction and three patients with degenerative disease, K1 and Vd values estimated by the functional IMP SPECT were significantly correlated with those estimated by non-linear least squares fitting analysis based on the 2-compartment model, and the mean errors of K1 and Vd estimated by the functional IMP SPECT were approximately 8.0% and 11.2% respectively, suggesting the validity of the new method. We conclude that the functional IMP SPECT is clinically useful because of the accuracy, less-invasiveness and convenience.

Amphetamines↗

[A functional diagnostic method by measuring of distribution volume of 123I-IMP with SPECT].

To measure distribution volume of 123I-IMP with one-point sampling of arterial blood and 2 times SPECT scans using the Magic square method (Rate constant square method), we introduced a program on a SPECT computer system. In this program four functional images; distribution volume, CBF (K1), k2 and delayed/early ratio, and absolute values with S.D. are obtained on the computer. We have been using the program on daily SPECT studies. In this study we discussed the usefulness of the method. Redistribution phenomenon of 123I-IMP, which is not exactly enough investigated, can be transformed into a functional parameter, distribution volume. Since distribution volume represents an extent of retention of 123I-IMP in brain tissue, it can play an important role to evaluate functional activity in the brain and to diagnose cerebral diseases.

Adult↗