Biomedical subjects

H Fukuyama

Publications and source records attributed to H Fukuyama.

At least 127 records · Page 7Linked to original sources

PubMed1996

Abulia from unilateral capsular genu infarction: report of two cases.

We report two cases of capsular genu infarction in patients showing pure abulia without motor weakness. One case is left-sided infarction, and another is right-sided. Single photon emission computed tomography (SPECT) examination in both disclosed hypoperfusion in the ipsilateral frontal cortex at the infarction. In one case, reversion of frontal hypoperfusion was observed later. We considered that the frontal hypoperfusion was due to trans-synaptic hypofunction of thalamo-frontal projections from the deep-seated capsular genu lesion and that it resulted in the pure abulia without neurological deficits.

Aged↗

PubMed1996

Cerebral activation during performance of a card sorting test.

The Wisconsin Card Sorting Test (WCST) is used clinically for evaluating frontal lobe function, but there is some controversy as to its specificity for detecting frontal lobe damage. To investigate the cerebral regions essential to the performance of the Card Sorting Test, we measured the regional cerebral blood flow (rCBF) in 18 normal subjects by PET under the three conditions: (i) during the Modified Card Sorting Test (MCST); (ii) during a matching-to-sample (MTS) task, based on the MCST, but with selective attention to one of three stimulus categories (colour, number or shape) as a control to cancel the effects of maintenance of sets in the MCST; (iii) under resting conditions as overall control. When rCBF during the MCST was compared with that during each MTS task separately, significant activations were observed during the MCST in the left or bilateral dorsolateral prefrontal cortex (DLPFC), bilateral inferior parietal lobes, left superior occipital gyrus and left cerebellum. Compared with all the MTS tasks inclusively, significant increase in rCBF was detected during the MCST in the bilateral DLPFC, inferior parietal lobes, striate cortex, cerebellum and left occipital cortex. These results suggest the involvement of the DLPFC and other related areas such as the inferior parietal cortex in the execution of the MCST, and may help explain why a variety of brain lesions can result in impaired performance on the Card Sorting Test.

Adult↗

PubMed1996

Cholinergic projection from the basal forebrain and cerebral glucose metabolism in rats: a dynamic PET study.

To investigate the influence of cholinergic projections from the basal forebrain on cerebral cortex metabolism, we evaluated the cerebral metabolic rate of glucose (CMRGlu) after selective inhibition of cholinergic neurons in the rat basal forebrain using the pyruvate dehydrogenase complex inhibitor 3-bromopyruvic acid (BPA), and compared the results with those obtained after lesioning the basal forebrain with ibotenic acid, as well as with those from a sham-operated control group. CMRGlu was measured using positron emission tomography (PET) with [18F]-2-fluoro-2-deoxy-D-glucose (FDG). Three days after surgery, CMRGlu and k3 (phosphorylation of FDG) were reduced similarly in the frontal cortex on the BPA-injected side and in the ibotenic acid-treated group, whereas K1 (transport rate of FDG from the plasma to brain) showed no marked changes. At 3 weeks postoperatively, the CMRGlu and k3 of the frontal cortex in both groups recovered to levels similar to those of the sham-operated group. The main difference between the BPA and ibotenic acid groups was that CMRGlu showed mild reduction on the side contralateral to the operation in the former, while such reduction was confined to the ipsilateral hemisphere in the latter. The present results indicate that the cholinergic system in the basal forebrain regulates cerebral cortex glucose metabolism through direct excitation of cortical neurons.

Analysis of Variance↗

PubMed1996

Evidence of misery perfusion and risk for recurrent stroke in major cerebral arterial occlusive diseases from PET.

OBJECTIVES: In major cerebral arterial occlusive diseases, patients with inadequate blood supply relative to metabolic demand (misery perfusion) may be at increased risk for cerebral ischaemia. This study investigated whether patients showing misery perfusion on PET have a high risk of recurrent ischaemic stroke. METHODS: The relation between the regional haemodynamic status of cerebral circulation and the subsequent risk of recurrent stroke was prospectively evaluated in 40 patients with symptomatic internal carotid or middle cerebral arterial occlusive diseases who underwent PET. Patients were divided into two haemodynamic categories according to the mean hemispheric value of oxygen extraction fraction in the hemisphere supplied by the artery with symptomatic disease: patients with normal oxygen extraction fraction and those with increased oxygen extraction fraction (misery perfusion). All patients were followed up for at least 12 months. RESULTS: The one year incidence of ipsilateral ischaemic strokes for patients with normal oxygen extraction fraction and those with increased oxygen extraction fraction were two of 33 and four of seven patients respectively. A significantly higher incidence of ipsilateral strokes was found in patients with increased oxygen extraction fraction (Fisher's exact test; P = 0.005). In patients with increased oxygen extraction fraction, three of four strokes were watershed infarctions and the location of the infarction corresponded with the area of increased oxygen extraction fraction. CONCLUSION: These findings contradict conclusions of a previous study and suggest that patients with major cerebral arterial occlusive diseases and misery perfusion have a high risk for recurrent ischaemic stroke.

Adult↗

PubMed1996

Bromocriptine therapy in early-stage Parkinson's disease.

We evaluated bromocriptine monotherapy during the early stage of Parkinson's disease (Hoehn and Yahr stage I or II). Of the 120 patients registered as participants in this trial, 96 were studied. The follow-up period was 48 weeks. For the first 24 weeks they were all placed on bromocriptine with or without anticholinergic drugs; for the second 24 weeks, 75 of them were still kept on the same medication, with 21 requiring additional levodopa. Clinically, the former group showed a good response to the bromocriptine monotherapy, while the latter responded poorly to it (requiring in addition levodopa). We think that Parkinson's disease encompasses a heterogeneous group of patients of whom about 75% are well treated by bromocriptine alone at the early stages of the illness.

Antiparkinson Agents↗

PubMed1996

[A phase 3 clinical trial of 123I-iomazenil, a new central-type benzodiazepine receptor imaging agent (Part 1)--report on clinical usefulness in diagnosis of various brain diseases].

Iomazenil (IMZ) is a partial inverse agonist of central-type benzodiazepine receptors (BZR) which binds specifically to BZR with high affinity. The safety and clinical effectiveness of 123I-IMZ SPECT in the diagnosis of brain diseases were evaluated in 655 patients with various brain diseases, such as epilepsy, cerebrovascular diseases, degenerative diseases and mental disorders relating to BZR. This was a Phase 3 study conducted as a multicenter trial at 52 collaborating institutions. There was no significant adverse reactions in the clinical symptoms or abnormal laboratory test values. The investigators judged 123I-IMZ SPECT to be effective in 95% of 638 analyzed cases. The injected dose did not correlate with the image quality or the clinical effectiveness of 123I-IMZ SPECT, suggesting that these items depend largely on the characteristics of the apparatus used, the disease or pathology of the patients, rather than the dose. We conclude that 123I-IMZ imaging is safe and provides effective information based on BZR binding which is useful in the diagnosis of various brain diseases.

Adolescent↗

PubMed1996

[A phase 3 clinical trial of 123I-iomazenil, a new central-type benzodiazepine receptor imaging agent (Part 2)--Report on clinical usefulness in diagnosis of degenerative neurological diseases and mental disorders].

Iomazenil (IMZ) is a partial inverse agonist of central-type benzodiazepine receptors (BZR) which binds specifically to BZR with high affinity. A multi-center Phase 3 clinical study was performed to evaluate the clinical usefulness of 123I-IMZ-SPECT in the diagnosis of brain disorders in 169 patients with degenerative neurological diseases and 37 patients with mental disorders such as neurotic, stress-related and somatoform disorders. In dementia, the decrease in activity in late images, obtained three hours after administration of 123I-IMZ, correlated negatively with the dementia score. In Parkinson's disease and spinocerebellar degeneration. 123I-IMZ showed a more profound decrease in uptake in late images than seen in the cerebral blood flow (CBF) images, and this decrease was in proportion to the duration and severity of the illness. In mental disorders, the ratio of the late to early image counts showed a negative correlation with Hamilton's anxiety scale in all regions in the brain cortices. In panic disorders, the ratio of the cerebral count to the cerebellar count in the late images correlated negatively with the severity of the attack in the frontal, temporal and parietal cortices. These results suggest that 123I-IMZ-SPECT enables us to evaluate the neuronal damage in degenerative diseases and the decrease in the BZR binding potential in mental disorders.

Adult↗

PubMed1996

[A phase 3 clinical trial of 123I-iomazenil, a new central-type benzodiazepine receptor imaging agent (Part 3)--Report on clinical usefulness in epilepsy].

A Phase 3 clinical trial of 123I-Iomazenil (IMZ), a tracer which binds specifically to central-type benzodiazepine receptors (BZR), was performed, and the clinical usefulness of IMZ was evaluated in 121 patients with epilepsy (106 cases with partial epilepsy and 15 cases with generalized epilepsy). A regional abnormality in the BZR distribution was detected in late IMZ images in 20 of 24 cases without abnormal MRI and/or X-ray CT findings. Moreover, only 16 of these 20 cases showed abnormal findings in the cerebral blood flow (CBF) images. In partial epilepsy, abnormal regions in late IMZ images agreed or partially agreed with epileptic foci estimated from the clinical symptoms of epileptic seizures, interictal EEG, and MRI and/or X-ray CT findings in 76%, 70% and 96% of the cases detected. These regions also agreed or partially agreed with the estimated epileptic foci in 92% of the cases with foci estimated by combination of those three methods and in 72% of those estimated by ictal EEG. The agreement or partial agreement rates of late IMZ images with each of the other methods were higher than those of CBF images, although the differences were not significant. For surgically-proven epileptic foci without any abnormality in the CBF image, abnormal regions were detected in late IMZ images. These findings suggest that IMZ SPECT is a useful new tool for detecting epileptic foci based on the distribution of BZR in the brain.

Adult↗

PubMed1996

[A phase 3 clinical trial of 123I-iomazenil, a new central-type benzodiazepine receptor imaging agent (Part 4)--Report on clinical usefulness in diagnosis of cerebrovascular diseases].

Single photon emission computed tomography (SPECT) using 123I-Iomanzenil (IMZ), a tracer which binds specifically to central-type benzodiazepine receptors, was performed in patients with cerebrovascular diseases (CVD) to determine the clinical signicigance of IMZ SPECT studies in evaluating the pathophysiology of CVD. IMZ SPECT images obtained three hours after administration of the tracer were compared with the images of cerebral blood flow (CBF) studies in 206 cases. In regions with decreased CBF, the uptake of IMZ was relatively preserved in patients with cerebral thrombosis in comparison with cerebral embolism, and in those with perforator branch infarction in comparison with cortical infarction. The uptake of IMZ decreased as a function of both the severity of the decrease in the CBF and the duration of illness in regions with a significantly decreased perfusion reserve. These results suggest that decreased IMZ binding in ischemic stroke reflects the neuronal damage caused by the cerebral ischemia. On the other hand, in patients with intracerebral hemorrhage, the cortical uptake of IMZ was relatively well-preserved in regions with decreased CBF, and the decrease in the uptake of IMZ was more profound as a function of the decrease in the CBF, especially in cases of putaminal hemorrhage. These results also suggest that the decreased cortical CBF is a remote effect caused by a neuronal disconnection, and neuronal damage may occur in regions with severely impaired CBF.

Brain↗

PubMed1996

[Phase 2 clinical study of 123I-iomazenil in various cerebral diseases: part 1--examination of injection dose and clinical indications].

A phase 2 study of 123I-Iomazenil (IMZ) was performed to evaluate its clinical usefulness in SPECT imaging of central-type benzodiazepine receptors (BZR). A total of 246 patients with various central nervous system disorders [82 with epilepsy, 94 with cerebrovascular disease (CVD), 47 with degenerative disorders, 14 with mental disorders relating to BZR and 9 with other diseases] were intravenously injected with 111-222 MBq of IMZ. Early and late images were obtained 15 min and 180 min after injection as the mid-scan time, respectively. In comparison with regional cerebral blood flow (rCBF) images, the uptake of IMZ in the late images, which reflect the regional distribution of BZR, was relatively preserved compared to the uptake of CBF tracers in most of the patients with CVD. In the area of hyperperfusion in the subacute phase of cerebral infarction, however, the defects of IMZ uptake were accompanied by increased uptake of the CBF tracers. On the other hand, late IMZ uptake in most of the patients with the other diseases was decreased more significantly than the uptake of the CBF tracers, suggesting that cortical neuronal damage is more prominent than rCBF in these diseases compared to the vascular perfusional state. No adverse reactions were recognized relating to the IMZ administration. These results suggest that IMZ may provide us with valuable information for assessing pathophysiological state in the brain, which are difficult to achieve with other imaging modalities.

Adult↗

PubMed1996

[Phase 2 clinical study of 123I-iomazenil in various cerebral diseases: part 2--clinical evaluation of central-type benzodiazepine receptor imaging with 123I-iomazenil SPECT].

A phase 2 clinical study of 123I-iomazenil (IMZ) was performed to evaluate its clinical usefulness as central-type benzodiazepine receptor imaging agent in 81 cases with epilepsy, 82 cases with cerebrovascular diseases (CVD), 35 cases with degenerative disorders and 14 cases with mental disorders. In epilepsy, IMZ SPECT images for detection of epileptic foci showed relatively high specificity compared with EEG recording in not only interictal but also ictal state, in spite of the fact that IMZ SPECT images was performed during interictally. It was surmised that IMZ SPECT provides valuable clinical information for detection of epileptic foci which are hard to be diagnosed by EEG. The frequency of abnormal findings by IMZ late images was higher than that by interictal blood flow images and comparable to that by ictal blood flow images. In patients with CVD, different observations were obtained between IMZ late images and blood flow images; for example, in regions of hemodynamic cerebral ischemia, postischemic reperfusion and other pathological perfusion, IMZ late images seemed to reflect the degree of cortical neuronal loss. In patients with degenerative disorders, the binding potential (calculated by a simple quantitative method for IMZ) and other parameters correlated with the dementia score. While the number of examined cases with mental disorders was limited, the frequency of abnormal findings with IMZ imaging was higher than that with morphological imaging.

Adult↗

PubMed1996

Altered energy metabolism in Alzheimer's disease.

To evaluate the energy metabolism in Alzheimer's disease (AD), the cerebral arteriovenous differences of oxygen, glucose, lactate, pyruvate, ketone bodies and free fatty acids, and regional cerebral blood flow (rCBF) were examined in 7 patients with Alzheimer's disease (AD). The ratio of oxygen and glucose molar utilization was significantly elevated to 9.86 in AD, compared with 5.63 for 7 age matched controls. Single-photon emission computed tomography revealed that the patients had significantly decreased rCBF only in the parietotemporal region. The glucose extraction fraction and global cerebral metabolic rate of glucose were significantly decreased, whereas the global cerebral metabolic rate of oxygen was slightly decreased. However, the elevated oxygen/glucose utilization ratio is not due to the oxygenation of ketone bodies or free fatty acids, because the cerebral metabolic rates of these substrates did not alter. We concluded that the marked elevated value of the oxygen/glucose utilization ratio suggests an altered energy metabolism in AD.

Aged↗

PubMed1996

[Amrinone (50 micrograms.kg-1.min-1) does not impair regional myocardial tissue metabolism during the 40%-decrease of left anterior descending coronary flow].

We investigated the effects of amrinone on metabolism of regional myocardial tissue during the 40%-decrease of left anterior descending coronary (LAD) flow in anesthetized dogs. Fourteen adult mongrel dogs weighing 15.4 +/- 5.1 kg were anesthetized with 0.5% isoflurane in 50% oxygen and ventilated mechanically to maintain normocapnia. After thoracotomy, regional myocardial tissue PO2 was measured using a monopolar polarographic needle electrode inserted in the myocardium. Electromagnetic blood flow probes were placed around LAD and circumflex artery. A 23-gauge catheter was inserted into a coronary vein which runs along LAD to obtain coronary venous blood for measuring oxygen content, lactate and pyruvate. A variable constrictor was placed distal to the flow-probe. After decreasing LAD flow for 40%, cardiac index (CI) decreased. Systemic venous resistance was decreased and CI was increased by amrinone (50 micrograms.kg-1.min-1) infusion. Myocardial tissue oxygen tension, venous lactate, lactate extraction, lactate-pyruvate ratio and excess lactate were all unchanged by amrinone. In conclusion, amrinone does not impair myocardial aerobic metabolism and increases CI under the stenosis of coronary artery.

Amrinone↗

PubMed1996

[A case of familial juvenile dystonia-parkinsonism: 18F-6-fluorodopa and 18F-fluoro-2-deoxyglucose PET study].

A 27-year-old Japanese woman was admitted to Kyoto University Hospital because of gait disturbance since age 25. Her elder sister had been suffering from childhood-onset dystonia-parkinsonism with diurnal fluctuation which initially responded well to levodopa therapy, but later larger dose of levodopa was needed because of severe treatment-related fluctuation of the clinical symptoms. Physical examination revealed left foot dystonia, mild parkinsonism with kinesie paradoxale and dyskinesia of lower limbs. Symptoms were relieved by sleep and worsened by walking. Laboratory data including serum ceruloplasmin, serum and urinary amino acid analysis, and hexosaminidase and beta-glucosidase activity in leukocytes were all normal. Homovanillic acid (HVA) in cerebrospinal fluid was normal (68 ng/ml) at 8 pm but markedly decreased (7 ng/ml) at 4 pm. Cranial MRI was normal. 18F-6-fluorodopa PET demonstrated decreased dopa uptake in the bilateral striatum, especially in the putamen. 18F-fluoro-2-deoxyglucose PET showed decreased regional glucose metabolism in the bilateral putamen. Levodopa therapy rendered equivocal effects while trihexyphenydil was effective. This case indicated that some cases of dopa-unresponsive dystonia with parkinsonism might be a clinical variant of juvenile parkinsonism. 18F-6-fluorodopa PET is useful in evaluating juvenile dystonia-parkinsonism, though it may not predict levodopa effectiveness. 18F-fluoro-2-deoxyglucose PET study will be helpful in predicting the effect of levodopa therapy, because decreased regional glucose metabolism in the putamen probably indicates poor response to levodopa. Further study including dopaminergic receptor imaging study is needed to clarify the physiological mechanism of co-existing dystonia and parkinsonism in patients with juvenile parkinsonism and related disorders.

Adult↗

PubMed1996

Extraction and retention of technetium-99m-ECD in human brain: dynamic SPECT and oxygen-15-water PET studies.

UNLABELLED: The kinetic behavior of 99mTc-ethyl cysteinate dimer (99mTc-ECD) in the human brain was investigated in six normal volunteers. METHODS: Dynamic SPECT and a three-compartmental model were used to estimate the rate constants of 99mTc-ECD in normal human brain. Extraction fraction (E), retention fraction (R) and permeability surface area product (PS product) of 99mTc-ECD were calculated using the rate constants. Regional cerebral blood flow (rCBF) was measured by PET with 15O-water. RESULTS: The rate constants in the cerebral cortex were estimated as 0.307 +/- 0.021 for K1 (influx constant), 0.201 +/- 0.047 for k2 (backdiffusion rate constant), 0.547 +/- 0.103 for k3 (lipophilic-to-hydrophilic conversion constant) and 0.0028 +/- 0.0012 for k5 (rate constant from lipophilic compartment to blood) at rCBF of 0.509 +/- 0.055 ml/g/min (mean +/- s.d.). The first-pass extraction, retention fraction and PS product were calculated as 0.608 +/- 0.069, 0.734 +/- 0.047 and 0.477 +/- 0.060, respectively. The first-pass extraction of 99mTc-ECD decreased significantly with increases in rCBF. The retention fraction and PS product of 99mTc-ECD did not show significant changes within the normal range of rCBF. The net extraction of 99mTc-ECD calculated from the static SPECT image obtained from 20 to 40 min was 0.358 +/- 0.039 in the cortex. CONCLUSION: Technetium-99m-ECD has a fairly high brain extraction, and its retention fraction and PS product appear to be independent of rCBF in the healthy human brain.

Adult↗

PubMed1996

[A case of intractable temporal lobe epilepsy: discrepancy between epileptogenic area and structural lesion demonstrated by subdural recording].

We reported a 25-year-old man with intractable right temporal lobe epilepsy in whom subdural recording successfully delineated the epileptogenic area in the right anterior mesial to basal temporal region in spite of the presence of a postoperative lesion in the right posterior temporal region. The patient underwent right posterior temporal resection due to ependymoma at the age of 8 years. Since age 19, he had suffered from medically intractable psychomotor seizures. Ictal scalp-recorded EEG suggested an epileptogenic area at the right temporal area, but it could not specifically demarcate the site because of bone deficits from the previous surgery. Ictal SPECT showed a hyperactive area in the right anterior temporal area, which was inconsistent with the MRI finding. In case of partial epilepsy associated with structural lesion like in the present case, if results of various non-invasive studies are discrepant as to the epileptogenic area, invasive studies using, for example, subdural EEG monitoring is necessary to determine the responsible area.

Adult↗

PubMed1996

Measurement of regional cerebral plasma pool and hematocrit with copper-62-labeled HSA-DTS.

UNLABELLED: We developed copper-62-labeled human serum albumin-dithiosemicarbazone (62Cu-HSA-DTS) as a blood-pool imaging agent for PET. To evaluate 62Cu-HSA-DTS for plasma-pool imaging and to measure the regional cerebral hematocrit, 12 normal volunteers and 7 patients with cerebrovascular disease underwent PET studies with 62Cu-HSA-DTS and 15O-labeled carbon monoxide (C15O). METHODS: The normal subjects were studied with both C15O and 62Cu-HSA-DTS. All patients were examined by 15O-gas studies to measure cerebral perfusion and oxygen metabolism, followed by measurement of plasma volume with 62Cu-HSA-DTS for analysis of regional cerebral hematocrit. Regional cerebral hematocrit was calculated from regional cerebral red cell volume (rCRCV) measured by C15O and regional plasma volume (rCPV) measured by 62Cu-HSA-DTS in each subject, and the regional cerebral/large-vessel hematocrit ratio was obtained for both cerebral hemispheres in each subject. RESULTS: Mean regional cerebral hematocrit and mean cerebral/large-vessel hematocrit ratio in the 12 normal volunteers were 38.3 +/- 3.45% and 0.88 +/- 0.06, respectively. In the seven patients with cerebrovascular disease, regional cerebral hematocrit was significantly lower on the hypoperfused side than the normal hemisphere. The images of rCPV and rCRCV from these patients demonstrated a greater increase in rCPV than rCRCV in the hypoperfused area. CONCLUSION: These results suggest that 62Cu-HSA-DTS can be used for measurement of plasma volume and that regional cerebral hematocrit may provide valuable information regarding the microcirculation in the brain.

Adult↗

PubMed1996

Respiratory impedance estimated from airway and intrapleural pressure curves.

At the cessation point of inspiratory flow on an airway pressure curve of constant-flow CMV (controlled mechanical ventilation), the pressure falls rapidly at first and then gradually tapers down to an endinspiratory plateau. By fitting these two pressure changes to the voltage changes in the respiratory circuit model, the resistance and compliances in the lung periphery and the resistance in the large airway can be estimated. We designed an algorithm estimating the values of circuit elements using a circuit simulator MicroCap III. The validity of this method was examined on the mechanical lung model. The sensitivity came to within +/- 15%. Further validation was carried out on five Beagles treated with methacholine. The large airway resistance, the small airway resistance and compliance, and alveolar compliance demonstrated a two- to three-fold increase in resistances and a two thirds to one-half decrease in compliances, when compared with the base-line values before administration of methacholine. This method can be applied not only to patients during CMV, but also during surgery.

Airway Resistance↗