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H Fukuyama

Publications and source records attributed to H Fukuyama.

At least 73 records · Page 4Linked to original sources

Selective cerebral hematocrit decrease in the centrum semiovale after carotid artery occlusion: a PET study.

The centrum semiovale may be susceptible to hypoperfusion as a result of carotid artery occlusion. Recent studies suggest that the cerebral hematocrit decreases with diminished cerebral perfusion pressure. To investigate whether the effect of carotid artery occlusion on the hematocrit in the centrum semiovale is different from that in the cerebral cortex, seven patients with unilateral carotid artery occlusion were studied with positron emission tomography. The distributions of the red blood cell and plasma volumes were assessed using carbon monoxide labeled with oxygen 15 and human serum albumin-dithiosemicarbazone tracers labeled with copper 62, respectively. The CBF and CMRO2 were also measured with the (15)O steady-state technique. The calculated values for the hematocrit in the centrum semiovale ipsilateral to the arterial occlusion were significantly decreased compared with those in any of the other regions examined (the overlying cortical region and the contralateral cortex and centrum semiovale). This decrease in hematocrit, which resulted from a more pronounced increase in plasma volume than in red blood cell volume, was associated with a decrease in CBF and an increase in the oxygen extraction fraction. Hemodynamic disturbance caused by carotid artery occlusion may induce selective decrease of hematocrit limited to the centrum semiovale.

Aged↗

Uncoupling of oxygen and glucose metabolism in persistent crossed cerebellar diaschisis.

BACKGROUND AND PURPOSE: The pathophysiology of deafferentation-induced changes after stroke remains unclear. Some supratentorial strokes cause persistent decreases in blood flow and metabolism in the contralateral cerebellum (persistent crossed cerebellar diaschisis[CCD]). Our previous study showed uncoupling of oxygen consumption and blood flow in this condition, which may reflect a characteristic change in brain metabolism caused by deafferentation. This uncoupling might be related to oxidation of some substrates other than blood-borne glucose, which could also lead to the uncoupling of oxygen consumption and glucose utilization. The purpose of this study was to investigate whether oxygen consumption is uncoupled from glucose utilization in persistent CCD. METHODS: Using positron emission tomography in 10 unilateral supratentorial stroke patients, we evaluated regional blood flow, oxygen consumption, and glucose utilization in the cerebellar cortex in the chronic stage. Eight patients with a significant cerebellar blood flow asymmetry, defined as outside the 95% confidence limits predefined in 9 normal subjects, were selected as patients with persistent CCD. RESULTS: In patients with CCD, the cerebellar cortex contralateral to the stroke showed significant decreases in both oxygen consumption and glucose utilization compared with the ipsilateral cerebellar cortex. The decrease in oxygen consumption was less than the decrease in glucose utilization, resulting in a significant increase in the oxygen consumption/glucose utilization ratio. CONCLUSIONS: Persistent CCD caused by stroke may induce uncoupling of oxygen consumption and glucose utilization, which may reflect a characteristic change in brain metabolism caused by deafferentation.

Aged↗

A decrease in regional cerebral blood volume and hematocrit in crossed cerebellar diaschisis.

BACKGROUND AND PURPOSE: The pathophysiology of crossed cerebellar diaschisis (CCD) remains to be elucidated. In CCD, the metabolic suppression resulting from deafferentation may cause vasoconstriction, which may result in a decrease in cerebral blood volume (CBV) and may differentially affect the flows of red blood cells and of plasma. The purpose of this study was to investigate whether CCD decreases the total CBV (cerebral red blood cell volume [CRCV] plus cerebral plasma volume [CPV]) and, if so, whether CCD differentially affects the CRCV and CPV, resulting in a change in hematocrit. METHODS: We used positron emission tomography to study 7 patients with a unilateral supratentorial infarct and CCD. The distributions of CRCV and CPV were assessed by using 15O-labeled carbon monoxide and 62Cu-labeled human serum albumin-dithiosemicarbazone tracers, respectively. The CRCV, CPV, and calculated hematocrit values were compared between the cerebellar hemispheres. RESULTS: In the cerebellar cortex contralateral to the supratentorial infarct, the values of CRCV, CPV, and total CBV were significantly decreased compared with those in the ipsilateral cerebellar cortex. The CRCV was decreased to a greater degree than the CPV, and the value of the hematocrit was decreased in the contralateral cerebellar cortex. CONCLUSIONS: CCD may decrease the total CBV, which may reflect vasoconstriction caused by decreased metabolism due to deafferentation. In addition, the more pronounced decrease in CRCV than in CPV may result in a decrease in hematocrit in CCD.

Aged↗

Waist to hip ratio, body mass index, and glucose intolerance from Funagata population-based diabetes survey in Japan.

To examine the association of body mass index (BMI) and waist-to-hip ratio (WHR) with glucose intolerance among adults age 45 and over, we conducted a population-based study using an oral glucose tolerance test as a primary examination in two areas of Funagata, Japan, in 1990 and 1992. The number of eligible subjects was 1673. The participation rate was 84% (1408/1673). Glucose tolerance was assessed by the 1985 World Health Organization criteria as having diabetes (DM), impaired glucose tolerance (IGT), or normal glucose tolerance (NGT). Analyses by the generalized linear model revealed that both BMI and WHR were higher in the subjects with DM and IGT than those with NGT in both men and women after controlling for age. Analyses employing multiple logistic regression indicated that BMI and WHR were independently associated with IGT and DM in both men and women, except for BMI with IGT for men. The odds ratios for IGT associated with BMI were 1.06 (p=0.19) for men and 1.11 (p<0.01) for women. Those associated with WHR were 2.14 (p<0.01) for men and 1.35 (p<0.01) for women. These results imply that WHR plays an important role for developing DM independent of BMI.

Aged↗

[SPM analysis on PET and SPECT data].

I described the methodological explanation of statistical parametric mapping (SPM) with the special attention to the clinical applications. SPM was designed mainly by K. Friston and R. Frackowiack to visualize the statistically significant regions on the CBF data sets obtained from PET or SPECT during a various kinds of activation. In short, images were realigned to the first scan to eliminate the head position movements, and were normalized to the standard brain shape (Talairach & Tournoux) by linear or non-linear transformation. After that, gausian filtering was done in order to eliminate the individual brain differences and to increase the signal to noise ratio. The pixel by pixel analysis was done with multiple comparison correction, and the statistically significant areas were displayed. In clinical applications, comparison of normal controls with Alzheimer's disease, diffuse Lewy body disease, and some activation study in the pathological vs normal condition. In SPECT, we can obtain the brain perfusion images by the injection of Tc-99m labeled CBF tracers, so that we can analyze the condition with the subjects not confined to the scanner.

Brain↗

[An epidemiologic examination on the prevalence of the periodontal diseases and oral pigmentation in Yusho patients in 1998].

An epidemiologic examination was carried out to reveal the prevalence of the periodontal diseases and oral pigmentation in patients with Yusho 30 years after PCBs exposure. The results obtained were as follows. 1) 69 patients out of 71 patients with Yusho, who were measured periodontal pocket depth using Ramfjord' methods, had at least one tooth with periodontal pocket deeper than 3 mm. Similarly, 241 teeth out of a total 348 examined teeth showed periodontal pocket with more than 3 mm depth. 2) Oral pigmentation was observed in 46 out of 79 patients with Yusho. In this study, gingival pigmentation was most predominant among oral pigmentation. In addition, it is of particular interest that oral pigmentation tended to be observed at a much higher frequency in younger patients with Yusho.

Adult↗

[Cerebral hemodynamics and risk for recurrent stroke in symptomatic internal carotid artery occlusion].

PURPOSE: In internal carotid artery occlusion, patients with inadequate blood supply relative to metabolic demand (misery perfusion) may be at increased risk for cerebral ischemia. This study investigated whether patients demonstrating misery perfusion on positron emission tomography (PET) have a high risk of subsequent stroke in symptomatic internal carotid artery occlusion. METHODS: We prospectively evaluated the relationship between the regional hemodynamic status of cerebral circulation and the subsequent risk of stroke in 40 patients with symptomatic internal carotid artery occlusion who underwent PET. Patients were divided into two hemodynamic categories according to the mean hemispheric value of oxygen extraction fraction (OEF) in the hemisphere supplied by the artery with symptomatic disease: patients with increased OEF and those with normal OEF. All patients were followed with medical treatment until the recurrence of stroke or death for 3 years. RESULTS: The three-year incidence of ipsilateral ischemic strokes for patients with normal OEF and those with increased OEF were 1 of 34 and 3 of 6 patients, respectively. A significantly higher incidence of ipsilateral strokes was found in patients with increased OEF (Kaplan-Meier analysis and log-rank test; p < 0.001). Multivariate analysis with the Cox proportional hazards model demonstrated that increased OEF significantly increased stroke recurrence: the relative risk was 19.5 (95% CI, 2.0-188.6) for ipsilateral stroke. An increase in the absolute OEF value was a better predictor of recurrent ischemic stroke than an OEF asymmetry. CONCLUSION: These findings suggest that patients with symptomatic internal carotid artery occlusion and misery perfusion have a high risk for subsequent stroke. Thus, identification and optimal treatment of patients with misery perfusion may be essential in preventing stroke.

Aged↗

[Phase 2 clinical study of 123I-IBF, a dopamine D2 receptor imaging agent, to evaluate clinical efficacy and safety in Parkinson's disease and Parkinson syndromes].

A Phase 2 multicenter trial of 123I-IBF, (S)-5-iodo-7-N-[(1-ethyl-2- pyrrolidinyl)methyl]carboxamido-2,3-dihydrobenzofuran, was conducted to evaluate its clinical efficacy and safety in 158 patients with Parkinson's disease (PD) or Parkinson syndromes (PS). SPECT data were acquired at two hours (2H-SPECT), after intravenous injection of 123I-IBF (167 MBq). Additional SPECT scan at three hours (3H-SPECT) and dynamic SPECT scan at most until one hour were performed when possible. No severe side effects due to 123I-IBF injection were observed. The sensitivity, specificity and accuracy for discriminating PS from PD using the striatal specific binding count-to-frontal cortex count ratio (St/Fc-1) in 3H-SPECT were 72.7%, 81.0% and 78.1% in 64 clinically definite cases (i.e., typical cases), respectively. The putamen-to-caudate ratios were significantly lower in striatonigral degeneration compared with those in PD. The contralateral-to-ipsilateral ratios against the symptomatic side of tremor and/or rigidity in the patients with PD (Hoehn & Yahr I) were significantly higher than the left-to-right ratios in the normal controls. St/Fc-1 in 3H-SPECT was significantly lower in the patients showing a poor response to levodopa than in those showing a good response. The dopamine D2 receptor binding potential (k3/k4), obtained by dynamic SPECT based on compartment model analysis, correlated well with the striatal specific binding count-to-occipital cortex count ratio. These results suggest that 123I-IBF is a promising agent for differential diagnosis and pathophysiological evaluation of PD and PS.

Adult↗

Significance of increased oxygen extraction fraction in five-year prognosis of major cerebral arterial occlusive diseases.

UNLABELLED: In major cerebral arterial occlusive diseases, patients with increased oxygen extraction fraction (OEF), which is measured with PET, may be at increased risk for cerebral ischemia. However, the clinical significance of increased OEF remains unclear. This study investigated whether increased OEF is an independent predictor of 5-y risk of subsequent stroke. METHODS: We prospectively evaluated the relationship between the regional hemodynamic status of cerebral circulation and the subsequent risk of stroke in 40 patients with symptomatic internal carotid or middle cerebral arterial occlusive diseases who underwent PET. Patients were divided into two hemodynamic categories according to the mean hemispheric value of OEF-in the hemisphere supplied by the artery with symptomatic disease: one group with increased OEF and one with normal OEF. All patients were followed for 5 y with medical treatment until the recurrence of stroke or death. RESULTS: During 5 y, 11 total and 9 ipsilateral ischemic strokes occurred. The incidences of all ischemic strokes in patients with increased OEF and in those with normal OEF were 5 of 7 and 6 of 33 patients, respectively. There were 4 ipsilateral ischemic strokes in patients with increased OEF and 5 in those with normal OEF. Kaplan-Meier analysis revealed that the risks of all stroke and ipsilateral ischemic stroke in patients with increased OEF were significantly higher than in those with normal OEF (log-rank test; P<0.0002 and P<0.0018, respectively). Multivariate analysis with the Cox proportional hazards model showed that increased OEF significantly increased stroke recurrence: the relative risk was 7.2 (95% confidence interval [CI], 2.0-25.5; P<0.005) for all stroke and 6.4 (95% CI, 1.6-26.1; P<0.01) for ipsilateral stroke. An increase in the absolute OEF value was a better predictor of recurrent ischemic stroke than was OEF asymmetry. CONCLUSION: These findings suggest that an increased OEF is an independent predictor of 5-y risk of subsequent stroke. Identification of patients with increased OEF may have clinical significance in preventing recurrent stroke.

Adult↗

[Approach to examining hypercalcemia in the clinical laboratory].

The investigation of hypercalcemia is carried out routinely in our laboratory to detect primary hyperparathyroidism (PHPT). In a retrospective study, seven patients with PHPT and fifty-one patients with non-parathyroid hypercalcemia (NPHC) were chosen in a particular year. To obtain a screening index for PHPT, discriminant analysis, using a stepwise variable select method, was applied to eight biochemical parameters in these patients. A discriminant function (F1) was derived from three biochemical parameters and then another discriminant function (F2) was also derived from three biochemical parameters in the F1-positive patients. In combination of these two functions (F1 and F2), the final sensitivity was 100% and specificity was 98% in diagnosing PHPT. This screening method was tested prospectively in fifty-six consecutive specimens of hypercalcemia (PHPT 4, NPHC 52) over the following six months. The result was also satisfactory with a sensitivity of 100% and specificity of 98%. It was proven that our screening method using discriminant functions (F1 and F2) was very useful for diagnosing patients with PHPT from the survey of hypercalcemia. Among these patients with hypercalcemia, the high ratio (54%) of those with malignancy was remarkable. This interesting result required us to investigate potential hypercalcemia, since the serum calcium concentration was masked by a lower level of serum albumin, which was frequently seen in these malignant patients. As the next step, we tried to adjust the serum calcium concentration based on the serum albumin concentration. A formula for adjusting the calcium concentration was derived from a linear structural relationship between calcium and albumin in 6,821 specimens within a +/- 2.5 second principal component score in 7,021 consecutive specimens in whom both calcium and albumin were measured in a particular year; Adjusted Calcium = Calcium - Albumin + 4. After adjustment using this formula, the calcium concentrations were elevated above the upper limit of the reference interval in 320 of 5,203 specimens (6%) within the reference interval and elevated to the reference interval in 1,390 of 1,579 specimens (88%) below a lower limit of reference interval. A prospective study was performed over the following three months. Fifty patients with hypercalcemia were screened using this formula. It was a surprise that thirty-one patients (62%) showed abnormal values after adjustment. These results suggest that calcium adjustment is necessary for interpreting the calcium concentration of patients with a reduced albumin concentration such as patients with malignancy.

Adult↗

The use of sevoflurane anesthesia during early pregnancy.

Sevoflurane has favorable pharmacodynamic properties such as a rapid, smooth induction and emergence from anesthesia. However, there is only one report of sevoflurane anesthesia during early pregnancy. We report the use of sevoflurane for maintenance of general anesthesia in a pregnant patient undergoing non-obstetric surgery. A 25-year-old, female patient, at 13 weeks gestation, was diagnosed as having a strangulated ileus. General anesthesia was performed and maintained with oxygen, nitrous oxide, and sevoflurane. Six months later a healthy infant without abnormalities was delivered.

Adult↗

Development of a new catheter-tip pressure transducer.

Two major disadvantages of the conventional catheter-tip transducer have been incapability to calibrate baseline pressure and to adjust sensitivity after insertion. A vast majority of conventional catheter-tip transducers are classified as gauge type. Due to their structure they are inherently incapable of recalibrating after insertion. We have overcome this problem by developing a new differential type catheter-tip transducer equipped with a lumen that connects a small chamber at the backside of the transducer to another external port. This lumen is capable of pressure passage. The output of this type depends on the difference between the two imposed pressures. This passage makes a baseline standard possible, when the end of the lumen is exposed to atmospheric pressure. When pneumatic pressure is imposed to the end of the lumen using a syringe, for example, the transducer output shifts up and down in accordance to that pressure, enabling baseline pressure recalibration and verifying the degree of sensitivity after insertion. By obtaining the following data, we confirmed the stability and availability of this transducer: Baseline drift less than 0.04 mmHg/8 hour, frequency characteristics flat up to 60 Hz, and common mode rejection ratio more than 46 dB.

Catheterization, Peripheral↗

Issues in measuring glucose metabolism of rat brain using PET: the effect of harderian glands on the frontal lobe.

We estimated the effect of the Harderian gland (an orbital gland of land vertebrates) on the measurement of cerebral metabolic rate of glucose (CMRGIc) of the rat brain using positron emission tomography (PET) for animal use. The Harderian gland had the high accumulation of 18-F labeled deoxyglucose (FDG) after intravenous injection. By placing the large regions of interest (ROI) (twice the full width at half maximum in diameter), the CMRGIc in the frontal region was slightly higher compared with the CMRGIc after Harderian gland resection, but the parietal and occipital regions and the cerebellum had the similar level of CMRGIc before and after Harderian gland resection. Therefore the Harderian gland has a slight effect on the frontal lobe CMRGIc, but such overestimation can be within the permissible range for PET study of rat brains.

Animals↗

Neural activity during attention shifts between object features.

To investigate the neural mechanisms involved in shifting attention we used positron emission tomography to examine regional cerebral blood flow (rCBF) during a task that demands shifting attention between color and shape. Significant activation was observed in the right dorsal prefrontal cortex and parieto-occipital cortex at all frequencies of attention shifts. The frequency of shifts between categories correlated significantly with rCBF in the rostral part of the supplementary motor area and the left precuneus, whereas the number of successive correct responses correlated with rCBF in the orbitofrontal cortex and the caudate nucleus. This study suggests that several prefrontal regions may participate in the processes of shifting attention in different ways.

Adult↗

Cerebral blood flow and metabolism in multiple system atrophy of the Shy-Drager syndrome type: a PET study.

To investigate the role of the autonomic nervous system in cerebral blood flow (CBF) and metabolism, CBF and oxygen metabolism in patients with multiple system atrophy of the Shy-Drager syndrome type were examined. Seven patients with Shy-Drager syndrome were imaged using positron emission tomography and 15O-labeled gases. There was excellent local coupling between CBF and the cerebral metabolic rate of oxygen in the resting state. Elevation of blood pressure induced by leg raising increased CBF. The inhalation of CO2 also increased CBF in the Shy-Drager patients. These results showed that autoregulation is impaired in Shy-Drager syndrome, but local metabolic-flow coupling in the resting state and the CBF response to CO2 inhalation are spared. We conclude that the autonomic nervous system plays an important role in autoregulation, but not in local metabolic-flow coupling in the resting state. We suggest that metabolic mechanisms may mediate resting metabolic-flow coupling.

Aged↗

Induction of Apg-1, a member of the heat shock protein 110 family, following transient forebrain ischemia in the rat brain.

Apg-1 (Osp94) and apg-2 belong to the heat shock protein (hsp) 110 family. In mouse somatic cells the apg-1 and hsp105/110 transcripts are inducible by a 32 degrees C to 39 degrees C heat shock, while apg-2 is not heat-inducible. Since ischemia is known to induce expression of hsp70, its effect on expression of apg-1 was assessed by using the 20-min forebrain ischemia model of the rat. In the cerebral cortex, Northern blot analysis and in situ hybridization histochemistry demonstrated an increased expression in neuronal cells of apg-1 transcripts 3 h after the onset of reperfusion, with a peak at 12 h, followed by a decline. In the hippocampus, the level was increased at 3 h, remained constant until 24 h, and then declined. Transcript levels of apg-2 as well as hsp 105 were also increased under the present conditions, indicating that the expression of apg-2 was differentially regulated in response to heat and ischemic stresses. The induction kinetics of hsp 105, but neither apg-2 nor hsp 70, were identical to those of apg-1. These results demonstrated that brain ischemia/reperfusion induced expression of each member of the hsp 110 family, although the regulatory mechanisms may not be the same. They also suggest a significant role of apg-1 in both the ischemic- and heat-stress responses and in the normal functioning of the non-stressed neuronal cells.

Animals↗

Peptidyl human heart chymase inhibitors. 2. Discovery of highly selective difluoromethylene ketone derivatives with Glu at P3 site.

Appropriate structural modification of the difluoromethylene ketone derivatives at both P3 and P' positions led us to the discovery of peptidyl human heart chymase inhibitor 12h which shows potent activity with Ki = 6 nM and high selectivity against closely related serine protease bovine alpha-chymotrypsin (chymotrypsin Ki = > 100 microM). Using the compound 12b, a docking study with human heart chymase was carried out to presume probable interactions.

Animals↗