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Biomedical subjects

N Yasui

Publications and source records attributed to N Yasui.

At least 145 records · Page 8Linked to original sources

Protective effect of nilvadipine on focal cerebral ischemia in spontaneously hypertensive rats.

The protective effect of nilvadipine, a Ca2+ antagonist, on cerebral ischemia was investigated in spontaneously hypertensive rats. The 12-week-old animals were treated for 7 days with either nilvadipine or vehicle using osmotic pumps implanted subcutaneously. Group 1 animals (n = 10) received the vehicle, and Group 2 (n = 10) and 3 animals (n = 10) received 1 and 3 mg/kg/day nilvadipine, respectively. The left middle cerebral artery was occluded under halothane anesthesia on the 6th day of treatment, and neuropathological outcomes were quantified 24 hours later. The systolic blood pressure measured before occlusion decreased to 137 +/- 9 mmHg (Group 2) and 130 +/- 9 mmHg (Group 3), compared to 189 +/- 12 mmHg for Group 1 (p < 0.05). The percentage infarct volumes in Groups 1-3 were 39 +/- 3%, 37 +/- 2%, and 34 +/- 3%, respectively (p < 0.05, Groups 1 vs. 3). Therefore, nilvadipine decreased the infarct size dose-dependently. Nilvadipine has a protective effect against cerebral ischemia in rats with chronic hypertension. Neuropathological findings suggest that nilvadipine may act at the ischemic penumbra. Nilvadipine may have the additional benefit of reducing the consequences of a possible later stroke in patients with hypertension (one of the risk factors for stroke).

Animals↗

Vascular response to hyperoxemia in rat brain surface microvessels.

The effects of hyperoxemia on pial vessel diameters were studied in rats using a cranial window technique. The brain surface was superfused with mock cerebrospinal fluid at 5 ml/hr, and the intracranial pressure was maintained at 5 mmHg. Animals were artificially ventilated, and the arterial carbon dioxide tension was constantly controlled in each animal. Arterioles (14-90 microns diameter during air inhalation) constricted significantly according to the arterial oxygen tension (PaO2) increase: 94 +/- 7% (30% O2), 91 +/- 8% (60% O2), and 88 +/- 8% (100% O2). The percentage diameter change per mmHg PaO2 increase was 0.1% under normoxemia, but became less under hyperoxemia (0.025% and 0.01% per mmHg during 30%-to-60% and 60%-to-100% O2 inhalations, respectively). The diameter change between 60% and 100% O2 inhalations was not significant. There was no significant relationship between the vascular response and the control diameter. Some small arterioles (< or = 50 microns diameter) underwent marked constriction (-20% to -35%), but there were no large vessels (> 50 microns diameter) showed a constriction greater than -20%. Venules (17-114 microns diameter) did not have a significant response to hyperoxemia. The vasoconstriction of pial arterioles was proportional to arterial O2, but the relationship was not linear.

Animals↗

Extracranial-intracranial high-flow bypass using the radial artery between the vertebral and middle cerebral arteries. Technical note.

Carotid ligation and vascular reconstruction following radical neck dissection were required in a patient with carotid artery rupture associated with an infected salivary fistula. An extracranial-intracranial high-flow bypass was performed using a radial arterial graft between the V3 segment of the vertebral artery and the M2 segment of the middle cerebral artery. Postoperative angiograms confirmed sufficient blood flow through the bypass graft into the ipsilateral internal carotid arterial system. No clinical signs of ischemia were observed postoperatively. This V3-M2 bypass procedure appears to be an effective means of controlling catastrophic bleeding from a ruptured carotid artery, thus allowing the wound to heal completely.

Carcinoma, Squamous Cell↗

Cerebral aneurysms: evaluation with three-dimensional CT angiography.

PURPOSE: To evaluate the usefulness of three-dimensional CT angiography (CTA), in which contrast material is used to create reformations of dynamic scans, in the diagnosis and the preoperative evaluation of cerebral aneurysms. METHODS: We used 3-D CTA to examine 65 patients with suspected or angiographically verified cerebral aneurysms. A blind study was performed to evaluate the diagnostic accuracy of 3-D CTA for cerebral aneurysms with the use of conventional angiography as the reference standard. RESULTS: In 50 patients, conventional angiography revealed 73 cerebral aneurysms ranging from 2 to 32 mm in maximum diameter. Three of the 73 cerebral aneurysms were located outside the imaging volume of 3-D CTA. The sensitivities of the two neuroradiologists for the remaining 70 aneurysms were 67% and 70%, respectively. Although 3-D CTA depicted cerebral aneurysms 5 mm or larger with good accuracy, it was less useful for the detection of smaller aneurysms. For the evaluation of giant aneurysms, this technique elucidated the relationships among the aneurysm, surrounding arteries, and neighboring bone structure. CONCLUSION: Three-dimensional CTA is useful for the diagnosis of cerebral aneurysms with diameters of 5 mm or more. This technique is especially useful in the preoperative evaluation of giant aneurysms.

Adult↗

[The relationship between single-oral dose kinetics of alprazolam and cytochrome P4503A and cytochrome P4502C19].

To clarify the involvement of cytochrome P4503A (CYP3A) and CYP2C19 in the metabolism of alprazolam, the effects of pretreatment with erythromycin, which is an inhibitor of CYP3A and S-mephenytoin 4-hydroxylation capacity on the single-oral dose kinetics of alprazolam were studied in 12 healthy male volunteers. Six each were extensive metabolizers (EMs) and poor metabolizers (PMs) of S-mephenytoin 4-hydroxylation. Each subject received erythromycin 1,200 mg/day or placebo for 10 days in a double-blind, crossover manner. At 9 AM of day 8 alprazolam 0.8 mg was given orally, and blood samplings were performed up to 48 hours postdosing. Erythromycin treatment compared with placebo treatment increased significantly plasma alprazolam concentrations from 6 to 48 hours postdosing. Erythromycin significantly decreased the apparent oral clearance and prolonged the elimination half-life of alprazolam. No significant difference was found in plasma concentrations and pharmacokinetic parameters of alprazolam between the EM and PM groups. The present study thus suggests that CYP3A, but not CYP2C19, is involved in the metabolism of alprazolam.

Administration, Oral↗

Clinical positron emission tomography for brain tumors: comparison of fludeoxyglucose F 18 and L-methyl-11C-methionine.

PURPOSE: To evaluate the differences between fludeoxyglucose F 18 (FDG) and L-methyl-11C-methionine (11C-methionine) as tracers for positron emission tomography (PET) in the evaluation of brain tumors. METHODS: We analyzed 10 patients with histologically verified cerebral glioma or meningioma and 1 patient with a neuroradiologic diagnosis of low-grade glioma by using FDG, 11C-methionine, and PET. We qualitatively and quantitatively evaluated the extent and degree of accumulation of FDG and 11C-methionine in the tumor tissue. RESULTS: Although PET with FDG depicted malignant tumors as a hot spot in all cases, it was not able to delineate the extent of the tumor. Conversely, PET with 11C-methionine outlined the tumors as areas of increased accumulation of 11C-methionine, regardless of the degree of malignancy. CONCLUSION: PET with FDG and with 11C-methionine can play complementary roles in the evaluation of brain tumors.

Blood Glucose↗

Cerebral blood flow and oxygen metabolism in hemiparetic patients with chronic subdural hematoma. Quantitative evaluation using positron emission tomography.

BACKGROUND: It remains unclear why chronic subdural hematoma (CSH) can cause hemiparesis, although the contribution of impaired cerebral blood flow and metabolism has been suggested. METHODS: We studied six hemiparetic patients (five men, one woman; mean age 60.5 +/- 7.5 years) with unilateral CSH using positron emission tomography. The 15O2 steady state technique was used to measure regional cerebral blood flow (rCBF), regional oxygen extraction fraction (rOEF), and regional cerebral metabolic rate of oxygen (rCMRO2), followed by the 1-minute inhalation of C15O to measure regional cerebral blood volume (rCBV). RESULTS: On the hematoma side, rCBF and rCMRO2 were significantly reduced in the caudate nucleus and the cingulate gyrus. We observed a tendency toward reduced levels of rCBF and rCMRO2 in the lentiform nucleus. rCBV was not elevated. rOEF was significantly elevated in the lentiform nucleus, the cingulate gyrus, the frontal gray matters under the hematoma and the semioval center. On the nonhematoma side, rCBF and rCMRO2 were normal except for the significant reduction in the cingulate gyrus. rCBV was elevated in the lentiform nucleus, the middle temporal gyrus and the inferior frontal gyrus. rOEF was elevated significantly in the cingulate gyrus, the precentral gyrus and the semioval center. CONCLUSIONS: Our hemiparetic patients with CSH were observed to have a circulatory disturbance of blood; it was manifested by an elevation of rOEF, specifically in the hemisphere adjacent to the hematoma. This circulatory disturbance was highly pronounced and resulted in a consistent reduction in rCBF and rCMRO2 in the anterior central cerebral area such as the caudate nucleus, the lentiform nucleus and the cingulate gyrus.

Aged↗

Trazodone treatment increases plasma prolactin concentrations in depressed patients.

m-Chlorophenylpiperazine (m-CPP), which is a metabolite of trazodone, is a serotonin agonist. To examine for the possibility that m-CPP is involved in biochemical effects during treatment with the parent compound, prolactin response to trazodone treatment (150 mg at bedtime for 3 weeks) was studied in 12 depressed patients. The means +/- S.D. of plasma prolactin concentrations before treatment, 12 h, and 1, 2 and 3 weeks after initiation of treatment were 9.1 +/- 5.6, 14.7 +/- 9.1, 15.3 +/- 8.5, 13.2 +/- 7.0 and 13.0 +/- 7.0 ng/ml, respectively. The mean prolactin concentrations at 12 h (p < 0.01), 1 week (p < 0.001) and 2 weeks (p < 0.05) were significantly higher than that before treatment. The present study thus shows that trazodone treatment increases prolactin concentrations, suggesting that m-CPP is involved in biochemical effects during treatment with the parent compound.

Adult↗

Effects of various factors on steady state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine.

Effects of various factors on steady state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine (mCPP) were studied in 43 depressed patients (19 males, 24 females) receiving trazodone 150 mg at bedtime for 1-3 weeks. Sixteen cases were smokers, and 19 cases were also receiving various benzodiazepines. The means (and ranges) of plasma concentrations of trazodone and mCPP, and the mCPP/trazodone ratio were 619 (251-1059) ng/ml, 59 (32-139) ng/ml and 0.100 (0.044-0.219), respectively. Smokers had significantly (p < 0.05) lower plasma concentrations of trazodone and higher mCPP/trazodone ratios than non-smokers. Age, sex and co-administration of benzodiazepines did not affect any plasma concentrations or the mCPP/trazodone ratio. In 11 cases where the dose was increased to 300 mg, neither plasma concentration/dose ratios nor the mCPP/trazodone ratio changed significantly. The present study thus suggests that: (1) there is a large Interindividual variation in the metabolism of trazodone; (2) smoking enhances the metabolism, but age, sex and co-administration of benzodiazepines do not affect it; (3) trazodone and mCPP have linear kinetics.

Adult↗

Inhibition of trazodone metabolism by thioridazine in humans.

To clarify the involvement of cytochrome P4502D6 (CYP2D6) in the metabolism of trazodone, the effects of coadministration of thioridazine, which is an inhibitor of this isozyme, on plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine (m-CPP) were studied. The subjects were 11 depressed patients receiving trazodone at bedtime for 1-18 weeks. The dose was 150 mg in 10 patients and 300 mg in one. Thioridazine 40 mg/day was coadministered for 1 week, and blood samplings were performed before and after the coadministration. Thioridazine significantly (p < 0.001) increased plasma concentrations of both trazodone (713 +/- 252 vs. 969 +/- 370 ng/ml) and m-CPP (61 +/- 22 vs. 94 +/- 34 ng/ml). The present study thus suggests that CYP2D6 is involved in the metabolism of trazodone.

Adult↗

High-performance liquid chromatographic determination of trazodone and 1-m-chlorophenylpiperazine with ultraviolet and electrochemical detector.

A high-performance liquid chromatographic (HPLC) assay was developed for the determination of trazodone and its metabolite, 1-m-chlorophenylpiperazine (m-CPP), in plasma. The high level of trazodone in plasma was detected by ultraviolet absorbance at 254 nm and the low level of m-CPP in plasma was detected by coulometric electrochemical detection at 840 mV on the series arrangement of two detectors. Pilsicainide as an internal standard for both compounds was monitored by both detectors. Trazodone and m-CPP in plasma were extracted by a rapid and simple procedure based on CN bonded-phase extraction, and C8 reversed-phase HPLC separation. Determination was possible for trazodone in the concentration range 100-2000 ng mL-1 and for m-CPP in the concentration range 5-100 ng mL-1. The recoveries of trazodone and m-CPP added to plasma were 81.0-84.2 and 68.0-73.2%, respectively, with coefficients of variation of less than 7.3 and 8.2%, respectively. The method is applicable to high level monitoring of trazodone and low level monitoring of m-CPP in plasma of healthy volunteers and patients treated with trazodone.

Chromatography, High Pressure Liquid↗

High-resolution and analytical electron microscopic studies of new crystals induced by a bioactive ceramic (diopside).

Diopside has been developed for use in dental root implants and for the filling of bone defects. In previous studies, diopside developed hydroxyapatite (HA) on its surface and achieved a direct bond with bone. The purpose of this study was to investigate the mechanism of crystal formation on the diopside surface. We ultrastructurally evaluated the interface between new diopside-induced crystals and diopside. Specimens were prepared in three experiments: (1) Granular diopside was immersed in simulated body fluid (SBF); (2) granular diopside was implanted into a cavity in rabbit bone; and (3) a diopside dental root implant was implanted into a Japanese monkey. The specimens were examined by contact microradiography, high-resolution transmission electron microscopy, and analytical electron microscopy. In the experiment with SBF, many platelet-like crystals formed in the diopside surface layer. The lattice of diopside and that of the new crystals were very close, but no clear continuation of the lattice was observed. In the experiments which used a rabbit and a monkey, contact microradiography showed close contact between bone and diopside. High-resolution transmission electron microscopy revealed crystal growth from the diopside surface layer, and continuity between the diopside lattice and that of the new crystals. The morphological characteristics of the new crystals and the results of these analyses suggest that these new crystals are HA. With regard to the mechanism by which crystals are formed on the diopside surface layer, it is possible that epitaxial crystal growth could originate as a nucleus on the surface. In this case, epitaxial crystal growth of primarily octacalcium phosphate (OCP) may have occurred, and this may have changed to HA by a phase transition. However, epitaxial growth of OCP on the diopside surface is still highly speculative, since there is no direct supporting evidence.

Animals↗

Mastoid canal and migrated bone wax in the sigmoid sinus: technical report.

A study of the migration of bone wax into the sigmoid sinus through the mastoid canal is reported here. In 7 of 161 patients who underwent retromastoid craniectomy, the postoperative soft tissue window image computed tomographic scans demonstrated a hypodense mass in the ipsilateral sigmoid sinus. The density value of the hypodense mass ranged from -34 to -79 Hounsfield units, which was neither as low as that of air nor as high as that of cerebrospinal fluid, but was comparable to that of fat tissue or bone wax. The continued presence of all of these masses in the sigmoid sinus was confirmed 1 month to 2 years after surgery. These computed tomographic findings suggested that this abnormal hypodense mass might be a migrated fragment of the bone wax that had been used for the control of venous bleeding from the mastoid emissary vein, because each of the seven affected patients had a large mastoid foramen and a large quantity of bone wax had been needed to control the bleeding during retromastoid craniectomy. No other material with the potential to migrate into the sigmoid sinus had been applied as a packing material. In two of the seven patients, venous magnetic resonance angiography after surgery demonstrated that the ipsilateral sigmoid sinus was not patent and the computed tomographic scans also revealed that the hypodense masses occupied the sigmoid sinus. It is concluded that the intrasurgical application of a large quantity of bone wax to control the bleeding from the large emissary veins carries a risk of the migration of bone wax into the sigmoid sinus.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Japan coma scale in the prediction of outcome after early surgery for aneurysmal subarachnoid hemorrhage].

The value of the 10-grade Japan Coma Scale (JCS) as a means of evaluating patients undergoing early aneurysm surgery was assessed in terms of its relationship to surgical outcome. The 13-grade Glasgow Coma Scale (GCS) was also assessed, and comparisons were made between the two. A series of 765 patients who underwent aneurysm surgery within 7 days after hemorrhage were evaluated both by JCS and GCS immediately prior to surgery, and outcome was assessed by the Glasgow Outcome Scale (GOS) 6 months postoperatively. Both the JCS and GCS scores were significantly correlated with surgical outcome (JCS vs GOS: rs = 0.586, GCS vs GOS: rs = 0.615, p < 0.001). There was no significant difference between the correlation coefficients for outcome of the JCS and GCS. In general, the better the JCS or GCS score was, the better the surgical outcome was, however, outcome among those with a JCS score of 3 was poorer than among those with a score of 10, 20, or 30. The results of this study indicate that both JCS and GCS are useful in predicting surgical outcome, but the GCS may be better than the JCS because of the problem with the score of 3 in the latter.

Acute Disease↗

Accessory nerve neurotization in infants with brachial plexus birth palsy.

We report the surgical results of 13 accessory nerve neurotizations in branchial plexus birth palsy. The mean age at operation was 5.9 months. The accessory nerve was transferred to three C5 roots, to three C6 roots, to four posterior division of the middle trunks, to one musculocutaneous nerve, and to two suprascapular nerves. Sixty-seven percent of the cases acquired M4 or more in the deltoid muscle, 88% in the infraspinatus muscle, and 100% in the biceps brachii muscle. Twenty-five percent of the cases acquired M4 or more in the triceps brachii muscle and the wrist extensor muscles. These results were much better than formerly reported for adult cases by other authors. No functional compromise of the trapezius muscle was noted. The accessory nerve neutrotization can be used safely and effectively in neurosurgical reconstruction of the brachial plexus palsy in infants.

Accessory Nerve↗

Therapeutic effects of nilvadipine on rat focal cerebral ischemia.

The present study was conducted to investigate the therapeutic effects of nilvadipine, a Ca2+ entry blocker, on rat focal cerebral ischemia. Under halothane anesthesia, a 3-0 nylon thread was introduced into the neck internal carotid artery to occlude the left middle cerebral artery. Either nilvadipine (3.2 mg/kg) or vehicle was administered subcutaneously 1, 2, 3, 4, 5 and 6 h following the occlusion (groups 1-6, respectively). Twenty-four hours after the occlusion, the percentage infarct volumes in nilvadipine-treated animals in groups 1-3 (21 +/- 11%, 24 +/- 11%, and 26 +/- 7%, respectively) were smaller than those in the respective control groups (36 +/- 5%, 35 +/- 3%, and 35 +/- 3%; P < 0.05). Compared with controls, the infarct size of the periphery of the fronto-parietal cortex decreased in nilvadipine-treated animals. The results indicate that nilvadipine decreases the size of infarction when administered up to 3 h after an ischemic insult. Thus, nilvadipine can be considered a potential therapeutic agent for acute focal cerebral ischemia, and may be clinically useful in stroke patients.

Animals↗

Effects of increased intracranial pressure in brain surface microcirculation in rats.

The effects of increased intracranial pressure (ICP) on pial vessel diameters were investigated in rats using a cranial window and fluorescence microscopy. The brain surface was superfused with mock cerebro-spinal fluid (CSF) at a constant rate (5 ml/h), and the ICP was raised up to 20 mmHg by elevating a CSF-reservoir connected to the CSF-outlet of the window. Arterioles dilated as the ICP increased (+ 12% dilation at 20 mmHg ICP). Following a rapid reduction of the raised ICP to normal, arteriolar diameters did not return to control values (+ 7% dilatation), while venules dilated (+ 3%), indicating reactive hyperaemia. At this time, CO2 inhalation induced a low response in the arterioles (+ 0.4%/mmHg PaCO2 increase) and an over-response in the venules (+ 0.3%/mmHg). The CO2 response decreased in smaller arterioles (< or = 30-40 microns phi). In addition, a few animals showed extravasation of Na(+)-fluorescein administered intravenously. Our results indicate that reactive hyperaemia can take place following a rapid return from an increased ICP to an normal level, even in cases of mild intracranial hypertension; a disruption of the blood-brain barrier may follow.

Animals↗

Haemodynamic and metabolic changes following extra-intracranial bypass surgery.

In order to study the haemodynamic and metabolic changes following bypass surgery, the regional cerebral blood flow (rCBF), the oxygen extraction fraction (rOEF), the cerebral metabolic rate of oxygen (rCMRO2), and the cerebral blood volume (rCBV) were measured using a positron emission tomograph (PET) on 13 patients who had unilateral internal carotid artery and/or middle cerebral artery occlusion. The patients were divided into two subgroups according to pre-operative rOEF values from the arterial occlusion side: the misery perfusion group, which had high rOEF values (> or = 0.56), and the coupling perfusion group, which had normal rOEF values (0.38-0.48). A post-operative PET study was performed 1-2 months and/or 1-5 years following the surgery. Six of the misery perfusion cases showed a post-operative CBF increase, where an accompanying OEF decreased to its normal level, indicating an attenuated misery perfusion state. The CMRO2 values, however, remained low. The other 7 coupling perfusion cases had an ipsilateral CBF increase in the earlier PET study. We conclude that misery perfusion is attenuated following bypass surgery, although the procedure does not consistently improve oxygen metabolism.

Aged↗