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Biomedical subjects

Setsuro Ibayashi

Publications and source records attributed to Setsuro Ibayashi.

At least 19 recordsLinked to original sources

A nonsynonymous SNP in PRKCH (protein kinase C eta) increases the risk of cerebral infarction.

Cerebral infarction is the most common type of stroke and often causes long-term disability. To investigate the genetic contribution to cerebral infarction, we conducted a case-control study using 52,608 gene-based tag SNPs selected from the JSNP database. Here we report that a nonsynonymous SNP in a member of protein kinase C (PKC) family, PRKCH, was significantly associated with lacunar infarction in two independent Japanese samples (P = 5.1 x 10(-7), crude odds ratio of 1.40). This SNP is likely to affect PKC activity. Furthermore, a 14-year follow-up cohort study in Hisayama (Fukuoka, Japan) supported involvement of this SNP in the development of cerebral infarction (P = 0.03, age- and sex-adjusted hazard ratio of 2.83). We also found that PKCeta was expressed mainly in vascular endothelial cells and foamy macrophages in human atherosclerotic lesions, and its expression increased as the lesion type progressed. Our results support a role for PRKCH in the pathogenesis of cerebral infarction.

Case-Control Studies↗

Role of substantia innominata in cerebral blood flow autoregulation.

Ascending projections from the substantia innominata (SI) may have an important role in the regulation of cerebral blood flow (CBF). However, several reports have suggested that unilateral lesion of the SI does not affect CBF autoregulation. On the other hand, it is also reported that several cortical and subcortical functions may be regulated not only by ipsilateral SI, but also by contralateral SI. Thus, the objective of this study is to test the hypothesis that bilateral lesions of the SI affect CBF autoregulation. Experiments were performed on anesthetized male Sprague-Dawley rats. Ibotenic acid or physiological saline was microinjected into bilateral SI. Rats were classified into four groups as follows: bilateral SI lesion rats (ibotenic acid was injected bilaterally), left or right SI lesion rats (ibotenic acid was injected into the unilateral SI and saline into the contralateral SI), and control rats (saline was injected bilaterally). Ten days after injection, CBF in the left frontal cortex was measured by laser-Doppler flowmetry during stepwise controlled hemorrhagic hypotension. In bilateral SI lesion rats, CBF was started to decrease significantly at 80 mm Hg (p<0.01). In the other three groups, CBF was well maintained until 50 mm Hg. Changes in CBF through stepwise hypotension in bilateral SI lesion rats were significantly different from the other groups (p<0.01). These results suggest that bilateral SI regulates cortical vasodilator mechanisms during hemorrhagic hypotension. Under unilateral SI lesion, some compensatory effects from the contralateral SI may maintain CBF autoregulation.

Analysis of Variance↗

Antithrombotic therapy and predilection for cerebellar hemorrhage.

BACKGROUND: With the recent increase in the use of antithrombotic therapy, intracerebral hemorrhage (ICH) has been found to be a common complication. We determined whether the use of oral antithrombotic therapy and the patients' preexisting comorbidities were predictive of cerebellar hemorrhage (CH; previously reported to be associated with anticoagulants) as compared to other ICH, and whether antithrombotic therapy affected the clinical severity of CH. METHODS: A study of 327 consecutive patients hospitalized in our institute within 3 days after the onset of ICH, including 38 patients with a CH. RESULTS: CH accounted for 12% of all ICH, 75% of which occurred in patients on warfarin therapy with an international normalized ratio (INR) for prothrombin time >2.5 (p < 0.0001), and 33% of which occurred in patients on ticlopidine therapy (p = 0.017). Warfarin therapy with an INR >2.5 and high blood glucose on admission were independently predictive of CH as compared to other ICH. In addition, previous ischemic stroke (p = 0.002) and heart diseases (p = 0.018) were more prevalent in patients with CH than in those with other ICH. The number of major arteriosclerotic comorbidities and risk factors was also independently predictive of CH risk. CONCLUSIONS: We confirmed that warfarin therapy with an INR >2.5 is associated with CH. Patients with CH frequently had arteriosclerotic comorbidities requiring antithrombotic therapy that can complicate their acute management.

Administration, Oral↗

Postischemic gene transfer of soluble Flt-1 protects against brain ischemia with marked attenuation of blood-brain barrier permeability.

Brain edema is a major and often mortal complication of brain ischemia. Vascular endothelial growth factor (VEGF) is also known as a potent vascular permeability factor and may play detrimental roles at the acute stage of brain infarction. Our goal in this study was to explore protective effects of gene transfer of soluble flt-1 (sFlt-1), a natural inhibitor of VEGF, on focal brain ischemia. Adenoviral vector encoding sFlt-1 or beta-galactosidase as control was injected into the lateral ventricle 90 mins after photochemical distal middle cerebral artery occlusion in male spontaneously hypertensive rats. The transduced sFlt-1 was released to the cerebrospinal fluid from the ventricular wall and significantly increased 6 h, 1 and 7 days after sFlt-1 transfection. One day after brain ischemia, sFlt-1 gene transfer significantly reduced infarct volume (by 35%), brain edema (by 35%), and blood-brain barrier permeability (Evans blue extravasation; by 69%) with diminished phosphorylation of focal adhesion kinase (FAKtyr397 and FAKtyr861) in the ischemic vessels. Seven days after ischemia, sFlt-1 gene transfer also significantly attenuated infarct volume (by 29%) and monocyte/macrophage infiltration (by 27%), although there were no reductions in angiogenesis by sFlt-1 overexpression. These results suggest that sFlt-1 gene therapy targeting brain edema in acute stage of brain ischemia may be useful for brain infarction.

Animals↗

Blood pressure changes during the initial week after different subtypes of ischemic stroke.

BACKGROUND AND PURPOSE: The purpose of this study was to clarify the differences in the acute blood pressure course among different ischemic stroke subtypes. METHODS: We divided 588 consecutive patients with acute brain infarction into four clinical subgroups to study the blood pressure levels during the initial 6 hospital days. RESULTS: During the 6 days, systolic blood pressure of lacunar and atherothrombotic patients was higher (P=0.0001) and diastolic blood pressure of lacunar patients was higher (P=0.0371) than of patients with the other subtypes. Preexisting hypertension was associated with elevated acute systolic blood pressure in all patients and in each subtype and with elevated acute diastolic blood pressure in all patients, cardioembolic patients, and patients with stroke of other etiology. After adjustment by preexisting hypertension, diabetes mellitus with a hemoglobin A1c >7.0% was associated with elevated systolic blood pressure in all, lacunar, and cardioembolic patients and with diastolic blood pressure in all patients. CONCLUSIONS: Blood pressure course of patients sustaining acute stroke varied widely according to stroke subtypes. Poorly controlled diabetes mellitus, as well as preexisting hypertension, appeared to influence blood pressure during the initial week of stroke.

Acute Disease↗

High blood pressure in acute ischemic stroke and underlying disorders.

BACKGROUND: The Acute Candesartan Cilexetil Therapy in Stroke Survivors (ACCESS) study indicated that early treatment with an angiotensin type 1 receptor blocker in acute stroke patients who had relatively high blood pressure improved cardiovascular morbidity and mortality in the chronic stage. To better interpret the findings of this study, we determined whether stroke patients with high acute blood pressure had specific underlying conditions. METHODS: We divided 712 consecutive patients who were hospitalized within 48 h after the onset of brain infarction into two groups: 77 patients with high acute blood pressure that met the criteria of the ACCESS study and the 635 remaining patients. Underlying risk factors and comorbidities, stroke characteristics, as well as mortality, vascular events, and disability at 3 weeks were compared between the two groups. RESULTS: Patients with high acute blood pressure more frequently had diabetes mellitus (p < 0.01), intracranial arterial stenosis (p < 0.02), higher levels of hemoglobin A1c (p < 0.005), higher creatinine levels (p < 0.005), and tended to more frequently have ischemic heart disease (p < 0.09) and infarcts <1.5 cm in diameter (p < 0.09) than the other patients. On multivariate analysis, high levels of hemoglobin A1c, high creatinine levels, and intracranial arterial stenosis were independently predictive of high acute blood pressure. At 3 weeks after the stroke onset, patients with high acute blood pressure were more dependent in their daily living activities (p < 0.02) and more frequently developed vascular events or death (p < 0.005) than the other patients. CONCLUSIONS: Poorly controlled diabetes mellitus and advanced renal damage appeared to correlate with acute hypertension after stroke. Since intracranial arterial stenosis also seemed to contribute to high acute blood pressure, one should be careful not to induce cerebral hypoperfusion by the early use of antihypertensives.

Aged↗

Accuracy of conventional plus transoral carotid ultrasonography in distinguishing pseudo-occlusion from total occlusion of the internal carotid artery.

BACKGROUND: To investigate the accuracy of conventional carotid ultrasonography (CCU) combined with transoral carotid ultrasonography (TOCU) for distinguishing pseudo-occlusion from total occlusion of the internal carotid artery (ICA). METHODS: This study included 95 patients who were suspected of having an occlusion of the ICA on magnetic resonance angiography (MRA) and underwent both CCU and conventional digital subtraction angiography (DSA) in order to confirm the diagnosis. TOCU was also performed to observe the cervical portion of the ICA distal to the stenosis. We compared the ultrasonographic findings with the DSA findings. RESULTS: Twelve of the 95 patients were defined as having an ICA pseudo-occlusion on DSA. On B-mode images with CCU color Doppler, slight residual flow signals in the ICA lumen were shown in 20 patients. Among them, 2 patients had a pulsed Doppler waveform of the distal ICA occlusion pattern. Among the remaining 18 patients, 4 had a pulsed Doppler waveform of the to and fro flow pattern, and 14 had a weak antegrade flow pattern in the ICA lumen. The conventional ultrasonographic method showed 100% sensitivity with 93% specificity for diagnosing an ICA pseudo-occlusion. The addition of TOCU findings increased the specificity to 98%. In 2 patients, who were overdiagnosed as having an ICA pseudo-occlusion even using TOCU, DSA revealed an occlusion of the ICA distal to the ophthalmic artery with a severe stenosis of the proximal ICA. CONCLUSIONS: Using conventional and transoral carotid ultrasonography, an ICA pseudo-occlusion can be diagnosed with higher accuracy.

Aged↗

Changes in brain volume 2 years after extracranial-intracranial bypass surgery: A preliminary subanalysis of the Japanese EC-IC trial.

BACKGROUND AND METHODS: We studied changes in brain volume on magnetic resonance imaging in 10 patients with and without extracranial-intracranial (EC-IC) bypass surgery who met the inclusion criteria for the Japanese EC-IC Bypass Trial, a multicenter, randomized, prospective study of patients with hemodynamic brain ischemia due to cerebral artery occlusive disease. We also examined the association of cerebral hemodynamics on single-photon emission computed tomography with the changes in brain volume. RESULTS: The affected/unaffected ratio of the percent brain volume declined in patients without EC-IC bypass surgery (p < 0.02, n = 4), and the affected/unaffected percent regional cerebral blood flow ratio increased in patients with the surgery (p < 0.03, n = 6). Acetazolamide reactivity increased in the affected hemisphere of patients with surgery (p < 0.01). Two-year increase (decrease) in acetazolamide reactivity of the affected hemisphere showed a significant positive correlation with 2-year changes in the affected/unaffected percent brain volume ratio (R2 = 0.737, p = 0.0007). CONCLUSIONS: Change in acetazolamide reactivity might be a good predictor for brain atrophy in cerebral artery occlusive disease.

Acetazolamide↗

Venous infarction secondary to septic cavernous sinus thrombosis.

A 65-year-old woman with poorly controlled diabetes presented bilateral miosis, bilateral abducens nerve palsy, and left hemiparesis. On MRI, cavernous sinus thrombosis, subdural empyema and hemorrhagic infarction in the frontotemporal lobe were detected. Cerebral angiogram revealed filling defect in the cavernous sinus with venous congestion but no involvement of internal carotid artery. Postmortem examination demonstrated hemorrhagic infarction in the right frontotemporal lobe as well as hemorrhagic necrosis of the pituitary gland. It should be noted that venous congestion due to cavernous sinus thrombosis may cause these complications.

Aged↗

Serial evaluation of acute cerebral hyperperfusion by transcranial color-coded sonography.

Using transcranial color-coded sonography (TCCS), we evaluated the acute changes in the hemodynamics of cerebral hyperperfusion in two cases. The mean flow velocity of the cerebral arteries increased at the onset of clinical symptoms, together with an increase in the regional cerebral blood flow (rCBF). In serial follow-up studies, the flow velocity gradually returned to normal in parallel with the normalization of the rCBF values. TCCS can be useful for evaluation of acute cerebral hyperperfusion.

Acute Disease↗

Increased asymmetric pulvinar magnetic resonance imaging signals in Creutzfeldt-Jakob disease with florid plaques following a cadaveric dura mater graft.

A 9-year-old Japanese girl received a cadaveric dura mater graft during surgery following a head injury with brain contusion. She continued to do well, but when she became 19-years-old, she gradually showed a violent character and was treated in a psychiatric hospital. Another 6 years later, 200 months after the procedure, she developed a progressive gait ataxia, which subsequently led to her death within 10 months of onset. An autopsy showed she had CJD. This patient represents an atypical case of dura-associated CJD (dCJD) with unusual clinicopathological features including the late occurrence of myoclonus, an absence of periodic synchronous discharges in the electroencephalogram, and the presence of widespread florid plaques. However, our detection of an asymmetrical increase in the MRI-derived images of pulvinar nuclei has not been previously observed in other atypical cases of dCJD. Because atypical dCJD cases share several clinicopathological features with those of vCJD, and because asymmetrical hyperintense signals in the pulvinar have been observed in some neuropathologically confirmed vCJD cases, we had some difficulty in a differential diagnosis between atypical dCJD and vCJD. This is the first atypical dCJD case showing a pulvinar high signal compared with all other basal ganglia on MRI.

Brain Injuries↗

Valsartan improves the lower limit of cerebral autoregulation in rats.

The effects of angiotensin II type 1 receptor blockers (ARBs) on cerebral blood flow (CBF) autoregulation have not been fully clarified. Thus, we examined the acute effect of valsartan, the most selective ARB, on CBF autoregulation in spontaneously hypertensive rats. Intravenous administration of valsartan (0.3 mg/kg) reduced the mean arterial pressure (MAP) from 184+/-5 (mean+/-SEM) to 174+/-5 mmHg (p<0.001) without affecting CBF as measured by laser-Doppler flowmetry. The lower limit of CBF autoregulation (the MAP at which the CBF was 80% of the baseline value) in the valsartan-treated group (122+/-3 mmHg) was significantly lower than that in the control group (135+/-4 mmHg, p<0.05). Reverse transcribed-polymerase chain reaction and immunohistochemical staining demonstrated that both angiotensin II type 2 receptors and angiotensin II type 1 receptors (AT1Rs) were expressed in endothelial and smooth muscle cells of the rat cerebral arteries. These results suggest that specific inhibition of AT1Rs in the cerebral circulation causes the leftward shift of the lower limit of autoregulation.

Angiotensin II Type 1 Receptor Blockers↗

[Strategy for management of carotid arterial stenosis: analysis of 293 consecutive patients in a Japanese cerebrovascular center].

Carotid arterial stenosis is a major risk factor for ischemic stroke and is increasing in Japan as the life-style has been westernized. The purpose of this study was to clarify the detailed process of diagnosis and treatment of patients with carotid arterial stenosis. Of the consecutive 1,889 hospitalized patients in our cerebrovascular center during 2001 and 2003, 293 patients had carotid stenosis 50% or more in diameter by the NASCET method; 82 patients were hospitalized during the acute stage of ischemic stroke and 211 patients with or without past history of ischemic stroke were admitted in the chronic stage. Among acute ischemic stroke patients, 62 patients (76%) had mild neurological symptoms of NIH Stroke Scale score < or = 4 on admission. As the initial treatment during the acute phase, all patients underwent antithrombotic medication; 33 of them underwent carotid endarterectomy (CEA) or carotid arterial stenting (CAS) in the chronic stage. Of 211 chronic patients, 123 (58%) did not have a history of symptomatic ischemic stroke, and instead had nonspecific symptoms, including carotid bruit, headache, and vertigo, or were diagnosed as having carotid artery stenosis by examinations of preoperative screenings. One hundred and thirty-five chronic patients underwent CEA/CAS and all the others except for a patient with serious gastrointestinal bleeding underwent anti-thrombotic medication. Statin treatment was chosen for 59 acute patients and 66 chronic patients. Because many patients with carotid arterial stenosis had mild symptoms during the acute phase or did not have ischemic episodes, we might overlook carotid lesions unless we performed screening examinations using ultrasound or magnetic resonance angiography.

Acute Disease↗

C-reactive protein and risk of first-ever ischemic and hemorrhagic stroke in a general Japanese population: the Hisayama Study.

BACKGROUND AND PURPOSE: The role of high-sensitivity C-reactive protein (hsCRP) in the development of stroke is not clearly understood. We investigated the relationship between serum hsCRP levels and stroke occurrence in a general Japanese population. METHODS: We followed 2692 subjects > or =40 years of age for 12 years. The relative risks and 95% CIs for ischemic and hemorrhagic stroke occurrence were calculated according to the hsCRP quintiles. RESULTS: During the follow-up, 129 first-ever ischemic and 59 hemorrhagic strokes occurred. In men, the age-adjusted incidence of ischemic stroke significantly increased with elevated serum hsCRP levels; the difference between the first and fifth quintiles was statistically significant (1.4 versus 6.6 per 1000 person-years; P=0.02). This association remained significant even after adjustment for other confounding factors, such as age, systolic blood pressure, ECG abnormalities, diabetes, body mass index, total cholesterol, high-density lipoprotein cholesterol, smoking habits, alcohol intake, and regular exercise (adjusted relative risks, 3.11; 95% CI, 1.04 to 9.32; P=0.04). However, such associations were not observed for ischemic stroke in women or in hemorrhagic stroke in either sex. Among male subjects who were both in the fifth hsCRP level and had hypertension, diabetes, obesity, hypercholesterolemia, or a smoking habit, the risk of ischemic stroke was extremely increased, even after adjustment for other risk factors. CONCLUSIONS: Our findings suggest that elevated serum hsCRP levels are an independent risk factor for future ischemic stroke in Japanese men and that the coexistence of a high hsCRP level with another risk factor extremely increases the risk of ischemic stroke.

Adult↗

A case of hearing loss and quadriplegia after a pontine hemorrhage.

We herein describe the case of a 50-year-old female who developed a pontine hemorrhage with consciousness disturbance and quadriplegia. Her respiratory condition was so bad that she needed to be intubated and put on artificial respiration. After her consciousness and respiratory condition gradually recovered, we noticed that she had developed a bilateral hearing loss. The auditory brain stem response test revealed only I waves on both sides, thus suggesting that her hearing loss had been caused by an injury to the hearing-conducting pathway including the cochlear nuclei. In this case, the hematoma extended from the lower to the upper part of pons and, furthermore, it was also located broadly in the dorsal part of the pons. As a result, the cochlear nuclei and corpus trapezoideum appeared to have been destroyed by the hematoma. However, since most cases with a brain stem hemorrhage showing bilateral hearing loss tend to be in a severe condition, this condition is often easy to overlook. We should therefore carefully evaluate patients' reaction to hearing stimulation to avoid overlooking any hearing loss in such patients.

Evoked Potentials, Auditory, Brain Stem↗

Superficial temporal artery duplex ultrasonography for improved cerebral hemodynamics after extracranial-intracranial bypass surgery.

BACKGROUND: To investigate the utility of superficial temporal artery (STA) duplex ultrasonography (STDU) for evaluating the improvement of the cerebral hemodynamics after extracranial-intracranial (EC-IC) bypass. METHODS: This study included 40 consecutive patients who underwent EC-IC bypass for occlusive disease of cerebral arteries. STDU was performed to measure the flow velocity, pulsatility index, and diameter of the operated STA before and 14 days after EC-IC bypass. Regional cerebral blood flow (rCBF) and acetazolamide (ACZ) reactivity of the ipsilateral middle cerebral artery (MCA) territory were evaluated by quantitative single-photon emission computed tomography with the ACZ challenge test. We investigated the correlation between STA flow velocity/diameter and rCBF/ACZ reactivity in the ipsilateral MCA territory. RESULTS: Mean flow velocity (MFV; 26.3 +/- 8.8 to 55.3 +/- 16.3 cm/s, p < 0.0001) and diameter (1.57 +/- 0.24 to 2.26 +/- 0.29 mm, p < 0.0001) of the STA, and rCBF (29.1 +/- 3.1 to 35.0 +/- 6.4 ml/100 g/min, p < 0.0001) and ACZ reactivity (-0.02 +/- 0.10 to 0.28 +/- 0.21, p < 0.0001) of the MCA territory increased after EC-IC bypass compared with the baseline values. STA MFV was significantly correlated with the rCBF 14 days after EC-IC bypass (R = 0.70, p < 0.0001). A cutoff value of postsurgical STA MFV greater than 48.5 cm/s yielded the highest diagnostic accuracy (sensitivity 86%; specificity, 82%) for rCBF > or = 32 ml/100 g/min after EC-IC bypass. CONCLUSIONS: STDU was available for evaluating postsurgical patency of the bypass flow and the rCBF of the ipsilateral MCA territory. The mean blood flow velocity of the operated STA is a highly sensitive parameter for predicting rCBF in the ipsilateral MCA territory after EC-IC bypass.

Aged↗

Transcranial color-coded sonography for vertebrobasilar disorders in end-stage renal disease.

Because vertebrobasilar arterial disorders seem to be common in patients with end-stage renal disease, a neuroradiological evaluation of vertebrobasilar circulation is necessary for patients with possible vertebrobasilar insufficiency. In three patients on maintenance hemodialysis, contrast-enhanced transcranial color-coded real-time sonography (TCCS) through a suboccipital window delineated occlusion of bilateral vertebral arteries with reversal of the basilar artery, reversal of the left vertebral artery mimicking left subclavian steal phenomenon, and dolichoectasia of the basilar artery and bilateral vertebral arteries with signals of turbulent flow. TCCS has several advantages over computed tomographic angiography and magnetic resonance angiography, including the direction of blood flow, handy performance even during hemodialysis, and contrast agent free from nephrotoxicity. Thus, TCCS is useful in the evaluation of intracranial circulation in patients with end-stage renal disease.

Aged↗