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Biomedical subjects

Kazuo Minematsu

Publications and source records attributed to Kazuo Minematsu.

At least 19 recordsLinked to original sources

Aggravation of hemorrhagic transformation by early intraarterial infusion of low-dose vascular endothelial growth factor after transient focal cerebral ischemia in rats.

Vascular endothelial growth factor (VEGF) is a unique growth factor associated with angiogenesis, vascular permeability, and neuroprotection. The aim of this study was to observe the effects of early intraarterial infusion of low-dose VEGF on ischemia/reperfusion injury after transient focal cerebral ischemia in rats. Male Sprague-Dawley rats were subjected to 2 h of focal ischemia by middle cerebral artery occlusion. After the 2 h ischemia, the rats were infused with 0.3 microg/kg of VEGF (n = 15), or the vehicle as a control (n = 15), via the reperfused internal carotid artery. The brains were collected after a 1 h, 6 h, or 72 h reperfused period. Severity of ischemic cellular injury, serum extravasation, hemorrhagic transformation, and matrix metalloproteinase (MMP)-2 and -9 expressions were compared between the VEGF-treated and control groups. No significant difference in the extent of ischemic cellular injury and serum extravasation was observed between the two groups. However, vessel numbers with hemorrhagic transformation were significantly greater in the VEGF-treated group than in the control group after the 72 h reperfusion (9.4 +/- 1.6 versus 2.6 +/- 1.5; P = 0.028). The severity of hemorrhagic transformation was not correlated with the extent of ischemic cellular injury or serum extravasation. MMP-2 and -9 expressions were not enhanced in the VEGF-treated group compared with the control group. These results suggest that exogenous VEGF administered intravascularly at a very early point in reperfusion aggravates hemorrhagic transformation. The aggravated hemorrhagic transformation does not seem to depend on the enlargement of ischemic cellular injury, serum extravasation, or overexpressions of MMP-2 and -9.

Animals↗

Bilateral induction of the S-100A9 gene in response to spreading depression is modulated by the cyclooxygenase-2 activity.

Cyclooxygenase-2 (COX-2) was reported to be induced in the infarcted human brain. Spreading depression (SD) is thought to play a role in this induction. In this study, we correlated the expression of SD-associated genes with COX-2 production in brains after SD. Rats were divided into 3 groups: rats that did not undergo SD (group I saline controls, n=7), rats that underwent unilateral SD as a result of KCl application (group II, n=9), and rats that were pretreated with the selective COX-2 inhibitor, JTE-522 3 h before the induction of SD (group III, n=7). The expression of the SD-associated genes, S-100A9, and mitogen-activated proteinkinase phosphatase (cpg21) was analyzed 2 h later using a cDNA array. In group II, COX-2 and cpg21 mRNA expression, as determined by RT-PCR, were significantly upregulated in the hemisphere undergoing SD. While the expression of S-100A9 mRNA was bilaterally upregulated in these animals, this expression was significantly reduced in group III, and was accompanied by reduced bilateral production of PGE(2). Thus, the bilateral induction of expression of the S-100A9 gene in response to SD was associated with COX-2 activation.

Animals↗

Diagnosis of middle cerebral artery occlusive lesions with contrast-enhanced transcranial color-coded real-time sonography in acute stroke.

It is useful to evaluate the occlusive lesions of middle cerebral artery (MCA) occlusion with transcranial color-coded real-time sonography (TCCS). However, TCCS criteria for locating the site of the MCA occlusion has, as yet, remained unclear. The aim of the present study was to establish TCCS criteria for MCA occlusive lesions. We prospectively performed contrast-enhanced TCCS (CE-TCCS) in 75 consecutive acute stroke patients within 24 h of digital subtraction angiography. Patients were divided into four groups: occlusion of the MCA stem (MO group, n=12); occlusion of the MCA branch (MBO group, n=10); stenosis of the MCA stem (MS group, n=9); and no occlusive or stenotic lesions (control group, n=44). The following parameters were measured: peak systolic velocity (PSV) and end diastolic velocity (EDV) of bilateral MCA stems, and ED-ratio (the side-to-side ratio of the EDV). We establish the CE-TCCS criteria for MCA occlusive lesions using the sensitivity-specificity curve analysis. A PSV of 170 cm/s distinguished MCA stenosis from other groups (positive and negative predictive values and the accuracies were 100%, 99.0% and 99.1%, respectively). An EDV of 26 cm/s differentiated MO or MBO from the other groups (positive and negative predictive values and the accuracies were 84.6%, 100% and 96.5%, respectively). An ED-ratio of 2.5 discriminated MO from the MBO group (positive and negative predictive values and the accuracies were 88.9%, 85.7% and 87.5%, respectively). Measurement of MCA stem flow velocity with CE-TCCS can identify MCA stem stenosis and occlusion, as well as MCA branch occlusion.

Aged↗

A case-control analysis of intra-arterial urokinase thrombolysis in acute cardioembolic stroke.

BACKGROUND: Intra-arterial urokinase (IA-UK) thrombolysis is frequently given in Japan to selected patients with acute cerebral artery occlusion. However, it is not clear whether or not IA-UK thrombolysis has an efficacy for acute stroke patients. The purpose of this study was to assess the effects of IA-UK thrombolysis in acute cardioembolic stroke patients, by performing a case-control analysis using data from Japan's Multicenter Stroke Investigator's Collaboration (J-MUSIC). METHODS: 16,922 acute ischemic stroke patients were enrolled into J-MUSIC. From these patients, we selected 91 patients (UK group) who met the following criteria: treatment with IA-UK; 20-75 years of age; cardioembolic stroke; presenting with a carotid stroke; admission within 4.5 h of symptom onset, and a National Institutes of Health Stroke Scale (NIHSS) score of 5-22 points on admission. A control group of 182 patients without IA-UK treatment and matched to the NIHSS score, gender, and age was chosen. We compared the modified Rankin scale (mRS) score at discharge and the mortality between the 2 groups. RESULTS: In both groups, the mean age was 65 +/- 8 years, and the median NIHSS score was 14. The mean interval between symptom onset and UK administration was 3.4 +/- 1.3 h, and the IA-UK dose was 392,000 +/- 200,000 units. The mRS score at discharge was lower in the UK group than in the control group (mean, SD, median; 2.8, 2.9, 2 in UK group vs. 3.3, 1.8, 4, in the control, respectively p = 0.031). A favorable outcome (mRS of 0-2) was more frequently observed in the UK group (50.5%) than in the control group (34.1%, p = 0.0124). No difference in the mortality rate was seen between the UK group (11.0%) and the control group (13.3%). As well, there was no difference in the length of hospital stay between the UK group (46 +/- 41 days, mean +/- SD) and the control group (42 +/- 42 days, mean +/- SD). CONCLUSIONS: IA-UK thrombolytic therapy may improve the outcome in hyperacute cardioembolic stroke patients.

Acute Disease↗

Mortality and cause of death after hospital discharge in 10,981 patients with ischemic stroke and transient ischemic attack.

BACKGROUND: The aim of this study was to examine the 1-year cumulative mortality rate and cause of death, and to identify the predictive factors for death after hospital discharge following ischemic stroke and transient ischemic attack (TIA) using data from the Japan Multicenter Stroke Investigators' Collaboration study. METHODS: We prospectively registered 16,922 consecutive patients with acute ischemic stroke or TIA from May 1999 to April 2000 in 156 Japanese hospitals. We mailed a questionnaire to the 15,322 patients who were alive at hospital discharge. RESULTS: 10,981 patients (6,945 men, 4,036 women, age 70 +/- 11 years, median 71, range 19-100 years) were enrolled in the follow-up study. The mean follow-up period was 271 +/- 110 days (median 272 days; range 1-487 days). The 1-year cumulative mortality was 6.8% (7.0% for 10,234 stroke patients and 3.5% for 747 TIA patients). The causes of death were: cerebrovascular disease, 24.1%; pneumonia, 22.6%; heart disease, 18.1%; cancer, 11.0%, and miscellaneous causes, 24.1%. Multivariate analysis suggested that male gender, age, diabetes mellitus, atrial fibrillation, history of stroke, nonlacunar stroke, functional disability and transfer to another hospital or nursing home on discharge were significant independent predictors of death during the follow-up period. CONCLUSIONS: The major causes of death after hospital discharge were found to be cerebrovascular diseases, pneumonia and heart diseases. Thus, in order to improve survival after hospital discharge, in addition to appropriate management of vascular risk factors following stroke, it appears to be important to take measures to prevent pneumonia and to discharge patients to their own home, if possible.

Age Distribution↗

Optimal dose of prothrombin complex concentrate for acute reversal of oral anticoagulation.

We investigated optimal dose of prothrombin complex concentrate (PCC) for acute reversal of oral anticoagulation in patients with major hemorrhagic complications or who required invasive procedures. We also checked how rapidly international normalized ratio (INR) was reversed after PCC administration. INR was measured before and 10-60 min after administration of PCC with or without vitamin K in 42 patients (men 28, women 14, median age of 70 years old) who had received warfarin but required rapid reversal of INR because of a hemorrhagic complication or medical procedure. The amount of PCC administered was 200 IU in six patients, 500 IU in 30, 1000 IU in 3, and 1500 IU in the other 3. Additional administration of PCC was performed when the correction of INR was inadequate. In 10 of the 42 cases, INR was measured serially, before, 10 and 60 min and 12-24 h after the administration of PCC and vitamin K. In the six patients who received PCC of 200 IU, INR values of 3.34 median (range 2.06 to 5.08) decreased to 1.85 (range 1.23 to 2.43) significantly (Wilcoxon's rank sum test, p=0.028), but in three patients (50%), INR values were still above 2.0 after the administration. In 30 patients treated with PCC of 500 IU, values decreased from 2.49 median (range 1.54 to 10.00) to 1.19 (range 0.87 to 1.55) significantly (p<0.0001). The corrected INR values were below 1.5 in 25 of 26 patients (96%) who had initial INR values from 2.0 to 4.9. In four patients with initial INR of 5.0 or more, the reversed INR was below 1.5 in one (25%), between 1.5 and 2.0 in two (50%), and above 2.0 in one (25%) who had additional administration of 500 IU PCC lowering INR from 2.01 to 1.48. Values of INR in the six patients receiving 1000 IU or 1500 IU, INR decreased from 2.33 median (range 1.96 to 4.00) to 0.96 (range 0.87 to 1.24, p=0.028). In the 10 patients with serial measurement, INR changed from 2.67 median (range 2.05 to 10.00) to 1.17 (range 0.99 to 1.60) 10 min after the administration. The INR values remained stable 60 min and 12-24 h after the PCC administration. The 500 IU of PCC is likely to be optimal dose of PCC for emergent reversal of INR in patients requiring rapid correction of INR below 5.0, but to be inadequate dose in patients with INR of 5.0 or more. PCC administration with vitamin K may finish reversing INR rapidly within 10 min and keep the reversed INR values for 12-24 h.

Administration, Oral↗

Is stroke a paradoxical embolism in patients with patent foramen ovale?

OBJECTIVE: Purpose was to assess the stroke mechanism in patients with patent foramen ovale (PFO). METHODS: We reviewed the medical records of 111 stroke patients with PFO and sinus rhythm (PFO-S group), 25 with PFO and atrial fibrillation (AF) (PFO-AF group) and 67 with AF but not PFO (AF group), who had received contrast transesophageal echocardiography. The clinical and neuroradiological findings were then compared among the three groups. Deep vein thrombosis was investigated in 93 patients with PFO. We determined the number of patients with definite paradoxical embolism who met three criteria: deep vein thrombosis, neuroradiological features indicating embolic stroke, and the absence of other sources of emboli. We also evaluated those with probable paradoxical embolism who met two of the three criteria. RESULTS: The PFO-S group more frequently exhibited hypercholesterolemia (p<0.0001) and lesions limited to the posterior circulation (p<0.0004), and less frequently exhibited large or cortical lesions in the anterior circulation (p=0.0008, p<0.0001, respectively), than the PFO-AF and AF groups. In the PFO-S and PFO-AF groups, other sources of emboli such as a cardiac source of emboli, cerebral artery stenosis > or =50%, or complicated atheroma in the aortic arch were identified in 72 cases (52.9%). In the 93 patients with examination for deep vein thrombosis, the definite and probable criteria of paradoxical embolism were fulfilled only in three (3.2%) and 33 cases (35.5%), respectively. CONCLUSION: In stroke patients with PFO, not only paradoxical brain embolism through the PFO but also other causes of stroke may contribute to the development of stroke.

Age of Onset↗

Transoral carotid ultrasonography for evaluating internal carotid artery occlusion.

BACKGROUND AND PURPOSE: Transoral carotid ultrasonography (TOCU) has enabled the assessment of the distal portion of the extracranial internal carotid artery (ICA). We evaluated the ultrasonographic features of ICA occlusion using TOCU. METHODS: We studied 50 occluded ICAs in 42 stroke patients. The mechanism of ICA occlusion was embolic (group E) in 14 arteries and thrombotic (group T) in the other 36 arteries. We used a color flow imaging system equipped with special convex array transducers, and placed the probe on the postero-lateral pharyngeal wall to identify the distal extracranial ICA. We evaluated intraluminal echodensity (lucent or opaque) and measured the diameter of the ICA. Then, we examined the relationship of these early (<1 week after onset) and chronic (>4 weeks after onset) phase TOCU findings to the mechanism of ICA occlusion and the site of occlusion. RESULTS: In the early phase of a stroke, the intraluminal echodensity was more frequently lucent (9/11, 81.8%) in group E than in group T (5/20, 20%, p<0.05). In the chronic phase, echodensity became opaque in both groups. In the early phase, the lucent echodensity was more frequently seen in patients with distal occlusion than in those with proximal occlusion. Thus, it may represent blood or fresh thrombus formation. In patients with unilateral ICA occlusion, the occluded ICA was significantly smaller in diameter than the non-occluded contralateral artery both in the early and chronic phases. CONCLUSION: The echodensity and diameter of the extracranial ICA distal portion as found on TOCU can help to identify the mechanism of ICA occlusion.

Aged↗

Right-to-left shunt evaluated at the aortic arch by contrast-enhanced transesophageal echocardiography.

OBJECTIVE: The right-to-left shunt (RLS) is diagnosed by contrast-enhanced transesophageal echocardiographic monitoring of the bilateral atria (cTEE-BA). However, the procedure is often disturbed by nonsmoke spontaneous individual contrast (NSSIC) with fast motion, which appears in the left atrium after respiratory maneuvers without administration of a contrast medium and moves past in several seconds. We attempted to perform cTEE monitoring of the aortic arch (cTEE-AA) for evaluation of the RLS and compared the findings with those of cTEE-BA. METHODS: Both cTEE-BA and cTEE-AA were performed in 168 patients with ischemic stroke (133 men and 35 women; mean age +/- SD, 62.0 +/- 14.4 years). The frequency of NSSIC in the left atrium was compared with that in the aortic arch during the respiratory maneuver. When contrast much brighter than the NSSIC was visualized in the left atrium and the aortic arch during the respiratory maneuver with administration of the contrast medium, we considered the RLS to be positive in the cTEE-BA and cTEE-AA, respectively. Findings were then compared between the 2 examinations. RESULTS: Nonsmoke spontaneous individual contrast was more frequently observed in the left atrium than the aortic arch (61.3% versus 14.9%; chi2 test, P < .0001). The RLS was positive in 34 patients in the cTEE-BA and in 39 patients in the cTEE-AA. The sensitivity and specificity of the cTEE-AA for the cTEE-BA were 100% and 96.3%, respectively. CONCLUSIONS: The cTEE-AA may be an alternative method for detection of an RLS, especially in patients with a large amount of NSSIC in the left atrium.

Aorta, Thoracic↗

Atherosclerosis found on carotid ultrasonography is associated with atherosclerosis on coronary intravascular ultrasonography.

OBJECTIVE: Little has been reported on the relationship between left main coronary artery atherosclerosis and carotid ultrasonographic results. We evaluated the association between carotid and coronary atherosclerosis assessed by coronary intravascular ultrasonography (IVUS) in 45 patients. METHODS: We counted the number of plaques with intima-media thickness (IMT) greater than or equal to 1.1 mm and calculated a plaque score by summing all plaque thicknesses. With the use of IVUS, the percent plaque area was calculated at the proximal, middle, and distal sites of the left main coronary artery. The maximum percent plaque area and mean percent plaque area of the 3 sites were also calculated. Relationships among the degree of left main coronary artery atherosclerosis and carotid atherosclerosis and vascular risk factors were evaluated. RESULTS: The mean percent plaque area and maximum percent plaque area were increased in men and in patients with hypertension compared with women and those without hypertension (P < .1). Both the average of the maximum common carotid IMT and plaque number were correlated with both the mean percent plaque area and maximum percent plaque area (P < .05). Men, the presence of hypertension, and the average of the maximum common carotid IMT were correlated with both the mean percent plaque area and maximum percent plaque area by multiple linear regression analysis (P < .05). CONCLUSIONS: The average of the maximum common carotid IMT was significantly correlated with left main coronary artery atherosclerosis evaluated by IVUS.

Arteriosclerosis↗

Variation in ischemic stroke frequency in Japan by season and by other variables.

BACKGROUND AND PURPOSE: It is unclear whether acute ischemic stroke exhibits a seasonal pattern in Japan. The aim of the present study was to elucidate seasonal differences in acute ischemic stroke. METHODS: Our study enrolled 12,660 patients with ischemic stroke (7943 men, 4717 women; mean age, 70.1 years, S.D. 11.5; median 70; range 18-107). We divided the year into four parts: spring (March-May); summer (June-August); fall (September-November); and winter (December-February). Time of stroke onset was divided into three subgroups: daytime (08:00-16:00), evening (16:00-24:00), and night (24:00-08:00). We examined the association between clinical characteristics, season, and time of stroke onset. RESULTS: Stroke occurred least frequently in spring (22.9%), followed by winter (25.3%), fall (25.8%), and summer (26.0%) (P<0.001). No differences in age, National Institutes of Health Stroke Scale (NIHSS) score, modified Rankin Scale (m-RS) score, history of stroke/transient ischemic attack (TIA), or risk factors for stroke were observed among the four seasons. Stroke in men (63.8% vs. 62.4%; P<0.01), lacunar stroke (LS) (41.2% vs. 39.4%, P<0.01), atherothrombotic stroke (ATS) (34.0% vs. 32.3%; P<0.01), and nighttime stroke (26.5% vs. 24.8%; P<0.05) were observed more frequently in summer compared to other seasons. This contrasts with the findings for stroke in women (39.0% vs. 36.7%; P<0.05), cardioembolic stroke (CES) (23.4% vs. 20.6%; P<0.05), and daytime stroke (47.4% vs. 45.0%; P<0.05), which were more frequent in winter. CONCLUSIONS: Acute ischemic stroke displays seasonal characteristics according to gender, stroke subtype, and time of stroke onset. These results may have important clinical implications in ischemic stroke prevention.

Adolescent↗

Long-term prognosis, by stroke subtypes, after a first-ever stroke: a hospital-based study over a 20-year period.

BACKGROUND AND PURPOSE: The influence of stroke subtype on recurrence, and determinants of recurrence-free survival after a first-ever stroke are not fully understood. We aimed to clarify the long-term prognosis by stroke subtypes and to identify determinants for recurrence and death after a first-ever stroke. METHODS: We enrolled 1,732 consecutive patients (men/women = 1,134/598, mean age of 65 years) with a first-ever acute stroke who were admitted to our Stroke Care Unit during a period of 20 years. Stroke subtypes were classified as atherothrombotic brain infarction, lacunar infarction, cardioembolic infarction, other type of infarction, and brain hemorrhage. The prognosis was assessed by stroke subtypes. RESULTS: During the hospital stay (mean 61 days), 99 patients died: 73 died directly from stroke. A total of 198 patients had recurrent strokes, and 286 died within 3 years after the index stroke. The overall recurrence rate within the first year was 6.5%, which was different among stroke subtypes. Patients with cardioembolic infarction (9.0%) as well as other type of infarction (9.1%) had more recurrent strokes within the initial year compared with the other subtypes. A history of transient ischemic attack (relative risk = 1.38), atrial fibrillation (1.52), ischemic heart disease (1.40), and disability at discharge (2.64) were independent predictors for the recurrence and death within 3 years after the first-ever stroke. CONCLUSIONS: The recurrence rate was different among stroke subtypes within 1 year after the index stroke. Atrial fibrillation, ischemic heart disease, history of transient ischemic attack, and disability at discharge were important determinants for stroke recurrence and death.

Acute Disease↗