Losartan for microalbuminuria in normotensive type 2 diabetes mellitus.
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Albuminuria↗
Biomedical subjects
Kazuyuki Shimada
Publications and source records attributed to Kazuyuki Shimada.
Increase in circulating endothelial progenitor cells after aortic aneurysm repair.
Rapid endothelialization of prosthetic vessels is essential to avoid fatal complications. We hypothesized that there may be mobilization of endothelial progenitor cells (EPCs) in patients who received aortic aneurysm repair, and measured the number of CD34-expressing EPCs (CD34(+) cells) in these patients. Blood samples were taken preoperatively, 6, 24, and 48 h, and 7 days after surgery in 13 patients with aortic aneurysm. Samples were also obtained from ten age-matched control subjects. The number of CD34(+) cells in the peripheral blood was quantified by flow cytometry. The levels of serum vascular endothelial growth factor (VEGF) were measured using an enzyme-linked immunosorbent assay kit. Baseline CD34(+) cell counts in the peripheral blood showed a tendency to be lower in patients with aortic aneurysm compared with healthy control subjects. The number of CD34(+) cells did not change over 48 h after aortic aneurysm repair; however, it had doubled by the 7th day. On the other hand, the baseline serum VEGF levels did not differ between the patients and control subjects. The VEGF levels increased gradually after vascular repair with a significant elevation after 48 h, which was followed by an increase in CD34(+) cell counts. In conclusion, the circulating CD34(+) cell counts and serum VEGF levels are increased after vascular prosthesis replacement in patients with aortic aneurysm, which might contribute to the rapid endothelialization of prosthetic vessels.
Antigens, CD34↗
Comparison of valsartan and amlodipine on ambulatory and morning blood pressure in hypertensive patients.
BACKGROUND: Cardiovascular events occur most frequently in the morning. We aimed to study the effects of monotherapy with the long-acting angiotensin II receptor blocker valsartan compared with the long-acting calcium antagonist amlodipine on ambulatory and morning blood pressure (BP). METHODS: We performed ambulatory BP monitoring before and after once-daily dose of valsartan (valsartan group, n = 38) and amlodipine (amlodipine group, n = 38) therapy in 76 hypertensive patients. To achieve the target BP of < or =140/90 mm Hg, valsartan was titrated from 40 mg/day to 160 mg/day (mean dose 124 mg/day) and amlodipine was titrated from 2.5 mg/day to 10 mg/day (mean dose 6.4 mg/day). RESULTS: Both drugs significantly reduced clinic and 24-h systolic BP (SBP) and diastolic BP (DBP) (P <.002). However, the antihypertensive effect of amlodipine was superior to that of valsartan in clinical SBP (-26 mm Hg v -13 mm Hg, P =.001) and 24-h SBP (-14 mm Hg v -7 mm Hg, P =.008). In addition, morning SBP was significantly reduced by amlodipine from 156 to 142 mm Hg (P <.001) but not by valsartan. Both agents reduced lowest night SBP to a similar extent (amlodipine 121 to 112 mm Hg, P <.001; valsartan 123 to 114 mm Hg, P <.002). Reduction in morning SBP surge (morning SBP minus lowest night SBP) was significantly greater in patients treated with amlodipine compared with those treated with valsartan (-6.1 mm Hg v +4.5 mm Hg, P <.02). CONCLUSIONS: Amlodipine monotherapy was more effective than valsartan monotherapy in controlling 24-h ambulatory BP and morning BP in hypertensive patients.
Aged↗
Sleep pulse pressure and awake mean pressure as independent predictors for stroke in older hypertensive patients.
BACKGROUND: It remains uncertain which is the stronger predictor for stroke in older hypertensives, ambulatory pulse pressure (PP) or mean blood pressure (MBP). METHODS: We studied the prognosis for stroke in 811 older hypertensives in whom ambulatory BP monitoring was performed. We also assessed silent cerebral infarct (SCI) by brain magnetic resonance imaging. RESULTS: Silent cerebral infarcts were found in 50% of 515 subjects (64% of the total population) in whom we assessed SCI using brain magnetic resonance imaging. During a mean of a 42-month follow-up period, stroke events occurred in 59 subjects. After adjustment for covariates, for each 10 mm Hg increase in sleep PP, there was an independent 43% (95% confidence interval [CI]:16%-75%, P =.001) increase in the stroke risk, and sleep MBP was not a significant factor after controlling for sleep PP. On the other hand, for each 10 mm Hg increase in awake MBP, there was an independent 48% (95% CI: 21%-81%, P =.0002) increase in the stroke risk, and awake PP was not a significant factor after controlling for awake MBP. After adjusting for SCI (a strong predictor, P <.0001) at baseline, the effects of awake MBP (38% risk increase for each 10 mm Hg, P =.007) and sleep PP (32% risk increase for each 10 mm Hg, P =.016) remained significant. CONCLUSIONS: In older hypertensives, the impacts of PP and MBP on stroke risk are different during sleep and awake periods. Sleep PP and awake MBP are both predictors of stroke events independently of SCI.
Aged↗
Nocturnal onset ischemic stroke provoked by sleep-disordered breathing advanced with congestive heart failure.
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Aged↗
Morning blood pressure surge and hypertensive cerebrovascular disease: role of the alpha adrenergic sympathetic nervous system.
BACKGROUND: The morning surge of blood pressure (BP) is associated with alpha-adrenergic activity. We studied the association between the alpha-adrenergic morning surge in BP and silent cerebrovascular disease in elderly patients with hypertension. METHODS: We conducted ambulatory BP monitoring three times (twice at baseline and after nighttime dosing of the alpha1-blocker doxazosin) in 98 elderly hypertensive patients in whom the presence of silent cerebral infarcts (SCI) was assessed by brain magnetic resonance imaging. The morning BP surge (MBPS) was calculated as the mean systolic BP during the 2 h after waking minus the mean systolic BP during 1 h that included the lowest sleep BP. The alpha-adrenergic MBPS was calculated as the reduction of MBPS by doxazosin. RESULTS: The prevalence of multiple SCI was higher in the Surge group (top quartile: MBPS > or = 45 mm Hg, n = 24) than in the Nonsurge group (MBPS < 45 mm Hg, n = 74) (54% v 31%, P = .04), and in the higher alpha-adrenergic surge group (top quartile: alpha-adrenergic MBPS > or = 28 mm Hg, n = 25) than in the lower alpha-adrenergic surge group (< 28 mm Hg, n = 73) (68% v 26%, P < .0001). In the Surge group, subjects with higher alpha-adrenergic surge (n = 17) had a markedly higher frequency of multiple SCI, whereas none in the lower alpha-adrenergic surge group had multiple SCI (n = 7) (77% v 0%, P = .001). The alpha-adrenergic MBPS was closely associated with multiple SCI (10 mm Hg increase: OR = 1.96, P = .006), independently of age, MBPS, 24-h systolic BP, and other confounding factors. CONCLUSION: The morning BP surge, particularly that dependent on alpha-adrenergic activity, is closely associated with advanced silent hypertensive cerebrovascular disease in elderly individuals.
Adrenergic alpha-Antagonists↗
Transcriptional profile of genes induced in human atrial myocardium with pressure overload.
BACKGROUND: The molecular response of human myocardium to mechanical stimuli, particularly the difference between pressure or volume overload cardiac hypertrophy, remains incompletely defined. METHODS: We investigated the transcriptional profile of genes induced in human pressure- or volume-overloaded myocardium with DNA microarray technology. We used right atrial tissue from patients who underwent cardiac surgery. On the basis of pressure data and echocardiographic findings, the patients were divided into three groups: control group (n=3), pressure overload group (mean right atrial pressure of >7 mm Hg, n=3), and volume overload group (moderate or severe tricuspid regurgitation, n=3). Expression profiles of 2139 human genes were investigated with mRNA obtained from the samples. RESULTS: In the pressure overload group, expression of genes of cyclin-dependent kinase inhibitor 1A (CDKI1A, 11.7+/-3.1-fold vs. control), and mitogen-activated protein kinase phosphatase-1 (MKP-1, 26.2+/-2.1-fold) was significantly increased compared with those in control or volume overload group (P<0.05). The specificity of these gene expressions was confirmed by a quantitative "real-time" polymerase chain reaction (PCR) analysis. In addition, mechanical strain induced CDKI1A and MKP-1 protein expressions in neonatal rat cardiac myocytes in an amplitude-dependent manner. In contrast, transcripts of growth factors did not significantly increase. CONCLUSIONS: This study demonstrated that gene expressions of CDKI1A and MKP-1, but not growth factors, are induced in chronic pressure-overloaded myocardium. These findings suggest that suppressors of the cell cycle or cell proliferation may play a critical role in the pathophysiology of pressure overload.
Adolescent↗
The arterial circle of Willis of the mouse helps to decipher secrets of cerebral vascular accidents in the human.
The human brain represents an elaborate product of hominizing evolution. Likewise, its supporting vasculature may also embody evolutionary consequences. Thus, it is conceivable that the human tendency to develop cerebral vascular accidents (CVAs) might represent a disease of hominization. In a search for hominizing changes on the arterial circle of Willis (hWAC), we attempted an anatomical comparison of the hWAC with that of the mouse (mWAC) by injecting aliquots of resin into the vasculature of the mouse and then creating vascular endocasts of the mWAC. The internal carotid artery of the mouse (mICA) unites with the mWAC midway between the middle cerebral artery (mMCA) and posterior cerebral artery (mPCA). The mWAC does not complete a circle: the mWAC nourishes the anterior portion of the circle which branches out to the olfactory artery (OlfA) and mPCA, along with the mMCA, and the basilar artery (mBA) does not connect to the mPCA. The OlfA is thicker than the mMCA. The relative brain weight of the mouse was 74 g on average for a 60 kg male and 86 g for a 60 kg female, respectively, as compared with 1424 g for a 60 kg man. These findings are consistent with the mouse being a nocturnal carnivore that lives on olfactory information in contrast to the human that lives diurnally and depends on visual and auditory information. In man, the human ICA (hICA) unites with the hWAC at a point where the human middle cerebral artery (hMCA) branches out, and thus, blood from the hICA does not flow through the hWAC but drains into the hMCA directly. The hMCA is thicker than the anterior cerebral artery. The hPCA receives blood from the hBA rather than from the hICA, and thus, the entire hWAC forms a closed circuit. Since the hICA drains directly into the hMCA without flowing a distance through the hWAC, the capacitor and equalizer functions of the WAC will be mitigated so much that the resultant hemodynamic changes would render the hMCA more likely to contribute to CVAs. Thus, anatomical findings and possibly functions of the arterial circle of Willi may vary from one species to another, depending on one's specific cerebral evolution.
Animals↗
Communication between the buccal nerve (V) and facial nerve (VII) in the human face.
Terminal arrangements of communicating branches between the buccal nerve (V) and the facial nerve (VII) have yet to be precisely determined. To clarify distributions and relationships to facial muscles, detailed morphological examination of the two nerves was performed in the buccal region. The facial skin and underlying tissues of three cadavers were removed en bloc from the surface of the skulls and dissected from outside and inside. Arrangements of the facial muscles, nerves, and associated structures were observed. In all specimens, the communicating buccal nerve (CBN) was detected, largely covering the buccal region. The CBN gave off multidirectional twigs around the facial vein, some of which reached the anterior part of the zygomaticus major muscle. Several twigs of the CBN joined proximally with the zygomatic and buccal branches of the facial nerve. Ramified junctions that interconnected the lower zygomatic and upper buccal branches of the facial nerve were observed near sites where the CBN joined. Anterior twigs of the CBN supplied the longitudinal area lateral to the mouth, where many muscles converged. This study presents a precise morphological pattern of the CBN, suggesting functional contribution of the CBN to control of orofacial movements.
Aged↗
Usefulness of bone marrow aspiration for definite diagnosis of Asian variant of intravascular lymphoma: four autopsied cases.
The Asian variant of intravascular lymphoma (AIVL) is characterized by hemophagocytic syndrome, pancytopenia and hepatosplenomegaly but usually lacks any neurological abnormality and skin lesions, which are typical features of classical intravascular lymphoma (IVL). An ante-mortem diagnosis of AIVL is difficult due to the absence of visible lymphoma lesions and unspecific clinical manifestations. A definite diagnosis relies on the presence of neoplastic B cells in the lumina of small vessels. Paraffin block samples of aspirated bone marrow clots were obtained from 4 patients with clinically suspected IVL and subjected to immunohistopathological analysis. All samples exhibited CD 20+ or CD 79a+ lymphoma cells proliferating intravascularly as well as erythrocytic hemophagocytosis. The distribution of neoplastic cells in the structure of the bone marrow allowed IVL to be distinguished from bone marrow invasions due to other types of lymphoma. We demonstrated the successful establishment of a definite ante-mortem diagnosis of AIVL in 3 of 4 patients by the rapid and simple method of using aspirated bone marrow samples.
Aged↗
Risers and extreme-dippers of nocturnal blood pressure in hypertension: antihypertensive strategy for nocturnal blood pressure.
There is increasing evidence that disruption of diurnal blood pressure (BP) variation is a risk factor for hypertensive target organ damage and cardiovascular events. Especially, the risers (extreme non-dippers), who exhibit a nocturnal BP increase compared with daytime BP, have the worst cardiovascular prognosis, both for stroke and cardiac events. On the other hand, extreme-dippers (with marked nocturnal BP falls) are at risk for non-fatal ischemic stroke and silent myocardial ischemia, particularly extreme-dippers complicated with atherosclerotic arterial stenosis and excessive BP reduction due to antihypertensive medication. Extreme-dipping status of nocturnal BP is closely associated with excessive morning BP surge and orthostatic hypertension. Hypertensive patients who have these conditions and exhibit marked BP variations are likely to have silent cerebral infarct and to be at high-risk with regard to future stroke. Individualized antihypertensive medication targeting disrupted diurnal BP variation might thus be beneficial for such high-risk hypertensive patients.
Aged↗
High-throughput screening of genome fragments bound to differentially acetylated histones.
Although acetylation-deacetylation of histones contributes to regulation of gene expression, few methods have been available to determine the whole-genome histone acetylation profile in specific cells or tissues. We have now developed a genome-wide screening method, differential chromatin scanning (DCS), to isolate genome fragments embedded in histones subject to differential acetylation. This DCS screening was applied to a human gastric cancer cell line incubated with or without an inhibitor of histone deacetylase (HDAC) activity, resulting in the rapid identification of more than 250 genome fragments. Interestingly, a number of cancer-related genes were revealed to be the targets of HDAC in the cancer cells, including those for tumour protein 73 and cell division cycle 34. Such differential acetylation of histone was also shown to be linked to the regulation of transcriptional activity of the corresponding genes. Among the isolated genome fragments, 94% (32/34) of them were confirmed to be bound to differentially acetylated histones, and the genes corresponding to 78% (7/9) of them exhibited differential transcriptional activity consistent with the level of histone acetylation. With its high fidelity, the DCS method should open a possibility to rapidly compare the genome-wide histone acetylation profiles and to provide novel insights into molecular carcinogenesis.
Acetylation↗
Successful treatment of primary cardiac lymphoma with monoclonal CD20 antibody (rituximab).
Primary cardiac malignant lymphoma is extremely rare and almost all patients die within weeks. Monoclonal CD20 antibody (rituximab) was administered to a patient with primary cardiac B-cell non-Hodgkin's lymphoma expressing a CD20 molecule. The results suggest that rituximab may be a safe and effective new therapy for primary cardiac B-cell lymphoma.
Adult↗
Effects of bedtime vs. morning administration of the long-acting lipophilic angiotensin-converting enzyme inhibitor trandolapril on morning blood pressure in hypertensive patients.
Cardiovascular events occur most frequently in the morning. To study the effects of the long-acting lipophilic angiotensin-converting enzyme (ACE) inhibitor trandolapril on morning blood pressure (BP), we performed ambulatory BP monitoring (ABPM) before and after administration of trandolapril just before going to bed (bedtime-administered group: n=17) or in the morning (morning-administered group: n=20) in 37 hypertensive patients. Both sets of ABPM data were available in 30 patients. The 24-h systolic BP (SBP) levels were significantly decreased by 7.2 mmHg in the morning-administered group (p=0.02) and by 5.2 mmHg in the bedtime-administered group (p=0.04). In the bedtime-administered group, prewaking SBP (the average of the 2-h SBP values just before waking) and morning SBP (the average of the 2-h SBP values just after waking) were significantly decreased by 11 mmHg (p=0.005) and by 8.4 mmHg (p=0.03), respectively. On the other hand, in the morning-administered group, the reduction of prewaking SBP (3.9 mmHg, n.s.) and morning SBP (6.6 mmHg, n.s.) did not reach the level of statistical significance. However, the differences in the reductions of prewaking and morning SBPs between the two groups were not statistically significant. There was no additional reduction of the nighttime lowest BP in either administration group. In conclusion, bedtime administration of the long-acting ACE inhibitor trandolapril seems to be a safe and effective means of controlling morning BP in hypertensive patients without an excessive fall in nocturnal BP.
Aged↗
Greater change of orthostatic blood pressure is related to silent cerebral infarct and cardiac overload in hypertensive subjects.
Greater change of postural blood pressure (BP) is often seen in elderly hypertensives and is recognized as a risk factor for cognitive decline and poorer cerebrovascular outcome, but its clinical significance still remains to be clarified. We performed a head-up tilting test, ambulatory BP monitoring, and brain MRI in 59 hypertensives and 27 normotensive subjects. We measured plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels at rest to assess cardiac burden. The 59 hypertensive patients were classified into 3 groups: an orthostatic hypertension (OHT) group with orthostatic increase in systolic BP (SBP) > or = 10 mmHg (n=16); an orthostatic hypotension (OHYPO) group with orthostatic SBP decrease < or = -10 mmHg (n=18); and an orthostatic normotension (ONT) group with neither of these two patterns (n=25). A group of 27 normotensive subjects (NT) was also included as a control. Plasma BNP (72 +/- 92 vs. 29 +/- 24 pg/ml, p < 0.05) and BNP/ANP ratio (4.6 +/- 3.3 vs. 2.4 +/- 1.5, p < 0.05) were significantly higher in the OHYPO than in the NT group. The BNP/ANP ratio was also higher in the OHT than in the NT group (5.1 +/- 3.9 vs. 2.4 +/- 1.5, p < 0.01). The number of silent cerebral infarct (SCI), prevalence of SCI and number of multiple SCIs was the highest in the OHT group, followed in order by the OHYPO, ONT and NT groups. Blood pressure and left ventricular mass index were not significantly different among the 3 hypertensive groups. In conclusion, hypertensive patients with greater change of postural BP (OHT and OHYPO) were shown to have increased risk of advanced silent brain lesions and greater cardiac burden.
Aged↗
valsartan in elderly isolated systolic hypertension (VALISH) study: rationale and design.
Although antihypertensive therapy has been proven to reduce cardiovascular morbidity and mortality, it is unclear how much blood pressure should be decreased in elderly patients with hypertension. The Valsartan in Elderly Isolated Systolic Hypertension (VALISH) study is a multicenter parallel-group study comparing the incidence of cardiovascular events between two target systolic blood pressure levels, below 140 mmHg and below 150 mmHg, under treatment with valsartan, an angiotensin II receptor blocker, as an initial antihypertensive drug in elderly patients with isolated systolic hypertension. The number of patients to be recruited is 3,000 and the duration of follow-up is at least 2 years. This 3,000-patient trial was designed with a two-sided alpha level of 0.05 and 80% power to detect the difference in incidence of cardiovascular events between the target blood pressure levels based on estimation of the cardiovascular events ratio as 21.5/1,000 patient-years and 29.1/1,000 patient-years for the two blood pressure levels. The VALISH study, a large-scale investigator-initiated trial in Japan, will determine whether age should be considered in setting target blood pressure in treatment of isolated systolic hypertension in elderly patients.
Aged↗
Smoking is associated with silent cerebrovascular disease in a high-risk Japanese community-dwelling population.
We aimed to investigate the relationships between smoking and silent cerebrovascular damage. We performed brain MRI to evaluate silent cerebral infarct (SCI) and periventricular hyperintensity (PVH), and carotid-ultrasonography to investigate carotid atherosclerotic plaque in 170 high-risk community-dwelling subjects (mean age: 67.2 years; men: 28.7%) who met more than 3 of the following 9 criteria: 1) high blood pressure (BP); 2) hypercholesterolemia; 3) left ventricular hypertrophy; 4) high hemoglobin A1c; 5) proteinuria; 6) high waist-to-hip ratio; 7) smoking > or =30 cigarettes/day; 8) heavy alcohol intake; 9) family history of stroke. The subjects with SCI (SCI group) were older (70 years vs. 66 years, p=0.004) and had higher systolic BP (SBP) (160 vs. 148 mmHg, p <0.001) and higher carotid plaque score (2.3 vs. 1.5/person, p <0.05) than those without SCI. Among the variables, smoking status (r =0.34, p <0.001), SBP (r =0.28, p <0.001), male gender (r =0.29, p <0.001), left ventricular mass index (r =0.25, p =0.001), and serum creatinine (r =0.20, p =0.006) were significantly correlated with the number of SCIs. Among smokers, the number of SCIs was significantly higher in current smokers than in past smokers (1.9+/-2.2 vs. 0.5+/-0.8, p <0.01). In multiple regression analysis, smoking status (beta =0.183, p =0.045) and SBP (beta =0.196, p =0.011) were independent determinants of the increased number of SCIs. In conclusion, smoking status was an independent determinant of multiple SCIs in a high-risk Japanese community-dwelling population.
Aged↗
Reproducibility of arterial stiffness indices (pulse wave velocity and augmentation index) simultaneously assessed by automated pulse wave analysis and their associated risk factors in essential hypertensive patients.
Arterial stiffness is a strong determinant of cardiovascular risk. Pulse wave velocity (PWV) and the augmentation index (AIx) are widely used as arterial stiffness indices. We studied the reproducibility of these indices and their association with cardiovascular risk factors in hypertensives. We measured brachial blood pressure (BP), brachial-ankle PWV (baPWV) and carotid AIx (cAIx) twice (at the baseline and 4 weeks after the baseline) using an automatic device in 103 hypertensives. The mean intraobserver-intersession difference was 29.0 cm/s with an SD of 201.6 cm/s for baPWV, and 0.5% with an SD of 5.9% for cAIx, and the Bland-Altman plots demonstrated the good reproducibility of baPWV and cAIx. Both baPWV and cAIx (the average of the 1st and the 2nd measurements) were significantly correlated with age, systolic BP (SBP), and pulse pressure (all, p <0.005); however, these factors were not correlated with each other (r =0.06, NS). cAIx was correlated with height, heart rate (HR), total cholesterol, and low density lipoprotein cholesterol (LDL-C) (all, p <0.05). In multiple regression analysis, age, SBP, and HR emerged as significant independent predictors of baPWV (adjusted R(2)=0.43, p <0.0001), while height, SBP, HR, and LDL-C emerged as significant independent predictors of cAIx (adjusted R(2)=0.58, p <0.0001). Both PWV and AIx measured using an automatic device were fairly reproducible, and their associated risk factors appeared to be different. Automated simultaneous measurement of these arterial stiffness indices may be useful for risk stratification of hypertensives.
Aged↗