Naturally formed coronary arterial thrombus detected by In-111 oxine platelet imaging.
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Blood Platelets↗
Biomedical subjects
Kenjiro Kikuchi
Publications and source records attributed to Kenjiro Kikuchi.
Cost-effectiveness analysis of hypertension treatment: controlled release nifedipine and candesartan low-dose combination therapy in patients with essential hypertension--the Nifedipine and Candesartan Combination (NICE-Combi) Study.
Societal interest in pharmaco-economic analysis is increasing in Japan. In this study, the cost-effectiveness of low-dose combination therapy with controlled release nifedipine plus candesartan and up-titrated monotherapy with candesartan was estimated, based on the results of the NICE-Combi study. The NICE-Combi study was a double-blind, parallel arm, randomized clinical trial to compare the efficacy of low-dose combination therapy of controlled release nifedipine (20 mg/day) plus candesartan (8 mg/day) vs. up-titrated monotherapy of candesartan (12 mg/day) on blood pressure control in Japanese patients with mild to severe essential hypertension who were not sufficiently controlled by the conventional dose of candesartan (8 mg/ day). The incremental cost effectiveness of each cohort during the 8-week randomization period was compared, from the perspective of a third-party payer (i.e., insurers). The average total cost per patient was 29,943 Japanese yen for the combination therapy group and 33,182 Japanese yen for the candesartan monotherapy group, while the rate of achievement of the target blood pressure was significantly higher in the combination therapy group than in the up-titrated monotherapy group. In the combination therapy group, higher efficacy and lower incremental treatment cost ("Dominance") were observed when compared to the monotherapy group. The sensitivity analyses also supported the results. In conclusion, these results suggest that combination therapy with controlled release nifedipine and low-dose candesartan (8 mg) is "dominant" to up-titrated candesartan monotherapy for the management of essential hypertension. This conclusion was robust to sensitivity analysis.
Adult↗
A case of alternating bundle branch block in combination with intra-Hisian block.
We describe a 66-year-old woman who had an alternating bundle branch block consisting of coexisting occurrence of right bundle branch block (RBBB) and left bundle branch block (LBBB) combined with Mobitz type II atrioventricular block (AVB). A prolonged PQ interval was associated with the RBBB pattern whereas it was not apparent in the LBBB pattern. Electrophysiologic study revealed that the LBBB pattern was combined with a double His bundle potential. On the other hand, the RBBB pattern was combined with a markedly prolonged HV interval with a low voltage monophasic His bundle potential, which we speculated was the former part of the split His bundle potential seen during the LBBB pattern. A combination of the longitudinal dissociation in the His bundle and the gap phenomenon at the intra-Hisian block portion may account for this observation.
Aged↗
[Heart rate variability, arrhythmia and magnesium in hemodialysis patients].
Most of chronic hemodialysis patients are combined with cardiopathies, such as ischemic heart disease, heart failure, and arrhythmia. Heart rate variability as an index of cardiac autonomic activity is falling in many hemodialysis patients, which can have a concern with the arrhythmogenicity. In addition, QT dispersion as an index of an electrical variability in the ventricular repolarization process increases by hemodialysis, which may tightly relate to the occurrence of ventricular arrhythmia. On the other hand, tendency of the magnesium accumulation is observed in renal insufficiency patients. In our study, plasma concentration of ionized magnesium showed a positive correlation with pNN50 and HF, indicating that this ion may enhance the parasympathetic activity resulting in a cardioprotection. Plasma ionized magnesium also showed a negative correlation with QT dispersion, suggesting that magnesium plays a role of maintaining myocardial electrical stability in hemodialysis patients.
Arrhythmias, Cardiac↗
[Choice and administration sequence of antiepileptic agents for status epilepticus and frequent seizures in children].
We investigated the sequence of the administration, the efficacy and the safety of antiepileptic drugs (AED) given intravenously for the treatment of status epilepticus and frequent seizures in children. Our institute has a recommended sequence of AED administration for treatment of status epilepticus: the first-line agent is diazepam (0.3 - 0.5 mg/kg administered intravenously, once or twice). The second-line drugs include midazolam (0.15 - 0.4 mg/kg intravenously, once or twice, and if necessary, followed by continuous infusion at 0.06 - 0.18 mg/kg/hour), lidocaine (1 - 2 mg/kg intravenously, once or twice, and if necessary, followed by continuous infusion at 2 - 4 mg/kg/hour) and phenytoin (10 - 20 mg/kg, infused slowly). For those patients who previously experienced a seizure which was refractory to diazepam but responsive to the second-line agent, it was recommended to use the second-line agent as a first-line agent. When seizures were refractory to the first and second-line agents, thiopental was administered (3 - 10 mg/kg intravenously, and if necessary, followed by continuous infusion at 2 -5 mg/kg/hour). The etiologies of 177 occasions of status epilepticus and frequent seizures were categorized into two groups:epilepsy (n = 95) and situation-related seizures (n = 82). Situation-related seizures included febrile seizures (n = 44), acute encephalopathy/encephalitis (n = 31) and benign infantile convulsions (n = 7). The ages of the patients ranged from 0.1 to 18.4 years (average +/- SD:3.69 +/- 3.15 years). Diazepam was administered as the first-line drug on 157 of 177 occasions (88.7%). On 116 occasions the second-line agents were administered. Midazolam and lidocaine were injected as the second-line agent on 54 (46.6%), and on 33 (28.4%) occasions, respectively, although both midazolam and lidocaine injections were off-label use for seizure control in Japan. Thiopental was used as the third to fifth-line agent. Effective ratios (effective occasions/total occasions) of each drug were the following: thiopental 19/21 (90.4%), midazolam 57/99 (57.6%), lidocaine 25/60 (41.7%), phenytoin 16/41 (39.0%), diazepam 59/164 (36.0%). Thiopental was statistically more effective than midazolam, lidocaine, diazepam or phenytoin (p < 0.01), and midazolam was statistically more effective than diazepam (p < 0.01) or phenytoin (p < 0.05). Administration of thiopental caused complications more frequently than the other agents (p < 0.01): The complications by thiopental were severe in some cases requiring intratracheal intubations and artificial ventilation. From the viewpoint of both efficacy and safety, midazolam should be recommended as one of the first-line agents for status epilepticus.
Adolescent↗
[Evidence-based usefulness of Ca antagonists and ACEIs and ARBs for the primary and secondary prevention of major cardiovascular and renal events in patients with hypertension].
The benefits of reducing blood pressure (BP) on the risks of major cardiovascular event and preservation of renal function are well established in patients with hypertension. We estimated effects of strategies based on angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor antagonist (ARB) and calcium channel antagonist (CCB), which is predominantly prevalent in Japan in patients with hypertenstion than ACEI/ARB, on the risks of these events, overviewed with data from clinical trials and meta-analysis of these trials including underwent in Japan. ACEI and ARB-based regimens reduced the risks of heart failure and progression of renal dysfunction complicated with and without diabetes mellitus (DM) in patients with hypertension compared with control and CCB-based regimens. CCB-based regimens reduced the primary risks of cerebella event and dementia and primary and secondary risks of coronary events in patients with hypertension having many coronary risk factors compared with control and ARB/ACEI-based regimens. Greater risk reductions, however, were produced by regimens that targeted lower (BP) goals, by combined regimens based on ACEI/ARB and CCB and diuretics, demonstrated in mega-trial of ALLHAT and proposed in guideline of JSH 2004.
Angiotensin Receptor Antagonists↗
Unequal effects of renin-angiotensin system inhibitors in acute cardiac dysfunction induced by isoproterenol.
Several clinical trials have demonstrated that angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II type 1 receptor blocker (ARB) are equally effective in the treatment of chronic heart failure. However, this has not been confirmed for acute cardiac dysfunction. We examined whether ACEI or ARB prevents isoproterenol-induced acute left ventricular (LV) dysfunction in dogs. LV dysfunction induced by a large dose of isoproterenol (1 microg.kg(-1).min(-1), 3-h infusion) was compared in dogs treated with ACEI (temocaprilat) or ARB (olmesartan). Atrial pacing induced a constant heart rate and use of adjustable aortic banding provided a nearly constant afterload. LV systolic function (LV dP/dt, fractional shortening, and ejection fraction) and diastolic function (tau and LV end-diastolic pressure) were significantly deteriorated after isoproterenol infusion. The LV dysfunction was almost totally prevented by ARB but was only partially prevented by ACEI. The partial effect of ACEI was complemented by cotreatment with HOE-140, a bradykinin B2 receptor antagonist. At baseline, the response to low doses of isoproterenol was significantly attenuated by ACEI but not by ARB, and the ACEI-induced attenuation was totally abolished by cotreatment with HOE-140. The response to isoproterenol was significantly attenuated after 3 h of excess isoproterenol loading, and it was almost completely preserved by ARB but not by ACEI. In conclusion, acute LV dysfunction and beta-adrenergic desensitization induced by excess isoproterenol administration were almost totally prevented by ARB but only partially prevented by ACEI. These differences were attributable at least in part to bradykinin pathways activated by ACEI administration in acute LV dysfunction.
Acute Disease↗
Trends in incidence of end-stage renal disease in Japan, 1983-2000: age-adjusted and age-specific rates by gender and cause.
BACKGROUND: Trends in age-adjusted or age-specific incidence rates of end-stage renal disease (ESRD) have never been examined in Japan, a major ESRD epidemic area. METHODS: A nationwide registry has provided the number of ESRD patients commencing maintenance renal replacement therapy for time period from 1983 to 2000. We computed gender- and age-specific incidence rates of ESRD over 2-year periods, in total or by cause. Age-adjusted incidence rates were calculated using the 1985 Model Population of Japan as the standard. RESULTS: Causes of ESRD in 1999-2000 were, in order of decreasing frequency, diabetic nephropathy, chronic glomerulonephritis, unknown causes, nephrosclerosis and polycystic kidney disease in men, and chronic glomerulonephritis, diabetic nephropathy, unknown causes, nephrosclerosis and polycystic kidney disease in women. The age-adjusted all-cause incidence of ESRD increased until 1995-1996, but has since levelled off in both genders. The age-adjusted rate for diabetic nephropathy has been rapidly increasing, while that for chronic glomerulonephritis has decreased since 1995-1996. The former rate exceeded the latter in 1997-1998 in men. All-cause ESRD has rapidly increased in the eighties age group, whereas the increase slowed down in younger age groups in the late 1990s. The rate for diabetic nephropathy has linearly risen in almost every age group in men, whereas it began to level off in women aged 40-59 years at about 1995. For chronic glomerulonephritis, the rate had already started to decline in the mid-1980s in those aged <45 years. The rate of nephrosclerosis has been increasing independently of age. CONCLUSIONS: The present study shows changes in the epidemiological features of the incidence of ESRD in Japan from 1983 to 2000.
Adult↗
Thermal treatment attenuates neointimal thickening with enhanced expression of heat-shock protein 72 and suppression of oxidative stress.
BACKGROUND: The beneficial effects of thermal therapy have been reported in several cardiovascular diseases. However, it is unknown whether the thermal treatment has some beneficial roles against the development of atherosclerosis. METHODS AND RESULTS: The inflammatory arterial lesion was introduced by placement of a polyethylene cuff on femoral arteries of male Sprague-Dawley rats for 4 weeks. Thermal-treated group underwent daily bathing in 41 degrees C hot water for 15 minutes. Neointimal thickening along with immunohistochemical expression of heat-shock proteins (HSPs), monocyte chemoattractant protein-1 (MCP-1), and NADPH oxidase were compared with those of a thermally untreated (Control) group. Morphometric analysis demonstrated a significant suppression of neointimal thickening in thermal-treated group compared with the Control group (intimal/medial area ratios, 0.01+/-0.01 versus 0.31+/-0.04, P<0.01). Expression of MCP-1 and infiltration of ED-positive cells were enhanced in the adventitial layer of Control. More importantly, expression of HSP72 in media was enhanced by thermal treatment. Expression of p22-phox, the major membrane subunit of NADPH oxidase, and MCP-1 was augmented in cuff-injured adventitia of the Control but not the thermal-treated groups. CONCLUSIONS: Thermal treatment significantly attenuated infiltration of inflammatory cells in adventitia and suppressed neointimal thickening in cuff-injured arteries with the enhancement of HSP72 expression and suppression of oxidative stress.
Animals↗
[Evidence-based therapy for patients with hypertension following JSH2000 guidelines].
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Angiotensin II Type 1 Receptor Blockers↗
Human small cell lung cancer cells express functional VEGF receptors, VEGFR-2 and VEGFR-3.
Studies have suggested that the vascular endothelial growth factors (VEGFs)/VEGF receptors (VEGF-Rs) system plays an important role in tumour growth and metastasis. We conducted the present study to clarify whether small cell lung cancer (SCLC) cells express functional VEGF-Rs and VEGFs, and their biological significance in the SCLC progression. We examined expression of VEGF and VEGF-C, and their receptors, VEGFR-2 and VEGFR-3, in five SCLC cell lines, NCI-H82, H209, H510, H526 and H660, by Western blotting. We evaluated whether hypoxic conditions up-regulate these protein expressions. We also examined whether VEGF addition and VEGF-D addition cause phosphorylation of the mitogen-activated protein kinase (MAPK) as well as VEGFR-2 and VEGFR-3. Further, we investigated whether VEGF addition and VEGF-D addition induced the proliferation and migration of the SCLC cells. VEGF, VEGF-C, VEGFR-2 and VEGFR-3 were detectable by Western blotting in all five SCLC cell lines,. The VEGF-Rs and VEGFs expression levels were increased by an incubation under hypoxic conditions in NCI-H82. VEGF addition and VEGF-D addition caused phosphorylation of MAPK as well as the VEGF-Rs themselves, and induced proliferation and migration of the SCLC cells. These results suggested potential of VEGF signal-pathway inhibitors as anti-cancer agents in SCLC treatment disturbing growth and migration of the cancer cells.
Blotting, Western↗
Optimization of the uptake method for estimating renal clearance of 99mTc mercaptoacetyltriglycine.
OBJECTIVE: To improve the estimation of 99mTc mercaptoacetyltriglycine clearance in the renal uptake method by optimizing the conditions of renal depth, background, threshold for renal boundary determination, and time interval for integrating renal counts. METHODS: Dynamic renal imaging was performed in 232 patients with dual energy window acquisition (main, 140 +/- 14keV; sub, 122.5 3.5keV). For drawing renal regions of interest (ROIs), cut-off methods with 50% and 70% of the highest renal pixel counts were used. For drawing the backgrounds, circumferential and lateral-inferior quadrant peri-renal ROIs were used. For setting the time interval, periods of 1-2, 1-2.5, 1.5-2.5, 1.5-3 and 2-3 min post-injection were used. For determining renal depth, three methods of a theoretical exponential function using scatter fraction, Tønnesen's formula, and linear combination of scatter fraction and Tønnesen's formula were used. The scatter fraction was calculated using the counts in renal ROIs in the two energy windows. Using every combination of these conditions, renal uptake was calculated. As a reference, one-sample clearance was calculated from a blood sample taken at 30 min post-injection following Bubeck's formula. According to the methods for estimating renal depth, three non-linear regression models were derived to convert renal uptake to clearance. Using one-sample clearance and integrated renal counts as dependent and independent variables, data were fitted to the models to determine the necessary constants. The correlations between the model estimated clearances and one-sample clearance were investigated. RESULTS: One-sample clearance ranged from 11 to 404 ml x min(-1) per 1.73 m2. More than half of the regression using renal depth determined by the scatter fraction alone failed to converge. Among the successfully converged regressions, all model estimated clearances showed significant correlations (P<0.01) with one-sample clearance. The best correlation was observed in the model using renal depth determined by the combination of scatter fraction and Tønnesen's formulas, renal ROIs by 50% cut-off, lateral-inferior background and time interval of 2-3 min (r=0.898, P<0.001). CONCLUSION: The renal uptake method for estimating the clearance of mercaptoacetyltriglycine can be improved by the processing conditions proposed here.
Adolescent↗
An overview of regular dialysis treatment in Japan (as of 31 December 2001).
Questionnaire forms for an annual survey conducted at the end of 2001 were sent out to 3520 institutions, and 3485 replies were received (response rate, 99.00%). According to the survey, the dialysis population of Japan at year end was 219 183 patients, up 6.3% (13 049) over the year before. This equals 1721.9 dialysis patients per million population. The gross mortality rate was 9.3% for the year extending from the end of 2000 to the end of 2001. The mean age of patients beginning dialysis was 64.2 years (+/- 13.7 SD). The mean age of the overall dialysis population in the study year was 61.6 years (+/- 13.1 SD), which was also a higher age than the year before. Among dialysis patients, the primary disease was diabetic nephropathy in 38.1% of patients, slightly down from 39.1% the previous year. Chronic glomerulonephritis was the primary disease in 32.4% of cases, a decrease from 34.7% the previous year. This survey included for the first time the items of the lowest blood pressure during hemodialysis session, vasopressor therapy before dialysis and vasopressor therapy during dialysis session. An analysis of the relationship between the type of vascular access used at the initiation of dialysis and the survival prognosis revealed a significantly higher risk of death in patients undergoing dialysis with synthetic arterio-venous (AV) fistula, AV shunt, or catheter implantation into a central vein than in those receiving dialysis treatments with a native fistula. There was a significantly lower risk of death in the patient group in whom the vascular access was created at 3-6 months before initiation of dialysis than in those in whom such access was created at the time of initiation or within 3 months before the initiation of dialysis. An analysis of the risk factors affecting survival prognosis in maintenance hemodialysis patients showed that risk factors for death are post-dialysis systolic blood pressure over 180 mm Hg and lower than 120 mm Hg, blood pressure elevating progressively from the start to the end of dialysis, serum high density lipoprotein cholesterol concentration of less than 30 mg/dL, and a higher ultrafiltration rate. In comparisons of the death risk between the patient group with a history of intervention for ischemic heart disease and the patient group with a history of myocardial infarction or heart failure but without such intervention, among diabetes patients, those who underwent percutaneous transluminal coronary angioplasty had a significantly lower risk of death than those in whom no intervention was made.
Adolescent↗
Decreased susceptibility to renovascular hypertension in mice lacking the prostaglandin I2 receptor IP.
Persistent reduction of renal perfusion pressure induces renovascular hypertension by activating the renin-angiotensin-aldosterone system; however, the sensing mechanism remains elusive. Here we investigated the role of PGI2 in renovascular hypertension in vivo, employing mice lacking the PGI2 receptor (IP-/- mice). In WT mice with a two-kidney, one-clip model of renovascular hypertension, the BP was significantly elevated. The increase in BP in IP-/- mice, however, was significantly lower than that in WT mice. Similarly, the increases in plasma renin activity, renal renin mRNA, and plasma aldosterone in response to renal artery stenosis were all significantly lower in IP-/- mice than in WT mice. All these parameters were measured in mice lacking the four PGE2 receptor subtypes individually, and we found that these mice had similar responses to WT mice. PGI2 is produced by COX-2 and a selective inhibitor of this enzyme, SC-58125, also significantly reduced the increases in plasma renin activity and renin mRNA expression in WT mice with renal artery stenosis, but these effects were absent in IP-/- mice. When the renin-angiotensin-aldosterone system was activated by salt depletion, SC-58125 blunted the response in WT mice but not in IP-/- mice. These results indicate that PGI2 derived from COX-2 plays a critical role in regulating the release of renin and consequently renovascular hypertension in vivo.
Animals↗
Transient swelling of peripheral nerves in a case of neurosarcoidosis.
We present a case of neurosarcoidosis showing bilateral carpal tunnel syndrome which disappeared without any medication. This patient was also suffering from motor and sensory disturbance caused by peripheral neuropathy of the four extremities. Magnetic resonance image showed transient swelling of the median nerve, and subperineurial edema was unexpectedly observed in some fascicles in sural nerve biopsy. We hypothesize that the carpal tunnel syndrome in this case was induced by the intercanal high pressure due to edema inside the tunnel, which might be related to the high level of serum IL-2.
Aged↗
[Myocardial infarction in patients with hypertension].
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Adrenergic beta-Antagonists↗
[Symptoms in asthmatics living in cold districts during winter].
Exposure to cold is known as a potential exacerbating factor in asthmatics. However, few studies have investigated severity of symptoms during daily life in winter for asthmatics living in northern Hokkaido, the coldest region in Japan. We sent questionnaires to 126 asthmatics living in northern Hokkaido, and obtained answers from 116 patients (52 males, 64 females). Breathing difficulties during cold-air exposure were reported by 62.1% of patients. Furthermore, 19.6% of patients had experienced the need for bronchodilators following cold-air-induced attacks. Limitations to daily life in winter caused by exacerbated asthmatic symptoms were recognized by 48.3% of patients. Asthmatic exacerbation was experienced by 30% of patients in summer (May to August), compared to >35% in winter (September to April). No significant differences in results were noted between atopic and non-atopic patients. Improvements in respiratory symptoms during winter are thus necessary for better quality of life in asthmatics living in cold districts.
Adult↗