Support to prevent older people from becoming housebound through mutual aid among residents: a qualitative study.

BACKGROUND: As Japan faces super-aging of the population and a declining birthrate, the shortage of caregivers for older people who require support in the country and a decrease in their quality of life, have become prominent issues. The Ministry of Health, Labour and Welfare recommends mutual aid among local residents in providing such support. AIMS: To qualitatively analyse issues at hand with a focus on individual visits by welfare commissioners as part of the support to promote early detection and prevention of houseboundness in older people through mutual aid among residents. METHODS: Semi-structured interviews with welfare commissioners in two cities were conducted and and analysed. FINDINGS: Among issues faced during individual visits by welfare commissioners, six categories were identified as problems. CONCLUSION: Welfare commissioners conduct individual visits to provide psychological support for older people who are housebound, including those who refuse to participate in group settings. Our findings highlight the need to revive the community structure that previously existed in Japan, in which residents of all ages are acquainted with each other, and to assist in efforts to support older people through mutual aid among residents.

A coaching program to improve quality of life in older people in Japan: a randomised controlled trial.

As the world's population ages, efforts to improve quality of life (QOL) in old age are gaining public attention. In this study, a programme was conducted for older people with the aim of clarifying their life goals related to QOL and the meaning of their existence, and the effect of the programme in improving QOL was evaluated. Participants were randomly assigned to the intervention or control group after registration. The program consisted of four 90-minute classes. The primary outcome was the Philadelphia Geriatric Center Morale Scale score (PGC), and changes in outcomes were compared between groups. The intervention group had significantly improved PGC scores (P<0.003). Further, the scores of PGC subscales 'Acceptance of one's own ageing' and 'Lonely dissatisfaction' showed significant improvements after the intervention (P<0.001). The findings suggest the effectiveness of the developed program in improving QOL in people aged ≥65 years.

The effects of coaching on salivary cortisol stress marker in mothers with young children, a randomized controlled trial.

OBJECTIVES: The purpose of this study was to evaluate the effects of a coaching program on saliva cortisol sensitivity in normal healthy mothers with young children. METHODS: A randomized controlled trial (RCT) was conducted with objective and subjective outcome measurements of the stress indicator. A postal survey to assess emotional intelligence (EI) was administered by random sampling to mothers of young children aged 3 months to 6 years in Japan. A total of 74 mothers with median EI scores or lower were enrolled in a RCT involving the coaching program. The intervention group received a 3-month coaching program. The control group was given the coaching program at follow-up. Stress state outcomes (saliva cortisol level, EI score, and Profile of Mood States (POMS)) were measured at baseline and immediate follow-up, with salivary cortisol measured again at a one-month follow-up. RESULTS: Significant differences were found for saliva cortisol level and the EI score within and between the intervention and control groups. Some POMS subscale scores were significantly different within the intervention and control groups. CONCLUSION: The participants in the coaching program had significantly reduced saliva cortisol levels and better secondary outcomes than those in the control group.

An Analytical Model / Emotional Intelligence Quotient and QOL in Mothers with Infants in Japan.

OBJECTIVE: The purpose of this study was to examine the relationship between the emotional intelligence quotient and health-related quality of life using structural equation modeling. METHODS: A self-administered questionnaire survey was conducted among 1,911 mothers who visited the Health Center for an infant medical examination. A hypothetical model was constructed using variables of the emotional intelligence quotient, social support, coping, parenting stress, and perceived health competence. RESULT: There were a total of 1,104 valid responses (57.8%). Significant standardized estimates were obtained, confirming the goodness of fit issues with the model. The emotional intelligence quotient had a strong impact on physical and psychological quality of life, and showed the greatest association with coping. This study differed from previous studies in that, due to the inclusion of social support and explanatory variables in coping, an increase in coping strategies was more highly associated with emotional intelligence quotient levels than with social support. CONCLUSION: An enhanced emotional intelligence quotient should be considered a primary objective to promote the health of mothers with infant children.

Anti-atherogenic effects of the combination therapy with olmesartan and azelnidipine in diabetic apolipoprotein E-deficient mice.

Many studies have aimed to identify anti-atherogenic agents in cardiovascular medicine. We have recently demonstrated that the combination therapy with olmesartan (OLM), an angiotensin II receptor blocker, and azelnidipine (AZL), a dihydroprydine calcium-channel blocker, improves endothelial function in diabetic Apolipoprotein-deficient (ApoE(-/-)) mice. In the present study, we examined whether this combination therapy also inhibits atherosclerosis in mice. We used male control and streptozocin-induced diabetic ApoE(-/-) mice. Diabetic ApoE(-/-) mice were orally treated for 5 weeks with vehicle (Untreated), OLM (30 mg/kg/day), AZL (10 mg/kg/day), their combination (OLM+AZL), or hydralazine (HYD, 5 mg/kg/day) as an antihypertensive control. At 5 weeks, systolic blood pressure was significantly elevated in Untreated but was normalized in OLM+AZL and HYD. The atherosclerosis area in the thoracic aorta, perivascular fibrosis and medial thickness of the coronary arteries were increased in Untreated and were ameliorated in OLM+AZL but not in HYD. Staining with a fluorescent probe dihydroethidium showed that production of reactive oxygen species was increased in Untreated, and ameliorated in OLM+AZL. Consistent with these findings, macrophage infiltration in the kidney and the expression of receptor for advanced glycation end-products in the heart, kidney and liver were increased in Untreated and were all ameliorated in OLM+AZL, associated with up-regulation of endothelial NO syntheses (eNOS). In conclusion, the combination therapy with OLM and AZL exerts anti-atherogenic effect in diabetic ApoE(-/-) mice through suppression of oxidative stress and activation of eNOS, independent of its blood pressure-lowering effects. Clinically, this combination therapy may be useful for patients with hypertension, hyperlipidemia and diabetes.

Essential role of bone marrow for microvascular endothelial and metabolic functions in mice.

RATIONALE: We have previously demonstrated that the importance of endothelium-derived hyperpolarizing factor (EDHF) increases as the vessel size decreases and that endothelium-derived hydrogen peroxide (H(2)O(2)) is an EDHF in animals and humans, for which endothelial nitric oxide synthase (eNOS) is the major source. Recent studies have suggested the important role of the bone marrow (BM) in modulating cardiovascular and metabolic functions. OBJECTIVE: We aimed to examine whether BM plays a role in modulating microvascular endothelial and metabolic functions in mice, and if so, to elucidate the mechanisms involved. METHODS AND RESULTS: Male eNOS(-/-) mice were transplanted with BM cells from wild-type (WT) or eNOS(-/-) mice and were maintained for 6 weeks. Endothelium-dependent relaxations and hyperpolarizations of mesenteric arteries to acetylcholine were reduced in eNOS(-/-) mice and were markedly improved when transplanted with WT-BM but not with eNOS(-/-)-BM. The enhanced component of endothelium-dependent relaxations was abolished by catalase, indicating that the improved responses were mediated by H(2)O(2). In contrast, no such beneficial effect was noted in the aorta. Reduced plasma adiponectin levels and impaired glucose tolerance in eNOS(-/-) mice were also improved by WT-BM transplantation. Neuronal nitric oxide synthase (nNOS) in mesenteric arteries of eNOS(-/-) mice was significantly upregulated only when transplanted with WT-BM. Importantly, the beneficial effects of WT-BM transplantation were absent in eNOS(-/-)/adiponectin(-/-) or eNOS(-/-)/nNOS(-/-) mice. CONCLUSIONS: These results provide the first evidence that BM plays an important role in modulating microvascular endothelial and metabolic functions, for which adiponectin and nNOS may be involved.

Mechanisms for enhanced endothelium-derived hyperpolarizing factor-mediated responses in microvessels in mice.

BACKGROUND: Endothelium-derived relaxing factors play an important role in cardiovascular homeostasis. Among them, endothelium-derived hyperpolarizing factor (EDHF) is important especially in microcirculation. It has previously been demonstrated that endothelium-derived hydrogen peroxide (H(2)O(2)) is an EDHF in animals and humans and that endothelial nitric oxide synthase (eNOS) plays diverse roles as a nitric oxide (NO) generating system in conduit arteries and as an EDHF/H(2)O(2) generating system in microvessels. As compared with NO-mediated responses, those by EDHF are resistant to atherosclerosis, contributing to the maintenance of cardiovascular homeostasis. The aim of this study is to elucidate the molecular mechanisms for enhanced EDHF-mediated responses in microvessels. METHODS AND RESULTS: This study used male wild-type mice and caveolin-1-deficient mice (caveolin-1(-/-) mice). In the endothelium, eNOS was functionally suppressed in mesenteric arteries (microvessels) compared with the aorta (conduit arteries), for which Ca(2+)/calmodulin-dependent protein kinase kinase ß (CaMKKß) and caveolin-1 are involved, as EDHF-mediated responses were inhibited by STO-609 (an inhibitor of CaMKKß) and in caveolin-1(-/-) mice, respectively. In vascular smooth muscle, relaxation responses to H(2)O(2) were enhanced through a protein kinase G1α (PKG1α)-mediated mechanism in mesenteric arteries compared with the aorta, as they were inhibited by Rp-8-Br-cGMPS (an inhibitor of PKG1α). CONCLUSIONS: These results indicate that CaMKKß, caveolin-1, and PKG1α are substantially involved in the mechanisms for the enhanced EDHF-mediated responses in microvessels in mice.

Report from J-PULSE multicenter registry of patients with shock-resistant out-of-hospital cardiac arrest treated with nifekalant hydrochloride.

BACKGROUND: Nifekalant hydrochloride (NIF) is an intravenous class-III antiarrhythmic agent that purely blocks the K(+)-channel without inhibiting ß-adrenergic receptors. The present study was designed to investigate the feasibility of NIF as a life-saving therapy for out-of-hospital ventricular fibrillation (VF). METHODS AND RESULTS: The Japanese Population-based Utstein-style study with basic and advanced Life Support Education study was a multi-center registry study with 4 participating institutes located at the northern urban area of Osaka, Japan. Eligible patients were those treated with NIF because of out-of-hospital VF refractory to 3 or more precordial shocks and intravenous epinephrine. Between February 2006 and February 2007, 17 patients were enrolled for the study. The time from a call for emergency medical service to the first shock was 12(6-26)min. The time from the first shock to the NIF administration was 25.5(9-264)min and the usage dose of NIF was 25(15-210)mg. When excluding 3 patients in whom percutaneous extracorporeal membrane oxygenation was applied before NIF administration, the rate of return of spontaneous circulation was 86% and the rate of admission alive to the hospital was 79%. One patient developed torsade de pointes. CONCLUSIONS: Intravenous administration of NIF seems to be feasible as a potential therapy for advanced cardiac life-support in patients with out-of-hospital VF, and therefore further study is warranted.

[Novel mechanism of vasodilatation].

Endothelium-derived hyperpolarizing factor (EDHF) plays an important role in modulating vascular tone. Although several candidates for EDHF have been proposed, we have demonstrated that endothelium-derived hydrogen peroxide(H2(0)2) is an EDHF in mouse and human mesenteric arteries and porcine coronary microvessels, which was subsequently confirmed by other investigators in human and canine coronary microvessels. We have also demonstrated that endothelial nitric oxide synthase (eNOS) is a major source of EDHF/H2(0)2, where Cu, Zn-SOD is involved. Furthermore, we showed that genetic disruption of all three NOS isoforms abolishes EDHF responses in mice and that endothelial NOSs system has diverse vasodilator functions depending on the vessel size, mainly contributing to EDHF/H2(0)2 responses in microvessels while serving as a NO-generating system in large arteries.

Combination therapy with olmesartan and azelnidipine improves EDHF-mediated responses in diabetic apolipoprotein E-deficient mice.

BACKGROUND: The endothelium modulates vascular tone by synthesizing and releasing several vasodilating factors, including vasodilator prostaglandins, nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). In the present study, we examined whether an angiotensin-receptor blocker, a calcium-channel blocker or their combination improved EDHF-mediated responses in diabetic apolipoprotein E-deficient (ApoE(-/-)) mice. METHODS AND RESULTS: We used male C57BL/6N (control) and streptozocin-induced diabetic ApoE(-/-) mice. The diabetic ApoE(-/-) mice were administered oral vehicle (untreated), olmesartan (OLM, 30 mgxkg(-1)xday(-1)), azelnidipine (AZL, 10 mgxkg(-1)xday(-1)), their combination (OLM + AZL), or hydralazine (HYD 5 mgxkg(-1)xday(-1)) for 5 weeks. In the untreated group, systolic blood pressure was significantly higher and both EDHF-mediated relaxation and endothelium-dependent hyperpolarization were markedly reduced as compared with the control group. Although EDHF-mediated relaxation was not significantly improved in the HYD, OLM and AZL groups, it was significantly improved in the OLM + AZL group, as was also the case with phosphorylation of Akt and endothelial NO synthase (eNOS). In contrast, the endothelium-independent relaxation response to sodium nitroprusside or NS-1619 (a direct opener of K(Ca) channels) was unaltered in any group. CONCLUSIONS: OLM + AZL may improve the severely impaired EDHF-mediated responses in diabetic ApoE(-/-) mice, in which activation of the endothelial Akt - eNOS pathway may be involved.

Evidence for Rho-kinase activation in patients with pulmonary arterial hypertension.

BACKGROUND: Direct evidence for Rho-kinase activation in patients with pulmonary hypertension (PH) is still lacking. METHODS AND RESULTS: Rho-kinase activity in circulating neutrophils was examined by determining the ratio of phosphorylated/total forms of myosin-binding subunit, a substrate of Rho-kinase, in 40 consecutive PH patients and 40 healthy controls. Next, Rho-kinase expression and activity was examined in isolated human lung tissues (5 patients with idiopathic pulmonary arterial hypertension [IPAH], 5 controls) and vascular reactivity of isolated small human pulmonary arteries in vitro (4 IPAH, 4 controls). Rho-kinase activity in circulating neutrophils was significantly increased in the PH patients overall compared with controls (P<0.0001). Significant correlations were noted between Rho-kinase activity and the severity and duration of PAH (all P<0.05). Rho-kinase expression and activity in isolated lung tissues also were significantly increased in the IPAH patients compared with the controls (both P<0.0001). Endothelium-dependent relaxation was markedly impaired and serotonin-induced contraction (in the absence of the endothelium) markedly enhanced in the PAH patients compared with the controls, and the hypercontraction to serotonin was abolished by hydroxyfasudil, a specific Rho-kinase inhibitor. CONCLUSIONS: These results provide the first direct evidence for Rho-kinase activation in patients with PAH, suggesting the therapeutic importance of Rho-kinase in the disorder.

Roles of endothelial oxidases in endothelium-derived hyperpolarizing factor responses in mice.

The endothelium synthesizes and releases several vasodilator substances, including prostacyclin, nitric oxide (NO), and endothelium-derived hyperpolarizing factor (EDHF). We have demonstrated that endothelium-derived hydrogen peroxide (H2O2) is an EDHF in animals and humans and that superoxide anions derived from endothelial nitric oxide synthases (NOSs) system are an important precursor for EDHF/H2O2 in mice. There are several intracellular sources of superoxide anions other than NOSs, including NAD(P)H oxidase, xanthine oxidase, lipoxygenase, and mitochondrial electron transport chain. In this study, we examined the possible role of endothelial oxidases other than NOSs in the EDHF-mediated responses. In angiotensin II-infused mice, both EDHF-mediated relaxations and hyperpolarizations to acetylcholine were significantly reduced, nitric oxide-mediated relaxations were rather enhanced, and vascular smooth muscle responses were preserved. Antihypertensive treatment normalized blood pressure but failed to improve EDHF-mediated responses in those mice. Acute inhibition of endothelial oxidases other than NOSs, including NAD(P)H oxidase, xanthine oxidase, lipoxygenase, or mitochondrial electron transport chain, had no inhibitory effects on EDHF-mediated responses. Furthermore, in p47phox-knockout mice, EDHF-mediated responses were unaltered. These results suggest that endothelial oxidases other than NOSs are not involved in EDHF/H2O2 responses in mice, suggesting a specific link between endothelial NOSs system and EDHF responses under physiological conditions.

Crucial role of nitric oxide synthases system in endothelium-dependent hyperpolarization in mice.

The endothelium plays an important role in maintaining vascular homeostasis by synthesizing and releasing several relaxing factors, such as prostacyclin, nitric oxide (NO), and endothelium-derived hyperpolarizing factor (EDHF). We have previously demonstrated in animals and humans that endothelium-derived hydrogen peroxide (H(2)O(2)) is an EDHF that is produced in part by endothelial NO synthase (eNOS). In this study, we show that genetic disruption of all three NOS isoforms (neuronal [nNOS], inducible [iNOS], and endothelial [eNOS]) abolishes EDHF responses in mice. The contribution of the NOS system to EDHF-mediated responses was examined in eNOS(-/-), n/eNOS(-/-), and n/i/eNOS(-/-) mice. EDHF-mediated relaxation and hyperpolarization in response to acetylcholine of mesenteric arteries were progressively reduced as the number of disrupted NOS genes increased, whereas vascular smooth muscle function was preserved. Loss of eNOS expression alone was compensated for by other NOS genes, and endothelial cell production of H(2)O(2) and EDHF-mediated responses were completely absent in n/i/eNOS(-/-) mice, even after antihypertensive treatment with hydralazine. NOS uncoupling was not involved, as modulation of tetrahydrobiopterin (BH(4)) synthesis had no effect on EDHF-mediated relaxation, and the BH(4)/dihydrobiopterin (BH(2)) ratio was comparable in mesenteric arteries and the aorta. These results provide the first evidence that EDHF-mediated responses are dependent on the NOSs system in mouse mesenteric arteries.

[Primary aldosteronism with ventricular fibrillation: a case report].

A 60-year-old female had sudden onset of syncope. The emergency service noticed that she suffered cardiopulmonary arrest (ventricular fibrillation: VF). After defibrillation in the ambulance, she was transported to our emergency department. Electrocardiography monitoring showed QT prolongation. Serum potassium level was extremely low at 1.8 mEq/l. Although potassium and lidocaine were administered, it was difficult to maintain appropriate electrolyte balance and prevent VF after admission, so temporary overdrive pacing was required. She was diagnosed as having primary aldosteronism after laboratory and imaging examinations. VF was otherwise uncontrollable so a cardioverter defibrillator was implanted on the 24th hospital day. Laparoscopic adrenalglandectomy was performed about 1 month later. After the surgery, serum potassium level remained at an appropriate level without medication. No severe neurological deficits were found at discharge from our hospital.

[Primary effusion lymphoma complicating cardiac tamponade: a case report].

A 76-year-old woman was admitted to our hospital because of exertional dyspnea and leg edema during the previous month. Her systolic blood pressure on admission was 80 mmHg with 12 mmHg of pulsus paradoxous, and her pulse rate was 110 beats/min. Chest radiography revealed marked cardiomegaly and echocardiography showed massive pericardial effusion mainly behind the left ventricle and collapse of the right ventricle. The initial diagnosis was pericardial tamponade. Pericardiocentesis and pericardial drainage revealed bloody pericardial effusion. After drainage, her vital signs improved and her symptoms immediately disappeared. The cytological analysis of the pericardial effusion revealed numerous lymphoma cells. Computed tomography of the neck, chest and abdomen showed no evidence of tumor masses, lymph node enlargement, or hepatosplenomegaly. Infectious disease, collagen disease and aortic dissection were excluded. The final diagnosis was primary effusion lymphoma. The prognosis of primary effusion lymphoma is generally unfavorable because it is frequently accompanied by immunodeficiency disease. However, there was no human immunodeficiency virus infection in this patient. Fortunately, the effect of chemotherapy was excellent and the patient is doing well 1 year after the diagnosis.

[Efficacy of percutaneous balloon pericardiotomy and intrapericardial instillation for the management of refractory pericardial effusion: a case report].

Percutaneous balloon pericardiotomy and intrapericardial instillation seemed to be less invasive and effective treatments for refractory pericardial effusion. A 65-year-old man who suffered from refractory pericardial effusion associated with gastric cancer and had been hospitalized three times for pericardiocentesis, complained of dyspnea at rest and visited our emergency room. Echocardiography showed a large amount of pericardial effusion all around the heart and signs of cardiac tamponade. Percutaneous balloon pericardiotomy was performed and pericardial effusion turned to pleural effusion. We performed left thoracocentesis. One week later, massive pericardial effusion localized only around the right heart appeared, and pericardiocentesis was performed again. After another month, pericardial effusion around right heart appeared again and intrapericardial instillation with OK-432 (Picibanil) was tried. After the procedure, the pericardial effusion did not increase, and he has had few symptoms for 2 months as an outpatient.

Prevention of life-threatening ventricular tachyarrhythmia by a novel and pure class-III agent, nifekalant hydrochloride.

Nifekalant hydrochloride (NIF) is a novel intravenous class-III antiarrhythmic agent with a pirimidinedione structure that purely blocks the K+ channel without inhibiting beta-adrenergic receptors. The authors investigated the efficacy of NIF for refractory ventricular tachycardia/fibrillation (VT/VF). They studied 30 patients treated with an intravenous infusion of NIF [ 26 men, 4 women; age: 63 +/- 17 (mean +/- SD) years] at a dose of 0.19 +/- 0.14 mg/kg body weight per hour. Sixteen were patients with acute coronary syndrome (ACS), and 14 were patients with chronic structural heart disease (Chr-HD). Amiodarone and sotalol had already been administered to 9 patients with Chr-HD before the administration of NIF. The QT and T peak-end (Tp-e) intervals were measured and corrected by Bazett's method (QTc, cTp-e). The left ventricular ejection fraction was depressed (28 +/- 9%). NIF was effective for preventing VT/VF without proarrhythmia and hemodynamic deterioration in 21 patients (70%; 12 with ACS; 9 with Chr-HD), but ineffective in 4 patients (all with Chr-HD). The QTc prolongation in the responders was more pronounced than in the nonresponders (25% +/- 15% versus 5% +/- 7% increase; P < 0.05). Proarrhythmic torsade de pointes (TdP) developed transiently in the remaining 5 patients in whom the cTp-e was markedly increased compared with that in the responders (93% +/- 49% versus 37% +/- 41% increase; P < 0.05). In conclusion, these findings indicate that the intravenous administration of NIF is useful in the emergent treatment of inhibiting drug-refractory VT/VF, although proarrhythmic TdP owing to an enhancement of transmural dispersion of repolarization needs to be taken into account.