Traditional Chinese medicine Jia Wei Gui Pi Tang improves behavioural and psychological symptoms of dementia and favourable positive emotions in patients.

BACKGROUND: Behavioural and psychological symptoms of dementia (BPSD) are challenging to manage, leading to caregiver burden and often to subsequent transfer of patients to a nursing home or psychiatric hospital for treatment. Eliciting favourable positive emotions should be an important goal in the treatment of negative emotions associated with BPSD. To date, no data have indicated that antipsychotic medications can improve positive emotions. BPSD are known to be associated with anxiety in patients with dementia. The traditional Chinese medicine Jia Wei Gui Pi Tang is officially indicated and approved for anxiety treatment in Japan. METHODS: Here, we performed a multicentre, randomised, observer-blind control study of the effect of Jia Wei Gui Pi Tang on BPSD in Alzheimer's disease (AD) patients. Patients with AD or AD with cerebral vascular disease were randomly divided into the Jia Wei Gui Pi Tang treatment group and the control group that received no traditional Chinese medicine. BPSD were scored using the Neuropsychiatric Inventory Nursing Home Version (NPI-NH) and by favourable positive emotions using the Delightful Emotional Index (DEI). RESULTS: A total of 63 participants (18 male and 45 female; mean age: 83.3 ± 6.0 years) were included in the study. Changes in NPI-NH scores differed significantly between the two groups (one-way analysis of variance, P < 0.001). Within the treatment group, there was a significant improvement in the NPI-NH score from 29.8 ± 17.3 at baseline to 13.2 ± 9.4 at the endpoint (paired t-test, P < 0.001), whereas there was no statistically significant change in the control group. Changes in DEI scores differed significantly between the two groups. Within the treatment group, there was a significant improvement in the DEI score from 24.3 ± 23.0 at baseline to 32.5 ± 21.2 at the endpoint (paired t-test, P = 0.001), whereas there was no statistically significant change in the control group. CONCLUSION: The traditional Chinese medicine Jia Wei Gui Pi Tang significantly improved both BPSD and positive emotions.

Dramatic Performance by a Professional Actor for the Treatment of Patients with Behavioral and Psychological Symptoms of Dementia.

Behavioral and psychological symptoms of dementia (BPSD) challenge caregivers, leading to caregiver burden and subsequent nursing home or inpatient placement in a psychiatric hospital for dementia. Favorable positive emotions should be an important goal for the treatment of negative emotions of BPSD. Arts are one of the most profound areas to stimulate favorable emotions. We have asked a professional actor, who was not involved in the daily care and regular rehabilitations, to give a dramatic performance by reading selected stories as if the patients with BPSD felt to be in the audiences of a theater. We wondered whether a dramatic performance by the actor might be a way to respond to the complex needs of inpatients with BPSD, especially focused on favorable emotions. New inpatients (Alzheimer's disease, vascular dementia, or dementia with Lewy bodies) were randomly assigned to a control group (n = 20) and a dramatic performance group (n = 14) in Sendai Tomizawa Hospital, a psychiatric hospital for dementia, in Japan. Dramatic performances were performed for one and half hours once per week for 3 months. Neuropsychiatric Inventory for BPSD decreased in both groups and delightful emotional index (DEI) for favorable emotions increased in the intervention group but not in the control group after 3 months. At 3 months, there was an increase of DEI in intervention group compared with control group. We conclude that dramatic performance may be one of the appropriate interventions in patients with BPSD, as it appears to help in their favorable emotional state.

Antipsychotic drug use and favourable natures of emotional functions in patients with dementia.

AIM: To characterise the effects of antipsychotics on brain functions of patients with behavioural psychological symptoms of dementia (BPSD). METHODS: Studies were performed during 6 weeks of intervention with either a nonantipsychotic drug (group A, n = 38) or an antipsychotic drug (group B, n = 10). RESULTS: Neuropsychiatric Inventory scores were significantly decreased in both groups. Scores on the Mini-Mental State Examination did not change with intervention. By contrast, favourable natures of emotional functions, scored using the Delightful Emotional Index of 10 items, were significantly lower in the antipsychotic drug treatment group B relative to scores in the nonantipsychotic drug treatment group A. CONCLUSIONS: Antipsychotics reduce favourite emotions as well as BPSD, and this should be considered in prescribing medications for patients with dementia.

Emotional function in dementia patients.

Behavioural and psychological symptoms of dementia, which can be considered as hyperreactivity of the emotional functioning of dementia, can be alleviated or aggravated by the behavioural and psychological symptoms of the caregiver. Comfortable stimulations of emotional function through sensory stimulations are effective methods for alleviating behavioural and psychological symptoms of dementia. Although cognitive function deteriorates with age, emotional function is often retained even in advanced years. Thus, it is recommended that care in patients with dementia be focused mainly on the stimulation of emotional function (e.g. sympathy and empathy, which are human traits), rather than relying solely on the stimulation of cognitive function.

Exhaled carbon monoxide levels in preschool-age children with episodic asthma.

BACKGROUND: The concentration of exhaled carbon monoxide (eCO) in young children with stable asthma and during acute asthma attack is not known. METHODS: A sampling bag was developed to collect the exhaled air of preschool children. A total of 257 preschool-age children (≥ 3 years and ≤ 6 years old) were studied; 111 had a diagnosis of asthma (43 suffering a mild asthma attack and 68 without active asthmatic symptom), 99 had upper respiratory infection (URI) and 47 were healthy. RESULTS: In preschool-age children, eCO levels of those with asthma attacks (mean ± SE, 2.7 ± 0.3 p.p.m., n= 43) were significantly higher than those of subjects with asymptomatic asthma (0.5 ± 0.1 p.p.m., P < 0.05), URI (0.8 ± 0.1 p.p.m., P < 0.05) and healthy children (0.4 ± 0.1 p.p.m., P < 0.05). A multivariate linear regression model showed that eCO was higher in children with asthma attacks independent of age and gender. In 33 asthmatic children followed before and after treatment, eCO levels during asthma attacks significantly decreased after inhalation therapy with a combination of salbutamol and sodium cromoglycate (before therapy, 2.9 ± 0.4 p.p.m.; after therapy, 0.6 ± 0.1 p.p.m., P < 0.0001). CONCLUSIONS: The measurement of eCO using a novel collecting system is useful in the recognition of asthma in preschool children.

New lessons of nurturing life for geriatric patients.

Our new lessons of nurturing life to make happiness and well-being of geriatric patients suggest comprise several important steps. First, geriatric patient care should not be delegated to specialists who focus on individual organ system. Instead, we should respond to the patient's condition based on comprehensive assessment to identify the single pathogenesis. Second, we should appreciate that the behavioral and psychological symptoms of dementia (BPSD) often reflect the behavioral and psychological symptoms of the caregiver (BPSC), and in particular the caregiver's attitude. Third, pleasant stimulations to the limbic system should receive more emphasis than attempting brain training in atrophied portions of the neocortex. Fourth, we should aim not for "successful aging," but for "balanced aging." Fifth, we should rely less on drug-based therapy and utilize more non-pharmacologic approaches to appropriate therapy. Geriatric patients should be cared for based on our new lessons of nurturing life rather than the heavily medicalized treatment modalities that are in wide use today.

Toe Clearance Rehabilitative Slippers for Older Adults With Fall Risk: A Randomized Controlled Trial.

INTRODUCTION: To evaluate fall-prevention rehabilitative slippers for use by self-caring, independent older adults. MATERIALS AND METHODS: This assessor-blinded, randomized, and controlled 1-year study included 59 self-caring, independent participants (49 women) who attended day services. The mean age of participants was 84.0 ± 5.3 years. Participants were randomly selected from 8 nursing homes. We tested slippers top-weighted with a lead bead (200, 300, or 400 g). Intervention group participants walked while wearing the slippers for 10-20 min, 1-3 days/week at the day service center. Fall risk was measured using the Berg Balance Scale and the Tinetti Performance-Oriented Mobility Assessment (POMA) before and at 3-month intervals after the intervention/control phase. RESULTS: After 12 months, the intervention group demonstrated significant improvement. Berg Balance and POMA compared to the control group (p < .05 p < .01, respectively). Mobility scores improved significantly for both measurements in the intervention group before and after (p < .01), but the control group had significantly lower scores. DISCUSSION: Overall, falls decreased in the intervention group from 10 to 7, and control group falls increased from 9 to 16 (p = .02). No adverse events related to the intervention were reported. CONCLUSIONS: Rehabilitation training slippers may reduce falls in older adults.

Erythromycin attenuates MUC5AC synthesis and secretion in cultured human tracheal cells infected with RV14.

BACKGROUND AND OBJECTIVE: The common cold is a major cause of asthma exacerbation and chronic obstructive lung disease. Rhinovirus is reported to be responsible for more than 50% of cases of the common cold. In a previous study, we reported that rhinovirus infection of cultured airway cells induced MUC5AC mucin overproduction and hypersecretion by activating the p44/42 mitogen-activated protein kinase (p44/42 MAPK) pathway. The aim of this study was to examine the effect of erythromycin on RV14-induced airway mucin overproduction and hypersecretion. METHODS: RV14-infected human tracheal epithelial cells were treated with erythromycin. RESULTS: Erythromycin blocked RV14-induced MUC5AC protein overproduction and hypersecretion, and also blocked RV14-induced p44/42 MAPK activation in the cells. CONCLUSIONS: Erythromycin may attenuate RV14-induced MUC5AC overproduction and hypersecretion by blocking the p44/42 MAPK pathway or its upstream regulators.

Submucosal gland cells in human lower airways produce MUC5AC protein.

BACKGROUND AND OBJECTIVE: It is now considered that the major component of mucus, MUC5AC, is mainly produced by goblet cells but not submucosal glands, and the role of the submucosal glands in the production of MUC5AC is unclear. The aim of this study was to clarify whether human submucosal glands produce MUC5AC. METHODS: Immunohistochemical analysis with MUC5AC antibody of lower airways resected from six lung cancer patients and three patients with acute myocardial infarction was performed. RESULTS: The submucosal glands contained both MUC5AC-positive cells and non-positive cells. CONCLUSIONS: These data suggest that MUC5AC protein is produced in both goblet cells and in airway submucosal glands.

Signal-transducing adaptor molecules STAM1 and STAM2 are required for T-cell development and survival.

We previously reported that the STAM family members STAM1 and STAM2 are phosphorylated on tyrosine upon stimulation with cytokines through the gammac-Jak3 signaling pathway, which is essential for T-cell development. Mice with targeted mutations in either STAM1 or STAM2 show no abnormality in T-cell development, and mice with double mutations for STAM1 and STAM2 are embryonically lethal; therefore, here we generated mice with T-cell-specific double mutations for STAM1 and STAM2 using the Cre/loxP system. These STAM1(-/-) STAM2(-/-) mice showed a significant reduction in thymocytes and a profound reduction in peripheral mature T cells. In proliferation assays, thymocytes derived from the double mutant mice showed a defective response to T-cell-receptor (TCR) stimulation by antibodies and/or cytokines, interleukin-2 (IL-2) and IL-7. However, signaling events downstream of receptors for IL-2 and IL-7, such as activations of STAT5, extracellular signal-regulated kinase (ERK), and protein kinase B (PKB)/Akt, and c-myc induction, were normal in the double mutant thymocytes. Upon TCR-mediated stimulation, prolonged activations of p38 mitogen-activated protein kinase and Jun N-terminal protein kinase were seen, but activations of ERK, PKB/Akt, and intracellular calcium flux were normal in the double mutant thymocytes. When the cell viability of cultured thymocytes was assessed, the double mutant thymocytes died more quickly than controls. These results demonstrate that the STAMs are indispensably involved in T-cell development and survival in the thymus through the prevention of apoptosis but are dispensable for the proximal signaling of TCR and cytokine receptors.

Nitroglycerin treatment may enhance chemosensitivity to docetaxel and carboplatin in patients with lung adenocarcinoma.

PURPOSE: Nitroglycerin may improve the response to chemotherapy in advanced non-small cell lung cancer. The effects and mechanisms of nitroglycerin on the enhancement of chemosensitivity to docetaxel and carboplatin regimen (DCb) in patients with lung adenocarcinoma have not been reported. EXPERIMENTAL DESIGN: Seventeen patients with operable lung adenocarcinoma and stable angina pectoris were selected to investigate the effects of nitroglycerin on immunoreactivity for hypoxia-inducible factor 1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF), P-glycoprotein (P-gp), the production of which is regulated by HIF-1, and p53 proteins in their resected tumor by semiquantitative immunohistochemical analyses. Eight of 17 patients were treated with nitroglycerin patches before operation, but 9 of 17 patients were not. Furthermore, to study the relationship between changes in plasma VEGF levels by nitroglycerin treatment and response to DCb, 29 patients with advanced lung adenocarcinoma were treated with nitroglycerin for 3 days before chemotherapy using DCb. RESULTS: The rates of immunoreactive cells for HIF-1alpha, VEGF, and P-gp in tumor tissues treated with nitroglycerin were lower than those without nitroglycerin, but those for p53 were not different between those treated with and without nitroglycerin. Furthermore, the rates of immunoreactive cells for VEGF and P-gp proteins were significantly associated with those for HIF-1alpha in tumor tissue. The magnitude of decrease in plasma VEGF levels after treatment with nitroglycerin was significantly associated with response to DCb in patients with advanced lung adenocarcinoma. CONCLUSIONS: Nitroglycerin treatment may improve response to DCb in patients with lung adenocarcinoma, partly through decreasing VEGF and P-gp production via reduction of HIF-1alpha.

[The benefit of angiotensin converting enzyme inhibitor for geriatric syndrome in the elderly].

Angiotensin converting enzyme (ACE) inhibitor plays an important role not only as an antihypertensive drug but also for prevention of various complications related to geriatric syndrome. Pneumonia in the disabled elderly is mostly due to silent aspiration of oropharyngeal bacterial pathogens to the lower respiratory tract. Aspiration is related to the dysfunction of dopaminergic neurons by cerebrovascular disease, resulting in impairments in both the swallowing and cough reflexes. ACE inhibitor can increase in the sensitivity of the cough reflex particularly in older post-menopausal women, and improvement of the swallowing reflex. In a 2-year follow-up study in stroke patients, patients who did not receive ACE inhibitors had a higher risk of mortality due to pneumonia than in stroke patients who were treated with ACE inhibitor. Moreover, the mortality of pneumonia was significantly lower in older hypertensive patients given ACE inhibitors than in those treated with other antihypertensive drugs. On the other hand, we found a new benefit of ACE inhibitor on the central nervous system. The mortality in Alzheimer's disease patients who received brain-penetrating ACE inhibitor was lower than in those who received other antihypertensive drugs. In a 1-year follow-up study, cognitive decline was lower in patients receiving brain-penetrating ACE inhibitors than in patients receiving a non-brain-penetrating ACE inhibitor or a calcium channel blocker. Brain-penetrating ACE inhibitors may slow cognitive decline in patients with mild to moderate Alzheimer's disease. ACE inhibitor might be effective for the disabled elderly, resulting in the prevention of aspiration pneumonia and Alzheimer's disease for the elderly.

A randomized trial of olfactory stimulation using black pepper oil in older people with swallowing dysfunction.

OBJECTIVES: To determine the effect of olfactory stimulation with volatile black pepper oil (BPO) on risk factors for pneumonia. DESIGN: A 1-month randomized, controlled study. SETTING: Nursing homes in Japan that serve as long-term care facilities for older residents who are physically handicapped, mainly because of cerebrovascular disease. PARTICIPANTS: One hundred five poststroke residents. MEASUREMENTS: Latency of the swallowing reflex (LTSR), the number of swallowing movements, serum substance P (SP), and regional cerebral blood flow (rCBF). RESULTS: Nasal inhalation of BPO for 1 minute shortened LTSR, compared with that of lavender oil and distilled water (P < .03). Compared with the period before the study, the 1-month intervention using BPO improved LTSR with an increase of serum SP (P < .01). The number of swallowing movements for 1 minute during the nasal inhalation of BPO increased (P < .001). Multiple comparisons showed a poststudy increase in rCBF within the insular cortex (P < .001). Compared with the prestudy rCBF, BPO intervention increased rCBF in the right orbitofrontal and left insular cortex (P < .001). CONCLUSION: Inhalation of BPO, which can activate the insular or orbitofrontal cortex, resulting in improvement of the reflexive swallowing movement, might benefit older poststroke patients with dysphagia regardless of their level of consciousness or physical and mental status.

Exhaled carbon monoxide levels in school-age children with episodic asthma.

Carbon monoxide (CO) can be detected in exhaled air and is increased in adult and childhood persistent asthmatic patients. However, little is known about the exhaled CO concentration in episodic childhood asthma. This study aimed to clarify whether measurement of exhaled CO is useful in monitoring disease activity in children with episodic asthma. We measured exhaled CO concentration by modified Micro-Smokerlyzer in 217 elementary school children (132 boys; mean age, 10 +/- 1 (SE) years; range, 9-12 years), in whom 29 had infrequent episodic asthma without current exacerbations. We also measured exhaled CO concentrations in 22 children with episodic asthma (13 boys; mean age, 10 +/- 3 years; range, 8-12 years), who had acute mild asthmatic attacks during examination. In these patients with mild asthmatic attacks, exhaled CO was measured both before and after combination therapy with salbutamol and sodium cromoglycate (SCG) by powered nebulizer. Among 217 schoolchildren, exhaled CO levels in infrequent episodic asthmatic children (1.1 +/- 0.1 parts per million (ppm), n = 29) were not significantly different from those in healthy schoolchildren (1.0 +/- 0.1 ppm, n = 188, P > 0.68). The exhaled CO concentrations during asthma attacks in children with episodic asthma were significantly higher (5.1 +/- 0.4 ppm, n = 22) compared with those in healthy children (P < 0.001) or those in asymptomatic asthmatic children (P < 0.001). The elevated exhaled CO levels were significantly decreased after inhalation therapy of a combination of salbutamol and SCG (3.2 +/- 0.5 ppm, n = 22, P < 0.02). In conclusion, exhaled CO levels were significantly elevated during acute asthma exacerbations, and partially recovered after treatment with beta(2)-agonist and SCG in children with mild episodic asthma. These findings indicate that measurement of exhaled CO might provide another noninvasive measurement of asthma exacerbations that would be suitable for use in children with acute mild episodic asthma.

Mechanisms of mucin production by rhinovirus infection in cultured human airway epithelial cells.

Mucus hypersecretion relates to exacerbations of bronchial asthma and chronic obstructive pulmonary disease (COPD) caused by rhinovirus (RV) infection. We examined the mechanisms of RV infection-induced mucin production in human tracheal surface epithelial cells and submucosal gland cells. RV14 up-regulated the mRNA expression of MUC2, MUC3, MUC5AC, MUC5B and MUC6, and increased MUC5AC and total mucin concentration in supernatants and lysates of the surface cells. An inhibitor of the nuclear factor kappaB caffeic acid phenylethyl ester, inhibitors of selective p44/42 mitogen-activated protein kinase-kinase PD98059 and U0126, and a selective Src inhibitor PP1 attenuated MUC5AC mRNA expression, and secretion and production of MUC5AC and total mucin glycoprotein in the surface cells. In the gland cells, RV14 also increased mRNA expression of MUC2, MUC5AC, MUC5B and MUC7, and the inhibitors attenuated the secretion of total mucin glycoprotein. Src-related p44/42 mitogen-activated protein kinase pathway may be associated with RV-induced mucin hypersecretion in human airways.