Mosapride citrate prolongs survival in stroke patients with gastrostomy.
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Biomedical subjects
Publications and source records attributed to Satoru Ebihara.
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PURPOSE: To investigate the efficacy and safety of nitroglycerin plus vinorelbine and cisplatin in patients with previously untreated stage IIIB/IV non-small-cell lung cancer (NSCLC) as the experimental arm for the next phase III trial. PATIENTS AND METHODS: One hundred twenty patients with stage IIIB/IV NSCLC were randomly assigned to vinorelbine 25 mg/m2 on days 1 and 8 and cisplatin 80 mg/m2 on day 1, with transdermally applied nitroglycerin (25 mg/patient daily for 5 days; arm A) or with placebo patch (arm B) every 3 weeks for a maximum of four cycles in a double-blind and controlled trial. Primary efficacy end points were the best confirmed response rate and time to disease progression (TTP). RESULTS: The response rate in arm A (72%; 43 of 60 patients) was significantly higher than that for patients in arm B (42%; 25 of 60 patients; P < .001). Median TTP in arm A was longer than that in arm B (327 v 185 days). No severe adverse effect was recognized for either arm. The rate of grade 1 to 2 headache in arm A (30%; 18 of 60 patients) was significantly higher than that in arm B (2%; one of 60 patients; P < .001, chi(2) test). CONCLUSION: Use of nitroglycerin combined with vinorelbine and cisplatin may improve overall response and TTP in patients with stage IIIB/IV NSCLC. The arm A regimen is being evaluated in a large phase III trial.
We examined the association between dietary intakes and oxidative stress status in elderly Japanese. We analyzed cross-sectional data from a community-based Comprehensive Geriatric Assessment conducted in 2002. The subjects included 961 Japanese subjects aged 70 years or older who were non-daily antioxidant supplements users. We measured plasma total 8-iso-prostaglandin (PG)F(2alpha) concentrations, a measurable lipid peroxidation biomarker, using a specific enzyme immunoassay kit. Dietary intakes were assessed through a food frequency questionnaire. Subjects were divided into three groups according to their dietary intake frequencies. Logistic regression was applied to calculate the odds ratios (ORs) for being in the highest tertile of plasma 8-iso-PGF(2alpha) concentration. Frequent intake of orange or other citrus fruits, or persimmon, strawberry, or kiwi fruit was associated with lower plasma 8-iso-PGF(2alpha) concentrations, respectively. After adjustment for potential confounders, the ORs and 95% confidence intervals (CIs) for orange or other citrus fruits were 1.00 (reference), 0.66 (0.47, 0.92), and 0.58 (0.39, 0.87) (p for trend, 0.009). Intake of persimmon, strawberry, or kiwi fruit showed similar results. These associations were partly explained by vitamin C intake. Other dietary intakes had no association. Intake of fruits may have a beneficial effect against oxidative stress in elderly Japanese.
BACKGROUND: Although considerable experimental and animal evidence shows that green tea may possess potent activities of neuroprotection, neurorescue, and amyloid precursor protein processing that may lead to cognitive enhancement, no human data are available. OBJECTIVE: The objective was to examine the association between green tea consumption and cognitive function in humans. DESIGN: We analyzed cross-sectional data from a community-based Comprehensive Geriatric Assessment (CGA) conducted in 2002. The subjects were 1003 Japanese subjects aged > or =70 y. They completed a self-administered questionnaire that included questions about the frequency of green tea consumption. We evaluated cognitive function by using the Mini-Mental State Examination with cutoffs of <28, <26, and <24 and calculated multivariate-adjusted odds ratios (ORs) of cognitive impairment. RESULTS: Higher consumption of green tea was associated with a lower prevalence of cognitive impairment. At the <26 cutoff, after adjustment for potential confounders, the ORs for the cognitive impairment associated with different frequencies of green tea consumption were 1.00 (reference) for < or =3 cups/wk, 0.62 (95% CI: 0.33, 1.19) for 4-6 cups/wk or 1 cup/d, and 0.46 (95% CI: 0.30, 0.72) for > or =2 cups/d (P for trend = 0.0006). Corresponding ORs were 1.00 (reference), 0.60 (95% CI: 0.35, 1.02), and 0.87 (95% CI: 0.55, 1.38) (P for trend = 0.33) for black or oolong tea and 1.00 (reference), 1.16 (95% CI: 0.78, 1.73), and 1.03 (95% CI: 0.59, 1.80) (P for trend = 0.70) for coffee. The results were essentially the same at cutoffs of <28 and <24. CONCLUSION: A higher consumption of green tea is associated with a lower prevalence of cognitive impairment in humans.
AIMS: To investigate the effect of menthol on swallowing reflex sensitivity in elderly patients with dysphagia. METHODS AND RESULTS: The swallowing reflex sensitivity of institutionalized elderly patients was evaluated as a latent time of swallowing reflex (LTSR), induced by the injection of 1 ml solution into the pharynx. LTSR was significantly shortened in a concentration-dependent manner, from 13.8 s [95% confidence interval (CI) 11.1, 16.5] by distilled water to 9.4 s (95% CI 7.1. 11.8) by 10(-2)m menthol. CONCLUSION: Using menthol with elderly patients with dysphagia may improve the sensitivity of their swallowing reflex, resulting in prevention of aspiration pneumonia.
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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.
Recombinant granulocyte colony-stimulating factor (G-CSF) is used for cancer patients with myelosuppression induced by chemotherapy. G-CSF has been reported to progress tumor growth and angiogenesis, but the precise mechanism of tumor angiogenesis activated by G-CSF has not been fully clarified. N-terminal-mutated recombinant human G-CSF administration increased WBCs and neutrophils in peripheral blood and reduced bone marrow stromal cell-derived factor-1 in mice, indicating its biological relevance. Mice were inoculated with Lewis lung carcinoma cells (LLCs) or KLN205 cells and treated with G-CSF. G-CSF accelerated tumor growth and intratumoral vessel density, while it did not accelerate proliferation of LLCs, KLN205 cells or human umbilical vein endothelial cells in vitro. In the absence of tumors, G-CSF did not increase circulating cells that displayed phenotypic characteristics of endothelial progenitor cells (EPCs). In the presence of tumors, G-CSF increased circulating EPCs. In addition, G-CSF treatment increased immune suppressor and endothelial cell-differentiating Gr1+CD11b+ cells in tumor-bearing mice. We conclude that G-CSF promotes tumor growth by activating tumor angiogenesis via increasing circulating EPCs and Gr1+CD11b+ cells in cancer animal models.
Although M-CSF has been used for myelosuppression due to chemotherapy in patients with solid tumors, the effect of exogenous M-CSF on tumor angiogenesis has not been studied. In this study we showed that M-CSF has the ability to accelerate solid tumor growth by enhancing angiogenesis with a novel mechanism. M-CSF accelerated intratumoral vessel density in tumors inoculated into mice, although it did not accelerate the proliferation of malignant cells and cultured endothelial cells in vitro. In both the absence and the presence of tumors, M-CSF significantly increased the circulating cells that displayed phenotypic characteristics of endothelial progenitor cells in mice. Moreover, M-CSF treatment induced the systemic elevation of vascular endothelial growth factor (VEGF). VEGFR-2 kinase inhibitor significantly impaired the effect of M-CSF on tumor growth. In vivo, M-CSF increased VEGF mRNA expression in skeletal muscles. Even after treatment with carageenan and anti-CD11b mAb in mice, M-CSF increased VEGF production in skeletal muscles, suggesting that systemic VEGF elevation was attributed to skeletal muscle VEGF production. In vitro, M-CSF increased VEGF production and activated the Akt signaling pathway in C2C12 myotubes. These results suggest that M-CSF promotes tumor growth by increasing endothelial progenitor cells and activating angiogenesis, and the effects of M-CSF are largely based on the induction of systemic VEGF from skeletal muscles.
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RATIONALE: Exhaled carbon monoxide (CO) and arterial blood carboxyhemoglobin concentrations (Hb-CO) increase in inflammatory pulmonary diseases. OBJECTIVES: To study whether arterial Hb-CO is useful to monitor disease activity in patients with chronic obstructive pulmonary disease (COPD) who had stopped smoking. METHODS: We measured arterial Hb-CO, arteriovenous Hb-CO differences, and FEV1 in 58 patients with COPD and 61 ex-smoking control subjects. RESULTS: Arterial Hb-CO concentrations in patients at stable conditions were higher than those in control subjects (p < 0.0001). Furthermore, the Hb-CO concentrations in patients at the exacerbations (p < 0.0001) were higher than those at the stable conditions. Arterial Hb-CO concentrations in patients at stage III were higher than those in patients at stage II, and the Hb-CO concentrations in patients at stage IV were higher than those in patients at stage III at the stable conditions and exacerbations. Arterial Hb-CO correlated with exhaled CO in patients with COPD at stage II and stage III at the exacerbations. Arterial Hb-CO inversely correlated with the arterial blood partial oxygen pressure and FEV1. Arteriovenous Hb-CO differences in patients at the exacerbations did not differ from those in patients at stable conditions and from those in control subjects. Moreover, arterial Hb-CO correlated with serum C-reactive protein values and serum lipid peroxide concentrations. CONCLUSIONS: These findings suggest that increased arterial Hb-CO may relate to severity in patients with COPD because of lung and systemic inflammation and production of reactive oxygen species.
PURPOSE: To examine the association between body mass index (BMI) and the plasma level of a lipid peroxidation biomarker in a large sample of elderly healthy Asian population. This cross-sectional study included 1150 community-dwelling Japanese aged 70 years or older in 2002. METHODS: We measured the lipid peroxidation biomarker 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) using the ELISA method. We also measured the weight and height and calculated the BMI as weight (kg)/height (m)2. RESULTS: After adjustment for potential confounders, the mean +/- SE plasma 8-iso-PGF(2alpha) level was significantly higher in subjects with higher BMI: 21.1 +/- 0.8 pg/ml in those with BMI of 30.0 or more; 20.5 +/- 0.3 pg/ml in those with BMI between 25.0 and 29.9; 20.0 +/- 0.2 pg/ml in those with BMI between 18.5 and 24.9; and 19.0 +/- 0.7 pg/ml in those with BMI of less than 18.5 (p for trend = 0.011). CONCLUSIONS: Our results demonstrated that in the healthy Asian population, there was a modest but significant relationship between BMI and the plasma lipid peroxidation level.
Disseminated intravascular coagulation (DIC) is the most common complication of solid tumours. In this study, the effectiveness of three polysaccharide anticoagulants (PSAs), at therapeutic doses, at inhibiting solid tumour growth was investigated. Mice with tumour xenografts were subcutaneously injected with either unfractionated heparin (UFH; 200 units kg(-1) day(-1)), dalteparin (75 units kg(-1) day(-1)) or danaparoid (50 units kg(-1) day(-1)). At these concentrations, these PSAs are equieffective at inhibiting blood coagulation activated factor X. In mice with Lewis lung carcinoma (LLC) tumours dalteparin and, to a lesser extent, UFH inhibited both tumour growth and angiogenesis, whereas danaparoid did not. In contrast, in mice with KLN205 tumours, all the PSAs inhibited tumour growth and angiogenesis. All the PSAs significantly inhibited proliferation, migration of endothelial cells and vessel formation in matrigel plugs containing vascular endothelial growth factor (VEGF) and there were no significant differences between these effects of the PSAs. The PSAs had no effect on endothelial cell tubular formation in vitro. Although all the PSAs inhibited VEGF production in KLN205 tumours in vivo and cells in vitro, in LLC tumours and cells only UFH and dalteparin inhibited VEGF production, whereas danaparoid did not. In both LLC and KLN205 tumours in vivo, heparanase activity was inhibited by UFH and dalteparin, but not by danaparoid. Hence, UFH and dalteparin may be more effective than danaparoid at inhibiting cancer progression in DIC patients with solid tumours, due at least in part to their ability to suppress VEGF and heparanase in tumours.
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OBJECTIVES: To determine whether oral capsaicin troche supplementation with every meal upregulates the impairment of upper respiratory protective reflexes such as the swallowing reflex and the cough reflex. DESIGN: Randomized, controlled study with recruitment through nursing homes. SETTING: Sendai, Japan, from September 2002 through December 2003. PARTICIPANTS: Sixty-four participants in nursing homes with a mean age+/-standard deviation of 81.9+/-1.0 with stable physical status. INTERVENTION: Participants were randomly assigned to the program for the supplementation of capsaicin trochisci or placebo trochisci before every meal for 4 weeks. MEASUREMENTS: Assessment of individual latency time of the swallowing reflex (LTSR) and cough reflex sensitivity. RESULTS: Before the commencement of this study, there were no significant baseline differences in multiple parameters between the intervention group and control group. LTSR in participants in the intervention group was significantly shorter than in the control group (P<.05). The odds ratio (OR) of the shortening of the LTSR of more than 1 minute in the intervention group was 3.4 (95% confidence interval (CI)=1.1-10.4), compared with the control group (P=.03). In particular, daily capsaicin supplementation significantly increased the ratio of LTSR reduction at 4 weeks after the study to baseline LTSR in the high-risk group (baseline LTSR >6.0 seconds) compared with the low-risk group (baseline LTSR <3.0 seconds) and the intermediate group (3.0 seconds <baseline LTSR <6.0 seconds) (P<.005). Seventeen (52.1%) participants in the intervention group and seven (21.9%) in the control group showed improvement in cough reflex sensitivity (OR=4.1, 95% CI=1.4-12.2; P<.01). CONCLUSION: Daily capsaicin supplementation resulted in a significant improvement in upper protective respiratory reflexes, particularly in older people with a high risk for aspiration.