Onset heart rate of microvolt-level T-wave alternans provides clinical and prognostic value in nonischemic dilated cardiomyopathy.

OBJECTIVES: This study was designed to determine the prognostic value of onset heart rate (OHR) in T-wave alternans (TWA) in patients with nonischemic dilated cardiomyopathy (DCM). BACKGROUND: One of the current major issues in DCM is to prevent sudden cardiac death (SCD). However, the value of the OHR of TWA as a prognostic indicator in DCM remains to be elucidated. METHODS: We prospectively investigated 104 patients with DCM undergoing TWA testing. The end point of this study was defined as SCD, documented sustained ventricular tachycardia/ventricular fibrillation. Relations between clinical parameters and subsequent outcome were evaluated. RESULTS: Forty-six patients presenting with TWA were assigned to one of the following two subgroups according to OHR for TWA of < or = 100 beats/min: group A (n = 24) with OHR < or = 100 beats/min and group B (n = 22) with 100 < OHR < or = 110 beats/min. T-wave alternans was negative in 37 patients (group C) and indeterminate in 21 patients. The follow-up result comprised 83 patients with determined TWA. During a follow-up duration of 21 +/- 14 months, there was a total of 12 arrhythmic events, nine of which included three SCDs in group A, two in group B and one in group C. The forward stepwise multivariate Cox hazard analysis revealed that TWA with an OHR < or = 100 beats/min and left ventricular ejection fraction were independent predictors of these arrhythmic events (p = 0.0001 and p = 0.0152, respectively). CONCLUSIONS: The OHR of TWA is of additional prognostic value in DCM.     

Evolocumab Effects on Lipoproteins,Measured by High-Performance Liquid Chromatography

Aims: Profiling of lipoproteins can predict risk of cardiovascular disease; gel permeation high-performance liquid chromatography (HPLC) improves prediction accuracy by providing detailed data for specific lipoprotein subclasses. This study applied HPLC to examine the effects of evolocumab, which effectively treats hyperlipidemia and mixed dyslipidemia, on lipoprotein subclasses, specifically the number and size of lipoprotein particles.Methods: This post-hoc analysis used patient blood samples from YUKAWA-2, a phase 3 trial evaluating the efficacy of evolocumab in Japanese adult patients with hyperlipidemia or mixed dyslipidemia and at high risk for cardiovascular disease. We used HPLC to assess observed values and percent change from baseline in cholesterol and triglyceride (TG) concentrations, number of particles in lipoprotein subclasses to week 12, and mean observed values and mean percent change from baseline in variables to weeks 10 and 12. HPLC was also compared with conventional methods in assessing low-density lipoprotein (LDL) cholesterol (LDL-C) values.Results: Data for all 404 patients were analyzed. Evolocumab significantly decreased cholesterol and TG concentrations, and total particle count, in very low-density lipoprotein (VLDL) and LDL subclasses. Particle size increased slightly in LDL, high-density lipoprotein (HDL), and VLDL, but data varied widely. At very low L-DLC, HPLC measurements were higher than those from conventional methods.Conclusion: This research used HPLC to assess the effects of evolocumab in 20 lipid subclasses. By lowering lipid content and improving the lipid profile, evolocumab may reduce atherogenicity. This reduction is better quantified by HPLC than by conventional methods in the very low LDL-C range.     

Butyric acid induces apoptosis in both human monocytes and lymphocytes equivalently

Short-chain fatty acids (SCFAs) are metabolites from anaerobic periodontopathic bacteria that induce apoptosis in immune cells such as lymphocytes, monocytes and macrophages. However, it remains unclear if SCFAs from pathogens induce apoptosis in monocytes/macrophages similarly with lymphocytes. This study investigated whether SCFAs-induced apoptosis is equal among the immunoregulatory cells. Cell apoptosis of the employed human cells was evaluated after treatment with culture supernatants from various periodontopathic bacteria or sodium butyrate. Apoptosis and viability were determined by detection of DNA fragmentation and using an MTS assay kit, respectively. Porphyromonas gingivalis and Fusobacterium nucleatum culture filtrates strongly induced apoptosis whereas Prevotella nigrescens and Prevotella intermedia culture filtrates failed to induce apoptosis in the THP-1 and U937 human monocyte and macrophage cell lines. Healthy gingival fibroblasts and oral epithelial cells were resistant to all the culture filtrates. Gas-liquid chromatography detected butyric acid in P. gingivalis (21.0-34.0 mM) and F. nucleatum (36.0 mM) in culture filtrates, whereas, only trace levels were seen in P. nigrescens and P. intermedia. These results suggest that butyric acid produced by periodontopathic bacteria severely damages immunoregulatory cells in a consistent manner and, likewise, could be involved in mediating periodontal chronic inflammation.     

Clinical study on anti-fungal drug activity against clinically isolated strains of oral Candida species

ObjectivesThe present study was undertaken to evaluate the anti-fungal activity of amphotericin B (AMPH-B), flucytosine (5-FC), fluconazole (FLCZ), miconazole (MCZ), itraconazole (ITCZ), and micafungin (MCFG) against clinically isolated Candida strains from oral candidiasis (OC) patients and to collect information useful for the treatment of OC.Subjects and methodsThe study includes 116 strains of Candida isolated from patients. The Candida species were identified by polymerase chain reaction. The minimum inhibitory concentration (MIC) of each drug against each Candida species was determined.ResultsOf the 106 participants (30 males and 76 females), 57 had OC, including 42 cases of pseudomembranous OC, 11 cases of erythematous OC, 2 cases of hypertrophic OC, and 2 cases of mixed pseudomembranous/erythematous OC. The Candida species isolated were Candida albicans (93 strains), C. glabrata (19 strains), and C. tropicalis (4 strains). AMPH-B and 5-FC had low MIC values against all species of Candida and a low incidence of resistance development. In some species of Candida, FLCZ and ITCZ showed high MICs, but MCZ had a low MIC value. AMPH-B, MCZ, and ITCZ prescribed to OC patients were effective against OC with respect to alleviation of OC symptoms.ConclusionMIC values of anti-fungal drugs against Candida strains isolated from OC patients were obtained and the 3 anti-fungal drugs given to OC patients were found to be effective against OC in spite of differences in their MIC values and in the number of resistant strains (or strains with a high MIC value).     

Effect of switching from salmeterol/fluticasone to formoterol/ budesonide combinations in patients with uncontrolled asthma

BackgroundCombination therapy with an inhaled corticosteroid (ICS) and a long-acting β2-agonist (LABA) in a single inhaler is the mainstay of asthma management and salmeterol/fluticasone combination (SFC) and fixed-dose formoterol/budesonide combination (FBC) are currently available in Japan; however, there is nothing to choose between the two. The purpose of this study was to clarify the effect of switching from SFC to FBC in patients with asthma not adequately controlled under the former treatment regimen.MethodsThis was a prospective, multicenter, open-label, uncontrolled longitudinal study in 87 adult patients with an Asthma Control Questionnaire, 5-item version (ACQ5) score of greater than 0.75 under treatment with SFC 50/250 μg one inhalation twice daily (bid). SFC was switched to FBC 4.5/160 μg two inhalations bid. Study outcomes included ACQ5 score, peak expiratory flow (PEF), FEV₁, and fractional exhaled nitric oxide (FeNO) at the end of treatment period.ResultsEighty-three patients completed the study. ACQ5 scores improved and exceeded the clinically meaningful difference after 12 weeks of treatment and well-controlled asthma (ACQ5 score ≤ 0.75) was attained in 37 (44.6%) patients. Minimum and maximum PEF and FEV₁ values improved significantly, but not FeNO values, after switching from SFC to FBC.ConclusionsSwitching ICS/LABA combination therapy is a useful option in the management of asthma that is not optimally controlled.     

Comparison of the psychosocial quality of life in hemodialysis patients between the elderly and non‐elderly using a visual analogue scale: The importance of appetite and depressive mood

Aim: The number of hemodialysis (HD) patients is increasing along with their mean age in Japan. The assessment of their psychosocial status and quality of life (QOL) is therefore becoming more and more important along with laboratory data or comorbidities. Methods: We examined the psychosocial status of 211 HD patients (72 elderly and 139 non‐elderly) and compared the difference between elderly and non‐elderly patients using a visual analogue scale (VAS). We then examined how QOL affected mortality rate in 3‐year prospective follow up. We assessed 10 items of QOL: health condition, appetite, sleep, mood, memory, family relationships, friendship, economical status, life satisfaction in daily life, and happiness with qualified self‐evaluating questionnaires along with laboratory data and comorbidities. Furthermore, we investigated the correlation between the scores of mood and geriatric depression scale (GDS)‐15. Results: There was no difference in VAS scores between elderly and non‐elderly patients. Lower VAS scores for appetite and mood correlated with higher mortality in HD patients, especially in the non‐elderly. VAS scores for mood correlated with GDS‐15 in HD patients. Conclusions: More attention should be paid to appetite and the diagnosis and therapy of depressive mood to improve the prognosis of HD patients, especially for the non‐elderly. Geriatr Gerontol Int 2012; 12: 65–71.     

Effects of telmisartan on cognition and regional cerebral blood flow in hypertensive patients with Alzheimer's disease

Aim: Recent studies have shown that some antihypertensive medications are associated with a significant reduction in the incidence of Alzheimer's disease (AD). However, it remains uncertain whether antihypertensive drugs may have a preventive effect on cognitive decline in patients with AD. We investigated the effects of telmisartan, an angiotensin II type 1 receptor blocker with peroxisome proliferator‐activated receptor γ‐stimulating activity, on cognition and regional cerebral blood flow (rCBF) in elderly hypertensive patients with AD. Methods: A total of 20 patients with probable AD and essential hypertension were randomly assigned to the telmisartan group (n = 10, 40–80 mg daily) or the amlodipine group (n = 10, 5–10 mg daily) for 6 months. Results: The groups had a similar significant reduction in systolic and diastolic blood pressure after treatment. The telmisartan group did not show any changes in cognitive function test scores, while the amlodipine group showed significantly higher scores on the AD Assessment Scale‐Cognitive Subscale (Japanese version). Analysis of covariance to analyze treatment effect revealed that the telmisartan group showed increased rCBF in the right supramarginal gyrus, superior parietal lobule, cuneus, and lingual gyrus compared with the amlodipine group, while the amlodipine group showed increased rCBF only in the right cingulate gyrus compared with the telmisartan group at 6 months. Conclusion: These findings suggest that telmisartan may have additional benefits and be useful for the treatment of elderly hypertensive patients with AD. Geriatr Gerontol Int 2012; 12: 207–214.     

Mesenteric ischemia in acute aortic dissection

Mesenteric ischemia complicated by acute aortic dissection (AAD) is uncommon, but serious, as there is no established treatment strategy and it can progress rapidly to multi-organ failure. Diagnosing mesenteric ischemia before necrotic change is difficult, not only for primary care physicians, but even for gastrointestinal or cardiovascular surgeons as it can occur at any time during surgery. Thus, measures need to be in place at the bedside to enable us to obtain information on visceral perfusion. It is often difficult to decide which of laparotomy or aortic repair should be performed first, especially when there is associated shock or malperfusion of other vital organs. The standard surgical procedures for mesenteric ischemia are prompt revascularization of the mesenteric artery and, if needed, resection of necrotic intestine. However, the development of endovascular treatment and the introduction of hybrid ORs have improved the treatment strategies for mesenteric ischemia. This article reviews the issues of “diagnosis” in relation to the mechanism of mesenteric ischemia, and discusses the current “treatment strategies”.     

Distinctive evaluation of nonmucinous and mucinous subtypes of bronchioloalveolar carcinomas in EGFR and K-ras gene-mutation analyses for Japanese lung adenocarcinomas: confirmation of the correlations with histologic subtypes and gene mutations

Although adenocarcinomas of the lung are associated with epidermal growth factor receptor (EGFR) gene mutations and sensitivity to EGFR tyrosine kinase inhibitors, it remains unclear whether bronchioloalveolar carcinoma (BAC) components and/or subtypes affect these associations. We aimed to clarify correlations between EGFR gene mutations and BAC components and to establish the histologic features as reliable predictors for the mutations. We examined 141 non-small cell lung cancers (NSCLCs), including 118 adenocarcinomas, for mutations in exons 19 and 21 of the EGFR gene together with mutations in codon 12 of the K-ras gene using loop-hybrid mobility shift assays, a highly sensitive polymerase chain reaction-based method. Adenocarcinomas were subdivided into subtypes with a nonmucinous or mucinous BAC component and those without BAC components. In NSCLCs, EGFR mutations were detected in 75 cases (53.2%) and were significantly associated with adenocarcinoma, female sex, and never smoking. Among adenocarcinomas, nonmucinous and mucinous BAC components were significantly associated with EGFR and K-ras gene mutations, respectively. Because EGFR mutations were detected even in most pure nonmucinous BACs, ie, lung adenocarcinoma in situ, EGFR mutation is considered a critical event in the pathogenesis of nonmucinous BAC tumors.     

Effects of chlorogenic acid on carbachol-induced contraction of mouse urinary bladder

Chlorogenic acid (CGA) is a polyphenol found in coffee and medicinal herbs such as Lonicera japonica. In this study, the effect of CGA-induced relaxation on carbachol (CCh)-induced contraction of mouse urinary bladder was investigated. CGA (30–300 μg/ml) inhibited CCh- or U46619-induced contraction in a concentration-dependent manner. SQ22536 (adenylyl cyclase inhibitor) recovered CGA-induced relaxation of CCh-induced contraction; however, ODQ (guanylyl cyclase inhibitor) did not have the same effect. In addition, 3-isobutyl-1-methylxanthine (IBMX) enhanced CGA-induced relaxation; however, forskolin or sodium nitroprusside did not have the same effect. Moreover, Ro 20–1724, a selective phosphodiesterase (PDE) 4 inhibitor, enhanced CGA-induced relaxation, but vardenafil, a selective PDE5 inhibitor, did not have the same effect. In the presence of CCh, CGA increased cyclic adenosine monophosphate (cAMP) level, whereas SQ22536 inhibited the increase of cAMP levels. Moreover, higher cAMP levels were obtained with CGA plus IBMX treatment than the total cAMP levels obtained with separate CGA and IBMX treatments. In conclusion, these results suggest that CGA inhibited CCh-induced contraction of mouse urinary bladder by partly increasing cAMP levels via adenylyl cyclase activation.