Relationship between late potentials and left ventricular function in patients with coronary artery disease

We examined the relationship between late potentials and left ventricular function from a hemodynamic point of view in 50 patients with prior myocardial infarction. Late potentials were found in 15 (30%) of 50 patients. A left ventricular aneurysm was found in 28 patients. Late potentials were detected in 14 (50%) of 28 patients with the aneurysm but in 1 (5%) of 22 patients without it (p less than 0.01). In the 50 patients, a hemodynamic data from the late potential positive group (n = 15) were compared to those from the late potential negative group (n = 35). The late potential positive group had a significantly lower ejection fraction, cardiac index and stroke volume than the late potential negative group. We further studied the 28 patients with left ventricular aneurysm in a similar way. The cardiac index and stroke volume were also significantly lower in the late potential positive group. The ejection fraction tended to be lower in the late potential positive group. These results suggest that left ventricular function and left ventricular aneurysm are among the factors that influence the development of late potentials.     

Impact of Metabolic Syndrome on the Mortality Rate among Participants in a Specific Health Check and Guidance Program in Japan

Objective In Japan, the Specific Health Check and Guidance (Tokutei-Kenshin) program was started in 2008 to decrease the social burden related to metabolic syndrome (MetS). However, so far this program has not been found to have any impact on the mortality rate. Methods The subjects consisted of individuals who participated in the Tokutei-Kenshin in seven districts between 2008 and 2015. Using a National database of death certificates, we identified those who might have died and then further confirmed such deaths with the collaboration of the regional National Health Insurance agency and public health nurses. The diagnosis of MetS was made according to the Japanese criteria. The causes of death were classified by ICD-10. Mortality risk was evaluated after adjusting for age, sex, smoking, alcohol intake and past medical history such as stroke, heart disease and kidney disease. Results Among the total of 664,926 subjects, we identified 8,051 fatal cases by the end of 2015. The crude death rate was 1.6% for those with MetS, 1.3% for those with preliminary metabolic syndrome, and 1.1% those without MetS. In MetS, the adjusted hazard ratio (95% confidence interval) was 1.08 (1.02-1.15) for all-cause and 1.39 (1.22-1.58) for cardiovascular disease mortality when the reference was for those without MetS. Conclusion The death rate was found to be significantly higher among the participants with MetS.     

Ventricular wall stress and silent myocardial damage are associated with pulse pressure in the general population

Pulse pressure (PP) is a risk factor for cardiovascular diseases and is associated with increased afterload and myocardial oxygen demand. Brain natriuretic peptide (BNP) and heart‐type fatty acid–binding protein (H‐FABP) are known as biomarkers indicating ventricular wall stress and silent myocardial damage. However, the association between PP and ventricular wall stress and silent myocardial damage in the general population is unclear. The authors enrolled 3504 patients who participated in a community‐based annual health check. Serum levels of BNP and H‐FABP were measured as markers of ventricular wall stress and silent myocardial damage. Patients were divided into four groups according to the quartiles of PP. Patients in the highest PP group showed higher serum BNP and H‐FABP levels than that of the other groups. Multivariate logistic analysis showed that high PP was independently associated with ventricular wall stress and silent myocardial damage on the basis of BNP and H‐FABP levels. Compared with systolic blood pressure, diastolic blood pressure, and mean blood pressure, PP was superior in predicting ventricular wall stress and silent myocardial damage evaluated according to BNP and H‐FABP levels, which was reflected by the receiver operating characteristic analysis. Screening of healthy patients revealed that high PP was related to high BNP and H‐FABP levels, suggesting that an asymptomatic general population with high PP may be exposed to ventricular wall stress and myocardial damage and might be susceptible to silent heart failure.     

Deoxyspergualin, an immunosuppressant, in patients suffering from nephropathies with crescent formation: an open-label trial to evaluate safety and efficacy

Background Crescent formation in glomeruli means an acute active lesion that develops a rapidly progressive course. Therapies using pulse methylprednisolone, oral corticosteroids, and cyclophosphamide are recommended, but no agreement has been reached on the optimal therapy. There have been no controlled trials, because of the severity of this condition and because withholding treatment would become an ethical issue. Methods We evaluated the safety and efficacy of deoxyspergualin (DSG), an immunosuppressant, in a multicenter, prospective trial of 44 patients with crescent formation in over 10% of glomeruli, who were randomly placed into groups that received daily doses of 0.1 mg/kg (n = 21) and 0.2 mg/kg (n = 23) of DSG, given by a 1-h infusion for 4 weeks, and who were then monitored for 3 months. All patients received DSG in this open-label prospective study. We evaluated the levels of urinary protein and hematuria, and examined renal function after the DSG treatment. Results Urinary protein significantly decreased with each dose after starting the DSG administration and this efficacy was sustained for 2 months after the discontinuation of DSG. In the groups receiving 0.1 mg/kg and 0.2 mg/kg, mean urinary protein levels were 2.1 g/day and 2.3 g/day at the initiation of the DSG administration, 1.4 g/day and 1.6 g/day at week 4, and 1.5 g/day and 1.3 g/day at week 12, respectively. Hematuria was markedly improved by a dose of 0.2 mg/kg and was not exacerbated following the termination of DSG. Exacerbation of renal dysfunction, as measured by creatinine clearance, serum creatinine, and blood urea nitrogen was prevented by both doses of DSG. The most common adverse reaction was reversible neutropenia. Conclusions Short-term treatment with DSG may be effective and tolerated in patients suffering from nephropathies with crescent formation. Participating investigators and study centers in the present trial of deoxyspergualin are listed in the Appendix.     

Oxcarbazepine-induced cytotoxicity and genotoxicity in human lymphocyte cultures with or without metabolic activation

There has been considerable debate about the relationship between epilepsy and cancer. Oxcarbazepine (OXC) is used for treating certain types of seizures in patients with epilepsy. There have been no detailed investigations about genotoxicity of OXC and its metabolites. Therefore, the aim of this study is to investigate the cytotoxic and genotoxic effects of OXC and its metabolites on cultured human lymphocytes. The cytotoxicity and genotoxicity of OXC on human peripheral blood lymphocytes were examined in vitro by sister chromatid exchange (SCE), chromosomal aberration (CA) and micronucleus (MN) tests. Cultures were treated with 125, 250 and 500?μg/ml of OXC in the presence (3?h treatment) and absence (24?h and 48?h treatment) of a metabolic activator (S9 mix). Dimethyl sulfoxide (DMSO) was used as a solvent control. OXC showed cytotoxic activities due to significant decreases in mitotic index (MI), proliferation index (PI) and nuclear division index (NDI) in the absence of S9 mix when compared with solvent control. Metabolites of OXC also significantly reduced MI and PI in cultures with S9 mix. OXC significantly increased the CAs, aberrant cells, SCE and MN values in the presence and absence of S9 mix. Our results indicated that both OXC and its metabolites have cytotoxic, cytostatic and genotoxic potential on human peripheral blood lymphocyte cultures under the experimental conditions. Further studies are necessary to elucidate the relationship between cytotoxic, cytostatic and genotoxic effects, and to make a possible risk assessment in patients receiving therapy with this drug.     

Impairment of pulmonary function is an independent risk factor for atrial fibrillation: the Takahata study

Background: Chronic pulmonary disorders, such as chronic obstructive pulmonary disease (COPD) and fibrosing lung diseases, and atrial fibrillation (AF), are prevalent in elderly people. The impact of cardiac co-morbidities in the elderly, where pulmonary function is impaired, cannot be ignored as they influence mortality. The relationship between the prevalence of AF and pulmonary function is unclear. The aim of this study was to evaluate this relationship in participants in a health check.Methods: Subjects aged 40 or older (n = 2,917) who participated in a community-based annual health check in Takahata, Japan, from 2004 through to 2005, were enrolled in the study. We performed blood pressure measurements, blood sampling, electrocardiograms, and spirometry on these subjects.Results: The mean FEV₁ % predicted and FVC % predicted in AF subjects was significantly lower than in non-AF subjects. The prevalence of AF was higher in those subjects with airflow limitation or lung restriction than in those without. Furthermore, AF prevalence was higher in those subjects with severe airflow obstruction (FEV₁ %predicted < 50) than in those who had mild or moderate airflow obstruction (FEV₁ %predicted ≥ 50), although there was no difference between the prevalence of AF in subjects with 70≤ FVC %predicted <80 lung restriction and those with FVC %predicted <70. Multiple logistic regression analysis revealed that FEV₁ %predicted and FVC %predicted are independent risk factors for AF (independent of age, gender, left ventricular hypertrophy, and serum levels of B-type natriuretic peptide).Conclusion: Impaired pulmonary function is an independent risk factor for AF in the Japanese general population.     

Tea flavan-3-ols as modulating factors in endoplasmic reticulum function

Regular green tea consumption has been shown to reduce the risk of cancer and diabetes mellitus. These effects are attributed to tea flavan-3-ols, especially to epigallocatechin gallate; however, the molecular targets and mechanisms of action are still subject of extensive research. The special roles of the endoplasmic reticulum (ER) in biotransformation, protein synthesis, calcium homeostasis, and glucose production make this organelle a potential target of the antitumor and antidiabetic effects of tea flavan-3-ols. The purpose of this review is to present evidence for the biologic actions of tea flavan-3-ols on specific ER targets associated with normal function and disease. Reactivation of chemical carcinogens can be reduced by tea flavan-3-ols through inhibition of glucuronide transport across the ER membrane. Catechins modulate Ca²⁺ release from the ER lumen and interfere with glycoprotein maturation, which can lead to decreased viability and increased drug sensitivity of tumor cells. Epigallocatechin gallate inhibits glucose transport across the ER membrane, which can underlie the reduction of hepatic glucose production by tea flavan-3-ols. These mechanisms likely contribute to the chemopreventive and glucose-lowering effects of tea catechins. Investigating the effects of flavan-3-ols on ER functions is a promising field of medical and biochemical research to understand disease and improve health.     

No association of common VCP variants with sporadic frontotemporal dementia

Mutations in the gene for valosin containing protein (VCP) cause autosomal dominant inclusion body myopathy associated with Paget disease and frontotemporal dementia (IBMPFD). To investigate the role of this novel gene in sporadic forms of frontotemporal dementia (FTD), we genotyped 27 single nucleotide polymorphisms covering the entire VCP genomic region in 198 patients with sporadic FTD and 184 matched controls from Germany. No significant association could be demonstrated. There is no evidence, that common variants in VCP confer a strong risk to the development of sporadic FTD.