Taro Kojima

Bio: Taro Kojima is an academic researcher from University of Tokyo. The author has contributed to research in topics: Polypharmacy & Medicine. The author has an hindex of 17, co-authored 61 publications receiving 1982 citations.

Statins Protect Human Aortic Smooth Muscle Cells From Inorganic Phosphate-Induced Calcification by Restoring Gas6-Axl Survival Pathway

Abstract: Vascular calcification is clinically important in the development of cardiovascular disease. It is reported that hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins) inhibit...

Polypharmacy as a risk for fall occurrence in geriatric outpatients

Abstract: Objective: To investigate the predictors of falls, such as comorbidity and medication, in geriatric outpatients in a longitudinal observational study. Methods: A total of 172 outpatients (45 men and 126 women, mean age 76.9 ± 7.0 years) were evaluated. Physical examination, clinical history and medication profile were obtained from each patient at baseline. These patients were followed for up to 2 years and falls were self-reported to their physicians. The factors associated with falls were analyzed statistically. Results: A total of 32 patients experienced falls within 2 years. On univariate analysis, older age, osteoporosis, number of comorbid conditions and number of drugs were significantly associated with falls within 2 years. On multiple logistic regression analysis, the number of drugs was associated with falls, independent of age, sex, number of comorbid conditions and other factors that were significantly associated in univariate analysis. A receiver-operator curve evaluating the optimal cut-off value for the number of drugs showed that taking five or more drugs was a significant risk. Conclusion: In geriatric outpatients, polypharmacy is associated with falls. Intervention studies are needed to clarify the causal relationship between polypharmacy, comorbidity and falls. Language: en

Amelioration of vascular endothelial dysfunction in obstructive sleep apnea syndrome by nasal continuous positive airway pressure--possible involvement of nitric oxide and asymmetric NG, NG-dimethylarginine.

Abstract: Background Asymmetric NG,NG-dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide (NO) synthase and its plasma concentration is elevated in patients with cardiovascular risk factors, including hyperlipidemia, hypertension, diabetes, and hyperhomocysteinemia. Obstructive sleep apnea syndrome (OSAS) has been attracting attention as a risk factor for cardiovascular disorders because it often accompanies hypertension, obesity, glucose impairment, and dyslipidemia, all of which are factors in metabolic syndrome and risk factors for cardiovascular disease. Methods and Results In the present study, flow-mediated vasodilatation (FMD) of the brachial artery and plasma concentrations of ADMA were measured before and after nasal continuous positive airway pressure (nCPAP) therapy, which abrogates apnea, in 10 male patients aged 36-69 years old, who were given a diagnosis of OSAS by polysomnography. The percent FMD (%FMD) improved significantly from 3.3±0.3% to 5.8±0.4% (p<0.01) and 6.6±0.3% (p<0.01), before, 1 week, and 4 weeks after nCPAP, respectively. At the same time, the plasma NOx concentrations, metabolites of NO, tended to increase, but the plasma ADMA concentration decreased inversely to %FMD and NOx. A negative correlation between %FMD and plasma ADMA concentration, and a positive correlation between %FMD and plasma NOx concentrations were observed. Conclusion Nasal CPAP improves endothelial function, in part by the decreasing ADMA concentration, thereby potentiating NO production. (Circ J 2005; 69: 221 - 226)

High risk of adverse drug reactions in elderly patients taking six or more drugs: Analysis of inpatient database

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Clinical consequences of polypharmacy in elderly

Abstract: Introduction: Polypharmacy, defined as the use of multiple drugs or more than are medically necessary, is a growing concern for older adults. MEDLINE and EMBASE databases were searched from January 1, 1986 to June 30, 2013) to identify relevant articles in people aged > 65 years. Areas covered: We present information about: i) prevalence of polypharmacy and unnecessary medication use; ii) negative consequences of polypharmacy; and iii) interventions to improve polypharmacy. Expert opinion: International research shows that polypharmacy is common in older adults with the highest number of drugs taken by those residing in nursing homes. Nearly 50% of older adults take one or more medications that are not medically necessary. Research has clearly established a strong relationship between polypharmacy and negative clinical consequences. Moreover, well-designed interprofessional (often including clinical pharmacist) intervention studies that focus on enrolling high-risk older patients with polypharmacy have sh...

Vascular Calcification Pathobiology of a Multifaceted Disease

Abstract: Clinically, vascular calcification is now accepted as a valuable predictor of coronary heart disease.151 Achieving control over this process requires understanding mechanisms in the context of a tightly-controlled regulatory network, with multiple, nested feedback loops and cross-talk between organ systems, in the realm of control theory. Thus, treatments for osteoporosis such as calcitriol, estradiol, bisphosphonates, calcium supplements, and intermittent parathyroid hormone are likely to affect vascular calcification, and, conversely, many treatments for cardiovascular disease such as statins, antioxidants, hormone replacement therapy, ACE inhibitors, fish oils, and calcium channel blockers may affect bone health. As we develop and use treatments for cardiovascular and skeletal diseases, we must give serious consideration to the implications for the organ at the other end of the bone-vascular axis.

Vascular Calcification Pathobiological Mechanisms and Clinical Implications

Abstract: Once thought to result from passive precipitation of calcium and phosphate, it now appears that vascular calcification is a consequence of tightly regulated processes that culminate in organized extracellular matrix deposition by osteoblast-like cells. These cells may be derived from stem cells (circulating or within the vessel wall) or differentiation of existing cells, such as smooth muscle cells (SMCs) or pericytes. Several factors induce this transition, including bone morphogenetic proteins, oxidant stress, high phosphate levels, parathyroid hormone fragments, and vitamin D. Once the osteogenic phenotype is induced, cells gain a distinctive molecular fingerprint, marked by the transcription factor core binding factor alpha1. Alternatively, loss of inhibitors of mineralization, such as matrix gamma-carboxyglutamic acid Gla protein, fetuin, and osteopontin, also contribute to vascular calcification. The normal balance between promotion and inhibition of calcification becomes dysregulated in chronic kidney disease, diabetes mellitus, atherosclerosis, and as a consequence of aging. Once the physiological determinants of calcification are perturbed, calcification may occur at several sites in the cardiovascular system, including the intima and media of vessels and cardiac valves. Here, calcification may occur through overlapping yet distinct molecular mechanisms, each with different clinical ramifications. A variety of imaging techniques are available to visualize vascular calcification, including fluoroscopy, echocardiography, intravascular ultrasound, and electron beam computed tomography. These imaging modalities vary in sensitivity and specificity, as well as clinical application. Through greater understanding of both the mechanism and clinical consequences of vascular calcification, future therapeutic strategies may be more effectively designed and applied.

Sleep apnoea as an independent risk factor for cardiovascular disease: current evidence, basic mechanisms and research priorities

Abstract: Considerable evidence is available in support of an independent association between obstructive sleep apnoea syndrome (OSAS) and cardiovascular disease, which is particularly strong for systemic arterial hypertension and growing for ischaemic heart disease, stroke, heart failure, atrial fibrillation and cardiac sudden death. The pathogenesis of cardiovascular disease in OSAS is not completely understood but likely to be multifactorial, involving a diverse range of mechanisms including sympathetic nervous system overactivity, selective activation of inflammatory molecular pathways, endothelial dysfunction, abnormal coagulation and metabolic dysregulation, the latter particularly involving insulin resistance and disordered lipid metabolism. The present report, which arose out of a European Union Cooperation in the field of Scientific and Technical Research (COST) action on OSAS (COST B26), reviews the current evidence for an independent association and proposes research priorities to identify the underlying mechanisms involved, with a view to identifying novel therapeutic strategies. Large-scale collaborative studies of carefully defined patient populations with obstructive sleep apnoea syndrome, adequately controlled for potential confounders, are needed. Such studies carry the prospect of evaluating potential interactions between different basic mechanisms operating in obstructive sleep apnoea syndrome and cardiovascular disease, and interactions with other related disorders, such as obesity, diabetes and dyslipidaemia. Furthermore, translational studies involving cell culture and animal models linked to studies of obstructive sleep apnoea syndrome patients are necessary to integrate basic mechanisms with the clinical disorder.

Atorvastatin in Patients With Type 2 Diabetes Mellitus Undergoing Hemodialysis

Abstract: BACKGROUND Statins reduce the incidence of cardiovascular events in persons with type 2 diabetes mellitus. However, the benefit of statins in such patients receiving hemodialysis, who are at high risk for cardiovascular disease and death, has not been examined. METHODS We conducted a multicenter, randomized, double-blind, prospective study of 1255 subjects with type 2 diabetes mellitus receiving maintenance hemodialysis who were randomly assigned to receive 20 mg of atorvastatin per day or matching placebo. The primary end point was a composite of death from cardiac causes, nonfatal myocardial infarction, and stroke. Secondary end points included death from all causes and all cardiac and cerebrovascular events combined. RESULTS After four weeks of treatment, the median level of low-density lipoprotein cholesterol was reduced by 42 percent among patients receiving atorvastatin, and among those receiving placebo it was reduced by 1.3 percent. During a median follow-up period of four years, 469 patients (37 percent) reached the primary end point, of whom 226 were assigned to atorvastatin and 243 to placebo (relative risk, 0.92; 95 percent confidence interval, 0.77 to 1.10; P=0.37). Atorvastatin had no significant effect on the individual components of the primary end point, except that the relative risk of fatal stroke among those receiving the drug was 2.03 (95 percent confidence interval, 1.05 to 3.93; P=0.04). Atorvastatin reduced the rate of all cardiac events combined (relative risk, 0.82; 95 percent confidence interval, 0.68 to 0.99; P=0.03, nominally significant) but not all cerebrovascular events combined (relative risk, 1.12; 95 percent confidence interval, 0.81 to 1.55; P=0.49) or total mortality (relative risk, 0.93; 95 percent confidence interval, 0.79 to 1.08; P=0.33). CONCLUSIONS Atorvastatin had no statistically significant effect on the composite primary end point of cardiovascular death, nonfatal myocardial infarction, and stroke in patients with diabetes receiving hemodialysis.