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Find video protocols related to scientific articles indexed in Pubmed.
Antihypertensive effectiveness of combination therapy with losartan/hydrochlorothiazide for 'real world' management of isolated systolic hypertension.
Ther Adv Cardiovasc Dis
PUBLISHED: 11-05-2014
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The guidelines for hypertension require the presence of compelling indications for pharmacological management of hypertension associated with various diseases. Data mainly obtained through randomized controlled trials have provided evidence supporting effectiveness of the combination of losartan (Lo) and hydrochlorothiazide (HCTZ) for management of hypertensive patients. However, there have been few reports discussing the effectiveness of Lo/HTCZ (losartan 50 mg/hydrochlorothizide 12.5 mg) in the 'real world' in the management of isolated systolic hypertension (ISH). This study was designed to investigate the 'real world' effectiveness of Lo/HTCZ-based treatment of ISH associated with various diseases.
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Blood glucose levels in peritoneal dialysis are better reflected by HbA1c than by glycated albumin.
Adv Perit Dial
PUBLISHED: 10-24-2014
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A recent study indicated that, compared with glycated hemoglobin (HbA1c), glycated albumin (GA) provides a more accurate assessment of glycemic control in diabetic patients on hemodialysis. However, the suitability of GA for this purpose in peritoneal dialysis (PD) patients is questionable. We measured blood glucose, GA, HbA1c, serum albumin, protein losses in urine and dialysate, protein catabolic rate, hemoglobin, and dose of erythropoiesis-stimulating agents in 71 PD patients [20 with diabetes (DM), 51 without DM]. In both DM and non-DM patients, blood glucose levels correlated significantly with HbA1c (r = 0.47, p < 0.001), but not with GA (r = 0.18, p = 0.19). In patients with high serum albumin (> 3.2 g/dL), blood glucose levels correlated significantly with GA (r = 0.32, p = 0.047). Further, low protein losses in urine and dialysate (< 5.9 g daily) also significantly correlated with GA (r = 0.37, p = 0.041). In PD patients, HbA1c is better than GA as an indicator of blood glucose levels. Glycated albumin can be used as an indicator of glycemic control in PD patients with normal serum albumin and low protein losses in urine and dialysate.
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Long-term survival benefits of combined hemodialysis and peritoneal dialysis.
Adv Perit Dial
PUBLISHED: 10-24-2014
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Recently, it was reported that concomitant hemodialysis (HD) in peritoneal dialysis (PD) patients facilitated continuation of PD treatment and mitigated the deterioration of peritoneal function in patients with uremic symptoms and excess body fluid associated with loss of residual renal function. To determine the effect of combined HD and PD on patient and technique survival, we undertook a retrospective cohort study of patients who underwent PD at Saitama Medical University Hospital between 1995 and 2010. We compared patients who started PD during 1995 2002 with those who started during 2003- 2010. Because our center started a new strategy of supplementing PD with once-weekly HD in 2000, the effects of combination therapy could be determined by comparing the data obtained during the two periods. The 440 patients (274 men, 166 women) who started PD during the study period had a mean age of 60.2 +/- 73 years. The mean age was significantly higher in the 2003 - 2010 group than in the 1995 - 2002 group. Using a Kaplan-Meier plot, we observed a significant difference in technique survival (p < 0.001). The technique survival rate at 3 and 5 years was, respectively, 89% and 74% in the 2003-2010 group and 68% and 35% in the 1995 - 2002 group (p < 0.05). Cumulative patient survival at 3 and 5 years was, respectively, 87% and 72% in the 2003 - 2010 group and 69% and 51% in the 1995 - 2003 group (p < 0.01). Patient and technique survival were significantly improved in PD patients receiving the combination of HD and PD.
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Home hemodialysis and conventional in-center hemodialysis in Japan: A comparison of health-related quality of life.
Hemodial Int
PUBLISHED: 10-22-2014
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Health-related quality of life (HRQOL) is an important measure of how disease affects patients' daily life. Conventional in-center hemodialysis (CHD) patients have been found to have decreased HRQOL. Recent study reported that at-home hemodialysis (HHD) improved the long-term HRQOL compared with CHD; however, there have been no data from Japanese HHD patients. A sample of 80 Japanese hemodialysis patients (46 HHD and 34 CHD) was matched for age, sex, and cause of end-stage renal disease. Patient HRQOL was measured using two health surveys: Medical Outcomes Study 36 Item Short Form Health Survey-Version 2 and Kidney Disease Quality of Life-Short Form. HHD patients reported better scores on seven out of eight domains (all domains except general heath) of the Medical Outcomes Study 36 Item Short Form Health Survey-Version 2, as well as better Kidney Disease Quality of Life-Short Form scores with respect to symptoms and problems, effect of kidney disease, and work status. No significant differences were observed for burden of kidney disease, cognitive function, quality of social interaction, sexual function, or sleep. More than 65% of HHD patients stated that they were not bothered at all by limitations on food and water intake. Japanese HHD patients demonstrate significantly higher HRQOL scores. However, while their HRQOL and employment rate were high and they were able to enjoy fewer dietary restrictions, kidney disease remained a great burden.
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Clostridium difficile infection induced by pregabalin-associated agranulocytosis.
Intern. Med.
PUBLISHED: 09-15-2014
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A 33-year-old man who had recently undergone surgery for cervical spondylotic myelopathy was prescribed pregabalin for neuralgia, and the dose was increased to 600 mg/day during hospitalization. However, the patient was diagnosed with a Clostridium difficile infection on day 34 after admission. A complete blood count showed agranulocytosis (neutrophil count: 105/?L). We did not observe any changes in vital signs, a relative increase in band cells, or intestinal edema. The patient's agranulocytosis resolved after withdrawing pregabalin. This is the first reported case of agranulocytosis associated with pregabalin. Periodic monitoring of the white blood cell count is therefore considered to be useful in patients receiving high-dose pregabalin therapy.
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Recurrent somatic mutations underlie corticotropin-independent Cushing's syndrome.
Science
PUBLISHED: 05-24-2014
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Cushing's syndrome is caused by excess cortisol production from the adrenocortical gland. In corticotropin-independent Cushing's syndrome, the excess cortisol production is primarily attributed to an adrenocortical adenoma, in which the underlying molecular pathogenesis has been poorly understood. We report a hotspot mutation (L206R) in PRKACA, which encodes the catalytic subunit of cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA), in more than 50% of cases with adrenocortical adenomas associated with corticotropin-independent Cushing's syndrome. The L206R PRKACA mutant abolished its binding to the regulatory subunit of PKA (PRKAR1A) that inhibits catalytic activity of PRKACA, leading to constitutive, cAMP-independent PKA activation. These results highlight the major role of cAMP-independent activation of cAMP/PKA signaling by somatic mutations in corticotropin-independent Cushing's syndrome, providing insights into the diagnosis and therapeutics of this syndrome.
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The contribution of epithelial-mesenchymal transition to renal fibrosis differs among kidney disease models.
Kidney Int.
PUBLISHED: 05-17-2014
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The impact of the epithelial-mesenchymal transition (EMT) to the formation of renal fibrosis has been debated in several lineage-tracing studies, with conflicting findings. Such disparities may have arisen from varying experimental conditions such as different disease models, the mouse strain, and type of genetic alteration used. In order to determine the contribution of these factors to EMT, we generated four kidney disease models in several mouse strains genetically modified to express enhanced green fluorescence protein (EGFP) in cortical tubular epithelial cells under the control of the ?-glutamyl transpeptidase promoter. Using this approach, the EMT was visible and quantifiable based on a count of EGFP-positive interstitial cells in the fibrotic kidney sections of the four renal disease models found to be either EMT-prone or -resistant. The EMT-prone models consisted of unilateral ureteral obstruction and ischemic nephropathy in SJL mice. The EMT-resistant models consisted of ureteral obstruction in C57B/6 and F1(C57B/6 × SJL) mice, adriamycin nephrosis in 129 mice, and nephrotoxic serum nephritis in SJL mice. Analyses of these renal disease models suggest the emergence of EMT-derived fibroblasts arises in a disease-specific and strain-dependent manner. Thus, when considering molecular mechanisms and involvement of the EMT in renal fibrosis, it is important to take into account the experimental conditions, particularly the mouse strain and type of disease model.Kidney International advance online publication, 9 July 2014; doi:10.1038/ki.2014.235.
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Calcitriol supplementation improves endothelium-dependent vasodilation in rat hypertensive renal injury.
Kidney Blood Press. Res.
PUBLISHED: 03-28-2014
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Vitamin D increases renal expression of klotho in normotensive rats. Klotho reduces oxidative stress.
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Calcium channel blockers suppress daily variations of blood pressure in hypertensive patients with end-stage renal diseases.
Clin. Exp. Hypertens.
PUBLISHED: 03-15-2014
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Hypertension is a well-known cardiovascular risk. Patients with end-stage renal diseases frequently suffer hypertension. Furthermore, daily variations of blood pressure are relatively large in patients treated with hemodialysis, partly due to ultrafiltration. Twenty hypertensive patients with end-stage renal diseases whose blood pressure was controlled by a single antihypertensive agent, either angiotensin receptor antagonist (ARB) or calcium channel blocker (CCB), were enrolled into the study. Home blood pressure measurements were also performed. Average systolic and diastolic blood pressures were similar between two agents. However, variations of systolic blood pressure during ARB treatment were greater than those of CCB, and maximal differences in daily systolic blood pressure during treatment with ARB (19±7?mmHg) were greater than those with CCB (14±6?mmHg, p<0.01). Systolic blood pressure measured after hemodialysis under ARB therapy (110±6?mmHg) was lower than that of CCB (118±6?mmHg, p<0.05). Daily variations of diastolic blood pressure were similar between ARB and CCB periods. Our results indicate that variations of systolic blood pressure during ARB treatment are larger than CCB, and suggest that CCB is useful to obtain the better quality of blood pressure control, improving blood pressure stability by preventing substantial drops in blood pressure in hypertensive patients with end-stage renal diseases.
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Effects of cell-type-specific expression of a pan-caspase inhibitor on renal fibrogenesis.
Clin. Exp. Nephrol.
PUBLISHED: 03-05-2014
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The caspase family of enzymes is grouped into two major sub-families, namely apoptotic and inflammatory caspases, which play central roles in the induction of apoptosis, regulation of inflammation and immunity, and cellular differentiation.
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Spontaneous meningitis due to Streptococcus salivarius subsp. salivarius: cross-reaction in an assay with a rapid diagnostic kit that detected Streptococcus pneumoniae antigens.
Intern. Med.
PUBLISHED: 02-05-2014
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Streptococcus salivarius subsp. salivarius occasionally causes meningitis associated with iatrogenic or traumatic events. We herein describe a case of meningitis caused by this organism in a patient without any apparent risk factors. In an assay of the patient's cerebrospinal fluid, cross-reaction occurred with Streptococcus pneumoniae antigen-coated latex particles in the Pastorex Meningitis Kit. In the in vitro assays, three of the five clinically isolated S. salivarius strains showed cross-reactions with the kit, indicating that these strains expressed pneumococcal antigen-like antigens. This case shows that meningitis caused by S. salivarius can occur spontaneously and it may sometimes be misdiagnosed as S. pneumoniae infection.
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Acute kidney injury in a patient with polyarteritis nodosa and multiple myeloma.
Intern. Med.
PUBLISHED: 02-05-2014
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We herein report the case of a Japanese man with polyarteritis nodosa (PAN) accompanied by multiple myeloma (MM). The patient was diagnosed with PAN. Concurrently, IgG kappa paraprotein was detected, and bone marrow changes indicative of MM were observed. Prednisolone (PSL) administered at a dose of 30 mg/day was initiated; however, the serum creatinine level increased. In spite of increasing the dose of PSL to 45 mg/day and initiating treatment with double filtration plasmapheresis, the patient's renal dysfunction continued to progress and haemodialysis was introduced. He died from pneumonia 12 months after admission. We conclude that renal failure is an important risk factor in the prognosis of PAN accompanied by MM.
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Olig2 labeling index is correlated with histological and molecular classifications in low-grade diffuse gliomas.
J. Neurooncol.
PUBLISHED: 01-30-2014
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Diagnosis of low-grade diffuse gliomas based on morphology is highly subjective and, therefore, is often difficult, with significant intra- and interobserver variability. Here, we investigated WHO grade II diffuse astrocytomas, oligoastrocytomas and oligodendrogliomas for immunohistochemical expression of Olig2, measuring its labeling index (LI), and evaluated the significance of Olig2 LI in the histological and molecular classifications. The means of Olig2 LI in glioma cells were 43.7 % in diffuse astrocytomas, 59.3 % in oligoastrocytomas and 76.1 % in oligodendrogliomas. There was a statistically significant difference between all pairs of histological types. The mean of Olig2 LI of gliomas with 1p/19q loss ± IDH1/2 mutation, the majority of them being oligodendrogliomas, was significantly higher than the means of those with TP53 mutation ± IDH1/2 mutation and IDH1/2 mutation only, the majority of which were diffuse astrocytomas (70.1 vs. 47.2 and 46.5 %, respectively). When categorized according to the classification of Jiao et al., Olig2 LI of I-CF gliomas (cases with IDH and one or more of CIC, FUBP1 or combined 1p/19q loss; mean 71.0 %) was significantly higher than that of I-A gliomas (cases with IDH and ATRX alterations; mean 45.3 %). These molecular classifications were reported to correlate well with clinical outcome. However, borderlines of Olig2 LI were broad and could not clearly distinguish genotypes in the molecular classifications. In conclusion, Olig2 LI cannot be taken as a complete surrogate marker for molecular genotype, but could possibly provide some ancillary information when molecular assay is not availabe.
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Central nervous system infection caused by vancomycin-intermediate Staphylococcus aureus (SCCmec type IV, ST8).
J. Infect. Chemother.
PUBLISHED: 01-30-2014
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A 77-year-old Japanese man with a history of surgical treatment of chronic subdural hemorrhage was hospitalized for drainage of a subdural abscess and brain abscess in the right occipital area. Pus obtained from both the subdural abscess and brain abscess grew vancomycin-intermediate Staphylococcus aureus (VISA) (minimum inhibitory concentration = 4 ?g/mL), which was confirmed by population analysis. The SCCmec type and sequence type were subsequently identified as IV and ST8, respectively. The VISA strains were both sensitive to levofloxacin, clindamycin, minocycline, and linezolid. The patient was successfully treated with linezolid and discharged on day 51 after admission. We herein describe the first reported case of a brain abscess and subdural abscess caused by VISA in Japan.
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Purulent pericarditis with concurrent detection of Streptococcus pneumoniae and malignant squamous cells in pericardial fluid.
Intern. Med.
PUBLISHED: 06-19-2013
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Pneumococcal pericarditis complicated by a malignant effusion has not been reported previously. We experienced an independent 62-year-old man with lung cancer who was hospitalized for acute onset of atrial flutter and moderate pericardial effusion. He was afebrile; however, pericardiocentesis showed Streptococcus pneumoniae and malignant squamous cells in purulent pericardial fluid. This case shows that clinicians should keep in mind the possibility of afebrile bacterial pericarditis in cancer patients with pericardial effusions and that cultures of pericardial fluid should be performed in such patients along with cytological examinations.
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Impact of intensive infection control team activities on the acquisition of methicillin-resistant Staphylococcus aureus, drug-resistant Pseudomonas aeruginosa and the incidence of Clostridium difficile-associated disease.
J. Infect. Chemother.
PUBLISHED: 05-11-2013
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The transmission of multidrug-resistant organisms (MDROs) is an emerging problem in acute healthcare facilities. To reduce this transmission, we introduced intensive infection control team (ICT) activities and investigated the impact of their introduction. This study was conducted at a single teaching hospital from 1 April 2010 to 31 March 2012. During the intervention period, all carbapenem use was monitored by the ICT, and doctors using carbapenems inappropriately were individually instructed. Information related to patients with newly identified MDROs was provided daily to the ICT and instructions on the appropriate infection control measures for MDROs were given immediately with continuous monitoring. The medical records of newly hospitalized patients were reviewed daily to check previous microbiological results and infection control intervention by the ICT was also performed for patients with a previous history of MDROs. Compared with the pre-intervention period, the antimicrobial usage density of carbapenems decreased significantly (28.5 vs 17.8 defined daily doses/1000 inpatient days; p < 0.001) and the frequency of use of sanitary items, especially the use of aprons, increased significantly (710 vs 1854 pieces/1000 inpatient days; p < 0.001). The number of cases with hospital-acquired MRSA (0.66 vs 0.29 cases/1000 inpatient days; p < 0.001), hospital-acquired drug-resistant Pseudomonas aeruginosa (0.23 vs 0.06 cases/1000 inpatient days; p = 0.006) and nosocomial Clostridium difficile-associated disease (0.47 vs 0.11 cases/1000 inpatient days; p < 0.001) decreased significantly during the intervention period. Our study showed that proactive and continuous ICT interventions were effective for reduction of MDRO transmission.
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The landscape of somatic mutations in Down syndrome-related myeloid disorders.
Nat. Genet.
PUBLISHED: 05-03-2013
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Transient abnormal myelopoiesis (TAM) is a myeloid proliferation resembling acute megakaryoblastic leukemia (AMKL), mostly affecting perinatal infants with Down syndrome. Although self-limiting in a majority of cases, TAM may evolve as non-self-limiting AMKL after spontaneous remission (DS-AMKL). Pathogenesis of these Down syndrome-related myeloid disorders is poorly understood, except for GATA1 mutations found in most cases. Here we report genomic profiling of 41 TAM, 49 DS-AMKL and 19 non-DS-AMKL samples, including whole-genome and/or whole-exome sequencing of 15 TAM and 14 DS-AMKL samples. TAM appears to be caused by a single GATA1 mutation and constitutive trisomy 21. Subsequent AMKL evolves from a pre-existing TAM clone through the acquisition of additional mutations, with major mutational targets including multiple cohesin components (53%), CTCF (20%), and EZH2, KANSL1 and other epigenetic regulators (45%), as well as common signaling pathways, such as the JAK family kinases, MPL, SH2B3 (LNK) and multiple RAS pathway genes (47%).
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Integrated molecular analysis of clear-cell renal cell carcinoma.
Nat. Genet.
PUBLISHED: 04-15-2013
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Clear-cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer and its molecular pathogenesis is incompletely understood. Here we report an integrated molecular study of ccRCC in which ?100 ccRCC cases were fully analyzed by whole-genome and/or whole-exome and RNA sequencing as well as by array-based gene expression, copy number and/or methylation analyses. We identified a full spectrum of genetic lesions and analyzed gene expression and DNA methylation signatures and determined their impact on tumor behavior. Defective VHL-mediated proteolysis was a common feature of ccRCC, which was caused not only by VHL inactivation but also by new hotspot TCEB1 mutations, which abolished Elongin C-VHL binding, leading to HIF accumulation. Other newly identified pathways and components recurrently mutated in ccRCC included PI3K-AKT-mTOR signaling, the KEAP1-NRF2-CUL3 apparatus, DNA methylation, p53-related pathways and mRNA processing. This integrated molecular analysis unmasked new correlations between DNA methylation, gene mutation and/or gene expression and copy number profiles, enabling the stratification of clinical risks for patients with ccRCC.
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Various approaches for vascular health in elderly women.
Clin. Exp. Hypertens.
PUBLISHED: 03-29-2013
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Cardiovascular disease is one of the leading causes of morbidity and mortality in elderly women. Several previous studies evaluated various cardiovascular risk factors, such as brachial blood pressure (BP), systolic blood pressure (SBP), pulse pressure (PP), pulse wave velocity (PWV), central aortic pressure (CAP), and so on. More recently, measurement of ambulatory blood pressure (AMBP) was shown to be superior to clinic measurements in predicting cardiovascular mortality. However, the data are limited concerning the relationship among these variables in elderly women. In the present study, the data for clinic BP including PP, PWV, CAP, and AMSBP and AMCAP obtained using BPro were evaluated in 24 elderly hypertensive women. Although there was a significant correlation between AMSBP and AMCAP, no correlations were found between repeated measured values and values measured in the clinic on one occasion. In conclusion, measuring PWV and CAP in the clinic in patients with white coat hypertension or masked hypertension may not be an accurate way to measure these parameters.
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Aliskiren reduces morning blood pressure in hypertensive patients with diabetic nephropathy on hemodialysis.
Clin. Exp. Hypertens.
PUBLISHED: 03-27-2013
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Our previous study indicated that the exchange from an angiotensin receptor blocker (ARB) to aliskiren reduced morning blood pressure and albuminuria in hypertensive patients with diabetic nephropathy. We extended the above study and assessed the effects of exchanging from an ARB to aliskiren on home blood pressure in hypertensive patients with diabetic nephropathy on chronic hemodialysis. The patients who were persistently hypertensive despite antihypertensive therapy, including ARB, were considered as candidates for the exchange from the ARB to aliskiren. Patients age and durations of diabetes and hemodialysis were averaged as 62 ± 9 years old, 15 ± 8 and 7 ± 3 years, respectively. Aliskiren decreased morning systolic blood pressure (149 ± 14 to 144 ± 13 mm Hg, n = 30, P < .01) and plasma renin activity (3.5 ± 1.1 to 1.2 ± 0.6 ng/mL/h, P < .01) without changes in serum potassium. Aliskiren also reduced interdialytic weight gain (2.7 ± 0.6 to 2.5 ± 0.5 kg/interval, P < .05) and attenuated the magnitude of intradialytic declines in systolic (-20 ± 11 to -17 ± 10 mm Hg, P < .05) and diastolic blood pressure (-9 ± 6 to -5 ± 5 mm Hg, P < .01). The exchange from an ARB to aliskiren is safe and useful to control home blood pressure in hypertensive hemodialysis patients with diabetic nephropathy. Aliskiren reduced both intradialytic blood pressure drops and interdialytic weight gain in patients with DN.
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Direct Inhibition and Down-regulation by Uremic Plasma Components of Hepatic Uptake Transporter for SN-38, an Active Metabolite of Irinotecan, in Humans.
Pharm. Res.
PUBLISHED: 03-14-2013
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Clinical study has previously revealed that plasma concentration of 7-ethyl-10-hydroxycamptothecin (SN-38), an active metabolite of irinotecan, was higher in patients with end-stage renal failure than those with normal kidney function although SN-38 is mainly eliminated in the liver. Here, we focused on inhibition by uremic toxins of hepatic SN-38 uptake and down-regulation of uptake transporter(s) by uremic plasma in humans.
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Pneumococcal vertebral osteomyelitis at three teaching hospitals in Japan, 2003--2011: analysis of 14 cases and a review of the literature.
BMC Infect. Dis.
PUBLISHED: 01-28-2013
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Pneumococcal vertebral osteomyelitis (PVO) is a rare disease whose clinical characteristics have not been clarified. This study aimed to investigate the clinical features and outcomes of patients with PVO.
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Fibroblast growth factor 23 enhances renal klotho abundance.
Pflugers Arch.
PUBLISHED: 01-28-2013
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Klotho constitutes the receptor for fibroblast growth factor 23 (FGF23). However, the effects of FGF23 on renal and circulating klotho are not well-known. In vivo experiments were performed to assess the effects of FGF23 (10 ?g/kg), parathyroid hormone (PTH, 10 ?g/kg), and 1,25-dihydroxy-vitamin D3 (1,25VD, 1 ?g/kg) on renal expression and serum concentration of klotho in Wistar rats. Phosphate excretion was increased at 3 h after FGF23 administration (p?
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Combination therapy for hypertension in patients with CKD: a subanalysis of the Combination Therapy of Hypertension to Prevent Cardiovascular Events trial.
Hypertens. Res.
PUBLISHED: 01-24-2013
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The Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) trial was a multicenter, randomized, three-arm comparative study (N=3293) undertaken to determine the optimal combination therapy, based on the occurrence of cardiovascular events in patients treated with an angiotensin II receptor blocker (ARB), a ?-blocker (BB) or a thiazide diuretic (TD) in addition to the calcium antagonist benidipine as baseline medication. This subanalysis was conducted to compare the efficacy of three combination therapies in a subset of 834 patients with chronic kidney disease (CKD) (287 patients treated with benidpine-ARB, 283 patients treated with benidipine-BB and 264 patients treated with benidipine-TD). The incidence of composite cardiovascular events as the primary end point did not differ among these three groups. The incidence of hard end points and cerebrovascular events among these groups did not differ either, although the incidence among all patients in the COPE trial was lower in the benidipine-TD group than in the benidipine-BB group. The incidence of new-onset diabetes mellitus was higher in the benidipine-TD group than in the benidipine-ARB group among patients with CKD. The estimated glomerular filtration rate (eGFR) was maintained even after 12 months of treatment in patients with a baseline eGFR <60 ml min(-1) per 1.73 m(2) regardless of the treatment group, although the eGFR decreased over time in all patients in the three groups. In conclusion, in patients with CKD, all of the tested combination therapies demonstrated comparable efficacy in terms of prevention of cardiovascular events as well as maintenance of eGFR.
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Effects of a benidipine-based combination therapy on the risk of stroke according to stroke subtype: the COPE trial.
Hypertens. Res.
PUBLISHED: 01-19-2013
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The Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) trial compared the dihydropyridine T/L-type calcium channel blocker benidipine-based therapies when combined with an angiotensin receptor blocker (ARB), a ?-blocker (BB) or a thiazide diuretic (TD). The results suggested that benidipine combined with a BB appeared to be less beneficial in reducing the risk of stroke compared with the benidipine-TD combination (hazard ratio (HR): 2.31, P=0.0109). We further evaluated the treatment effects on different stroke subtypes among the three benidipine-based regimens. The COPE trial was an investigator-initiated, multicenter study with PROBE design. Patients with atrial fibrillation or flutter were excluded from the study. All stroke events were subclassified with the Trial of Org 10?172 in Acute Stroke Treatment (TOAST) criteria. The total incidence of stroke was 4.7, hemorrhagic stroke was 1.6 and ischemic stroke was 2.5 per 1000 person-years. The incidence of lacunar stroke was 1.1, large-artery stroke was 0.6, cardioembolic stroke was 0.3, unknown ischemic type was 0.6 and transient ischemic attack was 0.6 per 1000 person-years. Although few differences in stroke subtypes were observed among the three treatment groups, multi-adjusted HRs for the incidence rates of all types of stroke, hemorrhagic stroke and ischemic stroke were significantly higher with the benidipine-BB regimen than with the benidipine-TD regimen. The incidence of both hemorrhagic and ischemic stroke in the benidipine-ARB regimen was not different compared with the other two treatment regimens. This prespecified sub-analysis suggested that a blood pressure-lowering therapy with a benidipine-TD regimen might be beneficial for hypertensive patients to prevent both hemorrhagic and ischemic stroke.
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Does cinacalcet HCl, an oral calcimimetic agent for the treatment of secondary hyperparathyroidism, improve arterial stiffness in patients on continuous ambulatory peritoneal dialysis?
Adv Perit Dial
PUBLISHED: 11-12-2011
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Vascular calcification (VC) and arterial stiffness (AS) are major contributors to cardiovascular disease, and in chronic kidney disease, VC and AS are correlated. Disorders of calcium and phosphate metabolism contribute to the progression of VC and to increases in AS. The efficacy of cinacalcet (CIN) in reducing AS in patients on continuous ambulatory peritoneal dialysis (CAPD) has not been determined. The present study enrolled 19 CAPD patients (12 women, 7 men; mean age: 62.2 +/- 3.6 years) with serum intact parathyroid hormone (iPTH) greater than 500 ng/dL (mean value: 675 +/- 106 ng/dL) in whom daily oral treatment with CIN 25 mg was started. If administration of CIN for 3 months failed to reduce the level of iPTH to less than 300 ng/dL, the dose of CIN was increased to 50 mg daily. Before the start of CIN and at 3 years after the start of CIN, pulse wave velocity (PWV) was determined. In 11 patients, levels of iPTH were reduced to less than 300 ng/dL; levels in the rest of the patients remained high. We observed no significant differences in PWV before CIN and at 3 years after CIN start (1856 +/- 198 cm/s vs. 1726 +/- 187 cm/s). Multivariate regression analysis of PWV demonstrated that both systolic blood pressure and changes in serum levels of phosphate contributed to decreases in PWV In patients receiving CAPD, VC and AS might be the result of higher systolic blood pressure and increased serum levels of phosphate.
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Removal of the peritoneal dialysis catheter because of gastrointestinal disease in patients on continuous ambulatory peritoneal dialysis: a single-center case series.
Adv Perit Dial
PUBLISHED: 11-12-2011
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We previously reported that peritoneal dialysis (PD)-associated peritonitis is a major cause of PD catheter removal. Another major cause is disease of the gastrointestinal tract, including neoplasm and perforation. In the present study, we reviewed the records of patients who underwent catheter removal at our hospital for reasons other than peritoneal infection--and for gastrointestinal disease in particular. Data were collected from the records of patients who received continuous ambulatory PD (CAPD) therapy between 2004 and 2010 at the Department of Nephrology, Saitama Medical University. Mean duration of CAPD was 6.2 +/- 4.7 years, and mean age at onset was 64.5 +/- 9.6 years. During the investigation period, catheters were removed from 13 patients (4 men, 9 women) because of gastrointestinal disease: gastric cancer in 3 cases, colon cancer in 3 cases, perforation of the lower gastrointestinal tract in 3 cases, and other reasons in 4 cases. Examination of pathology specimens obtained from 6 patients-including 1 in whom contrast-enhanced computed tomography indicated the presence of encapsulating peritoneal sclerosis (EPS)-revealed mild fibrosis in the subserous layer. No patient died of infection after a surgical procedure. Moreover, throughout the observation period, no patient developed new EPS or postoperative ileus. The present study suggests that CAPD itself seems to be free of untoward effects during the postoperative course in these patients.
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Clinical presentation in patients more than 80 years of age at the start of peritoneal dialysis.
Adv Perit Dial
PUBLISHED: 11-12-2011
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The age of new dialysis patients is rapidly increasing. In the present study, we examined clinical presentation in new peritoneal dialysis (PD) patients 80 years of age or older at our hospital. Data were collected from the records of patients newly starting continuous ambulatory PD (CAPD) therapy between January 2005 and July 2010. During that period, 11 patients 80 years of age or older (average age: 83.1 +/- 3.8 years) were introduced to PD therapy. The reason for dialysis was hypertensive nephrosclerosis in 8 patients, and chronic glomerulonephritis, chronic tubulointerstitial nephritis, and an unknown primary disease in 1 patient each; there were no cases of diabetic nephropathy. At dialysis start, average serum creatinine was 6.1 +/- 1.4 mg/dL, arterial wall calcification was found by computed tomography or chest radiography in 10 of 11 patients (90.9%), and aortic or mitral valve calcification, or both, was found by echocardiography in 3 patients (27.3%). By the end of January 2011, 8 patients had died. Average survival after the start of PD was 31.9 +/- 22.3 months. Hypertensive nephrosclerosis, a cause less often seen in younger patients, was the most common primary disease among our elderly dialysis patients. As we previously reported, vascular and valvular calcification are important factors for determining prognosis; however, no significant relationships were observed in the present study, probably because almost all the patients had such calcifications.
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Testing a single monthly dose of darbepoetin alpha to maintain hemoglobin levels in continuous ambulatory peritoneal dialysis patients.
Adv Perit Dial
PUBLISHED: 11-12-2011
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The newly developed erythropoiesis agent darbepoetin alpha (DA) allows for once-monthly dosing in the treatment of anemia in patients on dialysis. This dosing schedule has prompted some studies to examine the efficacy of DA in patients on continuous ambulatory peritoneal dialysis (CAPD). In the present study, we assessed whether intravenous (IV) administration of DA once monthly is effective for maintaining hemoglobin levels near 10.5 g/dL in patients on CAPD. This single-center prospective cohort study included 52 clinically stable patients (25 men, 27 women; mean age: 59 +/- 10 years). All patients had been on a stable weekly or twice monthly regimen of recombinant human erythropoietin (rHuEPO) before initiation of the study. To determine the monthly dose of DA, the previously used mean weekly dose of rHuEPO was divided by 200 to determine the equivalent weekly dose of DA in micrograms; that number was then multiplied by 4 to generate the monthly dose requirement. For example, if 3000 IUrHuEPO was being administered weekly, then the monthly dose of DA was calculated to be 60 microg (3000/200 x 4). All patients received a monthly dose of DA the first month, and hemoglobin and other routine laboratory tests were performed monthly for 24 consecutive weeks. In 26 patients, the calculated monthly DA dose remained stable. The monthly dose was increased by 25% in 22 patients and by 50% in 4 patients. With regard to iron stores and iron availability for erythropoiesis, no significant differences were observed in the patients on various doses of DA. Nonsignificant differences in weekly creatinine clearance as determined using the PD Adequest software (Baxter Healthcare, Tokyo, Japan) were observed between the groups. No clinically meaningful differences in other laboratory values between the groups were observed. Once-monthly administration of DA is not always sufficient to maintain hemoglobin levels in patients on CAPD when adequate dialysis therapy is not achieved.
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Chronic kidney disease in postmenopausal women.
Hypertens. Res.
PUBLISHED: 09-08-2011
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Menopause is derived from the Greek words men (month) and pauses (cessation) and means permanent cessation of menstruation after the loss of ovarian activity. Chronic kidney disease (CKD) has recently been associated with cardiovascular events in several studies. CKD patients have a heavy burden of traditional cardiovascular risk factors in addition to a range of nontraditional risk factors such as inflammation and abnormal metabolism of calcium and phosphate. In this review, the association of CKD and cardiovascular disease (CVD), as well as of osteoporosis in postmenopausal women is discussed. CKD mineral and bone disorder, characterized by disturbances of calcium/phosphate/parathyroid hormone, bone abnormalities and vascular and soft tissue calcification, is highly prevalent in CKD and is a strong, independent predictor of bone fracture, CVD and death. Estrogen has been shown to: (a) decrease the expression of angiotensin type 1 receptors in vasculature and kidneys; (b) reduce the expression and activity of angiotensin-converting enzyme, and (c) cause the release of angiotensinogen substrate from the liver. However, the degree of activation or suppression of the renin-angiotensin-aldosterone system by estrogen has not been clearly established. Clinical data on the effects of estrogen therapy on bone mineral densities are extremely limited in the ESRD population. CVD is the most common cause of death in postmenopausal women with CKD and many contributing factors have been explored. Future research for prevention of CVD in postmenopausal women with CKD would focus on the biology of vascular calcification as well as bone loss.
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Lipopolysaccharide-induced overproduction of nitric oxide and overexpression of iNOS and interleukin-1? proteins in zinc-deficient rats.
Biol Trace Elem Res
PUBLISHED: 07-27-2011
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Zinc deficiency leads to decreased cellular immune responses. The overproduction of nitrogen species derived from inducible nitric oxide synthase (iNOS), its enzyme, and interleukine-1 beta (IL-1?), and inflammatory cytokine have been implicated in immune responses. The goal of this study was to investigate the effects of lipopolysaccharide (LPS)-induced changes in NO metabolites, iNOS, and IL-1? protein expression in the lungs of zinc-deficient rats. Male Sprague-Dawley rats (body weight, 100 g) were divided into two groups and were fed either a zinc-deficient diet (ZnD) or a zinc-containing diet (Cont). After 4 weeks on these diets, rats received a 10-mg/kg dose of LPS injected via the tail vein and were then maintained for an additional 72 h. To determine total NO concentrations in the blood, serum zinc concentration, iNOS protein expression, IL-1?, and iNOS immunohistochemistry, blood and lung samples were obtained at pre-LPS injection, 5, 24, and 72 h after injection. Total NO levels were significantly increased at 5, at 24, and at 72 h after LPS injection compared with pre-LPS injection level in ZnD group; significant changes in total NO levels was elevated at 5 h from at pre-LPS level but not significant changes from basal level at 24 and 72 h in the control group. Based on western blot analyses and immunohistochemistry, clear bands indicating iNOS and IL-1? protein expression and iNOS antibody-stained inflammatory cells were detected at 5 and 24 h in the ZnD group and 5 h in the Cont group, not observed at 24 and 72 h in the control group. These results suggest that zinc deficiency induces overexpression of iNOS and IL-1? proteins from inflammatory cells around the alveolar blood vessels, resulting in overproduction of total NO and persisted inflammatory response in the zinc-deficient rat lung. Taken together, overexpression of LPS-induced iNOS, overproduction of iNOS-derived NO, and overexpression of IL-1? may induce nitrosative and oxidative stresses in the lung, and these stresses may be involved low immunity of zinc deficiency states.
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Treatment of hypertension in patients 85 years of age or older: a J-BRAVE substudy.
Clin. Exp. Hypertens.
PUBLISHED: 07-27-2011
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Whether the strict control of blood pressure (BP) of patients with hypertension who are aged 85 years or older is beneficial is unclear. The Japans Benidipine Research on Antihypertensive Effects in the Elderly study is a prospective, observational 3-year study to evaluate the safety and effectiveness of treatment with a calcium channel blocker benidipine in 8897 hypertensive patients aged 65 years or older as a post-marketing surveillance. We examined the relationship between the achieved BP and cardiovascular events (i.e., stroke, myocardial infarction, and heart failure) in a subgroup of 415 patients aged 85 years or older (mean age 88 years). BP decreased significantly from 165 ± 14/84 ± 10 mmHg to 130 ± 11/71 ± 10 mmHg during treatment in patients with a treated systolic BP (SBP) < 140 mmHg (n = 230) and BP decreased significantly from 169 ± 16/86 ± 12 mmHg to 143 ± 13/75 ± 10 mmHg in those with a treated SBP ? 140 mmHg (n = 185). There was a nonsignificant trend toward a lower rate of cardiovascular events and higher rate of total death in patients with a treated SBP < 140 mmHg. On-treatment SBP ? 160 mmHg is tended to associate with a higher incidence of cardiovascular events. There was no significant difference in the incidence of adverse reactions between the controlled BP group (3.04%) and the less well controlled BP group (3.24%). In conclusion, although this study was not powered for definitive conclusion, there was a nonsignificant trend toward a lower rate of cardiovascular events and higher total death in patients aged 85 years or older with a treated SBP < 140 mmHg.
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Noninvasive evaluation of kidney hypoxia and fibrosis using magnetic resonance imaging.
J. Am. Soc. Nephrol.
PUBLISHED: 07-14-2011
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Interstitial fibrosis and hypoxia accelerate the progression of CKD, but clinical tools to quantitate these factors in patients are lacking. Here, we evaluated the use of two magnetic resonance imaging (MRI) techniques, diffusion-weighted (DW)-MRI and blood oxygen level-dependent (BOLD)-MRI, to assess kidney fibrosis and hypoxia of the cortex in 142 patients with either diabetic nephropathy (n = 43), CKD without diabetes (n = 76), or acute kidney injury (AKI) (n = 23). Apparent diffusion coefficient (ADC) values of DW-MRI correlated with estimated glomerular filtration rates (eGFR) in the diabetic nephropathy and CKD groups (r(2) = 0.56 and r(2) = 0.46, respectively). Although the T2* values of BOLD-MRI and eGFR displayed good correlation in the CKD group (r(2) = 0.38), we did not observe a significant correlation between these values in the diabetic nephropathy group, suggesting that factors other than tubulointerstitial alteration determine the degree of hypoxia in the renal cortex. In the AKI group, neither the T2* nor ADC values correlated with eGFR. Renal biopsies from patients with CKD demonstrated that the T2* and ADC MRI values correlated with renal pathology. Taken together, ADC and T2* values appear to serve as accurate indices for evaluating renal tubulointerstitial alterations and parenchymal hypoxia, respectively, in the cortex. Functional MRI can thus contribute to multilateral, noninvasive, in vivo assessment of kidney function.
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Amlodipine and loop diuretics as the second anti-hypertensive medication for the treatment of hypertension with chronic kidney diseases.
Clin. Exp. Hypertens.
PUBLISHED: 06-25-2011
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Renoprotective effects of renin-angiotensin system inhibitors are well known. However, hypertension with chronic kidney diseases (CKDs) is usually hard to manage with a single agent, and requires the addition of either a calcium antagonist or diuretics to achieve the goal of blood pressure (BP) lowering. Retrospective study was performed among the patients who regularly visited our office, and whose BP had not reached the goal of BP despite of treatment with an angiotensin receptor blocker. Clinical parameters were observed for 6 months. Comparisons of home BP and proteinuria were made between 16 patients prescribed additional calcium antagonists and 15 patients with diuretics. Patient background including age, sex BP, augmentation index, and renal function were similar between the two groups. Both calcium antagonists and diuretics considerably decreased BP. An addition of either agent resulted in similar control of home BP. While both agents reduced augmentation index (AI), calcium antagonist exerted greater improvements in AI (-7 ± 5 vs. -4 ± 3%, p < 0.01). Although urinary protein excretion in both groups was decreased, the degree of these decreases was greater among the patients treated with a calcium antagonist (-28 ± 15 vs. -11 ± 15%, p < 0.01). During observation periods, eGFR in both groups did not show any significant changes from the base line. Under the inhibition of a renin-angiotensin system, calcium antagonists elicited a greater decrease in urinary protein excretion than diuretics when BP similarly controlled. Calcium antagonists also improved AI more strongly than diuretics. Calcium antagonists appear suited for adding on renin angiotensin system inhibitors to treat hypertension with CKDs.
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Artificial RNA aptamer production by the marine bacterium Rhodovulum sulfidophilum: improvement of the aptamer yield using a mutated transcriptional promoter.
J. Biosci. Bioeng.
PUBLISHED: 05-31-2011
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Noncoding small RNAs and artificial RNA aptamers are now expected to be potential candidates for RNA therapeutic agents. We previously proposed a unique method for economical production of these RNAs using the marine phototrophic bacterium Rhodovulum sulfidophilum. This bacterium does not produce any ribonucleases but does produce extracellular nucleic acids in the culture medium in nature. Using this bacterium and an engineered plasmid containing the rrn promoter for the RNA expression, we developed a method for production of the streptavidin RNA aptamer in the culture medium. However, the yield of this RNA product in the culture medium by this method was not enough for practical use. In the present paper, we improved the yield of this product by modification of the -35 region of the rrn promoter so as to escape from the Fis protein control and the use of a new vector plasmid. Using this system, the extracellular RNA aptamer of approximately 200 ng and the total RNA aptamer (both extra- and intracellular form) of about 20 ?g from 1 L culture were accomplished by constitutive expression of the gene.
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Prevention of cardiovascular events with calcium channel blocker-based combination therapies in patients with hypertension: a randomized controlled trial.
J. Hypertens.
PUBLISHED: 05-26-2011
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Current guidelines recommend the use of multiple medications for hypertension. The present study was aimed at determining which combination was optimal to prevent cardiovascular events.
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Antihypertensive medication versus health promotion for improving metabolic syndrome in preventing cardiovascular events: a success rate-oriented simulation study.
BMC Med Inform Decis Mak
PUBLISHED: 02-13-2011
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In practice, it is difficult to compare the effectiveness of traditional antihypertensive treatment with that of health promotion in reducing incidence rate of cardiovascular disease (IRCVD, events/year). This simulation study compared the effectiveness of two approaches to reducing IRCVD in a sample population: a traditional approach, in which high-risk patients are treated with conventional antihypertensive medications, and a population-based approach, in which subjects participate in a health promotion program.
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Telmisartan lowers home blood pressure and improves insulin resistance without correlation between their changes.
Clin. Exp. Hypertens.
PUBLISHED: 01-26-2011
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Telmisartan is an angiotensin type 1 receptor blocker (ARB), which also partially activates liganding peroxisome proliferator-activated receptor gamma. However, the relationship between the effects of telmisartan on hemodynamics and metabolism has not sufficiently been elucidated in clinical settings. We examined the long-term effects of telmisartan on hemodynamics including home blood pressure (BP) and on insulin resistance representing as homeostasis model assessment (HOMA-R). Twenty-seven hypertensive patients were consecutively enrolled at our outpatient department. At entry, all of the participants were previously prescribed another ARB for more than 3 months and then the former ARB were replaced by telmisartan. Hemodynamic and metabolic parameters were measured before treatment and at points 1 and 3 months after treatment with telmisartan. Telmisartan significantly lowered home systolic blood pressure (SBP) and diastolic blood pressure (DBP) (DBP) and improved HOMA-R during the treatment period. However, the changes in home SBP and DBP were not correlated with that of HOMA-R. In conclusion, telmisartan lowers home BP and improves insulin resistance without correlation between their changes.
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Effect of antihypertensive treatment on cardiovascular events in elderly hypertensive patients: Japans Benidipine Research on Antihypertensive Effects in the Elderly (J-BRAVE).
Clin. Exp. Hypertens.
PUBLISHED: 01-26-2011
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The achievement rate of blood pressure (BP) target and the relationship between on-treatment BP and development of cardiovascular events (i.e., stroke, myocardial infarction, and heart failure) were investigated in a total of 8,897 patients in the Japans Benidipine Research on Antihypertensive Effects in the Elderly (J-BRAVE) study, a prospective, 3-year observational study of a calcium channel blocker-based treatment in hypertensive patients aged ?65 years as a post-marketing surveillance. Blood pressure decreased significantly from 164.8 ± 14.1/88.2 ± 10.3 mmHg to 137.0 ± 13.5/75.6 ± 9.5 mmHg and the percentage of patients who achieved BP <140/90 mmHg was 57.2% after 3 years. The incidence of cardiovascular events was 7.54/1,000 patient-years. Subgroups of patients stratified by on-treatment systolic blood pressure (SBP) were analyzed. Baseline BP, body mass index (BMI), the dose of benidipine, the mean number of anti-hypertensive drugs, and the incidence of cardiovascular events were higher in patients with on-treatment SBP ?160 mmHg than in those with an SBP of <130 mmHg. In patients aged 65 to 74 years (n = 5,092) and patients aged ?75 years (n = 3,805), the percentages of patients who achieved the BP target of <140/90 mmHg were 57.5% and 56.6% after 3 years, respectively, and the incidence of cardiovascular events was higher in patients with on-treatment SBP ?160 mmHg in both age subgroups. The results of the J-BRAVE study show that on-treatment SBP ?160 mmHg is associated with a higher incidence of cardiovascular events in elderly hypertensive patients.
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The impact of post-mastectomy radiation therapy on male breast cancer patients--a case series.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 01-15-2011
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To assess the impact of radiation management on male breast cancer (MBC) at London Regional Cancer Program (LRCP).
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[Association between long-term smoking and hypertension and early-onset nodular glomerulosclerosis].
Nihon Jinzo Gakkai Shi
PUBLISHED: 11-17-2010
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Diabetic nodular glomerulosclerosis, also known as Kimmelstiel-Wilson syndrome, is a specific pathological variant of diabetic nephropathy ; however, histological findings similar to diabetic nephropathy are observed occasionally without glucose intolerance. Therefore, such nodular glomerulosclerosis is called idiopathic nodular glomerulosclerosis. Several case reports that have been published recently indicate that smoking and hypertension, which are classical renal risk factors, may be attributed to this form of glomerular degeneration. Accordingly smoking- and hypertension-associated nodular glomerulosclerosis has been considered to be different from the idiopathic form. This novel form of nodular glomerulosclerosis is associated with a history of long-term smoking and hypertension, and the age of onset of this disease is more than 60 years. We present the case of a 27-year-old Japanese male who was admitted to our hospital with nephrotic syndrome, hypertension, and renal impairment. He had a smoking history of at least 13 years, and had been exposed to passive smoking for several years because his parents were smokers. Renal biopsy revealed diffuse and global nodular glomerulosclerosis, although the patient did not have any primary diseases such as diabetes mellitus or paraproteinemia, that can cause this condition. We diagnosed smoking- and hypertension-associated nodular glomerulosclerosis. Cessation of smoking and the administration of an angiotensin II receptor blocker decreased his proteinuria and showed recovery of kidney function. This case report suggests that long-term smoking is closely associated with nodular glomerulosclerosis. Further, in our case, the age of the patient was lower than that of patients with the same disease among cases that have been reported previously.
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Survival of patients over 75 years of age on peritoneal dialysis therapy.
Adv Perit Dial
PUBLISHED: 09-23-2010
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The number of elderly patients requiring dialysis therapy has been increasing in developed countries. Among elderly patients on dialysis, the incidence of death from cardiovascular complications has increased. Our objective was to study whether the presence of abnormal cardiac function at the initiation of peritoneal dialysis (PD) affects the prognosis of patients over the age of 75 years on PD therapy. A retrospective analysis of 46 patients more than 75 years of age who started PD therapy (average age: 79.4 +/- 3.5 years; 26 women, 20 men) collected demographic and comorbidity data. Survival was defined as time from the initiation of PD therapy. In 12 patients, ejection fraction measured by echocardiography was less than 50% ("abnormal EF" group); in 34 patients, ejection fraction was more than 50% ("normal EF" group). In the abnormal EF group, 9 patients (75%) survived 12 months; in the normal EF group, 26 patients (76%) survived that long. However, at 24 months, only 2 patients (16%) in the abnormal EF group and 18 patients (52%) in the normal EF group were still alive. Survival was significantly longer in the normal EF group (p < 0.0019). With the exception of serum albumin, other parameters such as age, serum creatinine, and hemoglobin were not significantly difference between the two groups at the initiation of dialysis therapy. Our study demonstrated that cardiac performance at the initiation of PD therapy predicts prognosis in PD patients more than 75 years of age.
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Efficacy and safety of ezetimibe and low-dose simvastatin as primary treatment for dyslipidemia in peritoneal dialysis patients.
Adv Perit Dial
PUBLISHED: 09-23-2010
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We previously reported that the level of low-density lipoprotein cholesterol (LDL-C) was higher in patients receiving continuous ambulatory peritoneal dialysis (CAPD) than in patients on hemodialysis (HD). One of the problems associated with reaching the LDL-C target during statin treatment of patients on CAPD is the emergence of laboratory or clinical side effects. The present study evaluated the efficacy and tolerability of daily combined treatment with ezetimibe 10 mg and simvastatin 10 mg in patients receiving CAPD. Our study enrolled 12 CAPD patients who were experiencing adverse effects from statin therapy. Their existing statin therapy was suspended for 1 month ("washout period"), and the patients were then shifted to treatment with the ezetimibe-simvastatin combination. The patients were again monitored for adverse events such as asthenia and myalgia during the subsequent 12 months. Body mass index and levels of glycated hemoglobin, fasting plasma glucose, total cholesterol, LDL-C, triglycerides, alanine amino-transferase, aspartate aminotransferase, and creatinine phosphokinase were also assessed. The combination of ezetimibe and low-dose simvastatin significantly reduced levels of total cholesterol (by a mean of 27%), triglycerides (by 9%), and LDL-C (by 33%) and increased levels of high-density lipoprotein cholesterol (by 15%). In 11 patients (92%), the target LDL-C level of less than 100 mg/dL was reached. No significant change in weekly creatinine clearance occurred, and no serious adverse effects were observed. No patient developed muscle pain or weakness, and no increase in creatinine kinase was found. Residual renal function declined, although not significantly when compared with initial values. In conclusion, the present study suggests that combined ezetimibe and low-dose statin treatment is a promising approach for safe and effective primary treatment of dyslipidemia in CAPD patients.
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Fibroblast expression of an I?B dominant-negative transgene attenuates renal fibrosis.
J. Am. Soc. Nephrol.
PUBLISHED: 09-16-2010
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It is not clear whether interstitial fibroblasts or tubular epithelial cells are primarily responsible for the profibrotic effects of NF-?B activation during renal fibrogenesis. Here, we crossed mice carrying a conditional I?B dominant-negative transgene (I?BdN) with mice transgenic for cell-specific FSP1.Cre (FSP1(+) fibroblasts) or ?GT.Cre (proximal tubular epithelia) and challenged all progeny with unilateral ureteral obstruction. We determined NF-?B activation by nuclear localization of phosphorylated p65 ((p)p65) in renal tissues after 7 days. We observed inhibition of NF-?B activation in interstitial cells and tubular epithelia in obstructed kidneys of FSP1.Cre;I?BdN and ?GT.Cre;I?BdN mice, respectively, compared with I?BdN controls (P < 0.05). Deposition of extracellular matrix, however, was significantly lower in the obstructed kidneys of FSP1.Cre;I?BdN mice but not in ?GT.Cre;I?BdN mice (P < 0.05). In addition, levels of mRNA encoding the profibrotic PAI-1, fibronectin-EIIIA, and type I (?1) procollagen were significantly lower in obstructed kidneys of FSP1.Cre;I?BdN mice compared with ?GT.Cre;I?BdN mice (P < 0.05). Taken together, these data support a profibrotic role for fibroblasts, but not proximal tubular epithelial cells, in modulating NF-?B activation during renal fibrogenesis.
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Granulomatous interstitial nephritis in chronic lymphocytic leukaemia.
Nephrol. Dial. Transplant.
PUBLISHED: 08-11-2010
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We present a case of granulomatous interstitial nephritis (GIN) associated with chronic lymphocytic leukaemia (CLL). GIN is a rare pathological finding noted in renal biopsy specimens. Furthermore, CLL does not usually cause GIN. In this case, acute renal injury probably resulted from GIN, and urgent dialysis was required, despite sufficient chemotherapy. Immunohistochemical analyses of a biopsy specimen revealed invasion of CD20(?+) CLL cells, surrounded by reactive T cells, and granuloma formation. Thus, CLL may induce secondary interstitial nephritis as a granulomatous reaction.
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Characterization of sensory neurons in the dorsal root ganglia of Bax-deficient mice.
Brain Res.
PUBLISHED: 07-17-2010
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During development, the rescue of spinal motoneurons as well as sensory neurons in the dorsal root ganglion (DRG) from programmed cell death (PCD) depends on the integrity of peripheral target innervation. Following deletion of the pro-apoptotic gene Bax, both motoneurons and DRG neurons are rescued from PCD. In the present paper, we asked whether different cell types in the DRG exhibit distinct responses to Bax deletion. In 1-month-old Bax-deficient (Bax-/-) mice, distinct subsets of DRG neurons that were immunopositive for TrkA, CGRP, TRPV1 or TrkC, were all increased in number and exhibited cell atrophy compared to wild type DRG neurons. In addition there was hyperinnervation of the epidermis by CGRP immunopositive processes and a correlated functional hypersensitivity of mechanical nociception in Bax-/- mice. By contrast, the functional properties of populations of rescued thermoreceptor and mechanoreceptor DRG neurons were unchanged. These data indicate that although Bax deletion rescues all of the DRG cell types examined here from PCD, the functional consequences of having excess cells differ between sensory phenotypes.
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Height constitutes an important predictor of mortality in end-stage renal disease.
Cardiol Res Pract
PUBLISHED: 07-16-2010
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Aim. Height is an important determinant of augmentation index (AI) that anticipates cardiovascular prognosis. There is a scanty of the data whether short height predicts survival in patients with end-stage renal diseases, a high risk population. Methods. Fifty two hypertensive patients with type 2 diabetic nephropathy receiving hemodialysis and 52 patients with nondiabetic nephropathy were enrolled. In addition to AI estimated with radial artery tonometry, classical cardiovascular risk factors were considered. Patients were followed for 2 years to assess cardiovascular prognosis. Results. Cox hazards regression revealed that both smoking and shortness in height independently contributed to total mortality and indicated that smoking as well as the presence of left ventricular hypertrophy predicted cardiovascular mortality. Our findings implicated that high AI, the presence of diabetes, and low high-density lipoprotein cholesterol were significant contributors to cardiovascular events. Conclusions. Our findings provide new evidence that shortness in height independently contributes to total mortality in hemodialysis patients.
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Seasonal variations of daily changes in blood pressure among hypertensive patients with end-stage renal diseases.
Clin. Exp. Hypertens.
PUBLISHED: 07-09-2010
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Hypertension is a well-known cardiovascular risk. Patients with end-stage renal diseases frequently suffer hypertension, and their blood pressure elevates in winter. However, seasonal changes in daily variations of blood pressure are poorly assessed in patients treated with hemodialysis. Thirty hypertensive patients with end-stage renal diseases were enrolled in the study. Dry weight and antihypertensive medications were altered when they were necessary. Home blood pressure measurements were performed at least for 1 week in each season; April-May 2008, July-August 2008, October-November 2008, and January-February 2009. Both morning and evening systolic blood pressures (SBPs) showed significant seasonal changes ( p < 0.01), with the highest blood pressure in winter (162 +/- 18 and 135 +/- 22 mmHg in morning and evening). Morning diastolic blood pressure (DBP) also exhibited seasonal changes ( p < 0.05), with the highest blood pressure in fall ( 78 +/- 8 mmHg). Evening DBP did not manifest seasonal deviations. Morning-evening differences in SBP and DBP were the greatest in winter (28 +/- 21 and 10 +/- 9 mmHg in SBP and DBP, p < 0.01), and the smallest in summer (16 +/- 12 and 6 +/- 5 mmHg). Daily variations of SBP and DBPs in spring (19 +/- 12 and 7 +/- 6 mmHg) and fall (20 +/- 13 and 9 +/- 8 mmHg) were between those of summer and winter. Our results indicate that not only averaged blood pressure but also variations of blood pressure in winter are larger than the other seasons, and suggest that these blood pressure variations participate in cardiovascular events in hypertensive patients with end-stage renal diseases.
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Selection of modality in continuous renal replacement therapy.
Contrib Nephrol
PUBLISHED: 05-07-2010
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Continuous hemoperfusion therapies are now widely used in critical care, and could prove to be life-saving for patients unable to receive regular hemoperfusion treatments. Unfortunately, due to the inherent difficulties in assessing the effects of treatment upon critically ill patients, the efficacy of this modality has yet to be proven. Instead of focusing exclusively on a particular form of continuous hemoperfusion or a direct comparison between the different types available, this report provides a general overview of the studies reporting on its efficacy across a wide range of conditions. The authors conclude that continuous hemoperfusion could be beneficial in some cases, but this is highly dependent upon the particular modality used.
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Application of polymyxin B convalently immobilized fiber in patients with septic shock.
Contrib Nephrol
PUBLISHED: 05-07-2010
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Sepsis and septic shock are major causes of morbidity and mortality in the intensive care unit. Endotoxin produced by Gram-negative bacteria contributes to the pathogenesis of sepsis and septic shock. As an adsorbent, a polymyxin B convalently immobilized fiber (PMX) was developed. This review discusses, designing of the PMX, its application in clinical practice and the clinical outcomes.
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Equipment and monitoring in continuous renal replacement therapy.
Contrib Nephrol
PUBLISHED: 05-07-2010
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Continuous renal replacement therapy is expected to improve unfavorable status in critical care. As precise volume control is most important to maintain the damaged circulation system, blood and solution control should be carried out precisely. Recently, further technical development was achieved in this area, and quality of these products--including disposable kits--has been improved. Nevertheless, incidental and accidental errors in human and equipment are sometimes happen. In order to decrease it, the staff understands the system of treatment and is familiar to the routine check point.
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Acute kidney injury of non-septic origin requiring dialysis therapy.
Contrib Nephrol
PUBLISHED: 05-07-2010
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Acute kidney injury (AKI) requiring dialysis occurs frequently, and its pathogenesis involves multiple pathways within which hemodynamic, inflammatory and nephrotoxic factors overlap. Several studies have tried to assess the risk factors leading to AKI, and found, among other factors, that preoperative renal dysfunction is important. Currently, it is uncertain when dialysis therapy should start. However, AKI after cardiac surgery should be treated early by continuous hemodialysis.
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Incidence of symptomatic stroke and cancer in chronic kidney disease patients treated with epoetins.
Clin. Exp. Nephrol.
PUBLISHED: 04-30-2010
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Use of erythropoiesis-stimulating agents (ESA) has been reported to increase the incidence of cardiovascular diseases at target Hb levels by more than 12.0 g/dl. The recent TREAT study found an increased incidence of stroke and cancer when maintaining the Hb level at 12.5 g/dl in diabetic patients.
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Cross-sectional characterization of all classes of antihypertensives in terms of central blood pressure in Japanese hypertensive patients.
Am. J. Hypertens.
PUBLISHED: 01-02-2010
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Central blood pressure (CBP) has been reported to be superior to brachial blood pressure (BP) as a cardiovascular risk predictor in hypertensive patients; however, the effects of antihypertensives on CBP have not been fully examined. This cross-sectional hypothesis-generating study aimed to tentatively characterize all classes of antihypertensives in relation to CBP.
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Zigzagged augmentation index in diabetes.
Clin. Exp. Hypertens.
PUBLISHED: 12-17-2009
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Although the patients with diabetic nephropathy suffered high cardiovascular risk, augmentation index (AI) in diabetic nephropathy has been poorly characterized. Cross-sectional studies were performed on 26 diabetic and 27 nondiabetic nephropathic patients. Home blood pressure was examined. In addition, blood pressure, pulse rate, and AI were measured in both supine and sitting positions. Patient backgrounds such as age, sex, sitting blood pressure, and pulse rate were similar between two groups. Circadian variations of home blood pressure were preserved in nondiabetic patients, but disappeared in diabetes. Changing from supine to sitting position induced greater decrements of systolic blood pressure (DeltaSBP -9 +/- 8 mmHg) and AI (DeltaAI -7 +/- 10) in the diabetic group than in nondiabetic patients (DeltaSBP -4 +/- 12 mmHg, DeltaAI -2 +/- 9). Multivariate regression analysis revealed that AI in a sitting position correlated positively to SBP and inversely to pulse rate. Of interest, AI in supine position related positively to age, the presence of diabetes and SBP, and inversely to pulse rate. The present data indicate autonomic dysfunction in patients with diabetic nephropathy. Furthermore, our findings provide the evidence that autonomic dysfunction elicits an inadequate physiological arterial contraction in response to postural change, thereby reducing AI that results in the fall of SBP. Finally, the present results suggest that AI in supine, but not sitting position, is suited for detecting cardiovascular risk in diabetes.
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Extracellular production of an RNA aptamer by ribonuclease-free marine bacteria harboring engineered plasmids: a proposal for industrial RNA drug production.
Appl. Environ. Microbiol.
PUBLISHED: 12-04-2009
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Natural noncoding small RNAs have been shown to be involved in a number of cellular processes as regulators. Using the mechanisms thus elucidated, artificial small interfering RNAs (siRNAs), ribozymes, and RNA aptamers are also expected to be potential candidates for RNA therapeutic agents. However, current techniques are too costly for industrial production of these RNAs for use as drugs. Here, we propose a new method for in vivo production of artificial RNAs using the marine phototrophic bacterium Rhodovulum sulfidophilum. Using engineered plasmids and this bacterium, which produces extracellular nucleic acids in nature, we developed a method for extracellular production of a streptavidin RNA aptamer. As the bacterium does not produce any RNases in the culture medium, at least within the cultivation period tested, the designed RNA itself is produced and retained in the culture medium of the bacterium without any specific mechanism for protection against degradation by nucleases. Here, we report that the streptavidin RNA aptamer is produced in the culture medium and retains its specific function. This is the first demonstration of extracellular production of a functional artificial RNA in vivo, which will pave the way for inexpensive production of RNA drugs.
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Effect of a novel kappa-receptor agonist, nalfurafine hydrochloride, on severe itch in 337 haemodialysis patients: a Phase III, randomized, double-blind, placebo-controlled study.
Nephrol. Dial. Transplant.
PUBLISHED: 11-19-2009
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Pruritus in haemodialysis patients is an intractable disease and substantially impairs their quality of life. Based on the results of our earlier clinical study, we hypothesized that the micro-(mu) opioid system is itch-inducible, whereas the kappa (kappa) system is itch-suppressive.
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Diabetes: Renal benefits of lowering BP in the absence of hypertension.
Nat Rev Nephrol
PUBLISHED: 06-27-2009
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Regardless of baseline blood pressure, treatment with a combination of an angiotensin-converting enzyme inhibitor and a diuretic decreases incidence of renal events in patients with type 2 diabetes. The combination therapy approach could be the key to achieving renoprotection.
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Therapeutic efficacy of renin-angiotensin blockade in patients receiving dialysis.
Ther Adv Cardiovasc Dis
PUBLISHED: 06-02-2009
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Observational data in dialysis patients has indicated an increased cardiovascular mortality. One pathophysiological cause of this cardiovascular mortality in these patients is volume overload. In addition, an inappropriately activated renin-angiotensin system (RAS) has been proposed as another possible mechanism for the increased cardiovascular mortality. With these possible causes in mind, blockade of the RAS with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) have both emerged as means of preventing cardiovascular events in this population. This review focuses on clinical evidence of the beneficial effects of ACE inhibitors and ARBs in dialysis patients with regard to the improvement of cardiovascular events as well as blood pressure control and maintenance of dialysis therapy.
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Time for reflection predicts the progression of renal dysfunction in patients with nondiabetic chronic kidney disease.
Clin. Exp. Hypertens.
PUBLISHED: 04-24-2009
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Our previous data indicated that both home blood pressure and arterial stiffness predicted the progression of renal dysfunction in the patients with chronic kidney diseases. In the present study, we examined both home blood pressure and the parameters of arterial stiffness as the indicator to the progression of chronic kidney diseases. Forty-two nondiabetic chronic kidney disease patients were enrolled and followed for 1 year. Anti-hypertensive therapy was adjusted to achieve office blood pressure below 130/80 mmHg. Home blood pressure was examined twice a day in the morning and evening. Pulse wave velocity (PWV) and augmentation index (AI) were measured as the index of arterial stiffness. The time for reflection (TR) was also determined. The relationship of annual changes in serum creatinine (Scr) with the above parameters was assessed. Multivariate regression analysis revealed that TR inversely correlated to annual increase in Scr (beta = -0.03, p < 0.05). Home blood pressure did not correlate to annual changes in Scr in the present study. The present data indicated that arterial stiffness is elevated despite good blood pressure control in chronic kidney disease, especially among the dippings. In addition, our data suggest that PWV and AI correlated to each other, while they were influenced differently by hemodynamic factors. Finally, the present findings provide the evidence that the arterial stiffness parameter is more sensitive than home blood pressure as an indicator to the progression of chronic kidney disease.
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Characterization of extracellular DNA production and flocculation of the marine photosynthetic bacterium Rhodovulum sulfidophilum.
Appl. Microbiol. Biotechnol.
PUBLISHED: 03-25-2009
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The marine photosynthetic bacterium Rhodovulum sulfidophilum produces extracellular nucleic acids involved in its flocculation. Previously, we showed that the RNA fraction of these extracellular nucleic acids released into the culture medium contains mainly non-aminoacylated fully mature-sized tRNAs and fragments of 16S and 23S rRNAs. Here, we report the characterization of extracellular DNA itself and its production during cultivation. No differences were detected in nucleotide sequence between the intracellular DNA and extracellular soluble DNA on Southern blotting. Whole intracellular DNA seemed to be released from the cell. The bacterial floc was degraded by deoxyribonuclease or ribonuclease treatment, indicating that at least the extracellular DNA and RNAs in the floc are involved in the maintenance of the floc. When cultivated in nutritionally rich medium, the bacteria formed small flocs and produced large amounts of extracellular DNA, which were solubilized in the medium. In nutritionally poor medium, however, huge flocs of cells appeared and almost no extracellular soluble DNA was observed in the medium. As the floc was degraded by deoxyribonuclease treatment, it seems likely that the extracellular soluble DNA observed in the rich medium may be incorporated into the large floc and play a role in floc maintenance in poor medium. Addition of an inhibitor of quorum sensing, alpha-cyclodextrin, inhibited huge floc maintenance in the nutritionally poor medium. In the presence of alpha-cyclodextrin, the floc was rapidly degraded and extracellular soluble DNA production increased.
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D1-like receptor antagonist inhibits IL-17 expression and attenuates crescent formation in nephrotoxic serum nephritis.
Am. J. Nephrol.
PUBLISHED: 02-24-2009
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A dopamine type 1-like receptor (D1-like-R) expressed on dendritic cells was involved in Th17 cell differentiation of naive CD4(+) T cells. Thus, we treated mice with nephrotoxic serum nephritis (NTN) with a D1-like-R antagonist to test whether Th17 cells play a role in this kidney disease.
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A case report suggesting the occurrence of epithelial-mesenchymal transition in obstructive nephropathy.
Clin. Exp. Nephrol.
PUBLISHED: 02-16-2009
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Epithelial-mesenchymal transition (EMT) has been well investigated using cultured kidney epithelial cell lines and the mouse obstructive nephropathy model. The role of EMT in the genesis or progression of human renal fibrosis remains controversial. We report a case of obstructive nephropathy that occurred in a pregnant woman. Renal tissue obtained by percutaneous renal biopsy after the delivery showed marked interstitial fibrosis and obstructive tubuli. Immunofluorescence images clearly demonstrated S100A4-positive tubular epithelial cells in these specimens. With regard to human obstructive nephropathy, this is the first report which proves that tubular epithelial cells become positive for the fibroblast-specific marker. EMT is probably a common event not only in mouse but also in human.
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Extracellular tRNAs of the marine photosynthetic bacterium Rhodovulum sulfidophilum are not aminoacylated.
Biosci. Biotechnol. Biochem.
PUBLISHED: 02-07-2009
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The marine photosynthetic bacterium Rhodovulum sulfidophilum produces nucleic acids extracellularly. We have identified these extracellular RNAs as fully mature sized tRNAs and fragments of 16S and 23S rRNAs. Most of the tRNAs have mature 3-terminal CCA sequences. In the present study we found that these extracellular tRNAs were not aminoacylated, although almost all intracellular tRNAs are aminoacylated.
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New modality of dialysis therapy: peritoneal dialysis first and transition to home hemodialysis.
Adv Perit Dial
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Recent studies have clearly demonstrated that start ing treatment with peritoneal dialysis (PD) is superior to starting with conventional hemodialysis (HD) because PD preserves residual renal function for a longer period. Similarly, because of the frequency of treatments, home HD (HHD) is also superior to conventional HD. The accumulated evidence suggests that a combination of PD and HHD might be a new and effective method for patients receiving dialysis therapy. We analyzed 10 patients who, over the past 10 years, were started on PD and who were then transferred to HHD. Electronic databases were used to examine changes in their health status. Mean age was 58 +/- 8 years in these 2 female and 8 male patients. Mean duration of PD was 6.9 +/- 2.4 years. The average total duration of dialysis therapy was 9.7 +/- 1.9 years. The main reason for the transition from PD to HHD was loss of residual renal function. To the time of writing, no serious complications (including cardiovascular events and calcium homeostasis) had occurred. All patients continue to receive dialysis therapy and have been able to lead a nearly normal social life. Major laboratory findings include serum albumin 4.2 +/- 0.2 g/dL, hemoglobin 10.2 +/- 1.4 g/dL (half the patients were not using erythropoiesis-stimulating agents), serum creatinine 7.5 +/- 2.5 mg/dL, blood urea nitrogen 36 +/- 17 mg/dL, serum phosphate 4.3 mg/dL. In two thirds of the patients, blood pressure was controlled without antihypertensive agents. No patient had left ventricular hypertrophy. In this analysis, we found that relatively young subjects preferred PD first, with later transfer to HHD; that PD is superior as an introduction to dialysis therapy; that patients starting with PD prefer self medical treatment; and that all patients were free from the various complications that are encountered during long-term dialysis therapy. We suggest that patients who need dialysis therapy consider this new dialysis approach of "PD first and transfer to HHD."
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Continuous ambulatory Peritoneal dialysis beyond a decade: cases from a single center.
Adv Perit Dial
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A broad consensus has not been reached on the appropriate timing for cessation of peritoneal dialysis (PD). Decreasing urine volume, repeated and refractory peritonitis, and deterioration of the peritoneal membrane are major reasons to stop PD. Also, the link between length of time on PD and encapsulating peritoneal sclerosis (EPS) should be an additional concern. The aim of the present study was to investigate patients who had been on continuous ambulatory PD (CAPD) for a long time. All patients undergoing CAPD at our kidney center for more than a decade from January 1990 to September 2011 were included in the study. Among more than 436 CAPD patients, 11 met the inclusion criteria. Their mean PD duration was 12.3 +/- 3.1 years. Mean age at CAPD introduction had been 46.0 +/- 10.1 years. All patients had nondiabetic nephropathy as the underlying cause of their end-stage renal disease. At least 2 of the 11 had developed EPS, and 1 had subsequently died from EPS. Patients on prolonged CAPD for more than a decade are still rare. The CAPD modality may be continued if it is efficiently maintained within an acceptable level, but EPS remains a serious complication of prolonged PD.
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Early start of combination therapy with hemodialysis and peritoneal dialysis prolongs survival and reduces cardiovascular events in male patients.
Adv Perit Dial
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Although peritoneal dialysis (PD) has been recommended for initial dialysis therapy, a larger proportion of patients with end-stage renal disease choose hemodialysis (HD) instead. Several previous studies comparing the outcomes of these two therapies, including survival rates and cardiovascular events, have not clearly demonstrated the superiority of one over the other. Our recent study indicated that, compared with HD or PD alone, renal replacement therapy with HD and PD in combination prolongs survival and reduces cardiovascular events. However, the use of combination dialysis therapy is not widely accepted. We set out to analyze the efficacy of combination dialysis therapy with PD and HD in patients who started with PD as initial dialysis therapy. Our single-center retrospective cohort study included 401 patients (165 women, 236 men; 61 +/- 12 and 62 +/- 9 years of age respectively) who started PD during 1995-2005. Chart and electronic databases were used to obtain information on the course of dialysis therapy, including mortality and cardiovascular events. Treatment with HD and PD in combination was used in 103 patients. During 5 years of follow-up after the start of PD, 80 patients died. We observed no differences in cumulative mortality between the men (49, 200%) and women (31, 18%) and no difference in the cumulative incidence of catheter removal for various reasons (35% vs. 31%). There was a significant difference (p < 0.05) in the time of HD start between men and women. In men on PD, HD therapy was started 22 +/- 2 months after the start of PD; in women, it was started 38 +/- 7 months after PD start. Although women have a survival advantage in both the general and the dialysis patient population, women on PD experience mortality similar to that in men. The reasons for those findings have not been fully explained. The present analysis suggests that an early start to HD therapy will prolong the survival of patients on PD, especially men.
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Aging is an important risk factor for peritoneal dialysis-associated peritonitis.
Adv Perit Dial
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Peritonitis remains a leading complication of peritoneal dialysis (PD). The aim of this observational retrospective cohort study, conducted at our single center, was to determine the risk factors for peritonitis. A Cox proportional hazards model was used for the multivariate analysis. The event investigated was peritonitis, and the variables studied were sex, age, diabetes mellitus, use of statins, and several laboratory values including albumin and total cholesterol. All PD patients who visited our clinic from January 2005 to September 2011 and who had complete medical records for at least 3 years were included. Among the 82 patients who met the criteria (mean period of observation: 1086 +/- 752 days; mean age: 62.0 +/- 12.3 years), 47 had experienced at least 1 episode of peritonitis. Aging was a significant risk factor for peritonitis, with a relative risk of 1.04 per year (p = 0.014). In our study, aging--rather than diabetes mellitus, efficiency of PD, or nutrition status--was an important risk factor for PD-associated peritonitis. Poor PD technique because of advanced age might be one of the reasons for this result.
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A retrospective cohort study of panipenem/betamipron for adult pneumococcal bacteremia at three teaching hospitals in Japan.
J. Infect. Chemother.
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Panipenem/betamipron (PAPM/BP) may be highly effective for life-threatening Streptococcus pneumoniae infection. However, the efficacy of PAPM/BP for S. pneumoniae infections has not been compared with that of other antimicrobial agents. We retrospectively compared PAPM/BP with other carbapenems for treatment of life-threatening infections in newly hospitalized adults with pneumococcal bacteremia. Clinical information for cases of pneumococcal bacteremia was collected from three teaching hospitals in Japan from January 2003 to December 2010. In total, 17 patients who received PAPM/BP therapy and 34 treated with other carbapenems (27 with meropenem, 4 with imipenem/cilastatin, and 3 with biapenem) were identified. The mean age (71 vs. 70 years old), sex distribution (women, 29 vs. 21 %), Charlson comorbidity index (CCI) (1.5 vs. 1.6), and rates of septic shock (29 vs. 38 %), and meningitis (5.9 vs. 8.8 %) did not differ significantly between the two groups. The inpatient mortality rates were lower in the PAPM/BP group (12 vs. 44 %, p = 0.03). Multiple logistic regression analysis adjusted for age, sex, CCI, and severe sepsis/septic shock showed that use of other carbapenems was associated with higher in-hospital mortality, with an odds ratio of 6.922 (95 % CI, 1.171-40.92) compared to PAPM/BP therapy. Initial PAPM/BP therapy might have a therapeutic advantage over other carbapenems in treatment of severe Streptococcus pneumoniae infections.
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