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K.‐H. LIESENFELD T. LEHR C. DANSIRIKUL P. A. REILLY S. J. CONNOLLY M. D. EZEKOWITZ S. YUSUF L. WALLENTIN S. HAERTTER A. STAAB 《Journal of thrombosis and haemostasis》2011,9(11):2168-2175
Summary. Background: Dabigatran etexilate (DE) is an orally absorbed prodrug of dabigatran, a thrombin inhibitor that exerts potent anticoagulant and antithrombotic activity. Objectives: To characterize the pharmacokinetics of dabigatran in patients with non‐valvular atrial fibrillation (AF) from the Randomized Evaluation of Long‐term Anticoagulant Therapy (RE‐LY) trial and to quantify the effect of selected factors on pharmacokinetic (PK) model parameters. Patients and methods: A total of 27 706 dabigatran plasma concentrations from 9522 patients who received DE 110 or 150 mg twice daily were analyzed with non‐linear mixed‐effects modeling. Results: The pharmacokinetics of dabigatran were best described by a two‐compartment disposition model with first‐order absorption. The covariates creatinine clearance (CRCL), age, sex, heart failure and the ethnic subgroup ‘South Asian’ exhibited statistically significant effects on apparent clearance of dabigatran. Body weight and hemoglobin significantly influenced the apparent volume of distribution of the central compartment. Concomitant medication with proton‐pump inhibitors, amiodarone and verapamil significantly affected the bioavailability. However, all of the statistically significant factors that were identified, except for renal function status, showed only small to moderate effects (< 26% change in exposure at steady state). On the basis of simulations from the final population PK model, a dose of 75 mg twice daily would result in similar exposure for severely renally impaired patients with CRCL of 15–30 mL min?1 and patients with normal renal function receiving 150 mg twice daily. Conclusions: The analysis provides a thorough PK characterization of dabigatran in the AF patient population from RE‐LY. None of the covariates investigated, with the exception of renal function, warrants dose adjustment. 相似文献
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Colonic carcinoma metastatic to the kidney is very rare. The usual anatomical localization for secondary renal neoplasms is the renal cortex. We report a case of sigmoid colon carcinoma with unilateral kidney metastasis localized only in the renal papillae without obvious metastatic disease. 相似文献
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SEZA APILIOGULLARI MD ATES DUMAN MD FUNDA GOK MD ISAK AKILLIOGLU MD 《Paediatric anaesthesia》2010,20(2):177-182
Background: In adults, pencil point spinal needles are known to be less traumatic and hence to be superior compared with cutting point needles in respect of postpuncture complications. In children, only a few trials have evaluated the difference in the incidence of postdural puncture headache (PDPH) using spinal needles with different tip designs. The aim of this study was to evaluate the success rate and the incidence of PDPH and backache following spinal anesthesia (SA) with the two types of needles currently in use for children. Methods: This is a retrospective study of prospectively collected data. The success rate and postpuncture complications of 26G cutting point (Atraucan®) spinal needle were compared with 27G pencil point (Pencan®) spinal needle in 414 children aged 2–17 years undergoing surgery with SA. Results: Both needles had similar first‐attempt success rates: 87% in the cutting point group and 91% in the pencil point group (P = 0.16). Pencil point needles caused less PDPH compared to cutting point needles; 0.4% vs 4.5%, respectively (P = 0.005). Both needles caused similar backache (P = 0.08). No severe neurologic symptom was reported for both needles. Conclusion: The data suggest that 27G pencil point spinal needles lead to less PDPH compared to 26G cutting point spinal needles in children. 相似文献
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Background: The effect of intrathecal fentanyl on the characteristics of spinal anesthesia has not been investigated in children undergoing inguinal hernia repair. The purpose of this study was to assess whether the incidence and severity of pain during peritoneal sac traction is decreased by addition of fentanyl to bupivacaine in children undergoing inguinal hernia repair with spinal anesthesia. Methods: Children (6–14 years) were randomized into two groups. Group F (n = 25): hyperbaric bupivacaine plus 0.2 μg·kg−1 of fentanyl. Group P (n = 25): hyperbaric bupivacaine plus 0.9% NaCl (placebo). The dose of bupivacaine was 0.4 mg·kg−1. The primary variable was the incidence and severity of pain during peritoneal sac traction. Spinal block characteristics, duration of spinal anesthesia assessed by recovery of hip flexion and duration of analgesia were the secondary variables measured, and the side effects were noted. Results: There were significant differences in incidence of pain and pain scores during sac traction with lower incidence and scores in the fentanyl group (P = 0.009). Two groups were similar regarding the level of sensory block during sac traction and duration of spinal anesthesia. Duration of spinal analgesia was prolonged significantly in the fentanyl group (P = 0.025). Conclusion: Intrathecal fentanyl at a dose of 0.2 μg·kg−1 added to bupivacaine significantly improves the quality of intraoperative analgesia and prolongs postoperative analgesia in children undergoing inguinal hernia repair with spinal anesthesia. 相似文献
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A multistep process for the dispersal of a Y chromosomal lineage in the Mediterranean area 总被引:6,自引:2,他引:4
P. MALASPINA M. TSOPANOMICHALOU T. DUMAN M. STEFAN A. SILVESTRI B. RINALDI O. GARCIA M. GIPARAKI E. PLATA A. I. KOZLOV G. BARBUJANI C. VERNESI F. PAPOLA G. CIAVARELLA D. KOVATCHEV M. G. KERIMOVA N. ANAGNOU L. GAVRILA L. VENEZIANO N. AKAR A. LOUTRADIS E. N. MICHALODIMITRAKIS L. TERRENATO A. NOVELLETTO 《Annals of human genetics》2001,65(4):339-349
In this work we focus on a microsatellite-defined Y-chromosomal lineage (network 1.2) identified by us and reported in previous studies, whose geographic distribution and antiquity appear to be compatible with the Neolithic spread of farmers. Here, we set network 1.2 in the Y-chromosomal phylogenetic tree, date it with respect to other lineages associated with the same movements by other authors, examine its diversity by means of tri- and tetranucleotide loci and discuss the implications in reconstructing the spread of this group of chromosomes in the Mediterranean area. Our results define a tripartite phylogeny within HG 9 (Rosser et al . 2000), with the deepest branching defined by alleles T (Haplogroup Eu10) or G (Haplogroup Eu9) at M172 (Semino et al . 2000), and a subsequent branching within Eu9 defined by network 1.2. Population distributions of HG 9 and network 1.2 show that their occurrence in the surveyed area is not due to the spread of people from a single parental population but, rather, to a process punctuated by at least two phases. Our data identify the wide area of the Balkans, Aegean and Anatolia as the possible homeland harbouring the largest variation within network 1.2. The use of recently proposed tests based on the stepwise mutation model suggests that its spread was associated to a population expansion, with a high rate of male gene flow in the Turkish–Greek area. 相似文献
18.
TAYFUN EYILETEN ALPER SONMEZ MUTLU SAGLAM ERDINC CAKIR KAYSER CAGLAR YUSUF OGUZ ABDULGAFFAR VURAL MUJDAT YENICESU MAHMUT ILKER YILMAZ 《Nephrology (Carlton, Vic.)》2010,15(2):225-229
Aim: Plasma visfatin levels are elevated in diabetic nephropathy in parallel to the severity of proteinuria and glomerular filtration rate. The aim of this study was to find out whether the renin–angiotensin–aldosterone system (RAAS) blockage has any effect on the plasma visfatin levels. Methods: Thirty‐two patients with diabetic proteinuria (>500 mg/day) with a normal glomerular filtration rate (GFR) and 33 healthy subjects were enrolled. Patients were treated with ramipril 5 mg daily for 2 months. Proteinuria, GFR, high‐sensitivity C‐reactive protein (hsCRP), visfatin, flow‐mediated dilatation (FMD) and homeostasis model assessment of insulin resistance (HOMA‐IR) index measurements were performed both before and after the treatment. Results: The plasma visfatin, and hsCRP levels of the patients were significantly higher and the FMD was significantly lower (P < 0.001 for all). The visfatin levels were significantly correlated to FMD, systolic and diastolic blood pressures, proteinuria, eGFR, HOMA‐IR and hsCRP. Ramipril treatment resulted in a significant decrease in plasma visfatin, proteinuria, hsCRP, HOMA‐IR and increase in FMD (P < 0.001) in patients (P < 0.001 for all). Conclusion: The present study suggests that plasma visfatin levels are related to the endothelial functions, inflammation and the severity of proteinuria in diabetic nephropathy. Treatment with ramipril causes a significant decrease in visfatin levels along with the improvement of proteinuria, endothelial dysfunction and inflammatory state in diabetic nephropathy. 相似文献
19.
K.‐H. LIESENFELD T. LEHR C. DANSIRIKUL P. A. REILLY S. J. CONNOLLY M. D. EZEKOWITZ S. YUSUF L. WALLENTIN S. HAERTTER A. STAAB 《Journal of thrombosis and haemostasis》2012,10(3):502-504
See also Liesenfled K‐H, Lehr T, Dansirikul C, Reilly PA, Connolly SJ, EzekowitzMD, Yusuf S,Wallentin L, Haertter S, Staab A. Population pharmacokinetic analysis of the oral thrombin inhibitor dabigatran etexilate in patients with non‐valvular atrial fibrillation from the RE‐LY trial. J Thromb Haemost 2011; 9: 2168–75; and Patel JP, Green B, Patel RK, Davies JG, Arya R. Population pharmacokinetic analysis of the oral thrombin inhibitor dabigatran etexilate in patients with non‐valvular atrial fibrillation from the RE‐LY trial: a rebuttal. This issue, pp 500–2. 相似文献
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目的 观察阻塞性睡眠呼吸暂停低通气综合征(Obstructive sleep apnea hypopnea syndrome,OSAHS)对2型糖尿病患者血糖水平及夜间血糖漂移的影响。 方法 选择2型糖尿病(Type 2 diabetes mellitus,T2DM)伴OSAHS患者31例及单纯T2DM患者18例,所有患者应用动态血糖监测系统(CGMS)连续进行动态血糖监测3 d,比较2组患者夜间血糖、空腹血糖、24 h血糖、夜间MAGE(Mean amplitude of plasma glucose excursion)、白天MAGE、24 h MAGE以及糖化血红蛋白(hemoglycoglobulin, GhBA1c)。 结果 单纯T2DM组及T2DM伴OSAHS组性别、年龄、病程差异无统计学意义,而体重指数、腰围、颈围差异有统计学意义(P0.05),体重指数、腰围、颈围校正后,T2DM伴OSAHS组患者夜间MAGE、24 h MAGE显著高于单纯T2DM组(P0.01),两组患者夜间血糖、空腹血糖、24 h血糖、白天MAGE及GhBA1c差异也有统计学意义(P0.05)。 结论 OSAHS引起T2DM夜间血糖、夜间MAGE增高,从而影响全天血糖及全天MAGE。 相似文献