Syncytiotrophoblast Microvesicles Released from Pre-Eclampsia Placentae Exhibit Increased Tissue Factor Activity

Background: Pre-eclampsia is a complication of pregnancy associated with activation of coagulation. It is caused by the placenta, which sheds increased amounts of syncytiotrophoblast microvesicles (STBM) into the maternal circulation. We hypothesized that STBM could contribute to the haemostatic activation observed in pre-eclampsia. Methodology/Principal Findings: STBM were collected by perfusion of the maternal side of placentae from healthy pregnant women and women with pre-eclampsia at caesarean section. Calibrated automated thrombography was used to assess thrombin generation triggered by STBM-borne tissue factor in platelet poor plasma (PPP). No thrombin was detected in PPP alone but the addition of STBM initiated thrombin generation in 14/16 cases. Pre-eclampsia STBM significantly shortened the lag time (LagT, P = 0.01) and time to peak thrombin generation (TTP, P = 0.005) when compared to normal STBM. Blockade of tissue factor eliminated thrombin generation, while inhibition of tissue factor pathway inhibitor significantly shortened LagT (p = 0.01) and TTP (P,0.0001), with a concomitant increase in endogenous thrombin potential. Conclusions/Significance: STBM triggered thrombin generation in normal plasma in a tissue factor dependent manner, indicating that TF activity is expressed by STBM. This is more pronounced in STBM shed from pre-eclampsia placentae. As more STBM are shed in pre-eclampsia these observations give insight into the disordered haemostasis observed in thi

Low-dose aspirin does not improve ovarian stimulation, endometrial response, or pregnancy rates for in vitro fertilization

BACKGROUND: The purpose of this study is to determine if low-dose aspirin improved ovarian stimulation, endometrial response, or IVF pregnancy rates in our program. METHODS: Retrospective analysis of 316 consecutive IVF cycles from 1995 through 2001. Aspirin 80 mg daily was initiated at the start of luteal leuprolide in 72 cycles. The 244 controls received no aspirin during treatment. RESULTS: The live birth rate in aspirin users was 29%, slightly lower compared to 41% in the no aspirin control group (p = 0.07). Implantation rates were 21% with aspirin and 30% in the control population (p = 0.01). There was no difference in the maximal endometrial thickness between aspirin and non-aspirin groups. The two groups were similar regarding age, gonadotropin ampules, embryos, number of embryos transferred, prior parity, diagnosis, use of intracytoplasmic sperm injection, and stimulation protocol. CONCLUSION: Low-dose aspirin was not beneficial to IVF patients in our program. Aspirin does not enhance endometrial thickness, augment the ovarian response, or improve pregnancy rates

Novel Nanohybrids of Silver Particles on Clay Platelets for Inhibiting Silver-Resistant Bacteria

We develop a novel nanohybrid showing a strong antibacterial activity on all of the tested pathogens, including methicillin-resistant Staphylococcus auerus and silver-resistant E. coli. The nanohybrid consists of silver nanoparticles (AgNPs) supported on 1 nm-thick silicate platelets (NSPs). The AgNP/NSP nanohybrid enables to encapsulate bacteria and triggers death signals from the cell membrane. The geographic shape of the NSPs concentrates AgNPs but impedes their penetration into attached cells, mitigating the detrimental effect of silver ion deposition in applied tissues. Moreover, the tightly tethered AgNPs on NSP surface achieve a stronger biocidal effect than silver nitrate, but bypassing Ag+ mechanism, on silver-resistant bacteria. This nanohybrid presents an effective and safe antimicrobial agent in a new perspective

A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe

Oxygen uptake kinetics and cardiopulmonary performance in lone atrial fibrillation and the effects of sotalol

BACKGROUND: Atrial fibrillation (AF) is associated with impaired exercise capacity. Oxygen uptake (VO2) kinetics determines cardiopulmonary performance during submaximal exercise, which may be impaired in patients with AF. AIM: To study oxygen kinetics and cardiopulmonary performance in patients with AF without structural heart disease and the effects of oral sotalol on these parameters. PATIENTS AND METHODS: Twenty consecutive patients (mean age, 56+/-8 years) with chronic AF were recruited. The protocol design was a randomized, single-blinded, and placebo-controlled trial. Patients received either sotalol or placebo for an 8-week study period, and the alternative treatment in the subsequent period. Cardiopulmonary function tests using constant workload and incremental workload protocols were performed at the end of each phase. Sixteen age-matched normal subjects were included as control subjects. RESULTS: During constant submaximal exercise, patients with AF had a larger oxygen deficit (425+/-140 mL vs 289+/-80 mL in normal subjects; p<0.05) and the time for achieving 63% of VO2 (mean response time) was also delayed (46+/-15 s vs 33+/-10 s; p<0.05). Compared with normal subjects, patients with chronic AF had a higher maximal exercise heart rate (180+/-34 beats/min vs 153+/-22 beats/min; p<0.05), but a lower maximal VO2 (20+/-4 mL/kg/min vs 26+/-6 mL/kg/min; p<0.05). Oral sotalol lowered the resting (72+/-15 beats/min vs 93+/-22 beats/min; p<0.05) and exercise heart rate compared with placebo (125+/-27 beats/min vs 180+/-34 beats/min; p<0.05, respectively), and normalized oxygen pulse and the heart rate to minute ventilation ratio during maximal exercise. There was no significant difference between those receiving sotalol and those receiving placebo in oxygen deficit (502+/-150 mL vs 425+/-140 mL; p=0.38), maximal VO2 (17.2+/-4.9 mL/kg/min vs 20.4+/-4.7 mL/kg/min; p=0.17), and other gas exchange variables. In patients with AF, oxygen deficit has a fair correlation with VO2 at the anaerobic threshold (r2=0.43; p<0.05) and at maximal exercise (r2=0.45; p<0.05). CONCLUSION: In addition to maximal exercise capacity and cardiopulmonary performance, patients with chronic AF without significant structural heart disease had impaired submaximal exercise performance as assessed by VO2 kinetics. These parameters were not significantly affected by sotalol used for rate control.published_or_final_versio

Clinical shock tolerability and effect of different right atrial electrode locations on efficacy of low energy human transvenous atrial defibrillation using an implantable lead system

Objectives. The objectives of this study were 1) to evaluate the effect of different right atrial electrode locations on the efficacy of low energy transvenous defibrillation with an implantable lead system; and 2) to qualitate and quantify the discomfort from atrial defibrillation shocks delivered by a clinically relevant method. Background. Biatrial shocks result in the lowest thresholds for transvenous atrial defibrillation, but the optimal right atrial and coronary sinus electrode locations for defibrillation efficacy in humans have not been defined. Methods. Twenty- eight patients (17 men, 11 women) with chronic atrial fibrillation (AF) (lasting ≤1 month) were studied. Transvenous atrial defibrillation was performed by delivering R wave-synchronized biphasic shocks with incremental shock levels (from 180 to 400 V in steps of 40 V). Different electrode location combinations were used and tested randomly: the anterolateral, inferomedial right atrium or high right atrial appendage to the distal coronary sinus. Defibrillation thresholds were defined in duplicate by using the step-up protocol. Pain perception of shock delivery was assessed by using a purpose-designed questionnaire; sedation was given when the shock level was unacceptable (tolerability threshold). Results. Sinus rhythm was restored in 26 of 28 patients by using at least one of the right atrial electrode locations tested. The conversion rate with the anterolateral right atrial location (21 [81%] of 26) was higher than that with the inferomedial right atrial location (8 [50%] of 16, p 0.05). The mean defibrillation thresholds for the high right atrial appendage, anterolateral right atrium and inferomedial right atrium were all significantly different with respect to energy (3.9 ± 1.8 J vs. 4.6 ± 1.8 J vs. 6.0 ± 1.7 J, respectively, p < 0.05) and voltage (317 ± 77 V vs. 348 ± 70 V vs. 396 ± 66 V, respectively, p < 0.05). Patients tolerated a mean of 3.4 ± 2 shocks with a tolerability threshold of 255 ± 60 V, 2.5 ± 1.3 J. Conclusions. Low energy, transvenous defibrillation with an implantable defibrillation lead system is an effective treatment for AF. Most patients can tolerate two to three shocks, and, when the staffing shock level (189 V) is close to the defibrillation threshold, they can tolerate on average a shock level of 260 V without sedation. Electrodes should be positioned in the distal coronary sinus and in the high right atrial appendage to achieve the lowest defibrillation threshold, although other locations may be suitable for certain patients.link_to_subscribed_fulltex

經靜脈體內心房除顫治療慢性心房顫動的臨床應用

目的評估經靜脈體內心房除顫治療慢性心房顫動(房顫)的技術方法、功效、安全性及可行性,確定慢性房顫患者體內心房除顫的閾值。方法經靜脈穿刺分別將除顫導管植入右房冠狀靜脈竇,由體外心房除顫器自右至左方向發放與 R 波同步的雙相低能量電流轉復慢性房顫患者76例,記錄并確定成功除顫的最小能量及電壓作為心房除顫閾值(ADFT)。結果 93.4%慢性房顫患者可急性成功轉復竇性心律,其體內心房除顫閾值為4.29±1.89 J,326.1±62.4 V。結論經靜脈體內心房除顫是慢性房顫更為有效安全的治療方法,有助于體內心房除顫器的進一步應用

Initial clinical experience with an implantable human atrial defibrillator

Low energy biatrial shock is an effective means of restoring sinus rhythm in patients with atrial fibrillation (AF). Ventricular proarrythmia is avoided provided that shocks are well synchronized to R waves that are not at closely coupled intervals or preceded by long-short cycles. Based on these principles, an implantable atrial defibrillator has been developed and was implanted in three patients with drug refractory paroxysmal AF. The device detects AF via an actively fixed right atrial and a self-retaining coronary sinus defibrillating leads, and delivers 3/3 ms biphasic shocks up to 300 V synchronized to the B wave. The mean implant threshold (ED50) was 195V (1.8 J), and minimum voltage at conversion during follow-up assessments at 1, 3, and 6 months were 260 V, 2.5 J. 250 V, 2.3 J, and 300 V, 3.0 J respectively. Detection of AF was 100% specific and shocks were 100% synchronized, although only a proportion of synchronized R waves were considered suitable for shock delivery primarily because of closely coupled cycles. Three patients had 9 spontaneous AF episodes, 8/9 (89%) successfully defibrillated by shocks of 260-300 V. Sedation was not used in 4 out of 9 (45%) episodes. Backup ventricular pacing was initiated by the device in 6 out of (67%) episodes. One patient had more frequent AF after lead placement, which subsided after a change of medication. There was no ventricular proarrhythmia. It is concluded that an implantable atrial defibrillator is a viable therapy for selected patients with paroxysmal AF. The device is capable of accurate AF detection, R wave synchronization and ventricular support pacing after successful defibrilation of AF.link_to_subscribed_fulltex