Impact of antimicrobial treatment duration on outcome of Staphylococcus aureus bacteraemia: a cohort study

ObjectivesTo assess the outcome of Staphylococcus aureus bacteraemia (SAB) according to factors associated with necessity for longer treatment in conjunction with the duration of treatment.MethodsWe prospectively collected the data of patients with SAB consecutively during 12 to 39 months from 11 hospitals. If multiple episodes of SAB occurred in one patient, only the first episode was enrolled. Factors associated with necessity for longer treatment were defined as follows: persistent bacteraemia, metastatic infection, prosthesis and endocarditis. If any of the factors were present, then the case was defined as longer antibiotic treatment warranted (LW) group; those without any factors were defined as shorter antibiotic treatment sufficient (SS) group. Poor outcome was defined as a composite of 90-day mortality or 30-day recurrence. Duration of antibiotic administration was classified as <14 or ≥14 days in the SS group and <28 or ≥28 days in the LW group.ResultsAmong 2098 cases, the outcome was analysed in 1866 cases, of which 591 showed poor outcome. The SS group accounted for 964 cases and the LW group for 852. On multivariate analysis, age over 65 years, pneumonia, higher Sequential Organ Failure Assessment (SOFA) score and chronic liver diseases were risk factors for poor outcome. Administration of antibiotics less than the recommendation was associated with poor outcome, but this significance was observed only in the LW group (adjusted odds ratio = 1.68; 95% confidence interval, 1.00–2.83; p 0.05).ConclusionsInappropriately short antibiotic treatment was associated with poor outcome in the LW group. Vigilant evaluation for risk factors to determine the duration of treatment may improve the outcome among patients with SAB.     

Topographic and histologic characteristics of the sural nerve for use in nerve grafting

The sural nerve (SN) is a sensory nerve supplying the skin of the lateral and posterior parts of the inferior third of the calf and the lateral side of the foot and is easy to harvest because of its location posterior and superior to the tip of the lateral malleolus. Seventy-one lower limbs from 42 Korean cadavers were dissected to describe the joining type and level of perforated the fascia of the SN. The segments of sural nerve were stained and measured. The communication and joining patterns of the SN formed by the medial sural cutaneous nerve and the communicating branch of the lateral sural cutaneous nerve could be divided into five types. The region where the medial sural cutaneous nerve and the communicating branch of the lateral sural cutaneous nerve join together was observed in 52 cases with this found in the lower two fifths of the calf in 28 (53.8%) of the specimens. The mean number of fascicles was 8.1 (range, 2-12) at the lower calf and 5.8 (range, 1-11) at the middle calf before where the medial sural cutaneous nerve and the communicating branch of the lateral sural cutaneous nerve joined. The mean total areas of the fascicles were 0.55 mm and 0.43 mm in the lower and middle calf, respectively. This study demonstrates that the anatomy of the SN affects its harvesting for use in nerve grafts with the reported results providing a useful reference for SN grafting procedures.     

An ASIC design for versatile receive front-end electronics of an ultrasonic medical imaging system--16 channel analog inputs and 4 dynamically focused beam outputs

An ultra large-scale ASIC is designed for the receive front-end electronics of an ultrasonic medical imaging system. The chip receives 16 channel analog rf signals and outputs 4 sets of sample-point-wise dynamically focused partial beam data. Four complete beam data sets are obtained in parallel by simply cascading as many chips as needed in an array system. High resolution of the focusing delay is obtained by nonuniformly selecting each channel data from a quadruply-interpolated rf data stream. The proposed ASIC can be applied to most practical array transducers in the frequency range of 2 to 10 MHz. The digital part of the designed ASIC can be implemented on a chip area of 17.9 microm2 with 0.18 mm CMOS technology, leaving sufficient room for 16 ADCs of 8 bits, 50 MHz on the 5.7 mm x 5.7 mm chip with a 208 pin package.     

兔骨髓间充质干细胞表面抗原检测及其变化特点

目的:应用流式细胞仪对兔骨髓间充质干细胞的表面抗原进行检测,观察骨髓间充质干细胞传代次数、克隆纯化与骨髓间充质干细胞表面抗原表达之间的关系。方法:实验于2004-01/2006-08在浙江省医学科学院生物工程所完成。取3月龄新西兰大白兔用于骨髓间充质干细胞的分离培养。兔骨髓间充质干细胞的克隆化:将铺满培养瓶底的原代骨髓间充质干细胞,用D-Hanks液小心的洗1次,加入0.25%胰蛋白酶消化约4min,弃消化液,加LG-DMEM培养液收集细胞,1000r/min,离心10min,然后用LG-DMEM培养液充分混匀沉淀细胞。细胞计数后以10倍递减稀释至细胞密度为103个/mL。取0.1mL稀释后的细胞悬液加入10mL培养液,使最终细胞密度为10个/mL。将细胞悬液加入96孔培养板,每孔100μL。置37℃、体积分数为0.05的CO2饱和湿度条件下培养,每天观察克隆细胞的增殖生长状况。待克隆细胞生长至60%～80%融合时,逐步扩大培养,在液氮冻存保种的同时进行细胞连续传代。将体外普通法分离的骨髓间充质干细胞第5代、第7代、第13代、第16代、第21代、第22代及克隆纯化的骨髓间充质干细胞第3代、第5代、第15代、第26代均标记上CD14-FITC及CD44-PE,通过流式细胞仪检测其阴性率及阳性率。结果:①普通法分离的骨髓间充质干细胞各代的CD44表达呈阳性,且随着培养代次的增加,其表达的阳性率逐渐增强,到P16代以后又呈下降趋势;各代骨髓间充质干细胞表面抗原CD14出现了微弱阳性,但随着培养代次增加,其阳性率呈下降趋势。②克隆纯化的骨髓间充质干细胞其CD44呈现阳性,表达在80%以上,至P26代时CD44表达下降到70.49%;其CD14基本呈阴性。结论:兔骨髓间充质干细胞其CD44呈阳性表达,CD14呈阴性表达。随着传代代数增加CD14阴性符合率逐渐提高,CD44阳性表达率也提高。普通法分离的骨髓间充质干细胞较克隆纯化的骨髓间充质干细胞CD14阴性符合率差,前者的CD44阳性表达率也较后者低。     

Papaverine blocks hKv1.5 channel current and human atrial ultrarapid delayed rectifier K+ currents

Papaverine, 1-[(3,4-dimethoxyphenyl)methyl]-6,-7-dimethoxyisoquinoline, has been used as a vasodilator agent and a therapeutic agent for cerebral vasospasm, renal colic, and penile impotence. We examined the effects of papaverine on a rapidly activating delayed rectifier K(+) channel (hKv1.5) cloned from human heart and stably expressed in Ltk(-) cells as well as a corresponding K(+) current (the ultrarapid delayed rectifier, I(Kur)) in human atrial myocytes. Using the whole cell configuration of the patch-clamp technique, we found that papaverine inhibited hKv1.5 current in a time- and voltage-dependent manner with an IC(50) value of 43.4 microM at +60 mV. Papaverine accelerated the kinetics of the channel inactivation, suggesting the blockade of open channels. Papaverine (100 microM) also blocked I(Kur) in human atrial myocytes. These results indicate that papaverine blocks hKv1.5 channels and native hKv1.5 channels in a concentration-, voltage-, state-, and time-dependent manner. This interaction suggests that papaverine could alter cardiac excitability in vivo.     

In Vivo Three-Dimensional Imaging Analysis of Femoral and Tibial Tunnel Locations in Single and Double Bundle Anterior Cruciate Ligament Reconstructions

Background

Anatomic footprint restoration of anterior cruciate ligament (ACL) is recommended during reconstruction surgery. The purpose of this study was to compare and analyze the femoral and tibial tunnel positions of transtibial single bundle (SB) and transportal double bundle (DB) ACL reconstruction using three-dimensional computed tomography (3D-CT).

Methods

In this study, 26 patients who underwent transtibial SB ACL reconstruction and 27 patients with transportal DB ACL reconstruction using hamstring autograft. 3D-CTs were taken within 1 week after the operation. The obtained digital images were then imported into the commercial package Geomagic Studio v10.0. The femoral tunnel positions were evaluated using the quadrant method. The mean, standard deviation, standard error, minimum, maximum, and 95% confidence interval values were determined for each measurement.

Results

The femoral tunnel for the SB technique was located 35.07% ± 5.33% in depth and 16.62% ± 4.99% in height. The anteromedial (AM) and posterolateral (PL) tunnel of DB technique was located 30.48% ± 5.02% in depth, 17.12% ± 5.84% in height and 34.76% ± 5.87% in depth, 45.55% ± 6.88% in height, respectively. The tibial tunnel with the SB technique was located 45.43% ± 4.81% from the anterior margin and 47.62% ± 2.51% from the medial tibial articular margin. The AM and PL tunnel of the DB technique was located 33.76% ± 7.83% from the anterior margin, 45.56% ± 2.71% from the medial tibial articular margin and 53.19% ± 3.74% from the anterior margin, 46.00% ± 2.48% from the medial tibial articular margin, respectively. The tibial tunnel position with the transtibial SB technique was located between the AM and PL tunnel positions formed with the transportal DB technique.

Conclusions

Using the 3D-CT measuring method, the location of the tibia tunnel was between the AM and PL footprints, but the center of the femoral tunnel was at more shallow position from the AM bundle footprint when ACL reconstruction was performed by the transtibial SB technique.     

Antiplatelet,anticoagulant, and profibrinolytic activities of cudratricusxanthone A

Cudratricusxanthone A (CTXA), a natural bioactive compound extracted from the roots of Cudrania tricuspidata Bureau, is known to possess hepatoprotective, antiproliferative and anti-inflammatory activities. However, antiplatelet, anticoagulant, and profibrinolytic properties have not been studied. The anticoagulant activities of CTXA were measured by monitoring activated partial thromboplastin-time (aPTT), prothrombin time (PT), and the activities of cell-based thrombin and activated factor X (FXa). The effects of CTXA on the expressions of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were also tested in tumor necrosis factor-α (TNF-α) activated human umbilical vein endothelial cells. Our data showed that CTXA inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation, prolonged aPTT and PT significantly and inhibited the activities and production of thrombin and FXa. CTXA prolonged in vivo bleeding time and inhibited TNF-α induced PAI-1 production. Furthermore, PAI-1/t-PA ratio was significantly decreased by CTXA. Collectively, these results indicate that CTXA possesses antithrombotic activities and suggest that the current study could provide bases for the development of new anticoagulant agents.     

Epigallocatechin-3-gallate,a green tea catechin,protects the heart against regional ischemia–reperfusion injuries through activation of RISK survival pathways in rats

Epigallocatechin-3-gallate (EGCG), the major catechin derived from green tea, has been shown to modulate numerous molecular targets in the setting of inflammation. This study aimed to determine whether EGCG protects against regional myocardial ischemia/reperfusion (I/R) injuries and its underlying mechanisms involving the role of reperfusion injury salvage kinase (RISK) pathways (PI3K-Akt and ERK 1/2) and GSK-3β or apoptotic kinases (p38 and JNK). The rats were subjected to I/R injuries consisting of 30 min ischemia followed by 2 h reperfusion. EGCG (10 mg/kg, intravenously) was administered alone or along with wortmannin (PI3K inhibitor, 0.6 mg/kg, intravenously) 5 min before the onset of reperfusion. Wortmannin was administered 10 min before the reperfusion. Infarct size was measured at the end of the reperfusion. The phosphorylation of Akt, GSK-3β, and MAPK kinases (ERK1/2, P38 and JNK) was determined by Western blotting after 10 min of reperfusion. EGCG reduced the infarct size compared with the control (25.4 ± 9.2 versus 43.2 ± 8.2 %, p < 0.05). Wortmannin alone did not affect the infarct size, but abolished the EGCG-induced infarct size limiting effect, indicating that EGCG may protect the heart by modulating the PI3K-Akt. EGCG significantly enhanced the phosphorylation of Akt and GSK-3β but not ERK1/2, while it reduced that of p38 and JNK. These results suggest that EGCG has a protective effect against regional myocardial I/R injuries through activation of the RISK pathway and attenuation of p38 and JNK. EGCG may have cardioprotective effects in patients undergoing surgeries prone to myocardial I/R injuries.     

Phase II clinical trials with time‐to‐event endpoints: optimal two‐stage designs with one‐sample log‐rank test

Phase II clinical trials are often conducted to determine whether a new treatment is sufficiently promising to warrant a major controlled clinical evaluation against a standard therapy. We consider single‐arm phase II clinical trials with right censored survival time responses where the ordinary one‐sample logrank test is commonly used for testing the treatment efficacy. For planning such clinical trials, this paper presents two‐stage designs that are optimal in the sense that the expected sample size is minimized if the new regimen has low efficacy subject to constraints of the type I and type II errors. Two‐stage designs, which minimize the maximal sample size, are also determined. Optimal and minimax designs for a range of design parameters are tabulated along with examples. Copyright © 2013 John Wiley & Sons, Ltd.