Clinical disorders affecting mesopic vision

Vision in the mesopic range is affected by a number of inherited and acquired clinical disorders. We review these conditions and summarize the historical background, describing the clinical characteristics alongside the genetic basis and molecular biological mechanisms giving rise to rod and cone dysfunction relevant to twilight vision. The current diagnostic gold standards for each disease are discussed and curative and symptomatic treatment strategies are summarized.     

Minimally-invasive LVAD Implantation: State of the Art

Nowadays, the worldwide number of left ventricular assist devices (LVADs) being implanted per year is higher than the number of cardiac transplantations. The rapid developments in the field of mechanical support are characterized by continuous miniaturization and enhanced performance of the pumps, providing increased device durability and a prolonged survival of the patients. The miniaturization process enabled minimally-invasive implantation methods, which are associated with generally benefitting the overall outcome of patients. Therefore, these new implantation strategies are considered the novel state of the art in LVAD surgery.In this paper we provide a comprehensive review on the existing literature on minimally-invasive techniques with an emphasis on the different implantation approaches and their individual surgical challenges.     

BD 方案与VAD 方案治疗多发性骨髓瘤的疗效比较

 目的比较硼替佐米联合地塞米松方案（BD方案）与VAD 方案治疗多发性骨髓瘤的临床疗效及安全性。方法回顾性
分析120 例多发性骨髓瘤病例,根据其治疗方案分为：（1）BD 组（ n=37）：其中初治16 例,复发/难治21 例;（2）VAD 组（ n=83）：
其中初治39 例,复发/难治44 例。化疗4~7 个疗程后全面评价两组疗效及副反应。采用EBMT/ABMT 标准判定疗效,并按WHO
标准判断不良反应。结果（1）BD组：中位生存期为43.5 个月,2 年和4 年生存率分别为86.4%和47.3%,平均起效疗程数为
2.06,总有效率为91.9%,其中CR/nCR 32.4%（12/37）,PR 48.6%（18/37）,MR 10.8%（4/37）。初治患者CR/nCR 37.5%（6/16）,
PR 50.0%（8/16）,MR 6.3%（1/16）,NR 6.3%（1/16）,有效率为93.8%;复发/难治患者CR/nCR 28.6%（6/21）,PR 47.6%（10/
21）,MR 14.3%（3/21）,NR 4.8%（1/21）,PD 4.8%（1/21）,有效率为90.5%;（2）VAD 组：中位生存期为29.1 个月,2 年和4 年生
存率分别为64.3%和33.5%,平均起效疗程数为3.09,总有效率为66.3%,其中CR/nCR 12.0%（10/83）,PR 38.6%（32/83）,MR
15.7%（13/83）。初治患者CR/nCR 15.4%（6/39）,PR 38.5%（15/39）,MR 12.8%（5/39）,NR 20.5%（8/39）,PD 12.8%（5/39）,有
效率66.7%;复发/难治患者CR/nCR 9.1%（4/44）,PR 38.6%（17/44）,MR 18.2%（8/44）,NR 18.2%（8/44）,PD 15.7%（7/44）,有
效率为65.9%。字2检验结果显示,2 组方案疗效之间比较差异有统计学意义（ < 0.05）;经Log-rank 检验发现,2 组生存率比较差
异有统计学意义（ < 0.05）;（3）与VAD组相比,BD 组不良反应较轻微,患者耐受性较好。结论与VAD方案相比,BD方案能
达到更高的缓解率,显著延长患者的生存期,并提高患者的生活质量,疗效显著,毒副反应小,耐受性好。     

The Hemodynamics of the Berlin Pulsatile VAD and the Role of its MHV Configuration

The 3D flow in a model of the Berlin ventricular assist device (VAD) chamber with monoleaflet valves placed in S-shape conduits was simulated numerically. The blood flow dynamics were described in terms of flow patterns, velocity, pressure, and shear stress. The hemodynamic properties and the VAD's potential risk for thrombosis were evaluated in terms of mixing and washout properties, and global estimations of platelet level of activation (LOA). In order to evaluate the role of valves on the flow in the chamber, the flow in a model with bileaflet valves in straight conduits was simulated and compared with the original case. The results showed that in both models a large rotating flow was developed in the chamber during filling. This vortex filled the entire chamber and moved constantly up to the peak ejection phase, resulting in relatively low shear stress (up to 0.4 Pa) and no lasting stagnation regions. Significant shear stresses were found near the valves with higher values near the outlet valve in both models. The configuration of valves and conduits had a large effect on VAD washout and mixing properties, with advantage to the bileaflet model. However, since the bileaflet valves exhibited higher shear stresses, higher LOA were found for the bileaflet model.     

PD与VAD方案对多发性骨髓瘤的疗效比较

本研究评价PD（硼替佐米、地塞米松）和VAD（长春新碱、阿霉素、地塞米松）两种方案对多发性骨髓瘤的疗效和毒副作用。分别有21和31例多发性骨髓瘤患者纳入PD和VAD治疗组,接受2—5个疗程治疗。所有52例患者中,48例为初治患者,4例曾应用过1—2个疗程M2或MP方案化疗,但未达到部分缓解。在PD组中,完成2、3、4、5个疗程的患者分别为4、4、8、5例;在VAD组中完成2、3、4、5个疗程的患者分别为6、11、12、2例。结果表明：两组患者的反应良好（CR和VOPR）的患者比例在PD组明显高于VAD纽,分别为57．1％和16．1％,差异有显著性意义（P=0．0052）。治疗有效（CR、VGPR和PR）的患者比例在PD和VAD两组中分别为95．2％和74．2％,差异无显著性意义（P=0．1108）。PD组所有患者无1例出现疾病进展,VAD组中有1例疾病进展。两组患者在血液学毒性、肝肾功能损害、周围神经病变、感染、间质性肺炎等主要不良反应发生率相似,差异无统计学意义。结论：与传统的一线治疗方案VAD相比,PD可提高多发性骨髓瘤治疗反应良好的比例,且不增加副反应发生率。     

New treatment strategies for multiple myeloma

During the past 5 years, several new treatments and strategies have been developed for patients with multiple myeloma. For patients with disease resistant to standard therapies, these include the VAD regimen, dexamethasone alone, high-dose melphalan, and intensive chemoradiotherapy with bone marrow transplantation. Alpha interferon appears to have its greatest potential as part of early induction therapy or during remission maintenance. The role of hemopoietic growth factors or blood stem cells in support of high-dose therapy and drugs that may overcome multiple drug resistance continues under study. A sequence of non-cross-resistant therapies early in the disease course seems worthy of investigation, especially in patients at high risk for early relapse.     

Computational Prediction of Hemolysis in a Centrifugal Ventricular Assist Device

Abstract: This paper describes the use of computational fluid dynamics (CFD) to predict numerically the hemolysis in centrifugal pumps. A numerical hydrodynamical model, based on the full Navier-Stokes equation, was used to obtain the flow in a vaneless centrifugal pump (of corotating disks type). After proper postprocessing, critical zones in the channel were identified by means of two-dimensional color-coded maps of %Hb release. Simulation of different conditions revealed that flow behavior at the entrance region of the channel is the main cause of blood trauma in such devices. A useful feature resulting from the CFD simulation is the visualization of critical flow zones that are impossible to determine experimentally with in vitro hemolysis tests.     

Carbazolequinone induction of caspase-dependent cell death in Src-overexpressing cells

We previously reported that RSV-transformed quail neuroretina cells (QNR-ts68) were highly resistant to apoptosis provoked by serum withdrawal, and that this property was due to v-Src kinase activity. The present study investigates the cytotoxic effect and the functional mechanism of carbazolequinone-mediated cell death in this system. QNR-ts68 cells were subjected to carbazolequinone treatment and both growth inhibition and cell death induction were examined using formazan assays. Cell death mechanism (both apoptosis and necrosis) was confirmed through phosphatidyl serine exposure and propidium iodide incorporation. Furthermore, the effect of active carbazolequinone was inhibited by a pan caspase inhibitor. Cytofluorimetric and immunofluorescence data demonstrated the activation of caspase-3 and the involvement of mitochondria. Therefore, this study clearly indicates that carbazolequinones could induce cell death in transformed cells displaying high levels of antiapoptotic tyrosine kinase activity. Further investigations would be necessary to elucidate the mechanisms by which these carbazolequinones act as antitumor agents.