Understanding the Influence of Nanocarrier-Mediated Brain Delivery on Therapeutic Performance Through Pharmacokinetic-Pharmacodynamic Modeling

This study aimed at evaluating how encapsulation in a regular nanocarrier (NC) (providing extended circulation time) or in a brain-targeting NC (providing prolonged circulation time and increased brain uptake) may influence the therapeutic index compared with the unformulated drug and to explore the key parameters affecting therapeutic performance using a model-based approach. Pharmacokinetic (PK) models were built with chosen PK parameters. For a scenario where central effect depends on area under the unbound brain concentration curve and peripheral toxicity relates to peak unbound plasma concentration, dose-effect and drug-side effect curves were constructed, and the therapeutic index was evaluated. Regular NC improved the therapeutic index compared with the unformulated drug due to reduced peripheral toxicity, while brain-targeting NC enhanced the therapeutic index by lowering peripheral toxicity and increasing central effect. Decreasing drug release rate or systemic clearance of NC with drug still encapsulated could increase the therapeutic index. Also, a drug with shorter half-life would therapeutically benefit more from a NC encapsulation. This work provides insights into how a NC for brain delivery should be optimized to maximize the therapeutic performance and is helpful to predict if and to what extent a drug with certain PK properties would obtain therapeutic benefit from nanoencapsulation.     

A peripherally inserted central catheter misplacement into lateral thoracic vein: A case report

IntroductionCentral venous catheter applications and complications are closely related to the tip position. Previous studies have reported some rare cases of catheter misplacement. Here, we report a case of misplacement of a peripherally inserted central catheter into the lateral thoracic vein.Case reportA 56-year-old cancer patient underwent placement of a peripherally inserted central catheter through the left basilic vein under ultrasound-guided puncture. The catheterisation procedure was uneventful, so the catheter was believed to be in the superior vena cava. However, the post-anterior chest X-ray image revealed that after the catheter advanced towards the axilla, it turned downwards and outwards in the direction of the left lateral thoracic region, with the projection of the catheter tip giving the appearance of termination in the subcutaneous tissue of the lateral thoracic wall on the two-dimensional image. The catheter was then repositioned in the distal superior vena cava.DiscussionPeripherally inserted central catheters can be potentially misplaced into the lateral thoracic vein because these catheters can pass through the orifice of the lateral thoracic vein which flows into the axillary vein. Some pathological cases and clinical conditions can cause dilatation of the lateral thoracic vein, which increases the probability of catheter misplacement. Three principles were proposed to avoid this rare complication: a comprehensive review of the patients’ medical history, real-time image-guided catheterisation and routine radiographic identification of the tip position.     

Kinetic modeling of PET-FDG in the brain without blood sampling

The aim in this work is to report a new method to calculate parametric images from a single scan acquisition with positron emission tomography (PET) and fluorodeoxyglucose (FDG) in the human brain without blood sampling. It is usually practical for research or clinical purposes to inject the patient in an isolated room and to start the PET acquisition only for some 10–20 min, about 30 min after FDG injection. In order to calculate the cerebral metabolic rates for glucose (CMRG), usually several blood samples are required. The proposed method considers the relation between the uptake of the tracer in the cerebellum as a reference tissue and the population based input curve. Similar results were obtained for CMRG values with the present method in comparison to the usual autoradiographic and the non-linear least squares fitting of regions of interest.     

前路病灶清除植骨内固定术治疗胸腰椎结核

目的探讨在胸、腰椎结核外科治疗中,前路病灶清除植骨内固定术对清除结核病灶,对脊髓神经的减压及重建脊柱稳定性的重要性。方法对2000年10月~2004年6月共收治的胸、腰椎结核患者46例,采用前路病灶清除自体髂骨植骨38例,异体深冻骨植骨并胸、腰椎前路钛钢板内固定8例。结果经过平均18个月的随访,长达1~1.5年的抗结核治疗,44例患者结核治愈,植骨融合时间平均为5.2个月。术前截瘫、不全瘫或伴有神经症状者均有不同程度的恢复;1例内固定松动、异体深冻骨植骨未融合;1例复发,但其异体深冻骨植骨块及内固定位置良好,经继续抗结核治疗6个月后结核治愈。结论前路病灶清除,自体髂骨植骨,钛钢板内固定对胸、腰椎结核疗效肯定,异体深冻骨植骨存在融合慢或不融合的问题。     

镍钛形状记忆合金环抱接骨板治疗桡骨近端1/3骨折

目的探讨治疗桡骨近端1/3骨折的理想内固定方法.方法 2001年8月～2004年4月,采用镍钛形状记忆合金环抱接骨板治疗24例桡骨近端1/3骨折.其中男19例,女5例.年龄16～48岁.摔伤9例,压砸伤5例,交通事故伤4例,直接暴力撞击伤3例,高处坠落伤3例.按照形状记忆合金环抱接骨板的安装方法进行骨折复位内固定.术后定期随访,观察骨折愈合及功能恢复情况.结果所有患者均获随访4～21个月,平均10个月.均无术中、术后并发症,切口Ⅰ期愈合;X 线片示骨折均于术后8～12周临床愈合,根据Anderson疗效标准,功能恢复优18例,良5例,可1例,优良率95.83%.结论应用镍钛形状记忆合金环抱接骨板治疗桡骨近端1/3骨折具有创伤小、操作简便安全、固定可靠、组织相容性好、并发症少等优点,有利于促进骨折愈合和肘、腕关节功能康复,是一种治疗桡骨近端1/3骨折的较好方法.     

单钉-棒固定在胸腰椎结核前路手术中的应用

目的探讨脊柱结核手术内固定的有效方式。方法2002年6月~2004年6月,在手术前有效抗结核化疗的基础上,采用前路病灶清除、植骨融合及单钉-棒内固定的手术方式治疗胸、腰椎结核患者54例。术中在保证彻底清创的基础上注意保留病椎有血供的部分和无明显破坏的椎间盘,以减少切除范围和融合的节段,有神经症状者注意行椎管前侧减压。骨缺损采用自体髂骨、异体髂骨 自体碎骨、或钛网 自体碎骨的方法修复,安置单钉-棒时注意对移植骨块适当加压。患者术后卧床10d左右,然后在支具的保护下下床活动。本组共有41例患者获得随访,手术后随访的时间7~31个月,平均18个月。结果患者所有的结核病灶均顺利愈合,植骨稳定,无明显移位和塌陷,内固定器无松脱和折断,其中37例达到骨性愈合标准;脊柱后凸角平均矫正达23°,患者术前伴有的神经症状也大部分消失,绝大部分患者恢复日常生活、工作。结论前路单钉-棒内固定不仅能够维持胸、腰椎结核手术后脊柱的稳定,防止移植骨块的脱位、塌陷和骨不愈合的发生,而且可以最大范围地减少融合节段,减少术中创伤,故是手术治疗胸、腰椎结核的可靠固定方式。