Development of biotube vascular grafts incorporating cuffs for easy implantation

We are developing functional autologous tubular tissues, called biotubes, as ideal small-caliber vascular grafts that have growth potential without immunological rejection. In this study, to improve surgical handling, a novel biotube reinforced at the anastomosis regions was designed. Silicone rods, 2 mm in diameter and used as a mold, were covered with two pieces of short polyurethane sponge tubing as anastomotic reinforcement cuffs at both ends. After the assembly was placed into dorsal subcutaneous pouches in rabbits for 1 month, seamless biotubes incorporating the cuffs were obtained. The interstices and surfaces of the cuffs were impregnated and covered with connective tissues similar to those of the biotubes, mainly consisting of collagen and fibroblasts. Since the tubular shape of both ends was rigidly maintained, end-to-end anastomosis by conventional microsurgery techniques between biotubes and native carotid arteries was very easy. In preliminary autoimplantation studies, angiographic observation of up to 2 months duration showed no formation of aneurysms or rupturing. Both K. Kanda and Y. Nakayama are the corresponding authors.     

Usefulness of polyurethane for small-caliber vascular prostheses in comparison with autologous vein graft

 For long-term patency of small-caliber vascular prostheses, antithrombogenicity and microporous structure are very important. We have developed a new technique to give a microporous structure to a polyurethane vascular prosthesis that has favorable antithrombogenicity. A solution of tetrahydrofuran/dimethylformamide (1 : 1) containing 13 wt% of segmented polyurethane (PTMG + MDI) and calcium carbonate (mean particle size, 8 μm) was dipcoated on a glass mandrel 3 mm in diameter and placed into distilled water. After the glass mandrel was removed, the polyurethane tube was placed into hydrochloric acid, and a microporous polyurethane vascular prosthesis was produced. Prostheses made in this fashion, and autologous jugular vein grafts were implanted into the femoral artery and the carotid artery of mongrel dogs. Patency was recognized on the arteriogram and duplex scanning (ultrasonography), and the removed grafts were inspected macroscopically and microscopically. This prosthesis was similar in elasticity to a vein graft. Patency was defined 8 weeks after implantation, and this prosthesis showed less intimal hyperplasia than the autologous vein graft. The new polyurethane prosthesis might be useful for small-caliber vascular reconstruction. Received: December 18, 2000 / Accepted: January 28, 2002     

Electrospun biodegradable elastic polyurethane scaffolds with dipyridamole release for small diameter vascular grafts

Acellular biodegradable small diameter vascular grafts (SDVGs) require antithrombosis, intimal hyperplasia inhibition and rapid endothelialization to improve the graft patency. However, current antithrombosis and antiproliferation approaches often conflict with endothelial cell layer formation on SDVGs. To address this limitation, biodegradable elastic polyurethane urea (BPU) and the drug dipyridamole (DPA) were mixed and then electrospun into a biodegradable fibrous scaffold. The BPU would provide the appropriate mechanical support, while the DPA in the scaffold would offer biofunctions as required above. We found that the resulting scaffolds had tensile strengths and strains comparable with human coronary artery. The DPA in the scaffolds was continuously released up to 91 days in phosphate buffer solution at 37 °C, with a low burst release within the first 3 days. Compared to BPU alone, improved non-thrombogenicity of the DPA-loaded BPU scaffolds was evidenced with extended human blood clotting time, lower TAT complex concentration, lower hemolysis and reduced human platelet deposition. The scaffolds with a higher DPA content (5 and 10%) inhibited proliferation of human aortic smooth muscle cell significantly. Furthermore, the DPA-loaded scaffolds had no adverse effect on human aortic endothelial cell growth, yet it improved their proliferation. The attractive mechanical properties and biofunctions of the DPA-loaded BPU scaffold indicate its potential as an acellular biodegradable SDVG for vascular replacement.     

超声乳化白内障吸除人工晶体植入治疗闭角型青光眼的临床优势分析

目的观察超声乳化白内障吸除人工晶体植入治疗闭角型青光眼的临床优势。方法选择2009年1月至2011年1月收住本院的闭角型青光眼64例（64眼）,根据入院顺序平分为两组-治疗组与对照组各32例。治疗组采用颞侧隧道式透明角膜切口超声乳化联合人工晶体植入术,对照组采用复合式小梁切除手术。结果两组术前视力相差不大,但是治疗后,治疗组术后最佳矫正视力大于0.8者8眼,0.3～0.8者20眼。治疗组的视力好转情况明显好于对照组（P〈0.05）。两组治疗前平均眼压比较无显著性差异（P〉0.05）,治疗后都有明显下降（P〈0.05）,治疗组的眼压下降幅度明显高于对照组（P〈0.05）。两组术中与术后并发症情况对比无显著性差异,具有可比性（P〉0.05）。结论超声乳化白内障吸除人工晶体植入治疗闭角型青光眼是一种可供选择的安全有效的手术方法,能有效提高视力与降低眼压,无术中与术后严重并发症发生,值得推广应用。     

Fabrication of highly interconnected porous silk fibroin scaffolds for potential use as vascular grafts

Silk fibroin (SF) scaffolds have been designed and fabricated for multiple organ engineering owing to SF’s remarkable mechanical property, excellent biocompatibility and biodegradability, as well as its low immunogenicity. In this study, an easy-to-adopt and mild approach based on a modified freeze-drying method was developed to fabricate a highly interconnected porous SF scaffold. The physical properties of the SF scaffold, including pore morphology, pore size, porosity and compressive modulus, could be adjusted by the amount of ethanol added, the freezing temperature and the concentration of SF. Fourier transform infrared spectroscopy illustrated that treatment of the lyophilized scaffolds with 90% methanol led to a structure transition of SF from silk I (random coil) to silk II (beta-sheet), which stabilized the SF scaffolds in water. We also incorporated heparin during fabrication to obtain a heparin-loaded scaffold which possessed excellent anticoagulant property. The heparin that was incorporated into the SF scaffolds could be released in a sustain manner for approximately 7 days, inhibiting the proliferation of human smooth muscle cells within the scaffold in vitro while promoting neovascularization in vivo. We therefore propose that the SF porous scaffold fabricated here may be an attractive candidate for use as a potential vascular graft for implantation based on its high porosity, excellent blood compatibility and mild fabrication process.     

Application of artificial palpation in vascular surgeries for detection of peripheral arterial stenosis

Palpation is one of the applied methods that surgeons usually use during surgery in order to verify the health condition of a tissue/organ. In fact, most of surgical assessments are based on analysis of the force feedback received from tissue/organ via palpation. Although palpation has a key role in efficient progress of surgery operations, it depends very much on the experience and skill of the surgeons. This limits the application of this technique in some cases to a large extent. In this regard, an artificial tactile sensing approach is an innovative technology that tries to make tactile data more available for surgeons, especially in situations where doing the palpation is not possible or is too difficult. In this paper, having considered the present problems of artery bypass surgery in peripheral arterial occlusive disease (PAOD), applicability of a new tactile sensory system capable of detecting arterial stenosis during surgery was evaluated. Presenting the modelling and numerical solution of the problem, it was demonstrated that the artificial tactile sensing approach is not only capable of detecting the presence of an arterial stenosis in an artery, but also its type. Furthermore, it was shown that the new tactile sensory system (previously designed, fabricated and tested in laboratory) is efficiently capable of detecting the simulated artery in the simulated biological tissue as well as diagnosis of the stenosis occurred inside it.     

Development and evaluation of silk fibroin-based nerve grafts used for peripheral nerve regeneration

Silk fibroin (SF), derived from natural silk long used as a textile material, has recently become an important biomaterial for tissue engineering applications. We have previously reported on good in vitro biocompatibility of SF fibers with peripheral nerve tissues and cells. In the present study, we developed a novel biomimetic design of the SF-based nerve graft (SF graft) which was composed of a SF-nerve guidance conduit (NGC) inserted with oriented SF filaments. The SF-NGC prepared via well-established procedures exhibits an eggshell-like microstructure that is responsible for its superior mechanical and permeable properties beneficial to nerve regeneration. The SF graft was used for bridge implantation across a 10-mm long sciatic nerve defect in rats, and the outcome of peripheral nerve repair at 6 months post-implantation was evaluated by a combination of electrophysiological assessment, FluoroGold retrograde tracing and histological investigation. The examined functional and morphological parameters show that SF grafts could promote peripheral nerve regeneration with effects approaching those elicited by nerve autografts which are generally considered as the gold standard for treating large peripheral nerve defects, thus raising a potential possibility of using these newly developed nerve grafts as a promising alternative to nerve autografts.     

Formation of the cardiac vascular system and ventricular compact wall

The corrosion cast method for scanning electron microscopy, transmission electron microscopy and auto-injection of tracers for light microscopy were used to examine the cardiac coronary development and the forming of the ventricular compact wall to the embryonal sponge-work wall. Our observations suggest that the coronary artery first extends over outer layer, and later over middle and inner layers. As intertrabecular spaces are closed by fusion to each endocardium in the inner layer position, the veins are formed by the remaining expanded sinusoidal intertrabecular spaces. The capillaries of the coronary vessels are then connected to the veins to finally complete the cardiac vascular system.     

Dynamically monitoring lymphatic and vascular systems in physiological and pathological conditions of a swine model via a portable NIR-II imaging system with ICG

Objective: NIR-II imaging with indocyanine green (ICG) has been clinically used in liver tumor resection. However, few data are available concerning the application of ICG-NIR-II in lymphatic and vascular systems in clinic. To expand the application and promote the clinical translation of this approach, we aimed to investigate the feasibility of ICG-NIR-II imaging for monitoring both lymphatic and vascular systems in physiological and pathological conditions using a swine model and compared it to ICG-NIR-I imaging.Methods: we constructed a portable NIR-II imaging system suitable for large animals. Different simulated clinical scenarios in lymphatic and vascular systems of pigs, including lymphatic drainage, lymphorrhea, lymphatic obstruction, lymphatic reconstruction in flaps, venous thrombus formation and vascular anastomosis were modeled to evaluate the reliability of our NIR-II imaging system and the imaging quality of ICG in the NIR-I/II window.Results: Under different simulated clinical scenarios, our portable NIR-II imaging system showed good reliability for pigs. With the help of the portable imaging system, dynamical visualization of lymph vessels, lymph nodes and blood vessels of pigs in different clinical scenarios could be achieved in NIR-II imaging by using the tail fluorescence of ICG. Moreover, ICG-NIR-II imaging has lower background fluorescence and higher resolution than ICG-NIR-I imaging.Conclusions: We demonstrated the first application of a portable NIR-II imaging system for dynamically monitoring both lymphatic and vascular systems in physiological and pathological conditions using a swine model. Our study indicates that ICG-NIR-II imaging be a promising approach for the diagnosis of malfunctions in lymphatic and vascular systems and the surgical navigation of microsurgery and reconstructive surgery.     

A systematic classification of the congenital bronchopulmonary vascular malformations: dysmorphogeneses of the primitive foregut system and the primitive aortic arch system

PURPOSE: We reviewed the cases of 33 patients from our clinic and 142 patients from the literature with congenital bronchopulmonary vascular malformations (BPVM), systematically analyzed the bronchopulmonary airways, pulmonary arterial supplies, and pulmonary venous drainages, and classified these patients by pulmonary malinosculation (PM). MATERIALS AND METHODS: From January 1990 to January 2007, a total of 33 patients (17 men or boys and 16 women or girls), aged 1 day to 24 years (median, 2.5 months), with congenital BPVM were included in this study. Profiles of clinical manifestations, chest radiographs, echocardiographs, esophagographs, computer tomography (CT), magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), cardiac catheterizations with angiography, contrast bronchographs, bronchoscopies, chromosomal studies, surgeries, and autopsies of these patients were analyzed to confirm the diagnosis of congenital BPVM. A total of 142 cases from the literature were also reviewed and classified similarly. RESULTS: The malformations of our 33 patients can be classified as type A isolated bronchial PM in 13 patients, type B isolated arterial PM in three, type C isolated venous PM in two, type D mixed bronchoarterial PM in five, type F mixed arteriovenous PM in one, and type G mixed bronchoarteriovenous PM in nine. CONCLUSION: Dysmorphogeneses of the primitive foregut system and the primitive aortic arch system may lead to haphazard malinosculations of the airways, arteries, and veins of the lung. A systematic classification of patients with congenital BPVM is clinically feasible by assessing the three basic bronchovascular systems of the lung independently.     

Design of a control system for maintaining a normal arterialpCO2 by artificial respiration

The paper describes the design of a feedback control system which maintains the arterial pCO₂ near the normal level during artificial respiration in spite of disturbances in variables such as the CO₂ production rate, the dead space and blood flow. Five models were used to analyse the control system. Using the linear model, a proportional controller with a lag/lead compensator was designed to satisfy the requirements derived from the performance of the biological respiratory system. Digital simulation confirmed that the control system responds well to the above mentioned disturbances and that it is little affected by parameter variations in the control system.     

新型呼吸机湿化器自动加水装置的研发

目的 研制一种新型的呼吸机湿化器自动加水装置.方法 利用输液器挂高后的重力持续加水,以传感器检测液面高度作为信号,通过电磁阀控制输液器皮管外套截止夹的关闭和开启.结果 当呼吸机湿化器内液面低于设置值时,输液器截止夹打开,输液瓶内的纯净水自动加入湿化器内;当湿化器内液面达到设置的液面高位时,截止夹受控关闭,停止加水.结论 此呼吸机湿化器自动加水装置工作有效、使用方便,实现了持续、相对匀速、少量的稳态加水过程;同时,湿化器内水量稳定,加热均匀,进入呼吸道的气体温度相对恒定,可以在临床推广使用.     

Development of a highly responsive needle-type glucose sensor using polyimide for a wearable artificial endocrine pancreas

To produce a long-life, stable, miniature glucose sensor for a wearable artificial endocrine pancreas (WAEP), we developed a novel microneedle-type glucose sensor using polyimide, designated the PI sensor (outer diameter, 0.3 mm; length, 16 mm), and investigated its characteristics in vitro and in vivo. In the in vitro study, we tested the sensor in 0.9% NaCl solution with varying glucose concentrations and observed an excellent linear relationship between the sensor output and glucose concentration (range: 0–500 mg/100 ml). In in vivo experiments, the PI sensor was inserted into the abdominal subcutaneous tissue of beagle dogs (n = 5), and interstitial fluid glucose concentrations were monitored after sensor calibration. Simultaneously, blood glucose concentrations were also monitored continuously with another PI sensor placed intravenously. The correlation and time delay between subcutaneous tissue glucose (Y) and blood glucose concentrations (X: 30–350 mg/100 ml) were Y = 1.03X + 7.98 (r = 0.969) and 6.6 ± 1.2 min, respectively. We applied the new WAEP system/PI sensor and an intravenous insulin infusion algorithm developed previously for glycemic control in diabetic dogs. The use of the WAEP system resulted in excellent glycemic control after an oral glucose challenge of 1.5 g/kg (post-challenge blood glucose levels: 176 ± 18 mg/100 ml at 65 min and 93 ± 23 mg/100 ml at 240 min), without any hypoglycemia. Thus, we confirmed that our new PI sensor has excellent sensor characteristics in vitro and in vivo. The new WAEP using this sensor is potentially suitable for clinical application.     

Sensitive force transducer system for mechanical studies of single isolated vascular smooth muscle cells

To measure forces of the order of 0·1 μN, generated by single isolated vascular smooth muscle cells, a sensitive transducer system has been developed. A video displacement detection system and an inductive position detector were used to control the tip displacement of a glass microneedle. The bending of the microneedle was used as a measure of the force generated by a single smooth muscle cell attached to the tip. During isometric contractions the stiffness of the system was 0·7 μN μm⁻¹. A signal limiter in one of the feedback loops made it possible to reduce the stiffness of the system to 4 nN μm⁻¹ when an adjustable force limit was exceeded. These two conditions of the system made it possible to measure both isometric and isotonic contractions of a single muscle cell. The force limiter may also be used to protect the preparation against excessive forces developed during contraction. A mechanical model of the system and the vascular smooth muscle cell was simulated and verified. The parameters of the model for a single vascular smooth muscle cell, two viscoelastic springs in parallel, could be estimated from the measurements. The bandwidth of the system during isometric contraction was 17 Hz.     

便携式大功率LED黄疸光疗仪的研制

提出一种基于发光二极管(LED)开发的便携式光强可调黄疸光疗仪。仪器选用蓝色LED实现特殊阵列排布,并基于芯片MAX5035构建恒流驱动电路,驱动电流受单片机ATmega16L程序控制,可实现对仪器光照强度的线性调节,并将其对应光强值显示在液晶12864。与传统黄疸光疗仪相比,仪器体积小,光照强度强,并能实现一定范围光强调节。     

Development of a real-time three-dimensional spinal motion measurement system for clinical practice

This paper presents an inertial based sensing system for real-time three-dimensional measurement of human spinal motion, in a portable and non-invasive manner. Applications of the proposed system range from diagnosis of spine injury to postural monitoring, on-field as well as in the lab setting. The system is comprised of three inertial measurement sensors, respectively attached and calibrated to the head, torso and hips, based on the subject’s anatomical planes. Sensor output is transformed into meaningful clinical parameters of rotation (twist), flexion-extension and lateral bending of each body segment, with respect to calibrated global reference space. Modeling the spine as a compound flexible pole model allows dynamic measurement of three-dimensional spine motion, which can be animated and monitored in real-time using our interactive GUI. The accuracy of the proposed sensing system has been verified with subject trials using a VICON optical motion measurement system. Experimental results indicate an error of less than 3.1° in segment orientation tracking.     

Assessment of the EuroSCORE risk scoring system for patients undergoing coronary artery bypass graft surgery in a group of Iranian patients

Results:Of the 2220 patients, in hospital deaths occurred in 270 patients (mortality rate of 12.2%). The accuracy of mortality prediction in the logistic EuroSCORE and APACHE II model was 89.1%; in the local EuroSCORE (logistic) was 91.89%; and in the local EuroSCORE support vector machines (SVM) was 98.6%. The area under curve for ROC curve, was 0.724 (95% confidence interval [CI]: 0.57–0.88) for logistic EuroSCORE; 0.836 (95% CI: 0.731–0.942) for local EuroSCORE (logistic); 0.978 (95% CI: 0.937–1) for Local EuroSCORE (SVM); and 0.832 (95% CI: 0.723–0.941) for APACHE II model. The HL test showed good calibration for the local EuroSCORE (SVM), APACHE II model and local EuroSCORE (logistic) (P = 0.823, P = 0.748 and P = 0.06 respectively); but there was a significant difference between expected and observed mortality according to EuroSCORE model (P = 0.033).Conclusion:We detected logistic EuroSCORE risk model is not applicable on Iranian patients undergoing CABG surgery.     

Development of a tripartite vector system for live oral immunization using a gram-negative probiotic carrier

The mucosa represents the primary target site and thus the first barrier for most microbial pathogens. Nevertheless, nearly all present-day vaccines are applied by an invasive route, target the systemic immune system, and do not confer efficient mucosal protection. Currently, mucosal immunity can only be achieved by the delivery of antigens via the mucosal route. Therefore, multiple efforts are under way to develop mucosal vaccines and particularly live oral vaccines as these would confer considerable advantages. We have engineered the AIDA autotransporter system for the surface presentation and/or release of heterologous polypeptides. This study is focused on the development and evaluation of a tripartite live bacterial vector system for oral vaccination based on the AIDA autotransporter, heterologous virulence factor-derived (poly-)peptides, and the apathogenic Escherichia coli Nissle 1917 strain as a live carrier. Potentially with this system also attenuated Salmonella or Shigella strains might be employed as carriers. Model antigens included e.g. the p60 antigen of Listeria monocytogenes, the OspA/OspG antigens of B. burgdorferi, the LT-B subunit of E. coli, and Stx-B subunits of enterohemorrhaghic E. coli (EHEC), all representing crucial virulence factors of important bacterial pathogens. Exemplary oral immunization studies were conducted using different regimes in BALB/c mice with candidate vaccines expressing Stx B-subunits and OspA and OspG proteins. To monitor the induction of immune responses, specific antibody titers in serum as well as secreted mucosal antibodies of local and distal mucosal surfaces were determined. Antigen-specific mucosal as well as systemic antibodies could be induced; however, thus far the response turned out to be heterogeneous and appeared not to be sufficient to mediate protection.     

Development and validation of an unsupervised scoring system (Autonomate) for skin conductance response analysis

The skin conductance response (SCR) is increasingly being used as a measure of sympathetic activation concurrent with neuroscience measurements. We present a method of automated analysis of SCR data in the contexts of event-related cognitive tasks and nonspecific responding to complex stimuli. The primary goal of the method is to accurately measure the classical trough-to-peak amplitude of SCR in a fashion closely matching manual scoring. To validate the effectiveness of the method in event-related paradigms, three archived datasets were analyzed by two manual raters, the fully-automated method (Autonomate), and three alternative software packages. Further, the ability of the method to score non-specific responses to complex stimuli was validated against manual scoring. Results indicate high concordance between fully-automated and computer-assisted manual scoring methods. Given that manual scoring is error prone, subject to bias, and time consuming, the automated method may increase the efficiency and accuracy of SCR data analysis.     

前交叉韧带侧向刚度在线测量系统研制及其对前交叉韧带重建效果的影响

前交叉韧带重建张力的设置主要依靠外科医生的经验。为提高膝关节恢复治疗中前交叉韧带重建后张力的有效性和适应性,本文建立具有松弛特性的侧向力学测量模型,设计前交叉韧带在线刚度测量系统,提出"术前检测,术中参考"的新方法。本文选取20个绵羊膝关节进行膝关节稳定性测试,分两组进行前外侧入路单束前交叉韧带重建对比实验,第一组手术医生常规流程进行术中检测;第二组使用前交叉韧带在线刚度测量系统在术中进行检测;之后对上述两组进行术后稳定性实验。研究结果表明,该测量系统测量的张力精度为(-2.3±0.04)%,位移误差为(1.5±1.8)%,术后对两组进行前向稳定性、内旋稳定性和外旋稳定性测试,结果均优于术前(P <0.05),但使用该系统的一组更接近术前膝关节测量指标,且与经验丰富的医生对比差异无统计学意义(P> 0.05)。最终,期待本文建立的该系统可以帮助临床医生判断手术过程中的前交叉韧带重建张力,有效提升手术效果。