Comparison of hydraulic and hemolytic properties of different impeller designs of an implantable rotary blood pump by computational fluid dynamics

A mixed-flow blood pump for long-term applications has been developed at the Helmholtz-Institute in Aachen, Germany. Central features of this implantable pump are a centrally integrated motor, a blood-immersed mechanical bearing, magnetic coupling of the impeller, and a shrouded impeller, which allows a relatively wide clearance. The aim of the study was a numerical analysis of hydraulic and hemolytic properties of different impeller design configurations. In vitro testing and numerical simulation techniques (computational fluid dynamics [CFD]) were applied to achieve a comprehensive overview. Pressure-flow charts were experimentally measured in a mock loop in order to validate the CFD data. In vitro hemolysis tests were performed at the main operating point of each impeller design. General flow patterns, pressure-flow charts, secondary flow rates, torque, and axial forces on the impeller were calculated by means of CFD. Furthermore, based on streak line techniques, shear stress (stress loading), exposure times, and volume percentage with critical stress loading have been determined. Comparison of CFD data with pressure head measurements showed excel-lent agreement. Also, impressive trend conformity was observed between in-vitro hemolysis results and numerical data. Comparison of design variations yielded clear trends and results. Design C revealed the best hydraulic and hemolytic properties and was chosen as the final design for the mixed-flow rotary blood pump.     

基于快速成型技术的个体化人工股骨髁关节面的设计与应用

目的设计、制造一种基于快速成型技术、复合异体半关节移植的个体化人工股骨髁关节面,探讨解决异体半关节移植中异体关节软骨坏死和异体-自体关节形状不匹配的方法。方法对异体半关节和骨肿瘤患肢股骨髁外表面行螺旋CT扫描,将CT断层图像进行矢量转换后在Surfacer 9．0软件进行矢量化三维重建,提取出合适的异体骨软骨下骨和患者关节软骨表面轮廓的三维图像,在计算机辅助下设计人工关节面,应用LPS600快速成型机制出快速成型树脂模型,以钛合金为材料铸造关节面假体主件,通过融合笼将关节面固定于关节上,抛光后获得人工关节软骨面成品。2002年2月对1例男性14岁右股骨下段骨肉瘤患者,行右股骨下段瘤段切除、人工股骨髁关节面复合大段同种异体骨移植重建股骨下端骨缺损术。结果新型复合异体半关节移植的个体化人工股骨髁关节假体与异体骨、对侧关节匹配良好;应用后随访16个月,膝关节功能良好。结论个体化股骨髁关节面明显改善了异体半关节移植患者的膝关节功能,为异体半关节移植中存在的异体关节软骨坏死和异体一自体关节形状不匹配提供一种解决方案。     

Fabrication of tissue engineered tympanic membrane patches using computer-aided design and injection molding

Objectives/Hypothesis: The goal of the current study was to use computer‐aided design and injection molding technologies to tissue engineer precisely shaped cartilage in the shape of butterfly tympanic membrane patches out of chondrocyte‐seeded calcium alginate gels. Methods: Molds were designed on SolidWorks 2000 and built out of acrylonitrile butadiene styrene (ABS) using fused deposition modeling (FDM). Tympanic membrane patches were fabricated using bovine articular chondrocytes seeded at 50 × 10⁶ cells/mL in 2% calcium alginate gels. Molded patches were cultured in vitro for up to 10 weeks and assessed biochemically, morphologically, and histologically. Results: Unmolded patches demonstrated outstanding dimensional fidelity, with a volumetric precision of at least 3 μL, and maintained their shape well for up to 10 weeks of in vitro culture. Glycosaminoglycan and collagen content increased steadily over 10 weeks in culture, demonstrating continual deposition of new extracellular matrix consistent with new tissue development. Conclusions: The use of computer‐aided design and injection molding technologies allows for the fabrication of very small, precisely shaped chondrocyte‐seeded calcium alginate structures that faithfully maintain their shape during in vitro culture. In vitro fabrication of tympanic membrane patches with a precisely controlled geometry may have the potential to provide a minimally invasive alternative to traditional methods for the repair of chronic tympanic membrane perforations.     

Use of the Paired-Comparison Technique to Determine the Most Valued Qualities of the McMaster Medical Programme Admissions Process

The Undergraduate Medical Programme at McMaster University selects students using a comprehensive set of tools. Attempts to modify the selection process over many years have been impeded by an inability to reconcile very strongly held views among stakeholders as to the importance of the selection tools and, indeed, the very purposes of the admission process. The objective of this study was to identify key 'qualities' of the selection process and to measure their relative importance to admissions process assessors. Through a qualitative review of internal research documents, Medical Programme Admissions Committee meeting minutes, memos and accreditation surveys eight qualities of the admissions process were identified: validity, fairness, accessibility, comprehensiveness, affordability, legal defensibility, contribution to class diversity and the role of the process as a public statement of the Programme's values. Faculty, students and community admissions assessors were surveyed, by mail, using a paired-comparisons technique. The overall response rate was 58%. By a wide margin, all three groups of admissions assessors valued validity and fairness most highly. The least valued qualities were affordability and the role of the process as a statement of our values. Possible applications of this approach to the admissions process deliberations are discussed.     

Prodrug research: futile or fertile?

The objective of this Commentary is to help clarify and illustrate what prodrugs are, what they are not, which benefits they can offer, and what their limits are. To this end, a number of criteria of classification and evaluation are presented. This is followed by a discussion of the pharmaceutical, pharmacokinetic and pharmacodynamic objectives of prodrug research. Recent examples (e.g. oseltamivir, bambuterol, capecitabine, clopidogrel and tirapazamine) are discussed in a biochemical perspective to illustrate these objectives and to demonstrate some of the therapeutic benefits afforded by successful prodrugs. Attention is also called to the fact that the in vitro and in vivo behavior of prodrug candidates may differ from that of the parent drug in ways that go beyond the original pharmaceutical, pharmacokinetic or pharmacodynamic objective being pursued. We conclude that prodrugs offer a viable strategy to disentangle pharmacodynamic and pharmacokinetic optimization.     

Rational redesign of inhibitors of furin／kexin processing proteases by electrostatic mutations

AIM:Tomodelthethree-dimensionalstructureandinvestigatetheinteractionmechanismoftheproproteinconvertasefurin/kexinandtheirinhibitors(eglincmutants).METHODS:Thethree-dimensionalcomplexstructuresoffurin/kexinwithitsinhibitors,eglincmutants,weregeneratedbymodellerprogramusingthenewlypublishedX-raycrystallographicalstructuresofmousefurinandyeastkexinastemplates.Theelectrostaticinteractionenergyofeachcomplexwascalculatedandtheresultswerecomparedwiththeexperimentallydeterminedinhibitioncon-stants…     

Advances in modeling of biomolecular interactions

Modeling of molecular interactions is increasingly used in life science research and biotechnology development. Examples are computer aided drug design, prediction of protein interactions with other molecules, and simulation of networks of biomolecules in a particular process in human body. This article reviews recent progress in the related fields and provides a brief overview on the methods used in molecular modeling of biological systems.     

Pharmacological treatments of cerebellar ataxia

The confirmed pharmacological treatment of cerebellar ataxia is still lacking. In a recent preliminary trial, we showed that D-cycloserine, a partial NMDA allosteric agonist, may relieve the symptoms. In this paper, major clinical trials to relieve ataxic symptoms are reviewed. Previous studies showed some efficacy of physostigmine in ataxic patients. However, physostigmine did not improve the ataxia in a recent double-blind crossover study. The replacement therapy of the deficient cholinergic system with choline or choline derivatives was tried in patients with Friedreich's ataxia and other ataxic patients, but the result was not definitive. A levorotatory form of hydroxytryptophan (a serotonin precursor), a serotoninergic 5-HT1A agonist, a serotoninergic 5-HT3 antagonist, and a serotonin reuptake inhibitor were also used for the therapy for ataxia. In a double-blind randomized study, buspirone, a 5-HT1A agonist was active in cerebellar ataxia, but the effect is partial and not major. The effects of the studies with the other serotoninergic drugs were not consistent. The effect of sulfamethoxazole-trimethoprim therapy in spinocerebellar ataxia type3/Machado-Joseph disease (MJD) was reported, although the therapy improved spasticity or rigidity, rather than ataxia. In contrast to previous studies, sulfamethoxazole-trimethoprim therapy in MJD had no effect in a 2001 double-blind crossover study. The thyrotropin-releasing hormone, D-cycloserine, and acetazolamide for SCA6 may have some efficacy. However, a well-designed double-blind crossover trial is needed to confirm the effect.     

Is depression related to subsequent diabetes mellitus?

OBJECTIVE: To compare the risk of developing diabetes mellitus (DM) in the general population between subjects who had a depression and subjects who never had a depression. METHOD: Retrospective cohort design. People with depression were diagnosed with a depression between 1975 and 1990; controls never had a depression. Both groups were followed for a diagnosis of type II diabetes until 2000. Data on 1334 depressed and 66 670 non-depressed subjects were available from a large general practice-based database. RESULTS: No overall relation was found, but among males below age 50 there was a 78% increase in the rate of development of DM compared with non-depressed patients (hazard ratio 1.78, 95% CI: 1.21-2.62). CONCLUSION: Depression in males between the age of 20 and 50 years is related to an increased risk of developing DM.