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Biomedical subjects

P Chabrand

Publications and source records attributed to P Chabrand.

16 recordsLinked to original sources

Modeling UHMWPE wear debris generation.

It is widely recognized that polyethylene wear debris is one of the main causes of long-term prosthesis loosening. The noxious bioreactivity associated with this debris is determined by its size, shape, and quantity. The aim of this study was to develop a numerical tool that can be used to investigate the primary polyethylene wear mechanisms involved. This model illustrates the formation of varying flow of polyethylene debris with various shapes and sizes caused by elementary mechanical processes. Instead of using the classical continuum mechanics formulation for this purpose, we used a divided materials approach to simulate debris production and release. This approach involves complex nonlinear bulk behaviors, frictional adhesive contact, and characterizes material damage as a loss of adhesion. All the associated models were validated with various benchmark tests. The examples given show the ability of the numerical model to generate debris of various shapes and sizes such as those observed in implant retrieval studies. Most of wear mechanisms such as abrasion, adhesion, and the shearing off of micro-asperities can be described using this approach. Furthermore, it could be applied to study the effects of friction couples, macroscopic geometries, and material processing (e.g. irradiation) on wear.

Biocompatible Materials↗

Divided medium-based model for analyzing the dynamic reorganization of the cytoskeleton during cell deformation.

Cell deformability and mechanical responses of living cells depend closely on the dynamic changes in the structural architecture of the cytoskeleton (CSK). To describe the dynamic reorganization and the heterogeneity of the prestressed multi-modular CSK, we developed a two-dimensional model for the CSK which was taken to be a system of tension and compression interactions between the nodes in a divided medium. The model gives the dynamic reorganization of the CSK consisting of fast changes in connectivity between nodes during medium deformation and the resulting mechanical behavior is consistent with the strain-hardening and prestress-induced stiffening observed in cells in vitro. In addition, the interaction force networks which occur and balance to each other in the model can serve to identify the main CSK substructures: cortex, stress fibers, intermediate filaments, microfilaments, microtubules and focal adhesions. Removing any of these substructures results in a loss of integrity in the model and a decrease in the prestress and stiffness, and suggests that the CSK substructures are highly interdependent. The present model may therefore provide a useful tool for understanding the cellular processes involving CSK reorganization, such as mechanotransduction, migration and adhesion processes.

Cell Adhesion↗

Comparison of compact bone failure under two different loading rates: experimental and modelling approaches.

Understanding the mechanical behaviour of bones up to failure is necessary for diagnosis and prevention of accident and trauma. As far as we know, no authors have yet studied the tensile behaviour of compact bone including failure under dynamic loadings (1 m/s). The originality of this study comes from not only the analysis of compact bone failure under dynamic loadings, the results of which are compared to those obtained under quasi-static loadings, but also the development of a statistical model. We developed a protocol using three different devices. Firstly, an X-ray scanner to analyse bone density, secondly, a common tensile device to perform quasi-static experiments, and thirdly, a special device based upon a hydraulic cylinder to perform dynamic tests. For all the tests, we used the same sample shape which took into account the brittleness of the compact bone. We first performed relaxation and hysteresis tests followed by tensile tests up to failure. Viscous and plastic effects were not relevant to the compact bone behaviour so its behaviour was considered elastic and brittle. The bovine compact bone was three to four times more brittle under a dynamic load than under a quasi-static one. Numerically, a statistical model, based upon the Weibull theory, is used to predict the failure stress in compact bone.

Animals↗

Mechanisms governing the visco-elastic responses of living cells assessed by foam and tensegrity models.

The visco-elastic properties of living cells, measured to date by various authors, vary considerably, depending on the experimental methods and/or on the theoretical models used. In the present study, two mechanisms thought to be involved in cellular visco-elastic responses were analysed, based on the idea that the cytoskeleton plays a fundamental role in cellular mechanical responses. For this purpose, the predictions of an open unit-cell model and a 30-element visco-elastic tensegrity model were tested, taking into consideration similar properties of the constitutive F-actin. The quantitative predictions of the time constant and viscosity modulus obtained by both models were compared with previously published experimental data obtained from living cells. The small viscosity modulus values (10(0)-10(3) Pa x s) predicted by the tensegrity model may reflect the combined contributions of the spatially rearranged constitutive filaments and the internal tension to the overall cytoskeleton response to external loading. In contrast, the high viscosity modulus values (10(3)-10(5) Pa x s) predicted by the unit-cell model may rather reflect the mechanical response of the cytoskeleton to the bending of the constitutive filaments and/or to the deformation of internal components. The present results suggest the existence of a close link between the overall visco-elastic response of micromanipulated cells and the underlying architecture.

Actin Cytoskeleton↗

An alternative ultrasonic method for measuring the elastic properties of cortical bone.

We studied the elastic properties of bone to analyze its mechanical behavior. The basic principles of ultrasonic methods are now well established for varying isotropic media, particularly in the field of biomedical engineering. However, little progress has been made in its application to anisotropic materials. This is largely due to the complex nature of wave propagation in these media. In the present study, the theory of elastic waves is essential because it relates the elastic moduli of a material to the velocity of propagation of these waves along arbitrary directions in a solid. Transducers are generally placed in contact with the samples which are often cubes with parallel faces that are difficult to prepare. The ultrasonic method used here is original, a rough preparation of the bone is sufficient and the sample is rotated. Moreover, to analyze heterogeneity of the structure we measure velocities in different points on the sample. The aim of the present study was to determine in vitro the anisotropic elastic properties of cortical bones. For this purpose, our method allowed measurement of longitudinal and transverse velocities (C(L) and C(T)) in longitudinal (fiber direction) and the radial directions (orthogonal to the fiber direction) of compact bones. Young's modulus E and Poisson's ratio nu, were then deduced from the velocities measured considering the compact bone as transversely isotropic or orthotropic. The results are in line with those of other methods.

Animals↗

Constitutive laws and failure models for compact bones subjected to dynamic loading.

Many biological tissues, such as bones and ligaments, are fibrous. The geometrical structure of these tissues shows that they exhibit a similar hierarchy in their ultra- and macro-structures. The aim of this work is to develop a model to study the failure of fibrous structures subjected to dynamic loading. The important feature of this model is that it describes failure in terms of the loss of cohesion between fibres. We have developed a model based on the lamellar structure of compact bone with fibres oriented at 0, 45 and 90 degrees to the longitudinal axis of the bone and have studied the influence of the model parameters on the failure process. Bone porosity and joint stress force at failure were found to be the most significant parameters. Using least square resolution, we deduced a phenomenological model of the lamellar structure. Finally, experimental results were found to be comparable with our numerical model.

Animals↗

A visco-hyperelastic model with damage for the knee ligaments under dynamic constraints.

The aim of this study was to identify the behaviour laws governing the knee ligaments, accounting for the damage incurred by the structure under dynamic constraints. The model is developed using a thermodynamic formulation based on the coupling between a viscoelastic model and a damage model. Identification is carried out using the results of dynamic traction tests performed on a bone ligament/bone complex to which traction velocities of around 1.98 m/s were applied. The results show the ability of the model to account for the brittle and ductile failure processes occurring in the cruciate and lateral ligaments, respectively.

Cadaver↗

Clozapine and metabolite concentrations during treatment of patients with chronic schizophrenia.

Results presented in this article are focused on the variability in pharmacokinetics. The purpose of this study was (1) to investigate intra- and interindividual variabilities of pharmacokinetic parameters of clozapine and its two main metabolites in plasma after multiple oral administration in 8 chronic schizophrenic patients (Study 1) and (2) to gain more information regarding plasma concentrations of these drugs after multiple doses in a group of 25 treatment-responsive patients (Study 2). Patients were treated with clozapine in fixed daily doses (given every 8-12 hours) between 200 and 900 mg. Plasma drug concentrations were determined by high-performance liquid chromatography. The mean volume of distribution and the total plasma clearance of clozapine, uncorrected for bioavailability, were 7 L/kg and 40.5 L/h, respectively. The terminal elimination half-lives averaged 10.5 hours for clozapine, 19.2 hours for norclozapine, and 8.6 hours for the N-oxide metabolite. Significant relationships were observed between clozapine and norclozapine (or clozapine N-oxide) plasma concentrations. Large inter- and intrapatient variations in pharmacokinetics were observed. Clozapine was generally well tolerated by the patients, with sedation, hypersialorrhea, and tiredness as the most common side effects encountered.

Adult↗

Multiple-dose pharmacokinetics of clozapine in patients with chronic schizophrenia.

The pharmacokinetic parameters of clozapine and its two main metabolites, N-desmethylclozapine (norclozapine, active metabolite) and clozapine N-oxide, were evaluated, after oral administration, in 19 patients with chronic schizophrenia. Plasma and red blood cell (RBC) drug concentrations were determined by high-performance liquid chromatography. Large interpatient variations in pharmacokinetic parameters of clozapine and its two metabolites were observed. Plasma clozapine concentration peaked, on average, at 2.3 hours. The mean volume of distribution and the total plasma clearance, uncorrected for bioavailability, were 6 L/kg and 38 L/hr, respectively. The terminal elimination half-lives averaged 7.6 hours for clozapine, 13 hours for norclozapine, and 7 hours for the N-oxide metabolite. The mean RBC/plasma concentration ratios were 23, 61, and 81% for clozapine, N-desmethylclozapine, and clozapine N-oxide, respectively. From RBC concentration data, the mean elimination half-lives were 7.6 hours for clozapine, 16 hours for N-desmethylclozapine, and 8 hours for the N-oxide metabolite. The average value for blood clearance of clozapine was 54.7 L/hr. Significant correlations were observed between dose and maximum plasma concentrations and between dose and area under the curve concentrations; these results suggested linear steady-state pharmacokinetics over the range of concentrations studied.

Adolescent↗

Marchiafava-Bignami disease. A case studied by structural and functional brain imaging.

Marchiafava-Bignami disease (MBD) is a rare complication of chronic alcoholism. The clinical features, X-ray, CT and MRI findings are well documented. However, functional brain imaging has not been used in cases of MBD. We used single-photon emission computed tomography (SPECT) to monitor the regional cerebral blood flow in a patient suffering from a acute form of MBD, from which he subsequently recovered. Several abnormalities were found. A more frequent use of functional brain imaging in MBD could improve our knowledge of pathogenesis and prognosis for MBD.

Adult↗

[Contribution of single photon emission computerized tomography (SPECT-HMPAO) to the study of schizophrenia].

The authors studied a group of thirteen schizophrenic patients with functional brain imaging, using single-photon-emission-computed tomography (S.P.E.C.T.). The radiotracer was the H.M.P.A.O. labelled with 99 m Technetium. All were being given neuroleptic drug. Forty-one lesions demonstrated decreased perfusion. These functional abnormalities are mainly located in the left hemisphere and this asymmetry is more pronounced in positive-symptom schizophrenics. However, at rest, these correlations are limited and finally we demonstrated a wide spectrum of metabolic dysfunctions in the same subtype of schizophrenia.

Adult↗