Biomedical subjects

S Sathasivam

Publications and source records attributed to S Sathasivam.

15 recordsLinked to original sources

PubMed2005

Characterization of the caspase cascade in a cell culture model of SOD1-related familial amyotrophic lateral sclerosis: expression, activation and therapeutic effects of inhibition.

There is increasing evidence that apoptosis or a similar programmed cell death pathway is the mechanism of cell death responsible for motor neurone degeneration in amyotrophic lateral sclerosis. Knowledge of the relative importance of different caspases in the cell death process is at present incomplete. In addition, there is little information on the critical point of the death pathway when the process of dying becomes irreversible. In this study, using the well-established NSC34 motor neurone-like cell line stably transfected with empty vector, normal or mutant human Cu-Zn superoxide dismutase (SOD1), we have characterized the activation of the caspase cascade in detail, revealing that the activation of caspases-9, -3 and -8 are important in motor neurone death and that the presence of mutant SOD1 causes increased activation of components of the apoptotic cascade under both basal culture conditions and following oxidative stress induced by serum withdrawal. Activation of the caspases identified in the cellular model has been confirmed in the G93A SOD1 transgenic mice. Furthermore, investigation of the effects of anti-apoptotic neuroprotective agents including specific caspase inhibitors, minocycline and nifedipine, have supported the importance of the mitochondrion-dependent apoptotic pathway in the death process and revealed that the upstream caspase cascade needs to be inhibited if useful neuro-protection is to be achieved.

Amyotrophic Lateral Sclerosis↗

PubMed2001

The effect of contact area on wear in relation to fixed bearing and mobile bearing knee replacements.

It is generally assumed that the wear rates in knee replacements are reduced as the contact area is increased. Hence, fixed bearing or mobile bearing designs with large contact areas throughout the full range of flexion wear less than partially conforming fixed-bearing designs. This hypothesis was investigated in an experimental model, where flat-ended ultra high molecular weight polyethylene pins of varying diameters were reciprocated and rotated on polished metal plates under a constant load with serum lubrication. The pin diameters ranged from 8-23 mm, giving nominal contact pressures from 23.9-2.8 MPa, covering the range associated with a wide spectrum of total knees including mobile-bearings. For pin diameters of 8-12 mm, the mean wear rates were in the range of 5.0-16.0 E-10 g/cycle. For diameters of 17 and 23 mm, the mean wear rates were approximately 1.0 E-10 g/cycle. The latter wear rates were significantly less than the former. Scanning electron microscopy indicated milder wear processes with the larger diameters, while the smaller diameters exhibited transverse ripples and cracks and detachment of thin layers from the surface. The percentages of granules (mostly submicron), fibrils and flakes, and the sizes of these particle types were similar among all pin diameters, except that, for the 23 mm pin diameter, the percentage of fibrils increased and of flakes decreased. This work supports the hypothesis that larger contact areas, up to the maximum area tested in our study, produce lower wear rates, and suggests that there is no disadvantage regarding particle type or size associated with the larger areas of contact.

Biocompatible Materials↗

PubMed2001

Apoptosis in amyotrophic lateral sclerosis: a review of the evidence.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease primarily affecting the upper and lower motor neurones of the central nervous system. Recently, a lot of interest has been generated by the possibility that a mechanism of programmed cell death, termed apoptosis, is responsible for the motor neurone degeneration in this condition. Apoptosis is regulated through a variety of different pathways which interact and eventually lead to controlled cell death. Apart from genetic regulation, factors involved in the control of apoptosis include death receptors, caspases, Bcl-2 family of oncoproteins, inhibitor of apoptosis proteins (IAPs), inhibitors of IAPs, the p53 tumour suppressor protein and apoptosis-related molecules. The first part of this article will give an overview of the current knowledge of apoptosis. In the second part of this review, we will examine in detail the evidence for and against the contribution of apoptosis in motor neurone cell death in ALS, looking at cellular-, animal- and human post-mortem tissue-based models. In a chronic neurodegenerative disease such as ALS, conclusive evidence of apoptosis is likely to be difficult to detect, given the rapidity of the apoptotic cell death process in relation to the relatively slow time course of the disease. Although a complete picture of motor neurone death in ALS has not been fully elucidated, there is good and compelling evidence that a programmed cell death pathway operates in this disorder. The strongest body of evidence supporting this comes from the findings that, in ALS, changes in the levels of members of the Bcl-2 family of oncoproteins results in a predisposition towards apoptosis, there is increased expression or activation of caspases-1 and -3, and the dying motor neurones in human cases exhibit morphological features reminiscent of apoptosis. Further supporting evidence comes from the detection of apoptosis-related molecules and anti-Fas receptor antibodies in human cases of ALS. However, the role of the p53 protein in cell death in ALS is at present unclear. An understanding of the mechanism of programmed cell death in ALS may provide important clues for areas of potential therapeutic intervention for neuroprotection in this devastating condition.

Amyotrophic Lateral Sclerosis↗

PubMed2000

A comparison between cemented, press-fit, and HA-coated interfaces in Kinemax total knee replacement.

There are possible advantages of using uncemented fixation in total knee replacement. In this prospective randomised multi-centre study, a comparison was made between cemented and two types of uncemented fixation for the Kinemax design. There were 12-14 cases in each group. Beads were inserted in the bones from which component migration was measured at time intervals up to 2 years. The axial migrations were significantly less for cemented and HA-coating, compared with press-fit, at all time intervals. The clinical data showed no differences at 2 years except for more cases of pain in the uncemented groups. Radiographically, the cemented interfaces showed the least change, press-fit showed a radiolucent line and a radiodense line, and HA showed a diffuse radiodensity adjacent to the components. It was concluded that for the Kinemax design of tibial component, press-fit was inferior to cemented, but that there was the potential for designing a special component for uncemented fixation for which HA-coating would be an advantage.

Journal Article↗

PubMed2000

Controlling the motion of total knee replacements using intercondylar guide surfaces.

Total knee replacements using intercondylar cams, such as posterior stabilized types, have been in use for many years. In a previous study, software was written to analyze an alternative shape of the intercondylar cams. The goal of the current study was to investigate in a more general way the potential of intercondylar cams, or guide surfaces, for reproducing the anterior-posterior motion of the natural knee throughout the flexion range. Typical sagittal outlines for the femoral and tibial bearing surfaces were defined, and a parametrized shape for the femoral guide surface was defined to produce a wide range of shapes. Software was written in which the femoral component was flexed in increments, with the posterior translation defined as a function of the flexion angle. The shape of the tibial guide surface was derived from the locus of the femoral guide surface at its multiple flexion positions. By iterating methodically through possible shapes of femoral guide surfaces, several types of total knee replacement components in common use today were identified, as well as other configurations of potential interest. For quantification of a given design, the software calculated the anterior and posterior laxity at each flexion angle. Laxity was defined as the motion before the femoral guide surface impacted the tibial guide surface or until the contact point of the bearing surfaces reached a specified slope. Convex femoral and concave saddle-shaped tibial guide surfaces produced small laxities in both directions over most of the flexion range. A saddle design with small laxities in the first half of flexion, combined with a posterior stabilized feature, was an interesting combination. Potential improvements to the currently used designs were shown in this study, and new shapes of intercondylar guide surfaces were derived that could be considered for application.

Arthroplasty, Replacement, Knee↗

PubMed2000

Brown-Vialetto-Van Laere syndrome: case report and literature review.

We describe a case of the Brown-Vialetto-Van Laere syndrome, which is a rare disorder characterized by progressive pontobulbar palsy associated with sensorineural deafness. More than 30 cases have been reported since the first case was described in 1894. We review the literature of this condition, comparing our case with those reported in the literature and emphasizing important features to improve our understanding of this syndrome.

Adult↗

PubMed2000

Methodology for long-term wear testing of total knee replacements.

This article begins to address the validation requirements of wear testing on total knee replacements in a knee simulator. The knee simulator has four stations. The axial force is variable but reaches a maximum of 2.3 kN. Physiologic anteroposterior shear force and rotational torques are supplied to the knee. The forces and displacements are timed to coincide with those of a typical gait cycle. Kinematics of the simulator are dependent on the type of knee being tested. Tests of designs with well known clinical histories were done to 10 million cycles. The relative amounts and types of wear shown by the designs were similar to that found in their clinical histories. Wear tracks on more conforming designs were larger, and the penetration into the plastic appeared to be less. This did not necessarily mean that wear, as measured by loss of material, was reduced on conforming designs. Delamination of the plastic was achieved only after aging the tibial components. Wear particles isolated from the lubricating fluid were similar in size and shape to those isolated from in vivo specimens. However, the relative amounts of wear particle shapes were different depending on the design. At the start of the tests, all of the flexibly mounted tibial components showed more motion than after 5 million cycles, indicating that the surface of the plastic became more conforming. This study showed that knee wear similar to wear observed in vivo can be reproduced in the laboratory. The parameters and methods elucidated in this introductory study should form the basis for use in preclinical wear tests of total knee replacements.

Biomechanical Phenomena↗

PubMed2000

Design forms of total knee replacement.

The starting point of this article is a general design criterion applicable to all types of total knee replacement. This criterion is then expanded upon to provide more specifics of the required kinematics, and the forces which the total knee must sustain. A characteristic which differentiates total knees is the amount of constraint which is required, and whether the constraint is translational or rotational. The different forms of total knee replacement are described in terms of these constraints, starting with the least constrained unicompartments to the almost fully constrained fixed and rotating hinges. Much attention is given to the range of designs in between these two extreme types, because they constitute by far the largest in usage. This category includes condylar replacements where the cruciate ligaments are preserved or resected, posterior cruciate substituting designs and mobile bearing knees. A new term, 'guided motion knees', is applied to the growing number of designs which control the kinematics by the use of intercondylar cams or specially shaped and even additional bearing surfaces. The final section deals with the selection of an appropriate design of total knee for specific indications based on the design characteristics.

Biocompatible Materials↗

PubMed1999

The conflicting requirements of laxity and conformity in total knee replacement.

Bearing surfaces of total condylar knees which are designed with a high degree of conformity to produce low stresses in the polyethylene tibial insert may be overconstrained. This study determines femoral and tibial bearing surface geometries which will induce the least destructive fatigue mechanisms in the polyethylene whilst conserving the laxity of the natural knee. Sixteen knee designs were generated by varying four parameters systematically to cover the range of contemporary knee designs. The parameters were the femoral frontal radius (30 or 70 mm), the difference between the femoral and tibial frontal radii (2 or 10 mm), the tibial sagittal radius (56 or 80 mm) and the posterior-distal transition angle (-8 or -20 degrees), which is the angle at which the small posterior arc of the sagittal profile transfers to the larger distal arc. Rigid body analyses determined the anterior-posterior and rotational motions as well as the contact points during the stance phase of gait for the different designs. In addition, a damage function which accumulated the fluctuating maximum shear stresses was used to predict the susceptibility to delamination wear of the polyethylene (damage score). This study predicted that of the 16 designs, the knee with a frontal radius of 70 mm, a difference in femoral and tibial frontal radii of 2 mm, a tibial sagittal radius of 80 mm and a posterior distal transition angle of -20 degrees would satisfy the conflicting needs of both resistance to delamination wear and natural kinematics.

Clinical Trials as Topic↗

PubMed1999

The design of guide surfaces for fixed-bearing and mobile-bearing knee replacements.

In the natural knee, the femoral tibial contacts move posteriorly as the knee is flexed, guided primarily by the cruciate ligaments. This kinematic behaviour is important regarding muscle lever arms and in achieving a high flexion range. Most contemporary total knee designs use either posterior cruciate preservation or a cam system to produce posterior displacement with flexion, but there is no specific provision for anterior displacement. In this study, a method for the design of cams is described where the cams would guide the motion in both posterior and anterior directions, without requiring cruciate ligaments. The cams consist of a femoral Guide Surface interacting with a tibial Guide Surface while the main lateral and medial bearing surfaces carry the forces across the knee. It is shown that Guide Surfaces can be designed which provide the required motion, but with some laxity at different flexion ranges. It is then demonstrated that the Guide Surfaces can be applied to a range of possible knee designs including mobile-bearing types, rotating-platform types, and fixed-bearing types. The relative advantages of the different possibilities are discussed.

Equipment Design↗

PubMed1998

Computer model to predict subsurface damage in tibial inserts of total knees.

Two designs of total knee replacements were analysed to determine how the geometry of their bearing surface would affect the susceptibility of their ultra high molecular weight polyethylene tibial inserts to delamination. Orientations of the femoral components on the tibial surfaces were calculated with use of rigid body analysis for discrete intervals during the stance phase of gait. For each successive orientation, finite element analysis was used to compress the components together to determine the stresses in the tibial inserts. A damage function analogous to strain energy density was defined to account for the accumulated amplitudes and frequencies of the maximum shear stress cycles and hence to predict fatigue failure. The damage function was applied to each polyethylene element in the tibial insert, and the highest value calculated for each design was its damage score. One knee had a damage score more than three times less than that of the other because of lower stresses and because the contact points moved in the medial-lateral as well as anterior-posterior directions during internal-external rotation. The femoral and tibial components of this knee had large outer frontal radii and close conformity in the frontal plane. We propose that this method, which accounts for the motions and stresses endured during walking, makes different predictions regarding the likelihood of delamination compared with the predictions made by conventional static compression tests performed when the knee is in a neutral position.

Anterior Cruciate Ligament↗

PubMed1997

A computer model with surface friction for the prediction of total knee kinematics.

A computer model was generated which modelled the bearing surfaces of total knees, and predicted the kinematics for a set of input forces and moments. The model included friction at the bearing surfaces and soft tissue restraint forces, including the effect of cruciate resection. Predictions from the model were compared with data from a Knee Simulating Machine. There was close agreement in the shapes of the curves and in the magnitudes of the displacements and rotations under most conditions. The model predicted major differences in kinematics when friction between metal and polyethylene was included, the differences being even greater at the friction levels associated with small embedded acrylic particles. Soft tissue restraint was shown to reduce the displacements and rotations for tibial surfaces of low constraint but for moderate to high constraint, the soft tissues affected the kinematics only slightly. When the model was used to predict the motions for different condylar geometries, widely different contact paths on the tibial surface were determined. This suggested that condylar geometries which appeared to be generally similar, could have important differences in kinematics, function and wear.

Acrylic Resins↗

PubMed1997

A knee simulating machine for performance evaluation of total knee replacements.

A knee simulating machine is required for the design and evaluation of total knee replacements, the kinematics and the long-term wear being aspects of particular importance. There are no generally agreed design criteria, such that existing designs of simulator have a wide variety of input and constraint conditions. In this study, it was postulated that in order to reproduce physiological wear patterns, the correct kinematics is required, on the basis that the wear will be a direct function of the sliding, rolling and tractive rolling conditions at the joint surfaces. In turn, the correct kinematics would only be achieved by the input of physiological forces, by the appropriate constraints on the fixtures holding the components, and by simulating the soft tissue restraints. A knee simulating machine based on these principles was constructed, and used to test the kinematics of a range of contemporary condylar replacement knees. The displacements and rotations varied over a range of almost two times, even with the soft tissue restraints. Without the restraints, the low constraint designs would have dislocated or moved unrealistically. It was concluded that a simulating machine should be based on the input of forces and moments, rather than on displacements and rotations, in order to provide data of kinematics and wear.

Biomechanical Phenomena↗

PubMed1994

Optimization of the bearing surface geometry of total knees.

Various design criteria were examined in combination to find the ideal geometry for a condylar knee replacement. The criteria were the contact stresses on the plastic, femoral-tibial size interchangeability, patella lever arm, laxity and stability and the amount of bone resection required. The variables were the radii of curvature of the femoral and tibial bearing surfaces in the sagittal and frontal planes. Metal toroidal indentors were loaded onto dished surfaces of UHMWPE covering a range of radii and the contact areas measured. Using elasticity equations, the apparent elastic modulus of UHMWPE ranged from 400 to 600 MPa for less conforming to closely conforming surfaces. Using a value of 600 MPa, contact stresses were predicted for a complete spectrum of radii of curvature. Finite element analysis was used to determine the stresses beneath the contact patches when different femoral-tibial sizes were interchanged. A computergraphics program was written to analyse the effects of flexion, rotation and femoral roll-back on the contact point locations. An influential variable was the sagittal curvature of the femoral component, notably the point of transition between the posterior curve of small radius and the distal curve of larger radius. This affected the patella lever arm, the stability, and the bone resection. Interchangeability was primarily dependent upon the relative frontal radii. Contact stresses and contact locations depended upon the combination of sagittal and frontal radii. The most suitable geometrical combinations overall were discussed.

Biomechanical Phenomena↗

PubMed1992

A simplified radiographic method for measuring bone-component motion in total knees.

Measurement of the relative motion between an implant and the surrounding bone over different time periods is valuable for assessing and comparing the component stability and predicting the potential future outcome. The RSA method, where small beads are implanted in the bone adjacent to the component, can measure implant-bone position to an accuracy of about 0.1 mm. However, the method involves special radiographic views and analytical software, not readily available. For purposes of component assessment on a more routine basis and for multi-centre trials, a method was developed where standard A-P and M-L radiographs were used. Computer software was written which estimated the out-of-plane rotations of the component relative to the plane of the film, and then carried out corrections to enhance the accuracy of calculation of the bead heights relative to the component. The theoretical errors were shown to be less than 0.04 mm for the expected range of out-of-plane rotations. When radiographs of components in simulated bones were taken at a range of rotations, the 95% confidence limits for axial displacement were found to be less than +0.3 mm, and for rotation in the plane to be 0.6 degrees. This indicated that the method was useful for studying knee components where the sinkage could reach a range of 0.5-2 mm in a 2 year period.

Biomechanical Phenomena↗