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Biomedical subjects

J J O'Connor

Publications and source records attributed to J J O'Connor.

At least 19 recordsLinked to original sources
PubMed2005

A novel method for in vivo knee prosthesis wear measurement.

Wear remains an important cause of failure in knee replacement. Of the current methods of early performance assessment or prediction, simulators have been un-physiological, single X-ray film analyses remain limited by accuracy and retrieval and survival methods have a prohibitive time scale. An accurate method is needed to allow a timely assessment of polyethylene component wear in vivo, when a new design is introduced, in order to predict likely outcome. We present a new method for measuring wear in vivo that we believe will allow this prediction of long-term wear. X-ray film pairs were taken of implanted prosthetic metal components. When the X-ray system was calibrated, projections of the appropriate Computer Aided Design (CAD) model could be matched to the shapes on the scanned X-ray films to find component positions. Interpenetration of the metal femoral component into the polyethylene component could then be established and represents our estimate of "wear". This method was used to measure in vivo prosthesis wear to an accuracy of 0.11 mm.

Arthroplasty, Replacement, Knee↗
PubMed2004

Dissection of tumor-necrosis factor-alpha inhibition of long-term potentiation (LTP) reveals a p38 mitogen-activated protein kinase-dependent mechanism which maps to early-but not late-phase LTP.

The pro-inflammatory cytokine tumor-necrosis factor-alpha (TNF-alpha) is elevated in several neuropathological states that are associated with learning and memory deficits. Previous work has reported that TNF-alpha inhibits the induction of LTP in areas CA1 [Neurosci Lett 146 (1992) 176] and dentate gyrus [Neurosci Lett 203 (1996) 17]. The mechanism(s) underlying this process of inhibition have not to date been addressed. Here, we show that perfusion of TNF-alpha prior to long-term potentiation (LTP) inducing stimuli inhibited LTP, and that in late-LTP (3 h post-tetanus) a depression in synaptic field recordings was observed (68 +/- 5%, n = 6 versus control 175 +/- 7%, n = 6, P < 0.001). We investigated the involvement of the mitogen-activated protein kinase (MAPK) p38 in the inhibition of LTP by TNF-alpha as p38 MAPK has previously been shown to be involved in interleukin-1beta inhibition of LTP in the dentate gyrus [Neuroscience 93 (1999b) 57]. Perfusion of TNF-alpha led to an increase in the levels of phosphorylated p38 MAPK detectable in the granule cells of the dentate gyrus. The p38 MAPK inhibitor SB 203580 (1 microM) was found by itself to have no significant effect on either early or late phase LTP in the dentate gyrus. SB 203580 was found to significantly reverse the inhibition of early LTP by TNF-alpha (SB/TNF-alpha 174 +/- 5%, n = 6 versus TNF-alpha 120 +/- 7%, n = 6, P < 0.001, 1 h post-tetanus) to values comparable to control LTP (control 175 +/- 7%, n = 6). Interestingly however, the depressive effects of TNF-alpha on late LTP (2-3 h) were clearly not attenuated by p38 MAPK inhibition (SB/TNF-alpha 132 +/- 5%, n = 6 versus control LTP 175 +/- 7%, n = 6, P < 0.001, 3 h post-tetanus). This work suggests that TNF-alpha inhibition of LTP represents a biphasic response, a p38 MAPK-dependent phase that coincides with the early phase of LTP and a p38 MAPK independent phase that temporally maps to late LTP.

Animals↗
PubMed2003

A constraint-based approach to modelling the mobility of the human knee joint.

A model of knee mobility able to predict the range and pattern of movement in the unloaded joint was proposed by Wilson et al. (J. Biomech. 31 (1998) 1127-1136). The articular surfaces in the lateral and medial compartments and isometric fascicles in three of the knee ligaments were represented as five constraints on motion between the femur and tibia in a single degree-of-freedom parallel spatial mechanism. The path of movement of the bones during passive flexion was found by solving the forward kinematics of the mechanism using an iterative method. The present paper shows that such a mechanism-based solution approach can lead to an underestimation of the flexion range. This is due to the mechanism reaching a 'stationary configuration' and 'locking'. A new, constraint-based approach to the solution of the model joint displacement is proposed. It avoids the representation of ligaments and articular surfaces by kinematically equivalent chains of one degree-of-freedom pairs which are prone to singularities. It relies instead on a numerical solution of five non-linear constraint equations to find the relative positions of the bones at a series of flexion angles. The method is successful both in its ability to predict motion through a physiological range and in its efficiency with a solution rate forty times faster than the original algorithm. The new approach may be extended to include more complex joint surface geometry, allowing a study of the effects of articular surface shape and ligament arrangement on joint kinematics.

Algorithms↗
PubMed2003

Ligament fibre recruitment and forces for the anterior drawer test at the human ankle joint.

Although the anterior drawer test at the ankle joint is commonly used in routine clinical practice, very little is known about the sharing of load between the individual passive structures and the joint response at different flexion angles.A mathematical model of the ankle joint was devised to calculate ligament fibre recruitment and load/displacement curves at different flexion angles. Ligaments were modelled as three-dimensional arrays of fibres, and their orientations at different flexion angles were taken from a previously validated four-bar-linkage model in the sagittal plane. A non-linear stress/strain relationship was assumed for ligament fibres and relevant mechanical parameters were taken from two reports in the literature. Talus and calcaneus were assumed to move as a single rigid body. Antero/distal motion of the talus relative to the tibia was analysed. The ankle joint was found to be stiffer at the two extremes of the flexion range, and the highest laxity was found around the neutral position, confirming previous experimental works. With a first dataset, a 20N anterior force produced 4.3, 5.5, and 4.4mm displacement respectively at 20 degrees plantarflexion, at neutral, and at 20 degrees dorsiflexion. At 10 degrees plantarflexion, for a 6mm displacement, 65% of the external force was supported by the anterior talofibular, 11% by the deep anterior tibiotalar and 5.5% by the tibionavicular ligament. Corresponding results from a second dataset were 1.4, 2.4 and 1.8mm at 40N force, and 80%, 0% and 2% for a 3mm displacement. A component of the contact force supported the remainder.

Ankle Joint↗
PubMed2003

Heelstrike and the pathomechanics of osteoarthrosis: a pilot gait study.

Involvement of mechanical factors in osteoarthrosis (OA) has been well documented. For OA of the human lower limb, the impulse imparted at heelstrike has been suggested as a pathogenic factor. It has also been reported that there is a large amount of variation in the level of impulse experienced by different individuals, and it is suggested that those who experience large impulses are at a greater risk of developing OA. The current study investigated gait patterns of 12 normal subjects to establish the gait determinants responsible for producing large impulses at heelstrike. The results suggest that subtle variations in the early part of the swing phase pattern are responsible for large differences in the impulse experienced at heelstrike; the usually reported gait variables mask these variations.

Acceleration↗
PubMed2003

Heelstrike and the pathomechanics of osteoarthrosis: a simulation study.

A simulation model and trajectory matching method were developed to investigate the differences between two swing phase gait patterns; one giving rise to a large impulse at heelstrike, the other giving a small impulse. Subtle changes in the kinematics of the swing leg dramatically reduced the vertical contact velocity of the ankle at the moment of heelstrike. Phasing of the hip flexor muscles at the start of swing was responsible for the level of impulse observed at heelstrike.

Adaptation, Physiological↗
PubMed2003

A role for COX-2 and p38 mitogen activated protein kinase in long-term depression in the rat dentate gyrus in vitro.

Long-term potentiation (LTP) and long-term depression (LTD) are two forms of activity-dependent synaptic plasticity that are thought to be involved in learning and memory. Evidence has shown that cyclooxygenase-2 (COX-2), an enzyme that converts arachidonic acid to prostaglandins, is expressed in postsynaptic dendritic spines and is regulated by synaptic activity. COX-2 inhibition has been shown to directly attenuate LTP in the dentate gyrus of the hippocampus. Also recently the p38 MAP kinase cascade, a pathway utilised by cells for COX-2 expression, has been implicated in LTD induction in the CA1 region of the hippocampus. Here we demonstrate for the first time a direct role for COX-2 and p38 MAP kinase in LTD and confirm the inhibitory role of COX-2 in LTP in the rat dentate gyrus. Perfusion of the COX-2 inhibitor NS-398 (1 micro M) 60 min before tetanic stimulation resulted in an attenuation of LTD (84+/-5%, n=5 compared to controls of 57+/-7%, n=6, P<0.05). Prolonged exposure (2 h) to NS-398 (1 micro M) resulted in a significant reduction in LTP (71+/-8%, n=5, P<0.01 compared to controls of 170+/-11%, n=5 at 60 min post HFS). The p38 MAPK inhibitor, SB220025 (250 nM) significantly attenuated LTD (88+/-5%, n=7; P<0.01 compared to vehicle controls at 60 min, 56+/-5%, n=6) but had no significant effect on LTP. Both NS-398 and SB220025 had no significant effect on the isolated NMDA-mediated EPSP. These data demonstrate a role for COX-2 and p38 MAPK in LTD in the dentate gyrus in vitro that is independent of NMDA receptor activation.

Animals↗
PubMed2003

A role for c-Jun N-terminal kinase in the inhibition of long-term potentiation by interleukin-1beta and long-term depression in the rat dentate gyrus in vitro.

Recent evidence has emphasised the importance of mitogen-activated protein kinase activation in the modulation of hippocampal synaptic plasticity. Whilst extracellular-regulated kinase activation is now regarded as a critical step in the induction of long-term potentiation (LTP), activation of p38 and c-Jun N-terminal kinase (JNK) is associated with its inhibition. Here, the effects of the novel JNK inhibitor anthra[1,9-cd]pyrazol-6(2H)-1 (SP600125) were investigated on the inhibition of LTP by cytokines interleukin-1beta, interleukin-18 and tumour necrosis factor-alpha in the dentate gyrus. Perfusion of SP600125 alone prior to tetanic stimulation of the medial perforant path did not significantly affect baseline synaptic transmission, post-tetanic potentiation or the magnitude of induced LTP. When SP600125 was perfused onto slices prior to application of cytokines, this resulted in a complete reversal of the cytokine-mediated inhibition of LTP. Moreover, the magnitude of LTP attained in these slices was significantly greater than that obtained in vehicle control slices. Next, we investigated the effects of the JNK inhibitor on the impairment of pharmacologically isolated N-methyl-D-aspartate receptor-mediated potentials (NMDA-EPSPs) by interleukin-18. Whilst not affecting baseline amplitude when perfused alone, prior perfusion of SP600125 alleviated the depressive effect of interleukin-18 on NMDA-EPSPs. Finally, we examined the possibility of JNK involvement in the induction of long-term depression (LTD) in the dentate gyrus. Perfusion of SP600125 prior to low-frequency stimulation of the perforant path resulted in a significant attenuation of induced LTD, which suggests that JNK activation is a critical mediator of LTD in the dentate gyrus. These results directly implicate, for the first time, differential activation of JNK in the modulation of distinct forms of hippocampal synaptic plasticity. Whereas acute over-activation of JNK by pathophysiological concentrations of cytokines is detrimental to LTP, physiologic activation of JNK appears necessary for the induction of LTD.

Analysis of Variance↗
PubMed2003

Development and numerical validation of a finite element model of the muscle standardized femur.

The human femur is one of the parts of the musculo-skeletal system most frequently analysed by means of the finite element (FE) method. Most FE studies of the human femur are based on computed tomography data sets of a particular femur. Since the geometry of the chosen sample anatomy influences the computed results, direct comparison across various models is often difficult or impossible. The aim of the present work was to develop and validate a novel three-dimensional FE model of the human femur based on the muscle standardized femur (MuscleSF) geometry. In the new MuscleSF FE model, the femoral attachment of each muscle was meshed separately on the external bone surface. The model was tested under simple load configurations and the results showed good agreement with the converged solution of a former study. In the future, using the validated MuscleSF FE model for numerical studies of the human femur will provide the following benefits: (a) the numerical accuracy of the model is known; (b) muscle attachment areas are incorporated in the model, therefore physiological loading conditions can be easily defined; (c) analyses of the femur under physiological load cases will be replicable; (d) results based on different load configurations could be compared across various studies.

Compressive Strength↗
PubMed2003

Strain distribution within the human femur due to physiological and simplified loading: finite element analysis using the muscle standardized femur model.

The aim of the current work was to study the effect of simplified loading on strain distribution within the intact femur using the Muscle Standardized Femur finite element model and to investigate whether the interaction between the intact human femur and the muscles which are attached to the bone surface could accurately be represented by concentrated forces, applied through the centroids of their attachment areas. An instant at 10 per cent of the gait cycle during level walking was selected as the reference physiological load case; nine load cases were analysed. Comparison of the calculated results for the physiological load case with muscle forces uniformly distributed over their attachment areas showed good agreement with in vivo measurements of strain values and femoral head displacement in humans. Simplified load cases generated unrealistic displacement results and high strain magnitudes, exceeding the physiological range. It was found that when muscles with large attachment areas are included in the model and the muscle forces are simplified, stress and strain distributions will be affected not only on the external bone surface in the vicinity of the load application node, but also on the internal surface of the cortical bone. However, applying muscle forces as concentrated loads at the centroids of the attachment areas can serve as first indicators of the physiological stress and strain levels, if results from nodes and elements in the vicinity of the load application nodes are discarded. Omitting muscle forces or fixing the femur in mid-shaft leads to large unphysiological strain values.

Compressive Strength↗
PubMed2002

Mechanical integrity of compression-moulded ultra-high molecular weight polyethylene: effects of varying process conditions.

Ultra-high molecular weight polyethylene (UHMWPE) bearing surfaces in knee and hip prostheses are frequently manufactured by direct compression moulding of the as-polymerised powder. A study was made of the important role of the temperature-time sequence in the melt state during processing, in determining the mechanical integrity of mouldings at 37 degrees C. Structural features were determined by calorimetry (for the degree of crystallinity), infra-red spectroscopy (for the degree of oxidation), density measurement, and scanning electron microscopy. Mechanical integrity was assessed by tensile tests at a constant nominal strain-rate of 10(-3) s(-1), with post-failure microscopic examination. For the whole range of melt temperatures 145-200 degrees C and times 10-90 min, essentially the same stress-strain path was followed, reflecting invariance of the degree of crystallinity. However, there were dramatic changes in elongation-to-break, from ca 10% for some mouldings at 145 degrees C to a mean of 560% at 175 degrees C where, at the 86% confidence level, there was evidence for a peak. The rise was explained by microscopy, that revealed two distinct types of fusion defect, of reducing severity with increasing temperature. Type 1 defects were voids arising from incomplete powder compaction, and persisted up to 165 degrees C. Type 2 defects were regions of enhanced deformability at inter-particle boundaries in apparently fully compacted mouldings, evidenced microscopically by localised relative displacements at particle interfaces, during the plastic deformation at 37 degrees C. They persisted up to 200 degrees C. Type 2 defects may be attributed to the slow self-diffusion of UHMWPE in the melt, leading to incomplete homogenisation. even after compaction is complete. The level of oxidation in the mouldings was small but rose with melt temperature, explaining the fall in elongation-to-break at temperatures higher than 175 degrees C.

Biocompatible Materials↗
PubMed2002

In vitro evaluation of the resistance to dislocation of a meniscal-bearing total knee prosthesis between 30 degrees and 90 degrees of knee flexion.

An increased incidence of dislocation is the most important potential disadvantage introduced by the use of meniscal-bearing prostheses. The aim of this in vitro study was to measure the resistance to dislocation of a meniscal-bearing total knee arthroplasty in various circumstances and to establish which anatomic structures contribute to bearing stability. The prosthesis was implanted into cadaver knee specimens mounted in a 6 df rig. Dislocation was provoked by applying anteriorly or posteriorly directed forces (20-100N) to the tibia in the plane of the tibial plateau. Dislocation was defined as any stable displacement of the bearing (relative to the tibia or the femur) that persisted after release of the load applied to provoke it. The specimens were tested in an arc of knee flexion between 30 degrees and 90 degrees, with and without simulated quadriceps loads, with and without abducting and adducting loads, and before and after division of the posterior cruciate ligament and the lateral retinaculum. In the presence of quadriceps load, dislocation could not be provoked. In the absence of quadriceps load, dislocation was not provoked by posteriorly directed force but sometimes was caused by anteriorly directed force. All but 1 of the dislocations were unicompartmental, the lateral compartment proving much less stable than the medial. The tendency toward dislocation increased from 30 degrees to 60 degrees and from 60 degrees to 90 degrees of knee flexion. Adducting moments applied to the knee caused lift-off of the lateral femoral condyle from the bearing and increased the tendency toward dislocation. Abducting moments had the opposite effect. Division of the posterior cruciate ligament had no significant effect. Division of the lateral retinaculum increased the tendency toward dislocation. A femoral component that can be implanted without lateral release is desirable.

Cadaver↗
PubMed2002

An investigation into the mechanism of action of almitrine on isolated rat diaphragm muscle fatigue.

BACKGROUND: Previous studies have shown that almitrine bismesylate, a respiratory stimulant which acts on the mitochondrial electron transport chain, enhances recovery of rat diaphragm muscle from fatigue. OBJECTIVES: Our aim is to investigate if the enhanced recovery is due to an anti-oxidant property of almitrine, since the electron transport chain is a major site of intracellular free radical production. METHODS: A low-frequency fatigue protocol was used (30 Hz; 250 ms; delivered once every 2 s for 5 min), and the effects of almitrine before and after fatigue onset were compared to those of the anti-oxidant compound N-acetylcysteine (NAC). RESULTS: Almitrine (6 and 10 microg/ml) given before fatigue gave better recovery rates than postfatigue application. In contrast, NAC (100 microM) application before fatigue onset was not as effective as NAC given immediately after the cessation of the fatigue protocol. However, almitrine (6 microg/ml) completely reversed the reduction in baseline twitch tension brought about by a free-radical-producing mixture of FeCl(3) + ADP (1 mM + 2.5 mM, respectively). CONCLUSION: The results of this study confirm that almitrine enhances recovery from fatigue and, in contrast to NAC prefatigue application, is more effective. Also, almitrine was shown to have an anti-oxidant effect, but it does not act like a typical anti-oxidant.

Almitrine↗