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1.
Bone Joint Res ; 8(7): 313-322, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31463040

ABSTRACT

OBJECTIVES: The paradoxical migration of the femoral neck element (FNE) superomedially against gravity, with respect to the intramedullary component of the cephalomedullary device, is a poorly understood phenomenon increasingly seen in the management of pertrochanteric hip fractures with the intramedullary nail. The aim of this study was to investigate the role of bidirectional loading on the medial migration phenomenon, based on unique wear patterns seen on scanning electron microscopy of retrieved implants suggestive of FNE toggling. METHODS: A total of 18 synthetic femurs (Sawbones, Vashon Island, Washington) with comminuted pertrochanteric fractures were divided into three groups (n = 6 per group). Fracture fixation was performed using the Proximal Femoral Nail Antirotation (PFNA) implant (Synthes, Oberdorf, Switzerland; n = 6). Group 1 was subjected to unidirectional compression loading (600 N), with an elastomer (70A durometer) replacing loose fracture fragments to simulate surrounding soft-tissue tensioning. Group 2 was subjected to bidirectional loading (600 N compression loading, 120 N tensile loading), also with the elastomer replacing loose fracture fragments. Group 3 was subjected to bidirectional loading (600 N compression loading, 120 N tensile loading) without the elastomer. All constructs were tested at 2 Hz for 5000 cycles or until cut-out occurred. The medial migration distance (MMD) was recorded at the end of the testing cycles. RESULTS: The MMDs for Groups 1, 2, and 3 were 1.02 mm, 6.27 mm, and 5.44 mm respectively, with reliable reproduction of medial migration seen in all groups. Bidirectional loading groups showed significantly higher MMDs compared with the unidirectional loading group (p < 0.01). CONCLUSION: Our results demonstrate significant contributions of bidirectional cyclic loading to the medial migration phenomenon in cephalomedullary nail fixation of pertrochanteric hip fractures.Cite this article: G. W. Law, Y. R. Wong, A. K-S. Yew, A. C. T. Choh, J. S. B. Koh, T. S. Howe. Medial migration in cephalomedullary nail fixation of pertrochanteric hip fractures: A biomechanical analysis using a novel bidirectional cyclic loading model. Bone Joint Res 2019;8:313-322. DOI: 10.1302/2046-3758.87.BJR-2018-0271.R1.

2.
Diabetes ; 68(6): 1251-1266, 2019 06.
Article in English | MEDLINE | ID: mdl-30936146

ABSTRACT

Genome-wide association studies have identified PTPN2 as an important non-MHC gene for autoimmunity. Single nucleotide polymorphisms that reduce PTPN2 expression have been linked with the development of various autoimmune disorders, including type 1 diabetes. The tyrosine phosphatase PTPN2 attenuates T-cell receptor and cytokine signaling in T cells to maintain peripheral tolerance, but the extent to which PTPN2 deficiency in T cells might influence type 1 diabetes onset remains unclear. NOD mice develop spontaneous autoimmune type 1 diabetes similar to that seen in humans. In this study, T-cell PTPN2 deficiency in NOD mice markedly accelerated the onset and increased the incidence of type 1 diabetes as well as that of other disorders, including colitis and Sjögren syndrome. Although PTPN2 deficiency in CD8+ T cells alone was able to drive the destruction of pancreatic ß-cells and the onset of diabetes, T-cell-specific PTPN2 deficiency was also accompanied by increased CD4+ T-helper type 1 differentiation and T-follicular-helper cell polarization and increased the abundance of B cells in pancreatic islets as seen in human type 1 diabetes. These findings causally link PTPN2 deficiency in T cells with the development of type 1 diabetes and associated autoimmune comorbidities.


Subject(s)
CD8-Positive T-Lymphocytes/metabolism , Diabetes Mellitus, Type 1/genetics , Protein Tyrosine Phosphatase, Non-Receptor Type 2/genetics , T-Lymphocytes/metabolism , Animals , Autoimmune Diseases/genetics , Autoimmune Diseases/immunology , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/immunology , Colitis/genetics , Colitis/immunology , Diabetes Mellitus, Type 1/immunology , Gene Knockout Techniques , Mice , Mice, Inbred NOD , Protein Tyrosine Phosphatase, Non-Receptor Type 2/immunology , Sjogren's Syndrome/genetics , Sjogren's Syndrome/immunology , T-Lymphocytes/immunology , Th1 Cells/immunology , Th1 Cells/metabolism
3.
Colorectal Dis ; 20(6): 502-508, 2018 06.
Article in English | MEDLINE | ID: mdl-29205835

ABSTRACT

AIM: In the UK Bowel Scope Screening Programme (BSSP), patients progress to colonoscopy based on high-risk features on flexible sigmoidoscopy (FS). We aim to assess the practice of colonoscopy conversion and predictors of detection of additional adenomas on colonoscopy. METHOD: The Bowel Cancer Screening database was interrogated and collated with endoscopic and histological findings from patients undergoing colonoscopy following FS between August 2013 and August 2016. Multivariate analysis was performed to identify predictors of new adenomas. RESULTS: FS was performed on 11 711 patients, with an adenoma detection rate (ADR) of 8.5% and conversion to colonoscopy in 421 (3.6%). The additional ADR at colonoscopy was 35.2%, with one additional malignant diagnosis (0.26%). The adenoma miss rate was 3.6%. On multivariate analysis, a polyp ≥ 10 mm was the only high-risk indication associated with additional ADR at colonoscopy (OR 3.68, 95% CI 1.51-3.65, P < 0.001), in addition to male gender (OR 2.36, 95% CI 1.46-3.83, P < 0.001). Predictors of detection of a new adenoma ≥ 10 mm included: villous adenoma (P = 0.002), polyp ≥ 10 mm (P = 0.007) and male gender (P = 0.039). The presence of any conversion criterion was associated with the detection of any proximal adenoma (P < 0.001) and adenoma ≥ 10 mm (P = 0.031). CONCLUSION: Male gender, polyps ≥ 10 mm and villous-preponderant histology at FS were predictors of adenomas < 10 mm and ≥ 10 mm at colonoscopy. Further data are required to assess the role for gender-based stratification of conversion criteria.


Subject(s)
Adenoma/diagnosis , Carcinoma/diagnosis , Colonic Polyps/diagnosis , Colonoscopy , Colorectal Neoplasms/diagnosis , Diagnostic Errors/statistics & numerical data , Sigmoidoscopy , Adenoma/pathology , Adenoma, Villous/diagnosis , Adenoma, Villous/pathology , Carcinoma/pathology , Colonic Polyps/pathology , Colorectal Neoplasms/pathology , Early Detection of Cancer , Female , Humans , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Sex Factors , Tumor Burden , United Kingdom
4.
Bone Joint Res ; 6(4): 216-223, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28420623

ABSTRACT

OBJECTIVES: External fixators are the traditional fixation method of choice for contaminated open fractures. However, patient acceptance is low due to the high profile and therefore physical burden of the constructs. An externalised locking compression plate is a low profile alternative. However, the biomechanical differences have not been assessed. The objective of this study was to evaluate the axial and torsional stiffness of the externalised titanium locking compression plate (ET-LCP), the externalised stainless steel locking compression plate (ESS-LCP) and the unilateral external fixator (UEF). METHODS: A fracture gap model was created to simulate comminuted mid-shaft tibia fractures using synthetic composite bones. Fifteen constructs were stabilised with ET-LCP, ESS-LCP or UEF (five constructs each). The constructs were loaded under both axial and torsional directions to determine construct stiffness. RESULTS: The mean axial stiffness was very similar for UEF (528 N/mm) and ESS-LCP (525 N/mm), while it was slightly lower for ET-LCP (469 N/mm). One-way analysis of variance (ANOVA) testing in all three groups demonstrated no significant difference (F(2,12) = 2.057, p = 0.171).There was a significant difference in mean torsional stiffness between the UEF (0.512 Nm/degree), the ESS-LCP (0.686 Nm/degree) and the ET-LCP (0.639 Nm/degree), as determined by one-way ANOVA (F(2,12) = 6.204, p = 0.014). A Tukey post hoc test revealed that the torsional stiffness of the ESS-LCP was statistically higher than that of the UEF by 0.174 Nm/degree (p = 0.013). No catastrophic failures were observed. CONCLUSION: Using the LCP as an external fixator may provide a viable and attractive alternative to the traditional UEF as its lower profile makes it more acceptable to patients, while not compromising on axial and torsional stiffness.Cite this article: B. F. H. Ang, J. Y. Chen, A. K. S. Yew, S. K. Chua, S. M. Chou, S. L. Chia, J. S. B. Koh, T. S. Howe. Externalised locking compression plate as an alternative to the unilateral external fixator: a biomechanical comparative study of axial and torsional stiffness. Bone Joint Res 2017;6:216-223. DOI: 10.1302/2046-3758.64.2000470.

5.
Proc Inst Mech Eng H ; 220(2): 311-9, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16669397

ABSTRACT

The deformation of metallic acetabular cups employed for metal-on-metal hip resurfacing procedures was considered theoretically using the finite element method in the present study, following on the experimental investigation reported in Part 1. Three representative cups, characterized by the cup wall thickness as thin, intermediate, and thick, were considered. For the intermediate cup, the effects of both the size and the diametral interference on the cup deformation were investigated. Both two-dimensional axisymmetric and three-dimensional finite element models were developed to examine the important parameters during and after the press-fit procedure, and in particular the deformation of the metallic cup. The theoretical prediction of the cup deformation was in reasonable agreement with the corresponding experimental measurement reported in Part 1. The most significant factor influencing the cup deformation was the cup wall thickness. Both the size and the diametral interference were also shown to influence the cup deformation. It is important to ensure that the cup deformation does not significantly affect the clearance designed and optimized for tribological performances of metal-on-metal hip resurfacing prostheses. Furthermore the contact parameters at the cup and bone interface associated with the press fit were also discussed.


Subject(s)
Acetabulum/physiopathology , Biocompatible Materials/chemistry , Computer-Aided Design , Hardness Tests/methods , Hip Prosthesis , Metals/chemistry , Models, Biological , Acetabulum/surgery , Arthroplasty, Replacement, Hip/instrumentation , Arthroplasty, Replacement, Hip/methods , Computer Simulation , Elasticity , Equipment Design , Equipment Failure Analysis/methods , Finite Element Analysis , Hardness , Humans , Materials Testing , Pressure , Prosthesis Design , Prosthesis Failure , Surface Properties
6.
Proc Inst Mech Eng H ; 218(5): 293-305, 2004.
Article in English | MEDLINE | ID: mdl-15532995

ABSTRACT

Finite-element method was employed to study the contact mechanics in metal-on-metal hip resurfacing prostheses, with particular reference to the effects of bone quality, the fixation condition between the acetabular cup and bone, and the clearance between the femoral head and the acetabular cup. Simple finite-element bone models were developed to simulate the contact between the articulating surfaces of the femoral head and the acetabular cup. The stresses within the bone structure were also studied. It was shown that a decrease in the clearance between the acetabular cup and femoral head had the largest effect on reducing the predicted contact-pressure distribution among all the factors considered in this study. It was found that as the clearance was reduced, the influence of the underlying materials, such as bone and cement, became increasingly important. Stress shielding was determined to occur in the bone tissue surrounding the hip resurfacing prosthesis considered in this study. However, the stress-shielding effects predicted were less than those observed in conventional total hip replacements. Both the effects of bone quality (reduction in elastic modulus) and the fixation condition between the cup and the bone were found to have a negligible effect on the predicted contact mechanics at the bearing surface. The loading was found to have a relatively small effect on the predicted maximum contact pressure at the bearing surface; this was attributed to an increase in contact area as the load was increased.


Subject(s)
Equipment Failure Analysis/methods , Hip Joint/physiopathology , Hip Joint/surgery , Hip Prosthesis , Models, Biological , Vitallium/chemistry , Computer Simulation , Elasticity , Finite Element Analysis , Fourier Analysis , Friction , Humans , Metals/chemistry , Prosthesis Design , Surface Properties
7.
Proc Inst Mech Eng H ; 218(1): 27-34, 2004.
Article in English | MEDLINE | ID: mdl-14982343

ABSTRACT

An elastohydrodynamic lubrication (EHL) analysis was carried out in this study for a typical McKee-Farrar metal-on-metal hip prosthesis under a simple steady state rotation. The finite element method was used initially to investigate the effect of the cement and bone on the predicted contact pressure distribution between the two articulating surfaces under dry conditions, and subsequently to determine the elastic deformation of both the femoral and the acetabular components required for the lubrication analysis. Both Reynolds equation and the elasticity equation were coupled and solved numerically using the finite difference method. Important features in reducing contact stresses and promoting fluid-film lubrication associated with the McKee-Farrar metal-on-metal hip implant were identified as the large femoral head and the thin acetabular cup. For the typical McKee-Farrar metal-on-metal hip prosthesis considered under typical walking conditions, an increase in the femoral head radius from 14 to 17.4 mm (for a fixed radial clearance of 79 microm) was shown to result in a 25 per cent decrease in the maximum dry contact pressure and a 60 per cent increase in the predicted minimum film thickness. Furthermore, the predicted maximum contact pressure considering both the cement and the bone was found to be decreased by about 80 per cent, while the minimum film thickness was predicted to be increased by 50 per cent. Despite a significant increase in the predicted minimum lubricating film thickness due to the large femoral head and the thin acetabular cup, a mixed lubrication regime was predicted for the McKee-Farrar metal-on-metal hip implant under estimated in vivo steady state walking conditions, depending on the surface roughness of the bearing surfaces. This clearly demonstrated the important influences of the material, design and manufacturing parameters on the tribological performance of these hard-on-hard hip prostheses. Furthermore, in the present contact mechanics analysis, the significant increase in the elasticity due to the relatively thin acetabular cup was not found to cause equatorial contact and gripping of the ball.


Subject(s)
Cementation/methods , Equipment Failure Analysis/methods , Hip Joint/physiopathology , Hip Joint/surgery , Hip Prosthesis , Acetabulum/physiopathology , Acetabulum/surgery , Elasticity , Femur/physiopathology , Femur/surgery , Friction , Humans , Lubrication , Metals , Models, Biological , Pressure , Rheology/methods , Rotation , Surface Properties
8.
Proc Inst Mech Eng H ; 217(5): 333-40, 2003.
Article in English | MEDLINE | ID: mdl-14558645

ABSTRACT

Contact mechanics analysis for a typical McKee-Farrar metal-on-metal hip implant was carried out in this study. The finite element method was used to predict the contact area and the contact pressure distribution at the bearing surfaces. The study investigated the effects of the cement and underlying bone, the geometrical parameters such as the radial clearance between the acetabular cup and the femoral head, and the acetabular cup thickness, as well as other geometrical features on the acetabular cup such as lip and studs. For all the cases considered, the predicted contact pressure distribution was found to be significantly different from that based upon the classical Hertz contact theory, with the maximum value being away from the centre of the contact region. The lip on the cup was found to have a negligible effect on the predicted contact pressure distribution. The presence of the studs on the outside of the cup caused a significant increase in the local contact pressure distribution, and a slight decrease in the contact region. Reasonably good agreement of the predicted contact pressure distribution was found between a three-dimensional anatomical model and a simple two-dimensional axisymmetric model. The interfacial boundary condition between the acetabular cup and the underlying cement, modelled as perfectly fixed or perfectly unbonded, had a negligible effect on the predicted contact parameters. For a given radial clearance of 0.079 mm, the decrease in the thickness of the acetabular cup from 4.5 to 1.5 mm resulted in an increase in the contact half angle from 15 degrees to 26 degrees, and a decrease in the maximum contact pressure from 55 to 20 MPa. For a given acetabular cup thickness of 1.5 mm, a decrease in the radial clearance from 0.158 to 0.0395 mm led to an increase in the contact half-angle from 20 degrees to 30 degrees, and a decrease in the maximum contact pressure from 30 to 10 MPa. For zero clearance, although the contact pressure was significantly reduced over most of the contact area, the whole acetabular cup came into contact with the femoral head, leading to stress concentration at the edge of the cup. Design optimization of the geometrical parameters, in terms of the acetabular cup thickness and the radial clearance, is important, not only to minimize the contact stress at the bearing surfaces, but also to avoid equatorial and edge contact.


Subject(s)
Acetabulum/physiopathology , Equipment Failure Analysis/methods , Femur Head/physiopathology , Hip Joint/physiopathology , Hip Prosthesis , Models, Biological , Weight-Bearing , Acetabulum/surgery , Chromium Alloys/chemistry , Femur Head/surgery , Finite Element Analysis , Friction , Hip Joint/surgery , Humans , Metals/chemistry , Pressure , Prosthesis Failure , Stress, Mechanical , Surface Properties
9.
Med J Malaysia ; 58(5): 717-22, 2003 Dec.
Article in English | MEDLINE | ID: mdl-15190658

ABSTRACT

BACKGROUND: The summary of various studies done looking at size selection of the laryngeal mask airway (LMA) in adults is that, selection based on sex is appropriate, and that both sizes 4 or 5 are adequate for adult females. However, in our local population these sizes may be too large especially the size 5 for adult females. OBJECTIVE: To determine the optimal size of LMA in Malaysian female adults. METHOD: 135 ASA 1 or 2 adult female patients coming for elective surgery, requiring general anaesthesia suitable for LMA insertion were randomised into 3 groups to receive either a size 3, 4 or 5 LMA. Optimal size of the LMA was assessed based on 4 parameters, the number of attempts at placement, the oropharyngeal leak pressure (OLP), fibre optic score and the percentage of the vocal cords seen. RESULTS: The 3 groups were demographically similar. There was no difference in the 3 groups in terms of number of attempts of placement, OLP and fibre-optic score. The percentage of vocal cords seen with the size 3 LMA was significantly less than for the size 4 and size 5 (p = 0.009). For the size 5 LMA group in 10/45 patients, the size 5 LMA was too big making it incorrectly positioned after successful insertion and in another 3/45 patients it was difficult to pass the size 5 LMA past the open mouth during insertion. There were no such problems with the size 3 or 4 LMA groups. CONCLUSION: The optimal size of LMA for the female Malaysian adult is size 4.


Subject(s)
Laryngeal Masks/standards , Adult , Female , Humans , Malaysia
10.
J Neurosci ; 22(7): 2963-76, 2002 Apr 01.
Article in English | MEDLINE | ID: mdl-11923461

ABSTRACT

Based on recent experimental data, we have developed a conductance-based computational network model of the subthalamic nucleus and the external segment of the globus pallidus in the indirect pathway of the basal ganglia. Computer simulations and analysis of this model illuminate the roles of the coupling architecture of the network, and associated synaptic conductances, in modulating the activity patterns displayed by this network. Depending on the relationships of these coupling parameters, the network can support three general classes of sustained firing patterns: clustering, propagating waves, and repetitive spiking that may show little regularity or correlation. Each activity pattern can occur continuously or in discrete episodes. We characterize the mechanisms underlying these rhythms, as well as the influence of parameters on details such as spiking frequency and wave speed. These results suggest that the subthalamopallidal circuit is capable both of correlated rhythmic activity and of irregular autonomous patterns of activity that block rhythmicity. Increased striatal input to, and weakened intrapallidal inhibition within, the indirect pathway can switch the behavior of the circuit from irregular to rhythmic. This may be sufficient to explain the emergence of correlated oscillatory activity in the subthalamopallidal circuit after destruction of dopaminergic neurons in Parkinson's disease and in animal models of parkinsonism.


Subject(s)
Basal Ganglia/physiology , Computer Simulation , Models, Neurological , Nerve Net/physiology , Neural Networks, Computer , Action Potentials/physiology , Animals , Biological Clocks/physiology , Globus Pallidus/physiology , Humans , Neural Inhibition/physiology , Neural Pathways/physiology , Neurons/physiology , Parkinson Disease/etiology , Periodicity , Subthalamic Nucleus/physiology , Synaptic Transmission/physiology
11.
J Nat Prod ; 64(1): 125-6, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11170686

ABSTRACT

The crude extract of the broth of Aspergillus ochraceus was found to inhibit the final stage of polyprotein processing during hepatitis C virus replication. Bioassay-guided fractionation led to the isolation of the known compound mellein as the active component of the extract. Also isolated were circumdatin F and a new alkaloid, circumdatin G. The structure of circumdatin G was determined by spectroscopic analysis.


Subject(s)
Alkaloids/isolation & purification , Antiviral Agents/isolation & purification , Aspergillus ochraceus/chemistry , Ochratoxins/isolation & purification , Alkaloids/chemistry , Alkaloids/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Fermentation , Hepacivirus/drug effects , Hepacivirus/enzymology , Isocoumarins , Magnetic Resonance Spectroscopy , Ochratoxins/chemistry , Ochratoxins/pharmacology , Protease Inhibitors/chemistry , Protease Inhibitors/isolation & purification , Protease Inhibitors/pharmacology , Virus Replication/drug effects
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