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Biomedical subjects

J Fisher

Publications and source records attributed to J Fisher.

At least 19 recordsLinked to original sources
PubMed2006

Isolation and characterization of UHMWPE wear particles down to ten nanometers in size from in vitro hip and knee joint simulators.

There is currently considerable interest in the wear debris and osteolytic potential of different types of bearings used in total joint replacements. The biological activity of the wear debris is dependent on the size and volume of the particles produced. Wear volume also plays an important role in the functional biological activity of a joint replacement. In vitro studies have shown that crosslinking of ultra high molecular weight polyethylene (UHMWPE) acetabular cups and tibial trays produces a reduction in wear volume, and crosslinking has now been introduced clinically for both types of prostheses. Previous studies have identified both micron and submicron-sized polyethylene wear particles. The aim of this study was to characterize the wear and wear particles generated from moderately crosslinked GUR 1,020 GVF UHMWPE acetabular cups and tibial trays in hip and knee joint wear simulators down to 10 nanometers in size. The wear rates of the two prosthesis types were very similar at 25.6 +/- 5.3 mm(3) per million cycles for the hip prostheses and 22.75 +/- 5.95 mm(3) per million cycles for the knee prostheses. Nanometer-sized wear particles were isolated and characterized from both hip and knee simulator lubricants for the first time. Significantly higher numbers (p < 0.05) of particles in the nanometer (<0.1 microm) size range were produced by the hip prostheses compared to the knee prostheses. The knee prostheses produced larger particles, with the mode of particle size in the 0.1-1.0 microm size range, compared to <0.1 microm size range for the hip prostheses. In addition, the knee prostheses produced a greater volumetric concentration of wear particles in the 1.0-10 microm size range, and consequently lower specific biological activity and functional biological activity indices. These results indicated that the knee prostheses had a lower osteolytic potential compared to the hip prostheses.

Biocompatible Materials↗
PubMed2006

Diagnostic utility of FLI-1 monoclonal antibody and dual-colour, break-apart probe fluorescence in situ (FISH) analysis in Ewing's sarcoma/primitive neuroectodermal tumour (EWS/PNET). A comparative study with CD99 and FLI-1 polyclonal antibodies.

AIMS: To compare the sensitivity and specificity of the recently commercially available FLI-1 monoclonal (FLI-1m) antibody with the currently used antibodies [CD99 and FLI-1 polyclonal (FLI-1p)] in the diagnosis of Ewing's sarcoma/primitive neuroectodermal tumour (EWS/PNET) and to determine the diagnostic value of the EWSR1 (22q12) dual-colour, break-apart rearrangement probe fluorescence in situ hybridization (FISH) technique. MATERIALS AND METHODS: Forty-three cases of well-documented EWS/PNET and 15 non-EWS/PNET cases were retrieved from the archival files. Immunohistochemistry (IHC) for FLI-1p, FLI-1m and FISH analysis was performed. RESULTS: The most sensitive and specific test panel for the diagnosis of EWS/PNET is the combination of CD99 and FLI-1p. FISH had a very high specificity (100%) but only a moderate sensitivity (50%). CONCLUSION: The combination of CD99 and FLI-1p is the method of choice for the diagnosis of EWS/PNET. EWRS1 (22q12) dual-colour, break-apart rearrangement probe FISH should be used as a confirmatory test in addition to CD99 and FLI1-p due to its high specificity.

12E7 Antigen↗
PubMed2006

Biological effects of clinically relevant wear particles from metal-on-metal hip prostheses.

The problems of osteolysis and late aseptic loosening associated with ultra-high molecular weight polyethylene (UHMWPE) particles has lead to a renewed interest in metal-on-metal prostheses. Wear particles generated by modern Co-Cr-on-Co-Cr prostheses are nanometre in size (range: 10-120 nm; mean: about 40 nm), an order of magnitude smaller than the size of UHMWPE known to be critical for activation of osteolytic cytokines by macrophages. Co-Cr wear particles will induce osteolytic cytokine production by human macrophages, but only at high volumetric concentrations. Unlike UHMWPE, Co-Cr particles are not inert. Co-Cr particles have the potential to release metal ions; they may be toxic to cells, induce deoxyribonucleic acid damage or cause host hypersensitivity. The nanometre size range of Co-Cr wear particles means that they may be disseminated widely in the body. The potential for metal-on-metal bearings to induce adverse effects clinically will be dependent upon the rate of wear. What constitutes a safe wear rate for modern metal-on-metal bearings is unknown. However, the wear of metal-on-metal prostheses is critically dependent upon the design and, in particular, the carbon content of the alloy, the radial clearance, and the head diameter. Thus, the potential for adverse biological reactions associated with metal-on-metal bearings can be reduced by selection of appropriately designed implants.

Chromium Alloys↗
PubMed2006

Metal-on-metal bearings surfaces: materials, manufacture, design, optimization, and alternatives.

When first introduced, total hip replacements offered pain relief and improved mobility in elderly patients. The success of this procedure in terms of long-term durability and restoration of function has led to its use in younger, more active patients. This has resulted in a commensurate increase in patient expectation regarding longevity and the degree to which function and lifestyle is restored. The bearing surface is a key feature of the performance of replacement joints. It is generally accepted that excessive amounts of wear debris preclude their long-term survivorship and hence there is an ongoing requirement for bearing surfaces which minimize debris generation. The purpose of this paper is to review the factors which affect the performance of so-called metal-on-metal bearings, to compare their performance with that of the other commonly used contemporary alternatives, metal and ceramic articulating against highly cross-linked polyethylene, and ceramic-on-ceramic, and finally to consider the potential solutions offered by new developments such as ceramic-on-metal and coatings applied to metal-on-metal bearings.

Arthroplasty, Replacement, Hip↗
PubMed2006

A simple fully integrated contact-coupled wear prediction for ultra-high molecular weight polyethylene hip implants.

A fully coupled contact and wear model was developed in the present study for hip implants employing an ultra-high molecular weight polyethylene (UHMWPE) cup in combination with a metallic or ceramic femoral head. A simple elasticity equation based on the concept of constrained column model was employed to solve the contact mechanics between the acetabular cup and the femoral head under the three-dimensional physiological loading condition. The wear model was based on the classical Archard-Lancaster equation in common with all other studies reported in the literature. The fully coupled contact and wear model was applied to both conventional and cross-linked UHMWPE cups under a wide range of design parameters such as the clearance and the femoral head radius. The predicted linear and volumetric wear as well as their rates for conventional UHMWPE cups were found to be in good agreement with those obtained from a similar analysis by Maxian but using the finite element method for the contact mechanics analysis. The predicted maximum contact pressure was found to decrease rapidly within the first 10(6) cycles, and below the limit to cause plastic deformation within the UHMWPE cup with a nominal radial clearance of 0.2 mm. The effect of the clearance between the head and the cup on the predicted wear was found to be negligible. For the cross-linked UHMWPE cup with relatively large diameters up to 48 mm and a fixed outside diameter of 50 mm, the predicted wear, which was found to increase with increasing femoral head radius, remained small owing to the small wear factor associated with these materials. Furthermore, if the head diameter increases beyond 42 mm, a rapid increase in the contact pressure was predicted, owing to the decrease in the wall thickness of the cross-linked UHMWPE cup.

Animals↗
PubMed2006

Influence of hyaluronic acid on the time-dependent friction response of articular cartilage under different conditions.

Therapeutic lubricant injections of hyaluronic acid are a relatively recent treatment for osteoarthritis. Their efficacy, however, in vivo has been subject to much debate. Frictional properties of cartilage-cartilage contacts under both static and dynamic loading conditions have been investigated, using healthy cartilage and cartilage with a physically disrupted surface, with and without the addition of a therapeutic lubricant, hyaluronic acid. Most of the cartilage friction models produced typical time-dependent loading curves, with a rise in static friction with loading time. For the dynamic loading conditions the rise in friction with loading time was dependent on the spatial (and time) variation in the load on the cartilage plate. For sliding distances of 4 mm or greater, when the cartilage plate was unloaded during sliding, the dynamic friction remained low whereas, with shorter sliding distances, the dynamic friction increased with increasing loading time. Static friction was higher than dynamic friction (under the same tribological conditions). The 'damaged' cartilage models produced higher friction than healthy cartilage under equivalent tribological conditions. It was shown that hyaluronic acid was an effective boundary lubricant for articular cartilage under static conditions with both healthy and damaged cartilage surfaces. Hyaluronic acid was less effective under dynamic conditions. However, these dynamic conditions had low friction values with the control lubricant because of the effectiveness of the intrinsic biphasic lubrication of the cartilage. It was only under the tribological conditions in which the cartilage friction was higher and rising with increasing loading time because of depletion of the intrinsic biphasic lubrication, that the role of hyaluronic acid as an effective therapeutic lubricant was demonstrated.

Animals↗
PubMed2006

The role of the surface amorphous layer of articular cartilage in joint lubrication.

Articular cartilage is a complex soft tissue that performs multiple functions in the joint. In particular, the amorphous layer that covers the surface of articular cartilage is thought to play some role in lubrication. This study aimed to characterize the surface amorphous layer (SAL) using a variety of techniques, including environmental scanning electron microscopy, transmission electron microscopy, white light interferometry, and biochemical analysis of its composition. Friction tests were conducted to investigate the role of the SAL in lubrication. A protocol to remove successfully the SAL without damaging the underlying cartilage was developed and the material removed from healthy cartilage was found to contain approximately equal quantities of glycosaminoglycan (GAG), protein, and lipid. Cartilage-on-cartilage friction tests were conducted on fresh, healthy cartilage with and without the SAL, under both dynamic and static operating conditions. Removal of the SAL was not found to change the friction coefficient. However, subsequent staining of specimens indicated that the SAL had replenished during the test following loading. The replenished SAL was characterized and found to contain lipids and sulphated GAGs with undetectable protein. This study revealed experimental evidence of surface layer replenishment in articular cartilage. It was postulated that the surface layer regeneration mechanism was purely mechanical and associated with movement of GAGs and lipids through the cartilage matrix during deformation, since the experimental set-up did not contain any means of biochemical activation.

Animals↗
PubMed2005

The internal dynamic modes of charged self-assembled peptide fibrils.

Photon correlation spectroscopy is used to study the internal dynamics of self-assembled charged peptide fibrils. Short neutral and charged polymeric aggregates have diffusive modes due to whole macromolecular motion. For long semiflexible fibrils the logarithm of the intermediate scattering function follows a q(2)t(3/4) scaling at long times consistent with a Kratky-Porod free energy and preaveraged Oseen hydrodynamics. Persistence lengths on the order of micrometers are calculated for the peptide fibrils consistent with estimates from the liquid-crystalline phase behavior. Fibril diameters (5-35 nm) calculated from the initial decay of the correlation functions are in agreement with transmission electron microscopy measurements.

Algorithms↗
PubMed2005

Effects of maternal hyperoxia with and without normocapnia in uteroplacental and fetal Doppler studies.

OBJECTIVE: One hundred percent oxygen is given in pregnancy to improve fetal oxygenation, yet has been shown in both animal and human studies ex utero to increase cerebral vascular resistance. Adjusting end-tidal pCO2 (ET-pCO2) levels to normocapnic levels during hyperoxygenation offsets this effect in non-pregnant individuals. We aimed to evaluate the effect of maternal hyperoxygenation with and without maintaining normocapnia on the fetal and uteroplacental circulations in healthy near-term human pregnancies. METHODS: Eight healthy pregnant women, serving as their own controls, sequentially breathed room air, breathed 100% oxygen, and underwent normocapnic hyperoxygenation (NH) in a three-phase experiment involving a tight-fitting facemask. Each phase lasted 10-15 min. After steady state had been reached, peak velocities and pulsatility index (PI) values were obtained from the uterine, umbilical and fetal middle cerebral arteries (MCA) by color/pulsed Doppler. In addition, maternal ventilation and ET-pCO2 were monitored. RESULTS: One hundred percent oxygen induced maternal hyperventilation and hypocapnea. Uterine artery PI and peak systolic velocities were stable during 100% oxygen. In contrast, during NH uterine artery PI values decreased by 21% (P=0.04). Umbilical artery PI and peak velocities were stable during 100% oxygen; PI increased by 16% during NH (P=0.056), with no change in peak velocities. Peak MCA velocities decreased by 8% during 100% oxygen, and by 9.6% during NH, while MCA-PI decreased by 13% during 100% oxygen and by 21% during NH (P=0.06). CONCLUSIONS: Maternal and fetal circulations exhibit divergent responses to 100% oxygen and NH. While no change is observed in the uteroplacental circulation on 100% oxygen, decreased resistance and increased flow velocity are evident during NH. Increased umbilical artery PI during NH with no change in absolute velocities may suggest a reduction in fetoplacental blood flow. Maintaining normocapnia during hyperoxygenation does not appear to beneficially influence the circulation of the near-term human fetus as it does in non-pregnant individuals.

Adult↗
PubMed2005

The influence of design, materials and kinematics on the in vitro wear of total knee replacements.

Debris-induced osteolysis due to surface wear of ultra high molecular weight polyethylene (UHMWPE) bearings is a potential long-term failure mechanism of total knee replacements (TKR). This study investigated the effect of prosthesis design, kinematics and bearing material on the wear of UHMWPE bearings using a physiological knee simulator. The use of a curved fixed bearing design with stabilised polyethylene bearings reduced wear in comparison to more flat-on-flat components which were sterilised by gamma irradiation in air. Medium levels of crosslinking further improved the wear resistance of fixed bearing TKR due to resistance to strain softening when subjected to multidirectional motion at the femoral-insert articulating interface. Backside motion was shown to be a contributing factor to the overall rate of UHMWPE wear in fixed bearing components. Wear of fixed bearing prostheses was reduced significantly when anterior-posterior displacement and internal-external rotation kinematics were reduced due to decreased cross shear on the articulating surface and a reduction in AP displacement. Rotating platform mobile bearing prostheses exhibited reduced wear rates in comparison to fixed bearing components in these simulator studies due to redistribution of knee motion to two articulating interfaces with more linear motions at each interface. This was observed in two rotating platform designs with different UHMWPE bearing materials. In knee simulator studies, wear of TKR bearings was dependent on kinematics at the articulating surfaces and the prosthesis design, as well as the type of material.

Biocompatible Materials↗
PubMed2005

Increased risk of hemorrhagic complications in renal allograft recipients receiving systemic heparin early posttransplantation.

UNLABELLED: The aim of this paper is to document the risk of hemorrhagic complications in renal allograft recipients requiring systemic heparinisation within the first 2 weeks posttransplantation. METHODS: A retrospective chart review of 326 RA recipients from January 1998 to July 2003 was subjected to statistics by SPIDA with P values <.05 considered significant. RESULTS: 16/326 (4.9%) recipients were initiated on intravenous (IV) heparin within the study period. Enoxaparin was subsequently used in 10/16 (62.5%) of these recipients. Intravenous heparin was instituted at a median 8 (1-14) days posttransplantation. Hemorrhagic complications occurred in 10/16 (62.5%) recipients on IV heparin versus 11/310 (3.5%) nonanticoagulated RA recipients (P = .0001). Hemorrhage occurred at a mean 9.75 (2-43) days into the course of IV heparin. The median peak APTT 24 hours prior to hemorrhage in RA recipients on heparin was 68.5 (58-180) versus a median peak APTT of 70 (50-140) among recipients on heparin who did not sustain a hemorrhagic complication (P = .30). A major intervention (predominantly surgery) was required in 6/16 (37%) recipients on IV heparin versus 7/310 (2.2%) nonheparinised RA recipients (P < .0001). Enoxaparin was instituted at a mean 22.5 (4-55) days posttransplantation. Delayed hemorrhage subsequently occurred in 4/10 (40%) recipients on enoxaparin. In conclusion, major and minor hemorrhagic complications occur more commonly among recipients requiring early post transplant IV heparin. Hemorrhage occurred despite APTT monitoring with APTT levels tending to be similar in RA recipients with versus without complications. Delayed hemorrhage was also seen with the subsequent use of enoxaparin.

Anticoagulants↗
PubMed2004

Reduced growth hormone secretion prolongs puberty but does not delay the developmental increase in luteinizing hormone in the absence of gonadal negative feedback.

Previous studies have shown that the growth hormone (GH) axis is important for timing the later stages of puberty in female monkeys. However, it is not clear whether these growth-related signals are important for the initiation of puberty and early pubertal events. The present study, using female rhesus monkeys, used two approaches to answer this question. Experiment 1 tested the hypothesis that reduced GH secretion would blunt the rise in nocturnal LH secretion in young (17 mo; n = 7) but not older adolescent ovariectomized females (29 mo; n = 6). Reduced GH secretion was induced by treating females with the sustained release somatostatin analogue formulation, Sandostatin LAR (625 microg/kg). Morning (0900-0930 h) and evening (2200-2230 h) concentrations of bioactive LH were higher in older adolescent compared to young adolescent females. However, diurnal concentrations were not affected by the inhibition of GH secretion in either age group when compared to the placebo-treated, control condition. Experiment 2 tested the hypothesis that reduced GH secretion induced in young juvenile females would delay the initial increase in nocturnal LH secretion and subsequent early signs of puberty. In order to examine this hypothesis, puberty in control females (n = 7) was compared to those in which puberty had been experimentally arrested until a late adolescent age (29 mo) by the use of a depot GnRH analogue, Lupron (750 microg kg(-1) mo(-1); n = 7). Once the analogue treatment was discontinued, the progression of puberty was compared to a group treated in a similar fashion but made GH deficient by continuous treatment with Sandostatin LAR (n = 6). Puberty occurred as expected in control females with the initial rise in evening LH at 21 mo, menarche at 22 mo, and first ovulation at 30 mo. As expected, Lupron arrested reproductive maturation, but elevations in morning and evening LH and menarche occurred within 2 mo of the cessation of Lupron in both Lupron and Lupron-GH-suppressed females. In contrast, first ovulation was delayed significantly in the Lupron-GH-suppressed females (41 mo) compared to the Lupron-only females (36 mo). These data indicate that within this experimental model, reduced GH secretion does not perturb the early stages of puberty but supports previous observations that the GH axis is important for timing the later stages of puberty and attainment of fertility. Taken together, the data indicate that factors that reduce GH secretion may have a deleterious effect on the completion of puberty.

Animals↗
PubMed2004

The wear and fracture behaviour of ultra high molecular weight polyethylene subjected to gamma-irradiation in an atmosphere of acetylene.

The wear and mechanical properties of GUR 1020 (Perplas IMP 2000-2) Ultra High Molecular Weight Polyethylene (UHMWPE) subjected to gamma-irradiation in an atmosphere of acetylene, were evaluated for a range of processing conditions of irradiation, annealing and ageing. The results were compared with those obtained for the virgin UHMWPE material and material processed using conventional gamma-irradiation in nitrogen. Cross-linking produced by irradiation in acetylene, followed by subsequent annealing was found to be significantly more effective in improving the mechanical and wear properties of UHMWPE compared to when the material was irradiated in nitrogen. Gel fraction analysis on its own, while being able to detect the degree of cross-linking, was found to be insufficient in determining the effectiveness of the cross-links and the resulting mechanical properties of the UHMWPE material. The results suggest that gamma-irradiation in an atmosphere of acetylene may provide significant advantages over conventional UHMWPE processing and irradiation cross-linking techniques.

Acetylene↗
PubMed2004

Influences of sterilising techniques on polyethylene wear.

Over the last 10 years there has been increasing concern over wear of polyethylene and osteolytic potential in the knee. During this period there have been considerable developments in both the design, materials and sterilisation techniques used for polyethylene in the knee. This paper reviews wear performance of polyethylene sterilised by different techniques, under a range of kinematics conditions in a single knee joint simulator system. Reducations in polyethylene wear were found with both stabilised polyethylene and cross-linked polyethylene, and with rotating platform mobile bearing designs.

Biomechanical Phenomena↗
PubMed2004

Effects of a peracetic acid disinfection protocol on the biocompatibility and biomechanical properties of human patellar tendon allografts.

Patellar tendon allografts, retrieved from cadaveric human donors, are widely used for replacement of damaged cruciate ligaments. In common with other tissue allografts originating from cadaveric donors, there are concerns regarding the potential for disease transmission from the donor to the recipient. Additionally, retrieval and subsequent processing protocols expose the graft to the risk of environmental contamination. For these reasons, disinfection or sterilisation protocols are necessary for these grafts before they are used clinically. A high-level disinfection protocol, utilising peracetic acid (PAA), has been developed and investigated for its effects on the biocompatibility and biomechanics of the patellar tendon allografts. PAA disinfection did not render the grafts either cytotoxic or liable to provoke an inflammatory response as assessed in vitro . However, the protocol was shown to increase the size of gaps between the tendon fibres in the matrix and render the grafts more susceptible to digestion with collagenase. Biomechanical studies of the tendons showed that PAA treatment had no effect on the ultimate tensile stress or Young's modulus of the tendons, and that ultimate strain was significantly higher in PAA treated tendons.

Adult↗
PubMed2004

Carbon-carbon composite bearing materials in hip arthroplasty: analysis of wear and biological response to wear debris.

Ultra-high molecular weight polyethylene wear particles have been implicated as the major cause of osteolysis, implant loosening and late aseptic failure in total hip arthroplasties in vivo. This study initially screened 22 carbon-carbon composite materials as alternatives for UHMWPE in joint bearings. New bearing materials should satisfy certain criteria--they should have good wear properties that at least match UHMWPE, and produce wear particles with low levels of cytotoxic and osteolytic activity. Initial screening was based on wear resistance determined in short-term tribological pin-on-plate tests. Three materials (HMU-PP(s), HMU-RC-P(s), and SMS-RC-P(s)) which had superior wear resistance were selected for long-term testing. All materials had very low wear factors and SMS-RC-P(s), which had a wear factor of 0.08 +/- 0.56 x 10(-7) mm3/Nm, was selected for the subsequent biological testing and particle size analysis. SMS-RC-P(s) showed good biocompatibility in bulk material form and also the wear particles had low cytotoxicity for L929 fibroblasts in culture compared to metal wear particles. Wear debris size analysis by transmission electron microscopy showed that the particles were very small, with the vast majority being under 100 nm in size, similar to metal wear particles. The potential osteolytic effect of SMS-RC-P(s) wear particles was investigated by culturing particles with human peripheral blood mononuclear cells and measuring TNFalpha production. SMS-RC-P(s) did not significantly stimulate TNFalpha production at a particle volume to cell number ratio of 80:1, indicating that the debris had a low osteolytic potential. The results of this study suggest that carbon-carbon composites, particularly those composed of PAN-based fibers may be important biomaterials in the development of next generation bearing surfaces for use in total joint replacements that have very low wear rates and reduced osteolytic and cytotoxic potential.

Animals↗
PubMed2004

Wear of surface engineered metal-on-metal hip prostheses.

The wear of existing metal-on-metal (MOM) hip prostheses (1 mm3/million cycles) is much lower than the more widely used polyethylene-on-metal bearings (30-100 mm3/million cycles). However, there remain some potential concerns about the toxicity of metal wear particles and elevated metal ion levels, both locally and systemically in the human body. The aim of this study was to investigate the wear, wear debris and ion release of fully coated surface engineered MOM bearings for hip prostheses. Using a physiological anatomical hip joint simulator, five different bearing systems involving three thick (8-12 microm) coatings, TiN, CrN and CrCN, and one thin (2 microm) coating diamond like carbon (DLC) were evaluated and compared to a clinically used MOM cobalt chrome alloy bearing couple. The overall wear rates of the surface engineered prostheses were at least 18-fold lower than the traditional MOM prostheses after 2 million cycles and 36-fold lower after 5 million cycles. Consequently, the volume of wear debris and the ion levels in the lubricants were substantially lower. These parameters were also much lower than in half coated (femoral heads only) systems that have been reported previously. The extremely low volume of wear debris and concentration of metal ions released by these surface engineered systems, especially with CrN and CrCN coatings, have considerable potential for the clinical application of this technology.

Biomedical Engineering↗