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Biomedical subjects

J Fisher

Publications and source records attributed to J Fisher.

At least 55 records · Page 3Linked to original sources
PubMed2002

Comparison of wear, wear debris and functional biological activity of moderately crosslinked and non-crosslinked polyethylenes in hip prostheses.

The wear, wear debris and functional biological activity of non-crosslinked and moderately crosslinked ultrahigh molecular weight polyethylene (UHMWPE) acetabular cups have been com pared when articulating against smooth and intentionally scratched femoral heads. Volumetric wear rates were determined in a hip joint simulator and the debris was isolated from the lubricant and characterized by the percentage number and volumetric concentration as a function of particle size. The volumetric concentration was integrated with the biological activity function determined from in vitro cell culture studies to predict an index of specific biological activity (SBA). The product of specific biological activity and volumetric wear rate was used to determine the index of functional biological activity (FBA). On smooth femoral heads the crosslinked UHMWPE had a 30 per cent lower wear rate, but it had a greater percentage volume of smaller, more biologically active particles, which resulted in a similar index of FBA compared with the non-crosslinked material. On the scratched femoral heads the volumetric wear rate was three times higher for the moderately crosslinked UHMWPE and two times higher for the non-crosslinked UHMWPE compared with the smooth femoral heads. This resulted in a higher wear rate for the moderately crosslinked material on the scratched femoral heads. All the differences in wear rate were statistically significant. There were only small differences in particle volume concentration distributions, and this resulted in similar indices of FBA which were approximately twice the values of those found on the smooth femoral heads. Both materials showed lower wear and FBA than for previously studied aged and oxidized UHMWPE gamma irradiated in air. However, this study did not reveal any advantage in terms of predicted FBA for moderately crosslinked UHMWPE compared with non-crosslinked UHMWPE.

Acetylene↗
PubMed2002

Effect of microseparation on contact mechanics in ceramic-on-ceramic hip joint replacements.

The contact mechanics in ceramic-on-ceramic hip implants are investigated in this study under the microseparation condition where the edge contact occurs between the superolateral rim of the acetabular cup and the femoral head. A three-dimensional finite element model is developed to examine the effect of the microseparation distance between the femoral head and the acetabular cup on the contact area and contact stresses between the bearing surfaces. It is shown that microseparation leads to edge contact and elevated contact stresses, and these are mainly dependent on the magnitude of separation, the radial clearance between the femoral head and the acetabular cup, and the cup inclination angle. For a small microseparation distance (less than the diametrical clearance), the contact occurs within the acetabular cup, and consequently an excellent agreement of the predicted contact pressure distribution is obtained between the present three-dimensional anatomical model and a simple two-dimensional axisymmetric model adopted in a previous study [5]. However, as microsegregation is increased further, edge contact between the superolateral rim and the femoral head occurs. Consequently, the predicted contact pressure is significantly increased. The corresponding contact area resembles closely the stripe wear pattern observed on both clinically retrieved and simulator-tested ceramic femoral heads [8, 9, 11]. Furthermore, introducing a fillet radius of 2.5 mm at the mouth of the acetabular cup is shown to reduce the contact stress due to edge contact, but only under relatively large microseparation distances.

Acetabulum↗
PubMed2002

An in vitro study of the reduction in wear of metal-on-metal hip prostheses using surface-engineered femoral heads.

Although the wear of existing metal-on-metal (MOM) hip prostheses (1 mm3/10(6) cycles) is much lower than the more widely used polyethylene-on-metal bearings, there are 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 possibility of reducing the volume of wear, the concentration of metal debris and the level of metal ion release through using surface-engineered femoral heads. Three thick (8-12 microm) coatings (TiN, CrN and CrCN) and one thin (2 microm) coating (diamond-like carbon, DLC), were evaluated on the femoral heads when articulating against high carbon content cobalt-chromium alloy acetabular inserts (HC CoCrMo) and compared with a clinically used MOM cobalt-chromium alloy bearing couple using a physiological anatomical hip joint simulator (Leeds Mark II). This study showed that CrN, CrCN and DLC coatings produced substantially lower wear volumes for both the coated femoral heads and the HC CoCrMo inserts. The TiN coating itself had little wear, but it caused relatively high wear of the HC CoCrMo inserts compared with the other coatings. The majority of the wear debris for all half-coated couples comprised small, 30 nm or less, CoCrMo metal particles. The Co, Cr and Mo ion concentrations released from the bearing couples of CrN-, CrCN- and DLC-coated heads articulating against HC CoCrMo inserts were at least 7 times lower than those released from the clinical MOM prostheses. These surface-engineered femoral heads articulating on HC CoCrMo acetabular inserts produced significantly lower wear volumes and rates, and hence lower volumetric concentrations of wear particles, compared with the clinical MOM prosthesis. The substantially lower ion concentration released by these surface-engineered components provides important evidence to support the clinical application of this technology.

Carbon↗
PubMed2002

Quantitative analysis of UHMWPE wear debris isolated from the periprosthetic femoral tissues from a series of Charnley total hip arthroplasties.

Submicrometer and micrometer-sized UHMWPE wear particles have been associated with osteolysis and failure of total hip replacements. A previous study by Tipper et al. examined the wear debris isolated from the acetabular periprosthetic tissues from 18 Charnley total hip replacements, and compared this data to the tribological variables of the prostheses. The present study aimed to isolate the UHMWPE wear debris from the femoral periprosthetic tissues from 10 of the same cohort of patients, and compare it with the debris isolated from the corresponding acetabular tissues. A variety of particle morphologies were observed, discrete submicrometer particles, along with flakes and fibrils. The particle size distributions ranged from 0.1 to >250 microm, however, the largest particles were only found in samples when the femoral head damage was characterised as low (R(pm) < 0.2 microm). The mode of the frequency distribution of particles was in the range of 0.1-0.5 microm for all the femoral tissues. Considerable variations were found in the mass distributions of the wear particles as a function of size for different patients. The net mass of debris isolated from the femoral tissues was significantly lower (p < 0.05, Student's t-test) than from the corresponding acetabular tissues. This along with considerable spatial variation in the net mass of debris isolated from the different regions of the same sample of acetabular tissue, indicates that the transportation of the debris has a marked effect on the net mass of debris accumulated in different tissues.

Acetabulum↗
PubMed2001

Increased post-traumatic survival of neurons in IL-6-knockout mice on a background of EAE susceptibility.

Axonal injury initiates a process of neuronal degeneration, with resulting death of neuronal cell bodies. We show here that in C57BL/6J mice, previously shown to have a limited ability to manifest a post-traumatic protective immunity, the rate of neuronal survival is increased if IL-6 is deficient during the first 24 hours after optic nerve injury. Immunocytochemical staining preformed 7 days after the injury revealed an increased number of activated microglia in the IL-6-deficient mice compared to the wild-type mice. In addition, IL-6-deficient mice showed an increased resistance to glutamate toxicity. These findings suggest that the presence of IL-6 during the early post-traumatic phase, at least in mice that are susceptible to autoimmune disease development, has a negative effect on neuronal survival. This further substantiates the contention that whether immune-derived factors are beneficial or harmful for nerve recovery after injury depends on the phenotype of the immune cells and the timing and nature of their dialog with the damaged neural tissue.

Animals↗
PubMed2001

Toxicity, efficacy, and pharmacology of suramin in adults with recurrent high-grade gliomas.

PURPOSE: To determine the toxicity, efficacy, and pharmacology of suramin in patients with recurrent or progressive recurrent high-grade gliomas. PATIENTS AND METHODS: Fifty adults were to receive suramin. However, if no responses were seen in the first ten patients, the study was to be terminated. A total of 12 patients were enrolled onto this trial. Ten patients had glioblastoma multiforme, and 11 had received prior nitrosoureas. RESULTS: Drug-related toxicities were modest and reversible. Three patients developed grade 3 to 4 neutropenia, constipation, diarrhea, or nausea. No CNS bleeding was observed. Median time to progression was 55 days (range, 17 to 242 days) and median survival was 191 days (range, 42 to 811 days). No partial or complete responses were seen at 12 weeks. However, the clinical outcome of three patients suggests that evidence of suramin activity may be delayed. One patient who "progressed" after 12 weeks of suramin had a subsequent marked reduction in tumor size and has maintained an excellent partial response for over 2 years without other therapy. Two others had disease stabilization and lived for 16 and 27 months. Pharmacokinetics from 11 patients revealed that all reached target suramin concentrations. CONCLUSION: This study demonstrates that suramin is well tolerated by patients with recurrent high-grade gliomas and may have efficacy in this disease. Its pharmacology seems unaffected by anticonvulsants. As a result of this data, suramin and radiation are now being administered concurrently to patients with newly diagnosed glioblastoma multiforme, with survival as the primary outcome.

Adult↗
PubMed2001

Vaccination for neuroprotection in the mouse optic nerve: implications for optic neuropathies.

T-cell autoimmunity to myelin basic protein was recently shown to be neuroprotective in injured rat optic nerves. In the present study, using the mouse optic nerve, we examined whether active immunization rather than passive transfer of T-cells can be beneficial in protecting retinal ganglion cells (RGCs) from post-traumatic death. Before severe crush injury of the optic nerve, SJL/J and C3H.SW mice were actively immunized with encephalitogenic or nonencephalitogenic peptides of proteolipid protein (PLP) or myelin oligodendrocyte glycoprotein (MOG), respectively. At different times after the injury, the numbers of surviving RGCs in both strains immunized with the nonencephalitogenic peptides pPLP 190-209 or pMOG 1-22 were significantly higher than in injured controls treated with the non-self-antigen ovalbumin or with a peptide derived from beta-amyloid, a non-myelin-associated protein. Immunization with the encephalitogenic myelin peptide pPLP 139-151 was beneficial only when the disease it induced, experimental autoimmune encephalomyelitis, was mild. The results of this study show that survival of RGCs after axonal injury can be enhanced by vaccination with an appropriate self-antigen. Furthermore, the use of nonencephalitogenic myelin peptides for immunization apparently allows neuroprotection without incurring the risk of an autoimmune disease. Application of these findings might lead to a promising new approach for treating optic neuropathies such as glaucoma.

Animals↗
PubMed2001

Quantitative characterization of polyethylene debris isolated from periprosthetic tissue in early failure knee implants and early and late failure Charnley hip implants.

This study isolated and characterized UHMWPE particles from 3 explant groups: early Charnley hip failures (ECE; < 10 years), late Charnley hip failures (LCE; > 10 years) and early knee failures (EKE; < 10 years). Debris isolated from the 3 groups had percentage particle number and percentage volumetric concentration distributions that were not significantly different. The greatest number of particles were found in the 0.1-0.5 microm size range and 19-20.6% of the volumetric concentration was below 1 microm in size in all groups. However, there were significant differences in the total volumetric concentration of debris isolated per g of tissue. LCE had significantly higher volumes of debris than ECE and EKE, there was no significant difference in the volume of debris from the EKE and ECE. The mean aspect ratio and mean irregularity ratio of the LCE group were also significantly higher than the ECE and EKE, suggesting that different wear mechanisms were occurring in the late Charnley group compared to the early Charnley and knee groups. These results also suggest that early knees, with normal surface wear, may have similar wear mechanisms to early Charnley hips and indicate that similar volumes of biologically active micrometer and sub-micrometer UHMWPE particles were produced. This may have important implications in the longer-term outcome of total knee arthroplasties, because it indicates a similar potential for osteolysis induced by wear debris.

Aged↗
PubMed2001

A novel low wearing differential hardness, ceramic-on-metal hip joint prosthesis.

Osteolysis and loosening of artificial joints caused by polyethylene wear debris has prompted renewed interest in alternative bearing materials for hip prosthesis designs. Lower wearing metal-on-metal (MOM) and ceramic-on-ceramic prostheses are being used more extensively, and there is considerable interest in further improving on their performance. This study investigated the wear properties and debris morphology of a novel differential hardness ceramic-on-metal (COM) prosthesis, in comparison with MOM articulations in a physiological anatomical hip joint simulator. The COM pairings were found to have wear rates approximately 100-fold lower than the MOM pairings. The MOM pairings showed a higher "bedding in" wear rate (3.09+/-0.46mm(3)/10(6) cycles) in the first million cycles, which then reduced to a steady state wear rate of 1.23+/-0.5mm(3)/10(6) cycles. The wear rate of the COM pairings over the duration of the test was approximately 0.01mm(3)/10(6) cycles with very little wear detected on the surface of the prosthesis components. The wear particles from both articulations were oval to round in shape and in the nanometer size range. After one million cycles the mean maximum diameter of the MOM and COM wear particles were 30+/-2.25 and 17.57+/-1.37nm, respectively. After five million cycles the wear particles were statistically significantly smaller than at one million cycles, 13.9+/-0.72nm for the MOM pairings and 6.11+/-0.40nm for the COM pairings. The wear rates of the MOM prostheses were representative of clinical values. The use of differential hardness COM pairings dramatically reduced the wear rate compared to MOM hip prostheses. The wear particles from the MOM articulation were similar to particles found in retrieved tissues from around MOM prostheses. The extremely low wearing differential hardness COM bearings presented in this study produced far smaller volumetric particle loads compared to MOM prostheses currently used clinically.

Biocompatible Materials↗
PubMed2001

Wear of HIPed and non-HIPed alumina-alumina hip joints under standard and severe simulator testing conditions.

Wear and the biological response to wear debris of artificial joints remain major concerns in total hip arthroplasty (THA). The long-term effects of UHMWPE wear debris are well documented and these have led to interest in alternate bearing materials for THA. Alumina ceramic-ceramic hip joints have been successfully used for more than 30 years with low wear and little incidence of osteolysis. The most common wear pattern observed on retrieved components is an elliptical wear 'stripe' on the heads and a corresponding worn area on the cup with an approximated wear rate of 1-5 mm3 pa. More severe wear has also occasionally occurred, usually in association with an abnormal clinical history. Modern alumina-alumina THAs use an improved HIPed (hot isostatically pressed) alumina ceramic-bearing material which may be more resistant to severe wear. Previous in vitro simulator studies have not replicated in vivo wear rates or mechanisms. The aim of this study was to compare previous generation non-HIPed alumina and modern HIPed alumina in a hip joint simulator under 'normal' and 'harsh' testing conditions. HIPed alumina was found to have a lower wear rate than non-HIPed alumina, although the difference was not statistically significant at the 95% confidence level. Testing in Gelofusine and water lubricants did not elevate the wear rates of either material. Elevated swing phase load testing also had no significant effect on the wear rates of either material. Testing in the absence of any lubricant produced very severe wear of the non-HIPed material in one specimen only.

Aluminum Oxide↗
PubMed2001

Comparison of the response of three human monocytic cell lines to challenge with polyethylene particles of known size and dose.

The response of three human monocytic cell lines (Monomac-1, U937 and THP-1) to challenge with polyethylene particles of known size and dose was evaluated. Particles with a mean size of 0.21, 0.49, 4.3, 7.2, and 88 microm were co-cultured with the cells for 24 hours prior to the assessment of cell viability and production of the pro-inflammatory cytokines, IL-1beta, IL-6 and TNFalpha. Additionally, GM-CSF and prostaglandin E2 were measured in culture supernatants from particle stimulated U937 cells. All particle fractions were evaluated at particle volume (microm3) to cell number ratios of 100 : 1, 10 : 1, 1 : 1 and 0.1 : 1. None of the test fractions had any effect on cell viability. Only the response of the U937 cell line was demonstrated to be comparable to that of primary macrophages as determined in a previous study. Furthermore only particle volume to cell number ratios of 10 : 1 or greater consistently stimulated significantly enhanced levels of cytokine secretion with particles within the phagocytosable size range (0.1 to 10 microm) being the most biologically active. No response was observed when U937 macrophages were stimulated with the largest (88 microm) particles at any of the volume ratios tested in this study. These results suggest that the size and volume of polyethylene particles are critical factors in macrophage activation. In addition, the U937 cell line has been shown to be a suitable model for the in vitro study of macrophage-particle interactions.

Journal Article↗
PubMed2001

The influence of acetabular cup angle on the wear of "BIOLOX Forte" alumina ceramic bearing couples in a hip joint simulator.

The wear of "Biolox Forte" alumina ceramic bearing couples has been investigated at two different acetabular cup angles in a physiological hip joint simulator. All cups were set in the anatomical position of 45 degrees inclination in the M/L plane for the first two million cycles and then four of the six cups were re-aligned to 60 degrees for a further three million cycles. A "running-in" wear of 0.14 mm3 per million cycles was observed for the first million cycles, after which a steady state wear rate of 0.05 mm3 per million cycles was observed. Increasing the acetabular cup angle to 60 degrees did not significantly affect the wear rate.

Journal Article↗
PubMed2001

The effect of molecular orientation and acetylene-enhanced crosslinking on the wear of UHMWPE in total artificial joints.

This paper investigates the benefits of combining roll-drawing and acetylene-enhanced crosslinking to alter the mechanical properties of the ultra high molecular weight polyethylene (UHMWPE) used in total hip and knee replacements, with the aim of improving its resistance to wear. UHMWPE was processed via crosslinking, roll-drawing and a combination of crosslinking and roll-drawing and subjected to gel content analysis, tensile tests, X-ray diffraction and wear tests using different types of motion and smooth and rough counterfaces. Purely roll-drawn materials with length and width draw ratios of lambda l x lambda w = 1.3 x 1.0 and lambda1 x lambdaw = 1.6 x 0.9 respectively, were found to have lower wear factors in a unidirectional motion test with a rough counterface when compared to the virgin material. The crosslinked roll-drawn material, with length and width draw ratios of lambda1 x lambdaw = 1.6 x 0.9, was seen to possess five crosslinks per initial number average molecule. This crosslinked and roll-drawn material showed 5.5 times less wear than the virgin material in a multidirectional motion test with a smooth counterface and 1.4 times more wear than the virgin material in a unidirectional motion test with a rough counterface. Hence this study supports previous work by the authors that acetylene-enhanced crosslinked materials may show benefits for a total hip replacement, but only where the femoral head remains smooth. The improvements in wear with the roll-drawn material in unidirectional tests were smaller, but may prove to have some benefits in the knee.

Journal Article↗
PubMed2001

Familial pseudohyperkalaemia Chiswick: a novel congenital thermotropic variant of K and Na transport across the human red cell membrane.

Two families with inherited abnormalities in Na and K transport across the red cell membrane are described. Both presented with 'pseudohyperkalaemia' as a result of loss of K from the red cells on storage at room temperature. Routine haematology was essentially normal, except for macrocytosis in one family. Studies of the temperature dependence of the passive leak to K showed a novel shoulder pattern with a minimum at 25 degrees C, a maximum at 10 degrees C, followed by a further fall. As in other cases of red cell-based pseudohyperkalaemia, the abnormal temperature dependence of this 'leak' flux could be held to account for the loss of K from the cells at room temperature. These cases represent a novel variant of the temperature dependence of the passive leak of K and Na across the red cell membrane, and can be classified as a mild, non-haemolytic form of the group known as the hereditary stomatocytosis and allied disorders'.

Anemia, Hemolytic, Congenital↗
PubMed2001

Two further British families with the 'cryohydrocytosis' form of hereditary stomatocytosis.

We describe two families with the 'cryohydrocytosis' form of stomatocytosis. Both show a mild stomatocytic anaemia with Hb levels of 12-16 g/dl and reticulocyte counts of 4.3-24%, with very marked autohaemolysis at refrigerator temperatures and pseudohyperkalaemia as a result of loss of K from red cells on storage at room temperature. The ouabain + bumetanide-insensitive 'passive leak' K influx showed a 'U'-shaped temperature dependence, with a minimum at 23 degrees C. In one family, there was consistent variation in haematological severity within the pedigree. In the other, the parents of the proposita were normal, but all three of her children were affected, consistent with a new mutation of a dominant condition. Cold storage of the red cells led to a very marked increase in osmotic fragility and macrospherocytosis, explaining why a diagnosis of 'hereditary spherocytosis' can easily be reached in these pedigrees.

Anemia, Hemolytic, Congenital Nonspherocytic↗
PubMed2001

A comparison of the wear and physical properties of silane cross-linked polyethylene and ultra-high molecular weight polyethylene.

Cross-linked polyethylenes are being introduced widely in acetabular cups in hip prostheses as a strategy to reduce the incidence of wear debris-induced osteolysis. It will be many years before substantial clinical data can be collected on the wear of these new materials. Silane cross-linked polyethylene (XLPE) was introduced into clinical practice in a limited series of acetabular cups in 1986 articulating against 22.225-mm alumina ceramic femoral heads and showed reduced wear rates compared with conventionally sterilized (gamma irradiation in air) ultra-high molecular weight polyethylene (UHMWPE). We compared the wear of XLPE manufactured in 1986 with the wear of UHMWPE manufactured in 1986 in nonirradiated and irradiated forms. In the nonirradiated forms, the wear of XLPE was 3 times less than UHWMPE when articulating against smooth counterfaces. The nonirradiated materials did not show signs of oxidation. In the irradiated forms, only UHMWPE showed high levels of oxidation, and this caused a substantial increase in wear. Antioxidants added to XLPE during processing gave resistance to oxidative degradation. When sliding against scratched counterfaces, the wear of UHMWPE increased by a factor of 2 to 3 times. Against the same scratched counterfaces, the wear of XLPE increased dramatically by 30 to 200 times. This difference may be attributed to the reduction in toughness of XLPE. Clinically, XLPE has been articulated against damage-resistant ceramic heads, and this probably has been an important factor in contributing to reduced wear. New cross-linked polyethylenes differ considerably from XLPE. This study indicates that it is prudent to examine the wear of new polyethylenes under a range of conditions that may occur in vivo.

Analysis of Variance↗