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Biomedical subjects

J Fisher

Publications and source records attributed to J Fisher.

At least 163 records · Page 9Linked to original sources
PubMed1999

A hip joint simulator study using simplified loading and motion cycles generating physiological wear paths and rates.

In some designs of hip joint simulator the cost of building a highly complex machine has been offset with the requirement for a large number of test stations. The application of the wear results generated by these machines depends on their ability to reproduce physiological wear rates and processes. In this study a hip joint simulator has been shown to reproduce physiological wear using only one load vector and two degrees of motion with simplified input cycles. The actual path of points on the femoral head relative to the acetabular cup were calculated and compared for physiological and simplified input cycles. The in vitro wear rates were found to be highly dependent on the shape of these paths and similarities could be drawn between the shape of the physiological paths and the simplified elliptical paths.

Analysis of Variance↗
PubMed1999

Analysis of debris from brushing the femoral canal with a plastic brush--a potential cause of loosening in total hip replacement.

The generation of submicrometre sized polyethylene particles has been shown to be one of the major causes of osteolysis, loosening and failure of total replacement joints. It has been reported that intramedullary brushing of the femoral canal with polymer brushes prior to total hip arthroplasty results in the release of polymer particles into the femoral canal. The aim of this study was to isolate and characterize these particles on the basis of morphology and size and to determine whether these particles may play a role in osteolysis and loosening of the total hip prostheses. It was found that the majority of the particles shed by the polymer brushes were submicrometre in size and were similar in morphology to UHMWPE wear particles isolated from periprosthetic tissues. In addition, the majority of the particles released by the brushes were in the biologically active size range (0.1-10 microns), and may contribute to osteolysis and loosening of hip prostheses.

Arthroplasty, Replacement, Hip↗
PubMed1999

The influence of continuous sliding and subsequent surface wear on the friction of articular cartilage.

Reciprocating motion friction tests were conducted upon cartilage-on-metal contacts while subjected to a constant load. Initial friction coefficients were compared with repeat friction coefficients following a sufficient load removal period. The repeat friction coefficients were marginally higher than the initial values and both were primarily dependent on the loading time. It was concluded that while a wear component had been identified, which modestly increased friction coefficients, the overriding parameter influencing friction was loading time. The authors postulate that fluid phase load carriage (being dependent on loading time) within the articular cartilage is largely responsible for low friction coefficients in the mixed and boundary lubrication regimes. This mechanism has been referred to as biphasic lubrication. Both synovial fluid and Ringer's solution were used as lubricants. Over the assessed 120 min loading time friction coefficients rose from 0.005 (for both lubricants) after 5 s to 0.50 and 0.57 for synovial fluid and Ringer's solution respectively. Synovial fluid was found to significantly reduce friction coefficients compared to Ringer's solution over broad ranges of the assessed loading times (p < 0.05). Stylus and non-contacting laser profilometry were successfully employed to provide reliable, quantitative and accurate measures of surface roughness. Laser profilometry before and after a continuous sliding friction test revealed a significant increase in surface roughness from Ra = 0.8 (+/- 0.2) micron to Ra = 2.1 (+/- 0.2) microns, (p < 0.0005); confirming that surface wear was occurring. Scanning electron microscopy (SEM) revealed the typical highly orientated collagen fibres of the superficial tangential zone. Environmental SEM (ESEM) of fully hydrated cartilage specimens provided largely featureless images of the surface which suggested that sample preparation for conventional SEM was detrimental to the authenticity of the cartilage surface appearance using SEM. Two distinct acellular, non-collagenous surface layers were identified using ESEM and transmission electron microscopy (TEM); respectively referred to as the boundary layer and surface lamina. The phospholipid/glycoprotein based boundary layer will provide boundary lubrication during intimate contact of opposing cartilage surfaces. The surface lamina, being a continuum of the proteoglycan interfibrillar matrix, is present to prevent fibrillation of the underlying collagen fibres. Both layers may contribute to the time dependent frictional response of articular cartilage. Although laser profilometry did reveal surface wear which was consistent with a small increase in friction, the primary variable controlling the friction coefficient was the period of loading.

Animals↗
PubMed1999

A comparison of the wear and debris generation of GUR 1120 (compression moulded) and GUR 4150HP (ram extruded) ultra high molecular weight polyethylene.

The wear debris generated from UHMWPE (ultra high molecular weight polyethylene) has been recognised as one of the major causes of failure in THR (total hip replacement). GUR 1120 (compression moulded) and GUR 4150HP (ram extruded) which are currently the most frequently used materials in THR were studied in pin-on-plate wear test. The wear particles generated from this test were observed by scanning electron micrograph and analysed by image analysis. The results from this study showed that GUR 4150HP had superior wear resistance than GUR 1120 under relatively high wear factor conditions. These results also highlighted the importance of multidirectional motion and its effect on the wear rates of UHMWPE. The multidirectional motion tended to show a higher wear factor than previous studies using unidirectional motion conducted under otherwise similar conditions. The wear debris analysis conducted with the wear particles collected from unidirectional (relatively rough) pin-on-plate wear tests (GUR 1120 and GUR 4150HP) showed that the greatest number of particles had a size range of 0.1-0.5 micron followed by 0.5-1.0 micron, 1.0-5.0 microns and 5.0-10.0 microns, in both GUR 1120 and GUR 4150HP. However, comparing the masses of the wear particles, the bigger size range of greater than 10 microns, had the highest percent mass followed by 1.0-5.0 microns, 0.5-1.0 micron, 0.1-0.5 micron and 5.0-10.0 microns.

Biocompatible Materials↗
PubMed1999

An experimental model of tibial counterface polyethylene wear in mobile bearing knees: the influence of design and kinematics.

Current designs of mobile bearing knees have different kinematics at the tibial counterface articulation; unidirectional represented by linear tracks and rotating platform designs, and multidirectional represented by reduced constraint designs with motion of the tibial surface in A-P and M-L directions simultaneously. One fifth scale experimental models of the tibial counterface articulation have been developed with mean contact stresses of 0.6 MPa. The unidirectional model had a linear reciprocating motion with a 10 mm stroke, the multidirectional model had a reciprocating motion with a 10 mm stroke and simultaneous rotation of +/- 7.5 degrees. Six specimens of GUR415 polyethylene were tested for each model, sliding on polished cobalt chrome counterfaces with Ra < 0.01 micron in 25% bovine serum lubricant. The mean +/- STERR wear rates were: unidirectional 0.045 +/- 0.015 mm3/million cycles and multidirectional 0.44 +/- 0.15 mm3/million cycles. Applying the scaling factor of 5, the predicted wear rates in actual knee prostheses were: unidirectional 0.23 mm3/million cycles and multidirectional 2.2 mm3/million cycles. The order of magnitude increase in wear rate was statistically significant (p = 0.05).

Arthroplasty, Replacement, Knee↗
PubMed1998

Chorioamnionitis: the association between clinical and histological diagnosis.

Objective: To determine the association between clinical and histological diagnoses of chorioamnionitis.Methods: A retrospective 9-year review of hospital records for all perinatal deaths (N = 804) occurring at a Western New York regional perinatal center between 1988 and 1996 was conducted. Information concerning clinical indicators of chorioamnionitis were recorded including: maternal fever, leukocytosis, uterine tenderness, foul smelling discharge, and fetal tachycardia. Histological examination of the placenta was conducted in 797 of 804 perinatal deaths and staged by a standardized method. Type and number of clinical signs and symptoms were correlated with severity of histologic grade to determine their relation.Results: Chorioamnionitis was diagnosed either clinically or histologically in 243 (30.5%) of 797 perinatal deaths. Of these, 72 cases (23.5%) occurred in the 307 fetal deaths and 171 (34.9%) occurred in the 490 neonatal deaths. Five cases were diagnosed only on autopsy. In 51 of 243 cases (21%) there was histologic confirmation of chorioamnionitis without any clinical indicators present. In 13 of 243 cases (5.4%) there were 1 or more clinical indicators of chorioamnionitis without histologic confirmation. Sensitivity and specificity for 1 or more clinical indicators was 77.8% and 97.7%, respectively.Conclusion: Chorioamnionitis was present in 30.5% of perinatal deaths in this cohort. Identification of one or more clinical signs or symptoms was found to be both a sensitive and specific screening method for a presumptive diagnosis of chorioamnionitis when using histologic confirmation as the gold standard.

Journal Article↗
PubMed1998

Association of germline p53 mutation with MLL segmental jumping translocation in treatment-related leukemia.

Segmental jumping translocations are chromosomal abnormalities in treatment-related leukemias characterized by multiple copies of the ABL and/or MLL oncogenes dispersed throughout the genome and extrachromosomally. Because gene amplification potential accompanies loss of wild-type p53, we examined the p53 gene in a case of treatment-related acute myeloid leukemia (t-AML) with MLL segmental jumping translocation. The child was diagnosed with ganglioneuroma and embryonal rhabdomyosarcoma (ERMS) at 2 years of age. Therapy for ERMS included alkylating agents, DNA topoisomerase I and DNA topoisomerase II inhibitors, and local radiation. t-AML was diagnosed at 4 years of age. The complex karyotype of the t-AML showed structural and numerical abnormalities. Fluorescence in situ hybridization analysis showed multiple copies of the MLL gene, consistent with segmental jumping translocation. A genomic region including CD3, MLL, and a segment of band 11q24 was unrearranged and amplified by Southern blot analysis. There was no family history of a cancer predisposing syndrome, but single-strand conformation polymorphism (SSCP) analysis detected identical band shifts in the leukemia, ganglioneuroma, ERMS, and normal tissues, consistent with a germline p53 mutation, and there was loss of heterozygosity in the ERMS and the t-AML. Sequencing showed a CGA-->TGA nonsense mutation at codon 306 in exon 8. The results of this analysis indicate that loss of wild-type p53 may be associated with genomic instability after DNA-damaging chemotherapy and radiation, manifest as a complex karyotype and gene amplification in some cases of t-AML.

Acute Disease↗
PubMed1998

Mutational analysis of stem-loops in the RNA packaging signal of the Moloney murine leukemia virus.

The retroviral RNA genome is targeted for incorporation into the nascent virion particle by the psi region, a specific block of RNA sequences near the 5' end. A number of deletions and linker insertion mutations were introduced into the psi region of cloned DNA of the Moloney murine leukemia virus, and the mutants were introduced into cells in culture and tested for their ability to direct the assembly of virions and the packaging of viral RNA. Only a small portion of the psi region was important for packaging, containing the so-called stem-loops C and D. Additional mutants were used to demonstrate that the base pairing of stem D, and the sequence of loop D, were essential for normal packaging of the RNA. Two mutants with alterations near the 5' splice donor were also replication-defective, probably due to effects on gene expression. The results allow a high-resolution definition of the RNA structures required during virus replication in culture.

3T3 Cells↗
PubMed1998

Increased 9-aminocamptothecin dose requirements in patients on anticonvulsants. NABTT CNS Consortium. The New Approaches to Brain Tumor Therapy.

BACKGROUND: High grade astrocytomas remain uniformly fatal despite aggressive surgery and radiotherapy. As existing chemotherapeutic agents are of limited benefit, clinical trials are underway to screen new drugs, such as 9-aminocamptothecin (9-AC), for activity in high grade astrocytomas. PURPOSE: This study was designed to estimate the efficacy of 9-AC in patients with newly diagnosed glioblastoma multiforme and recurrent high grade astrocytomas. The planned dose of 9-AC for this trial was 850 microg/m2 per 24 h as a 72-h continuous intravenous infusion every 2 weeks. This was the maximum tolerated dose (MTD) on this schedule in multiple phase I studies in patients with systemic malignancies. However, we found this dose subtherapeutic in our patient population. As a result, the purpose of the study was altered to determine the MTD. METHODS: A group of 32 patients were studied using 850 microg/m2 per 24 h with a provision to escalate to 1000 microg/m2 per 24 h if the first three cycles of 9-AC were without significant hematologic toxicity. Once it was determined that myelosuppression did not occur in patients on anticonvulsants, dose escalations were initiated using the continual reassessment method. Dose escalations were conducted independently in newly diagnosed and recurrent patients and in those taking and not taking hepatic enzyme-inducing anticonvulsants. Pharmacologic studies were conducted during the first cycle of 9-AC. Toxicity was determined using the NCI common toxicity criteria and efficacy was assessed using serial volumetric brain scans. RESULTS: 9-AC was administered to 59 patients, 31 with newly diagnosed glioblastoma multiforme and 28 with recurrent high grade astrocytomas. No grade III-IV myelosuppression was noted in the 29 patients (128 cycles) on phenytoin, carbamazepine, phenobarbital, and/ or valproic acid who received 850 microg/m2 per 24 h. In contrast, two of three patients (five cycles) who were not taking anticonvulsants developed grade IV myelosuppression. Steady-state total 9-AC plasma levels were lower in patients on anticonvulsants (median 25.3 nM) than in patients who were not taking anticonvulsants (median 76.5 nM). Dose escalations performed in 27 additional patients determined the MTD in patients taking anticonvulsants to be 1776 microg/m2 per 24 h for patients with newly diagnosed tumors and 1611 microg/m2 per 24 h for patients with recurrent disease. CONCLUSIONS: We describe a new and unexpected drug interaction between 9-AC and anticonvulsants. This is similar to recent findings with paclitaxel, and suggests that higher than "usual" doses of some chemotherapeutic agents are required in patients on anticonvulsants. Prospectively defined dose escalations and pharmacologic studies are essential for the careful evaluation of new chemotherapeutic agents in patients with brain tumors.

Adolescent↗
PubMed1998

A comparative tribological study of the wear of composite cushion cups in a physiological hip joint simulator.

A composite cushion acetabular cup for a total hip replacement has been designed and developed jointly by Leeds University and DePuy International. In order to assess the long-term performance of this novel design, two sets of simulator tests of more than 4 million cycles duration have been carried out with the cushion bearings using the Leeds PA hip joint simulator with bovine serum as the lubricant. The results of these simulator tests were compared to the results from a previously reported study that used 32 mm ultrahigh molecular weight polyethylene (UHMWPE) acetabular cups. Under a physiological walking cycle simulation, with continuous cyclic motion and loading, the composite cushion cups produced negligible wear compared to a volumetric wear rate of 32 mm3 per million cycles for the conventional UHMWPE acetabular cups. This study has demonstrated for the first time the beneficial effects of fluid film lubrication in reducing wear in composite cushion acetabular cups.

Animals↗
PubMed1998

Activity-stress induces atrophy of apical dendrites of hippocampal pyramidal neurons in male rats.

Recently, researchers have demonstrated the damaging effect of restraint-stress on hippocampal neurons. The purpose of the present study was to determine if a more chronic stressor, i.e., activity-stress (A-S), would also result in hippocampal dendritic atrophy. When activity-stress (n = 6) rats showed evidence of the criteria "stress symptoms" (after an average of 6 days), they were sacrificed and their brains were quickly removed, blocked, and placed in Golgi-Cox solution. Food-yoked control animals (n = 6) were sacrificed on the following day. Serial coronal sections (150 um) of the rostral hippocampus were cut so that the CA3 and CAI areas could be analyzed. Stressed short-shaft neurons were significantly shorter and had fewer branch points in CA1 and CA3 neurons than the control neurons. A similar nonsignificant trend was observed in long-shaft neurons. These data suggest that a short period of chronic stress (6 days as opposed to 21 days in prior studies) induces neuronal atrophy in the hippocampus.

Animals↗
PubMed1998

Polyethylene particles of a 'critical size' are necessary for the induction of cytokines by macrophages in vitro.

Particulate wear debris from total hip prosthetic components can stimulate macrophages to produce mediators of osteolysis which may cause aseptic implant loosening. This study evaluated the in vitro response of murine peritoneal macrophages to polyethylene particles of definitive size distributions at varying volume doses. Ceridust 3615 polyethylene particles with a mean size of 0.21, 0.49, 4.3 and 7.2 microm and GUR 120 polyethylene resin with a mean size of 88 microm were co-cultured with C3H murine peritoneal macrophages at volume (microm)3 to cell number ratios of 100:1, 10:1, 1:1 and 0.1: 1. The secretion of IL-6, IL-1beta and TNF-alpha was determined by ELISA. Significantly elevated levels of TNF-alpha and IL-1beta were determined at 100:1 ratios when the macrophages were challenged with particles with a mean size of 0.49, 4.3 and 7.2 microm, and at 10:1 ratios for particles with a mean size of 0.49 and 4.3 microm. IL-6 production was significantly elevated at 100:1 ratios for mean particle sizes of 0.49 and 4.3 microm. Particles outside this range produced considerably less cytokine suggesting that both the size and volume (or number) of polyethylene particles are critical factors in macrophage activation. Therefore particles in the phagocytosable size range of 0.3-10 microm appear to be the most biologically active.

Animals↗
PubMed1998

Investigation into the effects of proteins and lipids on the frictional properties of articular cartilage.

The aim of this study was to investigate the effects of the proteins and the lipids on the frictional properties of articular cartilage in the mixed and boundary lubricating regimes. Bovine articular cartilage that had been treated to remove the lipids, and cartilage that had been treated to remove the proteins, from the surface layer were studied in order to investigate differences in their lubricating abilities. Tests were carried out on a sliding friction rig under contact pressures of 0.5 and 4 MPa. The results of the friction tests carried out under the 4 MPa contact pressure showed a slight increase in friction coefficient for both the lipid and the protein deficient cartilage when compared with the control cartilage. These differences were more apparent at the shorter loading times but none of the differences were found to be statistically significant. The tests at the lower contact pressure of 0.5 MPa showed that removing the lipids by washing the surface with detergent increased the friction coefficient at the shorter loading times but had no effect at the longer loading times. Digesting the cartilage with trypsin to remove the proteins from the surface layer had no effect on the friction coefficient at the shorter loading times but reduced the friction coefficient at the longer loading times. Both these results were confirmed with specimens that had both the lipids and the proteins removed from the surface layer.

Animals↗
PubMed1998

Overgrowth of a leukemic culture by a minor CD34+ population.

We have investigated the differentiation potential of blast cells in a case of acute myeloid leukemia which comprised a majority CD34- population and a minor (2%) CD34+ fraction. Blasts were cultured for 2 weeks in a combination of cytokines--c-Kit ligand, interleukin 3 and granulocyte macrophage colony-stimulating factor (SIGm mix)--together with all-trans retinoic acid or 1alpha ,25-dihydroxy vitamin D3. Maturation of blasts was assessed by morphology on Romanowsky-stained slides, changes in surface CD markers and clonogenic culture. After 7 days of culture of unseparated blasts in SIGm, most maturation was monocytic, but with retinoic acid 63% of blasts had matured into granulocytes. Vitamin D3 enhanced monocytic differentiation, with 60% of cells becoming monocytic. The percentage of CD14 and CD15 positive cells decreased over 7 days in SIGm (from 62% to 17% and from 76% to 39% for CD14 and CD15, respectively). CD14+ cell numbers were maintained, or recovered, in cultures supplemented with vitamin D3 (59% at day 7), and CD15+ cell numbers, too, remained unchanged in the presence of retinoic acid (67%) or vitamin D3 (66%). Aberrant markers CD7 and CD56 declined under any conditions. When separated, both the CD34- and CD34+ fractions showed similar changes in morphology and surface maturation markers, suggesting that these two populations may be closely related. However, only a few CD34+ cells expressed the aberrant markers present on the majority blast population. The CD34- population declined in culture while the CD34+ fraction rapidly expanded. This probably reflects the difference in progenitor content; high numbers of colony-forming cells were concentrated in the CD34+ subpopulation. We conclude that both CD34- and CD34+ populations can differentiate but only the CD34+ fraction proliferates. Primitive clonogenic CD34+ cells from this patient may generate occasional aberrant CD34+ blasts which could then differentiate into the accumulating aberrant CD34- blast population.

Acute Disease↗
PubMed1998

Toso, a cell surface, specific regulator of Fas-induced apoptosis in T cells.

Fas is a surface receptor that can transmit signals for apoptosis. Using retroviral cDNA library-based functional cloning we identified a gene, toso, that blocks Fas-mediated apoptosis. Toso expression was confined to lymphoid cells and was enhanced after cell-specific activation processes in T cells. Toso appeared limited to inhibition of apoptosis mediated by members of the TNF receptor family and was capable of inhibiting T cell self-killing induced by TCR activation processes that up-regulate Fas ligand. We mapped the effect of Toso to inhibition of caspase-8 processing, the most upstream caspase activity in Fas-mediated signaling, potentially through activation of cFLIP. Toso therefore serves as a novel regulator of Fas-mediated apoptosis and may act as a regulator of cell fate in T cells and other hematopoietic lineages.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Telemedicine and wound care management.

Chronic wounds constitute a debilitating health care problem with significant clinical and social implications. Annual U.S. wound care costs are more than $20 billion and growing at 10% per year. The cost for these patients can be reduced dramatically by altering the wound care paradigm.

Chronic Disease↗