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Biomedical subjects

J Fisher

Publications and source records attributed to J Fisher.

At least 235 records · Page 13Linked to original sources
PubMed1996

Polyarteritis nodosa with pulmonary vasculitis.

Although early postmortem series reported pulmonary involvement as a relatively common manifestation of polyarteritis nodosa (PAN), using the modern classification of PAN pulmonary involvement is very uncommon. A 62-yr-old male with well-documented classic PAN was found to have an arteritis of medium-sized muscular pulmonary arteries. The patient subsequently demonstrated a complete response to treatment. Of the few reported cases of PAN with pulmonary manifestations, the majority are autopsy series and the vascular lesion involves the bronchial arteries. There are no case reports of patients with pulmonary involvement of PAN who responded successfully to treatment. This case is the first description of a premortum diagnosis of pulmonary arteritis in PAN in which the patient had a response to treatment.

Alkylating Agents↗
PubMed1996

Ultra-high molecular weight polyethylene wear debris generated in vivo and in laboratory tests; the influence of counterface roughness.

The objective of this study was to investigate the effect of counterface roughness and lubricant on the morphology of ultra-high molecular weight polyethylene (UHMWPE) wear debris generated in laboratory wear tests, and to compare this with debris isolated from explanted tissue. Laboratory tests used UHMWPE pins sliding against stainless steel counterfaces. Both water and serum lubricants were used in conjunction with rough and smooth counterfaces. The lubricants and tissue from revision hip surgery were processed to digest the proteins and permit filtration. This involved denaturing the proteins with potassium hydroxide (KOH), sedimentation of any remaining proteins, and further digestion of these proteins with chromic acid. All fractions were then passed through a 0.2 micron membrane, and the debris examined using scanning electron microscopy. The laboratory studies showed that the major variable influencing debris morphology was counterface roughness. The rougher counterfaces produced larger numbers of smaller particles, with a size range extending below 1 micron. For smooth counterfaces there were fewer of these small particles, and evidence of larger platelets, greater than 10 microns in diameter. Analysis of the debris from explanted tissues showed a wide variation in the particle size distribution, ranging from below 1 micron up to several millimetres in size. Of major clinical significance in relation to osteolysis and loosening is roughening of the femoral components, which may lead to greater numbers of the sub-micron-sized particles.

Adult↗
PubMed1996

Determination of lubricating film thickness for permeable hydrogel and non-permeable polyurethane layers bonded to a rigid substrate with particular reference to cushion form hip joint replacements.

The lubricating film thickness in a model of compliant layered bearings, using both permeable hydrogels and non-permeable polyurethane elastomers for total hip joint replacements, has been measured using optical interferometry, under both entraining and squeeze-film motion. The film thickness in the lubricated contact was measured for both water and a 40 per cent glycerol solution in water as a function of entraining velocity and squeeze-film time. The measured lubricating film thickness for the permeable hydrogel was compared to that of the non-permeable polyurethane elastomer and little difference was found when the lubricating film thickness was sufficiently large (greater than 150 nm). Comparison of the experimental results and the theoretical predictions based upon elastohydrodynamic lubrication analysis showed good agreement in the entraining experiments where the film thickness was greater than 150 nm. In the squeeze-film experiments the experimental measurements were greater than the theoretical predictions for all squeeze times due to the formation of a central pocket of fluid which was not predicted by the simple theory used. This also occurred for the hydrogels for films greater than 150 nm. For longer squeeze times the film thickness for the hydrogel fell below the theoretical prediction. This was considered to be due to the permeability of the hydrogel reducing the film thickness when the film thickness was less than 150 nm. The permeability of the hydrogel was not modelled in the theoretical lubrication analysis used in this study.

Biomechanical Phenomena↗
PubMed1996

The influence of loading time and lubricant on the friction of articular cartilage.

Friction of cartilage on metal, metal on cartilage and cartilage on cartilage contact configurations, within a mixed lubrication regime, was measured using synovial fluid, Ringer's solution or with no lubricant present. The main test variable was the period of stationary loading which ranged from 5 s to 45 min, prior to sliding and consequently measuring friction. The coefficient of friction rose gradually with increasing stationary loading time, up to a value of approximately 0.3 at 45 min for all the contact configurations. Following the re-application of load, after short periods of load removal, friction was also found to drop sharply. The flow of liquid in the biphasic cartilage and load carriage by the fluid phase was highlighted as being an important factor in reducing friction within the mixed or boundary lubrication regime. Movement of the contact zone over the cartilage counterface ensured very low friction as the slider moved over fully hydrated cartilage. For the cartilage--cartilage contacts synovial fluid significantly reduced friction compared to Ringer's solution. This was attributed to an effective boundary lubrication action, which was not as effective for the cartilage--metal contacts.

Animals↗
PubMed1996

Finite element stress analysis of a new design of synthetic leaflet heart valve.

This paper presents a parametric finite element analysis of the stresses in the leaflets of a new design of polyurethane heart valve in the closed position. The alpharabola geometry of the valve has previously been reported by Leat and Fisher (1) and has been shown to demonstrate good opening characteristics. The effects of variations in leaflet offset parameter, g, length, h, and local thickening have been determined for a valve where the frame is assumed rigid. A spherical leaflet geometry has also been analysed for comparative purposes. Results have shown that the alpharabola leaflet geometry can reduce the maximum principal tensile stress to 60 per cent of that for a spherical valve of the same mesh density.

Biocompatible Materials↗
PubMed1996

The influence of open leaflet geometry on the haemodynamic flow characteristics of polyurethane trileaflet artificial heart valves.

In vitro velocity data were obtained downstream of two versions of the Leeds polyurethane trileaflet heart valve in a simulated pulsatile flow regime using laser Doppler velocimetry. The main difference between the two valves studied was the manufacturing method used to create the valves. The film-fabricated valve was constructed from solvent-cast sheets of polyurethane, thermally formed into the correct leaflet geometry. The dip-cast valve used a stainless steel mould which was dipped into a polyurethane solution to produce the valve leaflets. Significant differences were visible between the fully open leaflet shape of each valve. The distribution of mean axial velocity and Reynolds normal stress (RNS) was shown to be dependent on the shape of the fully open valve orifice. For the film-fabricated valves, flow recirculation and high values of RNS were present downstream of the frame posts. The maximum value of RNS obtained downstream of the film-fabricated valve at peak systole was 147 N/m2. Results for the dip-cast valve showed a more uniform distribution of mean axial velocity and RNS resulting from the more circular central orifice produced by the dip-cast leaflets. The maximum value of RNS obtained downstream of the dip-cast valve at peak systole was 109 N/m2. These results demonstrate the effect of the open valve geometry on the flow characteristics downstream of trileaflet valves and that minor changes to the open leaflet geometry can significantly affect the flow characteristics and the possibility of flow-related blood damage occurring in vivo.

Aortic Valve↗
PubMed1996

Psychological aspects of nipple pain in lactating women.

The aim of the study was to assess the psychological impact of nipple pain in lactating women. Forty-eight lactating women with nipple pain completed mood scales at their first visit and following resolution of their pain, and 65 lactating women without nipple pain completed one set of mood scales. At the first visit, the mean score on the Edinburgh Postnatal Depression Scale (EPDS) in the nipple pain group was 12.4 and the control group was 7.6 (p < 0.0001). Eighteen women (38%) scored above the threshold for depression (> 12), compared to nine in the control group (14%): p < 0.01. Following pain resolution, the mean score on the EPDS decreased to 7.3 (p < 0.001); and six women (16%) scored 13 or over on the EPDS, significantly less than initially (p < 0.05). Similarly, on the Profile of Mood States (POMS), the nipple pain group scored significantly higher than control group on all mood factors (Tension, Depression, Fatigue, Confusion, Vigor [lower]), except Anger which did not reach a level of significance. After pain resolution, POMS scores returned to similar levels as the control group. In conclusion, both the EPDS and POMS indicated women with nipple pain were experiencing high levels of emotional distress. However, once the pain had resolved their distress also resolved.

Adult↗
PubMed1996

Cell cycle-specific behavior of erythropoietin.

The murine erythropoietin-dependent erythroleukemia cell line, HCD-57, was employed to study the cell cycle-specific behavior of erythropoietin. Cell cycle duration for HCD-57 cells was approximately 12 hours and was uninfluenced by erythropoietin. Populations of HCD-57 cells synchronized in G1 by centrifugal elutriation were able to pass through one complete cell cycle in the absence of erythropoietin but, thereafter, arrested in G1 as identified by propidium iodide staining and flow cytometry. Analysis of cell cycle behavior using the metachromic dye acridine orange, however, revealed that HCD-57 cells pass through a G0 cell cycle phase and, like serum-deprived 3T3 cells, actually arrest in G0 when deprived of erythropoietin. Expression of the cell cycle regulatory protein p34cdc2 was invariant throughout the cell cycle in HCD-57 cells. p34cdc2 was constitutively phosphorylated in G0 cells, and this effect was not modified by erythropoietin. Erythropoietin receptor distribution was log normal in HCD-57 cells in each phase of the cell cycle. The affinity of these surface receptors for erythropoietin was essentially invariant throughout the cell cycle, but receptor expression was upregulated in G2M cells as compared with cells in G1 or S phase. Taken together, these data indicate that erythropoietin has an important role in the G0-G1 to S phase transition but, based on receptor expression, is involved in other phases of the cell cycle as well.

Animals↗
PubMed1996

Autologous MHC-dependent leukaemia-reactive T lymphocytes in a patient with chronic myeloid leukaemia.

We have investigated the presence of T cells capable of recognizing autologous leukaemia cells in a patient with CML. We demonstrated that these cells were anergic to the leukaemia cells. They were estimated to be present at a frequency of 1:4000 T cells in the peripheral blood. However, following incubation with high dose rIL-2, these effector cells were able to proliferate, secrete TH1 cytokines and lyse target cells upon challenging with fresh autologous leukaemia cells. Both CD4 and CD8 T cells were involved in the proliferative responses. Moreover, the immune response was blocked by monomorphic anti-HLA antibodies, suggesting that the MHC molecules are needed by the T cells for leukaemia cell/antigen recognition. This work therefore indicates a potential reservoir of effector cells in CML patients which may be exploited for the modulation of leukaemia cell growth. It also provides evidence for a distinct T cell population capable of mediating GVL responses.

Autoimmunity↗
PubMed1996

Bone marrow engraftment following unrelated donor transplantation utilizing busulfan and cyclophosphamide preparatory chemotherapy.

Two major problems of unrelated donor transplantation have been an increased incidence of GVHD and graft failure. Even with HLA identity by microlymphocytotoxicity assay and non-reactive MLC, URD marrow transplant recipients have a higher incidence of graft rejection and GVHD. The preparative regimen busulfan 16 mg/kg and cyclophosphamide 120 mg/kg (BuCy2) has been shown to be at least as effective in preparation of recipients with CML of HLA-identical sibling grafts as cyclophosphamide and total body irradiation (Cy/TBI). However, concern about a high rejection rate in URD transplants has prevented most centers from using BuCy2 in this setting. From March 1990 to March 1994, 26 patients underwent URD transplantation following preparation with BuCy2. Patients received either standard cyclosporine and methotrexate or cyclosporine and methylprednisolone for GVHD prophylaxis. Two patients died on day 16 and 20 without evidence of hematopoietic engraftment. Of the 24 patients evaluable for engraftment, 23 (96%) had evidence of donor engraftment defined as an ANC > 0.5 x 10(9)/1. No patient who had initial engraftment had late graft failure. Within our study group the risk of graft rejection or graft failure does not appear to be higher than that reported for URD transplants utilizing TBI-containing regimens.

Acute Disease↗
PubMed1996

Radiation sensitisation by nitric oxide releasing agents.

Previous studies have shown that nitric oxide (NO) sensitises hypoxic cells to ionising radiation. In the present study, four different nitric oxide (NO) donor agents were evaluated for both NO release and hypoxic radiosensitisation. The S-nitrosothiol NO donor agents, S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylpenicillamine (SNAP), were shown to release sustained NO concentrations (microM) and significantly radiosensitise hypoxic cells. The extent of hypoxic radiosensitisation by both of these agents at 1.0 mM concentration was similar to that obtained with molecular oxygen. In contrast, neither 3-morpholinosydnonimine (SIN-1) nor sodium nitroprusside (SNP) released detectable NO concentrations and neither agent enhanced the hypoxic radiation response to the extent of that observed for GSNO or SNAP. NO-mediated hypoxic cell radiosensitisation by NO donor drugs may offer a new approach for clinical consideration, particularly if such agents can be selectively delivered to hypoxic cells.

Animals↗
PubMed1996

An initial investigation into the wear and damage within the pivots of three types of bileaflet mechanical heart valves.

Two 29 mm St. Jude Medical valves, two 29 mm CarboMedics valves and two 29 mm Sorin Bicarbon valves were tested in a real time fatigue test rig. The test rig was run at 72 beats/min with a stroke volume of 70 ml for approximately one million cycles. Optical microscopy was used to investigate the valve surfaces. Possible deterioration of the surface finish was observed on the stops of the hinge recesses in the St. Jude Medical and CarboMedics valves. In the Sorin valves areas of the pyrolytic carbon coating was worn away adjacent to and on the valve stops.

Biocompatible Materials↗
PubMed1996

Effect of FE idealisation, load conditions and interface assumptions on the stress distribution and fatigue notch factor in the human femur with an endoprosthesis.

The load transferred through the hip joint is one of the major forces occurring in the human body. After the replacement of this joint in THR arthroplasty, the load is transferred through the implant to the femoral bone. Loosening of the fixation of the implant and the fatigue failure of prosthetic stems create problems for both patient and surgeon. Both problems can be reduced by the use of Finite Element (FE) analysis to predict stresses and fatigue lifes but the results are sensitive to assumptions regarding the loading conditions and the idealisation of the components. Consequently the stress distributions and resulting fatigue notch factors in the human femur with an endoprosthesis have been determined for different assumptions regarding the form of the idealisation, the load conditions, and the interface conditions. The FE results show that a realistic loading condition without a tension banding force always produces the highest fatigue notch factor and von Mises stresses. An equivalent 2D plane stress model obtained by varying the thickness is likely to give more realistic stresses because it predicts more realistic strains than other 2D approximations. The full bonded interface is a satisfactory approximation for the real interface conditions because it predicts stress distributions of the correct form without excessive stress concentration.

Bone Cements↗
PubMed1996

Shape optimisation of a Charnley prosthesis based on the fatigue notch factor.

The femoral component of the artificial hip joint implanted in a patient's femur is subjected to a complex set of forces exerted due to normal life activities. It is thought that high values of stress in the cement in a cemented prosthesis can lead to fractures of the cement mantle and loosening of the stem. The incidence of such problems may be diminished by reduction of the fatigue notch factor in the cement, such that stress concentrations are avoided and the crack initiation time maximised. This study describes a method for numerical shape optimisation to determine an optimal shape for the femoral stem of a hip prosthesis in order to minimise the fatigue notch factor in the cement layer at the interfaces with the bone and stem whilst at the same time maintaining or increasing the stress levels in the proximal medial femoral bone to help prevent stress shielding. The method when used to optimise the shape of a stainless steel Charnley stem was found to be extremely efficient and effective. The resulting optimal shape was heavily waisted in the proximal region below the neck but distally was quite similar to the original design. The fatigue notch factors in the cement were reduced by 16% and 19% for medial and lateral cement/stem interfaces, respectively, and by 8% and 2% for the corresponding cement/bone interfaces. The fatigue notch factor in the proximal medial bone was increased by 57% which indicates that the general stress level in this region is markedly increased. Thus the optimised design should increase the fatigue life of the cement and at the same time reduce stress shielding in the proximal bone. Both of these effects may help prevent loosening of the femoral component and hence reduce the need for early revision operations.

Aged↗
PubMed1995

Enhanced glutathione peroxidase expression protects cells from hydroperoxides but not from radiation or doxorubicin.

Both radiation and anthracycline antibiotics may produce reactive oxygen species to cause cytotoxicity, and it has been suggested that some cellular antioxidant enzymes may be important for resistance to these agents. The human breast adenocarcinoma cell line MCF-7WT has a low level of glutathione peroxidase (GPX) activity. We have transfected MCF-7WT cells with a plasmid that contains the cDNA for human GPX under the transcriptional control of the human metallothionein IIA promoter. One transfected clone, MCF-GPX-6, contained multiple copies of GPX cDNA/cell and, after exposure to heavy metals, expressed a level of GPX enzyme activity that was 40-fold higher than that present in MCF-7WT cells and comparable to the GPX activity contained in the doxorubicin-resistant MCF-7DOX cell line. No differences in levels of glutathione, catalase, superoxide dismutase, glutathione S-transferase, or glutathione reductase were noted in MCF-GPX-6 cells compared to MCF-7WT cells. MCF-GPX-6 cells were relatively resistant to hydrogen peroxide and tert-butylhydroperoxide compared to MCF-7WT cells, e.g., exposure of both cell lines to 750 microM H2O2 for 1 h resulted in a relative surviving fraction of 0.07 for MCF-7WT and 0.35 for MCF-GPX-6 cells. However, no difference in sensitivity to either radiation or doxorubicin was noted between MCF-7WT and MCF-GPX-6 cells. These results suggest that GPX is not important for the development of cellular resistance to either radiation or doxorubicin.

Antibiotics, Antineoplastic↗
PubMed1995

Noncovalent binding of a mitomycin C metabolite, 2,7-diaminomitosene, to duplex DNA.

The major metabolite of mitomycin C, 2,7-diaminomitosene (DAM), interacts noncovalently with DNA. This was supported by ultraviolet-visible spectrum changes upon mixing with DNA and ethidium bromide displacement from DNA, measured as fluorescence changes. Moreover, DAM bound to DNA sufficiently strongly to hold DNA in a double stranded conformation under denaturing gel electrophoresis conditions commonly used to measure mitomycin C cross-links. These data show that generation of DAM and interaction with DNA represent a potential additional mechanism of DNA damage induced by mitomycin C.

Alkylation↗
PubMed1995

Cloning, characterization, and development expression of a rat lung alveolar type I cell gene in embryonic endodermal and neural derivatives.

We report here the identification and characterization of a novel gene, T1 alpha, expressed in high abundance in adult rat lung, fetal lung, and early fetal brain. T1 alpha was identified by a monoclonal antibody previously shown to be specific for an antigen expressed by alveolar epithelial type I cells. The cDNA for T1 alpha is 1.85 kb and identifies a single mRNA species of the same size on Northern blots of adult rat lung. The longest open reading frame of the cDNA is 498 bases which would encode a protein of approximately 18 kDa. The protein has a putative membrane spanning domain near the C-terminus but lacks consensus sequences for N-glycosylation. Northern blots and RT-PCR show high expression of T1 alpha in adult lung, with marginally detectable expression in adult brain, intestine, and kidney. RT-PCR analysis shows expression of T1 alpha in freshly isolated type I cells (50-60% purity) but not in highly purified type II cells or other lung cells. We believe therefore that T1 alpha is primarily if not uniquely expressed in alveolar type I cells in the adult rat. Polyclonal antisera against a 16-amino-acid peptide identified in the deduced sequence reacts with the apical membranes of adult type I cells in lung tissue sections but does not label other cell types. The above antiserum as well as the original monoclonal antibody recognize a single approximately 18-kDa protein derived from bacterial expression of a construct containing the T1 alpha open reading frame. By RT-PCR T1 alpha is detected in rat lung from Day 13.5 onward, but is detected by in situ hybridization earlier in lung, brain and neural derivatives, and foregut. Expression is down-regulated in all but lung tissues as development proceeds.

Amino Acid Sequence↗