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Biomedical subjects

John Fisher

Publications and source records attributed to John Fisher.

50 records · Page 3Linked to original sources
PubMed2003

Comparison of the response of human peripheral blood mononuclear cells to challenge with particles of three bone cements in vitro.

This study compared the effects of different sizes of three clinically relevant endotoxin free bone cement particles on primary human macrophage TNF-alpha production in vitro. The bone cements used were CMW original, CMW1RO and Palacos R. The cement wear debris was generated aseptically and then sequentially filtered to produce the size ranges 0.1-1 microm, 0.1-10 microm, 1-10 microm and >10 microm. The debris was cultured with human peripheral blood mononuclear cells at particle volume (microm(3)) per cell ratios of 100:1, 10:1 and 1:1. TNF-alpha production was determined by ELISA and cell viability by MTT conversion. CMW1RO particles induced increased TNF-alpha production by PBMNCs when tested in the size range 0.1-1 microm, and also to a lesser degree in the sizes 0.1-10 microm and 1-10 microm at the particle volume (microm(3)) to cell number ratios of 100:1 and 10:1. The increase in TNF-alpha production induced by Palacos R debris was only observed with the particle size ranges less than 10 microm at the ratio of 100:1. This study demonstrated that bone cement particles are capable of inducing raised TNF-alpha production in vitro. This is dependent upon cement particle size, volume and cement particle type, with cement particles containing radio-opaque additives being the most active.

Cell Adhesion↗
PubMed2003

Severe wear and fracture of zirconia heads against alumina inserts in hip simulator studies with microseparation.

The wear of zirconia femoral heads against alumina acetabular inserts with swing-phase microseparation was investigated in a hip joint simulator. Under mild microseparation conditions, the wear was very low, with an average wear rate of 0.05 mm(3)/million cycles reported over 5 million cycles of testing. However, under severe microseparation conditions representative of greater joint laxity, the wear rate of zirconia against alumina increased by 2 orders of magnitude, producing severe wear and, in one case, femoral head fracture. The adverse results of this study indicate that the combination of a zirconia femoral head articulating against an alumina acetabular insert is not recommended for clinical use. The results further raise concerns over the suitability of conventional simulators in evaluating the wear of ceramic hip prostheses.

Aluminum Oxide↗
PubMed2003

Kinematics of synthetic flexible leaflet heart valves during accelerated testing.

BACKGROUND AND AIMS OF THE STUDY: The study aim was to examine the effect of variation of test frequencies on the duration and kinematics of valve leaflets during opening, and at the fully open position. METHODS: Trileaflet polyurethane heart valves were tested in a Rowan Ash fatigue accelerator at 5, 10 and 15 Hz. Images of the valves were acquired using a high-speed camera and assessed qualitatively during opening and in the fully open position. The bending strains along the leaflet free edge and leaflet belly were also calculated from these images. Results were compared with those found at 1 Hz in a pulsatile flow simulator. The time duration of each phase of the cycle and the strain time integral when opening were also determined. RESULTS: In the fully open position, the maximum bending strain found at the commissural regions of the valve was not dependent on the cycle rate. During opening, one leaflet always deformed more than either of the others, but this leaflet was not necessarily the same one each time. The opening characteristics of the valves were dependent on cycle rate: increasing bending was observed in the belly of the leaflet with increasing frequency. The ratio of time of opening of the leaflets to time whilst fully open increased with the cycle rate, and the period of time when the valve was fully open and fully closed reduced markedly with increased cycle rate. CONCLUSION: Leaflet kinematics, bending strains, the proportion of time the valve was fully closed or open, and the strain time integral were dependent on cycle rate in accelerated testing. This may influence the relative severity of accelerated testers.

Acceleration↗
PubMed2003

Cement particles containing radio-opacifiers stimulate pro-osteolytic cytokine production from a human monocytic cell line.

Proponents of the biological theory of aseptic loosening have in recent years tended to concentrate on the production and distribution of particulate ultra-high-molecular-weight polyethylene (UHMWPE) debris around the potential joint space. However, mechanical loading of cemented implants with the differing elastic moduli of metal stems, polymethylmethacrylate (PMMA) cement and bone can result in relative micromotion, implying the potential for production of metal and PMMA particles from the stem-cement interface by fretting wear. In order to investigate the production and biological reactivity of debris from this interface, PMMA and metal particulate debris was produced by sliding wear of PMMA pins containing barium sulphate and zirconium dioxide against a Vaquasheened stainless steel counterface. This debris was characterised by SEM, energy-dispersive analysis by X-ray (EDAX) and image analysis, then added to cell cultures of a human monocytic cell line, U937, and stimulation of proosteolytic cytokines measured by ELISA. Large quantities of PMMA cement debris were generated by the sliding wear of PMMA pins against Vaquasheened stainless steel plates in the method developed for this study. Both cements stimulated the release of pro-osteolytic TNFalpha from the U937 monocytic cell line, in a dose-dependent fashion. There was a trend towards greater TNFalpha release with Palacos cement than CMW cement at the same dose. Palacos particles also caused significant release of IL-6, another pro-osteolytic cytokine, while CMW did not. The particulate cement debris produced did not stimulate the release of GM-CSF or IL1beta from the U937 cells. These results may explain the cytokine pathway responsible for bone resorption caused by particulate PMMA debris. Radio-opaque additives are of value in surgical practice and clinical studies to quantify the relevance of these in vitro findings are required before the use of cement containing radio-opacifier is constrained.

Biocompatible Materials↗
PubMed2002

Hydrodynamic function of the second-generation mitroflow pericardial bioprosthesis.

BACKGROUND: The hydrodynamic function of the smaller size Mitroflow Synergy stented pericardial bioprostheses has been studied in an in vitro fresh tissue aortic root model and compared with previous studies of free-sewn bioprostheses. METHODS: Three valves of each of the sizes 19, 21, and 23 mm were sutured into fresh tissue aortic roots and tested in a pulsatile flow simulator using two different ventricular input impedance conditions. A high-speed camera was used to study the leaflet opening and closing configurations. Mean pressure difference as a function of root mean square forward flow, effective orifice area, regurgitant volumes, and total energy loss across the valves was measured. RESULTS: Mean pressure difference with respect to root mean square forward flow decreased as the valve size increased. Thus effective orifice area increased as the valve size increased. The open leaflet configuration images showed that all three sizes of Mitroflow valves had a large circular orifice with minimal open leaflet deformation. All valves closed competently with no visible leakage and no closed regurgitant volume. The Mitroflow valves showed better effective orifice areas compared with previously tested frame-mounted porcine bioprostheses but lower effective orifice areas compared with porcine stentless bioprostheses; however, the open leaflet bending deformation was better than for any of the previously tested bioprosthetic valves. CONCLUSIONS: The hydrodynamic function of the Mitroflow Synergy stented pericardial bioprosthesis shows potential for good in vivo hemodynamic performance. The good hemodynamic performance combined with relative ease of implantation technique makes the pericardial valve a good valve in the aortic position, particularly in older patients with small annuli.

Animals↗
PubMed2002

The quantification of pulmonary valve haemodynamics using MRI.

The optimum slice location within the pulmonary root to quantify pulmonary valve haemodynamics was examined using magnetic resonance (MR) phase velocity mapping. MRI was carried out on 15 patients with congenital aortic valve disease. Although the patients had aortic valve disease, all measurements were made on the pulmonary valve. Systolic (Q(SYS)) and diastolic (Q(DIAS)) blood flow volume and cardiac index (CI) were determined at four pulmonary artery locations. The change in diastolic flow volume relative to slice 1, closest to the pulmonary valve, was also calculated. For a change in axial position of 1.5 cm, i.e. from 0.5 to 2 cm from the annulus, there was a change in diastolic flow volume of 4.4 ml. There was a significant increase in the mean diastolic flow from 3.4 to 7.7 ml (p = 0.01 between slice positions 0.5 and 2 cm. However, there was no significant change in CI, 3.4-3.7 l/min/m2 (p = 0.14) over the same distance. We believe that two factors are responsible for these results. The first is that of compliance, whose effects can be minimized by placing the MR slice close to the valve, however, this will not account for the second factor, being that of valve motion, and hence diastolic pulmonary valve flow or regurgitant volume will be underestimated. The degree of underestimation may only be important at mild and moderate levels of regurgitation or if changes in regurgitation are to be temporally measured.

Adolescent↗
PubMed2002

Comparison of the biological activity of grade GUR 1120 and GUR 415HP UHMWPE wear debris.

This study evaluated the in vitro response of murine macrophages to clinically relevant polyethylene particles from two grades of UHMWPE at varying volume doses. Clinically relevant UHMWPE wear debris was generated in vitro using a tri-pin-on-disc tribometer. The debris was observed using a scanning electron microscope and analysed by image analysis. There was no significant difference in the wear rates of the two grades of UHMWPE. Analysis of the wear debris showed that GUR 415HP produced a higher percentage of mass of debris in the submeter size range compared to GUR 1120. The wear debris was co-cultured with C3H murine peritoneal macrophages at particle volume (microm(3)): cell number ratios of 100 :1, 50 :1, 10 :1 and 1 :1 for both grades of UHMWPE and additionally at 0.5 :1 and 0.1 :1 for grade GUR 415HP. The secretion of TNF-alpha was determined by ELISA. Significantly elevated levels of TNF-alpha were secreted at 100 :1 ratio when macrophages were challenged with wear debris from GUR 1120 and at 10 :1 and 1 :1 for debris from GUR 415HP. The results suggested that the greater percentage mass of debris in the submicrometer size range from GUR 415HP lead to a substantial increase in biological activity for this grade of UHMWPE on a volume for volume basis when compared with GUR 1120.

Animals↗
PubMed2002

Tissue engineering of cardiac valve prostheses I: development and histological characterization of an acellular porcine scaffold.

BACKGROUND AND AIMS OF THE STUDY: Several deficiencies in current heart valve prostheses make them problematic for use in younger patients. Tissue valve substitutes are non-viable with a life expectancy of only 10-15 years, while mechanical valves require long-term anti-coagulation therapy. A solution to these problems would be to develop a tissue-engineered heart valve containing autologous cells, enabling the valve to maintain its biochemical and mechanical properties, yet grow with the patient. The study aim was to optimize a protocol to produce a porcine acellular matrix scaffold for use in developing a tissue-engineered heart valve. METHODS: Fresh porcine aortic valve leaflets were treated with Triton X-100, sodium dodecyl sulfate (SDS), sodium deoxycholate, MEGA 10, TnBP, CHAPS, and Tween 20, over a range of concentrations, in the presence of protease inhibitors for up to 72 h. Histological analysis was used to detect the major structural proteins of the heart valve, collagen I, elastin and glycosaminoglycans. RESULTS: After 72 h, most protocols resulted in the retention of large numbers of whole cells and cell fragments. Only SDS (0.03-1%) or sodium deoxycholate (0.5-2%) resulted in total decellularization at 24 h. Histological analysis of acellular matrices showed that the major structural proteins had been retained and appeared to be intact. CONCLUSION: Protocols utilizing SDS or sodium deoxycholate were successful for leaflet decellularization, and histological analysis showed that the major structural components of the valve matrix had been maintained. These methods are being developed further with a view to reseeding with autologous cells to produce tissue-engineered solutions for clinical implantation.

Animals↗
PubMed2002

Tissue engineering of cardiac valve prostheses II: biomechanical characterization of decellularized porcine aortic heart valves.

BACKGROUND AND AIMS OF THE STUDY: For both young patients with congenital heart disease and young, growing adults there is a need for replacement heart valves that will develop with the patient. Tissue-engineered heart valves coupled with in-vitro recellularization have this potential. One approach is to use acellular tissue matrices, but the decellularization treatment must not affect the biomechanical integrity of the valvular matrix. This study investigated the effect of 0.03% (w/v) and 0.1% (w/v) sodium dodecyl sulfate (SDS) on the mechanical integrity of porcine aortic valve leaflets. METHODS: Left coronary porcine leaflets were treated with SDS (0.03% or 0.1%, w/v) in hypotonic or isotonic buffer and buffer alone. SDS in hypotonic buffer produced accellularity. Circumferential and radial specimens of treated leaflets were subjected to uniaxial tensile testing, and the effect of the buffer on leaflet morphology was assessed. Whole porcine aortic roots were also treated with 0.1% (w/v) SDS and subjected to function testing. RESULTS: SDS treatment significantly increased extensibility of the leaflet specimens, which was greater in the circumferential than radial direction. This was seen as a significantly decreased slope of both the elastic and collagen phases of the stress-strain behavior. The ultimate tensile strength and transition stress were not affected significantly; nor was there any significant difference between hypotonic buffer and hypotonic buffer + SDS treatments. Study of the leaflet morphology suggested that the increased extensibility was due to shrinkage as well as to increased hydration of the treated leaflets caused by the hypotonic buffer. CONCLUSION: SDS treatment produced a more extensible tissue with equal strength compared with the fresh aortic valve. Functionality experiments with SDS-treated whole aortic roots showed complete valve leaflet competence under physiological pressures (120 mmHg) as well as physiological leaflet kinematics.

Animals↗
PubMed2002

The pulmonary bioprosthetic heart valve: its unsuitability for use as an aortic valve replacement.

BACKGROUND AND AIM OF THE STUDY: The porcine pulmonary bioprosthetic heart valve represents an alternative means of aortic valve replacement (AVR), though knowledge of its biomechanical function and characteristics is limited. The valve has potential advantages over the aortic bioprosthesis; notably, it lacks the muscular shelf of the right coronary cusp of the latter bioprosthesis. The study aim was to investigate the suitability of the porcine pulmonary bioprosthetic valve for AVR. METHODS: Porcine pulmonary and aortic roots were zero pressure-fixed with 0.5% buffered glutaraldehyde, characterized, and compared with fresh porcine pulmonary and aortic roots. The in-vitro analysis included assessment of mechanical properties, hydrodynamic function, geometry of the pulmonary root, and durability. RESULTS: The fixed pulmonary roots and fresh aortic roots were similar in certain aspects of mechanical response, notably leaflets in the radial direction and the root wall. The fixed pulmonary root was slightly more compliant than the fixed aortic root, and this led to an improvement in forward flow hydrodynamic function. The reverse flow hydrodynamic function of the pulmonary roots was poor; fresh pulmonary roots exhibited a trivial closed valve regurgitant volume. On fixation, this characteristic was aggravated, leading to a gross closed valve regurgitant volume in 50% of all fixed pulmonary roots. The cause of leakage was identified as a prolapsed anterior leaflet. Durability of the fixed pulmonary root was also inferior to that of the fixed aortic root; three fixed pulmonary roots subjected to accelerated fatigue testing showed signs of leaflet macroscopic damage. CONCLUSION: Overall, the performance of the porcine pulmonary bioprosthesis was far inferior to that of the currently used porcine aortic bioprosthesis. Hence, the porcine pulmonary bioprosthetic valve was deemed unsuitable for AVR.

Animals↗
PubMed1995

The anticoagulation factor protein S and its relative, Gas6, are ligands for the Tyro 3/Axl family of receptor tyrosine kinases.

We report the identification of ligands for Tyro 3 (alternatively called Sky, rse, brt, or tif) and Axl (alternatively, Ark or UFO), members of a previously orphan family of receptor-like tyrosine kinases. These ligands correspond to protein S, a protease regulator that is a potent anticoagulant, and Gas6, a protein related to protein S but lacking any known function. Our results are reminiscent of recent findings that the procoagulant thrombin, a protease that drives clot formation by cleaving fibrinogen to form fibrin, also binds and activates intracellular signaling via a G protein-coupled cell surface receptor. Proteases and protease regulators that also activate specific cell surface receptors may serve to integrate coagulation with associated cellular responses required for tissue repair and growth, as well as to coordinate protease cascades and associated cellular responses in other systems, such as those involved in growth and remodeling of the nervous system.

3T3 Cells↗
PubMedDate not supplied

Effective recruitment and retention of older adults in physical activity research: PALS study.

OBJECTIVES: To develop strategies to recruit and retain inactive older adults into a physical activity program. METHODS: Names of 7378 older adults were obtained from 60 neighborhoods. Then, 6401 potential subjects were matched to telephone numbers and phoned. Subjects meeting the screening criteria were invited to join the program (n = 4209). Walk leaders and social support were used to enhance retention. RESULTS: Five hundred seventy-three subjects were recruited (260 intervention and 313 control). The respective participation rate was 12.6% (260/2056) and 14.5% (313/2153), with low attrition of 31.9% (83/260) and 24.6% (77/313). CONCLUSION: Effective recruitment and retention strategies were identified.

Aged↗
PubMedDate not supplied

Improving access to clinical information in after hours community palliative care.

OBJECTIVE: To improve access to clinical information for nurses and doctors providing after hours community palliative care in a regional Australian setting. DESIGN: This was an action research project designed to improve collation and distribution of succinct, pertinent and timely information about unstable palliative care patients to nurses and general practitioners (GPs) involved in after hours care. Each week day, each patient's purpose-designed single-page information sheet was updated on the community palliative care service computers. This sheet was designed to give key abstracted information on each patient's history, current condition, treatment and plans for future care. Patients considered to be unstable had their sheets faxed to the GPs on call. SETTING AND SUBJECTS: This procedure was followed for all adult patients admitted to Ballarat Hospice Care Inc, Victoria, Australia between June and August 2004. The nurses and Executive Officer at Ballarat Hospice Care Inc and thirteen GPs from the Ballarat and District Division of General Practitioners were involved in the study. MAIN OUTCOME MEASURES: Surveys and feedback from palliative care nurses and GPs. RESULTS: A one-page information sheet provided essential clinical information to nurses and doctors. The nurses' confidence markedly increased with ready access to the information sheets on a hand held Palm Pilot. The nurses also reported improved outcomes for patients using this approach and there was favourable feedback from GPs. CONCLUSIONS: This project led to the development of a simple, effective and low cost means of improving communication between professionals caring for palliative care patients after hours.

Adult↗