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Biomedical subjects

John Fisher

Publications and source records attributed to John Fisher.

At least 37 records · Page 2Linked to original sources
PubMed2005

The osteolytic response of macrophages to challenge with particles of Simplex P, Endurance, Palacos R, and Vertebroplastic bone cement particles in vitro.

The capacity of clinically relevant wear particles from Simplex P, Endurance, Vertebroplastic and Palacos R bone cements to activate macrophages to produce cytokines and bone resorbing activity in vitro was compared. Cement particles were generated aseptically by using a pin on plate rig. The particles were irregular in shape, and there were no significant differences in the particle characteristics of the different bone cement types (mean equivalent circle diameter range 0.225--0.36 mum, mean area range 0.048--0.063 microm(2), mean aspect ratio range 1.481--1.593, and mean length 0.412--0.523 microm). The volumetric concentration of particles in the 0.1- to 1.0-microm size range was 85% Palacos R, 82% Endurance, 80% Simplex P, and 77% Vertebroplastic. Particles were cultured with C3H macrophages at 100 microm(3) per cell for 24 h. Cytokines were determined by enzyme-linked immunosorbent assay and bone resorption (BR) measured by Ca(45) release from murine calvarias. Particles of Palacos R and Endurance stimulated enhanced production of TNF-alpha, IL-1-beta, and IL-6 (p<0.05; ANOVA). Simplex P particles only stimulated IL-1-beta (p<0.05; ANOVA). Vertebroplastic particles did not stimulate production of any of the cytokines. Particles of Palacos R generated the highest BR (1.38), but this did not reach statistical significance. The BRs for the other bone cements were no greater than the control. Hence, compared with the same volumetric concentrations, particles of Palacos R and Endurance were the most, and particles of Vertebroplastic were the least biologically reactive.

Animals↗
PubMed2005

A unifying approach to registration, segmentation, and intensity correction.

We present a statistical framework that combines the registration of an atlas with the segmentation of magnetic resonance images. We use an Expectation Maximization-based algorithm to find a solution within the model, which simultaneously estimates image inhomogeneities, anatomical labelmap, and a mapping from the atlas to the image space. An example of the approach is given for a brain structure-dependent affine mapping approach. The algorithm produces high quality segmentations for brain tissues as well as their substructures. We demonstrate the approach on a set of 22 magnetic resonance images. In addition, we show that the approach performs better than similar methods which separate the registration and segmentation problems.

Algorithms↗
PubMed2005

Long-term clinical, radiological and histopathological follow-up of a well-fixed Mckee-Farrar metal-on-metal total hip arthroplasty.

Metal-on-metal is one potential bearing option for total hip arthroplasty (THA). Proponents of the bearing have suggested that if the tribology is optimal, volumetric wear may occur at levels at least one order of magnitude lower than metal-on-polyethylene bearings. We present a unique postmortem case of a well fixed, metal-on-metal, McKee-Farrar total hip arthroplasty implanted 30 years previously that was clinically asymptomatic in life. Clinical and radiological examination is supplemented by tribological examination of the bearing and histopathological examination of the cement-bone interface.

Arthroplasty, Replacement, Hip↗
PubMed2005

The role of macrophages in osteolysis of total joint replacement.

The osteolysis associated with conventional polyethylene on metal total joint replacements is associated with the formation of an inflamed periprosthetic membrane rich in macrophages, cytokines and implant-derived wear particles. There is a wealth of evidence to indicate that the presence and activation of macrophages in the periprosthetic tissues around joint replacements is stimulated by UHMWPE particles. Particles within the size range 0.1-1.0 microm have been shown to be the most reactive. Animal studies have provided increasing evidence that, of the milieu of cytokines produced by particle-stimulated macrophages, TNF-alpha is a key cytokine involved in osteolysis. Recent advances in the understanding of the mechanisms of osteoclastogenesis and osteoclast activation at the cellular and molecular level have indicated that bone marrow-derived macrophages may play a dual role in osteolysis associated with total joint replacement. Firstly, as the major cell in host defence responding to UHMWPE particles via the production of cytokines and secondly as precursors for the osteoclasts responsible for the ensuing bone resorption.

Animals↗
PubMed2005

Severe left ventricular systolic dysfunction increases atrial fibrillation after ablation of atrial flutter.

BACKGROUND: Atrial fibrillation (Afib) that occurs after a successful atrial flutter (AFL) ablation may negate the potential benefits of the ablation. Afib occurs more often when severe left ventricular systolic dysfunction (LVSD) is present. We hypothesized that even after a successful AFL ablation, the incidence of postablation Afib is increased when severe LVSD is present. METHODS: Ninety consecutive patients with LVSD who underwent ablation for AFL at Montefiore Medical Center from August 2001 to January 2005 were classified according to the severity of LVSD. Group 1 (n = 36) consisted of patients with EF < or = 35%, and group 2 (n = 54) consisted of patients with EF 36-55%. There were no statistically significant differences in baseline patient characteristics between the two groups. RESULTS: During a mean follow up of 350 days, Afib occurred in 31% (n = 11; 8 with prior history of AFib) in group 1, and 7.4% (n = 4; all with prior history of Afib) in group 2. Cumulative probability of remaining Afib-free in group 1 versus group 2 was 75% versus 96% at 365 days, and 69% versus 91% at 600 days (P = 0.01). A prior history of Afib did not interact with EF when analyzed with a logistic regression analysis. CONCLUSION: After an AFL ablation, the incidence of Afib is increased, and the probability of remaining free of Afib is decreased, when severe LVSD is present, independent of a prior history of Afib. This finding may have implications for optimal patient selection for AFL ablation, and the use of adjunctive therapies.

Atrial Fibrillation↗
PubMed2005

A multilevel analysis of change in neighborhood walking activity in older adults.

The article reports on a multilevel analysis conducted to examine change in neighborhood walking activity over a 12-month period in a community-based sample of 28 neighborhoods of 303 older adults age 65 and over. The study employed a multilevel (residents nested within neighborhoods) and longitudinal (4 repeated measures over 1 year) design and a multilevel analysis of change and predictors of change in neighborhood walking activity. Results indicated a significant neighborhood effect, with neighborhood-level walking characterized by a downward trajectory over time. Inclusion of baseline variables using selected perceived neighborhood-level social- and physical-environment measures indicated that neighborhoods with safe walking environments and access to physical activity facilities had lower rates of decline in walking activity. The findings provide preliminary evidence of neighborhood-level change and predictors of change in walking activity in older adults. They also suggest the importance of analyzing change in physical activity in older adults from a multilevel or macrolevel framework.

Aged↗
PubMed2005

Evaluation of training on the use of Graseby syringe drivers for rural nonspecialist nurses.

AIM: to assess the impact of a training programme on nurse confidence in: setting up the Graseby syringe driver (GSD); explaining the GSD to patient and family; setting the rate on the GSD; putting appropriate type and dose of drugs in the GSD. STUDY DESIGN: training programme with pre-training, post-training and follow-up questionnaires. SAMPLE AND SETTING: palliative care nurse consultants presented half-day training sessions to 270 non-specialist nurses throughout the rural Grampians Health Region of Victoria, Australia. Nurses were from rural acute and sub-acute care settings, aged care facilities, and district nursing and nurse education services. MEASUREMENTS: demographic details of participants, previous experience and training with GSDs, comparative analyses of the four confidence parameters and participants' assessment of interest, new knowledge and usefulness of the training programme. RESULTS: increases in confidence levels were found in participating nurses in relation to each of the four confidence parameters. A follow-up survey tested residual benefit three months after the training programme. Statistically significant variations were found in nurses' confidence levels in relation to frequency of use. CONCLUSIONS: regular use of, and/or refresher sessions about the GSD are recommended to maintain optimum confidence, effective and safe nursing use of the GSD in palliative care.

Education, Nursing, Continuing↗
PubMed2005

Biocompatibility and recellularization potential of an acellular porcine heart valve matrix.

BACKGROUND AND AIM OF THE STUDY: Tissue-engineered heart valves have the potential to overcome the limitations of present heart valve replacements. The study aim was to investigate the biocompatibility and recellularization potential of an acellular porcine valve matrix. METHODS: Acellular porcine valve matrix contact and extract cytotoxicity was tested against porcine fibroblasts and smooth muscle cells (SMC). Porcine cells were incubated with decellularized aortic valve leaflets and aortic wall, and then assessed for changes in morphology and contact inhibition of growth. Soluble tissue extracts were prepared from decellularized leaflets and aortic wall, and assessed for their effect on the viability of cultured porcine cells. Acellular leaflets were seeded with either fibroblasts or SMC at 1 x 10(3) to 1 x 10(6) cells/cm2 for 24 h, or 5 x 10(4) cells/cm2 for 1-4 weeks. Cell attachment onto, and migration into, the acellular matrix was assessed by scanning electron microscopy and histology. RESULTS: No contact inhibition of growth, or changes in fibroblast or SMC morphology, were observed following contact with the acellular valve matrix. No soluble extract cytotoxicity was found. Intermediate cell-seeding densities (2.5 x 10(4) to 7.5 x 10(4) cells/cm2) of both cell types produced confluent cell attachment; at the lowest concentration (1 x 10(3) cells/cm2) cell attachment was sparse, and at the highest (1 x 10(6) cells/cm2) it was multilayered. The SMC migrated throughout the leaflet matrix over four weeks, but there was no fibroblast migration into the matrix. CONCLUSION: The absence of contact and extract cytotoxicity indicated that the acellular valve matrix was biocompatible in vitro. The failure of porcine fibroblasts to grow on, or infiltrate into, the matrix suggested that the SMC may be the preferred cell type for future leaflet recellularization studies in the development of a tissue-engineered heart valve replacement.

Animals↗
PubMed2005

In-vitro assessment of the functional performance of the decellularized intact porcine aortic root.

BACKGROUND AND AIMS OF THE STUDY: Tissue-engineered heart valves offer the potential to deliver a heart valve replacement that will develop with the young patient. The present authors' approach is to use decellularized aortic heart valves reseeded in vitro or in vivo with the patient's own cells. It has been reported that treatment of porcine aortic valve leaflets with 0.1% (w/v) sodium dodecyl sulfate (SDS) in hypotonic buffer produced complete leaflet acellularity without affecting tissue strength. The present study aim was to investigate the effect of an additional treatment incorporating 1.25% (w/v) trypsin and 0.1% (w/v) SDS on the biomechanics and hydrodynamics of the aortic root. This treatment has been shown to produce decellularization of both the aorta and valve leaflets. METHODS: Fresh porcine aortic roots were treated to reduce the thickness of their aortic wall, and incubated in hypotonic buffer for 24 h. The leaflets were masked with agarose gel, and the aorta was treated with 1.25% (w/v) trypsin for 4 h at 37 degrees C. The trypsin and agarose were removed and the roots incubated with 0.1% (w/v) SDS in hypotonic buffer for 24 h. Fresh and treated circumferential and axial aortic specimens were subjected to uniaxial tensile testing, while intact porcine aortic roots were subjected to dilation and pulsatile flow testing. RESULTS: Decellularized aortic wall specimens demonstrated significantly decreased elastin phase slope and increased transition strain compared to the fresh control. However, the treatment did not impair tissue strength. Decellularized intact roots presented complete leaflet competence under systemic pressures, increased dilation and effective orifice areas, reduced pressure gradients, physiological leaflet kinematics and reduced leaflet deformation. CONCLUSION: The excellent leaflet kinematics and hydrodynamic performance of the decellularized roots, coupled with the excellent biomechanical characteristics of their aortic wall, form a promising platform for the creation of an acellular valve scaffold with adequate mechanical strength and functionality to accommodate dynamic cell repopulation in vitro or in vivo. This approach can be used for both allogeneic and xenogeneic tissue matrices.

Animals↗
PubMed2005

Tissue engineering of cardiac valves: re-seeding of acellular porcine aortic valve matrices with human mesenchymal progenitor cells.

BACKGROUND AND AIM OF THE STUDY: Tissue-engineered heart valves have the potential to overcome the limitations of present heart valve replacements. This study investigated the potential for re-seeding an acellular porcine heart valve matrix using human mesenchymal progenitor cells (MPC). METHODS: MPC were isolated from the bone marrow of patients undergoing hip replacement operations. Putative MPC were then cultured in several differentiation media in order to determine the multipotential differentiation capacity of the cells. The MPC were also characterized by FACS analysis. Cells at passage 8 were then seeded at between 1 x 10(4) and 1 x 10(5) cells/cm2 onto a decellularized porcine aortic valve matrix, and recellularization of the matrix was assessed. The phenotype of the re-seeded cells and re-seeded cell density was then determined by histology and immunohistochemistry. RESULTS: Putative MPC were successfully isolated and differentiated into cells of the adipogenic, neurogenic, and myogenic lineages. FACS analysis showed the cells to have a similar phenotype to those isolated by others (CD45-, CD13+, D7FIB+, CD105+, CD10+/-, LNGFR+/-, CD55+, BMP- and AP+/-). Cells seeded onto an acellular valve matrix penetrated the center of the tissue after four weeks to 2% of homograft cell density. Phenotypic analysis of the cells in the re-seeded matrix revealed the cells to have a similar phenotype to native valve interstitial cells (vimentin+, alpha-smooth muscle actin+, heavy chain myosin slow-, desmin-). However, re-seeded cells also expressed osteogenic markers (alkaline phosphatase, osteonectin, and osteopontin). CONCLUSION: This study has shown, for the first time, that human MPC have the capacity to infiltrate an acellular porcine valve matrix under static conditions in vitro. Future studies will comprise culture under pulsatile flow in a physiological heart valve bioreactor to maintain the desired cell phenotype and increase cell density.

Animals↗
PubMed2004

Variation in surface texture measurements.

Surface texture influences cellular response to implants, implant wear, and fixation, yet measurement and reporting of surface texture can be confusing and ambiguous. Seven specimens of widely different surface textures were submitted to three internationally renowned laboratories for surface texture characterization. The specimens were from dental implants, orthopedic implants, and femoral heads. Areas to be measured were clearly marked; simplified instructions were supplied but specific measurement parameters were not requested. Techniques used included contact profilometry, two- and three-dimensional laser profilometry, and atomic force microscopy. Four to thirteen parameters were reported, 2D or 3D, including R(a) or S(a); only three were common to all centers. The results varied by as much as +/-300-1000%, depending on technique and surface type. Some surfaces were not measurable by some techniques. One dental implant surface was reported with R(a) of 0.17, 0.85, 1.9, and 4.4 microm. The CoCr femoral head ranged from an R(a) of 0.011 to 0.10 microm; the zirconia head from 0.006 to 0.05 microm. Similar variability was reported for the other parameters. Useful surface texture characterization requires reporting of all measurement parameters. Comparisons between studies may be compromised if differences in technique are not considered.

Dental Implants↗
PubMed2004

Metal-on-metal bearing wear with different swing phase loads.

There is currently much discussion about the most clinically relevant testing methods for evaluating total hip replacements. This study examined the effect of different swing phase loads, including microseparation, on the wear, friction, and wear particles of metal-on-metal (MOM) hip replacements. MOM hip replacements were tested for 5 million cycles with the use of a hip simulator; prostheses were tested with a low (100-N) and ISO (280-N) swing phase load, and under microseparation conditions. Increasing the swing phase load from 100 to 280 N in the same hip simulator increased the wear of the MOM hip replacements by over tenfold. Introducing microseparation into the gait cycle increased wear further, and stripe wear was observed on the femoral heads, accompanied by corresponding rim damage on the acetabular cups. No significant difference in wear particle size was observed between wear particles produced by low load and microseparation hip simulator conditions. Introducing microseparation into the hip simulator gait cycle increased the wear of MOM prostheses. Joint laxity and separation may lead to increased wear rates of MOM prostheses in vivo. Additionally elevated positive swing phase loads may also increase wear. Variable swing phase load conditions in vivo may contribute to variations in clinical wear rates.

Chromium Alloys↗
PubMed2004

Comparative wear under different conditions of surface-engineered metal-on-metal bearings for total hip arthroplasty.

Metal-on-metal hip arthroplasties have demonstrated low wear rates. However, the ion release and toxicity of the metal wear particles remains a concern. Modifying the surface of metal bearings with thick chromium nitride (CrN) coatings has the potential to further reduce wear and ion release, and improve the biocompatibility of wear particles produced. The aim of this study was to investigate the application of surface engineering technology to modify metal-on-metal (MOM) bearings to reduce wear and improve the functional biocompatibility of metal-on-metal prostheses. CrN-on-CrN bearings had lower wear rates in comparison to metal-on-metal bearings, particularly under adverse loading conditions. CrN-on-CrN bearings produced similar nanometer-sized particles to metal-on-metal bearings, however, CrN wear particles were less cytotoxic when cocultured with macrophage and fibroblast cells.

Arthroplasty, Replacement, Hip↗
PubMed2004

The influence of molecular weight, crosslinking and counterface roughness on TNF-alpha production by macrophages in response to ultra high molecular weight polyethylene particles.

The response of murine macrophages to clinically relevant polyethylene wear particles generated from different polyethylenes at various time points and volumetric doses in vitro was evaluated. Clinically relevant ultra high molecular weight polyethylene (UHMWPE) wear debris was generated in vitro in a lubricant of RPMI 1640 supplemented with 25% (v/v) foetal calf serum using a multi-directional pin-on-plate wear rig under sterile conditions. Wear debris was cultured with C3H murine peritoneal macrophages at various particle volume (microm(3)): cell number ratios. The secretion of TNF-alpha was determined by ELISA. Initially the effect of molecular weight of UHMWPE was considered. Higher molecular weight GUR415HP was shown to have a lower wear rate than the lower molecular weight GUR1120, however a greater volume of the wear debris produced by the high molecular weight GUR415HP was in the 0.1-1.0 microm size range. Wear debris from GUR415HP produced significant levels of TNF-alpha at a concentration of 1 microm(3)/cell while at least 10 microm(3)/cell of GUR1120 wear debris per cell was needed to produce significant levels of TNF-alpha. Secondly the effects of crosslinking GUR1050 was examined when worn against a scratched counterface. The wear rate of the material was shown to decrease as the level of crosslinking increased. However the materials crosslinked with 5 and 10 Mrad of gamma irradiation produced higher percentages of 0.1-1.0 microm size wear particles than the non-crosslinked material. While the crosslinked material was able to stimulate cells to produce significantly elevated TNF-alpha levels at a particle concentration of just 0.1 microm(3)/cell only concentrations of 10 microm(3)/cell and above of the non-crosslinked wear debris were stimulatory. When the counterface was changed from scratched to smooth the wear rate for all three GUR1050 materials was further reduced. For the first time nanometre size wear particles were observed from polyethylene which reduced the percentage mass of debris in the 0.1-1.0 microm size range. For all three materials on the smooth counterface only concentrations of 50 microm(3)/cell and above were stimulatory. This study has demonstrated that molecular weight, crosslinking and counterface roughness are important factors in determining the biological activity of polyethylene.

Animals↗
PubMed2004

Wear, debris, and biologic activity of cross-linked polyethylene in the knee: benefits and potential concerns.

Cross-linked polyethylene currently is being introduced in knee prostheses. The wear rates, wear debris, and biologic reactivity of non cross-linked, moderately cross-linked, and highly cross-linked polyethylene have been compared in multidirectional wear tests and knee simulators. Multidirectional pin-on-plate wear studies of noncross-linked, moderately cross-linked (5 Mrad), and highly cross-linked (10 Mrad) polyethylene showed a 75% reduction in wear with the highly cross-linked material under kinematics found in the hip, but only a 33% reduction under wear in kinematics representative of the knee. In knee simulator studies, with the fixed-bearing press-fit, condylar Sigma cruciate-retaining knee under high kinematic input conditions, the wear of 5 Mrad moderately cross-linked polyethylene was 13 +/- 4 mm per 1 million cycles, which was lower (p < 0.05) than the wear of clinically used, gamma vacuum foil GUR 1020 polyethylene (23 +/- 6 mm/1 million cycles). For the low-contact stress mobile-bearing knee, the wear of moderately cross-linked polyethylene was 2 +/- 1 mm per 1 million cycles, which was lower (p < 0.05) than GVF GUR 1020 polyethylene (5 +/- 2 mm/1 million cycles). The wear debris isolated from the fixed-bearing knees showed the moderately cross-linked material had a larger percentage volume of particles smaller than 1 mum in size, compared with GVF GUR 1020 polyethylene. Direct cell culture studies of wear debris generated in sterile wear simulators using multidirectional motion showed a increase (p < 0.05) in tumor necrosis factor-alpha levels and reactivity for GUR 1050 cross-linked polyethylene debris compared with an equivalent volume of noncross-linked GUR 1050 polyethylene. The use of cross-linked polyethylene in the knee reduces the volumetric wear rate. However, the clinical significance of reduced fracture toughness, elevated wear in abrasive conditions, and the elevated tumor necrosis factor-alpha release from smaller more reactive particles warrant further investigation.

Analysis of Variance↗
PubMed2004

Quantification of pulmonary autograft characteristics using magnetic resonance imaging.

BACKGROUND AND AIM OF THE STUDY: The diameters and distensibility of the native pulmonary root and their effect on pulmonary autograft performance were examined pre- and postoperatively using cardiac ultrasound and magnetic resonance imaging (MRI). METHODS: Eight patients undergoing the Ross procedure were prospectively involved. The diameters of the native aortic, native pulmonary and autograft roots were measured at the level of the annulus, sinus, sinotubular junction and in the main root using MRI through the cardiac cycle. Ultrasound was also used to estimate the degree of regurgitation, both pre- and postoperatively. RESULTS: The pulmonary root implanted into the systemic circulation increased in size but decreased in distensibility significantly at the sinus, sinotubular junction and main root, but not at the annulus. Postoperatively, the pulmonary autograft annulus showed a similar size and distensibility to that of the native aortic annulus. A wide range of aortic annular sizes (22-30 mm) produced clinically competent valves postoperatively. All undersized pulmonary valves showed only trivial regurgitation postoperatively. Although there was no clear correlation between root shape and valve insufficiency, two patients with mild and moderate autograft regurgitation both had divergent pulmonary roots (diameter at sinotubular junction > annulus diameter) preoperatively. CONCLUSION: The pulmonary autograft using the root replacement technique functioned well in all but one case. The shape of the native pulmonary root may be a determinant of early autograft regurgitation, as well as the diameter and the size mismatch between the great arteries.

Adolescent↗
PubMed2003

Long-term wear of ceramic matrix composite materials for hip prostheses under severe swing phase microseparation.

The purpose of this study was to evaluate the long-term wear performance of alumina matrix composite (AMC) heads against alumina matrix composite inserts and alumina matrix composite heads against alumina (Al) inserts with the use of a hip-joint simulator incorporating severe swing phase joint microseparation. The wear of AMC on Al produced an average wear rate of 0.61 mm3/million cycles over the 5-million-cycle test duration. The wear of AMC on AMC produced an average wear rate of 0.16 mm3/million cycles over the 5-million-cycle test duration. Both the AMC on alumina and AMC on AMC produced significantly lower wear than previously tested HIPed alumina, where an average wear rate of 1.84 mm3/million cycles was reported over 5 million cycles. The wear mechanisms and wear debris of AMC on AMC and AMC on Al were similar to those observed in previous alumina retrieval studies with stripe wear caused by intragranular fracture and wear debris consisting of predominantly uniform 10-20-nm-sized particles and a few irregular particles up to 3 microm in size.

Aluminum Oxide↗