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Biomedical subjects

J E Sanders

Publications and source records attributed to J E Sanders.

At least 37 records · Page 2Linked to original sources
PubMed2002

Interface pressure and shear stress changes with amputee weight loss: case studies from two trans-tibial amputee subjects.

Interface pressures and shear stresses were measured at monthly intervals on two trans-tibial amputee subjects who lost more than 12% of their body weight over the course of the study. For one subject interface pressures and shear stresses during the weight-acceptance phase of gait decreased over the study interval at all 13 sites monitored, while the other subject experienced increased pressures distally but decreased pressures proximally. Subjects' stumps appeared to atrophy over the study interval, increasing distal end and patellar tendon loading, but not increasing interface shear stresses at other locations. Adding socks at the end of the study did not return interface pressures to first session values at all sites. It is expected that local stump shape changes occurred, causing a non-uniform change in interface stress patterns.

Amputees↗
PubMed2001

Administration of cyclosporine for 24 months compared with 6 months for prevention of chronic graft-versus-host disease: a prospective randomized clinical trial.

This study compared the incidence of clinical extensive chronic graft-versus-host disease (GVHD), transplantation-related mortality, survival, and relapse-free survival among recipients randomly assigned to receive a 24-month or a 6-month course of cyclosporine prophylaxis after transplantation of allogeneic marrow from an HLA-identical sibling or alternative donor. Patients who did not have clinical manifestations of chronic GVHD on day 80 after transplantation were eligible for the study if they previously had acute GVHD or if a skin biopsy showed histologic evidence of chronic GVHD. Clinical extensive chronic GVHD developed in 35 of the 89 patients (39%) in the 24-month group and 37 of the 73 patients (51%) in the 6-month group. The hazard of developing chronic GVHD was not significantly different in the 2 groups (hazard ratio = 0.76; 95% confidence interval, 0.48-1.21; P =.25). In addition, there were no significant differences between the 2 groups in transplantation-related mortality, survival, or disease-free survival.

Adult↗
PubMed2001

The role of NF-kappa B in TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis of melanoma cells.

Previous studies have shown that activation of NF-kappaB can inhibit apoptosis induced by a number of stimuli. It is also known that TNF-related apoptosis-inducing ligand (TRAIL) can activate NF-kappaB through the death receptors TRAIL-R1 and TRAIL-R2, and decoy receptor TRAIL-R4. In view of these findings, we have investigated the extent to which activation of NF-kappaB may account for the variable responses of melanoma lines to apoptosis induced by TRAIL and other TNF family members. Pretreatment of the melanoma lines with the proteasome inhibitor N-acetyl-L-leucinyl-L-leucinyl-L-norleucinal (LLnL), which is known to inhibit activation of NF-kappaB, was shown to markedly increase apoptosis in 10 of 12 melanoma lines with death receptors for TRAIL. The specificity of results for inhibition of NF-kappaB activation was supported by an increase of TRAIL-induced apoptosis in melanoma cells transfected with a degradation-resistant IkappaBalpha. Furthermore, studies with NF-kappaB reporter constructs revealed that the resistance of melanoma lines to TRAIL-induced apoptosis was correlated to activation of NF-kappaB in response to TRAIL. TRAIL-resistant sublines that were generated by intermittent exposure to TRAIL were shown to have high levels of activated NF-kappaB, and resistance to TRAIL could be reversed by LLnL and by the superrepressor form of IkappaBalpha. Therefore, these results suggest that activation of NF-kappaB by TRAIL plays an important role in resistance of melanoma cells to TRAIL-induced apoptosis and further suggest that inhibitors of NF-kappaB may be useful adjuncts in clinical use of TRAIL against melanoma.

Apoptosis↗
PubMed2001

Collagen fibril diameters increase and fibril densities decrease in skin subjected to repetitive compressive and shear stresses.

Understanding microstructural changes that occur in skin subjected to repetitive mechanical stress is crucial towards the development of therapies to enhance skin adaptation and load tolerance in patients at risk of skin breakdown (e.g. prosthesis users, wheelchair users). To determine if collagen fibril diameter, collagen fibril density, dermal thickness, epidermal thickness, basement membrane length, and dermal cell density changed in response to repetitive stress application, skin subjected to moderate cyclic compressive and shear stresses for 1h/d, 5d/week, for 4 weeks was compared with skin from an unstressed contralateral control. The lateral aspects of the hind limbs of 12 Landrace/Yorkshire pigs were used. Skin from under the stressed site and a contralateral control site was processed for electron microscopy and light microscopy analysis. Electron microscopy results demonstrated significant (p<0.01) increases in collagen fibril diameter of 15.9%, 22.4%, and 22.9% for the upper, mid, and lower layers of the dermis, respectively, for the stressed skin compared with the control skin. Collagen fibril density (fibrils/unit cross-sectional area) decreased significantly for stressed vs. control by 19.8%, 29.2%, and 31.8% for the upper, mid, and lower layers, respectively. Light microscopy results demonstrated trends of a decrease in dermal thickness and an increase in cell density for stressed vs. control samples, but the differences were not significant. Differences in epidermal thickness and basement membrane length were not significant. These results demonstrate that quantifiable changes occur in collagen fibril architecture but not in the gross tissue morphology following in vivo cyclic loading of pig skin.

Animals↗
PubMed2001

Standing interface stresses as a predictor of walking interface stresses in the trans-tibial prosthesis.

Interface pressures and shear stresses within the socket, in standing and walking, were measured for two unilateral, male, trans-tibial amputee subjects, during two sessions each. The ratios of equal weight-bearing standing stresses to peak walking stresses showed regional variation, ranging from 0.24:1 for pressure over the anterior region to 1.01:1 for resultant interface shear stress over the lateral region. Interface stresses in standing were only moderate predictors of peak walking stresses. The best correlation coefficient between standing in full weight-bearing and peak walking stress was 0.88 for pressure over the lateral region. As the amputees progressed from minimal to full weight-bearing in standing, and then to walking, the interface stresses increased in a nonlinear fashion, consistent with the assumption that the anterior tibia provides much resistance to the bending moment in the sagittal plane during walking.

Adult↗
PubMed2001

A device to apply user-specified strains to biomaterials in culture.

An apparatus was developed to apply user-specified displacements to biomaterial samples in culture. The device allowed cyclic waveforms of bandwidth 0 Hz to 20 Hz to be applied under physiologic thermal (37.5 degrees C) and [CO2] (5%) conditions. For a 0 Hz to 20 Hz bandwidth signal similar in shape to a ventricular pressure waveform, the mean displacement error was 0.26% of the full-scale output. The maximum overshoot was 0.700%. Environmental system evaluation tests demonstrated a specimen cartridge temperature of 37.20 +/- 0.15 degrees C during cyclic loading and 37.23 +/- 0.21 degrees C during static conditions. [CO2] was 5.29 +/- 0.54% during cyclic loading and 5.25 +/- 0.61% during static conditions. Laminar flow applied at the loading rod entrances to the specimen cartridge ensured the sample remained sterile during testing. As a preliminary evaluation, polyurethane samples were seeded with fetal foreskin fibroblasts and subject to intermittent cyclic displacements. Results demonstrated enhanced cell proliferation and increased [PGE2] for samples subjected to 10% strain compared with unstrained controls. A next step will be to evaluate cell response sensitivity to strain magnitude, duration, direction, and frequency. The long-term intent is to establish mechanical loading configurations that induce acceptable or adaptation-inducing responses for use in implant design and tissue engineering applications.

Animals↗
PubMed2000

Thalidomide for treatment of patients with chronic graft-versus-host disease.

In a randomized, placebo-controlled, double-blind trial, thalidomide or placebo together with glucocorticoids and either cyclosporine or tacrolimus was administered as initial therapy for clinical extensive chronic graft-versus-host disease (cGVHD). All patients had thrombocytopenia or cGVHD that evolved directly from acute GVHD as an indicator of a poor prognosis. The study drug (thalidomide or placebo) was administered initially at a dose of 200 mg orally per day, followed by a gradual increase to 800 mg/d if side effects were tolerable. Treatment with the study drug was discontinued before resolution of cGVHD in 23 (92%) of the 25 patients who received thalidomide and in 17 (65%) of the 26 patients who received placebo (P =.02). Neutropenia and neurologic symptoms were the most frequent reasons for early discontinuation of treatment with thalidomide. The duration of treatment with thalidomide was too short to assess its efficacy in controlling cGVHD. (Blood. 2000;96:3995-3996)

Actuarial Analysis↗
PubMed2000

Mechanisms of resistance of normal cells to TRAIL induced apoptosis vary between different cell types.

Resistance of normal cells to tumour necrosis factor related apoptosis inducing ligand (TRAIL) induced apoptosis is believed to be mediated by expression of two decoy receptors. Here we show that the expression and localisation of TRAIL receptors (TRAIL-Rs) vary between different cells and that resistance to TRAIL is mediated by different mechanisms. The decoy receptor, TRAIL-R3, appeared important in protection of endothelial cells, whereas lack of surface death receptor expression and as yet unknown intracellular inhibitor(s) of apoptosis downstream of caspase-3 may play a major role in protection of melanocytes and fibroblasts from TRAIL induced apoptosis, respectively. Differential subcellular location of decoy receptors may be an important determinant of their effectiveness in different types of normal cells.

Apoptosis↗
PubMed2000

Impact of bone marrow transplantation for symptomatic sickle cell disease: an interim report. Multicenter investigation of bone marrow transplantation for sickle cell disease.

Fifty children who had symptomatic sickle cell disease received matched sibling marrow allografts between September 1991 and March 1999, with Kaplan-Meier probabilities of survival and event-free survival of 94% and 84%, respectively. Twenty-six patients (16 male, 10 female) had at least 2 years of follow-up after transplantation and were evaluated for late effects of transplantation and for its impact on sickle cell-related central nervous system (CNS) and pulmonary disease. Patients ranged between 3.3 and 14.0 (median, 9. 4) years of age and had a median follow-up of 57.9 (range 38-95) months after transplantation. Among 22 of 26 patients who had stable donor engraftment, complications related to sickle cell disease resolved, and none experienced further episodes of pain, stroke, or acute chest syndrome. All 10 engrafted patients with a prior history of stroke had stable or improved cerebral magnetic resonance imaging results. Pulmonary function tests were stable in 22 of the 26 patients, worse in two, and not studied in two. Seven of eight patients transplanted for recurrent acute chest syndrome had stable pulmonary function. Linear growth measured by median height standard deviation score improved from -0.7 before transplantation to -0.2 after transplantation. An adverse effect of busulfan conditioning on ovarian function was demonstrated in five of seven evaluable females who are currently at least 13 years of age. None of the four males tested had elevated serum gonadotropin levels. These data confirm that allogenic bone marrow transplantation establishes normal erythropoiesis and is associated with improved growth and stable CNS imaging and pulmonary function in most patients. (Blood. 2000;95:1918-1924)

Adolescent↗
PubMed2000

Phase I topotecan preparative regimen for high-risk neuroblastoma, high-grade glioma, and refractory/recurrent pediatric solid tumors.

We evaluated the toxicity and maximum tolerated dose of topotecan in a novel myeloablative regimen as treatment for high-risk pediatric tumors. Patients received an assigned topotecan dosage in combination with fixed doses of carboplatin and thiotepa, followed by autologous hematopoietic stem cells infusion. Topotecan dose was escalated in cohorts of four patients until the maximum tolerated dose of topotecan was defined or until accrual of 30 patients. Pharmacokinetics of topotecan were examined, and event-free survival was estimated. We describe preliminary results following treatment of 25 pediatric patients with high-risk solid tumors.

Antineoplastic Agents↗
PubMed2000

Tissue response to single-polymer fibers of varying diameters: evaluation of fibrous encapsulation and macrophage density.

An in vivo study was conducted to assess the sensitivity of fibrous capsule thickness and macrophage density to polymer fiber diameter. Single polypropylene fibers of diameters ranging from 2.1 to 26.7 microm were implanted in the subcutaneous dorsum of Sprague-Dawley rats. Results at 5 weeks demonstrated reduced fibrous capsule thickness for small fibers. Capsule thickness was 0.6 (+/-1.8) microm, 11.7 (+/-12.0) microm, 20.3 (+/-11.6) microm, and 25.5 (+/-10.0) microm for fibers in the ranges of 2.1 to 5.9, 6.5 to 10.6, 11.1 to 15.8, and 16.7 to 26.7 microm, respectively. Fibers very near to blood vessels had smaller capsules than did those with local vasculature further away. The macrophage density in tissue with fiber diameters 2.1 to 5.9 microm (23.03 +/- 8.67%) was comparable to that of unoperated contralateral control skin (18.72+/-10.06%). For fibers with diameters in the ranges of 6.5 to 10.6, 11.1 to 15.8, and 16.7 to 26.7 microm, macrophage densities were 33.90+/-13.08%, 34.40+/-15.77%, and 41.68+/-13.98%, respectively, all of which were significantly larger (p<0.002) than that for the control. The reduced fibrous capsule thickness and macrophage density for small fibers (<6 microm) compared with large fibers could be due to the reduced cell-material contact surface area or to a curvature threshold effect that triggers cell signaling. A next step will be to extend the analysis to meshes to evaluate fiber-spacing effects on small-fiber biomaterials.

Animals↗
PubMed2000

Characterisation of three-dimensional anatomic shapes using principal components: application to the proximal tibia.

The objective of the research is to determine if principal component analysis (PCA) provides an efficient method to characterise the normative shape of the proximal tibia. Bone surface data, converted to analytical surface descriptions, are aligned, and an auto-associative memory matrix is generated. A limited subset of the matrix principal components is used to reconstruct the bone surfaces, and the reconstruction error is assessed. Surface reconstructions based on just six (of 1452) principal components have a mean root-mean-square (RMS) reconstruction error of 1.05% of the mean maximum radial distance at the tibial plateau. Surface reconstruction of bones not included in the auto-associative memory matrix have a mean RMS error of 2.90%. The first principal component represents the average shape of the sample population. Addition of subsequent principal components represents the shape variations most prevalent in the sample and can be visualised in a geometrically meaningful manner. PCA offers an efficient method to characterise the normative shape of the proximal tibia with a high degree of dimensionality reduction.

Adult↗
PubMed2000

Finite element estimates of interface stress in the trans-tibial prosthesis using gap elements are different from those using automated contact.

When compared with automated contact methods of finite element (FE) analyses, gap elements have certain inherent disadvantages in simulating large slip of compliant materials on stiff surfaces. However, automated contact has found limited use in the biomechanical literature. A non-linear, three-dimensional, geometrically accurate, FE analysis of the trans-tibial limb-socket prosthetic system was used to compare an automated contact interface model with a gap element model, and to evaluate the sensitivity of automated contact to interfacial coefficient of friction (COF). Peak normal stresses and resultant shear stresses were higher in the gap element model than in the automated contact model, while the maximum axial slip was less. Under proximally directed load, compared with automated contact, gap elements predicted larger areas of stress concentration that were located more distally. Gap elements did not predict any relative slip at the distal end, and also transmitted a larger proportion of axial load as shear stress. Both models demonstrated non -linear sensitivity to COF, with larger variation at lower magnitudes of COF. By imposing physical connections between interface surfaces, gap elements distort the interface stress distributions under large slip. Automated contact methods offer an attractive alternative in applications such as prosthetic FE modeling, where the initial position of the limb in the socket is not known, where local geometric features have high design significance, and where large slip occurs under load.

Artificial Limbs↗
PubMed2000

Effects of changes in cadence, prosthetic componentry, and time on interface pressures and shear stresses of three trans-tibial amputees.

OBJECTIVE: To evaluate the effects of changes in cadence, prosthetic componentry, and time on interface pressures and resultant shear stresses in trans-tibial amputee case studies. DESIGN: Interface stresses were monitored using custom-designed instrumentation at 13 sites on three subjects with unilateral trans-tibial amputation walking with patellar-tendon-bearing prosthetic limbs. BACKGROUND: Previous studies suggested that week-to-week residual limb changes altered interface stresses more than did alterations in prosthetic alignment. No studies investigating effects of changes in cadence or componentry on interface stress distributions nor comparing their influence with week-to-week changes have been conducted previously. METHODS: Five different prosthetic componentry configurations were tested at each of three cadences in four sessions. Data were analysed for the magnitudes and timings of peak pressures and resultant shear stresses as well as corresponding resultant shear angles. RESULTS: None of the three cadences or five componentry configurations consistently induced significantly (P<0.05) higher or lower interface stress magnitudes for all subjects. However, an Aluminium Pylon/SACH Foot combination compared with an AirStance (pneumatic shank)/Seattle LightFoot unit induced later peak interface stress timings as a percentage of stance phase. Higher and more frequent interface stress changes were seen between the weekly sessions than between different cadences or between different componentry configurations. CONCLUSION: The amputees' capabilities to compensate for week-to-week residual limb changes were less than those for intra-session cadence or componentry alterations. RELEVANCE: Results suggest that effective techniques to accommodate week-to-week residual limb fluctuations could have a greater impact on maintaining consistent interface stress distributions than do adjustments in cadence or componentry.

Adult↗
PubMed2000

Second allogeneic transplantation after failure of first autologous transplantation.

We evaluated the outcome of second allogeneic bone marrow transplantations (BMTs) in 59 patients aged 1-57 years who relapsed after initial autologous transplantation. Patients received a second transplantation for recurrent acute myeloid leukemia (AML) (n = 24), acute lymphoblastic leukemia (ALL) (n = 13), lymphoma (n = 18), multiple myeloma (n = 3), or chronic myelogenous leukemia (n = 1) from an HLA-matched related (n = 14), mismatched related (n = 25), or matched unrelated (n = 20) donor. The probabilities of nonrelapse mortality, relapse, and disease-free survival (DFS) 2 years after the second BMT were 51%, 26%, and 23%, respectively. The 2-year DFS estimates for AML, ALL, and lymphoma were 46%, 23%, and 0%. Univariate analysis demonstrated that superior DFS was associated with age < or =17 years at the time of the second transplantation, remission before the second transplantation, total-body irradiation-based preparative regimen for the second transplantation, and the diagnosis of AML. These data demonstrate that an allogeneic transplantation after a failed autologous transplantation can result in disease-free survivors, especially in the young. The outcomes after a second transplantation for patients aged >17 years and for those with lymphoma were especially grim. These data suggest that pediatric patients may be appropriate candidates for a second transplantation. In adults, however, the use of an allogeneic transplantation as salvage therapy after failure of the initial autologous transplantation is generally unsuccessful. Alternative experimental strategies, such as low-dose nonmyeloablative allogeneic minitransplantations, should be considered.

Adolescent↗
PubMed2000

Granulocyte colony-stimulating factor given to donors before apheresis does not prevent aplasia in patients treated with donor leukocyte infusion for recurrent chronic myeloid leukemia after bone marrow transplantation.

We conducted 2 sequential studies of donor leukocyte infusion (DLI) in 26 patients with chronic myeloid leukemia in hematologic relapse after unmodified allogeneic bone marrow transplantation. In the first study, cells for DLI were collected from 13 donors who were not treated with granulocyte colony-stimulating factor (G-CSF) (group 1). In the second study, cells were collected from 13 donors who received G-CSF before apheresis (group 2) in an attempt to avoid aplasia after DLI. Patients in group 2 received 550-fold more CD34+ cells than those in group 1. We found no significant difference in the incidence (31% versus 22%), onset time (41 vs. 48 days), or duration (15 vs. 14 days) of cytopenia after DLI in the 2 groups. G-CSF given to donors before collection of cells did not prevent aplasia. These findings support the hypothesis that the pathogenesis of aplasia after DLI is not restricted to the destruction of recipient hematopoietic cells but also involves failure of donor hematopoiesis by undefined mechanisms.

Adolescent↗
PubMed2000

Unrelated donor marrow transplantation for acute myeloid leukemia: an update of the Seattle experience.

Between 1985 and 1998, 161 patients with primary acute myeloid leukemia (AML) received T-replete bone marrow transplantation (BMT) from unrelated donors in Seattle. Median age was 30 (range 1-55) years. Conditioning for BMT consisted of cyclophosphamide and total body irradiation in 154 (96%) cases and graft-versus-host disease prophylaxis was the standard methotrexate and cyclosporine combination in 134 (83%) cases. Median post-transplant follow-up was 2.9 years. Leukemia-free survival (LFS) at 5 years was 50+/-12% for transplants during first complete remission (n = 16), 28+/-8% during second CR (n = 40), 27+/-17% during subsequent CR (n = 8), 7+/-3% during relapse (n = 81) and 19+/-10% during primary induction failure (n = 16). The cumulative incidences of relapse were 19%, 23%, 25%, 44% and 63%, for the five groups, respectively. Transplantation during remission, a marrow cell dose above 3.5 x 10(8)/kg, and cytomegalovirus seronegative status before BMT in both patient and donor were favorable prognostic factors. Adults in any CR who received a marrow cell dose above 3.5 x 10(8)/mg had a LFS of 54+/-9% at 5 years. These data extend our previous findings on the association between a high marrow cell dose and improved survival and support the use of unrelated donor BMT for treatment of patients with high risk AML when a family match is not available.

Acute Disease↗