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Biomedical subjects

J E Sanders

Publications and source records attributed to J E Sanders.

At least 55 records · Page 3Linked to original sources

Changes in interface pressure and stump shape over time: preliminary results from a trans-tibial amputee subject.

Interface stresses and stump shape were measured during sessions over a two-month interval on a trans-tibial amputee subject. Results from thirteen transducer sites monitored during four sessions showed greater interface pressure changes over time at anterior sites than at lateral or posterior locations. There was a trend of decreased pressure with stump swelling and increased pressure for stump atrophy. During one session in which stump shape was monitored over a 23.1 min interval after ambulation, stump swelling was localised. Swelling tended to increase in the regions of initial enlargement, as opposed to redistributing through different areas over time. Regions of swelling were anterior lateral and posterior proximal, areas of thick underlying soft tissue. Identification of localised areas of swelling and atrophy and understanding of their effects on interface pressures could be used to improve individual socket design.

Adult↗

Image processing techniques for quantitative analysis of skin structures.

Computer-based image processing and analysis techniques were developed for quantitative analysis of skin structures in color histological sections. Performance was compared with traditional non-image processing counting methods. Skin sections were stained with Masson's trichrome, hematoxylin and eosin, picrosirius red, or one of several elastin stains. The image processing software identified the top of the cellular epidermis and the dermal-epidermal junction and then calculated the volume of the cellular layer of the epidermis, epidermal thickness, and the ratio of the dermal-epidermal junction surface area to the in-plane surface area. It also identified cells and collagen and calculated cellular densities and collagen densities in the papillary and reticular layers of the dermis. Attempts to computationally process elastin-stained sections to determine elastin density were unsuccessful. The described techniques were used in a preliminary study to compare mechanically stressed skin with control skin. Results showed significant differences in cellular density in the papillary dermis and collagen density in the reticular dermis for skin subjected to combined shear/compression or tension compared with an unstressed control. Measurements made with the computer technique and traditional technique showed comparable results; the mean difference in measurements for epidermal features was 5.33% while for dermal features it was 2.76%. Significance testing between control and experimental groups showed similar results, though for three of the 28 comparisons the computer method identified a significant difference while the traditional method did not. The computer method took longer to conduct than the traditional method, though with recent advances in computer hardware this time difference would be eliminated.

Adaptation, Physiological↗

Stem-cell transplant preparative regimens.

Owing to the relatively high probability of recurrent disease in patients receiving hematopoietic stem-cell transplantation (HSCT) for malignancies, further development of new preparative regimens is warranted. Based on the data presented, one can predict that it will continue to be difficult to identify HSCT regimens that are more effective. Incremental improvements are expected to be small, difficult to measure, and will require inclusion of very large numbers of patients. Controlled trials to evaluate the effectiveness of specific treatment regimens for specific groups of patients will require only centers with large numbers of patients or co-operative groups to successfully conduct these studies. Development of HSCT regimens with low mortality and a minimum of morbidity without compromising efficacy are needed. This may be accomplished through the use of agents to protect normal, non-hematopoietic tissues from regimen-related toxicity (RRT), further exploration and expansion of applications of targeted radiolabeled antibody approaches and mixed chimerism approaches. The future holds much work, but great promise, in the development of new HSCT regimens.

Antineoplastic Combined Chemotherapy Protocols↗

Fluid mechanics analysis of a spring-loaded jet injector.

A syringe jet injector is a device designed to administer a drug quickly and painlessly through the skin. Though syringe jet injectors have been in use for almost 50 years, current designs still suffer from inconsistent performance. To better understand the fluid mechanics of jet injection and gain insight into how the design might influence performance, two theoretical analyses to determine the fluid pressure profile at the exit orifice were conducted. The first was a continuum analysis assuming static incompressibility. Results demonstrated that the maximum jet pressure was highly sensitive to the spring constant, initial piston velocity, and piston cross-sectional area while the time to achieve the maximum pressure was most sensitive to the injection chamber length, initial piston velocity, bulk modulus of the injectant, and the piston cross-sectional area. The second analysis was a shock wave analysis. Results demonstrated a stepwise pressure-time plot that was similar in magnitude to that for the continuum analysis assuming static incompressibility. Results from these two investigations are useful for design modification of the jet injector to achieve desired pressure-time profiles at the orifice. Control of pressure-time profiles may help to achieve a more consistent and effective injection process.

Equipment Design↗

Interface pressures and shear stresses: sagittal plane angular alignment effects in three trans-tibial amputee case studies.

Interface pressures and shear stresses at different sagittal plane angular alignment settings were measured on 3 trans-tibial amputee subjects ambulating with patellar-tendon-bearing total contact prostheses. Substantial socket-shank angular alignment modifications in the sagittal plane had minimal effect on stance phase peak interface pressures, though more substantial effects on stance phase peak resultant shear stresses. No consistent trend of a greater stress at misaligned vs nominally aligned settings was identified. Changes in interface stresses from session to session tended to be greater than those for different alignment settings, suggesting that subjects compensated well for misalignments but less well for session differences.

Adult↗

Bone marrow transplantation for children less than 2 years of age with acute myelogenous leukemia or myelodysplastic syndrome.

We analyzed results of 40 infants less than 2 years of age who received bone marrow transplants (BMT) between May 1974 and January 1995 for treatment of acute myelogenous leukemia (AML; N = 34) or myelodysplastic syndrome (MDS; N = 6) to determine outcome and survival performance. Among the AML patients, 13 were in first remission, 9 were in untreated first relapse or second remission, and 12 were in refractory relapse. Patients were conditioned with cyclophosphamide in combination with either total body irradiation (TBI; N = 29) or busulfan (N = 11). Source of stem cells included 6 autologous donors, 15 HLA genotypically identical siblings, 14 haploidentical family members, and 5 unrelated donors. Graft-versus-host disease (GVHD) prophylaxis was methotrexate (MTX) for 17, MTX plus cyclosporine (CSP) for 14, or CSP plus prednisone for 3. Incidence of severe (grade 3-4) regimen-related toxicity was 10% and transplant-related mortality was 10%. Acute GVHD (grades II-III) occurred in 39% of allogeneic patients, and chronic GVHD developed in 40%. Relapse, the most significant problem for patients in this study, occurred in 1 MDS patient and 23 AML patients and was the cause of death for 19 patients. The 2-year probabilities of relapse are 46%, 67%, and 92%, respectively, for patients transplanted in first remission, untreated first relapse or second remission, and relapse. One MDS and 8 AML patients received second marrow transplants for treatment of relapse, and 5 of these survive disease-free for more than 1.5 years. All 6 MDS patients and 11 of 34 AML patients survive more than 1.5 years later. The 5-year probabilities of survival and disease-free survival are 54% and 38% for patients transplanted in first remission and 33% and 22% for untreated first relapse or second remission. None of the patients transplanted with refractory relapse survive disease-free. Outcome was significantly associated with phase of disease at transplantation and pretransplant diagnosis of extramedullary disease. Long-term sequelae included growth failure and hormonal deficiencies. Survival performance was a median of 100% (80% to 100%) and neurologic development for all survivors was appropriate for age. This study indicates that infants with AML have similar outcome after BMT compared with older children and that BMT should be performed in first remission whenever possible. In addition, allogeneic BMT provides effective therapy for the majority of infants with MDS.

Acute Disease↗

Association between pretransplant interferon-alpha and outcome after unrelated donor marrow transplantation for chronic myelogenous leukemia in chronic phase.

Treatment options for patients diagnosed with chronic myelogenous leukemia (CML) in chronic phase (CP) who lack a suitable related donor for marrow transplantation include hydroxyurea, interferon-alpha (IFN-alpha), or transplantation from an unrelated donor (URD). Most studies support the view that treatment with IFN-alpha results in prolonged survival compared with hydroxyurea therapy. Some patients are offered URD transplantation as a second-line treatment; however, the impact of pretransplant IFN-alpha on the outcome of URD transplantation is uncertain. To address this question, we evaluated the effect of pretransplant IFN-alpha therapy in 184 patients undergoing URD transplantation for CML in CP at a single center. Of the 184 patients, 114 did not receive IFN-alpha, whereas 22, 23, and 25 patients received IFN-alpha for, respectively, 1 to 5, 6 to 12, and more than 12 months before transplant. Pretransplant IFN-alpha therapy administered for > or = 6 months was associated with an increased risk of severe (grades III-IV) acute graft-versus-host disease (GVHD; relative risk [RR], 3.0; 95% confidence interval [CI], 1.4 to 6.2; P = .004) and mortality (RR, 2. 1; 95% CI, 1.3 to 3.5; P = .003) relative to less than 6 months or no IFN-alpha therapy. Increased mortality occurred between 100 and 365 days after transplant (P = .005), was limited to patients with severe acute GVHD, and was due to chronic GVHD refractory to immunosuppressive therapy. Other variables associated with mortality included HLA-DRB1 or DQB1 (but not HLA-A or B) mismatched donors, age greater than 50 years, weight > or = 110% of ideal body weight, and the absence of cytomegalovirus (CMV) or fungal prophylaxis. For patients treated with IFN-alpha for less than 6 months before transplant, who were < or = 50 years of age, received a HLA-A, B, DRB1, and DQB1 matched URD transplant, and received CMV and fungal prophylaxis after transplant (n = 48), survival was 87% +/- 5% at 5 years. These data provide a rationale for immediate transplantation in preference to extended treatment with IFN-alpha when the patient is < or = 50 years of age and has an HLA-compatible unrelated volunteer donor.

Adolescent↗

Unrelated and HLA-nonidentical related donor marrow transplantation for thalassemia and leukemia. A combined report from the Seattle Marrow Transplant Team and the International Bone Marrow Transplant Registry.

Allogeneic marrow transplantation is curative therapy for thalassemia, but fewer than 30% of patients have an HLA-identical sibling marrow donor. Selection of alternative donors of hematopoietic stem cells (unrelated individuals or HLA-nonidentical family members) has been aided by establishment of world-wide donor registries now exceeding 3.6 million volunteers and by DNA-based HLA typing to more closely match potential donors. Coupled with improved methods to control graft-versus-host disease and prevent fungal and cytomegalovirus infection, remarkable progress has been made in alternative donor transplantation. For patients 50 years of age or younger, with recently diagnosed chronic myelogenous leukemia (CML) in chronic phase, 1- and 5-year survivals after HLA-A, B, DRB1 identical unrelated marrow transplantation in Seattle are 82% and 74%, respectively. These results are essentially identical to outcome in similar patients given HLA-matched sibling allografts. However, the world-wide number of alternative donor transplants for thalassemia remains limited to date: 4 unrelated and 60 HLA-nonidentical related transplants have been reported to the IBMTR since 1969 with actuarial overall survival of 75%. Using the paradigm of CML, it is likely that access to curative therapy of thalassemia will improve with optimal HLA typing and donor selection early in the course of disease.

Bone Marrow Transplantation↗

Bone marrow transplants from unrelated donors for patients with chronic myeloid leukemia.

BACKGROUND: Chronic myeloid leukemia can be cured by marrow transplantation from an HLA-identical sibling donor. The use of transplants from unrelated donors is an option for the 70 percent of patients without an HLA-identical sibling, but the morbidity and mortality associated with such transplants have been cause for concern. We analyzed the safety and efficacy of transplants from unrelated donors for the treatment of chronic myeloid leukemia and identified variables that predict a favorable outcome. METHODS: Between May 1985 and December 1994, 196 patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase received marrow transplants from unrelated donors. RESULTS: The median follow-up was 5 years (range, 1.2 to 10.1). Graft failure occurred in 5 percent of patients who could be evaluated. Acute graft-versus-host disease of grade III or IV severity was observed in 35 percent of patients who received HLA-matched transplants, and the estimated cumulative incidence of relapse at five years was 10 percent. The Kaplan-Meier estimate of survival at five years was 57 percent. Survival was adversely affected by an interval from diagnosis to transplantation of one year or more, an HLA-DRB1 mismatch, a high body-weight index, and an age of more than 50 years. Survival was improved by the prophylactic use of fluconazole and ganciclovir. The Kaplan-Meier estimate of survival at five years was 74 percent (95 percent confidence interval, 62 to 86 percent) for patients who were 50 years of age or younger who received a transplant from an HLA-matched donor within one year after diagnosis. CONCLUSIONS: Transplantation of marrow from an HLA-matched, unrelated donor is safe and effective therapy for selected patients with chronic myeloid leukemia.

Adolescent↗

Effects of alignment changes on stance phase pressures and shear stresses on transtibial amputees: measurements from 13 transducer sites.

Interface pressures and shear stresses were measured at 13 sites on two unilateral below-knee amputee subjects ambulating with lower-limb patellar-tendon-bearing prostheses. Interface stresses at the time of the first peak in the shank axial force-time curve were investigated at different socket-shank alignment settings. Stress magnitudes ranged from 1.2 to 214.7 kPa for pressure and 0.4 to 79.6 kPa for resultant shear stress, and changes in stress due to misalignment ranged from 1.3 to 80.7 kPa for pressure and from 0.2 to 38.0 kPa for resultant shear stress. For both subjects interface stress changes were much greater in the anterior socket region than in the lateral or posterior regions. Thus, alignment changes had a localized effect on interface stresses. Plots of alignment versus pressure or resultant shear stress were nonlinear for both subjects, in a number of cases maximizing or minimizing at the nominal alignment, indicating complex interface stress-alignment relationships. Variation (standard deviation/mean) was not significantly different for nominal versus misaligned steps, indicating that the subjects adapted well to the alignment changes. Session to session differences in interface stresses were typically larger than interface stress differences induced by alignment modifications. Thus, while these subjects compensated well for alignment changes to maintain consistent interface stresses within a session, they did not do so for different sessions conducted weeks apart.

Adult↗

An electromechanical testing device for assessment of hand motor function.

Instrumentation was designed and constructed to assess the strength and function of the intrinsic muscles of the index and long fingers of the hand. The device consisted of two beams instrumented with strain gages, signal conditioners, and a microprocessor-based embedded controller. A study conducted on four weak spinal cord injury (SCI), three nonweak SCI, and 21 control subjects demonstrated a trend of reduced maximum pinching force between the index and long fingers in weak SCI subjects compared with the other two groups. Weak SCI subjects also demonstrated a significantly slower rapid alternating movement speed of the index finger compared with the other two groups. The instrument has potential use as a clinical tool for quantitative evaluation of the progression of hand motor dysfunction.

Biomechanical Phenomena↗

Prevalence and predictors of sexual dysfunction in long-term survivors of marrow transplantation.

PURPOSE: To describe the prevalence of sexual difficulties in men and women after marrow transplantation (MT), and to define medical, demographic, sexual, and psychologic predictors of sexual dysfunction 3 years after MT. PATIENTS AND METHODS: Four hundred seven adult MT patients were assessed pretransplantation. Survivors repeated measures of psychologic and sexual functioning at 1 and 3 years posttransplantation. RESULTS: Data were analyzed from 102 event-free 3-year survivors who defined themselves as sexually active. Men and women did not differ in sexual satisfaction pretransplantation. At 1 and 3 years posttransplantation, women reported significantly more sexual dysfunction than men. Eighty percent of women and 29% of men reported at least one sexual problem by 3 years after MT. No pretransplantation variables were significant predictors of 3-year sexual satisfaction for women. For men, pretransplantation variables of older age, poorer psychologic function, not being married, and lower sexual satisfaction predicted sexual dissatisfaction at 3 years (R2=.28; P < .001). Women who were more dissatisfied 3 years after MT did not receive hormone replacement therapy (HRT) at 1 -year posttransplantation and were less satisfied at 1 year, but not pretransplantation (R2=.35; P < .001). CONCLUSION: Sexual problems are significant in the lives of MT survivors, particularly for women. Although HRT before 1 year posttransplantation improves sexual function, it does not ensure sexual quality of life. Intervention for women is needed to apply hormonal, mechanical, and behavioral methods to prevent sexual difficulties as early after transplantation as possible.

Adult↗

Material properties of commonly-used interface materials and their static coefficients of friction with skin and socks.

Compressive stiffness (CS) of different supporting materials used in prosthetics and orthotics and their static coefficients of friction (COF) with skin and socks were characterized. Materials tested included Spenco, Poron, nylon-reinforced silicone, Soft Pelite, Medium Pelite, Firm Plastazote, Regular Plastazote, and Nickelplast. A displacement-controlled testing device was constructed to assess the CS of 11.1 mm diameter material specimens under cyclic loading (1 Hz) to 220 kPa over 10- and 60-min periods. Results demonstrated local CS ranging from 687 kPa (Poron) to 3,990 kPa (Soft Pelite). To fit the cyclic stress-strain (S-S) data within an error of 4.0 percent full-scale output, the minimum order of fit required for Spenco, Poron, and nylon-reinforced silicone was a third-order polynomial; for Soft Pelite, Medium Pelite, Firm Plastazote, and Regular Plastazote, a second-order polynomial; and for Nickelplast, a linear fit. For all materials, the nonrecovered strains were related to loading time using an exponential fit. A biaxial force-controlled load applicator device was used to assess COF at skin-material, sock-material, and skin-sock interfaces for shear forces of 1 to 4 N applied to a 10.2 x 7.8 mm loading pad. COFs ranged from 0.48 (+/- 0.05) to 0.89 (+/- 0.09). COFs at skin-material interfaces were significantly (p < 0.05) higher than those at skin-sock interfaces. There was a trend of a higher COF at sock-material interfaces than at skin-sock interfaces. These data are of potential utility in finite element modeling sensitivity analysis of residual limb-prosthetic socket systems or body-orthosis systems to characterize effects of material features on interface pressure and shear stress distributions.

Biocompatible Materials↗

Mechanical characterization of biomaterials.

Experimental testing and computational modeling are two useful tools for mechanical characterization of biomaterials, providing insight into material stresses and strains and the possibility of mechanical failure and fatigue. Another interesting issue to consider, however, is tissue response to mechanical stress and strain and incorporation of that knowledge into design to create materials that form mechanically effective tissue-material interfaces in vivo. Experimental testing, computational modeling, and tissue response to stress and strain are discussed in the context of enhancing biomaterial design.

Animals↗

Marrow transplants from unrelated donors for treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia.

Transplantation of marrow from unrelated donors was investigated in patients with Philadelphia chromosome-positive (Ph1+) acute lymphoblastic leukemia (ALL) who lacked a suitable family donor. Eighteen patients underwent transplantation at our center between 1988 and 1995. The median patient age was 25 years (range, 1.7 to 51 years). Seven patients were in first complete remission, 1 in second remission, 3 in first relapse, and the remaining 7 had more advanced or chemotherapy refractory leukemia at transplant. All patients were conditioned with cyclophosphamide and total body irradiation followed by marrow transplants from closely HLA-matched, unrelated volunteers. Posttransplant graft-versus-host disease (GVHD) prophylaxis included methotrexate with either cyclosporine or FK506. Graft failure was not observed. Severe (grades III-IV) GVHD appeared in 6 of 17 evaluable patients and chronic extensive GVHD in 7 of 13 patients at risk. Five patients had recurrent ALL after transplantation and another 4 died from causes other than leukemia. Six patients transplanted in first remission, 2 in first relapse, and 1 in second remission remain alive and leukemia-free at a median follow-up of 17 months (range, 9 to 73 months). The probability of leukemia-free survival at 2 years is 49% +/- 12%. These data indicate that unrelated donor marrow transplantation is an effective treatment option for patients with early stage Ph1+ ALL without a family match and suggest that in such patients an unrelated donor search should be initiated as soon as possible after diagnosis.

Adolescent↗

Transplantation of marrow cells from unrelated donors for treatment of high-risk acute leukemia: the effect of leukemic burden, donor HLA-matching, and marrow cell dose.

Transplantation of hematopoietic stem cells from an HLA-compatible unrelated volunteer is an option for patients with acute leukemia lacking a family match. However, criteria for patient and donor selection and the most effective transplant procedures, including the number of hematopoietic cells, remain to be defined. We tested factors influencing outcome of 174 patients with primary acute leukemia receiving non-T-cell depleted marrow from unrelated donors. Median patient age was 20 years (range, 0.5 to 54 years). A multivariable analysis found that leukemia in remission at the time of transplantation was associated with improved leukemia-free survival (relative risk [RR] of treatment failure: 0.5, confidence interval [CI]: 0.3 to 0.7), and presence of blasts in the peripheral blood, as opposed to marrow involvement only or isolated extramedullary relapse, was associated with impaired outcome (RR of treatment failure: 2.5, CI: 1.7 to 5.0). The use of donors with a limited HLA-mismatch was associated with decreased leukemic relapse (RR: 0.5, CI: 0.3 to 0.9) but no improvement in leukemia-free survival compared with HLA-matched unrelated donors. Transplantation of a marrow cell dose above the median value of 3.65 x 10(8)/kg was associated with faster neutrophil (RR: 1.5, CI: 1.1 to 2.0) and platelet (RR: 4.5, CI: 2.7 to 7.5) engraftment, and decreased incidence of severe acute graft-versus-host disease (RR: 0.6, CI: 0.4 to 0.9). In patients transplanted in remission, the use of a marrow cell dose above the median translated into less nonleukemic death (RR: 0.2, CI: 0.1 to 0.4) and better leukemia-free survival (RR of treatment failure: 0.3, CI: 0.2 to 0.6). Transplant in remission with a high dose of marrow cells was associated with the best outcome in both children and adults.

Acute Disease↗