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Biomedical subjects

Margaret Lucas

Publications and source records attributed to Margaret Lucas.

13 recordsLinked to original sources

Methods for reducing cutting temperature in ultrasonic cutting of bone.

Ultrasonic cutting is widely used in food processing applications to produce a clean and accurate cut. However, it is yet to be adopted as an instrument of choice in orthopaedic applications, mainly due to the high temperatures that can be generated at the cut site and the consequent requirement to use additional cooling. For example, if cutting temperatures above 55-60 degrees C are reached, particularly for sustained periods, bone necrosis can occur, compromising post-operative recovery. A recent study by the authors has shown that the thermal response in natural materials, such as wood and bone, is affected by the absorption of ultrasonic energy and conduction of heat from the cut site. In this paper the dependency of cutting parameters, such as blade tip vibration velocity, applied load, tuned frequency and coupling contact conditions, on the thermal response are reported and results show that it is possible to maintain cutting temperatures within safety limits by controlling the cutting parameters. A novel cutting blade design is proposed that reduces frictional heat generated at the cut site. Through a series of experimental investigations using fresh bovine femur it is demonstrated that the cutting temperature, and hence thermal damage, can be reduced by selecting appropriate cutting parameters and blade profile.

Animals↗

A finite element model for ultrasonic cutting.

Using a single-blade ultrasonic cutting device, a study of ultrasonic cutting of three very different materials is conducted using specimens of cheese, polyurethane foam and epoxy resin. Initial finite element models are created, based on the assumption that the ultrasonic blade causes a crack to propagate in a controlled mode 1 opening, and these are validated against experimental data from three point bend fracture tests and ultrasonic cutting experiments on the materials. Subsequently, the finite element model is developed to represent ultrasonic cutting of a multi-layered material. Materials are chosen whose properties allow a model to be developed that could represent a multi-layer food product or biological structure, to enable ultrasonic cutting systems to be designed for applications both in the field of food processing and surgical procedures. The model incorporates an estimation of the friction condition between the cutting blade and the material to be cut and allows adjustment of the frequency, cutting amplitude and cutting speed.

Journal Article↗

Superimposed ultrasonic oscillations in compression tests of aluminium.

The application of ultrasonics in metal forming applications has been shown to reduce the forming load significantly in many research studies. The load reduction has been related to the stress superposition effect, rise in temperature and change in the friction condition between the specimen and die interfaces. This paper reports an investigation into the effects of superimposed ultrasonic oscillation of the die in compression tests on aluminium specimens. In particular, a finite element model is developed to simulate uniaxial compression and to model the effects of a change in the friction boundary condition when ultrasonic excitation is applied to the lower platen. The model predictions of the stress-strain relationship can be compared with test data to provide some insights into the effects of the interfacial condition. The paper shows how the analysis of the test data, combined with finite element models of ultrasonic compression test simulations, allows some initial conclusions to be drawn regarding the influence of the interfacial friction during ultrasonic compression.

Journal Article↗

A phase I/II study examining pentostatin, chlorambucil, and theophylline in patients with relapsed chronic lymphocytic leukemia and non-Hodgkin's lymphoma.

In an attempt to exploit bcl-2 overexpression and aberrant p53 function, two frequently encountered aberrations that predict marked treatment resistance and worse prognosis in patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL), we combined theophylline, pentostatin, and chlorambucil at two dose levels (cohort I: 30 mg/m(2); cohort II: 20 mg/m(2)) on a 21-day cycle for up to six courses. We employed a phase I/II design to determine feasibility, define the maximum tolerated dose (MTD), and explore the impact of biologic modulation on response and time to progression (TTP) in 20 patients with relapsed or refractory CLL and NHL. Eight patients were enrolled in cohort I. They demonstrated a response rate (RR) of 28% and a 16.5-month TTP after receiving a median of two cycles. A 50% RR was observed in this cohort when patients with adverse histologies were excluded. Because of myelotoxicity, this dose level defined the MTD, and de-escalation occurred. All 12 patients in cohort II received 20 mg/m(2) chlorambucil. A 50% RR and an 18-month TTP were observed after a median of 5.5 cycles. An RR of 47% and a complete remission (CR) of 5% were observed for the entire group, although responses and TTP varied greatly by histology. Significant activity was observed in patients with B-cell CLL and follicular lymphoma (FL). RR and TTP for fludarabine-sensitive/naïve and fludarabine-refractory (FR) B-cell CLL patients were 66 vs 25% and 20 vs 8.5 months, respectively. Both FL patients responded (one with partial remission and one with CR), with a 22.5-monthly median TTP. For responding patients, median TTP and overall survival (OS) was 21 and 69 months, respectively, compared to a median TTP of 2 months and an OS of 13.5 months for nonresponders. The combination of pentostatin, chlorambucil, and theophylline is the active regimen in patients with FL and B-cell CLL.

Adult↗

Alemtuzumab is an effective therapy for chronic lymphocytic leukemia with p53 mutations and deletions.

The presence of p53 mutation or deletion predicts for poor response to conventional therapy in chronic lymphocytic leukemia (CLL). We sought to determine whether the humanized anti-CD52 antibody alemtuzumab was effective in this patient group. Thirty-six patients with fludarabine-refractory CLL were treated with alemtuzumab, 15 (42%) of whom had p53 mutations or deletions. Clinical responses in patients with p53 mutations, deletions, or both were noted in 6 (40%) of 15 versus 4 (19%) of 21 of patients without. The median response duration for this subset of patients was 8 months (range, 3-17 months). These data suggest that alemtuzumab may be an effective therapy for patients with CLL with p53 mutations or deletions.

Aged↗

Antibody therapy for chronic lymphocytic leukemia: a promising new modality.

Therapeutic options for chronic lymphocytic leukemia (CLL) have been limited, with low complete response rates (CR) and no treatments demonstrating a survival advantage. The recent introduction of the monoclonal antibodies rituximab and alemtuzumab into clinical trials for patients with CLL has generated promising results. Rituximab targets the CD20 antigen and demonstrates varied single-agent activity that is highly dependent upon the dosing schedule and treatment status of the patient. More importantly, when rituximab is combined with fludarabine or fludarabine and cyclophosphamide, a high frequency of CR and prolonged progression-free survival are observed without an appreciable increase in significant toxicity. Alemtuzumab targets the more ubiquitously expressed CD52 antigen and is therefore associated with a higher frequency of toxicity, particularly immunosuppression, but has appreciable activity in fludarabine refractory CLL. Additionally, alemtuzumab is effective against CLL clones that have p53 mutations or deletions. Future efforts in developing combination strategies with rituximab, alemtuzumab, and potentially other new antibodies offer great promise for the future treatment of CLL.

Alemtuzumab↗

A novel multiple blade ultrasonic cutting device.

In ultrasonic devices consisting of serially coupled tuned components, components whose tuned length dimension is large compared to other dimensions, or components with profiles designed for high gain, the response of the device during operation is often characterised by modal interactions, and especially the excitation of combination resonances. The effects on ultrasonic devices are high noise levels, component failures and poor operating performance. In this paper, energy exchanges between modes are characterised to illustrate the adverse effects of combination resonances. Design solutions are proposed to eliminate these effects which concentrate on reducing the number of modes. In particular, a novel half-wavelength three-blade cutting system tuned to the first longitudinal mode has been designed by finite element modelling. An experimental investigation demonstrates that the measured response does not show evidence of modal interactions.

Journal Article↗

Post-transplant interleukin-2 in patients with low-grade lymphoid neoplasms previously treated with fludarabine is limited by hematologic toxicity.

Given the favorable immunologic effects of IL-2 post transplant, we conducted a feasibility study examining rIL-2 1.0x106 IU/m2/day (SQ) beginning on D+14 post-transplant and continuing for 90 days in 12 patients with low-grade lymphoproliferative disorders. Prior to high-dose chemotherapy and autologous peripheral blood stem cell transplantation (HDCT), 11 patients underwent cytoreduction with fludarabine and cyclophosphamide (Flu/Cy); 11 were in complete remission (CR) and one was in partial remission at the time of HDCT. All 12 patients were in CR 90 days post-HDCT. At a median follow-up of 30 (range 3-44) months, seven patients (58%) remain in remission, four are alive with disease, and one has died of disease progression, resulting in an overall survival of 92%. Kaplan-Meier estimates of progression-free survival (PFS) for the group demonstrate a median of 31 (range 3-43) months. Five patients required rIL-2 cessation at 8-58 days after starting the therapy due to hematologic toxicity. These results are comparable to those achieved in other published bone marrow and peripheral blood stem cell transplantion (PBSCT) series without the addition of rIL-2. Furthermore, rIL-2 using this schedule following fludarabine-based cytoreduction was associated with excessive hematologic toxicity.

Adult↗

Enhanced vibration performance of ultrasonic block horns.

Block horns are tuned components designed to vibrate in a longitudinal mode at a low ultrasonic frequency. Reliable performance of such horns is normally associated with the amplitude of vibration, uniformity of vibration amplitude at the working surface and the avoidance of modal participation by non-tuned modes at the operating frequency. In order to maximise vibration amplitude uniformity, standard slotting configurations are included in the horn design. However, defining a slotted block geometry which guarantees sufficient tuned frequency isolation from nearby modes as well as high amplitude and amplitude uniformity, is not straightforward. This paper discusses horn configurations which satisfy these criteria and investigates the design requirements of block horns which operate as intermediate components in ultrasonic systems, where the block horn dominates the vibration behaviour of the system. The importance of mode shape characterisation is discussed and modes are classified using experimental data from 3D laser Doppler vibrometer measurements and finite element analysis. In particular, the role of additional fine slots and castellations are studied with reference to two distinct ultrasonic applications involving a similar block horn.

Journal Article↗

Influence of ultrasonics on upsetting of a model paste.

This paper describes a preliminary study of the influence of ultrasonics on the boundary conditions associated with the equipment walls in a soft solid forming operation using Plasticine as a material model. A detailed finite element analysis is described involving the upsetting of a cylindrical specimen between two parallel rigid dies with kinematics and ultrasonic oscillatory loading conditions. A series of squeeze flow experiments has been conducted to validate the finite element models. The oscillation parameters were measured using a 3D laser Doppler vibrometer to complement the measurement of reaction forces.

Journal Article↗

Chronic lymphocytic leukemia.

This update of early stage B-cell chronic lymphocytic leukemia (B-CLL) embraces current information on the diagnosis, biology, and intervention required to more fully develop algorithms for management of this disease. Emphasis on early stage is based on the rapid advancement in our understanding of the disease parameters and our increasing ability to predict for a given early stage patient whether there is a need for more aggressive management. In Section I, Dr. Terry Hamblin addresses the nature of the disease, accurate diagnostic procedures, evidence for an early "preclinical" phase, the use of newer prognostic features to distinguish who will be likely to progress or not, and whether it is best to watch or treat early stage disease. In Section II, Dr. Neil Kay and colleagues address the biologic aspects of the disease and how they may relate to disease progression. Review of the newer insights into gene expression, recurring genetic defects, role of cytokines/autocrine pathways, and the interaction of the CLL B cell with the microenvironment are emphasized. The relationship of these events to both trigger disease progression and as opportunities for future therapeutic intervention even in early stage disease is also considered. In Section III, Dr. John Byrd and colleagues review the historical and now current approaches to management of the previously untreated progressive B-CLL patient. They discuss what decision tree could be used in the initial decision to treat a given patient. The use of single agents versus newer combination approaches such as chemoimmunotherapy are discussed here. In addition, the place of marrow transplant and some of the newer antibodies available for treatment of B-CLL are considered. Finally, a challenge to utilize our growing knowledge of the biology of B-CLL in the early stage B-CLL is proffered.

Antineoplastic Agents↗