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Biomedical subjects

F Wheeler

Publications and source records attributed to F Wheeler.

10 recordsLinked to original sources
PubMed2001

Microdosimetry model for boron neutron capture therapy: I. Determination of microscopic quantities of heavy particles on a cellular scale.

Due to the limitations of existing microdosimetry models, a new model called MICOR has been developed to analyze the spatial distribution of microscopic energy deposition for boron neutron capture therapy (BNCT). As in most existing models, the reactions independent of the incident neutron energy such as the boron and the nitrogen capture reactions can be considered. While other models do not include reactions that are dependent on the neutron energy such as the proton recoil reaction, the present model is designed so that the energy deposition resulting from these reactions is included. The model MICOR has been extended to enable the determination of the biological effects of BNCT, which cannot be done with the existing models. The present paper describes the determination of several microscopic quantities such as the number of hits, the energy deposition in the cell nucleus, and the distribution of lineal and specific energy deposition. The companion paper (Radiat. Res. 155, 000-000 2001) deals with the conversion of these microscopic quantities into biological effects. The model is used to analyze the results of a radiobiological experiment performed at the HB11 facility in the HFR in Petten. This analysis shows the value of the model in determining the dose depositions on a cellular scale and the importance of the extension to the energy deposition of the proton recoil.

Animals↗
PubMed2001

Microdosimetry model for boron neutron capture therapy: II. Theoretical estimation of the effectiveness function and surviving fractions.

A model has been developed to obtain a better understanding of the effects of boron neutron capture therapy (BNCT) on a cellular scale. This model, the microdosimetry model MICOR, has been developed to include all reactions important for BNCT. To make the model more powerful in the translation from energy deposition to biological effect, it has been designed to be capable of calculating the effectiveness function. Based on this function, the model can calculate surviving fractions, RBE values and boron concentration distributions. MICOR has been used to analyze an extensive set of biological experiments performed at the HB11 beam in Petten. For V79 Chinese hamster cells, the effectiveness function is determined and used to generate surviving fractions. These fractions are compared with measured surviving fractions, which results in a good agreement between the measured and calculated surviving fractions (within the uncertainties of the measurements).

Animals↗
PubMed1993

Capacity building and resource needs of state health agencies to implement community-based cardiovascular disease programs.

State Health Agencies play a critical role in the Nation's efforts for health promotion and disease prevention. This role is especially critical in efforts to reduce the burden of CVD through community-based programs. Resources SHAs need to facilitate implementation of community-based CVD prevention programs fall into three general categories: (a) Adequate time to plan, carry out and evaluate, (b) Financial resources to support staff, community organization and demonstration programs, and (c) Personnel with requisite technical expertise, skills and technological resources. Six critical activities for building state-level CVD program capacity include: (1) Forming a statewide CVD oversight committee, (2) Developing a state CVD plan, (3) Developing quality assurance standards and guidelines, (4) Developing new paradigms of community assessment and evaluation, (5) Planning for institutionalization, and (6) Translation of research to application. SHA roles vary from direct service delivery to serving as a linking agent, transferring information and resources and coordinating efforts between agencies.

Cardiovascular Diseases↗
PubMed1990

Basal and stimulated release of substance P from dissociated cultures of vagal sensory neurons.

Substance P, the widely distributed 11 amino acid neuropeptide, is present in up to 20% of vagal sensory cell bodies and the fibers emanating from them. To study the factors regulating the release of SP, vagal sensory (nodose or nodose/jugular) ganglia were obtained from neonatal rats and dissociated using neutral protease. Survival of plated neurons on collagen substrate was 10-20% at 2 weeks and 20-30% when neurons were plated over previously dissociated rat atriacytes. Substance P content was low in cultures for the first several days, then rose linearly to 0.1-0.2 pg/surviving neuron. Substance P was released into a 4.5 mM potassium medium at a steady rate of 0.036%/min. In 50 mM K+ supplemented medium, total release during 20 min increased 5-8-fold and steady-state release increased 4-5-fold to 0.15%/min. The sensory neuron specific excitatory neurotoxin, capsaicin, evoked SP release in similar amounts to 50 mM K+. Both net K(+)- and capsaicin-evoked, but not basal release were completely inhibited by 3.5 mM cobalt chloride. Bradykinin, 1-100 nM, stimulated SP release 2-4 times above basal levels. Forskolin and phorbol ester also increased SP release 1.5-3 times basal amounts. In summary, substance P is present in cultured vagal sensory neurons in amounts similar to in vivo and is released in response to sensory specific stimuli. These cultures should allow exploration of some of the tissue specific factors regulating neurotransmitter release in the sensory vagus nerve.

Animals↗
PubMed1989

Recent developments in neutron capture therapy.

The conditions for the possible initiation of clinical trials with neutron capture therapy at a number of locations in the U.S. is reviewed. There are several new technical developments or plans at the Brookhaven Medical Research Reactor (BMRR), the Power Burst Facility (PBF) at INEL, the Massachusetts Institute of Technology Reactor (MITR) and the Georgia Institute of Technology Research Reactor (GTRR). Emphasis is on the development of epithermal beams for the treatment of deepseated tumors with neutron fluxes in between 10(9) to 10(10) n/cm2s. Therapeutic dose gains, defined as the ratio of tumour dose to maximum normal tissue dose in the treatment volume are expected to be between 2 and 4, depending on the degree of suppression of fast neutron dose. Boron concentrations considered in this case in the tumour are around 35 micrograms 10B/g and tumour/normal tissue concentrations are around 10. The compound development throughout three generations is discussed. The compound proposed nowadays, Na2B12H11SH (or BSH), employed in the treatments in Japan, will likely be replaced in the future by analogous of biomolecules being enriched in the tumour by physiological pathways. Examples are p-boronophenylalanine or boronated porphyrius. The most promising solution envisaged would be the employment of tumour cell specific brononated monoclonal antibodies. Finally the mode of therapy is discussed which will likely be based on a fractioned scheme, to achieve optimized results.

Fast Neutrons↗
PubMedDate not supplied

Physical activity and public health: training courses for researchers and practitioners.

The authors explore development of courses in continuing education intended to provide additional research and practice capacity for addressing the growing burden of chronic disease and disability from physical inactivity. Two annual training courses on physical activity and public health are described. The courses are developed with funding from the Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Division of Nutrition and Physical Activity. The University of South Carolina, School of Public Health, Prevention Research Center has been an active collaborator and was responsible for developing and implementing the courses. An eight-day "Course on Research Directions and Strategies," is offered to postdoctoral researchers, and practitioners may take a six-day "Practitioners' Course on Community Interventions." Both courses are designed to increase the number of professionals qualified to implement physical activity community interventions and conduct physical activity and public health research.

Chronic Disease↗
PubMedDate not supplied

Optimization of boron and neutron delivery for neutron capture therapy.

A number of groups in the United States have received funding that will permit evaluation of the clinical efficacy of the neutron capture therapy (NCT) procedure. Various reactors are being modified to allow the construction of an epithermal neutron beam. At the Brookhaven Medical Research Reactor (BMRR), the patient irradiation facility is being modified to produce an optimized epithermal neutron beam. An 80-cm-thick A1-D2O mixture (184 g/cm2, 25% D2O by volume) is being installed in the shutter assembly. One-dimensional calculations indicate that this configuration should provide an epithermal neutron flux density of approximately 1 x 10(9) n/cm2/sec at 3 MW and a concomitant fast neutron dose rate of approximately 2 x 10(-11) rad per epithermal neutron (assuming a homogeneous A1-D2O mixture). The actual geometry will be an inhomogeneous array of D2O and A1 layers producing parameters somewhat less favorable than those listed above; experimental verification is in progress. Significant gains have recently been made in selectively targeting B to melanoma with various melanaffinic compounds, including p-boronophenylalanine, and with boronated porphyrins that may be applicable to a variety of tumors. Neutron capture radiographs have been obtained with the above compounds, and efforts have been made to quantitate boron uptake in growing and quiescent or necrotic regions of tumor via double-labeling techniques obtained with tritiated thymidine. A correlation between therapeutic efficacy and the ability to deliver boron to viable areas of tumor has been observed.

Animals↗