PubMed HealthSearch

Biomedical subjects

F Wheeler

Publications and source records attributed to F Wheeler.

6 recordsLinked to original sources

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

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

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

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