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Biomedical subjects

P D Higgins

Publications and source records attributed to P D Higgins.

At least 37 records · Page 2Linked to original sources
PubMed1991

Basic radiobiological investigations of fast neutrons.

The radiobiological properties of a cyclotron-produced 43-MeV (p----Be) fast-neutron beam relative to gamma rays have been investigated using Chinese hamster V79 cells in culture. As expected, the relative biological effectiveness (RBE) of this neutron beam for cell killing was shown to increase as dose decreased, and the effectiveness per unit dose was slightly less compared to a 25-MeV (d----Be) neutron beam. By tracing single cells that formed microcolonies after irradiation, we found cell proliferation kinetics to be retarded to a greater extent by fast neutrons than by gamma irradiation. Following either neutron or gamma irradiation, a fraction of the irradiated cells failed to divide in the first postirradiation division and another fraction could produce as many as four generations of progeny before proliferation stopped. The properties of these cells presumed to be destined for death suggest that more than one mechanism and/or multistep process underlies the radiation-induced proliferative death. The fast-neutron beam was also found to be more effective quantitatively than gamma rays in producing DNA double-strand breaks (DSBs, measured by nondenaturing filter elution), and G1-phase chromosome fragments (measured by the premature chromosome condensation technique). However, the reverse was observed for DNA single-strand breaks (SSBs, measured by alkaline filter elution or hydroxylapatite uncoiling). Interestingly, both fast neutrons and gamma rays produced a large component of SSBs and DSBs with a fast-rejoining time constant of about 2-5 min, which appears to be independent of dose. The latter results could not resolve the possibility of lengthening the repair-time constant by increasing radiation dose within the range that is reflected by the shoulder of the survival curve, and consequently did not support the idea of repair saturation as a mechanism for the presence of the shoulder. The RBE for the hypoxanthine phosphoribosyl transferase mutation frequency per survivor at the 10% survival level was estimated to be 2.5, a value that is comparable to the RBE (2.1) for cell killing at the same survival level. Although most of the above-mentioned findings are compatible qualitatively with the relatively high-LET (linear energy transfer) nature associated with the fast-neutron beam, the significance of the action attributable to the mixture of LET could not be delineated in these experiments. Further, the biological significance of DSBs and chromosome aberration and the molecular mechanisms responsible for the repair and expression of these damaging processes remain to be elucidated.

Animals↗
PubMed1990

Phosphorus metabolites and the distribution of cell cycle phase of RIF-1 tumors in response to 14 Gy irradiation.

Simultaneous measurements of DNA cell phase cycle distributions and in vivo 31P NMR spectroscopy were performed on 40 RIF-1 murine tumors irradiated with 14 Gy of X-radiation. Diploid and tetraploid tumor populations were observed. The cells blocked in G2/M phase were measured as a function of the ratios of tetraploid cell number in G2/M phase versus total cell population measured. The G2/M population reached a maximum at 32 h post irradiation, dropping to control values by 72 h, while the ratio of inorganic phosphate to beta-nucleotide triphosphate dropped significantly at 32 h and remained significantly lower than control up to 72 h post irradiation. Measurements of PME, PDE, PCr, and pH showed no significant variations at any time point. No significant change in host cell population could be observed. Since the measured G2/M population never increased to more than 3% of the total cell population, the change observed in the 31P NMR spectra were not simply the result of possible differences in NMR profiles of the different cell phase populations but were more likely due to a change in the metabolic characteristics or environment of a majority of the cells.

Animals↗
PubMed1990

Influence of hip prostheses on high energy photon dose distributions.

Radiotherapy treatment of patients having a hip prosthesis is a common problem facing dosimetrists and physicists when the treatment plan requires irradiation of the pelvic area. To quantify the perturbation of these devices, attenuation studies were done with 6 and 18 MV photon beams using various hip prostheses models with varying size and composition. These studies have shown that an attenuation of as much as 50% can be found in a single beam profile under the prosthesis. We have studied the capability of a dose planning system to predict the transmission of these devices as compared with measurements.

Alloys↗
PubMed1989

Application of thermal dilution measurements for thermal treatment planning.

The use of thermal dilution measurements is demonstrated in quantifying effective thermal conductivity distributions through tumours. For focused acoustic sources these data are applied in the solution of the heat diffusion equation to estimate steady-state temperature distributions. The advantages and disadvantages of this approach are presented. The effective conductivity measurements are found to be useful in predicting the circumstances under which this simple model can be applied and in aiding the selection of the most appropriate heating modality.

Animals↗
PubMed1989

Clonogenic cells and rat mammary cancer: effects of hormones, X rays, and fission neutrons.

On Day 0, young adult female F344 rats were adrenalectomized and intrasplenically implanted with a pituitary gland and capsule containing estrone. All were thereafter given 2.5 mg deoxycorticosterone per week and the choice of saline or tap water. This treatment yields high prolactin levels and glucocorticoid deficiency (Prl+/Glc-). On Day +48, total recoverable mammary DNA was increased by more than sevenfold, tritiated thymidine uptake by nearly fourfold, and total mammary clonogens by about fivefold. Irradiation with 4, 40, and 80 cGy X rays on Day +48 increased total mammary carcinomas per rat day at risk linearly with dose, and 40 and 80 cGy significantly decreased first carcinoma latency. A dose of 40 cGy X rays on Day -1 yielded tumor latencies and frequencies insignificantly different from unirradiated controls and significantly different from the dose on Day +48. Total carcinomas per rat day at risk were better fit by a function of dose to the power 0.4 than by a linear function after exposure to 1, 10, and 20 cGy fission neutrons, and 10 and 20 cGy significantly shortened the time to appearance of the first cancer. In contrast to results with X rays, 10 cGy neutrons on Day -1 yielded tumor frequencies and latencies insignificantly different from 10 cGy neutrons on Day +48. The carcinogenic action of X rays was thus influenced by total clonogen numbers and/or proliferation rates; that of neutrons was not.

Animals↗
PubMed1989

Less well known parameters of in vitro radiosensitivity.

In addition to well known parameters used for measuring in vitro cellular radiosensitivity (mean lethal dose, extrapolation number, quasithreshold dose), there are other, less well known measures that may be more important. The authors recently surveyed the literature and found that mean activation dose (D) has been neglected in the analyses. Among 70 articles published in the radiation oncology and biology literature that used cell survival curves or parameters to measure radiosensitivity, only two used the values of D in their analysis. By recalculating D from published survival curves, different conclusions may be drawn. The authors see a definite need for more prospective application of D and surviving fraction at 2 Gy.

Cell Survival↗
PubMed1988

Posterior spinal cord block: a dosimetric study.

To determine the optimal width of a midline posterior spinal block (MPSB) (to avoid delivering too great a dose to the cord and too small a dose to adjacent tissue), the authors determined with magnetic resonance (MR) imaging normal ranges of cord depth and width and correlated them with film dosimetric data. In 59 randomly selected patients there was a wide range for both depth and width. The average depths of the anterior and posterior surfaces of the cord were 6.7 cm +/- 1.4 and 5.4 cm +/- 1.3, respectively. The average cord width was 1.6 cm +/- 0.4. Optimal cord block width as a function of cord width was determined for a 6-MV photon beam. The optimal cord block width at the surface (half-value layer [HVL] thickness = 6) varied from 1.5 to 3.0 cm for cord widths of 0.8-2.4 cm, which correspond to two standard deviations from the average. There was no significant dependence on depth of the cord. For optimal treatment outcome, the MPSB width may have to be determined for each patient individually.

Film Dosimetry↗
PubMed1988

Thermal dosimetry of normal porcine tissue.

The response of normal porcine fat and muscle to graduated doses of hyperthermia provided by an annularly focused acoustic source was measured. Temperatures and exposure times were varied between 43 degrees C (20-90 min), 45 and 47 degrees C (20-60 min), and 49 degrees C (20 min). Response, based on histologic grading of the treated sites 30 days after exposure, was found to correlate well when mapped against several methods of estimating thermal energy deposition. The threshold for damage production was at or near 43 degrees C. For a given temperature, a nearly exponential increase in relative tissue damage as a function of increased exposure time was found. A twofold increase in tissue damage was produced in fat relative to muscle at any given thermal dose.

Adipose Tissue↗
PubMed1985

Determination of contamination-free build-up for 60Co.

Experimental verification of the difference between absorbed dose in tissue and the collision fraction of kerma requires precise knowledge of the absorbed dose curve, particularly in the build-up and build-down regions. A simple method for direct measurement of contamination-free build-up for 60Co, which should also be applicable for most of the photon energies commonly employed for treatment, is presented. It is shown that the contribution from air-scattered electrons to the surface dose may be removed by extrapolating measurements of build-up to zero field size. The remaining contribution to contamination from the collimators and other source-related hardware may be minimised by measuring these build-up curves sufficiently far from the source. These results were tested by measuring the build-up using a magnet to sweep scattered electrons from the primary photon beam and by measuring the surface dose in the limit of an evacuated beam path. The relative dose at zero depth in polystyrene was found to be approximately 8.9 +/- 0.3% of the dose at the depth of maximum build-up.

Cobalt Radioisotopes↗
PubMed1985

Chronic response of normal porcine fat and muscle to focused ultrasound hyperthermia.

Annular focused ultrasound (1.13 MHz) hyperthermia was used to evaluate chronic histologic effects of a range of high thermal dosages on normal porcine tissues. The effects of three peak temperatures (45, 47, and 49 degrees C) at a focal depth of 2 cm in thirty 4-cm-diameter sites were studied as a function of exposure time (10-60 min). Relative fat and muscle damage were histologically graded 1 month post-treatment. Unlike reports of radiofrequency hyperthermia, no necrosis or abscess formation was observed, even at 49 degrees C for 40 min. Fat sustained a greater percentage maximal tissue damage than muscle, although less than 4% of sections evaluated had histologic evidence of severe injury. Focused ultrasound provides a relatively uniform heat distribution in normal tissues. It should therefore be possible to raise normal tissues surrounding tumors to high temperatures using focused ultrasound, potentiating tumoricidal effects with minimal associated complications.

Adipose Tissue↗
PubMed1984

Versatility of distributed focus ultrasound in treatment of superficial lesions.

In order to study the efficacy of hyperthermia as a cancer treatment modality, it is important to be able to define the specific volume being raised to hyperthermic temperatures corresponding to the selected method of heating. Measurements have been made of temperature distributions in rat mammary tumors during steady state heating with annular focused ultrasound (2.0 MHz). Biological response in terms of growth inhibition is compared with uniformity of induced temperature throughout the tumors as a function of annular focusing dimensions.

Animals↗
PubMed1984

Effect of pulsed dose in simultaneous and sequential irradiation of V-79 cells by 14.8-MeV neutrons and 60Co photons.

The effect of irradiating V-79 Chinese hamster cells with a mixture of 40% 14.8-MeV neutrons and 60% 60Co photons with simultaneous or sequential exposures is investigated. Sample doses are obtained by irradiating cells with alternating 3-min pulses of neutrons and photons (in the sequential case) or with mixed neutrons and photons followed by equal beam-off periods to ensure equal total exposure times for sequential and simultaneous irradiations. Differences between the survival results under each beam configuration that are consistent with previous observations with nonpulsed irradiations are observed.

Animals↗
PubMed1983

V79 survival following simultaneous or sequential irradiation by 15-MeV neutrons and 60Co photons.

A unique tandem source irradiation facility, composed of an intense d-T neutron source and a 60Co teletherapy unit, was used to investigate biological responses for different neutron/photon configurations. V79 Chinese hamster cells, attached as monolayers in log-phase growth, were irradiated at 37 degrees C by either 14.8-MeV neutrons, 60Co, or a mixture of 40% neutrons and 60% photons in simultaneous or sequential application. Measurements of cell survival indicate an increased effectiveness in cell killing for simultaneously administered neutrons and photons compared to that measured or predicted for sequentially applied beam modalities. An understanding of the magnitude of these interactive effects is important both for calculating accurate effective doses for neutron radiotherapy of deep-seated tumors, for which the photon component is appreciable, and for determination of environmental hazards to people occupationally exposed to mixtures of photons and neutrons.

Animals↗
PubMedDate not supplied

Calculational methods for estimating skin dose from electrons in Co-60 gamma-ray beams.

Several methods have been employed to calculate the relative contribution to skin dose due to scattered electrons in Co-60 gamma-ray beams. Either the Klein-Nishina differential scattering probability is employed to determine the number and initial energy of electrons scattered into the direction of a detector, or a Gaussian approximation is used to specify the surface distribution of initial pencil electron beams created by parallel or diverging photon fields. Results of these calculations are compared with experimental data. In addition, that fraction of relative surface dose resulting from photon interactions in air alone is estimated and compared with data extrapolated from measurements at large source-surface distance (SSD). The contribution to surface dose from electrons generated in air is 50% or more of the total skin dose for SSDs greater than 80 cm.

Cobalt Radioisotopes↗
PubMedDate not supplied

Performance characteristics of A 150 plastic-equivalent gases in A 150 plastic proportional counters for 14.8-MeV neutrons.

Two recently developed A 150 plastic-equivalent gas mixtures have been tested for suitability in proportional counter applications. Methane- and propane-based "tissue-equivalent" gases were also included for comparison purposes. Event-size weighted dose distributions were measured in a 14.8-MeV neutron beam. Resolution was found to be independent of gas mixture. Moreover the gains of the two A 150 mixtures were the same, and comparable to that of the methane-based gas mixture. The ionization yield per event size was also independent of the hydrogenous gas mixture employed. Neutron doses determined with the proportional counter were in reasonable agreement with those obtained from an ionization chamber.

Fast Neutrons↗