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Biomedical subjects

G K Lam

Publications and source records attributed to G K Lam.

At least 55 records · Page 3Linked to original sources
PubMed1987

The survival response of a biological system to mixed radiations.

The concept of additive radiation action is applied to the process of merging of the intermediate lesions at a common stage in the radiation inactivation pathways for lesions produced by different radiations. This gives rise to a natural nonindependent effect for combined irradiation. Even though the exact nature of this common intermediate lesion is unknown, the effect of this lesion additivity can still be formulated into a mathematical model using the assumptions: (1) there exists a stage in the chain of radiation inactivation events where different types of lesion precursors, produced by different types of radiations in a mixture, inflict lesions which become functionally indistinguishable and hence additive thereafter, to produce the same end point observed; (2) all precursors of all types are simultaneously competing for the opportunity to inflict lesions at the stage indicated in assumption 1, and each precursor has equal opportunity regardless of its origin; (3) if the radiations are delivered sequentially within a sufficiently short time, the lesion precursors of both radiations arrive at the above stage at about the same time and hence inflict lesions which are additive as described in assumptions 1 and 2. The model is quantitative but contains no free-fitting parameters. It is shown to be capable of explaining a large variety of apparently unrelated published experimental results observed for mixtures of high- and low-LET radiations.

Cell Survival↗
PubMed1986

The use of positron emission tomography in pion radiotherapy.

The radioactive debris produced by pion radiotherapy can be imaged by the technique of Positron Emission Tomography (PET) as a method of non-invasive in situ verification of the pion treatment. This paper presents the first visualization of the pion stopping distribution within a tumor in a human brain using PET. Together with the tissue functional information provided by the standard PET scans using radiopharmaceuticals, the combination of pion with PET technique can provide a much better form of radiotherapy than the use of conventional radiation in both treatment planning and verification.

Brain Neoplasms↗
PubMed1985

Preparatory clinical studies of Pi-mesons at TRIUMF.

Eighty patients have been treated with Pi-mesons (pions) at TRIUMF between 1979-1984. The patients had tumors rarely curable by standard methods and had no prior radiotherapy. The distribution by site included skin, metastatic nodules (13), brain, glioblastoma multiforme (32), pelvis, rectosigmoid (15), prostate (12), bladder (7), and ovary (1). The studies involve serial escalations of pion dose until maximum tissue tolerance is reached, monitoring the response at each dose increment. Sites were chosen for study where lack of local control is a significant cause of treatment failure with conventional radiation therapy. The low dose rate and the available beam access at TRIUMF limit the number of patients treated and the volume treatable. A 3-D treatment planning program is in use, and a 3-D display of the dose distribution delivered in brain tumor treatments has been developed using the PET scanner. In practice, new methods introduced for measurement of tissue response include tumor growth delay curves, fine-needle biopsy mapping, and PET scanning of brain tumors. The use of endoscopic assessment of the rectosigmoid region is emphasized. Treatment results of glioblastoma multiforme show that the median survival for patients treated to 125 pion cGy/fx is in the range of 187-198 days; for patients receiving 170 cGy per dose/fraction (fx) the range is 290-315 days, and for those receiving 200-220 cGy/fx the median survival is in excess of 290 days. For pelvic malignancies the local control obtained with doses of 2500 cGy or less was 50% in 12 assessable patients; it was 75% in 20 patients who had 3000 cGy or more.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

In vitro and in vivo studies of the TRIUMF pion therapy beam.

Patient treatments at TRIUMF (Tri-University Meson Facility, Vancouver, B. C.) use a moving spot raster scan technique where the pion range is modulated in depth for each position of the moving spot. The spot scans in a stepwise fashion and can produce any desired field shape. This approach provides very good dose uniformity across the treatment field and allows maximum flexibility in shaping the treatment volume. Survival of cultured cells has been used as a biological dosimeter to test the isoeffectiveness of the pion dose distributions, which must be shaped in depth to compensate for the depth-dependent LET distribution. Isoeffectiveness across the treatment field has also been verified using this system, which involves irradiating cells supported in a gelatin matrix. The response of pig skin to pion irradiation at TRIUMF has provided a check on the in vivo RBE for acute effects derived from our earlier studies with mouse foot. In addition, the pig skin reactions have been followed for several months to assess the later dermal response. The RBE of our pion beam relative to 270 kVp X rays is approximately 1.5 for both the acute epidermal and the later dermal responses.

Animals↗
PubMed1982

Radiobiology of pions at TRIUMF.

Radiobiological studies at TRIUMF of the effects of pion beams have been carried out using cultured cells, mice and pigs. CHO cells in gel/medium were used for RBE determinations throughout the dose distributions. The RBE was shown to increase with depth in the stopping region, while the average RBE value decreased with increasing width of the stopping peak and also increased with increasing field size. The results suggest that the effects of peak width and field size will approximately cancel out when treatment volumes are changed, provided that all three dimensions are changed more or less proportionally. The peak center RBE values ranged from 1.2-1.3 for single doses. The oxygen enhancement ratio (OER) for pions was 2.2 compared to 2.8 for X rays. Split dose recovery was found to be somewhat reduced in the peak region. In vivo studies with mouse and pig skin have been done for 1 to 20 fractions. For mouse skin, pions showed an RBE of 1.5-1.6 for fraction numbers greater than 10. The RBE for pig skin was 1.4 for early reactions, but it may be higher for medium term reactions.

Animals↗
PubMed1982

Pions, Vancouver.

Clinical treatments at TRIUMF started in November, 1979. Ten patients with malignant subcutaneous nodules had 14 lesions treated with pions and 37 other nodules treated with 280 kV X rays. Three different fractionation regimens were used with X ray doses spanning the expected RBE range of pions. The RBE for pions for acute skin reaction for 10 fractions had a mean value about 1.5, while for 3 fractions it was 1.3 maximum. No dissociation of acute and late skin effects was seen with follow-up to 27 months after treatment. Phase 1-2 studies of Pion-Boost Therapy for patients with glioblastoma multiforme will begin in May, 1982. These will be followed in August with treatments of advanced pelvic malignancies using pions only. The existing beam line at TRIUMF will be upgraded and commitments have been given to go to higher beam currents. As a result, the dose rate should increase by a factor of at least two, allowing treatment of clinically relevant volumes in acceptable times by 1983-1984.

Brain Neoplasms↗
PubMed1979

Pre-clinical studies of the negative pi-meson beam at TRIUMF.

The pi- flux from the biomedical channel at TRIUMF increases with increasing channel momentum, while the contaminating electron flux decreases. Since the electrons appear to result from conversion of the high energy gamma-rays produced by pi0 decay in the production target, the electron contamination can be reduced further by target configurations which minimize gamma conversion. The attenuation of pi- beams by in-flight interactions was found to decrease from an initial value of 1.67 +/- 0.02% per g/cm2 at zero depth to 1.48 +/- 0.02% per g/cm2 near the stopping peak. The inactivation of cultured CHO cells by an extended-peak pi- dose distribution has been measured using the gel technique. The survival data have been fitted by a model which characterizes the physical quality of the dose profile by means of measured star densities. This model provides a convenient method of analysis for large sets of survival data and may be useful for prediction of the biological effect of new pi- dose distributions. The RBE value for 50% survival measured at the centre of a 7 cm extended peak was found to be approximately 1.4, in reasonable agreement with recent values obtained at LAMPF and SIN.

Animals↗
PubMed1979

Uniform depth dose distribution for biological irradiation using negative pions.

A simple, flexible technique has been developed to generate uniform depth dose profiles for the biomedical pion beam at TRIUMF using dynamic momentum control and linear programming. Either the entrance dose or the irradiation time required for a certain dose over the uniform region can be minimised. The dynamic momentum control can operate automatically under computer control even with a highly unstable beam. Cell survival profiles have been obtained for this uniform dose distribution using the gelatin technique. The RBE increases with increasing depth through the uniform dose region.

Animals↗
PubMed1979

The comparative survival of clonogenic cells of a murine epithelioma irradiated in vivo with 250 kVp X rays, 60Co gamma rays, or negative pions produced by the cyclotron at TRIUMF.

Squamous carcinomas in WHT/Ht mice were exposed to the biomedical pion beam at TRIUMF. The biological effects of the pion beam were compared to those of 250 kVp x rays. The dose rates were 2-3 rad/min. (.02-.03 Gy/min.) for pions and 56 rad/min. (.56 Gy) for x rays. The surviving fraction of epithelioma cells irradiated in vivo was studied using the TD50 assay. RBE values for pions were calculated from the ratio of the x-ray and pion D0 values and were found to be 1.6 +/- 0.3 for oxic cells and 2.1 +/- 0.4 for hypoxic cells. OER values were 1.8 +/- 0.5 for pions and 2.4 +/- 0.4 for 250 kVp x rays.

Animals↗
PubMed1978

Membrane effects of imidoesters in hereditary stomatocytosis.

The marked increase in cation (Na+, K+) permeability that results in swollen, cup-shaped red cells in the hereditary stomatocytosis syndrome can be corrected in vitro with a bifunctional crosslinking reagent, dimethyl adipimidate (DMA). 45Ca influx in intact RBC, 45Ca efflux in red ghosts, and 45Ca retention in red ghosts are normal and not influenced by DMA. Endocytosis in resealed red ghosts is strikingly impaired but becomes normal if cells are first treated with 2 mM DMA. Protein kinase mediated phosphorylation of membrane proteins by AT32P--only 20--40% of normal control values in both shortterm (5 min) and more extended (60 min) incubations--is not improved by DMA. After reaction of 14C-DMA with stomatocytes, radiolabel is found associated with phosphatidyl serine and phosphatidyl ethanolamine and is also widely distributed among membrane proteins. Cation permeability of stomatocytes in corrected at DMA concentrations (1 mM) that result in barely detectable crosslinking of aminophospholipids or proteins, suggesting that either crosslinking of a minor component present in only small quantities or intramolecular (rather than intermolecular) crosslinking is responsible for the permeability effects. DMA, whose maximal crosslinking dimension is 7.3--9 A, is the most effective bifunctional imidoester of those tested. Shorter (dimethyl malonimidate) or longer (dimethylsuberimidate) reagents are either less effective than DMA or totally without effect.

Anemia, Hemolytic↗