Dependence on neutron energy of the OER and RBE.
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Biomedical subjects
Publications and source records attributed to E J Hall.
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An established line of mouse fibroblasts (10T1/2 cells) cultured in vitro was used to compare the incidence of oncogenic transformation produced by x rays, the hypoxic cell radiosensitizer misonidazole, and a range of commonly used chemotherapy agents. A 3-day exposure to misonidazole at a concentration obtainable during treatment produced an incidence of transformation similar to that of about 50 rad. When chemotherapy agents were tested at concentrations comparable to those used clinically and matched to produce similar cell killing, the incidence of transformation varied widely: some agents, such as vincristine, did not produce transformation at a level detectable above background, while others, such as cis-platinum, appear to be potent carcinogens and produce transformation at a rate orders of magnitude higher than that achieved with x rays.
Mammalian cells cultured in vitro were used to study the radiobiological characteristics of neutron beams generated by 43 MeV protons on beryllium or 25 MeV deutrons on beryllium. For an unfiltered beam of neutrons generated by 43 MeV p+ leads to Be the relative biological effectiveness was found to be 8-12% higher at a depth of 2 cm than at a depth of 12 cm due to the presence of a large component of low-energy neutrons. The addition of a hydrogenous filter 4 cm thick preferentially removed the low-energy neutrons from the beam and, as a result, the neutron RBE was independent of depth. There was no significant difference in the oxygen enhancement ratio between the filtered neutrons produced by 43 Mev p+ leads to Be and neutrons produced by 25 MeV d+ leads to Be; for both beams the OER value was about 1.6.
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Chinese hamster V79 cells cultured in vitro were used to investigated the cytotoxicity of various anti-cancer drugs subsequent to a prolonged treatment of the cells with Misonidazole (MISO). The sensitivity of the cells to Bleomycin (BLM), Melphalan or cis-Platinum (cis-DDP) was significantly increased by prior incubation with MISO under hypoxic conditions. When cysteamine, a radical scavenger, was present during the pretreatment with MISO, this enhancement of cytotoxicity was greatly reduced. These experiments, suggest that MISO by virtue of its selective toxicity towards hypoxic cells and its enhancement of cell killing by anti-neoplastic drugs, can play an important role in cancer chemotherapy.
Heavy charged particles represent the ultimate that the physicist can contribute to the development of radiation sources for therapy. Of the heavy charged particles, protons are the least expensive to accelerate and can be manipulated to give a sharply defined high-dose volume with a rapid fall-off of dose outside the target area. The biological properties of protons do not differ significantly from X or gamma rays. Negative pi mesons require an elaborate accelerator for their production. Pions offer the possibility of concentrating energy, some of it densely ionizing with a reduced oxygen enhancement ratio and elevated biological effectiveness within the designated tumour volume, while minimizing the dose of sparsely ionizing radiation to the normal tissues traversed. High-energy heavy ions offer the greatest flexibility and allow localized dose distributions and also, with the higher Z particles, a substantial reduction of the oxygen enhancement ratio can be achieved. The ultimate choice of particle depends upon what turns out to be the most important factor in radiotherapy--an improved localization of dose or a reduction in the dependence of cell killing on the presence of molecular oxygen.
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Sophisticated procedures are now available to replace both sensory and motor loss. These are all possible through the advances in microsurgical techniques. The renewed interest in nerve repair and nerve grafting has been discussed. Improved results are now obtainable because of microsurgery. Standard neurovascular island flaps are being modified and superseded by neurovascular free flaps, with their improved sensation and accurate cortical representation. Examples of free tissue transfers that provide not only cover and sensation but structure, function, and innervated muscle have been illustrated. Microsurgical nerve grafting and transplantation are only in their infancy. New flaps and techniques await discovery and application.
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This study compared free flap survival rates following end-to-end and end-to-side arterial anastomoses. A groin flap was transferred to the anterior cervical region in 40 rats. There were 20 rats in each experimental group. The end-to-side group was further divided into subgroups depending on the angle of the anastomosis, which was either 60 degrees or 90 degrees. The results revealed no significant difference in the survival rates between any of the groups (which varied between 80 and 85 percent). A discussion of previous experimental work and the significance of these results has been presented. The advantages and disadvantages of end-to-side anastomoses have also been discussed.
Recently, the advantages of end-to-side anastomoses in reconstructive microvascular surgery have been emphasized. This article describes a practical laboratory model for practicing end-to-side anastomoses and a simplified technique for suturing the posterior wall in such anastomoses. The left common iliac artery of a rat is transected and an end-to-side anastomosis with the right common iliac artery is performed. A single clamp is manipulated to present the posterior wall for suturing.
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The potential of hyperthermia for producing oncogenic transformation in vitro was assessed using C3H/10T 1/2 mouse embryo cells. Temperatures in the range of 40 degrees to 45 degrees C caused no transformations, whether or not the heat treatment was associated with significant cell killing. In addition modest hyperthermia appreciably reduced the transformation frequencies associated with X-ray doses. The findings suggest an additional benefit in combining ionizing radiations with hyperthermia.
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The C3H/10T 1/2 cell line, cultured in vitro, was used to study the induction of oncogenic transformations produced by electron affinic compounds which function as hypoxic cell radiosensitizers. The relationship between the incidence of oncogenic transformations and drug concentration was obtained for 3-day exposures to misonidazole. At a concentration of 1 mM, a comparison was made of the carcinogenic potential of misonidazole, desmethylmisonidazole, Ro-07-0741, and SR 2508. Misonidazole and desmethylmisonidazole induced similar frequencies of transformation, while the frequency was doubled for Ro-07-0741 and increased by a factor of 5 for SR 2508. The relative carcinogenicity of the various alternatives to misonidazole is clearly a factor in choosing the next compound to be tested in the clinic.