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Biomedical subjects

P W Sheldon

Publications and source records attributed to P W Sheldon.

At least 55 records · Page 3Linked to original sources
PubMed1977

The effect of radiation on tumour growth delay, cell survival and cure of the animal using a single tumour system.

The response of a murine tumour to single doses of X rays has been measured using three different assays--animal cure, cell survival in vitro after irradiation in vivo, and tumour growth delay. The dose to cure 50% of the animals, the TCD50, was 79.0 Gy. This was not affected by clamping the tumours to render all the cells hypoxic at the time of irradiation, implying that most of the cells in the tumour were hypoxic already. The enhancement ratio for the hypoxic cell sensitizer Ro-07-0582 was 2.1. The cell survival assay gave an enhancement ratio of 1.6 and an hypoxic fraction of 5%. The discrepancy in the estimates of the hypoxic fraction can be explained by the ability of the naturally hypoxic cells, but not the oxic ones, to recover from potentially lethal damage in vivo. Neither the cell survival assay nor the growth delay assay agreed with the TCD50 assay as to the effect of the hypoxic cell sensitizer, even allowing for recovery from potentially lethal damage. It is doubtful whether the measured survival curve would predict the measured TCD50.

Animals↗
PubMed1977

Congenital deformities of the middle and external ear.

Congenital deformities of the external and middle ears were shown by tomography in 246 patients. Surgical exploration has been undertaken at some time in many of these ears. The appearance of the tomograms and their significance were reviewed in the light of the operative findings and the authors' experience of congenital ear lesions. In nearly every case a middle ear cavity could be demonstrated although this varied from a normally aerated middle ear and mastoid in association with an isolated unilateral atresia of the external auditory meatus to a small slit-like hypotympanum in patients with craniofacial abnormalities. The ossicles were nearly always present but deformed. The typical appearances of the ossicles and the frequently aberrant pathways of the facial nerve are described.

Ear↗
PubMed1976

The effect of low-dose pre-operative X-irradiation of implanted mouse mammary carcinomas on local recurrence and metastasis.

Pre-operative X-irradiation of s.c. implanted first-generation mammary tumours in C3H mice, using either 500 rad or two fractions of 350 rad, produced no improvement in the success of surgery in causing local control or in reduction of distant metastases. The metastasis rate was just significantly higher after the two-fraction treatment of the implanted tumour than after surgical removal alone. The results are in agreement with previously published results on carcinomas and a sarcoma but contrast with those for murine lymphomas.

Animals↗
PubMed1976

Hearing in patients with congenital deformity of the inner ear.

Congenital abnormalities of the bony labyrinth and internal auditory meatus range from complete absence to minor anomalies compatible with normal cochlea function. A 'follow-up' survey to assess the hearing of 56 patients with abnormalities of the inner ear shown by tomography was made. The hearing levels are discussed in relation to the tomographic appearances and comparison made with other series of inner ear abnormalities demonstrated both radiographically and histologically.

Adolescent↗
PubMed1976

Radiosensitization of C3H mouse mammary tumours using fractionated doses of x rays with the drug Ro-07-0582.

Three fractionated X-ray schedules were used, with and without the electron-affinic radiosensitizer of hypoxic cells, Ro-07-0582, to determine the local control of first-generation transplants of spontaneous mammary tumours in C3H mice. Three or five fractions were given in either four or nine days overall time. The results were compared with acute skin reactions in other mice caused by the same treatment schedules. For a given skin reaction, the local control of tumours varied widely, from good to bad, when different X-ray only schedules were used. All three schedules using Ro-07-0582 however yielded good results. It appears that the use of the hypoxic-cell radiosensitizer took the unreliability out of these short fractionated treatments.

Animals↗
PubMed1975

Modest radiosensitization of solid tumours in C3H mice by the hypoxic cell radiosensitizer NDPP.

The x-ray dose required to cure half the mice bearing first generation transplanted mammary carcinomata 150 days after irradiation was determined. NDPP proved to be a relatively poor radiosensitizer in mice, for although a maximum enhancement ratio of 1-3 was obtained when x-rays produced from a 1-4 MeVp electron accelerator were given between 10 and 17 min after the administration of NDPP, this was at a drug concentration sufficient to cause marked kidney abnormalities in 5-10% of the mice.

Animals↗
PubMed1975

Biological properties and response to x-rays of first-generation transplants of spontaneous mammary carcinomas in C3H mice.

First-generation transplants of spontaneous mouse mammary carcinomas have been used extensively for radiobiological investigations of fractionated irradiation schedules, r.b.e. of fast neutrons and effectiveness of radiosensitizers, as reported elsewhere. The present work investigates the growth characteristics of the tumours; the criteria for the choice of end-points used in the definition of 'local control' of irradiated tumours; the reason for a decrease of 30 per cent in X-ray dose required to control tumours in females as compared with male mice; the proportion of hypoxic cells and its variation with time (reoxygenation) after a single dose of 1500 rad of X-rays; and the repair capacity of tumour cells within 24 hours after a substantial first dose of X-rays. Evidence is presented that the male-female difference was due to a higher proportion of hypoxic cells in tumours in male than in female mice. The repair of sub-lethal injury in tumour cells made hypoxic was slightly less than in skin made hypoxic but not significantly so. In the two-dose experiments on clamped tumours, no evidence of induced synchrony was found.

Animals↗
PubMed1975

Relative effectiveness of 12-hourly fractionation and a non-uniform x-ray schedule in the optimum fractionation of C3H mouse mammary tumours.

In previous experiments the highest proportions of tumours controlled for 150 days at a particular level of skin reaction were obtained with five or nine fractions of X rays in nine or ten days respectively. Poor results were obtained for the same numbers of fractions given in 4 or 18 days respectively. The present work reports results of three "non-standard" fractionation schedules: two with equal doses given at 12-hour intervals over four or nine days and one with eight decreasing doses given at decreasing intervals over 11 days. The two 12-hour interval schedules gave results which were equal to the best obtained by any other schedule tested. The 8F/11d non-uniform schedule, however, gave mediocre results in spite of being close to the previously optimum overall time. When these results are compared with previously published results from the same tumour system two, phases of optimum fractionation are demonstrated. At short overall times, up to four days, the situation is finely balanced, so that fraction size and interval matter greatly and results of the schedules vary from good to bad. At longer overall times, of nine days or more in these tumours, the response is no longer so variable. Eighteen days (two to three times the average volume doubling time) is too long for any successful treatment with this system, presumably because of proliferation in the tumour.

Animals↗
PubMed1975

Deformity of the labyrinth and internal auditory meatus in congenital deafness.

In congenital deafness it is important that the radiological examination should exclude any deformities of the bony labyrinth or internal auditory meatus as well as demonstrating lesions of the middle and external ears. Radiological assessment of inner ear abnormalities should be used as a guide both to the feasibility of reconstructive surgery to the middle and external ears and for the future training of the child. Inner ear abnormalities demonstrated by tomography in 56 patients are discussed in relation to the cochlea function. The importance of demonstrating the central bony spiral of the cochlea and of assessing the size and shape the internal auditory meatus is stressed.

Cochlea↗
PubMed1974

The incidence of lung metastases in C3H mice after treatment of implanted solid tumours with x-rays or surgery.

C3H mice were implanted with pieces of spontaneous mammary carcinoma which were irradiated or removed surgically when they had grown to 6·5 mm mean diameter. The incidence of lung metastases was determined from samples taken at various times up to 6 months later. Single x-ray doses and fractionated schedules up to 15 fractions in 18 days were used, no significant difference being observed in the results for all these schedules.On the major question of whether radiation caused an increase in the number of lung metastases the study is inconclusive. The incidence of metastases was found to be 8% if the implanted tumour was cured by the radiation, whereas if the radiotherapy did not cure the tumours the incidence was 35%. This difference between the two groups was significant. If tumours recurred locally after radiotherapy and were then removed surgically, the incidence of lung metastases was significantly greater than that after surgery of unirradiated tumours. The incidence of metastases was similar after curative surgery and after curative radiotherapy.

Animals↗
PubMed1974

The effect of irradiating a transplanted solid sarcoma on the subsequent development of metastases.

A slowly growing solid sarcoma was implanted subcutaneously on the anterior chest wall of mice. On reaching a predetermined size the tumours were locally irradiated using 240 kV x-rays with single doses of 0, 2000 or 5000 rad. The mice were sacrificed 12 weeks after irradiation and examined for lung metastases, which were found to be less frequent in those mice whose implanted tumours had received the most irradiation.

Animals↗
PubMed1974

Radiosensitization of C3H mouse mammary tumours by a 2-nitroimidazole drug.

Local tumour control has been determined at 150 days after single doses of 240 kV x-rays given with or without 1 mg/g body weight of the hypoxic cell radiosensitizer Ro-07-0582. The dose required to control 50% of the tumours (TCD50) was reduced from 4380 to 2410 rad, yielding an enhancement ratio of 1·82 ± 0·07 s.e.mean. This compares favourably with the corresponding single dose gain factor for fast neutrons, which was about 1·7.

1-Propanol↗
PubMed1973

The effect of irradiating a transplanted murine lymphosarcoma on the subsequent development of metastases.

Mice were implanted with a lymphosarcoma on either the thorax or leg. Some of these tumours were given a single dose of 240 kV x-rays on reaching a predetermined size, whilst others were left unirradiated.Metastases developed in specific lymph nodes, depending on the position of the transplanted tumour, and were larger if the tumour had been irradiated than if not. The growth rate of metastases in the ipsilateral axillary lymph node was faster than that of the transplanted tumours, irrespective of the radiation dose the tumour had received.

Animals↗