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Biomedical subjects

J F Fowler

Publications and source records attributed to J F Fowler.

At least 199 records · Page 11Linked to original sources
PubMed1983

Is there a loss of repair capacity in mouse lungs with increasing numbers of dose fractions?

The capability of mouse lung to repair sublethal damage after up to 10 fractions of X rays was assessed by an in situ breathing rate assay and lethality. The whole thorax of mice was irradiated "daily" with 4, 7 or 10 fractions of 2.75 or 3.0 Gy of X rays followed at 24 hours by graded "test" doses of X rays or neutrons. Repair capability was measured by determining the difference in test dose between 4 and 7 fractions or 7 and 10 fractions at a given isoeffect. Damage was assessed monthly up to 76 weeks after irradiation, during pneumonitis and chronic fibrosis. The data from both assays for the pneumonitis phase suggested that there may be some loss of repair between 7 and 10 fractions, although it was not large enough in only 10 fractions to be clearly demonstrated. In contrast, there was no suggestion of loss of repair for late damage after up to 10 fractions of X rays using either assay.

Animals↗
PubMed1983

A murine model of lip epidermal/mucosal reactions to X-irradiation.

A new radiobiological test system has been developed for lip epidermal/mucosal reactions in mice. This is intended for use in investigations of the effect of non-standard fractionation and of modifying drugs on oral radiation reactions in human cancer patients. An arbitrary scale of scores was devised, with separate scores for oedema of the lips and for erythema or exudation. After single doses of 13-20 Gy, the mouse lip epidermal reactions began at 5 days, reached a peak about 10-13 days, and had fallen to low values, but not to zero, by 21 days. Several different periods for averaging the reaction scores were tested for relative steepness and variability, the most useful being 10-12 days inclusive or the 12th day score alone. The use of longer periods of averaging led to apparent saturation of the scores. It was found that large doses of X-rays repeated at 21-23 day intervals did not lead to escalating waves of reactions unless each dose was greater than 17 Gy. With these larger doses, escalation of reactions occurred even if the intervals were extended.

Animals↗
PubMed1983

Radiosensitization of a mouse tumour by Ro 03-8799: acute and protracted administration.

The nitroimidazole Ro 03-8799 has been tested as a sensitizer of hypoxic tumour cells, using regrowth delay of a mouse mammary carcinoma. This drug has a short biological half-life and has previously proved to be less promising in tumour experiments than was predicted from in vitro studies and from artificially hypoxic skin. The postulate that this might result from the delay in penetrating to poorly vascularized tumour regions has been tested by maintaining constant blood and tumour levels for 2 hours before irradiation, using an infusion pump. For equivalent gross tumour concentrations at the time of irradiation there was no significant difference in the radiosensitization achieved with a single dose or with prolonged administration. This indicates that slow penetration of the drug is not a problem.

Animals↗
PubMed1983

Panniculitis associated with hepatitis.

Panniculitis occurred in a 34-year-old man. The clinical features of the panniculitis were not consistent with erythema nodosum, Weber-Christian disease, or the other previously described panniculitides. Subsequent investigation showed concurrent hepatitis possibly caused by type A hepatitis virus. The skin lesions resolved following treatment with oral indomethacin. We believe this is the first report of a case of nonerythema nodosum panniculitis associated with viral hepatitis.

Adipose Tissue↗
PubMed1983

Repair in mouse lung between multiple small doses of X rays.

Multiple fraction experiments have been carried out to determine the response of mouse lung to repeated small doses of 240 kV X rays down to 150 rad/fraction using breathing rate and lethality to assess damage. Two experimental approaches were used to measure the effect of small doses in vivo: (1) multiple equal doses and (2) multiple priming doses followed by a large test dose. Analysis was performed using the multitarget two-component model and the linear quadratic model of cell survival. The amount of repair was calculated as a function of either dose per fraction (FR) or total dose (Frec). Both FR and Frec increased with decreasing dose per fraction but the change in FR was small. The advantage of Frec was that it varied more rapidly with dose per fraction than FR, so that possible differences between tissue repair capabilities are more visible on plots of repair as a function of dose per fraction. FR and Frec both decreased with the level of single-dose isoeffect injury; thus neither parameter is acceptable for comparing repair capability of different normal tissues with widely differing single-dose end point levels. Beta/alpha values were calculated and found to be a more acceptable index of repair capability than either FR or Frec because unlike those two parameters, beta/alpha varied little with level of damage. Beta/alpha values of 1.7 to 4.2 krad-1 were obtained for both lung death and increased breathing rate and are clearly intermediate between the lower beta/alpha ratios for acute reactions, i.e., skin and intestine, and the higher values for late reactions in kidney and spinal cord.

Animals↗
PubMed1983

The RBE for mouse skin irradiated with 3-MeV neutrons: single and fractionated doses.

Early skin reactions on the feet of mice were measured after irradiation with 240-kVp X rays or with neutrons from a 4-MV Van de Graaff accelerator. The results are compared with previous experiments using cyclotron-produced neutrons. Single doses, or 2, 5, or 9 equal fractions, were given to measure the RBE and repair capacity for neutrons and X rays over the neutron dose per fraction range from 1.0 to 13.0 Gy. The RBE increased with decreasing dose per fraction, and these data could be fitted with a straight line on a log-log plot. The RBE was 4.6 at 1.0 Gy and fell to 2.1 at 13.0 Gy. These RBE values are significantly higher than those from cyclotron-produced 7.5-MeV neutrons, especially at low doses per fraction. The repair capacity was calculated from a comparison of the single-dose and fractionated data over a skin reaction range from 0.6 to 2.4. The D2 - D1 value was 5-10 Gy for X-ray doses up to 18 Gy and less than 1.5 Gy for 7 Gy of neutrons. This reduced repair capacity after neutrons was even more apparent with further fractionation, becoming close to zero for neutron doses below 3 Gy. These data were used to construct quasi-survival curves for epidermal cells. The X-ray data conform to an alpha D + beta D2 model, whereas the neutron data indicate a predominant alpha component, with the initial response appearing linear from zero to 5.0 Gy. Beyond this dose, however, a potentially reparable beta component of neutron damage is detectable, with the same value of beta as for X rays. Thus it is the greatly increased efficiency of the alpha component relative to X rays, rather than an absence of a shoulder after neutrons, that gives rise to the low D2 - D1 values at low doses and to the high RBE. The ratio of alpha components for X rays and neutrons would indicate a limiting RBE of 7.2 at X-ray doses below 1.0 Gy.

Animals↗
PubMed1982

The time course of radioprotection by WR 2721 in mouse skin.

The radioprotective effect of 400 mg/kg of WR 2721 on mouse skin has been investigated over a series of times from 5 to 60 minutes after intravenous or intraperitoneal injection of the drug. The acute desquamation reaction on the hind leg of white mice was studied. Dose response curves were obtained for the average reaction over 15 to 25 days after single-dose irradiation. A high dose-rate electron beam (13--17 Gy/min) was used to minimize the irradiation time. Single doses of 20 to 60 grays were given. Dose modifying factors (DMFs) of 1.7--2.1 were obtained at 30 to 60 minutes, but only 1.1 to 1.3 at 5 minutes and intermediate values at 10 and 15 minutes. DMFs rose slightly faster and to slightly higher values after i.v. than after i.p. injection of WR 2721. We conclude that 30 minutes is the shortest interval which should be used between injection of Wr 2721 and irradiation with this normal tissue.

Amifostine↗
PubMed1982

Early and late effects in mouse lung and rectum.

No higher RBE's were found for late than for early damage in mouse rectum up to 70 weeks or mouse lungs up to 48 weeks after irradiation with 3.0 MeV neutrons (4 MeV deuterons on Be). The smallest neutron doses per fraction were 1.5 and 0.6 Gy for rectal and lung irradiation, respectively. There was a suggestion of higher late RBE's for small doses per fraction in the lung. Slow repair after 2 neutron doses split by 31 days was unequivocally demonstrated in the lung, of magnitude about 1 Gy, possibly decreasing after about 40 weeks.

Animals↗
PubMed1982

Seventh interim progress report of the british institute of radiology fractionation study of 3F/week versus 5F/week in radiotherapy of the laryngo-pharynx.

A fresh analysis of the data entered into the multicentre BIR fractionation trial of 3F/week versus 5F/week in radiotherapy of the laryngopharynx has been undertaken. Completed records of the 732 patients initially entered into the trial have now risen from 687 at the last report to 706. The data have been analysed in a manner similar to that adopted previously so as to measure the effects of the two regimes on both tumour and normal tissues, and some additional analyses have now also been made. There have been some modifications in the results in the various sub-groups which may be due to an inadequate number of patients having been followed up for long enough at the time of the previous analyses. More data for late radiation damage to normal tissues and new radiobiological findings have suggested possible explanations for the differences which have emerged between the two groups. The apparent differences between the sub-groups containing patients with highly localized tumours, which were reported in our previous report, are now less marked and not statistically significant.

Carcinoma, Squamous Cell↗
PubMed1982

Effect of X-rays and cyclophosphamide on solid tumors and naturally occurring metastases in mice.

Combinations of single doses of X-rays given locally to a transplanted tumor and single i.p. doses of cyclophosphamide (CY) were tested in mice bearing solid transplanted fibrosarcomas. The end points examined were growth delay and local control of the implanted tumor, the incidence of distant metastases, and survival times free of either local recurrence or metastases. Growth delay and local control increased more steeply with X-ray dose than with dose of CY. From 8 to 10 days of extra regrowth delay required only 10 to 20% extra X-ray dose, but it required a doubling of CY dose from three-eighths to three-fourths of the maximum tolerated dose. The incidence of metastases and the survival time of the mice also depended more upon the local dose of X-rays than that of CY. This result was not expected and suggests that metastases are eliminated more certainly if the primary (implanted) tumor is locally controlled on a long-term basis. A significant proportion of mice, over 50%, was cured of both the transplanted tumor and distant metastases only when the highest doses of both X-rays and CY were given simultaneously. Extended intervals between the two agents gave inferior results, intervals of 8 days giving significantly worse results, but 4 days giving not significantly worse results than simultaneous administration, especially when the X-ray treatment was given first. The interval of 4 days would, however, be sufficient to avoid the enhancement of radiation injury in normal tissues in mice.

Animals↗
PubMed1981

Effect of cyclophosphamide or x-rays on spontaneously occurring metastases from tumors transplanted into the tails of mice.

A spontaneous metastases model in mice is being used to test the efficiency of various treatments in eliminating metastases. Solid tumors were transplanted into the tails of mice and removed by tail transection when they had grown to a 4- to 5- or 6- to 7-mm mean diameter. Subsequently, 70 to 95% of mice not given other treatment developed metastases in the lungs or in regional lymph nodes (lumbar sacral region), or in both sites. The present paper reports the effects of whole-body or partial-body treatment on these metastases. The treatments, which started at the time of surgical transection of the tail, included a range of single or fractionated doses of cyclophosphamide (CTX) or X-rays given either to the whole body or locally to the lungs only. CTX reduced the incidence of metastases in both sites although the incidence of lung metastases was reduced by smaller doses of CTX than that of the lumbar sacral metastases. Whole-body irradiation of 6 grays (600 rads) had no effect on the incidence of metastases, whereas local irradiation of the lungs with single doses of 14.5 or 20 grays reduced the number substantially, as did 95 mg or more of CTX per kg. Thus, CTX or radiation reduced the incidence of lung metastases in a system where metastases developed from cells seeded from a primary tumor rather than from a cell suspension injected into the tail vein.

Animals↗