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Biomedical subjects

H R Withers

Publications and source records attributed to H R Withers.

At least 163 records · Page 9Linked to original sources
PubMed1978

Radiobiological considerations in multifraction irradiation.

The initial shape of a cellular dose-survival curve is a factor of major importance in determining radiotherapy responses. It is probable that survival curves for mammalian cells exposed to X- and gamma-rays, as well as higher LET beams have an initial exponential region after which they bend downwards. The slope of this initial segment of the curve, and more importantly, the width of the shoulder before it bends significantly are the subject of the investigations to be reported. Because of the difficulty in measuring the biological effects of low doses of radiation--particularly in vivo--we have used multifraction experiments to determine the effects of the fractional doses. Such studies help determine the width of the shoulder and, with less precision, the slope of the initial part of the curve. The tissues we have studied include the bone marrow, testis, fibrovasculature, transplantable tumors, and the gastrointestinal tract. The results will be presented and some of the difficulties in their interpretation will be discussed.

Animals↗
PubMed1977

Single dose response curves of normal cells in situ.

Analysis of data on the response of normal tissues (skin, lung, spinal cord, intestine, testis) to single and multifractionated irradiation schedules revealed the characteristics of the single dose survival curves of target cells responsible for skin, lung, and spinal cord reactions, and of stem cells of colonic, jejunal, gastric mucosae, and testis exposed in situ to relatively low doses of x- or gamma-rays. The single dose survival curves of these cells seem to be complex (unlike those of cells studied in vitro), that is, simply exponential in the initial portion up to approximately 250 rads, and downward-bending thereafter in a curve which includes one or two linear portions on a semilogarithmic scale.

Cells↗
PubMed1977

Dose effect relationship for epilation and late effects on spinal cord in rats exposed to gamma rays.

The response of rat spinal cords (T7-T12) exposed to single and multifractionated gamma-ray exposures revealed no significant differences between the threshold doses for 2 fractions given with a 24-hr. interval and 2 fractions given with a 15-day interval. The latent period for spinal cord damage was about 190 days when the incidence of paralysis was high; it was less than this in animals with a lower probability of paralysis. There was a marked sparing effect from dose fractionation: the initial part of a Strandqvist type of isoeffect curve had a slope of 0.44 for doses causing paralysis in 50% of the animals, and 0.36 for "threshold" doses. The level of epilation was not useful for predicting spinal cord damage.

Animals↗
PubMed1977

RBE of neutrons generated by 50 MeV deuterons on beryllium for control of artificial pulmonary metastases of a mouse fibrosarcoma.

Artificial pulmonary metastases of a mouse fibrosarcoma were produced by the intravenous injection of 10(4) cells admixed with 2 X 10(6) plastic microspheres into mice preconditioned with 600 rad whole-body irradiation 24 hours earlier. Four days after injection of tumour cells, mice were irradiated with neutrons generated by 50 MeV deuterons on Be at the Texas A & M Variable Energy Cyclotron or with 137Cs gamma rays. One, three or six fractions of radiation were delivered on a three-hour fractionation schedule. Surviving lung metastases were scored macroscopically 16 days after irradiation. The data indicate that: (1) the RBE (n/gamma) was in the range 1.6-2.6 depending on the size of dose per fraction; (2) the slopes of the gamma-ray curves decreased with increasing fraction number (i.e. decreasing fraction size); (3) the slopes of the neutron curves decreased only slightly with increasing fraction number (and decreasing fraction size); (4) no additional sparing was achieved by further fractionating doses of neutrons of 300 rad or less.

Animals↗
PubMed1977

Cell cycle dependency of metastatic lung colony formation.

Exponentially growing FSA 1233 cells, one of the clones isolated from a mouse fibrosarcoma, were synchronized by fractionation according to cell size by centrifugal elutriation. Cells from each fraction were analyzed by flow microfluorometry to determine the stages of the cell cycle and were injected i.v. to determine lung colony-forming efficiency. In vitro plating efficiency of these cells was similar throughout the cell cycle except for a slight reduction at G2 + M. On the other hand, lung colony-forming efficiency showed marked cell cycle and cell size dependencies, being lowest at G1, highest at S, and declining slightly at G2.

Animals↗
PubMed1976

Nonspecific immunotherapy of malignant tumors.

At present, nonspecific immunotherapy of malignant tumors seems to be the most promising among immunotherapeutic modalities. Potent nonspecific immunostimulants, Bacillus Calmette-Guerin (BCG) and Corynebacterium parvum, exhibit an antitumor activity in experimental animals, which is commonly manifested by reduced tumor growth and sometimes by complete regression of tumors. Antitumor effectiveness of these bacteria is largely related to tumor immunogenicity and host immunocompetence. Recently, BCG has frequently been used for clinical immunotherapy and has provided therapeutic benefit in many instances, particularly when combined with chemotherapy, radiotherapy or surgery. Clinical experience with C. parvum is so far limited.

Adjuvants, Immunologic↗
PubMed1976

Method of constructing a dose-response curve for normal cells in situ.

A method is presented for planning experiments and analysing data with a view to determining in detail the shape of a single-dose survival curve for normal cells exposed in situ to relatively low doses of radiation. Applying this method to data published on the responses of gastric mucosal and colonic stem cells showed that the single-dose survival curves for these cells were linear up to about 250 rads, after which they bent downwards. Some applications of this method are discussed.

Animals↗
PubMed1976

Experience with twice-a-day fractionation in clinical radiotherapy.

Theoretical reasons have led to the treatment of 24 patients with advanced, rapidly growing squamous cell carcinomas of the head and neck, and 17 patients with inflammatory carcinoma of the breast with twice-a-day fractionation. After initial reduction in dose in both series, acute reactions and sequelae are similar to those in conventionally treated patients. The relative control rates are better than would be expected from conventional irradiation.

Breast Neoplasms↗