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Biomedical subjects

K L Mossman

Publications and source records attributed to K L Mossman.

At least 37 records · Page 2Linked to original sources

Education and training in health physics--a look to the future.

The next 15 to 20 y promise to be a challenging period in health physics education. The U.S. Department of Energy, in a review of current and projected labor market conditions for professional health physicists and health physics technicians, reports current shortages of professional health physicists in the civilian nuclear industry and predicts a high potential for shortages during the next 15 y. The academic health physics community is also faced with the following issues that compound the difficulty in meeting the high employment demands for qualified health physicists in the near future. (1). A decreasing number of programs--In the past few years, several programs have folded or have undergone reorganization, thus reducing the availability of quality programs to train health physicists and health physics technicians. (2). Decreasing federal funding--Government funding of health physics programs is limited, necessitating programs to obtain support from the private sector or from within the colleges and universities themselves. (3). Accreditation of programs--Should programs be accredited to standardize quality and program content? (4). Recruiting quality students--What can programs do to attract high-quality students into the health physics profession? In this paper, each of these issues is examined and possible solutions proposed. Our discussion is primarily meant to be provocative--in this way we hope to stimulate much-needed discourse as a first step in addressing and solving these problems which face the academic health physics community.

Education↗

Radiation-induced reduction of the glial population during development disrupts the formation of olfactory glomeruli in an insect.

Interactions between neurons and between neurons and glial cells have been shown by a number of investigators to be critical for normal development of the nervous system. In the olfactory system of Manduca sexta, sensory axons have been shown to induce the formation of synaptic glomeruli in the antennal lobe of the brain (Hildebrand et al., 1979). Oland and Tolbert (1987) found that the growth of sensory axons into the developing antennal lobe causes changes in glial shape and disposition that presage the establishment of glomeruli, each surrounded by a glial envelope. Several lines of evidence lead us to hypothesize that the glial cells of the lobe may be acting as intermediaries in developmental interactions between sensory axons and neurons of the antennal lobe. In the present study, we have tested this hypothesis by using gamma-radiation to reduce the number of glial cells at a time when neurons of the antennal system are postmitotic but glomeruli have not yet developed. When glial numbers are severely reduced, the neuropil of the resulting lobe lacks glomeruli. Despite the presence of afferent axons, the irradiated lobe has many of the features of a lobe that developed in the absence of afferent axons. Our findings indicate that the glial cells must play a necessary role in the inductive influence of the afferent axons.

Animals↗

Inhibition of potentially lethal radiation damage repair in normal and neoplastic human cells by 3-aminobenzamide: an inhibitor of poly(ADP-ribosylation).

The effect of 3-aminobenzamide (3AB), an inhibitor of poly(ADP-ribose) synthetase, on potentially lethal damage repair (PLDR) was investigated in normal human fibroblasts and four human tumor cell lines from tumors with varying degrees of radiocurability. The tumor lines selected were: Ewing's sarcoma, a bone tumor considered radiocurable and, human lung adenocarcinoma, osteosarcoma, and melanoma, three tumors considered nonradiocurable. PLDR was measured by comparing cell survival when cells were irradiated in a density-inhibited state and replated at appropriate cell numbers at specified times following irradiation to cell survival when cells were replated immediately following irradiation. 3AB was added to cultures 2 hr prior to irradiation and removed at the time of replating. Different test radiation doses were used for the various cell lines to obtain equivalent levels of cell survival. In the absence of inhibitor, PLDR was similar in all cell lines tested. In the presence of 8 mM 3AB, differential inhibition of PLDR was observed. PLDR was almost completely inhibited in Ewing's sarcoma cells and partially inhibited in normal fibroblast cells and osteosarcoma cells. No inhibition of PLDR was observed in the lung adenocarcinoma or melanoma cells. Except for the osteosarcoma cells, inhibition of PLDR by 3AB correlated well with radiocurability.

Benzamides↗

Differential radiosensitization of human tumour cells by 3-aminobenzamide and benzamide: inhibitors of poly(ADP-ribosylation).

The effect of 3-aminobenzamide (3AB) and benzamide (BZ) (inhibitors of poly(ADP-ribose) synthetase) on radiosensitivity was investigated in normal human fibroblasts and three human cell lines established from tumours with varying degrees of clinical radiocurability. The human tumour cell lines selected were: Ewing's sarcoma, a bone tumour usually considered radiocurable with moderate radiation doses; lung adenocarcinoma, a tumour considered radiocurable with high doses of radiotherapy; and osteosarcoma, a very resistant tumour which is rarely controlled by standard doses of radiotherapy. Poly(ADP-ribose) synthetase inhibitors were added to cultures 2 h prior to irradiation and removed 24 h after. Inhibitors were used at doses producing little or no toxicity in cells. In the presence of these inhibitors, a differential radiosensitization was observed. Ewing's sarcoma cells and normal human fibroblasts were sensitized to an equal extent by either 8 mM 3AB or 4 mM BZ. However, no sensitization was observed at these concentrations in the lung adenocarcinoma cells or osteosarcoma cells. The degree of radiosensitization in vitro by 3AB and BZ correlates well with the clinical radiocurability of these tumours in vivo.

Benzamides↗

Guidelines for health physics program content: master's level.

Guidelines for the content of master's degree programs in general and reactor health physics are presented, with the level of presentation for each topic identified as "descriptive," "standard coverage" or "theoretical/specialized coverage." Assumptions about program type and prerequisite course work are specified.

Education, Graduate↗

Testosterone treatment of constitutional delay in growth and development: effect of dose on predicted versus definitive height.

The outcome of treatment in 3 groups of boys with constitutional delay in growth and development given monthly intramuscular injections of testosterone enanthate 200 mg (22 subjects) 100 mg (10 subjects) and 50 mg (12 subjects) was compared with the outcome in a control group (14 subjects) without treatment. The 4 groups were similar in chronological age, height, height age, bone age, height age/bone age ratio, pubertal development and had similar predicted adult heights. All treated subjects achieved an excellent growth response with growth velocities reflecting androgen dose. Bone age advanced commensurate with height age in all the treated groups and delta height age/delta bone age ratios at the end of therapy did not differ significantly. Nor was there a significant difference in the height prediction by the RWT method before and at the end of treatment. However, the year following treatment, growth velocities reversed so that those who received the largest steroid dose and had grown the fastest, decelerated the most and eventually ended up significantly shorter than their predicted adult height. In contrast the control group and those treated with smaller doses of testosterone achieved their predicted heights. The present study confirms that large doses of androgens compromise adult height and are contraindicated in the treatment of constitutional delay in growth and development. Testosterone enanthate 50 mg/mo did not affect predicted adult height adversely, but to the contrary, permitted it to be fully realised. The data caution against drawing conclusions based on changes observed during androgen therapy in the absence of extended follow-up.

Adolescent↗

Response of mouse tumor to interferon inducer and radiation.

The antitumor effect of interferon inducer poly(ICLC), given prior to the radiation treatment of Lewis lung carcinoma in C57Bl mice was studied. To induce the tumors, the mice were injected subcutaneously into the hind leg with 3 X 10(4) or 3 X 10(5) tumor cells. The combination treatment consisted of poly(ICLC) given at 1.25 mg/kg 6 hours before 400 cGy of 60Co gamma rays. All treatments were given three times over 1.5 weeks. The local response, as measured by the delay in the tumor growth, was significantly higher in the combination treatment group than in poly(ICLC) or local irradiation groups. Following the termination of treatment, tumor regrowth was observed. The survival of poly(ICLC) treated mice was influenced by the number of transplanted tumor cells. Thus, untreated mice which received 3 X 10(4) or 3 X 10(5) (2 or 20 TD50) of tumor cells had similar mean survival time of 25.4 +/- 1.9 and 22 +/- 84 days, respectively (p greater than 0.05). The mice, treated by a combination of poly(ICLC) and local irradiation survived 48.2 +/- 2.1 days and 30.7 +/- 1.2 days (p less than .01), with higher survival in 2 TD50 tumor cell groups. Thus, data obtained in this study in mice showed that administration of an interferon inducer poly(ICLC) prior to local irradiation can improve tumor response and survival.

Animals↗

Medical radiodiagnosis and pregnancy: evaluation of options when pregnancy status is uncertain.

There are 4 options available to the referring physician in considering radiodiagnostic examinations of patients with uncertain pregnancy status. In the first option, the referring physician in consultation with the radiologist may elect to perform a complete or modified examination, based on a complete evaluation of the risks and benefits of the procedure. Risks, in this case, would include the possibility of irreparable damage to an unsuspected conceptus. In the second option, the referring physician may cancel the examination altogether. In the third option, the referring physician may perform a pregnancy test before the examination to screen for the patients who are actually pregnant. The fourth option is to postpone the examination to the first half of the menstrual cycle when it is relatively certain that the patient is not pregnant (elective scheduling). The last 2 options are recommendations designed to minimize the occurrence of radiation exposures in unsuspected pregnancies. Using cost/benefit analysis and simple probability calculations, it is shown that, as general public policy, pregnancy tests and elective scheduling procedures are of little value and that the first 2 options are sufficient in deciding to perform the radiodiagnostic examination.

Cost-Benefit Analysis↗

Stability of an injectable disulfiram formulation sterilized by gamma irradiation.

Stability of an injectable disulfiram suspension sterilized by gamma(gamma) irradiation was tested. Single doses of disulfiram powder in plastic syringes were subjected to 50,000 rads of gamma radiation. Culture media were inoculated with the irradiated drug to test for growth of bacteria, fungi, and mycobacteria. The irradiated drug and nonirradiated controls were analyzed by high-performance liquid chromatography (HPLC) for disulfiram and its major degradation product, diethyldithiocarbamate (DDC). Ultraviolet absorption spectra of irradiated and nonirradiated disulfiram were obtained. No organisms grew in any of the culture media. HPLC analysis indicated that disulfiram content of the irradiated specimens was not reduced, and DDC was not detected. There were no important differences between the ultraviolet spectra of the irradiated and nonirradiated samples. Disulfiram can be sterilized by gamma irradiation without chemical degradation.

Chromatography, High Pressure Liquid↗

Radiosensitization of human fibroblasts by 3-aminobenzamide: an inhibitor of poly(ADP-ribosylation).

The poly(ADP-ribose) synthetase inhibitor 3-aminobenzamide (3AB) increases the radiosensitivity of normal human fibroblasts in tissue culture in a dose-dependent manner at noncytotoxic concentrations. 3AB was also found to inhibit the repair of potentially lethal damage as well as the recovery occurring when radiation was delivered as fractionated vs single exposures. However, repair as measured by an increased survival when radiation is delivered at low dose rate compared to high dose rate was not effected by 3AB administration.

Benzamides↗

Response of human fibroblasts to low dose rate gamma irradiation.

Cells from 11 human strains, including fibroblasts from patients with the genetic diseases of ataxia telangiectasia (AT), xeroderma pigmentosum (XP), and Fanconi's anemia (FA), were exposed to gamma radiation at high (1.6-2.2 Gy/min) and at low (0.03-0.07 Gy/min) dose rates. Survival curves reveal an increase in the terminal slope (D0) when cells are irradiated at low dose rates compared to high dose rates. This was true for all cell lines tested, although the AT, FA, and XP cells are reported or postulated to have radiation repair deficiencies. From the response of these cells, it is apparent that radiation sensitivities differ; however, at low dose rate, all tested human cells are able to repair injury.

Ataxia Telangiectasia↗

Nutritional consequences of the radiotherapy of head and neck cancer.

Nutrition-related complications of radiotherapy were evaluated in 74 head and neck cancer patients. Subjective changes of mouth dryness, taste, dysphagia, appetite, and food preferences were determined by questionnaire before and at weekly intervals during curative radiotherapy. Changes in body weight during therapy were also recorded. In addition, 24-hour dietary histories were taken from eight patients at the beginning and end of treatment. Results of the study indicate that patients were subjectively aware of nutritional problems prior to therapy and that therapy exacerbated these problems. As many as 25% of the patients experienced oral complications such as taste loss and/or dry mouth prior to initiation of radiotherapy. By the end of radiotherapy, over 80% of the patients were aware of oral and nutritional problems. Patients had an average weight loss of 5 kg prior to therapy; this loss of weight did not change during therapy. Diet histories of eight patients indicate significant caloric deficiencies early and late in radiotherapy. The oral and nutritional problems experienced by patients, even prior to therapy, support the idea that nutritional evaluation and maintenance are important not only during therapy, but prior to radiotherapy as well. Nutritional evaluation should be made a routine, integral part of therapy for every cancer patient.

Adolescent↗

Quantitative radiation dose-response relationships for normal tissues in man. II. Response of the salivary glands during radiotherapy.

A quantitative dose-response curve for salivary gland function in patients during radiotherapy is presented. Salivary-function data used in this study were obtained from four previously published reports. All patients were treated with 60Co teletherapy to the head and neck using conventional treatment techniques. Salivary dysfunction was determined at specific dose levels by comparing salivary flow rates before therapy with flow rates at specific dose intervals during radiotherapy up to a total dose of 6000 cGy. Fifty percent salivary dysfunction occurred after 1000 cGy and eighty percent dysfunction was observed by the end of the therapy course (6000 cGy). The salivary-function curve was also compared to the previously published dose-response curve for taste function. Comparisons of the two curves indicate that salivary dysfunction precedes taste loss and that the shapes of the dose-response curves are different. A new term, tissue tolerance ratio, defined as the ratio of responses of two tissues given the same radiation dose, was used to make the comparisons between gustatory and salivary gland tissue effects. Measurements of salivary gland function and analysis of dose-response curves may be useful in evaluating chemical modifiers of radiation response.

Cobalt Radioisotopes↗