The Assistant Executive Director FDI (M Barker). Interview by Colin Davis.
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Biomedical subjects
Publications and source records attributed to M Barker.
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The Objective Measure of Ego Identity Status (Adams, Shea, & Fitch, 1979) was administered to 350 adolescents (12 to 18 years old) to test the Eriksonian theory of a developmental continuum from role diffusion to identity achievement. The results offer construct validity for the dynamic process proposed by Blos and Erikson, but do not support the categorization procedure as set forth by Adams, Shea, and Fitch. The OMEIS questionnaire lends itself to a qualitative and dynamic interpretation rather than to a quantitative and normative approach. It is suggested that the dynamic interpretation is more sensitive to the psychological reality of the developmental process.
A woman presented with persistent ileostomy diarrhoea unresponsive to conventional drug treatment and necessitating parenteral nutrition. Output was four to six litres of watery fluid per 24 hours while she was receiving oral nutrition and two to three litres when she was starved. Treatment with a long acting analogue of somatostatin (50 micrograms subcutaneously every 12 hours) reduced the ileostomy output to 2.0-2.5 litres/24 hours with an oral diet and the effluent became semiformed. Parenteral fluids could be stopped. Somatostatin may have a role in the treatment of secretory diarrhoea, but prospective controlled trials are necessary.
This study was designed to examine the relative effect of each of four fractions of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) against 9L rat brain tumor multicellular spheroids and to compare the results of the cell survival and growth delay assays. Similar levels of cell kill resulted when BCNU was administered either as single fractions of 1.5, 3.0, 4.5, or 6.0 micrograms/ml for 1 hr or as one to four fractions of 1.5 micrograms/ml that were administered sequentially for 1 hr each. Survival was increased if the assay was delayed until 24 hr after drug treatment, which indicates that 9L cells in spheroids recover from BCNU-induced potentially lethal damage. When BCNU was administered in 1.5-micrograms/ml fractions, plating efficiencies depended markedly on the interval between the fractions. The 12-hr protocol produced an overall higher cell kill. Fractionation schedules of 24 and 36 hr produced less cell kill than did the other schedules. Survival plateaued for the last three treatments with BCNU in the 36-hr schedule. Cells in S phase at the time of administration of the initial 1.5-micrograms/ml fraction of BCNU moved into G1- and G2-M phases by 12 hr after treatment. For time periods longer than 12 hr, cells began to appear in the BCNU-resistant S phase. Thus, the movement of cells into the drug-sensitive and -resistant phases after the first fraction correlates well with the corresponding overall cytotoxic effect produced by treatment with the combined BCNU (1.5 micrograms/ml) fractions. For a higher concentration (3.0 micrograms/ml for 1 hr), maximum cell kill was reached within the 12- to 18-hr interval, after which cell kill plateaued. Cells were not found in the S-phase fraction 12 to 36 hr after the first treatment with 3.0 micrograms/ml; maximum cell kill for the fractionated protocols resulted at these times. Therefore, BCNU, which is classified as a cell cycle-nonspecific drug, can induce a partial synchrony in 9L spheroid cells, which determines the overall cytotoxicity produced by fractionated BCNU protocols. Although spheroids did not shrink during or after exposure to BCNU, growth was retarded by treatment with all doses and schedules. An optimum time point for growth delay measurement could not be determined from the data. However, correlations between cell survival and growth delay were obtained with arbitrarily chosen end point volumes of four and ten times the volume at the time of treatment.
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Nonverbal expressions of power and control in the daily lives of old people are examined from a life span perspective that combines social exchange theory, Goffman's classic work on deference and demeanor, and Henley's power theory of nonverbal communication and paralinguistics. Because of societal devaluation of the aged and the typical later life declines in power resources, old people are likely to experience a loss of status and social control during everyday nonverbal rituals of dominance nd deference. Supporting evidence is drawn from studies of the social impact of the physical setting and interactions between institutional old people and staff members. Discussion emphasizes the generally subtle nature of nonverbal expressions of dominance and deference, the impact of normal sensory declines in typical later life role transitions, and the potential for ageist interpretations of nonverbal cues.
Human pituitary adenomas proliferate neither in cell culture nor in athymic "nude" mice. We propose that one or several of the humoral factors necessary for the growth of pituitary adenomas is missing in these experimental environments. The purpose of our experiments was to examine the possible influence of the hypothalamus in supporting cellular proliferation, and thus adenoma growth. Fragments from four human pituitary adenomas (three pituitary prolactinomas; one ACTH-secreting adenoma) were transplanted into the pituitary fossa of total-body irradiated, hypophysectomized rats. The rats were killed after two weeks and perfused with a mixture of formalin and India ink. Histologic examination of serial sagittal sections through the pituitary fossa and the adjacent brain showed: vascularization of the grafts from the pituitary stalk and from the scar tissue in the sphenoid bone; survival of some adenomas; and numerous mitoses in an ACTH-secreting specimen obtained from a patient who had Cushing's disease. We conclude from these experiments that as yet unidentified hypothalamus factors are essential for the growth of certain types of pituitary adenomas.
Animal models allow determination of tumor response to anticancer agents under various experimental conditions. The chemically induced 9L rat brian tumor has been developed as both in vivo and in vitro models. Animal survival, clonogenic cell survival, and tumor growth delay provide means to measure the effectiveness of treatment modalities in this tumor model. Monolayer cultures, multicellular spheroid cultures, brain tumors, and flank tumors have been used to study the influence of different biological entities of the 9L model on the response to treatment with radiation and/or BCNU (1,3-bis (2-chloroethyl)-1-nitrosourea).
Many furocoumarins found in several species of plant are potent photosensitizing agents known to cause lethal and mutagenic effects in a wide range of organisms, from viruses to man. Their role in the aetiology of cancer is debatable, but work has focused on the PUVA (psoralen-UVA) treatment of psoriasis with 8-methoxypsoralen (8-MOP) and near UV radiation. Bergaptene (5-methoxypsoralen, 5-MOP) is a major constiutent of oil of bergamot, and might be expected to have qualitatively similar photosensitizing properties to 8-MOP. Although 5-MOP is widely used as a stimulus to melanin deposition in several suntan preparations surprisingly little is known about its basic photobiology. We report here that 5-MOP has the expected properties of other biologically active furocoumarins. These properties include lethal and mutagenic photosensitization of bacteria, 'dark' induced frameshift mutagenesis in bacteria, and lethal and clastogenic effects on mammalian cells in tissue culture.
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In Fischer 344 rats, 9L tumors were implanted in the left cerebral hemisphere. Compared with control animals not operated on, rats treated with an LD10 dose of BCNU 1 hour before or 1 or 12 hours after surgery on Day 16 postimplant had an increased life span of over 200% (greater than a 6 log cell kill). Minimal effect on survival was found when BCNU was administered during surgery. On the other hand, BCNU administered 12 hours before or 24 or 72 hours after surgery did not show any additive effect of surgery on BCNU treatment. These results suggest that in a clinical setting, a bolus of BCNU administered to tumor patients within 12 hours of surgery might increase substantially the total tumor cell kill compared with surgical resection alone.
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