Expensive new drugs and the costs of avoiding a small risk.
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Biomedical subjects
Publications and source records attributed to A Leonard.
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The bromodeoxyuridine-Giemsa technique has been used to study systematically the incidence of cells in first or subsequent mitoses at different fixation times of human lymphocyte control cultures as well as the influence of ionizing radiations on cell kinetics. Second divisions appear (3%) in cultures harvested 48 h after initiation. In 72 h cultures 40% of the dividing cells are in second and 33% in third division. Administration of 200 rads of X-rays before PHA stimulation results in a mitotic delay but does not increase the incidence of SCE. The yield of dicentrics after an exposure to 200 rads was the same for all cells in first mitosis regardless of fixation time. These results demonstrate that there is no evidence for the existence of sensitive subpopulations that could be distinguished by the time of the first mitotic division following stimulation.
Individual differences in learning style should be one factor that is considered in medical education program planning and instruction, and this can be accomplished by using Kolb's learning style inventory (LSI) in a primary care internal medicine residency program. Case accounts are presented to suggest how the LSI can be used to enrich teaching-learning encounters. To our knowledge, these case accounts are the first reports of an important use of knowledge about learning style, obtained through instruments such as the LSI. Other educational applications are suggested with respect to evaluation formats and choice of instructional methods.
The mouse is an unsuitable species for cytogenetical studies to the extent that it has 40 acrocentric chromosomes and the only criterion which could be used to differentiate them is size. We envisaged using in the case of cell grafts donors or recipients of different sex. This technique has, however, been used to a limited extent. Among the other markers which have been utilized, T6T6 of CBA mice must be mentioned. The discovery in 1966 by Léonard and Dekundt of the presence in AKR mice of fusions of the Robertson type (between chromosomes 6 and 15) has generated new interest in experimental work based on the utilisation of chromosome markers. Being interested in the mechanisms of radio-induced leukemia, the authors described how they have introduced the chromosome marker of AKR mice into the C57B1 strain which is very sensitive to the induction of radio-induced leukemias.
Male BALB/c mice were whole body exposed to 0, 100, 200 or 300 R of X-rays or were given an i.p. injection of 5 mg/kg of thio-TEPA at 3 months or at 12 months of age. One hundred days after treatment the testes were examined for the presence of reciprocal translocations induced in spermatogonia and detectable in the dividing spermatocytes. Our results show that ages does not influence the yield of scorable chromosome rearrangements.
Dietary lead (0.5%) was given to mice which, after mating, exhibited a vaginal plug. Estradiol, progesterone and prostaglandins E and F 2 alpha were determined in the plasma by radioimmuno assay at different times thereafter. The increase in estradiol and decrease in prostaglandins prior implantation are not greatly altered by lead treatment, whereas the subsequent increase in progesterone and later in estradiol is abolished. It is concluded that the lower number of pregnancies seen in lead-treated mothers is due to a maternal hormonal imbalance caused by lead.
The yield of chromosomal aberrations induced by exposure to X-irradiation in vitro was studied in the lymphocytes of the chimpanzee (Pan troglodytes), a hominoid ape phylogenically and chromosomally closely related to man. In agreement with the similarity of the chromosome characteristics, no significant difference was observed between man and chimpanzee with respect to the incidence of dicentrics and fragments. It is obvious that the nuclear area, which apparently constitutes the most evident difference between the nuclei of man and chimpanzee lymphocytes, did not play an important role in the yields of aberrations.
Cattle which grazed in the vicinity of a plant manufacturing enamel and which displayed signs of chronic fluoride poisoning such as osteosclerosis and mottled enamel or dental fluorosis were investigated for the presence of structural chromatid and chromosome aberrations. Venous blood was incubated for 48 h, and 100 cells were analyzed for each animal. No statistical difference in the incidence of such anomalies was observed between the controls and the intoxicated animals.
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Inherited anophthalmia was observed in the progeny of a female rat irradiated with 50 R of X-irradiation at 17 days of age. Observations on the inheritance of the condition indicated that this anophthalmia can be considered as the result of polygenic factors with incomplete penetrance.
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In five adult patients (aged 44 to 74 years) with idiopathic nephrotic syndrome, irreversible acute renal failure developed. Prior renal disease, associated systemic illness or occlusion of major renal vasculature was not present. All patients continued to excrete large amounts of proteins (8.6 to 15 g/24 hours) despite a minimal glomerular filtration rate and severe oliguria. One patient died after five months without recovering renal function. Four patients have required hemodialysis for a period of 12 to 58 months. The failure to recover renal function could not be explained by the light microscopic findings. It is suggested that the irreversibility of the renal failure may be related to either permanent alterations in renal blood flow or ultrastructural changes, or to both. Clinically, adult patients in whom acute renal failure develops during the course of idiopathic nephrotic syndrome seem to have a grave prognosis. Protracted oliguria or irreversible renal failure can be expected to occur.
Dose-effect curves for X-irradiation in vitro were determined on cultured blood lymphocytes of four mammalian species-cow, goat, sheep and pig-having approximately the same number of chromosome arms, the same nuclear volume and the same DNA content. The data from cow, but not those from the other species, exhibited significant inhomogeneity between the experiments. On inspection the numerical yields appear not to differ greatly in the lower dose range. Evaluation of the parameters according to the quadratic law and the power law, however, demonstrate significant differences. Pig differs from the other species regardless of which presentation is chosen. For the power law a significant difference is also found between goat and sheep.