Surgical treatment of renal hypertension in children.
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Biomedical subjects
Publications and source records attributed to J M Kaufman.
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The age-dependent characteristics of compensatory renal growth were studied in neonatal, weanling and young adult rats. Compensatory growth was demonstrated to be greater in young, sexually immature animals than in adults following unilateral nephrectomy. In the four-week interval following surgery in 21-day-old weanling rats, renal mass increased 240% in control animals (group A) and 407% after unilateral nephrectomy (group B). In similarly prepared adult animals, renal weight increased 31 and 81% in the same groups, respectively. The remarkable response in compensatory growth achieved by the young animal was further demonstrated by a greater absolute increase in renal mass in the experimental kidney of young rats compared to adults. Further studies were performed to determine whether the mechanism of compensatory growth in young rats involved formation of new nephrons. The total glomerular count in the remaining kidney of rats after removal of one kidney at 5 (neonatal) and 21 (weanling) days of life did not differ from the value obtained in control neonatal, weanling or adult kidneys. These data indicate that compensatory renal hypertrophy is age-dependent and is greater in young animals. The mechanism for enhanced compensatory renal growth in young animals does not involve glomerular neogenesis since there was no evidence for formation of additional nephrons following nephrectomy either in weanling or neonatal animals.
Removal of renal tissue stimulates functional and anatomical adaptation in the remaining renal parenchyma. Since recent studies have demonstrated no apparent limitation in compensatory growth following progressive surgical ablation, experiments were performed to determine the changes in glomerular filtration rate and renal blood flow. After removal of 50% of the renal mass mean nephron glomerular filtration rate increased 60%, and after ablation of 75% of the renal tissue it increased 150%. These changes paralleled the increases in renal growth under the same conditions. In comparison, mean glomerular blood flow rose 90% and 240% after 50% and 75% nephrectomy, respectively; these changes in relation to the changes in glomerular filtration rate resulted in a progressive fall in the filtration fraction. Intrarenal blood flow distribution was examined with labeled microspheres. The marked increase in renal blood flow after surgical ablation was characterized by a disproportionate rise in blood flow to the inner cortex. The present investigation, therefore, described the remarkable functional changes that occur as overall glomerular filtration rate declines and provides further insight into the mechanism responsible for maintaining water and electrolyte homeostasis after loss of functioning renal mass.
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We used positron emission tomography to monitor the distribution of radioactivity in dog brain and muscle following i.v. administration of 11C-labelled antipyrine, imipramine, and quinidine. Twenty-five sequential scans of a transaxial slice of the head were performed within 90 min; radioactivity in plasma was measured in a gamma-counter. Following i.v. injection of [11C]antipyrine (50 mg kg-1; 9-68 mCi; n = 10), the decay of plasma activity was accompanied by rapid uptake in brain and variable uptake in muscle, immediately followed by a redistribution leading to equalization of the radioactivity in the tissues. Administration of [11C]imipramine (4 mg kg-1; 30-110 mCi; n = 8) was followed by a rapid build-up of a sustained gradient between high brain, and low plasma and muscle radioactivity. After i.v. injection of [11C]quinidine (1 mg kg-1; 11-87 mCi; n = 10), radioactivity in brain was low, with higher activity in plasma and muscle throughout the experiment. Positron emission tomography thus revealed for each drug a distinct pattern of distribution consistent with established properties of the compounds. This technique seems promising for the study of early drug distribution, notwithstanding certain limitations.
The aim of the present study was to assess the activities of the progesterone (Pr) transforming enzyme systems 3alpha-oxidoreductase (3alpha-OR), 5alpha-reductase (5alpha-R) and 20alpha-oxidoreductase (20alpha-OR) in the hypothalamus of the male rat, at different stages of sexual maturation and following castration and adrenalectomy. Special attention was paid to transformation to 3alpha-reduced compounds previously shown to inhibit FSH synthesis and secretion. Homogenates of hypothalamic tissue were incubated with 14C-progesterone. Pr-metabolites were isolated, identified by gas chromatography/mass-spectrometry (GC/MS) and measured by liquid scintillation counting (LSC). In adult rats a ratio of 6:2.5:1 for 5alpha-R:3alpha-OR:20alpha-OR enzyme- activities was found. The hypothalamic 5alpha-R and particularly 3alpha-OR activities were considerably higher before puberty (10-20 day old rats) than in adulthood. Adrenalectomy in adult rats resulted in an increased activity of the three enzyme systems. No significant changes were seen following castration. Among the isolated metabolites, 3alpha-hydroxy-pregn-4-en-20-one (3alpha-Pr) and 3alpha-hydroxy-5alpha-pregnane-20-one (5alpha,3alpha-Pr) were identified. Conversion to both these neurosteroids was considerably higher during prepuberty than in adulthood. The finding that before puberty the hypothalamus has a markedly increased capacity to convert Pr to 3alpha-reduced compounds, such as 3alpha-Pr, known to effectively inhibit FSH release, warrants further research into the mechanisms regulating the hypothalamic formation of biologically active Pr derivatives and their role in the regulation of gonadotropin secretion.
By example of two cases a newly available tool, the recombinant humane thyroid stimulating hormone (rhTSH) is discussed in its use as an adjunct in diagnosing and treating differentiated thyroid carcinoma with radio-iodine. This product is an easier and safe alternative to the necessary rise of TSH induced by thyroid hormone withdrawal and concurrent hypothyroidism. Although discrepancies in favour of the classical approach have been demonstrated in some patients, the clinical relevancy of these must be weighted against the advantage of avoiding undesirable symptoms and possible tumour growth by the use of rhTSH. The role of rhTSH in the follow-up diagnosis and radioiodine treatment of thyroid carcinoma will undoubtedly increase in importance.
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The Guinea pig is a potentially interesting alternative small animal model for the study of the neuroendocrine regulation of reproduction. However, appropriate gonadotropin assays are not widely available for this species. The aim of the present study was to validate a bioassay procedure for guinea pig luteinizing hormone (LH). The well-established interstitial cell-testosterone in vitro bioassays with the use of dispersed mouse or rat Leydig cells, successfully applied for measurement of LH from a variety of mammalian species, were found to be unsuitable for assay of guinea pig LH because of a marked species specificity of guinea pig LH. An alternative bioassay procedure was established with the use of dispersed guinea pig Leydig cells. This assay has been shown to allow for the assessment of serum LH response to exogenous gonadotropin-releasing hormone and of the expected spontaneous pulsatile pattern of basal LH secretion, with an apparent mean serum LH pulse interval of 31.4 minutes and 51.9 minutes, in long-term castrated and sham operated male guinea pigs, respectively. This bioassay can be a useful tool for more intensive exploration of guinea pig reproductive physiology.