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Biomedical subjects

C Robyn

Publications and source records attributed to C Robyn.

At least 19 recordsLinked to original sources

Time related bias in longitudinal studies using dual photon absorptiometry.

Examining the bone mineral density (BMD's) slope of patients regularly followed in our department, we observed recently that the group of patients who had their last BMD during the last 6 months of 1989, had a different slope than patients who had their last BMD during the following 6 months. In order to investigate if a small time-related bias of measurement, unsuspected by the former quality control investigations, could exist, we performed the following analyses. A regression equation between BMD and time was calculated and a slope was obtained for 95 women who had been followed for at least 3 yr and had had at least 3 BMD measurements during that time. The women were divided in 3 groups according to when the last BMD measurement had been performed (July-December 1989, January-June 1990 or July-December 1990). The slopes of the 3 groups of patients were compared. For each value of BMD of every patient, a predicted BMD (BMDp) was calculated using the regression equation and the relative difference (RD) between BMDp and BMD was calculated and analysed in relation to time. There was a significant difference (p < 0.05) between the slopes of patients in relation to the time when the last BMD had been measured. Significant fluctuations (p < 0.001) in RD were observed in relation to time. These RD variations suggested the existence of a time-related error. The presence of this error is also substantiated by the fact that a parallelism existed between the curve of the RD variations and the curve of the mean values of BMD of all patients referred to our department, calculated per period of 4 months. Although the fluctuation of the latter curve was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon

Choice of parameter for expressing bone mineralization.

In this cross-sectional study, the relative importance of anthropometric factors and that of biological parameters on bone mineralization were evaluated and their practical implications inferred on the choice of the parameter to be used for the estimation of bone mineralization. A close relationship between anthropometric factors and bone mineral content (BMC) was observed and this relationship was shown to be independent of age. Furthermore, by regression analyses, anthropometric parameters appeared to explain a large part of the variance in BMC and preceded the hormonal parameters in the stepwise analysis of this model. Using bone mineral density (BMD) data, however, we observed a weaker relationship between anthropometric factors and bone mineralization and a relatively stronger relationship between steroid hormones and bone mineralization than those observed using the BMC data. Furthermore, by multiple regression analysis the hormonal factors preceded the anthropometric parameters in the stepwise analysis of the model. As strong epidemiological and clinical evidence exists on the relationship between steroid hormones and bone loss, these results constitute a supplementary argument for the use of BMD for the estimation of bone mineralization.

Adult

Age, steroids and bone mineral content.

The possible existence of correlations between bone mineral content (BMC), age and serum levels of steroid hormones was investigated. It was found that dehydroepiandrosterone sulphate (DHEA-S), oestradiol (E2) and delta-4-androstenedione (A) were correlated with BMC, whereas oestrone (E1) and testosterone (T) were not. Partial correlations after adjustment for age were significant (P less than 0.05) only between E2 and DHEA-S and BMC at the L2-L4 lumbar site (BMC-1) and between DHEA-S (P less than 0.01) and BMC at the midradius site (BMC-r). Stepwise multiple regression analysis showed that, apart from age, E2 was the only factor to fit (P less than 0.05) into the mathematical model with BMC-1 as the dependent variable, while DHEA-S was the only factor to fit (P less than 0.01) with BMC-r as the dependent variable. These data suggest that different hormonal influences are related to BMC at different sites, namely E2 to lumbar trabecular bone (L2-L4) and DHEA-S to cortical bone (midradius).

Adult

Regulation of maternal thyroid during pregnancy.

A prospective study was undertaken in 606 healthy women during pregnancy to evaluate the changes occurring in maternal thyroid economy as a result of 1) the increased thyroid hormone-binding capacity of serum, 2) the effects of increased levels of hCG on TSH and on the thyroid, and 3) a marginally low iodine intake in the population (50-75 micrograms/day). Four main features were observed. First, thyroidal activity adjusted to the marked increase in serum T4-binding globulin: pregnancy was accompanied by an overall reduction in the T4/T4-binding globulin ratio, with lower free T4 and T3 levels, although in most cases free hormone levels remained within the normal range. The adjustment of thyroidal output of T4 and T3 did not occur similarly in all subjects. In approximately one third of the women, there was relative hypothyroxinemia, higher T3/T4 ratios (presumably indicating preferential T3 secretion), and higher, although normal, serum TSH concentrations. Second, high hCG levels were associated with thyroid stimulation, both functionally (lower serum TSH) and anatomically (increased thyroid size). The data are consistent with a TSH-like effect of hCG on the thyroid. Hence, regulation of the maternal thyroid is complex, resulting from both elevated hCG (mainly in the first half of gestation) and increasing TSH (mainly in the second half of gestation). Third, a significant increase in serum thyroglobulin levels was observed throughout gestation, especially during the last trimester. Fourth, increased thyroid volume was common, and goiter formation not uncommon (goiter was found in 9% of women at delivery). In conclusion, the alterations in maternal thyroid function during gestation are intricate and far from fully understood. In areas of marginally low iodine intake, gestation is associated in a significant number of women with relative hypothyroxinemia, increased thyroglobulin, and enlarged thyroid.

Chorionic Gonadotropin

Effects of the short-acting benzodiazepine triazolam, taken at bedtime, on circadian and sleep-related hormonal profiles in normal men.

Studies in rodents have shown that triazolam, a commonly used hypnotic, may shift circadian rhythms, with the direction and magnitude of the phase-shifts being dependent on the time of drug administration. To determine whether benzodiazepine, taken at standard bedtime, modifies the amount and/or temporal organization of hormonal secretion, six normal men were studied during basal conditions and on the first and third days of treatment with 0.5 mg triazolam. In each study, sleep was polygraphically monitored and plasma cortisol, growth hormone (GH), melatonin, and prolactin (PRL) (i.e., hormones influenced by circadian rhythmicity and/or sleep) were measured at 20-min intervals for 24 h. The sleep latency and the number and duration of awakenings were reduced during triazolam treatment as compared to baseline conditions. The only alteration of sleep architecture was a partial suppression of stages III + IV (SW) in late sleep. Triazolam did not affect the mean cortisol and melatonin levels or the total amount of GH secreted over the 24-h span. The circadian timings of the onsets of cortisol and melatonin secretions were essentially unaltered. The nocturnal rise of melatonin was prolonged by 45 to 60 minutes. Sleep-associated GH release was not modified by triazolam. Sleep-associated PRL secretion persisted, but in half of the nights studied was enhanced almost threefold. This effect of the drug on nocturnal PRL secretion was not specific to either the first or the third night of treatment, nor was it specific to certain subjects. Irrespective of the magnitude of the nocturnal elevation, morning PRL levels were slightly but consistently higher after triazolam treatment than under basal conditions. Normal PRL levels resumed around noon. In conclusion, administration of 0.5 mg triazolam at normal bedtime (2230) for three consecutive days may induce a transient hyperprolactinemia, but does not abolish sleep-related hormone secretion and does not affect the timing of endocrine events controlled by the circadian clock. These findings are consistent with studies in hamsters where treatment with triazolam in the early subjective night was also without effect on the rodent circadian clock.

Animals

[Anthropometric factors in the prevention of osteoporosis].

Osteoporosis, an important health problem, essentially concerns postmenopausal women since women have a lower peak bone mass than men when they reach adulthood and since the menopause is associated with an accelerated bone loss. We retrospectively analysed the bone measurements of 318 women, age less than 50. The bone mineral contents and densities of the mid- and distal radius (BMC m-rad, BMD m-rad, BMC d-rad, BMD d-rad) and of the lumbar L2-L4 vertebra (BMC L2-L4, BMD L2-L4) were measured using single and dual photon absorptiometer, respectively. The relations between age, height, weight, body mass index and the bone measurements were studied using multiple regression analyses. The anthropometric factors were accepted as first factors in the equations. R2 were respectively 17%, 17%, 28% for BMC m-rad, BMC d-rad, BMC L2-L4 and 7%, 5%, 8% for BMD m-rad, BMD d-rad, BMD L2-L4. These data suggest that anthropometric factors have an important influence on the different bone measurements. They also draw attention on the importance of preventive measures to achieve and to maintain an optimal bone reserve in premenopausal women.

Adult

Serum levels of gonadotrophins and steroid hormones in the post-menopause and later life.

Changes in the serum levels of gonadotrophins and steroid hormones with increasing age were studied in 449 women aged 40 and over to investigate the relationships between these hormones even very late in life. The levels of oestradiol (E2) and dehydroepiandrosterone sulphate (DHEA-S) fell after age 50 and remained low thereafter. However, while serum oestrone (E1), testosterone (T), delta-4-androstenedione (A) and prolactin (PRL) concentrations also decreased initially after age 50 they subsequently rose again progressively and this increase was in fact significant in the case of E1. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) rose after age 50, but whereas FSH remained elevated, LH decreased late in life. Cortisol (F) increased significantly after age 70. There was a significant correlation between androgens and E1 as well as between E2 and LH, even after age 60. Owing to the great heterogeneity of the population studied, it is not yet possible to speculate as to the physiopathological significance of these observations. It would seem, however, that the negative feedback effect of oestrogens on LH secretion remains operational very late in life.

Aged

Modulation of immunoreactive somatomedin-C levels by sex steroids.

Among 28 menstruating women tested once randomly during the cycle, somatomedin-C (Sm-C) values were lower in the 10 women in normal follicular phase than in the 10 women in normal luteal phase or the 8 women with hyperandrogenism. Among these 28 subjects, Sm-C showed a positive correlation with testosterone and a positive correlation of borderline significance with oestradiol. A positive correlation was also evidenced between Sm-C and in progesterone among the 20 women of this group who were not hyperandrogenic. In 5 other normal women investigated daily throughout an entire menstrual cycle, Sm-C concentrations were higher during days +4 to +9 of this cycle (luteal phase) than during days -3 to -8 (follicular phase). In another group of 21 healthy women, Sm-C values were increased during medroxyprogesterone acetate (150 mg trimestrially) treatment. In 7 normal men, Sm-C decreased during ethinyl-oestradiol (1 mg daily for 5 days) administration. These findings suggest that circulating Sm-C levels are modulated by variations of sex steroids which occur during the menstrual cycle as well as by pharmacological doses of oestrogens and progestagens.

Adult

Evidence against growth hormone-releasing factor deficiency in children with idiopathic obesity.

The mechanisms whereby growth hormone (GH) secretion is decreased in human obesity remain obscure. We studied the response of plasma GH and prolactin (PRL) to an I.V. dose of 0.5 mcg/kg of growth hormone releasing factor (GRF) in three groups of children: lean (N = 12), obese (N = 15) and GRF-deficient, i.e. children with complete GH deficiency on the basis of conventional provocative testing and evidence of hypothalamic dysfunction on the basis of thyrotropin-releasing hormone testing (N = 7). Mean (+/- SEM) peak plasma GH after GRF was blunted to the same extent in obese and in GRF deficient children (11.1 +/- 2.2 and 8.3 +/- 2.8 ng/ml) as compared to lean control children (34.7 +/- 4.7 ng/ml). The pattern of PRL response to GRF was however different in GRF deficient children, whose high basal PRL levels increased further after GRF injection, and in obese and lean children, who had n alpha acute change in PRL levels after GRF. Baseline plasma somatomedin C concentrations were low for age in GRF deficient children and tended to be high for age in obese children. On the basis of these discrepant patterns of response of PRL to GRF and plasma somatomedin C concentrations, we conclude that GRF deficiency does not account for the decreased GH secretion observed in obese children.

Adolescent

Rapid electrotransfer of proteins from polyacrylamide gel to nitrocellulose membrane using surface-conductive glass as anode.

A new type of inexpensive horizontal apparatus for the electrophoretic transfer of proteins from a gel to an immobilization membrane has been developed. In this system, gel and membrane were directly pressed between two flat electrodes. A surface-conductive glass was used as anode and a stainless-steel plate as cathode. Proteins could be transferred from polyacrylamide gel to nitrocellulose sheet, with a yield of at least 90% in 60-90 min, without overheating, using a voltage gradient of 30-40 V/cm. Moderate volumes of separate anodic (with 20% methanol) and cathodic (with 0.1% sodium dodecyl sulfate) buffers were suited for optimal transfer of proteins with relative molecular mass (Mr) in the 14,000-94,000 range.

Animals

Comparative study of nursing mothers in Africa (Zaire) and in Europe (Sweden): breastfeeding behaviour, nutritional status, lactational hyperprolactinaemia and status of the menstrual cycle.

A total of 1036 nursing mothers were investigated for their nursing behaviour, status of nutrition and menstrual cycle, serum prolactin and progesterone; 61 in Sweden, 457 in an urban area of Zaïre (Bukavu, Kivu) and 518 in a rural area of the same region (Kabare, Kivu). Lactational hyperprolactinaemia is influenced by the frequency but not by the duration of suckling. The return of luteinization of follicles, but not that of menstrual bleeding, was inversely related to the degree of lactational hyperprolactinaemia. Significant luteinization took place in only some 10% of the mothers during the first three months of lactation in Sweden and within the first year in Zaïre. In these mothers with luteinized follicles the average progesterone was only slightly above 1.0 ng/ml indicating poor luteinization. Lactational hyperprolactinaemia, the return of menstruation and luteinization during lactation were not related to the nutritional status as evaluated by the body weight indices and serum albumin. However, suckling and hyperprolactinaemia do not appear to be the only factors involved in the control of fertility during lactation. When serum prolactin levels were equally low, i.e. below 500 microU/ml, twice the number of lactating mothers with signs of luteinization were found in the urban than in the rural population of Zaïre.

Body Weight

Effect of growth hormone-releasing factor on plasma growth hormone, prolactin and somatomedin C in hypopituitary and short normal children.

We studied the effect of a single intravenous bolus of 0.5 microgram/kg of growth hormone-releasing factor (GRF) on plasma GH, prolactin (PRL) and somatomedin C (SMC) in 12 short normal children and 24 patients with severe GH deficiency (GHD), i.e. GH less than 5 ng/ml after insulin and glucagon tolerance tests. GRF elicited an increase in plasma GH in both short normal and GHD children. The mean GH peak was lower in the GHD than in the short normal children (8.2 +/- 2.5 vs. 39.2 +/- 5.1 ng/ml, p less than 0.001). In the GHD patients (but not in the short normals) there was a negative correlation between bone age and peak GH after GRF (r = -0.58, p less than 0.005); GH peaks within the normal range were seen in 5 out of 8 GHD children with a bone age less than 5 years. In the short normal children, GRF had no effect on plasma PRL, which decreased continuously between 8.30 and 11 a.m. (from 206 +/- 22 to 86 +/- 10 microU/ml, p less than 0.005), a reflection of its circadian rhythm. In the majority of the GHD patients, PRL levels were higher than in the short normal children but had the same circadian rhythm, except that a slight increase in PRL was observed 15 min after GRF; this increase in PRL was seen both in children with isolated GHD and in those with multiple hormone deficiencies; it did occur in some GHD patients who had no GH response to GRF. Serum SMC did not change 24 h after GRF in the short normal children. We conclude that: (1) in short normal children: (a) the mean GH response to a single intravenous bolus of 0.5 microgram/kg of GRF is similar to that reported in young adults and (b) GRF has no effect on PRL secretion; (2) in GHD patients: (a) normal GH responses to GRF are seen in patients with a bone age less than 5 years and establish the integrity of the somatotrophs in those cases; (b) the GH responsiveness to GRF decreases with age, which probably reflects the duration of endogenous GRF deficiency, and (c) although the PRL response to GRF is heterogeneous, it does in some patients provide additional evidence of responsive pituitary tissue.

Adolescent

Cleaving of disulfide bridges and apparent molecular weight of human prolactin variants as revealed by immunoperoxidase electrophoresis.

Five highly purified preparations of human pituitary prolactin, widely used in radioimmunoassays, were analyzed by immunoperoxidase electrophoresis with rabbit antisera raised against ovine and rat prolactin. When unreduced, the prolactin content of these preparations was separated into one major prolactin-like immunoreactive band of Mr 23,000, and four fainter immunoreactive bands of Mr's 16,000, 22,000, 25,000, and 45,000. Increasing the 2-mercaptoethanol concentration modified the relative proportions and the Mr of immunoreactive bands so that, after extensive reduction, only two immunoreactive bands were separated, one major band of Mr 25,000 and one fainter band of Mr 17,000. A direct relationship existed between the load of prolactin submitted to electrophoresis in the 0.25 to 75 ng range and the optical density of the separated bands.

Animals

Plasma glucose, insulin, glucagon and prolactin during long lasting lactation.

Circulating levels of glucose and particularly those of insulin are significantly lower in African mothers (Kivu, Zaire) nursing their infants than in non pregnant and non lactating women of the same area. Furthermore, the glycemia and the insulinemia increase relatively less after a glucose load in the breastfeeding mothers. The lack of glucose available to the mammary gland may explain the low volumes of milk produced by the lactating mothers in this region of Africa.

Adult