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Biomedical subjects

M Roger

Publications and source records attributed to M Roger.

At least 145 records · Page 8Linked to original sources

The pituitary-gonadal axis in cryptorchid infants and children.

We have attempted to document in cryptorchid children that there is an LH deficiency and a secondary deficiency of testosterone. We have shown a diminished LH peak after LH-RH in cryptorchid versus normal infants (P less than 0.05). The postnatal surge of testosterone is significantly low (P less than 0.001) in permanent cryptorchids versus infants with secondary testicular descent, whose levels are similar to those in controls. In permanent cryptorchids during the same period (0-4 months), LH and testosterone levels were significantly lower (P less than 0.01 and P less than 0.05 respectively) than in infants with secondary descent, and the levels of testosterone and LH were correlated in both populations. In children, a low basal level of LH was observed at pubertal stage P2, and LH peak after LH-RH was significantly reduced at stages P1 and P2 (P less than 0.01 and P less than 0.05 respectively). The post-stimulatory levels of testosterone after hCG were reduced at the same stages (P less than 0.01, P less than 0,05), and the two levels were correlated (P less than 0.01). No differences are seen for LH and testosterone afterwards. It has been possible to show by immunofluorescence on pituitary cells the occurrence of antigonadotropin cell antibodies (AGCA) in more than 50% of our patients, with no relation to age and no correlations between endocrinological data and the presence or absence of AGCA. The relatively low success rate of hCG treatment, mainly in young children, and of GnRH irrespective of the regimen of treatment, does not exclude the role of primary LH deficiency in cryptorchidism.

Child↗

Anatomical evidence of a reciprocal connection between the posterior thalamic nucleus and the parvocellular division of the red nucleus in the rat. A combined retrograde and anterograde study.

The functional and anatomical organizations of the magnocellular part of the red nucleus are now well established. Our knowledge of the parvocellular part is, however, more limited. Using both anterograde and retrograde tracing methods, the present study suggests in the rat the existence of a large projection from the posterior thalamic nucleus to the parvocellular part of the red nucleus. In turn, the parvocellular part of the red nucleus sends a weaker projection to the posterior thalamic nucleus. Three different tracers were utilized (horseradish peroxidase alone, horseradish peroxidase conjugated to wheat germ agglutinin and Phaseolus vulgaris leucoagglutinin), all of which gave similar results. The posterior thalamic nucleus is known to receive a large proportion of somatosensory afferents. It is suggested, therefore, that in addition to receiving cerebellar and cortical inputs, the parvocellular part of the red nucleus has access to highly integrated somatosensory and/or nociceptive information delivered by the posterior thalamic nucleus.

Animals↗

Trypanosoma musculi: influence of uric acid on in vitro formation of metacyclic trypomastigotes.

Uric acid is the most important constituent in the urine of insects. Infective metacyclic forms of the stercorarian trypanosomes are produced in the rectum of their insect vector and are thus in contact with uric acid. Using a culture system which permitted the growth of the insect stages of Trypanosoma musculi, we studied the influence of uric acid on the metacyclogenesis of this parasite. When added to the culture, uric acid enhanced the production of metacyclic forms. Furthermore, it rendered these trypanosomes highly infective by the oral route. It is suggested that uric acid may play an important role on the metacyclogenesis of T. musculi.

Animals↗

Treatment of precocious puberty with a long-acting preparation of D-Trp6-LHRH.

D-Trp6-LHRH was tested in 6 girls 1-8 years old and 7 boys 2-10 years old with precocious puberty. All children had advanced bone age, breast or testis enlargement and a pubertal LH response to LHRH. 60 micrograms LHRH-A/kg body weight was given intramuscularly on days 1 and 21 and thereafter every 4 weeks for 6-21 months. In girls, breast enlargement disappeared and mean uterus size decreased within 6 months. Mean ovary length decreased from 25.0 +/- 1.9 to 16.0 +/- 2.7 (p less than 0.02). In boys, mean testis volume decreased from 8.0 +/- 1.1 to 6.7 +/- 1.4 ml (p less than 0.05) within 6 months. In both sexes, growth velocity decreased significantly and bone maturation was reduced. Plasma levels of estradiol or testosterone and FSH levels decreased significantly within 3 weeks. The LH response to LHRH was reduced to normal prepubertal values after 7 weeks. No secondary clinical or biochemical escape occurred. No side effects occurred except for transient vaginal bleeding in one girl after the first and second injection. No antibodies to LHRH-A were detected in the patients' sera. This study demonstrates the ability of a delayed release formulation of D-Trp6-LHRH to suppress pituitary and gonadal secretion and pituitary response to LHRH for as long as 2 years of therapy. This treatment appears to be more efficient in treating both clinical and biochemical abnormalities than does treatment with inhibitory steroids. Additionally the method of administration is more practical and ensures better patient compliance.

Bone Development↗

Gonadotropin and alpha-subunit secretion during long term pituitary suppression by D-Trp6-luteinizing hormone-releasing hormone microcapsules as treatment of precocious puberty.

Short term treatment with GnRH agonists has been reported to increase plasma gonadotropin alpha-subunit (Gn alpha) levels while decreasing plasma immunoreactive LH (IR-LH) levels. In this study we examined the effect of D-Trp6-LHRH (LHRH-A) in microcapsules (60 micrograms/kg, im, every 28 days for 1 yr) in 13 girls suffering from precocious puberty. Plasma IR-Gn alpha was measured by RIA; plasma IR-LH and IR-FSH were measured by both polyclonal RIAs and monoclonal immunoradiometric assays (IRMA). Before treatment, basal IR-LH and IR-FSH levels and peak responses to LHRH measured by both RIA and IRMA were similar, and the Gn alpha response paralleled that of LH. After the first injection of LHRH-A, RIA LH levels were significantly higher than pretreatment levels until day 21, while IRMA LH levels transiently increased, but returned to pretreatment levels by day 7 and became lower thereafter (P less than 0.005). Plasma IR-Gn alpha levels increased from days 3-21 (P less than 0.05). After 1.5 months of treatment, basal RIA LH levels remained detectable and not different from pretreatment levels; IRMA LH levels were very low. The mean RIA and IRMA LH responses to LHRH were decreased at 1.5 and 12 months (P less than 0.01). Basal plasma RIA and IRMA FSH levels were similar during treatment (P greater than 0.05) and significantly lower than pretreatment values (P less than 0.01). The mean RIA and IRMA FSH responses to LHRH decreased significantly at 1.5 months (P less than 0.001). After 12 months, both RIA and IRMA FSH responses were increased, but IRMA values were significantly lower than RIA values. A sustained increase in basal Gn alpha values occurred, but there was a tendency for the peak levels after LHRH treatment to decrease, becoming significantly lower than pretreatment peak levels after 1 yr. The chromatographic analysis on Sephadex G-100 of a pool of plasma samples collected during a LHRH test in three children treated for 6 months indicated that IR-Gn alpha coeluted with [125I]Gn alpha. The large discrepancy between RIA and IRMA LH values suggests the secretion of unusual LH molecules which are recognized by RIA but not by IRMA. The sustained release of large amounts of IR-Gn alpha indicates dissociated effects of LHRH-A on alpha- and beta-subunit secretion by the gonadotrophs. The sustained response of Gn alpha to LHRH demonstrates that gonadotroph cell LHRH receptors are still responsive to LHRH during treatment with a LHRH agonist.

Capsules↗

[Immunological assay of chorionic gonadotropin during pregnancy. Multicenter study of 5 reagents].

Five commercial kits for the quantitative determination of human chorionic gonadotropin (hCG) used for detection and monitoring of pregnancy were evaluated. Five kits used two-sites "sandwich" enzymoimmunoassay and monoclonal antibodies. Precision, standardization and sensitivity were tested and practicability was assessed. Good results are obtained for four kits (Beckman had poor results), sensitivity and specificity are good. Practicability of five kits was evaluated but choose was in relation to configuration of laboratory.

Chorionic Gonadotropin↗

Variations of growth factors in pregnant women during labor and in newborns at delivery.

To study physiological variations in serum growth factors during peripartal period, we have measured levels of a serum growth-promoting activity (thymidine activity, TA) and radioimmunoassayable somatomedin C (Sm-C) during labor in 39 women who delivered spontaneously (group A), by caesarean section (group B) and by legal abortion (LA) (group C). TA values were higher in the group A than in the group B and C, suggesting an important effect of uterine contractions in TA generation. A major role in Sm-C production seems to be played by the length of gestation since Sm-C concentrations were significantly higher in mothers delivered by caesarean section than in LA women. During labor influence of estrogens and progesterone in growth factor production seems unlikely because of the lack of correlation with TA and Sm-C levels. The lower TA values in placental flow than in the capillary blood of newborn suggest that serum growth factors, measured as TA, are produced by the newborn and do not cross through the placenta. These data suggest that the absolute dependence of the fetus on the mother does not preclude instances of fetal autonomy.

Abortion, Legal↗

Pulsatile luteinizing hormone releasing hormone treatment for induction of ovulation. Radioimmunoassay of plasma LHRH and comparative study of subcutaneous versus intravenous routes of administration.

To investigate the efficacy of the different routes of luteinizing hormone releasing hormone (LHRH) administration upon pituitary responsiveness, we compared plasma LHRH concentrations and pituitary LH responses in four patients with hypothalamic amenorrhea treated with pulsatile LHRH. A portable computerized infusion pump delivered sc or iv LHRH pulses of 5, 10 or 20 micrograms every 90 min. Comparison of the two modes of LHRH delivery was performed using radioimmunoassay of exogenous LHRH and studying its pharmacokinetics for a 3 pulses period. With 10 micrograms of LHRH given iv, plasma LHRH levels increased between 700 and 1000 pg/ml within 3 min and returned to basal levels in 30 min. When given sc (10 micrograms), plasma LHRH levels peaked between 80 and 100 pg/ml in 15 min and returned to basal levels 60 min later. In one patient treated with 5 micrograms per pulse iv or sc, plasma LHRH increased to 380 and 60 pg/ml respectively. In all patients, computerized analysis of LH pulses was performed during sc and iv LHRH administration. LH pulsatile release displayed a similar rhythm period with both routes. However, for the same dose of LHRH (10 micrograms), the adjusted mean of LH plasma levels was lower with the sc route. In conclusions, the pharmacokinetics of LHRH administered sc or iv displayed a similar pattern but, with equivalent doses, higher plasma LHRH levels are attained with the iv route. Concomitantly, the mean LH levels were also greater after iv administration. Ovulation can be successfully induced by both pulsatile iv and sc LHRH therapy. However, with the sc route, a higher dose of LHRH should be used to prevent a delay of ovulation or a luteal deficiency.

Adult↗

[Isolated secretion of testosterone by an adrenocortical tumor in a menopausal woman].

A case of adrenal tumor with isolated secretion of testosterone in a menopaused woman is reported. All other androgens (Déhydro-épi-androstérone, Sulfate de Déhydro-épi-androstérone, Delta 4 androstène-dione) were normal as well as other adrenal hormones. This tumor produced a mild hirsutism. A treatment with Cyproterone Acetate, then with Dexamethasone did not produce a significant change. A complete review of literature points out the rarity of this observation, since only twelve similar cases have been previously reported.

Adenoma↗

In vitro production of metacyclic forms of Trypanosoma musculi and their infectivity in CBA mice.

Bloodstream forms of Trypanosoma musculi, cultured in Schneider's drosophila medium at room temperature, multiply and differentiate through a series of developmental stages into infective metacyclic trypomastigotes in 10 days. Oral inoculation with these culture forms into CBA mice produced a parasitemia similar to that produced by intraperitoneal infection with bloodstream forms except for a three-day longer prepatent period. Attempts to induce parasitemia with bloodstream forms given orally were unsuccessful.

Animals↗

Long term treatment of male and female precocious puberty by periodic administration of a long-acting preparation of D-Trp6-luteinizing hormone-releasing hormone microcapsules.

The efficacy and safety of a delayed release formulation of the LHRH agonist D-Trp6-LHRH (LHRH-A; im microcapsules) were tested in 16 girls, 0.9-8.8 yr old, and 10 boys, 2.0-10.5 yr old, with precocious puberty. All children had advanced bone age, breast or testis enlargement, and a pubertal LH response to LHRH. Precocious puberty was idiopathic in 19 subjects and secondary to a brain tumor or other central nervous system abnormality in 7. Nine girls and 6 boys had been previously treated unsuccessfully with medroxyprogesterone and/or cyproterone acetate. The microcapsules were made of 2% LHRH-A dispersed in a biocompatible biodegradable polymeric matrix of DL-lactide-coglycolide. Sixty micrograms of LHRH-A/kg BW were given im on days 1 and 21 and thereafter every 4 weeks for 10-27 months. Plasma LHRH-A levels were measured in 13 children by means of a specific RIA. On days 3, 7, 14, and 21, mean concentrations (+/- SEM) were 295 +/- 44, 218 +/- 31, 215 +/- 45, and 224 +/- 39 pg/ml, respectively. In girls, breast enlargement disappeared, and mean uterus size decreased from 44.4 +/- 2.5 to 38.1 +/- 3.1 mm (mean +/- SEM; P less than 0.02) within 6 months. Mean ovary length decreased from 23.0 +/- 1.5 to 16.2 +/- 1.5 mm (P less than 0.01). In boys, mean testis volume decreased from 8.1 +/- 1.2 to 6.7 +/- 1.2 ml (P less than 0.02) within 6 months. In both sexes, growth velocity decreased significantly, and bone maturation was generally reduced. Plasma levels of estradiol or testosterone and FSH levels decreased significantly within 3 weeks. The LH response to LHRH was reduced to normal prepubertal values after 7 weeks. No secondary clinical or biochemical escape occurred. In 1 boy, all biological features of puberty recurred within 1 month after omission of the fifth injection. No side-effects occurred, except for transient vaginal bleeding in girls after the first or second injection. No antibodies to LHRH-A were detected in the patients' sera. This study demonstrates the ability of a delayed release formulation of LHRH-A to achieve stable levels of the drug in plasma for at least 21 days after a single im injection and to suppress pituitary and gonadal secretion and pituitary response to LHRH for as long as 2 yr after therapy. This treatment appears to be more efficient in treating both clinical and biochemical abnormalities than does treatment with inhibitory steroids. Additionally, the method of administration is more practical and ensures better patient compliance.

Antibodies↗

[Treatment of prostatic cancers by periodic administration of a delayed-release preparation of D-Trp(6)-LHRH].

The hormonal effects of a delayed-release intramuscular (IM) preparation of D-Trp-6-LH-RH (TRP-6 microcapsules) were investigated in men aged 65-75 years. Six men with a prostatic adenoma (group A) received subcutaneously (SC) 500 micrograms TRP-6/day from day 0 to day 6. Seven men with a prostatic carcinoma (group B) were given the same SC treatment, but in addition received on days 7, 28 and 56 an intramuscular injection of 3 mg TRP-6 microcapsules. During SC treatment, plasma TRP-6 levels rose to 2-4 ng/ml. Plasma LH peaked on day 1, whereas high testosterone levels were maintained from day 2 to day 4, and then fell abruptly on day 6. In five subjects from group B, plasma TRP-6 was detectable in all plasma samples from day 10 to day 49. Testosterone levels were in the castrate range after day 24. Mean LH level decreased progressively from day 14 to day 56. These data provide evidence for the efficacy of periodic administration of TRP-6 microcapsules for suppressing testicular secretion.

Aged↗

[Treatment of precocious puberty with LH-RH agonists. Multicenter study using D-Trp-6-LH-RH in a programmed-release form].

LH-RH analogs, substituted in position 6 by D-tryptophane, D-serine(tBu), D-leucine or D-alanine induce a strong stimulation of the gonadotrophs, followed by a desensitization of the LH-RH receptors, which leads to a blockade of the gonadotropin secretion and to a hypogonadism. A delayed release preparation of D-Trp-6-LH-RH (Decapeptyl in microcapsules), designed to release the peptide for 28 days after intramuscular injection, was given to 69 girls and 18 boys with precocious puberty. In both, plasma levels of gonadotropins and gonadal steroids were suppressed within 3 weeks, whilst pituitary responses to LH-RH were almost abolished within 7 weeks. A significant improvement of secondary sex characteristics, as well as gonadal size, was obvious within 6 months. Growth velocity was markedly lowered and, more, in most of children, bone maturation was blocked. This study shows that Decapeptyl in microcapsules is more rapidly and more constantly efficient than LH-RH agonists given discontinuously by subcutaneous or intranasal route.

Bone Development↗