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Biomedical subjects

M Roger

Publications and source records attributed to M Roger.

At least 109 records · Page 6Linked to original sources

Effects of gonadotrophin releasing hormone antagonist and agonist on the pulsatile release of gonadotrophins and alpha-subunit in postmenopausal women.

OBJECTIVE: The present study was designed to further assess the mechanism of action of GnRH and GnRH analogues. DESIGN AND PATIENTS: Both the Nal-Glu GnRH antagonist and the D-Trp6 GnRH agonist were administered sequentially to nine normal, post-menopausal women. MEASUREMENTS: A baseline study of pulsatile LH, FSH and free alpha-subunit secretion was performed, with sampling every 10 min for 8 h, and then repeated 8 h after a single subcutaneous injection of Nal-Glu GnRH antagonist (5 mg). Sampling was repeated 21 days after the intramuscular injection of a depot preparation of D-Trp6 GnRH (3.75 mg) in the same women. RESULTS: The baseline sampling period showed synchronous pulses of LH and free alpha-subunit. The antagonist Nal-Glu decreased plasma LH (71%) and free alpha-subunit (43%). However, with the single dose of 5 mg, pulsatile LH and free alpha-subunit release were not completely suppressed and remained temporally correlated. The GnRH agonist had a potent inhibitory action on plasma immunoreactive LH (IRMA) (93%). In contrast, it increased the mean plasma levels of free alpha-subunit from 1.66 +/- 0.01 to 5.06 +/- 0.02 micrograms/l (205%). The pulsatile secretory patterns of both LH and free alpha-subunit were abolished by the agonist. Immunoreactive FSH levels were decreased by the antagonist (24%) and suppressed by the agonist (93%). CONCLUSIONS: The pulsatile study confirms the different mechanism of action of GnRH analogues. Following antagonist administration, low amplitude free alpha-subunit pulses persist and are synchronous with residual LH pulses. In contrast, LH and free alpha-subunit are not maintained under agonist treatment. These data provide evidence for the differential regulation of LH and free alpha-subunit by GnRH.

Female↗

Long-term results of long-acting luteinizing-hormone-releasing hormone agonist in central precocious puberty.

Thirty children with precocious puberty (24 girls aged 6.5 +/- 2.3 years and 6 boys aged 7 +/- 2.9 years) were treated over 5 years with Decapeptyl. In girls, the menses disappeared, breast enlargement regressed, and uterus and ovary sizes returned to prepubertal values. In boys, a significant decrease of testicular size was observed. Plasma levels of estradiol and testosterone, and basal and post-luteinizing hormone (LH)-releasing hormone (LHRH) LH and follicle-stimulating hormone (FSH) remained in the prepubertal range. Growth velocity decreased after 1 year from 9.7 +/- 3.5 to 5.5 +/- 1.3 cm/year, while the height age/bone age ratio was normalized in both sexes after 3 years. In 15 girls, Decapeptyl was interrupted after 2.3 years. During those 2.3 years, bone age increased from 11.6 +/- 0.8 to 12.5 +/- 0.7 years with a growth velocity of 5.3 +/- 1.8 cm/year. During the year following interruption, height increased from 152.2 +/- 4.9 to 157.7 +/- 4.9 cm (growth velocity 5.5 cm/year) and bone age from 12.5 +/- 0.7 to 13.5 +/- 0.6 years. One year after treatment, plasma levels of estradiol were 106.7 +/- 84.7 pg/ml, of LH, 25.5 +/- 17.6 mIU/ml, and of FSH, 10.8 +/- 5.9 mIU/ml. Menses appeared in 13 girls. Moreover, 18 months after interruption, bone age was 13.9 +/- 0.6 years and height 159.5 +/- 5.2 cm, being significantly superior to the final height of a historical control group: 151.5 +/- 4.8 cm (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Body Height↗

Etiologies of late puberty.

An expected lack of pubertal development can be due to an already diagnosed disease. The diagnosis of an unexpected lack of puberty is a difficult task. We have analyzed the etiologies of late puberty in 106 adolescents: 68 boys aged over 15 years and 38 phenotypic girls aged over 13 years. According to their clinical and biological (gonadotropin) data, they were classified in 3 groups. In the first group, hypergonadotropism was observed only in 19 females; pure gonadal dysgenesis was found in 2 cases with 46,XY, in 2 with 46,Xdel(Xq) karyotypes and 9 cases were 46,XX constitutions; 2 sisters had also blepharophimosis; in 3 cases the ovarian failure was due to autoimmune disease, and 1 case, genetically male, had 17 alpha-hydroxylase deficiency. The second group had gonadotropin insufficiency and consisted of 68 adolescents, 57 males and 11 females, with low gonadotropin levels: 33 were anosmic; in the boys, cryptorchism was present in 68% and micropenis in 31%; 38 had a familial history of hypogonadism, the transmission of which was matrilineal in 16, patrilineal in 13 and recessive autosomal in 7. The third group had low or low-normal gonadotropin levels: 22 cases of constitutional delay of puberty (11 cases in both sexes), demonstrated by further normal puberty during the follow-up. No clinical marker and familial history in 50% were noted.

Adolescent↗

Relationship between first-phase insulin secretion and age, HLA, islet cell antibody status, and development of type I diabetes in 220 juvenile first-degree relatives of diabetic patients.

OBJECTIVE: To assess the adequacy of the first-phase insulin response for predicting development of insulin-dependent diabetes. RESEARCH DESIGN AND METHODS: Determinations were made of 1- and 3-min insulin responses to glucose (0.5 g/kg i.v.), islet cell antibodies (ICAs), insulin autoantibodies (IAAs), and HLA. We studied 220 first-degree relatives (aged 3-29 yr) of diabetic patients; 75 underwent two or more tests. RESULTS: At the first test, insulin responses correlated with age in ICA- children less than or equal to 11 yr old (r = 0.46, p less than 0.001). Individual responses varied widely in all ages, and low values were common (5th percentile: 108 pM in children less than 5 yr old, 180 pM thereafter). No correlation was found between insulin responses and IAAs or HLA. The responses of 15 ICA+ subjects were not significantly different from those of ICA- subjects after excluding the influence of age. At subsequent tests, ICA+ and ICA- subjects displayed distinct changes; the mean +/- SE insulin response increased in ICA- subjects from 619.2 +/- 40.8 to 716.4 +/- 50.4 pM (P less than 0.001) but declined in ICA+ subjects from 403.2 +/- 91.8 to 313.8 +/- 67.2 pM (P less than 0.02). During follow-up, 5 of 9 (56%) consistently ICA+ siblings developed diabetes or impaired glucose tolerance compared with 1 of 54 (2%) consistently ICA- subjects. The sensitivity and specificity of two or more low insulin responses (300 pM) for predicting progression to diabetes were 60 and 96%, respectively; the predictive value was 43%. The highest predictive value (75%) was achieved by the combination consistently ICA+, consistently low insulin response, and HLA-DR3/4. However, in no subject could the time of onset of diabetes be deduced from the decline of the insulin response. CONCLUSIONS: Consecutive intravenous glucose tolerance tests are a useful complement for predicting progression to diabetes but not its onset.

Age Factors↗

[Decrease of early insulin secretion, risk factor of insulin-dependent diabetes. Prospective study in families with diabetic children].

In order to study the capacity of the first phase insulin response (FPIR) for predicting insulin-dependent diabetes (IDDM), we have performed one or more intravenous glucose tolerance tests (IVGTT) and determined islet-cell antibodies (ICA) and HLA-types in 220 first degree relatives of IDDM patients (194 siblings, 26 offsprings) aged 2 to 29 years. They were prospectively followed for periods ranging from 18 months to 8 years. The immunological and metabolic changes in 9 subjects who have developed IDDM or impaired glucose tolerance during the study and in 3 ICA-positive non-diabetic subjects were compared to those in ICA-negative subjects. Although the mean FPIR (1 + 3 min. plasma insulin) was significantly lower in ICA-positive compared with ICA-negative subjects, a unique low FPIR had no predictive value at the individual level. At repeated tests, the two groups followed distinctive evolutive patterns: ICA-negative subjects usually had higher FPIRs at a 2nd test, while FPIRs remained low or still decreased in ICA-positive subjects. Follow-up of subjects at high risk showed good concordance between the different predictive factors: among the 9 subjects who have developed IDDM, 7 had persisting ICA, 8 were HLA-DR3, DR4; the FPIR was consistently low in 3 and low at least once in 4. Progressive loss of the FPIR allowing to predict the time of onset of IDDM, was not observed.

Adolescent↗

Ibotenic acid-induced lesion of the peripeduncular area does not impair the lordosis reflex in the cyclic female rat.

In the ovariectomized, hormone-primed rat the peripeduncular area (PPA) has been reported to play a key role in sexual receptivity by integrating the sensory and endocrine inputs necessary for the elicitation of the lordosis reflex. The present study was undertaken to investigate the effect of bilateral peripeduncular lesions induced by ibotenic acid on the lordosis behavior of the normal, cyclic rat. Sexually unexperienced females received a bilateral microinjection of either ibotenic acid (n = 14; lesion group) or phosphate buffer (n = 8; sham-operated group) in the PPA. Following recovery, the receptivity expressed as the lordosis quotient was controlled in the presence of a sexually active male. The results indicate that in both groups the females display a high lordosis quotient (LQ greater than 90%). Therefore, in the cyclic female rat, the manifestation of sexual receptivity does not seem to be affected following bilateral destruction of the PPA.

Animals↗

Ventral temporal cortex in the rat: connections of secondary auditory areas Te2 and Te3.

The present study in the rat deals with the hodological organization of two cytoarchitectonically distinct areas lying caudoventrally (Te2) or ventrally (Te3) to the primary auditory area (Te1). The afferent and efferent systems of connections were identified by using the properties of retrograde and anterograde transport of wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP). Large tracer deposits in the ventral temporal cortex involving Te2, Te3, and the dorsal bank of the perirhinal cortex induced a dense retrograde and anterograde pattern of labeling in the following nuclei of the medial geniculate (MG) complex: caudodorsal (MGCD), dorsal (MGD), medial (MGM), suprageniculate (SG), and peripeduncular area (PPA). The ventral nucleus (MGV) was only slightly labeled in its caudal division. Several extrageniculate structures were also labeled. Retrograde cell labeling occurred in centers giving rise to ascending systems of diffuse projections: locus coeruleus (LC), dorsal raphe nucleus (DR), and basal magnocellular nucleus (B). Slight anterograde labeling was present in the dorsal and external cortices of the inferior colliculus (IC), central gray, deep layers of the superior colliculus (SC), reticular thalamic nucleus (RT), and caudate putamen (CPU). Callosal connections were also noted with the contralateral homotopic cortex. In the cases in which there was a notable extension of the zone of diffusion of the tracer into the dorsal bank of the perirhinal cortex, a characteristic pattern of labeling in the subparafascicular, reuniens and paraventricular thalamic nuclei, mammillary complex, lateral and dorsal hypothalamic nuclei, amygdaloid complex, laterodorsal tegmental nucleus, subiculum, and retrosplenial cortex was displayed. Tracer deposits restricted to Te2 induced a dense labeling of the caudal, ventrolateral MGD, lateral PPA and, to a lesser extent, MGCD. The MGM and SG were only slightly labeled. Extrageniculate afferents essentially consist of sparse projections from LC, DR, and B, whereas efferent fibers are directed to the dorsal cortex of the IC, central gray, deep SC layers, and CPU. Callosal connections were also identified. Following tracer deposits restricted to Te3, dense labeling occurred in the MGD, mostly in its medial division, in the caudal MGM, and in the PPA. The MGCD, SG, and MGV were only sparsely labeled. Extrageniculate afferents arise from LC, DR, and B, and efferents are directed to the RT and dorsal cortex of the IC. Contralateral connections with the homotopic cortical area were also noted. Te2 and Te3 share some degree of similitude in their pattern of connections with the MG complex.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Fetal cortical transplants reduce motor deficits resulting from neonatal damage to the rat's frontal cortex.

Motor deficits in the execution of grasping movements of the right forelimb were compared in normal female Wistar rats, in animals which sustained a neonatal lesion of the left frontal cortex and in animals which received immediately after the lesion a transplant obtained from the frontal cortex of E16 embryos. Behavioral testing was carried out from postnatal day 48 (D48) to D108. The animals were placed at the center of a circular wire grid which was turned upside down so that they hung by their 4 paws at a distance of 40 cm above the floor. The precision of grasping movements of the right limb and the number of falls were recorded during a 1 min session of active moving across the grid. The lesioned subjects were most impaired on both motor indices whereas the grafted animals although performing slightly poorer than the controls were, however, less impaired than the lesioned animals. Fetal cortical transplants, therefore, seem to promote functional recovery from neonatal cortical damage.

Animals↗

Age-related decline of plasma bioavailable testosterone in adult men.

Plasma bioavailable and total testosterone (T), gonadotropins (FSH, LH) and prolactin (PRL) were determined in 70 ambulatory men subdivided into 3 groups according to age: group I (n = 22; age 20-35 yr), group II (n = 22; age: 36-50 yr) and group III (n = 26; age 51-70 yr). Bioavailable T levels declined significantly with age (r = -0.42; P less than 0.01) while those of total T decreased less significantly (r = -0.28; P less than 0.05). In addition, the decrease of bioavailable T occurred earlier. FSH was shown to increase with age (r = 0.41; P less than 0.01) whereas LH and PRL were not found to change significantly. Bioavailable T was correlated with total T (r = 0.25; P less than 0.05) and inversely correlated with FSH (r = -0.26; P less than 0.05). No correlation could be demonstrated between LH and either bioavailable or total T. In view of the age-related increase of sex hormone binding globulin, a fact generally observed in the literature, bioavailable T may be considered a more reliable index than total T for the evaluation of T production. Thus it may be concluded that the early decrease of bioavailable T in ambulatory men not known to have any pathology or any medication altering testicular function corresponds in fact to age-related decline of T secretion by the testes.

Adult↗

Distribution of the efferent projections of the rat posterior thalamic nucleus as revealed by Phaseolus vulgaris immunohistochemistry.

Following iontophoretic injection of Phaseolus vulgaris in the rat posterior thalamic nucleus (PT) dense terminal fields were labeled in the ipsilateral red nucleus, zona incerta, intermediate and deep layers of the superior colliculus, pretectum, basilar pontine gray, and dorsal pole of the caudal division of the ventral lateral thalamic nucleus. Several other structures were more sparsely labeled; the reticular gigantocellular and pontine oral nuclei, nucleus of the mesencephalic tract of the trigeminal nerve, deep mesencephalic and posterior hypothalamic nuclei and the rostral part of the lateral posterior thalamic nucleus. The motor and, to a lesser extent, somatosensory cortices were labeled only following tracer injection in the rostral PT. The posterior thalamic nucleus thus projects to several centers primarily treating somatosensory and/or nociceptive messages, and to precerebellar and motor nuclei. Since a previous study has established that the PT also receives a major somatosensory and/or nociceptive input (Roger and Cadusseau, 1984), a non-specific, modulatory role of the PT is therefore proposed in the treatment of some aspects of somatosensory and/or nociceptive information.

Animals↗

[Result of 3 years of screening for preclinical phase of juvenile insulin-dependent diabetes mellitus].

We screened 1,000 individuals for pre-type I diabetes mellitus: 927 were first degree relatives of patients treated at our institution, 31 other had related autoimmune diseases, 42 had fortuitously discovered slight hyperglycemia. Islet cell antibodies were present in 31 subjects, 13 adults and 18 children. Among these 18 children, 7 also had complement-fixing islet cell antibodies, and 5 anti-insulin antibodies. All but one initially had a normal insulin response to intravenous glucose. The child with the abolished response, as well as another whose insulin secretion fell down during the study period, became diabetic. Based on these preliminary data, we are developing large scale family screening of pre-type I diabetes.

Adolescent↗

Changes in gonadotropin and alpha-subunit secretion after a single administration of gonadotropin-releasing hormone antagonist in adult males.

The suppressive effect of the gonadotropin-releasing hormone (GnRH) antagonist Nal-Glu ([Ac-D2Nal1, D4ClPhe2, D3Pal3, Arg5, D-4-p-methoxybenzoyl-2-aminobutyric acid6, DAla10]-GnRH), injected intramuscularly with 5 mg, was studied in six men. Testosterone decreased by 87 +/- 2.3%, whereas the mean drops were 50 +/- 10%, 43 +/- 6.6%, and 39 +/- 5.6% for radioimmunoassayable luteinizing hormone (LH), follicle-stimulating hormone, and free alpha-subunit, respectively (mean +/- SEM). Immunological characteristics of plasma LH were modified during the inhibition and recovery phases as evidenced by comparison between polyclonal and monoclonal assays. In two additional subjects sampled every 10 minutes, both LH and alpha-subunit pulses were suppressed by NalGlu injection and restored by pulsatile GnRH infusion. However, a nonpulsatile and possibly non-GnRH-dependent alpha-subunit secretion was maintained after NalGlu administration.

Adult↗

[Age-related changes in plasma androstanediol glucuronide in men].

Plasma 5 alpha-androstane-3 alpha, 17 beta diol (Adiol) glucuronide levels were determined using a reliable radioimmunoassay involving hydrolysis with E. coli beta-glucuronidase, diethylether extraction, and Celite column chromatography. Conditions ensuring optimal hydrolysis were determined as well as quality control criteria. Sixty-eight male out-patients wre studied. These subjects were divided into three age groups: I (n = 21; age 20-35 years), II (n = 21; age: 36-50 years), and III (n = 26; age: 51-70 years). Patients under 50 years of age had infertility with no abnormalities upon sperm analysis. Older patients had erectile dysfunction. All subjects had serum gonadotropin (FSH and LH) and prolactin levels within the normal range for age. Adiol glucuronide levels (mean +/- SD) were as follows: 5.0 +/- 2.2 ng/ml (range: 1.6-9.5), 5.4 +/- 3.8 ng/ml (range 1.4-16.0) and 4.5 +/- 2.5 ng/ml (range 1.2-9.3) in groups I, II and III respectively. A trend towards lower Adiol glucuronide levels with advancing age was found but there was no significant difference between group III and the other two groups. Similarly, no significant correlation was found between Adiol glucuronide levels and age (r = -0.12). Conversely, a significant correlation (r = 0.37; p less than 0.01) was observed between Adiol glucuronide levels and bioavailable testosterone (T) levels. This finding might be the consequence of a certain enhancement of 5 alpha-reductase activity with age and/or the non significant decrease with age of another precursor.

Adult↗

Anatomical study of the connections of the primary auditory area in the rat.

The aim of the present study was to identify in the rat the overall input-output pattern of connections of the primary auditory field, with special attention to the topographical organization of the geniculocortical auditory projection. By using cytoarchitectural criteria, three temporal cortical fields were distinguished in the rat: Te1, Te2, and Te3. The primary auditory field Te1 is characterized by a relatively specific differentiation of its layers when compared with other temporal fields. The afferent and efferent connections of Te1 were identified by using the retrograde and anterograde transport of wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP). The results indicate that Te1 is connected by a dense and reciprocal system of fibers with the auditory thalamus. Based on the nomenclature of Morest ('64) in the cat, five cytoarchitectural subdivisions of the medial geniculate complex (MG) were identified in the rat: ventral (MGv), dorsal (MGd), medial (MGm), suprageniculate (Sg), and peripeduncular (PPA). The major rostrocaudal extent of the MGv is connected to Te1. The surrounding cortical fields Te2 and Te3 do not receive a projection from the MGv, except from its most caudal pole. The MGv projection is topographically organized. When the deposit area of the tracer is shifted from dorsal to ventral upon Te1, the corresponding labeled zone within the MGv moves from rostral to caudal, whereas a cortical displacement of the deposit area of the tracer from rostrodorsal to caudoventral leads to a medial to lateral shift of the labeled zone in the MGv. In addition, more dorsal parts of the MGv project on more dorsal sectors of Te1. Te1 receives a sparser, topographically organized projection from the deep dorsal subdivision of the MGd. The MGm and the lateral part of the posterior group of thalamic nuclei (Pol) also distribute fibers to the primary auditory field. Te1 is reciprocally connected by a system of callosal fibers with the contralateral homotypic cortex. Finally, Te1 sends fibers to the dorsal and, to a lesser extent, external cortices of the inferior colliculus, caudomedial caudate-putamen complex, and caudoventral thalamic reticular nucleus.

Afferent Pathways↗