[Effect of an antiprogesterone (RU 486) on extra-uterine pregnancy].
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Biomedical subjects
Publications and source records attributed to M Roger.
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The aim of this work is to study the effects of an antiprogesterone drug (RU 486) on extrauterine pregnancy and to draw from it possible inferences for therapy. The study was carried out on 28 patients presenting an extrauterine pregnancy, the levels of plasma chorionic gonadotrophins of whom were higher than or equal to 250 mIU/ml. Different modes of administration were employed and a coelioscopic salpingotomy was carried out for a pathological study.
In a first set of experiments, the retrograde transport of horseradish peroxidase (HRP) was utilized to investigate the afferent projections to the zona incerta (ZI) in the hooded rat. HRP was introduced in its crystalline form into various sectors of the ZI of seven subjects. The largest contingent of afferents arises from the following centers: the cingulate and somatosensory cortices, central amygdaloid nucleus, ventromedial hypothalamic nucleus, posterior thalamic nucleus, anterior pretectal nucleus, peripeduncular area, deep and intermediate layers of the superior colliculus, dorsal and ventral parabrachial nuclei, principal and interpolar trigeminal subnuclei, and cuneate nucleus. Other centers less systematically or more sparsely labeled were the lateral hypothalamic area, ventrobasal complex, lateral geniculate nucleus pars ventralis, medial geniculate nucleus, interstitial nucleus of Cajal, Darkschewitsch nucleus, perirubral fields, cuneiform, tegmental pedunculopontine, and deep mesencephalic reticular nuclei, pontine reticular nucleus pars oralis, lateral and interpositus cerebellar nuclei, and gracile nucleus. In a second set of experiments, an anterograde tracer (WGA-HRP) was injected in several centers projecting to the ZI in order to localize their terminal fields within this structure. It has been thus possible to distinguish a ventral zone (ventral sector of pars caudalis and pars ventralis) in which the somesthetic (somatosensory cortex, trigeminal complex, and dorsal column nuclei (DCN), collicular, and cerebellar projections terminate, from a dorsal zone (pars dorsalis) to which a limbic input (cingulate cortex and ventromedial hypothalamic nucleus) is directed. In most cases, the labeled terminal fields consisted of well-delimited, narrow bands disposed obliquely, parallel to the cerebral peduncle or the internal capsule. The contingent of somatosensory afferents is relatively large and there is a high degree of overlapping between the different somatosensory terminal fields within the ventral ZI. This suggests a participation of this structure in the treatment of somesthetic information and/or in the transmission of noxious stimuli.
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This study describes a large reciprocal connection between zona incerta and posterior nucleus of the thalamus in the rat. The incerto-thalamic contingent of fibers arises essentially from pars caudalis of the ZI and is directed towards the caudal three quarters of the PT. The thalamo-incertal bundle originates from the central portion of the PT and is mainly directed to pars caudalis of the ZI.
Seventeen prepubertal girls 1 to 8 years of age were studied for the complaint of vaginal bleeding of apparent uterine origin. The bleeding was considered as isolated menses because it lasted two to five days and no other signs of sexual development or any detectable vaginal or uterine abnormalities were found. Eleven girls had two or more apparent menstrual periods, six experienced only one period. Height and bone age were not significantly different from normal. Laparoscopy or ultrasonography showed normal prepubertal uterine size, with either prepubertal ovaries or ovaries containing follicular cysts. Plasma gonadotrophins and their response to luteinizing hormone-releasing hormone were at prepubertal levels. Plasma estradiol level was significantly above the normal prepubertal range, suggesting transient ovarian activity and instability of the pituitary-gonadal axis in these girls. Isolated menses occurred mainly during the months of September to January, thus leading us to speculate about possible seasonal variations of hormonal regulation.
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Sources of afferent projections to the superior colliculus (SC) of the rat were determined by means of the retrograde horseradish peroxidase (HRP) method. The experiments were conducted first to provide a comprehensive map of all the brain structures which supply input to the SC, and secondly to pinpoint the sources of afferents to the deep collicular layers. Experiments conducted after large HRP deposits invading almost all the collicular layers resulted in the labeling of visual centers (cortical areas 17, 18 and 18a, ventral lateral geniculate nucleus, nucleus of the posterior commissure, nucleus of the optic tract, anterior and olivary pretectal nuclei, parabigeminal nucleus); somatosensory centers (cortical area SmI, principal and spinal tract trigeminal nuclei) auditory centers (auditory cortex, inferior colliculus and nuclei of the lateral lemniscus) and various other centers (zona incerta, substantia nigra, cingulate and motor cortices, and some hypothalamic, thalamic, pontine reticular and deep cerebellar nuclei). Deposits limited to the deep SC layers resulted in the labeling of a smaller number of structures: visual centers (cortical area 18a, nucleus of the posterior commissure, parabigeminal nucleus); somatosensory centers (cortical area SmI, principal and spinal tract trigeminal nuclei); auditory centers (inferior colliculus, nuclei of the lateral lemniscus); and various other centers (zona incerta, substantia nigra, cingulate cortex, some hypothalamic nuclei, posterior thalamic nucleus, central gray, cuneiformis and subcuneiformis nuclei, pontine reticular nucleus pars oralis). The pattern of the afferent connections to the rat's SC appears identical to the general plan of organization in mammals; the sources of afferents are extensive and allow the SC to be influenced by multisensory, limbic and even motor-related systems.
In two patients with severe hypogonadotrophic hypogonadism intermittent pulsatile delivery of gonadotrophin hormone (LHRH) 5 to 20 micrograms every 90 minutes by means of the Zyklomat pump promptly resulted in ovulation and pregnancy. The comparative effectiveness of the intravenous and subcutaneous routes was evaluated by radioimmuno assay of LHRH in plasma. The pulsatile patterns of LH was satisfactory with both routes, but plasma levels of LHRH were about 7 times lower with the subcutaneous route. The dosage range (5-20 micrograms) of LHRH must be adjusted to the severity of the hypothalamic deficiency and to the route of administration. The use of the pump, the monitoring of ovulation and the indications for this type of treatment are discussed.
The only reliable method of predicting spontaneous ovulation relies on the detection of the preovulatory luteinizing hormone (LH) surge in urine or plasma. The efficiency of the detection by means of plasma LH radioimmunoassay, urine LH radioimmunoassay or urine LH agglutination inhibition immunoassay were compared in 33 patients. The detection of the onset of LH surge was simultaneous in plasma and urine in only 11 cases. In two thirds of the patients, the urine LH surge onset is delayed by 3 to 21 h as compared with plasma LH surge onset. In some of these cases the oocyte would probably be missed if the laparoscopy had been scheduled according to urine data.
The detection of pregnancy through the rise of human chorionic gonadotropin hormone secretion, on maternal plasma level, has been studied in normally developed pregnancies following in vitro fertilization and embryo transfer (IVF-ET), and compared with two other groups of pregnancies, the first group being pregnancies following artificial insemination with donor semen (AID) in spontaneous cycles ("AID group") and the second group being pregnancies following in vivo fertilization in a stimulated cycle ("stimulated group"). The day of human chorionic gonadotropin detection level significant for pregnancy (Dd) has been first defined and then determined for each pregnancy. Thereafter, mean levels for Dd (Dd) have been compared for each pregnancy group. It has been found that in pregnancies following IVF-ET, Dd is 12.05 +/- 0.8 days after ovulatory stimulus, which is delayed in comparison with spontaneous cycle pregnancies (Dd = 9.5 +/- 1.0) and with stimulated cycle pregnancies (Dd = 8.0 +/- 1.5). The hypothesis to explain this observation is then discussed.
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Pregnancy specific beta 1 glycoprotein (PS beta 1G), human choriogonadotropin (hCG), alpha-foetoprotein (AFP) and carcinoembryonic antigen (CEA) were measured simultaneously in 58 patients with a progressive germinal testicular tumour, and in 20 patients in complete remission. All markers were negative in all the cases in remission, and in 1 case of progressive teratoma. The specificity of the association of these 4 markers was 76 p. 100, higher than any of them measured alone. There was no correlation between individual markers with respect to histological classification. The highest diagnostic specificity was obtained with hCG in all types of tumours. PS beta 1G was associated with hCG but with a lower specificity. AFP is mainly related to embryonic carcinoma but may be raised in all forms of tumour, except seminomas. CEA was positive less often, irrespective of the type of tumour, and never alone. The value of measuring these tumour markers is double: on the one hand it allows better characterisation of the tumour, and on the other, the clinical course and efficacy of treatment can be followed-up more closely and tumour recurrence may be diagnosed at an early stage.
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Fourteen cases of sexual precocity due to choriogonadotropin (hCG) secreting tumors are reported. One pineal and 4 gonadal tumors were observed in 5 girls, whilst 2 supra-sellar, 4 mediastinal, 1 gonadal and 2 hepatic tumors were observed in 9 boys. In all children, immunoreactive plasma LH was high (4 to 30 mIU/ml) but non-responsive to LH-RH, due to the presence of hCG (15 to 6,000 mIU/ml). In the 4 boys with mediastinal tumors the karyotype was 47,XXY. In girls, hCG secreting tumors are a uncommon cause of sexual precocity (less than 1 p. 100). In boys their incidence seems to be the same as the incidence of idiopathic precocious puberty, that is 21 p. 100 of sexual precocities due to androgenic secretion of testicular origin.