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Biomedical subjects

R Rolland

Publications and source records attributed to R Rolland.

At least 73 records · Page 4Linked to original sources

The effectiveness, safety, and tolerability of CV 205-502 in hyperprolactinemic women: a 12-month study.

Forty-one hyperprolactinemic women (prolactin [PRL] greater than 2,000 mU/L) were treated between 12 and 52 weeks with the new nonergot, long-acting dopamine agonist octahydrobenzo [g] quinoline (CV 205-502). The treatment resulted in normalization of PRL secretion in 71% of the women at a once-daily dose of less than or equal to 0.100 mg. All women responded with a significant decrease in serum PRL. Menstrual function normalized in all women except 1, whereas galactorrhea disappeared in all but 2 patients. During the observation period, four pregnancies were recorded with an additional three in the immediate posttreatment period. Until now, four healthy children have been born. Regarding tolerability, women with fair or poor response bromocriptine (Parlodel) in the past tolerated CV 205-502 better. Two women with no PRL decrease while on Parlodel responded with a decrease while on CV 205-502. All safety parameters remained normal while on treatment, and no significant changes were observed in blood pressure (supine and standing), pulse rate, or electrocardiogram (ECG) recordings. CV 205-502 therefore seems to be a valuable new compound in the management of patients with hyperprolactinemia.

Aminoquinolines↗

Human follicular fluid adverses hamster spermatozoa motility.

To determine the optimal conditions for in vitro spermatozoa vitality, human and hamster spermatozoa were incubated at 37 degrees C in T6 medium supplemented with different biologic fluids (10% v/v). The fluids tested were human serum (HUS), hamster serum (HAS), and human follicular fluid (HUF). After incubation the spermatozoa were investigated for their qualitative and quantitative motility. Human spermatozoa maintained a good vitality in all fluids tested (approximately 25% motility after 18-h incubation). The hamster spermatozoa had after an incubation of 4 h a motility of 28.4% in HUS, 14.2% in HAS, and 2.2% in HUF. The quality of the motility was also extremely low in HUF, whereas it was adequate in HUS and in HAS. The presence of species-specific substances in mammalian follicular fluid is discussed.

Animals↗

Pregnancy outcome in luteinizing hormone-releasing hormone induced cycles: a multicentre study.

In a retrospective international study 223 pregnancies induced with pulsatile hormone-releasing hormone (LH-RH) were evaluated. In patients with hypothalamic amenorrhea (HA) and polycystic ovarian disease (PCOD) the abortion rate was similar (10% vs 8.7%). The premature delivery rate was significantly higher, however, in the patients with HA, but this could be explained by the higher incidence of multiple pregnancies in this group. Thirty multiple pregnancies were observed in the HA group (n = 174) compared with none in the PCOD group (n = 24; p less than 0.05). The incidence of multiple pregnancies in the HA group correlated to the pulse dose (p less than 0.05). The 1st treatment cycle resulted in more multiple pregnancies than did subsequent cycles (p less than 0.05). Difference in pulse interval did not affect the incidence of multiple pregnancies, nor did the route of administration (intravenous or subcutaneous). The incidence of congenital anomalies was comparable to that with spontaneously achieved pregnancies.

Adult↗

Inverse relationships between steroid concentration and volume in preovulatory follicles of the golden hamster.

In order to investigate variations in the microenvironment of oocytes within a cohort of maturing follicles the follicular volumes as well as the intrafollicular concentrations of oestradiol (E2) and progesterone (P) were measured in the golden hamster. At 10 h before ovulation the follicular volumes varied from 0.009 to 0.037 mm3 (mean +/- SD: 0.0187 +/- 0.0071 mm3; n = 36). Large follicles (greater than 0.025 mm3; n = 8) contained statistically significantly lower E2 and P levels (30.1 +/- 10.4 and 517 +/- 113 mumol/l, respectively) than the medium sized group (less than 0.025 and greater than 0.015 mm3; n =20): 46.9 +/- 16.0 (P less than 0.02) and 919 +/- 264 (P less than 0.0001) mumol/l, respectively. Small follicles (less than 0.015 mm3) showed the highest steroid levels: 97.0 +/- 33.3 and 1590 +/- 517 mumol/l for E2 and P (P less than 0.001 versus the medium sized group values). Correlation coefficients for the steroid concentrations and the follicular volumes appeared to be -0.674 for E2 and -0.612 for P (P less than 0.001). At the time studied a positive correlation between E2 and P concentrations in the follicles was found: r = 0.655 (P less than 0.001). The mean ratios of intrafollicular over serum steroid concentrations appeared to be approx 36 x 10(3) in the case of E2 and about 17 x 10(3) in the case of P. These results clearly show that there is an inverse relationship between follicular volume and intrafollicular steroid concentrations. The presence of a fine regulatory mechanism for a collective maturation of follicles is hypothesized.

Animals↗

Human chorionic gonadotrophin measurements in the luteal phase of the menstrual cycle of infertile and fertile women.

Serum human chorionic gonadotrophin (HCG) determinations were performed every other day during the luteal phase of the menstrual cycle of 20 women suffering from unexplained infertility and of 20 women assumed to be fertile. HCG was determined by a specific radioimmunoassay which applied an antiserum directed against the HCG-beta subunit. The group of infertile patients demonstrated detectable serum HCG in only three cases. No clinically confirmed pregnancies were achieved in this group. Eighteen of the 20 women presumed to be fertile showed detectable HCG levels. Five of these achieved ongoing pregnancies, while 13 women revealed increased HCG levels without delayed menstrual periods. The first day of detection of HCG during the luteal phase did not differ between the two groups. In the five women with ongoing pregnancies the time of detection of HCG ranged from day 5 until day 12 after ovulation. It is concluded that the high rate of increased HCG values in the fertile group may represent early conceptual loss, but the apparently disorderly HCG results indicate the need for cautious interpretation of HCG determinations during the luteal phase. Furthermore, early conceptual loss forms no major explanation for unexplained infertility.

Chorionic Gonadotropin↗

Endocrine effects of 17 alpha-hydroxyprogesterone caproate during early pregnancy: a double-blind clinical trial.

The clinical and endocrine effects of progestogen therapy in early pregnancy were investigated using a double-blind randomized trial in 64 patients who had a viable fetus at 6 weeks gestation and had an increased risk of miscarriage. The patients were randomly allocated to receive either 17 alpha-hydroxyprogesterone caproate or a placebo between 7 and 12 weeks gestation. Four fetal ultrasonographic variables and 17 maternal endocrine variables were studied in each woman. Only four maternal serum variables (17 alpha-hydroxyprogesterone, prolactin, thyroxin and thyroxin binding globulin) rose significantly. The serum progesterone levels in the hormone supplemented group were on average 20% higher than in the placebo group but the difference was not statistically significant. However, the relation between the progesterone levels and the fetal outcome was not clear. Therefore it is not advisable to prescribe 17-OHP-C during early pregnancy to prevent a miscarriage.

17 alpha-Hydroxyprogesterone Caproate↗

Endocrine effects of CV 205-502, a new dopamine agonist, in hyperprolactinemic women.

CV 205-502 (CV) is a potent dopaminergic compound which exerts a strong and sustained suppression of prolactin secretion in healthy volunteers. In a prospective double-blind, randomized, placebo-controlled trail, 12 hyperprolactinemic women (greater than or equal to 2000 mU/l), divided into 2 groups of 6 women each, were treated for 4 weeks. Combined pituitary challenge tests (GnRH, TRH, CRH and GHRH) were performed before and after treatment. The 6 CV-treated women (0.05 micrograms daily) showed approximately a 64% decrease of their initial prolactin serum concentrations after 4 weeks of capsule intake. Placebo-treated women showed no change in their prolactin serum level. After TRH administration, a blunted prolactin response was present in all women before treatment. After CV treatment a trend towards normalization of the prolactin response to TRH was seen, whereas the response pattern in the placebo group remained unaltered. The responses of GH, TSH, LH and ACTH to their releasing hormones and cortisol showed no significant changes after administration. FSH, however, showed a significant decrease in response to LH-RH, which could be explained by an increase in estradiol (E2) as ovarian function normalized in CV-treated women. In conclusion, CV shows strong dopamine agonistic properties in hyperprolactinemic women treated with 0.05 micrograms daily. The profile of this new quinoline compound, as judged from the pituitary challenge tests, does not differ from that of dopamine agonists of the ergoline type.

Adult↗

Cell of the mucous membrane of the female genital tract in culture: a comparative study with regard to the histogenesis of endometriosis.

Cellular elements from the mucous membrane of the uterus and oviducts and from peritoneal washings were cultured. The in vitro behavior of these cells was compared to elucidate the histogenesis of endometriosis and the role of various diagnostic procedures. In 65% of the cultured material obtained by uterine-tubal flushing, proliferating cells of the uterine-tubal mucous membrane were present. Their morphology and behavior corresponded to those of cultured cells obtained by separate washing of the uterine cavity and the tubes, respectively, curetted material, and biopsies of endometriosis lesions. Epithelial and stromal cells were identified using phase contrast microscopy, electron microscopy, and immunohistochemical methods. These cell types did not occur in peritoneal washings before the flushing of uterus and tubes. It was therefore assumed that they were detached and transported to the pelvic cavity during the above-mentioned procedures. In view of their intensive proliferation they may form the basis in the development of nodules of endometriosis. This would support the implantation theory concerning the pathogenesis of endometriosis. Interactions between epithelial and mesothelial cells point to the possible role of the latter in encapsulating the endometrial elements.

Cell Communication↗

Pharmacokinetics of intravenous luteinizing hormone-releasing hormone administration in men: effects of various dosages.

Exogenous luteinizing hormone-releasing hormone (LH-RH) was intravenously administered as a single-bolus injection to 26 healthy normal men. LH-RH doses were selected at 1, 2.5, 5, and 20 micrograms for exploration of the optimum LH-RH dose to obtain adequate pituitary stimulation. Blood samples (for LH-RH and LH determinations) were collected at frequent intervals from 10 minutes before to 60 or 90 minutes after injection. LH-RH peak levels varied, in a dose-dependent way, between 119 +/- 16 and 517 +/- 70 ng/l. Peak values were all reached between 1 and 3 minutes after injection, and elimination occurred rapidly, with half-lives between 2.6 +/- 0.4 and 5.2 +/- 1.0 minutes. The area under the curves increased significantly (P less than 0.01) if the doses of LH-RH had been augmented from 1 to 20 micrograms. Maximum LH values were reached more rapidly in the low-dose (1 and 2.5 micrograms) experiments (between 13.5 and 16.3 minutes), with an obvious decline afterwards. The area under the LH curves increased (P less than 0.01) if the doses of LH-RH had been elevated from 1 to 2.5 micrograms, but no further increase of LH release occurred (P greater than or equal to 0.21) if LH-RH doses were further elevated from 2.5 to 20 micrograms. The current study demonstrates that a 2.5-micrograms intravenous LH-RH dose is best suited for an adequate pituitary stimulation in normal men.

Adult↗

Importance of sperm motility after capacitation in interpreting the hamster ovum sperm penetration assay.

Routine semen analysis and a zona-free hamster ovum sperm penetration assay (SPA) were carried out for 220 men from a group of infertile couples. The grade of sperm motility was determined after a preincubation period. For both the normal and abnormal semen samples, the number of positive SPAs was significantly higher when the postcapacitation motility was normal. This difference was observed also when the routine semen characteristics of density, motility, and morphologic features were considered separately regarding their relationship with the SPA. Motility after preincubation showed the most significant positive correlation with the SPA result. Therefore, the SPA score should be limited to semen samples showing adequate postincubation motility.

Animals↗

Survival of spermatogonial stem cells in the rat after split dose irradiation during LH-RH analogue treatment.

A rat model has been created in which a single injection of an LH-RH analogue depot preparation (Zoladex, ICI 118630) produced a temporary interruption of the pituitary-gonadal axis. This effect applied during irradiation was investigated as a possible mechanism to protect the testis from radiation damage. A local testicular irradiation dose of 6.0 Gy was given either as a single dose or as a fractionated (2 X 3.0 Gy) dose at different time intervals ranging from 8 to 72 h. Stem cell survival was measured 11 weeks after irradiation by means of the repopulation index and the number of haploid cells (spermatids) measured by flow cytometry. Serum gonadotrophins and testosterone concentrations were measured to evaluate hormonal recovery. No significant differences were observed between serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone and the duration of the fractionation interval. Stem cell survival was higher following fractionated irradiation in comparison with the single dose. For the 8 h interval an increase in recovery ratio was found, amounting to a factor of 5 of the single dose value. The fluctuating pattern of the recovery curves indicated changes in radiosensitivity of stem cells. The combination of hormonal inhibition of spermatogenesis and fractionated irradiation led to a decrease in the absolute numbers of stem cells. However, the stem cell recovery curves were identical to those seen without hormonal inhibition. It was concluded that hormonal pretreatment with Zoladex during split dose irradiation had no protective effect on stem cell survival.

Animals↗

Cortisol and loss of malaria immunity in human pregnancy.

The concentration of both total (bound to corticoid-binding-globulin plus free) and free cortisol was determined in sera from two groups of pregnant women in Tanzania. One group consisted of 152 pregnant women (57 nulliparas and 95 multiparas) exhibiting clinical malaria during pregnancy, and the other group comprised 527 pregnant women (105 nulliparas and 422 multiparas), who did not have a record of malaria during pregnancy. The serum concentration of total cortisol was significantly higher in women with clinical malaria than in women without recorded malaria, and this is true for both nulliparae and multiparae. Free cortisol fractions did not differ significantly between these groups. Indications were obtained that higher total cortisol levels cause loss of malaria immunity rather than being concomitant with malaria infection only. The data are compatible with those of a murine malaria model.

Female↗

Amenorrhea after immunosuppressive treatment of multiple sclerosis.

Interviews on changes in the menstrual cycle were taken from 38 women of fertile age, several years after immunosuppressive treatment (IS) with prednisone and cyclophosphamide (CP) for definite multiple sclerosis (MS). Serum FSH, LH and 17-beta-oestradiol levels were determined at the time of interview. MS in itself did not change the experience of menstrual cycles; 17 patients developed hypergonadotrophic amenorrhea during or after IS. Symptoms related to climacterium (c. q. flushing) were present in 15 of these patients. The onset of amenorrhea depended on the age at the time of IS and on the cumulative dose of CP. Older patients developed amenorrhea at a lower cumulative dose of CP than did younger patients. High estrogen oral contraceptives are advocated in oncology to prevent disturbance of ovarian function by anti-mitotic treatment. This policy is advisable in female MS patients treated with drugs like CP or azathioprine.

Adult↗

Prolactin suppressant effect of CQP 201-403, a new dopamine agonist, in hyperprolactinemic women.

To meet the need for a dopamine agonist compound which would offer longer action and improved tolerability, CQP 201-403 has been developed. CQP is a propyl-ergoline which has shown specific and strong 24-hour prolactin suppression in healthy volunteers at oral doses from 0.01 mg and higher. In the study 24 hyperprolactinemic women were given once daily doses of 0.01 mg, 0.02 mg or 0.03 mg CQP 201-403, or placebo for 7 days in a double-blind study to assess the prolactin suppressant action and tolerability of the compound. The results show dose-dependent prolactin suppression following the initial CQP dose which was sustained in steady state, when a clear 24-hour action was seen. Tolerability was good and no drug attributable changes in safety measures occurred. On the basis of its facility to suppress prolactin at well tolerated once daily doses, CQP would offer an advantage over currently available drugs. Long-term therapeutic studies in hyperprolactinemia are therefore warranted.

Clinical Trials as Topic↗

Cortisol levels in human pregnancy in relation to parity and age.

Data are presented of a study on the relationship between cortisol, amenorrhea, parity, and age among pregnant women. Total cortisol concentrations were measured by a radioimmunoassay in healthy pregnant women (n = 527), including 105 nulliparas and 422 multiparas. The serum concentration of total cortisol increased linearly with progression of amenorrhea. Significantly higher cortisol levels were found in nulliparas compared to multiparas and independent of amenorrhea. Since parity and age are strongly correlated, age-dependent changes may contribute to the difference in cortisol level between nulliparas and multiparas. Analysis of the age-dependent changes on this difference in cortisol level showed no significant influence.

Adolescent↗

Prevention of puerperal lactation with Parlodel long-acting (Parlodel LA).

Thirty women who did not want to breast-feed postpartum were treated with Parlodel LA. Immediately after birth 50 mg Parlodel LA were injected i.m. by means of a double-chamber syringe. The aim was to investigate in an open study the clinical efficacy and tolerability of Parlodel LA in the prevention of postpartum lactation. The overall efficacy was very good in 29 women (96.6%) and good in 1 woman (3.4%). In 27 women no symptoms of tenderness, engorgement or milk secretion were found (90%). In two cases slight and moderate mammary pain were reported during a few days, engorgement in only one case during one day and in three cases a slight milk let-down was seen for 1-2 days. In all cases the breast symptoms ceased spontaneously and no rebound lactation occurred in any of the women treated with Parlodel LA. The general tolerability was very good in 29 cases (96.6%) and good in one case (3.4%). No adverse effects were reported in any case. No obvious changes in blood pressure were noticed after the injection. In general a slight decrease occurred in systolic and/or diastolic blood pressure post-partum well within the range of non-treated healthy postpartum women. There were also no signs of orthostatic hypotension or changes in pulse rate accompanying the slight decrease in blood pressure. The local tolerability at the injection site was very good in 23 women (76.6%). Seven had short-lasting pain, slight in 6 cases and moderate in 1. Slight redness was reported in one case.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗