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Biomedical subjects

A Ulmann

Publications and source records attributed to A Ulmann.

At least 55 records · Page 3Linked to original sources
PubMed1988

Termination of early pregnancy by a single dose of mifepristone (RU 486), a progesterone antagonist.

Mifepristone (RU 486) is a new steroid which is a progesterone antagonist and which is able to interrupt early pregnancy without any major side-effects. The purpose of our study was to evaluate the clinical effect of a single oral dose of 600 mg on early pregnancy. The study included 150 healthy women applying for a legal abortion with an amenorrhea of no more than 42 days. Pregnancy was confirmed by clinical and ultrasound examination and plasma HCG assessment. Success was assumed by repeating these exams on the eighth day. 131 patients had a complete abortion (87.3%), with a very few side-effects. Only two patients needed curettage for heavy bleeding. Mifepristone is able to terminate early pregnancy by an easy ambulatory method under medical supervision.

Abortifacient Agents↗
PubMed1988

Anti-progesterones in obstetrics, ectopic pregnancies and gynaecological malignancy.

Table 2 summarizes the proven and potential uses of anti-progesterones in obstetrics and gynaecology. In addition to their role in the induction of menstruation and the interruption of first-trimester pregnancy, anti-progesterones can definitely accelerate cervical ripening and promote the termination of second-trimester pregnancy, especially in combination with exogenous prostaglandins. Furthermore, anti-progesterones can also initiate labour in the obstetric complication of fetal death in utero, leading to delivery of the fetus and placenta without additional medical treatment and without surgery in the majority of patients. The wider use of anti-progesterones for the induction of labour, with or without other adjuvants such as oxytocin or prostaglandin analogues, is still uncertain and awaits further study. Anti-progesterones may also be useful in the medical treatment of early ectopic pregnancy, either alone or in combination with other medicines. Preliminary results indicate that progesterone receptor antagonists may also be useful both for the initiation and promotion of lactation as well as the possible management of advanced breast cancer containing progesterone receptors. Finally, the usefulness of anti-progesterones in other gynaecological malignancies containing progesterone receptors, such as endometrial or ovarian cancers, awaits further study.

Animals↗
PubMed1988

Mifepristone (RU486) and therapeutic late pregnancy termination: a double-blind study of two different doses.

An antiprogesterone, mifepristone (RU486), was administered to 35 patients undergoing a therapeutic interruption of pregnancy during the second and third trimester for maternal or fetal indications. A randomized double-blind study test was performed using 150 and 450 mg of mifepristone as pretreatment prior to prostaglandins. No toxicity or maternal morbidity were recorded. In three patients the onset of labour occurred spontaneously before prostaglandin administration. Mifepristone produced a modification in the consistency of the cervix with a statistical improvement in cervical calibration in the two groups, but the cervical effect was independent of the dose.

Abortifacient Agents↗
PubMed1988

Effects of an antiprogesterone (RU486) on the hypothalamic-hypophyseal-ovarian-endometrial axis during the luteal phase of the menstrual cycle.

The impact of the antiprogesterone RU486 [17 beta-hydroxy-11 beta-(4-dimethylaminophenyl) 17 alpha-(1-propynyl)estra- 4,9-dien-3-one] on the hypothalamic-pituitary-ovarian-endometrial axis was examined in normal cycling women during the mid (MLP)- and late (LLP) luteal phases. During the MLP, 10 women received 3 mg/kg RU486 for 3 days. During the LLP, a single dose of 600 mg RU486 was administered to 4 women, and in another 4 women a single dose of 3 mg/kg was given during corpus luteum rescue by hCG. Longitudinal studies with daily and frequent blood samples (every 10 min for 10 h) were conducted during 3 consecutive cycles (control-treatment-recovery). During the MLP, RU486-induced uterine bleeding occurred in all 10 women 36-72 h after the first dose. No histological evidence of endometrial breakdown was found in endometrial biopsies taken 12-24 h before the onset of bleeding. Significant decreases in LH secretion (P less than 0.001) and LH pulse amplitude (P less than 0.006) and blunted pituitary responses to GnRH (P less than 0.01) were evident by the last treatment day, but LH pulse frequency did not change. Complete luteolysis occurred in 2 of the 10 women. Incomplete luteolysis occurred in 8 women and was associated with an initial decline of serum estradiol (P less than 0.001), but not progesterone levels, followed by rebound increases (P less than 0.001) in LH, estradiol, and progesterone levels 3 days later, which may have reversed the luteolytic processes and prolonged corpus luteum function. Spontaneous luteolysis ensued 3-5 days later with the onset of second episodes of uterine bleeding. For serum FSH, an early rise occurred during the luteal phase in advance of the onset of the second episodes of uterine bleeding. This rise may have resulted in early follicle recruitment and accounted for the shorter duration of the follicular phase during recovery cycles. During the LLP, the single RU486 dose resulted in significant decreases in LH pulse amplitude (P less than 0.03), frequency (P less than 0.05), and secretion (not significant) within 12 h. The recovery cycle was entirely normal. Corpus luteum rescue with incremental doses of hCG did not prevent uterine bleeding after RU486 treatment. These findings indicate that RU486 operates at multiple sites and implies that progesterone is important in the control of luteal function. Further, our data provide a basis for exploring the potential use of RU486 as a once a month birth control agent.

Adrenocorticotropic Hormone↗
PubMed1988

Contragestion with late luteal administration of RU 486 (Mifepristone).

The efficacy and tolerance of RU 486 prescribed as a late luteal contragestive agent have been evaluated in 139 women at risk of pregnancy. They were given 400 or 600 mg of RU 486 once on the day before the expected menses. Among these women, 48 (34.5%) were pregnant (positive plasma beta-human chorionic gonadotropin, [beta-hCG]) at the time of RU 486 intake. Bleeding occurred in all but six women. An ongoing pregnancy after treatment was found in nine cases (failure rate, 9/48, 18.8%), which was subsequently terminated by surgical procedure in all cases. There was no disturbance in the menstrual cycle, and the tolerance was very satisfactory. In conclusion, this method is acceptable for women at risk of pregnancy in whom other usual postcoital contraceptive methods cannot be prescribed.

Abortion, Induced↗
PubMed1988

[Abortion induced by RU 486: importance of its combination with a prostaglandin derivative].

The antiprogesterone steroid RU 486 (17 beta-hydroxy-11 beta-(4-dimethylaminophenyl l)-17 alpha-(prop-1-ynyl) estra-4,9-dien-3-one), orally administered once (600 mg), is an efficient contragestive agent in approximately 80% of pregnant women who have been amenorrheic for up to 41 days. Later on, its use is not recommended since after 41 day of amenorrhea there is an increase in the number of incomplete expulsions. A vaginal suppository of 1 mg Gemeprost, a synthetic PG-E1 analogue, has been prescribed 36-48 hrs. after the administration of RU 486. Such a suppository cannot provoke the interruption of the pregnancy by itself. In 106 women seeking for the interruption of pregnancy, and who were amenorrheic for 49 days or less, RU 486 plus prostaglandin association led to the interruption of pregnancy in all cases, and no further instrumental intervention was required. This preliminary report suggests that this method is an efficient alternative to conventional techniques available presently.

Abortifacient Agents↗
PubMed1988

[Early pregnancy interruption using an antiprogesterone steroid: Mifepristone (RU 486)].

Mifepristone (RU 486) is a new steroid which is a progesterone antagonist and which is able to interrupt early pregnancy. The purpose of our study was to evaluate clinical efficacy and tolerance of two doses of Mifepristone (600 and 200 mg) in a single intake. The study included 205 women applying for a legal abortion with pregnancies under 7 weeks. Clinical examination was confirmed by ultrasound and plasma HCG assessment. Success was assumed by repeating these exams on 8th day. 175 patients took 600 mg of Mifepristone and 147 (84%) had a complete abortion. 30 patients took 200 mg of mifepristone and only 19 (63%) had a complete abortion. Very few side effects were observed. So, Mifepristone in able to terminate early pregnancy under medical supervision.

Abortifacient Agents↗
PubMed1987

Contragestion by antiprogestin RU 486: a review.

The steroidal derivative RU 486 (17 beta-hydroxy-11 beta-(4-dimethyl-aminophenyl 1)-17 alpha-(prop-1-ynyl)-estra-4,9-dien-3-one) is the first potent antiprogestin in medical use. Acting reversibly at the molecular level of receptor binding, RU 486 blocks progesterone action and allows endocrine functions to return quickly to normal after its use. However, target cells dynamics that depend upon a continuity of progesterone action will be irreversibly disrupted. In normal women RU 486 acts during the luteal phase in the endometrium, provoking bleeding, and also decreases LH secretion which results in luteolysis. In pregnant women, if affects the decidual, increases myometrial contractility and ripening of the cervix, and ultimately leads to termination of pregnancy. Detachment of the trophoblast leads to a fall in chronic gonadotrophin. Clinical studies indicate that RU 486 can be a very efficient agent for the termination of early pregnancy, and as a postcoital menstrual regulator. The failures observed when RU 486 is given alone may be overcome by the additional use of oxytocics. A small amount of prostaglandin given at the end of RU 486 treatment gives satisfactory results at up to 8 weeks of amenorrhea. Treatment with RU 486 is short term, and apparently has no significant side-effects despite the compound's antiglucocorticosteroid activity.

Abortifacient Agents↗
PubMed1987

The antiprogestins: a recent advance in fertility regulation.

RU 468 (mifepristone) is the first antiprogestin available for clinical purposes. Its pharmacological properties are presented. It possesses antiprogestin and antiglucocorticoid activities. It is now in phase II-III clinical studies as a fertility control agent. The drug appears useful per se in four circumstances: (1) for early pregnancy (amenorrhea of less than 5 weeks' duration). Complete interruption is obtained in approximately 90% of women with a single dose of 600 mg. For this stage of pregnancy, RU 486 appears to be an interesting alternative to vacuum aspiration; (2) for late occasional luteal contraception when given as a single dose on the date of the expected period in women at risk of pregnancy; (3) for dead fetus expulsion in the 2nd or 3rd trimester of pregnancy, and (4) for cervical ripening before obstetrical procedures in pregnant women, such as D and C or vacuum aspiration. The antiglucocorticoid activity of the molecule can be demonstrated in humans by a rise in plasma cortisol, ACTH and LPH after RU 486 intake, and by blockade of some peripheral effects of cortisol. Results obtained in more than 1000 women undergoing short-term treatment with RU 486 (600 or 800 mg once) clearly indicate that the antiglucocorticoid activity of the molecule has no clinical relevance at the doses used for fertility control purposes. In conclusion, RU 486 appears to be a promising new tool for fertility control, but large-scale trials are necessary to confirm its safety and to define its optimal mode of utilization for each indication.

Abortifacient Agents, Steroidal↗
PubMed1987

Fertility control with RU 486.

RU 486 is a synthetic steroid possessing antiprogestin and antiglucocorticoid activities. This paper summarizes the main pharmacological properties of this molecule. It is now under the phase II-III clinical studies in the world for early pregnancy interruption. By itself, the drug shows a 85% complete efficacy provided it is given at the dose of 600 mg (3 X 200 mg) once in pregnancies below or equal to 41 days of amenorrhea. The clinical tolerance of the drug is extremely satisfactory, but metrorrhagia can in some instances be heavy, thus necessitating an adequate medical monitoring. The antiglucogenic activity of the molecule has no clinical relevance. In the future, soma data suggest that adjunction of a synthetic prostaglandin analog could somehow increase the success rate, but further studies are necessary to evaluate the effectiveness of such a combination.

Abortifacient Agents↗
PubMed1987

Disruption of follicular maturation and delay of ovulation after administration of the antiprogesterone RU486.

To investigate the role of progesterone in the follicular phase, we examined the effects of RU486 in eight normal cycling women studied with daily and frequent blood sampling (every 10 min for 10 h) during three menstrual cycles (control-treatment-recovery). RU486 (3 mg/kg, orally) was administered for 3 consecutive days after ultrasound documentation of a dominant follicle. In six of the eight women, RU486 was given after emergence of the dominant follicle, while in two women, RU486 was initiated during the preovulatory period when estradiol levels had exceeded 917 pmol/L. In the six women given RU486 after emergence of the dominant follicle, RU486 significantly prolonged the follicular phase duration from 15.6 +/- 1.9 (+/- SD) to 28.6 +/- 9.3 days (P less than 0.01) and extended the treatment cycle length to 42.3 +/- 9.1 (+/- SD) days (P less than 0.01). During RU486 treatment, mean serum estradiol levels decreased from 385 +/- 43 to 228 +/- 28 pmol/L (P less than 0.01), while LH, FSH, ACTH, cortisol, and progesterone levels changed little. LH pulse frequency and amplitude on the last day of RU486 administration did not differ from control values. Collapse of the dominant follicle was evident on ultrasound after RU486 administration and was not accompanied by uterine bleeding. In the two women treated during the preovulatory period, the follicular phase was not prolonged, and RU486 failed to delay the onset of the LH surge. Our findings indicate that RU486 treatment during the follicular phase interrupts normal follicular development, resulting in a delay of ovulation and a reinitiation of follicular recruitment.

Adrenocorticotropic Hormone↗
PubMed1987

Prolactin secretion in benign breast diseases.

In order to evaluate the importance of prolactin in the pathogenesis of benign breast diseases (BBD), serum prolactin (PRL) levels were determined before and during a TRH challenge test in 50 patients affected by various BBD studied during the luteal phase of their cycle. They were compared to 15 normal women also studied during the luteal phase. In all the subjects estradiol (E2) and progesterone (P) were also measured. The patients were studied as a total group and in different subgroups according to the type of their disease, before and after 3 months of treatment with a potent progestin, lynestrenol. No significant differences appeared between any group of patients and the control group either on the basal prolactin secretion or on its dynamic secretory pattern after TRH injection before and during treatment. The only significant difference observed between patients and controls was the progesterone values, respectively 6.86 +/- 0.9 ng/ml and 21.2 +/- 1.4 ng/ml. It can therefore be concluded that benign breast diseases are more likely to be related to an inadequate luteal phase than to any abnormality of prolactin secretion.

Adult↗
PubMed1987

The antiprogestin RU486 in advanced breast cancer: preliminary clinical trial.

Twenty-two oophorectomized or postmenopausal women with metastatic breast cancer resistant to several medical therapies (tamoxifen, or other endocrine therapy, and chemotherapy) were treated in a first trial with 200 mg per day of RU486 for 1 to 3 months. The long-term tolerance was good but there was a moderate decrease in plasma potassium. Plasma cortisol was increased 2-fold without clinical hypo- or hypercorticism. Twelve patients had a partial response or a stabilization of secondary deposits for 6 weeks but the response rate at 3 months was 18%. When available, estrogen and progesterone receptor levels were positive in these patients. This preliminary trial shows for the first time that the antiprogestin RU486 is well tolerated for medium term treatment. It suggests that it might be active on advanced breast cancer becoming resistant to tamoxifen.

Breast Neoplasms↗
PubMed1987

[Value of RU 486 in failed terminations of pregnancy].

One of the complications of therapeutic termination of pregnancy is the complete retention of the embryo. The authors present four cases of repeated failure to evacuate the uterus associated with multiple fibroids or a malformation of the uterus. The use of RU 486 to soften the cervix and to allow it to dilate spontaneously made it possible in each case to aspirate the products completely. This action on the cervix of RU 486 could be used to make it easier to terminate early pregnancies up to the 12th week and particularly when there is associated uterine pathology.

Abortifacient Agents↗
PubMed1986

Termination of early pregnancy by the progesterone antagonist RU 486 (Mifepristone).

We studied the effects of the progesterone antagonist RU 486 in 100 women with early, unwanted pregnancy (within 10 days of the expected onset of the missed menstrual period). Thirty-four women received oral doses of 400 mg (in four days), 26 received 600 mg (in four days), and 40 received 800 mg (in two days). Uterine bleeding occurred in all patients within four days of the first dose and continued for 5 to 17 days. In 85 of the women, a dramatic decrease in the plasma chorionic gonadotropin level was observed on day 6, and an empty uterus was confirmed by ultrasonography on day 13. Hence, these women were considered to have had a complete abortion. Fifteen subjects had persistently elevated plasma chorionic gonadotropin levels on day 6 and were considered not to have responded to RU 486. They all had uterine evacuation, which was facilitated by a softening of the cervix. The percentage of women with complete abortion was similar in all dosage groups. Furthermore, plasma levels of immunoreactive RU 486 were similar in subjects with and without complete abortion. The only important side effect observed in the responders was prolonged uterine bleeding in 18 percent, but neither blood transfusion nor curettage was required. We conclude that RU 486 is an effective and safe method for termination of very early pregnancy but that it should be used only under close medical supervision.

Abortifacient Agents↗
PubMed1986

Synergism between cytosolic and mitochondrial oxidation: its possible relevance to the metabolism of vitamin D3 in the kidney.

Using frozen liver sections and quantitative cytochemistry it has been established that when cells are allowed to oxidize a cytoplasmic and a mitochondrial substrate simultaneously the resulting oxidative activity is markedly higher than the sum of the oxidation of each substrate measured separately. In the present study this type of synergistic interaction has been confirmed in the kidney, particularly in cells of the pars recta. Our results support the evidence of the influence of cytoplasmic NADPH on the intramitochondrial oxidative process and it is suggested that, in cells of the pars recta, cytosolic NADPH may be involved in intramitochondrial mixed function oxidases such as 1 alpha-hydroxylase: these results could further elucidate the mechanism responsible for the production of the hormonal form of vitamin D3.

Anaerobiosis↗