Biomedical subjects

A Ulmann

Publications and source records attributed to A Ulmann.

At least 37 records · Page 2Linked to original sources

PubMed1991

Effects of the converting enzyme inhibitor trandolapril on short-term variability of blood pressure in essential hypertension.

Short-term fluctuations in blood pressure and heart rate were analysed in a group of eight males with essential hypertension. Indirect finger blood pressure was measured by a non-invasive device (Finapres). Analogue-to-digital conversion of the blood pressure was used to determine systolic and diastolic blood pressure and heart rate every second. The equidistant sampling allowed a direct spectral analysis using a fast Fourier transformation algorithm. The effect of 7-day administration of the angiotensin converting enzyme inhibitor, transolapril (2 mg/day), was assessed in a double-blind, randomized, placebo-controlled cross-over study. After trandolapril there was a significant reduction in systolic blood pressure levels (-15 mmHg). The reduction in diastolic blood pressure did not reach significance. The standard deviation of systolic and diastolic blood pressure levels were significantly reduced (-20% and -22% for systolic and diastolic respectively). Neither average heart rate nor standard deviations of heart rate time series was affected by the angiotensin converting enzyme inhibitor. Spectral analysis of fluctuation in blood pressure showed a reduction in the variability underlying the standard deviation changes of systolic and diastolic blood pressure. Trandolapril selectively reduced the amplitude of systolic and diastolic oscillations in the 66-129 mHz region, corresponding to Mayer waves. The significant decrease in the 10 s period oscillations of blood pressure after chronic angiotensin converting enzyme blockade with trandolapril could reflect reduced sympathetic outflow to vascular smooth muscle.

Adult↗

PubMed1991

Endocrine responses to long-term administration of the antiprogesterone RU486 in patients with pelvic endometriosis.

OBJECTIVE: To examine endocrine and clinical responses to long-term administration of RU486 in patients with endometriosis. DESIGN: Prospective open trial. SETTING: Faculty practice of the authors. PATIENTS, PARTICIPANTS: Six normally cycling women with endometriosis were recruited. INTERVENTIONS: Subjects received RU486 100 mg/d for 3 months. MAIN OUTCOME MEASURE(S): Hormonal changes during RU486 were compared with control data obtained in the preceding cycle during the early follicular phase. Clinical responses were determined by patient assessment and second-look laparoscopy. RESULTS: All women became amenorrheic, and daily urinary levels of ovarian steroid metabolites remained acyclic. Mean luteinizing hormone (LH) (P less than 0.02) and LH pulse amplitude (P less than 0.05) were increased without changes in LH pulse frequency. An antiglucocorticoid effect was demonstrated by an increase in serum cortisol (P less than 0.01) and adrenocorticotropic hormone (P less than 0.05) levels. Treatment resulted in an improvement in pelvic pain in all subjects without significant change in the extent of disease as evaluated by follow-up laparoscopy. CONCLUSIONS: Daily administration of RU486 results in acyclic ovarian function and improvement in the subjective painful symptoms of endometriosis.

Adolescent↗

PubMed1990

Voluntary interruption of pregnancy with mifepristone (RU 486) and a prostaglandin analogue. A large-scale French experience.

In 2115 women seeking voluntary termination of pregnancy after 49 days of amenorrhea or less, we studied the effect of a single 600-mg dose of mifepristone (RU 486), followed 36 to 48 hours later by the administration of one of two prostaglandin analogues, either gemeprost (1 mg by vaginal suppository) or sulprostone (0.25, 0.375, or 0.5 mg by intramuscular injection). The women were monitored for four hours after prostaglandin administration. Efficacy was indicated by the complete expulsion of the conceptus without the need of an additional procedure. All other results were considered failures, and the pregnancy was then terminated by a surgical method. The overall efficacy rate was 96.0 percent (95 percent confidence interval, 95.0 to 96.8). The failures included persisting pregnancies (1.0 percent), incomplete expulsions (2.1 percent), and the need for hemostatic procedure (0.9 percent). The mean time to expulsion was significantly shorter when sulprostone was given in the high dose (4.5 hours) than when it was given in the two lower doses (13.1 and 19.3 hours) or when gemeprost was given (22.7 hours). The mean duration of uterine bleeding was 8.9 days (range, 1 to 35); one woman received a blood transfusion. Most women had transient abdominal pain after receiving prostaglandin, but there were few other side effects. We conclude that the administration of mifepristone followed by a small dose of a prostaglandin analogue is an effective and safe method for the early termination of pregnancy.

Abortifacient Agents↗

PubMed1990

Tolerance of perinidatory primate embryos to RU 486 exposure in vitro and in vivo.

Monkey embryos were exposed to RU 486 both in vitro and in vivo (with and without progesterone therapy) in the perinidatory interval. These primate embryos were highly tolerant of RU 486, except when RU 486 alone terminated early pregnancy. There were no indications of teratogenicity in this limited trial when the embryos were exposed to RU 486 either before implantation (10(-7)M in 24-hour cultures) or during the immediate post-implantation interval (50 mg orally/day; days 32 to 39 LMP).

Animals↗

PubMed1990

RU 486.

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Abortion, Induced↗

PubMed1989

[Use of mifepristone in the termination of early pregnancy. The experience in France].

Are reported the results obtained with mifepristone, administered alone or followed by a low dose of prostaglandin derivative, as an alternative to endometrial aspiration for termination of early pregnancy. Mifepristone was first used alone in doses of 600 mg in 1,841 women. Subsequently, 703 other women received, 36 to 48 hours after mifepristone, either sulprostone (a prostaglandin E2 analogue) 0.25 mg intramuscularly, or gemeprost (a prostaglandin E1 analogue) 1 mg as pessary, or meteneprost (a prostaglandin E2 analogue) 10 mg as pessary. Mifepristone administered alone was successful in 80 per cent of pregnant women with less than 42 days of amenorrhoea. The mifepristone-prostaglandin combination was successful in more than 95 per cent of pregnant women with less than 50 days of amenorrhoea. Expulsion of the ovum was difficult to date when mifepristone was used alone; it occurred within 24 hours of prostaglandin dosing in more than 80 per cent of the other women. Uterine bleeding was almost constant. It was more copious than the usual menses in the majority of women, with or without prostaglandin, and it sometimes required aspiration or curettage (mifepristone alone 1.3 per cent, with prostaglandin 0.28 per cent) and/or blood transfusion (mifepristone alone 0.4 per cent, with prostaglandin 0.14 per cent). Administered alone, mifepristone was very well tolerated. When prostaglandin analogues were added the women complained of lower abdominal pain which required a minor antalgic treatment in 30 to 50 per cent of the cases. Gastrointestinal side-effects were mild, probably due to the low doses of prostaglandin administered.

Abortifacient Agents↗

PubMed1989

[Efficacy and tolerance of tiaprofenic acid in pharyngitis in adults. Results of a randomized study vs placebo].

Tiaprofenic acid (Surgam) is a non steroidal anti-inflammatory drug used in France for the treatment of acute inflammation, during episodes of upper respiratory tract infections of children and adults. The efficacy and tolerance of tiaprofenic acid for the treatment of inflammation during adult tonsillitis and pharyngitis were evaluated by a randomized double-blind study versus placebo. We used evaluation criterion taking into consideration dysphagia and inflammatory physical indications of tonsillitis and opinions of investigators and patients. Sixty patients have been included in this study. They received either tiaprofenic acid or placebo during five days together with penicillin V. After 48 hours and 5 days of treatment, the efficacy of tiaprofenic acid was significantly superior to placebo on all principal test studied. Tolerance was good in both groups.

Acute Disease↗

PubMed1989

Progesterone antagonist (RU 486) for cervical dilation, labor induction, and delivery in monkeys: effectiveness in combination with oxytocin.

A progesterone antagonist (RU 486), combined with oxytocin, was effective in achieving cervical dilation, labor induction, and early delivery in near-term monkeys. Effects of RU 486 included accelerated flow of colostrum and transiently enhanced weight gain in infants. No overt toxicity on fetuses, mothers, or newborns was detected with the use of a single oral dose of 25 mg.

Animals↗

PubMed1989

Contraceptive potential of RU 486 by ovulation inhibition: I. Pituitary versus ovarian action with blockade of estrogen-induced endometrial proliferation.

In previous studies, RU 486 administration arrested spontaneous folliculogenesis. To investigate the central versus peripheral effects of RU 486 on the ovarian/menstrual cycle, including endometrial proliferation, RU 486 was administered daily (10 mg/kg/day, im) from menstrual cycle day 3 or 7 to day 25 in normal adult cynomolgus monkeys receiving hMG treatment (37.5 IU/day) from days 3-8 (n = 6). RU 486 administration with hMG/hCG therapy did not inhibit ovarian response, as evidenced by steroidogenesis and ovulation. Nine of 23 oocytes retrieved by lavage or follicular aspiration at laparotomy after ovulation induction were morphologically classified as mature preovulatory status. Whereas an endometrial biopsy performed on cycle day 25 in control monkeys revealed an in phase mature secretory endometrium, histologic sections from RU 486 plus hMG/hCG treated females uniformly demonstrated atrophic to weakly proliferative endometrium on cycle day 25, despite serum estradiol levels greater than 300 pg/ml. Three months after the initial 25-day study endometrial biopsies revealed persistent atrophic endometrium, even though repeated ovulation induction with hMG/hCG therapy elevated serum estrogen concentrations. The findings prevailed whether RU 486 treatment began on cycle day 3 or 7. The intermenstrual interval was significantly (P less than 0.01) lengthened by RU 486 treatments (28.5 +/- 2.0, control vs 131.3 +/- 11.5 days, RU 486). In summary, RU 486 consistently blocked ovulation unless hCG was provided and elicited a persistent retardation of early proliferative endometrium when administered daily beginning in early or mid-follicular phase. The normal mitogenic effects of elevated ovarian estrogen secretion on endometrial tissue were quelled, uniformly resulting in amenorrhea. The long-lasting action of RU 486, causing ovulation inhibition and atrophic endometrium, may be due to the depot effect of im injection. In addition, RU 486 did not prevent ovarian steroidogenesis, ovulation or oocyte maturation when an ovulation induction regimen of hMG/hCG was given. These findings show that RU 486 prevented ovulation by diminishing pituitary gonadotropin secretion, rather than by direct effects on ovarian folliculogenesis, and induced amenorrhea by inhibiting estrogen-induced endometrial proliferation.

Animals↗

PubMed1989

Contraceptive potential of RU 486 by ovulation inhibition: II. Suppression of pituitary gonadotropin secretion in vitro.

That the antiprogestin RU 486 delays or inhibits the LH surge, and induces premature luteolysis in monkeys and women concurrent with a reduction in LH/FSH secretion has been reported. Whether this inhibition of gonadotropin release was a result of action at the hypothalamic and/or pituitary level is unknown. Here, we utilized a rat pituitary cell culture system to evaluate direct RU 486 actions on pituitary gonadotropin secretion in vitro. Cell cultures were primed with 10 nM estradiol for 48 h in order to maintain progesterone receptors. Basal and GnRH-induced secretion were evaluated after a 4-hour incubation period. The progesterone antagonist RU 486 inhibited GnRH-induced LH and FSH secretion in a dose-dependent manner, without affecting basal gonadotropin release. This inhibition of gonadotropin secretion was specific and antagonized by addition of progesterone in vitro.

Animals↗

PubMed1989

Contraceptive potential of RU 486 by ovulation inhibition: III. Preliminary observations on once weekly oral administration.

Acute administration of the potent progesterone antagonist RU 486 during the luteal/secretory phase of the menstrual cycle induces premature menses in women and monkeys. Using a variety of regimens, administration of RU 486 during the follicular/proliferative phase causes anovulation and amenorrhea. Single treatment in the late follicular phase blocks the preovulatory LH surge and ovulation; mid-luteal phase administration of RU 486 can cause premature luteolysis. The objective of the present study was to evaluate the contraceptive potential of the antiprogesterone RU 486 during once weekly oral administration in normally cycling cynomolgus monkeys. Oral administration of 25 mg of RU 486 on cycle days 3, 10, 17 and 24 blocked the expected midcycle LH/FSH surges. Interestingly, whereas progesterone remained undetectable throughout the treatment cycle, estradiol levels began to increase during the last two weeks of treatment. In contrast, halving the dose to 12.5 mg did not inhibit apparent ovulation or luteal function, as judged by serum LH, estradiol and progesterone levels. We conclude that at adequate doses, RU 486 effectively blocks ovulation when administered orally in a once weekly regimen. Further studies are warranted to evaluate RU 486 and other progesterone antagonists as potential contraceptive agents.

Animals↗

PubMed1989

Comparative effects of 17 beta-estradiol, progestin R5020, tamoxifen and RU38486 on lactate dehydrogenase activity in MCF-7 human breast cancer cells.

The effects of 17 beta-estradiol (estradiol), synthetic progestin R5020 and their antagonists, tamoxifen (Tam) and synthetic RU38486 on lactate dehydrogenase (LDH) activity in MCF-7 human breast cancer cells during the growth period were studied. A specially developed quantitative cytochemical assay was used; LDH activity is expressed per cell, and is thus independent of the positive and negative growth effects of the hormones and antagonists. Estradiol and R5020 stimulated LDH activity after similar exposures (6-48 h) and the stimuli were concentration dependent over the range 10(-7) M to 10(-10) M. As for the antagonists, RU38486 stimulated LDH activity in much the same way as estradiol and R5020; Tam alone, on the other hand, does not stimulate LDH, but when added to estradiol, Tam inhibits estradiol mediated LDH activation. When present at half-stimulant concentration, estradiol + R5020 and estradiol + RU38486 exhibit additive effects on LDH activity. Thus LDH appears to be an interesting tool for the study of hormone and antagonist effects in MCF-7 breast cancer cells.

Breast Neoplasms↗

PubMed1989

Noncompetitive antiestrogenic effect of RU 486 in blocking the estrogen-stimulated luteinizing hormone surge and the proliferative action of estradiol on endometrium in castrate monkeys.

The noncompetitive antiestrogenic effects of RU 486 were examined using estradiol (E2)-treated ovariectomized monkeys given RU 486, progesterone (P), or both. The E2-induced luteinizing-hormone (LH) surge of control animals was abrogated by P and/or RU 486. Secretory transformation by P was inhibited by RU 486 coadministration. RU 486 alone (1 mg/kg) induced endometrial secretory transformation, but higher doses (5 mg/kg) inhibited proliferation and secretory activity. Thus in the presence of P, RU 486 is antagonistic but, in absence of P, exhibits endometrial progestational effects at low doses and an antiproliferative (antiestrogenic) effect at higher doses. These data encourage continued evaluation of RU 486 as a potential contraceptive agent acting at the pituitary and/or endometrial level.

Animals↗

PubMed1989

Clinical trials with RU 486 (mifepristone): an update.

This paper reviews much of the clinical data obtained with the antiprogestin RU 486 (mifepristone) in the fields of obstetrics and gynecology. To interrupt early pregnancy (less than 50 days of amenorrhea) RU 486 as a single dose of 600 mg followed 36-48 hours later by a prostaglandin derivative, constitutes an alternative to vacuum aspiration or dilatation and curettage (D and C). All three methods have comparable efficacy, provided that they are performed in centers with adequate medical facilities. RU 486 is the first antiprogestational steroid available for clinical purposes. Its pharmacological properties have been reviewed in detail elsewhere (1,2). The present paper reviews the main clinical data obtained during trials monitored by Roussel Uclaf.

16,16-Dimethylprostaglandin E2↗

PubMed1988

Transplacental passage of a progesterone antagonist in monkeys.

The progesterone antagonist RU 486 dramatically increases myometrial contractility of the pregnant uterus, making it a potential adjunctive therapy for labor induction or therapeutic pregnancy termination. Sixteen female cynomolgus monkeys were studied during the second or third trimester of pregnancy. Hysterotomies were performed with the animals under anesthesia, providing access to the intact placental vasculature. RU 486 (25 mg) was injected intravenously into the mothers. Serial blood samples were drawn from the maternal and fetal-placental compartments for a period of 2 hours. RU 486 achieved a gradient equilibrium between the maternal and fetal-placental circulation within 5 minutes, suggesting free passage by simple diffusion. The clearance kinetics of immunoreactive RU 486 are consistent with an open three-compartment system in mother and fetus. The fetal-placental index decreased from 31.2% to 17.8% between the second and the third trimester of pregnancy. There was no acute toxicity of the RU 486 noticed during the experimental course.

Animals↗

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↗