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Biomedical subjects

A Ulmann

Publications and source records attributed to A Ulmann.

At least 19 recordsLinked to original sources
PubMed1996

Treatment of endometriosis with the antiprogesterone mifepristone (RU486)

OBJECTIVE: To evaluate the safety and efficacy of an antiprogesterone (mifepristone, RU486; Roussel-Uclaf, Romaineville, France) on endometriosis. DESIGN: An open, prospective clinical trial. SETTING: The clinical practice of an academic faculty. PATIENTS: Nine women with endometriosis were studied. INTERVENTIONS: RU486 (50 mg/d) was administered for 6 months. MAIN OUTCOME MEASURES: Daily symptom inventories and urinary steroid metabolites were assessed before, during, and after treatment. Blood for hormone analysis was obtained weekly for 4 weeks and monthly thereafter. The extent of endometriosis, bone mineral density, circadian rhythm of cortisol, and LH pulsatility were determined before and after treatment. Safety laboratory measurements were made before and at 1, 2, and 6 months of treatment. RESULTS: Pelvic pain and uterine cramping improved in all patients. Endometriosis regressed by 55%. All patients exhibited endocrine features of anovulatory amenorrhea without hypoestrogenism. A rise in serum LH and T levels was observed during the first month of treatment and one patient developed an elevation of liver transaminases during the last month of treatment. All other measurements were unchanged. CONCLUSION: RU486 appears to be effective in improving the symptoms and causing regression of endometriosis in the absence of significant side effects.

Adolescent↗
PubMed1995

[Mifepristone (RU 486): present status, prospectives].

Mifepristone (RU 486) has many therapeutic possibilities, which largely exceed simple interruption of pregnancy. They are due to its unique properties of progesterone--and glucocorticosteroid--receptor blockage. In early interruption of pregnancy, the association with a prostaglandin analogue represents an efficient and well-tolerated method. The safety and comfort of the method have been improved by the association with misoprostol, an oral prostaglandin analogue. Mifepristone can also be used in late pregnancy interruptions for medical reasons, as well as for expulsion of an in utero dead fetus. In these indications, its use allows to decrease or even to avoid the use of prostaglandins, thus diminishing the side-effects due to these products. Several other gynaecological and obstetrical indications seem promising in the future: dilatation and ripening of uterine cervix, induction of labour for medical reasons, contraception. Trials are ongoing to evaluate the antitumoral activity of mifepristone in meningiomas and breast cancer. Finally, its anti-glucocorticosteroid effect is used in the treatment of Cushing's syndromes due to ectopic secretion of ACTH and other indications may be foreseen.

Abortion, Legal↗
PubMed1995

Termination of early pregnancy (up to 63 days of amenorrhea) with mifepristone and increasing doses of misoprostol [corrected].

The efficacy and tolerability of mifepristone in combination with misoprostol for termination of early pregnancy (up to 49 days of amenorrhea) are established. We studied the efficacy and tolerability of this combination therapy for termination of pregnancy in women up to 63 days of amenorrhea. We also examined the effect of an additional dose of misoprostol in cases of nonexpulsion within 3 hours after the first dose. The multicenter trial included 1,108 women, mean age 27.9 +/- 6.2 years. The mean duration of pregnancy was 51.7 +/- 9.2 days. On day 1, the women received an oral dose of mifepristone, 600 mg. On day 3, they received an oral dose of misoprostol, 400 micrograms, and were monitored for up to 3 hours. If they did not expel the conceptus within 3 hours, an additional dose of 200 micrograms of misoprostol was given and they were monitored for 2 more hours. From days 10 to 18, the women were followed up with clinical examination, human chorionic gonadotropin measurement, or ultrasound examination. Overall, the procedure was successful in 92.9% of women. Efficacy decreased with the duration of pregnancy, especially after 56 days of amenorrhea. Up to 42 days of amenorrhea, the success rate was 97.6%; between days 42 and 49, 94.8%; between days 50 and 56, 93.4%; between days 57 and 63, 86.8%; and after day 63, 83.3%. The most common side effects were moderate uterine cramps (80.5%) and gastrointestinal (GI) symptoms (34.9%), especially vomiting (18.3%) and diarrhea (10.5%). GI symptoms were generally mild. A second dose of misoprostol was given to 61.6% of the women. In a subgroup analysis, we assessed the efficacy of 600 mg of mifepristone plus 400 or 600 micrograms of misoprostol (one or two doses) in women with up to 49 days of amenorrhea and compared it with the efficacy in women who received mifepristone plus only 400 micrograms (one dose) of misoprostol in a previous study. The overall rate of success (termination of pregnancy) was 95.5% in the current study compared with 95.4% in the previous study. The additional dose of misoprostol did not significantly increase the overall rate of success, but did increase the rate of termination within the monitoring period (69.7% versus 64.9% (and within 72 hours after administration of mifepristone (92.7% versus 90.4%). We have confirmed that the combination of mifepristone and misoprostol was effective, safe, and well tolerated for termination of pregnancies at 49 or fewer days of amenorrhea. The efficacy decreased slightly between 49 and 56 days, and then decreased significantly between 56 and 63 days. For maximal safety and tolerability, we recommend this method only for women with 49 or fewer days of amenorrhea. A second dose of misoprostol did not improve overall efficacy, but did increase the rate of early termination.

Abortifacient Agents↗
PubMed1994

RU486: the French experience.

RU486 (mifepristone) followed by a prostaglandin (PG) analogue has been marketed in France since April 1990 as a medical alternative to surgery for early pregnancy termination. By law, the drug is used only in the centres approved for voluntary pregnancy termination, and its distribution is strictly controlled. Before being marketed, it was distributed to more than 20,000 women, as part of a training programme for the prescribers. Analysis confirmed an efficacy rate of 95.3%. Failures included incomplete ovular expulsion (2.8%), premature vacuum aspiration (0.7%) and ongoing pregnancy (1.2%). Pelvic pain and malaise were reported as side-effects in 1.6 and 1.2% of the cases respectively. Infectious complications were reported in 0.2% of the cases. Three severe adverse events (one of which was fatal) occurred, including myocardial infarction and ventricular arhythmia, in the hours following PG administration and justify a careful medical monitoring in the centre 3-4 h after administration of PG. For this reason, a trial was undertaken to evaluate the efficacy of an oral form of a PGE1 analogue (misoprostol). When RU486 was followed 36-48 h later by 400 micrograms of misoprostol, the efficacy rate was 96.9%, indicating an efficacy equivalent to that obtained with the other PG analogues. The distribution procedures were adequately followed by the prescribers and by the patients. In summary, RU486 constitutes a safe and efficient medical means of pregnancy termination, provided that the manufacturer's recommendations are properly followed.

Abdominal Pain↗
PubMed1994

Glomerular hemodynamics during abortion induced by RU 486 and sepsis in rats.

1. Acute renal failure is a very common consequence of septic abortion. Whole kidney and glomerular hemodynamics were evaluated in virgin (V), pregnant (PREG) and aborted (ABOR) euvolemic Munich-Wistar rats before and after E. coli (0111-B4) endotoxin (LPS) infusion in order to evaluate the effect of septic abortion on the renal microcirculation. 2. Abortion induced by RU 486 blunted the increase in glomerular filtration rate (GFR) induced by normal pregnancy (0.86 +/- 0.03 vs 0.63 +/- 0.07 ml/min, P < 0.05). In virgin rats, RU 486 did not modify the parameters of renal function. Significant alterations occurred in whole kidney and single nephron function. However, the changes in whole kidney function in the ABOR group were significantly higher than those observed for the V group (reductions in GFR were 42% in V and 80% in ABOR, RPF decreased 34% in V and 76% in ABOR, TRVR increased 82% in V and 400% in ABOR). 3. Mean single nephron glomerular filtration rate (SNGFR) was reduced in all groups after LPS (44% in V, 43% in V+RU, 55% in PREG, 60% in ABOR), due to significant decreases in glomerular plasma flow rate, QA (42% in V, 55% in V+RU, 53% in PREG, 57% in ABOR) and in glomerular ultrafiltration coefficient, Kf (46% in V, 47% in V+RU, 45% in PREG, 67% in ABOR). 4. These data show that LPS induced significant alterations in renal function in all groups. However, aborted rats were more sensitive to the effects of LPS than V rats. These results indicate that abortion may potentiate the effects of endotoxemia on renal function elevating the extent of acute renal failure and thus the mortality rate.

Abortion, Induced↗
PubMed1993

Early termination of pregnancy with mifepristone (RU 486) and the orally active prostaglandin misoprostol.

BACKGROUND AND METHODS: The combination of mifepristone (RU 486) and a prostaglandin analogue given either intramuscularly or intravaginally is effective in terminating early pregnancy, but the prostaglandin component of the regimen is cumbersome to administer and has side effects. We conducted two studies to determine the efficacy of 600 mg of mifepristone followed by a small dose of misoprostol, an orally active prostaglandin E1 analogue, for the same purpose. In the first study, 505 women who had had amenorrhea for less than 50 days received 400 micrograms of misoprostol 48 hours after receiving mifepristone, if the pregnancy was not terminated within that period. In the second study, 390 women initially received the same treatment, but if the pregnancy was not terminated within four hours after the administration of misoprostol, they were offered an additional 200-micrograms dose of misoprostol. RESULTS: In study 1, the rate of success (termination of pregnancy and complete expulsion of the conceptus) was 96.9 percent (95 percent confidence interval, 94.1 to 97.7 percent)--similar to the success rate of approximately 95 percent for mifepristone followed by the intramuscular or intravaginal administration of prostaglandin. Abortion occurred in 2.9 percent of the women within 48 hours after the administration of mifepristone, in 60.9 percent within 4 hours after the administration of misoprostol, and in 33.2 percent thereafter. The failures included ongoing pregnancies in four women (0.8 percent) and incomplete abortions in nine (1.8 percent); two other women (0.4 percent) required vacuum aspiration for prolonged uterine bleeding. In study 2, pregnancy was terminated in 5.5 percent of the women before the administration of misoprostol and within four hours after the first dose of misoprostol in 69.1 percent. Among the 71 women who received a second dose of misoprostol, 67 had complete abortions, 2 had partial retention of the conceptus, 1 had synechia with ongoing pregnancy, and 1 had an ectopic pregnancy. One ongoing pregnancy, which was terminated by vacuum aspiration, was recorded among the 27 women who declined to take the second dose of misoprostol. The overall rate of success of the regimen with the optional second dose of misoprostol was 98.7 percent (95 percent confidence interval, 96.8 to 99.5 percent). No woman had any serious adverse event. CONCLUSIONS: The combination of mifepristone and misoprostol is effective for the termination of early pregnancy in terms of success, tolerance, safety, and practicality.

Abortion, Induced↗
PubMed1993

Progesterone antagonist RU 486 accommodates but does not induce labour and delivery in primates.

The hormonal mechanisms of parturition in primates remain controversial. Even so, the well-known decrease of plasma progesterone concentration near term is considered by many as the 'labour inducer'. The progesterone antagonist RU 486, which blocks progesterone activity at the cellular receptor level, appears to be a useful hormonal tool by which to study this tissue. Here, we tested its capacity to induce labour and delivery. A total of 23 Cynomolgus monkeys (Macaca fascicularis), within 9-17 days of expected term, were assigned to four different protocols to study various doses, routes and regimens of RU 486 administration. Observations included uterine contractile patterns, pharmacokinetics of RU 486 in plasma and passage of RU 486 into breast milk. None of the protocols tested successfully induced labour resulting in vaginal delivery within 24 h. Instead, the data demonstrate that blockade of progesterone activity by the progesterone antagonist was not sufficient by itself to achieve parturition in these primates. Uterine myometrial contractile activity under RU 486 exposure was not sufficient to induce labour and delivery. Moreover, the progesterone antagonist concentration in breast milk was very low, indicating little passage to suckling newborn infants.

Animals↗
PubMed1992

Medical abortion.

Explore the source record for details and available documents.

Abnormalities, Drug-Induced↗
PubMed1992

Medical termination of early pregnancy with mifepristone (RU 486) followed by a prostaglandin analogue. Study in 16,369 women.

We report the results of a large-scale trial with mifepristone (RU 486) followed by the administration of a prostaglandin (PG) analogue for the medical termination of early pregnancy. Altogether, 16,173 patients from 300 centers were evaluated. 48 women (0.3%) were lost to follow-up prior to, and 416 (2.6%) after the PG administration, and therefore the efficacy was evaluated in 15,709 women. Overall, the success rate was 95.3%, with no statistical difference regarding the nature and dose of PG used. The median duration of bleeding was 8 days, being 12 days or less in 89.7% of the women. Bleeding was significant enough to necessitate a vacuum aspiration or a dilatation and curettage in 0.8% of the cases. A blood transfusion was necessary in 0.1% of the women (11 patients). Serious cardio-vascular side-effects were reported in 4 cases after the PG (sulprostone) injection: they consisted of one acute myocardial infarction attributed to a coronary spasm, and in marked hypotension in the other 3 women. All patients recovered uneventfully. In conclusion, RU 486 followed by a PG analogue provides an efficient and safe medical alternative to surgery for early pregnancy termination, provided that the recommended protocol is adequately followed and the contraindications to prostaglandins are respected.

Abortifacient Agents, Nonsteroidal↗
PubMed1991

[Natural history of renal calcium lithiasis. Data obtained from a cohort of 667 patients].

Between January 1st, 1988 and May 31st, 1989, 667 patients (419 men, 248 women) with radioopaque, non cystinic and apparently idiopathic (lack of severe renal disease) renal stones were entered in a prospective study. The data obtained at entry enabled us to build up, retrospectively, a quantified presentation of the natural history of calcium nephrolithiasis. At the time the disease was discovered the patients' mean age was 40.4 years, and its presence had been known for 7.9 years on average in both sexes. The mean number of stones formed by the patients was 3.5. In 218 of the 277 patients who had only one stone the nephrolithiasis had been present for less than 3 years, as compared with at least 6 years in the 184/252 patients who had 3 stones or more; this suggests that in many of the patients studied the stones had rapidly become symptomatic. Women had a significantly (chi 2: P less than 10(-3)) more frequent history of urinary tract infection than men, and notably more frequent episodes of febrile infection (31.5 percent in women, 7.1 percent in men). A familial history of nephrolithiasis was found in 34.7 percent of women and 31 percent of men, but its presence had no influence on the number of stones formed or on the duration of the disease. On the other hand, the stones were discovered significantly earlier in men who has a familial history of nephrolithiasis (37.3 years) than in those who had no such history (42 years; P less than 10(-3)). These data will be used as baselines to a prospective evaluation of the course of nephrolithiasis in these patients.

Adult↗
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↗