Search PubMed⌕ Search

Biomedical subjects

L Marions

Publications and source records attributed to L Marions.

12 recordsLinked to original sources
PubMed2004

Mechanisms of action of mifepristone and levonorgestrel when used for emergency contraception.

An emergency contraceptive method is used after coitus but before pregnancy occurs. The use of emergency contraception is largely under-utilized worldwide. One of the main barriers to widespread use is concern about the mechanism of action. Recently, treatment with either 10 mg mifepristone or 1.5 mg of levonorgestrel has emerged as the most effective hormonal method for emergency contraception with very low side-effects. However, the knowledge of the mechanism of action of mifepristone and levonorgestrel in humans, when used for contraceptive purposes and especially for emergency contraception, remains incomplete. The objective of this review is to summarize available data on the effects of mifepristone and levonorgestrel on female reproductive functions relevant to the emergency use of the compounds. When summarized, available data from studies in humans indicate that the contraceptive effects of both levonorgestrel and mifepristone, when used in single low doses for emergency contraception, involve either blockade or delay of ovulation, due to either prevention or delay of the LH surge, rather than to inhibition of implantation.

Contraception, Postcoital↗
PubMed2000

Medical termination of early pregnancy: the Swedish experience.

Abortion has been legal up to the 22nd week of gestation in Sweden since 1975. Most women terminate their pregnancies early; 96% before the 12th week and 75% in less than 63 days. Termination of early pregnancy (up to 63 days' gestation) using mifepristone followed by gemeprost was approved in Sweden in 1992. Use of the medical method has slowly but steadily increased since then. Currently about 40% of the women eligible for the procedure choose it. Both the surgical (vacuum aspiration) and the medical methods are regarded as effective and safe. The medical method will not replace vacuum aspiration, but be an alternative to it.

Abortifacient Agents, Nonsteroidal↗
PubMed1999

Comparison between oral and vaginal administration of misoprostol on uterine contractility.

OBJECTIVE: To compare the degree of absorption and the effect on uterine contractility of the prostaglandin E1 analogue misoprostol after vaginal and oral administration. METHODS: Thirty women with a normal intrauterine pregnancy between 8 and 11 weeks' gestation who requested termination of pregnancy were given either 0.2 mg (orally n = 5; vaginally n = 6) or 0.4 mg (orally n = 10; vaginally n = 9) of misoprostol. Intrauterine pressure was recorded using a Grass polygraph connected to a pressure transducer 30 minutes before misoprostol was given and for 4 hours thereafter. At the end of the recording, suction curettage was performed. Blood samples were obtained at 0, 0.5, 1, 2, 4, and 6 hours for measurement of misoprostol, which was assayed by high-pressure liquid chromatography-mass spectrometry. RESULTS: In all patients, the first effect was an increase in uterine tonus. After 0.4 mg of misoprostol administered orally, uterine tonus started to increase after a mean (+/- standard deviation) time of 7.8+/-3.0 minutes and reached its maximum after 25.5+/-5.0 minutes. The corresponding times after vaginal administration were 20.9+/-5.3 minutes and 46.3+/-20.7 minutes, respectively. The initial increase in tonus was also more pronounced after oral than after vaginal administration. After vaginal administration, all patients developed uterine contractions; the activity, measured in Montevideo units, increased continuously during the observation period. This was not the case after oral administration. Plasma levels of misoprostol were measured in 18 patients. The highest levels were found 30 minutes after oral treatment and 1-2 hours after vaginal administration. CONCLUSION: The long-lasting and continuously increasing uterine contractility after vaginal administration can be explained only in part by a direct effect of misoprostol. The longer period of elevated plasma levels of misoprostol may also have initiated the prolonged events leading to increased uterine contractility.

Abortifacient Agents, Nonsteroidal↗
PubMed1999

Contraceptive efficacy of daily administration of 0.5 mg mifepristone.

The antiprogestin mifepristone has shown potential to be used as a contraceptive. If 200 mg mifepristone is administered immediately after ovulation, the endometrium shows sufficient impairment of secretory development to prevent implantation. Low daily doses of mifepristone have been shown to reduce several of the local factors regarded as crucial for implantation in human endometrium. To find out if this regimen is sufficient to prevent pregnancy, 32 women were recruited for a study where 0.5 mg mifepristone was administered daily. A total of 141 cycles were studied. Five pregnancies occurred, which was significantly less than if no contraceptive method had been used. However, the dose chosen did not seem sufficient to act as a contraceptive although it is probably not possible to increase the dose without disturbing ovulation and bleeding pattern.

Adult↗
PubMed1999

Expression of cyclo-oxygenase in human endometrium during the implantation period.

Prostaglandins (PG) are known to be involved in the process of human implantation. In several animal species treatment with prostaglandin synthesis inhibitors will prevent implantation. Cyclo-oxygenase (COX) is the rate-limiting enzyme in the synthesis of PGs and exists in two isoforms, COX-1 and COX-2. Defective implantation in COX-2-deficient mice has been demonstrated recently. In the present study, the expression of COX-1 and COX-2 was studied during the implantation period in healthy fertile women before and after treatment with the antiprogesterone, mifepristone. The study consisted of one control cycle and one treatment cycle. The subjects served as their own control. During the treatment cycle the subjects received 200 mg of mifepristone 2 days after the luteinizing hormone (LH) surge. Endometrial biopsies were obtained in the mid-luteal phase (LH + 6 to LH + 8) in both cycles. Using polyclonal antibodies against COX-1 and COX-2, immunostaining for COX-1 was found mainly in the glandular and luminal epithelium and for COX-2 mainly in the luminal epithelium and the perivascular cells. After treatment with mifepristone, expression of COX-1 in glandular epithelium and COX-2 in luminal epithelium significantly decreased whilst the immunostaining for COX-2 in the perivascular cells remained strong. This study shows the expression of both COX-1 and COX-2 during the implantation period and also indicates that treatment with mifepristone in early luteal phase impairs glandular epithelial function and endometrial receptivity.

Animals↗
PubMed1999

Contraceptive use of antiprogestin.

OBJECTIVES: To study the effect of antiprogestin on ovarian function and endometrial development during the menstrual cycle and the possibility of using these compounds for contraceptive purposes. METHODS: Administration of different doses of the antiprogestin mifepristone during the menstrual cycle; intermittent measurements of luteinizing hormone, progestin and estrogen in blood and/or urine; endometrial morphology and concentration of markers for endometrial receptivity; efficacy trials of the contraceptive effect of mifepristone. RESULTS: A high dose of mifepristone administered in the follicular phase will inhibit follicular development. If mifepristone is given immediately after ovulation, the secretory development of the endometrium and the expression of, for instance, leukemia inhibitory factor and integrins will be inhibited. Similar effects on the endometrium are obtained with small weekly doses (2.5 or 5.0 mg) or small daily doses (0.5 mg) of mifepristone, which do not inhibit ovulation. Once-monthly administration of 200 mg mifepristone on the day after ovulation, and emergency postcoital treatment, are highly effective methods for preventing pregnancy. Even 5 mg once weekly has a significant contraceptive effect. CONCLUSIONS: The antiprogestin mifepristone has a number of effects during the menstrual cycle which makes the compound suitable for contraceptive use. Treatment after a single act of unprotected intercourse, and once-a-month treatment immediately after ovulation, have shown high contraceptive efficacy. A low-dose regimen which does not influence ovulation also has a contraceptive effect, but the efficacy needs to be improved before routine clinical use.

Contraceptives, Oral, Synthetic↗
PubMed1998

Contraceptive efficacy of low doses of mifepristone.

OBJECTIVE: To determine whether a 5-mg dose of mifepristone is sufficient to prevent pregnancy. DESIGN: Clinical study. SETTING: Academic research center. SUBJECT(S): Healthy, fertile, sexually active female volunteers. INTERVENTION: Volunteers received a 5-mg dose of mifepristone once weekly, starting on cycle day 2, for up to 6 months. This was their only contraceptive method. MAIN OUTCOME MEASURE(S): Number of pregnancies. RESULT(S): The treatment resulted in a significant decrease in pregnancy rate without affecting the menstrual cycle or causing disturbing side effects. CONCLUSION(S): A low dose of mifepristone, which does not inhibit ovulation, reduces fertility significantly by affecting the endometrium. However, the contraceptive effect needs to be improved for the drug to compete with other contraceptive methods.

Adult↗
PubMed1998

The effect of antiprogestin on integrin expression in human endometrium: an immunohistochemical study.

Integrins are cell surface receptors for the extracellular matrix and connect extracellular cell adhesion proteins to cytoskeletal components. Several investigators have recently described the expression of different integrins in the human endometrium as markers of receptivity. In the present study we investigated the effect of various doses of the antiprogestin mifepristone on the endometrial expression of integrins during the implantation phase. Endometrial biopsies from healthy fertile women were obtained in the midluteal phase. The study included one control and one, two or three treatment cycles. In treatment cycles either 2.5 (n = 9) or 5 mg (n = 5) of mifepristone was administered once weekly, 0.5 mg daily (n = 5), or 200 mg as a single dose administered on day 2 after the luteinizing hormone surge (day LH + 2; n = 8). By using polyclonal antibodies against integrin alpha(v)beta3, subunit beta3 and subunit alpha4 we found reduced immunostaining for alpha4 and beta3 subunit in glandular epithelium after treatment with mifepristone while alpha(v)beta3, expression appeared to be unaffected. No differences between treatment groups were noted. This study demonstrates that treatment with mifepristone interferes with integrin distribution during the implantation window. This may imply that the contraceptive effect of mifepristone is primarily due to impaired endometrial receptivity. However, since no effect was shown on the distribution of the vitronectin receptor, this integrin might be regulated differently by other factors such as cytokines.

Adult↗
PubMed1991

Six cases of massive feto-maternal bleeding causing intra-uterine fetal death.

Six patients in whom intra-uterine fetal death (IUFD) near term resulted from massive feto-maternal hemorrhage are reported. Two of the mothers were Rh-negative, which necessitated the administration of large volumes of anti-D. In order to detect such patients, the Kleihauer-Betke test should be performed in all cases of IUFD of unknown etiology.

Adult↗
PubMed1989

Left ventricular output during postnatal circulatory adaptation in healthy infants born at full term.

Left ventricular output was measured non-invasively at predefined time intervals from less than 15 minutes to 72 hours after birth in 16 infants who had been born at full term. The blood flow velocity in the ascending aorta was measured by a range gated Doppler technique and multiplied by the cross sectional diameter measured by cross sectional and M mode echocardiography. Left ventricular output remained high in the first two hours, 235-243 ml/min/kg, despite a 10% decrease in heart rate. The fall in heart rate was compensated for by a 15% increase in stroke volume. Between 2 and 24 hours there was a significant fall in mean (SD) left ventricular output to 187 (35) ml/min/kg caused mainly by a reduction in stroke volume. The fall in left ventricle output after two hours may reflect an adaptation to the decreased demand on the left ventricle as the ductus constricts.

Adaptation, Physiological↗
PubMedDate not supplied

Pregnancy termination.

During pregnancy, the antiprogestin mifepristone will induce uterine contractions, increase the sensitivity of the myometrium to prostaglandin, and ripen the cervix. These effects indicate that mifepristone can be used for termination of pregnancy. The clinical experience has shown that mifepristone is sufficiently effective for this purpose only if combined with a suitable prostaglandin, e.g. gemeprost or misoprostol. The combined treatment has been used for termination of early pregnancy (up to 63 days of amenorrhea) and for termination of second trimester pregnancy. During early pregnancy, the recommended dose of mifepristone is 600 mg (although 200 mg seems sufficient), followed 36-48 h later by 0.4-0.8 mg misoprostol administered either orally or vaginally, or vaginal administration of 1.0 mg gemeprost. For termination of second trimester pregnancy, the treatment with mifepristone is most commonly combined with 1.0 mg gemeprost repeated at 3-6-h intervals. The combined treatment is as effective and safe during early pregnancy as is the alternative vacuum aspiration and is also equally acceptable if the woman is allowed to choose the method she prefers. During the second trimester, the pretreatment will significantly reduce the duration of labor, dose of prostaglandin, and the frequency of side effects.

Abortifacient Agents, Nonsteroidal↗