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Biomedical subjects

M Elstein

Publications and source records attributed to M Elstein.

At least 73 records · Page 4Linked to original sources

Effects of 180 micrograms and 250 micrograms norgestimate on pituitary-ovarian function and cervical mucus.

A double-blind cross-over study of 16 healthy women was carried out to evaluate the effects of norgestimate, a new progestogen, on pituitary ovarian function and cervical mucus. Treatment from cycle day 7 to 16 with 180 micrograms and 250 micrograms norgestimate led to suppression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, while progesterone (P) remained suppressed in 28 of 32 cycles studied, indicating inhibition of ovulation. Lack of ovulation in 30 cycles was associated in all but 3 with functional follicles, 2 of which luteinized. With 250 micrograms norgestimate, estradiol (E2) concentrations reached levels similar to those achieved during control follicular phase, but significantly higher concentrations of E2 were achieved with 180 micrograms norgestimate. Cervical mucus score was significantly depressed in all but 5 cycles (3 norgestimate 180 micrograms and 2 norgestimate 250 micrograms cycles). In conclusion, both dosages of norgestimate show good suppression of the hypothalamic-pituitary axis and cervical mucus.

Adult↗

Fixed minidose warfarin: a new approach to prophylaxis against venous thrombosis after major surgery.

A prospective study was carried out to see whether a small fixed dose of warfarin (1 mg daily) given before operation (mean 20 days) would prevent deep vein thrombosis in patients having major gynaecological surgery. One hundred and four patients were randomised into three groups: fixed minidose warfarin; full dose oral anticoagulation; and no treatment (controls). There was a significantly lower incidence of deep vein thrombosis in the minidose warfarin and full dose anticoagulant treatment groups (9% (3/32) and 3% (1/35) respectively) than in the controls (30%; 11/37) but no significant difference between the two anticoagulant treatment groups. Prothrombin time and the activated partial thromboplastin time were normal on the day of surgery in the warfarin treatment group, whereas times were prolonged in the group given full dose anticoagulation. Mean haemoglobin concentrations fell in all three groups after operation but the fall was significantly less in the minidose warfarin treatment group than after full dose anticoagulation. The benefit from full dose oral anticoagulant prophylaxis, based on a preoperative international normalised ratio of 1.5-2.5 with rabbit brain Manchester reagent, was similar to the protection achieved in an oral anticoagulant treatment group controlled with human brain Manchester comparative reagent at a similar level of anticoagulation. The lack of disturbance of normal haemostasis at the time of operation together with a significant reduction in deep vein thrombosis may encourage surgeons to introduce minidose prophylaxis with warfarin.

Adult↗

The relative bioavailability of levonorgestrel and ethinylestradiol when administered in tablet and capsule form.

The relative bioavailability of levonorgestrel (LNG) and ethinylestradiol (EE2) administered as a conventional tablet (150/30) or capsule has been assessed in a randomized two-period crossover study in 9 healthy volunteer women. Serum concentrations were monitored for 24h post-dosing. There was no significant difference in any of the pharmacokinetic parameters determined for either steroid. Hence the relative bioavailability is similar after tablet and capsule formulations.

Adolescent↗

Pharmacologic production of luteinized unruptured follicles by prostaglandin synthetase inhibitors.

Serial ultrasonic scans of follicular development were performed throughout 46 spontaneous cycles in 20 healthy female volunteers. Human chorionic gonadotropin was then given to induce follicle rupture on a particular day. Luteinized unruptured follicles (LUFs) were seen in 10.7% of untreated cycles. When prostaglandin synthetase inhibitor drugs were administered over the ovulatory period the incidence of LUF was greatly increased (to 50% with azapropazone and 100% with indomethacin). Serum estradiol concentrations and length of luteal phase were unaltered in LUF cycles. Progesterone concentrations were lower in the first half of the luteal phase if follicles remained unruptured.

Anti-Inflammatory Agents, Non-Steroidal↗

Ovarian follicular development in oral contraceptive cycles.

The cyclic changes in serum hormone concentrations, ovarian follicular development, uterine size, and endometrial appearance have been observed in 58 spontaneous ovulatory cycles and compared with 22 initial cycles of oral contraceptive (OC) therapy. A far greater inhibitory effect on the ovary was achieved by starting contraception on day 1 of the cycle rather than on day 5. The relevance of these findings with regard to OC failures is discussed.

Adult↗

Gonadotrophin responses to oestrogen provocation in women with minimal endometriosis.

The gonadotrophin responses to the negative and positive feedback effects of orally administered ethinyl oestradiol in 12 women with minimal endometriosis were compared with those in six normal women of proven fertility. Basal concentrations of LH, FSH and oestradiol did not differ between the two groups. LH and FSH concentration declined within 12-24 h of starting treatment and there was no difference between minimum values, which occurred in both groups after 12-48 h. In five women with minimal endometriosis, LH concentrations subsequently increased above basal values to maximum values indistinguishable in magnitude and timing from those in the control group. An exaggerated LH response to oestrogen positive feedback occurred in one subject. In the remaining six women LH concentrations increased above levels which could be attributed to episodic variation in basal LH secretion but maximum LH values were below control limits. There was no relationship between previously documented progesterone secretion nor LH concentrations during the early luteal phase of the cycle and the LH response to oestrogen positive feedback. These data suggest that minor abnormalities of hypothalamopituitary function may contribute to infertility associated with minimal endometriosis.

Adult↗

Comparison of the action of nonoxynol-9 and chlorhexidine on sperm.

The effect on sperm motility of nonoxynol-9 chlorhexidine diacetate was compared in semen and cervical mucus. Both compounds had similar spermicidal potency in semen, abolishing sperm motility within 3 minutes at 0.5 mg/ml. When these compounds were allowed to diffuse into mucus, the subsequent survival of sperm in the mucus was different. Restricted penetration and loss of motility occurred rapidly after treatment with 0.1 mg/ml chlorhexidine, whereas sperm survived normally in mucus after prolonged contact with 200 mg/ml chlorhexidine. When the compounds were mixed directly with the mucus before sperm penetration was attempted, chlorhexidine still immobilized sperm, but concentrations of nonoxynol-9 that would be spermicidal in semen had no effect in mucus.

Animals↗

Cyclical gonadotrophin and progesterone secretion in women with minimal endometriosis.

Concentrations of LH, FSH, oestradiol (E) and progesterone (P) were measured in serum of 12 women with minimal endometriosis and otherwise unexplained infertility. Values were compared with those on corresponding days relative to the pre-ovulatory LH peak (Day 0) in six fertile women. Three women exhibited cycle profiles of LH, FSH, E and P indistinguishable from those in the control group. In the remaining nine women cycle profiles for FSH and follicular phase profiles for LH were normal but eight exhibited a delay in P secretion and reduced total P output. LH concentrations were elevated during the early luteal phase in five subjects, two of whom had a second LH surge. These data suggest that luteal dysfunction and abnormal secretory patterns for LH may be contributory to infertility associated with endometriosis.

Adult↗

A comparison of prostaglandin E2 pessaries and laminaria tents for ripening the cervix before termination of pregnancy.

Forty primigravid women aged 15-45 years were randomly allocated to receive either an intravaginal pessary of 3 mg prostaglandin E2 (PGE2) or an intracervical 5-mm laminaria tent (LT) 12-16 h before termination of pregnancy at 6-14 weeks gestation. The degree of dilatation of the cervix at operation and its resistance to further dilatation during the procedure were assessed by a 'blind' operator. Laminaria tents were more effective in achieving dilatation and softening of the cervix than were PGE2 pessaries and in 40% of women no further dilatation was necessary. There were no associated side-effects or complications. A cervical tear occurred in two of 20 patients treated with PGE2 pessaries and all 20 required further dilatation of the cervix. Laminaria tents provide a simple, safe, acceptable and effective means of 'ripening' the cervix prior to termination of early pregnancy.

Abortion, Therapeutic↗

The progestagen releasing vaginal ring.

The results of the Manchester study and its reinforcement from data from the multicenter study indicate that the ring is a well-tolerated delivery system for low-dose progestagens. The expulsion rate is low and vaginal tolerance satisfactory. The pregnancy rate and bleeding pattern is of the same order as oral low-dose progestagens. Indeed, there is an indication that the pregnancy rate and abnormal bleeding rate may be even lower. Data from other more extensive phase 3 studies will be required to confirm this impression. The subjective assessment is that the majority of patients are enthusiastic about this method of contraception, bearing in mind that many of them had become disenchanted with existing marketed contraceptive methods. Because of its high level of acceptability, the gap between theoretical and use-effectiveness in narrowed and once inserted, a high degree of motivation is not required since the existing ring only needs to be reinserted after 90 days of use. The acceptability of vaginal methods of contraception as evidenced by the rapid uptake of the vaginal sponge suggests that there is considerable potential for increased use of vaginal methods. In the present state of knowledge, it would appear that the woman for whom the progestagen only conception is particularly appropriate is the one who is lactating or for the older woman whose fertility is on the wane. For the woman who wishes to space her family, the progestagen only contraceptive is also appropriate. With increased refinements and experience of this method, there is a likelihood that the ring may extend the use and application of progestagen only contraception to a wider range of potential patients.

Biology↗

Sperm survival studies in peritoneal fluid from infertile women with endometriosis and unexplained infertility.

Peritoneal fluid (PF) volume and sperm survival (motility and velocity) were studied in PF from women with unexplained infertility, infertile women with endometriosis and fertile women without endometriosis using a laser light scattering technique. PF volume was significantly larger in the group of women with unexplained infertility (P less than 0.025) and in infertile women with endometriosis (P less than 0.003) when compared with fertile women. There was a significant reduction in the percentage motile sperm in women with unexplained infertility (P less than 0.001) and in infertile women with endometriosis when compared with fertile women (P less than 0.001). In infertile women with endometriosis a positive correlation was observed between peritoneal fluid volume and reduction in the percentage of motile sperms (P less than 0.01).

Body Fluids↗

Effects of the anti-oestrogens, clomiphene and tamoxifen, on the cervical factor in female infertility.

The anti-oestrogens clomiphene and tamoxifen are successful therapeutic agents in the induction of ovulation but the associated pregnancy rates are low. One cause for this may be a direct anti-oestrogenic effect on cervical mucus, reducing its sperm penetrability. This potentially adverse effect has been shown to occur with clomiphene. In this study the effects of clomiphene and tamoxifen on the cervical factor are compared in women who were anovulatory or had defective ovulation. Forty fully investigated infertile women were randomly allocated to different treatment sequences after being observed for three control cycles. A double-blind placebo technique was used with four different treatment regimes. Serial serum progesterone and oestradiol were assayed. Cervical mucus from the periovulatory phase was assessed by means of the cervical score and in vitro sperm penetration tests. Both these anti-oestrogens can affect cervical mucus but their effect seems to be related more to the end-organ sensitivity of the individual than to a specific action of the drug per se.

Cervix Mucus↗

Degradation of the copper-releasing intrauterine contraceptive device and its significance.

Measurements were made of the copper remaining on used Gravigard intrauterine contraceptive devices (IUCDs) that had been in utero for up to 40 months. The topography and composition of the surface deposits were analysed by scanning electron microscopy and energy-dispersive X-ray analysis. The rate of copper loss decreased exponentially from 0.42 mumol d-1 (26.7 micrograms d-1) upon insertion to 0.056 mumol d-1 (3.6 micrograms d-1) after 26 months of use; between 27 and 40 months of use a linear release of 0.32 mumol d-1 (20.3 micrograms d-1) was observed. There was no correlation between this changing rate of copper loss and the pregnancy rate with the device in situ. The changes in the rate of copper loss were probably due to the growth of a surface corrosion product which, due to internal stresses, fractured after about 2 years and exposed fresh copper; this results in a progressive increase in breakage of the copper wire after 3 years. It is recommended that a copper IUCD of this type be replaced after 3 years.

Copper↗