Triage practices in stroke units: Physicians' perceptions and ethical issues.

OBJECTIVE: We aimed to explore acute stroke admission decisions and to discuss ethical issues in triage practices in stroke units (SUs) in France. METHODS: In this study, 337 questionnaires were sent to physicians involved in acute admission to SUs in Île-de-France (neurologists and physicians from emergency medical services). The questionnaires comprised questions about physicians' perceptions of the reasonable allocation of SU beds and admission criteria for patients in SU in clinical vignettes illustrating complex situations. RESULTS: In total, 162 questionnaires were fully completed. There were some discrepancies in perceptions and reporting practices between emergency physicians and neurologists concerning patient admission criteria. Triage choices were more frequently declared by emergency physicians than by neurologists and were related to the difficulty of obtaining a positive response for the admission of certain complex patients (particularly those with comorbidities). CONCLUSIONS: Despite recommendations stating that all patients with stroke should be admitted to SUs, this study has shown that triage practices exist in stroke admission decisions. The triage depends on the role and perceptions of each physician in acute stroke management. These decisions suggest reflections on the applicability of distributive justice theories and on ethical issues in triage practices in medicine.

Effect of gonadotrophin-releasing hormone (GnRH) antagonist during the LH surge in normal women and during controlled ovarian hyperstimulation.

OBJECTIVE: Several studies have suggested that GnRH is instrumental in triggering the LH surge. The present studies were performed to evaluate the effect of GnRH antagonist administration in women after the beginning of the LH surge. DESIGN: In study one, six normal cycling women were given a GnRH antagonist (20 mg Nal Glu s.c.) during an unstimulated cycle. Nal-Glu was administered when the LH level was higher than 10 U/l and associated with an oestradiol (E2) level higher than 730 pmol/l. In study two, a GnRH antagonist (3 mg Cetrorelix, ASTA-Medica, Frankfurt, Germany) was administered on day 8 of an IVF-ET cycle, in 157 women. Eighteen women among this cohort received the antagonist, when their LH level was higher than 10 U/l. RESULTS: In normal volunteers (study one), Nal-Glu was administered on day 13.7 +/- 1.4 (mean +/- SD) of the cycle when the LH level was 13.7 +/- 3.5 U/l with an E2 plasma level reaching 980 +/- 131 pmol/l. Twenty-four hours after administration of the antagonist, the LH surge had been interrupted in all subjects; it was postponed in three of the women, and abolished in the remaining three. LH levels fell by 68.5%, E2 by 42% and FSH by 53.2%. In study two, LH plasma levels 24 h after the antagonist administration fell by 94%. No premature ovulation occurred in any of the patients treated. Administering the antagonist before (n = 139) or during the LH surge (n = 18) made no statistically significant difference to the results of the IVF-ET attempt. CONCLUSIONS: Our results indicate that GnRH is required throughout the gonadotrophin surge in women, not only for the initiation but also for the maintenance of the LH surge. In addition, in our study, the suppression of the rise in LH, when the antagonist was given during the surge, had no detrimental impact on IVF-ET outcome. This suggests, if confirmed on a larger scale, that late follicular phase GnRH antagonist administration to prevent the LH surge in controlled ovarian hyperstimulation (COH) is a safe and useful treatment.

Effect of administration of a gonadotropin-releasing hormone (GnRH) antagonist (Nal-Glu) during the periovulatory period: the luteinizing hormone surge requires secretion of GnRH.

In primates, the LH surge that triggers ovulation is induced by an increase in circulating estradiol (E2) levels. Although several studies suggest that E2 acts on the pituitary, it is still not clear whether GnRH is involved. We investigated the role of GnRH during the periovulatory period in normal women by treating them with the GnRH antagonist Nal-Glu ([Ac-D2Nal1,D4-ClPhe2,D3Pal3,Arg5,DGlu6 (AA),DAla10] when E2 levels exceeded 550 pmol/L. In the first study (A), Nal-Glu was administered in five regimens (n = 4 in each group): a single sc injection of 10 mg (group 1), a single injection of 20 mg (group 2), and an injection of 10 mg, sc, on 2 (group 3), 3 (group 4), and 5 consecutive days (group 5). In the second study (B; n = 4), Nal-Glu (10 mg, sc, on 3 consecutive days) was coadministered with E2 benzoate (EB; 0.5 mg, im, every 12 h on 3 consecutive days). Controls (n = 4) were treated with EB alone at the same stage of the cycle. In the third study (C), three women received 10 mg/day Nal-Glu, sc, on 3 consecutive days together with pulsatile GnRH therapy (25 micrograms/pulse, one pulse every 90 min, sc, for 3 days); the first pulse was given 12 h after the first Nal-Glu injection. In study A, gonadotropin suppression resulted in a transient decline in E2 in groups 1 and 2. Relative to control cycles, the LH surge occurred with a delay of 24-48 h in group 1 and 24-120 h in group 2. In groups 3, 4, and 5, Nal-Glu administration resulted in the demise of the dominant follicle in half of the women in each group. The remaining women showed a profile similar to that of groups 1 and 2, i.e. a transient decline in E2 levels followed by a recovery, and a LH surge occurring 4 +/- 0.3 days after the last Nal-Glu injection. In study B, simultaneous administration of Nal-Glu and EB induced a rise in E2 levels from 951.3 +/- 79.6 to 4000.1 +/- 772.5 pmol/L 24 h after the beginning of treatment. Serum LH and FSH levels both decreased and remained low throughout Nal-Glu treatment. None of the women showed a LH rise in response to the EB injection. In controls, however, EB administration was followed by a significant gonadotropin discharge 48 h after the first EB injection.(ABSTRACT TRUNCATED AT 400 WORDS)

The combination of gonadotrophin-releasing hormone (GnRH) antagonist and pulsatile GnRH normalizes luteinizing hormone secretion in polycystic ovarian disease but fails to induce follicular maturation.

To evaluate the role of altered luteinizing hormone (LH) release in the mechanism of polycystic ovarian disease (PCOD) anovulation, we have co-administered a gonadotrophin-releasing hormone (GnRH) antagonist and pulsatile GnRH therapy to two clomiphene citrate-resistant PCOD patients. The aim was to correct their inappropriate gonadotrophin secretion. Nal-Glu was administered s.c. every 72 h to both subjects for 3 weeks. On day 7 after commencing the study, intravenous pulsatile GnRH therapy was initiated (10 micrograms/pulse) every 90 min for 15 days to both subjects. In one subject, Nal-Glu treatment was continued and the GnRH dose was increased to 20 micrograms/pulse for 10 additional days. Prior to Nal-Glu, mean serum LH levels were 10.4 +/- 1.6 and 9.3 +/- 1.3 mIU/ml (mean +/- SEM) and mean interpulse intervals were 67.1 and 60 min in patients 1 and 2, respectively. Mean serum FSH levels were 4.9 +/- 0.4 and 4.2 +/- 0.2 mIU/ml for patients 1 and 2, respectively. LH pulsatility was abolished following Nal-Glu, mean serum LH decreased to 1.1 +/- 0.1 and 1.3 +/- 0.5 mIU/ml and mean FSH to 1.8 +/- 0.1 and 2 +/- 0.1 mIU/ml in the two subjects. On the 4th day of the combined therapy, mean serum LH increased to 5.4 +/- 1.3 and 3.9 +/- 0.9 mIU/ml with a mean interpulse interval of 72 and 80 min, respectively. Mean FSH levels increased to 3 +/- 0.1 and 2.8 +/- 0.1 mIU/ml, respectively and to 5.5 +/- 0.2 mIU/ml after the GnRH dose was increased in patient 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Suppression of corpus luteum function by the gonadotropin-releasing hormone antagonist Nal-Glu: effect of the dose and timing of human chorionic gonadotropin administration.

OBJECTIVE: To assess the effect of gonadotropin-releasing hormone antagonist Nal-Glu administration in the luteal phase and the potential rescue by exogenous human chorionic gonadotropin (hCG) of corpus luteum (CL) after antagonist treatment. DESIGN: We studied the dose of Nal-Glu required for luteolysis and subsequently we coadministered low doses of hCG for 3 consecutive days either simultaneously to Nal-Glu administration (n = 5), or 48 (n = 5), or 72 hours (n = 5) later. Six additional participants received pharmacological doses of hCG 48 hours after the luteolytic dose of Nal-Glu. SETTING: Participants were studied in Clinique Endocrinologique, Nantes, and in Service d'Endocrinologie, Hôpital Bicêtre, Le Kremlin Bicetre, France. PARTICIPANTS: Twenty-nine normal young women (ages 20 to 35) were studied. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Measurements of follicle-stimulating hormone, luteinizing hormone (LH), estradiol, Progesterone (P) levels were performed by radioimmunoassay before, during, and after the various treatment regimens. RESULTS: Complete luteolysis occurred in women who received 10 mg of Nal-Glu daily on days 4 and 5 after the LH surge. The coadministration of Nal-Glu and hCG overrode the effect of the antagonist (P = 48.8 +/- 22.5 versus 60.8 +/- 3.1 nmol/L in controls treated with hCG alone [NS]). When hCG treatment was started 48 hours after Nal-Glu, a partial luteolysis occurred (P = 33.8 +/- 10.9 versus 117 +/- 12.9 nmol/L, P less than 0.01). When hCG was started 72 hours after Nal-Glu, a complete luteolysis occurred (P = 5.8 +/- 2.05 versus 36.2 +/- 0.6 nmol/L, P less than 0.01). Higher doses of hCG (1,500 or 5,000 IU) administered 72 hours after Nal-Glu resulted in a significant rescue of CL function (P = 37.7 +/- 4.8 and P = 43.8 +/- 22.2 versus 74.5 +/- 19.8 and 130.2 +/- 14.3 nmol/L, P less than 0.05), respectively. CONCLUSIONS: These results confirm the LH dependence of CL function. The suppression of CL LH support for 72 hours induced a compromise of the CL nonreversible by low doses of hCG mimicking early pregnancy but reversible with pharmacological doses.

PIP: Researchers studied 29 women 20-35 years old at endocrinology clinics in Nantes and Kremlin Bicetre, France to determine if administering human chorionic gonadotropin (hCG) in addition to the pulsatile gonadotropin releasing hormone antagonist called Nal-Glu would rescue corpus luteum (CL) function. The study consisted of 3 parts: single and repeated administration of Nal-Glu; administration of Nal-Glu and low doses of hCG; and administration of Nal-Glu and pharmacological doses and hCG. The results showed that suppressing the release of luteinizing hormone (LH) for at least 3 days caused luteolysis, but small doses of exogenous hCG did not rescue CL function. On the other hand, if suppression lasted only 2 days, small doses of hCG partially rescued CL function. Nevertheless most participants who experienced suppression for at least 3 days had a spontaneous recovery of CL function, perhaps because suppression did not persist long enough to cause complete luteolysis. 2 injections of Nal-Glu on days 4-5 of the luteal phase did, however, suppress LH support for 72 hours thereby inducing complete luteolysis. 1 woman did not experience complete luteolysis though. Higher doses of hCG did rescue CL function, albeit incompletely. In conclusion, Nal-Glu administration progressively damages CL dose of hcg which maintains CL function may be reached if implantation occurs within 3 days after administration of the antagonist. Therefore it is questionable if hCG can be used as a postcoital contraception.