Influence of sodium valproate on late follicular phase pulsatile LH secretion in normal women

OBJECTIVE: The present study was designed to further assess the mechanism of action of GnRH and GnRH analogues. DESIGN AND PATIENTS: Both the Nal-Glu GnRH antagonist and the D-Trp6 GnRH agonist were administered sequentially to nine normal, post-menopausal women. MEASUREMENTS: A baseline study of pulsatile LH, FSH and free alpha-subunit secretion was performed, with sampling every 10 min for 8 h, and then repeated 8 h after a single subcutaneous injection of Nal-Glu GnRH antagonist (5 mg). Sampling was repeated 21 days after the intramuscular injection of a depot preparation of D-Trp6 GnRH (3.75 mg) in the same women. RESULTS: The baseline sampling period showed synchronous pulses of LH and free alpha-subunit. The antagonist Nal-Glu decreased plasma LH (71%) and free alpha-subunit (43%). However, with the single dose of 5 mg, pulsatile LH and free alpha-subunit release were not completely suppressed and remained temporally correlated. The GnRH agonist had a potent inhibitory action on plasma immunoreactive LH (IRMA) (93%). In contrast, it increased the mean plasma levels of free alpha-subunit from 1.66 +/- 0.01 to 5.06 +/- 0.02 micrograms/l (205%). The pulsatile secretory patterns of both LH and free alpha-subunit were abolished by the agonist. Immunoreactive FSH levels were decreased by the antagonist (24%) and suppressed by the agonist (93%). CONCLUSIONS: The pulsatile study confirms the different mechanism of action of GnRH analogues. Following antagonist administration, low amplitude free alpha-subunit pulses persist and are synchronous with residual LH pulses. In contrast, LH and free alpha-subunit are not maintained under agonist treatment. These data provide evidence for the differential regulation of LH and free alpha-subunit by GnRH.     

Temporal changes in geographic disparities in access to emergency heart attack and stroke care: are we any better today?

The objective of this study was to investigate temporal changes in geographic access to emergency heart attack and stroke care. Network analysis was used to compute travel time to the nearest emergency room (ER), cardiac, and stroke centers in Middle Tennessee. Populations within 30, 60, and 90 min driving time to the nearest ER, cardiac and stroke centers were identified. There were improvements in timely access to cardiac and stroke centers over the study period (1999-2010). There were significant (p<0.0001) increases in the proportion of the population with access to cardiac centers within 30 min from 29.4% (1999) to 62.4% (2009) while that for stroke changed from 5.4% (2004) to 46.1% (2010). Most (96%) of the population had access to an ER within 30 min from 1999 to 2010. Access to care has improved in the last decade but more still needs to be done to address disparities in rural communities.