A dose-finding, cross-over study to evaluate the effect of a Nestorone®/Estradiol transdermal gel delivery on ovulation suppression in normal ovulating women.

OBJECTIVE: This study aims to determine the lowest effective of three Nestorone (NES)/estradiol (E2) transdermal gel doses to ensure ovulation suppression in 90-95% of cycles. METHODS: This was a randomized, open-label, three-treatment-period cross-over study to evaluate the effects of NES/E2 transdermal gel on ovulation inhibition, suppression of follicular growth and pharmacokinetic parameters. The doses were low (1.5 mg NES/0.5 mg E2), medium (3.0 mg NES/1.0 mg E2) and high (4.5 mg NES/1.5 mg E2). Participants applied gel daily to a fixed area on the abdomen for 21 consecutive days. They were interviewed regarding their experiences using the gel. RESULTS: Eighteen participants were randomized; 16 completed the study. Median NES C(max) values for low, medium and high dose groups at day 21 were 318.6 pmol/L, 783.0 pmol/L and 1063.8 pmol/L, respectively. Median maximum follicular diameter was higher with the lowest dose with 16.2 mm versus 10.0 and 10.4 mm with the medium and high doses, respectively. Among adherent participants, ovulation was inhibited in all dose groups, except for one participant in the medium dose (6.7%) that had luteal activity and an ultrasound image suggestive of a luteinized unruptured follicle. There were few reports of unscheduled bleeding, with more episodes reported for the lower dose. Adverse events were mild, and no skin irritation was reported from gel application. CONCLUSION: While all three doses blocked ovulation effectively and were evaluated as safe and acceptable, the medium dose was considered the lowest effective dose based on a more adequate suppression of follicular development. Further development of this novel contraceptive delivering NES and E2 is warranted and has potential for improved safety compared to ethinyl-estradiol-based methods.

Vaginal myofibroblastoma with prostatic glands: is there an association with tamoxifen use? A case report.

BACKGROUND: Both ectopic prostate tissue in the female genital tract and vaginal myofibroblastoma have rarely been reported in the literature. Tamoxifen use has been associated with the development of vaginal myofibroblastoma. CASE: A 76-year-old, multiparous woman who had taken tamoxifen for breast cancer presented with postmenopausal bleeding and a vaginal mass. Endometrial work-up revealed a benign polyp, and the polypoid tumor in the vagina was found to be a myofibroblastoma harboring ectopic prostatic glands. CONCLUSION: To our knowledge this is the first case of these two rare pathologic entities occurring together. Of note, this patient also had a history of tamoxifen therapy, like some of the previous patients with vaginal myofibroblastoma.

Examining the vector-host-pathogen interface with quantitative molecular tools.

We developed PCR assays to detect and quantitate Yersinia pestis, the bacterial agent of plague, in flea vector and mammalian host tissues. Bacterial numbers in fleas, fleabite sites, and infected lymph nodes were determined using real-time PCR with primers and probes for a gene target on a multi-copy plasmid specific to Y. pestis. Tissue-matched standard curves used to determine absolute bacterial numbers in unknown samples were linear over at least five orders of magnitude. The methods were applied to studies of transmission of Y. pestis by the rat flea Xenopsylla cheopis, but should be generally useful to investigate the transmission dynamics of any arthropod-borne disease.

Poor vector competence of fleas and the evolution of hypervirulence in Yersinia pestis.

Population genetics and comparative genomics analyses of the pathogenic Yersinia species have indicated that arthropodborne transmission is an evolutionarily recent adaptation in Yersinia pestis, the agent of plague. We show that the infectivity of Y. pestis to its most proficient vector, the rat flea Xenopsylla cheopis, and subsequent transmission efficiency are both low. The poor vector competence of fleas likely imposed selective pressure that favored the emergence and continued maintenance of a hypervirulent Y. pestis clone. In particular, the rapidly fatal gram-negative sepsis that typifies plague is a consequence of the high threshold bacteremia level that must be attained to complete the transmission cycle. Epidemiological modeling predicts that, to compensate for a relatively short period of infectivity of the mammalian host for the arthropod vector, plague epizootics require a high flea burden per host, even when the susceptible host population density is high.