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1.  Role of Androgen Receptor CAG Repeat Polymorphism Length in Hypothalamic Progesterone Sensitivity in Hyperandrogenic Adolescent Girls 
Endocrine  2011;41(1):156-158.
PMCID: PMC3253981  PMID: 22081303
androgen receptor; polycystic ovary syndrome; hyperandrogenemia; adolescence; gonadotropin-releasing hormone
2.  Extensive Genetic Diversity, Unique Population Structure and Evidence of Genetic Exchange in the Sexually Transmitted Parasite Trichomonas vaginalis 
Trichomonas vaginalis is the causative agent of human trichomoniasis, the most common non-viral sexually transmitted infection world-wide. Despite its prevalence, little is known about the genetic diversity and population structure of this haploid parasite due to the lack of appropriate tools. The development of a panel of microsatellite makers and SNPs from mining the parasite's genome sequence has paved the way to a global analysis of the genetic structure of the pathogen and association with clinical phenotypes.
Methodology/Principal Findings
Here we utilize a panel of T. vaginalis-specific genetic markers to genotype 235 isolates from Mexico, Chile, India, Australia, Papua New Guinea, Italy, Africa and the United States, including 19 clinical isolates recently collected from 270 women attending New York City sexually transmitted disease clinics. Using population genetic analysis, we show that T. vaginalis is a genetically diverse parasite with a unique population structure consisting of two types present in equal proportions world-wide. Parasites belonging to the two types (type 1 and type 2) differ significantly in the rate at which they harbor the T. vaginalis virus, a dsRNA virus implicated in parasite pathogenesis, and in their sensitivity to the widely-used drug, metronidazole. We also uncover evidence of genetic exchange, indicating a sexual life-cycle of the parasite despite an absence of morphologically-distinct sexual stages.
Our study represents the first robust and comprehensive evaluation of global T. vaginalis genetic diversity and population structure. Our identification of a unique two-type structure, and the clinically relevant phenotypes associated with them, provides a new dimension for understanding T. vaginalis pathogenesis. In addition, our demonstration of the possibility of genetic exchange in the parasite has important implications for genetic research and control of the disease.
Author Summary
The human parasite Trichomonas vaginalis causes trichomoniasis, the world's most common non-viral sexually transmitted infection. Research on T. vaginalis genetic diversity has been limited by a lack of appropriate genotyping tools. To address this problem, we recently published a panel of T. vaginalis-specific genetic markers; here we use these markers to genotype isolates collected from ten regions around the globe. We detect high levels of genetic diversity, infer a two-type population structure, identify clinically relevant differences between the two types, and uncover evidence of genetic exchange in what was believed to be a clonal organism. Together, these results greatly improve our understanding of the population genetics of T. vaginalis and provide insights into the possibility of genetic exchange in the parasite, with implications for the epidemiology and control of the disease. By taking into account the existence of different types and their unique characteristics, we can improve understanding of the wide range of symptoms that patients manifest and better implement appropriate drug treatment. In addition, by recognizing the possibility of genetic exchange, we are more equipped to address the growing concern of drug resistance and the mechanisms by which it may spread within parasite populations.
PMCID: PMC3313929  PMID: 22479659
3.  Hyperandrogenemia in adolescent girls: origins of abnormal GnRH secretion 
Polycystic ovarian syndrome is a common disorder characterized by ovulatory dysfunction and hyperandrogenemia (HA). Its origins begin peripubertally, as adolescent HA commonly leads to adult HA and decreased fertility. HA reduces inhibition of gonadotropin releasing hormone pulse frequency by progesterone, causing rapid LH pulse secretion and further increasing ovarian androgen production. Obese girls are at risk for HA and develop increased LH pulse frequency with elevated mean LH by late puberty. Many girls with HA do not exhibit normal LH pulse sensitivity to progesterone inhibition. Thus, HA may adversely affect LH pulse regulation during pubertal maturation leading to persistent HA.
PMCID: PMC2994606  PMID: 20002394
polycystic ovarian syndrome; gonadotropin releasing hormone; GnRH pulse generator; obesity; puberty; hyperandrogenemia; adolescent
4.  Estradiol and progesterone-induced slowing of gonadotropin-releasing hormone pulse frequency is not reversed by subsequent administration of mifepristone 
Endocrine  2009;36(2):239-245.
Following suppression of LH (GnRH) pulse frequency by progesterone (P) and estradiol (E2), LH pulse frequency remains slow for 7 days after P withdrawal if mid-luteal E2 concentrations are maintained. This may reflect an ability of E2 to potentiate the suppressive effects of low P levels. We explored this notion in a similar experimental paradigm by administering a P-receptor antagonist (mifepristone) after P withdrawal while continuing E2. Studies were performed in seven ovulatory, non-obese women. Transdermal E2 (0.2 mg/day) and oral micronized P (100 mg every 8 hours) were started within 24 hours of the LH surge and continued for 10 days. Subjects then underwent a 13-hour blood sampling protocol for determination of LH pulse characteristics and various hormone concentrations. Oral P was then discontinued, and oral mifepristone (50, 100, or 200 mg daily) and transdermal E2 (0.2 mg/day) were administered for 7 days, after which the above sampling protocol was repeated. Results with all mifepristone doses were similar and therefore pooled. Mean LH, LH amplitude, and mean FSH markedly decreased after 7 days of mifepristone, but LH pulse frequency did not change (3.3 ± 1.5 vs. 2.4 ± 1.5 pulses/13 hours). Prolactin and androstenedione increased between the first and second admissions, with no changes in E2, cortisol, testosterone, or DHEAS. In conclusion, blockade of P action by mifepristone does not reverse a suppressed LH pulse frequency within 7 days when E2 concentrations are maintained, suggesting that P withdrawal alone may not explain the luteal-follicular increase of GnRH pulse frequency.
PMCID: PMC2758640  PMID: 19609733
gonadotropin-releasing hormone; luteinizing hormone; progesterone; mifepristone; estradiol; luteal-follicular transition
5.  Monitoring Temporal Changes in the Specificity of an Oral HIV Test: A Novel Application for Use in Postmarketing Surveillance 
PLoS ONE  2010;5(8):e12231.
Postmarketing surveillance is routinely conducted to monitor performance of pharmaceuticals and testing devices in the marketplace. However, these surveillance methods are often done retrospectively and, as a result, are not designed to detect issues with performance in real-time.
Methods and Findings
Using HIV antibody screening test data from New York City STD clinics, we developed a formal, statistical method of prospectively detecting temporal clusters of poor performance of a screening test. From 2005 to 2008, New York City, as well as other states, observed unexpectedly high false-positive (FP) rates in an oral fluid-based rapid test used for screening HIV. We attempted to formally assess whether the performance of this HIV screening test statistically deviated from both local expectation and the manufacturer's claim for the test. Results indicate that there were two significant temporal clusters in the FP rate of the oral HIV test, both of which exceeded the manufacturer's upper limit of the 95% CI for the product. Furthermore, the FP rate of the test varied significantly by both STD clinic and test lot, though not by test operator.
Continuous monitoring of surveillance data has the benefit of providing information regarding test performance, and if conducted in real-time, it can enable programs to examine reasons for poor test performance in close proximity to the occurrence. Techniques used in this study could be a valuable addition for postmarketing surveillance of test performance and may become particularly important with the increase in rapid testing methods.
PMCID: PMC2928264  PMID: 20811502
6.  Obesity and Sex Steroid Changes Across Puberty: Evidence for Marked Hyperandrogenemia in Pre- and Early Pubertal Obese Girls* 
Peripubertal obesity is associated with abnormal sex steroid concentrations, but the timing of onset and degree of these abnormalities remain unclear.
To assess the degree of hyperandrogenemia across puberty in obese girls, and to assess overnight sex steroid changes in Tanner 1–3 girls.
Cross-sectional analysis.
General Clinical Research Centers.
Thirty normal weight (BMI-for-age < 85%) and 74 obese (BMI-for-age ≥ 95%) peripubertal girls.
Blood samples (circa 0500–0700 h) while fasting. Samples from the preceding evening (circa 2300 h) were obtained in 23 Tanner 1–3 girls.
Main outcome measures
Hormone concentrations stratified by Tanner stage.
Compared to normal weight girls, mean free testosterone (T) was elevated 2- to 9-fold across puberty in obese girls, while fasting insulin was 3-fold elevated in obese Tanner 1–3 girls (P < 0.05). Mean LH was lower in obese Tanner 1 and 2 girls (P < 0.05), but not in more mature girls. In a subgroup of normal weight Tanner 1–3 girls (n = 17), mean progesterone (P) and T increased overnight 2.3- and 2.4-fold, respectively (P ≤ 0.001). In obese Tanner 1–3 girls (n = 6), evening P and T were elevated, and both tended to increase overnight (mean 1.4- and 1.6-fold, respectively [P = 0.06]).
Peripubertal obesity is associated with hyperandrogenemia and hyperinsulinemia throughout puberty, being especially marked shortly before and during early puberty. Progesterone and testosterone concentrations in normal weight Tanner 1–3 girls increase overnight, with similar but less evident changes in obese girls.
PMCID: PMC2196134  PMID: 17118995
hyperandrogenemia; testosterone; progesterone; estradiol; PCOS; puberty; adolescence; obesity; adiposity; overweight; hyperinsulinemia; insulin; LH
7.  An Ounce of Prevention is a Ton of Work: Mass Antibiotic Prophylaxis for Anthrax, New York City, 2001 
Emerging Infectious Diseases  2003;9(6):615-622.
Protocols for mass antibiotic prophylaxis against anthrax were under development in New York City beginning in early 1999. This groundwork allowed the city’s Department of Health to rapidly respond in 2001 to six situations in which cases were identified or anthrax spores were found. The key aspects of planning and lessons learned from each of these mass prophylaxis operations are reviewed. Antibiotic distribution was facilitated by limiting medical histories to issues relevant to prescribing prophylactic antibiotic therapy, formatting medical records to facilitate rapid decision making, and separating each component activity into discrete work stations. Successful implementation of mass prophylaxis operations was characterized by clarity of mission and eligibility criteria, well-defined lines of authority and responsibilities, effective communication, collaboration among city agencies (including law enforcement), and coordination of staffing and supplies. This model can be adapted for future planning needs including possible attacks with other bioterrorism agents, such as smallpox.
PMCID: PMC3000161  PMID: 12780998
anthrax prophylaxis; bioterrorism; public health response; policy review

Results 1-7 (7)