Placental Transport of Zidovudine in the Rhesus Monkey

Objective: This study was undertaken to characterize the pharmacokinetics of zidovudine (ZDV) and ZDV-glucuronide (ZDVG) in the material and :fetal circulations of the rhesus monkey

Mediator Kinase Disruption in MED12-Mutant Uterine Fibroids From Hispanic Women of South Texas

Context: Mutations in the gene encoding Mediator complex subunit MED12 are dominant drivers of uterine fibroids (UFs) in women of diverse racial and ethnic origins. Previously, we showed that UF-linked mutations in MED12 disrupt its ability to activate cyclin C-CDK8/19 in Mediator. However, validation of Mediator kinase disruption in the clinically relevant setting of MED12-mutant UFs is currently lacking. Objective: The objective of this study was twofold. First, to extend the ethnic distribution profile of MED12 mutations by establishing their frequency in UFs from Hispanic women of South Texas. Second, to examine the impact of MED12 mutations on Mediator kinase activity in patient-derived UFs. Methods: We screened 219 UFs from 76 women, including 170 tumors from 57 Hispanic patients, for MED12 exon 2 mutations, and further examined CDK8/19 activity in Mediator complexes immunoprecipitated from MED12 mutation-negative and MED12 mutation-positive UFs. Results: MED12 exon 2 mutations in UFs from Hispanic women are somatic in nature, predominantly monoallelic, and occur at high frequency (54.1%). We identified a minimal cyclin C-CDK8 activation domain on MED12 spanning amino acids 15 through 80 that includes all recorded UF-linked mutations in MED12, suggesting that disruption of Mediator kinase activity is a principal biochemical defect arising from these pathogenic alterations. Analysis of Mediator complexes recovered from patient UFs confirmed this, revealing that Mediator kinase activity is selectively impaired in MED12-mutant UFs. Conclusions: MED12 mutations are important drivers of UF formation in Hispanic women of South Texas. MED12 mutations disrupt Mediator kinase activity, implicating altered CDK8/19 function in UF pathogenesis.Peer reviewe

Unilateral Labial Hypertrophy in Adolescents: when should we Interfere? Two Case Reports

Synopsis: Adolescent and pre-menarchal patients with symptomatic unilateral labial hypertrophy should be counselled extensively prior to surgical management regarding risks of recurrence or contralateral occurrence. Purpose: Present the management of two unique cases of adolescent girls with unilateral labial hypertrophy. Case 1: 9 year-old pre-menarchal patient with a five-month history of unilateral labial hypertrophy causing discomfort that limited daily activities. External pelvic examination revealed grossly asymmetric labia minora. The left labia minora measured 5 cm in length. After counseling, the patient underwent unilateral labioplasty with resolution of symptoms. Patient returned after two years complaining of contralateral labial hypertrophy.The patient again underwent surgical management due to discomfort and interference with normal daily activities. Case 2: 12 year-old post-menarchal patient with a history of unilateral labial hypertrophy causing irritation and discomfort starting prior to menarche. External pelvic exam revealed grossly asymmetric labia minora. The right labia minora measured 4.5cm in length. The patient underwent unilateral labioplasty with resolution of her symptoms. After 2 years of follow up, patient remained asymptomatic. Conclusion: Adolescence unilateral labial hypertrophy may represent a normal variant and surgery should be delayed until achieving full puberty. However, when it causes significant discomfort or interferes with normal daily activities, surgical management should be considered after counseling regarding recurrence or contralateral occurrence

Risk of cardiovascular disease among postmenopausal women with prior pregnancy loss: the women's health initiative.

PurposeMetabolic, hormonal, and hemostatic changes associated with pregnancy loss (stillbirth and miscarriage) may contribute to the development of cardiovascular disease (CVD) in adulthood. This study evaluated prospectively the association between a history of pregnancy loss and CVD in a cohort of postmenopausal women.MethodsPostmenopausal women (77,701) were evaluated from 1993-1998. Information on baseline reproductive history, sociodemographic, and CVD risk factors were collected. The associations between 1 or 2 or more miscarriages and 1 or more stillbirths with occurrence of CVD were evaluated using multiple logistic regression.ResultsAmong 77,701 women in the study sample, 23,538 (30.3%) reported a history of miscarriage; 1,670 (2.2%) reported a history of stillbirth; and 1,673 (2.2%) reported a history of both miscarriage and stillbirth. Multivariable-adjusted odds ratio (OR) for coronary heart disease (CHD) for 1 or more stillbirths was 1.27 (95% CI, 1.07-1.51) compared with no stillbirth; for women with a history of 1 miscarriage, the OR=1.19 (95% CI, 1.08-1.32); and for 2 or more miscarriages the OR=1.18 (95% CI, 1.04-1.34) compared with no miscarriage. For ischemic stroke, the multivariable odds ratio for stillbirths and miscarriages was not significant.ConclusionsPregnancy loss was associated with CHD but not ischemic stroke. Women with a history of 1 or more stillbirths or 1 or more miscarriages appear to be at increased risk of future CVD and should be considered candidates for closer surveillance and/or early intervention; research is needed into better understanding the pathophysiologic mechanisms behind the increased risk of CVD associated with pregnancy loss