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1.  The Role of Oxidative Stress in the Developmental Origin of Adult Hypertension 
American journal of obstetrics and gynecology  2011;205(2):155.e7-155.e11.
To determine whether oxidative stress plays a role in the development of hypertension using a mouse model of fetal programming induced by endothelial nitric oxide synthase (NOS3) deficiency
Study design
Homozygous NOS3 knockout and wild type (WT) mice were cross-bred producing maternal (NOS3+pat/-mat) and paternal (NOS3+mat/-pat) heterozygous offspring. RNA from liver and kidney tissues of female pups were obtained at 14 weeks of age. Relative expression of the heat shock protein-B6 (HspB6), Peroxiredoxin-3 (PeriRedox), superoxide dismutase-1 (SOD-1), Peroxisome proliferator-activated receptor gamma (PPAR-γ), nitric oxide synthase-1 (NOS1) and 2 (NOS2) were determined.
In the kidneys, expression of NOS2, PeriRedox, HspB6 and SOD-1 was upregulated in NOS3+pat/-mat but not in NOS3+mat/-pat compared to WT offspring. In the liver, there were no significant differences in the expression of NOS1, NOS2, PeriRedox, SOD-1, or PPAR-γ; however, HspB6 was downregulated in both heterozygotes offspring compared with WT.
The intrauterine environment alters oxidative pathways gene expression in the kidneys of offspring, which may be a mechanism in the development of adult hypertension.
PMCID: PMC3202020  PMID: 21531372
Fetal programming; oxidative stress; gene expression
2.  Transgenerational Effect of Fetal Programming on Vascular Phenotype and Reactivity in Nitric Oxide Knockout Mouse Model 
To investigate the transgenerational effect of fetal vascular programming
Homozygous NOS3 knockout and wild type controls (NOS3+/+WT) were cross-bred to obtain heterozygous offspring that developed in (KO−/−) mothers lacking a functional NOS3 (KOM) versus wild-type control mothers (KOP). The first generation (F1) KOM(+/−) and KOP(+/−) female mice were then bred with WT(+/+) males to obtain a second generation (F2). F2 offspring were genotyped and WT(+/+)-F2 mice were then used for in vivo blood pressure and in-vitro vascular reactivity studies.
WT-F2 mice born to KOM mothers (KOM-F2WT) had significantly higher systolic BP, mean arterial and pulse pressure compared to WT-F2 born to KOP mothers. Male KOM-F2WT offspring had significantly increased response to phenylephrine (PE) compared with male KOP-F2WT. Male offspring had increased contractile responses to PE when compared to female. Acetylcholine responses were decreased in female KOM-F2WT compared with female KOP-F2WT, but the difference was not statistically significant
Our findings support a transgenerational effect of fetal programming on the vascular phenotype, and suggest possible gender specific adaptation
PMCID: PMC2796619  PMID: 18771972
Fetal programming; vascular phenotype; transgenerational
3.  Prospective randomized trial of iliohypogastric-ilioinguinal nerve block on post-operative morphine use after inpatient surgery of the female reproductive tract 
To determine the impact of pre-operative and intra-operative ilioinguinal and iliohypogastric nerve block on post-operative analgesic utilization and length of stay (LOS).
We conducted a prospective randomized double-blind placebo controlled trial to assess effectiveness of ilioinguinal-iliohypogastric nerve block (IINB) on post-operative morphine consumption in female study patients (n = 60). Patients undergoing laparotomy via Pfannenstiel incision received injection of either 0.5% bupivacaine + 5 mcg/ml epinephrine for IINB (Group I, n = 28) or saline of equivalent volume given to the same site (Group II, n = 32). All injections were placed before the skin incision and after closure of rectus fascia via direct infiltration. Measured outcomes were post-operative morphine consumption (and associated side-effects), visual analogue pain scores, and hospital length of stay (LOS).
No difference in morphine use was observed between the two groups (47.3 mg in Group I vs. 45.9 mg in Group II; p = 0.85). There was a trend toward lower pain scores after surgery in Group I, but this was not statistically significant. The mean time to initiate oral narcotics was also similar, 23.3 h in Group I and 22.8 h in Group II (p = 0.7). LOS was somewhat shorter in Group I compared to Group II, but this difference was not statistically significant (p = 0.8). Side-effects occurred with similar frequency in both study groups.
In this population of patients undergoing inpatient surgery of the female reproductive tract, utilization of post-operative narcotics was not significantly influenced by IINB. Pain scores and LOS were also apparently unaffected by IINB, indicating a need for additional properly controlled prospective studies to identify alternative methods to optimize post-surgical pain management and reduce LOS.
PMCID: PMC2621114  PMID: 19040739
4.  Successful obstetrical management of 110-day intertwin delivery interval without cerclage: counseling and conservative management approach to extreme asynchronous twin birth 
This report describes a patient counseling approach and non-surgical management of a dichorionic-diamniotic twin pregnancy where delivery of the second twin followed the delivery of the first by 110 days.
Case presentation
An early transvaginal sonogram at 19 1/2 weeks suggested cervical dilation with protruding amniotic membranes. Tocolytic and antibiotic therapy was initiated; no cerclage was placed. Spontaneous rupture of membranes and cord prolapse occurred 48 h later, resulting in delivery of a stillborn female infant. Conservative management was offered after counseling for possible risks associated with maternal sepsis, need for extended hospitalization, potential for hysterectomy and death. The cervix appeared closed after delivery and the umbilical cord was ligated, with subsequent spontaneous cord retraction in utero. Reassuring fetal status was observed for twin B without evidence of contractions or chorioamnionitis. A viable male infant (2894 g) was delivered vaginally at 35 1/2 weeks.
This report outlines a counseling approach useful for patients with premature delivery of one twin, and presents application of conservative obstetrical management principles for the aftercoming twin even when delivery interval is extreme.
PMCID: PMC539248  PMID: 15581427
5.  Correlations from gadopentetate dimeglumine-enhanced magnetic resonance imaging after methotrexate chemotherapy for hemorrhagic placenta increta 
To describe pre- and post-methotrexate (MTX) therapy images from pelvic magnetic resonance imaging (MRI) with gadopentetate dimeglumine contrast following chemotherapy for post-partum hemorrhage secondary to placenta increta.
Material and method
A 28-year-old Caucasian female presented 4 weeks post-partum complaining of intermittent vaginal bleeding. She underwent dilatation and curettage immediately after vaginal delivery for suspected retained placental tissue but 28 d after delivery, the serum β-hCG persisted at 156 IU/mL. Office transvaginal sonogram (4 mHz B-mode) was performed, followed by pelvic MRI using a 1.5 Tesla instrument after administration of gadolinium-based contrast agent. MTX was administered intramuscularly, and MRI was repeated four weeks later.
While transvaginal sonogram suggested retained products of conception confined to the endometrial compartment, an irregular 53 × 34 × 28 mm heterogeneous intrauterine mass was noted on MRI to extend into the anterior myometrium, consistent with placenta increta. Vaginal bleeding diminished following MTX treatment, with complete discontinuation of bleeding achieved by ~20 d post-injection. MRI using identical technique one month later showed complete resolution of the uterine lesion. Serum β-hCG was <5 IU/mL.
Reduction or elimination of risks associated with surgical management of placenta increta is important to preserve uterine function and reproductive potential. For selected hemodynamically stable patients, placenta increta may be treated non-operatively with MTX as described here. A satisfactory response to MTX can be ascertained by serum hCG measurements with pre- and post-treatment pelvic MRI with gadopentetate dimeglumine enhancement, which offers advantages over standard transvaginal sonography.
PMCID: PMC280697  PMID: 14617375
magnetic resonance imaging; placenta increta; methotrexate
6.  Monochorionic-triamniotic triplet pregnancy after intracytoplasmic sperm injection, assisted hatching, and two-embryo transfer: first reported case following IVF 
We present a case of monochorionic-triamniotic pregnancy that developed after embryo transfer following in vitro fertilization (IVF).
After controlled ovarian hyperstimulation and transvaginal retrieval of 22 metaphase II oocytes, fertilization was accomplished with intracytoplasmic sperm injection (ICSI). Assisted embryo hatching was performed, and two embryos were transferred in utero. One non-transferred blastocyst was cryopreserved.
Fourteen days post-transfer, serum hCG level was 423 mIU/ml and subsequent transvaginal ultrasound revealed a single intrauterine gestational sac with three separate amnion compartments. Three distinct foci of cardiac motion were detected and the diagnosis was revised to monochorionic-triamniotic triplet pregnancy. Antenatal management included cerclage placement at 19 weeks gestation and hospital admission at 28 weeks gestation due to mild preeclampsia. Three viable female infants were delivered via cesarean at 30 5/7 weeks gestation.
The incidence of triplet delivery in humans is approximately 1:6400, and such pregnancies are classified as high-risk for reasons described in this report. We also outline an obstetric management strategy designed to optimize outcomes. The roles of IVF, ICSI, assisted embryo hatching and associated laboratory culture conditions on the subsequent development of monozygotic/monochorionic pregnancy remain controversial. As demonstrated here, even when two-embryo transfer is employed after IVF the statistical probability of monozygotic multiple gestation cannot be reduced to zero. We encourage discussion of this possibility during informed consent for the advanced reproductive technologies.
PMCID: PMC184457  PMID: 12906712
triplet pregnancy / IVF / monochorionic / cerclage / outcome

Results 1-6 (6)