Loop Electrosurgical Excisional Procedure (LEEP) Done for Discrepancy: Does the Time from HGSIL Affect Pathologic Grade of CIN in LEEP Specimen?

Objective. When pathologic discrepancy arises between high-grade cytology on Papanicolaou (Pap) smear and low-grade histology on cervical biopsy, Loop Electrosurgical Excisional Procedure (LEEP) is one management alternative. Our objective was to determine whether the time from initial HGSIL Pap to LEEP affects the pathologic grade of the LEEP specimen. Study Design. We performed a retrospective case-control study identifying LEEPs performed for discrepancy over a 10-year period (1997–2007). 121 subjects were separated into two groups based on LEEP pathology (≤CIN 1 and CIN 2,3) and compared using χ2. Results. Of the 121 LEEP specimens, 67 (55.4%) had CIN 2,3. CIN 2,3 was more often discovered when LEEP was performed within 3 months of the HGSIL Pap smear versus after 5 months (55.2% versus 16.4%, P = .096). Conclusion. Women undergoing LEEP for discrepancy >5 months from their HGSIL Pap demonstrated a trend toward less CIN 2,3 on LEEP pathology

Clinical Study Loop Electrosurgical Excisional Procedure (LEEP) Done for Discrepancy: Does the Time from HGSIL Affect Pathologic Grade of CIN in LEEP Specimen?

Objective. When pathologic discrepancy arises between high-grade cytology on Papanicolaou (Pap) smear and low-grade histology on cervical biopsy, Loop Electrosurgical Excisional Procedure (LEEP) is one management alternative. Our objective was to determine whether the time from initial HGSIL Pap to LEEP affects the pathologic grade of the LEEP specimen. Study Design. We performed a retrospective case-control study identifying LEEPs performed for discrepancy over a 10-year period (1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007). 121 subjects were separated into two groups based on LEEP pathology (≤ CIN 1 and CIN 2,3) and compared using χ 2 . Results. Of the 121 LEEP specimens, 67 (55.4%) had CIN 2,3. CIN 2,3 was more often discovered when LEEP was performed within 3 months of the HGSIL Pap smear versus after 5 months (55.2% versus 16.4%, P = .096). Conclusion. Women undergoing LEEP for discrepancy >5 months from their HGSIL Pap demonstrated a trend toward less CIN 2,3 on LEEP pathology

Effects of Pregnancy on Plasma Sphingolipids Using a Metabolomic and Quantitative Analysis Approach

Changes in the maternal metabolome, and specifically the maternal lipidome, that occur during pregnancy are relatively unknown. The objective of this investigation was to evaluate the effects of pregnancy on sphingolipid levels using metabolomics analysis followed by confirmational, targeted quantitative analysis. We focused on three subclasses of sphingolipids: ceramides, sphingomyelins, and sphingosines. Forty-seven pregnant women aged 18 to 50 years old participated in this study. Blood samples were collected on two study days for metabolomics analysis. The pregnancy samples were collected between 25 and 28 weeks of gestation and the postpartum study day samples were collected ≥3 months postpartum. Each participant served as their own control. These samples were analyzed using a Ultra-performance liquid chromatography/mass spectroscopy/mass spectroscopy (UPLC/MS/MS) assay that yielded semi-quantitative peak area values that were used to compare sphingolipid levels between pregnancy and postpartum. Following this lipidomic analysis, quantitative LC/MS/MS targeted/confirmatory analysis was performed on the same study samples. In the metabolomic analysis, 43 sphingolipid metabolites were identified and their levels were assessed using relative peak area values. These profiled sphingolipids fell into three categories: ceramides, sphingomyelins, and sphingosines. Of the 43 analytes measured, 35 were significantly different during pregnancy (p < 0.05) (including seven ceramides, 26 sphingomyelins, and two sphingosines) and 32 were significantly higher during pregnancy compared to postpartum. Following metabolomics, a separate quantitative analysis was performed and yielded quantified concentration values for 23 different sphingolipids, four of which were also detected in the metabolomics study. Quantitative analysis supported the metabolomics results with 17 of the 23 analytes measured found to be significantly different during pregnancy including 11 ceramides, four sphingomyelins, and two sphingosines. Fourteen of these were significantly higher during pregnancy. Our data suggest an overall increase in plasma sphingolipid concentrations with possible implications in endothelial function, gestational diabetes mellitus (GDM), intrahepatic cholestasis of pregnancy, and fetal development. This study provides evidence for alterations in maternal sphingolipid metabolism during pregnancy

Plasma Retinoid Concentrations Are Altered in Pregnant Women

Vitamin A is vital to maternal–fetal health and pregnancy outcomes. However, little is known about pregnancy associated changes in maternal vitamin A homeostasis and concentrations of circulating retinol metabolites. The goal of this study was to characterize retinoid concentrations in healthy women (n = 23) during two stages of pregnancy (25–28 weeks gestation and 28–32 weeks gestation) as compared to ≥3 months postpartum. It was hypothesized that plasma retinol, retinol binding protein 4 (RBP4), transthyretin and albumin concentrations would decline during pregnancy and return to baseline by 3 months postpartum. At 25–28 weeks gestation, plasma retinol (−27%), 4-oxo-13-cis-retinoic acid (−34%), and albumin (−22%) concentrations were significantly lower, and all-trans-retinoic acid (+48%) concentrations were significantly higher compared to ≥3 months postpartum in healthy women. In addition, at 28–32 weeks gestation, plasma retinol (−41%), retinol binding protein 4 (RBP4; −17%), transthyretin (TTR; −21%), albumin (−26%), 13-cis-retinoic acid (−23%) and 4-oxo-13-cis-retinoic acid (−48%) concentrations were significantly lower, whereas plasma all-trans-retinoic acid concentrations (+30%) were significantly higher than ≥3 months postpartum. Collectively, the data demonstrates that in healthy pregnancies, retinol plasma concentrations are lower, but all-trans-retinoic acid concentrations are higher than postpartum

The Effects of Pregnancy on Amino Acid Levels and Nitrogen Disposition

Limited data are available on the effects of pregnancy on the maternal metabolome. Therefore, the objective of this study was to use metabolomics analysis to determine pathways impacted by pregnancy followed by targeted confirmatory analysis to provide more powerful conclusions about metabolic alterations during pregnancy. Forty-seven pregnant women, 18&ndash;50 years of age were included in this study, with each subject serving as their own control. Plasma samples were collected between 25 and 28 weeks gestation and again &ge;3 months postpartum for metabolomics analysis utilizing an HILIC/UHPLC/MS/MS assay with confirmatory targeted specific concentration analysis for 10 of the significantly altered amino acids utilizing an LC/MS assay. Principle component analysis (PCA) on metabolomics data clearly separated pregnant and postpartum groups and identified outliers in a preliminary assessment. Of the 980 metabolites recorded, 706 were determined to be significantly different between pregnancy and postpartum. Pathway analysis revealed three significantly impacted pathways, arginine biosynthesis (p = 2 &times; 10&minus;5 and FDR = 1 &times; 10&minus;3), valine, leucine, and isoleucine metabolism (p = 2 &times; 10&minus;5 and FDR = 2 &times; 10&minus;3), and xanthine metabolism (p = 4 &times; 10&minus;5 and FDR = 4 &times; 10&minus;3). Of these we focused analysis on arginine biosynthesis and branched-chain amino acid (BCAA) metabolism due to their clinical importance and interconnected roles in amino acid metabolism. In the confirmational analysis, 7 of 10 metabolites were confirmed as significant and all 10 confirmed the direction of change of concentrations observed in the metabolomics analysis. The data support an alteration in urea nitrogen disposition and amino acid metabolism during pregnancy. These changes could also impact endogenous nitric oxide production and contribute to diseases of pregnancy. This study provides evidence for changes in both the ammonia-urea nitrogen and the BCAA metabolism taking place during pregnancy