Resident Research Presentation Day
Association of Abdominal Adiposity with Markers of Metabolic Risk and the Metabolic Syndrome in Obese Adolescents with Polycystic Ovary Syndrome (PCOS)
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Preceptor
Kathleen M. Hoeger, MD
Collaborators
David S. Guzick, MD, PhD
Jodi Forand, BS
Objective
Metabolic disturbances in PCOS are exacerbated by obesity. Visceral fat, specifically, has been associated with metabolic disturbances in adults. We aimed to assess the impact of visceral adiposity in obese adolescents with PCOS. We hypothesize that visceral adipose tissue (VAT) will better correlate with markers of metabolic risk and predict the presence of the metabolic syndrome, when compared with subcutaneous adipose tissue (SAT).
Method
We performed a cross-sectional study of 37 obese adolescents with PCOS. Subjects underwent physical exam, fasting blood sampling, and insulin sensitivity measurement. Computerized tomography was used to measure SAT and VAT. Statistical analysis included Pearson's correlation, one-way ANOVA and logistic regression.
Results
Subjects had a mean age of 15.7 years. The association of metabolic parameters with SAT and VAT are shown below. The metabolic syndrome was present in 24% of subjects. VAT, but not SAT, showed a significant, stepwise increase with the number of features of the metabolic syndrome. VAT had the strongest independent effect on the presence of the metabolic syndrome (OR=1.06, p=0.009) when accounting for other markers of metabolic risk.
Conclusions
In obese adolescents with PCOS: serum markers of metabolic risk correlate with abdominal adiposity; features of the metabolic syndrome increase with increasing VAT, but not SAT; and VAT has the strongest independent effect on the presence of the metabolic syndrome when accounting for other risk factors. These findings suggest that VAT, in comparison to SAT, has a stronger influence on metabolic disease in obese adolescents with PCOS.
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SAT |
VAT |
Parameter |
Mean |
R |
p |
R |
p |
BMI |
36.2+6.3 |
0.81 |
<0.001 |
0.50 |
0.002 |
PAI-1 |
52.0+33.9 |
0.45 |
0.005 |
0.75 |
<0.001 |
Si |
1.7+1.4 |
-0.55 |
<0.001 |
-0.48 |
0.003 |
Adiponectin |
8.9+3.9 |
-0.33 |
0.04 |
-0.36 |
0.03 |
Total Cholesterol (TC) |
163.4+24.9 |
0.28 |
0.10 |
0.33 |
<0.05 |
LDL |
114.2+22.8 |
0.28 |
0.10 |
0.33 |
0.04 |
CRP |
0.6+0.4 |
0.35 |
0.03 |
0.28 |
0.09 |
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Association of Ultrasound Findings with Decision to Terminate Down Syndrome Pregnancies |
Preceptor
Eva K. Pressman, MD
Objective
To evaluate the association of ultrasound findings with the decision to terminate Trisomy 21 pregnancies. We hypothesized that termination rates would be higher amongst those with abnormal ultrasound findings as compared to those with normal ultrasounds.
Method
We identified pregnancies diagnosed with trisomy 21 prior to 24 weeks’ gestation using a genetics database of abnormal karyotypes at the University of Rochester from 1997-2005. We performed a retrospective review of the medical records and ultrasound databases for each affected pregnancy.
Results
Fifty-nine pregnancies were eligible for study. The overall termination rate was 72.9% (43/59) which is significantly different from other reported termination rates in the literature (84-92%). We found no statistically significant difference in gestational age at diagnosis, gravity, and parity between those who terminated and those who continued their pregnancies. Using logistic regression, termination was more likely in older patients with the average age of 36.1 in those who terminated and 32.3 in those who continued their pregnancies. This difference was not significant (p = 0.059). Major and minor ultrasound abnormalities were associated with statistically significant lower termination rates of 50% and 64%, respectively as compared to those with normal or limited ultrasound examinations with termination rates of 93% and 90% (p = 0.026 and p=0.022, respectively).
Conclusions
Patients with abnormal ultrasound results were more likely not to terminate a Trisomy 21 pregnancy. Maternal age approached statistical significance with older patients more likely to terminate. The termination rate was significantly lower in our series than in other reported studies. |
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A Survey of Contraceptive Experience, Knowledge, and Plans in Young Pregnant Women |
Preceptor
Nancy Stanwood, MD, MPH
Objective
Most young pregnant women want effective, reversible contraception after their pregnancy. Modern intrauterine devices (IUDs) are safe, effective and reversible, but only 2.1% of women use IUDs. We aimed to assess this population’s contraceptive experience and plans, and their knowledge of IUDs
Method
We surveyed 170 women ages 13 to 25 in prenatal or abortion care with a questionnaire on contraceptive history, plans and knowledge. We asked if they had heard of IUDs and queried them on IUD characteristics.
Results
The subjects were on average 20 years old and 29% had education past high school. Over half were in prenatal care and 90% had not planned their current pregnancy. Over half wished to wait four or more years before their next pregnancy and 27% did not want to be pregnant ever again. Safety and efficacy were the most important factors in choosing a contraceptive method. Fifty-two percent had heard of IUDs, but of these 71% did not know about IUD safety and 59% did not know about IUD efficacy. Respondents who knew of IUDs were significantly older (21 vs. 19, p<0.001) and parous (55% vs. 39%, p=0.04).
Conclusions
This population has contraceptive plans that compliment IUD characteristics, as most want a safe, effective method for more than four years. Only 54% had heard of IUDs, and most did not have specific knowledge about IUD safety or efficacy. Clinicians must teach young pregnant women about the safety and efficacy of contraceptive methods, including IUDs, so that more patients can make fully informed contraceptive plans. |
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Cell Adhesion Molecule Expression in Complete Hydatidiform Moles |
Preceptor
Brent DuBeshter, MD
Objective
The expression of cell adhesion molecules (CAMs) may be prognostic in a variety of malignancies. We know little about the expression of CD44 and E-cadherin, two cell adhesion molecules and nm23-H1, a tumor protein, in complete hytaditiform moles (CHM). We aimed to measure the expression of CD44, E-cadherin, and nm23-H1 in CHMs. We hypothesized that lack of expression of these molecules would be associated with a higher rate of invasive molar disease.
Method
We performed a retrospective review of 27 patients with CHM identified through a pathology database. We abstracted demographic and clinical information from the clinical charts. A pathologist performed immunohistochemical staining for CD44, E-cadherin, and nm23-H1 on the tumor blocks of these cases. We looked for associations between the tumor markers and invasive disease using chi-square analysis and the Student’s t-testing.
Results
The risk of invasive molar disease for CD44(-) and CD44(+) cases was 40% versus 57% (p=0.62), respectively. The risk of invasive disease did not differ significantly according to E-cadherin localization (p = 0.69) or staining intensity (p = 0.99). The risk of invasive disease for weak, moderate, and strong nm23-H1 expression was 100%, 33%, and 43% (p=0.5), respectively.
Conclusions
We found no association between the expression of CD44, E-cadherin and nm23-H1 and the risk of invasive molar disease in patients with complete hydatidiform molar pregnancies. Other molecular markers may be predictive of invasive molar disease and future studies may enable clinicians to safely discontinue beta-hCG surveillance earlier than six months. |
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Ex vivo Peripheral Blood Mononuclear Cell Cytokine Response to Antigenic Challenge in Preeclampsia |
Preceptor
William Curtin, MD
Objective
Cell mediated immunity may play a role in the pathogenesis of preeclampsia. We aimed to determine the Th1-cell response to various antigens in preeclamptic subjects as compared to pregnant and non-pregnant controls.
Method
We isolated the peripheral blood mononuclear (PBM) cells from blood samples of 10 women with preeclampsia, 10 healthy pregnant women, and 10 healthy non-pregnant women. We incubated these cells with different antigens (trophoblast, phytohemagglutinin, R8, RSV, and JEG-3 cells), and assayed for cytokines associated with Th1-cells (tumor necrosis factor b and interferon g) and Th2-cells (interleukin 4 and 10) via the ELISPOT test. We expressed the results as the median number of spot forming cells (SFC) per 2x105 peripheral blood mononuclear cells.
Results
The mean gestational age in the preeclamptic patients was 29±3 weeks. The PBM cells from preeclampsia subjects produced a median of 184.5 SFC of TNF b as compared to 671.5 SFC for healthy pregnant controls and 649.5 SFC for healthy non-pregnant controls in response to phytohemagglutinin (p=0.046). The PBM cells of preeclamptic subjects produced a median of 101 SFC of interfon g, the healthy pregnant controls produced 382 SFC, and the healthy non-pregnant controls produced 472 SFC (p=0.001). None of the results for the other antigen and cytokine combinations were statistically significant.
Conclusions
We found a statistically significant decrease in production of Th1 cytokines (TNF b and interferon g) in response to phytohemagglutinin in patients with preeclampsia. These findings may indicate that cell mediated immunity is disrupted as part of the pathophysiology of preeclampsia. |
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Pelvic Organ Prolapse in Postmenopausal Parous Women and Their Nulliparous Sisters |
Preceptor
Gunhilde Buchsbaum, MD
Objective
To compare pelvic prolapse in postmenopausal parous women and their nulliparous sisters, in order to determine the importance of vaginal delivery in the development of pelvic organ prolapse.
Method
We used a matched-pair design to examine parity as a risk factor for pelvic organ prolapse in postmenopausal women. We evaluated sister pairs, one nulliparous and one with a prior vaginal delivery, to minimize the differences that would be found in a random cohort sample. Both sisters completed a survey about history and symptoms of urinary incontinence and pelvic organ prolapse. Subjects then had a clinical assessment for pelvic support using the Baden-Walker staging. We used chi-square analysis to evaluate for statistical significance.
Results
We evaluated 101 sister pairs. Other than parity, we found no statistically significant differences variables between the nulliparous and the parous groups. The majority of sister pairs had concordant vaginal prolapse staging in anterior (74%), posterior (75%) and apical compartments (91%). The parous sister had the more advanced prolapse in most of the discordant sister pairs. We found no association between incontinence and degree of prolapse.
Conclusions
Most women do not have clinically relevant pelvic organ prolapse regardless of parity status. However, vaginal delivery is a risk factor for prolapse beyond the hymen. |
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Prediction of Parity by Physical Exam |
Preceptor
Gunhilde Buchsbaum, MD
Erin Duecy, MD
Objective
An on-going research protocol requires the examiners to be blinded to the subjects’ parity status at the time of the evaluation. However, if clinicians are able to determine parity by physical exam, blinding may not be maintained. In the current study, we aimed to determine if clinicians can accurately predict parity by physical exam.
Method
We performed a retrospective chart review of postmenopausal sister pairs enrolled in a study evaluating the relationship between parity and pelvic floor dysfunction. Pairs consisted of nulliparous women and their parous sisters. Women underwent gynecologic examination by a single blinded examiner who predicted parity status and noted specific exam findings that influenced the prediction
Results
We analyzed exam findings for 146 subjects. Parity status was correctly predicted for 85% of the subjects, which was statistically significant (p 0.001 by z-test). Higher parity did not increase correct prediction in parous subjects. Abdominal striae, parous cervical os, and absence of hymen were significantly associated with parity (p<0.0001 by chi-square). We found a a strong correlation between abdominal striae and hymen, with correlation coefficient 0.87.
Conclusions
Examiners can predict parity status by physical exam in most women. The physical exam parameter most consistently associated with correct prediction is the condition of the hymen. A research design that requires blinding of examiners to parity status may not be feasible. |
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The Effect of Intrapartum Antiobiotics on Vaginal Group B Streptococcus Colony Counts |
Preceptor
J. Christopher Glantz, MD, MPH
Collaborating with Dr. Dwight Hardy, PhD, Dept. of Microbiology
Objective
Intrapartum antibiotic prophylaxis is an effective strategy for prevention of early-onset neonatal GBS disease. It is unclear whether antibiotic prophylaxis acts by loading the fetus and amniotic fluid, by decreasing maternal vaginal colony counts, or a combination of these mechanisms. This study examines the temporal relationship between intrapartum antibiotics and vaginal colony counts in GBS-positive women.
Method
In a pilot study using serial distal vaginal swabs from GBS-positive controls, we evaluated the quantitation technique and whether colony counts were stable over 8 hours. In the main study, we collected vaginal swabs from laboring GBS-positive women before the first antibiotic dose and then every two hours for four samples or until delivery. Lab technicians inoculated the swabs in Columbia CNA Agar, Selective Strep Agar and Todd Hewitt broth. Following isolation, they determined quantitative colony counts by serial dilution. We performed repeated measures ANOVA for the analysis.
Results
Seven of fifty-seven subjects (12%) in the pilot study were positive for GBS in the vagina. The degree of colonization varied greatly between subjects, but colony counts appeared stable over 8 hours within individual (p=0.58). Of 15 subjects enrolled in the main study to date, 10 (67%) were positive for vaginal GBS. Preliminary results suggest that colony counts reach non-detectable levels rapidly. Enrollment continues. 7.
Conclusions
Serial dilution appears to be a useful technique in determining GBS colony counts. The degree of initial colonization varies greatly, but colony counts are stable over a short time period. Maternal intravenous penicillin administration rapidly leads to undetectable vaginal colony counts. |
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The Placenta: To Submit or Not to Submit |
Preceptor
William Curtin, MD
Objective
To determine the proportion of placental submission for pathologic exam at Strong Memorial Hospital using 1997 College of American Pathologist (CAP) guidelines and to evaluate the completeness of the history given on the pathology requisition.
Method
Retrospective review of all deliveries from 2001. This included a review of multiple databases searching maternal and neonatal records for CAP indications for placental submission. Descriptive statistics, 95% confidence intervals, and the binomial test were used to evaluate the data
Results
The expected rate of placental submission is 37.2% (95% CI 35.6, 38.9). The observed rate of placental submission is 18.1% (95% CI 16.7, 19.4). The difference is significant with a p<0.001. The actual rate of indicated placentas submitted is 48.5% (95% CI 45.6, 51.4). The difference between the expected and observed rates for individual indications was statistically significant for severe diabetes, all diabetes, collagen disease, suspected chorioamnionitis, oligohydramnios, thick meconium, NICU admission, weight < 10%, and congenital anomalies. Only 2.8% of all histories on the pathology requisition were adequate.
Conclusions
We submit too few placentas. Our suboptimal rate of placental submission may have medicolegal and research implications. The ACOG committee opinion should be updated to reflect current data, and in addition, we may benefit from formal guidelines for placental submission on our obstetrics service. Finally, submitting a delivery summary with each placenta may improve communication with the pathologist and will help correlate histologic changes with clinical diagnosis. |
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Uterine Carcinosarcoma: Clinical and Molecular Correlation |
Preceptor
Brent DuBeshter, MD
Objective
Uterine carcinosarcoma (MMMT) is a highly aggressive malignancy without markers to guide treatment. The expression of CAMs, or cell adhesion molecules, (E-cadherin, CD44) and cell cycle mediator, Nm23H1 have not been studied in MMMT. We aimed to characterize the expression of these molecules in MMMT, and to look for associations between their expression and clinical outcomes.
Method
We performed a retrospective chart review of 14 patients with MMMT, abstracting clinical data, treatment, pathology, and recurrence rates. One pathologist reviewed the histopathology of each case and performed immunohistochemical staining for E-cadherin, CD44, and Nm23H1.
Results
E-cadherin, CD44, and Nm23H1 expression were present in 57%, 43%, and 100% of cases, respectively. CD44 and Nm23H1 expression was not associated with myometrial invasion, nodal spread or disease recurrence. E-cadherin expression was associated with disease recurrence (p,0.05). The positive and negative predictive values of E-cadherin expression for recurrence were 0% and 50%, respectively.
Conclusions
E-cadherin expression has a statistically significant correlation with disease recurrence in patients with MMMT. This CAM may be useful in selecting patients with MMMT who are at higher risk for recurrence and who may benefit from adjuvant treatment. |
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Vitamin C, Alpha- Fetoprotein and Interleukin-6 in Mid-trimester Amniotic Fluid: Correlation with Pregnancy Outcome |
Preceptor
Eva K. Pressman, MD
Objective
Early intra-amniotic inflammation as measured by an elevated level of IL-6 is associated with a decreased level of vitamin C. We aimed to prospectively compare mid-trimester amniotic fluid levels of vitamin C, IL-6 and AFP in patients with adverse pregnancy outcomes to those with uncomplicated pregnancies.
Method
Enrolled patients undergoing genetic amniocentesis for uncomplicated singleton gestations. We analyzed amniotic fluid for vitamin C, IL-6 and AFP. We obtained pregnancy outcomes from hospital records and patient questionnaires. Our main outcomes were gestational age at delivery and birth weight. We defined adverse pregnancy outcome as delivery < 37 weeks or birth weight < 2500 grams.
Results
We have follow up data on 216 subjects. Twenty-four pregnancies had adverse outcomes. Mean IL-6 levels were significantly higher for subjects who had adverse outcome compared to those did not (327 vs. 179 pg/ml, p=0.01). Elevated IL-6 values ( > 600 pg/ml) were strongly associated with adverse pregnancy outcome, p=0.008. In patients with elevated IL-6, amniotic fluid AFP levels were significantly lower in those with adverse pregnancy outcome (AFP MoM 0.81 vs. 1.09, p= 0.018).
Conclusions
Elevated mid-trimester amniotic fluid IL-6 levels are associated with preterm birth and low birth weight. Amniotic fluid levels of vitamin C were not associated with adverse pregnancy outcome. In patients with elevated second-trimester amniotic fluid IL-6, lower levels of amniotic fluid AFP were associated with adverse outcome. Our findings suggests that second-trimester amniotic fluid AFP may play a protective role in preventing preterm birth in patients with intra-amniotic inflammation.
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