Continued Validation of Ultrasound Guidance Targeting Tasks: Assessment of Internal Structure.

RATIONALE AND OBJECTIVES: We previously demonstrated validity evidence for our novel ultrasound-guided invasive procedure targeting tasks in the content, response process, relations with other variables, and consequences validity domains. Here, we investigate their internal structure by assessing their interrater, intrarater, and test-retest reliability. METHODS: In this Institutional Review Board approved nonrandomized interventional trial first year medical students performed our previously described dowel and straw ultrasound guidance targeting tasks as a pretest. Afterward, the training group had four weekly 1-hour training sessions. The control group had no further training. Both groups then had a posttest for both tasks. The training group was re-evaluated 2 and 5 months later. Completion time in seconds, errors, and error adjusted time (5 seconds penalty/error) were recorded. Pretest and posttest performance was compared within groups, and the amount of improvement from pretest to posttest was compared between groups. Interrater, intrarater, and test-retest interclass correlation coefficients (ICC) were calculated. RESULTS: Although some improvements from pretest to posttest were seen in both groups, greater improvements were seen in the training group. This skill was retained for at least several months. The interrater and intrarater ICCs were excellent (range 0.83-0.93). The test-retest ICCs were good to excellent in all but one performance measure (0.50-0.78). CONCLUSION: Student performance on the targeting tasks improved markedly after training and persisted for several months. The interrater and intrarater reliability were excellent, while the test-retest reliability was good. This provides additional validity evidence for our novel ultrasound-guided invasive procedure targeting curriculum.

OS052. Preeclampsia candidate genes differentially methylated in maternal leukocyte DNA.

INTRODUCTION: Altered gene expression in biomarkers associated with preeclampsia/ eclampsia (PE) could be explained in part by epigenetic phenomena such as variable methylation OBJECTIVES: We sought to characterize the methylation profiles of candidate genes known to be associated with the preeclampsia phenotype in maternal leukocyte DNA in preeclamptic cases and normotensive controls at the time of delivery. METHODS: Methylation profiles of maternal leukocyte DNA were evaluated in 14 PE cases and 14 normotensive controls. Subjects were nulliparous, non-smokers, age and BMI matched. Genomic DNA was run on a commercially available beadchip human methylation assay. Mean methylation at sites in genes from a well-defined preeclampsia gene set present on our platform were compared using a t-test. RESULTS: QC confirmed high correlation of replicates and detection p values >95%. Of the 39 genes in the "preeclampsia gene set", 34 were present on our platform with 73 CpG sites. Seven out of 34 tested in this gene set had differential methylation with p value <0.05. Two genes were found to be less methylated in PE which may result in more expression. AGT (-3%;p= 0.027), angiotensin, is a potent vasoconstrictor with exaggerated effect in PE. DDAH1 (-6%;p=0.031) is involved in nitric oxide generation, via asymmetric dimethylarginine (ADMA), levels of which are known to be altered in PE. Five genes were more methylated and therefore may correlate with reduced transcription. CALCA (+4%;p=0.001) forms calcitonin-gene related peptide, a potent vasodilator decreased in the PE . F5 (+1%;p=0.016), coagulation Factor V, is a target of activated protein C, and increased resistance related to genetic variants (Factor V Leiden) or pregnancy have been associated with PE. MTHFR (+3%;p=0.041) regulates homocysteine; high levels are associated with a 20X increase in risk for PE. POMC (+4%;p=0.014) produces beta endorphin and through ACTH stimulates aldosterone, both decreased in PE. PTGS2 (+3%;p=0.03) is part of the COX 2 prostaglandin pathway involved in inflammation. CONCLUSION: Differential methylation of these 7 genes may affect transcription and explain known alterations in gene product associated with PE.

In-utero stenting: development of a low-cost high-fidelity task trainer.

OBJECTIVE: To develop an in-utero stent placement training model. METHODS: The in-utero stent task trainer was constructed using a formalin-preserved gravid pig uterus. Altering the size of the uterine segment, changing the fluid level in the uterus and addition of a large Ziploc freezer bag variably filled with differing amounts of ultrasound gel can vary the procedural skill required. RESULTS: Thoracoamniotic and vesicoamniotic shunts can be simulated using this life-like model. The cost of eight to 10 learning stations is approximately US $ 60. Fetal position, maternal size and amniotic fluid status can be altered rapidly to increase the complexity of the procedure. CONCLUSIONS: This low-cost and realistic task trainer can provide the opportunity to practice in-utero shunt procedures in a non-clinical environment. This model should enhance learning and reinforce acquired skills.

Successful term pregnancy following MR-guided focused ultrasound treatment of uterine leiomyoma.

OBJECTIVE: Term vaginal delivery after magnetic resonance-guided focused ultrasound therapy (MRgFU) for symptomatic uterine leiomyoma. STUDY DESIGN: A 38-year-old nulligravida underwent MRgFU treatment per study protocol for a solitary 9 x 10 x 10 cm uterine myoma and conceived 18 months following the procedure. She was counseled on the unknown implications of MRgFU during subsequent pregnancy. Myoma size increased significantly during gestation. At 39 weeks, she underwent indicated labor induction with vacuum-assisted vaginal delivery of a healthy male infant. CONCLUSION: In one pregnancy following MRgFU, there were no associated antepartum or intrapartum obstetrical complications.

Sonographic characteristics of linear nevus sebaceous sequence.

Linear nevus sebaceous is a hamartomatous lesion most commonly seen on the face and head of infants and diagnosed after birth. We describe a patient with sonographic findings of linear nevus sebaceous seen initially at 30 weeks' gestation. Other associated sonographic findings include macrocephaly and polyhydramnios. When associated with a midline soft tissue mass, these findings are highly suggestive of the presence of congenital linear nevus sebaceous sequence.

Development of antibodies to topical bovine thrombin after abdominal hysterectomy. A case report.

BACKGROUND: Topical thrombin spray is frequently used as a hemostatic agent in surgery, particularly following cardiovascular, orthopedic and neurologic surgery. Acquired coagulation factor inhibitors to thrombin and factor V may develop following gynecologic surgery with repeat topical thrombin use. CASE: A 45-year-old woman underwent total abdominal hysterectomy/bilateral salpingo-oophorectomy. Her past medical history included idiopathic thrombocytopenic purpura and Marfan's syndrome and past surgery included splenectomy and aortic valve replacement with a three-vessel coronary artery bypass graft. She was converted from Coumadin (DuPont Pharmaceuticals, Wilmington, Delaware) to heparin preoperatively, and heparin was stopped six hours before surgery, with normalization of her prothrombin time (PT) and partial thromboplastin time (PTT). Topical bovine thrombin spray was applied to the surgical field in anticipation of early resumption of heparin anticoagulation. Seven days after surgery, after recovering from some acute bleeding problems, the patient began to have elevation of her PT in spite of being off Coumadin for 10 days. Her PT and international normalized ratio (INR) continued to rise, reaching peak values of 31.4 and 6.99, respectively. A mixing study did not correct the problem, confirming the presence of coagulation inhibitors. The patient was given intravenous immunoglobulins and corticosteroids, and her PT/PTT and INR values slowly normalized. CONCLUSION: Acquired coagulation factor may develop following gynecologic surgery with topical thrombin use. This potential complication should be strongly considered in any patient prior to using topical bovine thrombin, especially those with a prior exposure or history of surgical procedures in which bovine thrombin is commonly used.

Should intravenous tocolysis be considered beyond 34 weeks' gestation?

OBJECTIVE: Our purpose was to assess the incidence of respiratory distress syndrome in nonindigent women with uncomplicated preterm labor between 34 and 36 weeks' gestation. STUDY DESIGN: All women seen between June 1, 1992, and April 15, 1999, with uncomplicated preterm labor and intact membranes and delivering between 34 and 36 weeks' gestation were analyzed. Rates of respiratory distress syndrome after delivery were calculated. A chi(2) analysis was performed, and a P value of <.05 was considered statistically significant. RESULTS: Respiratory distress syndrome was noted in 8 (17.4%) of 46 infants delivered at 34 weeks' gestation, in comparison with 5 (6.3%) of 80 infants and 7 (4.2%) of 165 infants delivered at 35 and 36 weeks' gestation, respectively (P =.008). The rate of respiratory distress syndrome after delivery at 34 weeks was significantly higher than at 35 weeks (P =.048). CONCLUSION: The rate of respiratory distress syndrome after delivery at 34 weeks is significantly higher than at either 35 or 36 weeks' gestation in our population.

Effect of fetal presentation on the amniotic fluid index.

OBJECTIVE: The aim of this study was to determine whether the amniotic fluid index differs according to whether a fetus is in breech or cephalic presentation. STUDY DESIGN: Between January 1995 and April 1996 the amniotic fluid index was measured both immediately before and after attempted external cephalic version. Amniotic fluid indexes were measured by a senior obstetric resident or attending physician. Preprocedure amniotic fluid indexes and change in amniotic fluid index after successful and failed external cephalic version were compared with unpaired and paired Student t tests, respectively. P <.05 was considered statistically significant. RESULTS: Thirty consecutive women between 36 and 40 weeks' gestation with breech presentations were evaluated before undergoing an attempt at external cephalic version. The preprocedure amniotic fluid index was not different (P =.61) between women who had success (12.1 cm) and failure (11.4 cm) of attempts at external cephalic version. Successful external cephalic version was associated with a statistically significant increase (P <.0001) in amniotic fluid index with respect to gestations with a persistent breech presentation (3.14 vs -0.35). CONCLUSION: Successful version from a breech to a cephalic presentation resulted in a significant increase in the amniotic fluid index. This should be considered when a breech presentation with a low normal amniotic fluid index is evaluated. Presentation of the fetus should be considered in evaluating amniotic fluid index distribution curves.

Abnormal presentation in labor and fetal growth of affected infants with type III Ehlers-Danlos syndrome.

Information about labor presentation and birth weight of infants with connective tissue disorders such as Ehlers-Danlos syndrome is scarce. We report a case of abnormal fetal presentation and decreased birth weight in 2 infants affected by type III Ehlers-Danlos syndrome; their siblings were unaffected.

Management of cervical cancer in pregnancy.

Carcinoma of the cervix is the most common gynecologic cancer found during pregnancy. Management and treatment of this condition depend on cancer stage, estimated gestational age, and ethical, religious, and personal desires. Review of the medical literature in English from 1965 to 1998 is presented with recommendations for management.

Effect of hemodialysis on serum progesterone level in pregnant women.

The objective of this study is to evaluate the effect of chronic hemodialysis on serum progesterone level in pregnancy. Serum progesterone levels were measured predialysis and postdialysis using the radioimmunoassay technique in seven gravid women with renal failure requiring hemodialysis. Uterine contractions were measured before and after hemodialysis using home uterine activity monitoring (HUAM) in two patients. Thirty-three paired serum samples were obtained between 14 and 39 weeks' gestation. The mean change in serum progesterone level postdialysis throughout pregnancy ranged from -52.0% to +8.7% for each individual patient. The change in serum progesterone level was unrelated to gestational age. The woman experiencing the most significant decrease in serum progesterone level with dialysis continued her pregnancy to greater than 39 weeks. No significant increase in uterine contraction frequency was noted on HUAM postdialysis (P = 0.22), although both monitored patients experienced a small increase in serum progesterone levels. In conclusion, serum progesterone values showed a variable patient-specific response when measured predialysis and postdialysis in pregnancies complicated by renal failure. There was no significant increase in uterine activity noted postdialysis. Progesterone withdrawal does not appear to explain the increased frequency of preterm delivery in women after dialysis.

Hydropic degenerating leiomyoma presenting as pseudo-Meigs syndrome with elevated CA 125.

BACKGROUND: Leiomyomas rarely cause pseudo-Meigs syndrome. Increased levels of CA 125 often are associated with some types of malignancy. No reported case of pseudo-Meigs syndrome presenting with hydropic degeneration of uterine leiomyoma and an elevated CA 125 level could be found on a MEDLINE search. CASE: A 46-year-old woman presented with a pleural effusion and a pelvic mass measuring 30 x 18 cm. Preoperative evaluation was remarkable for a CA 125 level of 254 U/mL. At laparotomy, the diagnosis was a benign leiomyoma with focal hyaline and extensive hydropic degeneration. Her pleural effusion resolved completely by 4 months postoperatively. CONCLUSION: Pseudo-Meigs syndrome can present with an elevated CA 125 level.

A randomized clinical trial of prostaglandin E2 intracervical gel and a slow release vaginal pessary for preinduction cervical ripening.

OBJECTIVE: Our purpose was to compare the efficacy of 2 different prostaglandin E2 delivery methods for preinduction cervical ripening. STUDY DESIGN: Ninety patients admitted for labor induction with a Bishop score <8 were randomized to either 0.5 mg prostaglandin E2 intracervical gel (Prepidil) every 6 hours for 2 doses or 10 mg prostaglandin E2 slow release vaginal pessary (Cervidil). Oxytocin induction was begun after 12 hours. It was estimated that enrollment of 90 women would be required to identify a 30% difference in the percent delivered in <24 hours (1 - beta = .80, alpha = .05). Data were analyzed with use of chi2 analysis or the Student t test. RESULTS: There were 45 subjects in each treatment arm. The percent delivered by 24 hours was 53% with intracervical gel and 63% with vaginal pessary (P = .28). Mean change in Bishop score was 1.8 +/- 1.9 for the intracervical gel versus 3.2 +/- 3.1 for the vaginal pessary (P = .01). No difference was demonstrated in mean time to delivery, 28.3 versus 24.0 hours (P = .19) or percent requiring cesarean section. CONCLUSION: Preinduction cervical ripening with a slow release prostaglandin E2 vaginal pessary resulted in greater change in Bishop score than with intracervical prostaglandin E2. There was a trend toward shorter time to delivery with the pessary. There was no statistically significant difference in percent delivered in <24 hours.

Monocyte activation in congestive heart failure due to coronary artery disease and idiopathic dilated cardiomyopathy.

OBJECTIVE: To investigate plasma tumor necrosis factor (TNF)alpha, tumor necrosis factor alpha soluble receptor I, interleukin-1beta and neopterin concentrations as markers of monocyte activation in patients with heart failure. STUDY DESIGN: The group consisted of patients with heart failure due to dilated cardiomyopathy (n=19) and coronary artery disease (n=11). Patients without cardiac failure served as controls (n=10). RESULTS: TNFalpha concentrations were elevated only in heart failure patients with coronary artery disease (2.9+/-0.3 pg/ml versus 1.7+/-0.3 pg/ml; P<0.05). When the patients were grouped according to acute and chronic failure, TNFalpha concentrations were significantly elevated in acute failure (3.1+/-0.4 pg/ml, n=6 versus 1.7+/-0.2 pg/ml, n=8; P<0.05). TNFalpha concentrations were elevated in patients with coronary artery disease and chronic heart failure compared to coronary artery disease patients without failure (2.0+/-0.4 pg/ml, n=6 versus 1.8+/-0.3 pg/ml, n=7; P<0.05). A higher proportion of patients with myocardial insufficiency showed increased lipopolysaccharide-inducible TNFalpha concentrations (10/30 versus 0/9, P<0.05). CONCLUSIONS: TNFalpha is elevated in patients with acute cardiac decompensation. Among patients with chronic heart failure only those with coronary artery disease exhibit increased levels. Cytokine concentrations are similar in heart failure due to dilated cardiomyopathy and coronary artery disease. Monocytes of patients suffering from cardiac insufficiency show an increased sensitivity towards stimuli such as lipopolysaccharides.

The maternal and fetal effects of tuberculosis therapy.

Tuberculosis can cause significant morbidity in the pregnant woman, fetus, and members of the community. The first-line agents suggested by the CDC for use during pregnancy (isoniazid, rifampin, and ethambutol) seem to have minimal risk of induced congenital anomalies. Maternal morbidity associated with therapy does not seem increased above rates observed in the nonpregnant population. Education of the patient concerning the potential adverse side effects may decrease maternal morbidity. Therapy should be started as soon as the diagnosis of tuberculosis is confirmed (or when suspected in the HIV-infected woman) or after the first trimester in women younger than 35-years-old with recent TB tine test conversion. Monitoring for medication compliance during pregnancy is important to provide effective therapy and to decrease the development of resistant organisms.

The Preterm Prediction Study: association of cesarean delivery with increases in maternal weight and body mass index.

OBJECTIVE: Our purpose was to evaluate whether maternal weight and body mass index measured either before or during pregnancy are associated with an increased risk of cesarean delivery. STUDY DESIGN: Maternal weight and height were prospectively collected on 2929 women in the National Institutes of Health Maternal-Fetal Medicine Units Network Preterm Prediction Study. Prepregnancy and 27- to 31-week maternal weight and height were used to calculate the body mass index, and its contribution to the risk of cesarean delivery was determined. Women with prenatally diagnosed congenital anomalies (n = 89) and pregestational diabetes (n = 31) were excluded from analysis. RESULTS: Univariate analysis of risk factors for cesarean delivery in the 2809 eligible women revealed a decreased risk of cesarean delivery with maternal age < 18 years and multiparity; increased risk of cesarean delivery was noted with maternal age > 35 years and a male fetus. Increases in either prepregnancy or 27- to 31-week maternal weight (5-pound units) or body mass index (1.0 kg/m2 units) were significantly associated with an increased odds of cesarean delivery (p = 0.0001). Each unit increase in prepregnancy or 27- to 31-week body mass index resulted in a parallel increase in the odds of cesarean delivery of 7.0% and 7.8%, respectively. Multivariable stepwise logistic regression analysis confirmed the association of male fetus, age, nulliparity, and body mass index as significant variables contributing to cesarean delivery risk. CONCLUSIONS: The risk of cesarean delivery is associated with incremental changes in maternal weight and body mass index before and during pregnancy after adjustment for potential confounding factors. Prepregnancy counseling about optimizing maternal weight and monitoring weight gain during pregnancy to decrease the risk of cesarean delivery are supported by this study.