Hyaluronidase modifies the biomechanical properties of the rat cervix and shortens the duration of labor independent of myometrial contractility.

OBJECTIVE: To investigate the effect of intracervical hyaluronidase on the biomechanical properties of the cervix and on uterine contractility. STUDY DESIGN: Sprague-Dawley rats (n = 33, term day 22) were injected with hyaluronidase (100 IU) or saline solution on day 18 of gestation (n = 8-9/group). On day 21, labor was induced with mifepristone (8 mg/rat). Injection-to-delivery times were recorded. Biomechanical properties of the cervix were assessed using stretch-tension analysis. Myometrial contractility was investigated in response to hyaluronidase (0.2-200 IU/mL), oxytocin (10(-10)M to 10(-5)M), and potassium chloride (60 mM). RESULTS: Delivery times were shorter in the hyaluronidase group (P = .03). Cervices of the treated animals showed higher measures of elasticity and plasticity (P = .02 for both). Myometrial sensitivity to hyaluronidase, oxytocin, or potassium chloride was not affected by the cervical application of hyaluronidase (P > .05 for all). CONCLUSION: Cervical hyaluronidase treatment shortens labor and alters the biomechanical properties of the cervix, independent of the myometrium.

Maternal hypercholesterolemia leads to activation of endogenous cholesterol synthesis in the offspring.

OBJECTIVE: The purpose of this study was to determine the effect of maternal hypercholesterolemia on hepatic cholesterol metabolism in the offspring in a mouse model. STUDY DESIGN: Male and female wild type and apoE(-/-KO) (knockout for the apoprotein E [apoE]) gene) mice were crossbred to obtain all 4 possible genetic offspring types. The litters were maintained on regular chow and sacrificed at 8 months of age. Liver samples were collected and the mRNA expression levels for SCAP, SREBP-1a, SREBP-2, HMGCR, and LDLR determined using real-time RT-PCR. RESULTS: We found a significant activation of the transcriptional activity of genes involved in endogenous cholesterol synthesis, as well as LDLR, in the liver of adult mice born to hypercholesterolemic dams. CONCLUSION: Reprogramming of hepatic cholesterol homeostasis may be the basis for an increased predisposition to hypercholesterolemia and atherosclerosis found in offspring of mice exposed to a high cholesterol environment during early life.

Characterization of a murine model of fetal programming of atherosclerosis.

OBJECTIVE: The objective of the study was to investigate the effect of fetal programming on the development of atherosclerosis in the offspring in a mouse model. STUDY DESIGN: Male and female mice of the wild type and the knockout for the apoprotein E (apoE) gene were cross-bred to obtain all 4 possible genetic offspring types. The offspring were kept on regular chow and killed at 8 months of age. Levels of total cholesterol and triglycerides were determined. The aortic arch was examined for the presence and severity of atherosclerosis. Kidney and liver sections were analyzed for pathologic changes. RESULTS: We found increased total cholesterol levels and incidence of atherosclerosis in offspring born to hypercholesterolemic mothers as compared with genomically similar animals born to wild-type mothers. These animals also showed kidney and liver lesions consistent with chronic hypercholesterolemia. CONCLUSIONS: There is a strong effect of fetal programming on the development of atherosclerosis in the apoE mouse model.

Conservative management of preterm premature rupture of membranes between 18 and 23 weeks of gestation--maternal and neonatal outcome.

OBJECTIVE: To evaluate the maternal and neonatal outcome of pregnancies after preterm premature rupture of membranes (PPROM) between 18 and 23 weeks of gestation. STUDY DESIGN: We performed a retrospective analysis of all deliveries at the University of Miami/Jackson Memorial Hospital after PPROM between 18 and 23 weeks of gestation from January 1997 to December 1999. All patients who delivered within 12 h of rupture of membranes were excluded. We further analyzed the data by dividing the patients into three groups based on the gestational age at which PPROM occurred as follows: (1) 18-19 weeks, (2) 20-21 weeks and (3) 22-23 weeks. For statistical analysis we combined two groups 18-19 weeks and 20-21 weeks. RESULTS: A total of 66 singleton pregnancies were included in our study. Median overall latency period until delivery was 62 h (range 12-654) with significantly prolonged latency at 22-23 weeks gestation in comparison to earlier gestation. Maternal complications were chorioamnionitis (n=19), placental abruption (n=3), retained placenta (n=6) and postpartum hemorrhage (n=5). Twenty fetuses were born alive (none between 18 and 19 weeks, 2 between 20 and 21 weeks and 18 between 22 and 23 weeks). These infants remained in the nursery between 1 and 555 days (median 106 days). A total of 12 infants were discharged home alive (1 between 20 and 21 weeks, 11 between 22 and 23 weeks). All surviving infants suffered at least one major neonatal complication. CONCLUSION: Conservative management of PPROM prior to 21 weeks of gestation was associated with very poor pregnancy outcome in our study. Although survival improved significantly after 22 weeks, all infants suffered major neonatal morbidity.

EP3-2 receptor mRNA expression is reduced and EP3-6 receptor mRNA expression is increased in gravid human myometrium.

OBJECTIVE: To assess relative expression levels of mRNA for EP3 isoforms EP3-2, EP3-3, and EP3-6 in human myometrium in various physiologic states. METHODS: Using semiquantitative reverse transcriptase-polymerase chain reaction, we analyzed myometrial samples from 46 women (ten menopausal, ten nongravid premenopausal, 19 gravidas, seven premenopausal misoprostol-treated nongravid women) for the specific expression of mRNA messages for the EP3 receptor isoforms EP3-2, EP3-3, and EP3-6. RESULTS: We found that the expression of EP3-2 was significantly lower in gravid than nongravid myometrium (P < .0001). Levels of the EP3-6 message were higher in gravid samples than in nongravid specimens (P < .02). EP3-3 mRNA was present in higher levels in menopausal samples compared with the other groups. CONCLUSIONS: The selective fluctuation of mRNA expression of the different EP3 isoforms suggests the possibility of an important regulatory role for these receptors in myometrial contractility. Additional studies are necessary to evaluate the exact mechanism of action of EP3 receptor isoforms in human myometrium.

Premature labor in a women with perforating appendicitis at 36 weeks of gestation. A case report.

BACKGROUND: Acute appendicitis during pregnancy is a serious complication because of the difficult diagnosis and increased perinatal morbidity and mortality. CASE: A 29-year-old woman underwent cesarean section and an appendectomy because of clinical symptoms of an acute abdomen and fetal distress. CONCLUSION: Acute appendicitis in pregnancy is rare but requires special attention to maternal and fetal morbidity and mortality. In this case, acute appendicitis and peritonitis were associated with uterine contractions and fetal distress. How extrauterine infections may mediate uterine contractions and fetal distress remains unsolved.

Pedigree analysis and descriptive investigation of three classic phenotypes associated with Holt-Oram syndrome.

OBJECTIVE: To determine the frequency of sporadic and familial cases of three classic phenotypes associated with Holt-Oran syndrome (HOS). STUDY DESIGN: We determined the frequency of sporadic and familial cases based on the 179 patients with HOS reported in the literature. RESULTS: Clinically, there are three variations of HOS: affected individuals may have only skeletal anomalies (27.4%), only cardiac defects (3.9%) or both (68.7%). Of the 179 affected individuals, 17.3% had sporadic and 82.7% had familial disease. CONCLUSION: The equal distribution between the sexes (female 53%, male 47%) indicates that HOS is transmitted as an autosomal dominant trait. In contrast to familial cases, cardiac involvement alone was not reported in any of the sporadic cases. When a cardiac malformation is diagnosed, the family members of the affected individual should be carefully screened for Holt-Oram syndrome.

Conservative management of cervical ectopic pregnancy.

OBJECTIVE: To evaluate the safety and efficacy of a minimally invasive approach in the management of cervical ectopic pregnancies. DESIGN: Retrospective case series. SETTING: University tertiary care hospital. PATIENT(S): Twenty-four women diagnosed with cervical ectopic pregnancy managed conservatively. INTERVENTION(S): Systemic methotrexate alone or combined with ultrasound-guided fetal intracardiac injection of potassium chloride. MAIN OUTCOME MEASURE(S): Reduction in hysterectomy rate, incidence of serious complications, and necessity for further intervention. RESULT(S): Conservative management of cervical ectopic pregnancy was successful in preventing the need for hysterectomy in all patients in our study. In two patients with a heterotopic gestation the intrauterine pregnancy could successfully be salvaged. Four patients experienced morbidity that required additional interventions. CONCLUSION(S): Most cervical ectopic pregnancies can be safely managed in a minimally invasive manner.

Hepatitis C in pregnancy.

Hepatitis C is the most common cause of chronic liver disease and liver transplantation, with 25,000 cases reported in the United States per year. By blood product screening, transfusion-related viral transmission has been virtually eliminated, and maternal fetal transmission is now one of the most important modes of transmission. Hepatitis C virus (HCV) infection is blood borne but only 25% of the infected pregnant women indicate a history of blood products transfusion or intravenous drug use. HCV transmission is 2- to 4-fold higher in women coinfected with HIV. Although cesarean delivery has not been shown to decrease perinatal transmission, it may have benefits in women with viremia at the time of delivery. During pregnancy, treatment of HCV is contraindicated, even though perinatal transmission is associated with a higher incidence of chronic liver disease. This review gives an update on the disease agent, risk factors, modes of transmission, diagnosis, treatment modalities, and perinatal issues that require further evaluation.

Expression of the oxytocin and V1a vasopressin receptors in human myometrium in differing physiologic states and following misoprostol administration.

OBJECTIVE: To assess relative expression levels of mRNA for the oxytocin receptor (OTR) and the V1a vasopressin receptor (V1aR) in human myometrium in various physiologic states and to determine if misoprostol exposure affects the expression of mRNA for these receptors. STUDY DESIGN: Using semiquantitative reverse transcription-polymerase chain reaction, we analyzed myometrial samples from 37 women (10 menopausal, 10 nongravid premenopausal, 10 gravidae, 7 premenopausal misoprostol-treated nongravid women) for the specific expression of mRNA messages for OTR and V1aR. The presence of the OTR and V1aR protein was confirmed by immunohistochemistry. RESULTS: We found that the expression of OTR was significantly higher in gravid compared to premenopausal nongravid (p < 0.0001), misoprostol-treated (p < 0.001) and menopausal myometrium (p < 0.0001). Differences in V1aR expression were not statistically significant among the four study groups. CONCLUSION: The expression of OTR mRNA in myometrium is markedly increased during late gestation. V1aR expression is present in all physiologic states, and does not appear to be altered by the presence or absence of labor. Misoprostol administration does not appear to have an effect on OTR and V1aR mRNA receptor expression.

FGL2 prothrombinase messenger RNA expression in gravid and nongravid human myometrium.

OBJECTIVE: Thrombin is a potent uterotonic agent that may play an important role in human parturition. FGL2 is a prothrombinase that cleaves prothrombin to thrombin. The purpose of this study was to determine FGL2 messenger RNA expression in human myometrium and to assess its relationship to the expression of EP3-6 prostaglandin receptor and inducible nitric oxide synthase. STUDY DESIGN: Myometrium was obtained from gravid women who underwent cesarean delivery (n = 19), from premenopausal (n = 10) and menopausal (n = 10) women who underwent hysterectomy, and from nonpregnant women who received 200 mg of misoprostol vaginally 12 hours before hysterectomy (n = 8). FGL2 messenger RNA expression was determined with the use of semiquantitative polymerase chain reaction and was compared with previously determined messenger RNA expression levels for EP3-6 and inducible nitric oxide synthase for the same samples. Statistical analysis was performed with the use of independent t test, Fisher exact test, analysis of variance, and linear regression, where appropriate. RESULTS: All samples that were analyzed contained demonstrable quantities of FGL2 messenger RNA. The highest FGL2 expression was found in gravid women, followed by women who were treated with misoprostol, by premenopausal nonpregnant women, and by menopausal women (P <.0001, analysis of variance). Significantly higher levels of FGL2 expression were found in the gravid women compared with the women who were treated with misoprostol (P <.001), the premenopausal nonpregnant women (P <.001), and the menopausal women (P <.0001). FGL2 messenger RNA expression correlated with EP3-6 and inducible nitric oxide synthase expression in all samples combined (r = 0.55, P <.0001; and r = 0.67, P <.001, respectively). CONCLUSION: The expression of FGL2 messenger RNA is increased in gravid myometrium compared with nonpregnant samples. Its expression significantly correlates to EP3-6 and inducible nitric oxide synthase expression. FGL2 prothrombinase expression may mediate the role of thrombin in human parturition.

The expression of EP3-6 and inducible nitric oxide synthase messenger RNA are correlated in pregnant and misoprostol-treated but not in nongravid or menopausal myometrium.

OBJECTIVE: Our purpose was to investigate the expression level of inducible nitric oxide synthase (iNOS) in nongravid and gravid human myometrium and assess its relation to the expression of EP3 prostaglandin receptor isoforms. STUDY DESIGN: Myometrial tissue from a cohort of gravid, nongravid, and menopausal subjects and from nongravid subjects exposed to misoprostol was obtained and analyzed for iNOS messenger RNA (mRNA) expression and compared with previously determined mRNA levels for the EP3-6 prostaglandin receptor from the same samples by means of semiquantitative polymerase chain reaction. RESULTS: Significantly higher levels of iNOS mRNA expression were found in the gravid compared with premenopausal nongravid (P <.02) and menopausal (P <.05,) samples. Linear regression analysis of iNOS versus EP3-6 expression showed a positive correlation between all studied samples (n = 47, P <.0001, r = 0.815). Among individual groups, a significant linear correlation was found only in pregnant (n = 10, P <.0001, r = 0.785) and misoprostol-exposed (n = 7, P =.0256, r = 0.815) subjects. No correlation between iNOS and EP3-6 mRNA levels was noted in the nongravid premenopausal groups (n = 10, P =.205, r = 0.350), although a nonsignificant trend was found for the menopausal group (n = 10, P =.0535, r = 0.624). When the data from pregnant patients were stratified, both laboring and nonlaboring women displayed the observed correlation (n = 6, P <.0001, r = 0.993; and n = 13, P =.008, r = 0.697, respectively). CONCLUSION: iNOS and EP3-6 expression are strongly correlated in gravid and misoprostol-treated, nongravid myometrium.