Nearly half of all severe fetal anomalies can be detected by first-trimester screening in experts' hands.

Objective To evaluate the detection rate of severe fetal anomalies at the first-trimester screening (FTS) and, vice versa, to evaluate the follow-up of pathological results at FTS at the time of mid-trimester screening (MTS) and throughout pregnancy and delivery in a partially selected population of low-risk pregnancies. Methods We conducted a prospective study on the detection of severe fetal anomalies at routine FTS in 9891 pregnant women with 10,294 fetuses between 11 + 0 and 13 + 6 weeks of gestation. The findings of FTS were compared to the results of MTS and pregnancy and neonatal outcomes. Only cases with severe fetal anomalies were taken for statistical analysis in this study. Results There were 232 cases of fetal anomaly altogether. At the time of FTS, sonographic anomalies were diagnosed in 113 cases and further ultrasound controls arranged. In four cases, fetal anomaly was not confirmed by MTS; in the remaining 109 cases, the sonographic anomaly seen at FTS was confirmed at MTS and in the course of pregnancy with a resulting sensitivity for fetal malformation at FTS of 47.8%, a specificity of 99.96%, a positive predictive value of 96.5% and a negative predictive value of 98.8%. Conclusion FTS can detect almost half of all severe fetal anomalies at an early stage of pregnancy with positive predictive values of 90% and more. Sensitivities varied depending on the organ system and reached the highest figures for anomalies of the heart, the abdomen, the spine and the skeletal system.

No increased bleeding events with continuation of oral anticoagulation therapy for patients undergoing cardiac device procedure.

BACKGROUND: Switching warfarin for heparin has been a practice for managing periprocedural anticoagulation in high-risk patients undergoing device-related procedures. We sought to investigate whether continuation of warfarin sodium therapy without heparin bridging is safe and, when it is continued, the optimal international normalized ratio (INR) without increased bleeding risk at time of device-related procedure. METHODS AND RESULTS: We retrospectively studied 766 consecutive patients taking warfarin long term who underwent device-related procedures. Patients were grouped by treatment: discontinued warfarin (-warfarin, n = 243), no interruption of warfarin (+warfarin, n = 324), and discontinued warfarin with heparin bridging (+heparin, n = 199). The study primary endpoint was systemic bleeding or formation of moderate or severe pocket hematoma within 30 days of the procedure. Thirty-one (4%) patients had bleeding events, including pocket hematoma in 29 patients. The bleeding events occurred more often for +heparin (7.0%) than -warfarin (2.1%) or +warfarin (3.7%, P = 0.029). For +warfarin group, INR of 2.0-2.5 at time of procedure did not increase bleeding risk compared with INR less than 1.5 (3.7% vs 3.4%; P = 0.72), but INR greater than 2.5 increased the bleeding risk (10.0% vs 3.4%; P = 0.029). Concomitant aspirin use with warfarin significantly increased bleeding risk than warfarin alone (5.6% vs 1.4%, P = 0.02). Median length of hospitalization was significantly shorter for +warfarin than +heparin (1 vs 6 days; P < 0.001). CONCLUSION: Continuation of oral anticoagulation therapy with an INR level of <2.5 does not impose increased risk of bleeding for device-related procedures, although precaution is necessary to avoid supratherapeutic anticoagulation levels.

Gene expression profiles of vascular smooth muscle show differential expression of mitogen-activated protein kinase pathways during captopril therapy of heart failure.

Congestive heart failure (CHF) is characterized by increased vascular tone and an impairment in nitric-oxide-mediated vasodilatation. We have demonstrated that the blunted response to nitric oxide is due, in part, to a reduction in the leucine-zipper-positive isoform of the myosin-targeting subunit (MYPT1) of myosin light-chain phosphatase. Additionally, we have shown that angiotensin-converting enzyme inhibition, but not afterload reduction with prazosin, preserves leucine-zipper-positive MYPT1 isoform expression in vascular smooth muscle cells and normalizes the sensitivity to cGMP-mediated vasodilatation. We therefore hypothesized that in CHF, growth regulators and cytokines downstream of the angiotensin II receptor are involved in modulating gene expression in vascular tissue. Rats were divided into control and captopril-treated groups following left coronary artery ligation. Gene expression profiles in the aorta and portal vein at baseline and 2 and 4 weeks after myocardial infarction (MI) were analyzed using microarray technology and quantitative real-time PCR. After MI, microarray analysis revealed differential mRNA expression of 21 genes in the aorta of captopril-treated rats 2 and 4 weeks after surgery when compared to gene expression profiles at baseline and without captopril therapy. Real-time PCR demonstrated that captopril suppressed the expression of protein kinases in the angiotensin-II-mediated mitogen-activated protein kinase signaling pathway, including Taok1 and Raf1. These data suggest that in CHF, captopril therapy modulates gene expression in vascular smooth muscle, and some of the beneficial effects of ACE inhibition may be due to differential gene expression in the vasculature.

Mechanism and outcomes of catheter ablation for ventricular tachycardia in adults with repaired congenital heart disease.

BACKGROUND: Repaired congenital heart disease (rCHD) is strongly associated with ventricular tachycardia (VT) as an important late cause of morbidity and mortality. Ventricular reentry most commonly includes anatomic isthmuses created during the repair procedures. OBJECTIVE: The purpose of this study was to analyze the long-term outcomes of catheter ablation, a commonly used standalone or adjunctive therapy, in a cohort of rCHD patients. METHODS: A retrospective analysis of 21 consecutive patients with rCHD (45.0 ± 3.0 years, 71.4% male) undergoing ablation for VT was performed. The primary composite outcome was defined as in-hospital arrhythmic death, out-of-hospital sudden cardiac death, or appropriate implantable cardioverter-defibrillator therapy. RESULTS: At initial electrophysiologic study, 14 patients (66.7%) had reentrant VT through an electroanatomic isthmus; the remaining 7 patients (33.3%) demonstrated focal VT. Isthmus-dependent reentry was identified as the mechanism for VT in 14 patients (66.7%), and conduction block was confirmed in 8 of these patients (57.1%). No patients with confirmed block developed VT recurrence. During long-term follow-up (33 ± 7 months), 20 of 21 patients (95.2%) had not reached the primary composite outcome. Three patients died of nonarrhythmic causes. CONCLUSION: Catheter-based VT ablation in patients with rCHD is associated with a low rate of VT recurrence. Focal VT was not uncommon in this cohort. If a reentrant mechanism is present, confirmation of conduction block across the isthmus is vital to prevent recurrence.

Anterior rectal wall excision for endometriosis using the circular stapler.

BACKGROUND: Endometriosis involving the rectum is rare but is associated with significant symptoms that are best relieved by resection of the involved segment of rectum. Resection necessitates either a segmental or anterior rectal wall excision with sutured closure. Application of a circular stapling device allows an alternative technique to resect endometriosis in this area. METHOD: Following laparoscopic ablation of endometriosis elsewhere in the pelvis, the rectum must be mobilized around disease present on the anterior rectal wall. This will involve lateral and anterior extraperitoneal rectal dissection; the latter dissection mobilizing the vagina from the rectum by a sufficient length necessary to allow imbrication of the diseased area. Insertion of a circular stapler per anus allows the diseased area to be imbricated into the stapler, resulting in simultaneous excision and closure of the anterior rectal wall. RESULTS: Thirty patients with anterior rectal wall endometriosis, estimated at <2 cm in diameter and not involving > one-third of the total circumference of the rectum, have undergone successful management using this technique. Morbidity occurred in four patients, with one patient requiring further surgery. CONCLUSIONS: Laparoscopic disc excision of deposits of endometriosis involving the anterior rectal wall can be safely performed utilizing the circular stapler without the need for open surgery, and with low morbidity.

Lipopolysaccharide binding protein in the early diagnosis of intraamniotic infection of pregnant women with premature rupture of the membranes.

AIMS: To investigate whether lipopolysaccharide binding protein (LBP) level is an early marker of intraamniotic infection in pregnant women with premature rupture of the membranes (PROM) and compare it to C-reactive protein (CRP). METHODS: Seventy-two pregnant women with PROM were included in the study if remained undelivered for more than 24 h. CRP and LBP concentrations were determined in 12-h-intervals and the last value before delivery was correlated with obstetrical data and placenta histology. RESULTS: LBP concentrations ranged from 1.6 to 48.7 microg/mL (median of 16 microg/mL) and CRP concentrations from 0.02 to 6.8 mg/dL (0.64 mg/dL). CRP was significantly elevated when full blown chorioamnionitis was proven by histology (P<0.01) and when the neonates had to be admitted to the intensive care unit because of suspected infection (P<0.05 mg/dL). There were significantly higher LBP levels when fetal tachycardia occurred (20.3 vs. 14.5 microg/mL, P<0.05) and when intraamniotic infection was diagnosed by histology (22.8 vs. 14.1 microg/mL, P<0.005), but the differences were too little to provide prognostic cut-off values. CONCLUSION: Increase of LBP and CRP levels after PROM seem to reflect intramniotic infection, but no cut-off values could be defined for the prediction of intraamniotic infection.

Decline of contractility during ischemia-reperfusion injury: actin glutathionylation and its effect on allosteric interaction with tropomyosin.

The severity and duration of ischemia-reperfusion injury is hypothesized to play an important role in the ability of the heart subsequently to recover contractility. Permeabilized trabeculae were prepared from a rat model of ischemia-reperfusion injury to examine the impact on force generation. Compared with the control perfused condition, the maximum force (F(max)) per cross-sectional area and the rate of tension redevelopment of Ca(2+)-activated trabeculae fell by 71% and 44%, respectively, during ischemia despite the availability of a high concentration of ATP. The reduction in F(max) with ischemia was accompanied by a decline in fiber stiffness, implying a drop in the absolute number of attached cross bridges. However, the declines during ischemia were largely recovered after reperfusion, leading to the hypothesis that intrinsic, reversible posttranslational modifications to proteins of the contractile filaments occur during ischemia-reperfusion injury. Examination of thin-filament proteins from ischemic or ischemia-reperfused hearts did not reveal proteolysis of troponin I or T. However, actin was found to be glutathionylated with ischemia. Light-scattering experiments demonstrated that glutathionylated G-actin did not polymerize as efficiently as native G-actin. Although tropomyosin accelerated the time course of native and glutathionylated G-actin polymerization, the polymerization of glutathionylated G-actin still lagged native G-actin at all concentrations of tropomyosin tested. Furthermore, cosedimentation experiments demonstrated that tropomyosin bound glutathionylated F-actin with significantly reduced cooperativity. Therefore, glutathionylated actin may be a novel contributor to the diverse set of posttranslational modifications that define the function of the contractile filaments during ischemia-reperfusion injury.

Captopril prevents myosin light chain phosphatase isoform switching to preserve normal cGMP-mediated vasodilatation.

Congestive heart failure (CHF) is characterized by abnormal vasoconstriction and an impairment in nitric oxide (NO)-mediated vasodilatation. We have previously demonstrated that the decrease in sensitivity to NO lies at least partially at the level of the smooth muscle and is due to a reduction in the relative expression of the leucine zipper positive (LZ(+)) isoform of the myosin targeting subunit (MYPT1) of myosin light chain phosphatase. We hypothesized that since the attenuated vasodilatory response to NO in CHF has been shown to be secondary to an increased activity of the renin-angiotensin system, angiotensin converting enzyme (ACE) inhibition could affect MYPT1 isoform expression. To test this hypothesis, a rat myocardial infarction (MI) model of CHF was used; following left coronary artery ligation, rats were divided into control and captopril-treated groups. A third group of rats was given prazosin for 4 weeks. In the untreated control group, left ventricular function (LVF) was reduced at 2 weeks post-MI and remained at this level. Captopril treatment attenuated the fall in LVF. In the control aorta and iliac artery, the expression of the LZ(+) MYPT1 isoform fell 44-52% between 2 and 4 weeks post-MI, whereas in animals treated with captopril, MYPT1 isoform expression did not change. A decrease in the sensitivity to cGMP-mediated smooth muscle relaxation occurred coincident with the decrease in LZ(+) MYPT1 expression. The change in LZ(+) MYPT1 expression was not due to the decrease in afterload, as prazosin therapy produced an improvement in LVF but did not increase the relative expression of LZ(+) MYPT1 isoform. These data suggest that ACE inhibition, unique from pure afterload reduction, prevents MYPT1 isoform switching, which would preserve normal flow, or NO-mediated vasodilatation.

Comparison of isosorbide mononitrate (Mono Mack) and misoprostol (Cytotec) for cervical ripening in the first trimester missed abortion.

OBJECTIVE: The objective of this study was to compare NO-donor isosorbide mononitrate to misoprostol, both applied as vaginal tablets for cervical ripening prior to first trimester curettage in patients with missed abortion. MATERIALS AND METHODS: Thirty women with missed abortion were assigned after a random list to be treated either with 200 microg gemeprost (Cytotec, Pfizer, Germany) or with 40 mg isosorbide mononitrate for cervical priming at least 3 h before curettage. Vaginal bleeding or the intracervical presence of products of conception was documented. The largest number of Hegar's dilator, which could be introduced without difficulty and the largest number of Hegar's dilator at which cervical dilation was performed and the ease of mechanical dilation was assessed. RESULTS: There were no significant differences in cervical ripeness before procedure nor in ease of dilation. In the misoprostol group, the cervical canal was more dilated before any procedure (median of Hegar's dilator 6 vs. 5) and after dilation (median of Hegar's dilator 11 vs. 10), although this difference was not significant. Vaginal bleeding occurred in two patients in each group. Products of conception were only found in the cervix of one patient of the misoprostol group. SYNOPSIS: Vaginal application of isosorbidemononitrate in cervical priming prior to curettage abortion is as effective as vaginal application of misoprostol.

Risk factors for fetal-to-maternal transfusion in Rh D-negative women--results of a prospective study on 942 pregnant women.

AIMS: To investigate the incidence of severe fetal-to-maternal transfusion after delivery and to identify risk factors. MATERIAL AND METHODS: In a prospective study at the Department of Obstetrics, Charité, Campus Virchow-Klinikum, Berlin, Germany, we analyzed the incidence of severe fetal-to-maternal transfusion (>10 ml) and fetal-to-maternal hemorrhage (>25 ml) in Rh D-negative pregnant women after delivery of Rh D-positive infants. 942 women were included in the study and Kleihauer-Betke tests were performed. The results were compared to perinatal data. RESULTS: Fetal-to-maternal hemorrhage occurred in 13 cases out of 942 (incidence of 1.3%) and severe fetal-to-maternal transfusion in 61 cases (6.5%). In all of the cases with fetal-to-maternal hemorrhage, mothers were compatible with their infants in ABO-system. The incidence of fetal-to-maternal transfusion and its severe form was significantly higher in twin pregnancies (7/21 cases and 5/21 cases respectively, 33.3% and 23.8%) than in singleton pregnancies (22.5%, and 5.9%, P<0.001). All other factors, such as maternal age, parity, ethnicity, mode of delivery, presentation, duration of first and second stage of labor, CTG, or Apgar score were not associated with an increased risk of severe fetal-to-maternal transfusion. CONCLUSIONS: Twin pregnancy is the only independent risk factor for severe fetal-to-maternal transfusion. ABO-incompatibility between mother and infant seems to be protective against Rh D-alloimmunization.