Boaz Weisz

Abstract: AIM: To assess the preferences of pregnant women regarding the type of assistance desired to alleviate the consequences of nausea and vomiting of pregnancy (NVP). METHODS: Women with NVP were asked to complete an online survey of 12 questions assessing the extent of NVP and the perspective on the importance of different healthcare professionals for their improvement. RESULTS: A total of 121 pregnant women completed the survey. The median maternal age was 29 years and the average gestational age was 12.4+/-7.6 weeks. Sixty-four of the women (52.9%) had NVP in their previous pregnancy, which resulted in an average of 14.6+/-21.1 lost days of paid work. NVP necessitated admission to the emergency room in 36 (29.7%). When asked to rate (max 4 points) which healthcare professional would provide the best assistance for NVP, the physician was rated as the most important (average score of 3.56/4), followed by dietician (3.40/4), nurse (3.05/4) and social worker/psychologist as least important (1.77/4). CONCLUSION: Our findings illustrate women's perspective on NVP. According to our online survey, women perceive medically- and nutritionally-based care as most useful, whereas psychosocial factors are perceived to be less useful despite playing a central role in NVP

Abstract: BACKGROUND: Fetal anaemia is a well-known complication of pregnancy, which might have an ominous effect on the course of pregnancy, labour and the child's development. OBJECTIVE: To assess the effect of the severity of fetal anaemia on the child's outcome. METHODS: A retrospective cohort study. Pregnancies treated by intrauterine transfusions for fetal anaemia at Sheba Medical Center (1996-2004) were divided into two groups: mild to moderate anaemia (fetal haematocrit >0.50 multiples of the median (MoM)) and severe anaemia (hydrops fetalis or fetal haematocrit < or =0.50 MoM). Data were retrieved from relevant obstetric and fetal medicine files. RESULTS: During the study period, 54 fetuses were treated by 154 (median 3; range 1-7) intrauterine transfusions for red cell alloimmunisation. The sensitising antigen was D in 70% of cases; 18/54 patients were sensitised to more than one antigen. Thirty-three of the 54 fetuses (61%) were in the severely anaemic category (haematocrit range 3-20%); six were hydropic. Twenty-one of the 54 fetuses (39%) were in the mild-moderate anaemic category (haematocrit range 20-37%). On prenatal evaluation, there were no sonographic markers of central nervous system abnormalities or intraventricular haemorrhage. There were no differences in the neonatal outcome between the two groups. Developmental outcome was available in 14/18 (78%) mild-moderate cases and 26/29 (89%) severe cases. There were no significant differences in motor development score, percentage of abnormal cognitive development, and percentage of children needing supportive therapy between the mild-moderate and severe cases. CONCLUSION: Neonatal and developmental outcome of fetuses treated for severe anaemia is comparable to cases of mild anaemia

Abstract:

Abstract: OBJECTIVE: To evaluate the role of various new models of 3- and 4-dimensional (3D and 4D) ultrasound (US) applications in prenatal assessment of fetal cardiac anomalies. METHODS: Volume data sets of 81 fetuses with fetal cardiac anomalies, as previously diagnosed by 2D US, were acquired by 3D and cine 4D using spatiotemporal image correlation (STIC) software. Various additional rendering tools were applied. Color, power, high definition Doppler and B-flow were added to the volumes acquired. A retrospective offline analysis of the cardiac defects was performed. RESULTS: The mean gestational age at diagnosis was 24 weeks (range 13-38); 128 anomalies were detected and were classified into the following categories: I, Situs anomalies in 8 cases; II, abnormal four-chamber view in 63 cases; III, outflows tract anomalies in 27 cases; IV, arches anomalies in 21 cases; and V, veins anomalies in 9 cases. Rendering tools differed in each groups of anomalies. CONCLUSIONS: Fetal cardiac anomalies can be evaluated adequately by the information gained by 3D and 4D volumes obtained by STIC. Since no single module is sufficiently accurate for the diagnosis of all cardiac anomalies, each of the cardiac anomaly categories requires different and appropriate module of visualization

Abstract: OBJECTIVE: To study three- (3D) and four-dimensional (4D) ultrasound applications for the evaluation of fetal thoracic anomalies. METHODS: Volume datasets of 23 fetuses with thoracic anomalies were acquired with static 3D and cine 4D ultrasound, i.e. spatiotemporal image correlation (STIC) mode. The volumes were analyzed and displayed by multiplanar and tomographic ultrasound imaging (TUI) modes and static volume contrast imaging (VCI). Color Doppler was added to the volumes acquired, and various rendering modes were used to display the volume datasets. RESULTS: The mean gestational age at evaluation was 22 (range, 14-34) weeks. The anomalies were identified as: diaphragmatic hernia (n = 5), lung dysplasia (n = 11), skeletal dysplasia with small thorax/thanatophoric dysplasia (n = 2), abnormal situs (n = 2), hydrothorax (n = 2) and esophageal atresia (n = 1). The TUI mode achieved optimal display of the thorax, thereby aiding the diagnosis of diaphragmatic hernia and lung dysplasia. In right diaphragmatic hernias, the VCI mode proved invaluable as it distinguished liver from lung tissue. High-definition color Doppler with glass-body rendering significantly contributed to the detection of abnormal vascularization in lung dysplasia. Maximal transparent mode with a transvaginal transducer provided accurate diagnosis of skeletal dysplasia in the first trimester. Situs abnormalities were best viewed with a minimal transparent mode, in which abnormal organs and positions of vessels were clearly identified. Pleuroamniotic shunt localization was monitored precisely by 3D in a fetus with hydrothorax, and inversion mode added important information regarding the size of an esophageal pouch in a fetus with esophageal atresia. CONCLUSION: The 3D-4D technique is a novel, useful sonographic tool for evaluating the fetal thorax. It enhances precise diagnosis and provides better spatial visualization of the anomalies involved

Abstract: OBJECTIVES: To evaluate the prevalence of fetal isolated short femur in a cohort of women screened for Down syndrome by the integrated test, and to compare the outcome of fetuses with isolated short femur in the mid-trimester with that of fetuses with normal femur length (controls). METHODS: This was a retrospective cohort study of 1262 women booked for antenatal care and delivery at University College London Hospital. All women had integrated testing in the late first and early second trimesters and a detailed anomaly scan in the mid-trimester. All scan reports, screening results and neonatal data were analyzed statistically. RESULTS: The fetal femur was short (< 5(th) percentile) in 5.1% of patients and 4.7% had isolated short femur. In pregnancies with isolated short femur, the birth weight was significantly lower and there were higher rates of small-for-gestational age (SGA) and low birth weight (LBW) infants, compared with controls (P < 0.01). The odds ratios for SGA and LBW in pregnancies with isolated short femur were 3.0 (95% CI, 1.5-5.9) and 2.60 (95% CI, 1.1-6.2), respectively. Isolated short femur was associated significantly with low levels of pregnancy-associated plasma protein-A (P = 0.001). CONCLUSIONS: Isolated short femur in the mid-trimester fetus is associated with fetal growth restriction and SGA. In the context of normal Down syndrome screening and a normal anomaly scan, this marker should be regarded as a predictor for SGA, and fetal growth should be monitored during these pregnancies

Abstract: OBJECTIVE: To survey the effect of tight glycemic control by insulin pumps, of pre-gestational Type 1 diabetic women on pregnancy outcome. METHODS: Twelve consecutive Type 1, insulin pump treated, diabetic patients followed in the high risk maternal - fetal clinic were ascertained. Data regarding glucose control was assessed and correlated with pregnancy outcome. RESULTS: A total of 14 deliveries (10 singleton) were assessed. There were no miscarriages, one baby that was born with a ventricular septal defect (VSD). Glycemic control was within the acceptable guidelines. HbA1c (%) by trimesters: 6.5 +/- 0.9, 5.9 +/- 0.7, 5.8 +/- 0.6 and average glucose (mg/dL) 121.0 +/- 15.2, 114.8 +/- 13.2, 116.0 +/- 21.1. Average birth weight was 3312.1 +/- 750.2 g with five babies (35%) weighting over 4.0 kg at birth. Birth weight was significantly correlated with HbA1c at the first trimester, mean glucose at trimester 1 and 2, and maternal weight at delivery (r = 0.74, p = 0.045; r = 0.72, p = 0.051; r = 0.74, p = 0.046; r = 0.74, p = 0.04, respectively). CONCLUSIONS: Our study of a limited number of patients suggest that women with pre-gestational diabetes obtaining acceptable glycemic goals with insulin pump therapy have increased risk of macrosomia. Current glycemic goals and therapies in treating pre-gestational diabetic patients therefore might not be sufficient to normalise pregnancy outcomes in of women with pre-gestational diabetes

Abstract: We have evaluated a cohort of women booked for antenatal care at University College London Hospitals. The uptake of screening was 64.4% and was significantly higher (73 versus 46%) in women who booked before 14 weeks. Of the women who booked before 14 weeks, 96.8% opted for the integrated test (IT). Overall, 5.3% failed to attend for the second blood test. The false-positive rate in the women who had the IT was 2.9%. All 11 cases of Down syndrome were detected prenatally. Our study is the first to evaluate implementation of the IT into routine clinical practice

Abstract: OBJECTIVE: To describe the prenatal diagnosis and outcome of fetal cardiomyopathy (CM). METHODS: The charts, photographs and videotapes of all fetuses with CM, who were assessed during pregnancy at two referral centers, were reviewed. RESULTS: The diagnosis of CM was established in 12 fetuses. All had structurally normal hearts, and all cases were diagnosed after 23 weeks of gestation, following normal early fetal echocardiogram. Three clusters of fetal CM appeared: Familial--two sib fetuses of a mother, who is a second generation of CM. Both had dilated CM and pathological findings were consistent with the diagnosis of endocardial fibroelastosis. Secondary--CM that was induced by another factor. Idiopathic--six cases of CM without an underlying specific etiology. Three women elected to terminate their pregnancy. Among the nine who delivered, four had a favorable outcome with normal cardiac function at the age of 1 month, in which three belonged to the secondary category, and five cases were complicated by fetal/infant death. CONCLUSIONS: CM may develop during fetal life and might be diagnosed by prenatal echocardiography. Normal cardiac findings in a midtrimester fetus do not exclude subsequent development of CM. Detailed prenatal sonographic examination may aid in determining the neonatal outcome

Abstract: OBJECTIVE: Emerging evidence indicates that chorioamnionitis is associated with a significant decrease in thymic size at birth in very low birth weight (VLBW) preterm infants. The aim of this study was to determine whether decreased fetal thymus size is associated with histological or clinical chorioamnionitis in patients with preterm premature rupture of membranes (PROM). METHODS: Twenty-one patients between 24 and 35 weeks of gestation with preterm PROM were included. Serial ultrasound examinations were performed during the latency period, and measurements of the fetal thymus size were obtained. Small thymus was defined as a thymus perimeter < or = 5th percentile according to a fetal thymus nomogram, which was based on measurements of 403 fetuses. Diagnosis of chorioamnionitis was made using neonatal clinical parameters and histological examinations of the placentas. RESULTS: In our study 13 patients presented with thymus size below the 5th percentile. Among the 13 patients with small thymus, nine (69%) had clinical or histological findings consistent with the diagnosis of chorioamnionitis. All eight women with a normal-sized thymus had no evidence of clinical or histological chorioamnionitis. Fetal thymus perimeter < or = 5th percentile yielded a sensitivity of 100%, specificity of 66.7%, a positive predictive value of 69% and a negative predictive value of 100% for identifying chorioamnionitis in patients with preterm PROM. CONCLUSIONS: Fetal thymus size is decreased in women with preterm PROM and chorioamnionitis. Measurement of the fetal thymus might allow an early diagnosis of chorioamnionitis in cases of preterm PROM. Normal thymus size might be used to rule out latent intrauterine infection

Abstract: OBJECTIVE: To evaluate the incidence and significance of fetal anomalies and "soft markers" after screening for Down syndrome using the integrated test. METHODS: This study is a retrospective study of 2,332 women at University College London Hospitals, United Kingdom. All women were screened for Down syndrome by the integrated test. Subsequently, a detailed anomaly scan was performed. All scan reports and screening results were analyzed statistically using SPSS 11.0 software. RESULTS: Sixty-eight (2.9%) patients were categorized as high risk. There were 12 cases affected by Down syndrome, 10 (10 of 68) in the high-risk group and two (two of 2,264) in the low-risk group. Soft markers or structural anomalies were found in 13.0% of the low-risk group, in 29.4% of the high-risk group, and in 50% of the fetuses affected by Down syndrome. Multiplying the likelihood ratio of each marker with the risk of Down syndrome from the integrated test reduced the false-positive rate of the integrated test from 2.5% to 1.8%, but was accompanied by a reduction in the detection rate from 83% to 75%. CONCLUSION: Absence of structural anomalies or markers should not prevent offering karyotyping to women in the high-risk group, because this would result in a significant reduction in the detection rate of Down syndrome. Women screened as low risk by the integrated test who have isolated soft markers should not be offered an amniocentesis

Abstract: Since the introduction of antenatal serum screening for Down's syndrome (DS) more than two decades ago, several screening approaches have been utilized in routine clinical practice. The current DS screening strategies involve mid-trimester serum biochemistry tests, first trimester tests combining sonographic markers and serum biochemistry and integration of first and second trimester markers. In this review, we evaluate the performance of DS screening strategies according to the Serum, Urine and Ultrasound Screening Study (SURUSS), the First and Second Trimester Evaluation of Risks (FASTER) Trial and the Serum Biochemistry and Fetal Nuchal Translucency Screening (BUN) Study. We also evaluate the performance of first trimester screening in studies and meta-analyses by other groups. Specific issues related to assisted reproduction technology (ART) pregnancies are also addressed in this review

Abstract: The twin-twin transfusion syndrome (TTTS) complicates approximately 15% of monochorionic twin pregnancies. Severe TTTS is associated with poor neonatal outcome and a relatively high rate of neurological abnormalities. Some studies have suggested this outcome to be more severe in cases treated by amnioreduction. In this paper we present a hypothesis that radical amnioreduction performed after 24 weeks of gestation might cause a shift of blood from the fetus into the placenta. This could explain some of the severe neurological outcomes, such as hypoxic ischemic brain damage, seen in these cases

Abstract: OBJECTIVE: To validate the use of the homeostasis model assessment (HOMA) for measurement of insulin sensitivity in obese women during gestation and the postpartum period. DESIGN: Three consecutive measurements of insulin resistance (IR) were performed during and after pregnancy to compare the homeostasis model assessment insulin sensitivity index (HOMA-IR) to glucose utilization rates obtained during hyperinsulinaemic euglycaemic clamps (G(Rd)). PATIENTS: Six obese women (mean second trimester BMI = 30.4 kg/m(2)) with normal glucose tolerance were studied during the second and third trimesters of pregnancy and once in the postpartum period. Thus, there were a total of 18 measurements for analysis. RESULTS: Correlations between the rate of glucose disappearance (G(Rd)) (the gold standard) and the HOMA-derived metabolic parameters of insulin sensitivity were significant, with a multiple R(2) of 43.5% (P = 0.003). However, when controlling for variations between patients using dummy variables, we observed that one patient differed from the other five in the relationship between G(Rd) and HOMA-IR. Applying this regression we obtained a R(2) of 72.6% (P < 0.001). When the regression constant was omitted, we observed that the individual trends during pregnancy and postpartum in two patients differed statistically from the other patients between the two assessments, and we obtained a multiple R(2) of 97.3% (< 0.001). CONCLUSIONS: HOMA estimation of insulin resistance is appropriate for use during both the second and third trimesters of pregnancy and postpartum in obese women with normal glucose tolerance. It lacks sensitivity for the evaluation of individuals, where more precise measures of insulin sensitivity should be utilized

Abstract: Targeting gene therapy vectors to the fetal intestinal tract could provide a novel means toward prevention of the early postnatal intestinal pathology of cystic fibrosis and other conditions, such as congenital enteropathy, that cause intestinal failure. Among these conditions, cystic fibrosis is by far the most common lethal genetic disease. It is caused by a functional absence or deficiency of the cystic fibrosis transmembrane conductance regulator and manifests in the gut as meconium ileus. Prenatal treatment of genetic disease may avoid early-onset tissue damage and immune sensitization, and may target cells that are less accessible in the adult. We investigated gene transfer to the fetal gut, using a minimally invasive injection technique. First-generation replication-deficient adenoviral vectors encoding the beta-galactosidase gene and transduction-enhancing agents were injected into the stomach of early-gestation fetal sheep (n = 8, 60 days of gestation; term, 145 days) under ultrasound guidance. Reporter gene expression was observed 2 days after injection in the villi of the gastrointestinal epithelia after 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside staining and beta-galactosidase immunohistochemistry of fetal tissues. Expression of beta-galactosidase, as measured by enzyme-linked immunosorbent assay, was enhanced after pretreatment of the fetal gut with sodium caprate, which opens tight junctions, and after adenovirus complexation with DEAE-dextran, which confers a positive charge to the virus. Instillation of the fluorocarbon perflubron after virus delivery resulted in tissue transduction from the fetal stomach to the colon. Using a clinically relevant technique, we have demonstrated widespread gene transfer to the fetal gastrointestinal epithelia

Abstract: OBJECTIVE: The purpose of this study was to evaluate noninvasive management of alloimmune thrombocytopenia that included only the blind administration of immunoglobulin. STUDY DESIGN: Seventeen women with 30 pregnancies that were at risk of neonatal alloimmune thrombocytopenia were included. Except for 6 cases, in which the women refused treatment, 24 pregnancies were managed by the weekly administration of intravenous immunoglobulin without monitoring platelet count. RESULTS: The mean platelet count at birth after intravenous immunoglobulin treatment was 118,000/microL, compared with 25,000/microL among the 17 first affected infants and 24,000/microL among the 6 infants whose mothers refused treatment (P < .05). Only 8% of the treated fetuses had platelet counts of <30,000/microL at birth, compared with 70% of the untreated infants (P < .05). None of the treated and nontreated fetuses had an intracranial hemorrhage. CONCLUSION: Noninvasive management of alloimmune thrombocytopenia that consists of only immunoglobulin administration is highly effective and seems safe in women without a history of fetal/neonatal intracranial hemorrhage

Abstract: OBJECTIVES: To access the fetal sheep trachea by ultrasound-guided transthoracic injection in order to deliver gene therapy vectors or occlude the trachea with a detachable balloon. METHODS: Fetal sheep were operated on at a mean gestational age of 102 (range, 81-116) days (term = 145 days). Under ultrasound guidance, either a 20-G spinal (for vector delivery) or a 16-G Kellett (for placement of an occlusive balloon) needle was inserted via the fetal thorax into the fetal trachea. RESULTS: Using the 20-G spinal needle the trachea was accessed successfully in 33/36 fetuses, with 97% survival. Failure to inject was related to fetal position and gestational age. Blood vessel damage causing significant morbidity occurred in two fetuses (6%). Tracheal occlusion was achieved by puncturing the trachea with the 16-G needle and advancing an endoluminal balloon in three out of five attempts in a mean time of 17 (range, 16-19) min, with 100% survival. In one case, the balloon became sited within the accessory lobe bronchus and was not inflated. At postmortem examination 21 days later, all balloons remained inflated and occluded the trachea, and the lung-to-body weight ratio and airways morphometric indices were consistent with relative pulmonary hyperplasia in the obstructed lungs. CONCLUSIONS: Ultrasound-guided transthoracic tracheal puncture is a reliable technique in fetal sheep, with low morbidity and mortality. Using this technique, a detachable endotracheal balloon can be placed to provoke pulmonary growth. Advances in needle design and balloon size may improve the success rate

Abstract: OBJECTIVE: To compare the rate of adverse perinatal outcomes among women with gestational diabetes mellitus (GDM), monitored by 1 versus 2 hour-postprandial glucose (PPG) measurements. METHODS: A total of 112 women diagnosed with GDM, by the criteria of Carpenter-Coustan, were included in the study population. Women were recruited from two different treatment settings, but were managed by the same team of health-care professionals using a standardized protocol. Allocation to treatment group was based on treatment setting. Glucose levels were measured fasting, and either 1 hour (1-hour monitoring group-target values <140 mg/dl) or 2 hours (2-hour monitoring group-target values <120 mg/dl) postprandially. Demographic data and perinatal outcomes were collected from their medical records. RESULTS: In all, 66 women were assigned to 1-hour monitoring group (1 h-PPG) and 46 women to 2-hour monitoring group (2 h-PPG). There were no differences in parity, family history of diabetes, rate of GDM in previous pregnancies, weight gain, pregestational BMI and 50-g-glucose challenge test (GCT) and 100-g oral glucose challenge test (OGTT) results. As expected, there was a significant difference in mean blood glucose levels between the two groups (108.1+/-19.2 and 94.9+/-21.2 mg/dl, 1- and 2 hours, respectively, p<0.0001); however, HbA1C levels were similar in the two groups. Perinatal outcomes were defined as gestational week at delivery; fetal weight (3325+/-471 vs 3309+/-608 g, respectively) and percentile (47.2+/-27 vs 49.6+/-30, respectively), and were similar for both groups. Insulin therapy was initiated more frequently in 2-hour monitoring group (28 and 40% of women in groups 1 and 2, respectively; p<0.05). Rates of macrosomia (7.5 versus 10.6%), large for gestational age (7.4 versus 15.2%), and delivery by cesarean section (24 versus 30%) were increased in group 2 (2 h-PPG) but these differences did not reach statistical significance. CONCLUSION: These data suggest that diet control in women with GDM managed by 1-hour PPG measurements is associated with a decreased rate of insulin therapy. However, neonatal and obstetrical outcomes are not determined by the timing of their glucose determinations

Abstract: The purpose of this study was to assess a possible correlation between insulin resistance and uric acid levels in gestational hypertension (GH) and preeclampsia. Fourteen pregnant, nondiabetic women with either GH (n = 7) or preeclampsia (n = 7) and nine pregnant healthy controls in the third trimester were enrolled onto the study. Fasting serum was collected and insulin sensitivity was determined by Homeostasis Model Assessment based on the algorithm developed by Turner and colleagues. Serum samples were also analyzed for creatinine and uric acid levels. Insulin resistance and uric acid levels were compared between hypertensive and control pregnant women, and the association between these two variables was calculated. There were no significant differences in mean age, weight, body mass index, and glucose challenge test between all hypertensive patients and controls. Significant differences were revealed in insulin sensitivity between hypertensive and nonhypertensive pregnant women (45 +/- 31.2% vs. 79.7 +/- 33%; p = 0.018). In our study, uric acid levels were not significantly higher for hypertensive patients (5.46 +/- 0.85 vs. 4.53 +/- 1.4 mg/dL in controls; p = 0.06). The elevated serum uric acid levels were highly correlated to insulin resistance in patients with GH. In contrast, uric acid levels did not correlate with insulin sensitivity in patients with preeclampsia and controls. Insulin resistance is associated with the elevated uric acid levels found in nonproteinuric gestational hypertensive disease

Abstract: Most published data on the detection of fetal anomalies at 11-14 weeks are from specialized centres with considerable experience in fetal anomaly scanning. However, there is still limited information on the feasibility and limitations of the screening of these anomalies compared with the now classical mid-gestation screening. This review indicates that overall, the detection rate of fetal anomalies at 11-14 weeks is 44% compared with 74% by the mid-pregnancy scan. Major abnormalities of the fetal head, abdominal wall and urinary tract, and of the umbilical cord and placenta, can be reliably detected at 10-11 weeks of gestation. Detection of other anomalies such as spina bifida, diaphragmatic hernia or heart defects is limited before 13 weeks of gestation. So far it cannot be stated that routine first trimester screening can be used on a large scale to evaluate the fetal spine and heart in the general population. In particular, in screening for congenital heart defects, the ability to perform a full cardiac examination increases from 20% at 11 weeks to 92% at 13 weeks. The early prenatal diagnosis of these anomalies may be improved by screening at 13-14 weeks rather than during the first trimester

Abstract: PURPOSE: To investigate the efficacy of gonadotrophin-releasing hormone (GnRH) antagonist supplementation during natural cycles in poor responders undergoing IVF-ET treatment. METHODS: We retrospectively evaluated 540 cycles of 433 suitable patients who were divided by treatment protocol into modified natural, antagonist, and long agonist groups. There were 52 modified natural cycles with GnRH antagonist supplementation, 200 stimulated cycles with GnRH antagonist, and 288 long GnRH agonist cycles. Cycle characteristics and treatment outcomes were compared between the groups. RESULTS: The mean number of oocytes retrieved in the modified natural group was significantly lower than in the stimulated antagonist and long agonist groups (1.4 +/- 0.5 vs. 2.3 +/- 1.1 and 2.5 +/- 1.1, respectively, p < 0.05). The respective implantation and pregnancy rates were 10% and 14.3%, 6.75% and 10.2%, and 7.4% and 10.6%. Cycle outcome and cycle properties were similar. CONCLUSIONS: Modified natural IVF cycle with GnRH antagonist supplementation is a feasible alternative to ovarian stimulation protocols in poor responders

Abstract: OBJECTIVE: To determine whether colchicine prescribed for familial Mediterranean fever is teratogenic. STUDY DESIGN: Reproductive histories were analyzed from 326 couples referred for prenatal diagnosis because 1 partner was affected. Numbers of chromosomal abnormalities and birth defects were compared with numbers expected from published rates. RESULTS: There were 901 pregnancies, and amniocentesis had been performed in 566, all but 3 conceived while taking colchicine. Seven numerical chromosomal abnormalities were found, not statistically significantly greater than the 4.99 expected from maternal age and gestation of diagnosis (P = .24): unbalanced structural abnormalities were 6, compared with 3.22 expected (P = .11). There were 7 birth defects, a considerably lower rate than reported in local malformation registers. CONCLUSION: The current policy of routine amniocentesis in pregnancies of couples taking colchicine should not be changed until sufficient data accumulates to establish whether the higher number of chromosomal anomalies in this group is significant

Abstract: Somatic gene delivery in utero is a novel approach to gene therapy for genetic disease based on the hypothesis that prenatal intervention may avoid the development of severe manifestations of early-onset disease, allow targeting of otherwise inaccessible tissues including expanding stem cell populations, induce tolerance against the therapeutic transgenic protein and thereby provide permanent somatic gene correction. This approach is particularly relevant in relation to prenatal screening programmes for severe genetic diseases as it could offer prevention as a third option to families faced with the prenatal diagnosis of a genetically affected child. Most investigations towards in utero gene therapy have been performed on mice and sheep fetuses as model animals for human disease and for the application of clinically relevant intervention techniques such as vector delivery by minimally invasive ultrasound guidance. Other animals such as dogs may serve as particular disease models and primates have to be considered in immediate preparation for clinical trials. Proof of principle for the hypothesis of fetal gene therapy has been provided during the last 2 years in mouse models for Crigler Najjar Disease, Leber's congenital amaurosis, Pompe's disease and haemophilia B showing long-term postnatal therapeutic effects and tolerance of the transgenic protein after in utero gene delivery. However, recently we have also observed a high incidence of liver tumours after in utero application of an early form of third-generation equine infectious anaemia virus vectors with SIN configuration. These findings highlight the need for more investigations into the safety and the ethical aspects of in utero gene therapy as well as for science-based public information on risks and benefits of this preventive gene therapy approach before application in humans can be contemplated

Abstract: OBJECTIVE: In most prenatal settings, twin pregnancies are initially evaluated by sonographers. Pregnancies diagnosed as monochorionic are subsequently referred to perinatologists or specialists in fetal medicine for the confirmation of chorionicity. In order to assess this screening strategy, we have compared the diagnosis of chorionicity made by the sonographers in the ultrasound department with the diagnosis done in the fetal medicine unit. METHODS: A cohort of women presenting with twin pregnancy and booked for prenatal care at University College London Hospitals over a 4-year period were investigated prospectively. All women were scanned at their initial visit at 11-14 weeks in the ultrasound department (US), and were subsequently referred to the Fetal Medicine Unit (FMU) for a second ultrasound evaluation. Ultrasound data were compared and diagnosis of chorionicity was confirmed by examination of the inter-twin membranes after delivery. RESULTS: Chorionicity was determined in 172 twin cases by the two different departments. The overall rate of concordant chorionicity determination between both units was 90.1%. The rate of discordant results in dichorionic pregnancies was extremely small, 1 in 119 pregnancies (0.8%). The rate of discordant results for monochorionic diamniotic pregnancies was 5.5%. Monoamniotic pregnancies were over-diagnosed by the US technicians. DISCUSSION: These results demonstrate that DC/DA chorionicity is accurately determined by sonographers at less than 14 weeks. In our opinion, it is both efficient and safe to rely on the diagnosis of the sonographers in DC/DA pregnancies in early pregnancy. In such pregnancies, a decision can be made either not to refer these patients for further evaluation of chorionicity by the fetal medicine team or to postpone the referral to after 14 weeks

Abstract: OBJECTIVE: Duchenne muscular dystrophy (DMD) is a lethal degenerative muscular disease. Fetal gene therapy may correct the primary genetic defect. Our aim was to achieve expression of a reporter gene in the respiratory muscles of early gestation fetal sheep. STUDY DESIGN: An adenovirus vector containing the beta-galactosidase reporter gene (AdRSVbetagal) was injected into the thoracic musculature (n = 3) and pleural cavity (n = 6) of fetal sheep (61-67 days' gestation) under ultrasound guidance. Tissues were harvested after 48 hours and site and intensity of beta-galactosidase expression were assessed. RESULTS: Limited transgene expression observed after a single injection was improved by multiple injections, but remained localized. Ultrasound-guided creation of a hydrothorax led to an increase in the intensity of beta-galactosidase expression (ELISA). X-gal staining and immunohistochemistry showed that vector spread was confined to the innermost intercostal musculature. CONCLUSION: Ultrasound-guided injection can deliver gene therapy vectors to the fetal pleural cavity and achieve transduction of the respiratory muscles

Abstract: The rising rate of multiple pregnancies and its association with advanced maternal age has expanded the need for prenatal diagnosis in twins and higher order gestations. The complexity of the invasive diagnostic procedures and the risk of loss of an unaffected twin raise significant clinical, technical and ethical issues. In this review we discuss the specific issues of early scanning, counseling and determination of chorionicity prior to invasive procedures in twins. We present the available data describing the risk associated with these procedures in twins and compare data of fetal loss rate from different studies. We also discuss the issues of fetal blood sampling and late karyotyping in twin pregnancies

Abstract: OBJECTIVE: To describe our management of pregnancies complicated by twin reversed arterial perfusion (TRAP) sequence. METHODS: This was a retrospective study involving all cases of TRAP sequence referred to our fetal medicine unit in a 3-year period (2000-2002). Patients were routinely managed by repeat sonographic surveillance with sonographic anatomical evaluation and detailed echocardiography. Cases with signs of impending cardiac failure were treated by in-utero YAG-laser coagulation of the umbilical vessels of the acardiac twin. RESULTS: Six cases were studied. Three patients in whom there were no signs of deterioration in the status of the pump twin, and in whom the acardiac twin was smaller than the pump twin, were managed conservatively. However, one of these with monoamniotic twins ended in intrauterine fetal death of the pump twin. The other two cases presented with spontaneous cessation of blood flow in the umbilical artery of the acardiac twin. Both delivered at term normal neonates whose follow-up revealed no signs of neurological sequelae. One case of quadruplet pregnancy (with TRAP sequence and two dichorionic twins) was treated by selective termination of the monochorionic twins. Two cases with signs of impending cardiac failure were treated by in-utero YAG-laser occlusion of the vessels in the acardiac mass. Both interventions had a favorable outcome. CONCLUSIONS: Conservative treatment is suitable for milder cases of TRAP sequence in which the pump twin is the larger one. Cases in which the acardiac twin is larger have a poorer prognosis and should be treated by invasive intervention and cord occlusion

Abstract: OBJECTIVE: To describe our experience in prenatal diagnosis of hemivertebra. METHODS: This is a case series of patients referred to our tertiary medical center over a 3-year period. All fetuses were scanned by high-resolution real-time scanners. The apparent vertebral anomaly was assessed in a real-time manner by a joint team of obstetricians, sonographers, and pediatric orthopedic surgeons. A complete anomaly survey of other fetal organs was performed on each fetus. All patients were given proper counseling by the same joint team. All patients had detailed obstetric and neonatal follow-up. Prenatal sonograms, neonatal medical records, and clinical courses were evaluated retrospectively. RESULTS: During the 3 years, 6 cases of hemivertebra were identified in our department. Gestational age at diagnosis was 14 to 23 weeks. Two patients had conception by assisted reproductive technology. Associated anomalies included VATER syndrome (vertebral defects, imperforate anus, tracheoesophageal fistula, and radial and renal dysplasia), gastroschisis, and pyelectasis. Outcomes in fetuses without major associated anomalies were fair. CONCLUSIONS: Diagnosis of isolated hemivertebra might be associated with a favorable outcome. The 3 key factors in achieving an optimal spine at maturity, early diagnosis, anticipation, and prevention of deterioration, might be enhanced by our joint multidisciplinary approach to the diagnosis of skeletal anomalies

Abstract: Cardiac anomalies may occur in isolation or can be part of a genetic syndrome. In this article, we describe some of the genetic syndromes commonly associated with cardiac anomalies where there are other sonographic features that may aid accurate prenatal diagnosis

Abstract: OBJECTIVE: To evaluate pulmonary blood flow in fetuses of diabetic mothers by measuring changes in fetal segmentary pulmonary artery blood flow velocimetry throughout pregnancy. METHODS: Thirty-eight women with pregestational diabetes between weeks 18 and 38 were compared with 99 women with singleton low-risk gestations as controls. Flow velocity waveforms at the proximal middle and distal segments of the right pulmonary artery were obtained with power and color Doppler sonography in all fetuses. The pulsatility index of each segment was compared between the 2 groups. The mean value and 95% confidence interval for each segment were determined in correlation with gestational age for both groups. RESULTS: The highest mean pulsatility indices were obtained in the proximal segment of the pulmonary artery and were 2.25 in the diabetes group and 2.36 in controls. The mean pulsatility indices were significantly decreased in the middle and distal segments to 1.59 and 1.10 in the diabetes group and to 1.57 and 1.02 in controls (P < .05). There were no significant differences in pulsatility indices measured at the proximal and middle segments between the study and control groups. However, the mean pulsatility index +/- SD measured at the distal segment in the diabetic group was 9% higher than in controls (1.10 +/- 0.13 versus 1.02 +/- 0.12; P = .01). The mean pulsatility index (in the study and control groups) in each arterial segment did not change significantly throughout gestation (P > .1). CONCLUSIONS:. In human fetuses throughout gestation, the pulmonary circulation maintains stable vascular resistance in both diabetic and normal pregnancies. However, in all gestations, the pulsatility index in each segment of the pulmonary artery is unique and reflects the proximity to the heart and the impedance at each location. The significantly higher pulsatility index in the diabetes group might be related to alterations in the microcirculation of diabetic patients

Abstract: Cancer is the second most common cause of death in the reproductive years and complicates up to one in 1000 pregnancies. When cancer is diagnosed during pregnancy, the management strategy must take into account both the mother and developing fetus. In this article, the four most common malignancies diagnosed in pregnant patients--cervical and breast cancer, malignant melanoma and lymphoma--will be reviewed, with an emphasis on the impact of the diagnosis and management on the pregnant patient and the developing fetus

Abstract: Group B Streptococcus (GBS) is a common inhabitant of the maternal genital and gastrointestinal tracts, and colonizes approximately 20% of pregnant women. About 50% of infants born to colonized women will become colonized at birth. Early onset GBS disease affects 5/1000 newborns, and is related to a 5-16% mortality rate and severe morbidity. Selective intra-partum chemoprophylaxis can prevent most cases of GBS early-onset disease. In 1996, the federal Centers for Disease Control and Prevention (CDC), the American College of Obstetricians and Gynecologists (ACOG) and the American Academy of Pediatrics (AAP) recommended either a culture-based or risk-based approach for prevention of early onset GBS disease. Understanding the epidemiology of the disease and comparing efficacy of the two prevention strategies may elucidate the dispute surrounding this issue. Accordingly, new recommendations from the CDC and the ACOG were published, and their implementation in Israel should now be considered

Abstract: OBJECTIVE: To evaluate our experience with sonography and color Doppler blood flow in the diagnosis and management of chorioangiomas of the placenta. METHODS: All cases with placental chorioangiomas diagnosed in our sonography unit between 1992 and 2001 were included in the study. Sonographic and color Doppler flow characteristics were evaluated in all cases. Our cases were compared with all cases of placental chorioangiomas diagnosed antenatally by sonography published in the English literature between 1978 and 2001. RESULTS: Six cases of placental chorioangioma were identified antenatally, with a mean size of 6.5 cm (range, 4-13 cm). With the use of color Doppler flow, all cases of chorioangioma were shown to have either abundant blood flow or a large feeding vessel within the tumor. During follow-up, 2 cases had reduction of the intratumoral blood flow, and the outcomes were favorable. Three of our cases had delivery before 33 weeks' gestation (1 with intrauterine fetal death and 1 with termination of pregnancy). Review of the literature revealed 72 cases of antenatally diagnosed placental chorioangioma. Two thirds of the cases had dismal outcomes. CONCLUSIONS: The sonographic diagnosis of chorioangiomas of the placenta is feasible and necessitates close surveillance of these pregnancies because of the dismal prognosis in more than half. The addition of color Doppler flow is important in the diagnosis and antenatal follow-up of these pregnancies

Abstract: OBJECTIVE: To identify the risk factors for preterm birth in primigravidae with twin gestation and the role of transvaginal ultrasonographic assessment of the cervix. METHODS: Between January 1996 and December 1996, 54 twin pregnancies were prospectively enrolled. All women were at their first pregnancy. All women conceived following infertility treatments and all had a normal uterine cavity proven by hysterosalpingography (HSG) or hysteroscopy. Multiple logistic regression analysis was used to evaluate the association between the length of the cervix at 18-24 weeks of gestation and outcome variables, controlling for possible confounding factors. RESULTS: The mean +/- SD maternal age was 30.9 +/- 5.3 years (range 22-46), and five of them were aged 40 or more. Nine patients (20.5%) delivered prematurely, defined as spontaneous delivery at or before 34 weeks of gestation. There was no statistically significant difference between women who delivered before or after 34 weeks of gestation in regard to maternal age, body mass index (BMI), weight gain in pregnancy, smoking and work during pregnancy. The mean cervical length of patients who delivered before 34 weeks of gestation (30.1 +/- 6.1 mm) was significantly shorter than that of women who delivered after 34 weeks of gestation (42.2 +/- 6.2 mm; P < 0.001). Cervical length longer than 35 mm predicted delivery after 34 weeks of gestation with sensitivity and specificity of 88.5% and 88.9%, respectively. The positive and negative predictive values were 96.9% and 66.7%. CONCLUSION: A transvaginal ultrasonographic measurement of the cervix > 35 mm at 18-24 weeks in twin gestation can identify patients at low risk for delivery before 34 weeks. Maternal age, BMI, weights gain, smoking and work during the pregnancy did not influence the duration of the pregnancy

Abstract: OBJECTIVE: This study aimed to evaluate topoisomerase II compared to Ki-67 expression as a marker for tumor behavior and for prognosis of patients with ovarian cancer. METHODS: In order to screen for potential prognostic markers, two groups of patients with advanced stage (FIGO stages III and IV) epithelial ovarian carcinoma were selected based on differences in survival (mean survival, 11 years versus 2 years). Pathology slides were reviewed, and immunohistochemistry using antibodies to topoisomerase II and Ki-67 was performed on the original cell blocks. No patients were lost to follow-up. RESULTS: Detectable expression of topoisomerase II was present in 70.0 +/- 30.3% of cells in patients with rapidly progressing disease, compared to only 12.3 +/- 12.4% of cells in long-term survivors (P = 0.0001). Ki-67 expression was also more frequent in short-term survivors compared to long-term survivors, but the difference was less prominent than with topoisomerase II (P = 0.01). Specificity and sensitivity as prognostic factors reached 88.2 and 93.8% for topoisomerase II, compared to 55.6 and 88.2% for Ki-67. CONCLUSIONS: Topoisomerase II expression as detected by immunohistochemistry in tumor samples emerged as a promising clinically relevant biomarker for survival in advanced epithelial ovarian cancer

Abstract: STUDY OBJECTIVE: To assess the validity of preoperative diagnosis in the emergency room in relation to the surgical diagnosis at laparoscopy. DESIGN: Retrospective study (Canadian Task Force classification II-2). SETTING: University-affiliated hospital. PATIENTS: One hundred consecutive nonpregnant women who underwent emergency laparoscopy for acute abdomen between 1997 and 1999. Intervention. Emergency diagnostic laparoscopy. MEASUREMENTS AND MAIN RESULTS: The preoperative diagnosis was confirmed by laparoscopy in 29 (44%) of 66 cases of ovarian torsion, 9 (82%) of 11 cases of ovarian cyst, and 12 (80%) of 15 cases of bleeding corpus luteum. Unsuspected diagnoses among nonconfirmed cases were ovarian cysts (24), adhesions (5), bleeding corpus luteum (3), degenerative myomas (3), pelvic inflammatory disease (2), and appendicitis (1). The preoperative diagnosis was confirmed by emergency laparoscopy in 56% of all patients. Diagnoses most likely to be predicted accurately were ovarian cysts and bleeding corpora lutea. Ovarian torsion was most difficult to diagnose preoperatively, as it was not confirmed during laparoscopy in over half patients. Ovarian cysts and adhesions were the most common unsuspected findings. CONCLUSION: Patients and surgeons alike should be aware of difficulty making accurate preoperative diagnoses of acute gynecologic pathologies in the emergency room. (J Am Assoc Gynecol Laparosc 8(1):92-94, 2001)

Abstract: STUDY OBJECTIVE: To assess the efficacy of and reproductive outcome after selective curettage of residual trophoblastic tissue directed by hysteroscopy compared with conventional, nonselective, blind curettage. DESIGN: Retrospective analysis (Canadian Task Force classification II-1). SETTING: Tertiary care medical center. PATIENTS: Seventy patients after curettage or delivery, with clinical and ultrasonographic signs of suspected residual trophoblastic tissue. MEASUREMENTS AND MAIN RESULTS: Twenty-four women underwent traditional curettage and 46 underwent hysteroscopic selective curettage. Five (20.8%) patients who underwent traditional curettage later required operative hysteroscopy due to persistent residual tissue. None of those who underwent hysteroscopic selective curettage needed a second operation. No patient in either group experienced anesthetic complications, perforation of the uterus, fluid overload, or other surgical complication. Reproductive outcome was similar in both groups, with tendency to conceive earlier in the hysteroscopy group, but no difference in overall pregnancy rates. CONCLUSION: Operative hysteroscopy for selective curettage of residual trophoblastic tissue should be considered an alternative to nonselective, blind curettage

Abstract: Cancer is the second leading cause of death in women during their reproductive years, and complicates approximately 0.1% of all pregnancies. When cancer occurs during gestation it poses immense pressure on the pregnant patient, her relatives and her physicians. As cancer is diagnosed during gestation, it raises conflicts between optimal maternal therapy and fetal well-being. In this review, the available data are analysed regarding the impact of pregnancy on the course of the disease, and the effects of the malignant process and its treatment on both the mother and her fetus. Here, attention is focused on the most common malignancies associated with pregnancy; cervical and breast cancer, malignant melanoma and lymphoma. In addition, attention is focused on the available data regarding the impact of cytotoxic and radiation treatments on the mother and fetus

Abstract: OBJECTIVE: This study was undertaken to compare the rate of abnormal glucose levels measured after 1 hour (>140 mg%) with those measured after 2 hours (>120 mg%) postprandially in women with gestational diabetes mellitus (GDM). STUDY DESIGN: Sixty-eight women were included in this study. All had GDM based on the criteria of Carpenter-Coustan. Women with fasting glucose levels of 105 mg% or more were excluded from the study. All women were initially treated by diet. All women measured daily capillary blood glucose levels when fasting as well as 1 hour and 2 hours postprandially for 1 week, immediately after diagnosis of GDM. Glucose levels were obtained by memory-based glucometers. All women were followed in a specialized gestational-diabetes clinic throughout the pregnancy. Insulin therapy was started on an individual basis according to common clinical criteria. Epidemiologic and perinatal data were collected from medical charts. RESULTS: The average age of the women was 30.8 +/- 5.4 years. Thirty-five percent of participants were primipara. The mean gestational age at diagnosis was 28.8 +/- 5.4 weeks. Glucose measurements included 618 readings during fasting and 2730 either 1 hour or 2 hours postprandial. Rates of abnormal glucose (>95 mg% when fasting; >140 mg% 1 hour or >120 mg% 2 hours after each meal) per person were the following: fasting, 27.1% abnormal glucose measurements; postbreakfast, 22.4% abnormal levels after 1 and 8.5% after 2 hours (P < .01); postlunch, 16.4% abnormal levels after 1 hour and 18.2% after 2 hours (not significant); postdinner, 16.3% abnormal levels after 1 hour and 30.1% after 2 hours (P < .01). CONCLUSION: The rate of abnormal values was 2.5-fold greater 1 hour postbreakfast than 2 hours postbreakfast, in contrast to an opposite ratio of a 2-fold increase in the rate of abnormal values 2 hours postdinner versus 1 hour postdinner. Therefore, differential measurement (1 hour after breakfast and 2 hours after dinner) might impose stricter criteria for controlling blood glucose levels. Further clinical research should explore whether differential measurements might reduce the rate of diabetes-associated complications

Abstract: Constitutively active Ras proteins, their regulatory components, and overexpressed tyrosine kinase receptors that activate Ras, are frequently associated with cell transformation in human tumors. This suggests that functional Ras antagonists may have anti-tumor activity. Studies in rodent fibroblasts have shown that S-trans, transfarnesylthiosalicylic acid (FTS) acts as a rather specific nontoxic Ras antagonist, dislodging Ras from its membrane anchorage domains and accelerating its degradation. FTS is not a farnesyltransferase inhibitor, and does not affect Ras maturation. Here we demonstrate that FTS also acts as a functional Ras antagonist in human pancreatic cell lines that express activated K-Ras (Panc-1 and MiaPaCa-2). In Panc-1 cells, FTS at a concentration of 25-100 microM reduced the amount of Ras in a dose-dependent manner and interfered with serum-dependent and epidermal growth factor-stimulated ERK activation, thus inhibiting both anchorage-dependent and anchorage-independent growth of Panc-1 cells in vitro. FTS also inhibited tumor growth in Panc-1 xenografted nude mice, apparently without systemic toxicity. Daily FTS treatment (5 mg/kg intraperitoneally) in mice with tumors (mean volume 0.07 cm3) markedly decreased tumor growth (after treatment for 18 days, tumor volume had increased by only 23+/-30-fold in the FTS-treated group and by 127+/-66-fold in controls). These findings suggest that FTS represents a new class of functional Ras antagonists with potential therapeutic value

Abstract: OBJECTIVE: Invasion of the extracellular matrix and blood vessels by malignant neoplasms, with subsequent distant dissemination, is a key event in tumor progression. This process appears to be mediated largely through the action of matrix metalloproteinases (MMPs), a family of proteolytic enzymes produced by both stromal and tumor cells. The role of gelatinases (MMP-2 and MMP-9) in basement membrane and matrix degradation was described in various tumors. We studied MMP-9 protein expression in cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma using immunohistochemistry and detected MMP-9 mRNA using in situ hybridization. METHODS: Fifty squamous cell carcinomas, 10 cases of CIN II-III, and 10 normal cervices were stained for MMP-9, using a monoclonal antibody. The presence of MMP-9 mRNA was studied using in situ hybridization. Results were correlated with patient survival during a follow-up period of up to 167 months (average, 41 months). RESULTS: Immunohistochemical staining of tumor cells for MMP-9 was noted in 36/50 (72%) carcinomas and 5/10 (50%) CIN lesions, but was uniformly absent from the nonneoplastic epithelium adjacent to tumors and from control cervices. Peritumoral staining of stromal cells was observed in 27/50 (54%) carcinomas, but only in 3/10 (30%) CIN lesions and 1/10 (10%) control cervices. The presence of MMP-9 mRNA was detected in tumor cells in 39 (78%) carcinomas and 8 (80%) CIN lesions, but only in 4 (40%) control cervices. An intense signal for MMP-9 mRNA was observed most frequently in carcinomas. MMP-9 mRNA was detected in stromal cells in the majority of cases. However, an intense signal was observed only in stromal cells around invasive tumors. In survival analysis, age (P = 0.016), grade (P = 0. 016), and stage (P = 0.001) showed independent correlation with poor survival. Neither MMP-9 protein expression nor an intense signal for MMP-9 mRNA was associated with poor survival, although the latter was observed more frequently in neoplastic cells of lethal tumors (8/14 tumors vs 11/36 nonlethal tumors). CONCLUSIONS: MMP-9 mRNA and protein expression are elevated in tumor and stromal cells of both high-grade CIN and invasive squamous cell carcinoma of the uterine cervix. Thus, MMP-9 is possibly an early marker of tumor progression in squamous lesions of the cervix. An intense stromal signal for MMP-9 mRNA characterizes some invasive carcinomas. Expression of MMP-9 in cervical carcinoma cells is present in both lethal and nonlethal tumors, consistent with the key role of this proteolytic enzyme in invasion, and does not appear to predict disease outcome

Abstract: A lipophilic farnesyl moiety attached to the carboxyl terminal cysteine of ras proteins structurally supports their membrane anchorage, required for ras-dependent growth-factor signaling and for transforming activity of ras oncoproteins. It has been shown that inhibition of ras farnesylation can block tumor growth in nude mice but that some ras-dependent tumors escape such blockage as a result of prenylation of ras. S-trans-transfarnesylthiosalicylic acid (FTS) is a potent ras-dislodging antagonist that does not affect ras prenylation but rather acts on the mature, membrane-bound ras and facilitates its degradation. Here we demonstrate that FTS induces reappearance of stress fibers in H-ras-transformed rat-1 cells (EJ cells) in vitro, inhibits their anchorage-independent growth in vitro, and blocks EJ-tumor growth in nude mice. The anchorage-independent growth of cells expressing ErbB2 (B104), but not that of v-raf-transformed cells, is also inhibited by FTS, suggesting specificity towards activated ras. FTS treatment (5 mg/kg i.p. daily) caused inhibition (75-80%) of tumor growth in nude mice implanted with EJ, but not in mice implanted with v-raf-transformed cells, with no evidence of systemic toxicity. Moreover, FTS treatment increased the survival rate of EJ-tumor-bearing mice from 48 to 68 days. Here we demonstrate anti-tumor potency in a synthetic, non-toxic, ras-dislodging antagonist acting independently of farnesyltransferases

Abstract: BACKGROUND/AIMS: Protooncogenes may play an important role, not only in carcinogenesis, but also in the regulation of normal cellular proliferation and differentiation. Several studies have indicated increased expression of the Ras protooncogenes in the liver in animal models and in patients with liver cirrhosis. The aim of the present study was to examine whether a synthetic Ras antagonist, S-farnesylthiosalicylic acid (FTS), which specifically dislodges Ras from the membrane of Ras-transformed fibroblasts (EJ cells), can prevent experimentally-induced liver cirrhosis in rats. METHODS: Cirrhosis was induced in male Wistar rats by intraperitoneal administration of thioacetamide (200 mg/kg twice weekly for 12 weeks). The Ras antagonist, farnesylthiosalicylic acid (FTS, 5 mg/kg), was administered during the study period 3 times a week. Ras expression in the liver was determined by Western blot analysis with pan anti-Ras antibodies and by immunohistochemistry. RESULTS: Rats treated with thioacetamide and the Ras antagonist, farnesylthiosalicylic acid (FTS), for 12 weeks had lower histopathologic scores of fibrosis and inflammation (p-values of 0.003 and 0.008, respectively) than those treated with thioacetamide only. There were no differences between the histopathologic scores in vehicle (control) and in Ras-antagonist (FTS) only treatments. Analysis of hepatic hydroxyproline levels from the two thioacetamide-treated groups and controls confirmed the histopathologic scores (7.7+/-0.9 mg/g protein in the TAA-treated vs. 3.8+/-0.5 mg/g protein in the TAA+FTS treated group, p = 0.007). Ras levels, determined by Western blot analysis, were markedly increased in the livers treated with TAA (17-fold over control) and significantly decreased (by about 70%) in the livers of rats treated with TAA and FTS. Studies in isolated human hepatic stellate cells demonstrated that FTS inhibited both DNA synthesis and migration of those cells (p<0.05). CONCLUSION: These results indicate that inhibition of Ras expression in the liver during fibrogenesis, prevents the development of experimentally-induced hepatic cirrhosis

Abstract: Exchange transfusion has an important role in the treatment of hyperbilirubinemia of the newborn. It is used in attempts to prevent kernicterus when bilirubin levels are high. We describe our experience in 203 exchange transfusions performed on 143 infants (81 males and 62 females) with hyperbilirubinemia during 1983-1992. In only 30% of cases was there a specific etiological diagnosis of the jaundice based on a positive Coombs test, G6PD deficiency, or the presence of sepsis or maternal diabetes; the rest were idiopathic. 57% of the neonates were premature (26-36 weeks of gestation). Premature neonates underwent more transfusions than full-term infants (1.6 vs 1.2). There was no direct death from exchange transfusion; morbidity was 6.3% (including bradycardia, apnea, thrombocytopenia, hypoglycemia and hyponatremia). Most complications occurred in preterm infants and those severely ill. All complications were treated immediately and there were no sequelae

Abstract:

Abstract: Intussusception, the invagination of a portion of the intestine into an adjacent segment, is the most common cause of intestinal obstruction in post neonatal children. Most cases are idiopathic, but in about 2-12% the intussusception evolves secondary to an underlying abnormality. Classically, there is sudden onset of attacks of screaming, accompanied by pallor, vomiting, and irritability in a previously health child. Some gradually become weaker and lethargic. We evaluated variations in presenting symptoms and outcome as related to age and time until admission. There were incidence peaks in the spring and autumn. 48% developed irritability, while 42% were described as apathetic. These results emphasize the importance of awareness that apathy can be a major presenting symptom. The younger the child, the greater the rate of success of reduction by hydrostatic pressure. In those admitted within 24 hours of onset, the rate of reduction was twice that in those admitted later. Awareness of atypical symptoms and early diagnosis may affect treatment and improve prognosis