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Biomedical subjects

C Rodeck

Publications and source records attributed to C Rodeck.

At least 19 recordsLinked to original sources
PubMed2006

Uterine vein and maternal urinary levels of activin A and inhibin A in pre-eclampsia patients.

OBJECTIVES: The aims of this study were to investigate if (i) urinary concentrations of activin A and inhibin A are altered in pre-eclampsia (PE) and (ii) to study the relationship between uterine vein and peripheral vein concentrations of these hormones in PE patients. DESIGN AND METHOD: In a retrospective study, maternal peripheral vein and uterine vein serum and maternal urine samples collected at the time of delivery were analysed. There were three groups of patients; (i) group 1: term normal pregnancies (n = 19) (ii) group 2: patients who developed PE < or = 37 weeks (n = 17) and (iii) group 3: patients who developed PE 37-40 weeks (n = 8). Serum and urinary activin A, follistatin, inhibin A and pro alpha C and urinary creatinine levels were measured using enzyme immunoassays in the laboratory. RESULTS: Normal pregnant urine samples had very low levels of activin A and inhibin A. Both groups 2 and 3 PE patients had significantly higher levels of inhibin A (P < 0.001) and activin A (P < 0.001) compared to the controls. Pro-alpha C was not altered and follistatin was below the detection limit of the assay in the urine. Maternal peripheral serum activin A and inhibin A were significantly higher in groups 2 (P < 0.001) and 3 (P < 0.05) patients compared to the controls. Pro-alpha C-containing inhibins were higher in group 2 patients (P < 0.05) compared to the controls in the peripheral circulation. Uterine vein serum activin A and inhibin A levels were also significantly higher in groups 2 (P < 0.001) and 3 (P < 0.05) patients compared to the controls. There was a highly significant positive correlation between peripheral and uterine vein serum concentrations of activin A, follistatin, inhibin A and pro alpha C, suggesting the same source for these proteins in PE. CONCLUSION: Urinary activin A and inhibin A are raised in groups 2 and 3 PE patients. The magnitude of rise (> 25-fold) suggests these proteins may rise in patients before the onset of the clinical symptoms of PE. Uterine vein levels of these proteins are also raised in PE.

Activins↗
PubMed2005

Gene therapy progress and prospects: fetal gene therapy--first proofs of concept--some adverse effects.

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.

Animals↗
PubMed2005

SURUSS in perspective.

BACKGROUND: Until the publication of the Serum Urine and Ultrasound Screening Study (SURUSS) report, it was difficult to compare the different antenatal screening tests for Down's Syndrome because of variations in study designs. We here present the main results from SURUSS, updated to take account of recent information on nuchal translucency in Down's Syndrome pregnancies, and discuss their implications. METHODS: SURUSS was a prospective study of 47,053 singleton pregnancies (including 101 pregnancies with Down's Syndrome) conducted in 25 maternity units. Nuchal translucency measurements were taken. Serum and urine samples collected between 9 and 13 weeks, and again between 14 and 20 weeks of pregnancy were stored. Samples from each affected pregnancy and five matched controls were tested for currently used or suggested biochemical Down's Syndrome screening markers. Pregnancies were followed up to determine the presence or absence of Down's Syndrome. For an 85% Down's Syndrome detection rate, the false-positive rate for the Integrated test (nuchal translucency and pregnancy associated plasma protein-A [PAPP-A] at 11 completed weeks of pregnancy, and alpha-fetoprotein, unconjugated oestriol [uE3], free beta or total human chorionic gonadotrophin (hCG) and inhibin-A in the early second trimester) was 0.9%, the Serum integrated test (without nuchal translucency) 2.7%, the Combined test (nuchal translucency with free beta-hCG and PAPP-A at 11 weeks) 4.3%, the Quadruple test (alpha-fetoprotein, uE3, free beta or total hCG and inhibin-A) 6.2%, and nuchal translucency at 11 weeks, 15.2%. All tests included maternal age. Using the Integrated test at an 85% detection rate, there would be six diagnostic procedure-related unaffected fetal losses following amniocentesis per 100,000 women screened compared with 35 using the Combined test or 45 with the Quadruple test. CONCLUSIONS: The Integrated test offers the most effective and safe method of screening for women who attend in the first trimester. The next best test is the Serum integrated test. The Quadruple test is the best test for women who first attend in the second trimester. There is no justification for retaining the Double (alpha-fetoprotein and hCG) or Triple (alpha-fetoprotein, uE3, and hCG) tests, or nuchal translucency alone (with or without maternal age) in antenatal screening for Down's Syndrome.

Case-Control Studies↗
PubMed2004

Procedure-related complications of rapid amniodrainage in the treatment of polyhydramnios.

OBJECTIVE: To investigate the procedure-related complications of rapid amniodrainage in the treatment of polyhydramnios. METHODS: We followed prospectively all patients with polyhydramnios treated with rapid amniodrainage under continuous ultrasound guidance using a vacuum wound-drainage system from 1995 to 2002 in the fetal medicine unit of a university teaching hospital. We recorded: maternal age, type of pregnancy (singleton/twin), cause of polyhydramnios, gestational age at amniocentesis, volume of amniotic fluid drained, duration of the procedure, other intrauterine procedures in addition to the amniodrainage, and procedure-related complications including placental abruption, premature rupture of membranes (PROM), chorioamnionitis, fetal bradycardia and preterm delivery within 48 h of amniodrainage. RESULTS: Seventy-four consecutive women had 134 rapid amniodrainage procedures during the study period. Four procedures were excluded because the women were already in labor at the time of amniodrainage and they delivered within 48 h of the procedure. The final database therefore consisted of 70 patients with 130 procedures. Sixty-two percent (80/130) of the procedures were performed for the treatment of twin-twin transfusion syndrome (TTTS). There were altogether four procedure-related complications (3.1%; 95% CI, 1.0-8.0%). Three of them occurred in the TTTS group (3/80 procedures, 3.8%; 95% CI, 1.0-11.0%): one case each of placental abruption, PROM and fetal bradycardia. One PROM occurred in the non-TTTS group (1/50 procedures, 2.0%; 95% CI, 0-11.0%). In both cases of PROM the women presented in labor. CONCLUSIONS: Rapid amniodrainage using a vacuum wound-drainage system is safe and efficient to treat severe polyhydramnios, with a 3.1% complication rate.

Amniocentesis↗
PubMed2004

Widespread and efficient marker gene expression in the airway epithelia of fetal sheep after minimally invasive tracheal application of recombinant adenovirus in utero.

Cystic fibrosis is a common lethal genetic disease caused by functional absence of the cystic fibrosis transmembrane conductance regulator (CFTR). Although a candidate disease for in utero gene therapy, demonstration of potentially therapeutic levels of transgene expression in the fetal airways after minimally invasive gene delivery is a mandatory prerequisite before application of this approach in humans can be considered. We report here on the delivery of a beta-galactosidase expressing adenovirus directly to the airways of fetal sheep in utero using ultrasound-guided percutaneous injection of the trachea in the fetal chest. Injection of adenoviral particles to the fetal airways was not associated with mortality and resulted in low-level expression in the peripheral airways. However, complexation of the virus with DEAE dextran, which confers a positive charge to the virus, and pretreatment of the airways with Na-caprate, which opens tight junctions, increased transgene expression, and a combination of these two enhancers resulted in widespread and efficient gene transfer of the fetal trachea and bronchial tree. Using a percutaneous ultrasound-guided injection technique, we have clearly demonstrated proof of principle for substantial transgene delivery to the fetal airways providing levels of gene expression that could be relevant for a therapeutic application of CFTR expressing vectors.

Adenoviridae↗
PubMed2004

Thromboembolic disease and air travel in pregnancy: a survey of advice given by obstetricians.

The objective of this study was to document the awareness of risk and the nature of advice given by obstetricians to pregnant women who intend to travel by air and to compare the results with the advice given in an opinion paper of the Royal College of Obstetricians and Gynaecologists. The results were based on a self-completed questionnaire. All registered members of the Royal College of Obstetricians and Gynaecologists comprising 1349 individuals, obtained from a list provided by the RCOG, were invited to participate. An anonymous postal questionnaire was completed by the individuals before publication of the opinion paper of the RCOG. A total of 862 (62%) questionnaires returned, and 690 (51%) were available for analysis; 67% of obstetricians regard flying as being safe throughout pregnancy, 33% only in the 2nd and 3rd trimester. Nearly all obstetricians advised on simple prophylactic measures such as mobilisation, fluid intake and leg exercise. Fifty-three per cent would advise the use of prophylactic aspirin (75 mg), 49% the use of compression stockings; 4% recommended heparinisation; 44% believed this advice to be applicable only for the 2nd and 3rd trimester, while the RCOG emphasises that the risk of developing venous thromboembolism begins in the 1st trimester. Obstetricians as well as other health professionals need to be made aware that advice on air travel in pregnancy needs to start in the 1st trimester. Further research is needed to explore the relevance of the duration of flight when considering the application of thromboprophylactic measures as well as the value and choice of pharmacological treatment such as aspirin and heparin.

Aircraft↗
PubMed2004

SURUSS in perspective.

BACKGROUND: Until the publication of the Serum Urine and Ultrasound Screening Study (SURUSS) report, it was difficult to compare the different antenatal screening tests for Down's Syndrome because of variations in study designs. We here present the main results from SURUSS, updated to take account of recent information on nuchal translucency in Down's Syndrome pregnancies, and discuss their implications. METHODS: SURUSS was a prospective study of 47,053 singleton pregnancies (including 101 pregnancies with Down's Syndrome) conducted in 25 maternity units. Nuchal translucency measurements were taken. Serum and urine samples collected between 9 and 13 weeks, and again between 14 and 20 weeks of pregnancy were stored. Samples from each affected pregnancy and five matched controls were tested for currently used or suggested biochemical Down's Syndrome screening markers. Pregnancies were followed up to determine the presence or absence of Down's Syndrome. For an 85% Down's Syndrome detection rate, the false-positive rate for the Integrated test (nuchal translucency and pregnancy associated plasma protein-A [PAPP-A] at 11 completed weeks of pregnancy, and alpha-fetoprotein, unconjugated oestriol [uE(3)], free beta or total human chorionic gondaotrophin (hCG) and inhibin-A in the early second trimester) was 0.9%, the Serum integrated test (without nuchal translucency) 2.7%, the Combined test (nuchal translucency with free beta-hCG and PAPP-A at 11 weeks) 4.3%, the Quadruple test (alpha-fetoprotein, uE(3), free beta or total hCG and inhibin-A) 6.2%, and nuchal translucency at 11 weeks, 15.2%. All tests included maternal age. Using the Integrated test at an 85% detection rate, there would be six diagnostic procedure-related unaffected fetal losses following amniocentesis per 100,000 women screened compared with 35 using the Combined test or 45 with the Quadruple test. CONCLUSIONS: The Integrated test offers the most effective and safe method of screening for women who attend in the first trimester. The next best test is the Serum integrated test. The Quadruple test is the best test for women who first attend in the second trimester. There is no justification for retaining the Double (alpha-fetoprotein and hCG) or Triple (alpha-fetoprotein, uE(3), and hCG) tests, or nuchal translucency alone (with or without maternal age) in antenatal screening for Down's Syndrome.

Antigens↗
PubMed2004

Ethical and legal controversies in cloning for biomedical research--a South African perspective.

Therapeutic embryonic stem cell research raises a number of ethical and legal issues. The promised benefits are new and important knowledge of human embryological development, gene action, and the production of transplantable tissue and organs that could be effective in reversing or curing currently irreversible disease processes. However, this research involves the deliberate production, use, and ultimate destruction of cloned embryos, hence re-awakening the debate on the moral status of the embryo. Other moral anxieties include the possibility that women (as donors of ova) would be exploited, that this research would land on the slippery slope of reproductive cloning, and that promises made too early could lead to false hope among sick patients. It also raises the question of intellectual and actual property rights in human cell lines and the techniques by which they are produced. Review of legal systems internationally reveals that there is no global consensus on therapeutic embryonic stem cell research. Legal considerations are very much influenced by ethical deliberations on the moral status of the embryo. The South African parliament is promulgating legislation permitting therapeutic cloning, thereby demonstrating a commitment by the state to act in the best interests of patients and of regenerative medicine.

Biomedical Research↗
PubMed2003

The hopes and fears of in utero gene therapy for genetic disease--a review.

Somatic gene delivery in utero is a novel approach to gene therapy for genetic disease. It is based on the concept that application of gene therapy vectors to the fetus in utero may prevent the development of early disease related tissue damage, may allow targeting of otherwise inaccessible organs, tissues and still expanding stem cell populations and may also provide postnatal tolerance against the therapeutic transgenic protein. This review outlines the hypothesis and scientific background of in utero gene therapy and addresses some of the frequently expressed concerns raised by this still experimental, potentially preventive gene therapy approach. We describe and discuss the choice of vectors, of animal models and routes of administration to the fetus. We address potential risk factors of prenatal gene therapy such as vector toxicity, inadvertent germ line modification, developmental aberration and oncogenesis as well as specific risks of this procedure for the fetus and mother and discuss their ethical implications.

Adult↗
PubMed2002

On the scientific and ethical issues of fetal somatic gene therapy.

Fetal somatic gene therapy is often seen as an ethically particularly controversial field of gene therapy. This review outlines the hypothesis and scientific background of in utero gene therapy and addresses some of the frequently raised questions and concerns in relation to this still experimental, potentially preventive gene therapy approach. We discuss here the choice of vectors, of animal models and routes of administration to the fetus. We address the relation of fetal gene therapy to abortion, to post-implantation selection and postnatal gene therapy and the concerns of inadvertent germ-line modification. Our views on the specific risks of prenatal gene therapy and on the particular prerequisites that have to be met before human application can be considered are presented.

Abortion, Therapeutic↗
PubMed2001

Rapid and radical amniodrainage in the treatment of severe twin-twin transfusion syndrome.

We have evaluated the role of a rapid and radical method of amniodrainage in the treatment of severe twin-twin transfusion. The outcome of 15 patients with severe twin-twin transfusion for which a amniodrainage was performed by means of a vacuum bottle system was compared with the outcome of 15 patients with a similar condition, matched for gestational age at the time of the initial procedure and drained using a standard procedure. In the study group the amniodrainage ended when no amniotic fluid could be aspirated, whereas the women in the standard group were drained with a syringe system and the fluid was removed until the deepest amniotic fluid pool was <8 cm. At the initial procedure, the mean volume of amniotic fluid drained was significantly (p<0.05) higher (3252 vs 2153 ml) and the length of the procedure significantly (p<0.001) shorter (21 vs 41 min) in the study group than in the standard group. The mean post-procedure amniotic fluid index was significantly (p<0.001) smaller (2.9 vs 7.7 cm) after radical amniodrainage than after the standard amniodrainage. The mean number of procedures was significantly (p<0.001) lower (1.5 vs 5.6) in the study group compared to the standard group. In the study group the mean placental thickness increased significantly (p<0.001) from 9 mm before the procedure to 49 mm after, and the overall perinatal survival rate was 80% and the proportion of pregnancies with at least one survivor was 93%. The present data indicate that early, rapid and radical amniodrainage is an effective and low-cost therapy for severe twin-twin transfusion syndrome. Compared to the standard amniodrainage technique it also appears to reduce the need for multiple procedures.

Amnion↗
PubMed2001

Postpartum intrauterine pressure studies of the uterotonic effect of oral misoprostol and intramuscular syntometrine.

OBJECTIVES: To investigate the effect of oral misoprostol in dosages varying from 200 microg to 800 microg on postpartum uterine contractility and to establish their side effects. DESIGN: A prospective descriptive study. PARTICIPANTS: Fifty-seven women who delivered vaginally after spontaneous labours not requiring augmentation. METHODS: Within 5 minutes of delivery of the placenta, a calibrated Gaeltec catheter with an intrauterine pressure transducer at its tip was inserted transcervically into the uterine cavity. Cumulative uterine activity was recorded for 30 minutes in each woman before administering the oral misoprostol tablets and continued for a further 90 minutes after its administration. Thus each woman acted as her own control regarding changes in uterine contractility. Uterine activity was recorded on a Sonicaid Meridian fetal monitor, which measures active contraction area automatically. The incidence of side effects was also recorded. RESULTS: There was no statistical difference (P = 0.887) in the adjusted mean difference in cumulative uterine activity following all the doses of oral misoprostol, compared with intramuscular syntometrine, the largest difference being seen in oral misoprostol 200 microg (adjusted mean difference -2282 kPas s, 95% CI -7954 to 3390 kPas s). The mean onset of action of oral misoprostol (6.1, SD 2.1 min) was significantly slower than that of intramuscular syntometrine (3.2, SD 1.5 min; P = 0.002), but their durations of action were similar (P = 0.637). In the misoprostol group the commonest side effects were shivering (36%) and a rise in body temperature above 38 degrees C (40%). In the syntometrine group, the most commonly observed side effect was moderate uterine pain (nine out of ten women) and a rise in diastolic blood pressure of 20 mmHg (two out of ten women). CONCLUSION: The results of this study show that oral misoprostol has a definite uterotonic effect on the postpartum uterus. At doses of 200 microg to 400 microg, oral misoprostol has a similar uterotonic effect to intramuscular syntometrine. Higher doses of oral misoprostol are associated with significantly more side effects.

Administration, Oral↗
PubMed2001

Monopolar thermocoagulation in acardiac twinning.

The paper describes the use of monopolar thermocoagulation in the treatment of acardiac twinning. The technique and outcomes of a series of 12 pregnancies which have presented for treatment at the Fetal Medicine Unit of University College London are presented.

Electrocoagulation↗