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Biomedical subjects

D Luton

Publications and source records attributed to D Luton.

At least 55 records · Page 3Linked to original sources

Management of fetal thyroid goitres: a report of 11 cases in a single perinatal unit.

Fetal thyroid goitres may reveal hormonal imbalance. This can jeopardize neurological development and fetal outcome even when early postnatal treatment is provided. We report a series of 11 goitres diagnosed antenatally in women with past or present thyroid disorders or discovered fortuitously on ultrasound scan. Fetuses presented with hyperthyroidism in three cases and hypothyroidism in eight. Hypothyroidism was iatrogenic in five cases, due to maternal anti-thyroid drugs. Hyperthyroidism was induced by transplacental transfer of thyroid stimulating antibodies (TSHrab). Accurate diagnosis of fetal thyroid status was obtained by fetal blood sampling but this invasive method was deemed necessary only in four cases as maternal clinical and biological data and ultrasound signs provided sufficient information to infer the type of thyroid disorder in the remaining patients. Fetal therapy relied on reduction of maternal antithyroid medication and, in selected cases, intra-amniotic injection of levothyroxin in hypothyroidism, and on administration of antithyroid drugs in hyperthyroidism. All newborns were healthy and none displayed consequences of severe thyroid imbalance. No caesarean section was performed for dystocia. Fetal thyroid goitres can be managed successfully with selected use of invasive diagnostic and therapeutic techniques.

Female↗

How accurate is the prenatal diagnosis of abnormal genitalia?

PURPOSE: The prenatal diagnosis of abnormal genitalia may have a major impact on prenatal counseling and postnatal outcome. We studied the accuracy and clinical implications of the prenatal diagnosis of abnormal genitalia. MATERIALS AND METHODS: Between 1991 and 1999 the prenatal and/or postnatal diagnosis of abnormal genitalia in 53 cases was made at our institution. All cases were prenatally assessed at our Obstetrics and Fetal Medicine Department. Outcome was confirmed postnatally or by a fetopathologist in the case of pregnancy termination. RESULTS: A genital anomaly was prenatally diagnosed in 43 cases and was accurate in 34, while in 9 cases anomalies were absent at birth. In 10 cases ambiguous genitalia were not detected prenatally. The primary anomalies suspected were male pseudohermaphroditism in 19 cases and female pseudohermaphroditism in 12, including 2 cases of congenital adrenal hyperplasia. Male pseudohermaphroditism was detected prenatally in 17 cases and diagnosis was confirmed at birth. Female pseudohermaphroditism was detected prenatally in 12 cases and only 5 were confirmed and the anomaly was discovered at birth in 6. The prognosis was highly altered when many malformations or aneuploidy was associated with ambiguous genitalia. Of the 15 patients with many malformations only 3 survived, and pregnancy was terminated in 3 of 4 cases of aneuploidy. CONCLUSIONS: When pseudohermaphroditism was detected in a male fetus by an experienced ultrasonographer at a tertiary center the prenatal diagnosis was accurate in 100% of cases. The prenatal diagnosis was less accurate (46% correct) in a female fetus.

Disorders of Sex Development↗

Defect of villous cytotrophoblast differentiation into syncytiotrophoblast in Down's syndrome.

The syncytiotrophoblast (ST) is one of the major components of the human placenta, as it is involved in feto-maternal exchanges and the secretion of pregnancy-specific hormones. The aim of this study was to elucidate the formation and function of the ST in trisomy 21 (Down's syndrome). We first used the in vitro model of cytotrophoblast differentiation into ST. Cytotrophoblasts were isolated from 15 trisomy 21-affected placentas (12-35 weeks gestation) and 10 gestational age-matched control placentas. In vitro cytotrophoblasts isolated from normal placenta fused to form the ST. This was associated with an increase in transcript levels and in the secretion of hCG, human placental lactogen, placental GH, and leptin. In trisomy 21-affected placentas, we observed a defect (or a delay) in ST formation and a dramatic decrease in the synthesis and secretion of these hormones compared to those in cultured cells isolated from control age-matched placentas. These results were confirmed by a significant (P < 0.001) decrease in gene expression in total homogenates of trisomy 21-affected placentas compared to controls. These results will be of help in understanding the maternal hormonal markers of fetal trisomy 21 and the consequences of placental defects for fetal development.

Adult↗

Prenatal diagnosis of a familial form of junctional ectopic tachycardia.

Junctional ectopic tachycardia (JET) is a rare cardiac arrhythmia characterized by atrio-ventricular dissociation, a high rate junctional escape rhythm and poor clinical tolerance in neonates and infants. Sudden infant death has been reported. The intra-uterine presentation of this arrhythmia is unknown. We report a familial form of JET with antenatal diagnosis. A sustained tachycardia at a rate of 170 beats/min with a 1:1 conduction was diagnosed in a hydropic fetus at a gestational age of 32 weeks. The older brother had presented with prenatal hydrops and junctional ectopic tachycardia was diagnosed at birth. Assuming that this arrhythmia was a JET, amiodarone was given to the mother in order to control the fetal tachycardia. The arrhythmia persisted with a 1/1 pattern but at a slower ventricular rate (140 beats/min). The ECG performed at birth revealed a narrow QRS tachycardia with a ventricular rate of 180 beats/min and a 1/1 retrograde conduction. Amiodarone therapy was continued with the addition of propanolol. Postnatal echocardiography revealed normal chambers and left ventricular dysfunction with a left ventricular shortening fraction of 17 per cent. Subsequent ECGs and Holter monitoring demonstrated typical electrocardiographic features of JET. Both parents had a normal ECG and Holter monitoring. A fetal tachycardia of moderately high rate with a 1/1 retrograde conduction and poor cardiac tolerance can be due to JET. In such cases, the use of amiodarone can be considered as a first line drug.

Adult↗

Outcome of posterior urethral valves: to what extent is it improved by prenatal diagnosis?

PURPOSE: To assess the impact of prenatal diagnosis and evaluation on the outcome of posterior urethral valves we studied all cases of valves detected prenatally, including cases of pregnancy termination due to posterior urethral valves. MATERIALS AND METHODS: Between 1989 and 1996, 30 neonates with prenatally detected posterior urethral valves were treated at our hospital. The prenatal parameters analyzed were age of gestation at diagnosis, ultrasonographic appearance of renal parenchyma and amniotic fluid volume. Fetal urine was analyzed in 9 cases. We reviewed the outcome of 10 neonates treated for posterior urethral valves which were not diagnosed prenatally during the same period. RESULTS: Of the 30 neonatal survivors 6 (20%) had renal failure, including end stage renal disease in 2, after a mean followup of 4 years. Renal failure developed in 2 of 5 cases detected before 24 weeks of gestation, in 1 of 6 with oligohydramnios and in 2 of 5 with abnormal parenchymal renal ultrasound. Normal parenchymal ultrasound and amniotic volume could not predict for good outcome. Renal failure developed in 2 of 7 cases predicted by fetal urinalysis as good prognosis and in 1 of 2 cases predicted as poor prognosis. Pregnancy was terminated for posterior urethral valves in 5 cases based on prenatal criteria of severe renal impairment. Considering these cases as poor outcome, the rate of poor prognosis increased from 20 to 31%. Among the 10 neonates without a prenatal diagnosis of posterior urethral valves renal failure developed in 2 (20%), including end stage renal disease in 1. CONCLUSIONS: When negative parameters were absent and/or fetal urine predicted good outcome there were no cases of end stage renal disease in early infancy, which was a significant help in parent counseling. The predictive value of the currently available prenatal parameters needs to be updated with larger series specifically dealing with posterior urethral valves. According to the current data, the outcome of posterior urethral valves is not yet significantly improved by prenatal diagnosis.

Female↗

In utero fetal cerebral intraparenchymal ischemia diagnosed by nuclear magnetic resonance.

Fetal brain damage can have many causes, the most common being possibly asphyxia which is often associated with intrauterine growth retardation. Early recognition of cerebral lesions is important in guiding obstetrical management. A case of antenatal cerebral intraparenchymal ischemia diagnosed by nuclear magnetic resonance (NMR) earlier than cerebral ultrasound examination is reported. This case report indicates that NMR may be a useful tool for the early detection of cerebral impairment in severe fetal growth retardation.

Adult↗

The c-ets1 protooncogene is expressed in human trophoblast during the first trimester of pregnancy.

Expression of the c-Ets1 protooncogene which codes for a transcription factor is associated with neovascularization and invasive processes. In order to determine c-Ets1 expression at the mRNA level, during the process of implantation during the first trimester of human pregnancy, samples of trophoblast were retrieved at the time of legal abortion and processed for in situ hybridization. We found that c-Ets1 mRNAs are transcribed in the endothelial cells of villous trophoblast and in the extravillous trophoblastic cells invading the uterine vessels. However, no transcript was found in maternal endothelial cells. We conclude that c-Ets1 plays a role in angiogenesis occurring in the development of the villous tree and is involved during the invasive process of the endometrium and maternal vessels by trophoblastic cells; this latter physiological event is crucial for a normal development of the fetus, its failure leading to pathological cases. We suggest that the role of the c-Ets1 protooncogene is related to the regulation of metalloproteinase genes transcription, a gene family which is known to be a target for Ets protein.

Antigens, CD34↗

Human placental growth hormone.

Placental growth hormone is the product of the GH-V gene specifically expressed in the syncytiotrophoblast layer of the human placenta. Placental growth hormone differs from pituitary growth hormone by 13 amino acids. It has high somatogenic and low lactogenic activities. Assays by specific monoclonal antibodies reveal that in the maternal circulation from 15 to 20 weeks up to term placental growth hormone gradually replaces pituitary growth hormone, which becomes undetectable. It is secreted by the placenta in a nonpulsatile manner. This continuous secretion appears to have important implications for physiologic adjustment to gestation and especially in the control of maternal insulin-like growth factor-I levels. Placental growth hormone secretion is inhibited by glucose in vitro and in vivo and is significantly decreased in the maternal circulation in pregnancies with intrauterine growth restriction. Placental growth hormone does not appear to have a direct effect on fetal growth because this hormone is not detectable in the fetal circulation. However, the physiologic role might also include a direct influence on placental development through an autocrine or paracrine mechanism, as suggested by the presence of specific growth hormone receptors in this tissue.

Growth Hormone↗

Fetal fibronectin in the cervical secretion predicts accurately the onset of labor at term.

OBJECTIVE: The objective of our study was to check if presence of fetal fibronectin in the cervical secretion of full term patient predicts accurately the onset of labour at term. STUDY DESIGN: 78 women in the term period were included in the study, serial samples for fetal fibronectin were assessed, each patient underwent spontaneous labour, delay between last sample and delivery were analysed. RESULTS: Patient with positive fetal fibronectin delivered within 3 +/- 1.9 days where as patient with negative fetal fibronectin delivered within 5.7 +/- 3.9 days (P = 0.01). CONCLUSION: Presence of fetal fibronectin in cervical secretions seems to be a powerful tool to predict in a short delay the onset of labour at term, it should be used in conjunction with clinical and fetal assessment data.

Adult↗

Fetal cord blood sampling in the diagnosis and the treatment of fetal hyperthyroidism in the offsprings of a euthyroid mother, producing thyroid stimulating immunoglobulins.

We described here three individual pregnancies in a euthyroid mother with a past history of Graves disease and high levels of thyrotropin receptor stimulating antibodies. Ten years prior to her first pregnancy the mother underwent a partial thyroidectomy for Graves disease and remained euthyroid since, but still produced high levels of thyrotropin receptor stimulating antibodies. Fetal and postnatal hyperthyroidism was not recognized for the first child who was referred to us at one year of age for craniostenosis. During the two next pregnancies fetal hyperthyroidism was suspected on the basis of fetal tachycardia, growth retardation, fetal goiter and fetal cord blood sampling confirmed high levels of free T3, free T4, suppressed fetal TSH levels, and high levels of fetal TRAb. The mother received propylthiouracil to control fetal hyperthyroidism. Neither baby was premature and each had a more favorable outcome than the first. Fetal cord blood sampling proved to be useful during these two pregnancies to ascertain the diagnosis of fetal hyperthyroidism and to monitor the dose of PTU administered to this euthyroid mother.

Adult↗

[Amnioinfusion: indications and results].

Amnioinfusion is a recent procedure introduced for routine obstetrical care fifteen years ago. The most widely recognized indication for amnioinfusion is in labor, to reduce fetal distress due to variable decceleration associated with oligohydramnios and probable presence of thick meconium stained amniotic fluid. During pregnancy, amnioinfusion can help in the diagnosis and morphologic evaluation in case of anamnios. The indication for amnioinfusion in the management of oligohydramnios at term before labour remains controversial. As a new procedure amnioinfusion must be managed with extreme caution.

Amnion↗

Aorta-associated CD34+ hematopoietic cells in the early human embryo.

Hematopoiesis is established from circulating blood stem cells that seed the embryonic rudiments of blood-forming tissues, a basic notion in developmental hematology. However, the assumption that these stem cells originate from the extraembryonic mesoderm, where primitive hematopoiesis is initiated by intrinsic precursors, has been reconsidered after analysis of blood cell development in avian embryo chimeras: yolk-sac-derived stem cells do not contribute significantly to the definitive blood system, whose first forerunners develop independently along the ventral aspect of the embryonic aorta. Recently, the homologous intraembryonic tissues of the mouse have been submitted to sensitive in vivo and in vitro assays, which showed that they also harbor multipotential hematopoietic stem cells. We have now identified a dense population of hematogenous cells, marked by the surface expression of the CD34 glycoprotein, associated with the ventral endothelium of the aorta in the 5-week human embryo. Therefore, we extend to the human species the growing evidence that intraembryonic hematopoietic cells developing independently of the yolk sac might be the real stem of the whole blood system.

Antigens, CD34↗

Two distinct endothelial lineages in ontogeny, one of them related to hemopoiesis.

We have shown previously by means of quail/chick transplantations that external and visceral organs, i.e., somatopleural and splanchnopleural derivatives, acquire their endothelial network through different mechanisms, namely immigration (termed angiogenesis) versus in situ emergence of precursors (or vasculogenesis). We have traced the distribution of QH1-positive cells in chick hosts after replacement of the last somites by quail somites (orthotopic grafts) or lateral plate mesoderm (heterotopic grafts). The results lead to the conclusion that the embryo becomes vascularized by endothelial precursors from two distinct regions, splanchnopleural mesoderm and paraxial mesoderm. The territories respectively vascularized are complementary, precursors from the paraxial mesoderm occupy the body wall and kidney, i.e., they settle along with the other paraxial mesoderm derivatives and colonize the somatopleure. The precursors from the two origins have distinct recognition and potentialities properties: endothelial precursors of paraxial origin are barred from vascularizing visceral organs and from integrating into the floor of the aorta, and are never associated with hemopoiesis; splanchnopleural mesoderm grafted in the place of somites, gives off endothelial cells to body wall and kidney but also visceral organs. It gives rise to hemopoietic precursors in addition to endothelial cells.

Animals↗