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Biomedical subjects

C H Rodeck

Publications and source records attributed to C H Rodeck.

At least 235 records · Page 13Linked to original sources

Prenatal diagnosis of ornithine carbamoyl transferase deficiency using a gene specific probe.

A gene specific DNA probe has been used to predict the genotype of two fetuses in families at risk for ornithine carbamoyl transferase deficiency. Although the probe does not detect the mutation directly, prediction was possible by examining restriction fragment length polymorphisms of the parents and sibs to identify the X chromosome carrying the mutation. It is suggested that in all pregnancies, regardless of the predicted outcome, the biochemical status of carrier mothers should be monitored because hyperammonaemia and arginine deficiency may have a deleterious effect on the fetus.

Amino Acid Metabolism, Inborn Errors↗

Rhesus disease: the model for fetal therapy.

During the past 40 years several therapeutic approaches have been tried in the management of rhesus-affected pregnancies, with the aim of ameliorating the severity of the condition and preventing intrauterine fetal death. These are reviewed below.

Adrenal Cortex Hormones↗

The management of severe rhesus isoimmunization by fetoscopic intravascular transfusions.

Twenty-five severely rhesus-isoimmunized fetuses, including 15 with hydrops fetalis, underwent a total of 77 intrauterine transfusions between 19 and 32 weeks' gestation. Fifty-eight of the procedures were fetoscopically directed intravascular transfusions, nine were ultrasound-guided intraperitoneal transfusions, and 10 were a combination of intravascular transfusion, fetal paracentesis, and intraperitoneal transfusion. The average number of antenatal procedures per patient was three (range, one to five). The survival rate for the 19 fetuses that received their initial intrauterine transfusion at or before 25 weeks' gestation was 84%; 11 of the 13 hydropic fetuses and five of the six fetuses without antenatal evidence of hydrops survived. In six cases hydrops fetalis was reversed in utero. The outcome in patients referred after 25 weeks' gestation was poor; neither of the two hydropic fetuses and only two of the four nonhydropic ones survived, which suggests the importance of early referral to a team experienced in the management of this problem. However, most of these fetal losses occurred early in the series. Seven of the 20 neonates were hydropic, and nine had severe thrombocytopenia (platelet count, less than 50,000 X 10(6)/L). The mean cord blood hematocrit and bilirubin of the neonates were 25.1% and 82 mumol/L, respectively. The babies required a total of 69 exchange transfusions (range, 0 to 9) and 68 simple transfusions (range, 0 to 25). One newborn infant who had had ultrasound evidence of hydrops fetalis at 22 weeks' gestation did not require any exchange transfusions. Nine patients required intermittent positive pressure ventilation (eight had respiratory distress syndrome and one had apnea) for a range of 1 to 86 days. The neonatal survival rate was 90% (18/20).

Blood Transfusion, Intrauterine↗

Pyruvate kinase in fetal plasma and amniotic fluid unsuccessful for the prenatal diagnosis of Duchenne muscular dystrophy.

A specific spectrophotometric assay of muscle-pyruvate kinase (M-PK) was used to measure the activity of this isozyme in fetal muscle, fetal plasma and amniotic fluid at about 17-24 wk of gestational age to assess its predictive value for the prenatal diagnosis of Duchenne muscular dystrophy (DMD). Fetal muscle obtained after termination was found to contain a high M-PK specific activity. No significant activity was detected in amniotic fluid from normal or at-risk fetuses. Pure fetal blood was obtained in utero by fetoscopy; significant plasma levels of M-PK activity were measured in a series of control samples, but at-risk fetal plasma contained no higher levels. We conclude that M-PK is of no use for the prenatal diagnosis of DMD.

Amniotic Fluid↗

The use of cloned Y chromosome-specific DNA probes for fetal sex determination in first trimester prenatal diagnosis.

Prenatal diagnosis by chorion biopsy in the first trimester of pregnancy has advantages over second trimester amniocentesis because diagnosis can be achieved at 9-12 weeks gestation, reducing prenatal anxiety and avoiding the trauma of late abortion. DNA can be prepared from chorionic villus biopsies in sufficient quantity and purity for use in prenatal diagnosis systems using specific DNA probes hybridised to restriction endonuclease digests. DNA probes derived from the Y chromosome have been used to determine fetal sex. The use of such probes means that the chromosomal sex of the fetus can be identified more quickly than by chromosome preparation and more accurately than by sex chromatin staining, and has the additional advantage that the same DNA preparation can be used for other diagnostic tests. A dot hybridisation method has been successfully used to provide even more rapid results than conventional hybridisation to Southern blots of restriction endonuclease digests. There is a risk that Y chromosome-specific DNA probes for sex determination may be subject to error if the parents have extreme Y chromosome variants such as a small or non-fluorescent Y or a Y autosome chromosome translocation. The precise extent to which such chromosome variants may lead to error has been investigated. Even extreme Y chromosome variants totally lacking fluorescence were identified as male by the cloned probes used. However, Y autosome translocations carried by females could cause error if not identified in the parents. The value of the probes has been confirmed provided that parental chromosomes and DNA are examined in parallel with the chorionic biopsy material.

Cloning, Molecular↗

The diagnostic value of plasma myoglobin levels in the adult and fetus at-risk for Duchenne muscular dystrophy.

In boys with Duchenne muscular dystrophy (DMD) plasma myoglobin levels remained approximately constant with age while creatine kinase (CK) activity progressively decreased. For carrier detection, plasma myoglobin level was found to be less reliable than CK activity. The myoglobin level was raised only in some of those subjects who also showed a raised CK activity and was normal in those with a normal CK activity. The myoglobin level in fetal muscle at 18-22 weeks gestational age was found to be low compared with adult skeletal muscle levels and, consequently, the myoglobin level in fetal plasma and in amniotic fluid was found to be negligible. It is concluded that measurement of myoglobin offers no advantage over CK for the investigation of any aspect of DMD.

Adolescent↗

Fetoscopy in the management of twin pregnancies discordant for a severe abnormality.

Selective feticide by fetoscopic air embolism was carried out in six twin pregnancies complicated by discordance for a severe abnormality. In three, a previous diagnostic fetoscopy had been performed. The procedure was effective and uncomplicated in all cases. One patient is undelivered and five have delivered healthy babies, three at term and two preterm. One of the latter, delivered at 28 weeks, died of complications in the neonatal period.

Adult↗

Normal glutathione content and some related enzyme activities in the fetal erythrocytes.

Pure fetal blood was obtained by direct-vision fetoscopy from 66 fetuses at 17-24 weeks gestation. The concentration of GSH and the activities of the enzymes gamma-glutamylcysteine synthetase (GCS), glutathione synthetase (GS), glutathione reductase (GR) and glutathione peroxidase (GPx) were analysed by established techniques to find the normal ranges for this gestational age. The ranges were relatively narrow and could serve as reference values for the prenatal diagnosis of defects in the GSH metabolism of erythrocytes. The results were compared with those obtained from 38 normal adults and with published values on neonatal blood. In the case of GR a comparison was also made with maternal blood. In comparison with adults, fetal erythrocytes showed higher GSH concentration and GCS activity and lower GS and GPx activities. This pattern resembled that found in neonatal erythrocytes except for the GCS activity, which was higher in the fetal cells. Furthermore the differences between fetal and adult erythrocytes were more pronounced than those between neonatal and adult cells. The GR activity of fetal erythrocytes was also higher than that of either normal adult or maternal blood. This difference, however, was reduced to an insignificant level when the enzyme was activated in vitro by flavin adenine dinucleotide (FAD) because of a relatively low per cent activation of the GR in the fetal erythrocytes.

Enzyme Activation↗

Rapid processing of fetal skin for prenatal diagnosis by light and electron microscopy.

A method has been developed for rapid processing of fetal skin for prenatal diagnosis of hereditary skin diseases by light and electron microscopy. Fixation, dehydration, embedding, and polymerisation can be achieved in about 5 h. The quality of tissue preservation compares favourably with that produced by slower conventional techniques. This procedure may provoke a wider interest in the potential use of fetal skin biopsy in prenatal diagnosis, especially if identification of structural abnormalities is a feasible alternative to more time consuming biochemical analysis.

Female↗

Gamma-glutamyl transferase activity in fetal serum, maternal serum, and amniotic fluid during gestation.

Gamma-glutamyl transferase activity was measured in fetal serum, maternal serum, and amniotic fluid in 173 pregnancies from 15 to 40 weeks' gestation. Fetal serum was obtained in the second trimester by fetoscopy and in the third trimester by umbilical cord puncture at caesarian section or vaginal delivery. Enzyme activities in maternal blood (10 IU/1, SD 2) and fetal blood (88 IU/1, SD 20) remained relatively constant throughout gestation, whereas in the amniotic fluid there was a significant decrease at term from the value in the second trimester (p less than 0.001). Electrophoretic separation of the enzyme showed one isoenzyme in the fetal blood and at least two in the amniotic fluid. The fetal isoenzyme had the same mobility as the major isoenzyme in the amniotic fluid.

Amniotic Fluid↗

Plasma amino acids of the mid-trimester human fetus.

The amino acid concentrations in umbilical cord plasma taken at fetoscopy were measured from 12 fetuses between 18 and 29 weeks gestation. Concurrent maternal plasma levels were measured. Fetal plasma showed consistently higher concentrations of plasma amino acids with the ratios varying between 1.1:1 and 3:1 and the difference always reached statistical significance. It is suggested that these results reflect the in vivo situation of the mid-trimester human fetus.

Amino Acids↗