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Biomedical subjects

J L Simpson

Publications and source records attributed to J L Simpson.

At least 145 records · Page 8Linked to original sources

Fetomaternal transfusion depends on amount of chorionic villi aspirated but not on method of chorionic villus sampling.

Transcervical and transabdominal chorionic villus sampling are believed, on the basis of indirect evidence, to result in fetomaternal transfusion. We sought to measure this phenomenon by devising a simple method that would allow us to identify variables that influence fetomaternal transfusion. We investigated patients undergoing transcervical-chorionic villus sampling (n = 15) and transabdominal-chorionic villus sampling (n = 15), restricting the sample to subjects who required only a single catheter passage or needle insertion to obtain villi. Maternal serum alpha-fetoprotein was measured before and after the procedure along with alpha-fetoprotein concentration of the transport medium into which the villi had been aspirated. We first confirmed that the change in maternal serum alpha-fetoprotein levels after chorionic villus sampling, an indirect measure of fetomaternal transfusion, was indeed correlated with the alpha-fetoprotein concentration of transport medium into which the villi were aspirated (p = 0.0350). Fetomaternal transfusion next proved to be correlated with the amount of villi obtained (p = 0.0279). However, when adjusted for the amount of villi obtained, no significant difference was observed between transcervical and transabdominal-chorionic villus sampling with respect to the change in maternal serum alpha-fetoprotein levels after chorionic villus sampling (p = 0.8512). These data suggest that the magnitude of fetomaternal transfusion depends on the amount of villi obtained but not on the chorionic villus sampling method used.

Adult↗

Direct analysis of uncultured cytotrophoblastic cells from second- and third-trimester placentas: an accurate and rapid method for detection of fetal chromosome abnormalities.

Transabdominal chorionic villus sampling can be readily used for detection of fetal chromosome abnormalities in the second and third trimesters of pregnancy. Although culture of chorionic villi offers little advantage over cultured amniotic fluid cells with respect to time required to obtain results, cytogenetic analysis of chorionic villi by direct analysis of uncultured cytotrophoblastic cells offers clear advantages because of the very short time required to obtain results. To determine whether direct analysis of uncultured cytotrophoblastic cells from second- and third-trimester placentas can routinely provide rapid and accurate assessment of fetal status, we evaluated chorionic villus specimens obtained from 57 placentas; 49 placentas were sampled in the second trimester whereas eight were sampled in the third trimester. Direct preparations yielded karyotypes in 56 (98.2%) preparations; all results of direct analyses were available within 72 hours and, when requested, within 12 hours. All results were confirmed by chromosome analysis of cultured mesenchymal core cells or cultured fetal tissue. We conclude that direct analysis of cytotrophoblastic cells from second- and third-trimester placentas is a very rapid and accurate method for determining fetal chromosome status that is comparable with, if not superior to, percutaneous umbilical blood sampling.

Adult↗

Diagnosis of trisomy 18 using spontaneously dividing cells from fetal umbilical cord blood: a novel approach for rapid late second and third trimester prenatal diagnosis.

Cytogenetic methodology recently developed by us allows spontaneously dividing cells in fetal cord blood to be used for rapid (24 hours) chromosome analysis. We utilized this methodology to diagnose trisomy 18 and facilitate clinical management in a 32-week pregnancy characterized by multiple fetal anomalies and intrauterine growth retardation.

Abnormalities, Multiple↗

Cytokeratin expression during AFB1-induced carcinogenesis.

The early stages of the carcinogenic process induced by aflatoxin B1 (AFB1) in rat liver during 24 weeks of feeding and the resulting tumours have been studied with respect to cytokeratin (CK) expression. A previously uncharacterized monoclonal antibody, MRCTU/J1, has been shown to recognize rat CK18 and together with antibodies against human CK8, 18 and 19, has been used to examine the possible lineage of tumour cells and also to identify the altered foci that might be most relevant to tumorigenesis. Results suggested that AFB1-induced transformation in liver may occur in more than one cell type, since tumours with the normal hepatocyte CK pattern and those with bile duct or oval cell CK phenotype were identified. Additionally, hepatocytes with a bile duct CK phenotype appeared during the early stages of carcinogenesis. The in vivo pattern of CK expression also appeared to be maintained in one normal and one hepatoma-derived cell line. Overexpression of CKs (particularly of CK19) was a much more selective marker for altered foci, compared to gamma-glutamyltranspeptidase, and was more consistently expressed at high levels in tumours, suggesting that it might be a more reliable way of identifying those cells involved in the transformation process.

Aflatoxin B1↗

Anaphase lag as the most likely mechanism for monosomy X in direct cytotrophoblasts but not in mesenchymal core cells from the same villi.

A 36 year old white female was referred for chorionic villus sampling for advanced maternal age. Direct (cytotrophoblast) preparations of chorionic villi were 45,X, but cultured mesenchymal core cells from the same villi were 46,XX. Study of embryonic and extraembryonic tissues showed the aneuploidy to be limited to cytotrophoblasts from specific placental sites. In aggregate, the cytogenetic findings can best be explained by anaphase lag during development of the cytotrophoblast, suggesting that this cytological mechanism and not non-disjunction is responsible for the common occurrence of monosomy X in villi.

Adult↗

Dilation and evacuation for second-trimester genetic pregnancy termination.

Dilation and evacuation (D&E) is the most common procedure for second-trimester pregnancy termination currently used by United States obstetrician-gynecologists. Although this method carries morbidity and mortality rates significantly lower than methods requiring labor induction, the procedure most commonly used for second-trimester genetic terminations seems to be labor induction (eg, vaginal prostaglandin suppositories). Many geneticists appear reluctant to recommend D&E over induction methods of pregnancy termination because they perceive that fetal abnormalities cannot be consistently confirmed by evaluation of the products of conception obtained by D&E. We report here 60 consecutive patients who underwent D&E (14-22 weeks' gestation) after detection of fetal abnormalities. The prenatal diagnoses were confirmed in all cases. Our experience thus indicates that D&E is reliable in confirming most prenatal diagnoses and should be the procedure of choice when second-trimester pregnancy termination is chosen because of fetal abnormalities.

Abortion, Eugenic↗

The absence of a relation between the periconceptional use of vitamins and neural-tube defects. National Institute of Child Health and Human Development Neural Tube Defects Study Group.

Whether taking multivitamins or folate around the time of conception can reduce a woman's risk of having a child with a neural-tube defect is controversial. To investigate this question, we examined the periconceptional use of vitamin supplements by women who had a conceptus with a neural-tube defect (n = 571), women who had had a stillbirth or a conceptus with another malformation (n = 546), and women who had had a normal conceptus (n = 573). Women with conceptuses with neural-tube defects were identified either prenatally or postnatally and were matched to control mothers for gestational age. To minimize recall bias, we interviewed nearly all the women within five months of the diagnosis of a birth defect or the birth of the infant (mean, 84 days); information on vitamin use was obtained by an interviewer who was unaware of the outcome of pregnancy. The rate of periconceptional multivitamin use among the mothers of infants with neural-tube defects (15.8 percent) was not significantly different from the rate among mothers in either the abnormal or the normal control group (14.1 percent and 15.9 percent, respectively). After adjustment for potential confounding factors, the odds ratio for having an infant with a neural-tube defect among women classified as having had full supplementation with multivitamins was 0.95 as compared with the mothers of the abnormal infants (95 percent confidence interval, 0.78 to 1.14) and 1.00 as compared with the mothers of normal infants (95 percent confidence interval, 0.83 to 1.20). There were no differences among the groups in the use of folate supplements. The adjusted odds ratio for having an infant with a neural-tube defect among those receiving the recommended daily allowance of folate was 0.97 as compared with the mothers of abnormal infants (95 percent confidence interval, 0.79 to 1.18) and 0.98 as compared with the mothers of normal infants (95 percent confidence interval, 0.80 to 1.20). We conclude that the periconceptional use of multivitamins or folate-containing supplements by American women does not decrease the risk of having an infant with a neural-tube defect.

Adult↗

Resorbed co-twin as an explanation for discrepant chorionic villus results: non-mosaic 47,XX,+16 in villi (direct and culture) with normal (46,XX) amniotic fluid and neonatal blood.

Non-mosaic trisomy 16 was observed in chorionic villus cytotrophoblasts (direct) as well as cultured mesenchymal core cells derived from the pregnancy of a 38-year-old woman. Chromosome preparations from amniotic fluid and neonatal cultures (cord blood) were 46,XX. Normal fetal growth as determined by serial ultrasound examinations occurred throughout the pregnancy, which resulted in a healthy 2724 g female. Multiple biopsies taken from the umbilical cord, placental cotyledons, and fetal membranes were 46,XX. However, a placental nodule and three of six cultures initiated from membranes (amnion and chorion) showed 46,XX/47,XX,+16 mosaicism. We propose that the trisomy 16 cells arose from residual villi derived from a trisomic co-twin that never developed. This case further demonstrates that normal fetal growth may presage normal outcome irrespective of cytogenetic findings in cytotrophoblasts (direct) and cultured mesenchymal core cells.

Adult↗

Transabdominal chorionic villus sampling for first-trimester prenatal diagnosis.

We report here our technique and initial experience with transabdominal chorionic villus sampling for first-trimester prenatal diagnosis at the University of Tennessee, Memphis. Eighty-seven patients underwent transabdominal chorionic villus sampling between 9 and 12 menstrual weeks of pregnancy. Sufficient chorionic villi (greater than or equal to 5 mg) were obtained from 83 of the 87 patients (95.4%); in 73 (88%) of the 83 successful samplings only a single needle passage was required. In one case a 47,XX, +21 complement was diagnosed; the patient elected to terminate the pregnancy and the diagnosis was confirmed in the abortus. In a second case a 46,XX,rcp(15;21)(p11;q21) woman had a fetus who also had the same balanced translocation. In a third case nonmosaic 47,XX, +16 was detected in both direct preparations of cytotrophoblast cells and cultured mesenchymal core cells. Amniocentesis performed at 15 weeks showed a normal 46,XX complement. The pregnancy continued, and the patient was delivered at term of a healthy female infant. Two spontaneous fetal losses occurred in this series, and one woman underwent an elective abortion after receiving the results of a 46,XX complement. To date, 39 of the women have been delivered and all infants are doing well; the remaining 44 pregnancies are continuing uneventfully. We conclude that transabdominal chorionic villus sampling can be a useful alternative to transcervical chorionic villus sampling, particularly when transcervical sampling is contraindicated (e.g., active genital herpes) or where the transcervical approach would be technically difficult.

Adult↗

Rapid chromosome analysis with the use of spontaneously dividing cells derived from umbilical cord blood (fetal and neonatal).

An accurate and reproducible method to obtain high-quality metaphases within 24 hours has been developed. Preparations can be derived from cord blood samples obtained either at delivery or by percutaneous umbilical blood sampling. Mitogens are not required. Rapid cytogenetic analysis can facilitate management of pregnancies characterized by malformations or intrauterine growth retardation.

Cell Division↗

Drug ingestion during pregnancy: infrequent exposure in a contemporary United States sample. National Institute of Child Health and Human Development Diabetes in Early Pregnancy Study Group.

Drug ingestion in a cohort of United States women proved consistently lower than in prior United States populations. Participating were 342 insulin-dependent diabetic and 387 control subjects who were enrolled before conception (76%) or no later than 21 days after conception (24%). Drug exposures were then recorded at entry and periodically throughout organogenesis (gestational weeks 6, 8, 10). During gestational weeks 1 to 10, approximately two thirds of the subjects were exposed to no agent other than oral iron, oral vitamins, or insulin (diabetic subjects). The mean exposures in gestational weeks 1 to 10 were 0.72 +/- 1.05 (SD) for diabetic women and 0.54 +/- 0.96 for control subjects; throughout pregnancy, the mean exposures were 1.26 +/- 1.66 and 1.58 +/- 1.78, respectively. The low exposure frequency in this contemporary United States population is highly encouraging. However, it follows that collaborative cohort efforts may be necessary in order to assess teratogenicity of drugs because relatively few women are now exposed.

Abnormalities, Drug-Induced↗

Transabdominal chorionic villus sampling in a patient with a bicornuate uterus.

In our preliminary experience with transabdominal chorionic villus sampling, we encountered a patient with a uterus bicornis bicollis and anterior fundal placenta, which posed particular technical difficulties for the transcervical approach, but in whom sampling was easily accomplished by the transabdominal route. A description of this case, as well as a discussion of our technique and experience to date, is provided.

Abdomen↗

Comparison of serum placental protein hormone levels in diabetic and normal pregnancy.

Conflicting data exist concerning maternal serum concentrations of placental hormones during pregnancy in women with diabetes mellitus. To resolve some of these discrepancies, women participating in the NICHD-Diabetes in Early Pregnancy Study were studied. In this collaborative study, pregnancy was identified within 21 days of conception by serum hCG measurements. We prospectively collected 185 blood samples from 35 insulin-dependent diabetic women and 166 blood samples from 31 control women, all between 5 and 37 weeks gestation. Serum concentrations of hCG, pregnancy-specific beta-1-glycoprotein, placental lactogen, and hCG alpha were measured serially. The relationship between serum hormone, fasting blood glucose, 1-h postprandial blood glucose, and glycosylated hemoglobin concentrations was compared. Serum hCG alpha levels were significantly lower in the diabetic women than in control women at multiple time points during the first and second trimesters, while no consistent differences in the serum concentrations of hCG or pregnancy-specific beta-1-glycoprotein were found between pregnant diabetic and control women. Serum placental lactogen levels were significantly lower in diabetic women at 9-10 weeks and 20 weeks gestation. There were no correlations between fasting blood glucose, 1-h postprandial blood glucose, or glycosylated hemoglobin and any of the placental protein levels in the diabetic women. These data are consistent with a defect in synthesis and/or secretion of hCG alpha by the cytotrophoblast during the first two trimesters of pregnancy in insulin-requiring diabetic women.

Adult↗