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J L Simpson

Publications and source records attributed to J L Simpson.

At least 73 records · Page 4Linked to original sources
PubMed1995

Characterization of an unbalanced de novo rearrangement by microsatellite polymorphism typing and by fluorescent in situ hybridization.

Unbalanced de novo rearrangements, difficult to characterize by conventional cytogenetic techniques, may be elucidated by molecular approaches. By dinucleotide repeat polymorphism typing and fluorescence in situ hybridization (FISH), we have defined the composition of an unbalanced de novo translocation (46,XX,15p+) in a child with multiple congenital anomalies. Use of a microsatellite repeat D5S208 (localized to 5p15) and polymerase chain reaction (PCR) analysis confirmed that the extra segment originated from the short arm of chromosome 5. Amplification of the patient's DNA with primers for dinucleotide repeats D5S350 and D5S118 showed that the entire 5p (from 5pter to 5q11) was present in 3 copies. FISH confirmed the trisomic status of 5p, and further revealed the presence of centromeres of both chromosomes 5 and 15 on the rearranged chromosome thus delineating its dicentric nature. This information allowed us to redefine the de novo rearrangement in this patient as 46,XX,dic der(15)t(5;15)(q11;p11).

Base Sequence↗
PubMed1995

Isolating fetal nucleated red blood cells from maternal blood: the Baylor experience--1995.

In our previous work we have isolated fetal cells from maternal blood and used fluorescent in situ hybridization (FISH) for chromosome-specific probes to detect aneuploidy. Current efforts in the Baylor College of Medicine programme are focusing on obtaining consistency in flow-sorting methodology and on determining sensitivity and specificity. To this end, systematic evaluation of five glycophorin A (gly A) antibodies all produced agglutination, leading us to abandon the use of gly A antibodies for positive selection of fetal cells. Conversely, we have found LDS-751 to be useful for nuclear selection. CD45 negative selection can best be accomplished by the use of flasks coated with goat antibodies against mouse antibodies. Positive selection by flow sorting for either CD71+ cells or gamma-globin-positive cells seems to be successful. Using these two approaches, we have recently detected male (fetal) cells in pregnancies in which the fetus was 46,XY in 10 of 18 and in 12 of 14 cases, respectively.

Cell Separation↗
PubMed1995

Detection of low-grade mosaicism in fetal cells isolated from maternal blood.

Recovering and analysing fetal erythrocytes from maternal blood is being pursued for non-invasive prenatal genetic diagnosis. We report the observation of 46,XY/47,XXY mosaicism in fetal cells from a woman whose first-trimester chorionic villus sampling (CVS) initially showed only 46,XY. Only after exhaustive (500 cells) analysis were four XXY cells found in cultured villi.

Adult↗
PubMed1995

Trisomy 21 and maternal age of menopause: does reproductive age rather than chronological age influence risk of nondisjunction?

The biological basis underlying the increased risk of nondisjunction in offspring of women of advanced maternal age is not understood. We sought to test the hypothesis that maternal reproductive age (distance in time from approaching menopause) rather than chronological age is pivotal in the etiology of nondisjunction. Our results found no difference in age of menopause between women > or = 30 years old at delivery of a child with trisomy 21 (i.e., age-related nondisjunction) compared to controls. Among women < 30 years of age at delivery of a child with trisomy 21, none underwent premature menopause. Therefore, our findings fail to support the theory that reproductive age plays a major role in the etiology of nondisjunction.

Adult↗
PubMed1995

Isolated fetal choroid plexus cysts and trisomy 18: a review and meta-analysis.

OBJECTIVE: Risk of trisomy 18 in a fetus with ultrasonographic diagnosis of choroid plexus cysts and no other anomalies is controversial. Using our data and current literature, we performed a meta-analysis and estimated the positive predictive value of isolated choroid plexus cysts for trisomy 18. STUDY DESIGN: Between Jan. 1, 1989, and Dec. 31, 1992, all women undergoing ultrasonographic examination at our institution were prospectively evaluated for fetal choroid plexus cysts and cytogenetic outcome. In addition, all reports dealing with fetal choroid plexus cysts obtained from MEDLINE (1983 through 1992) were assessed. Only prospective studies with > 10 cases of choroid plexus cysts were further evaluated to determine the total number of fetuses with choroid plexus cysts and otherwise normal sonograms. Frequency of aneuploidy was determined by analysis of our data and the included studies. To estimate the positive predictive value of choroid plexus cysts from trisomy 18, a theoretic 2 x 2 table was constructed with values available from the literature. RESULTS: Eighty fetuses with choroid plexus cysts were identified in our unit. Of 74 fetuses with isolated choroid plexus cysts, there were no cases of trisomy 18. Meta-analysis identified 2 cases of trisomy 18 among 748 fetuses with isolated cysts (1/374). To derive a positive predictive value of isolated choroid plexus cysts for trisomy 18, we reviewed the literature and found a total of 50 fetuses with trisomy 18 who underwent ultrasonographic examination in the midtrimester. There were 3 cases of isolated choroid plexus cysts, and 12 of 50 (24%) had otherwise normal ultrasonographic results. Using a midtrimester incidence of 1 in 2461 for trisomy 18 (Hsu LYF. In: Milunsky A, ed. Genetic disorders of the fetus. 3rd ed. Baltimore: Johns Hopkins University Press, 1992: 155-210; Hook et al. Am J Hum Genet 1989; 45:855-61) and a prenatal prevalence of 0.95% for choroid plexus cysts (based on a review of the literature), we obtained a positive predictive value of 1 in 390. CONCLUSION: On the basis of the risk for trisomy 18 obtained from our meta-analysis (1/374) and its close approximation to the estimated positive predictive value (1/390), our data do not support the routine offering of invasive prenatal cytogenetic testing in cases of isolated choroid plexus cysts.

Brain Diseases↗
PubMed1995

Associations between adverse perinatal outcome and serially obtained second- and third-trimester maternal serum alpha-fetoprotein measurements.

OBJECTIVE: Our purpose was to determine whether third-trimester maternal serum alpha-fetoprotein predicts adverse perinatal outcome and whether use of both second- and third-trimester maternal serum alpha-fetoprotein enhances the positive predictive value for various abnormal outcomes. STUDY DESIGN: A cohort study with obstetric outcome assessed by chart analysis after delivery was performed at Regional Medical Center (Memphis, Tennessee), a hospital staffed by university-based physicians serving a large urban population with many indigent patients. A total of 650 women attending prenatal clinics in the above setting with a singleton pregnancy without a neural tube defect, contributing a maternal blood samples in both the second and third trimesters, and delivered in the above hospital participated. Various pregnancy outcomes were correlated with maternal serum alpha-fetoprotein levels in the second and third trimesters and in both. RESULTS: In the third trimester no significant associations were found between maternal serum alpha-fetoprotein elevations and pregnancy complications. In the second trimester elevation ( > or = 2.0 multiples of the median) were, by contrast, significantly associated with preterm premature rupture of the membranes, preterm birth, and low birth weight. No association was found with certain other complications. When second-trimester data were grouped according to the types of complications occurring in individual women, only preterm premature rupture of the membrane proved statistically significant. CONCLUSIONS: Second-trimester but not third-trimester maternal serum alpha-fetoprotein is significantly elevated with preterm premature rupture of the membranes, preterm birth, and low birth weight; in this cohort study no association was found with preeclampsia, oligohydramnios, or polyhydramnios.

Cohort Studies↗
PubMed1995

Timing of conception and the risk of spontaneous abortion among pregnancies occurring during the use of natural family planning.

OBJECTIVE: Our purpose was to ascertain the effects of timing of conception on the risk of spontaneous abortion. STUDY DESIGN: To assess these effects, women who conceived while using natural family planning were identified in five centers worldwide between 1987 and 1993. Timing of conception was determined from 868 natural family planning charts that recorded day of intercourse and indices of ovulation (cervical mucus peak obtained according to the ovulation method and/or basal body temperature). Conceptions on days - 1 or 0 with respect to the natural family planning estimated day of ovulation were considered to be "optimally timed," and all other conceptions were considered as "non-optimally timed." The rate of spontaneous abortions per 100 pregnancies was examined in relation to timing of conception, ages, reproductive history, and other covariates with bivariate and multivariate statistical methods. RESULTS: There were 88 spontaneous abortions among 868 pregnancies (10.1%). The spontaneous abortion rate was similar for 361 optimally timed conceptions (9.1%) and 507 non-optimally timed conceptions (10.9%). However, among 171 women who had experienced a spontaneous abortion in a prior pregnancy, the rate of spontaneous abortion in the index pregnancy was significantly higher with non-optimally timed conceptions (22.6%) as compared with optimally timed conceptions (7.3%). This association was not observed among 697 women with no history of pregnancy loss. The adjusted relative risk of spontaneous abortion among women with non-optimally timed conceptions and a history of pregnancy loss was 2.35 (95% confidence intervals 1.42 to 3.89). The excess risk of spontaneous abortion was observed with both preovulatory and postovulatory conceptions. CONCLUSIONS: Overall, there is no excess risk of spontaneous abortion among the pregnancies conceived during natural family planning use. However, among women with a history of pregnancy loss, there is an increased risk of spontaneous abortion associated with preovulatory or postovulatory delayed conceptions.

Abortion, Spontaneous↗
PubMed1995

Isolating fetal cells in the maternal circulation.

Fetal cells exist in maternal blood and can be utilized for prenatal genetic diagnosis. The use of polymerase chain reaction (PCR) technology on maternal blood has enabled the detection of fetal sex, Mendelian disorders (e.g. beta-globin mutations), HLA polymorphisms and fetal Rhesus (D) blood type. Enrichment for erythroblasts and trophoblasts by various density gradient and flow sorting techniques followed by fluorescence in-situ hybridization (FISH) with chromosome-specific DNA probes has allowed detection of trisomy 21, trisomy 18, Klinefelter syndrome (47,XXY) and 47,XYY. The fetal cell type that has generated the most success is the nucleated erythrocyte; however, trophoblasts, lymphocytes and granulocytes are also considered to be present in maternal blood. Fetal cells circulate in maternal blood during the first and second trimesters, with frequency increasing as gestation advances. Emphasis is thus now directed toward determining the most practical and efficacious manner for this technique to be applied to prenatal genetic diagnosis. A large scale collaboration of clinical evaluations is underway in the USA, upon completion of which assessment can be made of whether this technology can serve as an alternative to conventional invasive and non-invasive methods of prenatal cytogenetic diagnosis.

Cell Separation↗
PubMed1995

Metabolic control and progression of retinopathy. The Diabetes in Early Pregnancy Study. National Institute of Child Health and Human Development Diabetes in Early Pregnancy Study.

OBJECTIVE: To evaluate the role of metabolic control in the progression of diabetic retinopathy during pregnancy. RESEARCH DESIGN AND METHODS: We conducted a prospective cohort study of 155 diabetic women in the Diabetes in Early Pregnancy Study followed from the periconceptional period to 1 month postpartum. Fundus photographs were obtained shortly after conception (95% within 5 weeks of conception) and within 1 month postpartum. Glycosylated hemoglobin was measured weekly during the 1st trimester and monthly thereafter. RESULTS: In the 140 patients who did not have proliferative retinopathy at baseline, progression of retinopathy was seen in 10.3, 21.1, 18.8, and 54.8% of patients with no retinopathy, microaneurysms only, mild nonproliferative retinopathy, and moderate-to-severe nonproliferative retinopathy at baseline, respectively. Proliferative retinopathy developed in 6.3% with mild and 29% with moderate-to-severe baseline retinopathy. Elevated glycosylated hemoglobin at baseline and the magnitude of improvement of glucose control through week 14 were associated with a higher risk of progression of retinopathy (adjusted odds ratio for progression in those with glycohemoglobin > or = 6 SD above the control mean versus those within 2 SD was 2.7; 95% confidence interval was 1.1-7.2; P = 0.039). CONCLUSIONS: The risk for progression of diabetic retinopathy was increased by initial glycosylated hemoglobin elevations as low as 6 SD above the control mean. This increased risk may be due to suboptimal control itself or to the rapid improvement in metabolic control that occurred in early pregnancy. Excellent metabolic control before conception may be required to avoid this increase in risk. Those with moderate-to-severe retinopathy at conception need more careful ophthalmic monitoring, particularly if their diabetes was suboptimally controlled at conception.

Adult↗
PubMed1995

Noninvasive screening for prenatal genetic diagnosis.

During the last two decades a number of methods of prenatal diagnosis have become available and have been used either in laboratory research or in routine genetic counselling. Despite the effectiveness of invasive sampling procedures in diagnosing genetic disorders, their use involves some risk. The advantage of noninvasive methods is that they provide an opportunity to make a genetic diagnosis without risk, and therefore are applicable for use in mass screening programmes. This article reviews three different approaches to noninvasive prenatal genetic diagnosis and offers conclusions and recommendations for their use. Maternal serum screening is a well-understood technique that should be universally offered to pregnant women, regardless of their risk status. Invasive tests can be used, as indicated, once serum testing results have been obtained. Although ultrasonography cannot be recommended for routine use, it can provide a useful adjunct to serum screening and deserves further investigation. Elaboration of fetal cells from maternal blood is a promising technique but can only be considered investigational on the basis of current research, and should not serve as the sole basis of clinical decision-making.

Female↗