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Biomedical subjects

M I Evans

Publications and source records attributed to M I Evans.

At least 19 recordsLinked to original sources
PubMed1992

Familial omphalocele: considerations in genetic counseling.

Nonsyndromal omphalocele is generally regarded as a sporadic malformation. Recurrence risk is considered negligible. We report on a patient in whom 5 consecutive pregnancies (by 2 separate nonconsanguineous partners) were complicated by omphalocele as an isolated defect. Neither the patient nor her partners had history of relatives with omphalocele, although the patient's brother and his son had large umbilical hernias requiring repair in infancy. Some familial cases of nonsyndromal omphalocele have been previously reported; most such pedigrees suggest vertical transmission, although there are a few cases with only a single generation involved. In our case, the multigenerational finding of ventral wall hernias makes an autosomal dominant mechanism with variable expressivity a tenable explanation. The collected instances of familial nonsyndromal omphalocele emphasize omphalocele heterogeneity and caution in counseling recurrence risks.

Female↗
PubMed1992

Triply discordant triplets: probability, management options, and risks.

The spontaneous occurrence of triplets is rare. With increased utilization of "assisted reproductive technologies," multifetal gestations have become more common. The empiric fetal risk for major malformation is approximately 3%. In a triplet pregnancy each fetus independently carries this risk so that the probability of having at least one malformed fetus is approximately 9%. It is much less likely to have 2 or 3 simultaneously but discordantly malformed fetuses in a multizygotic triplet gestation (.09% and .0027% risk, respectively). We report on the first case, to our knowledge, of an ovulation-stimulated triplet pregnancy complicated by 3-way discordance for major malformations diagnosed in the late second trimester by ultrasound. Fetus A was affected by congenital diaphragmatic hernia and trisomy 21; fetus B had encephalocele, a midline facial defect, and a cleft palate; and fetus C had evidence of unilateral claw hand but an otherwise normal fetal survey. At 19 weeks of gestation, fetus A was found to have spontaneously died, and a selective termination of triplet B was performed. We conclude: (1) the finding of a single major malformation in one fetus should lead to extensive search for malformations in all members of the pregnancy, and (2) the simultaneous occurrence of major malformations in more than one member of a multifetal gestation is a circumstance under which multiple selective termination deserves consideration. In this article we discuss important issues and caveats in the performance of selective termination for abnormal members of multifetal gestations.

Abnormalities, Multiple↗
PubMed1992

Functional analysis of regulatory regions upstream and in the first intron of the estrogen-responsive chicken very low density apolipoprotein II gene.

Estrogen regulates the expression of the yolk protein genes in the chicken liver during periods of egg laying. While all five of these genes, vitellogenins I, II, and III, very low density apolipoprotein II (apo VLDLII), and apolipoprotein B, respond to estrogen, individual controls are superimposed on their coordinate regulation with respect to the kinetics of induction, magnitude of response, and developmental expression. The estrogen-responsive Leghorn strain M hepatoma (LMH) cell line provides a model system for studying the molecular basis of the similarities and differences in the regulation of these genes. The apoVLDLII gene is regulated by estrogen in LMH cells in an appropriate time- and dose-dependent manner. Regulatory regions of the apoVLDLII gene have been identified by transient transfection studies in LMH cells. All four of the sequences previously shown to bind protein between the TAATA motif at -26 and proximal estrogen response element at -171 are essential in regulation of the apoVLDLII gene. Mutation of any single binding region reduces expression by more than 80%, indicating cooperative interactions of proteins across the entire region. While these sequences will direct assembly of a functional transcription complex, we demonstrate that addition of the first intron of the apoVLDLII gene to the promoter construct results in a 4-fold increase in estrogen-dependent expression following transient transfection into LMH cells. Results of deletion analyses indicate that two distinct regions of the intron contribute to this regulation.

Animals↗
PubMed1992

Estrogen-dependent expression of the chicken very low density apolipoprotein II gene in serum-free cultures of LMH cells.

The estrogen-responsive Leghorn strain M chicken hepatoma (LMH) cell line provides a model system for studying the estrogen-dependent, liver-specific expression of avian genes. Serum-free culture conditions have been established that allow expression of apolipoprotein B, very low density apolipoprotein II (apoVLDLII), serum albumin, and transferrin at levels detectable by Northern blot analysis. Regulation of apoVLDLII mRNA by estrogen occurred in an appropriate time- and dose-dependent manner in serum-free cultures of the LMH cells. The expression of apoVLDLII mRNA in serum-free culture was at least 100-fold higher than that expressed in cultures containing 10% serum. The level of estrogen receptors in LMH cells cultured with 10% serum was approximately 2000 receptors per cell, and in serum-free culture approximately 1000 receptors per cell. When these cells were transfected with estrogen receptor DNA and cultured in serum-free medium, apoVLDLII mRNA was decreased relative to that expressed in cells transfected with a control plasmid. These results indicate that when the LMH cells are cultured without serum, estrogen receptors are not the limiting factor for the expression of the apoVLDLII gene.

Animals↗
PubMed1992

Rapid prenatal diagnosis by fluorescent in situ hybridization of chorionic villi: an adjunct to long-term culture and karyotype.

OBJECTIVE: This series was designed to assess in a pilot study the feasibility of using fluorescence in situ hybridization on chorionic villi. STUDY DESIGN: We constructed probes derived from specific subregions of human chromosomes 21, 18, 13, X, and Y that give a single copylike signal when used in conjunction with suppression hybridization. RESULTS: In a blind series of 47 samples all, including one trisomy 21, were correctly identified. The samples were correctly classified as disomic for five chromosomes. CONCLUSIONS: The combination of chromosome-specific probe sets composed primarily of cosmid contigs and optimized hybridization and detection allowed accurate chromosome enumeration in uncultured human chorionic villi; these results are consistent with those obtained by traditional cytogenetic analysis and suggest a use for fluorescence in situ hybridization as an adjunct to karyotyping when rapid results are needed.

Chorionic Villi↗
PubMed1992

The smaller than expected first-trimester fetus is at increased risk for chromosome anomalies.

OBJECTIVE: Intrauterine growth retardation associated with fetal chromosome anomalies is usually documented on ultrasonography late in the second trimester. However, we believe and attempt to document here that the impact of aneuploidy on fetal growth is evident much earlier (i.e., the aneuploid fetus may appear smaller than dates on ultrasonography even in the first trimester). STUDY DESIGN: For the population referred to our center for chorionic villus sampling from January 1988 to July 1991, we compared gestational age as calculated from the last menstrual period to that derived from fetal size as measured by crown-rump length. A cutoff of 7 days was chosen to select the study group. The remainder of our chorionic villus sampling population in which fetal size was expected was used as controls. We also divided those chorionic villus sampling patients by when a fetal death was observed by size. RESULTS: In the study period 3194 chorionic villus sampling procedures were performed and in 277 (8.7%) fetal length was smaller than expected by at least 7 days. Sixty (1.9%) chromosome anomalies were diagnosed by first trimester chorionic villus sampling in the study period. The frequency of chromosome anomalies was 4.3% in the study group and 1.7% in controls (p < 0.004). The more aberrant the karyotype on "postmortem chorionic villus sampling," the greater the growth retardation tended to be. CONCLUSIONS: In our chorionic villus sampling population a fetal crown-rump length smaller than dates is associated with a significant increase in risk of chromosome anomalies. Moreover, the larger the size-dates discrepancy, the higher the possibility that the aneuploidy affecting that pregnancy is of the severe or lethal type.

Adult↗
PubMed1992

Peripheral magnesium sulfate enters the brain and increases the threshold for hippocampal seizures in rats.

OBJECTIVES: Our objectives were to determine whether magnesium sulfate crosses the blood-brain barrier and whether it has central anticonvulsant action. STUDY DESIGN: In experiment 1 34 female Long-Evans rats were divided into six groups: control (n = 7); single magnesium sulfate injection and evaluation after 20 minutes in 3 conditions: normal rats (n = 7), sham-operated animals (n = 5), and after electrical stimulation by hippocampal electrode (n = 5); single injection and evaluation after 2 hours (n = 5); and prolonged (2 hours) serum magnesium elevation (n = 5). Serum, cerebrospinal fluid, and specific brain areas were analyzed for magnesium concentrations. In experiment 2 threshold for electrical seizure was measured in eight rats before and after intraperitoneal injections of magnesium sulfate versus saline solution. RESULTS: In experiment 1 there was a significant correlation between blood and cerebrospinal fluid magnesium concentrations (r = 0.80, p < 0.0001). Magnesium concentrations were increased in the cortex and hippocampus, with the largest changes occurring after two hours of sustained serum magnesium concentrations (p < 0.01). Induction of hippocampal seizure activity resulted in further elevations in cerebrospinal fluid magnesium concentrations but did not change brain concentrations. In experiment 2 magnesium sulfate increased the electrical threshold required to induce seizures by 34% (p = 0.01). CONCLUSIONS: Magnesium sulfate enters the cerebrospinal fluid and brain and has a central anticonvulsant effect.

Animals↗
PubMed1992

First trimester interfetal size variation in well-dated multifetal pregnancies.

Sonographic measurements of multifetal pregnancy for dating and growth are considered identical to singleton pregnancies until the second trimester. Observations in 57 patients having triplets or more, who were referred for first trimester multifetal pregnancy reduction, suggest considerable size variability both within an individual pregnancy and among pregnancies of the same gestational ages (GAs). These data are unique because the GAs are precisely known, because the pregnancies were established by assisted reproductive technology. We observed a greater standard deviation at 12 and 13 weeks of GA. We also observed significant interfetal variation within an individual pregnancy. Because multifetal pregnancy reduction was performed, follow-up of any given fetus to term was not possible. We conclude that for high-order multiple gestations: (1) interfetal size variability begins much earlier than often stated; (2) differences in the degree of variability can be observed among different pregnancies of the same gestational age and within the same pregnancy, and (3) there is a trend for increasing variability with increasing gestational age.

Body Height↗
PubMed1992

Prenatal biochemical screening.

Most fetal abnormalities occur in low-risk pregnancies. Screening techniques have been developed to help determine who in the low-risk group may actually be at high risk. Biochemical screening for chromosomal abnormalities and neutral tube defects have significantly increased their detection, but there is still considerable room for improvement.

Amniocentesis↗
PubMed1992

Chorionic villus sampling: transabdominal versus transcervical approach in more than 4000 cases.

OBJECTIVE: To address the evolving trends in the choice of transabdominal or transcervical chorionic villus sampling (CVS) at a teaching hospital and to evaluate the influence of gestational age on the approach chosen. METHODS: We analyzed our CVS data base, which contained information from 1986-1991. The proportions of transabdominal and transcervical CVS were tabulated for each year. In addition, the distribution of the CVS approaches over the various gestational ages was examined. RESULTS: During the study period, 4290 CVS procedures were performed. The rate of the transabdominal technique was stable at about 15% per year except for the first 2 years, when essentially all procedures were transcervical. Use of transabdominal CVS increased with advancing gestational age, from 3.6% at less than 10 weeks' gestation to 97.6% at greater than 14 weeks (chi 2 = 120, P less than .001; r = 0.791). CONCLUSIONS: The choice between the transabdominal and transcervical approach to CVS largely reflects the route emphasized during the physician's training. When choice is based strictly on technical limitations due to placental position, the overall transabdominal CVS rate is approximately 15%. A shift from transcervical to transabdominal CVS occurs with increasing gestational age as the placenta gains bulk and moves away from the cervix. After 14 weeks' gestation, most procedures are performed transabdominally.

Chorionic Villi Sampling↗
PubMed1992

Determinants of parental decision to abort or continue after non-aneuploid ultrasound-detected fetal abnormalities.

OBJECTIVE: This study evaluated factors influencing the decision to abort after abnormalities in the karyotypically normal fetus were found through ultrasonography. METHODS: We reviewed all pregnancies complicated by ultrasound-detected abnormalities managed on our service from April 1990 through August 1991 (N = 262). Cases with associated karyotypic abnormalities were excluded (N = 35), as were cases diagnosed after the legal gestational age limit for abortion (N = 68). The remaining 159 cases were stratified into prognosis groups of "severe," "uncertain," and "mild." RESULTS: The prognostic severity of the ultrasound abnormality strongly correlated with the decision to abort (P less than .0001). Rates of termination were 0, 12, and 66% in the "mild," "uncertain," and "severe" groups, respectively. The patients' age, gravidity, and parity, and the fetal gestational age at diagnosis did not differ significantly between the groups. CONCLUSIONS: 1) In non-aneuploid pregnancies with an ultrasound diagnosis of fetal abnormality, the major predictor of the decision to abort was the severity of fetal prognosis. 2) The gestational age at diagnosis was not an important variable in the decision to abort for fetal structural abnormalities. 3) Parents who had fetuses with abnormalities associated with uncertain prognoses usually opted to continue the pregnancy. This appeared to be particularly true for defects that were potentially correctable in utero or by neonatal intervention (even if investigational).

Abortion, Induced↗
PubMed1992

Fetal intracardiac potassium chloride injection to avoid the hopeless resuscitation of an abnormal abortus: I. Clinical issues.

OBJECTIVE: With the intention of preventing the attendant medical, ethical, and legal problems arising from the birth of live-born, anomalous fetuses, we initiated a program offering fetal intracardiac potassium chloride injection as an adjunctive measure in the setting of genetically indicated second-trimester abortion. METHODS: A lethal fetal injection was offered to patients carrying chromosomally or structurally abnormal fetuses at 19-24 weeks' gestation who desired abortion. When the patient elected this procedure, real-time ultrasound guidance was used to inject 3-5 mL of potassium chloride (2 mEq/mL) directly into the fetal cardiac chambers, followed by observation of fetal heart activity to ascertain cessation. Labor was subsequently induced with uterotonic prostaglandins. RESULTS: The procedure caused immediate cessation of fetal heart motion in 20 of 21 cases. There were no maternal complications. No fetuses were live-born. CONCLUSIONS: Direct fetal intracardiac potassium chloride injection effectively causes immediate fetal cardiac arrest. This approach may be adopted in cases of abortion by labor-induction methods at advanced gestations to ensure that the abortus is stillborn.

Abortion, Eugenic↗
PubMed1992

Fetal intracardiac potassium chloride injection to avoid the hopeless resuscitation of an abnormal abortus: II. Ethical issues.

Following the diagnosis of a genetic anomaly, some couples choose to have a legal abortion. However, following later abortions at greater than 20 weeks, the rare but catastrophic occurrence of live births can lead to fractious controversy over neonatal management. To avoid this situation, we have added fetal intracardiac potassium chloride injection to cause fetal cardiac arrest before induction of labor. The ethical issues surrounding such a practice are complex. We support this practice for three reasons: 1) The women's decision for abortion is protected because this practice assures her right for non-interference; 2) potential psychological harm to the patient and other family members is avoided; and 3) the potential for coercive intervention by other health care personnel is eliminated. At least three objections can be raised: 1) All abortions are unjust; 2) newborns and second-trimester fetuses at similar weights with identical defects should be managed in like fashion; and 3) the patient is not entitled to death of the fetus, only to evacuation of the uterine contents. On balance, we believe that our approach is justifiable ethically as it reduces the burden of conflict between the wishes of the patient and those of the neonatal care givers. It should be introduced only in situations in which the likelihood of civil or criminal liability or unwarranted medical intervention is high.

Abortion, Eugenic↗
PubMed1991

Postmortem chorionic villus sampling: correlation of cytogenetic and ultrasound findings.

We performed chorionic villus samplings (CVS) in 795 cases in the first trimester during a 13-month period. Of these 35 were found to have a blighted ovum or missed abortion prior to the procedure. Nineteen women consented to have CVS. Ultrasonographic and cytogenetic findings in these 19 pregnancies were correlated. Expected gestational age was determined by last menstrual period. Observed gestational age was determined by crown rump length (CRL) (12 pregnancies) or gestational sac (GS) (7 pregnancies without fetal pole). The differences in days between the estimated and observed gestational ages was determined for each pregnancy. In all 19 CVS samples cytogenetic diagnosis documented aneuploidy. Ten cases had chromosome abnormalities virtually always lethal in the embryonic period (group I). Nine pregnancies had defects with moderate potential for fetal viability (group II). Gestations with low viability potential (group I) had estimated minus observed gestational age discrepancies (23.4 +/- 8.3 days) significantly greater than gestations with moderate viability potential (group II) (8.9 +/- 4.3 days) (P less than .001). The absence of a fetal pole was more common in group I. CVS in pregnancies with missed abortion or blighted ovum is feasible and has a high likelihood of documenting aneuploidy. Furthermore, the more severe the anomaly the more likely there will be very early fetal demise or intrauterine growth retardation.

Abortion, Missed↗