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Biomedical subjects

E Pergament

Publications and source records attributed to E Pergament.

At least 19 recordsLinked to original sources

Preference assessment of prenatal diagnosis for Down syndrome: is 35 years a rational cutoff?

OBJECTIVE: To compare the perceptions of miscarriage and birth of a child with Down syndrome among pregnant women and to evaluate the implications of these preferences for the traditional 35-year old maternal age risk boundary. METHODS: An interviewer-administered survey was given to 186 pregnant women receiving antepartum care at a university hospital. Preferences, as reflected by utilities, for birth of a child with Down syndrome and pregnancy miscarriage, stratified by patient characteristics, were assessed. RESULTS: The utility for the birth of a child with Down syndrome decreased (p < 0.001) as clinical severity increased from mild (0.78) to severe (0.65). Miscarriage of a pregnancy had a mean utility of 0.76 +/- 0.31. Women who desired prenatal diagnosis had a utility value for miscarriage (0.79 +/- 0.28) that was significantly higher than for the birth of a child with Down syndrome of unknown severity (0.73 +/- 0.27). In multivariable logistic regression, desire for prenatal diagnosis was the only factor associated with a preference of miscarriage over birth of an affected child (odds ratio 2.26, 95% confidence interval 1.03, 4.96). CONCLUSION: Women who desire prenatal diagnosis do not perceive the birth of a child with Down syndrome and a pregnancy miscarriage to be equivalent health states. This finding calls into question the rationale of the 35-year-old maternal age criterion and suggests that actual patient preferences should be better incorporated into the decision to offer definitive prenatal diagnosis.

Abortion, Spontaneous↗

Assessment of fetal status in multiple gestation pregnancies using interphase FISH.

The use of fluorescence in situ hybridization (FISH) for women with multiple gestation pregnancies has been evaluated. Women were referred for chromosome analysis because of advanced maternal age, abnormal ultrasound findings or a positive family history and/or prior to fetal reduction. FISH was successfully applied to all specimens obtained by amniocentesis or chorionic villus sampling (CVS). Based on FISH results, fetal-fetal contamination of specimens following CVS was 11.5% in twin pregnancies and 16% in triplet or higher multiples. FISH detected trisomy 21 in three cases with no false negatives or positives. Whereas FISH may provide rapid and useful assessment of fetal status in decision-making regarding fetal reduction, the present study also highlighted the obstetrical difficulty of ensuring a sample representative of each fetus following CVS in addition to the possibility of not identifying clinically significant chromosome aberrations using currently available FISH probes.

Amniotic Fluid↗

Guest editorial

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Journal Article↗

Recurrent triploidy of maternal origin.

We report the occurrence of triploid preimplantation embryos following in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in a woman with two previously-identified triploid conceptuses which spontaneously underwent fetal demise at 10 and 23 weeks' gestation. An error in maternal meiosis II is proposed as the most likely cause.

Abortion, Habitual↗

New molecular techniques for chromosome analysis.

The advent of molecular genetic technology has significantly advanced knowledge about the structure of chromosomes and their behaviour during meiosis and mitosis, as well as delineating cytogenetic aberrations that cannot be identified by conventional chromosome analysis. Molecular cytogenetics, the visualization of genetic loci using the dynamic recombinant technology of fluorescence in situ hybridization (FISH), now provides the obstetrician and gynaecologist with increasingly important diagnostic and prognostic information heretofore unavailable. The technical principles underlying FISH are briefly discussed. Emphasis is placed on the clinical applications of FISH and technologies derived from FISH, in particular comparative genome hybridization, microdissection FISH and multiplex FISH. These technologies play increasingly significant roles in preimplantation and prenatal genetic diagnosis, in the identification of microdeletion syndromes, cryptic translocations and marker chromosomes, and in defining chromosome mosaicism. FISH and related technologies also constitute essential diagnostic modalities in follow-up of organ transplantation, in a variety of haematological disorders and in determining the amplification of oncogenes associated with specific forms of cancer and neoplasia.

Female↗

The application of fluorescence in-situ hybridization to prenatal diagnosis.

Fluorescence in-situ hybridization has become essential in prenatal diagnosis for identifying chromosome aberrations as well as in preimplantation genetic diagnosis and the analysis of fetal cells in maternal blood. Comparative genome hybridization, multicolor fluorescence in-situ hybridization and telomere probes provide technical approaches for the characterization of fetal chromosome anomalies not possible by conventional karyotyping.

Chromosome Aberrations↗

The clinical application of interphase FISH in prenatal diagnosis.

Fluorescence in situ hybridization (FISH) for five chromosomes (13, 18, 21, X and Y) detected 87 of 107 (81%) of the chromosome aberrations identified by conventional chromosome analysis applied to fetal interphase cells obtained by chorionic villus sampling or amniocentesis. The choice of FISH was solely determined by prospective parents after formal genetic counselling concerning the advantages and disadvantages of FISH analysis. Excluding known familial chromosome aberrations, if FISH analysis revealed normal signals, there was an overall residual risk of 1 in 149 for an undetectable chromosome aberration. This risk varied according to the indication for prenatal diagnosis: 1 in 177 for women of advanced maternal age; 1 in 60 for women at increased risk for Down syndrome based on maternal serum screening; and, 1 in 43 for women whose ultrasound examination revealed fetal anomalies. There were 20 cases of discordance between the FISH results and standard karyotype analysis: four were the outcome of a failure to apply the appropriate FISH probe; 16 were not detectable by the available FISH probes. Of these 16, nine were chromosome abnormalities with clinical significance and seven were familial. If FISH is to become a standard part of prenatal genetic diagnosis, genetic counselling that is sensitive to patient health needs must be based on accurate information about the biological and obstetrical implications of the results of FISH analysis.

Adult↗

Guest editorial.

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Journal Article↗

The role of the preimplantation geneticist in human cloning.

If human cloning is to become a reality, the preimplantation geneticist must be responsible for determining the indications for undertaking cloning and for establishing the risks and benefits of human cloning. The unresolved issue is whether a compelling argument can be made for cloning a human for therapeutic reasons while outweighing legal, moral and ethical objections. At present, 'whole person' cloning does not seem justified under any circumstance, whereas cloning for the replacement of diseased cells, tissues or organ systems, i.e. 'spare parts', seems to be a likely, acceptable application of cloning strategies for humans.

Cloning, Organism↗

At the crossroads: the intersection of the Internet and clinical oncology.

The Internet is rapidly becoming a third party in the doctor-patient relationship. The World Wide Web, electronic mail (e-mail), and discussion groups have dramatically increased the quantity of medical and health information available to patients, who, in turn, vary greatly in their understanding of that newly discovered information. This article reviews the advantages and disadvantages of the Internet for both oncology patients and physicians. This forms the background for a discussion of three steps that clinical oncologists and other health care professionals can take to direct and control the potential of the Internet so as to optimize patient care. These steps include: (1) finding out what type of cancer information is being disseminated on the Web; (2) using Internet-derived material that patients bring to the clinic as a stepping-stone for patient education; and (3) becoming an active participant on the Web. Each of these strategies requires health professionals to be proactive. The appropriate and effective use of the Internet, as well as its boundaries, are rapidly expanding in medicine and are likely to co-evolve with changes in patient-health care provider relationships.

Humans↗

Hybridization of chromosome 18 alpha-satellite DNA probe to chromosome 22.

Fluorescence in situ hybridization (FISH) of uncultured chorionic villus diploid cells with a chromosome 18 alpha-satellite DNA probe (D18Z1) revealed a third small signal in addition to two large signals. FISH analysis of diploid metaphase cells from cultured chorionic villus cells and from maternal lymphocytes revealed that the third signal resulted from hybridization to the centromere of chromosome 22. This is the first report of a variant involving D18Z1 detected by FISH and of hybridization of alpha-satellite from a sub-metacentric chromosome to the centromere of an acrocentric chromosome. We propose that this inherited variant resulted from insertion of chromosome 18 specific alpha-satellite DNA sequences into the centromeric region of chromosome 22.

Adult↗

The expression of genes in human preimplantation embryos.

The study of gene expression in human preimplantation embryos is establishing itself as a necessary dimension of developmental biology and medical genetics. Transcripts identified in human preimplantation embryos include housekeeping genes, transcription and growth factor genes, sex-determining genes, tissue-specific genes and novel genes, as well as genes of unknown function. Strategies are being developed which will eventually permit the most sophisticated gene expression studies on single human embryos of co-ordinated transcription and translational regulation. There is both a need for international co-operation for the systematic construction of expression maps and a need to establish databases of expression patterns during different stages of human development. Understanding how genes are regulated in humans is essential for understanding both normal development and disease. Until recently, studies of gene expression and regulation during embryogenesis were almost exclusively limited to prokaryotes and to eukaryotes other than man. The introduction of artificial reproductive technologies in conjunction with the development of recombinant molecular technologies applicable to single cells has made possible the study of human development at its earliest stages (Pergament and Bonnicksen, 1994). Although there are still enormous technical challenges, robust strategies have been, and continue to be, developed for connecting DNA sequence to such endophenotypes as timing and level of genes expression at the single cell level. Questions currently being asked in human developmental genetic studies concern the pronucleus, the zygote and the preimplantation embryo: what genes are expressed? When are they expressed? What functions do they perform and how, in sequence or in combination? And, what elements control and regulate their expression? This review provides an overview of current knowledge about the expression of different embryonic genes during early human development and discusses future prospects, which includes a need for international co-operation similar to the Human Genome Project.

Embryo, Mammalian↗

Insulin receptor substrate-1 is expressed at high levels in all cells of the peri-implantation mouse embryo.

Insulin and insulinlike growth factors are important for embryonic growth and metabolism. Intracellular transduction for these factors has not been studied in the preimplantation mouse embryo. Peri-implantation mouse embryos synthesize insulinlike growth factor (IGF)-II ligand, insulin receptor, IGF-I receptor, and IGF-II receptor and respond to IGF-II, IGF-I, and insulin metabolically and mitogenically. Maternal tissues in the oviduct and uterus are also sources of IGF-I and insulin. Signaling of IGFs occurs through insulin receptor substrate (IRS)-1 and IRS-2. This paper shows that IRS-1 mRNA and protein are highly expressed in preimplantation mouse embryos, in embryonic cell lines, and in cultured blastocyst outgrowths. IRS-1 mRNA and protein are detected in embryo-derived cell lines cultured to produce the three cell lineages (stem cells, endoderm, and trophoblast cells). IRS-1 mRNA is detected by reverse transcription-polymerase chain reaction (RT-PCR) in the E3.5 blastocyst before implantation and in F9 teratocarcinoma stem cells and parietal endoderm cells. IRS-1 mRNA is detected by Northern blot hybridization at high levels in stem cells and in differentiated progeny of F9 cells and C3H/NE trophectoderm cells. IRS-1 protein was detected in these cell lines and in an overexpressing CHO-IRS-1 fibroblast cell line by immunocytochemistry. Cultured blastocyst outgrowths are a model for implantation events of the trophoblast/placenta lineage and endoderm/yolk sac lineage. In the blastocyst outgrowth, IRS-1 protein is detected in inner cell mass cells (ICM cells), primitive endoderm, parietal endoderm, and trophectoderm cells. These data suggest that IRS-1 is expressed in all cell lineages of the peri-implantation mouse embryo and mediates some effects of insulin and IGFs at this stage.

Animals↗

Factors associated with maternal cell contamination in amniocentesis samples as evaluated by fluorescent in situ hybridization.

OBJECTIVE: To determine which patient- and procedure-related factors contribute to maternal cell contamination in uncultured amniocentesis fluid. METHODS: One hundred thirty amniotic fluid (AF) samples were obtained by three operator groups: maternal-fetal medicine faculty (n=50), general obstetrician gynecologists (n=50), and obstetrics and gynecology residents supervised by maternal-fetal medicine faculty (n=30). These groups were designated "most," "intermediate," and "least experience," respectively. Study variables were recorded at the time of the procedure. Amniotic fluid cells from male fetuses underwent fluorescent in situ hybridization. Maternal cell contamination was calculated by analyzing 100 cells and determining the number of XX and XY cells. A control system was created to validate the methods used for AF processing and cell counting. RESULTS: Median maternal cell contamination was 2.0%. Maternal cell contamination did not vary with body mass index (r=-.13, P=.14), gestational age (r=.08, P=.35), or placental location (P=.55). Maternal cell contamination was significantly elevated with placental penetration (6.0% compared with 1.0%, P < .001), two passes (27.5% compared with 2.0%, P=.002), blood-tinged fluid color (14.0% compared with 2.0%, P < .001), and operator inexperience ("intermediate experience" compared with "most experience," 4.5% compared with 1.0%, P=.026). Maternal cell contamination did not differ between the "most experience" and "least experience" groups (1.0% compared with 2.0%, not significant). Concordance between detected and actual maternal cell contamination in the control system was extremely high (concordance coefficient=0.98, P=.008), confirming the validity of the techniques used. CONCLUSION: Our techniques of cell counting and maternal cell contamination calculation are accurate. Maternal cell contamination is increased with placental penetration, two passes, and operator inexperience. However, with expert supervision, inexperienced physicians can perform amniocentesis without an increase in maternal cell contamination.

Amniocentesis↗

Urorectal septal defects in a female and her offspring.

We report on a patient with an ectopic urethra opening into a septate vagina which was distended with urine. The anus and rectum were normal but separated from the urogenital sinus by a thin septum. After surgical repair the patient did well with the exception of recurrent urinary tract infections. At 16 years, she delivered a healthy boy by Cesarean section but miscarried a subsequent pregnancy 3 years later. The 12-13 week female fetus lacked a urethra and had an atretic vagina and cloacal anomalies consistent with a urorectal septum developmental defect. This report provides evidence that cloacal anomalies resulting from the improper development of the urorectal septum may have a genetic cause. Furthermore, we support the proposition previously set forth by Allen and Husmann [J Urol 145:1034-1039, 1991] that such anomalies be referred to as urorectal septal defects rather than cloacal anomaly variants. This terminology accurately represents the developmental defect and clearly distinguishes them from cloacal exstrophies, which are due to the abnormal development of the cloacal membrane and the subumbilical ventral abdominal wall.

Abortion, Missed↗