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Biomedical subjects

J Philip

Publications and source records attributed to J Philip.

At least 19 recordsLinked to original sources
PubMed1992

Randomised comparison of amniocentesis and transabdominal and transcervical chorionic villus sampling.

We have compared three methods of prenatal diagnosis in two large obstetric centres in Denmark. Women were randomly assigned transabdominal (TA) chorionic villus sampling (CVS), transcervical (TC) CVS, or second-trimester amniocentesis (AC); women at high genetic risk were randomised between the two CVS groups only. Analysis of 45 epidemiological variables showed the three procedure groups to be similar at enrollment. All women were followed up until completion of pregnancy. Among 3079 women at low genetic risk total fetal loss rates were 10.9% for TC CVS, 6.3% for TA CVS, and 6.4% for AC (p < 0.001). More women had bleeding after the procedure in the CVS groups (p < 0.001), whereas more amniotic fluid leakage (p < 0.001) was reported after AC. No uterine infections occurred in any group. No case of oromandibular-limb abnormality was seen in the CVS groups, but 1 child in the AC group had aplasia of the right hand. The two CVS approaches were compared among 2882 women at low and high genetic risk who were found to have cytogenetically normal fetuses. Rates of unintentional loss after the procedure were 7.7% for TC CVS and 3.7% for TA CVS (p < 0.001; 95% Cl of difference 2.3-5.8%). At baseline ultrasound scanning after establishment of optimum sampling conditions, more TC than TA procedures (p < 0.001) were judged not to be feasible. We found that TA CVS allows better access to the placental site than TC sampling, is an easier skill to acquire, and has the potential that more villi can be aspirated when needed. The risk of fetal loss is similar after TA CVS and AC. However, losses after AC are at a later stage and are therefore more distressing. TA procedures remain the first choice for prenatal diagnosis. Since, in our hands, TC sampling carries a greater risk to the fetus, we have abandoned TC CVS in our two study centres.

Adult↗
PubMed1992

New rapid test for prenatal detection of trisomy 21 (Down's syndrome): preliminary report.

OBJECTIVE: To devise and evaluate a rapid screening method for detecting trisomy 21 (Down's syndrome) in samples of uncultured amniotic fluid cells. DESIGN: Non-radioactive in situ hybridisation with HY128, a 500,000 base pair yeast artificial chromosome probe specific for chromosome 21. Blinded study of 12 karyotypically normal amniotic fluid samples and eight samples trisomic for chromosome 21. SETTING: Cytogenetic and obstetric services at a tertiary referral centre, Copenhagen. MAIN OUTCOME MEASURES: Time necessary to complete the test. Proportion of cell nuclei containing two and three hybridisation signals in karyotypically normal and abnormal amniotic fluid samples. RESULTS: The test could be completed within three to four days after amniocentesis. In the normal samples a mean of 73% (range 61-82%) of the amniotic cell nuclei showed two hybridisation signals and 6% (0-18%) showed three signals. By contrast, among the trisomic samples 29% (19-38%) of the nuclei exhibited two signals and 48% (31-60%) showed three signals. CONCLUSION: The technique clearly distinguished between normal and trisomic samples. Prenatal diagnosis with in situ hybridisation with chromosome specific probes was fast and may make it possible to screen for selected, aneuploidies. However, the technique is still at a preliminary stage and needs further evaluation and refinement.

Amniocentesis↗
PubMed1992

[Non-radioactive in situ hybridization with chromosome-specific probes].

Non-radioactive in situ hybridization (ISH) is a relatively new and sensitive method for analysis of chromosome aberrations. ISH may be performed on metaphase spreads or directly on interphase cells. By means of ISH, the so-called probes are bound to well-defined regions on the chromosomes of a cell. After a visualization process the probes and thus indirectly the chromosome regions may be observed in a microscope. Chromosome-specific probes become bound to chromosomal DNA segments which are specific for certain groups of chromosomes or only for a single chromosome. The chromosome-specific probes may be subdivided into 1) repetitive probes which are bound at or around the centromere, 2) painting probes which are bound to a certain chromosome in its entire extent or to a limited segment of this and 3) locus-specific probes which are bound to a single unique DNA sequence in the genome. ISH with chromosome-specific probes is of great scientific significance for chromosomal localization of genes. It is to be anticipated that this technique may be employed clinically e.g. in prenatal diagnosis and in the diagnosis of cancer and viruses.

Chromosome Aberrations↗
PubMed1992

Rapid prenatal diagnosis of trisomy 18 and triploidy in interphase nuclei of uncultured amniocytes by non-radioactive in situ hybridization.

Two biotinylated chromosome-specific DNA probes were used to quantify the number of chromosomes 18 and 1 in uncultured amniocytes. Thirty-three samples of uncultured amniocytes were hybridized with a chromosome 18-specific DNA probe. Uncultured cells from two of the 33 samples were also hybridized with a chromosome 1-specific probe. Thirty of the samples were disomic with respect to chromosome 18; two samples were trisomic with respect to chromosome 18, and one sample was trisomic with respect to chromosomes 1 and 18. The two cases of trisomy 18 and the single case of triploidy were identified on uncultured cells within 48-72 h after amniocentesis. They were found among five samples from pregnant women who had amniocentesis because of an ultrasonographically identified fetal malformation. A trisomic karyotype could be diagnosed with certainty in uncultured amniocytes because the majority of the responding nuclei exhibited three hybridization signals. In normal cells, the majority of nuclei exhibited two signals. In no cases was there discordance between the genotype as predicted by in situ hybridization and that determined by cytogenetic analysis.

Amniotic Fluid↗
PubMed1992

Genetic amniocentesis at 7-14 weeks of gestation.

Genetic amniocentesis performed at 7-14 weeks of gestation was studied in a series of 138 patients of whom 50 wanted termination of pregnancy (less than or equal to 12 weeks). The material for analysis consisted of 132 samples due to two sampling failures and four samples being handled incorrectly. Forty-eight samples (36 per cent) were taken at 7-12 weeks of gestation, mainly transvaginally (36/48: 75 per cent). The success rate of culture and karyotyping increased with the duration of pregnancy, but was only satisfactory from week 11 onwards. The time until harvest was then 14-15 days. The transvaginal approach is easy to perform and was accepted by the women, but we experienced bacterial or fungal overgrowth in 17 per cent of these samples, whereas no infection occurred in the samples taken transabdominally (n = 96). We conclude that genetic amniocentesis is feasible from week 11, but further studies concerning side effects, especially focusing on the procedure-related abortion risk, should be carried out before early amniocentesis is routinely applied.

Abdomen↗
PubMed1992

Carcinoma in situ, gonadoblastoma, and early invasive neoplasia in a nine-year-old girl with 46,XY gonadal dysgenesis.

Carcinoma in situ (CIS), gonadoblastoma, and early invasive neoplasia were detected in the dysgenetic gonad of a nine-year-old girl with 46,XY gonadal dysgenesis. A close relationship between the three neoplastic components was supported by morphological and immunohistochemical studies. Our findings support the hypothesis that all germ cell tumours, including gonadoblastomas, originate from CIS germ cells formed during early embryonic life.

Carcinoma in Situ↗
PubMed1992

Detection of human papillomavirus type 16 DNA sequences in archival cervical tissues by the polymerase chain reaction.

We have evaluated the polymerase chain reaction for the detection of viral DNA sequences in paraffin-embedded archival tissues. In 63 frozen cervical biopsy specimens that were taken from premalignant and invasive lesions, Southern blotting detected human papillomavirus (HPV) type 16 DNA in 28 (44%) of the samples. In the polymerase chain reaction analysis of the formalin-fixed, paraffin-embedded mirror biopsy specimens, 46 (73%) of the tissues were found to be positive for HPV type 16. In three Southern blotting-positive cases, the DNA of the paraffin-embedded sections was too scant or too degraded to allow the detection of HPV DNA by the polymerase chain reaction. In 21 Southern blotting-negative cases, HPV type 16 DNA could be demonstrated in the archival sections by the polymerase chain reaction technique--a sensitivity improvement of more than 80% over the standard method of HPV detection in tissues.

Base Sequence↗
PubMed1992

Different patterns of X inactivation in MZ twins discordant for red-green color-vision deficiency.

Two female identical twins who were clinically normal were obligatory heterozygotes for X-linked deuteranomaly associated with a green-red fusion gene derived from their deuteranomalous father. On anomaloscopy, one of the twins was phenotypically deuteranomalous while the other had normal color vision. The color vision-defective twin had two sons with normal color vision and one deuteranomalous son. X-inactivation analysis was done with the highly informative probe M27 beta. This probe detects a locus (DXS255) which contains a VNTR and which is somewhat differentially methylated on the active and inactive X chromosomes. In skin cells of the color vision-defective twin, almost all paternal X chromosomes with the abnormal color-vision genes were active, thereby explaining her color-vision defect. In contrast, a different pattern was observed in skin cells from the woman with normal color vision; her maternal X chromosome was mostly active. However, in blood lymphocytes, both twins showed identical patterns with mixtures of inactivated maternal and paternal X chromosomes. Deuteranomaly in one of the twins is explained by extremely skewed X inactivation, as shown in skin cells. Failure to find this skewed pattern in blood cells is explained by the sharing of fetal circulation and exchange of hematopoietic precursor cells between twins. These data give evidence for X inactivation of the color-vision locus and add another MZ twin pair with markedly different X-inactivation patterns for X-linked traits.

Chromosome Mapping↗
PubMed1991

Comparison of transabdominal and transcervical CVS and amniocentesis: sampling success and risk.

A total of 2931 women randomized to either transabdominal CVS, transcervical CVS, or amniocentesis were studied. Unless intended or unintended abortion had occurred, they had completed up to 28 weeks of pregnancy. No significant difference was seen between total fetal loss in the transabdominal CVS group and the amniocentesis group (6.5 and 6.8 per cent, respectively, SE difference = 0.92 per cent, p = 0.01). The total fetal loss in the transcervical CVS group was 10.1 per cent. After pooling our data with data from the Canadian randomized study and the American non-randomized study, the difference in risk between transcervical CVS and amniocentesis was 1.8 per cent (SE difference = 0.64 per cent, p = 0.8). When the number of failed procedures and those cases evaluated as unfeasible for the assigned method--for anatomical reasons--are compared, the overall sampling efficacy is poorer transcervically than transabdominally.

Adolescent↗
PubMed1991

Sensory and motor aspects of pseudoneglect, hemifield, and hemispace in the tactile modality.

Two experiments were conducted with right-handed adult subjects to investigate motor and sensory components of a tactual line bisection task performed under three conditions: at midline, in the left, and in the right hemispaces. In the sensory experiment we found a left-hand rather than a right-hand superiority under the midline condition and, in the motor experiment, a right-hand rather than a left-hand superiority. The results were discussed with respect to hemispheric specialization and hemispace theories. Furthermore, we found a pseudoneglect (subjects bisected to the left of the midpoint) in the sensory experiment and a surprising reversed pseudoneglect (subjects bisected to the right of the midpoint) in the motor experiment.

Adolescent↗
PubMed1991

The safety of chorionic villus sampling. A synthesis of the literature.

Altogether 10 reports on the safety of chorionic villus sampling, either by the transcervical (TC) or the transabdominal (TA) approach, were reviewed and combined with our own data. After discussion of how unintended fetal loss rates are best estimated, the excess total fetal loss after TC and TA compared with amniocentesis were estimated to be 1.70% (+/- 0.65%) and practically zero (+/- 1.0%), respectively (standard errors in parentheses). The absolute risk of unintended loss after TC is +2.7% (+/- 0.7%) and after TA 1.0% (+/- 1.0%). These estimates are still too uncertain to allow precise weighting of benefits and human costs. A uniform style of reporting studies in this area is proposed.

Abdomen↗
PubMed1990

A cost-benefit analysis of prenatal diagnosis by amniocentesis in Denmark.

A cost-benefit analysis of amniocentesis has been performed using both the excess-cost- and the replacement methods and several replacement and discount rates. In Denmark, amniocentesis is offered free of charge to various groups of pregnant women at risk for genetic disorders of the foetus. Most important is age greater than or equal to 35 years. The analysis is based on incidence and survival rates for Down syndrome (trisomy 21), Patau's syndrome (trisomy 13) and Edward's syndrome (trisomy 18), and on incidence and survival rates of children with neural tube defects. If amniocentesis were offered to all pregnant women independent of age, with a supposed participation rate of 75% and if only tangible costs and benefits were included, the analysis shows a benefit:cost ratio greater than 1.0 using discount rates of 4% and 7% (both for the excess-cost- and replacement method); a benefit:cost ratio less than 1.0 is found using 10%. The ratio is approximately 1.0, if pregnant women aged 15-19 and 20-24 years are excluded, using the discount rate 10%. Calculations for other participation rates have also been performed. If intangible costs and benefit are included, the results are uncertain.

Adult↗
PubMed1990

Which types of perinatal events are predictable? A look at a risk score model.

This study describes the association of a risk factor model for complicated delivery, perinatal morbidity and perinatal mortality with each of various types of delivery complications, types of perinatal morbidity and causes of perinatal mortality. The material comprises a total cohort, 4,066 pregnant women with singletons in a Danish county, and their newborn infants, of whom 494 (12%) had clinical morbidity during the first 5 days of life; 28 (0.7%) died perinatally. A set of 20 risk factors, identifiable before pregnancy, at any time during the pregnancy or at term, was devised by joining existing models for prediction of complicated delivery and of perinatal morbidity and mortality. Metabolic and disproportion-related events were well predicted by the model, inertia-related ones less so, and placental conditions not at all, except for abruption. All types of neonatal morbidity (except sepsis) were well predicted, as were deaths. The strongest predictors of perinatal death were signs of hydramnios (RR = 16.1) and growth retardation (RR = 7.2). The 20 risk factors affected 43% of the population, predicting 57% of the unfavorable perinatal events.

Cohort Studies↗
PubMed1989

Antenatal and perinatal conditions correlated to handicap among 4-year-old children.

The purpose of this study was to investigate the impact of maternal prepregnancy and pregnancy-related risk factors, complicated delivery, and perinatal morbidity on subsequent handicaps in children. We surveyed a birth cohort of 4102 mothers and 4138 children in Frederiksborg County, Denmark. Maternal risk factors were defined according to guidelines published by the Danish National Board of Health, and perinatal morbidity and handicaps according to World Health Organization guidelines. The incidence of handicaps: (cerebral palsy, mental retardation [mild and severe], epilepsy, severe defects of vision and hearing); was 44 of 4038 children (twins and neonatal deaths were excluded). A combination of three or more maternal risk factors was found to be a predictor of risk for children with later handicaps; the incidence of handicaps was 11 times higher than in mothers with no risk factors. Eleven percent of all mothers had three or more risk factors and they had 43% of the handicapped children. Multiparity increased the risk in all risk categories. Of complications at delivery, intrapartum asphyxia, as evident from Apgar scores of less than 7 at 1 minute and less than 10 at 10 minutes in particular, was a strong predictor of a later handicap. Premature rupture of membranes for more than 24 hours was also significantly associated with later handicaps. Perinatal morbidity was correlated with a later handicap. The perinatal complication most strongly associated with later handicaps was low birthweight. Forty-eight percent of the affected children had a birthweight of less than 2500 gm and were small for gestational age. We conclude that the incidence of handicaps could possibly be reduced if the causes of the following maternal risk factors were identified and, if possible, eliminated: previous delivery of a child with a birthweight less than 2500 gm, previous delivery of a stillborn child, repeated abortions, severe infection during pregnancy, intrauterine growth retardation, and preterm delivery. Improved intrapartum diagnosis and prevention of asphyxia and treatment of children born with low Apgar scores would reduce the incidence of handicaps, as would intervention to prevent premature rupture of the membranes of more than 24 hour's duration.

Cerebral Palsy↗