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Biomedical subjects

F J Los

Publications and source records attributed to F J Los.

At least 55 records · Page 3Linked to original sources
PubMed1995

Retrospective study of trisomy 18 in chorionic villi with fluorescent in situ hybridization on archival direct preparations.

Trisomy 18 in direct chorionic villus preparations needs further investigation since the chromosome abnormality may be confined to the placenta and may not represent the actual fetal karyotype. We performed, retrospectively, fluorescent in situ hybridization (FISH) with the chromosome 18 centromere probe (L1.84) on interphase nuclei of destained slides of all cases of full trisomy 18 (n = 22) and mosaic trisomy 18 (n = 8) detected among 7600 first-trimester chorionic villus samples during an 8-year period (1985-1992). More nuclei displaying three signals were encountered in cases of full and mosaic trisomy 18 confirmed in fetal tissue than in non-confirmed cases. FISH can be useful for the verification of trisomy 18 in direct chorionic villus preparations.

Chorionic Villi Sampling↗
PubMed1995

Sonographically determined anomalies and outcome in 170 chromosomally abnormal fetuses.

Structural pathology and outcome were studied in 170 chromosomally abnormal fetuses. Numerical chromosomal abnormalities were established in 158 (93 per cent) cases, of which 110 (71 per cent) represented trisomies, 30 (18 per cent) Turner syndrome, and 18 (11 per cent) triploidy. Structural chromosomal abnormalities were diagnosed in 12 (7 per cent) cases. Gestational age at referral was significantly shorter for pregnancies with Turner syndrome than for the other chromosomal abnormalities. Referral before 20 weeks of gestation was mainly based on fetal structural pathology alone (92 per cent); after 20 weeks, patients were referred because of structural pathology combined with small for gestational age, oligohydramnios, or polyhydramnios. Referral as a result of suspected multiple organ pathology occurred in 73.5 per cent of pregnancies. An abnormal amniotic fluid volume was present in 59/170 (34.5 per cent) chromosomally affected pregnancies, i.e., oligohydramnios in 31 and polyhydramnios in 28 cases. Birth weight was below the tenth percentile in over half of the chromosomally abnormal fetuses, except for Turner syndrome. Fetal outcome was poor, with a survival rate at 1 month of 30 per cent for trisomies which was mainly determined by trisomy 21 (14/18 = 77.5 per cent).

Adult↗
PubMed1995

Fetal ductus venosus flow velocity waveforms and maternal serum AFP before and after first-trimester transabdominal chorionic villus sampling.

Doppler flow velocity waveform recording in the fetal ductus venosus and umbilical artery as well as maternal blood sampling for serum alpha-fetoprotein (MSAFP) was performed before and after transabdominal chorion villus sampling (TACVS) in 36 women of advanced maternal age (> or = 36 years). Gestational age ranged between 11 and 13 weeks. No chromosomal anomaly was detected. No statistically significant difference was observed in ductus venosus velocity parameters or in the umbilical artery pulsatility index (PI) before and after CVS in 35 women with a normal pregnancy outcome. One case resulted in fetal loss. Post-CVS median MSAFP levels at 12 weeks (25 kIU/l) and 13 weeks (35 kIU/l) were significantly higher than pre-CVS levels. In three cases, post-CVS MSAFP levels were higher than 600 kIU/l, correlating with feto-maternal transfusions of approximately 1.0-1.4 ml, i.e., of around 40 per cent of feto-placental blood volume. One of these cases displayed absence of fetal peripheral blood flow velocities and fetal bradycardia following TACVS, resulting in fetal loss 1 week later. The remaining two cases had a normal pregnancy outcome, but showed a more than 50 per cent reduction in ductus venosus velocity after TACVS, whereas umbilical artery PI remained unchanged. However, similar velocity changes were associated with only small feto-maternal transfusions. Umbilical artery PI values remained unchanged.

Blood Flow Velocity↗
PubMed1995

A chromosome 21-specific cosmid cocktail for the detection of chromosome 21 aberrations in interphase nuclei.

Fluorescent in situ hybridization (FISH) with a 21q11-specific probe (CB21c1) consisting of three non-overlapping cosmids has been applied to interphase amniocytes of pregnancies at increased risk for fetal aneuploidy (N = 78) and to interphase lymphocytes, cultured and uncultured, of patients referred for Down syndrome (N = 19 and 28, respectively). In the uncultured amniocytes, six chromosome aberrations were detected: three cases of trisomy 21, a triploidy, a de novo 46,XX,t(21q21q), and a mosaic 46,XY/47,XY,+dic(21)(q11)/48,XY,+dic(21)(q11),+del(21)(q11). In 15 cultured and 20 uncultured blood samples, FISH correctly diagnosed trisomy 21 (full or mosaic) at the interphase level, which was confirmed in all cases by subsequent karyotyping. Because of specific and strong signals in interphase nuclei, CB21c1 appears to be a useful tool for the rapid detection of chromosome 21 abnormalities.

Amniocentesis↗
PubMed1995

Increased incidence of cytogenetic abnormalities in chorionic villus samples from pregnancies established by in vitro fertilization and embryo transfer (IVF-ET).

We studied 201 pregnancies that were established by in vitro fertilization and embryo transfer (IVF-ET) and compared the frequency of cytogenetic abnormalities with that found in a large control population matched for indication group (advanced maternal age) and time of sampling. A total of 252 IVF-ET fetuses were cytogenetically analysed by either chorionic villus sampling (CVS; n = 80) or amniocentesis (n = 172). Eleven chromosome abnormalities were found in the CVS group (13.8 per cent); among them, a 45,X/46,X,dic(Y)(q11)/46,X,del(Y)(q11) mosaic that was found in an IVF pregnancy established by intracytoplasmic sperm injection (ICSI), four cases of trisomy 21, and three cases of trisomy 7 confined to the placenta. The results indicate a statistically significant three- to five-fold increase in both confined placental abnormalities (P < 0.008) and true fetal chromosome anomalies (P < 0.04). In the amniocentesis group, identical rates (1.7 per cent) of chromosome abnormalities were found in the IVF-ET and control groups. It is concluded that late first trimester, but not early second trimester, IVF-ET pregnancies are characterized by an increased frequency of cytogenetic abnormalities found at prenatal diagnosis.

Adult↗
PubMed1995

Prenatal diagnosis of mosaic tetrasomy 12p/trisomy 12p by fluorescent in situ hybridization in amniotic fluid cells: a case report of Pallister-Killian syndrome.

A prenatally detected case of a rare mosaic tetrasomy 12p/trisomy 12p is reported, presenting as the well-known accessory isochromosome 12p and a supernumerary single 12p marker in 17/24 and 6/24 clones of cultured amniotic fluid cells, respectively. The chromosomal nature of both marker chromosomes was investigated in cultured amniotic fluid cells by fluorescent in situ hybridization with various probes: the 12-centromeric probes p alpha 12H8 and D12Z3, a whole chromosome 12 paint, and the chromosome 12p-specific paint M28. DNA analysis revealed a maternal origin of the extra 12p material. After counselling, the parents requested termination of pregnancy. Inspection and autopsy of the fetus revealed many of the dysmorphisms and internal structural abnormalities of the Pallister-Killian syndrome.

Adult↗
PubMed1995

DNA diagnosis of Prader-Willi and Angelman syndromes with the probe PW71 (D15S63).

Previously, 158 nuclear families with probands suspected of having either Prader Willi (PWS) or Angelman syndrome (AS) were analyzed with polymorphic DNA markers from the 15q11-13 region. These cases have been re-evaluated with the probe PW71 (D15S63), which detects parent-of-origin-specific alleles after digestion with a methylation-sensitive restriction enzyme (HpaII). Application of PW71 to DNA samples isolated from leucocytes, confirmed the deletions and uniparental disomies detected earlier by marker analysis, and resolved 50% of the previously uninformative (n = 18) cases. PW71 and restriction fragment length polymorphism analysis indicated that, in all resolved cases, disomies of the 15q11-13 region were present. The use of PW71 increased the percentage of disomies detected in our PWS and AS patient groups. Almost 50% of our PWS patients and 17% of the AS patients showed a disomy of maternal or paternal origin, respectively. DNA of first trimester chorionic villi and of fibroblast cultures was not suitable for analysis with PW71 because of different methylation patterns. The application of PW71 is recommended for the diagnosis of the PWS and AS, with respect to DNA samples from blood.

Alleles↗
PubMed1995

Concanavalin A variants of alpha-fetoprotein in first trimester fetuses with trisomy 21 and with normal karyotypes.

Total alpha-fetoprotein (AFP) concentrations and proportions of AFP non-reactive with the lectin concanavalin A (Con A) were studied in extracellular fluid of 22 first-trimester fetuses. Total AFP concentrations were significantly lower in fetuses with Down's syndrome than in those with Mendelian-inherited diseases and normal karyotypes. The proportion of non-Con-A-reactive AFP was low in the fetal compartment (< or = 3.5%) irrespective of the fetal karyotype. So the AFP production in the fetal liver as well as in the yolk sac seems to be reduced in Down's syndrome. The fetus itself contributes only marginally to the non-Con-A-reactive AFP pool of amniotic fluid, which is therefore almost entirely of yolk sac origin. This pool is preserved well into the second trimester of pregnancy, despite cessation of yolk sac AFP production at the end of the first trimester, indicating a very slow rate of disappearance of proteins out of amniotic fluid.

Concanavalin A↗
PubMed1994

Maternal serum markers in second-trimester oligohydramnios.

The levels of the maternal serum markers alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG), and unconjugated oestriol (uE3) in 35 pregnant women with early second-trimester oligohydramnios differed from those in a reference population of 1699 singleton pregnancies. Maternal serum AFP levels above the 95th centile of the population distribution were observed in 80 per cent (16/20) of oligohydramnios cases with a normal fetus and in only 20 per cent (3/15) of the cases with a fetus displaying urogenital tract malformations. Elevated levels of hCG (above the 95th centile) and decreased levels of uE3 (below the fifth centile) were encountered in 26 per cent (9/35) and 17 per cent (6/35) of the women, irrespective of the fetal condition. The abnormal profile of the serum markers in early second-trimester oligohydramnios resulted in 57 per cent (20 out of 35) of screen-positive cases for either fetal Down's syndrome or neural tube defects, compared with 8.4 per cent (143 out of 1699) in the reference population.

Chorionic Gonadotropin↗
PubMed1994

De novo deletion (2) (p11.2p13): clinical, cytogenetic, and immunological data.

We report a case of a boy with a de novo interstitial deletion of chromosome (2) (p11.2p13). Clinical features included dysmorphism of the face, genital region, and limbs, psychomotor retardation, and vitiligo. A reduced ratio of immunoglobulin (Ig) light chain expression (kappa/lambda ratio: 0.7) was found, compatible with deletion of one Ig kappa allele on chromosome 2p12. The patient had no clinical or laboratory signs of immunodeficiency.

Abnormalities, Multiple↗
PubMed1994

Prenatal diagnosis of ataxia-telangiectasia and Nijmegen Breakage syndrome by the assay of radioresistant DNA synthesis.

Prenatal diagnosis was performed in 16 pregnancies at risk of ataxia-telangiectasia (A-T) or Nijmegen Breakage Syndrome (NBS). Radioresistant DNA synthesis (RDS) was investigated in cultured chorionic villus (CV) cells and/or amniotic fluid (AF) cells. In four pregnancies, an affected foetus was diagnosed with increased RDS in cultured CV cells. In three of the four cases confirmation of the diagnosis was obtained by analysis of AF cells and/or skin fibroblasts from the foetus cultured after termination of the pregnancy; in the fourth case a fibroblast culture from the aborted foetus failed. In one case, only AF cells could be analysed in a late stage of pregnancy; pregnancy was terminated due to intermediate/equivocal results but the foetal fibroblasts showed normal RDS. Normal RDS was demonstrated in the other 11 pregnancies at 25% risk either by analysis of CV cells (nine cases) or of AF cells (two cases). In some cases the (normal) results on the CV cells were corroborated by subsequent analysis of AF cells. The results suggest that RDS analysis of CV cells allows reliable prenatal diagnosis of A-T/NBS. However, amniocentesis may be necessary to confirm normal results on CV cells if the foetus is female (because of the risk of maternal cell contamination) or in the rare case of equivocal results.

Amniotic Fluid↗
PubMed1993

Terminal transverse limb defects and early chorionic villus sampling: evaluation of 4,300 cases with completed follow-up.

Data from 4,300 consecutive cases following prenatal diagnosis by transcervical (TC) CVS (n = 1,570) and transabdominal (TA) CVS (n = 2,370) were evaluated. In the follow-up study only infants examined by a physician were included. Gestational age varied between 8.5 and 11.6 weeks (mean 10.3 weeks) for TC-CVS and between 9.3 and 20 weeks (mean 12.3 weeks) for TA-CVS 98% of TC-CVS was performed at 9-10 weeks, 80.7% of TA-CVS procedures were carried out at 12-15 weeks. Selective termination took place in 97 cases of TC-CVS (6.1%) and in 72 cases of TA-CVS (2.6%). Another 8 women had a termination for psychosocial reasons, resulting in 4,123 (1,469 TC, 2,654 TA) continuing pregnancies. The overall fetal loss rate < 28 weeks was 5.4% (n = 80) for TC-CVS and 2.6% (n = 70) for TA-CVS. The overall incidence of congenital abnormalities after birth was 0.9%. Two terminal transversal limb defects were detected in the TC-CVS group (0.14%) against one (0.04%) in the TA-CVS group.

Chorionic Villi Sampling↗
PubMed1993

Prenatal diagnosis of congenital cystic adenomatoid lung malformation: a report of seven cases.

Six cases of macrocystic and one case of microcystic congenital adenomatoid lung malformation were diagnosed by ultrasound between 20 and 31 weeks of gestation. Combined polyhydramnios and fetal hydrops was present in three cases, polyhydramnios alone in one case, and isolated fetal hydrops also in one case. In the remaining two cases, both polyhydramnios and fetal hydrops were absent. Fetal outcome was poor, i.e., two terminations of pregnancy, three early neonatal deaths, and two survivors.

Adult↗
PubMed1993

The 10,11-epoxide-10,11-diol pathway of carbamazepine in early pregnancy in maternal serum, urine, and amniotic fluid: effect of dose, comedication, and relation to outcome of pregnancy.

Epoxide metabolites of carbamazepine (CBZ) have been suggested to play a role in the occurrence of congenital malformations observed in infants exposed to CBZ. We have investigated the 10,11-epoxide-10,11-diol pathway of CBZ in pregnant epileptic patients receiving CBZ alone or in combination with other antiepileptic drugs in relation to the outcome of pregnancy in a prospective manner. The women were referred to our clinic before 16 weeks of gestation for prenatal diagnosis of fetal malformations, including neural tube defects, by ultrasound and amniocentesis. The availability of amniotic fluid samples enabled us to determine to what extent CBZ and its main metabolites reached the amniotic fluid. In 100 pregnancies with first trimester CBZ exposure (including 7 with malformed outcome), parent drug and metabolite concentrations in maternal serum were evaluated. CBZ-10,11-epoxide concentrations increased with increasing dose. Comedication with phenobarbital led to lower 10,11-epoxide concentrations in maternal serum and a higher percentage of the dose recovered in urine as 10,11-diol. Valproate comedication led to slightly higher 10,11-epoxide concentrations in maternal serum, in combination with lower CBZ concentrations and a lower percentage of the dose recovered in the urine as 10,11-diol. In amniotic fluid, concentrations of CBZ and its main metabolites in most patients were 2 to 2.5 times higher than the free concentrations in maternal serum. Metabolites and parent drug concentrations in amniotic fluid correlated with their free concentration in maternal serum, but stronger with each other in amniotic fluid. No significant differences in levels of CBZ and its metabolites were observed between pregnancies with normal and malformed outcome.

Abnormalities, Drug-Induced↗
PubMed1992

Prenatal diagnosis of Niemann-Pick disease type C.

Niemann-Pick disease type C (NPC) was demonstrated in two successive pregnancies by strongly reduced activity of sphingomyelinase in amniotic fluid cells. By contrast, chorionic villi from the first pregnancy had shown normal sphingomyelinase activity. The prenatal diagnosis of NPC in the two fetuses was confirmed, after termination of the pregnancies, by (phospho)lipid analyses of the fetal livers, by the assay of sphingomyelinase in the fetal fibroblasts and by the demonstration of a defective esterification of exogenous cholesterol and of cholesterol accumulation by filipin staining. Retrospective analysis of cultured amniocytes for cholesterol esterification and filipin staining confirmed the feasibility of these methods for prenatal diagnosis. In a recent pregnancy in the same mother the three available methods were applied to amniotic fluid cells and an unaffected child was correctly predicted. Lipid analysis of liver tissue from the patient with NPC and the two fetuses showed a 3-5 times increased level of cholesterol, a 2-3 times increased level of sphingomyelin and a remarkable increase of bis (monoacylglyceryl) phosphate.

Amniotic Fluid↗
PubMed1992

Origin of raised maternal serum alpha-fetoprotein levels in second-trimester oligohydramnios.

Concanavalin A (Con A) subtyping of alpha-fetoprotein (AFP) revealed higher concentrations of AFP non-reactive with Con A in sera of 12 pregnant women with second-trimester oligohydramnios and raised total serum AFP levels than in sera of 42 pregnant women with raised total serum AFP levels and a normal amniotic fluid volume. This suggests that in oligohydramnios the origin of excess AFP in the maternal compartment is amniotic fluid. It is proposed that oligohydramnios and the associated raised maternal serum AFP levels are caused by damage of the fetal membranes prior to 16 weeks of gestation resulting in leakage of amniotic fluid to the decidual tissue and resorption in the maternal circulation.

Amniotic Fluid↗