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In the practice of clinical genetics chromosomal aneuploidy in both mosaic and nonmosaic forms has long been recognized as a cause of abnormal prenatal and postnatal development. Traditionally, cytogenetic analysis of cultured lymphocytes has been used as a standard test for detection of constitutional aneuploidies. As lymphocytes represent only one lineage, chromosomal mosaicism expressed in other tissues often remains undetected. The purpose of this study was to assess the utilization of molecular cytogenetic analysis for detection of chromosomal aneuploidy in placental tissues. Using placentas from 100 pregnancies with viable nonmalformed livebirths, both trophoblast and chorionic stroma were analyzed using comparative genomic hybridization (CGH). In all cases with an indication of chromosomal imbalance by CGH, fluorescence in situ hybridization (FISH) analysis was performed to confirm the presence of aneuploidy. To differentiate between constitutional aneuploidy and confined placental mosaicism (CPM), amniotic membrane was analyzed by CGH and FISH techniques. Our results demonstrated five placentas with CPM for chromosomes 2, 4, 12, 13, and 18, respectively, and two constitutional nonmosaic aneuploidies (47,XXX and 47,XXY). Molecular cytogenetic studies of human placental tissues enables easy analysis of both embryonic (amnion) and extraembryonic (chorion) cell lineages. Detection at birth of chromosomal defects affecting intrauterine placental and fetal development is important because these chromosomal defects may continue to have an influence on postnatal development.

Detection of confined placental mosaicism (CPM) in term placental tissues is usually accomplished by conventional cytogenetic analysis of cultured chorionic stroma and direct preparations from trophoblast or, more recently, by fluorescence in situ hybridization (FISH) on interphase nuclei. In this study, we describe the use of comparative genomic hybridization (CGH) for detection of chromosomal aneuploidy in term placentas and evaluate the sensitivity of this novel approach for CPM diagnosis in multiple placental samples acquired from five pregnancies prenatally diagnosed with CPM7 and CPM16. Each sample of placental villi was separated enzymatically into trophoblast and chorionic stroma, and the level of aneuploidy (three signals/nuclei) in each tissue was determined by FISH analysis, using centromeric DNA probes specific for chromosome 7 (D7Z1/Z2) or 16 (D16Z2). Aneuploidy levels ranged from 5.2-96.1% in the 11 tissues with CPM7 and 9.8-93% in the 29 tissues with CPM16. Subsequently, CGH analysis of DNA from the trophoblast and chorionic stroma of the same tissue sites detected the trisomic clone in all placental tissues with aneuploidy (16%, as determined by FISH analysis). Our results demonstrate the sensitivity of CGH analysis for detection of chromosomal aneuploidy mosaicism and support our contention that the CGH technique is the most effective cytogenetic method for screening term placentas for the presence of CPM.

We present a case of maternal uniparental heterodisomy for chromosome 2 (UPD 2) detected after trisomy 2 mosaicism was found on placental biopsy. This case presented prenatally with severe intrauterine growth restriction (IUGR) and oligohydramnios. The diploid newborn had hypospadias and features consistent with oligohydramnios sequence. He died shortly after birth of severe pulmonary hypoplasia. The term placenta had high levels of trisomy 2 in both the trophoblast and the stroma. A comparison of this case with others reported in the literature suggests that the IUGR and oligohydramnios are likely related to placental insufficiency due to the high levels of trisomy 2 present in the trophoblast of the term placenta and the presence of UPD 2 in the diploid placental line.

Molecular studies were performed on 101 cases of confined placental mosaicism (CPM) involving autosomal trisomy. The origin of the trisomic cell line was determined in 54 cases (from 51 pregnancies), 47 of which were also analyzed for the presence of uniparental disomy (UPD) in the disomic cell line. An additional 47 cases were analyzed for parental origin in the disomic cell line only. A somatic (postmeiotic) origin of the trisomy was observed in 22 cases and included the majority of cases with CPM for trisomy 2, 7, 8, 10, and 12. Most cases of CPM involving trisomy 9, 16, and 22 were determined to be meiotic. Fetal maternal UPD was found in 17 of 94 informative CPM cases, involving trisomy 2 (1 case), 7 (1 case), 16 (13 cases), and 22 (2 cases). The placental trisomy was of meiotic origin in all 17 cases associated with fetal UPD (P = .00005). A meiotic origin also correlated with the levels of trisomy in cultured chorionic villi samples (CVS) (P = .0002) and trophoblast (P = .00005). Abnormal pregnancy outcome (usually IUGR) correlated with meiotic origin (P = .0003), the presence of fetal UPD (P = 4 x 10(-7)), and the level of trisomy in trophoblast (P = 3 x 10(-7)) but not with the level of trisomy in CVS or term chorion. The good fit of somatic errors with the expected results could have been observed only if few true meiotic errors were misclassified by these methods as a somatic error. These data indicate that molecular determination of origin is a useful predictor of pregnancy outcome, whereas the level of trisomy observed in cultured CVS is not. In addition, UPD for some chromosomes may affect prenatal, but not postnatal, development, possibly indicating that imprinting effects for these chromosomes are confined to placental tissues.

Prenatal diagnosis by chorionic villus sampling (CVS) documents placental chromosomal mosaicism in approximately 2% of viable pregnancies at 9-12 weeks of gestation and can involve various chromosomes and placental cell lineages. Confined placental mosaicism (CPM) is the result of postzygotic mitotic errors occurring in either diploid or trisomic zygotes. With trisomic zygote rescue, depending on the parental origin of the chromosome which is lost, uniparental disomy (UPD) or biparental disomy (BPD) may arise [Kalousek et al., Am J Hum Genet 52: 8-16, 1993]. In this paper, we present 14 pregnancies which were diagnosed by CVS as mosaic trisomy 7. All follow-up amniocenteses showed a normal diploid karyotype. Using both classical cytogenetics and interphase analysis, studies of term placentae showed variable levels of trisomy 7. DNA analysis was performed in nine cases to determine whether the diploid fetus had BPD 7 or UPD 7. Fetal UPD 7 was present only in one case; in eight other cases biparental inheritance was demonstrated. DNA analysis to establish the origin of trisomy 7 in the placenta was fully informative in six cases. One trisomy resulted from a meiotic error and was associated with fetal UPD 7, while the rest were somatic in origin. It is difficult to compare the effect of CPM for trisomy 7 to other trisomies confined to the placenta, as for most chromosomes there are few available cases. It appears that intrauterine fetal growth is not greatly affected by the presence of a trisomy 7 cell line in the placenta. This finding is in contrast to the serious effect of high levels of trisomy 16 within the placenta on fetal intrauterine growth in a series of well-documented cases of CPM 16 [Kalousek et al. 1993].

Karyotypically normal fetuses with completely trisomic or mosaic placentae may be at increased risk for intrauterine growth restriction (IUGR). Molecular and cytogenetic analyses on nine pregnancies with confined placental mosaicism (CPM) for trisomy 2 were performed at two collaborating centres. Seven cases were identified through prenatal testing of chorionic villi (CVS). Two of these seven cases demonstrated complete trisomy 2 while the remaining five cases showed various levels of trisomy 2 (33 per cent-75 per cent cells). Two cases identified after IUGR was observed in newborn infants demonstrated 65 per cent and 100 per cent trisomy 2 in cultured villi from term placentae. In all nine cases, blood chromosome analysis (n = 4), chromosome analysis of amniotic fluid cultures (n = 4), and cultured amnion (n = 5) were normal, failing to demonstrate any trisomic cells in tissues of fetal origin. Molecular studies on the fetal or newborn tissues using dinucleotide repeat polymorphisms on chromosome 2 revealed normal biparental inheritance of chromosome 2 in all nine cases. The parental origin studies of the extra chromosome 2 in the placenta showed that three cases were maternal in origin, at least two of which were consistent with a maternal meiotic non-disjunction giving rise to the trisomy 2, while in one case a paternal origin of the extra chromosome 2 was established.

Traditional first trimester chorionic villus sampling (CVS) for prenatal diagnosis can be performed by cytogenetic analysis of cytotrophoblast or chorionic villous stroma. Approximately 2% of pregnancies studied by CVS show confined placental mosaicism (CPM) involving either cytotrophoblast, stroma or both. We present the results of a cytogenetic study of nine term placentae from pregnancies with prenatally diagnosed CPM. The aneuploid++ cell lines involved trisomies for chromosomes 7,9,16, and X. The cytotrophoblast and villous stroma from multiple biopsies of these placentae were examined using a combination of interphase and metaphase cytogenetic analysis. CPM was detected in all nine of the term placentae and both tissue-specific and site-specific patterns of mosaicism could be discerned. These results indicate that the analysis of villous stroma and cytotrophoblast from multiple placental biopsies is necessary to improve our understanding of the evolution of CPM during pregnancy and its effect on the fetus.

There are relatively few reports concerning management of the musculoskeletal problems of children with renal failure. From a population group of 124 children with renal failure treated at The Children's Hospital, Camperdown, 16 were referred for management of skeletal problems. These problems included genu valgum, slipped capital femoral epiphysis, ankle valgus, procurvatum of the tibia, osteonecrosis, osteochondritis dissecans, "brown tumors," gout, and pathological fracture. The methods of management of these problems are discussed.

Fluorescence in situ hybridization (FISH) provides a rapid and accurate method for the detection of chromosomal aneuploidy. We have developed a technique for the use of FISH on single cell suspensions produced from either formalin-fixed or paraffin-embedded tissues. Preparation of such tissues involves sequential rehydration, enzymatic digestion to release single nuclei, and hybridization with a fluorescently labeled chromosome-specific centromeric probe. In a clinical setting formalin-fixed tissue from many tissue types is readily available for additional retrospective study. FISH on formalin-fixed tissues is especially beneficial in follow-up studies of cases involving termination after prenatal diagnosis or patients with a malignant disease where previous routine cytogenetics established the chromosomal aneuploidy. The use of this technique eliminates the biases of cytogenetic analysis due to clonal selection in tissue culture, the low number of cells analyzed, and the restriction to only dividing cell populations. We have demonstrated that this application of interphase cytogenetics to the study of various formalin-fixed tissues is amenable to the detection of chromosomal aneuploidies and has specific advantages over cytogenetic analysis.

This study describes a method for defining mosaic aneuploidy by interphase cytogenetics based on statistical limits established from control specimens. Fluorescence in situ hybridization (FISH) has been used to detect the number of copies of specific chromosomes in interphase nuclei from placental tissues of diploid controls and mosaic placentas. FISH was performed using probes D7Z1/D7Z2, D9Z1, D10Z1, and D18Z1, all purchased from Oncor, Inc. Statistical analysis of data obtained from diploid controls was used to determine the one-sided upper reference limit and corresponding 95% confidence interval for the proportion of cells with one and three signals for each of the probes used. The one-sided upper reference limits established the lower levels of monosomy and trisomy detectable using each of the four probes. These statistical parameters were then used to interpret the results obtained by FISH applied to the study of term placentas for the confirmation of prenatally diagnosed chromosomal mosaicism.

The cause of stillbirth can usually be determined in only 20% of cases. An increased frequency of adverse pregnancy outcome, including pregnancy loss, intrauterine growth restriction, and premature labor, has been observed in association with confined placental mosaicism (CPM), which is characterized by a discrepancy between the karyotype of the fetus and placenta. Specific chromosomal trisomies have been observed in CPM more frequently than others, with trisomy of chromosomes 7, 16, and 18 being the most prevalent. In pregnancies with CPM it has been shown that the zygote is often trisomic, and postzygotic loss of the additional chromosome occurred in the embryonic progenitor cells leading to a dichotomy between the placenta and the embryo/fetus. In one third of such cases fetal uniparental disomy (UPD), which is the presence of both homologues of a chromosome derived from one parent, can be expected. The specific role of the trisomic placenta and the presence of fetal UPD in cases of altered intrauterine fetal development has not been fully established for various chromosomes. Therefore, to enhance our understanding of the pathogenesis of stillbirth it is imperative that cytogenetic analysis of both fetal and placental tissues be performed in all cases of unexplained stillbirth.

Fluorescence in situ hybridization provides a rapid and accurate technique for detecting chromosomal aneuploidy. It is an excellent method for identifying mosaicism in placental tissues following prenatal diagnosis. Mosaicism, in the form of confined placental mosaicism, occurs im approximately 1%-2% of viable pregnancies studied by chorionic villus sampling at 9-11 weeks of gestation. It has been detected in pregnancies with both diploid and trisomic fetuses and appears to have an important effect on the intrauterine fetal survival. Using both standard cytogenetic analysis and fluorescence in situ hybridization, we have studied 12 placentas from pregnancies with trisomy 18 for the presence of chromosomal mosaicism. These included 2 that were spontaneously aborted, 5 that were terminated after prenatal diagnosis, and 4 that were delivered as either stillborn or liveborn. Significant levels of mosaicism, confined exclusively to cytotrophoblast, were detected in 7 pregnancies. This study demonstrates the usefulness of interphase cytogenetic analysis of uncultured tissues as an alternative method for the detection of mosaicism.

A retrospective study was undertaken of 24 infants with septic arthritis of one or both hips who presented to the Children's Hospital, Camperdown, during the 15 year period from 1973 to 1989. Staphylococcus aureus was found to be the most common pathogen. Umbilical catheterization was a significant aetiological factor in seven of 10 neonates studied. Young premature infants had the poorest outcome in regard to permanent bony changes in the upper femur, hip instability and leg length discrepancy. In patients with unstable and severely damaged upper femora, late salvage procedures were found to be unsatisfactory.

The association between chromosomal mosaicism observed on chorionic villus sampling (CVS) and poor pregnancy outcome has been well documented. CVS mosaicism usually represents abnormal cell lines confined to the placenta and often involves chromosomal trisomy. Such confined placental mosaicism (CPM) may occur when there is complete dichotomy between a trisomic karyotype in the placenta and a normal diploid fetus or when both diploid and trisomic components are present within the placenta. Gestations involving pure or significant trisomy in placental lineages associated with a diploid fetal karyotype probably result from a trisomic zygote which has lost one copy of the trisomic chromosome in the embryonic progenitor cells during cleavage. Uniparental disomy would be expected to occur in one-third of such cases. Trisomy of chromosome 7, 9, 15, or 16 is most common among the gestations with these dichotomic CPMs. Nine pregnancies with trisomy 16 confined to the placenta were prenatally diagnosed. Pregnancy outcome, levels of trisomic cells in term placentas, and fetal uniparental disomy were studied. Intrauterine growth retardation (IUGR), low birthweight, or fetal death was observed in six of these pregnancies and correlated with high levels of trisomic cells in the term placentas. Four of the five cases of IUGR or fetal death showed fetal uniparental disomy for chromosome 16. One of the infants with maternal uniparental disomy 16 had a significant malformation (imperforate anus). All infants with normal intrauterine growth showed term placentas with low levels of trisomic cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Confined placental chorionic mosaicism is reported in 2% of viable pregnancies cytogenetically analyzed on chorionic villi samplings (CVS) at 9-12 weeks of gestation. In follow-up studies this mosaicism has been shown to be associated with increased frequency of second and third trimester pregnancy loss or intrauterine fetal growth retardation. We have studied 54 spontaneous abortions (SA) for the detection of confined placental mosaicism and found 11 of them to be mosaic. All mosaic cases were identified among first trimester spontaneous abortions, and the mosaicism was confined to specific placental or embryonic/fetal cell lineages. These results indicate that the previously reported mosaicism in SA represents both confined and generalized types of mosaicism and that its accepted frequency of 5%-10% in SA will likely be higher. Over the whole gestational period, the confined placental mosaicism is more common than the reported rate of 1%-2% seen in viable pregnancies at CVS, and a higher proportion of pregnancy complications than previously suspected may be associated with confined placental mosaicism.

Gout, a common disorder in adults is exceedingly rare in the first decade of life and uncommon in teenagers. A recent book on bone diseases in childhood does not even mention gout [7]. Childhood podagra with a radiographic findings is a very unusual finding indeed.

About 2 per cent of specimens from chorionic villus sampling (CVS) analysed either on direct preparation of cytotrophoblast cells or after culture of mesenchymal stroma reveal confined placental mosaicism (CPM), most commonly involving chromosomal trisomy. A significantly higher rate of prenatal loss (22 per cent) as well as the presence of intrauterine growth retardation (IUGR) has been reported among pregnancies with CPM. To evaluate more precisely the effect of these aneuploid cell lines confined to the placenta on intrauterine fetal growth and fetal survival, we have studied 34 term placentae from pregnancies with CPM diagnosed on CVS and confirmed identical mosaicism in 17 of these placentae. There was a direct correlation between a high number of aneuploid cells present at CVS and a high likelihood of their detection in term placenta. Also, the proportion of aneuploid cells in the mosaic term placentae correlated with that observed in CVS specimens. Among 17 gestations with confirmed CPM at delivery, there were six cases of IUGR identified, five in liveborns and one associated with intrauterine death.

Two children presented with recurrent swelling and pain, one in the forearm the other in the leg, without a history of a penetrating injury. It was difficult to arrive at a precise clinical diagnosis. X-ray films showed periosteal thickening in the diaphysis of the adjacent long bone with some unusual features but were suggestive of infection or tumour. Other extensive investigations did not contribute to a diagnosis. This was only achieved after surgical exploration. Both children had a 3 cm length of brittle palm needle within a soft tissue cavity adjacent to the long bone. The needles were from a commonly grown palm, Phoenix canariensis. Palm needle induced pseudo-tumour should always be considered in the differential diagnosis of bone neoplasm, particularly in childhood.

Cubitus varus is the most common complication of supracondylar fracture of the humerus in children. Although function of the elbow is not greatly impaired, the deformity is unsightly. It usually results from malunion, since growth disturbance of the humerus after this fracture is uncommon. The normal carrying angle can be restored by supracondylar osteotomy. This operation was done in 32 patients over a ten-year period, 16 of them using the technique described by French (1959). The results in 27 patients are reviewed in the light of previous reports. French's method proved safe and satisfactory.

A twelve-year-old boy with double bone pathology (polyostotic fibrous dysplasia and chronic monofocal osteomyelitis), causing radiologic diagnostic difficulties is reported. The nuclear scan which was interpreted with disregard of the patient's history and physical examination lead to erroneous conclusions. Basic clinical signs and symptoms should always be taken into account when more sophisticated examinations are performed.

To ascertain the prognostic value of the radionuclide angiogram in ischemic cerebral vascular disease, we reviewed the results of this study in 2200 patients who underwent this procedure. The arterial phase showed decreased activity in 175 patients studied in detail during the acute phase of their neurologic illnesses. In the 120 patients who proved to have ischemic disease and persisting neurologic signs, two basic patterns appeared during the venous phase: (1) no increased (diminished or equal) perfusion, or (2) increased perfusion. Following the initial incident, the clinical course varied from no change to marked clinical improvement. In the first group with either diminished or equal venous perfusion, the chances against improvement are greater than 6:1. In the latter group the chances for improvement or deterioration are equal.

The glucocorticoid binding properties of 18 human lymphoid cell lines (HLCL) have been investigated. The specificity of steroid binding was confirmed with various glucocorticoid agonists and antagonists. A gradation in whole cell and cytoplasmic glucocorticoid binding capacity was observed in the different cell line types: lymphoblastoid greater than lymphoma greater than leukaemia. The cytoplasmic receptors of leukaemia and lymphoblastoid lines appeared to contain both proteinaceous and phospholipid components. Cytoplasmic steroid-receptor complexes exhibited a wide range of sedimentation coefficients (8.5-11.3S) in low ionic strength buffer but there was no correlation with cell line type or glucocorticoid sensitivity. Activation of these complexes by heat (37 degrees C) or exposure to high ionic strength buffer (0.3 M NaCl) induced nuclear binding of steroid but only complexes in high ionic strength buffer manifested changes in sedimentation coefficient. No correlation was observed between the level or nature of glucocorticoid binding and the cytolethal or cytostatic responsiveness of HLCL to glucocorticoid treatment in vitro. The resistance to cytolethal effects cannot be ascribed to a failure of cells to take up and bind steroid or to significant differences in the molecular species of cytoplasmic receptors present. The molecular mechanisms by which glucocorticoids achieve cytolethal responses in human lymphoid cells has still to be resolved.

The glucocorticoid binding properties and cytolethal responsiveness of leukaemic cells were studied in vitro in seven patients with hairy-cell leukaemia (HCL) and five with chronic lymphocytic leukaemia (CLL). Substantial levels of glucocorticoid binding were detected both in whole cell and cytosol preparations from all patients although the level of binding by HCL cells always exceeded that of CLL cells (P less than 0.05). In both leukaemic cell types the uptake and binding of prednisolone in vitro was significantly greater than that of dexamethasone (P less than 0.05). CLL cells showed a variable dose-related cytolethal response to methylprednisolone sodium succinate (MPSS) treatment in vitro although cytolytic effects were not marked in the usual pharmacological dose range (10(-5)-10(-6)M). Treatment of CLL patients with conventional doses of prednisone for extended periods or high intravenous infusions of MPSS over shorter periods had no consistent effect on the in-vitro level of steroid binding or the cytolethal responsiveness of CLL cells to glucocorticoid treatment. Although HCL cells proved highly resistant to the cytolethal effects of MPSS in vitro, the substantial binding of glucocorticoids by leukaemic cells from all HCL patients indicates the potential value of steroid therapy in this disease should be explored further.

A new technique of using 99mTc bone scan to assess partial closure of the growth plate is described. The site and degree of osseous fusion can be obtained by using the apex view. The technique has the potential of assessing serially the growth of a plate before and after surgery.

Seven per cent (10/145) of hybridomas raised against partially purified activated glucocorticoid receptor from rat liver produced monoclonal antibody to receptor. Six IgM secreting clones selected for further investigation bound equally well to activated and non-activated receptor from fresh rat liver, but significantly less well (11-25 per cent) to receptor from frozen rat liver. No interaction was found with oestrogen receptor from rat uterus but extensive cross reaction occurred with progesterone receptor. Although none of the antibodies bound to glucocorticoid receptor from human or porcine liver or lymphoid cells, several cross-reacted with mouse liver glucocorticoid receptor. Immunoelectroblotting of proteins from fresh and frozen rat liver cytosol showed the antibodies bound to 90,000 and 40,000 MW forms of receptor respectively. Immunostaining of both frozen and paraffin embedded sections of rat tissue showed that receptor is preserved during fixation and processing of tissues. Using both indirect immunoperoxidase and immunogold silver staining methods, the pattern of receptor staining observed correlates with the known glucocorticoid responsiveness of the tissues studied.

Two children with rhabdomyosarcoma who developed slipped capital femoral epiphyses following pelvic irradiation are described. Previous case reports are summarised, and the relevant orthopedic implications of the disorder discussed.

By using the arterial and venous phases of an anterior cerebral perfusion study, which showed downward displacement of the sagittal sinus, and the finding of a "rim" on the delayed scans, the specific diagnosis of epidural hematoma was established.

Normal human fibroblasts exposed to the mutagen 3-methyl 4-nitroquinoline 1-oxide (3me4NQO) were additionally incubated with or without the inhibitor of poly ADP-ribose polymerase, 3 aminobenzamide (3AB) either during or after mutagen treatment. The number of single strand DNA breaks detectable by alkaline sucrose sedimentation at any given time after exposure to this mutagen was reduced by the prior addition of 3AB, regardless of whether this drug was present during or after mutagen exposure. Furthermore, this effect is reversible upon 3AB removal. Finally, cell survival as analysed by cell growth was increased if cells were treated for one hour with 3AB directly following a 30 min exposure to 3-me4NQO. The data presented suggest an additional role for poly ADP ribose polymerase in DNA repair other than that of inhibiting the increase in ligase II, which occurs after exposure to monofunctional alkylating agents.

Using various genotypic and phenotypic markers 20 human lymphoid cell lines have been classified as lymphoblastoid, leukaemia or lymphoma subtypes. Each cell line type exhibited characteristic morphological and behavioural properties in suspension culture. Whilst most lymphoblastoid and lymphoma cell lines manifested B-cell phenotypes and contained Epstein Barr virus (EBV) genome, leukaemia lines demonstrated T-cell markers and lacked EBV genome. Individual cell lines demonstrated unique isoenzyme profiles for the seven polymorphic enzymes studied without subtype specificity. None of the cell lines studied was entirely homogeneous although lymphoblastoid lines contained only a minor subpopulation of other cell line types. The mixed population of cells indicate the need for caution in the use of these cell lines as in vitro models of lymphoid cancer and suggests further refinement of classification methods is required. Incubation of different cell line types with prednisolone for 48-168 h revealed most were highly resistant to cytolethal and cytostatic effects of glucocorticoids in vitro. Suprapharmacological doses of steroid (10(-3) M) were required in most instances before significant cytolethal responses occurred. Only one lymphoblastoid, one lymphoma and two leukaemia lines responded to pharmacological doses (10(-5)-10(-6) M) of prednisolone.

Cytogenetic analysis of 14 placentas from live newborn infants or from terminated pregnancies with trisomies 13 and 18 revealed that all were mosaic. The mosaicism was confined to the cytotrophoblast and not detected in villous stroma, chorionic plate, or amnion. The percentage of cells with a normal karyotype varied from 12% to 100%, the average being 70%. No such confined mosaicism could be detected in 12 placentas of trisomy 21 fetuses. These findings suggest that a postzygotic loss of a trisomic chromosome in a progenitor cell of trophectoderm facilitates the intrauterine survival of trisomy-13 and -18 conceptuses. They also imply that it is placental function which determines the intrauterine survival and that the mother plays no active role in rejection of trisomic conceptions. The combination of both a pre- and post-zygotic cell division defect in viable trisomy-13 and -18 conceptions points to the possibility of a genetic predisposition to such events. The detection of only a diploid cell line in the cytotrophoblast of some pregnancies with trisomies 13 and 18 also suggests that direct preparation is unreliable for prenatal diagnosis of these trisomies on chorionic villi sampling and that long-term villous culture should be used.