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Pericentric inversion of one chromosome 9 [inv(9)] is considered a polymorphic variation and is one of the most common forms of autosomal inversion diagnosed prenatally in amniocytes. Yet its clinical significance remains uncertain. Most publications suggest that this finding is insignificant. However, some articles report on abnormal ultrasonic findings in association, such as hydramnios, anhydramnios, hydroureter, hydronephrosis, encephalocele, and prune belly syndrome. Other reports suggest that inv(9) might be one of the etiologies of psychiatric disorders. The homozygote state, on the other hand, is rarely encountered. We report two cases of pericentric inversion of the two homologues of chromosome 9. Two similar cases were previously reported. One affected fetus was had intrauterine growth restriction and the other had Walker-Warburg syndrome as opposed to the normal outcome of our patients. Finally, a workup of this finding is suggested.

Removal of retained placental tissue postpartum and retained products of conception (RPOC) abortion is done by uterine curettage or hysteroscopy. Trauma to the endometrium from surgical procedures, primarily curettage, can cause intrauterine adhesions (Asherman's syndrome) and subsequent infertility. The incidence of malpractice claims relating to intrauterine adhesions is rising, justifying reevaluation of the optimal way of handling these complications.To review malpractice claims regarding intrauterine adhesions, and to explore the clinical approach that might reduce those claims or improve their medical and legal outcomes.We examined 42 Asherman's syndrome claims handled by MCI, the largest professional liability insurer in Israel. The clinical chart of each case was reviewed and analyzed by the event preceding the adhesion formations, timing and mode of diagnosis, and outcome. We also assessed whether the adverse outcome was caused by substandard care and it it could have been avoided by different clinical practice. The legal outcome was also evaluated.Forty-seven percent of the cases occurred following vaginal delivery, 19% followed cesarean section, 28% were RPOC following a first-trimester pregnancy termination, and 2% followed a second-trimester pregnancy termination.It is apparent that due to the lack of an accepted management protocol for cases of RPOC, it is difficult to legally defend those cases when the complication of Asherman syndrome develops.

We describe a man with pericentric inversion 9 and constitutive heterochromatin, and a high disomy rate in his sperm cells (with all probes analyzed). The disomy rate was estimated with the following probes: 8, 9, 18, X, and Y, and was significantly higher than that in control sperm cells, while chromosome 9 showed the highest disomy frequency. The probes of X and Y together showed the same disomy frequency as X and Y alone, which indicates the same nondisjunction rate in the first meiotic division. We suggest that the interchromosomal effect found in this man differed from other findings in sperm cells of men carrying an inversion in terms of the difference in the length of the heterochromatin between the two chromosomes 9. Also, it is well known that the effect of inversion 9 with increased heterochromatin is highly variable and may even vary in members of the same family.

Asynchronous replication of homologous loci was reported in lymphocytes of patients with lymphoma, ovarian and renal cancer as well as in lymphocytes of patients with premalignant conditions, for example, essential mixed cryoglobulinemia associated with hepatitis C virus and in monoclonal gammopathy of unknown significance. In the present study we evaluated the replication pattern in lymphocytes of four groups of patients with intermediate grade of non-Hodgkin lymphoma at various stages of their disease: 1) at diagnosis; 2) during cytotoxic treatment; 3) in remission; and 4) in relapse. A significantly higher proportion of the asynchronous pattern of replication at diagnosis, during cytotoxic treatment, and in relapse was noted as compared to healthy controls and to patients who achieved remission of their lymphoma. Also, the frequency of the two doublets (DD) pattern in every group studied was significantly lower than in the controls. If our findings can be confirmed in larger, long-term prospective studies, it may allow the use of a simple and inexpensive tool to closely observe patients with lymphoma who are at high risk for relapse.

Objective: This study was undertaken to compare the efficacy and safety of intravenous administration of atosiban versus ritodrine for the treatment of preterm labor. Study Design: Women with preterm labor and intact membranes diagnosed at 23 to 33 gestational weeks (n = 247) were randomly assigned to treatment arms and received atosiban (6.75 mg intravenous bolus, 300 μg/min for 3 hours, then 100 μg/min intravenously) or ritodrine (0.10-0.35 mg/min intravenously) for as long as 18 hours. Tocolytic effectiveness was assessed in terms of the numbers of women who had not been delivered after 48 hours and after 7 days. Safety was assessed in terms of maternal side effects and neonatal morbidity. Secondary outcomes included mean gestational age at delivery and mean birth weight. An intent-to-treat analysis was performed with the Cochran-Mantel-Haenszel test. Results: The proportion of women who had not been delivered at 48 hours was 84.9% (n = 107) in the atosiban group and 86.8% (n = 105) in the ritodrine group. At 7 days 92 women had still not been delivered in both the atosiban (73.0%) and ritodrine (76.0%) groups. Neither of these differences was statistically significant. The incidence of maternal cardiovascular side effects was substantially lower in the atosiban group (4.0% vs 84.3%, P < .001). In addition, intravenous therapy was terminated more frequently as a result of maternal adverse events in the ritodrine group (29.8%) than in the atosiban group (0.8%). The overall occurrences of fetal adverse events in the two treatment groups were comparable. Neonatal morbidity was similar between the treatment groups after adjustment for unbalanced enrollment of women with multiple pregnancies and for gestational ages within treatment groups. Conclusion: Atosiban was comparable in clinical effectiveness to conventional ritodrine therapy but was better tolerated than ritodrine, with no evidence of significant maternal or fetal adverse events. Neonatal morbidity, which was similar between the two treatment arms, was apparently related to the gestational age of the infant rather than to the exposure to either tocolytic agent. (Am J Obstet Gynecol 2000;182:1191-9.)

Objective. The aim of this study was to report the clinical features, management, and outcome of two cases of complete hydatidiform mole with a coexisting viable fetus and to review the literature. Patients. In this article, we report on the well-documented follow-up of 2 cases of twin pregnancies with complete hydatidiform mole and a viable fetus, both of which ended with the delivery of a normal infant at 41 and 26 weeks of gestation. It is of interest that both pregnancies were achieved following induction of ovulation with hMG/hCG. Since 1977, the year in which complete and partial moles were characterized as distinct pathologic entities, 15 cases (including our 2) have been reported. Results. Persistent GTT developed in eight patients (53.3%) and four patients (27.7%) developed metastatic disease. Seventy-five percent patients with persistent GTT were treated with single-agent chemotherapy. The median gestational age of the patients with subsequent persistent GTT was 34.5 weeks compared to 38 weeks in the patients without persistent GTT. Conclusion. Complete hydatidiform mole and coexistent fetus is a rare occurrence and is associated with an increased risk of persistent gestational trophoblastic tumor. Based on currently available information, it seems that in the presence of a stable pregnancy, normal karyotype, and a normal sonogram it is reasonable to allow the pregnancy to continue.

BACKGROUND Loss of replication synchrony during the S-phase of the cell cycle has been shown to be associated with aneuploidy in malignant cells. METHODS The replication pattern of cervical cells obtained from normal patients and from patients with preinvasive and invasive carcinoma of the cervix was evaluated. The fluorescence in situ hybridization technique was applied to Papanicolaou smear slides using p53 and 21q22 loci. Asynchrony was determined by the presence of one single and one set of double dots in the same cell. RESULTS The rate of asynchrony in low grade squamous intraepithelial lesions was not significantly different from that of normal controls. However, the rate of asynchrony was significantly higher in the high grade squamous intraepithelial lesions and even higher in the invasive carcinoma. CONCLUSIONS The authors believe these results reflect impairment of the replication control of homologous loci and that this phenomenon may be correlated to the phenotype of the tumor. Cancer 1998;83:1966-1971. © 1998 American Cancer Society.

OBJECTIVE: To ascertain the relative activity of five oxytocin antagonists (OTAs) in vivo in a tethered pregnant baboon model and compare these results to previously reported affinities in human and rat oxytocin receptor assays and median effective dose in rat uterotonic bioassays. METHODS: Pregnant tethered baboons between days 130 and 160 of pregnancy were given an oxytocin challenge test 1 minute after infusion of 1 mg of one of five randomly selected OTAs: ANTAG I, ANTAG II, ANTAG III, L366948, and Atosiban. Once the uterine response to oxytocin returned to normal (1-8 days) the OCT was repeated with one of the remaining, untested OTAs during the 130-160 day period. Uterine activity, the time until the first significant response, and the dose of oxytocin needed to induce this response were all factored into one expression, the antagonist-response interval (ARI). RESULTS: When expressed as ratio to ANTAG I the relative ARI for the OTAs were 0, .5, 1.0, 2.4 and 59.2 for L366948, Atosiban, ANTAG I, ANTAG II, and ANTAG III, respectively. ANTAG III and L366948 were significantly different from each other and the three other OTAs (P < .05). The log10 ARI for the 4 active OTAs when correlated with the log10 of the human and rat oxytocin receptor affinities and the rat uterotonic bioassay were all highly correlated (r = .99; P < .05). CONCLUSION: ANTAG III is a potent, long-acting OTA in vivo in the pregnant baboon and has the potential as a tocolytic in humans.

We have used FISH to determine the level of synchronisation in replication timing of four pairs of alleles, unrelated to chromosome 21 (p53, HER2, RB1, and c-myc), in foetal (amniotic fluid) cell samples of Down syndrome and in normal foetuses. All samples derived from the Down syndrome subjects showed large temporal differences in replication timing, in contrast to the high level of synchrony shown in all samples of normal individuals. Thus, as judged by four independent loci which are not associated with chromosome 21, the additional chromosome in the Down syndrome genome induces changes in the replication pattern of an allelic pair: from a synchronous pattern characteristic to concomitantly expressed alleles to an unsynchronised one shown by alleles displaying an allele-specific mode of expression.

In this study, in order to evaluate the replication pattern and the cell cycle dynamics of normal and malignant cells from patients with chronic lymphocytic leukemia, we applied the FISH technique with the p53 gene. Asynchrony was determined by the presence of one single and one set of double dots in the same cell. The rate of asynchronous replication was significantly higher in malignant cells than in normal cells (a mean of 28 vs 13, respectively, P = 0.023). There were proportionately more cells with two single dots among the normal cells (P = 0.0047). These results probably reflect the changes in gene replication and cell cycle progression that occur in malignant cells.

This study was undertaken in an attempt to determine the significance of elevated maternal serum human chorionic gonadotropin (MShCG), in the presence of an otherwise normal screen with respect to fetal malformations, chromosomal aberrations, and pregnancy outcome. Targeted ultrasound findings and perinatal outcome of 298 women in whom serum hCG was > or = 2.5 MOM and who were screen-negative for Down syndrome (the study group) were compared with a control group of 229 women in whom serum hCG as well as the other parameters were within the normal range. Genetic amniocentesis was performed in 125 women from the study group. Ultrasonically detected malformations were significantly more frequent among the study group (12 vs. 1, P = 0.01). Pregnancy complications were similar in the two groups, with the exception of pre-eclampsia-toxaemia, which was significantly more frequent in the study group (5 vs. 0, P = 0.02). There was one case of an abnormal karyotype (47,XXY). Although genetic amniocentesis does not appear warranted, isolated elevated MShCG levels during the second trimester screening was associated with an increased risk of fetal anomalies detected by ultrasound and of toxaemia of pregnancy.

Interleukin-11 (IL-11) is a novel cytokine that has been shown to stimulate human hematopoietic progenitors including the CD34+ CD33- DR- early progenitors. IL-11 has little effect on its own but it synergizes with other hematopoietic growth factors. We investigated the recovery of human myeloid progenitors incubated with IL-11 alone or in combination with other cytokines, including stem cell factor (SCF), interleukin-3 (IL-3) and granulocyte macrophage colony-stimulating factor (GM-CSF) following their in vitro treatment with ARA-C (10(-9) M) or Eilatin (10(-7) M). IL-11 in combination with IL-3 and GM-CSF markedly increased CFU-C colony growth pre- and post-ARA-C or Eilatin incubation from CML and normal individual bone marrow (BM) cells. Similarly, IL-11 alone or in combination with other cytokines increased cell recovery following 7-day suspension culture. A decrease in BCR/ABL fusion product was observed (by FISH analysis) after incubation of BM cells from CML patients in liquid culture for 7 days with 10(-9) M ARA-C or 10(-7) M Eilatin in the presence of IL-11 alone or in combination with other cytokines. These results indicate that following cytoreductive therapy IL-11 may enhance to a greater extent the growth of normal myeloid progenitors than the malignant clone and may, therefore, be of clinical importance for CML patients treated with chemotherapeutic agents.

The putative oncogenes BCL-1, BCL-2, and BCL-3 are commonly rearranged by translocations to the immunoglobulin genes in B-cell malignancies. However, Southern blotting rarely detected their involvement in chronic lymphocytic leukemia (CLL). This discrepancy could stem from some unique features of the oncogenesis of CLL or be due to shortcomings of Southern blotting. We have therefore evaluated the role of fluorescence in situ hybridization (FISH) in the detection of these oncogenes in CLL. Twenty consecutive CLL patients were studied by FISH for the detection of BCL-1, BCL-2, or BCL-3 rearrangement and for the presence of trisomy 12. Selected patients were also evaluated by classical cytogenetic techniques and by Southern blot analysis. Juxtaposition of JH and BCL-1 was demonstrated in 10 (50%), BCL-2 in three (15%), and BCL-3 in four (20%) of the patients. Trisomy 12 was detected by FISH in 11 (55%) patients. The coexistence of trisomy 12 and translocation of the BCL-1 oncogene was common. Three of the patients had chromosomal aberrations compatible with those detected by FISH. In contrast, in none of the five patients selected by their positive FISH findings was a rearrangement demonstrated by Southern blotting. We conclude that FISH is a sensitive method for the detection of oncogene involvement in CLL. Mainly BCL-1, but also BCL-2 and BCL-3, are commonly translocated to the immunoglobulin heavy chain locus on chromosome 14. These translocations are often associated with trisomy 12. These findings indicate that the BCL oncogenes are commonly involved in CLL and lend support to the multi-hit theory of cancer development.

Objective: A potent, long-acting oxytocin antagonist produced in our laboratory (ANTAG-III) can inhibit uterine response to oxytocin in the rat and baboon for hours and even days. The purpose of this study was to evaluate uterine response to prostaglandins subsequent to the administration of ANTAG-III. Study Design: For the rat study one cannula was inserted in the jugular vein, and another cannula to measure uterine activity was inserted in the uterus. In study 1 saline solution or 5 μg of ANTAG-III was administered to five rats each, followed by 100 mU of oxytocin at 0.1, 1, and 2 hours. In study 2 six rats each were infused with saline solution of 5 μg of ANTAG-111, followed 1 hour later by 5 μg of 15-methyl-prostaglandin F 2α and uterine activity monitored. After baseline activity returned to normal 100 mU of oxytocin was infused and the uterine response reassessed. For the baboon study ANTAG-III was administered into the aorta of tethered pregnant baboons ( n = 2). An oxytocin challenge test was performed starting with 10 mU/min and going up to 400 mU/min. After a significant uterine contractile response was established and activity returned to baseline, a 15-methyl-prostaglandin F2a challenge test was performed. Results: During the period in which the response to oxytocin was inhibited the uterine response to 15-methyl-prostaglandin F 2α of the estrous rat and pregnant baboon was maintained. Conclusions: The inhibition of the estrous rat and pregnant baboon uterus to oxytocin caused by ANTAG-III may be prolonged. During this period uterine response to prostaglandins is not altered.

As there are no proven optimal serum estradiol levels, we sought to evaluate the pharmacokinetic profiles of serum estradiol levels following a single oral dose of 2 mg estradiol and 1 mg of estriol (Trisequens) among 26 surgically induced, postmenopausal patients. Their serum estradiol levels were periodically measured over 24 h following oral administration of the drug. They were divided into two groups according to the computed hourly mean estradiol values: group A,250 pg/ml/h (918 pmol/l/h) and group B,250 pg/ml/h (918 pmol/l/h). The mean peak estradiol concentrations were noted 2 h after drug administration and amounted to 595 +/- 190 pg/ml (2,184 +/- 697 pmol/l) in the entire cohort; 435 +/- 117 pg/ml (1,597 +/- 430 pmol/l) in group A and 712 +/- 142 pg/ml (2,614 +/- 521 pmol/l) in group B (p0.001). The mean total area under the curve in group A was 4,887 pg/ml (17,940 pmol/l), which was significantly lower than that of 7,995 +/- 652 pg/ml/24 h (29,350 +/- 2,393 pmol/l/24 h) found for group B (p0.001). The mean body mass index showed a significant difference (p0.003) between group A and group B (29.4 +/- 0.56 vs. 24.3 +/- 0.24). We found that 57% of our patients were exposed to excessively high levels of estradiol during the 24-hour period following drug ingestion. We advise monitoring estradiol levels and individualizing estrogen replacement therapy, to avoid the long-term exposure of postmenopausal patients to superphysiological estradiol levels.

Objectives: Infants with intrauterine growth restriction (IUGR) have increased morbidity and mortality. The decision whether to induce labor at term or to expectantly manage these pregnancies is controversial. The aim of this study was to assess the outcomes of these two management strategies in term pregnancies. Study design: This retrospective cohort study compared neonatal and maternal morbidity and mortality of IUGR fetuses (estimated fetal weight below the 10th percentile) between induced and spontaneous labors. Results: Records of 669 IUGR newborns were reviewed; 499 were delivered through spontaneous labor and 170 were delivered through induced labor. Epidemiology and early perinatal outcomes between the two groups were similar. The cesarean section rate was significantly higher (P Conclusions: Expectant management for term IUGR pregnancies seems to be safe, with lower rates of cesarean deliveries. A large, prospective, randomized controlled trial with long-term neonatal follow-up is indicated.

Objective. To examine the theory that the postpartum shivering phenomenon is related to feto-maternal bleed during the third stage of labor.Methods. One hundred laboring low-risk women who had a normal vaginal delivery were observed for the presence of postpartum chills. The duration of the first and second stages of labor changes in body temperature, maternal and fetal blood types and the use of epidural anesthesia were recorded. Following the delivery maternal blood was examined for the presence of fetal red blood cells using the Kleihauer-Betke stain.Results. Complete data was available in 97 patients. Post-partum chills occurred in 31 of them (32%). Women with and without chills were similar in their maternal and gestational age, the use of epidural anesthesia, and length of second stage of labor. Women with chills delivered smaller babies but the difference did not reach significance. Maternal-fetal blood group incompatibility was significantly more common among shivering than non-shivering women (48% v...

Introduction Intrauterine growth restriction (IUGR) is a significant cause of both short- and long-term morbidity and mortality. IUGR secondary to placental dysfunction is correlated with telomere shortening. Telomerase is an enzyme complex that elongates telomeres. One of its components is encoded by the telomerase RNA component gene (TERC), which serves as the RNA template for the addition of telomeric repeats. We hypothesized decreased TERC gene copy number in IUGR placentas as part of the mechanism of telomere shortening in placental dysfunction. Methods We estimated the gene copy number of the TERC gene at 3q26 by applying FISH to trophoblasts of placental biopsies from five pregnancies with IUGR caused by placental insufficiency and compared them to placentas from five gestational-age matched, uncomplicated pregnancies. Results Significantly lower TERC gene copy number was observed in IUGR trophoblasts on the same chromosome and on other chromosomes, compared to the control samples (p Conclusions The TERC gene copy number is decreased in IUGR trophoblasts. These results support the observations of telomere shortening and decreased telomerase activity in IUGR placentas. We suggest that these findings might play a role in the pathophysiology of IUGR, perhaps by promoting senescence in trophoblasts of IUGR placentas.

Background. External cephalic version is attempted prior to the onset of labor. Women who present in labor with footling breech presentation are usually delivered by cesarean section. We present our experience of external version in women in labor.Material and methods. External cephalic version was attempted in thirteen patients in labor with footling breech presentation with the breech out of the pelvis.Results. The procedure was successful in twelve of the thirteen patients. Ten of them delivered vaginally. There were no maternal or neonatal complications.Conclusions. It may be reasonable to attempt external cephalic version in patients in labor prior to performing a cesarean section.

Although the comprehensive evaluation of the fetal heart includes echocardiography by an experienced pediatric cardiologist, economic constraints sometimes dictate the need to select patients.To analyze the usefulness of fetal echocardiography in the detection of congenital heart disease according to the referral indication.This retrospective survey relates to all 3965 FE studies performed in our center from January 2000 to December 2004. The diagnosed cardiac anomalies were classified as significant and non-significant malformations. All FE studies were done by a single operator (A.L.) at Meir Medical Center, a referral center for a population of about 400,000. The 3965 FE studies were performed for the following indications: abnormal obstetric ultrasound scans, maternal and family history of cardiac malformations, medication use during the pregnancy, and maternal request. The relative risk of detecting CHD was calculated according to the various referral indications.Overall, 228 (5.8%) cases of CHD were found. The most common indication for referral was suspicion of CHD during a four-chamber view scan in a basic system survey or during a level II ultrasound survey. No correlation was found between maternal age and gestational age at the time of scanning and the likelihood of finding CHD.Our data suggest that a suspicious level II ultrasound orthe presence of polyhydramnios is an important indication for FE in the detection of significant CHD.

In twelve twin pregnancies with normal amniotic fluid volume, the urine output of each twin was lower than in fetuses from singleton pregnancies, and the combined urine output of both twins was between the 50th and 95th centile for singletons. In three twin pregnancies at 21-24 weeks of gestation with acute polyhydramnios, presumed to be due to the twin-twin transfusion syndrome, the urine output of the smaller fetus was zero and that of the larger was above the 95th centile for normal singleton pregnancies. These three pregnancies were managed by repeated amniocenteses and rapid drainage of large volumes of amniotic fluid. With advancing gestation, there was a tendency for normalization of urine output in the twins.

In this study, we applied the fluorescent in situ hybridization (FISH) technique and compared the common numerical abnormalities with chromosomes 13, 16, 18, 21, X, and Y in spontaneous to artificial abortion. This would cover about 75% of the common aneuploidy in spontaneous abortion.Placentas were taken from 59 patients with a first trimester spontaneous abortion and 61 patients who underwent an elective first trimester pregnancy termination. The range of growth was from 5 to 12 gestational weeks. Placentas were processed according to direct chorionic villi preparation. Direct dual color FISH was performed according to Vysis protocol with the probes for the following chromosomes: 13, 16, 18, 21, X, and Y.The aneuploidy rate in spontaneous abortion was 55.9% and in artificial abortion 8.2%. There was a significant difference between the two groups in the aneuploidy rate (P = 6 x 10(-9)).FISH is a rapid, efficient, and relatively inexpensive tool in detecting aneuploidy in placentas from cases of spontaneous abortions. Our rate of detected aneuploidy is compatible with other reports in which conventional cytogenetics was utilized.

Objectives The detection of fetal lateral neck cysts (FLNC) may create anxiety and confusion among pregnant woman and their physicians. We attempted to determine the incidence and significance of FLNC. Also, we tried to define the importance of the associated findings: the laterality of the finding, triple test results, maternal age and other ultrasonographic findings. Methods and Materials Between January 2000 and September 2003, 80 fetuses were evaluated at our institution for FLNC out of 3350 ultrasonic scans done for fetal malformations at 14–16 weeks' gestation. Results The incidence of FLNC was 2.4% (80/3350). The majority of cases were isolated (53/80, 66%) and unilateral (46/80,58%). Down syndrome was associated with nonisolated FLNC. Conclusion Whether the finding was unilateral or bilateral had no significance. Associated increased nuchal translucency (NT) was of importance. Furthermore, the sole finding of increased NT is significant and the finding of the FLNC has no added value. There was no correlation between isolated FLNC without NT and fetal aneuploidy. However, other risk factors increase the risk for aneuploidy by up to 15 fold. Copyright © 2005 John Wiley & Sons, Ltd.

While most allelic pairs of DNA replicate synchronously during the S phase of the cell cycle, some genes normally replicate asynchronously, i.e., genes on the X chromosome and imprinted genes. The replication control mechanism is unknown but was shown to be impaired in malignancies and chromosomal trisomies where replication pattern becomes asynchronous.To determine the level of asynchronization in replication timing of cells from patients with microdeleted genomes.We applied monocolor fluorescent in situ hybridization with different probes on leukocytes from microdeleted genomes.All samples derived from the microdeleted genomes showed significantly higher levels of an asynchronized pattern compared to normal individuals.Even a "small" genetic imbalance (microdeletion) can interfere with gene replication and cell cycle progression, as previously shown in full trisomies.

We assessed possible inter- and intraindividual variations in the frequency of disomy in sperm cells from three men with abnormal sperm analysis parameters. Mono- and dual-color fluorescence in situ hybridization (FISH) was applied to sperm cells from different samples of the men. Four men with a normal sperm profile were used as controls. The samples were taken separately over a period of 6 months. FISH probes used for the disomy rate analysis were clones from the satellite region of chromosomes 8, 18, X, and Y. The study group showed a significantly higher disomy rate compared with the control group, whereas there was no significant difference in the disomy rate between three different samples from the same individuals. These results suggest that the sampling time has no importance in assessing the rate of nondisjunction in sperm cells.

Objectives: To examine the assumption that amniotic fluid alpha-fetoprotein (AFAFP) levels are different in female and male twin fetuses. Design: Amniotic fluid levels of AFP in pregnancies with female and male fetuses in gender-concordant and gender-discordant twins were compared. A t test of p < 0.05 was considered significant. Material and Methods: Between 1995 and 1999, 332 genetic amniocenteses on twin pregnancies were performed at Meir Hospital, Kfar Saba, and Rambam Hospital, Haifa, Israel. One hundred and sixty-six were concordant for gender (84 females and 82 males) while 166 pairs differed in their gender. The amniotic fluid AFP levels of each sac were measured using fluorescent immunoassay methods by an AutoDELFIA machine. Results: The mean levels of AFAFP were lower in female twins compared to their male counterparts in same-gender twins (p = 0.07), although the difference was quite small. Nevertheless, there was no such difference between AFAFP of male versus female fetuses in gender-discordant twins. Conclusions: The levels of AFAFP were higher in the male twins of gender-concordant twins in comparison to female twins. No such difference was found between female versus male fetuses in gender-disconcordant twins.

Various non-invasive techniques for prenatal diagnosis have been under investigation. We evaluated the success of fetal sexing using a non-invasive technique for obtaining fetal cells, uterine cervix brushing, in combination with FISH. Thirty pregnant women who completed between 6 and 10 weeks of gestation and who were scheduled to undergo pregnancy termination were included in the study. A Pap smear cytobrush was inserted through the external os to a maximum depth of 2 cm and removed while rotating it a full turn. The material that was caught on the brush was spread on four microscope slides. Two-color FISH was used for fetal sexing. Following pregnancy termination, a placental sample was used for full karyotyping. In 29/30 cases FISH diagnosis was confirmed by chromosomal analysis. The only male case in which a Y chromosome was not seen was from a pregnancy of 6 weeks 6 days gestational age. One case was mosaic of 46,XY/47,XXY (25%). In most cases (7/13) the Y chromosome was already identified in the first analyzed slide. With the use of a cytobrush fetal cells can be easily obtained for the purpose of prenatal diagnosis of chromosomal disorders.

We report a case in which mosaicism of trisomy 13 was detected in 4/10 cells (40 per cent) in amniotic fluid cell cultures, followed by a low rate of mosaicism (1/160 cells) detected in a fetal blood sample. This finding presents a dilemma both for the genetic counsellor and for the parents in determining whether or not to terminate the pregnancy.

A close association usually exists between replication timing of a given locus and its transcriptional activity: expressed loci replicate early whereas silent ones replicate late. Accordingly, alleles that show concomitant expression replicate synchronously, while those displaying an allele-specific mode of expression show temporal differences in their replication timing, i.e., they replicate asynchronously. We aimed in our study to see whether the cancer phenotype is accompanied by a relaxation in the temporal control of allelic replication. Fluorescence in situ hybridization (FISH) was used to determine the level of synchronization in replication timing of four pairs of homologous loci in samples of malignant cells derived from patients with chronic myeloid leukemia (CML) and lymphoma and in samples from healthy individuals. Four loci, HER2 mapped to 17q11.2-q12, a locus at 21q22, TP53 mapped to 17q13.1, and MYC mapped to 8q24 were studied. In each sample we analyzed two chromosomal regions, either 17q11.2-q12 and 21q22 or 17p13.1 and 8q24. The results showed distinct differences between healthy individuals and CML/lymphoma patients: all samples derived from noncancerous subjects showed high levels of synchrony in replication timing of alleles, whereas those of cancer patients displayed a large temporal difference in replication timing, indicating early and late replicating alleles. Thus, as judged by four unrelated loci, malignancy is associated with changes in the replication pattern of homologous loci.

We evaluated the feasibility of retrospective genetic testing for numerical chromosomal aberrations by applying the FISH technique to formalin-fixed fetal tissue. Fetal tissue from 10 old cases with known aneuploidy and from 13 cases with known fetal malformations, were tested with specific DNA probes for pericentromeric repeat regions of chromosomes 13/21, 18, X and Y. FISH diagnosis concurred with karyotype in all nine cases with sufficient cells. Numerical aberration was diagnosed in six out of 13 cases with fetal malformations.

Repeated attempts with oral oestrogens and injectable progesterone failed to induce secretory endometrium in a woman with 17-alpha-hydroxylase deficiency. The insertion of s.c. 17-beta-oestradiol implants dramatically improved the endometrial response and enabled the establishment of endometrial maturation. A viable pregnancy was achieved after the uterine transfer of in-vitro fertilized donated eggs.

Detection of minimal residual disease and relapse remain major problems in chronic myelogenous leukemia (CML) patients following bone marrow transplantation (BMT). In order to disclose the 9;22 Philadelphia translocation, we used a fluorescence in situ hybridization (FISH) technique. BCR and ABL gene fragments were used as probes for the detection of the BCR/ABL fusion product in peripheral blood and bone marrow cells from 11 CML patients in which 5 were post-BMT. The sensitivity and specificity of this approach were compared to conventional cytogenetic and polymerase chain reaction (PCR) methods. FISH demonstrated a high degree of sensitivity (1%) for the detection of the BCR/ABL translocation in these patients. A linear correlation was found between FISH detection of the BCR/ABL fusion product and routine chromosomal analysis (r = 0.995; p0.001). Detection of the BCR/ABL signal by FISH was observed in all patients showing a positive PCR signal. A significant reduction in BCR/ABL signal was observed post-transplant (p0.001). However, the BCR/ABL translocation was detected in four of five transplanted patients immediately (0.75-2.5 months) following transplant and was found in patients with a low expression of the translocation.

Indomethacin, a prostaglandin synthetase inhibitor, is an effective tocolytic agent that may have adverse fetal side effects such as constriction of the ductus arteriosus, pulmonary hypertension, and reduced urine production. We describe an unusual neonatal complication following 6 days of tocolysis with indomethacin. A 22-year-old gravida 5, para 3104 was admitted at 25 weeks of gestation in labor. Attempts to stop labor using magnesium sulfate and terbutaline failed. The contractions stopped following the administration of indomethacin, which was continued for 6 days. On day 7, due to contractions and vaginal bleeding, she underwent a classic cesarean section. The female newborn, weighting 1044 g, did well for 2 days, when she developed pneumoperitoneum. On laparotomy, an isolated midileal perforation was found, with otherwise normal-appearing bowel. Isolated intestinal perforation has been described in premature neonates who were treated with indomethacin for patent ductus arteriosus. This complication is caused by splanchnic ischemia secondary to the loss of the vasodilatory effect of prostaglandins. This case indicates that this rare but serious complication may also follow intrauterine exposure to indomethacin.

Objective To establish the predictive role of preovulatory ovarian ultrasonography in the occurrence of multiple pregnancy after hMG and hCG treatment for anovulatory infertility. Design Prospective. Setting Outpatient Infertility Clinic. Patients Ninety-five anovulatory women who conceived after gonadotropin therapy. Intervention Induction of ovulation by hMG and hCG monitored by plasma E 2 measurements and ovarian ultrasonography. Main Outcome Measures All follicles visualized on the day of hCG administration were recorded and divided into the following four groups: group I,10 to 12mm; group II, 13 to 15mm; group III, 16 to 18mm; and group IV, 19mm and larger. The sonographic findings were statistically evaluated to 80 singletons and 45 multiple pregnancies. Results No statistical correlation was found to exist between the number of follicles from the different groups and the number of fetuses. Conclusions The number and sizes of follicles visualized on the day of hCG administration have no predictive value regarding the occurrence of a multiple pregnancy.

To examine the theory that the postpartum shivering phenomenon is related to feto-maternal bleed during the third stage of labor.One hundred laboring low-risk women who had a normal vaginal delivery were observed for the presence of postpartum chills. The duration of the first and second stages of labor changes in body temperature, maternal and fetal blood types and the use of epidural anesthesia were recorded. Following the delivery maternal blood was examined for the presence of fetal red blood cells using the Kleihauer-Betke stain.Complete data was available in 97 patients. Post-partum chills occurred in 31 of them (32%). Women with and without chills were similar in their maternal and gestational age, the use of epidural anesthesia, and length of second stage of labor. Women with chills delivered smaller babies but the difference did not reach significance. Maternal-fetal blood group incompatibility was significantly more common among shivering than non-shivering women (48% vs. 20% respectively, p=0.006). Kleihauer-Betke test was positive in 11 women. The only two women in this group who experienced chills had maternal-fetal blood group incompatibility.Post-partum chills are a common phenomenon. It may be the clinical presentation of feto-maternal transfusion reaction. The small number of positive Kleihauer-Betke tests may reflect its low sensitivity in the detection of small feto-maternal bleeds.

Four cases of complete (three) and partial (one) agenesis were evaluated ultrasonographically. The frontal lobe/biparietal diameter ratio were evaluated in 113 normal fetuses and compared with those ratios in fetuses with corpus callosum agenesis. In the presence of the classic ultrasonographic features of agenesis of the corpus callosum, frontal lobe shortening, along with absence of the cavum septi pellucidi, might contribute to the diagnosis of complete agenesis of the corpus callosum and distinguish it from partial agenesis.

We report three cases in which triploidy (69,XXX) was detected by amniocentesis performed for very low maternal serum human chorionic gonadotropin levels. All three cases also had low maternal serum unconjugated estriol levels. We suggest placental insufficiency as the cause of the very low human chorionic gonadotropin because of histologic observations and because a known marker for placental insufficiency, estriol, was also very low.

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