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G Barkai

Publications and source records attributed to G Barkai.

At least 19 recordsLinked to original sources

Concurrent use of flow cytometry and fluorescence in-situ hybridization techniques for detecting faulty meiosis in a human sperm sample.

Routine semen analysis in an infertile patient revealed severe teratospermia associated with malformation of head and tail in 100% of the sperm cells. Flow cytometry and fluorescence in-situ hybridization (FISH) were shown to supplement routine semen analysis by providing information on the sperm chromatin. Using flow cytometry, propidium iodide-stained spermatozoa from the same sperm sample were compared with a normal reference pool, and with human lymphocytes. The results point to a population of diploid sperm cells rather than to mature haploid spermatozoa. Numerical chromosomal abnormalities of the spermatozoa were subsequently evaluated using FISH. A total of 1000 sperm cells were scored for X and Y chromosomes, and an additional 1128 sperm cells for chromosome 18. Aneuploidy of chromosomes X and Y was revealed in 96.9% of the cells and of chromosome 18 in 90.3% of the cells. Non-disjunction of chromosome X and Y in meiosis I and II occurred in 54.8 and 2.7% of the sperm cells respectively. Non-disjunction in both meiosis I and II occurred in 39.4% of the sperm cells. A normal haploid pattern for chromosomes X and Y was observed in only 3.1%, and for chromosome 18 in 9.7%, of the cells. Using three colour FISH for the sex chromosomes and for chromosome 18, diploidy was demonstrated in 19.4% of 500 sperm cells and aneuploidy in virtually all sperm cells (99.2%). The use of flow cytometry and FISH in cases where genetic and developmental chromatin abnormalities are suspected is a valuable adjunct to other available techniques, and can guide the clinicians to decide which samples are unsuitable for intracytoplasmic injection.

Adult

Comparative genomic hybridization analysis of nonfunctioning pituitary tumors.

Clinically nonfunctioning pituitary adenomas constitute about one third of pituitary neoplasms and are considered monoclonal tumors. The molecular mechanisms of tumorigenesis in these neoplasms are poorly understood, as evidenced by the paucity of reported somatic genetic alterations. Furthermore, the somatic mutations detected to date were primarily ascribed to candidate genes or chromosomal regions: gsp, ras, p53 mutations, and allelic losses of 11q and 13q. To gain insight into which chromosomal regions bear genes involved in nonfunctioning pituitary tumorigenesis, we examined 23 such tumors by comparative genomic hybridization. Four tumors showed no genetic abnormality, and the rest (17 of 23, 74%) exhibited at least one chromosomal region of abnormality. Gains and losses affected all chromosomes (except for chromosome 14). Notably, 8 of 23 tumors (34.7%) displayed sex chromosome and chromosome 18 aberrations (amplifications or deletions). Nonrandom DNA amplification of sub-chromosomal regions on 4q, 5q (5q13-->5q23), 9p (9p21-->9pter), 13q (13q21-->13q32), and 17q were detected in 10-30% of the tumors. Noteworthy, no tumor displayed deletion of 11q, the MEN1 gene locus. These findings suggest that genes localized to previously undescribed chromosomal regions play a role in the tumorigenesis of nonfunctioning pituitary adenomas.

Adenoma

[Water birth].

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Bacterial Infections

No founder effect detected in Jewish Ashkenazi patients with fragile-X syndrome.

Several studies on small homogenous populations suggested that fragile-X syndrome originated from a limited number of founder chromosomes. The Israeli Jewish population could serve as an adequate model for tracing a founder effect due to the unique ethnic makeup and traditional lifestyle. Furthermore, a common haplotype for Jewish Tunisian fragile X patients was recently reported. To test for a similar occurrence in the Jewish Ashkenazi population, we performed haplotype analysis of 23 fragile-X patients and 28 normal chromosomes, all Jewish Ashkenazi, using microsatellite markers within and flanking the FMR-1 gene: FRAXAC1, FRAXAC2, and DXS548. The combined triple-marker analysis identified a wide range of diverse haplotypes in patients and controls, with no distinct haplotype prevalent in the patient group. Our data suggest that no common ancestral X chromosome is associated with the fragile-X syndrome in the Israeli Jewish Ashkenazi patient population studied. These findings are in contrast to other reports on founder effect associated with fragile-X syndrome in distinct European as well as Jewish Tunisian populations. On this basis, a more complex mechanism for the development of fragile-X syndrome in the Jewish Ashkenazi population should be considered.

Europe

Induction of labor with use of a Foley catheter and extraamniotic corticosteroids.

OBJECTIVE: Our purpose was to examine the hypothesis that corticosteroids, when administered extraamniotically, can enhance the labor process and reduce the induction-to-delivery interval. STUDY DESIGN: A double-blind, randomized study was conducted on 98 women with a gestational age of 36 to 42 weeks, an unfavorable cervix, and medical indications for delivery, who were assigned to receive either 20 mg of dexamethasone in saline solution (study group, n = 50) or saline solution only (control group, n = 48) administered extraamniotically through an intracervical inflated Foley balloon catheter. The net effect of steroids was assessed with use of multivariant logistic regression analysis. RESULTS: The mean time intervals between induction of labor to the active phase and between induction of labor to delivery were significantly shorter in the study group compared with those of the control group (7.8 +/- 3.1 hours vs 9.9 +/- 3.9 hours, p < 0.03, 11.9 +/- 3.0 hours vs 14.5 +/- 4.8 hours, p < 0.01, respectively). Those not receiving steroids were at a 3.2 higher risk of having a longer time interval of induction to delivery (95% confidence interval 1.1 to 9.5). The general success rate in achieving vaginal delivery was, however, similar between the groups. CONCLUSIONS: Induction of labor with use of an intracervical Foley balloon catheter and extraamniotic corticosteroids reduces the time interval from induction of labor to delivery. This may indicate a possible role for corticosteroids in the parturition process.

Adult

Detection of adeno-associated virus type 2 sequences in the human genital tract.

Adeno-associated virus (AAV) is a defective parvovirus with unknown pathogenicity. It requires helper functions for its normal replication in human tissue and therefore is not readily isolated from clinical specimens. We have used the PCR method to examine the following clinical samples for the presence of AAV sequences: (i) 15 nasopharyngeal aspirates from symptomatic patients, (ii) 7 swab or fluid specimens from vesicles of patients suspected of having varicella-zoster virus infections, (iii) 21 human papilloma virus-positive genital biopsy specimens, (iv) 61 genital swab specimens from women suspected of having herpes simplex virus (HSV) infection examined either directly or following propagation in tissue culture, (v) 62 samples of first-trimester aborted material, including 38 samples from spontaneous abortions and 24 samples from induced abortions, (vi) 11 samples of chorionic villi taken from women undergoing genetic prenatal diagnosis, and (vii) three lots of cultured human embryonic cells. AAV sequences were detected only in samples taken from the genital tracts of women suspected of having HSV infection and not in any of the other types of samples. Samples from 11 patients were positive for AAV: for 4 patients the original swab sample was positive, for 4 patients the cultured swab sample was positive, and for 3 patients both the original swab samples and the cultures were positive. Five of the 11 patients were infected with HSV. Our study demonstrates the presence of AAV in the female genital tract. However, in contrast to a previous report (E. Tobiasch, M. Rabreau, K. Geletneky, S. Larue-Charlus, F. Severin, N. Becker, and J. R. Schlehofer, J. Med. Virol. 44:215-222, 1994), we did not find solid evidence of its replication in maternal or embryonal tissues from the first trimester of pregnancy. The questions of a potential pathogenic etiology of AAV and the interaction with HSV remain open.

DNA, Viral

Prelabour rupture of membranes at term: early induction of labour versus expectant management.

OBJECTIVES: To compare expectant management with early induction of labour in pregnant patients with prelabour rupture of membranes at term and unfavourable cervix. STUDY DESIGN: A prospective, randomised study of 154 women with prelabour rupture of membranes at term of whom 80 had been managed expectantly, and 74 had undergone oxytocin induction at a rate of 2.5 mU/min. Digital examination was not performed before oxytocin infusion, and the first was delayed until 4 h (nulliparae), or 2 h (multiparae) of regular uterine contractions. RESULTS: The mean period from rupture of membranes to delivery was significantly shorter in the induction group. The mean duration of labour was significantly shorter in the expectant group. Operative vaginal deliveries were more common in the induction group, and fetal distress was the most common cause of operative vaginal deliveries. The caesarean rates were low and similar in both groups. Maternal and neonatal infectious morbidity was similar and no difference was found in the length of hospitalisation. CONCLUSIONS: Expectant management in patients with ruptured membranes at term is safe and reduces the frequency of operative vaginal deliveries.

Adult

Pathogenic role of anti-endothelial cell antibodies in vasculitis. An idiotypic experimental model.

Idiotypic manipulation of naive mice has previously been used for induction of systemic autoimmune diseases (e.g., antiphospholipid syndrome, systemic lupus erythematosus, and Wegener's granulomatosis). The aim of this study focused on the utilization of this technique to induce the production of anti-endothelial cells Abs (AECA) and autoimmune vasculitis in a murine model. AECA were derived from a Wegener's granulomatosis patient's plasma. IgG was purified by absorption on a proteinase-3 affinity column resulting in the depletion of anti-neutrophil cytoplasmic Ab activity. The absorbed IgG fraction displayed a high titer of AECA as evidenced by a cyto-ELISA against unfixed human umbilical vein endothelial cells. BALB/c mice were actively immunized with the purified AECA. Three months after a boost injection with the human AECA, mice developed endogenous AECA (AB), but not Abs to proteinase-3, cardiolipin, or DNA. Histologic examination of lungs and kidneys revealed both lymphoid cell infiltration surrounding arterioles and venules; as well as deposition of Igs at the outer part of blood vessel walls. This experimental animal model of vasculitis, a product of our method of idiotypic manipulation, provides the first direct proof for the pathogenicity of AECA.

Animals

Effect of gravidity on maternal serum markers for Down's syndrome.

The effect of gravidity on maternal serum alpha-fetoprotein (AFP), unconjugated oestriol (uE3), and human chorionic gonadotrophin (hCG) levels was investigated in 27,592 women being screened for Down's syndrome. There was no difference in the median AFP level in primigravid and multigravid women, but the median hCG level in multigravid women was 5.9 per cent lower than in those tested in their first pregnancy (P < 0.0001) and the median uE3 level was 3.9 per cent lower (P < 0.0001). Among multigravid women, there was no material difference in hCG levels according to the number of previous pregnancies or livebirths, whereas uE3 levels declined steadily with increasing numbers. Both markers declined with advancing maternal age: for hCG this was an independent effect, but for uE3 it was due to the correlation between age and gravidity. Allowing for these effects will not greatly alter the Down's syndrome screening detection and false-positive rates.

Adult

Down's syndrome screening marker levels following assisted reproduction.

Maternal serum alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG), and unconjugated oestriol (uE3) levels were examined in 1632 women who had ovulation induction and 327 who had in vitro fertilization. There was a highly statistically significant increase in hCG and reduction in uE3 among those with ovulation induction. The median levels were respectively 1.09 and 0.92 multiples of the normal gestation-specific median (MOM) based on a total of 34582 women. Ovulation induction appeared to have no material effect on the median AFP level but this masked a significant increase when treatment was with Clomiphene (1.05 MOM) and a significant decrease when Pergonal was used (0.93 MOM). There was a highly statistically significant reduction in uE3 among women having in vitro fertilization with a median level of 0.92 MOM. Those fertilized with a donor egg (21) had significantly higher AFP and uE3 levels than when their own egg was used. Our results were confounded by differences in gravidity, but formally allowing for this factor did not materially change the findings. None of the observed effects is great enough to warrant routine adjustment of marker levels to allow for them. Moreover, women with positive Down's syndrome screening results can be reassured that this is unlikely to be due to them having had assisted reproduction.

Biomarkers

Early oral feeding after cesarean delivery.

OBJECTIVE: To assess the gastrointestinal function and patient acceptability of early initiation of oral feeding after cesarean delivery. METHODS: Two hundred twenty-one healthy women delivered by cesarean were assigned in an alternating manner to receive either a high-protein, low-residue pudding initiated within 6 hours of delivery and given every 6 hours thereafter (n = 108), or a standard postoperative diet, consisting of sips of water 12 hours after surgery and a liquid diet permitted only after bowel sounds returned and flatus passed (n = 113). RESULTS: Compared with the control group, the early-feeding group had a shorter mean (+/- standard deviation) duration of intravenous fluid administration, 18.6 +/- 6.3 versus 30.5 +/- 8.1 hours (P < .001); more rapid return to regular oral diet, 26.8 +/- 6.3 versus 39.7 +/- 8.8 hours (P < .001); and a shorter time to first bowel movement, 30.0 +/- 10.0 versus 43.3 +/- 11.7 hours (P < .001). There was no significant increase in gastrointestinal morbidity: 17.4 versus 15.6%, respectively. CONCLUSION: Early feeding after cesarean delivery was well tolerated and was associated with a more rapid return to a normal diet. This approach may facilitate early hospital discharge.

Adult

Maternal and neonatal outcome of 846 term singleton breech deliveries: seven-year experience at a single center.

OBJECTIVE: Our purpose was to evaluate the maternal and neonatal outcome of 846 consecutive term singleton breech deliveries at a single center. STUDY DESIGN: We reviewed the maternal and neonatal charts of all women who delivered singleton breech fetuses between 1984 and 1990 and divided them into two groups: women who fulfilled the criteria for trial of labor (group 1, n = 613) and those who did not meet these criteria and underwent scheduled cesarean section (group 2, n = 233). RESULTS: In group I, 326 women (53.2%) were delivered vaginally. There were no maternal deaths. Febrile morbidity and length of hospitalization were significantly higher in the women who required cesarean section in labor compared with those delivered vaginally. In the total study population there were no stillbirths and eight neonatal deaths, 6 of which had major malformations incompatible with life. The remaining two deaths occurred in group I (0.33% corrected neonatal mortality in group 1). Newborns in Group 1 exhibited a higher rate of trauma with borderline statistical significance (3.0% vs 0.5%, p = 0.052). No significant differences were found in the rates of low Apgar scores, intubation, and intensive care unit admission. CONCLUSION: Although certain short-term outcome variables may appear less favorable in term singleton breech infants delivered vaginally, large randomized studies of short- and long-term outcome should be undertaken because current data are not sufficiently conclusive to warrant routine cesarean section for term breech presentation.

Adult

Second-trimester serum fluorescence polarization in patients who subsequently develop pregnancy-induced hypertension.

To determine whether the midtrimester serum lipid profile, as expressed by fluorescence polarization (FP) values, is decreased in patients who subsequently develop pregnancy-induced hypertension (PIH). Stored serum samples of normotensive patients who had undergone midtrimester biochemical screening for Down's syndrome were used in this case-control study. Forty patients who subsequently developed PIH comprised the study group, and were divided into subgroups with proteinuric PIH (P-PIH, n = 18) and those with nonproteinuric PIH (NP-PIH, n = 22). Sixty randomly selected patients who remained normotensive throughout pregnancy comprised the control. Serum total cholesterol (CL) and triglycerides (TG) were determined using enzymatic colorimetric kits. FP values were determined by optical microviscosimeter. Both study subgroups had significantly lower FP values and higher TG concentrations than the control group. Total CL concentrations were slightly higher in the P-PIH subgroup. There were no differences in mean. Total CL or TG concentrations or mean FP values were found between those patients who developed mild and severe PIH. Using FP value cutoff points of 0.250, 0.245, and 0.240 sensitivity was 95%, 90%, and 78%, respectively, in detecting patients who subsequently developed PIH. Midtrimester serum FP values may have some predictive value for the development of P- and NP-PIH.

Adult

A prospective cohort study of oxytocin plus ergometrine compared with oxytocin alone for prevention of postpartum haemorrhage.

OBJECTIVE: To determine the safety and efficacy of intramuscular oxytocin plus ergometrine compared to intravenous oxytocin for prevention of postpartum haemorrhage, and the significance of administration at the end of the second stage of labour compared with that after the third stage. DESIGN: A prospective cohort study. SETTING: A university affiliated tertiary medical centre. PARTICIPANTS: Two thousand one hundred and eighty-nine women delivering singletons during 40 consecutive weeks. MAIN OUTCOME MEASURES: Postpartum haemorrhage (> 500 ml), prolonged third stage (> 30 min), retained placenta (> 60 min), elevated blood pressure (systolic > 150 mmHg, diastolic > 100 mmHg). RESULTS: The rate of postpartum haemorrhage was not significantly different for oxytocin-ergometrine compared with oxytocin, when administered at the end of the second stage of labour (odds ratio 1.10, 95% confidence interval (CI) 0.75-1.61) or after the third stage (odds ratio 0.95, 95% CI 0.68-1.34). The patients receiving oxytocics at the end of the second stage of labour had significantly lower rates of postpartum haemorrhage, for both oxytocin-ergometrine (odds ratio 0.69, 95% CI 0.49-0.98) and oxytocin (odds ratio 0.60, 95% CI 0.41-0.87), compared with those treated after the third stage. CONCLUSION: Administration of oxytocin alone is as effective as the use of oxytocin plus ergometrine in the prevention of postpartum haemorrhage, but associated with a significantly lower rate of unpleasant maternal side effects. Oxytocics administered after delivery of the fetal head compared with after the placental expulsion are associated with a significantly lower rate of postpartum haemorrhage.

Adult

A prospective study of high- versus low-dose oxytocin for induction of labor.

BACKGROUND: To assess the efficacy and safety of a high-dosage oxytocin induction regimen. METHODS: A randomized prospective study of 179 patients who received an initial dose of either 2.5 (n = 98) or 1.25 (n = 81) mU/minute of oxytocin, with increments of 2.5 mU/minute or 1.25 at 30-minute intervals. RESULTS: Failure rates (15.3% versus 19.8%), time to delivery, the number of assisted vaginal deliveries, cesarean sections, and maternal and fetal complications were not significantly different in the two protocols. However, the use of a high oxytocin dose resulted in significantly higher mean peak doses and increased total cumulative amounts. These were associated with a significant need to modify the oxytocin infusion protocol for hyperstimulation and fetal heart rate changes (65.1% versus 46.2%). CONCLUSIONS: Induction with higher dose oxytocin increments did not shorten time to delivery, but was associated with an increase in uterine hyperstimulation. Low-dose oxytocin was found to be appropriate and safe for labor induction.

Adult

Amniocentesis rate and the detection of Down syndrome and other chromosomal anomalies in Israel.

We investigated the contribution of different screening criteria to the prenatal detection of Down syndrome (DS) as well as other chromosomal anomalies in the Jewish population in Israel during 1990 and 1992. There was a significant decrease (P < 0.03) in the incidence of DS live-births during 1992 (40:78 442) compared with 1990 (69:73 751) which paralleled a marked increase in total prenatal testing and in DS cases detected prenatally. Private laboratories, which perform amniocenteses mostly for women with a low risk of DS and without genetic counselling, had a significantly lower detection rate (1:917) compared with that of the genetic institutes, which following genetic counselling test both women > or = 37 years of age (1:91) and women younger than 37 years (1:113). The detection of chromosomal anomalies other than DS was less affected by the reason for amniocentesis. Amniocentesis indicated by maternal serum marker screening of women younger than 37 years identified a greater number of chromosomal anomalies other than DS than amniocentesis based on age (> or = 37 years) alone (111:9604 versus 94:9810; P < 0.06). Prenatal detection of DS is most effective when the indication for amniocentesis follows genetic counselling. The increasing use of maternal serum marker screening leads to a significant improvement in the positive detection rate of chromosomal anomalies other than DS in young women.

Adult

Solar activity cycle and the incidence of foetal chromosome abnormalities detected at prenatal diagnosis.

We studied 2001 foetuses during the period of minimal solar activity of solar cycle 21 and 2265 foetuses during the period of maximal solar activity of solar cycle 22, in all women aged 37 years and over who underwent free prenatal diagnosis in four hospitals in the greater Tel Aviv area. There were no significant differences in the total incidence of chromosomal abnormalities or of trisomy between the two periods (2.15% and 1.8% versus 2.34% and 2.12%, respectively). However, the trend of excessive incidence of chromosomal abnormalities in the period of maximal solar activity suggests that a prospective study in a large population would be required to rule out any possible effect of extreme solar activity.

Adult