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Biomedical subjects

E Geva

Publications and source records attributed to E Geva.

At least 19 recordsLinked to original sources

In utero angiopoietin-2 gene delivery remodels placental blood vessel phenotype: a murine model for studying placental angiogenesis.

Angiopoietin (Ang)-2, the natural antagonist of the Ang1/Tie2 receptor is a complex regulator of blood vessel plasticity that plays a pivotal role in both vessel sprouting [in the presence of vascular endothelial growth factor (VEGF)-A] and vessel regression (in the absence of VEGF-A). Based on the spatial and temporal expression of Ang2 throughout human gestation, we recently suggested that the Ang2 may play a pivotal role in placental angiogenesis. Further, to examine this tenet we have developed a novel murine model system in which in utero Ang2 gene delivery via a non-replicating adenoviral expression vector has the potential to manipulate the blood vessel phenotype in vivo during pregnancy. Ang2 overexpression selectively and rapidly remodels the labyrinth perivascular extracellular matrix, subsequently promoting plasticity of the maternal and fetal vessels, which appear honeycombed due to a 2-fold increase in blood vessel luminal area. High levels of Ang2 impair endothelial cell adhesiveness, leading to vascular leakiness with perivascular oedema, which increases placental weight. These observations suggest that the Ang2 overexpression may play a key role in placental vascular remodelling. Furthermore, we suggest a novel new model to study the pathobiology of placental vascularization and the effect of placental blood vessels on fetal phenotype.

Angiopoietin-2↗

Soluble endothelial and platelet selectins in serum and ascitic fluid of women with ovarian hyperstimulation syndrome.

PROBLEM: The selectins, a group of cell adhesion molecules, are major mediators of inflammatory, immunologic, and angiogenic reactions. Their possible involvement and levels of the soluble isoform in serum and ascitic fluid of women with ovarian hyperstimulation syndrome (OHSS) were not previously evaluated. METHOD OF STUDY: This prospective, case-control study involved 16 women with OHSS. Ten matched women treated by controlled ovarian stimulation and eight healthy women with normal diagnostic laparoscopy served as controls. Serum and peritoneal fluid samples obtained from all subjects were assayed for soluble endothelial selectin (sES) and soluble platelet selectin (sPS) by specific enzyme-linked immunosorbent assay. RESULTS: Significantly higher levels of sES (median, 17.1 [9-41] vs 9.3 [2.4 21.3] ng/mL [P = 0.03]) and sPS (median, 23 [13-277] vs 6.5 [1.6-28.7] ng/mL [P = 0.001]) were observed in the peritoneal fluid of women with OHSS than the basal levels of healthy, non-stimulated women. Women with OHSS had significantly lower sES serum levels than those treated by controlled ovarian hyperstimulation without OHSS, while their sPS serum levels were comparable. CONCLUSIONS: Ascitic fluid of women with OHSS contains appreciable amounts of soluble selectins, suggesting their ovarian origin and possible involvement in the syndrome.

Adult↗

Serum levels of inhibin B, unlike inhibin A and activin A, are not altered in women with preeclampsia.

PROBLEM: To investigate whether inhibin A, inhibin B, and activin A serum levels are altered in women with preeclampsia. METHOD OF STUDY: Serum samples of 20 women with preeclampsia (study group) and 20 normotensive pregnant women, matched for maternal and gestational age and parity, were assayed for inhibin A, inhibin B and activin A by specific enzyme-linked immunosorbent assay. RESULTS: Median serum concentrations of inhibin A and activin A were significantly higher among women with preeclampsia than in women with normotensive pregnancies, while inhibin B levels were comparable in both groups. Activin A levels were positively correlated with those of inhibins A and B, and inhibin A levels were positively correlated with diastolic blood pressure and inhibin B concentration in the study group. CONCLUSIONS: Inhibin A and activin A, but not inhibin B, serum levels are markedly increased in women with preeclampsia. These hormones might serve as an endocrine marker for preeclampsia.

Activins↗

Morphologic and histopathologic characteristics of placentas from twin pregnancies spontaneously conceived and from reduced and nonreduced assisted reproductive technologies.

OBJECTIVE: To prospectively evaluate morphologic and histopathologic characteristics of placentas from twin pregnancies obtained by assisted reproductive technologies (ART) and non-ART and to evaluate the influence of previous fetal reduction on placental features. STUDY DESIGN: Fifty-five placentas from consecutive deliveries of ART-obtained and 50 placentas from consecutive deliveries of non-ART-conceived twin pregnancies were investigated by one pathologist, who was blinded to specimen origins. The patients' demographic and clinical data were also recorded. RESULTS: The mean maternal and gestational ages were similar in both groups. ART-obtained pregnancies were associated with an increased incidence of pregnancy complications and lower mean birth weight. Placentas from ART-obtained pregnancies were mostly of the dichorionic type and were thinner, weighed less and had more infarctions as compared to non-ART-conceived pregnancies. Placental characteristics of reduced ART-obtained twin pregnancies were comparable to those of nonreduced ones. The second twin's placenta in all groups weighed less and had a higher incidence of anomalous umbilical cord insertion. CONCLUSION: Placentas from ART-obtained twin pregnancies appear to have more pathologic features as compared to those of non-ART-conceived ones. Fetal reduction does not significantly affect the remaining placentas.

Case-Control Studies↗

Contribution of human papillomavirus testing by hybrid capture in the triage of women with repeated abnormal pap smears before colposcopy referral.

OBJECTIVE: The purpose of this work was to evaluate the ability of testing for high-risk human papillomavirus (HPV) types using the hybrid capture technique to predict the presence of cervical intraepithelial neoplasia (CIN) II,III in patients with repeated atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LGSIL) on Pap smears. METHODS: Hybrid capture testing and tissue biopsy were performed on 503 consecutive women with ASCUS or LGSIL on repeated Pap smears who were referred for colposcopy. RESULTS: A highly significant association (P < 0.0001) was found between a positive test for high-risk HPV types and CIN II,III, with an 87.0% positive predictive value and a 95.7% negative predictive value. In 226 women with ASCUS on repeated Pap smears, a positive test for high-risk HPV types had a 85.7% sensitivity and a 97% specificity for CIN II,III. In 277 patients with LGSIL on repeated Pap smears, a positive test for high-risk HPV types had an 88.2% sensitivity and a 94.7% specificity for CIN I,II. Reserving colposcopy examination for women who were positive for high-risk HPV types would have reduced the number of referrals for colposcopy to 24.6% and maintained a sensitivity of 87.0% for CIN II,III. CONCLUSIONS: A positive hybrid capture test for high-risk HPV types was highly sensitive and specific for the presence of CIN II,III in patients with ASCUS and LGSIL on repeated Pap smears. We believe that improved methodology will eventually enable more selective colposcopy referrals without affecting patient safety among these women.

Adolescent↗

Role of vascular endothelial growth factor in ovarian physiology and pathology.

OBJECTIVE: To review the current literature on the role of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) in ovarian physiology and pathology. DESIGN: A computerized search was conducted to identify relevant in vitro and in vivo studies published in English. MEDLINE, Current Contents, and the Index Medicus were searched for studies published before January 2000. RESULT(S): VEGF/VPF is an angiogenic factor and a potent mitogen for vascular endothelium. During reproductive life, VEGF/VPF plays a role in the cyclic growth of ovarian follicles and corpus luteum development and maintenance, mediating ovarian angiogenesis. VEGF/VPF expression and secretion are induced by both FSH and LH/hCG receptor-activated pathways. CONCLUSION(S): VEGF/VPF expression and production within the ovary are critical for normal reproductive function. Defects in angiogenesis may contribute to a variety of disorders including anovulation and infertility, pregnancy loss, ovarian hyperstimulation syndrome, and ovarian neoplasms.

Animals↗

Analysis of 104 twin pregnancies conceived with assisted reproductive technologies and 193 spontaneously conceived twin pregnancies.

OBJECTIVE: To evaluate pregnancy outcome of assisted reproductive technology (ART)-conceived twin pregnancies. DESIGN: Retrospective study. SETTING: A tertiary obstetric care center. PATIENT(S): All twin pregnancies delivered > or = 24 weeks of gestation from January 1, 1996, to December 31, 1997. INTERVENTION(S): Maternal and neonatal record review. MAIN OUTCOME MEASURE(S): Pregnancy and perinatal outcome. RESULT(S): The study group comprised 104 ART-conceived twin pregnancies, and 193 non-ART-conceived pregnancies served as controls. Mean maternal age, the proportion of nulliparae, and the percentage of women who delivered before 34 weeks' gestation was higher among the study women, whereas mean gestational age was younger. The incidences of pregnancy-induced hypertension, uterine bleeding, premature contractions, intrauterine growth retardation, fetal death, discordance, and cesarean section were significantly higher in the study group. Correspondingly, in the study group, the mean birth weight of both twins was lower; more neonates weighed < 1, 500 g, more had Apgar scores of < 7 at 5 minutes, more were admitted to the intensive care unit, and more second twin neonates died. The outcome of twin pregnancies conceived spontaneously was comparable with those conceived by ovulation induction. CONCLUSION(S): Assisted reproductive technology-conceived twin pregnancies are at greater risk than non-ART-conceived ones for pregnancy complications and adverse perinatal outcome.

Female↗

Second-trimester multifetal pregnancy reduction facilitates prenatal diagnosis before the procedure.

OBJECTIVE: To evaluate the pregnancy outcome of selective second-trimester multifetal pregnancy reduction (MFPR) compared to first-trimester MFPR. DESIGN: Cohort analysis. SETTING: In Vitro Fertilization Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. PATIENT(S): The study groups comprised 38 and 70 patients who underwent selective second-trimester MFPR (group 1) and first-trimester MFPR (group 2) at mean gestational ages of 19.7 +/- 3.3 weeks and 11.7 +/- 0.7 weeks, respectively. INTERVENTION(S): Ultrasonographically guided intracardiac injection of potassium chloride (KCl) solution. MAIN OUTCOME MEASURE(S): Pregnancy outcome and obstetric complications. RESULT(S): No statistically significant difference was found between group 1 and group 2 regarding mean gestational age at delivery (35.4 +/- 3.4 weeks and 35.9 +/- 3.1 weeks, respectively); mean birth weight (2,318.9 +/- 565.7 g and 2, 138.1 +/- 529.4 g); and the incidence of obstetric complications. These complications included pregnancy loss (5.2% and 15.7%), pregnancy-induced hypertension (0 and 10%), discordancy (12% and 18. 4%), intrauterine growth restriction (0 and 40%), and gestational diabetes (0% and 6%). However, the rate of all pregnancy complications was lower among second-trimester MFPR patients. CONCLUSION(S): Selective second-trimester MFPR is associated with favorable perinatal outcome and may facilitate detection of structural and chromosomal anomalies before the procedure and selective reduction of the affected fetus.

Adult↗

Intrauterine insemination before transfer of frozen-thawed embryos may improve the pregnancy rate for couples with unexplained infertility: preliminary results of a randomized prospective study.

OBJECTIVE: To evaluate whether a combination of IUI and frozen-thawed embryo transfer (FT-ET) with ovulation induction would improve the PR in couples with unexplained infertility. DESIGN: Prospective, randomized study. SETTING: In Vitro Fertilization Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. PATIENT(S): Sixty-two patients with unexplained infertility were assigned into two groups. The study group was composed of 32 women (38 cycles) who received ovulation induction followed by IUI and FT-ET. The control group was composed of 30 women (33 cycles) who received ovulation induction followed by FT-ET. INTERVENTION(S): Clomiphene citrate (CC) and hCG, IUI, and FT-ET. MAIN OUTCOME MEASURE(S): Pregnancy rate (PR) per cycle, PR per ET. RESULT(S): In the study group, the PR per cycle and per ET were 36.8% (14 of 38) and 40.6% (13 of 32), respectively. In the control group, the PR per cycle and per ET were 12.1% (4 of 33) and 14.3% (4 of 28), respectively. Statistically significant differences were found between the two groups in the PR per cycle (P=.02) and PR per ET (P=.03). No statistically significant difference was found between the groups for the stage in which the embryos were cryopreserved, the survival cleavage rates after thawing, grading of thawed embryos, and number of embryos transferred. CONCLUSION(S): In couples with unexplained infertility, the PR may be improved by combining IUI and FT-ET with ovulation induction. Performing IUI before thawing may prevent treatment cancellation in cycles with no surviving embryos.

Abortion, Spontaneous↗

Rectal carcinoma during pregnancy: a reminder and updated treatment protocols.

Rectal carcinoma is rare during pregnancy. Prognosis is usually unfavorable due to late diagnosis, and management, especially regarding the mode of delivery, is controversial. Current treatment of rectal carcinoma includes neoadjuvant chemoradiotherapy, which may influence obstetrical management. We present a case report and discuss obstetrical management in view of updated knowledge and therapeutic approaches.

Adenocarcinoma↗

The risk of fragile X premutation expansion is lower in carriers detected by general prenatal screening than in carriers from known fragile X families.

The Fragile X syndrome is the most common cause of inherited mental retardation. For a female premutation carrier, the risk of having a child with a full mutation is positively correlated with the size of the premutation. The current study was performed to evaluate the risk of premutation expansion in the offspring of average-risk carriers detected by general prenatal screening. Over a 4-year period, 9,660 women underwent DNA screening for FMR1 mutation/premutation at the Tel Aviv Sourasky Medical Center. A premutation was defined as a CGG repeat number >50 in the 5' untranslated region (UTR) of exon 1 in the FMR1 gene. The study included only individuals with no family history of X-linked mental retardation or known FMR1 mutations. A premutation was found in 85 women (1 in 114), 68 of whom consented to have prenatal diagnoses in 74 pregnancies. The abnormal allele was transmitted to the offspring in 44 pregnancies. Of these, no change in allele size was noted in 35 pregnancies (79.6%), and expansion within premutation range was evident in 4 pregnancies (9%). In 5 pregnancies (11.4%), expansion to the full mutation was noted. This occurred only in carriers having more than 90 repeats. We conclude that the likelihood of Fragile X premutation expansion to full mutation is significantly lower in individuals ascertained by general prenatal carrier testing than in those from known Fragile X families.

Female↗

Role of angiopoietins in reproductive tract angiogenesis.

UNLABELLED: Components of the female reproductive system undergo a number of programmed angiogenic processes coupled with cyclic evolution and decline of ovarian, endometrial, and placental structures. The development of a new vascular network requires a remarkable degree of coordination between different cell types undergoing complex changes. This implies that the expression of the inciting angiogenic factors are hormone dependent. Recently, a second family of vascular endothelial growth factors was identified, the angiopoietins. Angiopoietins are vascular endothelial cell-specific growth factors that play important roles principally during the later stages of angiogenesis, after the induction of new capillaries by vascular endothelial growth factor (VEGF). There are four known angiopoietins, and their specificity for the vascular endothelium results from the restricted expression pattern of their tyrosine kinase receptor, Tie2. In this review, we discuss the molecular characterization and mechanism of action of angiopoietin-1 and angiopoietin-2 in reproductive tract angiogenesis. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES: After completion of this article, the reader will be able to describe the angiogenic process and specifically explain the role of angiopoietics in reproductive tract angiogenesis and compare the differences between the various proteins that are involved in angiogenesis.

Angiopoietin-1↗

Prednisone and aspirin improve pregnancy rate in patients with reproductive failure and autoimmune antibodies: a prospective study.

PROBLEM: The study was conducted to investigate the efficacy of prednisone and aspirin in autoantibody seropositive patients with repeated in vitro fertilization embryo transfer (IVF ET) failure. METHODS OF STUDY: The study group comprised 52 consecutive patients seropositive for non-organ-specific autoantibodies, i.e., anti-cardiolipin antibodies (ACA), anti-nuclear antibodies (ANA), anti-double-stranded (ds) DNA, rheumatoid factor (RF), and lupus anti-coagulant (LAC). These patients were treated with prednisone, 10 mg per day, and aspirin, 100 mg per day, starting 4 weeks before induction of ovulation in 52 IVF cycles. RESULTS: The clinical pregnancy rate per cycle was 32.7% (17/52). No increased incidence of pregnancy complications, including premature labor, gestational diabetes mellitus, and pregnancy-induced hypertension, were found. CONCLUSIONS: Combined treatment of prednisone for immunosuppression and aspirin as an anti-thrombotic agent, starting before ovulation induction, may improve pregnancy rate in autoantibody seropositive patients who have had repeated IVF-ET failures.

Antibodies, Anticardiolipin↗

Vascular cell adhesion molecule-1 in normal, failed, and ectopic pregnancy.

PROBLEM: Vascular cell adhesion molecule-1 (VCAM-1) is involved in early pregnancy establishment. This study sought to determine whether soluble VCAM-1 (sVCAM-1) serum levels differ among normal, failed, and ectopic pregnancy, its capacity to serve as a marker for pregnancy viability or ectopic pregnancy, and its correlation with serum progesterone and beta human chorionic gonadotrophin (PHCG) levels. METHOD OF STUDY: Maternal serum samples were obtained from 20 women with ectopic, 10 with normal, and 10 with failed intra-uterine pregnancy, all of comparable gestational age. Samples were assayed for sVCAM-1, progesterone, and betaHCG by specific assays. RESULTS: The median serum level of sVCAM-1 was comparable between the three pregnancy types (normal: 578.3 ng/mL, range 434.4-699.5 ng/mL; failed: 567.8 ng/mL, range 401.9 669.5 ng/mL; and ectopic: 470.7ng/mL range, 328.2-1151.1 ng/mL). Serum levels sVCAM-1 were not significantly correlated with betaHCG or progesterone levels. CONCLUSION: sVCAM-1 is not appropriate to serve as a marker for pregnancy viability or ectopic pregnancy.

Abortion, Spontaneous↗

Do soluble cell adhesion molecules play a role in endometriosis?

PROBLEM: Endometriosis is a chronic inflammatory disease associated with diverse immunologic disturbances. Cell adhesion molecules are essential for the development of immune and inflammatory reactions. This study was conducted to investigate whether or not serum and peritoneal levels of soluble cell adhesion molecules are altered in women with endometriosis. METHOD OF STUDY: The study group comprised five women with moderate-to-severe endometriosis. Eight healthy women with a normal diagnostic laparoscopy served as controls. Serum and peritoneal fluid samples from both groups were analyzed for the soluble isoform of intercellular cell adhesion molecule-1 (sICAM-1). vascular cell adhesion molecule-1 (sVCAM-1), endothelial selectin (sES), and platelet selectin (sPS). RESULTS: Serum levels of sICAM-1 were significantly increased in women with endometriosis (median levels: 410.4 ng/mL; range: 233.9 ng/mL 598.4 ng/mL vs. 235.7 ng/mL; range: 187.4 ng/mL -323.7 ng/mL; P = 0.02). Although the levels of sVCAM-1, sES, and sPS in both samples were higher in the study group, the differences did not reach significance. CONCLUSIONS: Our results suggest a role of ICAM-1 in the pathophysiology of endometriosis. However. the role of other investigated cell adhesion molecules should be confirmed by further studies.

Adult↗

Is amniotic fluid volume influenced by a 24-hour fast?

OBJECTIVE: To assess the influence of fasting for 24 hours on the amniotic fluid index (AFI). STUDY DESIGN: The AFI of 22 parturients in the second trimester of uncomplicated pregnancy was evaluated on the morning after a 24-hour fast. Patients were prospectively matched to another group of 25 patients who did not fast. Both groups were reevaluated after one week. Two different observers, blind to each other's results, performed the examinations. RESULTS: A statistically significant difference was found in the AFI between the two groups on the day after fasting (11.73 +/- 2.12 versus 15.4 +/- 1.2, respectively; P < .01). After one week there was no difference in AFI between the two groups (15.35 +/- 1.2 and 15.42 +/- 1.2, respectively; P > .01). CONCLUSION: Fasting may reduce the amniotic fluid volume as shown by the AFI, and fluid intake may restore the normal amount of amniotic fluid volume.

Amniotic Fluid↗