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Biomedical subjects

Eliezer Shalev

Publications and source records attributed to Eliezer Shalev.

At least 37 records · Page 2Linked to original sources

For how long should oxytocin be continued during induction of labour?

OBJECTIVE: To answer the question of whether oxytocin induction of labour should be discontinued when active labour begins. DESIGN: We enrolled patients admitted for induction of labour with oxytocin. Exclusion criteria for induction of labour included non-vertex presentation, past history of more than one caesarean delivery, multiple pregnancies, persistent non-reassuring fetal heart rate before induction of labour and estimated fetal weight of more than 4250 g. SETTING: Department of Obstetrics and Gynecology, Ha'Emek Medical Center, Afula, Israel. POPULATION: Patients who were admitted for induction of labour in Ha'Emek Medical Center from 1st February 1998 to 29th February 2000. METHODS: Patients were randomly divided into two groups. In group A, infusion of oxytocin was incremental until 5 cm dilation and maintained at the same level from that point throughout the labour. In group B, infusion of oxytocin was incremental but was discontinued when cervical dilatation reached 5 cm. Comparison between the two groups was made using Wilcoxon rank-sum test and Fisher's exact test. MAIN OUTCOME MEASURE: Primary outcome variable was duration from induction to delivery. The secondary outcome variables included: duration of labour stages, maximal dosage and total amount of oxytocin used, the use of analgesia, abnormalities in fetal heart rate and episodes of uterine hyperstimulation. We also recorded mode of delivery, together with maternal and neonatal outcome. RESULTS: One hundred and four patients participated in this study. The active phase of labour was shorter in group B compared with group A, but this difference was not statistically significant (2.6 +/- 2 vs 3.3 +/- 2.9, P= 0.07). In group A there were six caesarean deliveries and in group B only three. No significant differences were found when the other outcome parameters were compared. CONCLUSIONS: There is no advantage in continuing oxytocin infusion after the onset of active labour.

Adult↗

Thrombophilia and stillbirth: possible connection by intrauterine growth restriction.

OBJECTIVE: To define the association between thrombophilia and unexplained stillbirth. DESIGN: A case-control study. SETTING: Obstetric department in a university affiliated hospital (Ha'Emek Medical Center, Afula). POPULATION: A total of 53 women who delivered stillborns between March 1998 and June 2002 and 59 women with unremarkable obstetric history who delivered at the same period. METHODS: Presence of genetic and acquired markers of thrombophilia was investigated. MAIN OUTCOME MEASURE: Presence or absence of thrombophilia. RESULTS: Thrombophilia was found in 34% of the women who delivered stillborns and in 20% of the 59 women with normal pregnancies (non-significant). However, significantly higher prevalence of thrombophilia (73%) was found in women who delivered small for gestational age stillborns compared with women who delivered normal birthweight stillborns (73%vs 18.4%, P < 0.0001). CONCLUSIONS: There is no association between thrombophilia and stillbirth, overall. However, there is a clear association between thrombophilia and stillbirth of extremely growth restricted infants.

Adult↗

The role of the matrix metalloproteinases in human endometrial and ovarian cycles.

The matrix metalloproteinases (MMPs) are part of an expanded family of proteins called the astacin family of zinc metalloproteinases. The MMPs, probably balanced by their tissue inhibitors of metalloproteinases (TIMPs), are essential effectors of developmental processes participating in cell migration, cell proliferation, apoptosis and tissue morphogenesis. The MMPs regulate the function of biologically active molecules as well as fulfilling an important role in endothelial cell invasion, angiogenesis and in tumor progression. The dynamic normal physiology of the human reproductive system involves almost all of the above-mentioned aspects of MMPs activity. This review presents and discusses new insights into the role of MMPs, and their TIMPs, in human endometrial cycle and ovarian function.

Endometrium↗

Prenatal diagnosis of 5p deletion syndrome following abnormally low maternal serum human chorionic gonadotrophin.

Prenatal diagnosis of 5p deletion syndrome, or cri du chat, following an abnormally low measurement of a screening of serum human chorionic gonadotrophin (hCG), is reported. Karyotyping following amniocentesis revealed a terminal deletion in the short arm of one chromosome 5. The pregnancy was electively terminated. 5p deletion syndrome has been described with abnormally high hCG levels and normal hCG levels. This is the first report of its association with abnormally low levels. The association between chromosomal abnormalities and hCG is discussed.

Abortion, Induced↗

Mechanisms of matrix metalloproteinase-9 and matrix metalloproteinase-2 inhibition by N-acetylcysteine in the human term decidua and fetal membranes.

OBJECTIVE: The purpose of this study was to evaluate the effect of N-acetylcysteine on the activity and secretion of the matrix metalloproteinases in the decidua, amnion, and chorion and the secretion of the tissue inhibitor of matrix metalloproteinase-1. STUDY DESIGN: Samples from eight nonlaboring women were taken at elective cesarean section and incubated in an in vitro organ culture in the absence or presence of N-acetylcysteine. Matrix metalloproteinase-2 and matrix metalloproteinase-9 activity was measured with the use of gel zymography. Western blot analysis was used to measure matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase-1 secretion. Data were analyzed with the paired Student t test. RESULTS: N-acetylcysteine had a direct inhibitory effect on matrix metalloproteinase-2 and matrix metalloproteinase-9 activity, regardless of tissue origin, starting at 1.0 mmol/L. In cultured media, 20 mmol/L N-acetylcysteine inhibited matrix metalloproteinase-2 and matrix metalloproteinase-9 activity in all three tissues. A differential response was demonstrated for matrix metalloproteinase-2 secretion, depending on the tissue that was studied. Its secretion was decreased in decidua at 10 mmol/L and 20 mmol/L; in amnion, the secretion was inhibited at 0.1 mmol/L and not affected at all in chorion. Matrix metalloproteinase-9 secretion was not affected in a statistically significant manner in any tissue. In the chorion, matrix metalloproteinase-9 showed a trend toward increased secretion. Tissue inhibitor of matrix metalloproteinase-1 secretion significantly decreased in the decidua at 20 mmol/L. CONCLUSION: N-acetylcysteine, at higher concentrations, has an inhibitory effect on matrix metalloproteinase-2 and matrix metalloproteinase-9 activity, regardless of the tissue origin and the differential effect on secretion depending on the tissue and N-acetylcysteine concentration.

Acetylcysteine↗

Regulation of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of MMP, and progesterone secretion in luteinized granulosa cells from normally ovulating women with polycystic ovary disease.

OBJECTIVE: To investigate the regulation of MMP-9, TIMP-1, and progesterone via three signal transduction pathways in luteinized granulosa cells from normal ovulatory and PCOD women. DESIGN: In vitro study. SETTING: Laboratory for Research in Reproductive Sciences, Department of Obstetrics and Gynecology, Ha'Emek Hospital, Afula, Israel. PATIENT(S): Ten normal ovulatory and 10 women with polycystic ovary disease (PCOD) treated in an assisted reproduction program. INTERVENTION(S): Cultured cells were exposed to phorbol 12-myristate 13-acetate (TPA), acting via protein kinase C (PKC), to epidermal growth factor (EGF), acting via protein tyrosine kinase (PTK), and to forskolin, acting via protein kinase A (PKA). MAIN OUTCOME MEASURE(S): Secretion of MMP-9, TIMP-1, and progesterone. RESULT(S): Phorbol 12-myristate 13-acetate elicited an increase in MMP-9 and TIMP-1 secretion in both groups and apparently did not affect progesterone secretion. Epidermal growth factor did not change significantly neither MMP-9 nor TIMP-1 secretion but dose dependently decreased MMP-9-TIMP-1 ratio and increased progesterone secretion in the PCOD group. Forskolin inhibited MMP-9 activity and increased TIMP-1 and progesterone secretion in both groups. Progesterone production was inversely related to the ratio of MMP-9-TIMP-1 regardless of cell origin. CONCLUSION(S): In this preliminary study, similar and divergent patterns have emerged in the regulation of MMP-9 and TIMP-1 in human luteinized granulosa cells. Repressing MMP-9-TIMP-1 ratio may have an important modulatory effect on progesterone secretion.

Adult↗

Gonadotropin-releasing hormone and reproductive medicine.

The hypothalamic gonadotropin-releasing hormone (GnRH) is a key regulator of the reproductive system, mainly through its effects on pituitary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release. Gonadotropin-releasing hormone analogues are modifications of the natural decapeptide, being either agonists (GnRHa) or antagonists. GnRHa may imitate the native hormone and induce an endogenous LH surge; however, sustained treatment with GnRHa results in complete refractoriness of LH and FSH production. This aspect of GnRHa action is the main application of the GnRHa in reproduction today. The hypogonadotropic hypogonadal state that results from the sustained treatment is the basis for additional applications of the GnRHa. The agonists appear to be effective, to some extent, for the treatment of endometriosis and were proved to be beneficial prior to surgery for fibroma uteri. GnRHa is used in assisted reproduction for both induction of an endogenous LH surge and for induction of ovulation, and its capacity to cause refractoriness of the pituitary may be used to avoid a premature LH surge. It is suggested that the GnRHa have a direct effect on ovarian steroidogenesis, which is independent of its action on the pituitary. This unwanted effect and other possible drawbacks of the agonists are thought to be eliminated with the use of the antagonists. The mechanism of action of these antagonists is through competitive blocking of the GnRH receptor, which results in a rapid but reversible suppression of gonadotropin secretion. As for GnRHa, GnRH antagonists have been proven effective to prevent the LH surge and to reduce the incidence of severe ovarian hyperstimulation syndrome in controlled ovarian stimulation cycles.

Embryo Implantation↗

Assessment of uterine placental circulation in thrombophilic women.

Thrombophilia is associated with several complications of pregnancy including first and second trimester fetal loss, intrauterine fetal death, intrauterine growth restriction, preeclampsia, and placental abruption. Few studies have documented thrombotic lesions observed on the pathologic examination of the placenta in women with severe pregnancy complications. Moreover, a significantly higher rate of factor V Leiden and prothrombin G20210A gene mutations have been found in placentas with thrombotic events compared with normal placentas. In addition, clinical studies have been performed, using Doppler ultrasonography, to assess the uterine placental circulation in women with thrombophilia. Doppler studies of the umbilical artery in cases of intrauterine growth retardation have shown a high systolic to diastolic ratio (S/D) ratio, suggesting an increase in the resistance of the placental small vessels. When these placental vessels were examined after delivery, significant differences were found in comparison with placental vessels of normal pregnancies. Most of the Doppler studies of the umbilical and uterine arteries in pregnancies with thrombophilia were performed in women with antiphospholipid antibodies. The other pathologic conditions associated with thrombophilia and complications of pregnancy were published only recently. These few studies have demonstrated abnormal umbilical and uterine arteries blood flow in complicated pregnancies. Finally, few Doppler studies also suggest improved uterine placental circulation when women with thrombophilia received thromboprophylaxis.

Blood Circulation↗

Graves' disease in pregnancy: prospective evaluation of a selective invasive treatment protocol.

OBJECTIVE: Graves' disease in pregnancy carries a risk of fetal thyrotoxicosis from the transplacental transfer of thyroid-stimulating antibodies or fetal hypothyroidism from transplacental transfer of antithyroid drugs and thyroid-blocking antibodies. STUDY DESIGN: From 1991 through 2002, all pregnant women with Graves' disease underwent follow-up evaluations that included serial thyroid-stimulating antibody level, thyroid function, and ultrasound examinations. Umbilical blood sampling was recommended if the thyroid-stimulating antibody level was abnormally high or if fetal tachycardia, goiter, intrauterine growth retardation, or hydrops were present. For fetal hyperthyroidism, the mother received antithyroid drugs; for fetal hypothyroidism, maternal antithyroid treatment was reduced, and thyroxine was injected into the amniotic sac. RESULTS: Of 40000 deliveries, 24 pregnancies (26 fetuses) occurred in 18 women with Graves' disease. Nine of 14 mothers with positive findings elected umbilical blood sampling. In 4 of the mothers, the results were normal. Hyperthyroidism and hypothyroidism were diagnosed in 2 and 3 fetuses, respectively. All the fetuses were treated successfully by the protocol with up to four repeated umbilical blood samplings. No complications were recorded in any of the 20 umbilical blood sampling. In the 5 patients who had only elevated thyroid-stimulating antibody levels and who did not elect umbilical blood sampling, sonographic findings remained normal up to term, and the newborn infants were normal. One of 12 children (in whose case we did not recommend umbilical blood sampling) was born with transient hypothyroidism caused by maternal propylthiouracil treatment. All children, whose cases were followed for up to 9 years, are normal. CONCLUSION: In women with Graves' disease, umbilical blood sampling in selected cases may improve the control of fetal thyroid function.

Amniotic Fluid↗

Clinical and ultrasonographic weight estimation in large for gestational age fetus.

OBJECTIVE: To examine prospectively the effect on pregnancy outcome of a management protocol, that adds ultrasonographic weight estimation in fetuses suspected clinically as large. STUDY DESIGN: Prospective follow up study of all singleton deliveries during a 1 year period. All patients underwent routine clinical estimation of fetal weight. When clinical estimation of fetal weight was > or = 3700 g, patients were referred for ultrasonographic estimation of fetal weight. When the latter was > or = 4000 g the patient was informed about the risks of birth trauma. Cesarean section was recommended only when > or = 4500 g. Ultrasonography was repeated every 4 days when possible. Predictive values of clinical and ultrasonographic estimations of fetal weight for diagnosing macrosomia, defined for the purpose of this study as 4000 g or more, and their effect on the rate of cesarean sections. RESULTS: Five hundred fifty-five (14.4%) out of 3844 singletons were estimated as 3700 g or more. Only 315 fetuses had ultrasonographic estimation of weight within 3 days of delivery. The sensitivity of clinical and ultrasonographic prediction of macrosomia was 68 and 58%, respectively. Cesarean section rate in newborns weighing 4000 g or more was 22% when macrosomia was clinically suspected compared to 11% when it was not (P<0.05). In fetuses estimated ultrasonographically as 4000 g or larger the cesarean section rate was doubled (50.7% versus 24.9%, P<0.05) compared to those estimated as smaller than 4000 g, although actual weight of 4500 g or more was recorded in 10.6 and 8.5% of these groups, respectively. There were no cases of shoulder dystocia in macrosomic babies when macrosomia was not detected by ultrasound compared to two cases of shoulder dystocia (2.7%) when macrosomia was detected by ultrasound. CONCLUSION: Antenatal suspicion of macrosomia increased the cesarean section rate while the associated improvement in pregnancy outcome remains questionable. The contribution of ultrasound, added to routine clinical estimation of fetal weight, was clinically insignificant apart from a further increase in cesarean section rate.

Cesarean Section↗

Tumor chemoconversion following surgery, chemotherapy, and normalization of serum tumor markers in a woman with a mixed type germ cell ovarian tumor.

BACKGROUND: Malignant germ cell tumors of the ovary are often curative after conservative surgery and adjuvant chemotherapy. Persistent tumors despite normalization of serum tumor markers may represent retroconversion to benign masses, but this is rare in ovarian tumors without teratoma elements. The management in such cases has not been defined. CASE: A young woman with a stage IIIC mixed germ cell ovarian tumor containing endodermal and dysgerminoma elements and elevated serum tumor markers underwent conservative surgery followed by chemotherapy. Residual tumor persisted on CT despite the normalization of serum tumor markers. The residual tissue was resected and contained benign tissue. CONCLUSIONS: In cases where masses persist and serum tumor markers normalize, attaining a histological diagnosis, and not chemotherapy, should be considered.

Adult↗

Immunosuppressive properties of follicular fluid and media conditioned by zygotes correlate with subsequent conception in in vitro fertilization.

PROBLEM: Our objective in this study was to correlate immunosuppressive properties of follicular fluid (FF) and media conditioned by zygotes and early embryos with the occurrence of conception in an in vitro fertilization (IVF) program. METHOD OF STUDY: Fifty-seven IVF patients were studied. Donor lymphocytes were incubated with mitogens and FF from mature oocytes or conditioned media from zygotes and early embryos. Proliferation was assessed by radioactive thymidine incorporation. Proliferation Index (PI) was the ratio between radioactive labeling of lymphocytes incubated in the presence and absence of a mitogen. RESULTS: The FFs and media conditioned by zygotes from conception cycles had higher immunosuppressive activity than those from non-conception cycles. CONCLUSIONS: Immunosuppressive activity present in FF and media conditioned by zygotes may be a major determinant of conception in IVF, and may serve as a marker for embryo quality.

Culture Media, Conditioned↗

Early brain atrophy in persistent hyperinsulinemic hypoglycemia of infancy.

We present two siblings with persistent hyperinsulinemic hypoglycemia of infancy, accelerated intrauterine growth and early neonatal brain atrophy. Fetal plasma glucose and insulin levels in the second sibling revealed normoglycemia despite hyperinsulinemia. The absence of intrauterine hypoglycemia suggests that the brain damage is not secondary to hypoglycemia and other etiologies must be considered.

Atrophy↗

The significance of coasting duration during ovarian stimulation for conception in assisted fertilization cycles.

BACKGROUND: Withholding gonadotrophin administration and postponing HCG injection, termed coasting, has been suggested as a treatment modality in cases of impending ovarian hyperstimulation syndrome (OHSS). It presents an opportunity to reduce the risk of OHSS and salvage the treatment, without apparent compromise to outcome. However, the duration of the coasting period, which would maintain the advantage without reducing conception rate, has not been fully established. In this retrospective study, we attempted to define the optimal interval of coasting in patients at risk of developing OHSS. METHODS: Patients were grouped according to the number of days elapsed between cessation of gonadotrophins and administration of HCG. Overall, out of 207 patients (mean age 30.76 +/- 0.33 years) coasting lasted 1 day in 39 cycles (18.8%), 2 days in 61 cycles (29.4%), 3 days in 49 cycles (23.6%) and > or = 4 days in the remaining 58 cycles (28.5%). RESULTS: There was no difference between the groups in patients' age, serum estradiol concentrations at the time of HCG administration, oocyte maturity, fertilization and embryo cleavage rates. However, patients in whom coasting lasted > or = 4 days had significantly reduced implantation (10.5%) and pregnancy (26.7%) rates compared with patients with a shorter coasting interval (ranges 18.4-27.9 and 41-55.7% respectively; P < 0.05). CONCLUSION: Coasting for >3 days appears to reduce implantation and pregnancy rates while in-vitro oocyte and embryo quality do not appear to be affected. We suggest that in patients who need coasting for >3 days, cryopreservation of embryos should be considered.

Adult↗

Bacterial colonization of the uterine cervix and success rate in assisted reproduction: results of a prospective survey.

BACKGROUND: Overgrowth of bacteria in the birth canal is associated with an increased risk of late miscarriage, preterm labour, post-partum endometritis and low birthweight. Conception rates in assisted reproduction treatments (ART) remain frustratingly low. We examined whether the nature of bacterial flora, found in the uterine cervical canal at embryo transfer, is associated with the rate of conception in ART. METHODS: We sampled for bacteriological culture the cervical canal of 204 patients who underwent embryo transfer. Of these, 139 (68%) were of fresh embryos, following recent vaginal oocyte retrieval and prophylactic antibiotic therapy, and 65 (32%) of frozen-thawed embryos, without any vaginal intervention in the preceding days. Bacteriological work-up included identification, colony count and antibiotic susceptibility profile. Conception was correlated with bacterial type and colony count. RESULTS: In 75 patients (36.8%) sterile cervical cultures or lactobacillus were recorded. Of these 75 patients, 23 (30.7%) conceived, whereas among the 129 in whom any pathogenic micro-organism was recovered only 21 (16.3%) conceived (P = 0.002). No difference in colonization was found between women who underwent frozen-thawed versus fresh embryo transfer (57 and 67% respectively). Any Gram-negative colonization was associated with no conception. All Gram-positive, and 90% of the Gram-negative bacteria, were sensitive to augmentin. CONCLUSIONS: Failure to conceive in ART is significantly associated with bacterial colonization of the uterine cervix.

Adult↗

The effects of gonadotropin-releasing hormone (GnRH) I and GnRH II on the urokinase-type plasminogen activator/plasminogen activator inhibitor system in human extravillous cytotrophoblasts in vitro.

The regulated expression of the urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor (PAI-1) is believed to modulate the invasive capacity of human trophoblastic cells in vitro and in vivo. To date, the factors capable of regulating the expression of uPA and PAI-1 in these cells remain poorly characterized. In these studies, we have examined the ability of the classical mammalian GnRH I and the second form of GnRH (GnRH II) to regulate uPA and PAI-1 mRNA and protein expression levels in primary cultures of human extravillous cytotrophoblasts using quantitative competitive PCR and ELISA, respectively. Both GnRH I and II increased uPA and concomitantly decreased PAI-1 mRNA and protein expression levels in our extravillous cytotrophoblast cultures in a dose- and time-dependent manner. Cetrorelix, a peptide GnRH antagonist specific for the GnRH I receptor, was capable of inhibiting the regulatory effects of GnRH I, but not GnRH II on uPA and PAI-1 expression levels in primary cell cultures. Taken together, these observations suggest that GnRH I and GnRH II may facilitate trophoblast invasion by increasing the ratio of uPA/PAI-1 expression via interactions with two distinct GnRH receptors.

Cells, Cultured↗

Diagnosis of congenital cardiac defects between 11 and 14 weeks' gestation in high-risk patients.

OBJECTIVE: To examine the feasibility of diagnosing congenital cardiac defects between 11 and 14 weeks' gestation in a high-risk population. METHODS: Fetal echocardiography was first offered at 11 to 14 weeks' gestation to all patients at risk for congenital heart defects. Echocardiography performed at 11 to 14 weeks with normal results was repeated at 14 to 16 and 20 to 24 weeks. Final diagnoses of cardiac anomalies that had been observed at 11 to 14 weeks were established at 14 to 16 weeks or later Fetal echocardiography performed at 14 to 16 weeks with normal results was repeated at 20 to 24 weeks. Ascertainment of cardiac anomalies was obtained by postnatal echocardiography or pathologic examination of the fetal heart after termination of pregnancy. Most of the examinations were performed transvaginally until 16 weeks. The transabdominal approach was used at this stage only when patients refused the transvaginal examination or because of technical difficulties. Three hundred ninety-two fetal echocardiographic examinations were performed between 11 and 14 weeks' gestation; 438 examinations were performed between 14 and 16 weeks; and 777 examinations were performed between 20 and 24 weeks. The major indications for fetal echocardiography at 11 to 14 weeks were maternal diabetes and previous pregnancy with congenital heart defects. RESULTS: Six of 7 major fetal cardiac anomalies were detected. The only major cardiac anomaly that was not detected between 11 and 14 weeks was correctly diagnosed at 22 weeks. Only 1 of 5 minor fetal cardiac anomalies was detected between 11 and 14 weeks. Another 2 minor fetal cardiac anomalies were detected at 23 weeks. Four incorrect diagnoses of minor cardiac anomalies were excluded on repeated fetal echocardiography between 20 and 24 weeks. CONCLUSIONS: The initial attempt to diagnose congenital heart defects should be offered at 11 to 14 weeks' gestation.

Female↗