Climacteric symptoms in women undergoing risk-reducing bilateral salpingo-oophorectomy.

BACKGROUND: The most effective strategy for prevention of ovarian and breast cancer in high-risk women is bilateral salpingo-oophorectomy. The inevitable consequence of the procedure is early menopause with the associated climacteric symptoms. Little is known about the nature of the symptoms in women who undergo risk-reducing bilateral salpingo-oophorectomy. OBJECTIVES: To compare the nature, frequency, severity, duration, and overall effects of climacteric symptoms in a group of women who underwent preventive bilateral salpingo-oophorectomy as compared to women who experienced natural menopause. METHODS: Forty-eight women at high risk for ovarian cancer who had risk-reducing bilateral salpingo-oophorectomy were compared to 60 postmenopausal women who had natural menopause. The participants were interviewed about their climacteric complaints, thoughts and feelings regarding the surgical procedure and their general well-being. The climacteric symptoms were evaluated by a modified Greene Climacteric Scale. RESULTS: Surgical menopause, as compared to natural menopause, was associated with more severe psychological, vasomotor and somatic climacteric symptoms (total score 17.36 vs. 8.65, respectively, p < 0.001) and more significant sexual dysfunction (1.848 vs. 0.900, respectively, p < 0.01). On a 0-10 scale, the satisfaction rate from the surgical procedure was 8.23 +/- 2.21. The surgery did not affect the perceived quality of life (p = 0.347) and decreased the score of anxiety and cancer fear (from 7.75 +/- 3.31 preoperatively to 2.94 +/- 3.08 postoperatively, p < 0.001). CONCLUSIONS: Risk-reducing bilateral salpingo-oophorectomy as compared to natural menopause is associated with more severe climacteric symptoms. However, the procedure does not interfere with the overall perceived quality of life and improves the perception of cancer risk.

Ehlers-Danlos type IV in pregnancy. A case report and a literature review.

BACKGROUND: Ehlers-Danlos syndrome is a heterogeneous group of connective tissue disorders, characterized by a defect in the synthesis of collagen. The syndrome is subdivided into different clinical subtypes, the most hazardous of which is type IV, the vascular type. It can manifest itself in various complications such as rupture of arteries and hollow organs. The obstetrical manifestations are the risk of uterine rupture during labor, damage to the vagina and perineum, bleeding and rupture of blood vessels and colon during the puerperium. CASE REPORT: We describe a primigravida suffering from Ehlers-Danlos type IV who was followed and successfully delivered by a cesarean section at 36 weeks of gestation and made an uneventful recovery. CONCLUSION: Following a thorough literature review, it seems wise to perform early delivery by cesarean section for pregnant women suffering from Ehlers-Danlos type IV.

Maternal morbidity following routine second trimester genetic amniocentesis.

Two cases of septic complications of routine second trimester amniocentesis are presented. The first case is a 37-year-old gravida suffering from ulcerative colitis who was admitted for amniocentesis in the 18th week of her third pregnancy. An uncomplicated transabdominal amniocentesis was performed using a sterile technique and ultrasound guidance. Twenty-eight hours later the patient had a septic abortion and sepsis. The second case is a 34-year-old gravida in the 24th week of her pregnancy who was admitted with amnionitis 10 h after an uncomplicated amniocentesis, and subsequently had a septic abortion. A high index of suspicion and rapid intervention were crucial in both cases.

Monoamniotic twins: an update on antenatal diagnosis and treatment.

OBJECTIVE: Monoamniotic twins are very uncommon and are characterized by a high perinatal mortality rate. Cord entanglement, prematurity, congenital anomalies and twin to twin transfusion are reportedly the main causes of death, which usually occurs before 24 weeks' gestation. The aim of this study was to review the newly developed methods for diagnosis and treatment and suggest a reasonable approach to the management of these rare cases. METHOD: We reviewed the English-language literature in the past 15 years through Medline search and subsequent examination of individual publications. RESULTS: In the past two decades, newer technologies such as advanced ultrasonography and color flow Doppler studies have enabled early diagnosis of this condition and its complications. Furthermore, new treatment modalities such as fetoscopy with laser coagulation of vascular anastomoses and treatment with non-steroidal anti-inflammatory drugs such as sulindac, to reduce amniotic fluid volume, may have contributed to a better outcome. Also, occlusion of one umbilical cord (fetal reduction) at an early stage has been suggested to prevent late complications. CONCLUSION: Cumulative experience suggests that the majority of cases can be diagnosed reliably at an early gestational age. Treatment with medical amnioreduction, surgical amnioreduction or fetal reduction in selected cases may be offered before 24 weeks' gestation. Later, intensive antepartum fetal surveillance should probably be offered until 32 weeks, at which point elective preterm delivery may be considered to prevent possible fetal death.

Cell death in cultured human Saos2 osteoblasts exposed to low-density lipoprotein.

Osteoporosis (OP) and atherosclerotic-cardiovascular diseases (and possibly dementia) constitute emerging age-related co-morbidity states that might share risk factors. Blood-born lipids, like LDL involved in atherosclerosis and apolipoprotein-E4 (ApoE4) involved in dementia, may also be implicated in development of OP. We examined osteoblast cell lines as a culture model for OP by exposure to lipoproteins. ApoE expression in Saos2 and U2OS osteoblasts was confirmed by PCR. ApoE4 did decrease cell counts relatively to ApoE3, especially in Saos2 cells in which it was less selective for cells with higher alkaline phosphatase (ALP, an osteoblast marker) activity than ApoE3. This associates with ApoE4, being a risk factor for both dementia and OP. Saos2, but not U2OS, showed a decrease in cell counts after 48 h exposure to native LDL (NLDL). Both cell lines had decreased cell counts already after 24 h when exposed to oxidized-LDL (OxLDL) for which Saos2 also showed a higher sensitivity than U2OS. Exposure of Saos2 to both, OxLDL at low concentration (5 microg/ml) and NLDL revealed a shrunken size cell fraction of 17-23% on the fluorescence-activated cell sorter (FACS) analysis. Such shrunken cell fraction was not seen when Saos2 cells were exposed to 50 microg/ml of OxLDL or to OxLDL combined with 10 nM dexamethasone (DEX, a stimulator of osteoprogenitor differentiation). DEX treatment has lysed the cells earlier than 24 h post exposure and has selected more resistant cells that did not show apoptotic shrinkage in the FACS analysis done after 24 h. We interpret this as a failure to detect the apoptotic cell fraction due to their lysis prior to the FACS analysis. Western blots performed at different time points (10 min, 30 min, 4 h, 24 h, and 48 h) under OxLDL + DEX revealed a fall in the positive regulator of pp60Src-kinase phosphotyrosine (pY)418 relative to the DEX controls during the first 4 h. This is consistent with DEX osteogenic induction, known to be negatively regulated by c-Src, although the pY418/pY529 ratios (negative/positive kinase regulation) fell only at the 10 min time point. Contrarily the pY418/pY529 ratio increased, relative to untreated controls, under 5 microg/ml and 50 microg/ml of NLDL at the 4 h time point and under 50 microg/ml NLDL only at the 10 min time point, being consistent with the ability of a higher dose of LDL to antagonize osteoblast differentiation. This could be even more acceptable if the NLDL would have become minimally oxidized during its long purification procedure. Under NLDL, the Bcl-2/Bax ratio was pro-apoptotic at 10 min, 30 min, and 4 h only under 50 microg/ml, whereas under OxLDL + DEX it was pro-apoptotic only after 4 h suggesting that additional pathways contribute to cell death. These results indicate that lipid effects on human osteoblast lines in culture may be used as a model to identify molecular targets shared between OP and atherosclerosis for intervention in this co-morbidity.

Pregnancy outcome after laparoscopy or laparotomy in pregnancy.

STUDY OBJECTIVE: To assess obstetric performance and fetal outcomes after laparoscopy or laparotomy performed during pregnancy. DESIGN: Nationwide, multicenter, retrospective chart review (Canadian Task Force classification II-2). SETTING: Seventeen hospitals throughout Israel: 12 university or university-affiliated hospitals and 5 general hospitals. PATIENTS: Three hundred eighty-nine pregnant women. INTERVENTION: Laparoscopy or laparotomy for various indications. MEASUREMENTS AND MAIN RESULTS: Of 192 laparoscopies performed, 141 were during the first, 46 during the second, and 5 during the third trimester; respective figures for 197 laparotomies were 63, 110, and 24. No intraoperative complications were reported for either procedure. Six and 25 women had complications after laparoscopy and laparotomy, respectively. There was no significant difference in abortion rates between groups. Mean gestational age at delivery and mean birthweight were comparable between groups. No significant difference was found in frequency of fetal anomalies between groups or when compared with the Israel register of anomalies. CONCLUSION: Operative laparoscopy seems to be as safe as laparotomy in pregnancy.

Placenta accreta--summary of 10 years: a survey of 310 cases.

The objective was to study the incidence, risk factors, and outcome of pregnancies complicated by placenta accreta in our population. Retrospective analysis of all deliveries between the years 1990-2000, and identification of all cases of placenta accreta, defined by clinical or histological criteria. For comparison purposes we defined two sub-groups: (i) all cases that ended with severe outcome and (ii) all patients who had a previous event of placenta accreta in one or more of their previous deliveries. We evaluated the potential risk factors leading to these conditions. The SPSS software package was used for statistical analysis. Univariate and multivariate analyses were performed by stepwise logistic regression. The study covered 34 450 deliveries from which 310 cases of placenta accreta were diagnosed (0.9 per cent). The risk factors associated with placenta accreta were previous cesarean delivery (12 per cent), advanced maternal age, high gravidity, multiparity, previous curettage and placenta previa (10 per cent). Hysterectomy was performed in 11 patients (3.5 per cent) with one case of maternal death, whereas 21 per cent of the patients required postpartum blood products transfusion. Antenatal diagnosis of placenta accreta or percreta by ultrasound or MRI, was achieved only in eight of the cases. In the sub-group of 15 patients (4.8 per cent) with severe outcome, the only significant risk factors were increased parity (O.R.=1.29, 95 per cent CI 1.056-1.585), anteriorly low placenta (O.R.=6.1, 95 per cent CI 1.4-25.3) and repeated cases of caesarean sections (O.R.=3.3, 95 per cent CI 0.9-12.5), whereas in the 49 (16 per cent) patients with repeated cases of placenta accreta the only significant risk factor was the number of deliveries (O.R.=1.5, 95 per cent CI 1.0-2.2). Repeated cesarean delivery, high parity, and anteriorly low placental location are associated with severe outcome in case of placenta accreta. Women with repeated events of placenta accreta may have better outcome and a genetic factor may serve as a cause for this condition.

Induction of labor in breech presentation.

OBJECTIVE: Induction of labor in breech presentation, although not contraindicated, has rarely been reported. We have undertaken to evaluate the safety and outcome of this practice in two Israeli institutions along with a literature review of this controversial subject. METHOD: The research design was a retrospective case control study covering the years: 1980-1999. We have studied 53 term (>37 weeks) breech deliveries induced for various medical and obstetrical reasons, in two major regional hospitals in Israel. Induction was performed with prostaglandin E(2) for the unripe cervix and with oxytocin for induction or augmentation when the cervix was ripe. Six women were induced by nipple stimulation. Controls were 53 women with spontaneous labor in breech presentation that had a trial of vaginal delivery, and 54 women with breech presentation who delivered by elective cesarean section. RESULT: No significant difference in the various maternal and fetal outcomes was observed. CS rate was comparable in both study and control groups (34% vs. 32%) and two-thirds gave birth vaginally. CONCLUSIONS: In properly selected and carefully managed cases of breech presentation, induction of labor seems a safe and reasonable option.

Laparoscopic surgery during pregnancy.

In the last decade, operative laparoscopic procedures are performed increasingly in both gynecology and general surgery. The major advantages of this newer minimally invasive approach are: decreased postoperative morbidity, less pain and decreased need for analgesics, early normal bowel function, shorter hospital stay, and early return to normal activity. With the advancement of laparoscopic surgery, its use during pregnancy is becoming more widely accepted. The most commonly reported laparoscopic operation during pregnancy is laparoscopic cholecystectomy (LC). Other laparoscopic procedures commonly performed during pregnancy include: management of adnexal mass, ovarian torsion, ovarian cystectomy, appendectomy, and ectopic pregnancy. The possible drawbacks of laparoscopic surgery during pregnancy may include injury of the pregnant uterus and the technical difficulty of laparoscopic surgery due to the growing mass of the gravid uterus. Also, the potential risk of decreased uterine blood flow secondary to the increase in intraabdominal pressure and the possible risk of carbon dioxide absorption to both the mother and fetus should be taken into account. To date, data on laparoscopic surgery during pregnancy are insufficient to draw conclusions on its safety and exact complication rate. This is due to the few cases reported and the lack of prospective studies. Furthermore, there is a common tendency to underreport unsuccessful cases. Finally, most reports in the literature come from centers and surgeons with special interest, experience, and skills in laparoscopy, and their results may not reflect the real complication rates. We have reviewed the pertinent English literature from the last decade. The cumulative experience suggests that laparoscopic surgery may be performed safely during pregnancy, although more studies are needed to establish its exact rate of adverse events.

[Residents training in gynecologic operative endoscopy: a review of Israeli and world experience].

Two decades ago, Gynecologic procedures performed by endoscopy were basically limited to diagnostic procedures. Since 1990, operative endoscopy is increasingly used to treat a growing variety of gynecologic conditions, resulting in shorter hospital stay and smaller, less painful incisions. One of the greatest tasks facing today's academic gynecologic surgeons is training residents and attendant physicians to perform endoscopic surgery adequately and safely. Clearly, there is a need to provide basic knowledge of endosurgical principles, and understanding of equipment and technologies used in operative endoscopy. Also, information on minimization, early recognition and treatment of endoscopic complications is of great importance as well as hands-on experience in these new procedures. We have reviewed the world as well as the Israeli experience in the field and out of this growing base of knowledge we have tried to delineate and forge guidelines for adequate teaching, training and accreditation.

Seasonal variability in fertilization and embryo quality rates in women undergoing IVF.

OBJECTIVE: IVF-ET provides unique controlled conditions for the study of seasonal influences on the human reproductive process. This study was designed to evaluate the effects of seasonality on fertilization rate, embryo quality, and conception rates. DESIGN: A retrospective observational cohort study. A chart review of all individuals undergoing IVF-ET from 1988 to 1991 at our institution was performed. SETTING: An assisted reproduction unit at a university-based tertiary medical center. PATIENT(S): 657 women, for a total of 1074 IVF-ET treatment cycles, were evaluated. From this population, we chose 305 women undergoing their first IVF-ET cycle for reasons of pure mechanical infertility. INTERVENTION(S): IVF-ET cycles. MAIN OUTCOME MEASURE(S): Seasonal variability in fertilization rates and quality-A embryo rates, and the correlation with the absolute number of light hours, as well as the influence of temperature, humidity, and other environmental parameters. RESULT(S): A significant seasonal variability in the fertilization rate and the quality-A embryo rate was demonstrated. The highest fertilization and quality-A embryo rates were observed during the spring and the lowest in the autumn. These changes correlated with the absolute number of light hours and its increment over time, but not with the temperature, humidity, or other environmental parameters. CONCLUSION(S): Seasonality seems to have a significant influence on the fertilization process and on the quality of the human embryos that are obtained in vitro, possibly because of the light/dark variations over time. If this finding is confirmed, these seasonal changes should be taken into account when evaluating infertility data and in everyday clinical practice.

Induction of bone formation in rat osteoprogenitor cell culture by sera of climacteric women before and after hormone replacement therapy.

OBJECTIVE: To evaluate the effect of hormone replacement therapy (HRT) on growth and differentiation of cultured osteoprogenitor cells. DESIGN: Prospective clinical study. SETTING: Outpatients in a menopause clinic. PATIENT(S): Women with climacteric symptoms. INTERVENTION(S): Daily oral conjugated estrogen, 0.625 mg, and medroxyprogesterone acetate, 2.5 mg, for 7-12 months. Bone density measurement before HRT and blood sampling before and after HRT. MAIN OUTCOME MEASURE(S): Sera of climacteric women were added to the culture of rat osteoprogenitor cells, and indices of cell proliferation and differentiation (alkaline phosphatase activity and mineralization) were measured before and after HRT. RESULT(S): Sera after HRT significantly decreased cell counts but not alkaline phosphatase activity or mineralization as compared with sera before HRT. However, mineralization induced in the bioassay by both sera showed a positive correlation (r = 0.56) with E2 levels before treatment and a negative correlation (r = -0.6181) with time in menopause of serum donors. The change in mineralization showed a significant correlation with hip bone mineral density z scores (r = -0.67) but not with spine z scores (r = -0.1915), whereas the change in cell count correlated with spine bone mineral density z scores (r = 0.49) only. CONCLUSION(S): Changes in serum-induced cell proliferation and mineralization may be helpful in studying the response to HRT in climacteric women. Serum-induced mineralization is more efficient in diagnosing osteopenia than in monitoring HRT effects.

Parasitic ovarian dermoid tumor of the omentum-A review of the literature and report of two new cases.

Two cases of a parasitic omental teratoma which originated from an ovarian dermoid that underwent torsion, autoamputation and omental reimplantation are presented. A review of the literature revealed 23 additional cases of omental teratoma which occurred mostly in females. In some cases, the mature teratoma of the omentum showed histological evidence of ovarian stroma, and was associated with a dermoid tumor of the remaining contralateral ovary. It is generally believed that autoamputation and reimplantation of an ovarian dermoid cyst is the most common etiology of omental teratomas. Abdominal pain is the main presenting symptom of these tumors, and on physical examination a mobile abdominal or pelvic mass is often found. Both ultrasonography with colour flow Doppler and CT-scan are helpful in the diagnosis of dermoid tumors, but the correct diagnosis of omental localisation is extremely difficult. Mature omental teratomas may be treated by simple resection. The immature teratomas of the greater omentum, however, are potentially malignant tumors requiring postoperative chemotherapy and radiotherapy.

Opposing effects of cyclosporin A and tyrphostin AG-1478 indicate a role for Src protein in the cellular control of mineralization.

Cyclosporin A (CsA) induces osteoporosis but not through direct activation of osteoclasts. CsA also inhibits cell-mediated mineralization in marrow stromal cell culture, whereas the tyrphostin AG-1478 increases mineralization. These antagonistic effects on mineralization were used to discern molecules that underwent phosphorylation changes in association with their opposing effects on mineralization. In parallel, quantitative changes in Src protein were followed. Multiple dexamethasone (DEX)-stimulated stromal cell cultures were grown with and without a mineralization-inhibiting dose (0.1 microM) of CsA and were harvested on different days of DEX stimulation. Immunoblots of gel-fractionated cell extracts showed that the most noticeable changes in tyrosine phosphorylated proteins (TPP) were seen on day 8 of DEX stimulation. At least 15 TPP bands, mostly smaller than 53 kDa, were more prominent in CsA-treated cultures on day 8. Under CsA, Src protein quantity decreased on day 8, but its cleavage product (52/54 kDa) was sixfold more abundant then on day 7. Day 8 was chosen to test the effect of AG-1478 on the CsA-induced TPP changes. Dimethyl sulfoxide (DMSO) alone, the solvent of AG-1478, increased mineralization in CsA-treated versus CsA-untreated cultures and slightly decreased Src and its cleavage product. AG-1478 at 5 microM, in CsA cultures increased the specific alkaline phosphatase activity threefold, with a slight change in mineralization relative to controls grown with DMSO alone. This was accompanied by decreased intensity of several TPP bands smaller than 36 kDa. In contrast, treatment with 50 microM of AG-1478 increased the intensity of TPP bands at the same molecular size range. This high AG-1478 dose decreased cell counts selecting mineralizing cells. The results indicate that increased Src protein cleavage product on day 8 by CsA is associated with mineralization inhibition, which is opposed by DMSO and 50-microM AG-1478, thus antagonizing the effect of CsA on mineralization. Direct or indirect interaction between Src and TPP, antagonistically affected by CsA and AG-1478, is likely to underlay cellular control of mineralization. Changes in p19 and p29 intensity showed association with mineralization that was reflected by a significant direct and inverse correlation, respectively, with calcium precipitation per cell.