The trend of VEGF-A and PlGF in pregnant patients: a perspective case-control study on 214 women.

OBJECTIVE: The aim of this study was to measure plasmatic concentrations of vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PIGF) in pregnant women, and to evaluate their relationship with age, hormonal status, gestational age, and different diseases of pregnancy. METHODS: We selected a control group of 163 patients (96 fertile and 67 in menopause) and a group of 214 pregnant patients during the whole gestational period. VEGF-A and PlGF were assayed by ELISA and EIA methods, respectively. Statistical analysis was performed using the Mann-Whitney test. RESULTS: The control group showed mean VEGF-A and PlGF values of 89.87 pg/ml and 10.22 pg/ml, respectively; PlGF showed the highest values in menopausal patients. The group of pregnant patients showed VEGF-A values of 27.05 pg/ml and PlGF values of 231.36 pg/ml respectively, with lower (for the VEGF-A) and higher (for the PlGF) statistical significance. These values were not influenced by biological age, but were related to gestational age: VEGF-A showed a decrease and PlGF an increase particularly after the 20th gestational week. PlGF showed a statistically significant decrease compared to physiological gestation in spontaneous and threatened abortions (p < 0.0001) and in ectopic pregnancies (p < 0.0001), an increase in ultrasound and CTG alterations (p < 0.05), and threatened premature delivery and uterine hypercontractility (p < 0.01); on the other hand VEGF-A showed a statistically significant increase in ectopic pregnancies (p < 0.05). CONCLUSIONS: VEGF-A and PlGF may play a diagnostic and prognostic role in pregnancy. Further studies are required to better understand the meaning of variability of their values.

Correlation between fetal movement revealed in actography and fetal-neonatal well-being: observational study on 3,805 pregnancies followed in a Northern Italy tertiary care hospital.

PURPOSE OF INVESTIGATION: To evaluate the correlation between fetal movement revealed in cardiotocography and fetal-neonatal well-being as well as to assess the value of cardiotocography in our clinical practice. METHODS: Retrospective analysis of 3,805 pregnancies followed at Parma General Hospital. Exclusion criteria were cesarean section, preterm delivery, and stillbirth. We analyzed the predictive power of actography during the dilating and expulsive phases of labor by establishing a correlation between number of fetal movements and our neonatal indexes of well being, i.e., cardiotocographic score, Apgar index and neonatal pH value. Statistical tests used were Fisher's test, chi-square test (X2), Pearson correlation and Spearman Rho; p value was considered significant if it was less than 0.05. RESULTS: We considered 2,389 vaginal deliveries. Analyzing the correlation between fetal movement and cardiotocographic score in the two different phases of labor, the comparison among subpopulations identified by different cardiotocograph scores revealed no statistical difference. CONCLUSION: Cardiotocography is reconfirmed as a good instrument to evaluate neonatal outcome, while actigraphy cannot be used alone to define fetal well-being, mainly due to the inability to standardize assessment of the actographic study.

Pelvic lymphadenectomy in endometrial cancer: our current experience.

OBJECTIVE: Lymph node involvement is the single most important factor in the prognosis of endometrial cancer, because it is predictive of locoregional and distant metastases. The purpose of our study was to determine whether lymphadenectomy is useful in the surgical staging of endometrial cancer and if it may help establish a more accurate prognosis and reduce the need for postoperative therapy in patients without surgical complications. STUDY DESIGN: We conducted a retrospective study on 55 patients with diagnosis of endometrial cancer. RESULTS: Surgical staging of patients undergoing pelvic lymphadenectomy (47/55) showed that 59.6% of cases (n = 28) had Stage I cancer (IA in 4, IB in 16, IC in 8), 17.02% (n = 8) Stage II (IIA in 3, IIB in 5), 21.2% (n = 10) Stage III (IIIB in 5, IIIC in 5), and 2.1% (n = 1) Stage IVA. In the remaining eight patients with a very high anesthesiologic risk (ASA 4), surgical staging was incomplete because they underwent only node palpation. CONCLUSION: In conclusion, as we wait for the sentinel lymph node technique to demonstrate satisfactory results and be standardized also for endometrial cancer, we believe that surgical lymph node dissection plays a crucial role in debulking this type of cancer. When performed by a good surgical oncology team, it does not entail a significantly increased operative risk.

A perspective study on correlation between HPV DNA and lymph nodes in surgically treated cervical carcinoma patients. Preliminary data.

UNLABELLED: The purpose of this study was to analyze the presence of HPV DNA in lymph nodes in patients with cervical cancer. STUDY DESIGN: A prespective study was performed on a total of 18 patients with cervical cancer in FIGO Stage I-II. The surgical procedure consisted of systematic pelvic lymphadenectomy with removal of the common/external/internal (obturator) iliac lymph node chains, followed by radical hysterectomy depending on the clinical stage, or by Piver's type II radical laparohysterectomy for Stage IA2 carcinoma and Piver's type-III laparohysterectomy for Stage IB or Stage II carcinoma. After removal by a technique not yet described in the literature, the lymph nodes were processed directly in the operating room. HPV DNA testing was done using a cytobrush device. At the end of this operation, the lymph nodes were sent to the hospital's pathologist for metastasis detection. RESULTS: The correlation between a positive HPV DNA test in the cervix and lymph node metastasis was non significant (p < 0.63). By contrast, the correlation between a positive HPV DNA test in the lymph nodes and lymph node metastasis was highly significant (p < 0.005), as was the correlation between positive HPV DNA tests in the cervix and lymph nodes (p < 0.005). Finally, the correlation between disease stage and positive HPV DNA testing in the lymph nodes was also significant (p < 0.05). CONCLUSIONS: In conclusion, the technique that we used for HPV DNA extraction appears safe and reproducible. The results are comparable with, if not better, than those obtained with other techniques reported in the literature. The presence of HPV DNA in the lymph nodes is probably an early indicator of metastasis and as such it could be used as a predictor of relapse. Normally untreated patients who have this marker could then receive adjuvant therapy.

Preterm delivery and premature rupture of membranes after conization in 80 women. Preliminary data.

AIM: Cervical intraepithelial neoplasia is most frequently in young women in reproductive age. Cold knife conization, laser ablation, laser conization and large loop excision are conservative methods of treatment to remove the transformation zone and preserve the cervical function. Previous studies have shown conflicting results on the outcomes of pregnancy following these therapies that might increase the risk of preterm delivery. The purpose of this study was to evaluate the outcome of pregnancy after conization and its role as predictive risk factor. METHODS: A retrospective study was performed. The study group comprised 80 women who had a conization and that had a subsequent singleton pregnancy. Variables considered includes maternal excision date, surgery procedure, previous surgery treatments, time interval between excisional procedure and subsequent pregnancy; duration and week of pregnancy, mode of delivery, histological grading (no cervical intraepithelial neoplasia [CIN], CIN 1, CIN 2-3) and cone excised depth. RESULTS: In group study 45 women underwent loop electrosurgical excision procedure (LEEP) conization, 32 cold knife conization and 3 laser CO2. The authors found 11 cases of cone tissue depth<1 cm, and remaining one>1 cm. Eight preterm delivery have been reported to data: 5 between 28 and 34 weeks, 2 lower than 28 weeks and 1 between 34 and 37 weeks. CONCLUSION: In these preliminary data the percentage of preterm birth appears as 10% and in range 6-15% evaluated for women not submitted to excisional procedures.

Interleukin-6 and insulin-like growth factor system relationships and differences in the human placenta and fetus from the 35th week of gestation.

The integrity of the insulin-like growth factor (IGF) system is essential for normal fetal growth. Cytokine and IGF-IGFBP relationships have been shown in specific tissues, but it is unknown whether these occur in the placenta. We aimed to assess possible differences in the IGF system depending on gestational age (GA) from week 35 to 40, and to study relationships of IL-6 with components of the IGF system in the placenta and newborn infant. We followed 32 normal births and collected whole villous tissue and cord serum. Total RNA was extracted from the placenta samples, reverse transcribed and then real-time quantitative (TaqMan) RT-PCR was performed to quantify cDNA for IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IL-6. The corresponding proteins were assayed in placenta lysates and cord serum using specific commercial kits. Two groups of subjects (Group 1, 35-37 weeks GA, N=12 and Group 2, 38-40 weeks GA, N=20) were studied. In placenta, IGF-I mRNA was more abundant than IGF-II mRNA at all times and together with IGFBP-1mRNA were less expressed at term. IGFBP-2 and IL-6 mRNAs were higher after week 37 GA. IL-6 and IGFBP-2 gene expression were closely related. The corresponding proteins showed similar differences to the genes but IGF-I was undetectable in the lysates, whereas IGF-II was abundant. IGFBP-2 concentrations were very high and greater than those of IGFBP-1. In the newborn, no difference was seen in any cord serum protein after week 35 GA. IGFBP-1 was negatively correlated with parameters of neonatal size. In conclusion, this study reports new insights into IL-6, IGF-IGFBP relationships within the human placenta and shows the importance of comparing subjects with the same GA.

Factors associated with climacteric symptoms in women around menopause attending menopause clinics in Italy.

OBJECTIVE: To obtain data on correlates of climacteric symptoms in women around menopause attending menopause clinics in Italy. METHODS: Since 1997 a large cross sectional study has been conducted on the characteristics of women around menopause attending a network of first level menopause outpatient's clinics in Italy. A total of 66,501 (mean age 54.4 years) women are considered in the present paper. RESULTS: The odds ratios of moderate and severe hot flashes/night sweats were lower in more educated women and (for severe symptoms only) in women reporting regular physical activity. Depression, difficulty to sleep, forgetfulness and irritability tended to be less frequent in more educated women and (depression only) in women reporting regular physical activity. Parous women reported more frequently these symptoms. CONCLUSIONS: This large study confirms in Southern European population that low education, body mass index and low physical activity are associated with climacteric symptoms. Parous women are at greater risk of psychological symptoms.

Seasonal onset of the menopause.

OBJECTIVES: A seasonal rhythm of reproduction is evident in humans. Herein it was investigated whether also the cessation of woman's fertile life follows a seasonal rhythm. METHODS: A retrospective study was performed on 2436 women in postmenopause for more than 12 months, in our menopause centres. Time of menopause was stratified for month and season. The variation was compared to the seasonal rhythm of 14,310 conceptions. RESULTS: The onset of menopause was more frequent (p<0.0001) in winter (32.5%) than in spring (20.8%), autumn (20.3%) and summer (26.2%), in which a minor peak was also observed (p<0.0001 vs. spring and autumn). The two peaks were temporally coincident with the transitions between the high to low and low to high rate of conceptions. CONCLUSIONS: The present data show that in women, like reproduction also the onset of menopause shows a seasonal modulation.

Risk factors for type 2 diabetes in women attending menopause clinics in Italy: a cross-sectional study.

OBJECTIVE: To analyze risk factors for type 2 diabetes among women attending menopause clinics in Italy for counselling about the menopause. SUBJECTS: Women attending a network of first-level outpatient menopause clinics in Italy for general counselling about menopause or treatment of menopausal symptoms. METHODS: Cross-sectional study with no exclusion criteria. Type 2 diabetes was defined according to National Diabetes Data Groups Indications and the fasting blood glucose at an oral glucose tolerance test within the previous year. RESULTS: Out of the 44 694 considered in this analysis, 808 had a diagnosis of diabetes type 2 (1.8%). In comparison with women aged < 50 years, the multivariate odds ratios (OR) of type 2 diabetes were 1.31 (95% confidence interval (CI), 0.99-1.74) for women aged 50-52 years, 1.66 (95% CI, 1.27-2.17) at 53-56 years and 2.84 (95% CI, 2.20-3.67) in women aged > or = 57 years. Type 2 diabetes was less frequently reported in more educated women (OR high school/university vs. primary school = 0.44 (95% CI, 0.36-0.55)). Being overweight was associated with an increased risk of type 2 diabetes. In comparison with women reporting a low level of physical activity, the multivariate OR of type 2 diabetes was 0.67 (95% CI, 0.54-0.84) for women reporting regular physical activity. In comparison with premenopausal women, the multivariate OR of type 2 diabetes was 1.38 (95% CI, 1.03-1.84) in women with natural menopause. This finding was present also after allowing for the potential confounding effect of age. The multivariate OR of diabetes for users of hormonal replacement therapy was 0.58 (95% CI, 0.46-0.73). CONCLUSIONS: This large cross-sectional study suggests that postmenopausal women are at higher risk of type 2 diabetes after allowance for the effect of age. Other main determinants of risk of type 2 diabetes in women around menopause were low socioeconomic status and being overweight. Diabetes was found less frequently in those taking hormone replacement therapy.

The effects of transdermal estradiol on the response to mental stress in postmenopausal women: a randomized trial.

PURPOSE: Estrogens inhibit adrenomedullary catecholamine release and catecholamine-mediated responses to stress. We examined whether estrogen supplementation reduces the sympathoadrenal response to mental stress in postmenopausal women. MATERIALS AND METHODS: We compared the effects of 3-week treatment with transdermal 17-beta-estradiol and placebo in 10 postmenopausal women using a randomized, blinded, crossover design. We measured plasma catecholamine levels and the cardiovascular and metabolic responses to a 15-minute stress with mental arithmetic. Treatments were compared using repeated measures analysis of variance. RESULTS: During placebo treatment, mean (+/- SD) epinephrine levels reached a peak of 431 +/- 135 pmol/liter after 15 minutes of stress; the epinephrine response was blunted during estradiol treatment, with a peak of 357 +/- 77 pmol/liter (P <0.05). Estradiol also blunted the diastolic blood pressure response to stress (baseline levels of 78 +/- 15 mm Hg vs peak of 90 +/- 6 mm Hg during placebo; baseline of 80 +/- 8 mm Hg vs peak of 84 +/- 6 mm Hg during estradiol; P <0.05). Estradiol treatment also blunted the decrease in the standard deviation of the mean of the electrocardiographic RR intervals and the increase in the ratio between the low-frequency and high-frequency bandwidths. CONCLUSION: We observed a moderate, although significant, reduction in markers of the stress response to mental arithmetic in postmenopausal women treated with transdermal 17-beta-estradiol.

Experimental evidence of the effect of heat flux on thomson scattering off ion acoustic waves

Thomson self-scattering measurements are performed in a preionized helium gas jet plasma at different locations along the laser propagation direction. A systematic and important variation of the intensity ratio between the blue and the red ion spectral components is observed, depending on whether the location of the probed region is in front of or behind the focal plane. A simple theoretical calculation of Thomson scattering shows that this behavior can be qualitatively understood in terms of a deformation of the electron distribution function due to the return current correlated with the classical thermal heat flux.

Determinants of age at menopause in Italy: results from a large cross-sectional study. ICARUS Study Group. Italian Climacteric Research Group Study.

OBJECTIVE: To identify the determinants of age at menopause in an Italian population, using data from the Italian Climacteric Research Group Study (ICARUS). METHODS: ICARUS is a prospective study of the effect of menopause on women's health that has been running in menopause clinics throughout Italy since 1995. A total of 4300 women with spontaneous menopause, aged 55 years or more and observed for the first time at the participating centres are included in the present analysis. RESULTS: The mean age at menopause in the total population was 50.9 years. After taking into account potential covariates, the women reported smoking, had a slightly lower mean age at menopause than non smokers 50.4 versus 50.9 years; P = 0.01. The mean age at menopause in nulliparae was 50.0 years, and, respectively 50.4, 50.6, 50.9, 51.2 and 50.9 years in those reporting 1, 2, 3, 4 and 5 or more births (P < 0.01). A low body mass index and an early age at menarche were associated with early menopause in the crude analysis, but these associations disappeared after taking into account the confounding factors. CONCLUSIONS: This study offers an estimate of the mean age at menopause of women attending menopause clinics in Italy, on the basis of the data obtained from a large sample. It also indicates that smoking and nulliparity are associated with early menopause.

Sociodemographic and clinical factors associated with HRT use in women attending menopause clinics in Italy.

OBJECTIVE: The aim of this analysis is to find any association between the use of hormone replacement therapy (HRT) and sociodemographic and clinical factors among women attending 54 menopause clinics in Italy. METHODS: The analysis includes data relating to 17,851 women who attended one of 54 menopause clinics in Italy for general gynecological evaluations and counselling between 1995 and 1997. The characteristics of women reporting ever HRT use were compared with those of never users. The odds ratios (ORs) of HRT use were computed in relation to selected reference categories, together with their 95% confidence intervals (CIs). RESULTS: Of the 17,851 women interviewed, 8539 reported ever HRT use. The mean age of the never and ever HRT users was 52.8 years and 53.7 years, respectively. Higher education was associated with an increased frequency of HRT use: in comparison with women reporting no or primary-/middle-school education, the OR of HRT use of women reporting a high-school diploma or university degree was 1.3 (95% CI 1.1-1.6). HRT use tended to be less frequently reported with increasing body mass index (BMI): in comparison with women whose BMI was < 23.4 kg/m2, the OR of HRT use in those with a BMI of 23.4-26.1 kg/m2 and > or = 26.2 kg/m2 was 0.8 (95% CI 0.8-0.9) and 0.6 (95% CI 0.5-0.7), respectively. Among the postmenopausal women, those who had undergone surgical menopause had an OR of HRT use of 1.3 (95% CI 1.2-1.4). A history of breast cancer was associated with a lower frequency of HRT use (OR 0.3, 95% CI 0.2-0.4). Likewise, a history of thromboembolic disease (OR 0.5, 95% CI 0.4-0.7) or myocardial infarction (OR 0.7, 95% CI 0.6-0.9) was associated with a lower frequency of HRT use. CONCLUSIONS: In our study population, the variable most closely related to HRT use was education/social class, thus underlining the impact of information campaigns on HRT and women's health. Among the medical determinants, our analysis indicates that a history of myocardial infarction, thromboembolic disease or breast cancer is associated with less frequent use of HRT.

The effect of menopause on blood lipid and lipoprotein levels. The Icarus Study Group.

There is increasing evidence from epidemiological studies that exogenous estrogen (hormone replacement therapy) protects against the elevated risk of cardiovascular disease in women after the menopause. However, it is still uncertain whether the postmenopausal decrease in endogenous estrogen in itself contributes significantly to this increase in risk. Most of the studies that have provided evidence linking cardiovascular disease with menopause have involved North American women, who may differ significantly from Europeans in terms of lifestyle and diet. ICARUS (Italian Climacteric Research Group Study) is an observational study that involves Italian Menopause Clinics, with the objective of collecting observational data on menopause and its management. The results of a cross-sectional analysis of 9309 women, free from any hormonal treatment and enrolled up to March 1997, are reported here. Data show that the menopause has a marked effect on the circulating levels of lipids and lipoproteins. From pre- to post-menopause there are significant increases in total cholesterol (6.9% before and 4.4% after adjustment for covariates including chronological age, educational level, center, BMI, smoking habits, hypertension and diabetes, previous contraceptive use, and time since menopause), LDL (7.5% before, 4.0% after), and triglycerides (9.0% before, 3.2% (ns) after). However, there is no significant change in HDL. Among postmenopausal women, no effect on lipid profile of time since menopause was observed.

Formation of plasma channels in the interaction of a nanosecond laser pulse at moderate intensities with helium gas jets.

We report on a detailed study of channel formation in the interaction of a nanosecond laser pulse with a He gas jet. A complete set of diagnostics is used in order to characterize the plasma precisely. The evolution of the plasma radius and of the electron density and temperature are measured by Thomson scattering, Schlieren imaging, and Mach-Zehnder interferometry. In gas jets, one observes the formation of a channel with a deep density depletion on axis. Because of ionization-induced defocusing which increases the size of the focal spot and decreases the maximum laser intensity, no channel is observed in the case of a gas-filled chamber. The results obtained in various gas-jet and laser conditions show that the channel radius, as well as the density along the propagation axis, can be adjusted by changing the laser energy and gas-jet pressure. This is a crucial issue when one wants to adapt the channel parameters in order to guide a subsequent high-intensity laser pulse. The experimental results and their comparison with one-dimensional (1D) and two-dimensional hydrodynamic simulations show that the main mechanism for channel formation is the hydrodynamic evolution behind a supersonic electron heat wave propagating radially in the plasma. It is also shown from 2D simulations that a fraction of the long pulse can be self-guided in the channel it creates. The preliminary results and analyses on this subject have been published before [V. Malka et al., Phys. Rev. Lett. 79, 2979 (1997)].

Oestrogens prevent the increase of human serum soluble interleukin-6 receptor induced by ovariectomy in vivo and decrease its release in human osteoblastic cells in vitro.

OBJECTIVE: Interleukin-6 (IL-6) seems to be a key mediator of the increased bone loss that follows loss of ovarian function. Based on this and on evidence that oestrogen deficiency may also increase cell sensitivity to IL-6, we studied the effects of ovariectomy and of oestrogen replacement therapy on the serum levels of IL-6 and of soluble IL-6 receptor (sIL-6R) in vivo. DESIGN AND PATIENTS: Thirty-seven fertile women undergoing surgery for benign uterine diseases were divided into 3 groups and monitored for 12 months: hysterectomized women (n = 9), ovariectomized untreated women (n = 12) and ovariectomized women starting treatment with transdermal estradiol (E2, 50 microg/d) 1 month after surgery (n = 16). RESULTS: Hysterectomy alone caused no significant changes of sIL6R whereas serum levels of sIL-6R rose progressively after ovariectomy (mean +/- SEM: 31 +/- 9% and 38 +/- 7% over baseline, at 6 and 12 months, respectively; P < 0.01). Oestrogen replacement therapy prevented the increase of sIL6R over a 1-year period. A similar pattern was also found for serum IL-6 but the changes did not reach statistical significance. In ovariectomized (OVX) women there were significant correlations between serum sIL-6R levels and FSH (r = 0.59; P < 0. 01), oestradiol (r = - 0.43; P < 0.01), testosterone (r = - 0.41; P < 0.05), osteocalcin (r = 0.42; P < 0.05) and bone alkaline phosphatase (r = 0.44; P < 0.05). To examine whether oestrogen directly regulates sIL-6R secretion by bone cells, we studied in vitro the basal and phorbol ester (PMA) stimulated release of sIL-6R in a human osteoblastic cell-line (MG-63) and in a tumour-derived osteoclastic cell line (GCT-51). Osteoblastic (but not osteoclastic) cells spontaneously produced considerable amounts of sIL-6R and the protein kinase-C activator PMA (10-8 M) increased the release of sIL-6R by osteoblasts more than 3-fold. More strikingly, 17beta E2 (but not 17alpha) significantly inhibited both the spontaneous- and PMA-induced release of sIL-6R by osteoblastic cells (P < 0.05). CONCLUSIONS: These results indicate that oestrogen loss causes alterations of the IL-6 system, and that sIL-6R is under the direct inhibitory control of oestrogens both in vivo and in vitro.

Efficient generation of narrow-bandwidth picosecond pulses by frequency doubling of femtosecond chirped pulses.

We demonstrate efficient generation of picosecond narrow-bandwidth pulses by frequency mixing of broadband opposite chirped pulses in a type I doubling crystal. This procedure allows us to produce picosecond pulses that are perfectly synchronized with femtosecond pulses. The experiment shows a decrease of the initial bandwidth by a factor of more than 30, while a high conversion efficiency is maintained.