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Fabio FACCHINETTI

Professore Ordinario
Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto


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Pubblicazioni

2022 - BRCA mutation carriers’ perception about benefits and risks associated with combined hormonal contraceptives use [Articolo su rivista]
Grandi, G.; Monari, F.; Boggio Sola, V.; Cortesi, L.; Toss, A.; del Savio, M. C.; Melotti, C.; Centurioni, M. G.; Gustavino, C.; Varesco, L.; Facchinetti, F.; Barra, F.
abstract

To evaluate the actual perceptions about combined hormonal contraceptives (CHCs) use in BRCA mutation carriers in comparison to women from the general population.


2022 - Chronic deciduitis in stillbirths: are there any specific clinical associations? [Articolo su rivista]
Avagliano, L.; Monari, F.; Salerno, C.; Menichini, D.; Facchinetti, F.; Bulfamante, G.
abstract

Introduction: Placental chronic deciduitis is a lesion consistent with the presence of plasma cells within the placental basal plate. It could be associated with adverse pregnancy outcomes, including stillbirth. Methods: We retrospectively evaluated a cohort of 180 antepartum stillborn cases from singleton pregnancies, with the aim of investigating the clinical-histopathological relationship. Placental slides were reviewed following the standard protocol proposed by the “Amsterdam consensus statement”. Results: We observed an association between chronic deciduitis and lesions consistent with maternal vascular malperfusion, delayed villous maturation, villitis of unknown etiology and maternal autoimmunity. Conclusions: The observed clinical-histopathological associations suggest that an extensive maternal investigation could improve the comprehension of factors interfering with the placental development and the increasing risk of adverse pregnancy outcomes. Highlights Chronic deciduitis is associated with lesions consistent with maternal vascular malperfusion Chronic deciduitis is associated with delayed villous maturation Chronic deciduitis is associated with villitis of unknown etiology Chronic deciduitis is associated with maternal autoimmunity.


2022 - Chronic endometritis in recurrent implantation failure: Use of prednisone and IVF outcome [Articolo su rivista]
Giulini, S.; Grisendi, V.; Sighinolfi, G.; Di Vinci, P.; Tagliasacchi, D.; Botticelli, L.; La Marca, A.; Facchinetti, F.
abstract

In recurrent implantation failure patients (RIF), the main criteria for diagnosis of chronic endometritis, is the presence of plasma cells CD138+ in endometrial biopsy. The aim of the present study was to evaluate if treatment with prednisone, in patients with RIF and chronic endometritis, improve IVF outcome. A retrospective study was performed between 2019 and 2020. A total of 27 patients with RIF and an endometrial biopsy positive for CD56+ cells were enrolled. The treatment with prednisone 10 mg per day is began together with controlled ovarian stimulation (COS). Among endometrial biopsies, 13 (48.14%) were positive also for CD138 cells, and an antibiotic treatment was added. In all patients, after therapy, in the subsequent IVF cycle, the clinical pregnancy rate was 25.9% and the live birth rate was 22.2%. Analysing pregnancies according to the percentage of CD 56 cells on endometrial biopsy, the live birth rate in the subgroup of patients with marked endometritis (defined by the presence of >10% CD56+cells) was 29.41%, while in the subgroup with mild endometritis (CD 56 >5% and <10%) was 10%. In the subgroup with mild endometritis with CD 138 positive the live birth was 25%, while in patients with CD 138 negative no live birth were observed. In patients with RIF the count of at least two cell types (CD 138 and CD 56 cells) on endometrial biopsies is advisable. Our study suggests a benefit of prednisone and antibiotic treatment on live birth rate in a subsequent IVF cycle.


2022 - Coffee intake during pregnancy and neonatal low birth weight: data from a multicenter Italian cross sectional study [Articolo su rivista]
Mannucci, C.; Attard, E.; Calapai, F.; Facchinetti, F.; D'Anna, R.; Vannacci, A.; Santamaria, A.; Lenti, M. C.; Righi, M.; Perone, M.; Sorbara, E. E.; Alibrandi, A.; Oteri, A.; Inferrera, G.; Calapai, G.
abstract

Aim: Coffee intake is common during pregnancy. However, the influence of coffee and caffeine on pregnancy has not yet been fully determined. Some studies show that high coffee intake could cause miscarriage, preterm birth or reduction of fetal growth, but other studies do not support these findings. The aim of the present study was to analyze data collected from a database focusing on coffee intake during pregnancy, which was specifically created for multicenter studies carried out in the maternity units of Italian general hospitals. Principal outcomes of pregnancy during pregnancy were considered. Methods: Data of 5405 pregnancies were collected by a direct questionnaire supplemented with data from patients’clinical records during the survey named PHYTO.VIG.GEST. Results: We observed that 42.3% of the total sample had consumed at least one coffee a day during pregnancy. Analysis of a dose–response relationship showed that, in pregnant women starting from the consumption of three coffees a day (6% of pregnant women consuming coffee), there is a statistically significant association between number of coffees and reduction of babies birth weight (< 2500 g). Coclusion: Even though high coffee intake is known to influence negatively birth weight, our results indicate that a significant percentage of pregnant women maintain this habit.


2022 - Complete hydatidiform mole in higher-order multiple pregnancies [Articolo su rivista]
Sileo, F. G.; Giuliani, G. A.; Facchinetti, F.; Contu, G.; Chiossi, G.; Bertucci, E.
abstract

Molar degeneration of the trophoblast is a rare, yet possible, complication of pregnancies. Complete hydatidiform mole is the most common histological type among all trophoblastic tumors and it is the result of the fertilization of an empty oocyte from two sperms or by one sperm that then duplicates. Complete mole is characterized by hydropic degeneration of abnormal chorionic villi, diffused trophoblast hyperplasia and the absence of identifiable embryonic or fetal tissue; the hyperplastic trophoblast justifies the common finding of high serum beta HCG levels. Twin molar pregnancy is an uncommon obstetric event, and even less frequent are triplet/quadruplet molar pregnancies. We hereby report a case of a complete hydatidiform mole with two coexistent fetuses in a triplet pregnancy after in vitro fertilization procedure; the pregnancy ended with a therapeutic abortion. During the follow-up, the serum beta human chorionic gonadotropin concentration started to rise, and the diagnosis of post-molar gestational trophoblastic neoplasia was made and consequently methotrexate treatment was started. Due to the rarity of this condition, there are no specific guidelines for the management of multiple pregnancies complicated by complete hydatidiform mole. We therefore performed a review of the literature including all reported cases of triplets/quadruplets pregnancies complicated by complete mole of a fetus focusing on ultrasound diagnosis, treatment and outcomes of this rare and life-threatening condition.


2022 - Confirmation of the safety of combined oral contraceptives containing oestradiol on the risk of venous thromboembolism [Articolo su rivista]
Grandi, G.; Facchinetti, F.; Bitzer, J.
abstract


2022 - Contraception During Perimenopause: Practical Guidance [Articolo su rivista]
Grandi, G.; Di Vinci, P.; Sgandurra, A.; Feliciello, L.; Monari, F.; Facchinetti, F.
abstract

Climacteric is by no means in itself a contraindication to safe contraception. On the contrary, there are several conditions related to the perimenopause that could benefit from the use of modern contraceptives, mainly hormonal, with the goals of avoiding unintended pregnancies and giving further possible benefits beyond contraception (menstrual cycle control, a reduction of vasomotor symptoms and menstrual migraines, a protection against bone loss, a positive oncological risk/benefit balance). This narrative review aims to provide practical guidance on their possible use in this particular life stage, both short- and long-acting reversible contraceptives, and to assist clinicians for women transitioning from contraception to their menopausal years, including the possible initiation of postmenopausal hormone therapy. Comprehensive contraceptive counselling is an essential aspect of the overall health and wellbeing of women and should be addressed with each such patient irrespective of age.


2022 - Delivery indication matters for perinatal outcomes in late preterm newborns [Articolo su rivista]
Monari, F.; Chiossi, G.; Gargano, G.; Ballarini, M.; Baronciani, D.; Coscia, A.; Facchinetti, F.
abstract

Background: The late preterm (LP) rate in Western countries is 3–6% of all births, accounting for about two-thirds of the entire preterm population. However, all LP babies are not the same. Aims: To identify pregnancies at risk for adverse outcomes in the LP period, we investigated how gestational age (GA) at delivery, delivery indication and prenatal risk factors may affect neonatal outcomes. Study design: Prospective cohort study among singleton infants born between 34 + 0 and 36 + 6 weeks, in Emilia Romagna, Italy, during 2013–2015. Outcomes measures: The primary outcome was a composite of adverse perinatal outcomes. Multivariate logistic regression models were used to, respectively, investigate the effects of GA at delivery, circumstances at parturition and prenatal risk factors, on study outcomes after controlling for confounding variable. Results: Among 1867 births, 302, 504, and 1061 infants were born at 34, 35, and 36 weeks, respectively. There were no neonatal deaths. An increased risk of composite neonatal outcome was observed among 34 and 35 weeks deliveries compared with 36 weeks, and among indicated deliveries compared with spontaneous. When studying prenatal risk factors, neonatal morbidity was associated with pre gestational diabetes, preterm premature rupture of membranes (pPROM), maternal obesity, bleeding and polyhydramnios; instead, preeclampsia had a protective effect. Conclusion: LP with indicated deliveries at 34 or 35 weeks, or with specific prenatal risk factors have worse neonatal outcome when compared to 36. Such differences should be considered when counseling patients and planning interventions such as timing of delivery in LP period.


2022 - Drospirenone 4 mg in a 24 + 4 regimen in women with contraindications to oestrogen use for contraception: bleeding patterns according to previous menstrual characteristics [Articolo su rivista]
Grandi, Giovanni; Del Savio, Maria Chiara; Melotti, Chiara; Facchinetti, Fabio
abstract

Purpose A new POP consisting of 4 mg drospirenone (DRSP) for 24 days with a 4-day hormone-free interval was developed to improve bleeding predictability during POP use. The aim of this study was to evaluate the effect on bleeding patterns during use of this oral contraceptive (OC) in comparison with previous menstrual cycles before the start of OC use. Methods This is a pilot, prospective trial. A diary was used to collect information about daily bleeding and pelvic pain before and during treatment. During OC use, women were categorised as having (1) unscheduled bleeding or spotting days (UB), (2) scheduled bleeding or spotting days (SB) and (3) absence of bleeding/spotting (AB). SF-36 and FSFI questionnaires were used to quantify health-related quality of life and the quality of sexual life in sexually active participants. Results Eighteen out of twenty-five (72%) women completed the entire follow-up. Women with UB (44.4%) were older at inclusion (p < 0.001) and had higher BMIs (p = 0.02) than those with AB (22.2%) or SB (33.4%). Women recorded a significant reduction of menstrual flow intensity during OC use (p < 0.0001). Those with UB also experienced a significant reduction of menstrual pain intensity (p = 0.006). Women with SB during OC use had a longer baseline cycle than those who reported UB during OC use (p = 0.008). Satisfaction with this OC was very high (8.4 +/- 2.2 points) with no modification in SF-36 and FSFI values. Conclusion A DRSP-only pill is a good OC option for women with contraindications to oestrogen use. Features of the menstrual cycle before the start of OC use may be used to predict associated changes in bleeding patterns.


2022 - Early-life exposure to phthalates among infants in Italy: characterization and time trends [Abstract in Atti di Convegno]
Righi, E; Palandri, L; Ferrari, A; Barbieri, R; Lugli, C; Trevisani, V; Passini, E; Facchinetti, F; Lucaccioni, L
abstract

BACKGROUND AND AIM: Human exposure to phthalates, endocrine disruptors, and reproductive toxicants, is ubiquitous. Urine is the matrix of choice for biomonitoring and in utero exposure is well documented. Evidence of early life exposure to phthalates is scarce. The aim of this study is to assess phthalate exposure and its changes over time in a cohort of healthy infants in the province of Modena, Italy. METHODS: In this prospective birth-cohort study, we assessed phthalate exposure(8 metabolites of 6 phthalates)in urine samples collected from mothers just after delivery and in infants at birth, 3 and 6 months using phthalate-free bags. Mother-infant pairs were enrolled in a university hospital in Modena(Italy) between January 2019 and May 2020. After solid-phase extraction, samples were analyzed by triple Quad LC/MS Mass Spectrometry. RESULTS: 188 mother-infant pairs were enrolled. MEP was always detectable and showed the highest levels, increasing over time. MMP and DEHP metabolites showed as well an increasing trend, however, they were detected at lower levels, while MnBP and MBzP showed intermediate concentrations and decreasing trends over time. Significant associations between mother-infant pairs at birth were found only for a few metabolites(MMP, MEP, and MnBP). Infant levels at 3 and 6 months appeared more related, suggesting a continuative exposure to these chemicals inside the indoor environment. CONCLUSIONS: Phthalate exposure appears wide and extended over time. Infants were exposed to several phthalates, including those more toxic and strictly regulated in infant toys, personal care products and food contact materials in the European Union. Their unregulated use in other consumers’products, building and decorating materials or home furniture may explain the potential exposure of at-risk groups, such as infants or pregnant women. To effectively protect the most vulnerable subjects, public health preventive and regulatory actions should address this specific issue as well.


2022 - Exposure to phthalates, potential endocrine disruptors, in an infant cohort in Modena, Italy [Abstract in Rivista]
Lugli, C; Palandri, L; Ferrari, A; Barbieri, R; Trevisani, V; Passini, E; Lucaccioni, L; Facchinetti, F; Righi, E
abstract

Phthalates are pollutants ubiquitous in the environment. Human exposure to phthalates and their endocrine disrupting effects have been widely studied. Therefore, the European Union forbids phthalates in toys, cosmetic and kitchenware manufacturing. However, phthalate metabolites can still be found in human biological matrices. The purpose of this study is to investigate phthalate exposure over time in a group of Italian healthy newborns. In a prospective cohort study, we enlisted 187 women who gave birth in the University Hospital of Modena, Italy, between January 2019 and May 2020. Urine samples from women after delivery and from their infants at birth, 3 and 6 months were collected and 8 metabolites of 6 phthalates were analysed. Descriptive statistics were calculated and preliminary correlation coefficients tests were performed. Monoethylphthalate (MEP) was always detectable in urine samples. MEP, monomethylphthalate and diethylhexylphthalate metabolites showed an increasing trend over time, while monobutylphthalate and monobenzylphthalate showed decreasing levels over time. Associations between levels of phthalates metabolites in mother and infant pairs at birth were found for a few metabolites, while metabolites in infant samples at 3 and 6 months appeared often significantly associated. Infants’ phthalate exposure in Modena is still high and prolonged over time, even to those more toxic and strictly regulated. As phthalates presence in indoor environment can be a risk factor especially for the most fragile groups of population, such as children, public Health campaigns addressing childbearing age women should stress about the risk posed by these substances and how to avoid their exposure. Moreover, regulatory actions and a stricter legislation should be considered.


2022 - External validation of prognostic models to predict stillbirth using International Prediction of Pregnancy Complications (IPPIC) Network database: individual participant data meta-analysis [Articolo su rivista]
Allotey, J.; Whittle, R.; Snell, K. I. E.; Smuk, M.; Townsend, R.; von Dadelszen, P.; Heazell, A. E. P.; Magee, L.; Smith, G. C. S.; Sandall, J.; Thilaganathan, B.; Zamora, J.; Riley, R. D.; Khalil, A.; Thangaratinam, S.; Coomarasamy, A.; Kwong, A.; Savitri, A. I.; Salvesen, K. A.; Bhattacharya, S.; Uiterwaal, C. S. P. M.; Staff, A. C.; Andersen, L. B.; Olive, E. L.; Redman, C.; Sletner, L.; Daskalakis, G.; Macleod, M.; Thilaganathan, B.; Abdollahain, M.; Ramirez, J. A.; Masse, J.; Khalil, A.; Audibert, F.; Magnus, P. M.; Jenum, A. K.; Baschat, A.; Ohkuchi, A.; Mcauliffe, F. M.; West, J.; Askie, L. M.; Mone, F.; Farrar, D.; Zimmerman, P. A.; Smits, L. J. M.; Riddell, C.; Kingdom, J. C.; van de Post, J.; Illanes, S. E.; Holzman, C.; van Kuijk, S. M. J.; Carbillon, L.; Villa, P. M.; Eskild, A.; Chappell, L.; Prefumo, F.; Velauthar, L.; Seed, P.; van Oostwaard, M.; Verlohren, S.; Poston, L.; Ferrazzi, E.; Vinter, C. A.; Nagata, C.; Brown, M.; Vollebregt, K. C.; Takeda, S.; Langenveld, J.; Widmer, M.; Saito, S.; Haavaldsen, C.; Carroli, G.; Olsen, J.; Wolf, H.; Zavaleta, N.; Eisensee, I.; Vergani, P.; Lumbiganon, P.; Makrides, M.; Facchinetti, F.; Sequeira, E.; Gibson, R.; Ferrazzani, S.; Frusca, T.; Norman, J. E.; Figueiro, E. A.; Lapaire, O.; Laivuori, H.; Lykke, J. A.; Conde-Agudelo, A.; Galindo, A.; Mbah, A.; Betran, A. P.; Herraiz, I.; Trogstad, L.; Smith, G. G. S.; Steegers, E. A. P.; Salim, R.; Huang, T.; Adank, A.; Zhang, J.; Meschino, W. S.; Browne, J. L.; Allen, R. E.; Costa, F. D. S.; Klipstein-Grobusch Browne, K.; Crowther, C. A.; Jorgensen, J. S.; Forest, J. -C.; Rumbold, A. R.; Mol, B. W.; Giguere, Y.; Kenny, L. C.; Ganzevoort, W.; Odibo, A. O.; Myers, J.; Yeo, S. A.; Goffinet, F.; Mccowan, L.; Pajkrt, E.; Teede, H. J.; Haddad, B. G.; Dekker, G.; Kleinrouweler, E. C.; Lecarpentier, E.; Roberts, C. T.; Groen, H.; Skrastad, R. B.; Heinonen, S.; Eero, K.; Anggraini, D.; Souka, A.; Cecatti, J. G.; Monterio, I.; Pillalis, A.; Souza, R.; Hawkins, L. A.; Gabbay-Benziv, R.; Crovetto, F.; Figuera, F.; Jorgensen, L.; Dodds, J.; Patel, M.; Aviram, A.; Papageorghiou, A.; Khan, K.
abstract

Objective: Stillbirth is a potentially preventable complication of pregnancy. Identifying women at high risk of stillbirth can guide decisions on the need for closer surveillance and timing of delivery in order to prevent fetal death. Prognostic models have been developed to predict the risk of stillbirth, but none has yet been validated externally. In this study, we externally validated published prediction models for stillbirth using individual participant data (IPD) meta-analysis to assess their predictive performance. Methods: MEDLINE, EMBASE, DH-DATA and AMED databases were searched from inception to December 2020 to identify studies reporting stillbirth prediction models. Studies that developed or updated prediction models for stillbirth for use at any time during pregnancy were included. IPD from cohorts within the International Prediction of Pregnancy Complications (IPPIC) Network were used to validate externally the identified prediction models whose individual variables were available in the IPD. The risk of bias of the models and cohorts was assessed using the Prediction study Risk Of Bias ASsessment Tool (PROBAST). The discriminative performance of the models was evaluated using the C-statistic, and calibration was assessed using calibration plots, calibration slope and calibration-in-the-large. Performance measures were estimated separately in each cohort, as well as summarized across cohorts using random-effects meta-analysis. Clinical utility was assessed using net benefit. Results: Seventeen studies reporting the development of 40 prognostic models for stillbirth were identified. None of the models had been previously validated externally, and the full model equation was reported for only one-fifth (20%, 8/40) of the models. External validation was possible for three of these models, using IPD from 19 cohorts (491 201 pregnant women) within the IPPIC Network database. Based on evaluation of the model development studies, all three models had an overall high risk of bias, according to PROBAST. In the IPD meta-analysis, the models had summary C-statistics ranging from 0.53 to 0.65 and summary calibration slopes ranging from 0.40 to 0.88, with risk predictions that were generally too extreme compared with the observed risks. The models had little to no clinical utility, as assessed by net benefit. However, there remained uncertainty in the performance of some models due to small available sample sizes. Conclusions: The three validated stillbirth prediction models showed generally poor and uncertain predictive performance in new data, with limited evidence to support their clinical application. The findings suggest methodological shortcomings in their development, including overfitting. Further research is needed to further validate these and other models, identify stronger prognostic factors and develop more robust prediction models. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.


2022 - Fetal head malposition and epidural analgesia in labor: a case-control study [Articolo su rivista]
Menichini, D.; Mazzaro, N.; Minniti, S.; Ricchi, A.; Molinazzi, M. T.; Facchinetti, F.; Neri, I.
abstract

Background: The fetal head malposition in labor leads to prolonged labor, cesarean delivery and increased perinatal morbidity. Epidural analgesia has been associated with fetal head malposition, but it remains unknown if this relation is causal. Objective: To compare the incidence of fetal malposition during labor and maternal/fetal outcomes, between women who received epidural analgesia with those who did not use the analgesic method. Study design: Case control study including 500 women with a single fetus in vertex position who gave birth at term at the Policlinic Hospital of Modena between May 2019 and July 2019. Two-hundred and fifty women belonged to the epidural analgesia (EA) group and 250 to the control group. Results: The rate of posterior occiput positions occurred 4 times more frequently in the EA group than in the control group (8.8% vs 2.2%, p =.004). Cesarean sections were significantly higher in the EA group (11.6% vs 1.6%, p <.0000) as well as the need for augmentation with oxytocin (20% vs 8%, p =.0001) compared to the control group, in which spontaneous delivery prevailed instead. Women with epidural had labors that lasted on average 7.0 h against the 3.30 h of controls (p <.0000). The length of 2nd stage of labor was 55 vs 30 min (p =.009), respectively. No differences in blood loss and Apgar score between groups. Early breastfeeding was significantly higher among controls (82% vs 92.8%, p =.0004). Conclusions: Women receiving epidural analgesia in labor have higher rate of fetal malposition, prolonged labors, and more cesarean sections than controls. However, further studies are required to confirm a causal association between EA and fetal head malposition.


2022 - First trimester metabolomics 1H-NMR study of the urinary profile predicts gestational diabetes mellitus development in obese women [Articolo su rivista]
Piras, C.; Neri, I.; Pintus, R.; Noto, A.; Petrella, E.; Monari, F.; Dessi, A.; Fanos, V.; Atzori, L.; Facchinetti, F.
abstract

Objective: Obesity is one of the main risk factors for the development gestational diabetes mellitus (GDM). Thus, we aim to identify changes in the urinary metabolomics profile of obese women at first trimester of pregnancy in order to predict later GDM diagnosis. Research design and methods: In this nested case-control study, urine samples collected in the first trimester of pregnancy obtained from obese women who developed GDM (n = 29) and obese women who did not develop diabetes (n = 25 NO GDM) were analyzed with Nuclear Magnetic Resonance spectroscopy combined with Multivariate Statistical Analysis. GDM diagnosis was obtained with one-step oral glucose load. Results: OPLS-DA significantly separated the GDM women from NO GDM women. Specifically, GDM women were characterized by a higher level of tryptophan, trigonelline, hippurate, and threonine, and lower levels of 1-methylnicotinamide, 3-hydroxykynurenine, glycocholate, isoleucine, kynurenine, and valine compared to NO GDM women. Conclusion: In a prevalently Caucasian population, the changes of some metabolites such as tryptophan, trigonelline, and branch-chained amino acids in the urinary profile of obese women in the first trimester are able to make unequivocal prediction of those which later test positive for GDM. This approach could be useful to diagnose much earlier obese women with GDM allowing lifestyle counselling and other interventions.


2022 - First-trimester prediction model for placental vascular disorders: an observational prospective study [Articolo su rivista]
Monari, Francesca; Spano' Bascio, Ludovica; Banchelli, Federico; Neri, Isabella; Bertucci, Emma; Ferrari, Francesca; Menichini, Daniela; D'Amico, Roberto; Facchinetti, Fabio
abstract

This study aims to develop a multivariable predictive model for the risk of placental vascular complications (PVC), by using biochemical, biophysical, anamnestic and clinical maternal features available at the first trimester. PVC include gestational hypertension, preeclampsia, placenta abruption, intrauterine growth restriction (IUGR), and stillbirth. Prospective study that included all singleton pregnancies attending the first-trimester aneuploidy screening (11 +0–12 +6 weeks) at Obstetrics Unit of the University Hospital of Modena, in Northern Italy, between June 2018 and December 2019. In a total of 503 women included in the analysis, 40 patients were in the PVC group. The final prediction model for PVC included the following independent variables: pre-pregnancy BMI ≥ 30 (OR = 2.65, 95% CI = 1.04; 6.75, p = 0.0415), increasing values of mean arterial pressure (OR = 1.06, 95% CI = 1.02; 1.10, p = 0.0008), PAPP-A < 2.40465 U/L (OR = 0.43, 95% CI = 0.19; 0.96, p = 0.0388) and decreasing values of PlGf (MoM) (OR = 0.28, 95% CI = 0.10; 0.79, p = 0.0153). The area under the ROC curve was 79.4% indicating a satisfactory predictive accuracy. The best predictive cut-off for this score was equal to − 2.562, which corresponds to a 7.2 % probability of having PVC. By using such a cut-off, the risk of PVC can be predicted in our sample with sensitivity equal to 82,4 % and specificity equal to 69,9 %. This model for early prediction of PVC is a promising tool to early identify women at greater risk for placenta vascular complications.


2022 - First-trimester prediction of gestational hypertension through the bioelectrical impedance analysis of the body composition [Articolo su rivista]
Menichini, D.; Spelta, E.; Rossi, E.; Monari, F.; DI VINCI, P. L.; Petrella, E.; Facchinetti, F.; Neri, I.
abstract

OBJECTIVE: Obesity is a risk factor for the development of gestational hypertension, with important consequences for both the mother and fetus. This prospective observational study aims to propose an early prediction model of hypertensive disorders in pregnancy among obese women, through the bioelectrical impedance analysis (BIA) at the first trimester, thus allowing early recognition of obese women that are at risk to develop gestational hypertension, in order to target preventive interventions. PATIENTS AND METHODS: Singleton obese women (BMI ≥ 30 kg/m2) between the 9th and 12th week of pregnancy were included in the study. The exclusion criteria were chronic diseases, like type 2 diabetes mellitus, hypertension, and other medical pre-existing conditions. Eligible women were followed up at 20, 28, and 36 weeks of gestation by measuring blood pressure, weight, and body composition with the use of the BIA. The diagnosis of gestational hypertension was made after the 20th week of gestation. Pregnancy and perinatal outcomes were then recorded. RESULTS: Of the 479 women included in the study, 85 (17.7%) developed gestational hypertension; the remaining 394 (82.3%) resulted to be normotensive. A higher rate of nulliparous women was found in the hypertensive group (50.6% vs. 37.6%, p = 0.02), together with a higher rate of induction of labor (55.3% vs. 40.9%, p = 0.02) and of small for gestational age (SGA) newborns (12.9% vs. 6.9%, p = 0.03). Significant differences emerged in the body composition between the two groups already from the first trimester, indeed women developing gestational hypertension showed elevated values of Total body Mass, FM, FFM, TBW (p < 0.02), and of leg's FM, FFM (p < 0.006). At the multivariate logistics regression, the risk of developing gestational hypertension resulted higher in women with elevated total body water levels in the first trimester (OR 1.10 95% CI 1.04 -1.92). CONCLUSIONS: The BIA is a rapid, easy, non-invasive, and inexpensive tool to evaluate the body composition of obese pregnant women. It represents a promising predictor of hypertensive disorders in pregnancy, which allows an early identification of the patients at risk of developing gestational hypertension, thus opening a window of opportunity for strictly monitoring and target preventive intervention.


2022 - How adenomyosis changes throughout pregnancy: A retrospective cohort study [Articolo su rivista]
Bertucci, Emma; Sileo, Filomena G; Diamanti, Marialaura; Alboni, Carlo; Facchinetti, Fabio; La Marca, Antonio
abstract

Objective To study how adenomyosis changes during pregnancy and to possibly correlate these changes to maternal and fetal outcomes. Methods Retrospective exploratory cohort study including 254 women with a pre-conceptional/first-trimester scan to document adenomyosis and known obstetric outcome. If visible, adenomyosis signs were documented in each trimester and postpartum. Mann-Whitney U tests or chi(2) tests were used for continuous and categorical variables, respectively. Results A globular uterus was reported in 79% (n = 52) of women with adenomyosis in the first trimester, in 38% (n = 20) and 2% (n = 1) of women in the second and third trimesters, respectively, and postpartum in 77% (n = 34) of women. Asymmetrical thickening (n = 20, 30%) and cysts (n = 15, 23%) were only visible in 1st trimester. Adenomyosis was associated with miscarriage (odds ratio [OR] 5.9, 95% confidence interval [CI] 2.4-14.9, P < 0.001) also in normal conception only (OR 5.1, 95% CI 1.8-14.2, P = 0.002) or adjusting for maternal age (adjusted OR 5.9, 95% CI 2.3-15.2, P < 0.001). Gestational age at delivery was lower in adenomyosis (P = 0.004); the cesarean section rate was higher than in controls (OR 2.5, 95% CI 1.3-4.8, P = 0.007) also adjusting for age (adjusted OR 2.07, 95% CI 1.06-4.08, P = 0.035). Conclusions Signs of adenomyosis were visible but progressively disappeared in pregnancy; adenomyosis was associated with an increased risk of early miscarriage. Prospective studies are needed to confirm our results.


2022 - Ileocecal deep infiltrating endometriosis with intestinal mucinous metaplasia and high-grade dysplasia [Articolo su rivista]
Alboni, C.; Spano Bascio, L.; Camacho Mattos, L.; Gallo, G.; Botticelli, L.; Cabry, F.; Facchinetti, F.; Gelmini, R.
abstract


2022 - Impact of endocrine disorders on stillbirth: a prospective cohort study [Articolo su rivista]
Monari, F.; Menichini, D.; Salerno, C.; Donno, V.; Po', G.; Melis, B.; Facchinetti, F.
abstract

Objective: Among risk factors for SB, maternal endocrine diseases (ED), such as thyroids dysfunction and gestational diabetes mellitus (GDM), are the most frequent. This study aimed to investigate the rate of ED in a population of SB cases collected prospectively, and the relationship between these and causes of death. Methods: This is an area-based, prospective cohort study conducted in Emilia-Romagna, Italy between January 2014 and December 2020. Data included all cases of SB (>22 weeks). Results: From 2014 to 2020, 766 SB occurred out of a total of 232.506 births (SB rate:0.3/1000). The ED were present in 197/766 cases of SB (25.7%), respectively, 104 thyroid disease (52.8%), 74 GDM (37.5%), and 19 cases of concomitant GDM and thyroid disease (9.6%). Women who had SB associated with ED presented significantly higher mean maternal age (p < 0.001), BMI (p < 0.001), obesity (p < 0.001) and lower smoking habit (p = 0.02) respect with control group. Neonatal and placental weight of stillborn women with ED was significantly higher (p < 0.001) in respect to stillborn of the control group. Women with ED as associated condition (ReCODE classification), present significantly higher cases of SB caused by placenta pathologies (p = 0.009) namely abruptio placentae (p = 0.001) respect than control group. Conclusions: ED was more frequent in older and obese women experiencing SB. The main cause of death was abruptio placentae. This information can be helpful when counseling mothers with ED and planning antenatal management to prevent SB.


2022 - Implementation of guidelines about women with previous cesarean section through educational/motivational interventions in providers [Articolo su rivista]
Monari, Francesca; Menichini, Daniela; Bertucci, Emma; Neri, Isabella; Perrone, Enrica; Facchinetti, Fabio
abstract

Objective: The study reports the effect of a quality improvement project with an educational/motivational intervention, in northern Italy on the implementation of the trial of labor after Caesarean Section (CS). Method: A pre-post study design was used. Every birth center (23) of the Emilia-Romagna region was included. Gynecologists' opinion leaders were first trained about CS Italian recommendations. Barriers to implementation were discussed and shared. Educational/motivational interventions were implemented. Data of multipara with previous CS, with a single, cephalic pregnancy at term, were collected in 2 periods, before (2012-2014) and after (2017-2019) the intervention (2015-2016). The primary outcome was the rate of vaginal birth after CS (VBAC) and perinatal outcomes. Results: A total of 20,496 women were included. The VBAC rate increased from 18.1% to 23.1% after intervention (p<0.001). The likelihood of VBAC, adjusted for age ≥40, Caucasian, BMI ≥30, previous vaginal delivery, and labor induction, was increased by the intervention of 42% (OR=1.42, 95% CI 1.31-1.54). Neonatal well-being was improved by intervention, indeed neonates requiring resuscitation decreased from 2.1% to 1.6% (p=0.001). Conclusion: Educating and motivating gynecologists toward the trial of labor after CS is worth pursuing. Health quality improvement is demonstrated by increased VBAC even improving neonatal well-being.


2022 - Induction of Labor According to Medical Indications: A Critical Evaluation through a Prospective Study [Articolo su rivista]
Monari, F.; Pellegrini, R.; Menichini, D.; Spelta, E.; Tarozzi, G.; Grandi, G.; Facchinetti, F.
abstract

Background: The induction of labor (IOL) is a common obstetric intervention, steadily increasing (one out four pregnancies) in the last years. This procedure should be considered only when there is a medical indication, and when the benefits outweigh the maternal and/or fetal risks of waiting for spontaneous onset of labor. Therefore, this study aims to compare the efficacy of the IOL in terms of induction to delivery time, mode of delivery, and neonatal well-being among different evidence-based and non-evidence-based indications. Methods: This prospective study was conducted at the University Hospital of Modena, between January and December 2020. We included singleton pregnant women undergoing IOL, at the term. Intrauterine deaths, small for gestational age fetuses <5th centile as well women with hypertensive disorders were excluded. Women have been subdivided into 3 groups based on the indication to IOL: premature rupture of membranes (PROM), post-date pregnancy (>41 weeks + 3 days), and non-evidence-based indications (NEBI). The primary outcome is the time occurring between IOL and delivery (TIME), analyzing separately by parity. Moreover, mode of delivery and neonatal wellbeing were evaluated. Results: A total of 585 women underwent IOL in the study period. Overall, the median TIME between IOL and delivery was 19 hours, and the mean cesarean section CS rate was 15.5% (91/585). Pregnancies induced for postdate and non-evidencebased indications registered respectively a significantly higher mean time (p < 0.001), compared with women induced for PROM. This occurred both in nulliparous and multiparous women. Moreover, at multivariate analysis, the IOL TIME ≥24 hours was significantly influenced by Bishop score (p = 0.000) and NEBI (p = 0.02) in nulliparous and by gestational age (p = 0.000) and NEBI (p = 0.02) in multiparous. Moreover, CS rate was significantly influenced by Bishop score (p = 0.003) in nulliparous and by gestational age (p = 0.01) in multiparous. Finally, neonatal intensive care unit (NICU) admission resulted significantly influenced only by gestational age (p = 0.002) in multiparous. Conclusions: Our study confirms that IOL in non-evidence-based indications, leads to an increase in induction to delivery time comparing with women induced for PROM, both in nulliparous and multiparous women, thus it should be justified and carefully evaluated. Further randomized controlled trials (RCT) conducted in European/Italian settings are needed to determine the perinatal outcomes of IOL in non-evidence-based indications.


2022 - It is time to talk about replacement of subdermal implants from the same cut, is it always feasible? The slow process of the "armpit approach" [Articolo su rivista]
Grandi, Giovanni; Feliciello, Lia; Negro, Giulia; Sgandurra, Alice; Facchinetti, Fabio
abstract


2022 - Maternal dietary adherence during pregnancy to recommendations: a cross-sectional study in Modena [Abstract in Rivista]
De Pasquale, L; Palandri, L; Casalucci, Ma; Azzalini, D; Lucaccioni, L; Passini, E; Facchinetti, F; Righi, E
abstract

Background: Unbalanced nutrients intake and incorrect weight gain can lead to immediate and future adverse health consequences for both mother and child. The Italian Society of Gynaecology and Obstetrics (SIGO), has drawn up a series of nutritional recommendations with the aim of promoting a correct food intake for future mothers. The purpose of our study was to assess adherence to good dietary indications during pregnancy and to evaluate if voluptuary habits could play a role. Methods: This cross-sectional study investigated dietary habits during the last trimester of pregnancy. We evaluated the adherence to dietary SIGO recommendations of a sample of pregnant women representative of physiologic full-term pregnancies (n = 572, mean age 33.4 5.2) living in Modena (Italy), recruited between 2016 and 2020. Maternal diet during pregnancy was assessed by a self-administered questionnaire fill in at the hospital after childbirth, evaluating lifestyle habits and usual food intake. Descriptive statistics and bivariate associations (Chi-square tests) were performed. Results: More than 50% of women did not comply with SIGO dietary recommendations. Overall, adherence was very low, ranging between 8.4% (sweets) and 38.8% (seafood), for all food categories, excluding coffee and tea (89%), alcohol (76.2%), red wine (99.1%) and seasoning (olive oil 93.4%). Preliminary results suggest that several factors and behaviours, including BMI before pregnancy, age, smoking habits, education, are associated with levels of adherence to different food categories. Conclusions: Poor adherence to a proper dietary regimen during pregnancy is a missed opportunity for prevention and demonstrates the importance of promoting public health interventions to improve dietary recommendations adherence. Several initiatives, such as courses, information campaigns, use of social media and counselling can be useful for a nutrition education in pregnancy, raising awareness of the related benefits for both mother and child.


2022 - Mode of Delivery in Women with Stillbirth: Results of an Area-Based Italian Prospective Cohort Study [Articolo su rivista]
Monari, F.; Menichini, D.; Salerno, C.; Donno, V.; Melis, B.; Neri, I.; Facchinetti, F.
abstract

Introduction: The choice of the mode of delivery, in case of stillbirth (SB) (fetus non-viable >22 weeks' gestation), should consider maternal preference, gestational age, bishop score, the clinical condition of the woman, and her previous obstetric history. However, despite these clear indications, data on the effective implementation of the latter are lacking. The aim of our study is to evaluate the different modes of delivery in an Italian population of SBs, according to gestational age, parity, causes of death, obstetric history, and maternal characteristics. Material and Methods: This is an area-based, prospective cohort study conducted in Emilia Romagna, Italy between January 2014 to December 2020. Data included all cases of SB (>22 weeks). Results: From 2014 to 2020, 783 SB occurred out of a total of 232.506 births, with a SB rate of 3.3 per 1000. Labor was spontaneous in 85 (11%). Of remnant, 567 (73.6%) were induced and 118 (15.3%) had no labor. The mode of delivery was vaginal in most of the cases (649/770, 84.3%) and by cesarean section in 121/770 (15.7%) of cases. Emergency CS was most frequent and performed in 89/121 (73.5%) of total CS, representing 11.5% of SB deliveries. Mode of induction did not differ in relation to gestational age at stillbirth, while vaginal delivery was significantly higher in women induced with prostaglandins (p = 0.000) respect to other methods. Nulliparous women had a significantly higher need for multiple methods of induction (p = 0.000) respect multiparous and obese women used more frequently prostaglandins (p = 0.03) than other methods. Women with a history of previous CS presented a significantly higher rate of repeated elective CS (p = 0.000). Moreover, emergency CS was performed more frequent in obese (p = 0.02), diabetic (p = 0.04) and hypertensive (p = 0.04) women and in SB caused by placenta disorders, namely in abruptio placentae (p = 0.000). In the case of chorioamnionitis and funisitis women significantly were induced with prostaglandin (p = 0.000) and delivered vaginally (p = 0.000). Conclusions: The method of induction of labor and the mode of delivery in case of SB did not depend on gestational age at the diagnosis of death, while they are related to placenta disorders representing a relevant condition leading to emergency CS also after diagnosis of fetal death. These data could help obstetric providers in managing the deliveries of stillborn infants.


2022 - Nutraceuticals and polycystic ovary syndrome: a systematic review of the literature [Articolo su rivista]
Menichini, D.; Ughetti, C.; Monari, F.; Di Vinci, P. L.; Neri, I.; Facchinetti, F.
abstract

Background This study proposes a review of nutraceuticals used in the treatment of typical symptoms of Polycystic Ovary Syndrome (PCOS). The aim is to provide a classification of the most widely used nutraceutical supplements identifying the most effective nutraceuticals on glucose and insulin metabolism, the androgenic hormone profile, fertility, ovulatory capacity, inflammation, and oxidative stress. Material and Methods We included randomized controlled trials on PCOS patients undergoing administration of nutraceuticals, in particular vitamin D, vitamin E, probiotics, and inositols. These administrations are variable in terms of dosage, single supplementation, or combined with other compounds, dosage, and duration of the intervention. Results The supplementation of inositols, at the physiologic ratio of 40: 1 of myo- and D-chiro-inositols, resulted to be the most effective in improving the glucose homeostasis and fertility, with a restoration of ovulatory capacity and menstrual regularity. Other nutraceuticals are particularly effective in reducing hyperandrogenism, with promising results demonstrated by the combinations of vitamin D and probiotics, vitamin E and coenzyme Q10, and the enrichment of inositol therapy with group B vitamins. An improvement in the inflammatory status and antioxidant capacity is obtained with the co-supplementation of probiotics and selenium or with vitamin E combined with omega 3. Conclusions Inositol supplementation is effective in the treatment of insulin resistance and fertility. Probiotics reduced hyperandrogenism, inflammatory and oxidative conditions, and resulted more effective when combined with selenium. Although these results proved to be satisfactory, further studies are needed with larger samples and a more homogeneous analysis of the outcomes.


2022 - Perinatal outcomes in twin late preterm pregnancies: results from an Italian area-based, prospective cohort study [Articolo su rivista]
Monari, F.; Chiossi, G.; Ballarini, M.; Menichini, D.; Gargano, G.; Coscia, A.; Baronciani, D.; Facchinetti, F.; Basevi, V.; Tiziana, F.; Battagliarin, G.; Lenzi, M.; Ancora, G.; Corvaglia, L.
abstract

Background: Multiple gestations represent a considerable proportion of pregnancies delivering in the late preterm (LP) period. Only 30% of LP twins are due to spontaneous preterm labor and 70% are medically indicated; among this literature described that 16–50% of indicated LP twin deliveries are non-evidence based. As non-evidence-based delivery indications account for iatrogenic morbidity that could be prevented, the objective of our observational study is to investigate first neonatal outcomes of LP twin pregnancies according to gestational age at delivery, chorionicity and delivery indication, then non evidence-based delivery indications. Methods: Prospective cohort study among twins infants born between 34 + 0 and 36 + 6 weeks, in Emilia Romagna, Italy, during 2013–2015. The primary outcome was a composite of adverse perinatal outcomes. Results: Among 346 LP twins, 84 (23.4%) were monochorionic and 262 (75.7%) were dichorionic; spontaneous preterm labor accounted for 85 (24.6%) deliveries, preterm prelabor rupture of membranes for 66 (19.1%), evidence based indicated deliveries were 117 (33.8%), while non-evidence-based indications were 78 (22.5%). When compared to spontaneous preterm labor or preterm prelabor rupture of membranes, pregnancies delivered due to maternal and/or fetal indications were associated with higher maternal age (p < 0.01), higher gestational age at delivery (p < 0.01), Caucasian race (p 0.04), ART use (p < 0.01), gestational diabetes (p < 0.01), vaginal bleeding (p < 0.01), antenatal corticosteroids (p < 0.01), diagnosis of fetal growth restriction (FGR) (p < 0.01), and monochorionic (p < 0.01). Two hundred twenty-six pregnancies (65.3%) had at least one fetus experiencing one composite of adverse perinatal outcome. Multivariate analysis confirmed that delivery indication did not affect the composite of adverse perinatal outcomes; the only characteristic that affect the outcome after controlling for confounding was gestational age at delivery (p < 0.01). Moreover, there was at least one adverse neonatal outcome for 94% of babies born at 34 weeks, for 73% of those born at 35 weeks and for 46% of those born at 36 weeks (p < 0.01). Conclusion: Our study suggests that the decision to deliver or not twins in LP period should consider gestational age at delivery as the main determinant infants’ prognosis. Delivery indications should be accurately considered, to avoid iatrogenic early birth responsible of preventable complications.


2022 - Plasma and amniotic fluid concentrations of nitric oxide: Effects on uterine artery and placental vasculature in women who underwent voluntary pregnancy termination and in women with missed and threatened abortion. A pilot study [Articolo su rivista]
Battaglia, C.; Morotti, E.; Montaguti, E.; Mariacci, G.; Facchinetti, F.; Pilu, G.
abstract

Objectives: First trimester miscarriage is a multifactorial event. Various angiogenic factors have been proposed as possible early markers of non-viable pregnancies. The aim of the present study was to evaluate the systemic nitric oxide (NO) production in healthy early pregnancy and its possible role in first trimester miscarriage. Study design: We prospectively enrolled women referred to our Unit for elective termination of pregnancy, threatened abortion or missed abortion. Blood samples were taken for testing circulating NO plasma levels. Subsequently, all patients underwent 2-D ultrasonographic analysis and Color Doppler imaging to assess the pulsatility index of the uterine arteries. 3-D ultrasonographic and power Doppler analysis allowed a volumetric and vascular reconstruction of the placenta. During dilatation and vacuum aspiration, amniotic fluid was collected. Results: Seventy-two patients were enrolled: 25 with elective termination of pregnancy (Group I); 17 with threatened abortion (Group II); 30 with missed abortion (Group III). Group II showed greater placental volume and lower uterine arteries PI than others. The plasma NO concentration resulted statistically higher in women with threatened abortion, while amniotic fluid NO concentration were higher in the viable pregnancies (Group I) than in the aborted fetuses (Group III). Plasma NO was inversely correlated with both mean arterial pressure and uterine artery PI and was positively correlated with amniotic fluid NO and CRL; amniotic fluid NO was positively correlated with placental Vascularization Index and Vascularization-Flow Index. Conclusion: Amniotic NO concentration was higher in viable pregnancies and positively related to Doppler 3D indices of vascularization and blood flow within the placenta. Further studies are needed to elucidate its role in first trimester miscarriage.


2022 - Screening for Low-Tract Genital Infections in Women with Threatened Preterm Labor: Which Role? [Articolo su rivista]
Sileo, Filomena Giulia; Inversetti, Annalisa; Bonati, Francesca; Celora, Gabriella; Donno, Valeria; Giuliani, Giulia Andrea; Pellegrini, Rosamaria; Monari, Francesca; Locatelli, Anna; Facchinetti, Fabio
abstract

The aim of this study was to evaluate the possible relationship between cultural specimens and preterm birth in women admitted for threatened preterm labor. Preterm birth is the leading cause of neonatal mortality and antenatal hospitalization; several risk factors including intrauterine infections have been identified, but its real causes remain poorly understood.


2022 - Second trimester uterine arteries pulsatility index is a function of placental pathology and provides insights on stillbirth aetiology: A multicenter matched case-control study [Articolo su rivista]
Amodeo, S.; Cavoretto, P. I.; Seidenari, A.; Paci, G.; Germano, C.; Monari, F.; Donno, V.; Giambanco, L.; Avagliano, L.; Di Martino, D.; Fuse, F.; Masturzo, B.; Chiantera, V.; Facchinetti, F.; Ferrazzi, E.; Candiani, M.; Bulfamante, G.; Farina, A.
abstract

Introduction: The aim of this study was to investigate the relationships between maternal vascular malperfusions (MVM) and second trimester uterine arteries pulsatility index (UtA-PI) in cases of stillbirth (SB), compared to live-birth (LB) matched controls. Methods: This was a multicentre, observational, matched case-control study performed at five referral maternity centres over a 4-year period including SB and LB control pregnancies at high-risk for preeclampsia (PE) and/or fetal growth restriction (FGR), matched and stratified for UtA-PI MoM quartiles values of the SB cases. Logistic regression was used to assess the rates of each MVM finding, within each increasing MoM quartile subcategory in SB and matched LB controls. Results: 82 SB and 82 LB matched high-risk pregnancies were included. Placental hypoplasia, placental infarction, retroplacental hematoma, distal villous hypoplasia and accelerated villous maturation showed a significant correlation with UtA-PI. At univariable analysis, placental infarction and distal villous hypoplasia were more highly associated with the increasing quartile uterine Doppler measurements (odds ratio 2.24 and 2.23, respectively). Logistic regressions showed a significant positive and independent association between rates of retroplacental hematoma or distal villous hypoplasia and stillbirth within corresponding UtA-PI MoM quartiles (odds ratio 5.21 and 2.28, respectively). Discussion: We are providing evidence for characterization of two major etiological stillbirth categories, characterized by a positive or absent association with UtA-PI impairment and specific histopathological placental MVM lesions. Our results support a strict third trimester follow-up of cases with increased second trimester UtA-PI, in order to improve the reproductive chances of these pregnant patients.


2022 - Stillbirth occurrence during COVID-19 pandemic: A population-based prospective study [Articolo su rivista]
Salerno, C.; Donno, V.; Melis, B.; Perrone, E.; Menichini, D.; Facchinetti, F.; Monari, F.
abstract

Objectives: Data collected worldwide on stillbirth (SB) rates during the Covid-19 pandemic are contradictory. Variations may be due to methodological differences or population characteristics. The aim of the study is to assess the changes in SB rate, risk factors, causes of death and quality of antenatal care during the pandemic compared to the control periods. Methods: This prospective study is based on the information collected by the Emilia-Romagna Surveillance system database. We conducted a descriptive analysis of SB rate, risk factors, causes of death and quality of cares, comparing data of the pandemic (March 2020-June 2021) with the 16 months before. Results: During the pandemic, the SB rate was 3.45/1,000 births, a value in line with the rates of previous control periods. Neonatal weight >90th centile was the only risk factor for SB that significantly changed during the pandemic (2.2% vs. 8.0%; p-value: 0.024). No significant differences were found in the distribution of the causes of death groups. Concerning quality of antenatal cares, cases evaluated with suboptimal care (5.2%) did not change significantly compared to the control period (12.0%), as well as the cases with less than recommended obstetric (12.6% vs. 14%) and ultrasound evaluations (0% vs. 2.7%). Conclusions: During the COVID-19 pandemic, no significant differences in SB rates were found in an area that maintained an adequate level of antenatal care. Thus, eventual associations between SB rate and the COVID-19 infection are explained by an indirect impact of the virus, rather than its direct effect.


2022 - The ARRIVE trial will not “arrive” to Europe [Articolo su rivista]
Facchinetti, F.; Menichini, D.; Perrone, E.
abstract


2022 - The BLOSSoM study: Burnout after perinatal LOSS in Midwifery. Results of a nation-wide investigation in Italy [Articolo su rivista]
Ravaldi, C.; Carelli, E.; Frontini, A.; Mosconi, L.; Tagliavini, S.; Cossu, E.; Crescioli, G.; Lombardi, N.; Bonaiuti, R.; Bettiol, A.; Facchinetti, F.; Vannacci, A.
abstract

Background: Respectful care of bereaved parents after stillbirth plays a pivotal role in enabling the grieving process and reducing the traumatic impact of this life-changing event. Unfortunately, professionals and midwives, in particular, are often emotionally unprepared and frequently left alone when dealing with these stressful events. Aim: The BLOSSoM (Burnout after perinatal LOSS in Midwifery) study aims to address the levels of professional burnout in Italian midwives and evaluate the psychological impact of bereavement care on professionals. Methods: Web-based cross-sectional study, including socio-demographic questionnaire, survey on the knowledge of guidelines for stillbirth management and two psychometric tests: Maslach Burnout Inventory (MBI) and Impact of Event Scale - Revised (IES-R). Findings: Of 445 female midwives, mean age 35.1 (SD 9.9), working years 11.2 (SD 10.2), 149 (33.4%) reported specific training on stillbirth and 420 (94.6%) highlighted the need for further training and support. Medium to high levels of burnout (Emotional Exhaustion) were present in 65 midwives (15.9%) with a high prevalence of Reduced Personal Accomplishment (292, 64.2%). ‘Communicating the diagnosis of death’ was considered the hardest task, followed by ‘assisting the meeting with the baby’; 109 midwives (24.5%) reported high IES-R scores (>30), suggesting symptoms of PTSD related to stillbirth events; a good level of knowledge of guidelines favoured Personal Accomplishment (OR 0.3 [0.1 – 0.6]). The number of stillbirths assisted by midwives was not associated with burnout levels. Conclusion: Midwives are particularly at risk of developing professional burnout, as early as after five years of work, with a significant association with the psychological impact exerted by stressful events (stillbirth).


2022 - The role of Vitamin D in metabolic and reproductive disturbances of polycystic ovary syndrome: A narrative mini-review [Articolo su rivista]
Menichini, D.; Forte, G.; Orru, B.; Gullo, G.; Unfer, V.; Facchinetti, F.; Menichini, D.
abstract

Vitamin D is a secosteroid hormone that plays a pivotal role in several metabolic and reproductive pathways in humans. Increasing evidence supports the role of Vitamin D deficiency in metabolic disturbances and infertility in women with polycystic ovary syndrome (PCOS). Indeed, supplementation with Vitamin D seems to have a beneficial role on insulin resistance and endometrial receptivity. On the other hand, exceedingly high levels of Vitamin D appear to play a detrimental role on oocytes development and embryo quality. In the current review, we summarize the available evidence about the topic, aiming to suggest the best supplementation strategy in women with PCOS or, more generally, in those with metabolic disturbances and infertility. Based on the retrieved data, Vitamin D seems to have a beneficial role on IR, insulin sensitivity and endometrial receptivity, but high levels and incorrect timing of administration seem to have a detrimental role on oocytes development and embryo quality. Therefore, we encourage a low dose supplementation (400-800 IU/day) particularly in Vitamin D deficient women that present metabolic disturbances like PCOS. As far as the reproductive health, we advise Vitamin D supplementation in selected populations, only during specific moments of the ovarian cycle, to support the luteal phase. However, ambiguities about dosage and timing of the supplementation still emerge from the clinical studies published to date and further studies are required.


2022 - The use of different doses levonorgestrel-releasing intrauterine system (LNG-IUS): real-world data from a multicenter Italian study [Articolo su rivista]
Bastianelli, C.; Farris, M.; Rosato, E.; Varliero, F.; Del Savio, M. C.; Facchinetti, F.; Grandi, G.
abstract

Purpose: Current research fails to adequately inform about the differential use of available levonorgestrel-releasing intrauterine systems (LNG-IUSs) in real life. Aim of our study was to compare the characteristics, satisfaction, continuation rates, and adverse effects between users of the high-dose LNG-IUS (52 mg) and of the low dose LNG-IUS (13.5 mg and 19.5 mg). Materials and Methods: A prospective cohort study was performed in two Services for Family Planning in normal menstruating women with the inclusion of all new prescriptions of LNG-IUS for contraception. Women were followed for a mean of 9.1 ± 2.6 months after placement. Results: 109 women (mean age of 39.8 ± 8.7 years old) were included, 69.7% using a high dose LNG-IUS and 30.3% using a low dose LNG-IUS. Women with a low dose LNG-IUS were significantly younger, thinner, more nulliparous, with fewer vaginal deliveries and C-sections, with a lower menstrual flow length and with more previous use of short-acting reversible contraceptives (p < 0.05). LNG-IUS continuation was similar and very high at the last follow-up: 100 vs. 94.7% in the low and high dose LNG-IUS groups, respectively (p = 0.18). Satisfaction with treatment at the end of the study was similar between different LNG-IUS doses (p = 0.85), with 78.9% being satisfied/very satisfied. Bleeding patterns were significantly different between the two LNG-IUS doses (p < 0.0001). Diagnosis of dysfunctional cysts was more frequent in women with high dose compared to low dose LNG-IUS (22.2 vs. 12.1%), albeit not significantly. Conclusions: We have shown a clear differential use of available LNG-IUS in clinical practice, both as baseline characteristics and as different outcomes, primarily for bleeding patterns. However, all these systems were associated with a very high rate of satisfaction and continuation.


2022 - Ultrasound for antenatal diagnosis of placenta accreta spectrum in women with placenta previa: results from ADoPAD study [Articolo su rivista]
Fratelli, N; Prefumo, F; Maggi, C; Cavalli, C; Sciarrone, A; Garofalo, A; Viora, E; Vergani, P; Ornaghi, S; Betti, M; Tessitore, I Vaglio; Cavaliere, A F; Buongiorno, S; Vidiri, A; Fabbri, E; Ferrazzi, E; Maggi, V; Cetin, I; Frusca, T; Ghi, T; Kaihura, C; Di Pasquo, E; Stampalija, T; Belcaro, C; Quadrifoglio, M; Veneziano, M; Mecacci, F; Simeone, S; Locatelli, A; Consonni, S; Chianchiano, N; Labate, F; Cromi, A; Bertucci, E; Facchinetti, F; Fichera, A; Granata, D; Antonio, F D'; Foti, F; Avagliano, L; Bulfamante, G P; Calì, G
abstract

Objectives: To evaluate the diagnostic performance of third trimester ultrasound for the diagnosis of clinically significant Placenta accreta spectrum disorder (PAS) in women with a low-lying placenta (less than 20 mm from the internal cervical os) or placenta praevia (covering the os) METHODS: Pregnant women with a low-lying placenta or placenta praevia, age ≥ 18 years and gestational age at ultrasound ≥ 26+0/7 weeks of gestation were prospectively included in the study. Ultrasound suspicion of PAS was raised in the presence of at least one of these signs: (1) obliteration of the hypoechoic space between the uterus and the placenta; (2) interruption of the hyperechoic interface between the uterine serosa and the bladder wall; (3) abnormal placental lacunae. In order to assess the ability of ultrasound to detect clinically significant PAS, a composite outcome comprehensive of both active management at delivery and histopathological confirmation of PAS was considered as the reference standard. PAS was considered of clinical significance if, in addition to histological confirmation, at least one of these procedures was carried out after delivery: use of hemostatic intrauterine balloon, compressive uterine suture, peripartum hysterectomy, uterine/hypogastric artery ligation, uterine artery embolization. Results: A total of 568 women underwent transabdominal and transvaginal ultrasound examinations. Of them, 95 delivered in local hospitals and placental pathology according to the study protocol was therefore not available. Among the 473 for whom placental pathology was available, clinically significant PAS was diagnosed in 99 (21%). A normal hypoechoic space between the uterus and the placenta reduces post-test probability of PAS from 21% to 5% in women with a low-lying placenta or placenta previa in the third trimester of pregnancy, and from 62% to 9% in the subgroup of women with previous cesarean section and anterior placenta. The absence of lacunae reduces post-test probability of PAS from 21% to 9% in women with low-lying placenta or placenta previa in the third trimester of pregnancy, and from 62% to 36% in the subgroup with previous cesarean section and anterior placenta. On the other side, when lacunae are seen the post-test probability increases from 21% to 59% in the whole study population and from 62% to 78% in women with placenta previa, previous cesarean section and anterior placenta. Conclusions: Grey-scale ultrasound is a good test to identify pregnancies at low risk of PAS in this high risk population. Ultrasound can be safely used to guide management decisions, concentrating greater resources in patients with the higher risk of clinically significant PAS This article is protected by copyright. All rights reserved.


2022 - Ultrasound screening for fetal anomalies in a single center: diagnostic performances twenty years after the Eurofetus Study [Articolo su rivista]
Sileo, F. G.; Finarelli, A.; Contu, G.; Lugli, L.; Dipace, V.; Ballarini, M.; Guidi, C.; Facchinetti, F.; Bertucci, E.
abstract

Purpose: To establish the accuracy of ultrasound in detecting fetal anomalies looking at the concordance between prenatal and postnatal diagnosis. Materials and methods: Retrospective analysis of concordance between prenatal and postnatal/autoptic diagnosis of fetuses with congenital abnormalities. Data are from a single center (Policlinico di Modena); all fetuses included were born between 2017 and 2018 and with a follow-up of at least 6 months. We included all deliveries (including perinatal deaths) and termination of pregnancy (TOP) for fetal indication. We calculated sensibility, sensitivity, Positive and Negative Likelihood Ratio, positive and negative predictive value of ultrasound. Results: During the study period 5920 deliveries, including perinatal deaths, and 28 TOP for fetal indication were registered at our center. The prevalence of congenital malformations was 2.6% (153/5920). At least one ultrasound was performed in our center in 1250 women delivering in our unit. All 28 TOP had the anomaly scan performed in our center. Among the total 1278 women scanned in our unit, there were 128 (10%) suspicious scans. In 5/128 (3.9%) cases we diagnosed a false alarm; in 8/128 (6.2%) cases an evolutive malformation with in-utero regression. The prenatal diagnosis was confirmed in 77 (60.2%) cases at birth and in 28/128 (21.9%) at postmortem analysis while there were 10/128 false positive (7.8%). Among the 153 congenital malformations diagnosed at birth, the anomaly scan was performed in our Prenatal Medicine Unit in 92 (60.1%) fetuses. Among these, there were 15 false negatives (9.8%) while in 77/92 (83.7%) the malformation at birth agreed with the sonographic diagnosis. Sensitivity and specificity of ultrasound were 87.5% (IC95 80.2–92.8%) and 99.1% (IC95 98.4–99.6%) respectively with a Positive Likelihood Ratio and Negative Likelihood Ratio of 101.3 (IC95 54.5–188.5) and 0.13 (IC95 0.08–0.2); Positive Predictive Value and Negative Predictive Value were 91.3% (IC95 85–95.1%) and 98.7(IC95 98–99.2%). Conclusion: Anomaly scan in pregnancy allows the diagnosis of congenital malformations with a sensibility of 87.5% and specificity of 99.1%. The main limitations of this study are its retrospective design and that it was conducted in a single referral center.


2022 - Ultrasound-guided needle biopsy for preoperative assessment of uterine fibroids: Our experience and a review of the literature [Articolo su rivista]
Alboni, C.; Mattos, L.; Malmusi, S.; Galassi, M.; Facchinetti, F.; Mabrouk, M.
abstract

Leiomyomas are the most common uterine benign tumor, and their malignant counterpart leiomyosarcomas are extremely rare. Despite this, a preoperative diagnosis could be useful for safe surgical minimally invasive management. At present, some clinical and ultrasound findings help recognizing lesions at risk of malignancy. We tried to implement a technique for the preoperative diagnosis for lesions at risk performing ultrasound-guided biopsies of suspected lesions in ten patients. Among them, one case was diagnosed as malignant by the needle biopsy. All patients underwent surgery for myomectomy or hysterectomy, and the histology was confirmed in all cases. No complications occurred. The review of the literature shows other similar experiences of preoperative biopsy of uterine lesions, showing good results for the differential diagnosis between uterine sarcoma and leiomyoma. In our experience, despite the small number of patients enrolled, this technique is safe and effective to plan minimally invasive surgery of uterine fibroids.


2022 - Vitamin D and green tea extracts for the treatment of uterine fibroids in late reproductive life: a pilot, prospective, daily-diary based study [Articolo su rivista]
Grandi, G.; Del Savio, M. C.; Melotti, C.; Feliciello, L.; Facchinetti, F.
abstract

Objective: The beneficial effects of Vitamin D (VD) and Epigallocatechin gallate (EGCG), a polyphenol of green tea, on the growth of uterine fibroids (UF) were previously described in vitro and in vivo. We have decided to investigate their simultaneous administration in women with UFs in late reproductive life. Methods: >40 years old n = 16 premenopausal women with intramural (IM) or subserosal (SS) UF of ≥3 cm or several UFs of different sizes, even smaller but with a total diameter ≥3 cm but <10 cm, without further concomitant organic causes of abnormal uterine bleeding, treated with EGCG 300 mg, Vitamin B6 10 mg and VD 50 µg/day for 90 days. Women completed a diary on a daily basis to obtain information about bleeding and pelvic pain. Results: We have observed a significant reduction in UF’s mean size both at patient’s (−17.8%, p =.03) and at single UF’s level (−37.3%, p =.015). The effect was more evident in women with predominant IM (p =.016) in comparison to SS UFs. No significant changes were observed for uterine and ovarian volume and endometrial thickness during treatment. We reported a significant decrease in menstrual flow length of 0.9 day (p =.04) with no modification in cycle length, menstrual flow intensity and menstrual pain intensity. The satisfaction with treatment was in general very high, with no adverse effects reported. Conclusion: The concomitant administration of VD and EGCG represents a promising treatment of UF in women of late reproductive life for which hormonal manipulation is not foreseen.


2022 - We don´t have elements to scare women who use oral contraceptives based on nomegestrol or chlormadinone about the risk of meningioma. Let's be careful and honest! [Articolo su rivista]
Grandi, G.; Marani, G.; Facchinetti, F.; Bahamondes, L.
abstract


2021 - A first trimester prediction model for large for gestational age infants: a preliminary study [Articolo su rivista]
Monari, F.; Menichini, D.; Spano' Bascio, L.; Grandi, G.; Banchelli, F.; Neri, I.; D'Amico, R.; Facchinetti, F.
abstract

Background: Large for gestational age infants (LGA) have increased risk of adverse short-term perinatal outcomes. This study aims to develop a multivariable prediction model for the risk of giving birth to a LGA baby, by using biochemical, biophysical, anamnestic, and clinical maternal characteristics available at first trimester. Methods: Prospective study that included all singleton pregnancies attending the first trimester aneuploidy screening at the Obstetric Unit of the University Hospital of Modena, in Northern Italy, between June 2018 and December 2019. Results: A total of 503 consecutive women were included in the analysis. The final prediction model for LGA, included multiparity (OR = 2.8, 95% CI: 1.6–4.9, p = 0.001), pre-pregnancy BMI (OR = 1.08, 95% CI: 1.03–1.14, p = 0.002) and PAPP-A MoM (OR = 1.43, 95% CI: 1.08–1.90, p = 0.013). The area under the ROC curve was 70.5%, indicating a satisfactory predictive accuracy. The best predictive cut-off for this score was equal to − 1.378, which corresponds to a 20.1% probability of having a LGA infant. By using such a cut-off, the risk of LGA can be predicted in our sample with sensitivity of 55.2% and specificity of 79.0%. Conclusion: At first trimester, a model including multiparity, pre-pregnancy BMI and PAPP-A satisfactorily predicted the risk of giving birth to a LGA infant. This promising tool, once applied early in pregnancy, would identify women deserving targeted interventions. Trial registration: ClinicalTrials.gov NCT04838431, 09/04/2021.


2021 - Attitudes of women towards products containing hormones (hormonal contraceptives or hormone therapy): what changes from pre to postmenopause? [Articolo su rivista]
Grandi, Giovanni; Del Savio, Maria Chiara; Boggio Sola, Valentina; Monari, Francesca; Melotti, Chiara; Facchinetti, Fabio
abstract

To evaluate the actual perceptions of hormonal contraceptives (HC) in women of reproductive age in comparison with similar concerns of postmenopausal women in relation to hormone therapy (HT).


2021 - Author Correction: Endogenous control of inflammation characterizes pregnant women with asymptomatic or paucisymptomatic SARS-CoV-2 infection (Nature Communications, (2021), 12, 1, (4677), 10.1038/s41467-021-24940-w) [Articolo su rivista]
De Biasi, S.; Tartaro, D. L.; Gibellini, L.; Paolini, A.; Quong, A.; Petes, C.; Awong, G.; Douglas, S.; Lin, D.; Nieto, J.; Galassi, F. M.; Borella, R.; Fidanza, L.; Mattioli, M.; Leone, C.; Neri, I.; Meschiari, M.; Cicchetti, L.; Iannone, A.; Trenti, T.; Sarti, M.; Girardis, M.; Guaraldi, G.; Mussini, C.; Facchinetti, F.; Cossarizza, A.
abstract

The original version of this Article contained an error in Table 1. The correct version of the first row of the 2nd, 3rd, 5th and 7th columns states ‘CTR’, ‘PN’, ‘CTR vs PN’ and ‘PN vs PP’, instead of the original, incorrect ‘HD’, ‘NP’, ‘CTR vs NP’ and ‘CTR vs PP’. This has been corrected in both the PDF and HTML versions of the Article.


2021 - BRCA mutation carriers' perceptions on postmenopausal hormone therapy: An Italian study [Articolo su rivista]
Grandi, Giovanni; Boggio Sola, Valentina; Cortesi, Laura; Toss, Angela; Giuliani, Giulia Andrea; Del Savio, Maria Chiara; Facchinetti, Fabio
abstract

Objective To evaluate the actual perceptions of postmenopausal hormone therapy (HT) in BRCA mutation carriers (BRCAmc) in comparison with women from the general population.Methods Questionnaire-based study of 83 BRCAmc and a control group of 89 women without a genetic mutation. Perceptions were evaluated by specific questions and Likert scales (-5-+5).Results Present and past users of HT were more frequent in the control group (p = 0.01), with a longer time of use (p = 0.03). The preferred route of administration of HT was 'oral' (54.6%). The most frequently reported adverse effect of HT was venous thrombosis (0.8), while a protective effect on bone health was reported. No noticeable beneficial effects of HT have been recognised for hot flushes (0.2) and vaginal dryness (0.1). The most frequently perceived beneficial and adverse effects of HT were not significantly different between BRCA mutation carriers and controls. The greatest oncological fear was breast cancer (1.0). The protective role of HT on colorectal cancer was not known (0.1). These oncological impacts were mostly overestimated in BRCAmc, however this was not significant. Few BRCAmc would think of taking HT after risk-reducing surgeries.Conclusions Knowledge of the effects of HT on BRCAmc is relatively poor and they are likely to overstate its negative effects and underestimate its health benefits; however, this is not significant in comparison to the general population. More and better information should be given to BRCAmc to allow them to make informed decisions about the use of HT, especially before undergoing risk-reducing surgeries.


2021 - Comparison between Cerebroplacental Ratio and Umbilicocerebral Ratio in Predicting Adverse Perinatal Outcome in Pregnancies Complicated by Late Fetal Growth Restriction: A Multicenter, Retrospective Study [Articolo su rivista]
Di Mascio, Daniele; Herraiz, Ignacio; Villalain, Cecilia; Buca, Danilo; Morales-Rossello, Jose; Loscalzo, Gabriela; Sileo, Filomena; Finarelli, Alessandra; Bertucci, Emma; Facchinetti, Fabio; Rizzo, Giuseppe; Brunelli, Roberto; Giancotti, Antonella; Muzii, Ludovico; Maria Maruotti, Giuseppe; Carbone, Luigi; D’Amico, Alice; Tinari, Sara; Morelli, Roberta; Cerra, Chiara; Nappi, Luigi; Greco, Pantaleo; Liberati, Marco; Galindo, Alberto; D’Antonio, Francesco
abstract

Introduction: The role of cerebroplacental ratio (CPR) or umbilicocerebral ratio (UCR) to predict adverse intrapartum and perinatal outcomes in pregnancies complicated by late fetal growth restriction (FGR) remains controversial. Methods: This was a multicenter, retrospective cohort study involving 5 referral centers in Italy and Spain, including singleton pregnancies complicated by late FGR, as defined by Delphi consensus criteria, with a scan 1 week prior to delivery. The primary objective was to compare the diagnostic accuracy of the CPR and UCR for the prediction of a composite adverse outcome, defined as the presence of either an adverse intrapartum outcome (need for operative delivery/cesarean section for suspected fetal distress) or an adverse perinatal outcome (intrauterine death, Apgar score <7 at 5 min, arterial pH <7.1, base excess of >-11 mEq/mL, or neonatal intensive care unit admission). Results: Median CPR absolute values (1.11 vs. 1.22, p = 0.018) and centiles (3 vs. 4, p = 0.028) were lower in pregnancies with a composite adverse outcome than in those without it. Median UCR absolute values (0.89 vs. 0.82, p = 0.018) and centiles (97 vs. 96, p = 0.028) were higher. However, the area under the curve, 95% confidence interval for predicting the composite adverse outcome showed a poor predictive value: 0.580 (0.512-0.646) for the raw absolute values of CPR and UCR, and 0.575 (0.507-0.642) for CPR and UCR centiles adjusted for gestational age. The use of dichotomized values (CPR <1, UCR >1 or CPR <5th centile, UCR >95th centile) did not improve the diagnostic accuracy. Conclusion: The CPR and UCR measured in the week prior delivery are of low predictive value to assess adverse intrapartum and perinatal outcomes in pregnancies with late FGR.


2021 - Contraception and Cardiovascular Diseases [Capitolo/Saggio]
Del Savio, M. C.; Sammarini, M.; Facchinetti, F.; Grandi, G.
abstract

Women during reproductive years, who need safe contraception, can suffer from many different cardiovascular diseases. This is a comprehensive review about the possible use of different modern contraceptives (intrauterine devices, progestogen-only contraceptives, combined hormonal contraceptives) in women with cardiovascular diseases, such as hypertension, dyslipidaemia, valvular heart disease or arrhythmia or with history of high blood pressure during pregnancy, ischaemic heart disease, cerebrovascular accident or deep-vein thrombosis according to most updated International Guidelines. The main aim of this chapter is to suggest to the clinician when the theoretical or proven risks due to the disease outweigh the advantages of using a method of contraception, in order to avoid unsuitable prescriptions and serious adverse effects.


2021 - Diagnostic performance of cerebroplacental and umbilicocerebral ratio in appropriate for gestational age and late growth restricted fetuses attempting vaginal delivery: a multicenter, retrospective study [Articolo su rivista]
Villalain, C.; Galindo, A.; Di Mascio, D.; Buca, D.; Morales-Rossello, J.; Loscalzo, G.; Giulia Sileo, F.; Finarelli, A.; Bertucci, E.; Facchinetti, F.; Rizzo, G.; Brunelli, R.; Giancotti, A.; Muzii, L.; Maria Maruotti, G.; Carbone, L.; D'Amico, A.; Tinari, S.; Morelli, R.; Cerra, C.; Nappi, L.; Greco, P.; Liberati, M.; D'Antonio, F.; Herraiz, I.
abstract

Background: Cerebroplacental Doppler studies have been advocated to predict the risk of adverse perinatal outcome (APO) irrespective of fetal weight. Objective: To report the diagnostic performance of cerebroplacental (CPR) and umbilicocerebral (UCR) ratios in predicting APO in appropriate for gestational age (AGA) fetuses and in those affected by late fetal growth restriction (FGR) attempting vaginal delivery. Study design: Multicenter, retrospective, nested case-control study between 1 January 2017 and January 2020 involving five referral centers in Italy and Spain. Singleton gestations with a scan between 36 and 40 weeks and within two weeks of attempting vaginal delivery were included. Fetal arterial Doppler and biometry were collected. The AGA group was defined as fetuses with an estimated fetal weight and abdominal circumference >10th and <90th percentile, while the late FGR group was defined by Delphi consensus criteria. The primary outcome was the prediction of a composite of perinatal adverse outcomes including either intrauterine death, Apgar score at 5 min <7, abnormal acid-base status (umbilical artery pH < 7.1 or base excess of more than −11) and neonatal intensive care unit (NICU) admission. Area under the curve (AUC) analysis was performed. Results: 646 pregnancies (317 in the AGA group and 329 in the late FGR group) were included. APO were present in 12.6% AGA and 24.3% late FGR pregnancies, with an odds ratio of 2.22 (95% CI 1.46–3.37). The performance of CPR and UCR for predicting APO was poor in both AGA [AUC: 0.44 (0.39–0.51)] and late FGR fetuses [AUC: 0.56 (0.49–0.61)]. Conclusions: CPR and UCR on their own are poor prognostic predictors of APO irrespective of fetal weight.


2021 - Effect of L-arginine supplementation in pregnant women with chronic hypertension and previous placenta vascular disorders receiving Aspirin prophylaxis: a randomized control trial [Articolo su rivista]
Monari, F.; Menichini, D.; Pignatti, L.; Basile, L.; Facchinetti, F.; Neri, I.
abstract

BACKGROUND: The aim of the study is to evaluate the effects of supplementation with Arginine (L-Arg) 3g, (together with Magnesium (Mg) 350 mg and Salicilate (Sal) 100 mg) on maternal blood pressure (BP), uterine artery doppler PI and neonatal outcomes in women with high-risk pregnancy for chronic hypertension (CH) and other previous placenta vascular disorders (PVD) already treated with low dose of aspirin (LDA), as recommended by guidelines. METHODS: We enrolled women affected by CH and other previous PVD referred to the High-Risk Clinic of the Department of Maternal and Child’s Health at the University Hospital of Modena and Reggio Emilia from September 2017 to June 2019. The study design was a controlled, randomized trial of oral supplementation of L-Arg 3g (together with Mg 350 mg and Sal extract 100 mg) + LDA 100 mg/day versus only LDA 100 mg/day. Inclusion criteria were: singleton pregnancy; diagnosis of chronic hypertension, previous preeclampsia <34 weeks, previous intrauterine growth restriction (IUGR) <10th centile or previous stillbirth (SB) related to placenta vascular disorders; gestational age <14 weeks. Each woman was enrolled between 12-14 weeks gestation and underwent 24-hour ambulatory BP monitoring with an automatic device (SpaceLab 92710, Critikon, WA), repeated at 18-20th and 24-26th weeks. Moreover Uterine artery Doppler ultrasound evaluation including PI were performed at 18-20 weeks gestation and repeated at 24-26th weeks. Pregnancy outcomes data were collected in a password protected database. RESULTS: Seventy-nine women agreed to participate in the study. No significant differences between the demographic characteristics in the two groups were found at enrolment (Group LDA + L-Arg: 30 patients versus Group LDA: 49 patients). In the LDA-L-Arg group there is no significant increase in both systolic (127.22±12.02 and 132.75±7.51 mmHg, P=0.002) and diastolic (75.85±8.53 and 83.63±6.05 mmHg, P=0.0000) BP values at 24-26 weeks reveled in the LDA group. The value of the uterine artery Doppler median PI>95th centile at 24-26 weeks show a significant reduction in the LDA+L-Arg group respect the LDA group (seven women, 23.3% vs. 21 women, 42.9%; P=0.04). A significantly lower percentage of women received new antihypertensive drugs in the LDA+ L-Arg group than the LDA group (6.7% vs. 24.5%) (P=0.02). There was neither statistically significant difference in perinatal outcomes between the two groups, except for trend of significance. CONCLUSIONS: Although we found only trends of improvements of perinatal outcomes in LDA+L-Arg group, considering the promising results on BP values, uterine artery PI and the low need to start a new antihypertensive treatment, thus the resulting impact in reducing pregnancy medicalization, number of maternal-fetal well-being monitoring visits and the need of induction of labor, we believe that further studies should be performed to enlarge our observation and clarify the role of L-Arg 3g supplementation as a protective integration in high-risk pregnancies already in prophylaxis with LDA.


2021 - Endogenous control of inflammation characterizes pregnant women with asymptomatic or paucisymptomatic SARS-CoV-2 infection [Articolo su rivista]
De Biasi, S.; Tartaro, D. L.; Gibellini, L.; Paolini, A.; Quong, A.; Petes, C.; Awong, G.; Douglas, S.; Lin, D.; Nieto, J.; Galassi, F. M.; Borella, R.; Fidanza, L.; Mattioli, M.; Leone, C.; Neri, I.; Meschiari, M.; Cicchetti, L.; Iannone, A.; Trenti, T.; Sarti, M.; Girardis, M.; Guaraldi, G.; Mussini, C.; Facchinetti, F.; Cossarizza, A.
abstract

SARS-CoV-2 infection can affect all human beings, including pregnant women. Thus, understanding the immunological changes induced by the virus during pregnancy is nowadays of pivotal importance. Here, using peripheral blood from 14 pregnant women with asymptomatic or mild SARS-CoV-2 infection, we investigate cell proliferation and cytokine production, measure plasma levels of 62 cytokines, and perform a 38-parameter mass cytometry analysis. Our results show an increase in low density neutrophils but no lymphopenia or gross alterations of white blood cells, which display normal levels of differentiation, activation or exhaustion markers and show well preserved functionality. Meanwhile, the plasma levels of anti-inflammatory cytokines such as interleukin (IL)-1RA, IL-10 and IL-19 are increased, those of IL-17, PD-L1 and D-dimer are decreased, but IL-6 and other inflammatory molecules remain unchanged. Our profiling of antiviral immune responses may thus help develop therapeutic strategies to avoid virus-induced damages during pregnancy.


2021 - From Myo-inositol to D-chiro-inositol molecular pathways [Articolo su rivista]
Kiani, A. K.; Paolacci, S.; Calogero, A. E.; Cannarella, R.; DI RENZO, G. C.; Gerli, S.; DELLA MORTE, C.; Busetto, G. M.; DE BERARDINIS, E.; DEL GIUDICE, F.; Stuppia, L.; Facchinetti, F.; Dinicola, S.; Bertelli, M.
abstract

OBJECTIVE: Inositol is a carbocyclic sugar polyalcohol. By epimerization of its hydroxyl groups, nine possible stereoisomers can be generated, two of major physiological and clinical relevance: Myo-inositol and D-chiro-inositol. Myo-inositol and D-chiro-inositol are normally stored in kidney, brain and liver and are necessary for functions, such as signal transduction, metabolic flux, insulin signaling, regulation of ion-channel permeability, stress response and embryo development. In this narrative review, we summarize the mechanisms by which myo-inositol and D-chiro-inositol can be synthesized and absorbed and their possible role in the etiopathogenesis of neural tube defects. MATERIALS AND METHODS: We performed an online search in the PubMed database using the following keywords: "inositol", "D-chiro-inositol", "myo-inositol", "neural tube defects and inositol". RESULTS: Inositol requirements are partly met by dietary intake, while the rest is synthesized endogenously. Inositol deficiency may be involved in the pathogenesis of diseases, such as metabolic syndrome, spina bifida (a neural tube defect), polycystic ovary syndrome and diabetes. Supplementation of the two inositol stereoisomers, D-chiro-inositol and myo-inositol is important to prevent these conditions. CONCLUSIONS: Inositol is fundamental for signal transduction in the brain, kidneys, reproductive organs and other tissues in response to neurotransmitters, hormones and growth factors. Various genes are involved in inositol metabolism and associated pathways. Altered inositol concentrations are observed in several diseases. Analysis of the genes involved in inositol metabolism may provide important information for the clinical management of these conditions.


2021 - Hyaluronic acid in obstetrics: role in Physiological Pregnancy [Capitolo/Saggio]
Facchinetti, F.; Unfer, V.
abstract

Pregnancy is a physiologically fine-balanced condition, characterized by radical hormonal and physical changes necessary for successful blastocyst implantation, optimal embryo development and safe birth. During gestation, several biological modifications are adopted by maternal body to accept the fetus (e.g., immune tolerance). In this context, Hyaluronic Acid (HA) is an interesting molecule, seemingly involved in many steps of the process, with a pivotal role in ovulation, fertilization, blastocyst implantation, inhibition of uterine contraction, immunomodulation of T cells or labour-related cervical modifications.


2021 - Inositols: From established knowledge to novel approaches [Articolo su rivista]
Dinicola, S.; Unfer, V.; Facchinetti, F.; Soulage, C. O.; Greene, N. D.; Bizzarri, M.; Lagana, A. S.; Chan, S. -Y.; Bevilacqua, A.; Pkhaladze, L.; Benvenga, S.; Stringaro, A.; Barbaro, D.; Appetecchia, M.; Aragona, C.; Espinola, M. S. B.; Cantelmi, T.; Cavalli, P.; Chiu, T. T.; Copp, A. J.; D'anna, R.; Dewailly, D.; Lorenzo, C. D.; Diamanti-Kandarakis, E.; Marin, I. H.; Hod, M.; Kamenov, Z.; Kandaraki, E.; Monastra, G.; Oliva, M. M.; Nestler, J. E.; Nordio, M.; Ozay, A. C.; Papalou, O.; Porcaro, G.; Prapas, N.; Roseff, S.; Vazquez-Levin, M.; Vucenik, I.; Wdowiak, A.
abstract

Myo-inositol (myo-Ins) and D-chiro-inositol (D-chiro-Ins) are natural compounds involved in many biological pathways. Since the discovery of their involvement in endocrine signal transduction, myo-Ins and D-chiro-Ins supplementation has contributed to clinical approaches in ameliorating many gynecological and endocrinological diseases. Currently both myo-Ins and D-chiro-Ins are well-tolerated, effective alternative candidates to the classical insulin sensitizers, and are useful treatments in preventing and treating metabolic and reproductive disorders such as polycystic ovary syndrome (PCOS), gestational diabetes mellitus (GDM), and male fertility disturbances, like sperm abnormalities. Moreover, besides metabolic activity, myo-Ins and D-chiro-Ins deeply influence steroidogenesis, regulating the pools of androgens and estrogens, likely in opposite ways. Given the complexity of inositol-related mechanisms of action, many of their beneficial effects are still under scrutiny. Therefore, continuing research aims to discover new emerging roles and mechanisms that can allow clinicians to tailor inositol therapy and to use it in other medical areas, hitherto unexplored. The present paper outlines the established evidence on inositols and updates on recent research, namely concerning D-chiro-Ins involvement into steroidogenesis. In particular, D-chiro-Ins mediates insulin-induced testosterone biosynthesis from ovarian thecal cells and directly affects synthesis of estrogens by modulating the expression of the aromatase enzyme. Ovaries, as well as other organs and tissues, are characterized by a specific ratio of myo-Ins to D-chiro-Ins, which ensures their healthy state and proper functionality. Altered inositol ratios may account for pathological conditions, causing an imbalance in sex hormones. Such situations usually occur in association with medical conditions, such as PCOS, or as a consequence of some pharmacological treatments. Based on the physiological role of inositols and the pathological implications of altered myo-Ins to D-chiro-Ins ratios, inositol therapy may be designed with two different aims: (1) restoring the inositol physiological ratio; (2) altering the ratio in a controlled way to achieve specific effects.


2021 - Intrapartum stillbirth for sepsis complicating Arabin cervical pessary placement in a twin pregnancy [Articolo su rivista]
Monari, F.; Salerno, C.; Torcetta, F.; Po, G.; Facchinetti, F.
abstract

There is little evidence regarding the best treatment in case of dilated cervix and exposed membranes in twins. Current options for its management include vaginal progesterone, cervical cerclage and cervical pessary, but none of them had shown effectiveness compared to expectant management. We presented a case of twin pregnancy at 22 6/7 weeks gestation admitted to the hospital because of cervical insufficiency with bulging of membranes. An Arabin pessary was positioned after a failed attempt of cervical cerclage and no antibiotic was given in absence of signs of infection. Cesarean delivery was performed at 24 weeks gestation because of spontaneous preterm labor and spontaneous rupture of membranes with the first baby in a transverse lie position. At the uterus section, the first baby was stillborn, with Arabin pessary strictly adherent to his ecchymotic head, while the second baby was born alive. After diagnostic histopathological and microbiological investigations, we hypothesized that the first twin died for funisitis/sepsis and mechanical insult due to the strict adhesion of the pessary to the fetal head. We concluded that in case of bulging membranes and dilated cervix, antibiotic treatment should be evaluated, also in absence of signs/symptoms of infection or suspicion of rupture of the membranes, and pessary insertion should be avoided, namely at second trimester, because of the risk of its dislocation inside the uterus when contractions start and potential hurt to extremely preterm fetus.


2021 - Low risk delivery today [Capitolo/Saggio]
Facchinetti, F.; Dante, G.; Ricchi, A.; Volpe, A.
abstract


2021 - Maternal and neonatal outcomes of pregnancies complicated by late fetal growth restriction undergoing induction of labor with dinoprostone compared with cervical balloon: A retrospective, international study [Articolo su rivista]
Di Mascio, D.; Villalain, C.; Rizzo, G.; Morales-Rossello, J.; Sileo, F. G.; Maruotti, G. M.; Prefumo, F.; Galindo, A.; D'Antonio F, induction of labor in late fetal growth restriction COLLEGE study Group: Di Mascio D.; Villalain, C.; Buca, D.; Herraiz, I.; Rizzo, G.; Morales-Rossello, J.; Loscalzo, G.; Sileo, Fg.; Finarelli, A.; Bertucci, E.; Facchinetti, F.; Brunelli, R.; Giancotti, A.; Muzii, L.; Maruotti, Gm.; Carbone, L.; Saccone, G.; D'Amico, A.; Tinari, S.; Cerra, C.; Prefumo, F.; Nappi, L.; Greco, P.; Monaci, R.; Fichera, A.; Fratelli, N.; Liberati, M.; Galindo, A.; D'Antonio, F.
abstract

Introduction: The aim of this study was to compare vaginal dinoprostone and mechanical methods for induction of labor (IOL) in pregnancies complicated by late fetal growth restriction. Material and methods: Multicenter, retrospective, cohort study involving six referral centers in Italy and Spain. Inclusion criteria were pregnancies complicated by late fetal growth restriction as defined by Delphi consensus criteria. The primary outcome was the occurrence of uterine tachysystole; secondary outcomes were either cesarean delivery or operative vaginal delivery for non-reassuring fetal status, a composite score of adverse neonatal outcome and admission to neonatal intensive care unit (NICU). Univariate and multivariate logistic regression analysis was used to analyze the data. Results: A total of 571 pregnancies complicated by late fetal growth restriction undergoing IOL (391 with dinoprostone and 180 with mechanical methods) were included in the analysis. The incidence of uterine tachysystole (19.2% vs. 5.6%; p&nbsp;=&nbsp;0.001) was higher in women undergoing IOL with dinoprostone than in those undergoing IOL with mechanical methods. Similarly, the incidence of cesarean delivery or operative delivery for non-reassuring fetal status (25.6% vs. 17.2%; p&nbsp;=&nbsp;0.027), composite adverse neonatal outcome (26.1% vs. 16.7%; p&nbsp;=&nbsp;0.013) and NICU admission (16.9% vs. 5.6%; p&nbsp;&lt;&nbsp;0.001) was higher in women undergoing IOL with dinoprostone than in those undergoing IOL with mechanical methods. At logistic regression analysis, IOL with mechanical methods was associated with a significantly lower risk of uterine tachysystole (odds ratio 0.26, 95% confidence interval 0.13-0.54; p&nbsp;&lt;&nbsp;0.001). Conclusions: In pregnancies complicated by late fetal growth restriction, IOL with mechanical methods is associated with a lower risk of uterine tachysystole, cesarean delivery or operative delivery for non-reassuring fetal status, and adverse neonatal outcome compared with pharmacological methods.


2021 - Mode of birth in women with low-lying placenta: protocol for a prospective multicentre 1:3 matched case-control study in Italy (the MODEL-PLACENTA study) [Articolo su rivista]
Ornaghi, S.; Colciago, E.; Vaglio Tessitore, I.; Abbamondi, A.; Antolini, L.; Locatelli, A.; Inversetti, A.; Pintucci, A.; Cetin, I.; Bracco, B.; Fabbri, E.; Sala, V.; Meroni, M.; Volpe, G.; Benedetti, S.; Bulfoni, C.; Marconi, A.; Lagrasta, F.; Paolini, C. L.; Mazza, E.; Candiani, M.; Valsecchi, L.; Smid, M.; Pasi, F.; Pozzoni, M.; Castoldi, M.; Vignali, M.; Dal Molin, G.; Guarano, A.; Pellegrino, A.; Callegari, C.; Betti, M.; Lazzarin, S.; Prefumo, F.; Zanardini, C.; Parolin, V.; Catalano, A.; Barbolini, E.; Antonazzo, P.; Pignatti, L.; Tintoni, M.; Spelzini, F.; Martinelli, A.; Facchinetti, F.; Chiossi, G.; Vergani, P.
abstract

Introduction The term placenta praevia defines a placenta that lies over the internal os, whereas the term low-lying placenta identifies a placenta that is partially implanted in the lower uterine segment with the inferior placental edge located at 1-20 mm from the internal cervical os (internal-os-distance). The most appropriate mode of birth in women with low-lying placenta is still controversial, with the majority of them undergoing caesarean section. The current project aims to evaluate the rate of vaginal birth and caesarean section in labour due to bleeding by offering a trial of labour to all women with an internal-os-distance &gt;5 mm as assessed by transvaginal sonography in the late third trimester. Methods and analysis The MODEL-PLACENTA is a prospective, multicentre, 1:3 matched case-control study involving 17 Maternity Units across Lombardy and Emilia-Romagna regions, Italy. The study includes women with a placenta located in the lower uterine segment at the second trimester scan. Women with a normally located placenta will be enrolled as controls. A sample size of 30 women with an internal-os-distance &gt;5 mm at the late third trimester scan is needed at each participating Unit. Since the incidence of low-lying placenta decreases from 2% in the second trimester to 0.4% at the end of pregnancy, 150 women should be recruited at each centre at the second trimester scan. A vaginal birth rate ≥60% in women with an internal-os-distance &gt;5 mm will be considered appropriate to start routinely admitting to labour these women. Ethics and dissemination Ethical approval for the study was given by the Brianza Ethics Committee (No 3157, 2019). Written informed consent will be obtained from study participants. Results will be disseminated by publication in peer-reviewed journals and presentation in international conferences. Trial registration number NCT04827433 (pre-results stage)


2021 - Neonatal outcomes and risk of neonatal sepsis in an expectantly managed cohort of late preterm prelabor rupture of membranes [Articolo su rivista]
Chiossi, G.; Di Tommaso, M.; Monari, F.; Consonni, S.; Strambi, N.; Zoccoli, S. G.; Seravalli, V.; Comerio, C.; Betti, M.; Cappello, A.; Vergani, P.; Facchinetti, F.; Locatelli, A.
abstract

Objective: Expectant management in patients with prelabor preterm rupture of membranes between between 340/7 and 36 6/7 weeks (late preterm pPROM or LpPROM) has been shown to decrease the burden of prematurity, when compared to immediate delivery. As the severity of prematurity depends on gestational age (GA) at PROM, and PROM to delivery interval, we first investigated how such variables affect neonatal outcomes (NO). Second, we assessed the risk of neonatal sepsis. Study design: retrospective cohort study on neonatal morbidity among singleton infants born to expectantly managed mothers with LpPROM in five hospitals affiliated with three Italian academic institutions. The primary NO was a composite of neonatal death, non-invasive (cPAP) or invasive (mechanical ventilation) respiratory support, hypoglycemia (&lt; 44 mg/dl needing therapy), newborn sepsis, confirmed seizures, stroke, intraventricular hemorrhage (IVH), basal nuclei anomalies, cardiopulmonary resuscitation, umbilical-cord-blood arterial pH &lt; 7.0 or base excess &lt; -12.5, and prolonged hospitalization (≥ 5 days). Univariate analysis described differences in the population according to GA at delivery. Multivariate logistic regression was then used to investigate the effects of GA at PROM, and PROM to delivery interval on the NO. Results: 258/606 (42.6 %) women with LpPROM were expectantly managed, as they did not deliver within the first 24 h. The median latency duration was 2 (95 %CI 1−3) days, having no effect on neonatal morbidity on multivariate analysis. Multivariate analysis also showed increased risks of adverse NO among PROM at 34 (OR 2.3 95 %CI 1.03−5.1) but not at 35 weeks when compared to 36 weeks, and among women receiving antenatal corticosteroids (OR 3.6 95 %CI 1.3−9.7), while antibiotic treatment showed a non-significant protective effect (OR 0.2 95 %CI 0.04−1.02). Prevalence of neonatal sepsis was 0.8 % (2/258) Conclusion: Expectant management of LpPROM should be encouraged especially between 34+0 and 34+6 weeks’, when the burden of prematurity is the greatest. Antibiotics may have beneficial effects, while careful consideration should be given to antenatal corticosteroids until future studies specifically address LpPROM.


2021 - Perinatal outcomes in women affected by different types of headache disorders: A prospective cohort study [Articolo su rivista]
Neri, I.; Menichini, D.; Monari, F.; Bascio, L. S.; Banchelli, F.; Facchinetti, F.
abstract

Objective: This study aims to investigate pregnancy and perinatal outcomes in women with tension-type headache, migraine without aura and migraine with aura by comparing them to women without any headache disorders. Study design: Prospective cohort study including singleton pregnancies attending the first trimester aneuploidy screening at the University Hospital of Modena, in Northern Italy, between June 2018 and December 2019. Results: A total of 515 consecutive women were included and headache disorders were reported in 43.5% of them (224/515). Tension-type headache was diagnosed in 24.3% of the cases, while 14% suffered from migraine without aura and 5.2% from migraine with aura. Birthweight was significantly lower in women affected by migraine with aura respective to other groups, and a significantly higher rate of small for gestational age infants was found in tension-type headache (10.4%) and in migraine with aura (24.9%) groups respective to the others (p &lt; 0.001). Moreover, the admission to the neonatal intensive care unit was significantly higher in all the headache groups (p = 0.012). Multivariate analysis showed that women presenting tension-type headache (OR 4.19, p = 0.004), migraine with aura (OR 5.37, p = 0.02), a uterine artery pulsatility index &gt;90th centile (OR 3.66, p = 0.01), low multiple of the median (MoM) of Pregnancy-associated plasma protein-A (PAPP-A) (OR 0.48, p = 0.05) and high MoM of Inhibin-A (OR 3.24, p = 0.03) at first trimester, are independently associated with the delivery of small for gestational age infants when compared to women without headache disorders. Conclusion: Migraine with aura and tension type headache expose women to an increased risk of delivering small for gestational age infants, in association with some utero-placenta markers evaluated at first trimester. These women with headache disorders have an additional indication to undergo first trimester aneuploidy screening and would possibly benefit from specific interventions.


2021 - Potentially preventable antepartum stillbirths in a high-resource setting: a prospective audit-based study [Articolo su rivista]
Po', G.; Salerno, C.; Monari, F.; Grandi, G.; Facchinetti, F.
abstract

Objectives: The primary objective was the identification of sub-standard care in antepartum stillbirths in Emilia-Romagna Region (Italy), hence the number of potentially preventable cases. Secondly, we seek to evaluate any association between inadequate care and either risk factors for stillbirth or causes of death. Study Design: This study was based on prospectively-collected data in an institutional stillbirth audit project, involving all 29 hospital with a maternity unit in Emilia-Romagna Region. For each stillbirth occurred in the area from 2014 to the first semester of 2019 the same diagnostic workup was performed and a clinical record with data about mother and stillborn was completed. Every case was discussed in a multidisciplinary local audit to assess both the cause of death and the quality of care. Two aspects of care quality were evaluated: clinical management and women's access to care. Data were then reviewed by the Regional Audit Group. Results: Elements of inadequate care were identified in 56 out of 524 (10.7 %) fetal deaths. Non-Italian women and pregnancies with fetal growth restriction had double the risk of having received inadequate care during pregnancy, compared to Italian women (aOR 2.0, 95 % CI 1.1–3.6) and a normally developing fetus (aOR 2.0, 95 % CI 1.1–4.1), respectively. Women whose stillbirth was caused by maternal disorders were at higher risk for inadequate care compared to women who had stillbirth explained by other cause (aOR 5.89, 95 %CI 2.2–15.4). Sub-optimal clinical management and barriers to access to care were observed to equal extents. Inappropriate ultrasound monitoring was the most frequent suboptimal care element. Conclusions: About one out of ten stillbirths was potentially preventable. Interventions to reduce stillbirth occurrence in our high-resource setting should focus on appropriate diagnosis and management of maternal disorders and fetal growth restriction, as well as improving access to antenatal care.


2021 - Pregnant woman infected by Coronavirus disease (COVID-19) and calcifications of the fetal bowel and gallbladder [Articolo su rivista]
Sileo, Fg; Tramontano, Al; Leone, C; Meacci, M; Gennari, W; Ternelli, G; La Marca, A; Lugli, L; Berardi, A; Facchinetti, F; Bertucci, E
abstract

COVID-19 was declared to be a pandemic due to the rapid increase of cases around the world, including the number of pregnant women. Data about vertical transmission of COVID-19 are still limited and controversial: in most cases, although a positive mother, the virus could not be isolated in amniotic fluid, cord blood, breast milk or neonatal throat swab in these patients. No data have been published about possible intrauterine sonographic signs of infection. A pregnant woman was diagnosed with SARS-CoV-2 at 35 t5 weeks of gestation and managed conservatively at home. At transabdominal ultrasound at 38+3 weeks, fetal bowel and gallbladder calcifications were noted. CMV and other infectious agents were ruled out an iterative caesarean section was performed at 38+5 weeks without complications. Placenta resulted negative for SARS-CoV-2; the umbilical cord blood sample was IgG positive and IgM negative as per maternal infection. The baby developed respiratory distress syndrome requiring endotracheal surfactant administration and nasal-CPAP for one day but nasopharyngeal swabs at birth and after 48 hours were SARS-CoV-2 negative. Neonatal abdominal ultrasound showed normal liver, acalculous gallbladder with mild parietal thickening. The baby was discharged in good conditions. Although gallbladder calcifications and echogenic bowel are highly suspicious of viral infection and were thought to be due to the vertical transmission of SARS-CoV-2, these findings were not corroborated by the results of our diagnostic tests; these sonographic findings might represent a false positive of fetal infection in mother affected by COVID-19 since vertical transmission appears to be rare.


2021 - Prevalence of low antithrombin levels in preeclamptic women and perinatal outcome [Articolo su rivista]
Neri, I.; Pignatti, L.; Furia, G.; Facchinetti, F.
abstract

Objective. The aim of this study is to evaluate the prevalence of low antithrombin levels in our population in order to assess an intervention trial feasibility. Methods. This is a retrospective study. A database was created by using queries to find out medical records of patients requiring hospitalization for preeclampsia or gestational hypertension or superimposed preeclampsia to chronic hypertension at Modena University Hospital between June 2015 and July 2019. Results. We screened 11845 deliveries. Overall, 221 (1.9%) cases of preeclampsia were identified. Antithrombin level was available for 201 women, thus included in the analysis. Median antithrombin value was 87% (IQ range: 77-98). The prevalence of low antithrombin levels was 9%. Antithrombin &lt; 80% was found in 21% of the subjects. The remnant showed normal values. Median antithrombin was significantly lower in severe respect with mild preeclampsia (83% ± 14 vs 89% ± 14, p = 0.003). The rate of small for gestational age was significantly higher in low antithrombin levels group (44.4% vs 22.4%, p = 0.042). Considering mean values, antithrombin levels were also significantly lower in case of small for gestational age (84% ± 14 vs 89% ± 14; p = 0.040). Conclusions. In our population, low antithrombin levels (1 in 10 patients) were associated with severity of preeclampsia, namely with small for gestational age babies. Data suggest this subpopulation as a better target for trials assessing the efficacy of antithrombin supplementation.


2021 - Prevalence of uterine rupture among women with one prior low transverse cesarean and women with unscarred uterus undergoing labor induction with pge2: A systematic review and meta-Analysis [Articolo su rivista]
Chiossi, G.; Amico, R. D.; Tramontano, A. L.; Sampogna, V.; Laghi, V.; Facchinetti, F.
abstract

Background As uterine rupture may affect as many as 11/1000 women with 1 prior cesarean birth and 5/10.000 women with unscarred uterus undergoing labor induction, we intended to estimate the prevalence of such rare outcome when PGE2 is used for cervical ripening and labor induction. Methods We searched MEDLINE, ClinicalTrials.gov and the Cochrane library up to September 1st 2020. Retrospective and prospective cohort studies, as well as randomized controlled trials (RCTs) on singleton viable pregnancies receiving PGE2 for cervical ripening and labor induction were reviewed. Prevalence of uterine rupture was meta-Analyzed with Freeman-Tukey double arcsine transformation among women with 1 prior low transverse caesarean section and women with unscarred uterus. Results We reviewed 956 full text articles to include 69 studies. The pooled prevalence rate of uterine rupture is estimated to range between 2 and 9 out of 1000 women with 1 prior low transverse cesarean (5/1000; 95%CI 2-9/1000, 122/9000). The prevalence of uterine rupture among women with unscarred uterus is extremely low, reaching at most 0.7/100.000 (&lt;1/100.000.000; 95%CI &lt;1/100.000.000 0.7/100.000, 8/17.684). Conclusions Uterine rupture is a rare event during cervical ripening and labor induction with PGE2.


2021 - Prophylactic risk-reducing salpingo-oophorectomy in BRCA mutation carriers: what is going on in a region of northern Italy? [Articolo su rivista]
Grandi, G.; Perrone, A. M.; Perrone, A.; Mandato, V. D.; Comerci, G.; Sammarini, M.; Merisio, C.; Amadori, A.; Stefanetti, M.; Martinello, R.; Facchinetti, F.; De Iaco, P.; Aguzzoli, L.; Arcangeli, V.; Berretta, R.; Cortesi, L.; De Domenico, R.; Nuzzo, M. D.; Friso, S.; Greco, P.; Rosati, F.; Scutiero, G.; Toss, A.
abstract

Background: BRCA1 mutation carriers are recommended to undergo prophylactic risk-reducing salpingo-oophorectomy (RRSO) between the ages of 35 and 40 or when child bearing is complete, with a possible delay until age 40–45 for BRCA2 mutation carriers. Study Question: Primary outcome was the rate of unsuspected cancer findings during RRSO in a region of northern Italy (Emilia Romagna) and secondary outcomes were details of RRSO: age at surgical intervention, the venue of the procedures in relation to the surgical/pathological quality and the rate/role of concomitant opportunistic hysterectomies. Study Design: Multicentre data collection by invitation to report current RRSO practices. Results: A total of 222 RRSOs (54.5 % BRCA1, 34.7 % BRCA2, 1.8 % BRCA1 and BRCA2 combined, 5.8 % BRCA-VUS and 3.2 % BRCA not better specified) were reported from 9 different centres, half in non-university hospitals and the remainder in university hospitals. Breast cancer survivors (56.3 %) underwent the RRSO at a younger age (47.8 vs 50.6 years, p = 0.02). The mean and median ages at surgical intervention (49.0 and 48.0, respectively) were similar for BRCA1 and BRCA2 mutation carriers, as was the temporal trend in age distribution, and proportions treated in university and non-university hospitals. A diagnosis of ovarian invasive cancer was reported in 3.5 % of subjects, all BRCA1 or BRCA-combined subjects, at a median and mean age of 57 years (range 42–68). Abnormal tubal findings, such as serous tubal intraepithelial lesions (STIL) (100 %), secretory cell outgrowth (SCOUT) (100 %) and STIC (71.4 %), were mainly reported by pathologists in university hospitals. Of the 222 procedures, 15 (6.7 %) included hysterectomies: in none of these cases was a primitive uterine endometrioid or serous cancer found. Conclusions: The results from this multicentre regional study should guide future preventive health policies for RRSO in BRCA mutation carriers.


2021 - Role of prenatal magnetic resonance imaging in fetuses with isolated anomalies of corpus callosum: multinational study [Articolo su rivista]
Sileo, Filomena Giulia; Pilu, Gianluigi; Prayer, Daniela; Rizzo, Giuseppe; Khalil, Asma; Managanaro, Lucia; Volpe, Paolo; Van Mieghem, Tim; Bertucci, Emma; Morales Roselló, José; Facchinetti, Fabio; Di Mascio, Daniele; Stampalija, Tamara; Buca, Danilo; Tinari, Sara; Oronzi, Ludovica; Ercolani, Giada; D’Amico, Alice; Matarrelli, Barbara; Cerra, Chiara; Fantasia, Ilaria; Pasquini, Lucia; Masini, Giulia; Olivieri, Claudiana; Ghi, Tullio; Frusca, Tiziana; Dall’Asta, Andrea; Visentin, Silvia; Cosmi, Erich; D’Errico, Ignazio; Villalain, Cecilia; Quintero, Olivia Mendez; Giancotti, Antonella; D’Ambrosio, Valentina; Antonelli, Amanda; Caulo, Massimo; Panar, Valentina; De Santis, Marco; Mappa, Ilenia; Prefumo, Federico; Pinelli, Lorenzo; Loscalzo, Gabriela; Bracalente, Gabriella; Liberati, Marco; Filippi, Elisa; Trincia, Elena; Pateisky, Petra; Kiss, Herbert; Curado, Joana; Almeida, Marta; Santos, Antonia; Galindo, Alberto; D’Antonio, Francesco
abstract

To assess the performance of fetal magnetic resonance imaging (MRI) in detecting associated anomalies in fetuses diagnosed with isolated corpus callosal (CC) anomaly on multiplanar ultrasound evaluation of the fetal brain (neurosonography).


2021 - Satisfaction with prophylactic risk-reducing salpingo-oophorectomy in BRCA mutation carriers is very high and little dependent on the participants' characteristics at surgery: a prospective study [Articolo su rivista]
Grandi, Giovanni; Sammarini, Margaret; Cortesi, Laura; Toss, Angela; Botticelli, Laura; Varliero, Federico; Sighinolfi, Giovanna; Barbieri, Elena; Facchinetti, Fabio
abstract


2021 - Serial cervical-length measurements after first episode of threatened preterm labor improve prediction of spontaneous delivery prior to 37 weeks' gestation [Articolo su rivista]
Chiossi, G.; Facchinetti, F.; Vergani, P.; Di Tommaso, M.; Marozio, L.; Acaia, B.; Pignatti, L.; Locatelli, A.; Spitaleri, M.; Benedetto, C.; Zaina, B.; D'Amico, R.
abstract

Objective: To assess whether repeat cervical-length (CL) measurement in women discharged from hospital after their first episode of threatened preterm labor can predict their risk of spontaneous preterm birth. Methods: This was a secondary analysis of a randomized controlled trial of maintenance tocolysis, in which CL was measured on transvaginal ultrasound at the time of hospital discharge and after 2, 4, 8 and 12 weeks, in women who remained undelivered after their first episode of threatened preterm labor. After univariate analysis, multivariate logistic regression analysis was used to assess whether CL &lt; 10 mm at the time of hospital discharge or at any follow-up evaluation could predict spontaneous delivery prior to 37 weeks of gestation. Results: Of 226 women discharged after a diagnosis of threatened preterm labor, 57 (25.2%) delivered spontaneously prior to 37 weeks' gestation. The risk of spontaneous preterm birth was higher among women with CL &lt; 10 mm at hospital discharge compared to those with CL ≥ 10 mm (adjusted odds ratio (aOR), 3.3; 95% CI, 1.2–9.2). Moreover, spontaneous preterm delivery was more common when CL &lt; 10 mm was detected up to 2 weeks (aOR, 2.9; 95% CI, 1.1–7.3) or up to 4 weeks (aOR, 7.3; 95% CI, 2.3–22.8) post discharge, as compared with when CL was persistently ≥ 10 mm. The association was not significant when considering CL measurements at 8 weeks, and there was insufficient information to assess the effect of measurements obtained at 12 weeks. Conclusions: Women who remain undelivered after their first episode of threatened preterm labor continue to be at high risk of spontaneous preterm birth if their CL is below 10 mm at the time of hospital discharge or at any follow-up visit up to 4 weeks later. CL measurement could be included in the antenatal care of these women in order to stratify their risk of preterm birth, rationalize resource utilization and help clinicians improve pregnancy outcome. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.


2021 - Surgical treatment of deep endometriosis with adenomyosis externa: a challenging case in an infertile woman [Articolo su rivista]
Alboni, C.; Mattos, L. C.; Botticelli, L.; Malmusi, S.; Facchinetti, F.; Pecchi, A.
abstract

Objective: To describe the management and the fertility-enhancing potential of surgery in an infertile patient with deep-infiltrating endometriosis and adenomyosis externa. Design: Video case report. Setting: Minimally invasive and robotic gynecologic surgery unit of a university hospital. Patient(s): A 31-year-old nulliparous patient with dysmenorrhea, dysuria, dyspareunia, and primary infertility. Intervention(s): Bimanual examination, transvaginal ultrasound, and magnetic resonance imaging (MRI) were performed as a comprehensive preoperative workup. The findings were consistent with bladder endometriosis and a 4-cm right pararectal cystic mass suggestive of adenomyosis externa. Laparoscopic excision of all visible endometriosis was performed. A pararectal lesion was found, completely developing in the retroperitoneal spaces, from the right medial pararectal space to the rectovaginal space, reaching the pelvic floor fascia without infiltration of the levator ani muscle. According to Koninckx classification, this kind of lesion corresponds to type III endometriosis or adenomyosis externa. Nerve-sparing eradication of the nodule was performed. The decision to use these techniques was taken with the intention to treat the patient, and not with the aim of testing the procedures performed. Therefore, as a common clinical practice in our institution and for the above reasons, there was no need for consultation of the institutional review board for approval. Main Outcome Measure(s): Improvement of symptoms and spontaneous conception after surgical removal of all endometriotic implants. Result(s): There were no intraoperative or postoperative complications, and the patient was discharged after 3 days. She discontinued postoperative hormone therapy with gonadotropin-releasing hormone analogue after 3 months because she desired fertility. She conceived spontaneously after 2 months of attempting. She delivered vaginally and had no complications during pregnancy and labor. Neither recurrence of pain symptoms nor voiding or rectal dysfunctions were reported by the patient. Conclusion(s): In the management of a case of deep endometriosis, the preoperative assessment should be carefully carried out to give the surgeon the most accurate information about the extent of the disease and the patient's main objectives. Imaging techniques such as ultrasound and MRI play a fundamental role along with the clinical evaluation in also detecting lesions that are not visible at first laparoscopic inspection. In this case of a young woman without any detectable fertility issues except for endometriosis, the laparoscopic excision of endometriosis was feasible, safe, and effective in improving the patient's fertility and pain symptoms. The fertility-enhancing potential of complete eradication of pelvic endometriosis, including removal of deep posterior localizations such those presented in this case, has been hypothesized by various investigators. It has been suggested that skilled surgical management for symptomatic deep endometriosis may be followed by a high pregnancy rate, with most pregnancies resulting from postoperative natural conception even in patients with primary infertility.


2021 - The appropriate counseling on prenatal screening test for foreign women in Emilia-Romagna [Articolo su rivista]
Menichini, Daniela; Sciutti, Giovanna; Miano, Maria Vittoria; Ricchi, Alba; Infante, Ramona; Molinazzi, Maria Teresa; Bertucci, Emma; Facchinetti, Fabio; Neri, Isabella
abstract

Objective: The increase in the migratory phenomenon entails the need to adapt obstetric care to the population which includes foreign pregnant women. In this context, it emerged a little adherence to the prenatal screening test among foreign women compared to Italian women, which is assumed to be attributable to an inadequate counseling. This study aims to evaluate midwife's perception of the&nbsp;&nbsp;counseling effectiveness in foreign women for the combined test and subsequently assess its adequacy through an external evaluation. Methods: this is a cross-sectional study conducted from September to November 2019. An ad hoc questionnaire was administered to midwives working in the territorial district of the Emilia-Romagna Region, investigating their counseling skills. Then an external evaluation of the counseling was conducted by observing the interview between the midwives and the patients (N = 10), to analyze its appropriateness. Results: Seventy-five midwives completed the questionnaire with a positive response rate of 57.2%. In general, 69.3% of midwives are satisfied with the training received from the regional course, but 85% found many difficulties in counseling foreign women. The 14% of midwives state that they always have the cultural and linguistic mediator available and 44% of them state that they use brochures translated into several foreign languages. In the interviews observed, the counseling to foreign women was found to be shorter and more limited than that provided to Italian women. Conclusions: Most of the consulting midwives declare that they feel prepared to perform a correct prenatal counseling also for foreign women, but the external evaluation of the interviews, and the regional data on adherence to the antenatal screening of foreign women, show many critical points. It becomes necessary to carry out further studies that investigate not only the counseling skills of midwives, but also the needs of assisted women about prenatal diagnosis.


2021 - The challenging screen detection of ovarian cancer in BRCA mutation carriers adhering to a 6-month follow-up program: results from a 6-years surveillance [Articolo su rivista]
Grandi, G.; Fiocchi, F.; Cortesi, L.; Toss, A.; Boselli, F.; Sammarini, M.; Sighinolfi, G.; Facchinetti, F.
abstract

OBJECTIVE: Approximately 25% of ovarian cancer (OC) cases are related to an inherited predisposition. Genetic mutations for the oncosuppressor genes BRCA1 and 2 have the best-known linkage to a higher incidence of OC and breast cancer, in approximately 70% to 80% of hereditary OC cases. To provide the first comprehensive clinical description of screen-detected (SD) OCs during a 6-years surveillance of a cohort of young BRCA carriers and carriers who refuse risk-reducing salpingo-oophorectomy. METHODS: A prospective cohort study in a university hospital describing 191 women with BRCA1 and 2 mutations adhering continuously to our surveillance between 2015 and 2020, including a 6-monthly evaluation of cancer antigen 125 (CA 125) with concomitant transvaginal ultrasound (TVUS) performed by a dedicated specialist. Main outcomes were tumor's laterality, CA 125 at diagnosis, TVUS and computed tomography (CT) findings. RESULTS: Risk-reducing salpingo-oophorectomy was performed in 58/191 (30.4%) of mutation carriers during the study period (one OC case identified). Nine SD-OCs and no interval OCs were found in the remaining 133 women. OCs (FIGO stage I or II: 88.9%) occur mainly in BRCA 1 (77.8%), being bilateral in 85.7% BRCA 1 and unilateral in 100% BRCA 2. No lesions involved only the tubes: left ovaries/tubes were more frequently involved. We have described three new possible scenarios regarding imaging: 1) Evident cases (33.3%, TVUS and CT obvious for OC, CA 125 sensitivity: 100%), 2) Possible cases (55.6%, TVUS and CT are in general accordance, documenting new TVUS signs: increased solid pattern of the ovary with peripheral cortical small cysts, hypoechoic circular mass near the ovary, intraparenchymal small hyperechoic foci), and 3) Hidden cases (11.1%, the smallest lesion but the highest stage (IIIA2), with CA 125 44.2 U/mL and concomitant endometrial hyperplasia). CONCLUSIONS: Different diagnostic tools must integrate to ensure early diagnosis of OC in BRCA mutation carriers adhering to a follow-up program.


2021 - The establishment of the experts group on inositol in basic and clinical research (EGOI), a scientific association of the foremost experts on inositol applications [Articolo su rivista]
Unfer, V.; Facchinetti, F.
abstract


2021 - The importance of myo-inositol and D-chiro-inositol to support fertility and reproduction [Articolo su rivista]
Facchinetti, F.; Dewailly, D.; Soulage, C. O.; Unfer, V.; Marialuisa, A.; Cesare, A.; Daniele, B.; Salvatore, B.; Arturo, B.; Salome, B. E. M.; Mariano, B.; Tonino, C.; Pietro, C.; Shiao-Yng, C.; Yu, C. T. T.; Copp Andrew, J.; D'Anna, R.; Di Lorenzo, C.; Evanthia, D. -K.; Simona, D.; Greene Nicholas, D.; Imelda, H. M.; Moshe, H.; Zdravko, K.; Kandaraki Eleni, A.; Simone, L. A.; Giovanni, M.; Mario, M. O.; Nestler John, E.; Maurizio, N.; Cenk, O. A.; Olga, P.; Lali, P.; Giuseppina, P.; Nikos, P.; Roseff Scott, J.; Annarita, S.; Hebe, V. -L. M.; Ivana, V.; Artur, W.
abstract

This review details the physiologic roles of two insulin sensitizers, myo-inositol (MI) and D-chiro-inositol (DCI). In the human ovary, MI is a second messenger of follicle stimulating hormone (FSH) and DCI is an aromatase inhibitor. These activities allow a treatment for polycystic ovary syndrome (PCOS) to be defined based on the combined administration of MI and DCI, where the best MI:DCI ratio is 40:1. In addition, MI plays a pivotal role in the physiology of reproduction, and has beneficial effects on the development of oocytes, spermatozoa, and embryos. By contrast, DCI has little effect on spermatozoa, but high concentrations in the ovary can negatively affect the quality of oocytes and the blastocyst. Overall, the evidence in the literature supports the beneficial effects of MI in both female and male reproduction, warranting clinical use of MI in assisted reproductive treatment (ART).


2021 - The paradigm of norgestimate: a third-generation testosterone-derivative progestin with a peripheral anti-androgenic activity and the lowest risk of venous thromboembolism [Articolo su rivista]
Grandi, G.; Del Savio, M. C.; Facchinetti, F.
abstract

Introduction: Norgestimate (NGM) is a testosterone derivative with peculiar receptor activities. Areas covered: This is a narrative review of the available data on the pharmacotherapy of NGM in combined hormonal contraceptives (CHCs) in terms of contraceptive efficacy, venous thromboembolism (VTE) risk, safety, tolerability and bleeding patterns. A comprehensive literature review was conducted in August 2020 using PubMed with the keyword ‘norgestimate’. Expert Opinion: NGM shows a mild estrogenic activity associated with anti-mineralocorticoid and anti-androgenic properties, largely responsible for the cardiovascular safety profile. The anti-androgenic property depends on the androgen receptor (AR) nuclear translocation (AR trafficking and its subnuclear distribution), the inhibition of 5α-reductase activity (it possesses higher activity compared to other available progestins), and the increase on sexual hormone binding globulin (SHBG) levels if combined with an estrogenic counterpart. NGM is one of the molecules that best modulates the power of ethinyl-estradiol on the thromboembolic risk, being associated with the lowest VTE risk between different CHCs. NGM has the advantage of retaining peripheral anti-androgenic activity, demonstrated by the impact on lipid and glucose metabolism, and it should be preferred if compared with other similar progestins of the same class of risk which are much more androgenic, such as levonorgestrel.


2021 - Treatment of menopausal symptoms: concomitant modification of cortisol [Articolo su rivista]
Cagnacci, A.; Xholli, A.; Fontanesi, F.; Neri, I.; Facchinetti, F.; Palma, F.
abstract

OBJECTIVES: To evaluate whether change in menopausal symptoms is related to modification of 24-hour urinary cortisol. METHODS: Sixty-nine postmenopausal women were treated for their menopausal symptoms with either estrogen progestin therapy (0.3 mg conjugate equine estrogens and 1.5 mg medroxyprogesterone acetate; n = 25), phytoestrogens (75 mg isoflavones, twice daily; n = 21) or acupuncture (once a week; n = 23). Baseline and treatment-induced changes of total and subscale scores (vasomotor, depression, anxiety, somatization, sexuality) of the Greene's Climacteric Scale and of 24-hour urinary cortisol were evaluated. RESULTS: At baseline, 24-hour urinary cortisol was related to Greene's Climacteric Scale score (P &lt; 0.0001). Independent determinants (R2 = 0.319) were the Greene's subscales scores of depression (with a mean difference of 24-h cortisol for score unit expressed as beta coefficient of regression (b) of 4.91, 95% CI 2.14-7.7; P = 0.0007), and of somatization (b 3.04 95% CI 0.69-5.4; P = 0.012). The Greene's Climacteric Scale score (-5.67 ± 6.8; P = 0.0001) and 24-hour cortisol (-23.6 ± 45.7 μg/24 h; P = 0.0001) declined after 3 months of treatment. Changes of 24-hour cortisol values were linearly related to changes of total Greene's Climacteric Scale score with a mean change for unit score (b) of 2.10, 95% CI 0.47-3.73; P = 0.012). CONCLUSIONS: Present data indicate that greater reduction in menopausal symptoms is associated with a larger decrease in cortisol levels. Possible implication of this finding on the long-term consequences for women's health needs to be explored.


2021 - Vertebral artery dissection in term pregnancy after cervical spine manipulation: a case report and review the literature [Articolo su rivista]
Monari, F.; Busani, S.; Imbrogno, M. G.; Neri, I.; Girardis, M.; Ghirardini, A.; Cavalleri, F.; Facchinetti, F.
abstract

Background: Vertebral artery dissection is an uncommon, but potentially fatal, vascular event. This case aimed to describe the pathogenesis and clinical presentation of vertebral artery dissection in a term pregnant patient. Moreover, we focused on the differential diagnosis, reviewing the available evidence. Case presentation: A 39-year-old Caucasian woman presented at 38&nbsp;+&nbsp;4&nbsp;weeks of gestation with a short-term history of vertigo, nausea, and vomiting. Symptoms appeared a few days after cervical spine manipulation by an osteopathic specialist. Urgent magnetic resonance imaging of the head was obtained and revealed an ischemic lesion of the right posterolateral portion of the brain bulb. A subsequent computed tomography angiographic scan of the head and neck showed a right vertebral artery dissection. Based on the correlation of the neurological manifestations and imaging findings, a diagnosis of vertebral artery dissection was established. The patient started low-dose acetylsalicylic acid and prophylactic enoxaparin following an urgent cesarean section. Conclusion: Vertebral artery dissection is a rare but potential cause of neurologic impairments in pregnancy and during the postpartum period. It should be considered in the differential diagnosis for women who present with headache and/or vertigo. Women with a history of migraines, hypertension, or autoimmune disorders in pregnancy are at higher risk, as well as following cervical spine manipulations. Prompt diagnosis and management of vertebral artery dissection are essential to ensure favorable outcomes.


2020 - An update on the use of inositols in preventing gestational diabetes mellitus (GDM) and neural tube defects (NTDs) [Articolo su rivista]
Facchinetti, F.; Cavalli, P.; Copp, A. J.; D'Anna, R.; Kandaraki, E.; Greene, N. D. E.; Unfer, V.
abstract

Introduction: Obstetric history and maternal body composition and lifestyle may be associated with serious complications both for the mother, such as gestational diabetes mellitus (GDM), and for the fetus, including congenital malformations such as neural tube defects (NTDs). Areas covered: In view of the recent knowledge, changes in nutritional and physical activity habits ameliorate glycemic control during pregnancy and in turn improve maternal and neonatal health outcomes. Recently, a series of small clinical and experimental studies indicated that supplemenation with inositols, a family of insulin sensitizers, was associated with beneficial impact for both GDM and NTDs. Expert opinion: Herein, we discuss the most significant scientific evidence supporting myo-inositol administration as a prophylaxis for the above-mentioned conditions.


2020 - Blood pressure and cardiovascular risk factors in women treated for climacteric symptoms with acupuncture, phytoestrogens, or hormones [Articolo su rivista]
Palma, F.; Fontanesi, F.; Neri, I.; Xholli, A.; Facchinetti, F.; Cagnacci, A.
abstract

Objective: To evaluate the response of cardiovascular risk factors to the treatment of climacteric symptoms. Methods: In this prospective study, women reporting climacteric symptoms were randomized to 3 months of treatment with either acupuncture (n ¼ 19), phytoestrogens (75 mg soy isoflavones, BID; n ¼ 22), or low-dose hormone therapy (HT; 0.3 mg conjugated equine oestrogens plus 1.5 mg medroxyprogesterone acetate; n ¼ 20). Greene’s climacteric scale, blood pressure (BP), lipids, glucose, insulin, and homeostatic model assessment of insulin resistance were assessed before and after treatment. Observed changes were compared by analysis of variance. Results: HT and acupuncture reduced Greene climacteric score to a similar extent, but the effect of phytoestrogens was significantly lower (P &lt; 0.05). With acupuncture, systolic (-7.4 ± 15.3 mm Hg; P &lt; 0.05) and diastolic BP (-8.3 ± 7.7mm Hg; P &lt; 0.01) decreased, and the same occurred with phytoestrogens (-8.4 ± 9.0 mm Hg [P &lt; 0.01] and -6.6 ± 7.9 mm Hg [P &lt; 0.01]). Neither BP systolic (1.9 ± 17.5 mm Hg) nor BP diastolic (-1.4 ± 9.6 mm Hg) changed during HT. Low-density lipoprotein cholesterol decreased with phytoestrogens (-9.9 ± 19.6 mg/ dL; P &lt; 0.05), and triglycerides increased with both HT (34.5 ± 12.2 mg/dL; P &lt; 0.01) and phytoestrogens (17.41 ± 24.4 mg/dL; P &lt; 0.01). A slight but significant increase in homeostatic model assessment of insulin resistance (0.14 ± 0.5; P &lt; 0.05) was observed after HT. Conclusions: Treatment of climacteric symptoms with acupuncture and phytoestrogens, but not HT, is associated with a clear BP reduction, and phytoestrogens with potentially positive alterations in low-density lipoprotein cholesterol level.


2020 - Breakthroughs in the Use of Inositols for Assisted Reproductive Treatment (ART) [Articolo su rivista]
Facchinetti, F.; Espinola, M. S. B.; Dewailly, D.; Ozay, A. C.; Prapas, N.; Vazquez-Levin, M.; Wdowiak, A.; Unfer, V.; Appetecchia, M.; Aragona, C.; Bertelli, M.; Bevilacqua, A.; Bizzarri, M.; Cavalli, P.; Copp, A.; D'Anna, R.; Greene, N.; Marin, I. H.; Kamenov, Z. A.; Kandaraki, E.; Diamanti-Kandarakis, E.; Lagana, A. S.; Monastra, G.; Oliva, M. M.; Nestler, J. E.; Papalou, O.; Pkhaladze, L.; Porcaro, G.; Soulage, C. O.; Stringaro, A.
abstract

It is well known that myo-inositol (MI) and D-chiro-inositol (DCI) are insulin-sensitizing agents, and MI is of proven utility in polycystic ovary syndrome (PCOS). In addition, MI plays a pivotal role in the physiology of reproduction, and has beneficial effects on the development of oocytes, spermatozoa, and embryos. By contrast, DCI has little effect on spermatozoa, but high concentrations in the ovary can negatively affect the quality of oocytes and the blastocyst. Overall, the evidence in the literature supports the beneficial effects of MI in both female and male reproduction, warranting clinical use of MI in assisted reproductive treatment (ART).


2020 - Child growth, neurodevelopment and pre and postnatal exposure to phthalates: first exposure data [Abstract in Rivista]
Maione, D; Lucaccioni, L; Arletti, M; Panciroli, G; Poluzzi, F; Ferrari, A; Facchinetti, F; Fantuzzi, G; Righi, E
abstract


2020 - Clinical Findings and Disease Severity in Hospitalized Pregnant Women With Coronavirus Disease 2019 (COVID-19) [Articolo su rivista]
Savasi, Valeria M; Parisi, Francesca; Patanè, Luisa; Ferrazzi, Enrico; Frigerio, Luigi; Pellegrino, Antonio; Spinillo, Arsenio; Tateo, Saverio; Ottoboni, Mariacristina; Veronese, Paola; Petraglia, Felice; Vergani, Patrizia; Facchinetti, Fabio; Spazzini, Donata; Cetin, Irene
abstract

To investigate the clinical evolution of coronavirus disease 2019 (COVID-19) in hospitalized pregnant women and potential factors associated with severe maternal outcomes.


2020 - Contemporary prescriptions pattern of different dose levonorgestrel-releasing intrauterine systems in an Italian service for family planning [Articolo su rivista]
Grandi, G.; De Fata, R.; Varliero, F.; Del Savio, M. C.; Facchinetti, F.
abstract

Objective: Current research informations fail to adequately inform about when levonorgestrel-releasing intrauterine system (LNG-IUS) 52 mg is used instead of other lower dose LNG-IUSs (13.5 and 19.5 mg) and other long-acting reversible contraceptives (LARCs) in clinical practice. Methods: A retrospective cohort study was performed in a third-level Service for Family Planning of Modena University hospital about all the first modern contraceptives prescriptions in the whole year 2019 performed by the same group of physicians. All women included underwent a detailed transvaginal ultrasound (TVUS) at prescription and a second evaluation within 3 months when they were still using the prescribed method. Results: To 69/160 (43.1%) women a short-acting reversible contraceptive (SARC), while to 91/160 (56.9%) a LARC was prescribed. Women with a LARC prescription were older than them with a short-acting (SARC) (p &lt;.0001). Women with LNG-IUS 52 mg prescription were significantly the oldest (42.9 ± 5.3), while those with intrauterine copper device and lower dose LNG-IUS were of similar age (36.5 ± 7.3 and 34.9 ± 2.3), significantly lower (p &lt;.005). Women with implant prescription had the same age as SARC, being the youngest (30.7 ± 8.9 and 31.0 ± 9.5) (p &lt;.0001). Women with LNG-IUS 52 mg prescription mg presented with bigger uterine volume (p =.001). In multivariate analyses, the LNG-IUS 52 mg prescription was significantly linked only to age (OR 1.24; 95% CI 1.11–1.37, p &lt;.0001) and presence of adenomyosis (OR 4.56; 95% CI 1.45-14.33, p =.009). Conclusions: The use of LNG-IUS 52 mg instead of other LARCs is preferred for older women, with uteri of increased volume due to adenomyosis, suggesting a possible differential use of available LNG-IUSs in the contemporary clinical practice.


2020 - Drospirenone 4 mg-only pill (DOP) in 24+4 regimen: a new option for oral contraception [Articolo su rivista]
Chiara Del Savio, M.; De Fata, R.; Facchinetti, F.; Grandi, G.
abstract

Introduction: The use of progestin-only pills (POPs) is still relatively infrequent, mainly for their unpredictable effect on menstrual bleeding. A new POP consisting of 4 mg drospirenone (DRSP) for 24 days plus 4-day hormone-free interval has been developed to address this need. DRSP is a potent progestin analogue of spironolactone, with antiandrogenic and antimineralocorticoid properties. Areas covered: This is a narrative review of the available data on the pharmacotherapy of the new DRSP-only pill. The research includes aspects of pharmacokinetics/pharmacodynamics of the compound: the main focus is on the clinical effects of DRSP-only pill in terms of contraceptive efficacy, haemostatic effect, safety, tolerability and bleeding patterns. Expert Opinion: The DRSP-only pill presents a similar Pearl Index to that of common combined hormonal contraceptives: it is a POP with a better bleeding profile than traditional POPs (higher rates of scheduled bleedings and much lower rates of unscheduled intracyclic bleeding/spotting) which could increase its acceptability and the panorama of possible users. For these reasons, DRSP-only pill represents a real step forward in oral contraception with only progestins, even if the bleeding patterns during its use are still different to oestrogen-containing products (i.e. lower rates of scheduled bleedings and higher rate of amenorrhea).


2020 - Effectiveness of Progestogens as Maintenance Tocolysis and Urogenital Cultures: Secondary Analysis of the PROTECT Trial [Articolo su rivista]
Pignatti, L.; D'Amico, R.; Vergani, P.; Di Tommaso, M.; Acaia, B.; Benedetto, C.; Facchinetti, F.
abstract

Background In a recently published multicenter randomized controlled trial, we demonstrated that progestogens are not effective as maintenance tocolysis. Objective This study was aimed to evaluate if previous finding may be affected by positive urine culture and/or vaginal swab. Study Design We performed a secondary analysis of the PROTECT trial (NCT01178788). Women with singleton pregnancy between 22 and 31 6/7weeks' gestation, admitted for threatened preterm labor were considered. At admission, we collected urine culture and vaginal swabs. At discharge, women with a cervical length ≤25 mm were randomized to vaginal progesterone or 17α-hydroxyprogesterone caproate or observation group. We used Chi-square statistics, considering 97.5% CI (confidence interval) and p -value less than 0.025 for significance. Results Urine culture and vaginal swabs were collected in 232 out of 235 patients included in the primary analysis. Overall, 31 out of 232 women (13.4%) had positive urine culture and 60 out of 232 (25.9%) had positive vaginal swab. In women with negative urine culture, a higher rate of preterm birth was found in vaginal progesterone group (27/69, 39.7%) respect with controls (14/68, 20.6%; relative risk [RR] = 1.90; 97.5% CI: 1.01-3.57; p = 0.018). Conclusion Among women with negative urine culture, the rate of preterm birth &lt;37 weeks' gestation was significantly increased in those receiving vaginal progesterone, reinforcing our previous findings in symptomatic women.


2020 - Effects of vitamin D supplementation in women with polycystic ovary syndrome: a review [Articolo su rivista]
Menichini, D.; Facchinetti, F.
abstract

Increasing evidence supports the contribution of vitamin D deficiency (VDD) in metabolic disturbances among women with polycystic ovary syndrome (PCOS). This review aims to assess the associations between vitamin D levels and metabolic/endocrine dysregulations and to determine the effects of vitamin D supplementation on glucose metabolism, insulin sensitivity, lipid profile, and hormones functionality in PCOS patients. We searched in PubMed human randomized controlled trials (RCTs) published in English between 2016 and 2019 on the effects of vitamin D supplementation on PCOS. Nine studies were included and analyzed. Vitamin D supplementation restored physiological serum 25(OH)D levels in PCOS women in all the studies included. In six studies, it significantly decreased fasting plasma glucose and brought to improvements in insulin resistance (IR) and serum fasting insulin. In addition, four studies reported decreases of serum triglycerides, while discordant data are reported as far as LDL, HDL, and total cholesterol levels. High-doses of vitamin D (4000 IU), compared with low-dose (1000 IU), and placebo, showed beneficial effects on total testosterone, sex hormone-binding globulin (SHBG) and free androgen index (FAI). Vitamin D supplementation at high doses for a period of at least 12&nbsp;weeks, may lead to improvement in terms of glucose level, insulin sensitivity, hyperlipidemia, and hormonal functionality in PCOS women.


2020 - Estetrol (E4): the new estrogenic component of combined oral contraceptives [Articolo su rivista]
Grandi, Giovanni; Chiara Del Savio, Maria; Lopes da Silva-Filho, Agnaldo; Facchinetti, Fabio
abstract


2020 - Experts’ opinion on inositols in treating polycystic ovary syndrome and non-insulin dependent diabetes mellitus: a further help for human reproduction and beyond [Articolo su rivista]
Facchinetti, F.; Appetecchia, M.; Aragona, C.; Bevilacqua, A.; Bezerra Espinola, M. S.; Bizzarri, M.; D'Anna, R.; Dewailly, D.; Diamanti-Kandarakis, E.; Hernandez Marin, I.; Kamenov, Z. A.; Kandaraki, E.; Lagana, A. S.; Monastra, G.; Montanino Oliva, M.; Nestler, J. E.; Orio, F.; Ozay, A. C.; Papalou, O.; Pkhaladze, L.; Porcaro, G.; Prapas, N.; Soulage, C. O.; Stringaro, A.; Wdowiak, A.; Unfer, V.
abstract

Introduction: This Experts’ opinion provides an updated scientific support to gynecologists, obstetricians, endocrinologists, nutritionists, neurologists and general practitioners on the use of Inositols in the therapy of Polycystic Ovary Syndrome (PCOS) and non-insulin dependent (type 2) diabetes mellitus (NIDDM). Areas covered: This paper summarizes the physiology of Myo-Inositol (MI) and D-Chiro-Inositol (DCI), two important molecules present in human organisms, and their therapeutic role, also for treating infertility. Some deep differences between the physiological functions of MI and DCI, as well as their safety and intestinal absorption are discussed. Updates include new evidence on the efficacy exerted in PCOS by the 40:1 MI/DCI ratio, and the innovative approach based on alpha-lactalbumin to overcome the decreased therapeutic efficacy of Inositols in some patients. Expert opinion: The evidence suggests that MI, alone or with DCI in the 40:1 ratio, offers a promising treatment for PCOS and NIDDM. However, additional studies need to evaluate some still unresolved issues, such as the best MI/DCI ratio for treating NIDDM, the potential cost-effectiveness of reduced gonadotropins administration in IVF due to MI treatment, or the benefit of MI supplementation in ovulation induction with clomiphene citrate in PCOS patients.


2020 - Inositols in Polycystic Ovary Syndrome: An Overview on the Advances [Articolo su rivista]
Facchinetti, F.; Unfer, V.; Dewailly, D.; Kamenov, Z. A.; Diamanti-Kandarakis, E.; Lagana, A. S.; Nestler, J. E.; Soulage, C. O.
abstract

This review details the physiologic roles of two insulin sensitizers, myo-inositol (MI) and D-chiro-inositol (DCI). In the human ovary, MI is a second messenger of follicle-stimulating hormone (FSH) and DCI is an aromatase inhibitor. These activities allow a treatment for polycystic ovary syndrome (PCOS) to be defined based on the combined administration of MI and DCI, where the best MI:DCI ratio is 40:1. Moreover, MI enhances the effect of metformin and clomiphene on the fertility of PCOS women seeking pregnancy. As impaired intestinal transport may lead to unsuccessful inositol treatment, we also discuss new data on the use of alpha-lactalbumin to boost inositol absorption. Overall, the physiological activities of MI and DCI dictate the dosages and timing of inositol supplementation in the treatment of PCOS.


2020 - Lactational exposure to phthalate monoesters among breastfed infants in Italy. [Abstract in Rivista]
Arletti, M; Maione, D; Fioretti, E; Panciroli, G; Predieri, G; Pinetti, D; Bargellini, A; Facchinetti, F; Fantuzzi, G; Righi, E
abstract


2020 - Magnesium supplementation in obstetrics and gynaecology: A brief review [Articolo su rivista]
Diamanti, M.; Facchinetti, F.
abstract

Magnesium (Mg), is the second most important intracellular cation. It has been recognized as a cofactor for more than 325 enzymatic reactions involved in a) protein, DNA and RNA synthesis, b) fat, carbohydrates and protein metabolism, and c) cellular energy production and storage. It is essential for the regulation of muscular contraction, blood pressure, insulin metabolism, cardiac excitability, vasomotor tone, nerve transmission and neuromuscular conduction. On these grounds, the possible therapeutic properties of Mg have been investigated in almost every medical field includ-ing Obstetrics and Gynecology, namely exploring oral supple-mentation. The aim of this study is to briefly review existing evidences on the clinical effects of Mg treatment in perinatology as well as in non-pregnant women. During pregnancy, there is a 15% decrease of Mg circulating levels together with a concomitant 25% increase of urinary excretion. Mg supplementation on blood pressure had few impact while it is useful for the alleviation of uterine hyper-activity. Parenteral administration is a standard for the prophylaxis of Eclampsia as well as for neural protection of early preterm baby. A number of studies highlighted a positive correlation between oral magnesium and relief/ prevention of premenstrual syndrome, dysmenorrhea, and postmenopausal symptoms, thus suggesting that magnesium supplementation may repre-sent a valid treatment for these conditions.


2020 - Marked T cell activation, senescence, exhaustion and skewing towards TH17 in patients with Covid-19 pneumonia. [Articolo su rivista]
De Biasi, S; Meschiari, M; Gibellini, L; Bellinazzi, C; Borella, R; Fidanza, L; Gozzi, L; Iannone, A; Lo Tartaro, D; Mattioli, M; Paolini, A; Menozzi, M; Milić, J; Franceschi, G; Fantini, R; Tonelli, R; Sita, M; Sarti, M; Trenti, T; Brugioni, L; Cicchetti, L; Facchinetti, F; Pietrangelo, A; Clini, E; Girardis, M; Guaraldi, G; Mussini, C; Cossarizza, A.
abstract

We provide an in-depth investigation of the T cell compartment and functionality, cytokine production and plasma levels in a total of 39 patients affected by Covid-19 pneumonia. At admission, patients were lymphopenic; for all, SARS-CoV-2 was detected in a nasopharyngeal swab specimen by real-time RT-PCR, and pneumonia was subsequently confirmed by X-rays. Detailed 18-parameter flow cytometry coupled with unsupervised data analysis revealed that patients showed similar percentages of CD4+ and CD8+ T cells, but a decreased absolute number in both populations. For CD4+ T lymphocytes, we found a significant decrease in the number of naïve, central and effector memory cells and an increased percentage of terminally differentiated cells, regulatory T cells, and of those that were activated or that were expressing PD1 and CD57 markers. Studies on chemokine receptors and lineage-specifying transcription factors revealed that, among CD4+ T cells, patients displayed a lower percentage of cells expressing CCR6 or CXCR3, and of those co-expressing CCR6 and CD161, but higher percentages of 62 CXCR4+ or CCR4+ cells. No differences were noted in the expression of T-bet or GATA-3. Analyses of patients' CD8+ T cells showed decreased numbers of naïve and central memory and increased amounts of activated cells, accompanied by increased percentages of activated cells and of lymphocytes expressing CD57, PD1, or both. CD8+ T cells expressed lower percentages of CCR6+, CXCR3+ or T-bet+ cells and of CXCR3+,T-bet+ or CCR6+,CD161+ lymphocytes. We also found higher percentages of cells expressing CCR4+, CXCR4 or GATA-3. Analyses of lymphocyte proliferation revealed that terminally differentiated CD4+ and CD8+ T cell from patients had a lower proliferative index than controls, whereas cellular bioenergetics, measured by the quantification of mitochondrial oxygen consumption and extracellular acidification rate, was similar in CD4+ T cells from both groups. We measured plasma level of 31 cytokines linked to inflammation, including T helper (TH)type-1 and TH2 cytokines, chemokines, galectins, pro- and anti-inflammatory mediators, finding that most were dramatically increased in Covid-19 patients, confirming the presence of a massive cytokine storm. Analysis of the production of different cytokines after stimulation by anti-CD3/CD28 monoclonal antibodies revealed that patients not only had a high capacity to produce tumour necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-2, but also showed a significant skewing of CD4+ T cells towards the TH17 phenotype. A therapeutic approach now exists based on the administration of drugs that block IL-6pathway, and seems to improve the disease. IL-17 is crucial in recruiting and activating neutrophils, cells that can migrate to the lung and are heavily involved in the pathogenesis of Covid-19. We show here that a skewing of activated T cells towards the TH17 functional phenotype exists in Covid-19 patients. We therefore suggest that blocking the IL-17 pathway by biological drugs that are already used to treat different pathologies could provide a novel, additional strategy to improve the health of patients infected by SARS-CoV-2.


2020 - Maternal Supplementation of Inositols, Fucoxanthin, and Hydroxytyrosol in Pregnant Murine Models of Hypertension [Articolo su rivista]
Menichini, D.; Alrais, M.; Liu, C.; Xia, Y.; Blackwell, S. C.; Facchinetti, F.; Sibai, B. M.; Longo, M.
abstract

BACKGROUND: Myoinositol (M) and D-chiro-inositol (D) are insulin sensitizer compounds, while fucoxanthin (F) and hydroxytyrosol (H) are antioxidant substances. We aim to investigate if the combination of these compounds, will improve the vascular responses in pregnant mouse models of hypertension: a genetic model, transgenic heterozygous mice lacking endothelial nitric oxide synthase gene (eNOS-/+); and environmental, wild-type (WT) mice. Those mouse models will allow a better understanding of the genetic/environmental contribution to hypertension in pregnancy. METHODS: eNOS-/+ and WT female were fed high fat diet for 4 weeks, then at 7-8 weeks of age were mated with WT male. On gestational day (GD) 1, they were randomly allocated to receive MDFH treatment or water as control: eNOS-/+ MDFH (n = 13), eNOS-/+ (n = 13), WT-MDFH (n = 14), and WT (n = 20). Systolic blood pressure (SBP) was obtained at GD 18, then dams were sacrificed; fetuses and placentas collected, and 2 mm segments of carotid arteries isolated for vascular responses using the wire-myograph system. Responses to phenylephrine (PE), with/without the NOS inhibitor (N-nitro-l-arginine methyl ester (l-NAME)), and to acetylcholine (Ach) and sodium nitroprussiate (SNP) were performed. RESULTS: SBP decreased in eNOS-/+ and WT dams after MDFH supplementation. In eNOS-/+, MDFH lower the contractile response to PE and l-NAME and improved Ach vasorelaxation. In WT dams, MDFH treatment did not affect PE response; MDFH treatment lowered the vascular PE response after incubation with l-NAME. No differences were seen in SNP relaxation in both models. CONCLUSIONS: MDFH decreased SBP in both genetically and environmentally hypertensive dams and improved vascular responses mostly in the eNOS-/+ dams.


2020 - MRI of placenta accreta: diagnostic accuracy and impact of interventional radiology on foetal-maternal delivery outcomes in high-risk women [Articolo su rivista]
Fiocchi, Federica; Monelli, Filippo; Besutti, Giulia; Casari, Federico; Petrella, Elisabetta; Pecchi, Annarita; Caporali, Cristian; Bertucci, Emma; Busani, Stefano; Botticelli, Laura; Facchinetti, Fabio; Torricelli, Pietro
abstract

To assess accuracy and reproducibility of MRI diagnosis of invasive placentation (IP) in high-risk patients and to evaluate reliability of MRI features. Secondary aim was to evaluate impact of interventional radiology (IR) on delivery outcomes in patients with IP at MRI.


2020 - Physical activity during pregnancy in Italy: prevalence, intensity and associated factors. [Abstract in Rivista]
Fioretti, E; Palandri, L; Fantuzzi, G; Facchinetti, F; Righi, E
abstract


2020 - Physical activity in low risk pregnant women: a cross-sectional study [Articolo su rivista]
Menichini, D.; Fanetti, O.; Molinazzi, M. T.; Facchinetti, F.; Ricchi, A.; Neri, I.
abstract

OBJECTIVES: The aim of this study is to analyze the quality and quantity of physical activity (PA) practiced by low-risk pregnant women before and during pregnancy. DESIGN: This cross-sectional study assesses the dietary habits, exercise habits and body mass index. We used an ad hoc health lifestyle multiple choice questionnaire. The data collection lasted 7 months, from the beginning of September 2018 to the end of March 2019. POPULATION: We recruited 175 Italian women with a singleton, low-risk pregnancy at 32-36 weeks of gestational age. RESULTS: In the periconceptional period, 52.6 % of women do not perform any PA. For the other 47.4% of women, the most practiced activities, both before and during gestation, are walking and swimming. Data on the sedentariness showed that about a quarter of the population remains inactive watching TV for more than two hours a day. Interestingly, the most statistically significant risk factor for sedentariness is the BMI &gt; 25 kg/m². Therefore, overweight or obese women are more likely to maintain a sedentary lifestyle during pregnancy. CONCLUSIONS AND IMPLICATION FOR THE PRACTICE: Our study highlighted a high rate of sedentariness in pregnancy, especially among overweight and obese women. Thus, it is important to undertake interventions aimed at informing pregnant women of various benefits that PA can bring. In particular, because of the significant association between sedentariness and BMI greater than 25 kg/m2, it results crucial to direct these recommendations particularly to overweight/obese pregnant women, addressing them to a healthy lifestyle.


2020 - Postmenopausal hormone therapy in BRCA gene mutation carriers: to whom and which? [Articolo su rivista]
Grandi, G.; Caroli, M.; Cortesi, L.; Toss, A.; Tazzioli, G.; Facchinetti, F.
abstract

Introduction: Risk-reducing-salpingo-oophorectomy (RRSO) inevitably leads BRCA mutation carriers to premature menopause. Areas covered: To evaluate the existing evidence for use of postmenopausal hormone therapy (HT) in BRCAmc, after RRSO or menopause occurring naturally, for both breast cancer (BC) survivors and those without BC. Expert opinion: All BC survivors are excluded from any HT treatment: in other BRCAmc, before 51&nbsp;years of age the benefits of HT overcome the risks after RRSO and/or premature ovarian insufficiency (POF). After 51&nbsp;years of age, it is important to treat only women with important vasomotor symptoms, after the failure of alternative therapies. Estrogens-only therapy plays a key role in hysterectomized women (HW). In the case of an intact uterus (UW), associations with the lowest dose of progestins/natural progesterone derivatives have to be preferred, as progestins has been shown to play an important role in BC transformation, especially in BRCA1mc. No studies have been performed in BRCAmc with regard to ‘progestin-free’ HT, in particular the old tibolone (both in HW and UW) and the new tissue-selective estrogen complex (in UW). However, preliminary data obtained from the general population are reassuring about the use of these ‘progestin-free’ preparations and BC safety.


2020 - Primary fallopian tube carcinoma (PFTC) in a BRIP-1 mutation carrier: the first case report [Articolo su rivista]
Grandi, G.; Caroli, M.; Alboni, C.; Cortesi, L.; Toss, A.; Barbieri, E.; Botticelli, L.; Facchinetti, F.
abstract

Some hereditary ovarian cancer cases can be associated with a mutation of a gene involved in the DNA double-strand break repair system other than BRCA, such as BRIP1. This mutation is an emerging indication for prophylactic risk-reducing salpingo-oophorectomy (RRSO): however, anomalous tubal pathologic lesions have not yet been reported during RRSO performed for this specific indication (BRIP1), as largely reported for BRCA mutation carriers.An asymptomatic 64-year-old woman with a family history of ovarian and breast cancer agreed to undergo RRSO for a pathogenic variant of the BRIP1 gene (heterozygous NM_032043.2: c.124delT, p. Cys42Valfs) with normal BRCA genes. Histological examination showed the presence of high-grade serous carcinoma of the fimbria of the right tube of a maximum diameter of 0.4 cm (final FIGO stage IIB).The pathogenic mechanism that leads to the development of high-grade serous ovarian/fallopian tube cancer in patients with mutations of BRIP1 should be the same as for patients with mutations of BRCA1 and 2. Our case confirms to consider BRIP1 mutation to be sufficient to justify RRSO at 45–50 years old.


2020 - Robot-Assisted Nerve-sparing Resection of Bilateral Parametrial Deep Infiltrating Endometriosis [Articolo su rivista]
Alboni, C.; Farulla, A.; Facchinetti, F.; Ercoli, A.
abstract

Objective: To demonstrate the surgical steps used to perform a robotic radical parametrectomy in a woman with deep infiltrating endometriosis. Design: Description of the procedure using video. Setting: University hospital, referral center for endometriosis and minimally invasive surgery. Interventions: A 47-year-old woman, with a body mass index of 31 kg/m2, who had undergone a supracervical hysterectomy for fibromatosis 5 years earlier, presented for definitive surgical management of parametrial and rectal endometriosis-associated pain. Robot-assisted nerve-sparing eradication of endometriosis, trachelectomy, and rectal shaving were planned. On the right side, the retroperitoneum was opened to widely expose the ureter, and a right adnexectomy was performed, gently separating the ureter from the diffuse periadnexal fibrosis. Right medial pararectal space was developed, and after right partial uterolysis, a nerve-sparing resection of the posterior parametrial endometriosis was performed. On the left side, endometriotic infiltration penetrated into the lateral and anterior (cranial portion) parametrium, wrapping the left uterine artery and the ureter. Left paravesical and pararectal spaces were developed. The left uterine artery was clipped at its origin, and the resection of the lateral and anterior parametrial nodules was completed following the shape of the nodule, dividing the lesion in 2 parts, and following the plane of the deep uterine vein to avoid excision of the nerve branches from the left inferior hypogastric plexus. Rectal endometriosis was removed by shaving, and the surgery ended with trachelectomy and robotic suture of the vaginal cuff. Conclusion: Robot-assisted laparoscopy is a safe and effective technique for nerve-sparing resection of parametrial endometriosis.


2020 - Surface roughness of different contraceptive vaginal rings: evaluation by scanning electron microscope (SEM) [Articolo su rivista]
Grandi, G.; Timo, A.; Sammarini, M.; Del Savio, M. C.; Facchinetti, F.
abstract

Objective: The aim of the study was to evaluate whether the compositions of the ethylene vinyl acetate (EVA) membrane of two different contraceptive vaginal rings could influence the surface roughness, which is associated with the possible accumulation of vaginal biomass on the rings during use. Methods: We measured and compared the surface roughness of unused vaginal rings, NuvaRing and Ornibel, using a scanning electron microscope (SEM) and dedicated software that can convert SEM images into 3D models. Average roughness (Ra), average quadratic roughness (Rq) and mean height of the irregularities at 10 points (Rz) were calculated. Results: Different thicknesses of the EVA membranes between the two rings were noted. No significant differences were found between the two rings in the three evaluated values of surface roughness (NuvaRing vs Ornibel, respectively: Ra, 1.53 ± 0.14 vs 1.61 ± 0.14 µm, p = 0.141; Rq, 2.03 ± 0.25 vs 2.07 ± 0.16 µm, p = 0.688; Rz, 11.4 ± 3.1 vs 11.4 ± 2.4 µm, p = 0.987). Conclusion: The different composition of the vaginal rings’ EVA membrane is not associated with different surface roughness. Ornibel is equivalent to NuvaRing in terms of surface roughness, despite the different composition of the membrane polymers.


2020 - The Burden of Placental Histopathology in Stillbirths Associated With Maternal Obesity [Articolo su rivista]
Avagliano, L.; Monari, F.; Po', G.; Salerno, C.; Mascherpa, M.; Maiorana, A.; Facchinetti, F.; Bulfamante, G. P.
abstract

OBJECTIVES: Obesity is an increasing health problem that has become a common medical disorder among women of childbearing age, representing worldwide a risk factor for stillbirth. The aim of the study is to evaluate the association between placental histopathologic findings and obesity in stillbirth. METHODS: Placentas were analyzed according to the Amsterdam consensus statement. Histologic findings in stillbirth from obese and lean mothers were analyzed and compared with those observed in liveborn controls. RESULTS: Stillbirth in obese mothers displayed placental pathology in all gestational ages, mostly at term of pregnancy. The most observed placental lesions were those consistent with maternal vascular malperfusion of the placental bed. Decidual arteriopathy and placental infarcts appeared specifically associated with maternal obesity. Moreover, obese women with stillbirth showed the highest cumulative number of placental lesions. CONCLUSIONS: Considering the significant association between stillbirth, maternal obesity, and placental histopathologic findings, health care providers should be aware about the importance of placental examination in obese women, especially in stillborn cases. The high prevalence of lesions consistent with vascular malperfusion of the placental bed suggests that stillbirth prevention strategies in obese women should rely on the development of tools to study and improve decidual artery functioning early in pregnancy.


2020 - The gendered impact of coronavirus disease (COVID-19): do estrogens play a role? [Articolo su rivista]
Grandi, G.; Facchinetti, F.; Bitzer, J.
abstract

Objective: Although sex-disaggregated data for COVID-19 show equal numbers of cases between men and women, there seem to be sex differences in mortality rate and vulnerability to the disease: more men than women are dying. Methods: We have explored the potential role of estrogens in this COVID-19 gendered impact. Results: Estrogens stimulate the humoral response to viral infections, while testosterone and progesterone give an immune suppression of both innate and cell-mediated immune responses. We hypothesise that estrogens, in particular estradiol but also synthetic estrogen such as ethinylestradiol, could protect women from the most serious complications of COVID-19. The use of medications that keep hormonal levels high and stable, such as combined hormonal contraceptive, could therefore play a protective role. These potential benefits overtake the thrombotic risk in healthy women. As stated by the World Health Organization, all modern methods of contraception were safe to use during the COVID-19 pandemic.


2020 - The generally low sensitivity of CA125 for FIGO stage I ovarian cancer diagnosis increases for endometrioid histotype [Articolo su rivista]
Grandi, G.; Perrone, A. M.; Toss, A.; Vitagliano, A.; Friso, S.; Facchinetti, F.; Cortesi, L.; Cascinu, S.; Deiaco, P.
abstract

BACKGROUND: The serum marker CA125 is still the most widely used biomarker for ovarian cancer (OC) diagnosis in gynecological and oncological setting, but its predictive role in early-stage OCis still debated. The aim of this study was to explore the value of CA125 in distinguishing between early-stage OCand borderline ovarian tumor (BOT) and to evaluate the accuracy of CA125 in the detection of early stage OC. METHODS: Aretrospective cohort study was performed at the University Hospital of Bologna (Italy) on 1296 consecutive women suffering from OCor BOT (diagnosed at histology) between 1988-2017. Patients for whom CA125 level was determined preoperatively were included. The positive cut-off level used was &gt;35 U/mL. RESULTS: Of 910 patients, 192 (21.1%) were diagnosed with BOT and 718 (78.9%) with OC. The sensitivity of CA125 for stage IOCwas 54.4 (95% CI: 45.3-63.3) (51.5 for IA, 54.6 for IB, 58.3 for IC), but it increased to 78.0 (95% CI: 63.7-88.0) for stage II. Interestingly, in stage I OC, CA 125 presented a significantly higher sensitivity for the endometrioid histotype [72.4 (95% CI: 52.5-86.5) vs. 49.0 (95% CI: 38.6-59.4), P=0.026]. The positive likelihood ratio of CA125 for early-stage OCcompared to BOT was 1.29 (95% CI: 1.06-1.58). CONCLUSIONS: Despite its limited sensitivity for early-stage OCs, CA125 still represents a useful serum marker to early differentiate between OCs and BOTs. Its sensitivity for stage IOCincreases in endometrioid histotype.


2020 - The impact of an early lifestyle intervention on pregnancy outcomes in a cohort of insulin-resistant overweight and obese women [Articolo su rivista]
Menichini, D.; Petrella, E.; Dipace, V.; Di Monte, A.; Neri, I.; Facchinetti, F.
abstract

Obese women are more likely to have decreased insulin sensitivity and are at increased risk for many adverse pregnancy outcomes. An early lifestyle intervention (LI) may have the potential to reduce the impact of insulin resistance (IR) on perinatal outcomes. We report post hoc analysis of an open-label randomized control trial that includes IR women with body-mass index ≥25 randomly assigned to a LI with a customized low glycemic index diet or to standard care (SC) involving generic counseling about healthy diet and physical activity. Women were evaluated at 16, 20, 28, and 36 weeks of gestation, at which times perinatal outcomes were collected and analyzed. An oral-glucose-tolerance test (OGTT) showed that women in the LI group had lower plasma glucose levels at 120 min at 16–18 weeks of gestation, and at 60 and 120 min at 24–28 weeks. More importantly, these women had a lower rate of large-for-gestational-age (LGA) infants (p = 0.04). Interestingly, the caloric restriction and low-glycemic index diet did not increase the rate of small-for-gestational-age (SGA) babies in the LI group. A lifestyle intervention started early in pregnancy on overweight and obese women had the potential to restore adequate glucose tolerance and mitigate the detrimental role of IR on neonatal outcomes, especially on fetal growth.


2020 - The impact of COVID-19 lockdown on admission to gynecological emergency departments: Results from a multicenter Italian study [Articolo su rivista]
Grandi, G.; Del Savio, M. C.; Caroli, M.; Capobianco, G.; Dessole, F.; Tupponi, G.; Petrillo, M.; Succu, C.; Paoletti, A. M.; Facchinetti, F.
abstract

Objective: To evaluate the impact of the COVID-19 lockdown on admissions to gynecological emergency departments (ED) of three Italian university hospitals with different rates of COVID-19 incidence. Methods: A retrospective study was conducted in the gynecological EDs of Modena (Emilia-Romagna), Sassari and Cagliari (Sardinia) regarding all admissions to gynecological EDs during November 1 to 30, 2019, and March 11 to April 9, 2020 (lockdown period). Results: A total of 691 women (mean age 38.3&nbsp;±&nbsp;14.3&nbsp;years) who were admitted to the gynecological EDs were included. The relative decrease in women evaluated from March 11 to April 9, 2020, was −56.6% (95% confidence interval [CI] 52.2–61.1). Time spent in the ED was also significantly shorter during this period (P=0.02) in comparison to November 1 to 30, 2019. The most evident decrease was observed for pelvic pain (−68.9% [95% CI 60.3–76.7]; −91 cases). The management of women suggests a more effective use of the ED, with higher rates of hospitalization (P=0.001) and recourse to emergent surgeries (P=0.005) and lower rates of discharge to home (P=0.03). Conclusion: The COVID-19 lockdown greatly reduced the rate of admission to gynecological EDs, but the real emergencies were filtered from the more deferrable ones.


2020 - The Italian arm of the PREPARE study: an international project to evaluate and license a maternal vaccine against group B streptococcus [Articolo su rivista]
Berardi, Alberto; Cassetti, Tiziana; Creti, Roberta; Vocale, Caterina; Ambretti, Simone; Sarti, Mario; Facchinetti, Fabio; Cose, Stephen; Heath, Paul; Le Doare, Kirsty
abstract

BACKGROUND: Group B streptococcus (GBS) is a leading cause of sepsis, pneumonia and meningitis in infants, with long term neurodevelopmental sequelae. GBS may be associated with poor pregnancy outcomes, including spontaneous abortion, stillbirth and preterm birth. Intrapartum antibiotic prophylaxis (IAP) is currently the only way to prevent early-onset disease (presenting at 0 to 6days of life), although it has no impact on the disease presenting over 6days of life and its implementation is challenging in resource poor countries. A maternal vaccine against GBS could reduce all GBS manifestations as well as improve pregnancy outcomes, even in low-income countries.MAIN BODY: The term "PREPARE" designates an international project aimed at developing a maternal vaccination platform to test vaccines against neonatal GBS infections by maternal immunization. It is a non-profit, multi-center, interventional and experimental study (promoted by the St George University of London. [UK]) with the aim of developing a maternal vaccination platform, determining pregnancy outcomes, and defining the extent of GBS infections in children and mothers in Africa. PREPARE also aims to estimate the protective serocorrelates against the main GBS serotypes that cause diseases in Europe and Africa and to conduct two trials on candidate GBS vaccines. PREPARE consists of 6 work packages. In four European countries (Italy, UK, Netherlands, France) the recruitment of cases and controls will start in 2020 and will end in 2022. The Italian PREPARE network includes 41 centers. The Italian network aims to collect: GBS isolates from infants with invasive disease, maternal and neonatal sera (cases); cord sera and GBS strains from colonized mothers whose infants do not develop GBS infection (controls).SHORT CONCLUSION: PREPARE will contribute information on protective serocorrelates against the main GBS serotypes that cause diseases in Europe and Africa. The vaccine that will be tested by the PREPARE study could be an effective strategy to prevent GBS disease.


2020 - The reduction of CA 125 serum levels in BRCA 1/2 mutation carriers after risk-reducing salpingo-oophorectomy is only partially associated with surgery: A prospective cohort, other biomarker controlled, study [Articolo su rivista]
Grandi, G.; Del Savio, M. C.; Sammarini, M.; Cortesi, L.; Toss, A.; Piombino, C.; Facchinetti, F.
abstract

Objectives A significant reduction in CA 125 postoperative serum levels was observed after risk-reducing salpingo-oophorectomy (RRSO) in BRCA mutation carriers. In contrast to previous studies, where control groups were absent, we conducted a prospective study including also a screening only group (RSSO refusal) and a group having previously undergone RRSO. Methods Consecutive BRCA1 and BRCA2 mutation carriers, not hysterectomised, &gt;35 years old and with completed childbearing, were recruited. Some women had previously undergone RRSO (previous RRSO group). The others, who had either chosen RRSO (actual RRSO group) or screening only (screening only group), were enrolled (patient-preference trial). A prospective evaluation (basal and 6-month) of CA 125 and CEA (control biomarker) was performed. Results The study consisted of 116 women, 44.8% BRCA1 and 55.2% BRCA2 mutation carriers (n = 25 in the previous RRSO group, n = 29 in the actual RRSO group, n = 62 in the screening only group). For all subjects, we observed a 6-month decrease in CA 125 (-7.8%, P = 0.003), which was significantly linked only to endometriosis history (odds ratio 1.4; 95% confidence interval 1.1-1.8; P = 0.002). Between different groups, we recorded a non-significantly different decrease in CA 125. CEA showed a 6 months significant increase (+15.4%, P &lt; 0.0001), which was similar between groups. Conclusion The decrease in CA 125 in BRCA mutation carriers after RRSO was only partially associated with surgery, depending also on a physiological decline: This is extremely important in their longitudinal monitoring for the prevention of ovarian cancer.


2020 - Use of strictureplasty technique for surgical treatment of ileal endometriosis: a case series [Articolo su rivista]
Alboni, Carlo; Camacho Mattos, Ludovica; Facchinetti, Fabio; Cabry, Francesca; Serra, Francesco; Ricciardolo, Andrea; Mabrouk, Mohamed; Gelmini, Roberta
abstract

Intestinal deep infiltrating endometriosis is the most frequent extragenital localisation and its traditional surgical treatment is segmental resection of the affected tract. The need for implementing alternative techniques in the treatment of intestinal endometriosis arises from those cases of multiple ileal and recto-sigmoidal localisations, in which removing excessive lengths of intestine could lead to a higher rate of adverse events. Ileal endometriosis represents 4.7% of all intestinal localisations, often associated with multiple lesions and yet, to the best of our knowledge, there are no data on techniques other than intestinal resection for its treatment. Since its capacity to solve fibrostenotic lesions without removing centimeters of intestine, strictureplasty is widely implemented in the management of Crohn’s disease. We propose the use of strictureplasty for the treatment of ileal endometriosis. We performed surgical treatment for symptomatic deep infiltrating endometriosis in two patients with either ileal and sigmoidal localisations. We approached ileal nodules with strictureplasty technique, while sigmoidal nodules were removed by traditional segmental resection. No complications occurred and both patients are now asymptomatic after a 12 months-follow up. Therefore, strictureplasty could provide a tool to eliminate small bowel endometriosis maintaining a regular caliber of the ileal tract without modifying its length.


2020 - Vaginal delivery in SARS-CoV-2-infected pregnant women in Northern Italy: a retrospective analysis [Articolo su rivista]
Ferrazzi, E.; Frigerio, L.; Savasi, V.; Vergani, P.; Prefumo, F.; Barresi, S.; Bianchi, S.; Ciriello, E.; Facchinetti, F.; Gervasi, M. T.; Iurlaro, E.; Kustermann, A.; Mangili, G.; Mosca, F.; Patane, L.; Spazzini, D.; Spinillo, A.; Trojano, G.; Vignali, M.; Villa, A.; Zuccotti, G. V.; Parazzini, F.; Cetin, I.
abstract

Objective: To report mode of delivery and immediate neonatal outcome in women infected with COVID-19. Design: Retrospective study. Setting: Twelve hospitals in northern Italy. Participants: Pregnant women with COVID-19-confirmed infection who delivered. Exposure: COVID 19 infection in pregnancy. Methods: SARS-CoV-2-infected women who were admitted and delivered from 1 to 20 March 2020 were eligible. Data were collected from the clinical records using a standardised questionnaire on maternal general characteristics, any medical or obstetric co-morbidity, course of pregnancy, clinical signs and symptoms, treatment of COVID 19 infection, mode of delivery, neonatal data and breastfeeding. Main outcome and measures: Data on mode of delivery and neonatal outcome. Results: In all, 42 women with COVID-19 delivered at the participating centres; 24 (57.1%, 95% CI&nbsp;41.0–72.3) delivered vaginally. An elective caesarean section was performed in 18/42 (42.9%, 95% CI 27.7–59.0) cases: in eight cases the indication was unrelated to COVID-19 infection. Pneumonia was diagnosed in 19/42 (45.2%, 95% CI 29.8–61.3) cases: of these, 7/19 (36.8%, 95% CI 16.3–61.6) required oxygen support and 4/19 (21.1%, 95% CI&nbsp;6.1–45.6) were admitted to a critical care unit. Two women with COVID-19 breastfed without a mask because infection was diagnosed in the postpartum period: their newborns tested positive for SARS-Cov-2 infection. In one case, a newborn had a positive test after a vaginal operative delivery. Conclusions: Although postpartum infection cannot be excluded with 100% certainty, these findings suggest that vaginal delivery is&nbsp;associated with a low risk of intrapartum SARS-Cov-2 transmission to the newborn. Tweetable abstract: This study suggests that vaginal delivery may be associated with a low risk of intrapartum SARS-Cov-2 transmission to the newborn.


2020 - Vitamin D for the prevention of miscarriage and spontaneous preterm birth [Capitolo/Saggio]
Menichini, D.; Facchinetti, F.
abstract

Pregnancy represents a dynamic period with physical and physiological changes in both the mother and the developing fetus. Vitamin D was shown to exert many physiological activities during the very early stages of gestation in perfect synchrony with progesterone. Both the molecules mutually help and reinforce the activity exerted by each one. Vitamin D contributes to prepare the endometrium to be receptive and supports the implantation process and the course of pregnancy through similar pathways to those used by progesterone, giving rise to a significant synergy of action. It is increasingly evident that vitamin D gives an essential support from the luteal phase onwards exerting an important role in the establishment and maintenance of pregnancy through its immunomodulatory action and its effects on inflammation within the placenta, preventing miscarriage and preterm birth (PTB). Thus, it is important to guarantee the appropriate levels of vitamin D before placentation (and trophoblast invasion); however further research is needed to decipher vitamin D requirements of pregnant women and the optimal timing of supplementation, taking into account a variety of lifestyles, body types and baseline vitamin D status. Determining the role of vitamin D in non-classical, immune pathways continues to be a challenge that once answered will substantiate recommendations and public health policies.


2019 - A comprehensive review of hormonal and biological therapies for endometriosis: latest developments [Articolo su rivista]
Barra, F.; Grandi, G.; Tantari, M.; Scala, C.; Facchinetti, F.; Ferrero, S.
abstract

Introduction: Endometriosis is a chronic benign estrogen-dependent disease characterized by the presence of endometriotic glands and stroma outside the uterine cavity. Although combined hormonal contraceptives and progestins, currently available first-line treatments for endometriosis, are efficacious and well tolerated for treating disease-related pain, some women experience partial or no improvement of pain or its recurrence is frequent after discontinuation of the therapies. For these reasons, new drugs are under investigation for the treatment of endometriosis. Areas covered: This review aims to give to the reader a complete and updated overview of hormonal and biological therapies for the treatment of endometriosis, underlining the latest developments in this field of research. Expert opinion: Among the new drugs investigated, late clinical trials on gonadotropin-releasing hormone (GnRH) antagonists and aromatase inhibitors (AIs) have demonstrated the most promising results. For this reason, elagolix, a new GnRH-antagonist, recently received the approval by the Food and Drug Administration (FDA) for treating pain associated to endometriosis. Other drugs with innovative targets have been identified, but the majority of these compounds have only been evaluated in pre-clinical studies or early clinical trials. Thus, a further extensive clinical research is necessary to better elucidate their pharmacologic characteristics, their efficacy, and safety for the treatment of this benign chronic disease.


2019 - A regional audit system for stillbirth: A way to better understand the phenomenon [Articolo su rivista]
Po, G.; Monari, F.; Zanni, F.; Grandi, G.; Lupi, C.; Facchinetti, F.; Mancini, L.; Lugli, L.; Lanzoni, C.; Sgarbi, L.; Chiossi, C.; Ricchieri, F.; Roberta, C.; Contiero, R.; Garani, G.; Pedriali, M.; Rossi, S.; Fini, S.; Di Bartolo, M.; Radi, D.; Vancini, A.; Donati, A.; Guadalupi, E.; Righetti, F.; Salerno, A.; Cocchi, G.; Morandi, R.; Gabrielli, L.; Graziano, C.; Seri, M.; Caprara, G.; Mario, S. N. C.; Fantuz, F.; Ferlini, F.; Righi, E.; Silvestrini, D.; Foschi, F.; Fieni, S.; Frusca, T.; Ferretti, A.; Galli, L.; Magnani, C.; Silini, E.; Balduzzi, L.; Bellini, M.; Rodolfi, A. M.; Sgarabotto, M. P.; Fragni, G.; Comitini, G.; Bonasoni, M. P.; Fioroni, L.; Rozzi, C.; Tuzio, A.; Vito, I.; Mammoliti, P.; De Ambrosi, E.; Ricci, M.; Bandini, A.; Belosi, C.; Muratori, C.; Zago, S.; Turci, A.; Vitarelli, M.
abstract

Background: Implementation of high-quality national audits for perinatal mortality are needed to improve the registration of all perinatal deaths and the identification of the causes of death. This study aims to evaluate the implementation of a Regional Audit System for Stillbirth in Emilia-Romagna Region, Italy. Methods: For each stillbirth (≥ 22 weeks of gestation, ≥ 500 g) occurred between January 1, 2014 to December 1, 2016 (n = 332), the same diagnostic workup was performed and a clinical record with data about mother and stillborn was completed. Every case was discussed in a multidisciplinary local audit to assess both the cause of death (ReCoDe classification) and the quality of care. Data were reviewed by the Regional Audit Group. Stillbirth rates, causes of death and the quality of care were established for each case. Results: Total stillbirth rate was 3.09 per 1000 births (332/107,528). Late stillbirth rate was 2.3 per 1000 (251/107,087). Sixteen stillbirths were not registered by the Regional Birth Register. The most prevalent cause of death was placental disorder (33.3%), followed by fetal (17.6%), cord (14.2%) and maternal disorders (7.6%). Unexplained cases were 14%. Compared to local audits, the regional group attributed different causes of death in 17% of cases. At multivariate analysis, infections were associated with early stillbirths (OR 3.38, CI95% 1.62-7.03) and intrapartum cases (OR 6.64, CI95% 2.61-17.02). Placental disorders were related to growth restriction (OR 1.89, CI95% 1.06-3.36) and were more frequent before term (OR 1.86, CI95% 1.11-3.15). Stillbirths judged possibly/probably preventable with a different management (10.9%) occurred more frequently in non-Italian women and were mainly related to maternal disorders (OR 6.64, CI95% 2.61-17.02). Conclusions: Regional Audit System for Stillbirth improves the registration of stillbirth and allows to define the causes of death. Moreover, sub-optimal care was recognized, allowing to identify populations which could benefit from preventive measures.


2019 - Acupuncture or phy(F)itoestrogens vs. (E)strogen plus progestin on menopausal symptoms. A randomized study [Articolo su rivista]
Palma, F.; Fontanesi, F.; Facchinetti, F.; Cagnacci, A.
abstract

The effect of acupuncture and phytoestrogens on climacteric symptoms was compared to the effect of hormone therapy (HT) with estrogen plus progestin. A total of 75 postmenopausal women with hot flushes were randomized to receive for 3&nbsp;months conjugated estrogens/medroxyprogesterone acetate (0.30 mg/1.5 mg/d), acupuncture weekly or soy isoflavones (75 mg/2/d). Evaluations were performed prior to, at the end, and 3&nbsp;months after treatments. Main outcomes were modification of the Greene’s climacteric scale and menopause quality of life (MenQoL). The Greene’s score significantly declined (p &lt;.05) during HT (−5.6 ± 3.1), acupuncture (−6.9 ± 4.5) and phytostrogens (−3.4 ± 4.3) (p &lt;.05 vs. HT). Mean Greene’s vasomotor sub-score declined less during phytoestrogens than HT (−0.8 ± 2.0 vs. −2.0 ± 1.9; p &lt;.05) and a ≥ 80% reduction was observed in 17.4% of women on phytoestrogens (p &lt;.05 vs. HT), 44% of women on HT, and 41.7% of women on acupuncture. MenQoL score improved similarly (p &lt;.05) during HT (−1.4 ± 1.3), acupuncture (−1.7 ± 1.0) and phytoestrogens (−1.0 ± 1.3). Three months after treatment end, benefits on MenQoL were conserved more following acupuncture than HT (p &lt;.006). The present data indicate that acupuncture, and in lesser extent phytoestrogens, can be effective therapies for climacteric symptoms. Trial registration: EudraCT Number 2008-006053-4.


2019 - Combined hormonal contraceptives in BRCA gene mutation carriers: why not? [Articolo su rivista]
Grandi, Giovanni; Sammarini, Margaret; del savio, maria chiara; Toss, Angela; Facchinetti, Fabio
abstract

not available


2019 - Easy tools to screen Italian women suffering from migraine with and without aura in early reproductive age [Articolo su rivista]
Grandi, G.; Imbrogno, M. G.; Cainazzo, M. M.; Pini, L. A.; Baraldi, C.; Guerzoni, S.; Nappi, R. E.; Facchinetti, F.
abstract

Objective: Early diagnosis of migraine with (MA)/without aura (MO) is vitally important to prevent adverse events during combined hormonal contraceptive (CHC) use and to provide personalized surveillance programs during pregnancy. The aim of this study is to provide clinicians with simple and fast tools to diagnose MO and MA in daily clinical practice. Study design: This study was based on a questionnaire to women of early reproductive age (18–35 years old) then randomized to undergo a neurological consultation. The ID-migraine questionnaire (PIN) and visual aura rating scale (VARS) were used. Results: A total of 240 subjects were included in the study, with a total prevalence of MO diagnosed by PIN of 67.0% of subjects with headache, 49.2% of the total study population, and of MA by VARS of 12.5% subjects with headache, 9.2% of the total study population. Eighty-seven neurological examinations were randomly performed: PIN showed a sensitivity of 85.7% (95% CI 75.3%–92.9%) and a specificity of 52.9% (95% CI 27.8%–77.0%), while VARS displayed a sensitivity of 100.0% (95% CI 69.2%–100.0%) and a specificity of 45.5% (95% CI 16.8%–76.6%). Conclusion: High sensitivity, in particular for the presence of MA, associated with low specificity suggest that PIN and VARS questionnaires can be effective tools to identify those young patients who require specific neurological examinations in view of the prescription of a CHC or pregnancy planning.


2019 - Esposizione prenatale e postnatale a ftalati ed effetti sullo sviluppo infantile: presentazione dei primi dati raccolti [Abstract in Rivista]
Maione, Domenico; Lucaccioni, Laura; Facchinetti, Fabio; Plessi, Carlotta; Poluzzi, Francesca; Ferrari, Angela; Fantuzzi, Guglielmina; Righi, Elena
abstract

Gli ftalati, potenziali interferenti endocrini comunemente addizionati alle materie plastiche, si ritrovano in numerosi prodotti di largo consumo quali involucri alimentari, cosmetici, prodotti per l’igiene personale, giocattoli e articoli per l’infanzia. A causa dei processi di migrazione ed evaporazione essi sono in grado di contaminare diverse matrici ambientali, determinando una esposizione umana continua e diffusa che può avvenire attraverso diverse vie e modalità. In più tali sostanze sono capaci di attraversare la barriera placentare, interferendo così anche con lo sviluppo fetale e neonatale. Le conoscenze sui livelli di esposizione prenatale e, soprattutto, postnatale a ftalati dei neonati sono tuttavia ancora molto limitate. Questo studio ha quindi l’obiettivo di valutare, attraverso il biomonitoraggio urinario, l’esposizione prenatale e postnatale a questi composti in neonati della provincia di Modena e, di indagare il potenziale effetto di questa esposizione sull’accrescimento corporeo, sui livelli ormonali e sullo sviluppo neuro-cognitivo nei primi due anni di vita


2019 - Esposizione prenatale e postnatale a ftalati ed effetti sullo sviluppo infantile: presentazione del protocollo di ricerca. [Abstract in Rivista]
Maione, D; Lucaccioni, L; Facchinetti, F; Pignatti, L; Ferrari, A; Fantuzzi, G; Righi, E
abstract

Introduzione: Gli ftalati, potenziali endocrine disruptors comunemente addizionati alle materie plastiche, si ritrovano in numerosi prodotti di largo consumo quali involucri alimentari, giochi, cosmetici e prodotti per l’igiene personale. Le conoscenze sui livelli di esposizione prenatale e, soprattutto, postnatale a ftalati dei neonati sono tuttavia molto limitate. Questo studio ha l’obiettivo di valutare, attraverso il biomonitoraggio urinario, l’esposizione prenatale e postnatale a ftalati in neonati della provincia di Modena e di indagare il ruolo/effetto di questa esposizione sull’accrescimento corporeo, sui livelli ormonali e sullo sviluppo neuro-cognitivo nei primi due anni di vita. Materiali e metodi: Si tratta di uno studio di coorte che prevede l’arruolamento, subito dopo il parto, di donne e dei loro bambini, nati a termine e normopeso, presso l’AOU di Modena. L’esposizione prenatale verrà valutata tramite il dosaggio di ftalati nelle urine (materne e neonatali) raccolte all’arruolamento e la somministrazione di un questionario che indaga le fonti espositive durante la gravidanza. L’esposizione postnatale verrà valutata raccogliendo le urine dei bambini a 6 mesi e la somministrazione di un secondo questionario espositivo. Alla nascita e durante i primi due anni di vita, mediante visite periodiche, verranno misurati accrescimento corporeo, livelli ormonali urinari (LH, FSH, testosterone/estradiolo), sviluppo neuro-motorio (metodo di Prechtl ed esame obiettivo neurologico) e sviluppo neuro-cognitivo (Scala di Griffiths). La determinazione analitica dei 6 diesteri più diffusi e dei relativi metaboliti verrà effettuata tramite cromatografia liquida e spettrometria di massa. Risultati: Le analisi dei campioni di urine raccolti dai neonati in diversi momenti permetteranno di quantificare sia l’esposizione prenatale che quella postnatale agli specifici ftalati e ai loro principali metaboliti, valutandone anche i trend temporali, di individuare le principali fonti espositive, sia durante la gravidanza che durante i primi 6 mesi di vita, e di indagare le correlazioni tra tali esposizioni e le caratteristiche antropometriche, i livelli ormonali del sistema riproduttivo e lo sviluppo neuro-motorio e neuro-cognitivo nei primi due anni di vita dei bambini. Conclusioni: Grazie al coinvolgimento dei neonati nel monitoraggio biologico, questa indagine migliorerà le conoscenze dirette sui livelli di esposizione prenatale e, soprattutto, postnatale a ftalati dei neonati, e apporterà contributi su possibili effetti sul loro accrescimento corporeo e sviluppo neurocognitivo. Inoltre, le informazioni ottenute potranno essere utilizzate per la pianificazione di strategie di prevenzione e promozione della salute della popolazione femminile in età fertile al fine di ridurre l’esposizione a queste sostanze in gravidanza e nei primi mesi di vita neonatale.


2019 - Estradiol in non-oral hormonal contraception: a “long and winding road” [Articolo su rivista]
Grandi, G.; Barra, F.; Ferrero, S.; Facchinetti, F.
abstract


2019 - Food glycemic index changes in overweight/obese pregnant women enrolled in a lifestyle program: a randomized controlled trial [Articolo su rivista]
Facchinetti, F.; Vijai, V.; Petrella, E.; Gambigliani Zoccoli, S.; Pignatti, L.; Di Cerbo, L.; Neri, I.
abstract

BACKGROUND: The calculation of the glycemic index of food mirrors a rise in blood sugar levels. A low-glycemic index carbohydrate diet in pregnancy has been associated with normal infant birthweight. Thus, strategies to lower the food glycemic index could be successful in improving pregnancy outcomes. OBJECTIVE: The purpose of this study was to compare different prescribed diets on food glycemic index intake and its relationship with rate of large-for-gestational-age infants. STUDY DESIGN: At the 9th-12th week of gestation (with a gynecologist and a dietitian both present), 273 Italian women with a body mass index of ≥25 kg/m2 were assigned randomly either to a customized low-glycemic index diet that was detailed by a dietitian (customized intervention; n=139 women; 1800 kcal/d+30 minutes walking 4 times/wk) or to generic lifestyle advice (standard care; n=134 women) with counseling about a prudent diet and physical activity, according to Italian guidelines. At enrollment and at the 36th week of gestation, the food frequency questionnaire was completed. In 73 Italian foods, the glycemic index was assessed with the use of a classic formula (available carbohydrate×glycemic index prescribed/total carb content of the meal) then was subdivided according to meal pattern. The main outcome was the change in food- glycemic index. RESULTS: Sociodemographic features were similar between the groups. One hundred fifty-six women completed the study (customized intervention=81; standard care=75). The mean daily glycemic index decreased from 58.4±19 to 52.5±11.2 (P=.008) in the customized intervention group although it remained unchanged in the standard care group. After the intervention, women in the customized intervention group reported a significant decrease in the diet glycemic index at dinner compared with both lunch and breakfast values (P&lt;.02). Lower birthweight and fewer large-for-gestational-age infants were observed in the customized intervention group. CONCLUSION: A customized low-glycemic index, calorie-restricted diet that was associated with constant physical activity effectively reduced the food glycemic index. This reduced food glycemic index is associated with lower rate of large-for-gestational-age newborn infants.


2019 - Future directions in endometriosis treatment: discovery and development of novel inhibitors of estrogen biosynthesis [Articolo su rivista]
Barra, F.; Romano, A.; Grandi, G.; Facchinetti, F.; Ferrero, S.
abstract


2019 - Gestational weight gain outside the Institute of Medicine recommendations and adverse pregnancy outcomes: Analysis using individual participant data from randomised trials [Articolo su rivista]
Rogozinska, E.; Zamora, J.; Marlin, N.; Betran, A. P.; Astrup, A.; Bogaerts, A.; Cecatti, J. G.; Dodd, J. M.; Facchinetti, F.; Geiker, N. R. W.; Haakstad, L. A. H.; Hauner, H.; Jensen, D. M.; Kinnunen, T. I.; Mol, B. W. J.; Owens, J.; Phelan, S.; Renault, K. M.; Salvesen, K. A.; Shub, A.; Surita, F. G.; Stafne, S. N.; Teede, H.; Van Poppel, M. N. M.; Vinter, C. A.; Khan, K. S.; Thangaratinam, S.; Coomarasamy, A.; Devlieger, R.; El Beltagy, N.; Guelfi, K.; Harrison, C.; Khoury, J.; Luoto, R.; Morkved, S.; Motahari, N.; Mcauliffe, F.; Perales, M.; Petrella, E.; Poston, L.; Rauh, K.; Sagedal, L. R.; Scudeller, T. T.; Shen, G. X.; Tonstad, S.; Vistad, I.; Vitolo, M.; Yeo, S.
abstract

Background: High Body Mass Index (BMI) and gestational weight gain (GWG) affect an increasing number of pregnancies. The Institute of Medicine (IOM) has issued recommendations on the optimal GWG for women according to their pre-pregnancy BMI (healthy, overweight or obese). It has been shown that pregnant women rarely met the recommendations; however, it is unclear by how much. Previous studies also adjusted the analyses for various women's characteristics making their comparison challenging. Methods: We analysed individual participant data (IPD) of healthy women with a singleton pregnancy and a BMI of 18.5 kg/m2 or more from the control arms of 36 randomised trials (16 countries). Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were used to describe the association between GWG outside (above or below) the IOM recommendations (2009) and risks of caesarean section, preterm birth, and large or small for gestational age (LGA or SGA) infants. The association was examined overall, within the BMI categories and by quartile of GWG departure from the IOM recommendations. We obtained aOR using mixed-effects logistic regression, accounting for the within-study clustering and a priori identified characteristics. Results: Out of 4429 women (from 33 trials) meeting the inclusion criteria, two thirds gained weight outside the IOM recommendations (1646 above; 1291 below). The median GWG outside the IOM recommendations was 3.1 kg above and 2.7 kg below. In comparison to GWG within the IOM recommendations, GWG above was associated with increased odds of caesarean section (aOR 1.50; 95%CI 1.25, 1.80), LGA (2.00; 1.58, 2.54), and reduced odds of SGA (0.66; 0.50, 0.87); no significant effect on preterm birth was detected. The relationship between GWG below the IOM recommendation and caesarean section or LGA was inconclusive; however, the odds of preterm birth (1.94; 1.31, 2.28) and SGA (1.52; 1.18, 1.96) were increased. Conclusions: Consistently with previous findings, adherence to the IOM recommendations seem to help achieve better pregnancy outcomes. Nevertheless, even in the context of clinical trials, women find it difficult to adhere to them. Further research should focus on identifying ways of achieving a healthier GWG as defined by the IOM recommendations.


2019 - Hereditary ovarian cancers: State of the art [Articolo su rivista]
Toss, A.; Molinaro, E.; Sammarini, M.; Del Savio, M. C.; Cortesi, L.; Facchinetti, F.; Grandi, G.
abstract

The identification of a mutation in ovarian cancer (OC) predisposition genes plays a crucial role in the management of cancer prevention, diagnosis, and treatment. In healthy carriers, the detection of a specific mutation might justify more intensive and personalised surveillance programmes, chemopreventive measures, and prophylactic surgeries. Moreover, the identification of a mutation in affected OC patients might provide fundamental knowledge of the tumour pathogenesis, thus guiding treatment choices. This is a comprehensive review of the molecular pathways involved in the pathogenesis of hereditary ovarian cancers, the clinical-pathological features of these tumours, and the potential implications for their prevention and clinical management.


2019 - Hormonal contraception in women with endometriosis: a systematic review [Articolo su rivista]
Grandi, G.; Barra, F.; Ferrero, S.; Sileo, F. G.; Bertucci, E.; Napolitano, A.; Facchinetti, F.
abstract

Objective: A systematic review was carried out of studies of women with endometriosis, to examine the evidence for efficacy of the use of hormonal contraception to improve disease-related pain and decrease postoperative risk of disease recurrence. Methods: A search of the Medline/PubMed and Embase databases was performed to identify all published English language studies on hormonal contraceptive therapies (combined hormonal contraceptives [CHCs], combined oral contraceptives [COCs], progestin-only pills [POPs] and progestin-only contraceptives [POCs]) in women with a validated endometriosis diagnosis, in comparison with placebo, comparator therapies or other hormonal therapies. Main outcome measures were endometriosis-related pain (dysmenorrhoea, pelvic pain and dyspareunia), quality of life (QoL) and postoperative rate of disease recurrence during treatment. Results: CHC and POC treatments were associated with clinically significant reductions in dysmenorrhoea, often accompanied by reductions in non-cyclical pelvic pain and dyspareunia and an improvement in QoL. Only two COC preparations (ethinylestradiol [EE]/norethisterone acetate [NETA] and a flexible EE/drospirenone regimen) demonstrated significantly increased efficacy compared with placebo. Only three studies found that the postoperative use of COCs (EE/NETA, EE/desogestrel and EE/gestodene) reduced the risk of disease recurrence. There was no evidence that POCs reduced the risk of disease recurrence. Conclusions: CHCs and POCs are effective for the relief of endometriosis-related dysmenorrhoea, pelvic pain and dyspareunia, and improve QoL. Some COCs decreased the risk of disease recurrence after conservative surgery, but POCs did not. There is insufficient evidence, however, to reach definitive conclusions about the overall superiority of any particular hormonal contraceptive.


2019 - Iatrogenic late preterm birth: when is it recommended? A Delphi survey promoted by the Italian Society of Perinatal Medicine [Articolo su rivista]
Monari, F.; Parazzini, F.; Cetin, I.; Ballarini, M.; Facchinetti, F.
abstract

Background: The rate of iatrogenic Late Preterm (LP) Birth varies in different settings. This is due to the lack of strong evidence/guidelines on the management of the different maternal, fetal and placental complications affecting pregnancy in the LP window. Steroid prophylaxis is also under discussion. Aim: To build recommendations about the management of main medical complications (pregestational diabetes, placenta previa, preeclampsia, cholestasis, p-PROM, intrauterine growth restriction -IUGR-) occurring in the LP period to reduce clinical heterogeneity. Methods: A group of Italian Perinatal experts were identified by Scientific Societies. A Delphi consensus methodology was used to reach agreement on different clinical sceneries. Two rounds of consultation by using a purpose built on-line survey and a third open panel discussion were performed. Results: The panel of 50 experts reached agreement for the vast majority of clinical sceneries (Placenta Previa, Preeclampsia, Diabetes, Cholestasis). Overall, there was agreement to be conservative at 34 weeks and in favor of delivery at 36 weeks. The management of p-PROM and mostly of IUGR were characterized by a minor degree of consensus. Corticosteroids were found necessary at the 34th week and unnecessary at the 36th week. Conclusions: Besides providing some guidance on clinical indications for LP iatrogenic delivery, these results represent a stimulus for designing future trials investigating the grey areas in this field.


2019 - Impact of maternal education on response to lifestyle interventions to reduce gestational weight gain: Individual participant data meta-Analysis [Articolo su rivista]
O'Brien, E. C.; Segurado, R.; Geraghty, A. A.; Alberdi, G.; Rogozinska, E.; Astrup, A.; Barakat Carballo, R.; Bogaerts, A.; Cecatti, J. G.; Coomarasamy, A.; De Groot, C. J. M.; Devlieger, R.; Dodd, J. M.; El Beltagy, N.; Facchinetti, F.; Geiker, N.; Guelfi, K.; Haakstad, L.; Harrison, C.; Hauner, H.; Jensen, D. M.; Khan, K.; Kinnunen, T. I.; Luoto, R.; Willem Mol, B.; Morkved, S.; Motahari-Tabari, N.; Owens, J. A.; Perales, M.; Petrella, E.; Phelan, S.; Poston, L.; Rauh, K.; Rayanagoudar, G.; Renault, K. M.; Ruifrok, A. E.; Sagedal, L.; Salvesen, K. A.; Scudeller, T. T.; Shen, G.; Shub, A.; Stafne, S. N.; Surita, F. G.; Thangaratinam, S.; Tonstad, S.; Van Poppel, M. N. M.; Vinter, C.; Vistad, I.; Yeo, S.; Mcauliffe, F. M.
abstract

Objectives To identify if maternal educational attainment is a prognostic factor for gestational weight gain (GWG), and to determine the differential effects of lifestyle interventions (diet based, physical activity based or mixed approach) on GWG, stratified by educational attainment. Design Individual participant data meta-Analysis using the previously established International Weight Management in Pregnancy (i-WIP) Collaborative Group database (https://iwipgroup.wixsite.com/collaboration). Preferred Reporting Items for Systematic reviews and Meta-Analysis of Individual Participant Data Statement guidelines were followed. Data sources Major electronic databases, from inception to February 2017. Eligibility criteria Randomised controlled trials on diet and physical activity-based interventions in pregnancy. Maternal educational attainment was required for inclusion and was categorised as higher education (≥tertiary) or lower education (≤secondary). Risk of bias Cochrane risk of bias tool was used. Data synthesis Principle measures of effect were OR and regression coefficient. Results Of the 36 randomised controlled trials in the i-WIP database, 21 trials and 5183 pregnant women were included. Women with lower educational attainment had an increased risk of excessive (OR 1.182; 95% CI 1.008 to 1.385, p =0.039) and inadequate weight gain (OR 1.284; 95% CI 1.045 to 1.577, p =0.017). Among women with lower education, diet basedinterventions reduced risk of excessive weight gain (OR 0.515; 95% CI 0.339 to 0.785, p = 0.002) and inadequate weight gain (OR 0.504; 95% CI 0.288 to 0.884, p=0.017), and reduced kg/week gain (B-0.055; 95% CI-0.098 to-0.012, p=0.012). Mixed interventions reduced risk of excessive weight gain for women with lower education (OR 0.735; 95% CI 0.561 to 0.963, p=0.026). Among women with high education, diet based interventions reduced risk of excessive weight gain (OR 0.609; 95% CI 0.437 to 0.849, p=0.003), and mixed interventions reduced kg/week gain (B-0.053; 95% CI-0.069 to-0.037,p&lt;0.001). Physical activity based interventions did not impact GWG when stratified by education. Conclusions Pregnant women with lower education are at an increased risk of excessive and inadequate GWG. Diet based interventions seem the most appropriate choice for these women, and additional support through mixed interventions may also be beneficial.


2019 - Increasing BMI is associated with both endometrioid and serous histotypes among endometrial rather than ovarian cancers: a case-to-case study [Articolo su rivista]
Grandi, G.; Perrone, A. M.; Chiossi, G.; Friso, S.; Toss, A.; Sammarini, Margaret; Facchinetti, F.; Botticelli, L.; Palma, F.; De Iaco, P.
abstract

Aim: Although obesity has been associated with endometrioid (type I) and, to a lesser extent, with serous (type II) endometrial cancer (EC), the association with the same histotypes of ovarian cancer (OC) remains unclear. Therefore, we intended to compare the role of BMI in carcinogenesis of endometrioid and the serous malignancies, at both ovarian and endometrial level. Methods: A retrospective case-to-case study was performed in the University Hospital of Bologna (Italy), through the review of primary EC matched with the corresponding OC cases in the same period (1988–2017). Results: We included 1052 women diagnosed with EC (n = 897 endometrioid, n = 52 serous) and 955 women affected by OC (n = 132 endometrioid, n = 627 serous). EC patients had higher median BMI than women diagnosed with OC (27.3 [23.4–31.9] vs 24.9 [21.7–27.5], p &lt; 0.01). After controlling for confounding, 1 unit increase in BMI was associated with a 5% higher odds of endometrial as opposed to ovarian cancer (OR for ovarian as opposed to endometrial cancer 0.95; 95% CI 0.91–0.98, p = 0.004). Conclusions: Increasing BMI is associated with endometrial rather than ovarian cancer, among both serous and endometrioid histotypes.


2019 - Maternal interventions to improve offspring outcomes in rodent models of diet-induced obesity: a review [Articolo su rivista]
Menichini, Daniela; Longo, Monica; Facchinetti, Fabio
abstract

Maternal obesity is an adverse factor that affects the intrauterine environment during critical periods of fetal developmental causing adverse lifelong effects on offspring health. Several different interventions have been performed in animal models of obesity to ameliorate maternal conditions and consequently reduce the adverse effects on offspring. Our aim was to critically review studies involving murine models of obesity induced by high fat diet (HFD), assessing maternal outcomes during pregnancy and the related offspring conditions. We carried out a computerized literature search of PubMed and Medline. We identified eight studies that fulfilled the inclusion criteria and have performed interventions in pregnancy with natural, synthetized compounds, and lifestyle modifications. Metabolic profile and lipid metabolism were improved by inositols, resveratrol, germinated brown rice (GBR), and exercise in the mother. The offspring whose mother received resveratrol, adiponectin, GBR, and exercise, showed an improvement in leptin, triglycerides, adiponectin levels, and a decrease in insulin resistance. These experimental studies demonstrate that several interventions in pregnant rodents improve the metabolic profile of both the mother and the offspring. Clinical research could now explore the efficacy and safety of such interventions, interrupting the vicious circle that an obese mother generates a child prone to develop metabolic (and cardiovascular) disease in adult life.


2019 - Myo-inositol for the prevention of gestational diabetes mellitus. A brief review [Articolo su rivista]
D'Anna, R.; Santamaria, A.; Alibrandi, A.; Corrado, F.; Benedetto, A. D.; Facchinetti, F.
abstract

Gestational Diabetes Mellitus (GDM) is one of the most frequent complications of pregnancy and is characterized by a carbohydrate intolerance which is diagnosed with the oral glucose tolerance test. The prevalence of GDM in our population is about 12%, but risk factors like a previous GDM, ethnicity, a parent with diabetes mellitus type 2 and maternal overweight may increase its occurrence. Complications of GDM are a pre-term birth (before 37 wk gestation), macrosomia (birth weight ≥4 kg) and gestational hypertension. Actually, GDM is principally treated with diet and, if it is necessary, with insulin; but the challenge is the prevention of GDM. Among the measures used, changes in life-style (diet1exercise) failed to prevent GDM whereas metformin showed conflicting results. A promising supplement is myo-inositol (MI) which was given from first trimester until delivery to women at risk for GDM reporting a significant decrease in GDM occurrence by more than 60% comparing to the placebo group. Recently, a secondary analysis from 3 randomized controlled trials demonstrated that MI may also significantly reduce some of GDM complications such as pre-term birth and macrosomia with a favorable impact on mother and fetus well being.


2019 - Short-term effects of metformin and myo-inositol in women with polycystic ovarian syndrome (PCOS): a meta-analysis of randomized clinical trials [Articolo su rivista]
Facchinetti, F.; Orru, B.; Grandi, G.; Unfer, V.
abstract

Metformin (MET), the most commonly used insulin sensitizer, is the reference off-label drug for the treatment of polycystic ovary syndrome (PCOS), worldwide. However, its use may be limited mainly by gastrointestinal adverse effects. Myo-inositol (MI), a well-recognized food supplement, also represents an evidence-based treatment for PCOS women, popular in many countries. Our aim is to provide a systematic review of the literature and a meta-analysis which compares these two treatments, for their short-term efficacy and safety in PCOS patients. Systematic review and meta-analysis of randomized clinical trials (RCTs). RCTs were identified from 1994 through 2017 using MEDLINE, Cochrane Library, PubMed, and ResearchGate. Included studies were limited to those one directly comparing MET to MI on several hormones changes. Standardized mean difference (SMD) or risk ratios (RRs) with 95% CIs were calculated. Changes in fasting insulin was the main outcome of measure. Six trials with a total of 355 patients were included. At the end of treatment, no difference between MET and MI was found on fasting insulin (SMD=0.08&nbsp;µU/ml, 95% CI: −0.31–0.46, p=.697), HOMA index (SMD =0.17, 95% CI: −0.53–0.88, p=.635), testosterone (SMD= −0.01, 95% CI: −0.24–0.21, p=.922), SHBG levels (SMD= −0.50 nmol/l, 95% CI: −1.39–0.38, p=.263) and body mass index (BMI) (SMD= −0.22, 95% CI: −0.60–0.16, p=.265). There was strong evidence of an increased risk of adverse events among women receiving MET compared to those receiving MI (RR =5.17, 95% CI: 2.91–9.17, p&lt;.001). No differences were found in the effect of MET and MI on short-term hormone changes. The better tolerability of MI makes it more acceptable for the recovery of androgenic and metabolic profile in PCOS women.


2019 - Vascular and metabolic profiles in offspring born to pregnant mice with metabolic syndrome treated with inositols [Articolo su rivista]
Longo, M.; Alrais, M.; Tamayo, E. H.; Ferrari, F.; Facchinetti, F.; Refuerzo, J. S.; Blackwell, S. C.; Sibai, B. M.
abstract

Background: Inositols (INOs) supplementation during pregnancy, specifically the combination of myo-inositol (MI) and D-chiro-inositol (DCI), has been reported to improve vascular parameters in women with gestational diabetes mellitus. We demonstrated previously that offspring born to pregnant mice lacking the endothelial nitric oxide synthase (eNOS+/–) gene have hypertension (HTN) as adults and, when fed a high-fat diet (HFD), develop a metabolic syndrome (MS) phenotype. Objective: Our aim was to evaluate whether INOs treatment in pregnancy complicated by MS improves the vascular and metabolic profile in mice offspring programmed in utero to develop HTN and MS. Materials and Methods: Heterozygous eNOS+/– mice fed an HFD manifest a MS phenotype. Female eNOS+/– mice with MS were bred with a wild-type (WT) male. On gestational day 1, pregnant females were randomly allocated to receive either a mixture of INOs (MI/DCI: 7.2/0.18 mg/mL) or water as placebo until delivery. The female offspring obtained were genotyped and categorized as: WT (genetically normal, with eNOS gene) and eNOS+/– offspring (genetically modified, heterozygous for eNOS gene). Both offspring developed in an abnormal uterine environment due to maternal MS. At 9–10 weeks of age, the offspring underwent a glucose tolerance test (GTT) and systolic blood pressure (SBP) measurement. The mice were then sacrificed, and the carotid arteries were isolated for evaluation of vascular responses. Responses to phenylephrine (PE), in the presence and absence of a nonspecific nitric oxide inhibitor (N-nitro-L-arginine methyl ester [L-NAME]), the vasodilator acetylcholine (ACh), and sodium nitroprusside (SNP) were assessed. Results: The GTT showed lower glucose levels in both eNOS+/–INOs (P = .03) and WT-INOs (P = .05) offspring born to MS dams on INOs supplementation compared to offspring born to untreated dams. SBP was higher in eNOS+/– offspring compared to WT (169 ± 7 vs 142 ± 9 mm Hg, respectively, P = .04) and INOs treatment decreased SBP in WT-INOs (110 ± 10 mm Hg, P = .01) but not in eNOS+/–INOs offspring. Maximal (%Max) contractile response to PE was higher in eNOS+/– offspring born to MS dams and was decreased in those born to MS dams treated with INOs (%Max, eNOS+/–, 123 ± 7 vs eNOS+/–INOs, 82 ± 11 mm Hg, P = .007). No differences were seen in PE contractile responses in WT offspring born to MS dams treated or not treated with INOs (WT, 92 ± 4 vs WT-INOs, 75 ± 7). The L-NAME response was decreased in eNOS+/–INOs and WT-INOs offspring compared to untreated ones. The ACh vasorelaxation was impaired in eNOS+/– and WT offspring born to MS dams, and maternal INOs treatment improved offspring vascular relaxation in both offspring (P = .01 and P = .03, respectively). No differences were seen in response to SNP. Conclusion: Inositols supplementation improved glucose tolerance, SBP, and vascular responses in adult eNOS+/– and WT offspring born to dams with MS. Interestingly, WT born to MS dams show an altered vascular profile similar to eNOS+/– offspring and exhibit an improved response to INOs treatment. Our findings suggest that the benefits of INOs treatment are more pronounced in offspring exposed to environmental factors in utero, and less likely in those due to genetic factors.


2019 - Vigilance on use of drugs, herbal products, and food supplements during pregnancy: focus on fosfomycin [Articolo su rivista]
Mannucci, C.; Dante, G.; Miroddi, M.; Facchinetti, F.; D'Anna, R.; Santamaria, A.; Lenti, M. C.; Vannacci, A.; Calapai, F.; Perone, M.; Migliardi, G.; Alibrandi, A.; Navarra, M.; Calapai, G.
abstract

Purpose: Urinary tract infection (UTI) is defined as a common bacterial infection that can lead to significant morbidity such as stricture, fistula, abscess formation, bacteremia, sepsis, pyelonephritis, and kidney dysfunction with a mortality rates reported of 1% in men and 3% in women because of development of pyelonephritis. UTIs are more common in women and the 33% of them require antimicrobials treatment for at least one episode by the age of 24 years. UTIs are the most common infections observed during pregnancy and up to 30% of mothers with not treated asymptomatic bacteriuria may develop acute pyelonephritis which consequently can be associated to adverse maternal and fetal outcomes. All bacteriuria in pregnancy should be treated with antimicrobial treatments being safe for both the mother and the fetus. Approximately one every four women receives prescription of antibiotic treatment during pregnancy, nearly 80% of all the prescription medications during gestation. The use of fosfomycin to treat cystitis in pregnancy generally considered safe and effective. Even though use on antibiotics for urinary tract infections is considered generally safe for the fetus and mothers, this opinion is not based on specific studies monitoring the relationship of among urinary infections, consumption of antibiotics, and pregnancy outcomes. Materials and methods: On this basis we decided to analyze data from the database of our multicenter study PHYTOVIGGEST, reporting data from 5362 pregnancies, focusing on use of fosfomycin. Principal outcomes of pregnancy in women treated with fosfomycin were taken into consideration. Results: Women who have been treated with urinary antibiotics during the pregnancy were 183. With respect to the total number of pregnancies of our sample, these women represented the percentage of 3.49% (187/5362). Analysis of different outcomes of pregnancy such as gestational age, neonatal weight, and neonatal Apgar index did not show any significant difference. At the same time, analysis of data of pregnancy complicancies (such as urgent cesarean delivery, use of general anesthesia, need to induce labor) did not show any difference in women taking fosfomycin during pregnancy and those not taking it. Conclusions: Our data, based on a large number of pregnancies, confirm the safety use of fosfomycin use in pregnancy.


2018 - Acupuncture in Postdate Pregnancy Management [Articolo su rivista]
Neri, Isabella; Pignatti, Lucrezia; Fontanesi, Francesca; Facchinetti, Fabio
abstract

Pharmacological labor induction is obtained through prostaglandins application and/or oxytocin infusion; however, the use seems to be related to fetal and maternal side effects. Traditional Chinese Medicine advocates the use of acupuncture to soften the cervix and induce uterine contractions. at which presented for The primary outcome was the rate of women admitted for labour induction in case of prolonged pregnancy at 41&nbsp;+&nbsp;5&nbsp;weeks, and the secondary outcome was the rate of induction planning for other indications.


2018 - An early-customized low glycaemic-index diet prevents adverse pregnancy outcomes in overweight/obese women [Articolo su rivista]
Petrella, Elisabetta; Tamborrino, Valeria; Di Cerbo, Lidia; Neri, Isabella; Facchinetti, Fabio
abstract

To determine whether the prescription and follow-up of a behavioral program (customized nutritional advices and a constant physical activity) influences the occurrence of unfavorable maternal/neonatal outcomes among overweight/obese women.


2018 - Are postnatal ampicillin levels actually related to the duration of intrapartum antibiotic prophylaxis prior to delivery? A pharmacokinetic study in 120 neonates [Articolo su rivista]
Berardi, Alberto; Pietrangiolillo, Zaira; Bacchi Reggiani, Maria Letizia; Bianco, Valentina; Gallesi, Daniela; Rossi, Katia; Facchinetti, Fabio; Ferrari, Fabrizio
abstract

To assess ampicillin levels according to the duration of intrapartum antibiotic prophylaxis (IAP).


2018 - Castor oil for induction of labour: a retrospective study [Articolo su rivista]
Neri, Isabella; Dante, Giulia; Pignatti, Lucrezia; Salvioli, Chiara; Facchinetti, Fabio
abstract

The aim of this study is to investigate the safety and efficacy of castor oil to induce labour.


2018 - Clinical and metabolic outcomes in pregnant women at risk for gestational diabetes mellitus supplemented with myo-inositol: a secondary analysis from 3 RCTs [Articolo su rivista]
Santamaria, A; Alibrandi, A; Di Benedetto, A; Pintaudi, B; Corrado, F; Facchinetti, F; D'Anna, R
abstract

Gestational diabetes mellitus is defined as carbohydrate intolerance that begins or is first recognized during pregnancy. Insulin sensitizing substances such as myo-inositol have been considered for the prevention of gestational diabetes mellitus and related complications.


2018 - Clinical use of vaginal lipoic acid in pregnancy [Capitolo/Saggio]
Pignatti, L.; Facchinetti, F.
abstract

Pregnancy is generally considered as an anti-inflammatory condition and a shift in the type of cytokines produced leads to the onset of an inflammation state that would lead to abortion or pregnancy complications. It is known that lipoic acid (ALA) and its reduced form dehydrolipoic acid (DHLA) constitute a powerful redox couple, that can directly scavenge reactive oxygen species and reactive nitrogen species and several mechanisms of action of ALA/DHLA seems to be associated to the modulation of NF-κB activity. Indeed, ALA acts on several inflammatory pathways involved in the onset of cervical ripening, uterine contractions and premature preterm rupture of membranes, and the specific anti-inflammatory actions exerted on pregnancy-related tissues such as amnion and cervix warrants its clinical application in this field. In particular, vaginal administration of ALA is a novel approach specifically directed to pregnacy-related tissue. As a local treatment, administration of vaginal ALA may exert more rapid and strong effects than a sistemic (i.e., oral) administration.


2018 - Combined Hormonal Contraceptive Use and Risk of Breast Cancer in a Population of Women With a Family History [Articolo su rivista]
Grandi, Giovanni; Toss, Angela; Cagnacci, Angelo; Marcheselli, Luigi; Pavesi, Silvia; Facchinetti, Fabio; Cascinu, Stefano; Cortesi, Laura
abstract

We estimated the association between combined hormonal contraceptive (CHC) use and breast cancer (BC) incidence in a well-selected population of women at familial risk of BC at the Modena Family Cancer Clinic.


2018 - Effect of maternal age, height, BMI and ethnicity on birth weight: an Italian multicenter study [Articolo su rivista]
Spada, Elena; Chiossi, Giuseppe; Coscia, Alessandra; Monari, Francesca; Facchinetti, Fabio
abstract

To assess the effect of maternal age, height, early pregnancy body mass index (BMI) and ethnicity on birth weight.


2018 - Indagine di prevalenza sull'attività fisica in gravidanza e i fattori ad essa correlati in un campione di donne della provincia di Modena. [Abstract in Atti di Convegno]
Fioretti, Elisabetta; Righi, E.; Fantuzzi, G.; Facchinetti, F.; Pignatti, Lucrezia; Aggazzotti, Gabriella
abstract

INTRODUZIONE La gravidanza rappresenta un periodo durante il quale le donne possono essere più motivate a migliorare il proprio stile di vita. L’Organizzazione Mondiale della Sanità (OMS) e altre organizzazioni nazionali ed internazionali raccomandano la pratica di un’adeguata attività fisica sia prima che durante la gravidanza, in assenza di controindicazioni mediche. Lo scopo dello studio è stato quello di valutare le abitudini delle donne in relazione all'attività fisica svolta prima e durante la gravidanza. MATERIALI E METODI Lo studio epidemiologico osservazionale trasversale ha coinvolto 390 donne in gravidanza (età media: 33±5 anni) arruolate presso l’U.O. di Ostetricia e Ginecologia dell’Azienda Ospedaliero-Universitaria del Policlinico di Modena. Le informazioni relative all’attività fisica sono state raccolte mediante un questionario costruito ai fini dello studio. RISULTATI Delle 390 donne che hanno partecipato allo studio, solo il 35,1% delle donne (137) ha dichiarato di aver svolto attività fisica sia prima che durante la gravidanza. Prima della gravidanza 196 donne (50,3%) hanno svolto attività fisica e, tra queste, il 53,1% (104) ha praticato almeno 150 minuti di attività fisica a settimana come raccomandato dall'OMS. La ginnastica (33,2%) e le camminate (30,1%) rappresentano le attività maggiormente praticate. Durante la gravidanza 202 donne (51,8%) hanno dichiarato di aver svolto attività fisica: in particolare nel I trimestre 145 donne (71,8%) hanno fatto esercizio fisico, nel II trimestre 176 (87,1%) e nel III trimestre 167 (82,7%). Solamente 116 donne (57,4%) hanno praticato attività fisica in tutti e 3 i trimestri e solo 107 donne hanno raggiunto gli standard consigliati dall'OMS. Le attività più rappresentate durante la gravidanza sono le camminate (62,9%) e il nuoto (27,7%). La pratica regolare dell’attività fisica risulta influenzata da variabili demografiche (età, nazionalità, titolo di studio, attività lavorativa) e dalle condizioni di salute delle donne. CONCLUSIONI Sebbene la pratica dell’attività fisica prima e durante la gravidanza apporti dei benefici per la salute sia della mamma che del bambino, il numero di donne che svolgono regolare attività fisica durante la gravidanza risulta limitato. Appare, quindi, necessario individuare efficaci strategie di promozione di un corretto stile di vita in questa fascia di popolazione.


2018 - Levonorgestrel-releasing intra-uterine systems as female contraceptives [Articolo su rivista]
Grandi, Giovanni; Farulla, Antonino; Sileo, Filomena Giulia; Facchinetti, Fabio
abstract

The availability and use of long-acting reversible contraceptives (LARCs), such as levonorgestrel intrauterine systems (LNG-IUSs), have increased in recent times. Areas covered: The authors provide a narrative review of the LNG-IUSs currently available worldwide as female contraceptives (LNG-IUS 13.5, 19.5 and 52&nbsp;mg). Specific features of the devices and their parameters of efficacy and tolerability were considered as outcomes. Expert opinion: The one-handed 3.8-mm-diameter inserter of LNG-IUS 13.5&nbsp;mg and 19.5&nbsp;mg may be particularly suitable in nulliparous women. While LNG-IUSs 13.5, 19.5&nbsp;mg and LNG 52&nbsp;mg should be used by women simply looking for an effective contraceptive method for up to 3, 4 or 5&nbsp;years, LNG-IUS 52&nbsp;mg has also been approved for the treatment of heavy menstrual bleeding and endometrial protection during hormone replacement therapy. LNG-IUS 52&nbsp;mg is ideal for women who are experiencing a certain hyperestrogenic hormonal environment, with heavy menstrual bleeding due to hormonal imbalances, adenomyosis or fibroids, in the case of symptomatic endometriosis or for endometrial protection during hormone estrogenic replacement therapy in non-hysterectomized women.


2018 - Needlestick injuries among obstetrics and gynecology trainees: A study design to investigate an underestimated priority [Articolo su rivista]
Scambia, G.; Raffaelli, R.; Baggio, S.; Garzon, S.; Lagana, A. S.; Sartori, E.; Vanzo, F.; Vizza, E.; Angioli, R.; Benedetto, C.; Cagnacci, A.; Candiani, M.; Carta, G.; Caserta, D.; Cherchi, P. L.; Ciavattini, A.; Cicinelli, E.; Cobellis, L.; Cosmi, E.; D'Anna, R.; De Leo, V.; Di Paola, R.; Di Pinto, A.; Ercoli, A.; Facchinetti, F.; Ferrazzi, E.; Frusca, T.; Ghezzi, F.; Greco, P.; Liberati, M.; Loverro, G.; Nappi, L.; Palumbo, M.; Neri, M.; Perino, A.; Clemenza, S.; Piccione, E.; Peterlunger, I.; Rizzo, N.; Negri, B.; Simoncini, T.; Spinillo, A.; Venturini, P. L.; Vergani, P.; Zullo, F.; Chiantera, A.; Colacurci, N.; Viora, E.; Franchi, M.
abstract

Risk of needlestick injuries (NSIs) is high in surgical staff. Medical students and trainees have reported the highest rate of NSIs, and Obstetrics and Gynecology is considered a high-risk specialty. The risk associated to NSIs is further increased by the high prevalence of blood borne pathogens in the population. Nevertheless, the degree of concern about contraction of these serious infections has been reported significantly lower over time, showing diminishing attitudes toward prevention of exposure and lack of consideration as a major problem, in fact most of NSIs resulted unreported. Therefore, education is fundamental to change individual attitudes and behaviors, to improve awareness and increase the use of standard protections, in order to reduce the injury rate and implement reporting to hospital surveillance systems. The proposed study aims to assess NSIs in trainees currently attending residency programs in Obstetrics and Gynecology in all academic hospitals of Italy, with a standardized, pre-piloted, national-based survey. At this purpose, we developed the Obstetrics Needlestick Injury Questionnaire (ONSI-Q), a 40-items survey that will be completed via a web-based platform. The ONSI-Q investigates real incidence of NSIs, adopted protection practices, presence of associated risk factors, and attitudes and rate of the reported accidents among trainees during obstetric procedures (suture of perineal tear/episiotomy and cesarean section). These results will provide the opportunity to investigate an underestimated priority, in order to encourage educational practices with the aim to improve prevention and reporting strategies, and therefore increase occupational safety in this high-risk surgical specialty.


2018 - [New methods for preterm birth prediction: the PAMG-1 test] [Articolo su rivista]
Di Fabrizio, Laura; Giardina, Irene; Cetin, Irene; Di Tommaso, Mariarosaria; Ciavattini, Andrea; Locci, Mariavittoria; Facchinetti, Fabio; Zonca, Marina; Di Renzo, Gian Carlo
abstract

The aim of this study was to assess the efficacy of PAMG-1 test (placental alpha microglobulin-1) in cervicovaginal secretions collected immediately following transvaginal ultrasound (TVUS) of women with signs and symptoms of preterm labor (PTL), clinically intact membranes and cervical length between 15 and 30 mm for the prediction of imminent spontaneous delivery (within 7 days of testing), as well as delivery <34 weeks of gestation.


2018 - Preeclampsia and migraine: a prediction perspective [Articolo su rivista]
Facchinetti, Fabio; Sacco, Alessia
abstract

Preeclampsia and migraine: a prediction perspective


2017 - Adherence to a lifestyle programme in overweight/obese pregnant women and effect on gestational diabetes mellitus: a randomized controlled trial [Articolo su rivista]
Bruno, Raffaele; Petrella, Elisabetta; Bertarini, Valentina; Pedrielli, Giulia; Neri, Isabella; Facchinetti, Fabio
abstract

This study aims to determine whether the prescription of a detailed lifestyle programme in overweight/obese pregnant women influences the occurrence of gestational diabetes (GDM), and if this kind of prescription increases the adherence to a healthier lifestyle in comparison to standard care. The study was designed as a randomized controlled trial, with open allocation, enrolling women at 9-12 weeks of pregnancy with a BMI ≥ 25 kg/m(2) . The women assigned to the Intervention group (I = 96) received a hypocaloric, low-glycaemic, low-saturated fat diet and physical activity recommendations. Those assigned to the Standard Care group (SC = 95) received lifestyle advices regarding healthy nutrition and exercise. Follow-up was planned at the 16(th) , 20(th) , 28(th) and 36(th) weeks. A total of 131 women completed the study (I = 69, SC = 62). The diet adherence was higher in the I (57.9%) than in the SC (38.7%) group. GDM occurred less frequently in the I (18.8%) than in the SC (37.1%, P = 0.019) group. The adherent women from either groups showed a lower GDM rate (12.5% vs. 41.8%, P &lt; 0.001). After correcting for confounders, the GDM rate was explained by allocation into the I group (P = 0.034) and a lower BMI category (P = 0.039). The rates of hypertension, preterm birth, induction of labour, large for gestational age babies and birthweight &gt; 4000 g were significantly lower in I group. The incidence of small for gestational age babies was not different. These findings demonstrate that the adherence to a personalized, hypocaloric, low-glycaemic, low-saturated fat diet started early in pregnancy prevents GDM occurrence, in women with BMI ≥ 25 kg/m(2) .


2017 - An area-based study on intrapartum antibiotic prophylaxis for preventing group B streptococcus early-onset disease: advances and limitations. [Articolo su rivista]
Berardi, Alberto; Rossi, Cecilia; Bacchi Reggiani, Maria Letizia; Bastelli, Annalisa; Capretti, Maria Grazia; Chiossi, Claudio; Fiorini, Valentina; Gambini, Lucia; Gavioli, Sara; Lanari, Marcello; Memo, Luigi; Papa, Irene; Pini, Luana; Rizzo, Maria Vittoria; Zucchini, Andrea; Facchinetti, Fabio; Ferrari, Fabrizio
abstract

The prevalence of maternal group-B-streptococcus (GBS) colonization and risk factors (RFs) for neonatal early-onset disease (EOD) in Europe are poorly defined. Large-scale information concerning adherence to recommendations for preventing GBS-EOD are lacking.


2017 - Antiphospholipid antibody profile based obstetric outcomes of primary antiphospholipid syndrome: the PREGNANTS study [Articolo su rivista]
Saccone, Gabriele; Berghella, Vincenzo; Maruotti, Giuseppe Maria; Ghi, Tullio; Rizzo, Giuseppe; Simonazzi, Giuliana; Rizzo, Nicola; Facchinetti, Fabio; Dall'Asta, Andrea; Visentin, Silvia; Sarno, Laura; Xodo, Serena; Bernabini, Dalila; Monari, Francesca; Roman, Amanda; Eke, Ahizechukwu Chigoziem; Hoxha, Ariela; Ruffatti, Amelia; Schuit, Ewoud; Martinelli, Pasquale
abstract

Antiphospholipid syndrome is an autoimmune, hypercoagulable state that is caused by antiphospholipid antibodies. Anticardiolipin antibodies, anti-β2 glycoprotein-I, and lupus anticoagulant are the main autoantibodies found in antiphospholipid syndrome. Despite the amassed body of clinical knowledge, the risk of obstetric complications that are associated with specific antibody profile has not been well-established.


2017 - Corrigendum to "Inositol(s) from Bench to Bedside in Endocrinology and Gynecology" [Articolo su rivista]
Unfer, Vittorio; Nestler John, E; Kamenov Zdravko, A; Prapas, Nikos; Facchinetti, Fabio
abstract

[This corrects the article DOI: 10.1155/2017/8515703.].


2017 - Editorial – Update on inositol(s) [Articolo su rivista]
Unfer, V.; Facchinetti, F.
abstract


2017 - Effect of diet and physical activity based interventions in pregnancy on gestational weight gain and pregnancy outcomes: meta-analysis of individual participant data from randomised trials [Articolo su rivista]
Rogozińska, Ewelina; Marlin, Nadine; Pilar Betrán, Ana; Astrup, Arne; Barakat, Ruben; Bogaerts, Annick; G Cecatti, Jose; Devlieger, Roland; M Dodd, Jodie; El Beltagy, Nermeen; Facchinetti, Fabio; RW Geiker, Nina; J Guelfi, Kym; AH Haakstad, Lene; L Harrison, Cheryce; Hauner, Hans; M Jensen, Dorte; I Kinnunen, Tarja; Khoury, Janette; Luoto, Riitta; Mcauliffe, Fionnuala; Motahari, Narges; Mørkved, Siv; Owens, Julie; Perales, María; Petrella, Elisabetta; Phelan, Suzanne; Poston, Lucilla; Rauh, Kathrin; M Renault, Kristina; R Sagedal, Linda; Å Salvesen, Kjell; X Shen, Garry; Shub, Alexis; Scudeller, Tânia; G Surita, Fernanda; N Stafne, Signe; Teede, Helena; Tonstad, Serena; NM van Poppel, Mireille; A Vinter, Christina; Vistad, Ingvild; Yeo, Seonae; Dodds, Julie; Kerry, Sally; Jackson, Louise; Barton, Pelham; Molyneaux, Emma; A Martin, Alba; Rayanagoudar, Girish; E Ruifrok, Anneloes; Roberts, Tracy; JM de Groot, Christianne; Coomarasamy, Arri; WJ Mol, Ben; Zamora, Javier; S Khan, Khalid; D Riley, Richard; Thangaratinam, Shakila
abstract

Objective To synthesise the evidence on the overall and differential effects of interventions based on diet and physical activity during pregnancy, primarily on gestational weight gain and maternal and offspring composite outcomes, according to women’s body mass index, age, parity, ethnicity, and pre-existing medical condition; and secondarily on individual complications. Design Systematic review and meta-analysis of individual participant data (IPD). Data sources Major electronic databases from inception to February 2017 without language restrictions. Eligibility criteria for selecting studies Randomised trials on diet and physical activity based interventions in pregnancy. Data synthesis Statistical models accounted for clustering of participants within trials and heterogeneity across trials leading to summary mean differences or odds ratios with 95% confidence intervals for the effects overall, and in subgroups (interactions). Results IPD were obtained from 36 randomised trials (12 526 women). Less weight gain occurred in the intervention group than control group (mean difference −0.70 kg, 95% confidence interval −0.92 to −0.48 kg, I2=14.1%; 33 studies, 9320 women). Although summary effect estimates favoured the intervention, the reductions in maternal (odds ratio 0.90, 95% confidence interval 0.79 to 1.03, I2=26.7%; 24 studies, 8852 women) and offspring (0.94, 0.83 to 1.08, I2=0%; 18 studies, 7981 women) composite outcomes were not statistically significant. No evidence was found of differential intervention effects across subgroups, for either gestational weight gain or composite outcomes. There was strong evidence that interventions reduced the odds of caesarean section (0.91, 0.83 to 0.99, I2=0%; 32 studies, 11 410 women), but not for other individual complications in IPD meta-analysis. When IPD were supplemented with study level data from studies that did not provide IPD, the overall effect was similar, with stronger evidence of benefit for gestational diabetes (0.76, 0.65 to 0.89, I2=36.8%; 59 studies, 16 885 women). Conclusion Diet and physical activity based interventions during pregnancy reduce gestational weight gain and lower the odds of caesarean section. There is no evidence that effects differ across subgroups of women.


2017 - Effects of antenatal diet and physical activity on maternal and fetal outcomes: individual patient data meta-analysis and health economic evaluation [Capitolo/Saggio]
Rogozińska, Ewelina; Marlin, Nadine; Jackson, Louise; Rayanagoudar, Girish; Ruifrok, Anneloes E; Dodds, Julie; Molyneaux, Emma; van Poppel, Mireille Nm; Poston, Lucilla; Vinter, Christina A; McAuliffe, Fionnuala; Dodd, Jodie M; Owens, Julie; Barakat, Ruben; Perales, Maria; Cecatti, Jose G; Surita, Fernanda; Yeo, SeonAe; Bogaerts, Annick; Devlieger, Roland; Teede, Helena; Harrison, Cheryce; Haakstad, Lene; Shen, Garry X; Shub, Alexis; Beltagy, Nermeen El; Motahari, Narges; Khoury, Janette; Tonstad, Serena; Luoto, Riitta; Kinnunen, Tarja I; Guelfi, Kym; Facchinetti, Fabio; Petrella, Elisabetta; Phelan, Suzanne; Scudeller, Tânia T; Rauh, Kathrin; Hauner, Hans; Renault, Kristina; de Groot, Christianne Jm; Sagedal, Linda R; Vistad, Ingvild; Stafne, Signe Nilssen; Mørkved, Siv; Salvesen, Kjell Å; Jensen, Dorte M; Vitolo, Márcia; Astrup, Arne; Geiker, Nina Rw; Kerry, Sally; Barton, Pelham; Roberts, Tracy; Riley, Richard D; Coomarasamy, Arri; Mol, Ben Willem; Khan, Khalid S; Thangaratinam, Shakila
abstract

Diet- and physical activity-based interventions in pregnancy have the potential to alter maternal and child outcomes.


2017 - Estradiol in hormonal contraception: real evolution or just same old wine in a new bottle? [Articolo su rivista]
Grandi, Giovanni; Facchinetti, Fabio; Bitzer, Johannes
abstract

The first combined hormonal contraceptive (CHC) was introduced in 1960 by Gregory Pincus [1 Pincus G, Garcia CR, Rock J, et al. Effectiveness of an oral contraceptive. Science. 1959;30:81–83. [Crossref], [Web of Science ®], [Google Scholar] ] composed by an oral estrogenic and progestin component mestranol and norethinodrel, respectively. Over the last 55 years, the traditional pill has constantly evolved. After the early attempts with mestranol, the use of ethinyl-estradiol (EE) became predominant for decades until a few years ago [2 Grandi G, Cagnacci A, Volpe A. Pharmacokinetic evaluation of desogestrel as a female contraceptive. Expert Opin Drug Metab Toxicol. 2014;10:1–10. [Taylor &amp; Francis Online], [Web of Science ®], [Google Scholar] ]. The EE doses were gradually decreased up to 15 µg. At the same time, numerous different generations of progressively weaker androgenic and even anti-androgenic progestins were tested in order to have products that better fits individual needs. The replacement of EE with estradiol (E2), the estrogen naturally secreted by the granulosa cells of the human ovary, was difficult because of the failure to achieve a satisfactory bleeding control [3 Fruzzetti F, Bitzer J. Review of clinical experience with estradiol in combined oral contraceptives. Contraception. 2010;81:8–15. [Crossref], [PubMed], [Web of Science ®], [Google Scholar] ].


2017 - Evaluation of quantitative fFn test in predicting the risk of preterm birth [Articolo su rivista]
Centra, Michela; Coata, Giuliana; Picchiassi, Elena; Alfonsi, Luisa; Meniconi, Samanta; Bini, Vittorio; Di Tommaso, Maria Rosaria; Cozzolino, Mauro; Facchinetti, Fabio; Ferrari, Francesca; Gervasi, Maria Teresa; Rusconi, Silvia; Todros, Tullia; Frisina, Valentina; Rizzo, Nicola; Bisulli, Maria; Di Renzo, Gian Carlo
abstract

To evaluate diagnostic accuracy of quantitative fetal fibronectin (qfFN) test in predicting preterm birth (PTB) risk &lt;34 weeks' gestation or within 14 days from testing. We explored the predictive potential of the test in five-predefined PTB risk categories based on predefined qfFN thresholds (&lt;10, 10-49, 50-199, 200-499 and ≥500 ng/mL).


2017 - Inositol(s) from Bench to Bedside in Endocrinology and Gynecology [Articolo su rivista]
Unfer, Vittorio; Nestler, John E; Kamenov, Zdravko A; Prapas, Nikos; Facchinetti, Fabio
abstract

The family of inositol(s) is a primordial group of ubiquitary molecules, which appeared at the beginning of evolution of life. Nature has used inositol(s) for several biological functions exploiting minimal changes in the structure. This family plays a pivotal role in regulating many metabolic pathways and hormonal signalling, and its essential function is well known in reproduction process. Plenty of experimental and clinical data have shown that inositols play a pivotal role, as drugs, in treating several pathologies such as PCOS, metabolic syndrome, and gestational diabetes; these natural molecules allow avoiding congenital anomalies and they are very effective in improving assisted reproduction technology (ART); moreover, they have demonstrated promising anticancer activities as shown in numerous studies. This special issue will take in consideration reviews, original research articles, short communications, and any scientific contribution providing both new insights from old data and updated results from experimental or clinical studies, thus pushing forward the boundaries of knowledge of inositol(s) in endocrinology and gynecology.


2017 - Myo-inositol effects in women with PCOS: a meta-analysis of randomized controlled trials [Articolo su rivista]
Unfer, Vittorio; Facchinetti, Fabio; Orrù, Beatrice; Giordani, Barbara; Nestler, John
abstract

Myo-inositol (MI) supplementation in women with polycystic ovary syndrome (PCOS) has been evaluated over the last years. Many hormonal and reproductive impairments associated with this disorder seem relieved by the supplement. The objective of the meta-analysis was to assess the effects of MI alone or combined with d-chiro-inositol (DCI) on the endocrine and metabolic abnormalities of women with PCOS. Literature was retrieved from selected databases, MEDLINE, EMBASE, PubMed and Research Gate (up to November 2016). Only randomized controlled trials (RCTs) investigating the effects of MI alone or combined with DCI were reviewed. Nine RCTs involving 247 cases and 249 controls were included. Significant decreases in fasting insulin (SMD = -1.021 µU/mL, 95% CI: -1.791 to -0.251,P = 0.009) and homeostasis model assessment (HOMA) index (SMD = -0.585, 95% CI: -1.145 to -0.025,P = 0.041) were identified after MI supplementation. The trial sequential analysis of insulin meta-analysis illustrates that the cumulativez-curve crossed the monitoring boundary, providing firm evidence of the intervention effect. A slight trend toward a reduction of testosterone concentration by MI with respect to controls was found (SMD = -0.49, 95% CI: -1.072 to 0.092,P = 0.099), whereas androstenedione levels remained unaffected. Throughout a subgroup's meta-analysis, a significant increase in serum SHBG was observed only in those studies where MI was administered for at least 24 weeks (SMD = 0.425 nmol/L, 95% CI: 0.050-0.801,P = 0.026). These results highlight the beneficial effect of MI in improving the metabolic profile of women with PCOS, concomitantly reducing their hyperandrogenism.


2017 - Preterm Labor and Birth Management: Recommendations from the European Association of Perinatal Medicine [Articolo su rivista]
Di Renzo, G. C.; Cabero Roura, L.; Facchinetti, F.; Helmer, H.; Hubinont, C.; Jacobsson, B.; Jorgensen, J. S.; Lamont, R. F.; Mikhailov, A.; Papantoniou, N.; Radzinsky, V.; Shennan, A.; Ville, Y.; Wielgos, M.; Visser, G. H. A.
abstract


2017 - Progestogens for Maintenance Tocolysis in Women With a Short Cervix: A Randomized Controlled Trial [Articolo su rivista]
Facchinetti, Fabio; Vergani, Patrizia; Di Tommaso, Mariarosaria; Marozio, Luca; Acaia, Barbara; Vicini, Roberto; Pignatti, Lucrezia; Locatelli, Anna; Spitaleri, Marina; Benedetto, Chiara; Zaina, Barbara; DʼAmico, Roberto
abstract

To assess the efficacy of progestogens for maintenance tocolysis in women undelivered after their first preterm labor episode.


2017 - The association between progestins, nuclear receptors expression and inflammation in endometrial stromal cells from women with endometriosis [Articolo su rivista]
Grandi, Giovanni; Mueller, Michael D; Bersinger, Nick A; Facchinetti, Fabio; Mckinnon, Brett D.
abstract

Endometriosis is an inflammatory disease and nuclear receptors play a crucial role in mediating the inflammatory response. In endometrial stromal cells (ESC), nuclear receptors expression can be influenced by the local environment. Progestins are first-line, on-label treatments of endometriosis that may have direct effects on endometriotic lesions through these nuclear receptors. Therefore, we investigated whether there was an association between nuclear receptors expression and the influence of progestins on inflammatory cytokines production in a preliminary, in vitro study with primary cultures. ESC from endometrial biopsies of six subjects with histologically confirmed endometriosis were treated for 6 h with medium alone or with TNF-α (10 or 100 ng/ml) in the presence of dienogest (DNG), medroxyprogesterone acetate (MPA) and norethisterone acetate (NETA) 10-5 M. The progestin-mediated change in IL6, IL8 and MCP-1 mRNA transcription was measured, as was the PRA, PRB, GR, AR and MCR protein expression. The change (medium versus TNF-α 10 ng/ml and medium versus TNF-α 100 ng/ml) in IL6 mRNA transcription was positively associated with the change in PRB, but not PRA with both DNG and NETA treatment. The change in IL8 mRNA was negatively associated with AR expression in the presence of NETA. The change in MCP-1 mRNA expression was positively associated with GR expression and negatively associated with MCR after MPA treatment. The associations between the change in cytokines mRNA expression and nuclear receptors protein expression in response to progestins activity may indirectly suggest different activities of these compounds at a local level worthy of further investigations.


2017 - The Jellyfish Sign: A New Sonographic Cervical Marker to Predict Maternal Morbidity in Abnormally Invasive Placenta Previa [Articolo su rivista]
Bertucci, E.; Sileo, F. G.; Grandi, G.; Fenu, V.; Cani, C.; Mancini, L.; Mataca, E.; Facchinetti, F.
abstract

Purpose -To investigate the value of a new cervical sonographic sign, called the jellyfish sign (JS), for predicting the risk of maternal morbidity in cases of abnormally invasive placenta (AIP) previa totalis. Materials and Methods -Retrospective evaluation of transvaginal (TV) and transabdominal (TA) scans performed in all singleton pregnancies with placenta previa totalis. JS, i.e. the absence of the normal linear demarcation between the placenta previa and the cervix, was evaluated by TV scans. The presence/severity of AIP and outcomes of maternal morbidity were related to this sign. Results -JS was noted in 8/39 (20.5%) patients. The two analyzed groups, i.e. with and without JS, were similar. The specificity of JS in AIP diagnosis, histological findings of accreta/increta/percreta, need for caesarean hysterectomy or blood loss &gt;2000ml ranges between 92% and 96.2%, with the PPV and NPV ranging between 71.4% and 85.7% and 61.3% and 80.6%, respectively. The JS group had a significant increase in blood loss (ml) (p=0.003), transfusions (%) (p=0.016), red blood cells (p=0.002) and plasma (p=0.002), admission to an postoperative intensive care unit (ICU) (%) (p=0.002), hospitalization length (p&lt;0.001) and the need of cesarean hysterectomy (%) (p&lt;0.001). JS was independently correlated to cesarean hysterectomy (OR 25.6; 95% CI 2.0:322.3, p=0.012) and blood loss &gt;2000ml (OR 16.6; 95% CI 1.5:180.1, p=0.021) also in a logistic regression model. Conclusion -JS is useful in predicting the increase in maternal morbidity: massive transfusion, admission to the ICU and cesarean hysterectomy related to intraoperative bleeding in patients with a previa AIP.


2017 - Vaginal alpha-lipoic acid shows an anti-inflammatory effect on the cervix, preventing its shortening after primary tocolysis. A pilot, randomized, placebo-controlled study [Articolo su rivista]
Grandi, G.; Pignatti, L.; Ferrari, F.; Dante, G.; Neri, I.; Facchinetti, F.
abstract

Introduction: Inflammation might be an important underlying cause of preterm birth. Our aim is to explore whether vaginal administration α-lipoic acid reduces cervical inflammation and shortening after primary tocolysis. Materials and methods: Singleton pregnancies between 24–30 weeks remaining undelivered after hospitalization for preterm labor were randomly allocated to placebo (20 women, 15 analyzed) or vaginal ALA 400 mg (active ingredient 10 mg) daily (20 women, 17 analyzed) for 30 days. A cervical swab to quantify pro-inflammatory (IL1, IL2, IL6, IL8, TNFα) and anti-inflammatory (IL4, IL10) cytokines as well as transvaginal ultrasound cervical length measurement (CL) were performed before and after treatment. Results: The % changes of pro-inflammatory cytokines do not differ between treatment groups, while IL4 significantly increases by vaginal ALA in comparison to placebo (118.0 ± 364.3% versus 29.9 ± 103.5%, p = 0.012). Combined anti-inflammatory cytokines show same trend (292.5 ± 208.5% versus 64.5 ± 107.4, p = 0.03). CL remains similar in vaginal ALA group (from 23.1 ± 6.6 to 20.80 ± 7.9 mm), while it significantly decreased in placebo group (from 20.4 ± 6.5 to 13.8 ± 7.5 mm, p &lt; 0.001 versus Baseline; p = 0.003 versus vaginal ALA). Conclusion: Vaginal ALA significantly stimulates anti-inflammatory ILs in the cervix of undelivered women after a preterm labor episode. This effect is associated with a stabilization of the CL.


2016 - A modified prediction model for VBAC, in a European population [Articolo su rivista]
Annessi, E.; Del Giovane, C.; Magnani, L.; Carossino, E.; Baldoni, G.; Battagliarin, G.; Accorsi, P.; Facchinetti, F.
abstract

Objective: The first aim of the study is to validate the Grobmans Nomogram on Italian population, and then to include other variables with the purpose to increase the accuracy of the Nomogram.Methods: This is a multicenter study in which eligible subjects were pregnant women reaching term having one prior cesarean section (CS) and then choosing for a trial of labor. Multivariate logistic regression model have been performed, and then the predicted percentages of vaginal delivery (VD) success were divided into 10 groups and compared with the observed ones.Results: Among 1161 women, 1100 were enrolled, of which 857 (77.9%) delivered vaginally. At the multivariate logistic regression, the variables predicting vaginal birth after cesarean (VBAC) in the validation were maternal age (p &lt; 0.001), maternal body mass index (p = 0.007), having had a VD (p = 0.008) and recurring indication for CS (p &lt; 0.001). By adding the two new variables in the proposed model, was reached the significance of "African ethnicity" (p = 0.037) and especially "years of education" (p = 0.032).Conclusions: The Grobmans Nomogram seems to be applicable to Italian population too, even if with less accuracy than in the US population. The addition of the level of maternal education increases the accuracy of the model, underlining the importance of the social context in the choice of VBAC.


2016 - Acupressure on Self-Reported Sleep Quality During Pregnancy [Articolo su rivista]
Neri, Isabella; Bruno, Raffaele; Dante, Giulia; Facchinetti, Fabio
abstract

The aim of this study was to investigate the short-term effect of acupression at the H7 point on sleep quality during pregnancy. After oral consent had been obtained, the midwife invited the women claiming to have poor sleep quality and anxiety symptoms to complete the Pittsburgh Sleep Quality Index questionnaire and the State-Trait Anxiety Inventory-1. Then, the same midwife, previously trained by an expert acupuncturist (I.N.), advised the women to put on the wrist overnight compression H7 Insomnia Control half an hour before going to bed and to take it off upon awakening, for 10 consecutive days and thereafter every odd day (active group). Women refusing to wear the device for low compliance toward acupression were considered as the control group. After 2 weeks, a second questionnaire evaluation was completed. In the active, but not in the control, group, a significant improvement of sleep quality was observed after H7 device application. The study suggests that H7 acupression applied for 2 weeks improves sleep quality in pregnant women. This preliminary result should serve to stimulate further studies on the long-term effects of acupression.


2016 - Adverse perinatal outcome in subsequent pregnancy after stillbirth by placental vascular disorders [Articolo su rivista]
Monari, Francesca; Pedrielli, Giulia; Vergani, Patrizia; Pozzi, Elisa; Mecacci, Federico; Serena, Caterina; Neri, Isabella; Facchinetti, Fabio
abstract

Objective: To evaluate outcome in the pregnancy following a stillbirth (SB) by a placental vascular disorders. Study Design: A prospective, observational, multicenter study was conducted in woman with a history of stillbirth (> 22 weeks) between 2005 and June 2013, in 3 Italian University Hospitals. Causes of SB were previously identified after extensive investigations. Pregnant women were enrolled within the first trimester. The main outcome was "adverse neonatal outcome", including perinatal death, fetal growth restriction, early preterm birth <33+6 weeks, hypoxicischemic encephalopathy, intracranial hemorrhage or respiratory distress. Results: Out of 364 index pregnancies, 320 women (87.9%) had a subsequent pregnancy during the study period. Forty-seven had an early pregnancy loss. Out of 273 babies, 67 (24.5%) had an adverse perinatal outcome, including 1 SB and 1 early neonatal death (3.7/1000). Women who had a SB related to placental vascular disorders (39.6%), were at higher risk of an adverse neonatal outcome compared with women whose SB was unexplained or resulted from other causes (Adj. OR = 2.1, 95%CI: 1.2-3.8). Moreover, also obesity independently predicts an adverse perinatal outcome (Adj OR = 2.1, 95%CI: 1.1-4.3). Conclusion: When previous SB is related to placental vascular disorders there is a high risk for adverse neonatal outcomes in the subsequent pregnancy. Maternal obesity is an additional risk factor.


2016 - Effects of Inositol(s) in Women with PCOS: A Systematic Review of Randomized Controlled Trials [Articolo su rivista]
Unfer, Vittorio; Nestler, John E; Kamenov, Zdravko A; Prapas, Nikos; Facchinetti, Fabio
abstract

Polycystic ovary syndrome (PCOS) is a common endocrine disorder, with complex etiology and pathophysiology, which remains poorly understood. It affects about 5-10% of women of reproductive age who typically suffer from obesity, hyperandrogenism, ovarian dysfunction, and menstrual irregularity. Indeed, PCOS is the most common cause of anovulatory infertility in industrialized nations, and it is associated with insulin resistance, type 2 diabetes mellitus, and increased cardiovascular risk. Although insulin resistance is not included as a criterion for diagnosis, it is a critical pathological condition of PCOS. The purpose of this systematic review is the analysis of recent randomized clinical trials of inositol(s) in PCOS, in particular myo- and D-chiro-inositol, in order to better elucidate their physiological involvement in PCOS and potential therapeutic use, alone and in conjunction with assisted reproductive technologies, in the clinical treatment of women with PCOS.


2016 - Myo-inositol may prevent gestational diabetes onset in overweight women: a randomized, controlled trial [Articolo su rivista]
Santamaria, Angelo; Di Benedetto, Antonino; Petrella, Elisabetta; Pintaudi, Basilio; Corrado, Francesco; D’Anna, Rosario; Neri, Isabella; Facchinetti, Fabio
abstract

Objective: To evaluate whether myo-inositol supplementation may reduce gestational diabetes mellitus (GDM) rate in overweight women. Methods: In an open-label, randomized trial, myo-inositol (2 g plus 200 μg folic acid twice a day) or placebo (200 μg folic acid twice a day) was administered from the first trimester to delivery in pregnant overweight non-obese women (pre-pregnancy body mass index ≥ 25 and < 30 kg/m2). The primary outcome was the incidence of GDM. Results: From January 2012 to December 2014, 220 pregnant women were randomized at two Italian University hospitals, 110 to myo-inositol and 110 to placebo. The incidence of GDM was significantly lower in the myo-inositol group compared to the placebo group (11.6% versus 27.4%, respectively, p = 0.004). Myo-inositol treatment was associated with a 67% risk reduction of developing GDM (OR 0.33; 95% CI 0.15–0.70). Conclusions: Myo-inositol supplementation, administered since early pregnancy, reduces GDM incidence in overweight non-obese women.


2016 - Perinatal and maternal outcomes in a midwife-led centre in Italy: a comparison with standard hospital assistance [Articolo su rivista]
Dante, Giulia; Neri, Isabella; Bruno, R; Salvioli, Chiara; Facchinetti, Fabio
abstract

Abstract BACKGROUND: In many countries midwives are the primary providers of care for childbearing women. The aim of the present study was to compare the outcomes of childbirth occurring in the birth benter (midwifery-lead) vs. the traditional delivery room organization (doctor-lead) of the Policlinico of Modena Hospital. METHODS: A prospective observational study was conducted over four years. At 35-36th week, women with a single, uneventful pregnancy, being classified at low-risk according to The National Institute for Health and Care Excellence (NICE) guidelines on intrapartum care, were offered to deliver with standard care assistance (SC) in a doctors-led unit or in the Birth Centre (BC). RESULTS: The number of women included was 3156. Overall emergency cesarean sections were lower in BC vs. SC group, and a significant decrease in the rate of augmentation of labor with intravenous oxytocin, in the use of episiotomy and operative deliveries in women of BC were recorded more than in the SC group. More women with intact perineum were present in BC group, while no significant differences in perineal tears was described between groups. CONCLUSIONS: Our results suggest that midwifery care can result in a decrease of medical interventions during labor, namely a reduction of cesarean section and episiotomy rate. Also, the BC remains a valid option for women who satisfy low-risk criteria and wish to give birth in a hospital setting. In Italy the concern to education of all midwives, obstetricians and women at a global level is urgently required, with specific focus on ethics, communication and philosophy of care to enable normalization and humanization of birth.


2016 - Placental telomere shortening in stillbirth: a sign of premature senescence? [Articolo su rivista]
Ferrari, Francesca; Facchinetti, Fabio; Saade, George; Menon, Ramkumar
abstract

The objective of this study is to investigate placental telomere shortening in unexplained stillbirths (SBs) as an indication of premature senescence.


2016 - The effect of combined inositol supplementation on maternal metabolic profile in pregnancies complicated by metabolic syndrome and obesity [Articolo su rivista]
Ferrari, Francesca; Facchinetti, Fabio; Ontiveros, Alejandra E; Roberts, Robyn P; Saade, Mia M; Blackwell, Sean C; Sibai, Baha M; Refuerzo, Jerrie S; Longo, Monica
abstract

Myoinositol and D-chiroinositol improve insulin resistance in women with obesity and gestational diabetes and in postmenopausal women with metabolic syndrome. We previously reported that offspring born to hypertensive dams lacking endothelial nitric oxide synthase and fed a high-fat diet develop metabolic-like syndrome phenotype.


2016 - The Ratio of MI to DCI and Its Impact in the Treatment of Polycystic Ovary Syndrome: Experimental and Literature Evidences [Capitolo/Saggio]
Facchinetti, F.; Dante, G.; Neri, I.
abstract

Myo-inositol (MI) and d-chiro-inositol (DCI), two second messengers of insulin in various insulin-dependent processes, are implicated in polycystic ovary syndrome (PCOS). MI and DCI exert distinct functions in insulin signaling. While MI is involved in the activation of glucose transporters and glucose utilization, DCI is mainly involved in the glycogen synthesis. At ovarian level, MI plays a pivotal role in the FSH signaling while DCI promotes insulin-dependent androgen synthesis. Although MI and DCI fulfill different roles, often their biological activities are confused. A key point is the physiological plasma ratio of 40:1, between MI and DCI, in healthy subjects. It was shown in the PCOS treatment the efficacy of therapies based on the restoration of the appropriate MI:DCI ratio, in such a way as to prompt a new approach in the researches and clinical trials. Moreover, it has been demonstrated that MI is able to increase oocyte and sperm cell quality, opening new possibilities to assisted reproduction technology (ART). With the aim to clarify these two sets of issues and answer a number of research questions and also to develop future studies, the International Consensus Conference on myo- and d-chiro-inositol in obstetrics and gynecology was held in Florence in 2013. In this chapter are summarized the main conclusions on MI and DCI and the role of MI in ART.


2015 - A challenging case of pregnancy with placenta accreta and very rare irregular antibodies versus Cromer blood group system: a case report [Articolo su rivista]
Busani, Stefano; VOLPI GHIRARDINI, Annamaria; Petrella, Elisabetta; Neri, Isabella; Casari, Federico; Venturelli, Donatella; De Santis, Mario; Montagnani, Giuliano; Facchinetti, Fabio; Girardis, Massimo
abstract

ntroduction: This report describes the challenges of treating a pregnant woman who had a rare case of critical placenta accreta with concurrent Cromer system anti-Tc(a) and anti-Kidd A alloantibodies. No previous case of such alloimmunization in a patient with placenta accreta has been reported. Case presentation: A 28-year-old African woman with anti-Cromer Tc(a) antibodies, anti-Kidd A antibodies and placenta accreta was admitted to the obstetric emergency department at our university hospital with persistent vaginal bleeding. Her rare Cromer blood group system antibodies had been diagnosed 1 month earlier; no compatible blood had been found despite a worldwide search. We performed a cesarean section after placement of Fogarty balloons in her uterine arteries with preoperative endovascular interventional radiology. Other therapeutic interventions included preoperative iron administration to raise hemoglobin and the scheduled predeposit of autologous blood. Intraoperative therapeutic management was aimed at preventing coagulopathy and massive bleeding. With the use of alternative medical techniques determined during perioperative planning, her intraoperative blood loss was only 1000mL, despite the placenta accreta. She was discharged from the hospital 4 days after cesarean section. Conclusions: To the best of our knowledge, this is the first report of an alloimmunized patient with two different alloantibodies and concurrent high risk of bleeding because of placenta accreta. The close collaboration among obstetricians, anesthesiologists, interventional radiologists, blood bank pathologists and intensive care doctors prevented serious consequences in this patient. The exceptional feature of this case is the patient's double risk: the placenta accreta and the inability to transfuse compatible blood. These two extreme situations challenged the multidisciplinary medical team.


2015 - Erratum to: Study protocol: differential effects of diet and physical activity based interventions in pregnancy on maternal and fetal outcomes: individual patient data (IPD) meta-analysis and health economic evaluation [Articolo su rivista]
Ruifrok, Anneloes E; Rogozinska, Ewelina; van Poppel, Mireille N. M; Rayanagoudar, Girish; Kerry, Sally; de Groot, Christianne J. M; Yeo, Seonae; Molyneaux, Emma; Barakat Carballo, Ruben; Perales, Maria; Bogaerts, Annick; Cecatti, Jose G; Surita, Fernanda; Dodd, Jodie; Owens, Julie; El Beltagy, Nermeen; Devlieger, Roland; Teede, Helena; Harrison, Cheryce; Haakstad, Lene; Shen, Garry X; Shub, Alexis; Motahari, Narges; Khoury, Janette; Tonstad, Serena; Luoto, Riitta; Kinnunen, Tarja I; Guelfi, Kym; Facchinetti, Fabio; Petrella, Elisabetta; Phelan, Suzanne; Scudeller, Tânia T; Rauh, Kathrin; Hauner, Hans; Renault, Kristina; Sagedal, Linda Reme; Vistad, Ingvild; Stafne, Signe Nilssen; Mørkved, Siv; Salvesen, Kjell Åsmund; Vinter, Christina; Vitolo, Marcia; Astrup, Arne; Geiker, Nina Rica Wium; Mcauliffe, Fionnuala; Poston, Lucilla; Roberts, Tracy; Riley, Richard D; Coomarasamy, Arri; Khan, Khalid S; Mol, Ben Willem; Thangaratinam, Shakila
abstract

After publication of this work [1], we noted that we inadvertently failed to include the complete list of all coauthors and that sample sizes of some of the trials listed in Table two were incorrect. The full list of authors has now been added and includes the names of all authors within the i-WIP Collaborative Network. The Authors’ contributions and competing interests section modified accordingly. We are publishing this erratum to update the author list, which is as follows: Anneloes E Ruifrok, Ewelina Rogozinska, Mireille NM van Poppel, Girish Rayanagoudar, Sally Kerry, Christianne JM de Groot, SeonAe Yeo, Emma Molyneaux, Fionnuala McAuliffe, Lucilla Poston, Tracy Roberts, Richard D Riley, Arri Coomarasamy, Khalid Khan, Ben Willem Mol, Ruben Barakat Carballo, Maria Perales, Annick Bogaerts, Jose G Cecatti, Fernanda Surita, Jodie Dodd, Julie Owens, Nermeen El Beltagy, Roland Devlieger, Helena Teede, Cheryce Harrison, Lene Haakstad, Garry X Shen, Alexis Shub, Narges Motahari, Janette Khoury, Serena Tonstad, Riitta Luoto, Tarja I Kinnunen, Kym Guelfi, Fabio Facchinetti, Elisabetta Petrella, Suzanne Phelan, Tânia T Scudeller, Kathrin Rauh, Hans Hauner, Kristina Renault, Linda Reme Sagedal, Ingvild Vistad, Signe Nilssen Stafne, Siv Mørkved, Kjell Åsmund Salvesen, Christina Vinter, Marcia Vitolo, Arne Astrup, Nina Rica Wium Geiker and Shakila Thangaratinam. The sample sizes of trials included in Table two have been corrected (Table 1). We are publishing this erratum to update these trial sample sizes, which include Dodd 2014 (n = 2212), Prevedel 2003 (n = 41), Renault 2013 (n = 425), Stafne 2012 (n = 855), Vinter 2011 (n = 360), Walsh 2012 (n = 800) and Wolff 2008 (n = 66).


2015 - Herbal Supplements in Pregnancy: Effects on Conceptions and Delivery [Capitolo/Saggio]
Facchinetti, F.; Dante, G.; Neri, I.
abstract

Before and during pregnancy, women are apprehensive about the potential toxicity of conventional medicines, so they use herbal remedies (HR) to complement or to replace them, although much current practice is not evidence-based. The current stage of knowledge is still inadequate to sufficiently inform clinicians, researchers, and the public about the benefits or potential risks of the use of HR for female infertility treatments. The extent of herbal remedies use in pregnancy has been widely researched throughout the world. Epidemiological studies reported a wide range of use of herbal remedies in pregnancy. Too few studies have been devoted to safety and efficacy of singular herbs. With the exception of ginger, there are no consistent data to support the use of any other herbal supplement during pregnancy.


2015 - Induction of labor in women that had a previous cesarean delivery [Articolo su rivista]
Facchinetti, Fabio; DEL GIOVANE, Cinzia; Petrella, Elisabetta; Annessi, Eleonora
abstract

This study aims to evaluate factors that predict the likelihood of the success of induction of labor (IOL) in women that had a previous cesarean section (pCS).


2015 - Intrapartum antibiotic prophylaxis for Group B Streptococcus and risks of unnecessary antibiotics [Articolo su rivista]
Berardi, Alberto; Ferrari, Fabrizio; Facchinetti, Fabio
abstract

We much appreciated the Clinical Opinion by Turrentine1 regarding intrapartum antibiotic prophylaxis (IAP) for the prevention of neonatal group B Streptococcus (GBS) early-onset sepsis. The author raises concerns about cases of inadequate duration (&lt;4 hours) of IAP before delivery. Indeed, as much as 25-40% of GBS-colonized women will not receive the 4 hours of IAP that are recommended by guidelines. To optimize fetal exposure, Turrentine recommends strategies such as (1) to postpone artificial rupture of membranes (or administration of oxytocin) until 4 hours IAP is completed and (2) to start IAP before the initiation of uterotonic agents in women who are admitted for induction of labor. Although the first step is feasible, a woman with a Bishop score &lt;5 may be exposed to several antibiotic doses until delivery. The minimum duration of IAP for the prevention of early-onset GBS sepsis remains uncertain, because existing data are conflicting. There is evidence that bactericidal levels of β-lactam antibiotics in fetal blood are achieved as early as 3 minutes and that levels that exceed 10- to 179-fold of the minimal inhibitory concentration for GBS persist for up to 2 hours. Although neonatal colonization (NC) is only a proxy marker of infection, the study of NC gives useful information regarding the effects of IAP within the amniotic fluid. We demonstrated that intravenous ampicillin that is given &lt;2 hours before delivery is very effective in reducing NC.2 More recently, we evaluated NC in a larger prospective cohort study. Almost 40% of 44 neonates without IAP exposure get colonized at 24-48 hours of birth, whereas rates of NC were low (between 9.3% and 0) in the 458 neonates who were exposed to IAP.3 Interestingly, rates of NC did not vary significantly in the range of &lt;1–12 h before delivery (score test for trend of odds; P = .13). No cases of NC were found after 12 hours of IAP. Both studies provide strong evidence of a rapid action of ampicillin within the amniotic fluid, although they do not provide firm evidence regarding the time necessary to ensure the effectiveness. Although the labor process is capricious, delivery is largely a slow, rather than a fast, event (unfortunately for women and their caregivers!). Therefore, we raise concerns regarding intrapartum management strategies that perhaps allow some neonatal benefit, while exposing a greater number of women to unnecessary antibiotics, which is a probable harmful consequence to public health.4


2015 - Lifestyle-induced maternal body composition changes and birthweight in overweight/obese pregnant women [Articolo su rivista]
Bruno, R; Petrella, E; Bertarini, V; Neri, I; Facchinetti, F
abstract

Introduction: Obesity and excessive gestational weight gain (GWG) have been associated with higher occurrence of large for gestational age (LGA) babies, and several interventions have been proposed to limit GWG, which, however, does not reflect adequately the subtle changes in body composition that happens during pregnancy. The aim of this study is to evaluate if the variations of body composition, induced by a lifestyle program intended to limit GWG and measured through bioelectrical impedence analysis (BIA), could affect the newborns' weight in overweight/obese women. Methods: One hundred and thirty-nine women with BMI &gt;= 25 kg/m(2) were enrolled between 9th-12th week and a lifestyle program, consisting of low glycemic diet with caloric restriction and physical activity, was prescribed to them. BIA was performed at enrolment and at 35th-36th week. Data regarding the newborns' weight were collected from clinical charts after delivery. Results: Women who exceeded recommended range of GWG had an higher occurrence of LGA babies. Analysing the body composition, fat free mass (FFM) showed a direct correlation with the birthweight centile, even after correcting for BMI at enrolment, age and gestational diabetes mellitus. Interestingly, women who had an increase in fat mass (FM) and visceral FM throughout pregnancy had an higher occurrence of small for gestational age (SGA) babies. Conclusion: The increase in FM and visceral FM during pregnancy in overweight/obese women is linked to a higher occurrence of SGA babies.


2015 - Myo-inositol Supplementation for Prevention of Gestational Diabetes in Obese Pregnant Women: A Randomized Controlled Trial [Articolo su rivista]
Dʼanna, Rosario; Di Benedetto, Antonino; Scilipoti, Angela; Santamaria, Angelo; Interdonato, Maria Lieta; Petrella, Elisabetta; Neri, Isabella; Pintaudi, Basilio; Corrado, Francesco; Facchinetti, Fabio
abstract

OBJECTIVE: To evaluate whether myo-inositol supplementation, an insulin sensitizer, reduces the rate of gestational diabetes mellitus (GDM) and lowers insulin resistance in obese pregnant women. METHODS: In an open-label, randomized trial, myo-inositol (2 g plus 200 micrograms folic acid twice a day) or placebo (200 micrograms folic acid twice a day) was administered from the first trimester to delivery in pregnant obese women (prepregnancy body mass index 30 or greater. We calculated that 101 women in each arm would be required to demonstrate a 65% GDM reduction in the myo-inositol group with a statistical power of 80% (0.05). The primary outcomes were the incidence of GDM and the change in insulin resistance from enrollment until the diagnostic oral glucose tolerance test. RESULTS: From January 2011 to April 2014, 220 pregnant women at 12-13 weeks of gestation were randomized at two Italian university hospitals, 110 to myo-inositol and 110 to placebo. Most characteristics were similar between groups. The GDM rate was significantly reduced in the myo-inositol group compared with the control group, 14.0% compared with 33.6%, respectively (P.001; odds ratio 0.34, 95% confidence interval 0.17-0.68). Furthermore, women treated with myo-inositol showed a significantly greater reduction in the homeostasis model assessment of insulin resistance compared with the control group, -1.0±3.1 compared with 0.1±1.8 (P.048). CONCLUSION: Myo-inositol supplementation, started in the first trimester, in obese pregnant women seems to reduce the incidence in GDM through a reduction of insulin resistance.


2015 - Poor Folate Intake in a North Italian Pregnant Population: an Epidemiological Survey [Articolo su rivista]
Dante, Giulia; Morani, Letizia; Bronzetti, Daisy; Garutti, Paola; Neri, Isabella; Calapai, Gioacchino; Facchinetti, Fabio
abstract

Background The association between folic acid (FA) insufficiency and congenital malformations has been demonstrated in over the past two decades. The aim of the present study was to investigate the use and timing of folate intake among a large sample of pregnant women in a north Italian region. Methods A multicentre prospective cohort study was conducted over a 14-month period in the maternity wards of five general hospitals (2301 women). Data were collected via a face-to-face interview. Results Seven hundred sixty women (33%) took at least one product containing FA. Seven hundred thirty-three (31.8%) women consumed multivitamins containing 413 (17.9%) consumed products containing FA only and 17 (0.7%) 15mg of levofolinic acid. Only 0.9% of all women took FA before pregnancy 72.5% of women who consumed FA started during the first trimester. The most common dosage was 0.4mg (19.4%). Conclusions Very few women in the population are taking FA before pregnancy. Moreover, while most women consuming FA started in the first trimester, it is likely that they did so after closure of the neural tube. An important action is the recommendation that periconceptional supplementation programmes be promoted.


2015 - Recurrence of hypertensive disorders of pregnancy: an individual patient data metaanalysis [Articolo su rivista]
van Oostwaard, Miriam F.; Langenveld, Josje; Schuit, Ewoud; Papatsonis, Dimitri N. M.; Brown, Mark A.; Byaruhanga, Romano N.; Bhattacharya, Sohinee; Campbell, Doris M.; Chappell, Lucy C.; Chiaffarino, Francesca; Crippa, Isabella; Facchinetti, Fabio; Ferrazzani, Sergio; Ferrazzi, Enrico; Figueiró Filho, Ernesto A.; Gaugler Senden, Ingrid P. M.; Haavaldsen, Camilla; Lykke, Jacob A.; Mbah, Alfred K.; Oliveira, Vanessa M.; Poston, Lucilla; Redman, Christopher W. G.; Salim, Raed; Thilaganathan, Baskaran; Vergani, Patrizia; Zhang, Jun; Steegers, Eric A. P.; Mol, Ben Willem J.; Ganzevoort, Wessel
abstract

We performed an individual participant data (IPD) metaanalysis to calculate the recurrence risk of hypertensive disorders of pregnancy (HDP) and recurrence of individual hypertensive syndromes.


2015 - Results from the International Consensus Conference on myo-inositol and D-chiro-inositol in Obstetrics and Gynecology - assisted reproduction technology [Articolo su rivista]
Bevilacqua, Arturo; Carlomagno, Gianfranco; Gerli, Sandro; Montanino Oliva, Mario; Devroey, Paul; Lanzone, Antonio; Soulange, Christophe; Facchinetti, Fabio; Di Renzo, Gian Carlo; Bizzarri, Mariano; Hod, Moshe; Cavalli, Pietro; D'Anna, Rosario; Benvenga, Salvatore; Chiu, Tony T; Kamenov, Zdravko A.
abstract

A substantial body of research on mammalian gametogenesis and human reproduction has recently investigated the effect of myo-inositol (MyoIns) on oocyte and sperm cell quality, due to its possible application to medically assisted reproduction. With a growing number of both clinical and basic research papers, the meaning of several observations now needs to be interpreted under a solid and rigorous physiological framework. The 2013 Florence International Consensus Conference on Myo- and D-chiro-inositol in obstetrics and gynecology has answered a number of research questions concerning the use of the two stereoisomers in assisted reproductive technologies. Available clinical trials and studies on the physiological and pharmacological effects of these molecules have been surveyed. Specifically, the physiological involvement of MyoIns in oocyte maturation and sperm cell functions has been discussed, providing an answer to the following questions: (1) Are inositols physiologically involved in oocyte maturation? (2) Are inositols involved in the physiology of spermatozoa function? (3) Is treatment with inositols helpful within assisted reproduction technology cycles? (4) Are there any differences in clinical efficacy between MyoIns and D-chiro-inositol? The conclusions of this Conference, drawn depending on expert panel opinions and shared with all the participants, are summarized in this review paper.


2015 - Results from the International Consensus Conference on Myo-inositol and d-chiro-inositol in Obstetrics and Gynecology: the link between metabolic syndrome and PCOS [Articolo su rivista]
Facchinetti, Fabio; Bizzarri, Mariano; Benvenga, Salvatore; D'Anna, Rosario; Lanzone, Antonio; Soulage, Christophe; Di Renzo, Gian Carlo; Hod, Moshe; Cavalli, Pietro; Chiu, Tony T; Kamenov, Zdravko A; Bevilacqua, Arturo; Carlomagno, Gianfranco; Gerli, Sandro; Montanino Oliva, Mario; Devroey, Paul
abstract

In recent years, interest has been focused to the study of the two major inositol stereoisomers: myo-inositol (MI) and d-chiro-inositol (DCI), because of their involvement, as second messengers of insulin, in several insulin-dependent processes, such as metabolic syndrome and polycystic ovary syndrome. Although these molecules have different functions, very often their roles have been confused, while the meaning of several observations still needs to be interpreted under a more rigorous physiological framework. With the aim of clarifying this issue, the 2013 International Consensus Conference on MI and DCI in Obstetrics and Gynecology identified opinion leaders in all fields related to this area of research. They examined seminal experimental papers and randomized clinical trials reporting the role and the use of inositol(s) in clinical practice. The main topics were the relation between inositol(s) and metabolic syndrome, polycystic ovary syndrome (with a focus on both metabolic and reproductive aspects), congenital anomalies, gestational diabetes. Clinical trials demonstrated that inositol(s) supplementation could fruitfully affect different pathophysiological aspects of disorders pertaining Obstetrics and Gynecology. The treatment of PCOS women as well as the prevention of GDM seem those clinical conditions which take more advantages from MI supplementation, when used at a dose of 2g twice/day. The clinical experience with MI is largely superior to the one with DCI. However, the existence of tissue-specific ratios, namely in the ovary, has prompted researchers to recently develop a treatment based on both molecules in the proportion of 40 (MI) to 1 (DCI).


2015 - Transvaginal ultrasound assessment of uterine scar after previous caesarean section: comparison with 3T-magnetic resonance diffusion tensor imaging [Articolo su rivista]
Fiocchi, Federica; Petrella, Elisabetta; Nocetti, Luca; Currà, Serena; Ligabue, Guido; Costi, Tiziana; Torricelli, Pietro; Facchinetti, Fabio
abstract

This study aimed to evaluate 3-T magnetic resonance imaging in the analysis of caesarean scars in women with prior caesarean section (pCS) and investigate the potential added value of diffusion tensor imaging (3T-MR-DTI) with fibre tracking reconstruction, compared with transvaginal ultrasound (TVUS). Thirty women who had previously undergone elective CS in a singleton pregnancy at term were examined (19 women with one pCS formed group 1 and 11 women with two pCS formed group 2). Patients underwent TVUS and 3T-MR-DTI within 2 days. Twelve women with prior vaginal delivery served as controls and underwent only 3T-MR. Uterine fibre architecture was depicted by MR-DTI with 3D tractography reconstruction providing quali-quantitative analysis of fibre, described as the reduction of number of longitudinal fibres that run through the uterine scar. Six subjects were excluded. According to 3T-MR morphology, scars were described as linear (n = 12) and retracting (n = 12); disagreement with TVUS was 54 %. The thickness of myometrium at the scar level was found to be significantly greater with 3T-MR compared to TVUS in linear scars (p = 0.01). No difference was found among retracting scars. In controls, according to 3T-MR-DTI, longitudinal myometrial fibres running in the anterior wall were similar to those in the posterior wall at same level -2 %; -27 % + 22 %). In groups 1 and 2 there was significant reduction in anterior fibres compared to posterior ones (-53 %; -77 % - 34 %; p = 0.0001). Among retracting scars, fibre reduction was significantly higher compared to linear scars, p &lt; 0.016. The added value of 3T-MR with DTI lies in the prompt evaluation of muscle fibre remaining at scar level.


2015 - [11-OR]: Myo-inositol in the prevention of gestational diabetes and its complications [Abstract in Rivista]
D'Anna, Rosario; Santamaria, Angelo; Corrado, Francesco; Benedetto, Antonino Di; Petrella, Elisabetta; Facchinetti, Fabio
abstract

To check the hypothesis that myo-inositol supplementation, an insulin sensitizing substance, may reduce gestational diabetes mellitus (GDM) onset and insulin resistance in obese pregnant women.


2014 - Acupuncture in post-date pregnancy: a pilot study. [Articolo su rivista]
Neri, Isabella; F., Monari; C. S., Midwife; Facchinetti, Fabio
abstract

Pharmacological labor induction is obtained through intracervical/vaginal prostaglandins and/or oxytocin infusion; however, the use of these agents produces fetal and maternal side effects. Traditional Chinese medicine advocates the use of acupuncture to soften the cervix and induce uterine contractions. The aim of the present study is to investigate the effect of acupuncture to induce labor. Acupuncture was applied in post-date pregnancies one week before a planned induction; the primary outcome was the rate of women submitted to labor induction for prolonged pregnancy at week 41 + 5.After informed consent, 221 undelivered women ranging between 40 + 2/40 + 6 gestational age were considered eligible for the study and 202 were randomized to receive acupuncture or observation. Sessions of acupuncture were planned every odd day from the randomization till 41a week plus 4 days. At 41 + 5 week a pharmacological induction of labor was planned.The total rate of labor induction did not significantly differ between observation and acupuncture group (20\% versus 17\%). Moreover no differences were found as far as the indications to induce labor, in particular "prolonged pregnancy" was similar between groups (8/96 versus 5/99). To investigate between-group differences in time elapsed between inclusion and delivery, survival analysis was performed excluding women requiring labor induction: women receiving acupuncture showed a trend to deliver earlier than women in the observation group (p < 0.09).The present study demonstrated that acupuncture applied every odd day for one week seems ineffective in reducing the rate of labor induction performed for prolonged pregnancy at 41 + 5 weeks. Previous reports reached similar conclusions, independently of the different timing, duration and mode of stimuli application.


2014 - Dietary interventions, lifestyle changes, and dietary supplements in preventing gestational diabetes mellitus: a literature review [Articolo su rivista]
Facchinetti, Fabio; Dante, Giulia; Petrella, Elisabetta; Neri, Isabella
abstract

Gestational diabetes mellitus (GDM) is associated with increased rates of fetal morbidity and mortality, both during the pregnancy and in the postnatal life. Current treatment of GDM includes diet with or without medications, but this management is expensive and poorly cost-effective for the health care systems. Strategies to prevent such condition would be preferable with respect to its treatment. The aim of this literature review was to evaluate studies reporting the efficacy of the most used approaches to prevent GDM as well as evidences of efficacy and safety of dietary supplementations. Systematic literature searches were performed in electronic databases, covering the period January 1983 to April 2014. Randomized controlled clinical trials were included. Quality of the articles was evaluated with the Jadad scale. We did not evaluate those articles that were already entered in the most recent systematic reviews, and we completed the research with the trials published thereafter. Of 55 articles identified, 15 randomized controlled trials were eligible. Quality and heterogeneity of the studies cannot allow firm conclusions. Anyway, trials in which only intake or expenditure has been targeted mostly reported negative results. On the contrary, combined lifestyle programs including diet control (orienting food intake, restricting energy intake) associated with moderate but continuous physical activity exhibit better efficacy in reducing GDM prevalence. The results from dietary supplements with myoinositol or probiotics are promising. The actual evidences provide enough arguments for implementing large-scale, high-quality randomized controlled trials looking at the possible benefits of these new approaches for preventing GDM.


2014 - Factors associated with intrapartum transmission of group B Streptococcus [Articolo su rivista]
Berardi, Alberto; Rossi, Cecilia; Guidotti, Isotta; Vellani, Giulia; Lugli, Licia; Bacchi Reggiani, Maria Letizia; Ferrari, Filippo; Facchinetti, Fabio; Ferrari, Fabrizio
abstract

Data regarding the minimum duration of intrapartum antibiotic prophylaxis (IAP) required for preventing group B Streptococcus (GBS) early-onset sepsis are conflicting. Understanding factors that influence neonatal colonization (NC) might help us understand factors associated with failure of prophylaxis.


2014 - Gestational weight gain in overweight and obese women enrolled in a healthy lifestyle and eating habits program [Articolo su rivista]
Petrella, Elisabetta; Malavolti, M; Bertarini, V; Pignatti, Lucrezia; Neri, Isabella; Battistini, N. C; Facchinetti, Fabio
abstract

OBJECTIVES: To determine whether changes in lifestyle in women with BMI &gt; 25 could decrease gestational weight gain and unfavorable pregnancy outcomes. METHODS: Women with BMI &gt; 25 were randomized at 1st trimester to no intervention or a Therapeutic Lifestyle Changes (TLC) Program including diet (overweight: 1700 kcal/day, obese: 1800 kcal/day) and mild physical activity (30 min/day, 3 times/week). At baseline and at the 36th week women filled-in a Food Frequency Questionnaire. OUTCOMES: gestational weight gain, gestational diabetes mellitus, gestational hypertension, preterm delivery. Data stratified by BMI categories. RESULTS: Socio-demographic features were similar between groups (TLC: 33 cases, CONTROLS: 28 cases). At term, gestational weight gain in obese women randomized to TLC group was lower (6.7 ± 4.3 kg) versus controls (10.1 ± 5.6 kg, p = 0.047). Gestational diabetes mellitus, gestational hypertension and preterm delivery were also significantly lower. TLC was an independent factor in preventing gestational weight gain, gestational diabetes mellitus, gestational hypertension. Significant changes in eating habits occurred in the TLC group, which increased the number of snacks, the intake of fruits-vegetables and decreased the consumption of sugar. CONCLUSIONS: A caloric restriction associated to changes in eating behavior and constant physical activity, is able to reduce gestational weight gain and related pregnancy complications in obese women.


2014 - Herbal therapies in pregnancy: what works? [Articolo su rivista]
G., Dante; G., Bellei; Neri, Isabella; Facchinetti, Fabio
abstract

The aim of this article is two-fold: to report the prevalence of herbal products used by pregnant women and to evaluate the evidence of efficacy and safety of the most popular remedies.Of the 671 articles identified, 15 randomized controlled trials (RCTs) and 16 non-RCTs were eligible. Ginger was the most investigated remedy and it was consistently reported to ameliorate nausea and vomiting in pregnancy. Although raspberry, blue cohosh, castor oil, and evening primrose oil are believed to facilitate labor in traditional medicine, very few scientific data support such indication. Moreover, they have been associated with severe adverse events. Data on the safety of Hypericum perforatum in pregnancy or lactation are reassuring, whereas efficacy was demonstrated only in nonpregnant individuals. There is still insufficient evidence regarding the efficacy and safety of Echinacea, garlic, and cranberry in pregnancy.Epidemiological studies reported a wide range of use of herbal remedies in pregnancy. Too few studies have been devoted to the safety and efficacy of singular herbs. With the exception of ginger, there are no consistent data to support the use of any other herbal supplement during pregnancy. Severe adverse events have been reported using blue cohosh and evening primrose oil.


2014 - Metabolic alterations in HIV-infected pregnant women: moving to metabolic tailoring of antiretroviral drugs. [Articolo su rivista]
Guaraldi, Giovanni; Stentarelli, Chiara; A. D., Da Silva; K., Luzi; Neri, Isabella; M., Cellini; E., Petrella; E., Garlassi; Menozzi, Marianna; Facchinetti, Fabio; Mussini, Cristina
abstract

The most striking effect of increased survival and improved quality of life in HIV-infected women undergoing antiretroviral therapy is the feasibility of motherhood-desire satisfaction. However, such advantages are often associated with drug-related metabolic toxicities, particularly relevant in the pregnancy context. Recent guidelines provide recommendations and trends for the use of antiretroviral therapy in pregnant women, but current literature falls short of providing specific insights on the need for metabolic monitoring and treatment in HIV-infected pregnant women. In this review we provide specific insight into the state-of-the-art of: detection, evaluation, and management of metabolic alterations in this special population. Pregnancy is in fact a metabolic transition process, potentially associated with specific diseases in the mother, in the newborn, and in the adulthood of the child. We will not simply discuss antiretroviral therapy metabolic toxicities, but rather their interaction with the physiological metabolic changes occurring during pregnancy. Close monitoring is needed to diagnose metabolic alterations that can lead to adverse outcomes in the mother, in the newborn, and potentially in adulthood. Lifestyle interventions and an appropriate metabolic tailoring of antiretroviral therapy drugs need to be considered in the prevention and treatment of metabolic alteration during pregnancy.


2014 - Study protocol: Differential effects of diet and physical activity based interventions in pregnancy on maternal and fetal outcomes-individual patient data (IPD) meta-analysis and health economic evaluation [Articolo su rivista]
Ruifrok, A. E.; Rogozinska, E.; van Poppel, M.; Rayanagoudar, G.; Kerry, S.; De Groot, C. J. M.; Yeo, S.; Molyneaux, E.; McAuliffe, F. M.; Poston, L.; Roberts, T.; Riley, R. D.; Coomarasamy, A.; Khan, K.; Mol, B. W.; Thangaratinam, S.; Carballo, R. B.; Bogaerts, A.; Cecatti, J. G.; Lopez, B.; Dodd, J.; Beltagy, N. E.; Devlieger, R.; Haakstad, L.; Shen, G.; Shub, A.; Motaharim, N.; Khoury, J.; Luoto, R.; Guelfi, K.; Facchinetti, F.; Phelan, S.; Poston, L.; Prevedel, T. T. S.; Rauh, K.; Renault, K.; Sagedal, L. R.; Stafne, S. N.; Morkved, S.; Vesco, K.; Vinter, C.; Vitol, O.; Astrup, A.; Yeo, S.
abstract

Background: Pregnant women who gain excess weight are at risk of complications during pregnancy and in the long term. Interventions based on diet and physical activity minimise gestational weight gain with varied effect on clinical outcomes. The effect of interventions on varied groups of women based on body mass index, age, ethnicity, socioeconomic status, parity, and underlying medical conditions is not clear. Our individual patient data (IPD) meta-analysis of randomised trials will assess the differential effect of diet- and physical activity-based interventions on maternal weight gain and pregnancy outcomes in clinically relevant subgroups of women.Methods/design: Randomised trials on diet and physical activity in pregnancy will be identified by searching the following databases: MEDLINE, EMBASE, BIOSIS, LILACS, Pascal, Science Citation Index, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and Health Technology Assessment Database. Primary researchers of the identified trials are invited to join the International Weight Management in Pregnancy Collaborative Network and share their individual patient data. We will reanalyse each study separately and confirm the findings with the original authors. Then, for each intervention type and outcome, we will perform as appropriate either a one-step or a two-step IPD meta-analysis to obtain summary estimates of effects and 95% confidence intervals, for all women combined and for each subgroup of interest. The primary outcomes are gestational weight gain and composite adverse maternal and fetal outcomes. The difference in effects between subgroups will be estimated and between-study heterogeneity suitably quantified and explored. The potential for publication bias and availability bias in the IPD obtained will be investigated. We will conduct a model-based economic evaluation to assess the cost effectiveness of the interventions to manage weight gain in pregnancy and undertake a value of information analysis to inform future research.Systematic review registration: PROSPERO 2013:CRD42013003804.


2014 - The l-arginine/nitric oxide pathway is impaired in overweight/obese pregnant women [Articolo su rivista]
Petrella, Elisabetta; Pignatti, Lucrezia; Neri, Isabella; Facchinetti, Fabio
abstract

To evaluate the l-arginine/NO system and its role in insulin signaling and endothelial function during the pregnancy of women of different BMI categories.


2013 - ABCB4 and ABCB11 mutations in intrahepatic cholestasis of pregnancy in an Italian population [Articolo su rivista]
Anzivino, Claudia; Odoardi, Maria Rosaria; Meschiari, Erica; Baldelli, Enrica; Facchinetti, Fabio; Neri, Isabella; Ruggiero, Giuseppe; Zampino, Rosa; Bertolotti, Marco; Loria, Paola; Carulli, Lucia
abstract

Background: Genetic alterations in the ATP-binding cassette subfamily B member 4 (ABCB4) and ATPbinding cassette subfamily B member 11 (ABCB11) have been associated to the onset of intrahepatic cholestasis of pregnancy (ICP) in predisposed women. Aims: To identify new and/or frequent ABCB4 and ABCB11 genes variants in a cohort of Italian patients with ICP and to evaluate the possible pathogenetic role for the novel mutations identified. Methods: DNA of 33 unrelated Italian women with obstetric cholestasis were screened for mutations in the entire coding sequence of ABCB4 and ABCB11 genes. Polymerase chain reaction and automated sequencing was performed on the 27 coding exons of both genes. Results: Genotyping revealed 11 mutations, 5 of whom were novel variants: 2 localized on ABCB4 (p.I587DfsX603, p.I738LfsX744) and 3 on ABCB11 (p.V284D, p.Q558H, p.P731S). The most severe phenotypes were associated with the variants p.I587DfsX603, p.I738LfsX744 and p.V284D. Moreover, the already described mutation p.N510S found in ABCB4 seems to be strictly involved in the onset of ICP in that particular patient. Conclusions: Our data support the hypothesis of a significant involvement of ABCB4 mutations in the onset of ICP, but also confirm an important role for ABCB11 mutations in increasing the susceptibility to cholestasis of pregnancy.


2013 - Authors reply [Articolo su rivista]
Facchinetti, F.
abstract


2013 - Considerations on "late preterm" newborns [Articolo su rivista]
Baronciani, D.; Facchinetti, F.
abstract


2013 - Effects of pregnancy on endothelial function and cardiovascular disease risk in HIV-infected women [Articolo su rivista]
K., Luzi; A. R., Eckard; A., Lattanzi; ZONA, Stefano; MODENA, Maria Grazia; FACCHINETTI, Fabio; GUARALDI, Giovanni
abstract

– This study assessed flow–mediated vasodilation (FMD) and brachial artery diameter (BAD) in HIV–infected pregnant women compared to healthy pregnant controls, and determined their relationships to variables of interest, including the HIV status. No differences were observed in FMD or BAD between HIV–infected and healthy pregnant women, and neither measure changed significantly during pregnancy. HIV status did not affect endothelial function or brachial artery diameter. Pregnancy does not appear to further increase the CVD risk associated with HIV infection.


2013 - Fetal bacterial infections in antepartum stillbirth: a case series [Articolo su rivista]
Monari, Francesca; Gabrielli, L; Gargano, Giuseppe; Annessi, Eleonora; Ferrari, Francesca; Rivasi, Francesco; Facchinetti, Fabio
abstract

OBJECTIVES: This study aims to assess the frequency of fetal bacterial infections in stillbirth (SB) and to evaluate the best samples for the diagnosis of infection-related SB. STUDY DESIGN: Consecutive cases of antepartum SB were enrolled. Vaginal and placental swabs, as well as heart blood cultures and surface swabs from the neonate, were collected. Histological examinations were performed by the same examiner. Immunohistochemistry for leukocyte common antigen was performed in the placenta and fetus. Each case was discussed in a multidisciplinary audit. RESULTS: One hundred and nine cases were enrolled. Fetal blood cultures were positive in 20/95 cases (21%). Significant histological findings in the placenta/cord and in at least one fetal organ were observed in 8 cases of them (4 Group B Streptococcus GBS, 2 Listeria monocytogenes, 1 Coagulase negative Staphylococcus, 1 Pseudomonas aeruginosa). Neither tissue damage nor inflammatory infiltrate was found in the 12 remnant cases. Funisitis while not histological chorioamnionitis was associated with microbiological findings. Positive findings in maternal/placental/fetal swabs occurred in 18-32% of cases with both negative fetal blood cultures and histopathological findings. With the exception of GBS, no other bacteria agent could be detected by any of the swabs. CONCLUSIONS: Eight cases (8.4%) fulfilled both microbiological and histology criteria allowing the diagnosis of SB-related fetal infection demonstrating that search for infections is essential in SB evaluation. Fetal blood culture, placenta swab for GBS and search for histological funisitis are mandatory actions within the SB work-up in order to guide pathology examination and reach clinical conclusions.


2013 - Herb remedies during pregnancy: a systematic review of controlled clinical trials [Articolo su rivista]
Dante, Giulia; Pedrielli, Giulia; Annessi, Eleonora; Facchinetti, Fabio
abstract

OBJECTIVE: The use of herbal remedies has been documented both among various patient groups and in the general population to promote health. The aim of this systematic review is to analyze the benefits of herb use during pregnancy. METHODS: A systematic literature search covering the period from January 1990 to September 2010 was performed using various electronic databases. Randomized controlled clinical trials (RCTs) were included. Paper quality was evaluated using the Jadad scale. RESULTS: Of the 511 articles identified, 14 RCTs were eligible. Ginger was the most investigated remedy and was consistently reported to ameliorate nausea and vomiting during pregnancy better than placebo; its efficacy in doing so was noted to be equal to that of vitamin B6 and dimenhydrinate. A single trial also supported the use of Hypericum perforatum for wound healing. Cranberry, however, was not efficacious in the treatment of urinary tract infections; finally, raspberry leaf did not shorten the first stage of labor, and garlic did not prevent pre-eclampsia. CONCLUSIONS: Despite the widespread, popular use of herbal remedies during pregnancy, too few studies have been devoted to specific clinical investigations. With the exception of ginger, there is no data to support the use of any other herbal supplement during pregnancy.


2013 - Long QT syndrome-associated mutations in intrauterine fetal death. [Articolo su rivista]
L., Crotti; D. J., Tester; W. M., White; D. C., Bartos; R., Insolia; A., Besana; J. D., Kunic; M. L., Will; E. J., Velasco; J. J., Bair; A., Ghidoni; I., Cetin; D. L., Van; M. J., Wick; B., Brost; B. P., Delisle; Facchinetti, Fabio; A. L., George; P. J., Schwartz; M. J., Ackerman
abstract

Intrauterine fetal death or stillbirth occurs in approximately 1 out of every 160 pregnancies and accounts for 50\% of all perinatal deaths. Postmortem evaluation fails to elucidate an underlying cause in many cases. Long QT syndrome (LQTS) may contribute to this problem.To determine the spectrum and prevalence of mutations in the 3 most common LQTS susceptible genes (KCNQ1, KCNH2, and SCN5A) for a cohort of unexplained cases.In this case series, retrospective postmortem genetic testing was conducted on a convenience sample of 91 unexplained intrauterine fetal deaths (mean [SD] estimated gestational age at fetal death, 26.3 [8.7] weeks) that were collected from 2006-2012 by the Mayo Clinic, Rochester, Minnesota, or the Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. More than 1300 ostensibly healthy individuals served as controls. In addition, publicly available exome databases were assessed for the general population frequency of identified genetic variants.Comprehensive mutational analyses of KCNQ1 (KV7.1, LQTS type 1), KCNH2 (HERG/KV11.1, LQTS type 2), and SCN5A (NaV1.5, LQTS type 3) were performed using denaturing high-performance liquid chromatography and direct DNA sequencing on genomic DNA extracted from decedent tissue. Functional analyses of novel mutations were performed using heterologous expression and patch-clamp recording.The 3 putative LQTS susceptibility missense mutations (KCNQ1, p.A283T; KCNQ1, p.R397W; and KCNH2 [1b], p.R25W), with a heterozygous frequency of less than 0.05\% in more than 10 000 publicly available exomes and absent in more than 1000 ethnically similar control patients, were discovered in 3 intrauterine fetal deaths (3.3\% [95\% CI, 0.68\%-9.3\%]). Both KV7.1-A283T (16-week male) and KV7.1-R397W (16-week female) mutations were associated with marked KV7.1 loss-of-function consistent with in utero LQTS type 1, whereas the HERG1b-R25W mutation (33.2-week male) exhibited a loss of function consistent with in utero LQTS type 2. In addition, 5 intrauterine fetal deaths hosted SCN5A rare nonsynonymous genetic variants (p.T220I, p.R1193Q, involving 2 cases, and p.P2006A, involving 2 cases) that conferred in vitro electrophysiological characteristics consistent with potentially proarrhythmic phenotypes.In this molecular genetic evaluation of 91 cases of intrauterine fetal death, missense mutations associated with LQTS susceptibility were discovered in 3 cases (3.3\%) and overall, genetic variants leading to dysfunctional LQTS-associated ion channels in vitro were discovered in 8 cases (8.8\%). These preliminary findings may provide insights into mechanisms of some cases of stillbirth.


2013 - The "late preterm" birth: Frequency, outcomes, perinatal management [Articolo su rivista]
Baronciani, D.; Facchinetti, F.
abstract


2013 - The role of oral probiotic for bacterial vaginosis in pregnant women. A pilot study [Articolo su rivista]
Facchinetti, F.; Dante, G.; Pedretti, L.; Resasco, P.; Annessi, E.; Dodero, D.
abstract

Aim. The aim of this study was to compare the effects of a dietary supplementation with oral probiotic, and the treatment with vaginal clindamycin in pregnant women with bacterial vaginosis. Methods. Fouty pregnant women, with a diagnosis of bacterial vaginosis according to the Amsel criteria, were enrolled between the 10th and the 34th week of gestation. The patients were randomized in two groups. Patients in the group A were treated with probiotic orally (VSL3®Ferring), 2 tablets a day for 5 days, followed by 1 tablet daily for 10 days. Patients in group B were treated with vaginal clindamycin 100 mg daily for 15 days. After 5-10 days from the end of the treatment the patients returned for the follow-up. Results. After treatment the vaginal discharge was completely absent in group A, and reduced in group B. The itching occurred only in 10% of patients in each of the two groups. The improvement of constipation occurs only in the group A (P=0.002). Vaginal swabs resulted negative in both groups in particular for Gardnerella V. Conclusion. The oral treatment with VSL#3® is effective in the treatment of VB in pregnant women as a topical treatment with clindamycin. In particular for the resolution of leukorrhea, itching and in particular in the bacterial vaginosis caused by Gardnerella V.


2012 - Editor's reply [Articolo su rivista]
Di Renzo, G. C.; Roura, L. C.; Facchinetti, F.
abstract


2012 - EFFECTS OF MYO-INOSITOL IN WOMEN WITH PCOS: A SYSTEMATIC REVIEW OF RANDOMIZED CONTROLLED TRIALS. [Articolo su rivista]
V., Unfer; G., Carlomagno; Dante, Giulia; Facchinetti, Fabio
abstract

..


2012 - Exam-indicated cerclage in patients with fetal membranes at or beyond external os: A retrospective evaluation [Articolo su rivista]
Curti, A.; Simonazzi, G.; Farina, A.; Mehmeti, H.; Facchinetti, F.; Rizzo, N.
abstract

Aim: To evaluate pregnancy outcome in women with fetal membranes at or beyond external os who underwent exam-indicated cerclage or conservative management. Material and Methods: Retrospective cohort study including 52 patients with fetal membranes at or beyond external os between 17 and 27 weeks of gestation, treated in two third-level hospitals, between January 2001 and April 2009. The outcomes of interest of the study, prolongation of pregnancy and neonatal survival rate, were stratified according to type of management, parity, clinical conditions and blood tests at admission and calculated using the Kaplan-Meier algorithm. Results: Of 52 women, 37 received exam-indicated cerclage and 15 were managed conservatively. The rate of patients still pregnant beyond 180 days within the cerclage group differed significantly from those of the conservative management group (80% vs 0%, respectively) (P-value &lt; 0.001). No difference has been found according to neonatal survival (82% versus 53%, respectively). Conclusion: Exam-indicated cerclage appears to prolong gestation compared to expectant management. © 2012 Japan Society of Obstetrics and Gynecology.


2012 - Headache and adverse pregnancy outcomes: a prospective study [Articolo su rivista]
L., Marozio; Facchinetti, Fabio; G., Allais; R. E., Nappi; M., Enrietti; Neri, Isabella; E., Picardo; C., Benedetto
abstract

..


2012 - Heparin in pregnant women with previous placenta-mediated pregnancy complications: a prospective, randomized, multicenter, controlled clinical trial. [Articolo su rivista]
I., Martinelli; P., Ruggenenti; I., Cetin; G., Pardi; A., Perna; P., Vergani; B., Acaia; Facchinetti, Fabio; LA SALA, Giovanni Battista; M., Bozzo; S., Rampello; L., Marozio; O., Diadei; G., Gherardi; S., Carminati; G., Remuzzi; P., Mannuccio Mannucci; for the HAPPY Study, Group
abstract

To assess whether antithrombotic prophylaxis with low-molecular-weight heparin effectively prevents recurrence of late pregnancy complications, 135 women with previous history of preeclampsia, hemolytic anemia, elevated liver enzymes and low platelet count syndrome, intrauterine fetal death, fetal growth restriction, or placental abruption who had been referred within the 12th gestational week were randomized to medical surveillance alone (n = 68) or combined to open-label nadroparin (3800 IU daily subcutaneous injections) treatment (n = 67) in the setting of a randomized, parallel-group, superiority trial, run in Italy from April 2007 to April 2010. Primary outcome was a composite end point of late-pregnancy complications. Analysis was by intention to treat. The study was stopped for futility at the time of the first planned interim analysis. Among the 128 women eventually available for final analyses, 13 of the 63 (21%) randomized to nadroparin compared with 12 of the 65 (18%) on medical surveillance alone progressed to the primary end point. The absolute event risk difference between treatment arms (2.2; -1.6 to 16.0) was not statistically significant (P = .76). Thus, nadroparin did not prevent late-pregnancy complications in women at risk of recurrence. This finding challenges the role of antithrombotic prophylaxis with low-molecular-weight heparin in the prevention of recurrent late pregnancy complications The trial was registered at http://ricerca-clinica.agenziafarmaco.it as EudraCT 2006-004205-26.


2012 - Herbal supplements in pregnancy: unexpected results from a multicentre study. [Articolo su rivista]
Facchinetti, Fabio; G., Pedrielli; G., Benoni; M., Joppi; G., Verlato; G., Dante; S., Balduzzi; L., Cuzzolin
abstract

STUDY QUESTION: How common is the use of herbal supplements during pregnancy and does it adversely affect the pregnancy outcome? SUMMARY ANSWER: The use of herbal products during pregnancy is very common and daily almond oil spreading is associated with preterm birth (PTB). WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Herbal drugs are often promoted as 'natural' and 'safe' and such claims attract pregnant women. More than a quarter of Italian pregnant women consume herbs every day for at least 3 months during pregnancy. We raise an alert over the habit of daily almond oil spreading since it seems to be associated with PTB. DESIGN: A multicenter retrospective cohort study performed over a 15-month period. PARTICIPANTS AND SETTING: Seven hundred women interviewed within 3 days of childbirth, in three public hospitals in northern Italy. MAIN RESULTS AND ROLE OF CHANCE: One hundred and eighty-nine women were considered 'regular users', since they consumed herbs every day, for at least 3 months. Almond oil, chamomile and fennel were the most commonly used herbs. Both length of gestation and birthweight were affected by herb consumption. Almond oil users showed more pre-term birth (29 of 189) than non-users (51 of 511). After adjusting for multiple pregnancies, smoking, advanced age and drug intake, almond oil users maintained an increased risk to give birth <37th week (odds ratio = 2.09, 95\% confidence interval: 1.08-4.08). BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION: The association between daily spreading of almond oil and PTB only raises a hypothesis that requires confirmation in larger trials devoted to this topic. The relatively small sample size did not allow the investigation of other adverse pregnancy outcomes in herb users. GENERALIZABILITY TO OTHER POPULATIONS: The population under investigation did not significantly differ from the general population attending the same hospitals. STUDY FUNDING/COMPETING INTEREST(S): No conflict of interest exists. The study has been supported by a public grant from the University of Modena and Reggio Emilia. TRIAL REGISTRATION NUMBER: None.


2012 - Pre-induction of labour: comparing dinoprostone vaginal insert to repeated prostaglandin administration: a systematic review and meta-analysis. [Articolo su rivista]
Facchinetti, Fabio; F., Fontanesi; Giovane, C. D.
abstract

To assess the efficacy and safety of the dinoprostone vaginal insert compared to repeated prostaglandin administration (including dinoprostone and misoprostol) in women at term.Electronic databases and additional handsearching were used to identify randomized controlled trial (RCT). We included studies reporting data separately for nulliparous and/or multiparous in women with unfavourable cervix (Bishop <5) and intact membranes. The primary efficacy outcome was caesarean section (CS) rate. Primary safety outcome was uterine hyperstimulation requiring immediate delivery.Eighteen RCTs were eligible and seven studies were included (totally 911 patients). The dinoprostone vaginal insert reduces CS rate in nulliparous women of 24\% compared to the other ways of administration (RR = 0.76, 95\% CI = 0.59, 0.98). The risk of oxytocin use is reduced with the use of vaginal insert (RR = 0.64, 95\% CI = 0.42, 0.99). The risk of hyperstimulation is statistically higher in nulliparous women using vaginal insert than the other ways of administration with RR = 2.17, 95\% CI = 1.08,4.33.In nulliparous women with unprepared cervix and intact membranes vaginal insert perform better than repeated vaginal doses since it is associated with more vaginal deliveries and less oxytocin use. Although vaginal insert is associated with more uterine hyperstimulation, it shows a protective effect toward caesarean section.


2012 - RELATION BETWEEN MATERNAL THROMBOPHILIA AND STILLBIRTH ACCORDING TO CAUSES/ASSOCIATED CONDITIONS OF DEATH [Articolo su rivista]
Monari, Francesca; Alberico, S; Avagliano, L; Cetin, I; Cozzolino, S; Gargano, G; Marozio, L; Mecacci, F; Neri, Isabella; Tranquilli, Al; Venturini, P; Facchinetti, Fabio
abstract

OBJECTIVE: To investigate maternal thrombophilia in cases of Stillbirth (SB), also an uncertain topic because most case series were not characterised for cause/associated conditions of death. STUDY DESIGN: In a consecutive, prospective, multicentre design, maternal DNA was obtained in 171 cases of antenatal SB and 326 controls (uneventful pregnancy at term, 1:2 ratio). Diagnostic work-up of SB included obstetric history, neonatologist inspection, placenta histology, autopsy, microbiology/chromosome evaluations. Results audited in each centre were classified by two of us by using CoDAC. Cases were subdivided into explained SB where a cause of death was identified and although no defined cause was detected in the remnants, 64 cases found conditions associated with placenta-vascular disorders (including preeclampsia, growth restriction and placenta abruption - PVD). In the remnant 79 cases, no cause of death or associated condition was found. Antithrombin activity, Factor V Leiden, G20210A Prothrombin mutation (FII mutation) and acquired thrombophilia were analysed. RESULTS: Overall, the presence of a thrombophilic defect was significantly more prevalent in mothers with SBs compared to controls. In particular, SB mothers showed an increased risk of carrying Factor II mutation (OR=3.2, 95\% CI: 1.3-8.3, p=0.01), namely in unexplained cases. Such mutation was significantly associated also with previous SB (OR=8.9, 95\%CI 1.2-70.5). At multiple logistic regression, Factor II mutation was the only significantly associated variable with SB (adj OR=3.8, 95\% CI: 1.3-13.5). CONCLUSION: These data suggest that Factor II mutation is the only condition specifically associated with unexplained SB and could represents a risk of recurrence. PVD-associated condition is unrelated to thrombophilia.


2012 - Single-nucleotide polymorphisms in genes involved in placental function and unexplained stillbirth. [Articolo su rivista]
Ferrari, F; Facchinetti, Fabio; Yin, H; Saade, Gr; Longo, M.
abstract

OBJECTIVE: The purpose of this study was to evaluate the association between unexplained stillbirth (SB) and single-nucleotide polymorphisms (SNPs) in genes involved in placental function using a well-characterized cohort. STUDY DESIGN: Placentas were obtained from 50 unexplained SB and 46 live birth controls. Classification of stillbirth was by Wigglesworth criteria. SBs were stratified by weight: appropriate (AGA-SB) and small for gestational age (SGA-SB, less than the 10th percentile) and gestational age: before 32 and after 32 weeks. Placental DNA was extracted and various SNPs in the endothelial nitric oxide synthase (eNOS), Klotho, hypoxic inducible factor-1α, and and tumor necrosis factor-α genes were evaluated. RESULTS: None of the SNPs were associated with SB overall. Significantly different genotype distribution emerged for eNOS-SNP rs1800783 when comparing AGA-SB with SGA-SB and control (P = .004). Its allele-A was more frequent in AGA-SB compared with both controls (P = .03) and SGA-SB (P = .001). No differences were seen accordingly to gestational age. CONCLUSION: Unexplained stillbirth in the setting of adequate growth is associated with carrier of allele A of rs1800783 eNOS gene in the placenta.


2012 - THE PREGNANT UTERUS AS A PSYCHO-ENDOCRINE ORGAN [Articolo su rivista]
Facchinetti, Fabio; Annessi, E; Ottolini, F.
abstract

The pathogenesis of preterm birth (PTB) is largely unknown and the endocrine stress pathway is likely to participate in the mechanisms allowing onset of labor. However, the vast majority of the studies evaluating psychosocial distress denied an association with PTB. Uterine contractility rather than PTB seems associated with distress in pregnancy.


2011 - A multicenter, case-control study on risk factors for antepartum stillbirth. [Articolo su rivista]
Facchinetti, Fabio; S., Alberico; C., Benedetto; I., Cetin; S., Cozzolino; G. C., Di Renzo; Giovane, C. D.; F., Ferrari; F., Mecacci; G., Menato; A. L., Tranquilli; D., Baronciani; I. S., Study Group
abstract

As the influence of socio-demographic variables, lifestyle and medical conditions on the epidemiology of stillbirth (SB) is modified by population features, we aimed at investigating the role played by these factors on the incidence of SB in a developed country.Multivariate logistic regression analysis (OR with 95\% CI) was utilized in a prospective multicentre nested case-control study to compare in a 1:2 ratio stillborn of &gt;22 weeks gestation with matched for gestational age live-born (LB) infants. Intrapartum SB were excluded.Two hundred fifty-four consecutive SBs and 497 LBs were enrolled. Socio-demographic variables were equally distributed. Fetal malformations (7.96, 2.69-23.55), severe intrauterine growth restriction (IUGR) (birthweight ≤ 5(th) \%ile) (4.32, 2.27?8.24), BMI &gt; 25 (2.87, 1.90-4.33), and preeclampsia (PE, 0.40, 0.21-0.77) were recognized as independent predictors for SB. At term, only BMI &gt; 25 was associated with SB (7.70, 2.9-20.5).Fetal malformations, severe IUGR and maternal BMI &gt; 25 were associated with a significant increase in the risk of SB; PE presented instead a protective role. Maternal BMI &gt; 25 was the only risk factor for SB identified in term pregnancies.


2011 - Acupuncture treatment as breastfeeding support: preliminary data. [Articolo su rivista]
Neri, Isabella; G., Allais; V., Vaccaro; S., Minniti; G., Airola; P., Schiapparelli; C., Benedetto; Facchinetti, Fabio
abstract

This article investigates the efficacy of acupuncture for the maintenance of breastfeeding during the first 3 months of a newborn's life.After written informed consent was obtained, 90 women were randomly divided into two groups: acupuncture treatment or observation. Acupuncture sessions were performed twice weekly for 3 weeks (total six sessions). The control group made weekly visits to the clinic and the midwife observed their breastfeeding, giving routine care. In both groups, a semistructured clinical assessment of breastfeeding quality was carried out by the midwife at enrollment and after 3 weeks. Moreover, in both groups a telephone interview was conducted by the midwife at the third month of the infants' lives, regarding the continuation of breastfeeding.No significant difference in the exclusive breastfeeding rate before treatment was observed between acupuncture and observation groups (51.2\% versus 48.8\%). However, at 3 weeks post-enrollment, exclusive breastfeeding was significantly lower in the observation group than in the acupuncture group (60\% versus 100\%; p < 0.03). At the third month of the newborns' lives, breastfeeding was reported in 35\% of the acupuncture group, compared to 15\% of the observation group (p < 0.03).Such preliminary data suggest that 3 weeks of acupuncture treatment were more effective than observation alone in maintaining breastfeeding until the third month of the newborns' lives.


2011 - Effects of an estrogen-free, desogestrel-containing oral contraceptive in women with migraine with aura: a prospective diary-based pilot study. [Articolo su rivista]
R. E., Nappi; G., Sances; G., Allais; E., Terreno; C., Benedetto; Vaccaro, Valentina; F., Polatti; Facchinetti, Fabio
abstract

Migraine with aura (MA) is a contraindication to the use of combined oral contraceptives (COCs) because of the increased risk of ischemic stroke. Progestogen-only contraceptive pill (POP) is a safe alternative to COCs and it is preferable in women with cerebrovascular diseases or risk factors for stroke.Prospective diary-based pilot study. Thirty women with MA (n = 15 who have never used COCs and n = 15 who had previously used COCs were diagnosed according to the International Headache Society criteria. The observational period lasted 9 months during which women filled in a diary with the clinical characteristics of headache attacks. After a 3-month run-in period, each subject received an estrogen-free desogestrel (DSG) (75 mcg/day)-containing OC (Cerazette(®); Schering-Plough, formerly NV Organon, Oss, The Netherlands). Follow-up evaluations were planned at the end of the third and sixth month of treatment.The number (mean±S.D.) of migraine attacks was significantly reduced both in previous COCs users (from 3.9±1.0 to 2.9±0.8; p<.001) and nonusers (from 3.2±0.9 to 2.6±1.3; p<.02) following 6 months of POP use in comparison with the run-in period. Duration of headache pain did not differ significantly in both groups throughout the study. Interestingly enough, a beneficial POP effect on the duration (mean±S.D.) of visual aura (from 16.3±9.5 to 11.4±5.6 min) and on the total duration (mean±S.D.) of neurological symptoms (from 33.6±23.3 to 18.6±18.0 min) was only significantly reported by previous COCs users (p<.001, for both) by the end of the study period. The POP was well tolerated by each woman and the bleeding pattern was variable with a tendency towards infrequent bleeding.The present study supports the use of the POP containing desogestrel in a population of women with MA and underlines a positive effect on symptoms of aura, especially in MA sensitive to previous use of COCs.


2011 - Efficacy of intrapartum chemoprophylaxis less than 4 hours duration. [Articolo su rivista]
Berardi, A.; Rossi, C.; Biasini, A.; Minniti, S.; Venturelli, C.; Ferrari, Fabrizio; Facchinetti, Fabio
abstract

Objective. Current guidelines for prevention of group B streptococcus (GBS) early-onset infection recommend to administer antibiotic during labor at least 4 h prior to delivery (adequate prophylaxis). We aimed to determine if neonatal GBS colonization may be significantly decreased in case of inadequate (&lt;4 h) duration of ampicillin prophylaxis.Methods. In prospective, cohort study, 167 infants born to 167 GBS culture-positive mothers without additional risk factors were enrolled. Cultures were collected both, at 10–24 h after birth (admission) and at discharge.Results. Among 137 infants born to mothers who received inadequate prophylaxis, 5 (3.6%, C.I. = 0.5–6.8) were colonized (≥1 sites) at admission, at discharge, or both, at admission and discharge. Eighty-two women received prophylaxis &lt;2 h before delivery and two infants (2.4%) were colonized at discharge.Eighteen (60.0%, C.I. = 42.5–77.5) of 30 infants who were not exposed to prophylaxis were colonized at admission or both, at admission and discharge.Colonization was significantly more frequent among infants born to untreated mothers with respect to infants born to women who received inadequate prophylaxis (either &lt;2 or &lt;4 h).Conclusions. In this selected group, inadequate prophylaxis significantly interrupted vertical colonization. This effect was evident even if prophylaxis started &lt;2 h before delivery.


2011 - Genome-wide array-based copy number profiling in human placentas from unexplained stillbirths. [Articolo su rivista]
R. A., Harris; Ferrari, Francesca; S., Ben Shachar; X., Wang; G., Saade; I. V., Den; Facchinetti, Fabio; K., Aagaard Tillery
abstract

Accumulating evidence suggests that genomic structural variations, particularly copy number variations (CNV), are a common occurrence in humans that may bear phenotypic consequences for living individuals possessing the variant. While precise estimates vary, large-scale karyotypic abnormalities are present in 6-12\% of stillbirths (SB). However, due to inherent limitations of conventional cytogenetics, the contribution of genomic aberrations to stillbirth is likely underrepresented. High-resolution copy number variant analysis by genomic array-based profiling may overcome such limitations.Prospectively acquired SB cases > 22 weeks underwent classification of 'unexplained' stillbirth by Wigglesworth and Aberdeen criteria after extensive testing and rigorous multidisciplinary audit. Genome-wide analysis was conducted using high-resolution Illumina single nucleotide polymorphism (SNP) arrays (Human CNV370-Duo) on placental and fetal samples. Potential alternate detection methods were completed by one or more of three independent means (quantitative PCR, Illumina1M, or Agilent105K comparative genomic hybridization arrays).In our cohort of 54 stillbirths, 29 met strict unexplained criteria. Among these, we identified 24 putative novel CNVs. Subsequent interrogation detected 18 of 24 CNVs (75\%) in placental samples, 8 of which were also confirmed in available fetal samples; none were present in maternal blood.We describe the potential of whole-genome placental profiling to identify small genomic imbalances, which might contribute to a small proportion of well-characterized, unexplained stillbirths.


2011 - Ghid de management al naşterii spontane premature: Identificarea naşterii spontane premature, diagnosticul rupturii premature de membrane înainte de termen şi mijloace preventive pentru naşterea prematurǎ [Articolo su rivista]
Di Renzo, G. C.; Roura, L. C.; Facchinetti, F.; Antsaklis, A.; Breborowicz, G.; Gratacos, E.; Husslein, P.; Lamont, R.; Mikhailov, A.; Montenegro, N.; Radunovic, N.; Robson, M.; Robson, S. C.; Sen, C.; Shennan, A.; Stamatian, F.; Ville, Y.
abstract


2011 - Guidelines for the management of spontaneous preterm labor: identification of spontaneous preterm labor, diagnosis of preterm premature rupture of membranes, and preventive tools for preterm birth. [Articolo su rivista]
G. C., Di; L. C., Roura; Facchinetti, Fabio; A., Antsaklis; G., Breborowicz; E., Gratacos; P., Husslein; R., Lamont; A., Mikhailov; N., Montenegro; N., Radunovic; M., Robson; S. C., Robson; C., Sen; A., Shennan; F., Stamatian; Y., Ville
abstract

Preterm premature rupture of the membranes (preterm PROM) is a common and significant cause of preterm birth and perinatal morbidity and mortality. The obstetric caregiver has the opportunity significantly to alter pregnancy and perinatal outcome for women suffering from this complication. Although management is often predetermined by the presence of clinical infection, vaginal bleeding, labor, or nonreassuring fetal heart-rate pattern on admission, a gestational age-based approach to the management of the stable patient with preterm PROM offers the potential to reduce


2011 - Herbal treatments for alleviating premenstrual symptoms: a systematic review. [Articolo su rivista]
G., Dante; Facchinetti, Fabio
abstract

Premenstrual syndrome (PMS) is a condition of cyclical and recurrent physical and psychological discomfort occurring 1 to 2 weeks before menstrual period. More severe psychological symptoms have been described for the premenstrual dysphoric disorder (PMDD). No single treatment is universally recognised as effective and many patients often turn to therapeutic approaches outside of conventional medicine. This systematic review is aimed at analysing the effects of herb remedies in the above conditions. Systematic literature searches were performed in electronic databases, covering the period January 1980 to September 2010. Randomised controlled clinical trials (RCTs) were included. Papers quality was evaluated with the Jadad' scale. A further evaluation of PMS/PMDD diagnostic criteria was also done. Of 102 articles identified, 17 RCTs were eligible and 10 of them were included. The heterogeneity of population included, study design and outcome presentation refrained from a meta-analysis. Vitex agnus castus was the more investigated remedy (four trials, about 500 women), and it was reported to consistently ameliorate PMS better than placebo. Single trials also support the use of either Gingko biloba or Crocus sativus. On the contrary, neither evening primrose oil nor St. John's Wort show an effect different than placebo. None of the herbs was associated with major health risks, although the reduced number of tested patients does not allow definitive conclusions on safety. Some herb remedies seem useful for the treatment of PMS. However, more RCTs are required to account for the heterogeneity of the syndrome.


2011 - [Identification of preterm labor: the role of the firbronectine and ultrasound cervicometry and their association.] [Articolo su rivista]
G. C., Di; I., Giardina; G., Coata; M. D., Tommaso; Facchinetti, Fabio; F., Petraglia; A. L., Tranquilli; N., Rizzo
abstract

OBJECTIVE: The aim of this study was to evaluate the effectiveness of the fetal fibronetcin (fFN) test and ultrasonographic cervical length measurement used alone or in combination with each other in order to further improve the identification of patients in preterm labor. METHODS: Prospective multicenter observational study on patients between 24 and 32 weeks of gestation with symptoms of preterm labor (total patients = 132). The endpoint was the delivery at 34 weeks or more. The screening methods used were: the fFN test (group 1), the cervical length measurement by transvaginal ultrasound (group 2) or a combination of both tests (group 3) according to an established protocol. The statistical analysis was performed using the χ2 test using the SPSS software. RESULTS: Group 1: positive fFN test in 25.7\% of cases, incidence of preterm birth (<34 weeks) of 18\%. Group 2: cervical length <25 mm in 56.2\% of cases, incidence of preterm birth (<34 weeks) of 18.5\%. The negative predictive value is equivalent to 99.0\% for the fFN test and 95.2\% for cervicometry; combined use reaches 100\%, compared to 54\% positive predictive value. CONCLUSION: The identification of women at high risk of preterm delivery carried out with the fFN test or with transvaginal ultrasound cervicometry is clinically valid. The study also showed that the contextual use of biochemical and biophysical tests reaches a high negative predictive value (100\%), making it a very useful method to identify patients truly at risk and to further reduce the incidence of non adequate treatment.


2011 - Nitric oxide metabolite levels and assessment of cervical length in the prediction of preterm delivery among women undergoing symptomatic preterm labor. [Articolo su rivista]
L., Giannella; R., Beraldi; S., Giulini; L. B., Cerami; K., Mfuta; Facchinetti, Fabio
abstract

OBJECTIVE: To evaluate the diagnostic accuracy of measuring cervical length (CL) in combination with cervical and plasma nitric oxide metabolite (NOx) levels to identify women undergoing preterm labor (PTL) who will deliver preterm. METHODS: A hospital-based prospective cohort study of 730 women undergoing spontaneous PTL between 24 and 33weeks+6days of pregnancy was conducted. Measurement of cervical and plasma NOx levels and ultrasonographic assessment of CL were performed to find the best model to predict preterm delivery (PTD). Optimal cut-off values were calculated by receiver operating characteristic (ROC) curve analysis. Logistic regression analysis and rank correlation tests were also performed. RESULTS: CL of 15mm or less, cervical NOx levels greater than 87.6μmol/L, and plasma NOx levels greater than 123μmol/L (P<0.0001) were the only factors significantly associated with PTD within 7days of sampling. This combined model provided high diagnostic accuracy (sensitivity 80.0\%; specificity 99.2\%). Both cervical and plasma NOx levels were negatively correlated with CL (r=-0.453, P<0.0001 and r=-0.362, P<0.0001, respectively). CONCLUSION: Combined measurement of CL and levels of cervical and plasma NOx could help identify women undergoing symptomatic PTL who are at increased risk of PTD.


2011 - Stillbirth: issues and new insights [Articolo su rivista]
Facchinetti, Fabio; Ferrari, Francesca; Monari, Francesca; Neri, Isabella
abstract

Disparities in stillbirth (SB) are mainly related to socioeconomic factors. Developing countries have a SB rate five-times higher than that of developed countries, one-third of which occur intrapartum. Instead, in developed countries the access to antenatal care became the first preventive intervention for SB. In this article, we summarize strategies for SB prevention in the developing and developed world. Moreover, we report a critical evaluation of the six most used classification systems, highlighting the best performer. Similarly, we summarize the necessary diagnostic examinations for an appropriate classification of SB. Some of the new lines of investigation are reported here. However, any new finding on the cause of SB has to acknowledge a model of interpretation that takes into account a triad; the fetus and its characteristics, the uterine environment and the circumstances of death.


2011 - Universal antenatal screening for group B streptococcus in Emilia-Romagna [Articolo su rivista]
Nappi, R. E.; G., Sances; G., Allais; E., Terreno; C., Benedetto; V., Vaccaro; F., Polatti; Facchinetti, Fabio
abstract

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2011 - Universal antenatal screening for group B streptococcus in Emilia-Romagna. [Articolo su rivista]
Berardi, A.; Fazzio, G. D.; Gavioli, Sara; Di Grande, E.; Groppi, A.; Papa, I.; Piccinini, G.; Simoni, A.; Tridapalli, E.; Volta, A.; Facchinetti, Fabio; Ferrari, Fabrizio
abstract

Background: Group B streptococcus (GBS) is a leading cause of severe infections in newborns. Intrapartum antibiotic chemoprophylaxis (IAP) reduces the rate of early-onset disease. The aim of this study is to determine the degree of clinicians’ compliance with the suggested protocol for GBS prevention in Emilia-Romagna (Italy). Methods: Characteristics of each delivery were prospectively recorded in the period between October 2005 to December 2005. Standardized pro-forma were used to collect data. Results: Among 5118 babies, 7.2% (369) were preterm and 92.3% were born at term (4749). Antenatal screening was performed in 86.6% of women who delivered at term, of which 18.1% were GBS culture-positive. Information regarding culture site was available in 93.2% of women screened and recto-vaginal cultures were documented in 42.7%. IAP was administered to 28.7% of 3937 women at term who had either spontaneous delivery or emergency caesarean section. In this cohort, 15.9% were diagnosed GBS culture-positive, of which 92.6% received IAP. Prophylaxis was also administered to 8.4% (331) of women for no apparent reason. Compared with tertiary level hospitals, women delivering in primary/secondary hospitals were more likely to be both GBS screened (P &lt; 0.0001; OR 3.04; CI 2.33–3.97) and to receive prophylaxis ≥4 hours before delivery (P = 0.0025; OR 1.57; CI 1.17–2.12). Conclusions: GBS screening was performed in &gt;85% of women and &gt;90% of culture-positive women received prophylaxis. However, there is a need to educate clinicians about protocol adherence, as most cultures were suboptimal and cases of unnecessary IAP were administered. The screening was more effective in hospitals with fewer deliveries.


2011 - Vascular/Thrombotic [Capitolo/Saggio]
Facchinetti, F.; Monari, F.
abstract


2010 - Drospirenone and cardiovascular risk in lean and obese polycystic ovary syndrome patients: a pilot study. [Articolo su rivista]
F., Mancini; A., Cianciosi; N., Persico; Facchinetti, Fabio; P., Busacchi; C., Battaglia
abstract

OBJECTIVE: We sought to verify if an oral contraceptive (OC) containing drospirenone affects the cardiovascular risk of patients with polycystic ovary syndrome (PCOS). STUDY DESIGN: A total of 28 women with PCOS (16 lean [group A] and 12 overweight [group B]) were assessed at baseline and after 6 months therapy with an OC. Leptin, homocysteine, endothelin-1, and flow-mediated dilatation of brachial artery were measured. RESULTS: The brachial artery diameter and the pulsatility index, after the reactive hyperemia, did not change in group A; it improved significantly in group B after 6 months of treatment. At baseline and after therapy the plasma levels of homocysteine and endothelin-1 did not differ among the groups. Leptin was significantly lower at baseline in group A compared to group B. CONCLUSION: The OC containing drospirenone does not seem to affect the surrogate markers of cardiovascular risk in lean patients with PCOS.


2010 - l-arginine plus drospirenone-ethinyl estradiol in the treatment of patients with PCOS: a prospective, placebo controlled, randomised, pilot study. [Articolo su rivista]
C., Battaglia; F., Mancini; B., Battaglia; Facchinetti, Fabio; P. G., Artini; S., Venturoli
abstract

Objective. To verify the effects of a pill containing drospirenone on the surrogate markers of arterial function and to evaluate the possible improvements induced by the addition of l-arginine. Design. A prospective, placebo controlled, randomised, pilot study. Setting. University of Bologna. Population. Twenty-eight young women with PCOS. Methods. Random submission to: drospirenone + ethinylestradiol+ a placebo (Group I; n = 15) or drospirenone + ethinylestradiol + oral l-arginine (4 g x 2/daily) (Group II, n = 13). Main outcome measures. Medical examination; blood measurement of nitrites/nitrates, biochemical and hormonal parameters; ultrasonographic analysis and colour Doppler evaluation of uterine, stromal ovarian and ophthalmic arteries; analysis of brachial artery flow-mediated vasodilatation; and 24-h ambulatory blood pressure monitoring. The above parameters were evaluated before and after 6 months. Results. The low dose oral contraceptive containing drospirenone favoured a pre-hypertensive state The l-arginine supplementation increased the circulating levels of nitrites/nitrates and improved the endothelium-dependent vasodilatation counteracting the negative effect of the contraceptive pill. Conclusions. Although, the present pilot study was conducted in a limited number of patients, it seems that the l-arginine co-treatment may improve the long-term side effects of the pill reducing the risk of cardiovascular diseases.


2010 - L-arginine supplementation in women with chronic hypertension: impact on blood pressure and maternal and neonatal complications. [Articolo su rivista]
Neri, Isabella; Monari, Francesca; Sgarbi, L.; Berardi, A.; Masellis, G.; Facchinetti, Fabio
abstract

To evaluate L-arginine (L-Arg) supplementation in pregnant women with chronic hypertension and its effects on blood pressure (BP) and maternal and neonatal complications.We enrolled 80 women affected by mild chronic hypertension referred to the High Risk Clinic of the Mother-Infant Department of the University of Modena and Reggio Emilia. Each woman after obtaining oral consent was randomized to receive oral L-Arg versus placebo and thereafter submitted to 24-h ambulatory BP monitoring. The primary outcome was BP change after 10-12 weeks of treatment. Secondary outcomes were as follows: percentage of women on antihypertensive treatment at delivery, maternal, and fetal outcome.The BP changes after 10-12 weeks of treatment did not differ between groups. A lower percentage of women received antihypertensive drugs in the L-Arg group than the placebo group. The incidence of superimposed preeclampsia indicated delivery before the 34th weeks and certain neonatal complications tended to be higher in the placebo group.L-Arg supplementation in pregnant women with mild chronic hypertension does not significantly affect overall BP but is associated with less need for antihypertensive medications and a trend toward fewer maternal and neonatal complications. The results of the study were limited by the small sample size and by the exclusion of women with severe chronic hypertension. In our policy, these patients needed many hypertensive drugs and were normally managed by the cardiologist. Nevertheless, considering the promising results on maternal and fetal outcome, we believe that further studies should be performed to confirm such data and to clarify the role of L-Arg as a protective supplement in high-risk pregnancy.


2010 - Management of subsequent pregnancy after antepartum stillbirth. A review. [Articolo su rivista]
Monari, Francesca; Facchinetti, Fabio
abstract

In literature, there is a paucity of information about the management of the subsequent pregnancy after stillbirth (SB). we undertook a systematic review of the literature focusing on the evidence for antenatal interventions with the potential to prevent SB and we try to summarise the management of the pregnancy subsequent to a SB. The diverse interventions and their efficacy will be reported according to the possible causes and/or conditions associated to the previous SB. Few of the studies reported SB as an outcome and the evidence was frequently conflicting. Several interventions showed clear evidence of impact on SB, including the scrupulous control of blood sugar by using multiple doses of insulin, frequent antenatal foetal monitoring and timing of delivery in diabetic women; the prophylaxis with low dose of aspirin in high-risk women; or serial sonograms for foetal growth, Doppler studies and antepartum foetal testing in women with previous growth restricted foetus. Other interventions instead reduced know risk factors for SB but failed to show statistically significant impact on SB rate. Overall, early access to care, at least three ultrasounds examinations, screening for the main pregnancy-related disorders and timely delivery are the milestone of appropriate antenatal care in women with previous SB.


2010 - Measurement of endothelial function in HIV-infected pregnant women:case-control study. [Abstract in Rivista]
K., Luzi; Zona, Stefano; A., Lattanzi; R., Bruno; Facchinetti, Fabio; Esposito, Roberto; Guaraldi, Giovanni
abstract

Endothelial function play a significant role in cardiovascular adaptation of physiological changes occurring during pregnancy. Hypertension in a pregnant women may be considered an endothelial dysfunction secondary disease. No studies have explored functional integrity of vasculature by mean of brachial artery diameter and flow mediated dilation in HIV infected women during pregnancy so far. Our objective was to describe endothelial function chenges and predictors in pregnant women with and without HIV infection.


2010 - Polycystic ovary syndrome and cardiovascular risk in young patients treated with drospirenone-ethinylestradiol or contraceptive vaginal ring. A prospective, randomized, pilot study [Articolo su rivista]
Battaglia, C.; Mancini, F.; Fabbri, R.; Persico, N.; Busacchi, P.; Facchinetti, F.; Venturoli, S.
abstract

Objective: To compare the effects of a pill containing drospirenone with those of a combined contraceptive vaginal ring on the lipid and carbohydrate metabolism and on the surrogate markers of arterial function. Setting: Bologna University School of Medicine. Patient(s): Thirty-seven women with polycystic ovary syndrome (PCOS) were randomly submitted to drospirenone + ethinylestradiol (group I; n = 19) or combined contraceptive vaginal ring (group II; n = 18) therapy. The duration of the study was 6 months. Intervention(s): The effect of treatments was assessed after 6 months of therapy. Main Outcome Measure(s): Utero-ovarian ultrasound analysis and color Doppler evaluation of uterine and stromal ovarian arteries. In addition, analysis of brachial artery flow-mediated vasodilatation and 24-hour ambulatory blood pressure monitoring were performed. Fasting blood samples were drawn for testing biochemical and hormonal parameters and nitrites/nitrates. Result(s): Both treatments improved hirsutism, hyperandrogenemia, and ultrasound and color Doppler ovarian parameters. Both drospirenone + ethinylestradiol or contraceptive vaginal ring induced a slight but significant increase of diurnal and 24-hour blood pressure. Although both therapies worsened the lipid profile, the oral pill administration was associated with a more evident increase of circulating triglycerides. The 6-month treatment with the vaginal ring significantly improved the area under the curve for glucose, insulin, and C-peptide, whereas the drospirenone + ethinylestradiol pill induced an increase in the insulinogenic index and homeostatic model assessment estimate for insulin resistance values. Conclusion(s): Vaginal hormonal contraception appears to be preferable to oral ethinylestradiol + drospirenone administration in hyperinsulinemic patients with PCOS. Copyright © 2010 American Society for Reproductive Medicine, Published by Elsevier Inc.


2010 - Stillbirth: Understanding and Management [Curatela]
Facchinetti, Fabio; G. A., Dekker; D., Baronciani; G., Saade
abstract

Stillbirth remains a sufficiently frequent outcome of pregnancy to pose great problems for clinicians, who have to treat extremely distressed patients. This concise but comprehensive book from an international team of contributors sets out clear guidelines for clinical procedures and patient management for the obstetrician, as well as the gynecologist and the gynecologic pathologist.


2010 - Sumatriptan (50 mg tablets vs. 25 mg suppositories) in the acute treatment of menstrually related migraine and oral contraceptive-induced menstrual migraine: a pilot study. [Articolo su rivista]
Facchinetti, Fabio; G., Allais; R. E., Nappi; I. C., Gabellari; G. C., Di Renzo; A. R., Genazzani; M., Bellafronte; M., Roncolato; C., Benedetto
abstract

Migraine attacks are common in the perimenstrual period (menstrually-related migraine, MRM) and can be particularly exacerbated by the cyclic suspension of oral contraceptives (oral contraceptive-induced menstrual migraine, OCMM). This cross-over, randomised study evaluated the efficacy and tolerability of rectal (25 mg) and oral (50 mg) sumatriptan in the treatment of 232 menstrual migraine attacks (135 MRM and 97 OCMM). Two hours after suppository administration, 72\% of patients in the MRM group achieved pain relief and 24\% were pain free; after tablet administration, the percentages were 66\% and 27\%, respectively. In the OCMM group 55\% of patients improved at 2 h with suppositories and 46\% with tablets, 27\% of patients were pain-free after suppositories and 18\% after tablets. Fifty percent of patients given suppositories were pain-free at 4 h post-treatment and 47\% of those given tablets. Sumatriptan also effectively alleviated symptoms associated with migraine, such as nausea, vomiting and photo/phonophobia. A single dose of medication sufficed for pain relief without relapse in 47.4\% of the attacks (MRM: 66\%; OCMM: 33\%). Both formulations were well tolerated.


2010 - The problem of "late preterm" as obstetrician [Articolo su rivista]
Facchinetti, F.
abstract


2010 - The role of fetal autopsy and placental examination in the causes of fetal death: a retrospective study of 132 cases of stillbirths. [Articolo su rivista]
Bonetti, L. R.; P., Ferrari; N., Trani; L., Maccio; S., Laura; S., Giuliana; Facchinetti, Fabio; Rivasi, Francesco
abstract

PURPOSE: To investigate the most plausible cause of stillbirth by evaluating clinical records and postmortem examination findings including placental analysis. METHODS: A retrospective cohort study concerning 132 stillbirths from 124 pregnancies occurred in the Mother-Infant Department of the University Hospital of Modena, Italy, from January 2000 to December 2004. Collected data were reviewed and classified according to the Gardosi ReCoDe system. RESULTS: A reasonable cause of fetal death was identified in 99/124 pregnancies (79.84\%). No associated relevant factors were disclosed in 25 fetuses (20.16\%) classified as unexplained stillbirths. A succeeding scrupulous analysis of the placenta and an accurate clinical record review were useful to detect other conditions in 82 cases, including 5 cases of unexplained stillbirth. The major relevant conditions associated to stillbirths were feto-placental infection especially in the early fetal gestation age, under the 24th week of gestation, and placental insufficiency occurred both in early and late gestation age fetuses and mainly associated with a IUGR (<10th customized percentile). The main frequent secondary conditions were represented by placental anomalies including cluster of avascular villi with stromal fibrosis associated to thrombosis in minor and/or major vessel(s). Through the further analysis of the placenta, we were able to reduce the unexplained stillbirth rate from 20.16 to 15\%. CONCLUSION: Accurate fetal autopsy and placental examination related to meticulous clinical collecting data are requisites in the valuation of stillbirth and could play an important role in reduction of unexplained stillbirth rate.


2010 - 17-alpha-hydroprogesterone caproate and cervical changes. [Articolo su rivista]
Facchinetti, Fabio
abstract

ObjectiveThe purpose of this study was to evaluate whether 17-a-hydroxyprogesterone caproate (17P) treatment affect changes in cervical length.Study DesignWomen with singleton pregnancy, between 25 and 33 + 6 weeks of gestation, who were hospitalized for preterm labor were included. Patients with rupture of membranes and/or signs of chorioamnionitis were excluded. Sixty undelivered patients were allocated randomly to either observation or to receive 341 mg of 17P intramuscularly, twice each week until gestational week 36. Cervical length was measured by transvaginal ultrasound scanning at discharge and at day 7 and 21 after discharge. Statistical comparisons were done with analysis of variance and chi-square test.ResultsShortening of the cervix in the observation group (30 cases) was higher than in the 17P group (30 cases) both at day 7 (2.37 ± 2.0 mm vs 0.83 ± 1.74 mm; P = .002) and day 21 (4.60 ± 2.73 mm Vs 2.40 ± 2.46 mm; P = .002). Treatment with 17P was associated with both a reduction in the risk of cervical shortening of ≥4 mm (odds ratio, 0.18; 95% CI, 0.04-0.66) and in the risk of preterm delivery (odds ratio, 0.15; 95% CI, 0.04-0.58).ConclusionUndelivered patients after preterm labor undergo progressive shortening of the cervix, which is attenuated by 17P treatment.


2009 - Angeliq versus Activelle in normotensive postmenopausal women: a prospective, randomized pilot study. [Articolo su rivista]
C., Battaglia; A., Cianciosi; F., Mancini; N., Persico; G., Sisti; Facchinetti, Fabio; P., Busacchi
abstract

OBJECTIVE: The aim of this study was to compare, in normotensive postmenopausal women, the effects of drospirenone/estradiol and norethisterone acetate/estradiol on blood pressure and other surrogate markers of cerebrovascular and cardiovascular risk. METHODS: Thirty postmenopausal women were submitted to utero-ovarian ultrasonography and to color Doppler evaluation of ophthalmic arteries. Ultrasonographic and Doppler analysis of brachial artery flow-mediated vasodilatation and 24-hour ambulatory blood pressure monitoring were performed. Plasma concentrations of nitrites/nitrates were assayed. The participants were randomly assigned to drospirenone 2 mg/estradiol 1 mg (group 1; n = 15) or norethisterone acetate 0.5 mg/estradiol 1 mg (group 2; n = 15) treatment. The duration of the study was 6 months. RESULTS: The basal pulsatility index and the back pressure of the ophthalmic artery were similar in groups 1 and 2. After 6 months, no changes were observed. The nitrites/nitrates values were not different between groups 1 and 2 both in basal conditions and after therapy. The brachial artery flow-mediated vasodilatation and the pulsatility index of the brachial artery did not show any difference in groups 1 and 2 both in basal conditions and after the therapy. The 24-hour blood pressure monitoring showed no significant differences in the 24-hour time, daytime, and nighttime values either in basal conditions or after therapy. All participants were found to be dippers normally (nocturnal reduction > or =10\% in comparison with diurnal values). The wake-up blood pressure values were similar in the studied participants. CONCLUSIONS: A 6-month hormone therapy with drospirenone/estradiol or norethisterone acetate/estradiol is equally effective and does not seem to alter the surrogate markers of cardiovascular and cerebrovascular risk.


2009 - Angiotensin-converting enzyme and adducin-1 polymorphisms in women with preeclampsia and gestational hypertension. [Articolo su rivista]
C., Mandò; P., Antonazzo; S., Tabano; S., Zanutto; P., Pileri; E., Somigliana; F., Colleoni; A., Martinelli; A., Zolin; C., Benedetto; L., Marozio; Neri, Isabella; Facchinetti, Fabio; M., Miozzo; I., Cetin
abstract

The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and the Adducin-1 (ADD1) G460W nonsense single nucleotide polymorphism (SNP) have previously been associated to hypertension, whereas their association with preeclampsia (PE) and gestational hypertension (GH) is still controversial. We genotyped ACE I/D, ADD1 G460W, and ADD1 S586C polymorphisms in 672 unrelated pregnant women: 204 PE (81/204 mild PE), 56 GH, and 412 controls, evaluating both their single and combined effects on these pathologies. The genotype combination of the 3 polymorphisms was not statistically different in cases versus controls, nor were ACE and ADD1 polymorphisms in GH. Nevertheless, the distribution of ACE genotypes was different in PE. This was confirmed in mild PE, whereas no significance was found in severe PE. This could suggest that different factors may lead to mild and severe PE, with ACE polymorphism playing a more important role in the mild form.


2009 - Antithrombin plasma levels decrease is associated with preeclampsia worsening. [Articolo su rivista]
M., Marietta; L., Simoni; P., Pedrazzi; L., Facchini; D'Amico, Roberto; Facchinetti, Fabio
abstract

Antithrombin plasma levels (AT) have been found decreased in women with preeclampsia (PE), but little is known about the trend of AT during the course of this disease. We prospectively investigated AT in consecutive women admitted to our hospital with a diagnosis of PE, to assess if AT fluctuations could be associated with the evolution of the disease. AT, platelet count and D-dimer levels were determined every other day. In the 73 patients studied, AT, platelet count and fibrinogen progressively reduced during the observational period, reaching a nadir on the day of delivery, whereas D-dimer progressively increased over time. Statistical analysis was restricted to the 39 women that had an AT measurement performed on each of days -1, 0 and +1, with respect to the day of delivery. These subjects showed a significant decrease in AT on the day of delivery compared to the day just before (77.8 +/- 15.1\%vs. 85.4 +/- 14.2\%, P = 0.027), followed by a recovery on the first day after delivery (87.6 +/- 21.3\% from 77.8 +/- 15.1\%, P = 0.005). Our study demonstrates that a significant drop in AT levels is associated with the clinical worsening of PE, regardless of its severity.


2009 - Application of acupuncture in labor [Relazione in Atti di Convegno]
Neri, I.; Ricchi, A.; Salvioli, C.; Facchinetti, F.
abstract


2009 - Cardiovascular risk in normal weight, eumenorrheic, nonhirsute daughters of patients with polycystic ovary syndrome: a pilot study. [Articolo su rivista]
C., Battaglia; F., Mancini; A., Cianciosi; P., Busacchi; N., Persico; R., Paradisi; Facchinetti, Fabio; D. d., Aloysio
abstract

OBJECTIVE: To verify whether healthy daughters with polycystic ovaries (PCO) of patients with polycystic ovary syndrome (PCOS) have an increased risk of cardiovascular disease in comparison with healthy controls. DESIGN: Prospective observational study. SETTING: University hospital. PATIENT(S): Seventeen eumenorrheic daughters with PCO of patients with PCOS (group 1) and 20 healthy volunteers (group 2) with regular ovulatory cycles. INTERVENTION(S): Fasting blood sampling, ultrasonographic and Doppler analyses, 24-hour ambulatory blood pressure monitoring. MAIN OUTCOME MEASURE(S): Medical examination; blood measurement of nitrites and nitrates, biochemical and hormonal parameters; utero-ovarian ultrasonographic analysis and color Doppler evaluation of uterine and stromal ovarian arteries; brachial artery flow-mediated vasodilatation; 24-hour ambulatory blood pressure monitoring. An oral glucose tolerance test was performed to analyze glucose, insulin, and C-peptide levels. RESULT(S): At Doppler analysis a significantly higher uterine and a lower ovarian artery pulsatility index was found in group 1 compared with group 2. The brachial artery diameter, after the reactive hyperemia, showed a greater vasodilatation in controls in comparison with women with PCO. The 24-hour blood pressure monitoring demonstrated that patients with PCO have significant higher 24-hour, daytime, and nighttime diastolic and mean arterial pressure values than controls. The nitrites and nitrates plasma levels were lower in group 1 compared with group 2. The glucose and insulin plasma values were higher in patients with PCO than in controls. CONCLUSION(S): Eumenorrheic nonhirsute daughters of patients with PCOS who have PCO appearance on ultrasound have an increased cardiovascular risk.


2009 - Causes of death and associated conditions (Codac): a utilitarian approach to the classification of perinatal deaths. [Articolo su rivista]
J. F., Frøen; H., Pinar; V., Flenady; S., Bahrin; A., Charles; L., Chauke; K., Day; C. W., Duke; Facchinetti, Fabio; R. C., Fretts; G., Gardener; K., Gilshenan; S. J., Gordijn; A., Gordon; G., Guyon; C., Harrison; R., Koshy; R. C., Pattinson; K., Petersson; L., Russell; E., Saastad; G. C., S; R., Torabi
abstract

A carefully classified dataset of perinatal mortality will retain the most significant information on the causes of death. Such information is needed for health care policy development, surveillance and international comparisons, clinical services and research. For comparability purposes, we propose a classification system that could serve all these needs, and be applicable in both developing and developed countries. It is developed to adhere to basic concepts of underlying cause in the International Classification of Diseases (ICD), although gaps in ICD prevent classification of perinatal deaths solely on existing ICD codes.We tested the Causes of Death and Associated Conditions (Codac) classification for perinatal deaths in seven populations, including two developing country settings. We identified areas of potential improvements in the ability to retain existing information, ease of use and inter-rater agreement. After revisions to address these issues we propose Version II of Codac with detailed coding instructions.The ten main categories of Codac consist of three key contributors to global perinatal mortality (intrapartum events, infections and congenital anomalies), two crucial aspects of perinatal mortality (unknown causes of death and termination of pregnancy), a clear distinction of conditions relevant only to the neonatal period and the remaining conditions are arranged in the four anatomical compartments (fetal, cord, placental and maternal).For more detail there are 94 subcategories, further specified in 577 categories in the full version. Codac is designed to accommodate both the main cause of death as well as two associated conditions. We suggest reporting not only the main cause of death, but also the associated relevant conditions so that scenarios of combined conditions and events are captured.The appropriately applied Codac system promises to better manage information on causes of perinatal deaths, the conditions associated with them, and the most common clinical scenarios for future study and comparisons.


2009 - Computerized Evaluation of Fetal Heart Rate during Tocolytic Treatment: Comparison between Atosiban and Ritodrine. [Articolo su rivista]
Neri, Isabella; Monari, Francesca; Herbert, Valensise; Barbara, Vasapollo; Facchinetti, Fabio; Volpe, Annibale
abstract

We compared the effects of ritodrine and atosiban treatments on fetal cardiovascular behavior by computerized nonstress test (c-NST) analysis. Women diagnosed with preterm labor were randomized to receive either atosiban or ritodrine. A c-NST was performed at least 12 hours after the last corticosteroid administration. Differences in fetal cardiovascular behavior were evident when treatment was given before 30 weeks' gestation. Ritodrine induced higher fetal heart rates, lower long-term variation values, and lower low:high-frequency ratios compared with atosiban. Atosiban induced higher gestational ages at delivery and higher birth weights than ritodrine. The mean Apgar scores were similar for atosiban and ritodrine groups at 1 and 5 minutes. No 5-minute Apgar score was &lt; 7. With respect with atosiban, ritodrine treatment induces tachycardia and a lower variability of fetal heart rate. Such changes could be erroneously interpreted as signal of fetal distress, namely at lower gestational age.


2009 - Endothelial function and its relationship to leptin, homocysteine, and insulin resistance in lean and overweight eumenorrheic women and PCOS patients: a pilot study. [Articolo su rivista]
F., Mancini; A., Cianciosi; G. M., Reggiani; Facchinetti, Fabio; C., Battaglia; D. d., Aloysio
abstract

OBJECTIVE: To verify if patients with polycystic ovarian syndrome (PCOS), have an increased cardiovascular risk compared with healthy controls. DESIGN: Prospective case-control study. SETTING: University-based practice. PATIENT(S): Twenty eumenorrheic controls (ten lean [group A] and ten overweight [group B]) and 24 PCOS women (14 lean [group C] and ten overweight [group D]). INTERVENTION(S): Cardiovascular risk markers and hormonal parameters were assessed. MAIN OUTCOME MEASURE(S): Androgens, fasting glucose, insulin, leptin, fibrinogen, homocysteine, endothelin-1 and flow-mediated dilatation of the brachial artery were measured to investigate their relationship to weight and to PCOS. RESULT(S): The brachial artery diameter and the pulsatility index, after the reactive hyperemia, showed in group A the most intense vasodilatation compared with the other groups. Homocysteine levels did not differ among the groups. Endothelin-1 was significantly higher in group A compared with groups B and D. Leptin was significantly lower in groups A and C compared with groups B and D. Insulin resistance was higher in groups B and D. Group A had significantly higher glucose-insulin ratio compared with all of the other groups; group C had significantly higher glucose-insulin ratio only compared with group D. CONCLUSION(S): Weight and PCOS are two independent variables affecting the endothelial function.


2009 - Fitoterapia e integratori in ostetricia e ginecologia [Curatela]
Facchinetti, Fabio; V., Unfer
abstract

Fitoterapia e integratori in ostetricia e ginecologia


2009 - Maternal thrombophilia and the risk of recurrence of preeclampsia. [Articolo su rivista]
Facchinetti, Fabio; Marozio, L; Frusca, T; Grandone, E; Venturini, P; Tiscia, Gl; Zatti, S; Benedetto, C.
abstract

OBJECTIVE: The aim of this prospective study was to determine the impact of thrombophilia on the recurrence of preeclampsia. STUDY DESIGN: In a multicenter, observational, cohort design, 172 white patients with a previous pregnancy complicated by preeclampsia were observed in the next pregnancy. They were evaluated for heritable thrombophilia (factor V Leiden and factor II G20210A mutations, protein S, protein C, and antithrombin deficiency), hyperhomocystinemia, lupus anticoagulant, and anticardiolipin antibodies. Development of preeclampsia and maternal complications and both gestational age at delivery and birthweight were recorded. RESULTS: Sixty women (34.9%) showed the presence of a thrombophilic defect. They had a higher risk for the recurrence of preeclampsia (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.2-5.1), compared to patients without thrombophilia. Similar findings were observed considering only heritable thrombophilia. Thrombophilic patients were at increased risk for the occurrence of very early preterm delivery (< 32 weeks; OR, 11.6; 95% CI, 3.4-43.2). CONCLUSION: When counseling white women with a history of preeclampsia, screening for thrombophilia can be useful for preconceptional counseling and pregnancy management.


2009 - Migraine is a risk factor for hypertensive disorders in pregnancy: a prospective cohort study [Articolo su rivista]
Facchinetti, Fabio; G., Allais; R. E., Nappi; D'Amico, Roberto; L., Marozio; L., Bertozzi; A., Ornati; C., Benedetto
abstract

The aim was to assess whether women suffering from migraine are at higher risk of developing hypertensive disorders in pregnancy. In a prospective cohort study, performed at antenatal clinics in three maternity units in Northern Italy, 702 normotensive women with singleton pregnancy at 11-16 weeks' gestation were enrolled. Women with a history of hypertensive disorders in pregnancy or presenting chronic hypertension were excluded. The presence of migraine was investigated according to International Headache Society criteria. The main outcome measure was the onset of hypertension in pregnancy, defined as the occurrence of either gestational hypertension or preeclampsia. Two hundred and seventy women (38.5%) were diagnosed with migraine. The majority (68.1%) suffered from migraine without aura. The risk of developing hypertensive disorders in pregnancy was higher in migraineurs (9.1%) compared with non-migraineurs (3.1%) [odds ratio (OR) adjusted for age, family history of hypertension and smoking 2.85, 95% confidence interval (CI) 1.40, 5.81]. Women with migraine also showed a trend to increased risk for low birth weight infants with respect to women without migraine (OR 1.97, 95% CI 0.98, 3.98). Women with migraine are to be considered at increased risk of developing hypertensive disorders in pregnancy. The diagnosis of primary headaches should be taken into account at antenatal examination.


2009 - NITRIC OXIDE AS AN EARLY MARKER OF HUMAN EMBRYO METABOLIC CLEAVAGE IN ART USING FRESH OR THAWED OOCYTES [Articolo su rivista]
Gallinelli, A; Nicoli, A; Capodanno, F; Valli, B; Facchinetti, Fabio; LA SALA, Giovanni Battista
abstract

OBJECTIVE: To study a possible role of nitric oxide (NO) as a marker of development in the early phases of human embryo cleavage during assisted reproduction. STUDY DESIGN: 179 women having ART were included. 123 women used fresh oocytes and 56 oocyte thawing cycles in the Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Arcispedale S. Maria Nuova, between July 2005 and June 2006; 57 patients had IVF and 122 patients had ICSI. NO concentrations in IVF or ICSI embryo culture media were assessed by monitoring levels of NO stable oxidation products (nitrites/nitrates). Analysis of embryo quality was performed. Student's t-test or Mann-Whitney and logistic regression model tests were applied to the data. RESULTS: In patients using fresh oocytes, there were greater NO production in embryos derived from ICSI than from IVF after 52 h of culture (38.64 micromol/L vs 11.2 micromol/L, p<0.05). No correlation with embryo quality was observed. Embryos derived from fresh oocytes produce more NO than embryos from thawed oocytes both after 48 and 52 h of culture (16.12 micromol/L vs 6.83 micromol/L and 25.93 micromol/L vs 2.98 micromol/L respectively, p<0.05). CONCLUSION(S): NO in embryo culture media is not a metabolic cleavage marker or a marker of embryo quality in ART. However, it could be an important parameter in the investigation of metabolism in frozen/thawed oocytes.


2009 - Pharmacologycal use of progesterone and 17-α-hydroxyprogesterone caproate in the prevention of preterm delivery [Articolo su rivista]
Facchinetti, F.; Vaccaro, V.
abstract

Preterm delivery (PTD) is defined by the World Health Organization as birth before 37 completed weeks of gestation. In Western countries, PTD accounts for over 75% of all perinatal morbidity and mortality. The social importance of PTD derives from the consideration that it causes near three quarter of neonatal deaths not caused by malformations. Progesterone is a steroid hormone which plays a crucial role in each step of human pregnancy. Early in pregnancy progesterone is produced by the corpus luteum and it is fundamental for pregnancy maintenance until placenta takes over this function at 7-9 weeks of gestation. Late in pregnancy, the role of progesterone is less clear: certainly, it may be importance in maintaining uterine quiescence in the latter half of pregnancy by limiting the production of stimulatory prostaglandins and inhibiting the expression of contraction-associated protein genes (ion channels, oxytocin and prostaglandin receptors, and gap junctions) within the myometrium. In this review, the authors included those controlled clinical studies that have used either 17 hydroxy progesterone caproate (17P), or progesterone (P) or its synthetic derivatives (progestins) in order to avoid or reduce the incidence of preterm delivery, in populations of women at increased risk of preterm birth. The authors conclude that: 1) the treatment with 17P reduces the incidence of PTD in pluriparous women with a previous history of PTD or with recurrent abortion, as well as in nulliparous women with an actual risk; 2) the treatment with P reduces PTD in nulliparous women, namely in the presence of a silent cervical shortening; 3) 17P has no efficacy in multiple pregnancy and it is proven not to have adverse effects on the infants.


2009 - The experiences of the Birth Center in Modena [Articolo su rivista]
Salvioli, C.; Facchinetti, F.
abstract


2009 - The future: Fetal therapy and translational studies: Global alignment, coordination, and collaboration in perinatal research: The global obstetrics network (GONet) initiative [Capitolo/Saggio]
Mol, B. W.; Kilby, M. D.; Asztalos, E.; Dekker, G.; Facchinetti, F.; Metin Gulmezoglu, A.; Magee, L.; Morris, J.; Norman, J.; Poston, L.; Saade, G.; Shennan, A.; Thom, E.; Von Dadelszen, P.; Leung, T. Y.; Merialdi, M.; Alfirevic, Z.
abstract

Introduction Medical interventions should only be offered if there is evidence that they help the patient. At present, there is consensus that their effectiveness should be evaluated before incorporation into guidelines. Since the inception of fetal medicine as a subspecialty and the application of in-utero treatments for fetal therapy, there have been cohort studies presented. Initially these cohort series (mainly retrospective) were based on experiences from tertiary centers but in the last five to ten years there has been more of a focus on “population-based” cohort studies that at least have accurate denominator data from which to calculate outcomes. Critical appraisal of the literature and appraisal of fetal therapy has been aided by performing systematic reviews and, where practicable, meta-analysis of outcomes. However, although such methods are informative they summate evidence from relatively small and often heterogeneous case cohort studies. The randomized clinical trial is considered to be the best research tool to evaluate the effectiveness of medical interventions, and is the widely acknowledged design of choice for evaluating medical and surgical treatments [1 – 3].


2009 - The use of progesterone and 17-alphahydroxyprogesterone caproate in the prevention of preterm delivery [Articolo su rivista]
Facchinetti, F.
abstract


2009 - The 9th Congress of the Italian Society of Psychosomatic Obstetrics and Gynecology: "Psychosomatic notes in obstetrics and gynecology". Modena, February 20-21, 2009 - Introduction [Relazione in Atti di Convegno]
Facchinetti, F.; Volpe, A.
abstract


2009 - Use of phytotherapy in premenstrual syndrome [Articolo su rivista]
Dante, G.; Facchinetti, F.; Bellafronte, M.; Ricchi, A.
abstract


2009 - Vaginal birth after CESAREAN SECTION CS: Should it be recommended? [Articolo su rivista]
Facchinetti, F.
abstract


2008 - Exposure to active and passive smoking during pregnancy and severe small for gestational age at term [Articolo su rivista]
Fantuzzi, Guglielmina; Vaccaro, Valentina; Aggazzotti, Gabriella; Righi, Elena; Kanitz, S; Barbone, F; Sansebastiano, G; Battaglia, Ma; Leoni, V; Fabiani, L; Triassi, M; Sciacca, S; Facchinetti, Fabio
abstract

The objective of this study was to assess the relationship between active smoking as well as environmental tobacco smoke (ETS) exposure and severe small for gestational age (SGA) at term in a sample of pregnant Italian women. METHODS: A case-control study was conducted in nine cities in Italy between October 1999 and September 2000. Cases of severe SGA were singleton, live born, at term children with a birth weight <or= 5(th) percentile for gestational age. Controls (10:1 to cases) were enrolled from among singleton at term births that occurred in the same hospitals one or two days after delivery of the case, with a birth weight > 10(th) percentile for gestational age. A total of 84 cases of severe SGA and 858 controls were analyzed. A self-administered questionnaire was used to assess active smoking and ETS exposure, as well as potential confounders. RESULTS: Multivariate logistic regression analysis showed a relationship between active smoking during pregnancy and severe SGA (adjusted odds ratio (OR) 2.10, 95% confidence interval (CI) 1.13-3.68). ETS exposure was associated with severe SGA (adjusted OR 2.51, 95% CI 1.59-3.95) with a dose-response relationship to the number of smokers in the home.


2008 - Feto-Maternal Safety of Intracervical Sodium Nitroprusside Application in Sheep [Articolo su rivista]
Richardson, B; Volpe, Annibale; Facchinetti, Fabio; Immacolata, Blasi
abstract

The feto-maternal safety of sodium nitroprusside (SNP) administration in the cervix of pregnant sheep is evaluated. Chronically catheterized pregnant sheep at 0.9 gestation were divided into 2 groups that received 0.1 mg/kg maternal body weight of SNP gel (2%) or placebo into the internal cervical os. SNP or placebo gel was administered at 9 AM with both maternal and fetal blood gas/pH, and cardiovascular parameters were monitored for 6 hours. Except for a slight transient decrease of maternal oxygen and meta-hemoglobin content, and fetal oxygen content in the SNP group, no other significant changes were observed. However, such changes are minimal and unlikely to be of any clinical significance. Moreover, nitric oxide metabolites were unchanged in both maternal and fetal circulations.These data demonstrate few, if any, effects of intrauterine SNP administration on both cellular oxygenation and cardiovascular indexes. Thus, SNP treatment, once applied into the cervix, could be considered a safe procedure.


2008 - Integration and phytodrugs in the treatment of obstetric-gynecological diseases: Modena, March 8, 2008. Presentation [Relazione in Atti di Convegno]
Facchinetti, F.; Unfer, V.
abstract


2008 - INTERNATIONAL ISSUES IN STILLBIRTH [Articolo su rivista]
Facchinetti, Fabio; Reddy, U; STRAY PEDERSEN, B; Baronciani, D; HARRIS REQUEJO J., FOR THE STILLBIRTH GROUP
abstract

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2008 - La natimortalità: audit clinico e miglioramento della pratica assistenziale [Curatela]
D., Baronciani; G., Bulfamante; Facchinetti, Fabio
abstract

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2008 - L-arginine and hypertension in pregnancy [Relazione in Atti di Convegno]
Neri, I.; Monari, F.; De Pace, V.; Facchinetti, F.; Volpe, A.
abstract


2008 - MENSTRUAL CYCLE-RELATED MORPHOMETRIC AND VASCULAR MODIFICATIONS OF THE CLITORIS. [Articolo su rivista]
Battaglia, C; Nappi, Re; Mancini, F; Cianciasi, A; Persico, N; Busacchi, P; Facchinetti, Fabio; DE ALOYSIO, D.
abstract

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2008 - Obstetricians' and midwives' attitudes toward cesarean section [Articolo su rivista]
Monari, Francesca; Di Mario, S; Facchinetti, Fabio; Basevi, V.
abstract

BACKGROUND: The cesarean section rate has increased worldwide over the past 20 years; in Italy, it is now more than 35 percent. Although clinical factors are important, the attitudes of health practitioners toward cesarean section need further investigation to correctly identify facilitators and barriers to changes. The objective of this study was to explore the attitudes toward cesarean section of midwives and obstetricians who worked in the same geographical area. METHODS: Face-to-face structured interviews using an adaptation of the Survey of Clinicians' Views on Caesarean Section, an anonymous questionnaire with 35 open and closed answers on practitioners' views on cesarean section, were conducted. The questionnaire was given to the entire group of midwives and obstetricians working in Modena, a northern Italian district. RESULTS: Of 262 eligible practitioners, 248 were interviewed (response rate 94.6%). The midwives' attitudes toward cesarean section differed from those of the obstetricians. Sixty-five percent of midwives considered the rates of cesarean section in their hospitals to be too high compared with 34 percent of obstetricians (p < 0.001). Midwives were also less inclined to believe that cesarean section provides benefits to the mother (p = 0.02) or that it is indicated by previous cesarean delivery (p < 0.001). No differences were observed between male and female obstetricians. CONCLUSIONS: In this survey, the attitudes toward cesarean section were correlated more with professional role than with gender. This information can help policy makers to shape interventions aimed at providing better care for pregnant and childbearing women.


2008 - PCOS, sexuality, and clitoral vascularisation: A pilot study [Articolo su rivista]
Battaglia, C.; Nappi, R. E.; Mancini, F.; Cianciosi, A.; Persico, N.; Busacchi, P.; Facchinetti, F.; Sisti, G.
abstract

Introduction. In polycystic ovarian syndrome (PCOS) women, the changes in body appearance (mainly obesity and hirsutism) may influence the feminine identity of the patients with consequent depression and sexual disturbances. Aim. To evaluate if lean PCOS patients present an increased incidence of depression and sexual dysfunction in comparison with controls and if clitoral volume and vascularization are influenced by circulating androgens levels. Methods. 25 lean PCOS women (Group I) and 18 healthy nonhirsute volunteers (Group II) were submitted, on day 3-5 of the cycle, to ultrasonographic and Doppler analyses, and to hormonal and biochemical evaluations. Main Outcome Measures. Utero-ovarian and clitoral ultrasonographic analysis, and color Doppler evaluation of the uterine, stromal ovarian, and dorsal clitoral arteries. Hormonal and nitrites/nitrates plasma concentrations were analyzed. Each woman filled in the 2-factor Italian McCoy female questionnaire (MFSQ) and the Beck's Depression Inventory questionnaire (BDI). Results. Androgens resulted, as expected, more elevated in PCOS patients than in controls. However, the ultrasonographic (US) assessment of the clitoral body volume evidenced no significant differences between PCOS (0.72 ± 0.41 mL) and control (0.62 ± 0.20 mL) patients. The resistances registered at the level of the dorsal clitoral artery did not show any difference between Group I (PI = 1.55 ± 0.40) and Group II (PI = 1.79 ± 0.38). The 2-factor Italian MFSQ and the BDI did not show any difference between PCOS women and controls. Conclusions. In PCOS women, probably, the moderate hirsutism and hyperandrogenism do not induce the sense of loss of feminine identity and have no impact on sexual self-worth and sexual satisfaction. © 2008 International Society for Sexual Medicine.


2008 - Review of western phytotherapy in premenstrual syndrome [Relazione in Atti di Convegno]
Dante, G.; Bellafronte, M.; Facchinetti, F.
abstract


2008 - VASCULAR RISK IN YOUNG WOMEN WITH POLYCYSTIC OVARY AND POLYCYSTIC OVARY SYNDROME [Articolo su rivista]
Battaglia, C; Mancini, F; Cianciosi, A; Busacchi, P; Facchinetti, Fabio; Marchesini, Gr; Marzocchi, R; DE ALOYSIO, D.
abstract

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2008 - 17α-hydroxy-progesterone effects on cervical proinflammatory agents in women at risk for preterm delivery [Articolo su rivista]
Facchinetti, Fabio; Dante, Giulia; Venturini, P; Paganelli, S; Volpe, Annibale
abstract

We evaluated if the inhibitory effect of 17alpha-hydroxyprogesterone caproate (17P) on cervical ripening is mediated by cervical proinflammatory agents. Women with singleton pregnancy and intact membranes, between 25 and 33 weeks + 6 days, were randomly allocated either to observation (22 cases, controls) or to receive 341 mg of intramuscular 17P (23 cases, 17P group), twice a week, until 36 weeks. Just before randomization, 7 and 21 days later, a cervical swab for interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor alpha (TNF-alpha), and nitrates/nitrites (NOx) assays was collected. Moreover, an ultrasound measure of cervical length (CL) was performed at the same time. At randomization, both groups of women showed similar levels of cervical ILs and NOx. In the 17P group, cervical IL-1beta levels were significantly decreased at day 21 ( P = 0.036); in controls, they remained stable throughout the observation period. There was no significant change in IL-6, IL-8, TNF-alpha, and NOx in either group. Women in the control group had a progressive CL shortening until day 21 (median shortening of 4 mm), and this shortening was significantly less in the 17P group (median shortening of 2 mm; P = 0.017). In patients at risk of preterm labor, high-dose 17P simultaneously inhibits both cervical proinflammatory IL-1beta secretion and the progressive shortening of the cervix.


2007 - Cervical length changes during preterm cervical ripening: effects of 17-alfa hydroxy progesterone caproate [Articolo su rivista]
Facchinetti, Fabio; Paganelli, S; Comitini, G; Dante, G; Volpe, Annibale
abstract

OBJECTIVE: The purpose of this study was to evaluate whether 17-alpha-hydroxyprogesterone caproate (17P) treatment affect changes in cervical length. STUDY DESIGN: Women with singleton pregnancy, between 25 and 33 + 6 weeks of gestation, who were hospitalized for preterm labor were included. Patients with rupture of membranes and/or signs of chorioamnionitis were excluded. Sixty undelivered patients were allocated randomly to either observation or to receive 341 mg of 17P intramuscularly, twice each week until gestational week 36. Cervical length was measured by transvaginal ultrasound scanning at discharge and at day 7 and 21 after discharge. Statistical comparisons were done with analysis of variance and chi-square test. RESULTS: Shortening of the cervix in the observation group (30 cases) was higher than in the 17P group (30 cases) both at day 7 (2.37 +/- 2.0 mm vs 0.83 +/- 1.74 mm; P = .002) and day 21 (4.60 +/- 2.73 mm vs 2.40 +/- 2.46 mm; P = .002). Treatment with 17P was associated with both a reduction in the risk of cervical shortening of > or = 4 mm (odds ratio, 0.18; 95% CI, 0.04-0.66) and in the risk of preterm delivery (odds ratio, 0.15; 95% CI, 0.04-0.58). CONCLUSION: Undelivered patients after preterm labor undergo progressive shortening of the cervix, which is attenuated by 17P treatment


2007 - CLINICAL USE OF NITRIC OXIDE DONORS AND L-ARGININE IN OBSTETRICS. [Articolo su rivista]
DE PACE, V; Chiossi, G; Facchinetti, Fabio
abstract

..


2007 - DIETARY FAT INTAKES FOR PREGNANT AND LACTATING WOMEN [Articolo su rivista]
Koletzko, B; Cetin, I; Facchinetti, Fabio
abstract

..


2007 - Effects of three different stimulations (acupuncture, moxibustion, acupuncture plus moxibustion) of BL.67 acupoint at small toe on fetal behavior of breech presentation [Articolo su rivista]
Neri, Isabella; De Pace, V; Venturini, P; Facchinetti, Fabio
abstract

The aim of the study was to evaluate cardiovascular effects and fetal behavior during moxibustion, acupuncture or acupuncture plus moxibustion applied on the BL.67 acupoint of women (beside the outer corner of the 5th toenail) in fetal breech presentation. During the acupoint stimulation (20 min, two times a week), the women were submitted to computerized non-stress test. Fourteen cases were treated by both acupuncture and moxibustion, 15 cases by moxibustion and 10 cases by acupuncture. In 56% of cases, fetal position was converted from breech position to cephalic one; the success share was 80% for moxibustion, 28% for acupuncture, 57% for acupuncture plus moxibustion; the conversion, on average, was achieved after 3 sessions. Statistical analysis indicated that acupuncture plus moxibustion was able to reduce fetal heart rate during the application of stimuli while acupuncture and moxibustion separately did not affect such parameter. Moreover, moxibustion and acupuncture with moxibustion reduced fetal movements while acupuncture only appears ineffective. The present study suggests that fetal movements were reduced by both acupuncture plus moxibustion and moxibustion and that fetal heart rate was reduced just by acupuncture plus moxibustion. The mechanisms leading the effect on fetal heart rate and fetal movements remain to be clarified. Even though further studies are needed, such preliminar report mainly investigated the impact of different stimula on the BL.67 acupoint. Unfortunately these small series of data do not allow us to draw any conclusion about the effectiveness of the different treatments.


2007 - ELECTIVE CERVICAL RIPENING IN WOMEN BEYOND THE 290TH DAY OF PREGNANCY: A RANDOMIZED TRIAL COMPARING 2 DINOPROSTONE PREPARATIONS. [Articolo su rivista]
Facchinetti, Fabio; Venturini, P; Fazzio, M; Volpe, Annibale
abstract

OBJECTIVE: To determine the better performer among cervical ripening agents for the elective induction of labor. STUDY DESIGN: An open-label, randomized study was done in consecutive patients undergoing elective induction of labor at the 41st week and beyond. Inclusion criteria were: singleton pregnancy, gestational age ascertained through first-trimester ultrasound, Bishop score <4 and nulliparity. Exclusion criteria were: oligohydramnios, maternal/fetal disorder or pregnancy complication, previous uterine surgery, rupture of membranes and presence of uterine activity. Patients received either slow-release dinoprostone vaginal insert (VI) or 0.5-mg dinoprostone intracervical (IC) gel, twice, 6 hours apart. RESULTS: Women receiving VI showed increased risk of entering labor without further stimulation (OR = 6.48, 95% CI 2.06-21.67, p < 0.001) and delivering vaginally within 24 hours (OR = 2.71, 95% CI 1.19-6.21, p = 0.01) in comparison to those receiving IC gel. A stay in the hospital (> 4 days) was more prevalent in women treated with IC gel in comparison to those treated with VI (OR = 2.35, 95% CI 1.04-5.37). CONCLUSION: Preinduction cervical ripening with the dinoprostone slow-release vaginal insert is associated with a hight rate of women undergoing vaginal delivery within 24 hours, with a shorter stay. Considering its good performance, the dinoprostone slow-release vaginal insert is the first choice for elective induction of labor in postdate pregnancy.


2007 - L-arginine supplementation in patients with gestational hypertension: A pilot study [Articolo su rivista]
Facchinetti, Fabio; Saade, Gr; Neri, Isabella; Pizzi, C; Longo, M; Volpe, Annibale
abstract

Objective: To evaluate the effects of L-arginine (L-Arg) supplementation on clinical outcomes and blood pressure (BP) changes in patients with gestational hypertension. Methods: Patients with gestational hypertension and proteinuria (n = 28, &gt; 300 mg/ 24 h) and those without proteinuria (n = 46) were randomized in a double-blind design to receive either L-Arg (20g/500 mL intravenously daily, for 5 days followed by 4g/day orally for 2 weeks) or placebo (PL). The primary outcome variable was time from randomization to delivery (Latency). Automated BP readings were obtained every 2 hours, between 8.00 am and 8.00 pm daily, untill the sixth day after treatment. Results: At inclusion, gestational age and proportions of patients with proteinuria did not differ significantly between the PL and L-Arg group, Latency was significantly longer in the L-Arg group compared with the PL group (19.5 +/- 16.9 vs. 31.7 +/- 25.2 days; p = 0.008). Compared with baseline, both systolic and diastolic BP 6 days after treatment were significantly reduced in the L-Arg group but not in the PL group. The subgroup of patients without proteinuria randomized to the group receiving L-Arg showed a trend to prolong pregnancy, to attenuate the evolution to PE, and to reduce the rate of low birth weight. Conclusions: The treatment with L-Arg seems promising in prolonging pregnancy and reducing blood pressure, particularly in patients with gestational hypertension and without proteinuria. This benefit should be confirmed in larger studies with the power to evaluate the effectiveness of L-Arg in preventing the development to preeclampsia.


2007 - NITRIC OXIDE LEVELS IN WOMEN WITH MISSED AND THREATENED ABORTION: RESULTS OF A PILOT STUDY [Articolo su rivista]
Paradisi, R; Fabbri, R; Battaglia, C; Facchinetti, Fabio; Venturoli, S.
abstract

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2007 - Preterm delivery and exposure to active and passive smoking during pregnancy: a case-control study from Italy [Articolo su rivista]
Fantuzzi, Guglielmina; Aggazzotti, Gabriella; Righi, Elena; Facchinetti, Fabio; Bertucci, Emma; S., Kanitz; F., Barbone; G., Sansebastiano; M. A., Battaglia; V., Leoni; L., Fabiani; M., Triassi; S., Sciacca
abstract

The aim of this study was to assess the relationship between preterm/early preterm delivery and active smoking as well as environmental tobacco smoke (ETS) exposure in a sample of pregnant Italian women. A case-control study was conducted in nine cities in Italy between October 1999 and September 2000. Cases of preterm birth were singleton babies born before the 37th gestational week; babies born before the 35th gestational week were considered early preterm births. Controls were babies with gestational ages ≥ 37th week. A total of 299 preterm cases (including 105 early preterm) and 855 controls were analysed. A self-administered questionnaire was used to assess active smoking and ETS exposure, as well as potential confounders. Multivariable logistic regression analysis showed a relationship between active smoking during pregnancy and preterm/early preterm delivery [adjusted ORs: 1.53; 95% CI 1.05, 2.21 and 2.00; 95% CI 1.16, 3.45, respectively]. A dose-response relationship was found for the number of cigarettes smoked daily. The adjusted ORs were 1.54 and 1.69 for preterm babies and 1.90 and 2.46 for early preterm babies for 1-10 and >10 cigarettes/day respectively. ETS exposure was associated with early preterm delivery [adjusted OR 1.56; 95% CI 0.99, 2.46] with a dose-response relationship with the number of smokers in the home. Smoking during pregnancy was strongly associated with preterm delivery with a dose-response effect. ETS exposure in non-smoking women was associated only with early preterm delivery.


2007 - Psychosocial factors associated with preterm uterine contractions. [Articolo su rivista]
Ottolini, F; Facchinetti, Fabio; Rigatelli, Marco; Tomba, E; Belaise, C; Ruini, C; Fava, Ga
abstract

Not available


2006 - ABSENCE OF NEONATAL STREPTOCOCCAL COLONIZATION AFTER PLANNED CESAREAN SECTION [Articolo su rivista]
Berardi, A; Rossi, K; Pizzi, C; Baronciani, D; Venturelli, C; Ferrari, Fabrizio; Facchinetti, Fabio
abstract

no abstract


2006 - Biochemical mediators of the cervical modifications in the preterm birth [Articolo su rivista]
Facchinetti, F.; Paganelli, S.; Venturini, P.; Dante, G.; Palama, L.
abstract

Preterm birth (PTB) is an unresolved problem and its etiology remains nearly unknown. The actual trend is finding specific biochemical mediators produced during the prodromic phase of the PTB. These factors are the mediators of the inflammation, because the PTB is given in about 70% of cases by an inflammatory process not only during an infection. High levels of G-CSF, interleukin-1 (IL-1), IL-6, IL-8, fetal fibronectin, tumour necrosis factor-α (TNF-α.) in cervix or vagina; elevated plasmatic levels of IL-6, G-CSF, C-reactive protein, TNF-α and high concentrations in amniotic fluid of G-CSF, IL-1, IL-6 propose these molecules as mediators of intrauterine infection in patients during preterm labour. Other final mediators: α-fetus protein, alkaline phosphatase, lactoferrin, relaxin, are indirectly correlated to an infections state. Interleukin are also involved in the processes carring out the uterine hypercontractility, and in the mechanisms bringing to the induction of the cervical modifications through the activation of the Nitric Oxide production (NO). NO is considered the final mediator of the mechanisms that allow the cervical ripening. The most reliable marker is the fetal fibronectin, measurable after 20 weeks. When it is present in concentrations &gt; 50 mg/ml in cervix or vagina, it is highly predictive of PTB in the pregnant women between 22 and 24 weeks. © Copyright 2006, CIC Edizioni Internazionali.


2006 - Changes in cervical nitric oxide concentration correlate with bishop score and cervical length modifications in prostaglandin E2-mediated induction of labor [Articolo su rivista]
G., Chiossi; G., Verocchi; P., Venturini; Facchinetti, Fabio
abstract

OBJECTIVE: Nitric oxide (NO) plays a fundamental role in cervical ripening and it is synthesized in the human cervix. We studied the effect of the dinoprostone on cervical NO release in pregnant women, and we investigated the relationship between cervical NO metabolites, cervical length, and Bishop score. METHODS: Severity-seven women underwent induction of labor at >= 37 weeks of gestation, due to post-term pregnancy (23.8%), oligohydramnios (36.3) or preeclampsia (29.9%). Cervical fluid samples for NO metabolites (NOx), Bishop score, and cervical length were assessed immediately before (time 0 [T0]) and 6 hours after (T6) the local application of dinoprostone, a commercially available prostaglandin E2 (PGE2) analog. RESULTS: The mean patients' age was 34 +/- 3.2 years, mean gestational age at enrollment was 284 +/- 9.2 days, and nulliparous represented 31.2% of the study population. At time 0, Bishop score was less than 4 in 74% (57/77) of the subjects, mean cervical length was 28.6 +/- 5.8 mm, mean NOx concentration was 208.6 +/- 103.8 mu M/mL; 6 hours later, at T6, the mean cervical length decreased to 19.5 +/- 8.8 mm, and the mean NOx concentration increased up to 316.7 +/- 240.9 mu M/mL. Data were unaffected by parity or by regular uterine contraction patterns. A statistically significant positive correlation was found between changes in cervical NOx levels and Bishop score modification (P <.01; r = .494), as well as between the modification of NO metabolites concentration and cervical shortening (P <.01; r = .307).. CONCLUSIONS: Prostoglandin (PC)-indnced cervical ripening is associated with local NO release. NO plays an active role in cervical remodeling sir-ice it positively correlates with both cervical shortening and Bishop score increase. NO oxide and PG are the two pathways that, cross activating each outer, trigger the cascade of events responsible of cervical ripening.


2006 - Different effects of tibolone and low-dose EPT in the management of postmenopausal women with primary headaches [Articolo su rivista]
Nappi, Re; Sances, G; Sommacal, A; Detaddei, S; Facchinetti, Fabio; Cristina, S; Polatti, F; Nappi, G.
abstract

Objective: The present randomized prospective study aimed to compare the effect of tibolone (T) with conventional low-dose estrogen-progestogen therapy (EPT) administered in a combined continuous regimen on the course of primary headaches in postmenopausal women requesting hormone therapy (HT) for climacteric complaints. Design: Forty women presenting for clinical evaluation of headache (migraine without aura and episodic tension-type headache) were enrolled. The observational period lasted 7 months during which women kept a diary of the clinical characteristics of headache attacks and analgesic use. Climacteric symptoms and both anxiety and depression were also measured. After a 1-month run-in period, women received two different HT regimens: 1 mg 17 beta-estradiol + 0.5 mg norethisterone acetate (EPT) or 2.5 mg T. Follow-up evaluations were planned after 3 and 6 months of treatment. Results: Although T did not affect the number of days with migraine without aura, it significantly reduced the number of hours during which pain intensity prohibited daily activities (P < 0.001) and the number of analgesics (P < 0.001) after 3 months. Conventional low-dose EPT administered in a combined continuous regimen was confirmed to have a mild, but negative, effect on the course of migraine without aura by increasing the number of days with head pain (P < 0.001) and the number of analgesics (P < 0.001). Interestingly, both treatments were effective in the management of episodic tension-type headache, significantly reducing the number of days with head pain, severity, and analgesic consumption. Conclusions: In postmenopausal headache sufferers, analgesics are more effective in alleviating severe head pain when women are treated with T in comparison with low-dose EPT for climacteric complaints.


2006 - Effect of L-arginine on blood pressure in pregnancy-induced hypertension: A randomized placebo-controlled trial [Articolo su rivista]
Neri, Isabella; Jasonni, Valerio; Gori, Gf; Blasi, I; Facchinetti, Fabio
abstract

Objective. To evaluate the antihypertensive efficacy of L-arginine (L-Arg) repeated infusions in women affected by gestational hypertension. Methods. The women were referred to obstetric units in order to assess their clinical conditions and to exclude the presence of severe fetal and/or maternal complications. Inclusion criteria were: maternal age range 16 - 45 years, diagnosis of gestational hypertension without proteinuria ( patients normotensive until the 20th week), and gestational age ranging between 24 and 36 weeks. Each woman was allocated to receive either L-arginine ( 20 g/500 mL) or placebo treatment through an i.v. line. The infusion was carried out in the morning from 8 a. m. to 10 a. m. and it was repeated for the next four consecutive days. Systolic and diastolic blood pressure values as well as heart rate were recorded with the patient in an upright, seated position at 08: 00, 12: 00, 16: 00 and 20: 00 h. Results. Maternal clinical features such as age, height, weight, and gestational age at inclusion were similar between groups. Both systolic and diastolic blood pressures were reduced by treatment, the effect of L-arginine being significantly higher than that of the placebo ( systolic values F = 8.59, p<0.005; diastolic values F = 3.36; p<0.001). Twenty women assigned to the L-Arg group (32.2%) and 23 to the placebo group (37.7%) were concomitantly treated with antihypertensives before starting the study. Analyzing the subgroup of patients not receiving antihypertensive drugs we found that L-arginine was superior to placebo in lowering systolic ( F = 5.42, p<0.005) and diastolic ( F = 2.20, p<0.005) blood pressure values. Conclusions. In conclusion, these data support the use of L-Arg as an antihypertensive agent for gestational hypertension especially in view of the other beneficial effects nitric oxide donors display in pregnancy. Further, L-Arg seems well tolerated since in this sample none of the patients reported adverse effects requiring study interruption.


2006 - Effects of L-arginine infusion on vascular reactivity and nitric oxide metabolites production in normotensive and preeclamtic women. [Abstract in Rivista]
De Pace, V; Neri, Isabella; Volpe, Annibale; Facchinetti, Fabio
abstract

..


2006 - Evidence that natural benzodiazepine-like compounds increase during spontaneous labour [Articolo su rivista]
Facchinetti, Fabio; Avallone, Rossella; Modugno, Giuseppe; Baraldi, Mario
abstract

Natural benzodiazepine-like compounds (NBDZ) are present in the blood of normal people free of commercial benzodiazepine medication. In this work, we evaluated the Levels of NBDZ in maternal/foetal serum during delivery after spontaneous tabour (VD) or caesarean section (CS). For both the VD (n=11) and the CS (n=11) groups (VD+CS=22), three blood samples were collected at three different times: the first was collected three days before tabour, the second immediately after delivery or at fetal abdominal extraction and the third one was obtained at second day post-partum. NBDZ were measured by radioreceptor binding assay after HPLC extraction and purification white cortisol was measured through radioimmunoassay. In the VD group, a significant increase of NBDZ levels occurred at tabour in comparison with the levels found in pre- and post-partum periods. By the contrary, no differences in NBDZ Levels were found in the CS group at the three different times. The levels of cortisol in the VD group were found to be higher at tabour than that determined at pre- and post-partum. Again no significant changes were found in the CS group. These findings suggest for the first time that tabour is associated with a marked increase of NBDZ which could be envisaged as a stress-retated event.


2006 - Hyperemesis gravidarum complicated by Wernicke encephalopathy: Background, case report, and review of the literature [Articolo su rivista]
Chiossi, G; Neri, Isabella; Cavazzuti, Milena; Basso, G; Facchinetti, Fabio
abstract

Wernicke encephalopathy (WE) is a rare but known complication of severe hyperemesis gravidarum caused by thiamine deficiency. This article presents an unusual case that occurred at our institution and reviews the 48 previously published cases of WE in pregnancy. Considering all the 49 cases, the mean (standard deviation) patients' age was 26.7 +/- 4.9 years, the mean gestational age when WE manifested was 14.3 +/- 3.4 weeks, and the mean duration of vomiting and feeding difficulties was 7.7 +/- 2.8 weeks. Wernicke's classic triad (confusion, ocular abnormalities, and ataxia) manifested in only 46.9% (23 of 49) of the patients. Confusion affected 63.3% (31 of 49) of the patients, ocular signs 95.9% (47 of 49) and symptoms 57.1% (28 of 49), and ataxia 81.6% (40 of 49). Deterioration of consciousness affected 53.1% (26 of 49) of the subjects and memory impairment 61.2% (30 of 49). Complete remission of the disease occurred in only 14 of 49 cases. Symptom resolution required months and permanent impairments were common. The overall pregnancy loss rate, directly (spontaneous fetal loss) and indirectly (planned abortion) attributable to WE, was 47.9% (23 of 49). The diagnosis of WE is clinical and can be rapidly confirmed by magnetic resonance imaging. We emphasize the importance of thiamine supplementation to women with prolonged vomiting in pregnancy, especially before intravenous or parenteral nutrition. We also underline the necessity to promptly replace vitamin B1 when neurologic symptoms and/or signs develop in a patient with hyperemesis gravidarum.


2006 - Induction of labor at term using isosorbide mononitrate simultaneously with dinoprostone compared to dinoprostone treatment alone: A randomized, controlled trial [Articolo su rivista]
Wolfler, M. M.; Facchinetti, Fabio; P., Venturini; A., Huber; H., Helmer; P., Husslein; W., Tschugguel
abstract

Objective: We aimed to determine whether isosorbide mononitrate (IMN) given simultaneously with dinoprostone in term pregnancies is superior to dinoprostone alone to promote delivery. Study design: One hundred and twenty nulliparous women at term were randomly assigned to receive per vaginam IMN 40 mg or placebo in addition to 3 mg dinoprostone 2 times daily for up to 2 days. Analysis was by intention to treat. Results: Baseline characteristics of both groups were comparable. The induction to delivery intervals did not differ between the IMN and the placebo group (26.4 +/- 14.4 vs 23.4 +/- 14.8 hours, P = .408). IMN resulted in more headache compared to placebo (32/55 [58.2%] vs 2/55 [3.6%], P < .001). Conclusion: Vaginally administered IMN does not play a role in promoting delivery in term pregnancy if given at the same time as dinoprostone. This might reflect its relaxant effect on the uterine fundus, which may overcome its cervical softening effect. (c) 2006 Mosby, Inc. All rights reserved.


2006 - Integratori e fitoterapici le evidenze in ostetricia e ginecologia [Curatela]
Facchinetti, Fabio; V., Unfer
abstract

Integratori e fitoterapici le evidenze in ostetricia e ginecologia


2006 - The computerized fetal heart rate analysis in post-term pregnancy identifies patients at risk for fetal distress in labour [Articolo su rivista]
Valensise, H; Facchinetti, Fabio; Vasapollo, B; Giannini, F; Di Monte, I; Arduini, D.
abstract

Objective: To ascertain the diagnostic ability of a computerized fetal heart rate (FHR) analysis system in the identification of patients at risk of fetal distress in labour. Study design: Three hundred and two healthy post-term pregnancies were enrolled in a retrospective, cross-sectional study and subdivided into two groups, with (n = 42) or without (n = 260) fetal distress in tabour. The last computerized FHR recording before onset of labour was analyzed. Results: The two groups showed a significant difference only in FHR baseline and in percentage of small accelerations on total. The multivariate analysis showed that only the percentage of small accelerations was significantly related to the labour outcome. A higher diagnostic accuracy was obtained with use of neural network analysis, which allowed a sensitivity of 56%, specificity 91%, positive predictive value 53% and negative predictive value 92% with an overall accuracy of 86%. Conclusions: The increase in FHR baseline and in small FHR accelerations can be major factors in the prediction of subsequent fetal distress in healthy term fetuses. Use of neural networks seems to further improve the ability of computerized FHR analysis in the prediction of intrapartum distress.


2006 - Uterine vascularization and pregnancy outcome in patients undergoing intracytoplasmatic sperm injection: The role of nitric oxide [Articolo su rivista]
Battaglia, C; Persico, N; Mancini, F; De Iaco, P; Busacchi, P; Facchinetti, Fabio; de Aloysio, D.
abstract

Purpose: To evaluate whether, after pituitary desensitisation, the impedance to flow in the uterine vessels may be an indicator of an ICSI programme outcome, and to test the relationship between intrafollicular nitric oxide and oocyte/embryo quality. Methods: Thirty-eight women, on the basis of impedance to flow at the level of uterine artery, evaluated on the first day of COH, were divided in patients with normal (Pulsatility Index-PI, <= 2.5; Group I, n=11) and elevated (PI > 2.5; Group II, n=27) PI values. The patients were submitted to hormonal, ultrasonographic and Doppler evaluations. Plasma and follicular fluid concentrations of nitrites/nitrate (NO2-/NO3-) were assayed. Results: In the Group I, the impedance to flow remained lower than in Group II and was associated to good quality embryos and to a higher pregnancy rate. Follicular fluid NO2-/NO3- levels were inversely correlated with the embryo quality. The uterine artery PI and the pregnancy rate were inversely correlated. The PIs analysed on the day 1 of stimulation, were positively correlated with those registered on day 8 and on the day of ovum pick-up. Conclusions: A Doppler analysis done on day 1 of controlled ovarian hyperstimulation may be an useful indicator of ART outcome.


2006 - 17 alpha hydroxy-progesterone caproate (17P) treatment reduces cervical shortening inhibiting cervical interleukin-1 secretion [Abstract in Atti di Convegno]
Facchinetti, Fabio; Paganelli, S; Venturini, P; Dante, G.
abstract

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2005 - Acupuncture versus pharmacological approach to reduce Hyperemesis gravidarum discomfort. [Articolo su rivista]
Neri, Isabella; G., Allais; P., Schiapparelli; I., Blasi; C., Benedetto; Facchinetti, Fabio
abstract

Several reports have suggested the use of acupuncture as a useful treatment for hyperemesis gravidarum (HG), in particular the effects on nausea intensity was underlined. The aim of this study was to compare the efficacy of acupuncture sessions plus acupressure with a metoclopramide/vitamin B12 treatment.In this study we randomized 88 pregnant patients suffering from HG to receive either acupuncture sessions plus acupressure (acupuncture group) or metoclopramide infusion (metoclopramide group) supplemented by vitamin B12 complex. Somatic symptoms and the ability to achieve the daily routine activity (functioning) were evaluated. Acupuncture sessions were performed at the hospital twice a week for 2 weeks according to the traditional Chinese medicine criteria. Acupression was applied for 6-8 h/day. In the metoclopramide group, patients received at hospital metoclopramide infusion (20 mg/500 mL saline for 60 min) twice a week for 2 weeks. An oral supplementation with vitamin B12 complex (30 mg/day) was also prescribed.Both treatments reduced vomiting episodes and then nausea intensity with a consequent improvement in the rate of food intake. The effect of acupuncture seems to be progressive, increasing at the end of treatment whereas pharmacological approach has a prompt effect in responders remaining stable thereafter. Moreover, acupuncture was significantly more effective than drugs in improving functioning.In our study for the first time acupuncture, applied accordingly to Chinese formula, was compared to drugs demonstrating the same effect of both treatments on HG symptoms. Interestingly, functioning was significantly improved just by acupuncture. Even if the effect of acupuncture on HG discomfort remains to be confirmed, the reports on the effect of acupuncture on psychosocial variables could represent a further advantage of acupuncture application and provide an incentive to widen the base of the research.


2005 - Changes in the cervical competence in preterm labour [Articolo su rivista]
Facchinetti, Fabio; P., Venturini; I., Blasi; L., Giannella
abstract

Cervical competence is a key function in normal and abnormal labour. Remodelling of the cervical structure, by reorientation and changes in the integrity of collagen fibres by an alteration in the content of water, proteoglycans and hyaluronic acid, takes place before parturition. Such morphological changes have been associated with the activation of several biochemical pathways, sharing those of an apyretic, proinflammatory reaction, including the inducible isoform of the nitric oxide synthase (NOS). Nitric oxide (NO) is believed to be the final mediator in the mechanisms that allow ripening of the cervix. A reduction of NO activity in the uterus, together with its activation in the cervix, is hypothesised to be a facilitating factor in human parturition. The local application of NO donors in both animals and humans induces ultrastructural changes similar to those occurring during physiological cervical maturation. NO donors have proven to be clinically effective in facilitating first trimester dilation and curettage. Preliminary data also suggest that in women presenting with threatening preterm labour, there is increased activity of NO in the cervix, which is associated with shortening. A complex interaction between cytokines, prostaglandins (PGs) and NO is the key biochemical pathway accounting for the preterm ripening of the cervix.


2005 - Clinical applications of nimesulide in pain, arthritic conditions and fever [Capitolo/Saggio]
Bianchi, M.; Ehrlich, G. E.; Facchinetti, F.; Huskisson, E. C.; Jenoure, P.; La Marca, A.; Rainsford, K. D.
abstract

Conclusions: In comparison with conventional NSAIDs (with COX-1 as well as COX-2 inhibitory effects) and the coxibs, nimesulide has been shown in a large number of studies to be equivalent to, or in some cases more effective in relieving pain and inflammatory signs and symptoms. Recent evidence suggesting that nimesulide may have fast onset of action in acute pain may be an advantage for the drug in certain clinical situations. Nimesulide has proven to be an effective drug in comparison with other NSAIDs including the coxibs.


2005 - Comparison of two preparations of dinoprostone for pre-induction of labour in iparous women with very unfavourable cervical condition: a randomised clinical trial [Articolo su rivista]
Facchinetti, Fabio; P., Venturini; G., Verocchi; Volpe, Annibale
abstract

The aim of this study was to compare the clinical effects of preinduction cervical ripening by using two ways of dinoprostone administration. In a prospective, open-label trial, 144 consecutive nulliparous women with a Bishop score < 4 who required induction of labour at term were randomised to receive dinoprostone via either a vaginal insert (10 mg over 12 h)or a cervical gel(0.5 mg, twice in 12h). If labour did not start by 24 h after this preinduction, patients received 2 mg vaginal dinoprostone gel followed 6 h later by oxytocin infusion. The main outcome measure was the rate of caesarean sections (CS). Secondary measures were: changes in Bishop score at 6 h and 12 h, delivery within 12 h and 24 h, need for oxytocin for induction, failure of induction (delivery after > 48 h), need for pharmacological interventions to manage tachysystole/hyperstimulation, length of stay in hospital. The CS rate was lower in the vaginal insert group (22.9%) than in the cervical gel group (34.3%), though the difference did not reach statistical significant difference (P = 0.13). The indications for CS overlapped between the groups. The rate of vaginal delivery within 12 It and 24 h was similar, as was the rate of failure of induction. More women in the gel group (41.4% versus 24.3%) required the use of oxytocin (OR = 2.21: 95% CI = 1.07-4.55). Tachysystole or hyperstimulation in the vaginal insert group (7) was twice that with cervical gel (4). Four women in the vaginal insert group and three in the cervical gel group reported infectious complications. A long stay in hospital (> 4 days) was less frequent with vaginal inserts (21.4 versus 38.6%; OR = 0.43, 95% CI = 0. 19-0.97). The more challenging preinductions of labour at term are associated with increased obstetric interventions such as a high CS rate and a more frequent requirement for oxytocin inductions. In terms of success and failure, vaginal inserts releasing dinoprostone do not differ from dinoprostone given by the traditional cervical route. However, the use of vaginal inserts reduces the need for obstetric interventions and allows shorter periods in hospital.


2005 - Diclofenac pyrrolidine versus Ketoprofen for the relief of pain from episiotomy: A randomized controlled trial [Articolo su rivista]
Facchinetti, Fabio; Casini, Ml; Costabile, L; Malavasi, B; Unfer, V.
abstract

Background. The treatment of pain from episiotomy or from tearing of perineal tissues during childbirth is often unapplied, although discomfort may be severe. We performed a randomized double-blind controlled trial to compare the effectiveness and side-effects of two analgesics in the management of postpartum perineal pain. Patient preference toward the two medications was also analyzed. Methods. A total of 261 women were randomly assigned to receive either Diclofenac hydroxyethyl pyrrolidine (100 mg) (n = 133) or Ketoprofen (100 mg) (n = 128), both given orally every 12 hr up to 48 hr, as necessary. Inclusion criteria were vaginal birth with episiotomy and/or a second- to third-degree tear. Pain ratings were recorded before the administration of the drugs and at 1, 4, 12, and 24 hr after the first dose, according to a 10-cm visual-analog scale. Side-effects and overall opinion on the two treatments were assessed at 24 hr. Results. Diclofenac hydroxyethyl pyrrolidine and Ketoprofen had similar analgesic properties in the first 24 hr postpartum [mean pain rating 3.1 +/- 1.8 and 3.4 +/- 2.0, mean number of doses in 24 hr 1.4 +/- 1.4 and 1.3 +/- 1.5, and proportion of treatment failures 12.8% (17/133) and 16.4% (21/128), respectively]. Significantly fewer subjects in the Diclofenac hydroxyethyl pyrrolidine group than in the Ketoprofen group experienced side-effects (6.8% versus 15.6%; p = 0.038) with an odd risk = 0.39(95% C.I. 0.16-0.95). There were no significant differences in overall patient satisfaction between the two groups. Conclusions. No main differences were found concerning the relief of pain between the two treatments. Diclofenac hydroxyethyl pyrrolidine may be the preferred choice because it is associated with less adverse reactions, together with a faster action in the relief of pain.


2005 - Efficacy of Cimicifuga bRacemosa on climacteric complaints: a randomised study versus low-dose transdermal estradiol [Articolo su rivista]
Nappi, Re; Malavasi, B; Brundu, B; Facchinetti, Fabio
abstract

OBJECTIVE: To investigate, in a randomized clinical study, the efficacy of an isopropanolic aqueous extract of Cimicifuga racemosa (CR) on climacteric complaints in comparison with low-dose transdermal estradiol (TTSE2). Hormonal parameters, lipid profile and endometrial thickness were also evaluated. METHODS: Sixty-four postmenopausal women were enrolled and over the course of 3 months filled in a diary recording the number of hot flushes per day. Other climacteric symptoms (vasomotor and urogenital symptoms) as well as anxiety and depression, were evaluated at baseline and after 3 months. Gonadotropins (follicle-stimulating hormone (FSH), luetinizing hormone (LH)), prolactin (PRL), 17 beta-estradiol (17beta-E2) and cortisol, lipid profile (total cholesterol high-density lipoprotein (HDL)/low-density lipoprotein (LDL)-cholesterol, triglycerides, liver function (glutamic-oxalacetic transaminase, glutamic-pyruvic transaminase) and endometrial thickness were measured. Patients were randomly allocated to receive, for 3 months, either 40 mg isopropanolic aqueous CR extract daily or 25 microg TTSE2 every 7 days plus dihydrogesterone 10 mg/day for the last 12 days of the 3-month estradiol treatment. RESULTS: Both CR and low-dose TTSE2 significantly reduced the number of hot flushes per day (p < 0.001) and vasomotor symptoms (p < 0.001), starting at the first month of treatment. Such a positive effect was maintained throughout the 3 months of observation, without any significant difference between the two treatments. An identical effect was evident also for both anxiety (p < 0.001) and depression (p < 0.001) which were significantly reduced following 3 months of both CR and low-dose TTSE2. Total cholesterol was unchanged by CR treatment but significantly (p < 0.033) reduced by 3 months of low-dose TTSE2. A slight but significant increase of HDL-cholesterol (p < 0.04) was found only in women treated with CR, while LDL-cholesterol levels were significantly lowered by 3 months of both CR (p < 0.003) and low dose TTSE2 (p < 0.002). Triglycerides were not affected by both treatments, nor was liver function. FSH, LH and cortisol were not significantly affected after the 3-month treatment, while PRL (p < 0.005) and 17 beta-E2 (p < 0.001) were increased slightly only by low-dose TTSE2. Endometrial thickness was not affected by either CR or low-dose TTSE2. CONCLUSIONS: CR (40 mg/day) may be a valid alternative to low-dose TTSE2 in the management of climacteric complaints in those women who cannot be treated with or just refuse conventional strategies.


2005 - Efficacy of Cimicifuga racemosa on climacteric complaints: A randomized study versus low-dose transdermal estradiol [Articolo su rivista]
Nappi, Re; Malavasi, B; Brundu, B; Facchinetti, Fabio
abstract

Objective To investigate, in a randomized clinical study, the efficacy of an isopropanolic aqueous extract of Cimicifuga racemosa (CR) on climacteric complaints in comparison with low-dose transdermal estradiol (TTSE2). Hormonal parameters, lipid profile and endometrial thickness were also evaluated. Methods Sixty-four postmenopausal women were enrolled and over the course of 3 months filled in a diary recording the number of hot flushes per day. Other climacteric symptoms (vasomotor and urogenital symptoms) as well as anxiety and depression, were evaluated at baseline and after 3 months. Gonadotropins (follicle-stimulating hormone (FSH), luetinizing hormone (LH)), prolactin (PRL), 17 beta-estradiol (17 beta-E-2) and cortisol, lipid profile (total cholesterol high-density lipoprotein (HDL)/low-density lipoprotein (LDL)-cholesterol, triglycerides, liver function (glutamic-oxalacetic transaminase, glutamic-pyruvic transaminase) and endometrial thickness were measured. Patients were randomly allocated to receive, for 3 months, either 40 mg isopropanolic aqueous CR extract daily or 25 mu g TTSE2 every 7 days plus dihydrogesterone 10 mg/day for the last 12 days of the 3-month estradiol treatment. Results Both CR and low-dose TTSE2 significantly reduced the number of hot flushes per day (p < 0.001) and vasomotor symptoms (p < 0.001), starting at the first month of treatment. Such a positive effect was maintained throughout the 3 months of observation, without any significant difference between the two treatments. An identical effect was evident also for both anxiety (p < 0.001) and depression (p < 0.001) which were significantly reduced following 3 months of both CR and low-dose TTSE2. Total cholesterol was unchanged by CR treatment but significantly (p < 0.033) reduced by 3 months of low-dose TTSE2. A slight but significant increase of HDL-cholesterol (p < 0.04) was found only in women treated with CR, while LDL-cholesterol levels were significantly lowered by 3 months of both CR (p < 0.003) and low dose TTSE2 (p < 0.002). Triglycerides were not affected by both treatments, nor was liver function. FSH, LH and cortisol were not significantly affected after the 3-month treatment, while PRL (p < 0.005) and 17-beta E-2 (p < 0.001) were increased slightly only by low-dose TTSE2. Endometrial thickness was not affected by either CR or low-dose TTSE2. Conclusions CR (40 mg/day) may be a valid alternative to low-dose TTSE2 in the management of climacteric complaints in those women who cannot be treated with or just refuse conventional strategies.


2005 - Fetal safety of utero-vaginal sodium nitroprusside application in sheep [Abstract in Rivista]
Blasi, I; Richardson, B; Matushewski, B; Hemstreet, S; Facchinetti, Fabio
abstract

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2005 - Headache is a risk factor for the onset of hypertension in pregnancy [Abstract in Rivista]
Facchinetti, Fabio; Nappi, Re; Marozio, L; D'Amico, Roberto; Bertozzi, L; Enrietti, M; Ornati, A; Allais, G; Benedetto, C.
abstract

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2005 - Induction of labour in women with oligohydramnios [Articolo su rivista]
P., Venturini; G., Contu; V., Mazza; Facchinetti, Fabio
abstract

Objective. To prospectively evaluate the outcome of labor induction in women with oligohydramnios at term. Methods. This was a prospective case-control study which included 120 consecutive patients with Amniotic Fluid Index (AFI) <= 5 undergoing labor induction. One hundred and sixteen patients with normal amniotic fluid matched for gestational age (+/- 3 days) and Bishop-score served as controls. Inclusion criteria were: requirement of labor induction, singleton pregnancy, nulliparity, Bishop score <5, gestational age >= 266. Preinduction treatment included the use of up to 3 successive doses of dinoprostone intracervical gel (0.5 mg). Vaginal dinoprostone (2 mg) and/or oxytocin were then applied to induction labor, if necessary. Results. The rate of cesarean section in AFI <= 5 group (38.3%) was not significantly different to that in control group (34.2%). The interval from induction to vaginal delivery was not significantly different for AFI <= 5 group (1499 +/- 895 min.) and control group (1398 +/- 852 min.). The changes in Bishop score evaluated at 6th and 12th hour after dinoprostone were not significantly different in control and AFI <= 5 group. More women in the latter group (11.7% vs 3.3%, Chi Square: 4.86, p=0.027) required the use of drugs in order to manage tachysystole/hyperstimulation allowing a OR=3.83 (95% C.I.=1.13-14.27). The length of stay at hospital was 4.2 +/- 1.8 days for AFI 45 group and 4.3 +/- 1.3 for control group. Conclusions. Oligohydranmios at term did not influence the outcome of induction of labour in nulliparous women with unfavorable cervix.


2005 - Labor induction using isosorbide mononitrate in addition to prostaglandins compared to prostaglandin alone: A double-blind, randomized, placebo-controlled multicenter trial. [Abstract in Rivista]
Wolfler, Mm; Facchinetti, Fabio; Huber, A; Helmer, H; Tschugguel, W.
abstract

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2005 - Neonatal Group B streptococcal infection in a North Italian area [Articolo su rivista]
Berardi, A; Lugli, L; Rossi, K; Tridapalli, E; Roversi, Mf; Facchinetti, Fabio; Ferrari, Fabrizio; Emilia Romagan GBS Prevention Working, Group
abstract

Background Group B streptococcus (GBS) is the leading cause of early-onset infections (EOI) in the developed world. Few data are available in Europe about incidence and clinical findings of neonatal disease. We reviewed cases occurred in the last 2 years in Emilia-Romagna (an area with about 4 500 000 million people).Methods Neonatal, pediatric departments and laboratories fulfilled a chart for any case of disease observed during 2003 and 2004. GBS was recovered in blood or cerebrospinal fluid (CSF). Prenatal screening, risk factors, intrapartum chemoprophylaxis (IAP) and clinical findings were analysed.Results: We observed 21 EOI and 13 late onset (LOI). Incidence was 0.56 and 0.38/1.000 live birth in 2003 and 2004 respectively. Mortality was 12,5% (1 EOI and 3 LOI). Among 21 EOI, 7 were bacteraemia, 12 sepsis and 2 meningitis. CSF was not collected in 8/14 symptomatic infants. Six mothers were vaginally colonized; 13/21 were negative and 2 unscreened; 5/21 had one or more risk factors. Only 2 (suspected chorioamnionitis) received a complete IAP, while 19/21 were untreated. Among 13 LOI, 3/13 mothers were colonized and 5/13 had 1 or more risk factors. LOI were: 5 sepsis, 7 meningitis and 1 focal infection. CSF was not collected in 5/13.Conclusion: Incidence of GBS infection was similar to that currently reported in US. Most EOI (90.5%) had no prophylaxis. Risk factors were detected in 23.8 % of EOI (GBS bacteriuria was not routinely screened). Meningitis was diagnosed in 33.3 % symptomatic infants, but CSF analysis was not performed in 48.1% cases. More efforts are needed to improve prophylaxis strategies.


2005 - Polyunsaturated fatty acids and risk of preterm delivery [Articolo su rivista]
Facchinetti, F.; Fazzio, M.; Venturini, P.
abstract

Preterm delivery (PD) is characterized both by increased neonatal morbidity and mortality and by important late pathologic sequelae. From a clinical stand-point, PD may results from a medical condition where the continuation of pregnancy could bring about a marked risk for the foetus and/or for the mother, or from an adverse event where the pregnancy is going to end spontaneously before 37 weeks of gestation. In the past few years some epidemiological studies have shown that diet may interfere with complex multifactorial processes contributing to the preterm triggering of labour. The attention has been focused on polyunsaturated fatty acids (PUFA) such as alpha-linoleic acid, precursor of Omega-3 series, and linoleic acid, precursor Omega-6 series. Their importance in modulating Prostaglandin concentrations at different levels is already known. Moreover, it has been reported that in clinical situation, such as PD, the endogenous levels of PUFA are unbalanced, with a Omega-6 predominance. Experimental, observational and clinical studies suggest that dietary intake of Omega-3 fatty acids is capable of significantly prolonging the duration of gestation in the range of 4-7 days; such prolongation would possibly occur through the inhibition of prostaglandins E2 and F2 alpha. In Western population dietary intake of Omega-3 appears to be marginal, and recommended assumption could be reached only by a ten-fold increase in blue fish ingestion. The recommended intake of EPA + DHA should be 1.4 g/daily with a 1:2.5 EPA:DHA. It is therefore possible to conclude that in light of controlled clinical studies and of the actual categories of risk for preterm delivery, the dietary supplementation of Omega-3, in addition to other pharmacological measures (17α-hydroxyprogesterone caproate), could be implemented for the secondary and/or tertiary prophylaxis of preterm delivery.


2005 - Potential effects of nutrients on placental function and fetal growth [Relazione in Atti di Convegno]
Di Renzo, G C; Clerici, G; Neri, I; Facchinetti, F; Caserta, G; Alberti, A
abstract


2005 - Second trimester abortion using isosorbide mononitrate in addition to gemeprost compared with gemeprost alone: A double-blind randomized, placebo-controlled multicenter trial [Articolo su rivista]
W., Eppel; Facchinetti, Fabio; E., Schleussner; F., Piccinini; C., Pizzi; Dm, Gruber; B., Schneider; W., Tschugguel
abstract

Objective: We aimed to determine whether second-trimester abortion using isosorbide mononitrate (IMN) in addition to gemeprost is more effective and reduces side effects compared with gerneprost alone. Study design: Eighty women who were age 13 to 23 weeks´ gestation were randomly assigned to receive per vaginam either IMN 40 mg (group 1, 40 women) or placebo (group 2, 40 women) in addition to Gemeprost I mg up to 3 times daily 3 hours apart for 2 days. Analysis of variance, a chi 2 test, and a multivariate analysis were performed. Results: Of the 72 women analyzed, 68% (group 1) and 38% (group 2) underwent abortion within day 1 (P < .05). However, group 1 was associated with more headache (18% of women) 3 hours after induction compared to group 2 (0% of women, P = .038). Conclusion: IMN in addition to gemeprost is effective for second-trimester abortion, but is associated with more headache compared with gemeprost alone.


2005 - The relationship between headache and preeclampsia: a case-control study [Articolo su rivista]
Facchinetti, Fabio; G., Allais; D'Amico, Roberto; C., Benedetto; Volpe, Annibale
abstract

OBJECTIVES: Pregnancy-induced hypertension with proteinuria (preeclampsia-PE) is linked to increased vascular reactivity, increased vasoconstrictors, endothelial damage and platelet hyperaggregation, which are also typical features of migraine patients. Thus, we investigated the association between headache and PE. METHODS: In a case-control study, we evaluated the occurrence of primary headache forms in 75 women with a recent history of PE. Seventy-five controls were selected from women having uneventful pregnancy at term. Both groups were matched for age and parity. Subjects' headache history was evaluated by using an ad hoc structured questionnaire. The International Headache Society criteria for primary headaches were applied to diagnose the specific form of headache. RESULTS: In PE cases, gestational age at parturition was 34.2+/-3.8 weeks and birthweight was 1820+/-746 g, whereas in controls they were 39.3+/-1.5 weeks and 3365+/-437 g, respectively (P < 0.01). Sixty-six (44%) subjects suffered from headache. Headache was significantly more frequent in PE (47/75) than in controls (19/75), OR 4.95 (95% CI, 2.47-9.92). Migraine without aura was more frequently present in cases than in controls while episodic tension-type headache was equally distributed among groups. Fifty-two patients met the criteria of severe PE. The number of patients suffering from headache was significantly higher in severe patients (39 cases, 75%) than in those with moderate PE (8 cases, 34.8%), OR = 5.63 (95% CI, 1.97-16.03). With respect to controls, PE patients reported a more frequent onset at menarche, more menstrually related attacks and an increased rate of improvement during pregnancy. CONCLUSION: This study shows that there is a strong association between migraine history and PE development, namely with the severe form of PE.


2005 - Thrombophilia is significantly associated with severe preeclampsia - Results of a large-scale, case-controlled study [Articolo su rivista]
G., Mello; E., Parretti; L., Marozio; C., Pizzi; A., Lojacono; T., Frusca; Facchinetti, Fabio; C., Benedetto
abstract

The role of thrombophilia in the pathogenesis of preeclampsia is controversial. The aim of this case-controlled study was to determine whether thrombophilia increases the risk of preeclampsia or interferes with its clinical course. A total of 808 white patients who developed preeclampsia (cases) and 808 women with previous uneventful pregnancies (controls) matched for age and parity were evaluated for inherited and acquired thrombophilia ( factor V Leiden; factor II G20210A; methylenetetrahydrofolate reductase C677T; protein S, protein C, and antithrombin III deficiency; anticardiolipin antibodies; lupus anticoagulant; and hyperhomocysteinemia). Odds ratios (ORs) with 95% confidence intervals (CIs) for risk of being carriers of thrombophilia in cases compared with controls and for risk of maternal life-threatening complications and adverse perinatal outcomes in preeclamptic patients with or without thrombophilia were calculated. Women with severe preeclampsia (406 cases) had a higher risk (OR, 4.9; 95% CI, 3.5 to 6.9) of being carriers of either an inherited or acquired thrombophilic factor, except for protein S, protein C, and antithrombin deficiency. In women with mild preeclampsia (402 cases), only prothrombin and homozygous methylenetetrahydrofolate reductase gene mutations were significantly more prevalent than in the controls. Thrombophilic patients with severe preeclampsia are at increased risk of acute renal failure (OR, 1.8; 95% CI, 1.5 to 2.2), disseminated intravascular coagulation (OR, 2.7; 95% CI, 1.1 to 6.4), abruptio placentae (OR, 2.6; 95% CI, 1.2 to 6.0) and perinatal mortality (OR, 1.7; 95% CI, 1.5 to 2.2) compared with nonthrombophilic preeclamptic patients. Our study demonstrates a significant association between maternal thrombophilia and severe preeclampsia in white women. Thrombophilia also augments the risk of life-threatening maternal complications and adverse perinatal outcomes in preeclamptic patients.


2004 - A small randomised trial of low-dose aspirin in women at high risk of pre-eclampsia [Articolo su rivista]
F., Chiaffarino; F., Parazzini; D., Paladini; B., Acaia; W., Ossola; L., Marozio; Facchinetti, Fabio; A., DEL GIUDICE
abstract

Objective: To determine if aspirin (ASA) therapy reduces the incidence of pre-eclampsia in women at high risk of this condition. Study design: Randomised clinical trial. We recruited pregnant women with gestational age at randomisation < 14 weeks, who satisfied the following criteria: chronic hypertension, history of severe pre-eclampsia or eclampsia or intrauterine growth retardation (IUGR) or intrauterine foetal death. Nineteen women in the no-treatment group and 16 in the ASA group were successfully followed up. Results: The mean birthweight was higher in the ASA group than in the no-treatment group (2790 g (S.D. 340 g) versus 2616 g (S.D. 779 g)), but the difference was not statistically significant. We found no statistically significant differences between the groups in the proportion of infants with birthweight below 2500 g (13.3% versus 29.4%) and the number of cases with pregnancy-induced hypertension (PIH)/pre-eclampsia (31.3% versus 36.8%). Conclusion: These limited data give some support to the potential favourable effect of early treatment with ASA in pregnant women at risk of PIH and IUGR. (C) 2003 Elsevier Ireland Ltd. All rights reserved.


2004 - Acupuncture plus moxibustion to resolve breech presentation: a randomized controlled study [Articolo su rivista]
Neri, Isabella; Airola, G.; Contu, G.; Allais, G.; Facchinetti, Fabio; Benedetto, C.
abstract

OBJECTIVE: In many Western countries breech presentation is an indication for elective Cesarean section. In order to correct fetal presentation, the stimulation of the acupoint BL67 by moxibustion, acupuncture or both has been proposed. Since no studies had previously been carried out on Western populations, pregnant Italian women at 33-35 weeks gestational age carrying a fetus in breech presentation were enrolled in a randomized, controlled trial involving an active BL67 point stimulation and an observation group. METHODS: A total of 240 women at 33-35 weeks of gestation carrying a fetus in breech presentation were randomized to receive active treatment (acupuncture plus moxibustion) or to be assigned to the observation group. Bilateral acupuncture plus moxibustion was applied at the BL67 acupoint (Zhiyin). The primary outcome of the study was fetal presentation at delivery. RESULTS: Fourteen cases dropped out. The final analysis was thus made on 226 cases, 114 randomized to observation and 112 to acupuncture plus moxibustion. At delivery, the proportion of cephalic version was lower in the observation group (36.7%) than in the active-treatment group (53.6 %) (p = 0.01). Hence, the proportion of Cesarean sections indicated for breech presentation was significantly lower in the treatment group than in the observation group (52.3% vs. 66.7%, p = 0.03). CONCLUSIONS: Acupuncture plus moxibustion is more effective than observation in revolving fetuses in breech presentation. Such a method appears to be a valid option for women willing to experience a natural birth


2004 - Characteristics of menstrual and nonmenstrual attacks in women with menstrually related migraine referred to headache centres [Articolo su rivista]
F., Granella; G., Sances; G., Allais; Re, Nappi; A., Tirelli; C., Benedetto; B., Brundu; Facchinetti, Fabio; G., Nappi
abstract

Aim of this study was to determine whether menstrual attacks differ from nonmenstrual attacks (NMA) as regards clinical features or response to abortive treatment in women affected by menstrually related migraine (MRM) referred to tertiary care centres. Sixty-four women with MRM were enrolled in a 2-month diary study. Perimenstrual attacks were split into three groups - premenstrual (PMA), menstrual (MA) and late menstrual (LMA) - and compared to nonmenstrual ones. Perimenstrual attacks were significantly longer than NMA. No other migraine attack features were found to differ between the various phases of the cycle. Migraine work-related disability was significantly greater in PMA and MA than in NMA. Acute attack treatment was less effective in perimenstrual attacks. Pain-free at 2 h after dosage was achieved in 13.5% of MA (OR 0.41; 95% CI 0.22, 0.76) vs. 32.9% of NMA. We concluded that, in MRM, perimenstrual attacks are longer and less responsive to acute attack treatment than NMA.


2004 - Cognitive-behavioral treatment decreases cardiovascular and neuroendocrine reaction to stress in women waiting for assisted reproduction [Articolo su rivista]
Facchinetti, Fabio; M., Tarabusi; Volpe, Annibale
abstract

A higher cardiovascular vulnerability to stress is associated with a lower pregnancy rate during in vitro fertilization and embryo transfer (IVF-ET) program. The present study was carried out to assess whether cognitive-behavioral treatment (CBT) program attenuates autonomic and neuroendocrine response to a stressful task in infertile women waiting for IVF-ET. Forty-five consecutive couples referred to our Department for assisted reproduction were enrolled. Mean duration of infertility was 3.1 years. Two-thirds of them already failed an IVF-ET attempt. Once included in the waiting list women were administered the Stroop colorword (CW). Systolic BP, heart rate (HR) and plasma cortisol were serially measured. Subjects showing a positive HR reaction were selected to receive CBT (12 group sessions over 16 weeks) while the remnants just waited, for the same period of time (observation group). After 17-19 weeks subjects were re-submitted to the Stroop CW. The HR response to Stroop CW was significantly reduced by CBT while it remained unchanged in the observation group. Similarly, systolic BP response was reduced after CBT whereas an increase occurred in the observation group. After CBT, a significant decrease in the reaction of plasma cortisol to Stroop CW took place whereas no changes were observed in the other subjects. The present findings indicate that CBT is useful for decreasing the level of distress in patients submitted to IVF-ET treatment.


2004 - Effects of acute L-arginine infusion on non-stress test in hypertensive pregnant women [Articolo su rivista]
Neri, Isabella; Blasi, I.; Facchinetti, Fabio
abstract

OBJECTIVE: The present report evaluates the effect of acute L-arginine administration on fetal heart variables by a computerized non-stress test (NST) analysis. METHODS: Fifteen pregnant women at 30-34 weeks of gestational age affected by mild to moderate gestational hypertension were enrolled in the study. The study was performed in the second and third days of hospitalization. Each woman received both active (Arg) or placebo treatment (Placebo), in a double-blind, randomized, cross-over design. Women received saline infusion for 40 min, then they were infused with either placebo (saline infusion prepared by Damor Pharmaceutics and labeled as Arg-B) or Arg (L-Arg 20 g/500 ml labeled as Arg-A). RESULTS: Multiple analysis of variance (MANOVA) indicated that both placebo and Arg infusion were unable to affect cardiac variables and fetal movements. As far as maternal blood pressure changes were concerned, MANOVA indicated that active treatment showed an acute hypotensive effect on both systolic (F=8.98, p<0.001) and diastolic values (F=15.78, p>0.001). Conversely, placebo infusion does not seems to have induced any change. Considering each time of infusion we observed that Arg treatment was able to lower systolic and diastolic blood pressure after the 40 min of infusion, with this effect persisting for 20 min. CONCLUSIONS: These data indicate that the acute, intravenous administration of high-dose L-arginine does not induce significant changes in fetal heart rate (FHR), whereas it lowers maternal blood pressure. Such conclusions are reinforced by the observation that saline administration in the same pregnant women was neutral for both FHR and maternal blood pressure values. According to previous studies, it seems conceivable that maternal L-arginine treatment enters the fetal circulation by crossing the placenta. The lack of changes in FHR, however, suggests that no significant hemodynamic changes were induced by the treatment. Contrary to what happens in the mother, this may possibly be due to a low, if any, conversion of L-arginine to nitric oxide in the fetus.


2004 - Factor V Leiden in pregnancies complicated by placental abruption [Articolo su rivista]
FACCHINETTI, Fabio
abstract

No abstract available


2004 - Intravenous L-arginine is a new anti-hypertensive agent for pregnant women [Abstract in Rivista]
Neri, Isabella; Jasonni, Valerio; Gori, G; Blasi, I; Facchinetti, Fabio
abstract

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2004 - Nutrizione e integratori in Ostetricia e Ginecologia [Curatela]
Facchinetti, Fabio; V., Unfer
abstract

Nutrizione e integratori in Ostetricia e Ginecologia


2004 - Polyethylene glycol electrolyte solution (Isocolan) for constipation during pregnancy: An observational open-label study [Articolo su rivista]
Neri, Isabella; Blasi, I; Castro, P; Grandinetti, G; Ricchi, A; Facchinetti, Fabio
abstract

To evaluate the efficacy of a polyethylene glycol electrolyte solution (PEG-4000) in pregnant women affected by constipation, 40 consecutive pregnant women from 6 to 38 weeks' gestation were enrolled in this preliminary study. Constipation was defined as spontaneous evacuation less than four times a week or the presence of symptoms Such as defecation pain, rectal urgency, tenestmus, anal injury, or abdominal pain. A PEG-4000 solution (Isocolan, also marketed in the United States as Golitely/Nulitely) was administered for 15 days at a dose of 250 mL by mouth once or twice a day. The number of bowel movements per week, the presence or absence of liquid stools, tenesmus, urgency, defecation pain, anal lesions, and abdominal pain were evaluated before and after 15 days of treatment. Treatment with PEG-4000 significantly increased the evacuation episodes per week (from 1.66 +/- 0.48 to 3.16 +/- 1.05; P <.01), and constipation was resolved in 27 of 37 women (73%). Defecation pain, anal injury, and abdominal pain significantly improved after PEG-4000 administration. Improvement occurred in both patients with new-onset constipation during pregnancy as well as patients with a history of constipation before pregnancy. These preliminary findings that PEG-4000 may be an effective choice for the treatment of constipation during (C) 2004 by the American College of Nurse-Midwives.


2004 - Prevention of group B streptococcal infection in a North-Italian area [Articolo su rivista]
Berardi, A; Lugli, L; Rossi, K; Tridapalli, E; Facchinetti, Fabio
abstract

No abstract available


2004 - Psychological group support attenuates distress of waiting in couples scheduled for assisted reproduction [Articolo su rivista]
Tarabusi, M.; Volpe, A.; Facchinetti, F.
abstract

The aim of the study is to determine whether a cognitive-behavioral group treatment could lead to a decrease of psychological distress in couples waiting for assisted reproduction. Fifty consecutive couples included in the waiting list for IVF-ET or ICSI were randomly allocated either to receive Cognitive-Behavioral Treatment (CBT Group) or just waiting (Observation Group). The group is formed by 8-10 couples; 12 meetings are provided for a period of 4 months. Two psychometric test have been administered (Symptom Rating Test and Westbrook Coping Scales) at baseline and after 4 months. At baseline, females showed a higher level of SRT than males (F = 16.6 ± 14.1; M = 10.2 ± 9.0; p = 0.01). This became evident for anxiety (F = 5.6 ± 4.9; M = 3.3 ± 3.0, p = 0.004), somatization (F = 3.0 ± 2.5; M = 1.8 ± 2.1, p = 0.01) and feelings of inadequacy (F = 3.9 ± 3.7; M = 2.3 ± 2.7, p = 0.01). After 4 months in the males of Observation Group (from 2.3 ± 2.0 to 4.0 ± 2.8, p = 0.01) there was an increase of the level of anxiety. No other meaningful differences in other variables were found. In females of CBT Group a trend towards a significant decrease in the total value of psychological uneasiness (the SRT) (from 17.7 ± 13.7 to 14.1 ± 14.0, p = 0.07) was found. A long wait before the scheduled intervention of assisted reproduction increased anxiety levels, namely in male partners. CBT avoids such a 'waiting stress' and could be useful for stimulating discussion and awareness inside the couple. Shortening the waiting list and psychological support would be provided by infertility centres.


2004 - Stress and preterm delivery [Articolo su rivista]
Facchinetti, Fabio; F., Ottolini
abstract

No abstract available


2004 - Thrombophilia is a risk factor for severe preeclampsia and its recurrence [Abstract in Rivista]
Facchinetti, Fabio; Parretti, E; Marozio, L; Loiacono, A; Venturini, P; Benedetto, C; Frusca, T; Mello, G.
abstract

..


2003 - Elevated plasma levels of factor VIII in women with early recurrent miscarriage. [Articolo su rivista]
M., Marietta; Facchinetti, Fabio; L., Sgarbi; L., Simoni; M., Bertesi; G., Torelli; Volpe, Annibale
abstract

Inherited and acquired thrombophilia have been found to be associated with recurrent pregnancy loss. This paper examines whether or not elevated factor (F)VIII:C plasma levels, which have been demonstrated to be an independent risk factor for venous thromboembolism, are a risk factor for early recurrent miscarriages also.Consecutive women referred to our clinic with a history of early recurrent abortion (at least three pregnancy losses before week 13 of gestation) were eligible for the study. Exclusion criteria were endocrine, immunological, anatomical and genetic causes of embryo demise, as well as any thrombophilic abnormality, either congenital or acquired, or a personal or familial history of venous thromboembolism. FVIII:C plasma levels were determined in 51 cases and in 51 controls matched for age, ethnicity and blood group.The mean FVIII:C level in the control subjects was 106.8 IU dL-1, compared with 128.2 IU dL-1 in the patients group (P = 0.0002). Thirteen (25.5\%) of the 51 patients had FVIII:C values exceeding the 90th centile of the control population (145 IU dL-1), compared with four subjects in the control group (chi2 = 4.52; P = 0.033; odds ratio = 4.02, 95\% confidence interval 1.09, 16.05). No cases with increase in FVIII:C levels attributable to an acute-phase reaction, as assessed by C-reactive protein plasma concentration, were found.We found FVIII:C levels significantly higher in women with early recurrent miscarriage compared with controls. This finding suggests a possible association between this thrombophilic condition and early reproductive failures.


2003 - Embryonic production of nitric oxide and its role in implantation: a pilot study. [Articolo su rivista]
C., Battaglia; P., Ciotti; L., Notarangelo; R., Fratto; Facchinetti, Fabio; D. d., Aloysio
abstract

To investigate the ability of human embryos to produce nitric oxide (NO) and correlate its production with embryo quality and pregnancy rate.Twenty-three women participated in the study and were submitted to controlled ovarian stimulation and intracytoplasmic sperm injection. Embryos were singularly cultured in medium microdrops of 50 microL and were replaced, by transcervical transfer, at the 2- to 6-cell stage. In the culture media of each embryo the NO production was assessed by monitoring the levels of its stable oxidation products (nitrites/nitrates).All the 23 patients underwent embryo transfer. After microinjection 64 embryos were obtained. The mean number of transferred embryos was 2.61 +/- 0.46 and the pregnancy rate was 26\%. The mean nitrite/nitrate concentrations of culture medium of each embryo was significantly higher (5.88 +/- 2.34 micromol/L) than in pure P-1 medium (0.81 +/- 0.21 micromol/L; p < 0.001) demonstrating an embryonic secretion of NO. Comparing pregnant (7.34 +/- 2.72 micromol/L) versus nonpregnant patients (5.53 +/- 1.49 micromol/L; p = 0.022), the mean nitrite/nitrate concentrations were significantly higher. Furthermore, the best quality embryos of pregnant women produced significantly higher nitrite/nitrate concentrations than those of not pregnant patients.It seems that NO production in nidating embryos is increased and that it may be primarily associated with a better morphology and a better growth potential of developing embryos.


2003 - Endothelin-1 and nitric oxide levels are related to cardiovascular risk factors but are not modified by estradiol replacement in healthy postmenopausal women. A cross-sectional and a randomized cross-over study. [Articolo su rivista]
Cagnacci, Angelo; R., Tarquini; F., Perfetto; S., Arangino; A. L., Zanni; P., Cagnacci; Facchinetti, Fabio; Volpe, Annibale
abstract

To evaluate whether in healthy postmenopausal women endothelial substances such as endothelin-1 (ET-1) and nitric oxide are related to cardiovascular risk factors and can be influenced by estradiol replacement.A cross-sectional evaluation and a randomized, double-blind, placebo-controlled study with cross-over.In 20 healthy postmenopausal women it was investigated the relation of ET-1 and NOx with age, BMI, 24-h blood pressure, lipid and glucose metabolism, and coagulation parameters. In addition, in the same women, the role played by estrogens on circulating ET-1 and stable derivatives of nitric oxide (nitrite/nitrates) was investigated by administering for 2 months transdermal estradiol (50 microg/day) vs. placebo.ET-1 and NOx were inversely related to each other (r=0.458; P=0.016). Multivariate analysis of regression showed that ET-1 levels were related directly to LDL-cholesterol (r=0.585; P=0.0005) and protein C (r=0.516; P=0.0008), and inversely to insulin (r=0.488; P=0.0065). The ratio NOx/ET-1 was directly related to HDL-cholesterol (r=0.441; P=0.005). The above relations were not influenced by estradiol. Indeed, in comparison to placebo, transdermal estradiol, besides reducing nocturnal systolic (P=0.002) and diastolic (P=0.03) blood pressure, did not modify ET-1 or NOx levels, as well as, any of the parameters considered.The relation of several cardiovascular risk factors with ET-1 and NOx/ET-1 suggests a primary role for these endothelial products in the determination of the cardiovascular risk of women. The present data do not support a role for transdermal estradiol in modifying ET-1 or NOx levels of healthy postmenopausal women.


2003 - Evidence that endogenous benzdiazepine-like compounds increase during spontaneous delivery [Abstract in Atti di Convegno]
Avallone, Rossella; Modugno, Giuseppe; Facchinetti, Fabio; Baraldi, Mario
abstract

It has been established that endogenous benzodiazepines (EBDZ) play a role in the pathogenesis of different pathologies like hepatic encephalopathy or idiopathic recurring stupor(1-2). Evidences have not been provided about the role of EBDZ during pregnancy and delivery. In this work we evaluated a possible changes of EBDZ in maternal/foetal serum during delivery after spontaneous labour (VD) or caesarean section (CS). For both VD and CS groups (n=24) 3 blood samples were collected at 3 different times: the first was collected at least 3 days before labour and delivery, the second was collected at the moment of the delivery or at foetal abdominal extraction; the third sample was obtained at 2nd day post-partum. Determination of EBDZ was performed as already described (1) and cortisol was measured through commercially available radioimmunoassay kit. For the statistical analysis of EBDZ Wilcoxon test was used for within-subjects comparison and Mann-Whitney tests for between subjects comparison. For the statistical analysis of cortisol levels the analysis of variance and paired t-test was used. In the VD group a significant increase of EBDZ occurred at delivery respect with both baseline (P=0.008) and postpartum (P=0.028) values. Interestingly in CS group were found no differences in the 3 different analysed samples. The cortisol levels in VD group at delivery (560 ± 156 ng/ml) were found to be higher than that at baseline (252 ± 93, t= 5.47, P<0.0001) and post-partum (241 ± 44, t=6.11, P<0.0001) while in CS group no significant changes were found. These findings demonstrated for the first time that parturition is associated with a marked increase of EBDZ which could be attributed to stress present at delivery time.


2003 - Increased migraine prevalence in women with history of PreEclampsia (PE) [Abstract in Atti di Convegno]
Tirelli, A; Allais, G; Blasi, I; Volpe, Annibale; Benedetto, C; Facchinetti, Fabio
abstract

.


2003 - La trasmissione verticale di HIV nell’era della HAART [Abstract in Atti di Convegno]
Guaraldi, Giovanni; Ikonomou, A.; Orlando, G.; Borghi, R.; Verrocchi, G. L.; Neri, Isabella; Facchinetti, Fabio; Cellini, M.; Esposito, Roberto
abstract

L'introduzione della HAART in gravidanza ha ridotto la trasmissione verticale di HIV a una prevalenza attuale minore del 2%.


2003 - Psychoneuroendocrine correlates of secondary amenorrhea. [Articolo su rivista]
R. E., Nappi; Facchinetti, Fabio
abstract

Functional hypothalamic amenorrhea is a common, non-organic and theoretically reversible form of anovulation due to reduced hypothalamic GnRH drive. Numerous studies suggest that this altered hypothalamic homeostasis is caused by a synergism between psychogenic challenge, promoted in part by dysfunctional attitudes, and metabolic compromise induced by undernutrition and overexercise. The recent growing interest in psychiatric comorbidity underlines the importance of reconsidering the boundaries between psychological disorders and somatic conditions. That not withstanding, it is mandatory in gynecological endocrinology to explore the issue of secondary amenorrhea from a psychoneuroendocrine perspective in order to devise biopsychosocial interventions which address the individual distress. In this brief review we will try to critically discuss the issue providing evidences from personal studies as clues for better understanding the extent of the complex psychoneuroendocrine network controlling menstrual function.


2003 - Ripening of the cervix with sodium nitroprusside in nonpregnant women. [Articolo su rivista]
F., Piccinini; R. A., Fano; Volpe, Annibale; Facchinetti, Fabio
abstract

Few clinical trials have examined the effects of nitric oxide donors on the human cervix. We address the question of the ultrastructural and clinical effects of topical NO donor on the nonpregnant human cervix.Twenty patients admitted to the hospital for hysterectomy were randomly assigned to receive either placebo gel or 1\% nitroprusside-based gel into the cervical canal. After surgery, a small biopsy of the cervical canal was taken and analyzed by electron microscopy. Vital parameters were monitored after application.In the placebo group, the connective tissue was normal. In the experimental group, the collagen fibers were widely spaced, and no longitudinal collagen bundles were visible. Macrophages, leukocytes, and activated fibroblasts in treated tissues demonstrated a proinflammatory reaction. Adverse effects were reported in a minority of subjects. No significant changes in blood pressure or in nitrite and nitrate levels were reported.In both fertile and postmenopausal women, cervical sodium nitroprusside induced morphologic changes similar to those reported for the ripening process.


2003 - Thrombophilia and Reproduction [Curatela]
Volpe, Annibale; Facchinetti, Fabio
abstract

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2003 - Thrombophilic mutations are a main risk factor for placental abruption. [Articolo su rivista]
Facchinetti, Fabio; L., Marozio; E., Grandone; C., Pizzi; Volpe, Annibale; C., Benedetto
abstract

The aim of the present study was to evaluate inherited thrombophilic factor V Leiden and factor II A20210 mutations in women presenting with abruption of a normally implanted placenta.In a multi-center, case-control study, 50 consecutive women requiring immediate delivery because of abruption of the placenta were enrolled. Inclusion criteria were: abruptio placentae requiring immediate delivery, normally implanted placenta, Caucasian ethnic background, parity <3, delivery performed at Institutions. Exclusion criteria were: history of thromboembolism, history of 2 or more spontaneous abortions, uterine leiomyomas with a diameter >5 cm, illicit drug abuse, premature rupture of membranes, multiple pregnancy. One hundred Caucasian women with uneventful pregnancies carried to term, matched for parity and age, served as controls.Heterozygotes were found to be significantly more prevalent among women with abruptio placentae than among controls. The carriership of the FV Leiden mutation confers a OR of 9.12 (95\% C.I.: 2.18-31.7; p=0.0005). Women carrying F II A20210 mutation have a OR of 12.25 (95\% C.I.: 2.36-29.6; p=0.0004). No homozygotes or double heterozygotes were found. Twenty-three patients (46\%) also met the criteria for a diagnosis of pre-eclampsia (PE). In such cases the prevalence of mutations (factor V: 6 cases, 26.1\%; factor II: 5 cases, 21.7\%) was similar to that in women without pre-eclampsia (factor V: 5 cases, 18.7\%; factor II: 5 cases, 18.5\%).The presence of either of the above reported thrombophilic mutations represents a relevant risk factor for the occurrence of placental abruption in Caucasians. This risk is independent of the development of pre-eclampsia. Patients who have had dramatic abruption of a normally implanted placenta should undergo evaluation for the presence of genetic mutations of coagulation factors V and II.


2003 - Tibolone reduced analgesics consumption in postmenopausal women with primary headaches [Abstract in Atti di Convegno]
Detaddei, S; Nappi, Re; Sances, G; Facchinetti, Fabio; Brundu, B; Ghiotto, N; Polatti, F; Nappi, G.
abstract

..


2003 - UQCRH gene encoding mitochondrial Hinge protein is interrupted by a translocation in a soft-tissue sarcoma and epigenetically inactivated in some cancer cell lines. [Articolo su rivista]
P., Modena; M. A., Testi; Facchinetti, Fabio; D., Mezzanzanica; M. T., Radice; S., Pilotti; G., Sozzi
abstract

We previously reported the identification of a novel zinc-finger gene, designated ZSG, fused to Ewing sarcoma gene (EWS) by a submicroscopic paracentric inversion of 22q12 in a small round cell sarcoma presenting a translocation t(1;22)(p34;q12). We report here the molecular cloning and characterization of the breakpoint in 1p34, which encompasses the gene coding for mitochondrial Hinge protein ubiquinol-cytochrome C reductase hinge gene (UQCRH). All the three breakpoints, two on 22q12 and one in 1p34, interrupt different genes: EWS, ZSG and UQCRH. We determined the genomic structure of UQCRH, characterized its splicing variants and identified a transcribed processed pseudogene. The analysis of UQCRH expression in normal tissues and cancer cell lines revealed absent expression of UQCRH in two ovarian and one breast cancer cell lines and reduced expression in a further breast carcinoma cell line. CpG island methylation upstream exon 1 was detected in all the three cell lines with absent expression. Moreover, treatment with demethylating agent 5-azacytidine restored UQCRH expression in OAW42 ovarian cancer cells. These data provide preliminary evidence of the inactivation of UQCRH gene in cancer either by structural rearrangements or epigenetic mechanisms.


2002 - A comparison of glyceryl trinitrate with diclofenac for the treatment of primary dysmenorrhea: an open, randomized, cross-over trial. [Articolo su rivista]
Facchinetti, Fabio; L., Sgarbi; F., Piccinini; Volpe, Annibale
abstract

Primary dysmenorrhea is a syndrome characterized by painful uterine contractility caused by a hypersecretion of endometrial prostaglandins; non-steroidal anti-inflammatory drugs are the first choice for its treatment. However, in vivo and in vitro studies have demonstrated that myometrial cells are also targets of the relaxant effects of nitric oxide (NO). The aim of the present study was to determine the efficacy of glyceryl trinitrate (GTN), an NO donor, in the resolution of primary dysmenorrhea in comparison with diclofenac (DCF). A total of 24 patients with the diagnosis of severe primary dysmenorrhea were studied during two consecutive menstrual cycles. In an open, cross-over, controlled design, patients were randomized to receive either DCF per os or GTN patches the first days of menses, when menstrual cramps became unendurable. In the subsequent cycle the other treatment was used. Patients received up to 3 doses/day of 50 mg DCF or 2.5 mg/24 h transdermal GTN for the first 3 days of the cycle, according to their needs. The participants recorded menstrual symptoms and possible side-effects at different times (0, 30, 60, 120 minutes) after the first dose of medication on the first day of the cycle, with both drugs. The difference in pain intensity score (DPI) was the main outcome variable. Both treatments significantly reduced DPI by the 30th minute (GTN, -12.8 +/- 17.9; DCF, -18.9 +/- 16.6). However, DCF continued to be effective in reducing pelvic pain for two hours, whereas GTN scores remained more or less stable after 30 min and significantly higher than those for DFC (after one hour: GTN, -12.8 +/- 17.9; DFC, -18.9 +/- 16.6 and after two hours: GTN, -23.7 +/- 20.5; DFC, -59.7 +/- 17.9, p = 0.0001). Low back pain was also relieved by both drugs. Headache was significantly increased by GTN but not by DCF. Eight patients stopped using GTN because headache--attributed to its use--became intolerable. These findings indicate that GTN has a reduced efficacy and tolerability by comparison with DCF in the treatment of primary dysmenorrhea.


2002 - Adjuvant L-arginine treatment in controlled ovarian hyperstimulation: a double-blind, randomized study. [Articolo su rivista]
C., Battaglia; G., Regnani; T., Marsella; Facchinetti, Fabio; Volpe, Annibale; S., Venturoli; C., Flamigni
abstract

Enhanced vascularization appears to be important for follicular selection and maturation in both spontaneous and stimulated IVF cycles. Nitric oxide, formed in vivo from L-arginine, may play a key role in follicular maturation and ovulation.To evaluate the role of L-arginine supplementation in controlled ovarian hyperstimulation, 37 IVF patients were divided into two groups according to ovarian stimulation protocols: group I, GnRH agonist plus pure (p)FSH plus oral L-arginine (n = 18); and group II, GnRH agonist plus pFSH plus placebo (n = 19). Hormonal, ultrasonographic and Doppler evaluations were performed, and plasma and follicular fluid nitrite/nitrate concentrations were monitored.Thirty-two patients completed the study. In group I (n = 16), plasma L-arginine concentrations increased from (basal) 87 +/- 12 micromol to 279 +/- 31 micromol (P = 0.002) on the day of beta-HCG administration. In this group, pFSH treatment was shorter (P = 0.039) than in group II (n = 16). The number of the follicles > or =17mm was lower (P = 0.038) in group I than group II. The "good quality" embryos were fewer in number (P = 0.034) and pregnancy rate, both per patient (P = 0.024) and per embryo transfer (P = 0.019), was lower in group I. In the L-arginine group, an increased follicular fluid concentration of nitrite/nitrate was observed. On day 8 of the cycle, elevated plasma estradiol levels were associated with decreased blood flow resistances of perifollicular arteries. Follicular fluid concentrations of nitrite/nitrate were inversely correlated with embryo quality (r = -0.613; P = 0.005) and perifollicular artery pulsatility index (r = -0.609; P = 0.021).L-Arginine supplementation may be detrimental to embryo quality and pregnancy rate during controlled ovarian hyperstimulation cycles.


2002 - Chlorhexidine vaginal flushings versus systemic ampicillin in the prevention of vertical transmission of neonatal group B streptococcus, at term. [Articolo su rivista]
Facchinetti, Fabio; F., Piccinini; B., Mordini; Volpe, Annibale
abstract

To investigate the efficacy of intrapartum vaginal flushings with chlorhexidine compared with ampicillin in preventing group B streptococcus transmission to neonates.This was a randomized controlled study, including singleton pregnancies delivering vaginally. Rupture of membranes, when present, must not have occurred more than 6 h previously. Women with any gestational complication, with a newborn previously affected by group B streptococcus sepsis or whose cervical dilatation was greater than 5 cm were excluded. A total of 244 group B streptococcus-colonized mothers at term (screened at 36-38 weeks) were randomized to receive either 140 ml chlorhexidine 0.2\% by vaginal flushings every 6 h or ampicillin 2 g intravenously every 6 h until delivery. Neonatal swabs were taken at birth, at three different sites (nose, ear and gastric juice).A total of 108 women were treated with ampicillin and 109 with chlorhexidine. Their ages and gestational weeks at delivery were similar in the two groups. Nulliparous women were equally distributed between the two groups (ampicillin, 87\%; chlorhexidine, 89\%). Clinical data such as birth weight (ampicillin, 3,365 +/- 390 g; chlorhexidine, 3,440 +/- 452 g), Apgar scores at 1 min (ampicillin, 8.4 +/- 0.9; chlorhexidine, 8.2 +/- 1.4) and at 5 min (ampicillin, 9.7 +/- 0.6; chlorhexidine, 9.6 +/- 1.1) were similar for the two groups, as was the rate of neonatal group B streptococcus colonization (chlorhexidine, 15.6\%; ampicillin, 12\%). Escherichia coli, on the other hand, was significantly more prevalent in the ampicillin (7.4\%) than in the chlorhexidine group (1.8\%, p < 0.05). Six neonates were transferred to the neonatal intensive care unit, including two cases of early-onset sepsis (one in each group).In this carefully screened target population, intrapartum vaginal flushings with chlorhexidine in colonized mothers display the same efficacy as ampicillin in preventing vertical transmission of group B streptococcus. Moreover, the rate of neonatal E. coli colonization was reduced by chlorhexidine.


2002 - Effect of arginine supplementation in patients with gestational hypertension [Poster]
Facchinetti, F.; Piccinini, F.; Pizzi, C.; Radek, B.; Volpe, A.
abstract


2002 - Eleutherococcus senticosus reduces cardiovascular stress response in healthy subjects: a randomized, placebo-controlled trial [Articolo su rivista]
Facchinetti, Fabio; Neri, Isabella; M., Tarabusi
abstract

The number of studies devoted to the scientific evaluation of phytotherapy is rapidly increasing since Western patients seem more oriented towards so-called ´alternative medicine´. Bearing such arguments in mind we decided to address attention to Eleutherococcus senticosus, a root of the Ginseng family known for thousands of years in China as a remedy for psychological distress. Forty-five paid, healthy volunteers (20 males, 25 females) were recruited. Entry criteria were. good health, age 18-30 years, student and a Symptoms Rating Test score <10. At screening evaluation subjects were randomized to receive orally either placebo (PI group) or Eleutherococcus senticosus (Es group) for 30 days, in a double-blind design. Subjects were submitted to a stressful cognitive task, the Stroop Colour-Word test (Stroop CW), both before and after treatment. Stroop CW increased heart rate (HR) and systolic BP in every subject. In females there was a greater response than in males in terms of both systolic and diastolic BP. For both genders, the HR response to Stroop CW was reduced by Es treatment while no changes were found after Pl. In females, systolic BP was also reduced in Es group while it remained unchanged in PI group. This study demonstrated that treatment with Eleutherococcus senticosus is able to reduce cardiovascular responses to stress in healthy young volunteers, while placebo was ineffective. Eleutherococcus senticosus is confirmed to be helpful for stress adaptation. Copyright


2002 - Fas/CD95-mediated apoptosis in human glioblastoma cells: a target for sensitisation to topoisomerase I inhibitors. [Articolo su rivista]
E., Ciusani; P., Perego; N., Carenini; E., Corna; Facchinetti, Fabio; A., Boiardi; A., Salmaggi; F., Zunino
abstract

The expression of the death receptor Fas/CD95 is cell type-specific and can be modulated by different cytotoxic treatments. In spite of a frequent expression of Fas/CD95 in high-grade gliomas, these tumours are typically refractory to conventional therapy. Using a human glioblastoma cell line (GBM), we explored the possibility of modulating susceptibility to Fas/CD95-mediated apoptosis following cytotoxic treatment. GBM cells were sensitive to the antiproliferative effects of topoisomerase I inhibitors (topotecan and a novel lipophilic analog CPT83) and taxol, less sensitive to cisplatin and, in any case, rather resistant to drug-induced apoptosis. This pattern of cellular response was consistent with p53 mutation. GBM cells expressed low levels of Fas/CD95, which was associated with low susceptibility to antibody-stimulated Fas/CD95-mediated apoptosis. A significant up-regulation of Fas/CD95 expression was detected after exposure to topotecan and CPT83, whereas cisplatin induced a low increase and taxol did not modify Fas/CD95 expression. In addition, after treatment with topoisomerase I inhibitors, the up-regulation of Fas/CD95 resulted in an increased susceptibility of GBM cells to antibody-stimulated Fas/CD95-mediated apoptosis, while no synergistic effects were detected after treatment with cisplatin or taxol. Our data suggest that Fas/CD95 up-regulation can be a common response to DNA damage, whereas sensitisation to Fas/CD95-mediated apoptosis appears to be dependent on the type of DNA damage and on the pathway of cellular response. The observed effects might have important therapeutic implications for the design of novel therapeutic strategies in the treatment of malignant gliomas.


2002 - GESTOSI 2002. [Curatela]
G., Mello; Facchinetti, Fabio
abstract

..


2002 - Hormone supplementation differently affects migraine in postmenopausal women. [Articolo su rivista]
Facchinetti, Fabio; R. E., Nappi; A., Tirelli; F., Polatti; G., Nappi; G., Sances
abstract

To evaluate the effects of three schemes of oral hormone replacement therapy (HRT) on migraine course in postmenopausal women.Thirty-eight patients presenting for clinical evaluation of menopausal status and suffering from migraine were enrolled. The observational period lasted 7 months, during which women filled in a daily diary with the clinical features of headache attacks and analgesic use. We evaluated climacteric symptoms, anxiety and depression. After a 1-month run-in period, women were assigned to one of three regimens of HRT: estradiol hemihydrate 1 mg/day plus norethisterone 0.5 mg/day for 28 days, in a continuous combined scheme; oral conjugated estrogens 0.625 mg/day for 28 days plus medroxyprogesterone acetate 10 mg/day in the last 14 days, in a sequential continuous scheme; and estradiol valerate 2 mg/day for 21 days plus cyproterone acetate 1 mg/day from day 12 to 21 in a sequential cyclical scheme. Follow-up evaluations were performed at 3 and 6 months.During the run-in period, the three subgroups of patients were similar as far as the features of migraine are concerned. Overall, a progressive increase in attack frequency (from 2.2 +/- 1.0 to 3.8 +/- 1.3, P<.001), days with headache (from 3.4 +/- 1.3 to 4.9 +/- 1.9, P<.001), and analgesic consumption (from 3.4 +/- 1.3 to 5.6 +/- 2.2, P<.001) was observed after 6 months. Duration of attacks decreased (from 18.1 +/- 7.4 to 13.6 +/- 4.2 hours, P =.005), whereas severity worsened (from 1.9 +/- 0.2 to 2.1 +/- 0.2, P<.001). The increase in number of days with headache and number of analgesics used was smaller in the group receiving the continuous combined regimen than in the other two groups.Although HRT typically will lead to some worsening of headache syndrome, estradiol hemihydrate plus norethisterone given in a combined continuous scheme was the regimen best tolerated by our patients.


2002 - Hypothalamic amenorrhea: an example of reproductive disadaptation [Articolo su rivista]
Nappi, Re; Brundu, B; Farina, C; Detaddei, S; Sommacal, A; De Leonardis, C; Chiapparini, I; Vaccaro, P; Facchinetti, Fabio; Polatti, F.
abstract

Functional hypothalamic amenorrhea is a common, non-organic and theoretically reversible form of anovulation due to reduced hypothalamic GnRH drive. Numerous studies suggest that this altered hypothalamic homeostasis is caused by a synergism between psychogenic challenge, promoted in part by dysfunctional attitudes, and metabolic compromise induced by undernutrition and overexercise. The recent growing interest in psychiatric comorbidity underlines the importance of reconsidering the boundaries between psychological disorders and somatic conditions. That not with standing, it is mandatory in gynecological endocrinology to explore the issue of secondary amenorrhea from a psychoneuroendocrine perspective in order to devise biopsychosocial interventions which address the individual distress. In this brief review we will try to critically discuss the issue providing evidences from personal studies as clues for better understanding the extent of the complex psychoneuroendocrine network controlling menstrual function.


2002 - NEW PERSPECTIVES ON THE TREATMENT OF PREMENSTRUAL SYNDROME AND PREMENSTRUAL DYSPHORIC DISORDER. [Articolo su rivista]
Eriksson, E.; Endicott, J; Andersch, B.; Angst, J; Demyttenaere, K; Facchinetti, Fabio; Lanczik, M.; Montgomery, S.; Muscettola, G.; O`brien, Pms; Studd, J; Sunblad, C.; Young, A. H.
abstract

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2002 - Non-stress test changes during acupuncture plus moxibustion on BL67 point in breech presentation. [Articolo su rivista]
Neri, Isabella; M., Fazzio; S., Menghini; Volpe, Annibale; Facchinetti, Fabio
abstract

We assessed fetal heart variability and activity using a computerized non-stress test (NST) during acupuncture plus moxibustion on the BL67 point. For comparison, the same changes were assessed during placebo acupuncture (minimal acupuncture) in the same subjects.Twelve pregnant women in the 33rd week of gestation, carrying singletons in the breech presentation were enrolled in the study. In a single-blind design, each woman received a first session of minimal acupuncture followed 1-2 days later by true acupuncture. During the sessions, women were monitored using computerized non-stress testing starting 20 minutes before the stimuli and continuing for 20 minutes after treatment.During true acupuncture a significant reduction in fetal baseline heart rate, and more accelerations and movement were observed. During minimal acupuncture, there were no significant changes in these variables. No signs of fetal distress or changes in short- or long-term variability were noted, and there were no uterine contractions.In our study population, acute application of acupuncture plus moxibustion did not cause fetal distress as assessed by either fetal heart rate decelerations or changes in either short- or long-term variability. Considering that the modifications in fetal movement and heart rate occurred in true but not during minimal acupuncture, we could consider that such changes are related to the effect of the acupuncture stimulation. The mechanisms leading to the cephalic version remain to be clearly established.


2002 - REDUCED PLATELET SENSITIVITY TO NITRIC OXIDE DONORS IN PATIENTS WITH A HYSTORY OF PREECLAMPSIA. [Articolo su rivista]
Facchinetti, Fabio; Fazzio, M.; Pizzi, C.; Blasi, I.; Marietta, M.; Volpe, Annibale
abstract

..


2002 - Terapie non convenzionali nella medicina della riproduzione [Curatela]
Facchinetti, Fabio; G. B., Allais; C. M., Giovanardi
abstract

Terapie non convenzionali nella medicina della riproduzione


2001 - A novel 9-aza-anthrapyrazole effective against human prostatic carcinoma xenografts. [Articolo su rivista]
R., Supino; D., Polizzi; R., Pavesi; G., Pratesi; F., Guano; G., Capranico; M., Palumbo; C., Sissi; S., Richter; G., Beggiolin; E., Menta; G., Pezzoni; S., Spinelli; D., Torriani; N., Carenini; L. D., Bo; Facchinetti, Fabio; M., Tortoreto; F., Zunino
abstract

Systematic investigation of a novel series of intercalating agents, 9-aza-anthrapyrazoles, has led to the identification of a promising analogue, BBR 3438. This study describes the antitumour efficacy of the novel compound in human prostate carcinoma models and the molecular/cellular basis of its activity.The novel 9-aza-anthrapyrazole BBR 3438 was significantly more effective than doxorubicin and losoxantrone (DuP-941) in two of the three tested prostate carcinoma models. The superior activity was more evident in PC3 tumour, since BBR 3438 produced an appreciable rate of complete tumour regressions. Under these conditions, the drug-induced antiproliferative activity paralleled delayed apoptosis. Tumour response to in vivo drug treatment was associated with an early down-regulation of Bcl-2, which was somewhat more marked for the aza compound. In fact, the 9-aza-anthrapyrazole induced DNA cleavage in vitro with isolated DNA topoisomerase II (isoform alpha) and DNA strand breaks in prostatic carcinoma cells. Although the molecular effects of losoxantrone and the 9-aza analogue on the enzyme target were comparable, the cytotoxic effects of BBR 3438 could be enhanced by long-term exposure as a consequence of favourable cellular accumulation and prominent DNA-binding affinity. In addition, a lower reduction potential of the 9-aza-anthrapyrazole in comparison with classical anthrapyrazoles suggests an increased ability of the drug to induce oxidative stress following free radical production, which may be a contributing factor in determining the long-term response (i.e. delayed cell death) to genotoxic damage.BBR 3438 exhibited a unique profile of preclinical activity with a superior efficacy against prostatic carcinoma models compared to reference compounds (doxorubicin and losoxantrone). The antitumour efficacy of BBR 3438 against prostatic carcinoma could be the result of a combination of favourable events, including enhanced intracellular accumulation and an increased DNA-binding affinity favouring the accumulation of multiple sublethal or lethal damage. In spite of its enhanced cytotoxic potency, the 9-aza compound was better tolerated in vivo than losoxantrone, thus improving the therapeutic index. The preclinical profile of efficacy against prostatic carcinoma, a tumour resistant to conventional antitumour drugs, makes the novel 9-aza-anthrapyrazole BBR 3438 a promising candidate for clinical evaluation.


2001 - Course of primary headaches during hormone replacement therapy. [Articolo su rivista]
R. E., Nappi; Cagnacci, Angelo; F., Granella; F., Piccinini; F., Polatti; Facchinetti, Fabio
abstract

The aim of the present study was to evaluate how hormone replacement therapy (HRT) could influence the course of primary headaches in postmenopausal women.Fifty patients presenting for clinical evaluation of menopausal status and suffering from headache were enrolled. The observational period lasted 7 months during which women filled in a diary with the clinical characteristics of headache attacks (frequency, days with headache, severity) and the analgesic use (no. of analgesic/month). Climacteric symptoms and both anxiety and depression were also measured. At the first visit the patients were divided into two groups: those suffering from migraine without aura (MwA) and those suffering from episodic tension-type headache (ETTH) and separately randomized. After a month of run-in period, they received two different HRT regimen, either: (1) transdermal estradiol 50 mcg every 7 days for 28 days plus medroxyprogesterone acetate (MAP) 10 mg/day from 15th to 28th day, or (2) oral conjugated estrogens 0.625 mg/day for 28 days plus MAP 10 mg/day for the last 14 days. Follow up evaluations were planned after 1, 3 and 6 months of treatment.While we did not observe any significance change regarding headache parameters in ETTH patients during both transdermal and oral treatment, the course of migraine was significantly affected by the route of HRT. Both frequency of attacks (F = 8.5; P < 0.000) and days with headache (F = 6.9; P < 0.000) significantly increased during HRT in the subgroup assuming oral formulation. On the contrary, no changes in the same parameters were found in the group taking transdermal treatment. Moreover, while severity of migraine was unaffected by HRT, analgesic consumption was significantly increased in the subgroup on oral treatment (F = 6.3; P = 0.001).HRT significantly affects the course of headache in postmenopausal migraine sufferers. Indeed, while the clinical pattern of ETTH remained stable throughout the observational period, patients suffering from MwA worsened their symptoms within the first 3 months of treatment. In particular, the oral route of administration significantly worsened migraine in comparison to the transdermal route.


2001 - Effect of exogenous melatonin on vascular reactivity and nitric oxide in postmenopausal women: role of hormone replacement therapy. [Articolo su rivista]
Cagnacci, Angelo; S., Arangino; M., Angiolucci; G. B., Melis; Facchinetti, Fabio; S., Malmusi; Volpe, Annibale
abstract

Several effects of melatonin are modulated by gonadal steroids and are reduced in ageing women. Administration of melatonin reduces internal carotid artery pulsatility index (PI), and blood pressure in young individuals. Whether these effects are conserved in postmenopausal women and are influenced by hormone replacement therapy (HRT), was herein investigated.Randomised, double-blind placebo controlled study.Twenty-three postmenopausal women of which 11 were unreplaced with HRT and 12 on the oestrogenic phase of continuous transdermal estradiol (50 microg/day) plus cyclic medroxyprogesterone acetate (5 mg/day x 12 days every 28 days).Internal carotid PI, by colour Doppler, and supine blood pressure were evaluated 90, 180 and 240 minutes following the oral administration of melatonin (1 mg) or placebo. Levels of nitrites/nitrates (NOx), the stable derivatives of nitric oxide, were also evaluated in samples collected 90 minutes following the administration of placebo or melatonin.In women not on replacement therapy melatonin was ineffective. In HRT-treated women, melatonin reduced internal carotid artery PI (P = 0.005). The effect was maximal within 90 minutes, and maintained for at least 240 minutes, with melatonin levels in the nocturnal physiological range. Systolic and diastolic blood pressures were reduced of 8 mmHg (P = 0.038) and 4 mmHg (P = 0.045), respectively, while NOx levels were significantly increased (P = 0.024).The circulatory response to melatonin is conserved in postmenopausal women with but not without hormone replacement therapy. Maintenance of the cardiovascular response to melatonin, may be implicated in the reduced cardiovascular risk of postmenopausal women with hormone replacement therapy.


2001 - Endothelium dependence and gestational regulation of inhibition of vascular tone by magnesium sulfate in rat aorta. [Articolo su rivista]
M., Longo; V., Jain; Y. P., Vedernikov; Facchinetti, Fabio; G. R., Saade; R. E., Garfield
abstract

The aim of this study was to investigate the role of nitric oxide in the vasorelaxant effect of magnesium sulfate during pregnancy.Segments of 3 mm of the aorta, with or without intact endothelium, from 16- or 22-day-pregnant rats were mounted in organ chambers with standard Krebs solution or low-magnesium Krebs solution for measurement of isometric tension. The rings were contracted with phenylephrine, and cumulative concentration-response curves for magnesium were determined after incubation with various inhibitors.Magnesium relaxed the aortic rings from pregnant rats in a concentration-dependent manner. The relaxation was significantly lower on day 22 of gestation than on day 16 of gestation. Removal of the endothelium or incubation with 10(-4)-mol/L N omega-nitro-L -arginine methyl ester (a nitric oxide synthase inhibitor), 10(-5)-mol/L 6-anilino-5,8-quinolinedione (a guanylate cyclase inhibitor), or 10(-5)-mol/L indomethacin (a cyclooxygenase inhibitor) significantly decreased the relaxant effect of magnesium on aortic rings from 16-day-pregnant but not 22-day-pregnant rats. Treatment with minimally effective concentrations of a nitric oxide donor (3 x 10(-10)-mol/L sodium nitroprusside) or a cyclic guanosine monophosphate analog (10(-6)-mol/L 8-bromo-cyclic guanosine monophosphate) restored the response to magnesium.The relaxant effect of magnesium on rat aortic rings was dependent on both endothelium and gestational age and was lower at term than during late pregnancy. The endothelium appears to potentiate the vasorelaxant effects of magnesium through the nitric oxide-cyclic guanosine monophosphate and cyclooxygenase systems.


2001 - Female depression and menopause. [Articolo su rivista]
Facchinetti, Fabio
abstract

..


2001 - Immunological changes and stress are associated with different implantation rates in patients undergoing in vitro fertilization-embryo transfer. [Articolo su rivista]
A., Gallinelli; R., Roncaglia; M. L., Matteo; I., Ciaccio; Volpe, Annibale; Facchinetti, Fabio
abstract

To evaluate the possible correlation between immunological changes and implantation rates in patients who undergo in vitro fertilization-embryo transfer (IVF-ET).Controlled clinical study.University hospital.Forty infertile women undergoing IVF-ET.Stroop Color Word (CW) test, State-Trait Anxiety Inventory (STAI) test, blood sampling.Heart rate and systolic and diastolic blood pressure responses to Stroop CW; circulating T, B, T-helper (CD4), and T-suppressor (CD8) lymphocytes.The total number of T lymphocytes increased significantly during superovulation, resulting in significantly higher levels in subjects achieving embryo implantation than in those showing a failure of implantation. An opposite trend was observed for the activated T cells. The number of T-helper lymphocytes and the T-helper/T-suppressor ratio showed a significant increase from baseline to the time of pick-up only in patients with implantation.A prolonged condition of stress, which causes a decreased ability to adapt and a transitory anxious state, is associated with high amounts of activated T cells in the peripheral blood. Such a condition, in turn, is associated with a reduced implantation rate in women undergoing IVF-ET.


2001 - Intratesticular Doppler flow, seminal plasma nitrites/nitrates, and nonobstructive sperm extraction from patients with obstructive and nonobstructive azoospermia. [Articolo su rivista]
C., Battaglia; S., Giulini; G., Regnani; I., Madgar; Facchinetti, Fabio; Volpe, Annibale
abstract

To prospectively evaluate the role of intratesticular vascular flow in modulating sperm function in men with obstructive and nonobstructive azoospermia. The correlation of testicular Doppler values with nitric oxide and testicular sperm extraction was further evaluated.Prospective study.Assisted reproduction unit at a university center.Twenty-eight men with azoospermia undergoing sperm extraction for intracytoplasmic sperm injection.Ultrasound and color Doppler scanning of the testes. Testicular sperm retrieval and nitrite/nitrate assay.Doppler analysis of testicular transmediastinal artery, plasma and seminal plasma nitrite/nitrate values, and sperm extraction histopathology.The pulsatility index (PI) of the transmediastinal artery was higher in patients with nonobstructive azoospermia (PI = 1.40 +/- 0.13) than in those with obstructive azoospermia (PI = 1.09 +/- 0.15; P=.011). Seminal plasma nitrite/nitrate concentrations were more elevated in cases of obstructive azoospermia than in gonadal failure. Unsuccessful sperm recovery was observed in four patients who showed the worst indices of gonadal failure. In this subgroup, a transmediastinal PI value >1.50 was always observed.Doppler analysis of the transmediastinal artery and nitrite/nitrate seminal plasma concentrations are useful for distinguishing between obstructive and nonobstructive azoospermia and allow the identification of the presence of spermatozoa within the testes.


2001 - Nimesulide in the treatment of primary dysmenorrhea: A double-blind study versus diclofenac [Articolo su rivista]
Facchinetti, Fabio; F., Piccinini; L., Sgarbi; D., Renzetti; Volpe, Annibale
abstract

The aim of this randomized, double-blind study was the comparison of nimesulide (100 mg p.o., Aulin (R), Roche) vs, diclofenac (50 mg p.o., Dicloreuma (R), Alpha-Wassermann) in the treatment of primary dysmenorrhea. Patients requiring drug treatment in the last 6 months and having regular menstrual cycles were enrolled. Three hundred and eight subjects were randomized in two groups to receive up to 3 tablets/day (according to need), for the first 3 days of the cycle for two menstrual cycles. Abdominal pain was the primary endpoint and it was evaluated before and 30, 60, 120 min after the first drug administration, each of the two cycles, through a 100 mm visual analog scale (VAS). Secondary parameters were the associated symptoms (evaluated through a Likert scale 0-3) as well as the subjective global judgement. Side effects were also recorded. Statistical evaluations were done on 304 subjects (149 nimesulide and 155 diclofenac) who completed the study. Sociodemographic and clinical features of patients assigned to the two groups. were superimposable. Baseline pain was similar in the two cycles: 73.5 +/- 10.8 for nimesulide and 72.1 +/- 11.4 for diclofenac. Both drugs progressively and significantly decreased pain which was reduced by 82% (nimesulide) and 79% (diclofenac), at the second hour. However, nimesulide showed faster activity than diclofenac starting from 30 min, with a reduction of 35% vs. 27% (p < 0.01), at both the first and second cycle. Headache and lumbar pain were significantly and equally improved by both treatments. At the end of each cycle, a good efficacy assessment was indicated in 86% of the nimesulide cases and 81% of those with diclofenac. Tolerability was good with both drugs. However, 16 cases reported gastric side effects in the diclofenac group, whereas they were only seven in the nimesulide group.


2001 - Pituitary LH reserve suggests high risk of bulimia in amenorrheic women. [Articolo su rivista]
R. E., Nappi; Neri, Isabella; F., Veneroni; F., Polatti; F., Piccinini; Facchinetti, Fabio
abstract

The present study was aimed at investigating a) the risk of having bulimia in a heterogeneous population of secondary amenorrhea; b) the LH and FSH secretion under basal and stimulated conditions (GnRH challenge) according to the presence of bulimic risk in our study population; c) the clinical and endocrine factors predictive of the bulimic risk in amenorrheic women. Amenorrheic women (n=73; age: 23.1+/-4.8 yrs; BMI:20.2+/-2.2 kg/m2) filled in a self rating scale for bulimia (BITE) and were classified accordingly, as being at low risk (score <10), at medium risk (score between 10 and 24), and at high risk (score > or =25) of having bulimia. In each subject basal mean plasma LH levels were calculated over one hour, sampling every 10 minutes, while in a subgroup of 45 patients the area under the curve (AUC) of plasma LH and FSH levels following a challenge with two doses of GnRH (10+10 microg, every two hours), sampling every 15 minutes, was also evaluated. High risk of bulimia was present in 12.3\% of the population whereas 45.2\% showed a low risk and 42.5\% were at medium risk of developing the disorder. Mann-Whitney U test revealed that basal LH values were differently distributed with significantly lower levels (P<0.046) in amenorrheic women at high risk of bulimia in comparison with amenorrheic women at low risk. The AUC of LH secretion following the first challenge of GnRH was significantly higher in amenorrheic women with a high risk of bulimia in respect with both groups of women at low (P<0.034) and medium (P<0.009) risk. A similar result was found with FSH AUC following the first GnRH challenge (P<0.04 high risk vs low risk and P<0.014 high risk vs medium risk). In a multiple regression analysis, the best model predicting the risk of bulimia (BITE total score) included both the LH response to GnRH challenge and BMI. In conclusion, when facing secondary amenorrhea at first consultation, long before a precise pathophysiologic diagnosis of the disease, low basal plasma LH levels and LH response to GnRH challenge may allow one to suspect the presence of abnormal eating pattern of bulimic type.


2001 - SAFETY AND EFFICACY OF NITROPRUSSIDE GEL FOR CERVICAL RIPENING. [Articolo su rivista]
Facchinetti, Fabio; F., Piccinini; M., Fazzio; Volpe, Annibale
abstract

..


2001 - The PFA-100 system for the assessment of platelet function in normotensive and hypertensive pregnancies. [Articolo su rivista]
M., Marietta; I., Castelli; F., Piccinini; Neri, Isabella; M., Bertesi; Facchinetti, Fabio; G., Torelli
abstract

Platelet function was studied in 30 pregnant women: 14 normotensive (C), and 16 affected by pregnancy-induced hypertension (PIH). Platelet aggregometry (PA) on platelet-rich plasma according to Born was compared with the new PFA-100 System (Dade International Inc, Miami, USA). This device evaluates platelet function (expressed in seconds as closure time, CT) in anticoagulated whole blood ex vivo at high shear rates. PA (expressed as percentage of light transmission) and CT were measured at baseline and after incubation with L-Arginine (L-Arg). MANOVA for repeated measures showed that L-Arg incubation significantly decreased PA (F=7.2, P < 0.05) and increased CT (F=6.05, P < 0.05) in the whole population of pregnant women. Moreover, we analysed separately both parameters in C and in PIH subjects. No differences in PA were found in both groups, neither at baseline nor after L-Arginine incubation. In contrast, CT was significantly longer in PIH in comparison to C before (95.9 s vs. 84 s, P < 0.05) as well after (115 s vs. 92 s, P < 0.05) L-Arginine incubation. Data from PFA-100 confirm our previous reports that during pregnancy the L-Arginine: Nitric Oxide pathway regulates platelet function. In hypertensive patients a significant decrease in platelet function was found by using the PFA-100 system.


2001 - Transdermal estradiol does not modify endothelin-1 and nitric oxide levels in postmenopausal women without cardiovascular risk factors [Altro]
Zanni, Al; Cagnacci, Angelo; Malmusi, S; Arangino, S; Facchinetti, Fabio; Tarquini, R; Cagnacci, P; Volpe, Annibale
abstract

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2000 - Approccio non convenzionale ai disturbi ginecologici [Curatela]
Facchinetti, Fabio; G. B. Allais C. M., Giovanardi
abstract

pproccio non convenzionale ai disturbi ginecologici


2000 - Autonomic and neuroendocrine responses to stress in patients with functional hypothalamic secondary amenorrhea. [Articolo su rivista]
A., Gallinelli; M. L., Matteo; Volpe, Annibale; Facchinetti, Fabio
abstract

OBJECTIVE: To evaluate the ability of women affected by functional hypothalamic secondary amenorrhea (FHSA) or polycystic ovary syndrome (PCOS) to adapt to stress. DESIGN: Controlled clinical study. Setting: University hospital. PATIENT(s): Thirty-one patients affected by FHSA, 29 patients with PCOS, and 30 eumenorrheic women. INTERVENTION(s): The subjects took the Stroop Color Word (Stroop CW) test and underwent blood sampling. MAIN OUTCOME MEASURE(s): Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and serum cortisol levels. RESULT(s): The healthy controls had better Stroop CW scores than patients with FHSA. Serum cortisol levels significantly increased during Stroop CW with respect to the baseline in patients with FHSA or PCOS but not in the healthy controls. The SBP, DBP, and HR of the controls as well as SBP and DBP of patients with PCOS were significantly higher than those measured in patients with FHSA both at the baseline and during Stroop CW. CONCLUSION(s): Patients with FHSA do not cope as well as healthy patients, and their autonomic response to stress is worse than both controls and patients with PCOS.


2000 - Cardiotocography analysis during the BL67 acupoint stimulus for breech presentation [Articolo su rivista]
Facchinetti, Fabio
abstract

The BL67 acupuncture stimulus represents an effective and easy method to obtain the conversion of fetus in breech presentation. Notwithstanding this, traditional medicine still has several doubts about the safety of this technique. The aim of the present study is to prove that BL67 acupuncture stimuli application leads to no fetal risk, and that it doesn't induce any increase in uterine contractility. Actually, using computerized cardiotocography in 10 pregnant women who underwent acupuncture because of breech presentation, it was proved that either decrease or increase in fetal heartbeat or any changing in fetal heart rate hasn't occur both during and after the acupuncture practice, while was shown a decreasing in fetal movements. Moreover it was observed no uterine contractility during the observation period after the acupuncture session. It's so possible to conclude from this first experience that BL67 acupuncture stimulus absolutely causes no fetal risk and, what's more, in contrast to what is so often thought, the acute effect of acupuncture is to induce a quiet state in the fetus.


2000 - Cardiotocography analysis during the BL67 acupoint stimulus for breech presentation [Articolo su rivista]
Neri, I.; Ternelli, G.; Facchinetti, F.; Volpe, A.
abstract

The BL67 acupuncture stimulus represents an effective and easy method to obtain the conversion of fetus in breech presentation. Notwithstanding this, traditional medicine still has several doubts about the safety of this technique. The aim of the present study is to prove that BL67 acupuncture stimuli application leads to no fetal risk, and that it doesn't induce any increase in uterine contractility. Actually, using computerized cardiotocography in 10 pregnant women who underwent acupuncture because of breech presentation, it was proved that either decrease or increase in fetal heartbeat or any changing in fetal heart rate hasn't occur both during and after the acupuncture practice, while was shown a decreasing in fetal movements. Moreover it was observed no uterine contractility during the observation period after the acupuncture session. It's so possible to conclude from this first experience that BL67 acupuncture stimulus absolutely causes no fetal risk and, what's more, in contrast to what is so often thought, the acute effect of acupuncture is to induce a quiet state in the fetus.


2000 - Chemical ripening of the cervix with intracervical application of sodium nitroprusside: a randomized controlled trial. [Articolo su rivista]
Facchinetti, Fabio; F., Piccinini; Volpe, Annibale
abstract

Nitric oxide (NO) has been found to be involved in the processes of cervical ripening. In a randomized, placebo-controlled study, cervical softening by an intracervical application of sodium nitroprusside, one of the most clinically potent and effective NO donor agents, was evaluated. A total of 36 primigravid women undergoing pregnancy termination between 9 and 12.5 weeks were enrolled. In one series, 18 patients were randomized to receive intracervically either placebo or 1\% nitroprusside gel (5 mg), followed by uterine evacuation 6 h after treatment. In another series, 18 patients received either placebo or 2\% nitroprusside gel (10 mg) into the cervical canal followed by uterine evacuation 3 h later. The cervical resistance, i.e. the force required to dilate the cervix from 3 to 10 mm, was the main outcome variable. It was recorded using a force sensing apparatus (dynamometer). Blood pressure was measured. Adverse events were recorded until 2 h after surgery. Women treated with both doses of nitroprusside gel showed values of cervical resistance significantly lower than those treated with placebo gel, at any tested diameter. No differences were found between subjects treated with the two different doses of nitroprusside. No significant consistent changes in blood pressure were induced by either dose of nitroprusside. No headaches were found in subjects treated with the NO donor. This study demonstrates that sodium nitroprusside applied into the cervical canal induces a rapid and significant softening of the cervix, thus reducing the force required to dilate it, compared with placebo-treated subjects. The chemical ripening of the cervix with sodium nitroprusside intracervical gel is an efficacious procedure in first-trimester pregnancy.


2000 - Hypothalamic resetting at puberty and the sexual dimorphism of migraine. [Articolo su rivista]
Facchinetti, Fabio; L., Sgarbi; F., Piccinini
abstract

It is well known that migraine is far more represented in females than in males. However, this gender-related difference is present only during reproductive life since in prepubertal children, migraine prevalence figures are independent of sex. Thus, transition to puberty accounts for changes which render females more susceptible to migraine attacks. In females, the main driver of the hormonal events allowing sexual maturation is the pulsatile secretion of hypothalamic LHRH modulated by opioid activity. Clinical reports suggest that migraine attacks could be prevented by the abolition of this neurohormonal secretion. On the other hand, several clinical and experimental observations have focused on neuroendocrine systems (opiatergic, serotonergic, adrenergic) as participating in the constitution of the so-called "migraine trait", the biological predisposition in patients that would explain their sensitivity to migraine triggers. Such neuroendocrine secretions are mainly dependent upon hypothalamic activity where a sexual dimorphic nucleus has been discovered in the preoptic area. We suggest that the sexual dimorphism of migraine should be sought in hypothalamic networks related to LHRH secretion.


2000 - Increased L-citrulline/L-arginine plasma ratio in severe preeclampsia. [Articolo su rivista]
C., Benedetto; L., Marozio; Neri, Isabella; M., Giarola; Volpe, Annibale; Facchinetti, Fabio
abstract

To evaluate nitric oxide (NO) production in patients with pregnancy-induced hypertension or preeclampsia and in controls.Four groups of pregnant women were included: 17 patients with pregnancy-induced hypertension, ten with mild or moderate preeclampsia, 17 with severe preeclampsia, and 44 normotensive women matched for weeks of gestation at blood sampling with the cases. Plasma levels of L-citrulline and L-arginine were measured by using high-performance liquid chromatography.The mean plasma levels of L-citrulline and the ratio of L-citrulline to L-arginine, which reflects NO production, were higher in women with severe preeclampsia than in controls, patients with pregnancy-induced hypertension, and patients with mild or moderate preeclampsia.Nitric oxide production is enhanced in severe preeclampsia, possibly as a compensatory phenomenon for the increased synthesis and release of vasoconstrictors and platelet-aggregating agents.


2000 - Indirect evidence that estrogen replacement therapy stimulates nitric oxide synthase in postmenopausal women. [Articolo su rivista]
F., Piccinini; L., Rovati; A., Zanni; Cagnacci, Angelo; Volpe, Annibale; Facchinetti, Fabio
abstract

The aim of the study was to investigate the effects of estrogen replacement therapy (ERT) on nitric oxide (NO) activity in healthy postmenopausal women. The study group consisted of 22 postmenopausal women (last menses at least 12 months prior to study entry) who were randomized to receive treatment for 2 months with patches that delivered either 50 micrograms/day of 17 beta-estradiol or placebo in a cross-over design. Blood samples for measurements of serum citrulline and arginine were collected at the start of the study and at the end of each treatment course. Serum citrulline and arginine were measured using high-performance liquid chromatography with fluorometric detection. Arginine levels were significantly lower in the ERT group compared to the placebo group, while citrulline levels did not change. The percentage citrulline/arginine ratio was significantly higher in the ERT group (42.9 +/- 21.6) compared to the placebo group (33.9 +/- 18.5) (p < 0.01). The citrulline/arginine ratio, both at baseline and during either ERT or placebo administration demonstrated a positive linear correlation with body mass index (BMI). No correlations were found between follicle stimulating hormone, estradiol and insulin levels and BMI. No correlations were found between age, time since menopause and baseline arginine and citrulline levels or the citrulline/arginine ratio. These data indirectly demonstrate that transdermal estradiol replacement in postmenopausal women is able to stimulate NO production through the involvement of endogenous L-arginine. A positive linear correlation was found between BMI and the citrulline/arginine ratio, suggesting an additional protective cardiovascular effect in overweight women.


2000 - Nitric oxide in the prevention of pre-eclampsia [Articolo su rivista]
C., Picciolo; N., Roncaglia; Neri, Isabella; F., Pasta; A., Arreghini; Facchinetti, Fabio
abstract

Objective The purpose of this study was to determine whether nitric oxide improved maternal and fetal outcome in women at high risk for recurrent pre-eclampsia. Study design A total of 68 patients at risk for developing pre-eclampsia were randomly allocated into two arms: one included patients treated with glyceryl trinitrate transdermal patch (5 mg/24 h, Schwarz-Pharma, Italy) for 14-16 h/day, starting from the 16th until the 38th week and one consisting of patients undergoing observation only. Results The occurrence of pre-eclampsia was similar in the two groups, being 31.6% in the treated women and 23.4% in the untreated ones. The patients treated with glyceryl trinitrate showed a neonatal birth weight, gestational age at delivery, rate of emergency Caesarean section and rate of premature delivery similar to those of the untreated group. At entry, the bilateral notches on the uterine arteries were similar. At the 24th week, patients treated with glyceryl trinitrate showed a significant reduction in the bilateral notch (p < 0.05). No change in the umbilical artery and middle-cerebral artery pulsatility indices were observed in the two groups. Conclusions Nitric oxide donor significantly improved uteroplacental blood flow. No change in fetal outcome was observed.


2000 - Nonpharmacological treatment of Hyperemesis gravidarum [Articolo su rivista]
Neri, I.; Fazzio, M.; Facchinetti, F.
abstract

Hyperemesis gravidarum, with severe nausea and vomiting causing in patients weight loss and dehydration, is a real discomforting situation for pregnant women and for their family and working life. Currently the conventional treatments of Hyperemesis includes simple advises concerned how to eat and drugs such as metoclopramide, corticosteroids and group B complex vitamins, since it was shown their effectiveness in improving nausea and vomiting and their safety. Anyway still now no one of this drug could totally eliminate the symptoms, maybe because the Hyperemesis gravidarum has a multifactorial ethiology. For this reason, in the last ten years a non pharnmacological approach had been proposed. It was proved in severals works that acupuncture treatment, by the PC6 point stimulation, improves the Hyperemesis symptoms in half of the cases studied, but because of some methodologic mistakes is still impossible to confirm its real effectiveness. In a new study, real acupuncture versus sham acupuncture, patients were randomised in three different groups, according to Traditional Chinese Medicine. Notwithstanding the rigour of the study, there are still some limits in it, for instance sham acupuncture is still not considered a believable placebo. Moreover the only study published for the phytotherapy is about the use of ginger (Zingiber Officinale) in pregnant women with Hyperemesis; these women were treated with ginger (250 mg four time in a day) or with placebo. Ginger didn't improve nausea and vomiting more than placebo.


2000 - Platelet responsiveness to L-arginine in hypertensive disorders of pregnancy [Articolo su rivista]
Neri, Isabella; F., Piccinini; M., Marietta; Facchinetti, Fabio; Volpe, Annibale
abstract

Objective: In chronically hypertensive (CH), preeclamptic (PE), and normotensive pregnant women (N), we investigated ex vivo platelet aggregation in response to L-arginine (L-Arg) and sodium nitroprusside (SN), which are respectively the substrate and donor of nitric oxide (NO). Methods: Platelet aggregation was determined with a dual-channel aggregometer by measuring transmittance of light through the sample in comparison to platelet poor plasma, as a reference. Aggregation induced by adenosine diphosphate was continuously recorded for 3 min and measured before and after preincubation with L-Arg and SN. Results: Preincubation with L-Arg significantly reduced platelet aggregation in N and CH patients (p < 0.05) but not in PE women. Preincubation with SN affected aggregation in PE women also (p < 0.001). No correlation was found between platelet response to L-Arg or SN stimuli and the severity of hypertensive disorders expressed as week of gestation at delivery or birth weight. Conclusions: The present study demonstrates that a decreased platelet sensitivity to L-Arg characterizes PE women, whereas SN maintains its antithrombotic power. This impairment seems to be specific for PE, because platelets of CH patients utilize L-Arg normally. This finding supports the involvement of the L-Arg-NO pathway in the pathogenesis of the procoagulative features of PE and probably in the onset of the disease. The maintained response to SN in PE patients suggests a possible therapeutical use of NO donors in the disease.


2000 - Seminal plasma nitrite/nitrate and intratesticular Doppler flow in fertile and infertile subjects. [Articolo su rivista]
C., Battaglia; S., Giulini; G., Regnani; R. D., Girolamo; S., Paganelli; Facchinetti, Fabio; Volpe, Annibale
abstract

The objective of the present study was prospectively to evaluate the role of nitric oxide (NO) in modulating intratesticular blood flow and sperm function. A total of 56 males, undergoing assisted reproduction, were divided into three groups according to semen analysis: (i) normozoospermic (n = 16); (ii) oligozoospermic (n = 21); and (iii) azoospermic (n = 19). All the subjects were submitted to hormone analysis [luteinizing hormone, follicle stimulating hormone (FSH), growth hormone, testosterone, androstenedione, insulin], and to ultrasonographic (testicular volume) and Doppler (transmediastinal artery) evaluations. Plasma and seminal plasma nitrite/nitrate concentrations, and plasma insulin-like growth factor-I were assayed. All 56 patients completed the study. In normozoospermic patients, significantly greater testicular volume, lower transmediastinal resistances, and higher seminal plasma nitrite/nitrate concentrations were observed in comparison with both oligo- and azoospermic subjects. Testicular volume was inversely correlated with plasma FSH (r = -0.589; P = 0.005) and pulsatility index of transmediastinal artery (r = -0.402; P = 0.049). Furthermore, the seminal plasma nitrite/nitrate concentrations were inversely correlated with pulsatility index of transmediastinal artery (r = -0.511; P = 0.015). It was concluded that NO is involved in vascular modulation of testicular vessels and ultimately in sperm output.


2000 - Stress-response in male partners of women submitted to in vitro fertilization and embryo transfer. [Articolo su rivista]
M., Tarabusi; M. L., Matteo; Volpe, Annibale; Facchinetti, Fabio
abstract

In a previous work, we have reported the relationship between women and the outcome of in vitro fertilization and embryo transfer (IVF-ET). The goal of the present work is to evaluate the association between vulnerability to stress and treatment outcome in male partners of couples submitted to IVF-ET.The day of semen collection at the Assisted Reproduction Unit of the Department of Obstetrics and Gynecology, University of Modena, 45 subjects were submitted to Stroop Color Word Conflict, a task measuring the ability to cope with a cognitive stressor, involving the attentional and sympathoadrenal system. Systolic and diastolic blood pressure, as well as heart rate (HR), were measured at baseline, during the test and 10 min after the end of testing. The evidence of pregnancy (betahCG >250 mIU/ml 12 days after ET) is the main outcome measure; the couples were classed in either a 'success' or a 'failure' group.Thirteen couples became pregnant. Pregnancy progressed until term in 6 cases, while 7 cases showed only a preclinical evidence of pregnancy. Age, education, causes and duration of infertility were similar in the success and failure groups. No difference was found in the number and motility of spermatozoa both at baseline and after capacitation (a technique improving sperm motility). Moreover, the success group showed a higher number of both fertilized oocytes and embryos transferred compared with the failure group. The area under the curve of the cardiovascular parameters was calculated. The failure group showed a higher value for HR (50.6 +/- 36.7 of percent total change) than the success group (31.8 +/- 16.9; p = 0.006).The cardiovascular response to stress is a good correlate of success in infertile males submitted to the IVF-ET program.


1999 - Adjuvant L-arginine treatment for in-vitro fertilization in poor responder patients [Articolo su rivista]
Battaglia, C; Salvatori, M; Maxia, N; Petraglia, F; Facchinetti, Fabio; Volpe, Annibale
abstract

The objective of the present study was prospectively and randomly to evaluate the role of L-arginine in improving uterine and follicular Doppler flow and in improving ovarian response to gonadotrophin in poor responder women. A total of 34 patients undergoing assisted reproduction was divided in two groups according to different ovarian stimulation protocols: (1) flare-up gonadotrophin-releasing hormone analogue (GnRHa) plus elevated pure follicle stimulating hormone (pFSH) (n = 17); and (11) flare-up GnRHa plus elevated pFSH plus oral L-arginine (n = 17), During the ovarian stimulation regimen, the patients were submitted to hormonal (oestradiol and growth hormone), ultrasonographic (follicular number and diameter, endometrial thickness) and Doppler (uterine and perifollicular arteries) evaluations. Furthermore, the plasma and follicular fluid concentrations of arginine, citrulline, nitrite/nitrate (NO2-/NO3-), and insulin-like growth factor-1 (IGF-1) were assayed. All 34 patients completed the study. In the L-arginine treated group a lower cancellation rate, an increased number of oocytes collected, and embryos transferred were observed, In the same group, increased plasma and follicular fluid concentrations of arginine, citrulline, NO2-/NO3-, and IGF-1 was observed, Significant Doppler flow improvement was obtained in the L-arginine supplemented group. Three pregnancies were registered in these patients. No pregnancies were observed in the other group. It was concluded that oral L-arginine supplementation in poor responder patients may improve ovarian response, endometrial receptivity and pregnancy rate.


1999 - Disagio psicologico della sindrome climaterica: effetto del tempo [Relazione in Atti di Convegno]
Facchinetti, Fabio; Piccinini, F; Neri, Isabella; Cagnacci, Angelo; Volpe, Annibale
abstract

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1999 - Effect of L-Arginine load on platelet aggregation: a comparison between normotensive and preeclamptic pregnant women [Articolo su rivista]
Facchinetti, Fabio; Neri, Isabella; Piccinini, F; Marietta, M; Torelli, U; Bruschettini, Pl; Volpe, Annibale
abstract

Background In the present study we hypothesized that a derangement of the L-Arginine-Nitric Oxide system could be involved in the development of the hypercoagulative status found during preeclampsia. In order to verify such hypothesis we have compared the effects of Nitric Oxide substrate, L-Arginine on platelet aggregation. Moreover, we have also measured the L-Citrulline plasma levels as a stechiometric metabolite resulting from the conversion L-Arginine to Nitric Oxide. Methods. Nine preeclamptic women and 11 normotensive pregnant women were enrolled for the study. Subjects were infused with saline and with 30gr of L-Arginine. Blood samples were drawn during the saline infusion (30 min), during L-Arginine administration (30 min) and 30 min thereafter. ADP and Collagen-induced platelet aggregation was studied as per Born with a dual-channel aggregometer (Chrono-Log, Mascia Brunelli, Italy) and L-Citrulline was measured by HPLC. Results. In normotensive women the infusion significantly decreased ADP and Collagen-induced aggregation after 15 minutes of L-Arginine load; whereas no effects were observed in preeclamptic women. Similarly in normotensive but not in preeclamptic women L-Arginine load was able to increase L-Citrulline plasma levels. Conclusions. In normotensive women the in vivo L-Arginine administration decreases platelet aggregation with an increase of L-Citrulline plasma levels. On the contrary, no effects were observed in preeclamptic women. These findings confirm that a hypercoagulative status characterizes preeclampsia and that such phenomenon could be explained by a derangement of the platelet L-Arginine-Nitric Oxide pathway.


1999 - Effect of long-term local or systemic hormone replacement therapy on post-menopausal mood disturbances. Influences of socio-economic and personality factors. [Articolo su rivista]
Cagnacci, Angelo; Neri, Isabella; M., Tarabusi; Volpe, Annibale; Facchinetti, Fabio
abstract

To clarify the effect exerted by hormone replacement therapy (HRT) versus socio-economic and personality factors in improving postmenopausal mood disorders.The effect of the 1-year administration of systemic hormone replacement therapy (HRT; n = 22) or a vaginal cream of estriol (n = 14) versus no treatment (n = 26) was evaluated on mood states of anxiety, depression, somatization and inadequacy, as evaluated by the symptom rating test (SRT) scale. Results were correlated with the woman socio-economic status, and her capability to cope with daytime distresses, as evaluated by the Coping Style questionnaire.A spontaneous decline of all SRT scores, except that of inadequacy, was observed in the group with no treatment. In comparison HRT induced a greater improvement of only the SRT score of inadequacy (P < 0.01) and to a lesser extent of anxiety (P < 0.06). Similarly, vaginal estriol induced a greater decline of the SRT score of inadequacy (P < 0.01). Multiple regression analysis showed that modifications of the total SRT score and the SRT score of anxiety were related mainly to socio-economic factors, while those of the SRT score of depression were related only to the coping style of the woman. The decline of somatization was related only to time since the menopause while, the reduction of the SRT score of inadequacy was only the consequence of therapy, either systemic or local.In a 1-year period improvement of post-menopausal psychological discomfort, is spontaneous and independent of therapy. Only symptoms of inadequacy are improved by the hormonal therapy. Likely, the perceived menopausal 'losses' make the woman to feel inadequate and the use of sex-related hormones is capable to improve this feeling.


1999 - Effect of nitric oxide and carbon monoxide on uterine contractility during human and rat pregnancy [Articolo su rivista]
M., Longo; V., Jain; Yp, Vedernikov; Gr, Saade; L., Goodrum; Facchinetti, Fabio; Re, Garfield
abstract

OBJECTIVE: We sought to study the effects of authentic nitric oxide and carbon monoxide on the contractile activity of pregnant human and rat myometrium. STUDY DESIGN: Strips were prepared from uterine biopsy specimens of 10 pregnant, nonlaboring women at term gestation undergoing cesarean delivery. In addition, rings were prepared from the uteri of pregnant rats at midterm (day 14) and at term (day 22) gestation (n = 10-12). The tissues were mounted in organ chambers filled with Krebs-Henseleit solution continuously aerated with 5% carbon dioxide in air (37 degrees C, pH similar to 7.4) for isometric tension recording. The effects of nitric oxide and carbon monoxide gases on spontaneous contractile activity were studied. Responses to hemin (hemoxygenase substrate), which produces endogenous carbon monoxide, were also examined. Responses to nitric oxide and carbon monoxide were also studied in aortic and tail artery rings from pregnant rats after contraction with phenylephrine. RESULTS: Nitric oxide significantly inhibited contractility of human myometrium at term (area under the concentration-response curve, 145.36 +/- 30.02 vs 40.56 +/- 22.81 in controls; P < .05) and rat myometrium at midterm gestation (264.23 +/- 47.86 vs 121.82 +/- 23.50; P < .05) but not at term. No statistically significant inhibition was induced in human or rat myometrium by carbon monoxide, whereas hemin significantly attenuated contractility in human myometrium at term and in rat myometrium at midterm gestation (P < .05). Nitric oxide, carbon monoxide, and hemin relaxed aortic and tail artery rings. CONCLUSIONS: Authentic nitric oxide inhibits rat uterine contractile activity at midterm gestation but not at term. However, nitric oxide inhibits human myometrium activity at term. Authentic carbon monoxide does not appear to modulate uterine contractility, whereas hemin may have some inhibitory properties.


1999 - Effetti del trattamento a lungo termine sui disturbi dell’ umore in postmenopausa: influenza dei fattori psicosociali [Altro]
Facchinetti, Fabio; Piccinini, F; Neri, Isabella; Cagnacci, Angelo; Volpe, Annibale
abstract

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1999 - Effetto della terapia estrogenica sul ritmo circadiano della pressione arteriosa e sulla rattività vascolare della donna a basso rischio cardiovascolare. [Abstract in Atti di Convegno]
Cagnacci, Angelo; Zanni, A; Malmusi, S; Arangino, S; Landi, S; Facchinetti, Fabio; Volpe, Annibale
abstract

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1999 - Effetto della terapia estrogenica sul ritmo circadiano della pressione arteriosa e sulla reattività vascolare della donna a basso rischio cardiovascolare [Relazione in Atti di Convegno]
Cagnacci, Angelo; Zanni, Al; Malmusi, S; Arangino, S; Landi, S; Facchinetti, Fabio; Volpe, Annibale
abstract

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1999 - European pshychosomatic Obstetrics and ginecology 1999 [Curatela]
Facchinetti, Fabio; P., Nijs; D., Richter
abstract

..


1999 - Influence of melatonin on nitric oxide synthesis in postmenopausal women with and without estrogens [Altro]
Cagnacci, Angelo; Malmusi, S; Arangino, S; Facchinetti, Fabio; Volpe, Annibale
abstract

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1999 - L-arginine infusion reduces blood pressure in preeclamptic women through nitric oxide release [Articolo su rivista]
Facchinetti, Fabio; M., Longo; F., Piccinini; Neri, Isabella; Volpe, Annibale
abstract

OBJECTIVE: This study, investigates the biochemical and cardiovascular effects of L-arginine administration in normotensive pregnant women and women with preeclampsia. METHODS: The study groups consisted of 12 women with uncomplicated pregnancies and 17 preeclamptic patients, four of whom were on antihypertensive treatment. In both groups, saline infusion was started, followed by 30 g L-arginine administration, and finally more saline. Blood pressure was recorded every 5 minutes and blood samples were collected for measurement of serum citrulline, arginine, and nitrite levels. Amino acid assays were done by using high-performance liquid chromatography with fluorometric detection. RESULTS: L-Arginine infusion was associated with a significant reduction of blood pressure in both groups, the decrease being greater in the women with preeclampsia. Baseline serum citrulline and arginine level were nor significantly, different between the two groups. L-Citrulline levels were significantly increased during infusion of L-arginine, and the increase was significantly lower in the women with preeclampsia. Serum nitrite levels were increased only in controls and not in preeclampsia patients. The total citrulline production stimulated by L-arginine was related inversely to baseline blood pressure values and was unrelated to clinical parameters such as gestational age at delivery, birth weight, and Apgar score. CONCLUSIONS: L-Arginine load in pregnant women is associated with increased nitric oxide (NO) production and hypotension. Despite a reduced ability to produce NO, patients with preeclampsia may benefit from L-arginine supplementation. Overall, these findings partially support the hypothesis that preeclampsia is characterized by a dysfunction of the L-arginine-NO pathway. Copyright (C) 1999 by the Society for Gynecologic Investigation.


1999 - Physiological doses of estradiol decrease nocturnal blood pressure in normotensive postmenopausal women. [Articolo su rivista]
Cagnacci, Angelo; Rovati, L; Zanni, A; Malmusi, S; Facchinetti, Fabio; Volpe, Annibale
abstract

The effect of a 2-mo treatment with transdermal estradiol (50 microgram/day) versus placebo on 24 h of blood pressure rhythm was investigated in 18 normotensive healthy postmenopausal women. Whereas daytime blood pressure was not modified, nighttime blood pressure was reduced by estradiol. Estradiol magnified the nocturnal decrement of systolic (14.3 +/- 7.2 vs. 9.8 +/- 6.7 mmHg, P = 0. 0033), diastolic (11.6 +/- 5.0 vs. 7.5 +/- 7.3 mmHg, P = 0.028), and mean (10.8 +/- 5.6 vs. 7.2 +/- 4.5 mmHg, P = 0.011) blood pressure. As a consequence, the 24-h rhythm of mean blood pressure was restored in 50% of the subjects (P = 0.045) in whom it was absent and was amplified in the remaining 50% of the subjects. Body mass index was an independent determinant of blood pressure values being directly related to the amplitude of the 24-h mean blood pressure rhythm (r2 = 0.38; P = 0.0067). In normotensive postmenopausal women, physiological doses of estradiol amplify the nocturnal decline of blood pressure.


1999 - Platelet reactivity during estrogen replacement treatment in postmenopausal women [Abstract in Rivista]
Marietta, M; Castelli, I; Cagnacci, Angelo; Malmusi, S; Bertesi, M; Piccinini, F; Neri, Isabella; Facchinetti, Fabio; Torelli, G.
abstract

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1999 - Proopiomelanocortin (POMC) mRNA and POMC-derived peptides immunolocalization in the skin of Protopterus annectens, an African lungfish [Articolo su rivista]
Masini, Ma; Sturla, M; Pestarino, M; Facchinetti, Fabio; Gallinelli, A; Uva, Bm
abstract

Antisera against adrenocorticotropic hormone (ACTH), alpha-melanocyte stimulating hormone (alpha-MSH) and beta-endorphin were used to localize, by immunohistochemistry, proopiomelanocortin (POMC)-derived peptides in the skin excised from different regions of the African lungfish Protopterus annectens. Immunoreactivity was observed in the epidermis mainly in the germinal layer. Using human POMC cDNA as hybridization probe, POMC-like mRNA was identified in situ in epidermal cells. The demonstration in the same cells of POMC mRNA and POMC-related peptides immunoreactivity indicates a local production of opiate hormones.


1999 - 24 HOURS AMBULATORY BLOOD PRESSURE MONITORING: A COMPARISON BETWEEN TRANSDERMAL GLICERYL-TRINITRATE AND ORAL NIFEDIPINE [Articolo su rivista]
Neri, Isabella; H., Valensise; Facchinetti, Fabio; S., Menghini; C., Romanini; Volpe, Annibale
abstract

The objective of the present study is to compare the effectiveness of transdermal glyceryl-trinitrate versus oral nifedipine in lowering blood pressure in patients affected by pregnancy-induced hypertension (PIH). Thirty-six consecutive pregnant women have been evaluated at different gestational ages after the diagnosis of PIH or preeclampsia (PE). After a 24-h ambulatory blood pressure monitoring, patients were allocated to three groups: those receiving oral nifedipine and those receiving transdermal glyceryl-trinitrate in a continuous (24 h/day) or intermittent (16 h/day) administration. A second blood pressure monitoring was performed after 2 weeks of treatment. Systolic and diastolic blood pressure were compared by using the Cosinor method looking at mesor, amplitude, and acrophase. Baseline systolic and diastolic blood pressure was similar among the three groups. Neither the transdermal glyceryl-trinitrate administered for 24 or 16 h nor oral nifedipine affected systolic and diastolic blood pressure. Analysis of variance showed that the posttreatment values were similar among the groups. Further studies are needed to verify the possible use of transdermal glyceryl-trinitrate sis an antihypertensive drug during pregnancy.


1998 - A randomized comparison of vaginal prostaglandin E-2 with oxytocin plus amniotomy for induction of labour in women with intermediately ripe cervices [Articolo su rivista]
Parazzini, F; Benedetto, C; Danti, L; Zanini, A; Facchinetti, Fabio; Ettore, G; Franchi, M; Bertulessi, C; Caruso, A.
abstract

Objective: To compare the effects of oxytocin and amniotomy or vaginal prostaglandin E-2 (PGE(2)) for induction of labour. Study design: We conducted a randomized clinical trial. Eligible for the trial were women with normal pregnancy, parity 0-3, with intact membranes, >40 weeks of gestation documented by ultrasound examination before 20 weeks gestation, observed in a network of 13 general and teaching hospitals in Italy. Inclusion criteria were cervical Bishop's score 5-7, less than six uterine contractions per hour, single pregnancy, cephalic presentation, no history of cesarean section and uterine surgery. Eligible women were randomly assigned by phone to oxytocin plus amniotomy (163 women) or vaginal PGE(2) 2 mg, two doses at 6-h intervals (157 women). Results: Overall, 50 women (15.6%) delivered by cesarean section, 22 (13.5%) randomized to oxytocin, and 28 (17.8%) randomized to PGE(2) (not significant). Twelve hours after randomization, induction had failed in 26 women of the 163 randomized to oxytocin plus amniotomy (21.6%) and 34 out of the 157 randomized to PGE(2) (15.9%): the difference was not significant. Neonatal outcome was similar in the two groups. Conclusions: This study did not find marked differences in labour and neonatal outcome between women randomized to oxytocin plus amniotomy or vaginal PGE(2). A shorter induction delivery interval in the group receiving amniotomy and oxytocin after PGE(2) priming was observed. (C) 1998 Elsevier Science Ireland Ltd All rights reserved.


1998 - Acetyl salmon endorphin-like and interrenal stress response in male gilthead sea bream, Sparus aurata [Articolo su rivista]
Mosconi, G; Gallinelli, A; Polzonetti Magni, Am; Facchinetti, Fabio
abstract

The present study investigates the role of melanotrope proopiomelanocortinderived peptide in the interrenal stress response to different stressors in male gilthead sea bream, Sparus aur ata. Plasma cortisol and acetyl salmon endorphin (acetyl s-EP), as well as pituitary acetyl s-EP contents, were measured during two stress paradigms: (a) long-term (l-month) confinement and crowding, and (b) short-term (60-min) confinement, crowding, and manipulation. In addition, naltrexone, a highly specific opioid receptor antagonist, was employed in some experimental groups to evaluate the adaptability of the opioid response to interrenal stress. In the long-term (I-month) confinement and crowding, higher plasma cortisol levels and acetyl s-EP concentrations than in the control group were found. However, although plasma cortisol levels significantly increased in both types of stress paradigm, a significant rise in plasma acetyl s-EP was observed only in the case of confinement plus crowding. These data seem to suggest a direct correlation of acetyl s-EP plasma levels exclusively in cases of specific stress, and support previous observations about the different nature of the pituitary-interrenal stress response in salmonids and in mammals. The results obtained in the short-term (60-min) experiments demonstrate the double activation of both the opioid and corticotrope systems when manipulation plus crowding was applied.


1998 - Assessment of platelet function in pregnancy with the PFA-100 (TM) system [Abstract in Atti di Convegno]
Marietta, M; Neri, Isabella; Piccinini, F; Facchinetti, Fabio; Bertesi, M; Torelli, Giuseppe
abstract

Assessment of platelet function in pregnancy with the PFA-100 (TM) system


1998 - Diagnostic ability of the Italian version of the 'Calendar of premenstrual experiences' [Articolo su rivista]
Facchinetti, Fabio
abstract

Objective: We produced an Italian version of the Calendar of Premenstrual Experiences (COPE). We have reported its ability to assess premestrual syndrome in patients who believe themselves to be sufferers from this syndrome. Methods: Twenty-eight patients previously diagnosed with Menstrual Distress Questionnaire were included in Premenstrual Syndrome (PMS) group. Seventeen patients who believed themselves to be PMS sufferers but who did not fulfil the above diagnostic criteria formed the 'unconfirmed PMS' group. Twenty one candidates were screened as potential asymptomatic controls. The COPE was administered daily for 2 consecutive cycles. The individual follicular and luteal scores, as well as the total score were calculated. Results: A total luteal score 35 was enough to distinguish between controls and PMS subjects. A total luteal score 35 was unable to distinguish between PMS and unconfirmed PMS patients and a further criterion was necessary to discriminate between those groups. By using the percentage of luteal increase with respect to follicular value, a cut-off of 80% provided neither false positive or false negative values. Conclusion: Using the above reported criteria the Italian version of COPE makes it possible to correctly identify patients with PMS.


1998 - Estrogens and nitric oxide: a cardiovascular duet. [Relazione in Atti di Convegno]
Facchinetti, Fabio; Piccinini, F; Cagnacci, Angelo; Zanni, A; Volpe, Annibale
abstract

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1998 - Expression of pro-opiomelanocortin (POMC) in the cerebral ganglion and ovary of a protochordate [Articolo su rivista]
Masini, Ma; Sturla, M; Gallinelli, A; Candiani, S; Facchinetti, Fabio; Pestarino, M.
abstract

The distribution of neurones expressing POMC mRNA in the cerebral ganglion of he protochordate ascidian, Styela plicata, was investigated using a non-radioactive in situ hybridization technique. Nerve cell bodies of mono and bipolar types expressing POMC mRNA, were observed mainly in the outer layer of the ganglion. Discrete groups of neurones containing POMC mRNA were also localized in the inner portion of the ganglion, and few small monopolar perykaria expressing POMC mRNA were visible at the emergence of the main nerve trunks. POMC mRNA labeling was also found at level of the cytoplasm of previtellogenic and vitellogenic oocytes, and of follicular cells. Our results demonstrate the expression of one or more genes in the cerebral ganglion and ovary, that may be similar to one or more regions of the mammalian POMC gene. Therefore POMC-related molecules seem to be involved in neuromodulatory pathways and regulatory mechanisms of the oogenesis of ascidians.


1998 - Il decremento notturno della pressione arteriosa è potenziato dalla terapia ormonale sostitutiva in postmenopausa [Altro]
Cagnacci, Angelo; Zanni, A; Malmusi, S; Facchinetti, Fabio; Volpe, Annibale
abstract

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1998 - Il magnesio in -ginecologia e Ostericia [Monografia/Trattato scientifico]
F., Corica; A., Allegra; Facchinetti, Fabio
abstract

il magnesio


1998 - Medicina non convenzionale in Ginecologia e Ostretricia [Curatela]
Facchinetti, Fabio; G. B., Allais; C. M., Giovanardi
abstract

medicina non convenzionale


1998 - Premenstrual syndrome and anxiety disorders: A psychobiological link [Articolo su rivista]
Facchinetti, Fabio; Tarabusi, M; Nappi, G.
abstract

..


1998 - Reduction of serum citrulline levels in women at term toward the day of labor onset [Articolo su rivista]
Facchinetti, Fabio; Valensise, H; Neri, Isabella; Menghini, S; Romanini, C; Volpe, Annibale
abstract

Objective. To test the hypothesis that labor onset could be the result of a reduced release of nitric oxide (NO). Study design. Out of 91 consecutive healthy nulliparous women at term serum citrulline (Cit) and arginine (Arg) levels were measured at least twice in 37 subjects, by the means of HPLC with fluorometric detection. Twenty cases underwent a spontaneous onset of labor (group A) while in 17 cases labor was induced (group B) because of pregnancy prolongation or amniotic fluid reduction. Results. Cit and Arg levels were unaffected by the gestational age. In group A, Cit levels undergo a progressive decrease toward the day of labor (from 32.9 +/- 4.7 mu M/L the day -18,-5 to 27.7 +/- 7.8 the day -4,0; p=0.012) whilst they remained stable in group B (from 33.3 +/- 7.7 to 34.2 +/- 9.2). No significant changes were observed in Arg levels. Cit/Arg ratio remained stable in group A whereas it showed a trend to increase in group B. Conclusion. These data indirectly suggest a reduced release of NO toward term. This phenomenon could play a permissive role in the spontaneous onset of labor of healthy nulliparous women.


1998 - Serum nitrites predict the response to prostaglandin-induced delivery at term [Articolo su rivista]
Facchinetti, Fabio; A., Gandolfi; M., Longo; Volpe, Annibale
abstract

OBJECTIVE: To evaluate whether the clinical response to prostaglandin-induced labor is modulated by nitric oxide (NO) activity. METHODS: Fifty-two cases of nulliparous women at term who delivered vaginally after prostaglandin E (PGE) induction of labor were enrolled. The induction was required mainly for amniotic fluid reduction or late-onset gestational hypertension. Either intracervical (0.5 mg) or vaginal (2.0 mg) PGE was administered every 12 hours, according to the Bishop score. After the third PGE application, in absence of labor onset, intravenous oxytocin was used. Nitrites/nitrates (NOx) serum levels were used as a marker of NO activity. They were measured just before the start of induction by using an enzymatic reduction and then a colorimetric evaluation. Time to delivery from the first PGE application was the main outcome variable. RESULTS: Time to delivery ranged from 4 to 62 hours (median: 15.5). Nitrites/nitrates levels were unaffected by both gestational age, Bishop score at entry, indication allowing labor-induction, fetal position, and birth weight. In a multiple regression analysis including the previous factors, NOx levels significantly explained 33.9% of the variance of the time delivery. Indeed, patients delivering within 15 hours (26.4 +/- 6.9) showed NOx levels significantly lower than in patients delivering after more than 15 hours (39.5 +/- 16.4) from the first PGE application. CONCLUSIONS: A reduced level of NOx is associated with a prompt clinical response to PGE-induced labor. Provided we do not know the origin of NOx in the general circulation, these data indicate NOx levels as predictors of the response to PGE-induced delivery at term and support the hypothesis that labor onset is modulated by the endogenous NO activity. Copyright (C) 1998 by the Society for Gynecologic Investigation.


1998 - The L-arginine-nitric oxide system regulates platelet aggregation in pregnancy [Articolo su rivista]
Neri, Isabella; M., Marietta; F., Piccinini; Volpe, Annibale; Facchinetti, Fabio
abstract

OBJECTIVE: To investigate the ex vivo platelet aggregation in response to a substrate (L-arginine [L-Arg]) and a donor (sodium nitroprusside [SN]) of nitric oxide (NO) in nonpregnant women and in normotensive pregnancies. METHODS: Platelet aggregation was studied with a dual-channel aggregometer and expressed as a percentage of light transmission. Measurements were done at baseline and after preincubation with scalar doses of L-Arg and SN. The intraplatelet L-citrulline (L-Cit) levels were measured by high-performance liquid chromotography (HPLC). RESULTS: In both groups, the baseline aggregation values were similar for adenosine diphosphate (ADP) and collagen stimuli. Wilcoxon tank-sum testing demonstrated that in both groups the addition of L-Arg had a significant effect on aggregation: Doses of 50 to 5000 mu mol decreased ADP-induced aggregation. Conversely, collagen-induced aggregation was affected only by the highest dose of L-Arg. Sodium nitroprusside administered in doses of 2.5 to 250.0 nmol decreased ADP- and collagen-induced platelet aggregation equally. ADP-induced aggregation values obtained after (SN) incubation were positively correlated with gestational age. Intraplatelet L-Cit levels showed a significant rise after the incubation with L-Arg, and this effect was negatively correlated with gestational age. CONCLUSION: The L-Arg-NO system regulates platelet aggregation during pregnancy. Moreover, a physiologic reduction of platelet sensitivity to the antithrombotic effect of NO occurs. (J Soc Gynecol Invest 1998; 5:192-196). Copyright (C) 1998 by the Society for Gynecologic Investigation.


1998 - Transdermal estradiol reduces nocturnal blood pressure in postmenopausal women [Altro]
Cagnacci, Angelo; Rovati, L; Malmusi, S; Facchinetti, Fabio; Zanni, A; Volpe, Annibale
abstract

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1997 - Acetyl salmon endorphin-like immunoreactivity in the ovary of two teleostean species: Changes with environmental conditions [Articolo su rivista]
Facchinetti, Fabio; Radi, D; Mosconi, G; Carnevali, O; Pestarino, M; Polzonettimagni, Am
abstract

The presence of salmon acetylated endorphin (acetyl sEP) in the ovary of seabream and sea bass was investigated through immunocytochemical and biochemical techniques in order to compare aquatic species with terrestrial ones. Endorphin-like immunoreactivity was found in the cytoplasm of oogonia and similar immunostaining was present in the granulosa layer of mature follicles. In both pituitary and ovarian extracts of the two teleostean species, acetyl sEP-like immunoreactivity was distributed over three main peaks, the second one corresponding to the elution time of the reference synthetic peptide. Serial dilutions of HPLC fraction II of the ovaries of both fishes ran parallel with the standard curve obtained with reference peptide. The ovarian content of acetyl sEP, obtained by calculating the integrated area of the fraction II peak, indicates large and highly significant (p < 0.01) differences in the amount of peptide found in ovarian tissues of wild seabream in comparison with that of farmed fish. Increased peptide values in wild animals with respect to farmed fish were also found in the sea bass. These data indicate that not only the pituitary, but also the ovary is sensitive to environmental cues, and strongly suggest the role of opioid peptides in adaptation.


1997 - An increased vulnerability to stress is associated with a poor outcome of in vitro fertilization-embryo transfer treatment [Articolo su rivista]
Facchinetti, Fabio; Matteo, Ml; Artini, Gp; Volpe, Annibale; Genazzani, Ar
abstract

Objective: To evaluate the association between the vulnerability to stress and the treatment outcome of couples undergoing IVF-ET. Design: Controlled, prospective clinical study. Setting: The Assisted Reproduction Unit of the Department of Obstetrics and Gynecology, University of Modena. Patient(s): Forty-nine infertile women consecutively admitted to standard superovulation treatment. Mean age was 33.9 years, duration of infertility was 6.3 years. Reasons for assisted reproduction were mechanical factor in 22 cases, sperm problem in 9 cases, and endocrine disorder in 6 cases. In 12 cases, infertility was unexplained. More than 55% already had an IVF-ET attempt. Intervention(s): The day of oocyte pick-up, subjects were submitted to Stroop Color and Word test, a task measuring the ability to cope with a cognitive stressor, involving attentional and sympathoadrenal systems. Systolic (SEP) and diastolic blood pressure, as well as heart rate (HR) were measured at baseline, during the test, and 10 minutes after the end of testing. Main Outcome Measure(s): The evidence of a biochemical pregnancy (beta-hCG value 12 days after ET) define the success and failure groups. Result(s): Sixteen women (33%) had a biochemical pregnancy, 12 also had ultrasound evidence. Eight gave birth to healthy infants. Age, education, causes, and duration of infertility were similar in the success and failure groups. The latter were more involved in a job outside home than the former. Moreover, they had a lower number of both fertilized oocytes and transferred embryos. In response to the Stroop test, every subject reported an increase of cardiovascular parameters. However, women becoming pregnant showed a lower response of both SEP and HR than women who failed. Conclusion(s): Both a major cardiovascular vulnerability to stress and working outside home are associated to a poor outcome of IVF-ET treatment.


1997 - BODY IMAGE IN SECONDARY AMENORRHEA [Articolo su rivista]
E., Orlandi; G. P., Guaraldi; Facchinetti, Fabio
abstract

..


1997 - Cardiovascular response to cognitive stress in subjects with menstrually related disorders [Articolo su rivista]
Tarabusi, M; Caputo, As; Volpe, Annibale; Facchinetti, Fabio
abstract

We measured reactivity to a stress paradigm during the premenstrual period in 19 women affected by Menstrually Related Disorders (MRD) and in 11 normal controls. Eight had premenstrual syndrome diagnosed by the Menstrual Distress Questionnaire and 11 suffered menstrual migraine, diagnosed according to International Headache Society criteria. Subjects were observed during two menstrual cycles and submitted to a psychocognitive test (Stroop Color Word) during the luteal phase. in both groups the stimulation by Stroop C-W was present for systolic blood pressure (SEP) (F=18.14, p=0.000), diastolic blood pressure (DBP) (F=9.56, p=0.000), and heart rate (F=12.80, p=0.000). Moreover, an interaction of response by group was present for DBP (2.58, p=0.04); DBP values were higher in MRD subjects. Also baseline DBP values were higher in MRD with respect to controls. Area under the curve (AUG) subtracted from baseline for the SEP, DBP and heart rate did not differ between groups. In conclusion, MRD subjects facing a cognitive stress had normal cardiovascular response. However, patients had increased arousal of cardiovascular measures before and after testing. The significant differences during stress of testing were dissociated from those of experimental stress stimulation. MRD subjects may have less ability to cope with novelty than healthy volunteers.


1997 - Coping style and climacteric symptoms in a clinical sample of postmenopausal women [Articolo su rivista]
Neri, Isabella; Demyttenaere, K; Facchinetti, Fabio
abstract

Hormonal changes as well or sociocultural and personal factors account for climacteric symptoms. The aim of this study is to investigate in a clinical population the correlation between the severity of hot flashes and vaginal dryness and the 'coping-ineffectiveness of coping' construct. Out 120 women consecutively referring to the University Menopause Clinic, 85 subjects were evaluated for their climacteric complaints including anxiety and depression and for their coping style assessed with the Italian version of the Utrechtse Coping Lijst. Daily hot flashes and severe vaginal dryness were reported by almost half of the studied population, regression analyses were performed in order to investigate how much of the variance in such symptoms was explained by the psychosocial variables and by the coping mechanisms. A more recent menopause, a lower educational level and an active coping predict a higher severity of hot flashes; a longer time since last menstrual period and a coping of avoidance predict a higher severity of vaginal dryness. The present study suggests that the severity of hot flashes and vaginal dryness among a clinical sample of postmenopausal women is not only determined by biological and social variables, but personal resources also explain part of the variance of such climacteric complaints.


1997 - Effects of a yeast-based dietary supplementation on premenstrual syndrome - A double-blind placebo-controlled study [Articolo su rivista]
Facchinetti, Fabio; Nappi, Re; Sances, Mg; Neri, Isabella; Grandinetti, G; Genazzani, A.
abstract

A dietary approach has proven to be effective in alleviating symptoms of premenstrual syndrome. In our previous studies, magnesium improved premenstrual irritability and mood scoings. In this double-blind, placebo-controlled study, we evaluated the effects of a new dietetic preparation (Sillix Donna(R), Giuliani) in 40 patients affected by mild to moderate premenstrual syndrome. Premenstrual symptoms were scored in both follicular and luteal phases, at baseline, at 2nd, 4th and 6th month of treatment by using the Menstrual Distress Questionnaire (MDQ). Twenty patients were randomised to receive the active preparation and 20 placebo. MDQ scores at baseline were similar in the two groups. Five patients of the placebo group dropped out because of treatment failure. No side effects were observed. Both treatments reduced symptoms already in the 2nd month, but the active preparation was more effective at all time controls (p < 0.05); at the 6th month it significantly reduced premenstrual MDQ scores to 18% of baseline values, placebo only to 73%. These data demonstrate that Sillix Donna is effective in reducing premenstrual distress.


1997 - Estrogeni e ossido nitrico: un sinergismo. [Altro]
Facchinetti, Fabio; Longo, M; Malmusi, S; Cagnacci, Angelo; Piccinini, F; Volpe, Annibale
abstract

-


1997 - Headache and menstrually related disorders: in search of a consensus [Curatela]
G., Nappi; Facchinetti, Fabio; F., Rossi
abstract

cephalea, PMS


1997 - Headache and menstrually related disorders: In search of a consensus - Preface [Prefazione o Postfazione]
G., Nappi; Facchinetti, Fabio; F., Rossi
abstract

N/A


1997 - Influence of melatonin on nitrite levels of postmenopausal women with and without estrogens [Abstract in Rivista]
Cagnacci, Angelo; Facchinetti, Fabio; Longo, M; Malmusi, S; Tarabusi, M; Zanni, A; Volpe, Annibale
abstract

-


1997 - L-arginine displays antithrombotic effects through nitric oxide release in pregnant women [Articolo su rivista]
Facchinetti, Fabio
abstract

OBJECTIVE: Nitric Oxide (NO) has antiaggregating properties. Our aim was to evaluate if a load of I-Arginine (ARG), the substrate for NO production, could affect platelet aggregation in pregnancv. STUDY DESIGN: After informed consent, 9 healthy women in follicular phase (('.) and 8 women with uncomplicated pregnancy (P) at 3Q-36th week were infused with i.v. ARG &lt;30g/30 min). Blood samples were taken before and 15. 30, 60, &amp; 90 min thereafter. Aggregation was evaluated in vitro through the addition of ADP (2jJiM) or Collagen (4fxg/ml) to platelet-rich plasma, hv using a dual channel aggregometer. I-Citrulline (CIT) levels wert- evaluated in ihe serum bv using HPI.C with fluorimetric detection. RESULTS: In group C, ARG infusion significantly and transiently inhibited platelet aggregation induced by both ADP (from 65 ±5.5% to 42 ±10.4%) and Collagen (from 70.4 ±'.5.4% to 56.4 ±7.3%) (p &lt; 0.01 at 15tb min, for either stimulations). In group P a similar effect was observed, lasting also at 30th min of infusion. However, the reduction of aggregation induced bv ARG in C (ADP -28% &amp; Collagen -19%, in respect with baseline) was wider than in P group (ADP -13% &amp; Collagen - 11%, I' &lt; 0.05). In both C (from 32.3 ±4.2 jtM/L to 71.6 ±9.2) and P groups (from 31.1 ±3.6 to 53.1 ±6.8) CIT levels were increased at 30th min (P &lt; 0.02). The increase in P group (65%) was of lower magnitude than in C (112%, p &lt; 0.05). CONCLUSIONS: ARC. load in pregnant women as well as in non-pregnani controls is able to reduce the platelet aggregation, tested in vitro. Such an amithrombotic effect is correlated with an up-regulation of NO svnthase whose magnitude is reduced in pregnancy.


1997 - L-arginine infusion decreases platelet aggregation through an intraplatelet nitric oxide release [Articolo su rivista]
M., Marietta; Facchinetti, Fabio; Neri, Isabella; F., Piccinini; Volpe, Annibale; Torelli, Giuseppe
abstract

..


1997 - Modulazione della pressione arteriosa in donne in postmenopausa trattate con estradiolo transdermico [Altro]
Zanni, A; Cagnacci, Angelo; Sgarbi, L; Malmusi, S; Sgherzi, Mr; Longo, M; Facchinetti, Fabio; Volpe, Annibale
abstract

-


1997 - PROGRAMME AND BOOK OF ABSTRACTS OF THE INTERNATIONAL CONGRESS ON NITRIC OXIDE IN REPRODUCTIVE AND PERINATAL MEDICINE [Articolo su rivista]
G. C., Di Renzo; Facchinetti, Fabio; G. L., Bruschettini
abstract

..


1997 - Pro-opiomelanocortin (POMC) expression and immunolocalization of POMC-related peptides in the ovary of Protopterus annectens, an African lungfish [Articolo su rivista]
Masini, Ma; Sturla, M; Pestarino, M; Gallinelli, A; Facchinetti, Fabio; Uva, Bm
abstract

Antisera against adrenocorticotropic hormone (ACTH), alpha-melanocyte-stimulating hormone (alpha MSH) and beta-endorphin were used to localize pro-opiomelanocortin (POMC)-derived peptides in the ovary of the African lungfish Protopterus annectens by immunohistochemistry. Immunoreactivity was observed in the granulosa and the internal theca of the virellogenic follicles. No immunoreactivity was observed in immature follicles. Using human POMC cDNA as the hybridization probe, POMC-like mRNA was identified in situ in cells of the granulosa and internal theca of the vitellogenic follicles. No labeling was observed in primordial follicles. The demonstration in the same cells of POMC mRNA and POMC-related peptides immunoreactivity indicates a local production of the opiate hormones.


1997 - Role of melatonin in the regulation of women circadian rhythms [Abstract in Rivista]
Cagnacci, Angelo; Facchinetti, Fabio; Yen, Ssc; Volpe, Annibale
abstract

-


1997 - Stress and infertility: ''The chicken or the egg?'' Reply [Articolo su rivista]
Facchinetti, Fabio; Volpe, Annibale
abstract

..


1996 - Effects of L-arginine on utero-placental circulation in growth-retarded fetuses [Articolo su rivista]
Neri, Isabella; V., Mazza; Volpe, Annibale; Mc, Galassi; Facchinetti, Fabio
abstract

Background. To evaluate the effects of L-arginine (ARG) infusion, the nitric oxide as substrate, on the utero-placental circulation at third trimester. Methods. Three groups of nine pregnant women each were infused i.v. with 30 g ARG, for 30 minutes. One group served as control, and the two remnants were composed by patients with intrauterine growth retardation with (IUGR-B) or without (IUGR-A) increased resistances in the utero-placental circulation. Changes of blood flow velocity waveforms of both uterine arteries and umbilical artery were recorded for 60 minutes. Blood pressure, serum nitrites/nitrates and growth hormone levels were also measured. Results. No hemodynamic changes in utero-umbilical circulation were observed during infusion in any of the three groups. Considering the uterine arteries separately as placental and non-placental sided we found a significant decrease of non-placental side resistances in IUGR-B women. Indeed, the pulsatility index was lowered by 14%, in respect of baseline value. Serum nitrites/nitrates as well as serum growth hormone levels were significantly increased by ARG, in every woman, irrespective of the presence of fetal growth retardation. Blood pressure remained unaffected during infusion in every woman. Conclusions. These findings suggest that L-arginine infusion affects utero-placental circulation in patients with IUGR associated with increased uterine resistances. Such an action is specific and appears possibly to be mediated by a release of nitric oxide.


1996 - EFFECTS OF TRANSDERMAL GLYCERYLTRINITRATE ON 24-H BLOOD PRESSURE CHANGES IN PATIENTS WITH GESTATIONAL HYPERTENSION [Articolo su rivista]
Facchinetti, Fabio; S., De Martis; Neri, Isabella; A. S., Caputo; Volpe, Annibale
abstract

..


1996 - L-arginine infusion reduces preterm uterine contractions [Articolo su rivista]
Facchinetti, Fabio; Neri, Isabella; Genazzani, Andrea Riccardo
abstract

In order to investigate the role of nitric oxide in preterm labor, 10 women presenting with preterm onset of uterine contractions were infused with L-Arginine. In comparison to saline infusion, L-Arginine significantly reduced the number of contractions, together with an increase of both serum growth hormone and nitrates levels. These findings demonstrate that the enhancement of endogenous nitric oxide production through its physiological donor, L-Arginine, is able to transiently reduce preterm uterine spontaneous contractility.


1996 - Medicina Fetale [Curatela]
E., Moneta Caglio; F., Boselli; Facchinetti, Fabio; V., Mazza
abstract

.


1996 - Platelet serotonin pathway in menstrual migraine [Articolo su rivista]
Fioroni, L; Dandrea, G; Alecci, M; Cananzi, A; Facchinetti, Fabio
abstract

In order to understand the possible 5-hydroxytryptamine (5HT) anomalies in migraine, particularly in the period before the headache attack, we compared the levels of 5HT, its stable metabolite 5-hydroxyindoleacetic acid (5HIAA) and platelet monoaminoxidase (MAO) activity in patients with menstrual migraine with those of healthy female controls. In every subject, blood samples were drawn during both follicular and late luteal phases of the menstrual cycle. In controls, platelet 5HT levels remained stable, whereas 5HIAA levels and MAO activity were higher in the luteal than in the follicular phase, suggesting an increased catabolism of 5HT which occurs physiologically just before menses. In menstrual migraine 5HIAA levels and MAO activity showed similar changes with higher values in the luteal than in the follicular phase. The luteal phase values were significantly higher than those of controls. Also, and in contrast to controls, 5HT levels decreased in the luteal phase. These data suggest that 5HT availability is reduced in menstrual migraine, possibly due to an increased catabolism and/or to a reduced synthesis, and hence predisposes patients to migraine attacks.


1995 - Changes in Dopaminergic control of circulating melanocyte- stimulating hormone-related peptides at puberty. [Articolo su rivista]
Facchinetti, Fabio; S., Bernasconi; Iughetti, Lorenzo; Genazzani, Alessandro; L., Ghizzoni; A. R., Genazzani
abstract

Desacetyl alpha-melanocyte-stimulating hormone (MSH) (ACTH 1-13) is the main form of immunoreactive alpha-MSH circulating in human plasma. This study evaluates the possibility that a dopaminergic inhibitory mechanism could be operative during human development. Thus, alpha-MSH and ACTH 1-13 plasma levels were measured after dopaminergic blockade (domperidone (0.3 mg/kg body weight, maximum 10 mg, p.o.) in 13 prepubertal (aged 4.5-12.3 y) and 12 pubertal (aged 10.2-16.9 y) children. Both peptides were measured by RIA after plasma extraction on Sep-pak C-18 cartridges and reverse phase HPLC. The chromatographic profile of alpha-MSH immunoreactivity falls into two main peaks, corresponding to the retention time of alpha-MSH and ACTH 1-13. Moreover, in prepubertal children domperidone induced a significant increase of alpha-MSH from 1.7 (median) to 5.0 pmol/L, whereas no changes in alpha-MSH plasma levels were found in pubertal subjects (from 5.0 to 4.1 pmol/L). Similarly, ACTH 1-13 plasma levels significantly increased from 3.0 to 19.8 pmol/L in prepubertal children remaining stable in pubertal ones (from 7.8 to 4.6 pmol/L). Moreover, a significant negative correlation was found between basal DHEA-S levels and the plasma alpha-MSH increase after domperidone. These data demonstrate that: 1) ACTH 1-13 is the main form of immunoreactive alpha-MSH in prepubertal life and 2) the dopaminergic inhibition of both ACTH 1-13 and alpha-MSH plasma levels is apparent only in prepubertal subjects.


1995 - CHANGES OF NEUROENDOCRINE AXES IN PATIENTS WITH MENSTRUAL MIGRAINE [Articolo su rivista]
Fioroni, L; Martignoni, E; Facchinetti, Fabio
abstract

Menstrual migraine (MM) is a menstrually related disorder (MRD) characterized by several symptoms in common with premenstrual syndrome (PMS). It has been hypothesized that in both MM and PMS hormonal cyclicity could change the balance of neurotransmitters and neuromodulators like monoamine and opioid. In this article we analyze all the data collected by our group on the central opioid tonus and the adrenergic and serotonergic systems in patients affected by menstrual migraine.


1995 - EFFECTS OF FORMALIN-INDUCED PAIN ON ACTH, BETA-ENDORPHIN, CORTICOSTERONE AND INTERLEUKIN-6 PLASMA-LEVELS IN RATS [Articolo su rivista]
Aloisi, Am; Albonetti, Me; Muscettola, M; Facchinetti, Fabio; Tanganelli, C; Carli, G.
abstract

The behavioral and immunoendocrine effects of formalin-induced pain were studied in male rats following a subcutaneous injection of formalin (50 mu l; 0.1%, F01 groups, 10%, F10 groups) or sham injection (control groups). After treatment, animals were tested in a transparent open field for either 30 or 60 min and thereafter sacrificed by decapitation. Plasma was collected for adrenocorticotropic hormone (ACTH), corticosterone, beta-endorphin (beta-EP) and interleukin-6 (IL-6) determinations. Pain-evoked responses (licking, flexing, pawjerk), standard measures of activity (locomotion, rearing, olfactory exploration) and self-grooming were recorded. The higher formalin concentration induced stronger pain-evoked behavioral responses, paralleled by higher levels of ACTH, beta-EP and IL-6, but did not affect the other behavioral parameters. In contrast, the lower formalin concentration induced a marked increase in locomotion and rearing and a decrease in ACTH levels. In both formalin-injected groups, corticosterone did not differ from controls.


1995 - FACTORS ASSOCIATED WITH PAIN COMPLAINTS IN A CLINICAL-SAMPLE OF POSTMENOPAUSAL WOMEN [Articolo su rivista]
Bono, G; Neri, Isabella; Granella, F; Genazzani, Ar; Facchinetti, Fabio
abstract

The aims of this study were to evaluate the relationships occurring between pain complaints and postmenopausal status, and to look at the correlation between such complaints and other symptoms commonly related to the climacterium A clinical sample of 99 consecutive postmenopausal patients requiring medical help were studied: 36 complained of muscle-skeletal pains whereas 33 presented with headache limiting daily activity Climacteric syndrome, level of distress, coping style and bone mineral density were assessed with appropriate questionnaires and instruments. Neither bone mineral density, nor body mass index nor time since menopause were associated with either headaches or muscle-skeletal pains. According to the logistic regression being younger, being without a job, suffering from insomnia and having a lower ability in self-support by the means of comforting ideas predicts suffering from headache. A high level of distress and an avoidance behavior to problem facing predict the presence of pain complaints. In such cases the ineffectiveness of the coping mechanism (i.e. avoid the problem) could be the reason for the increased level of psychological distress. These findings indicate that complaining of pains or headache is not dependent upon postmenopausal status. Individual coping strategies and their effectiveness seem the main reasons for the presence of disabling musculoskeletal pains or headache.


1995 - FACTORS PREDICTING LABOR ONSET IN PATIENTS TREATED WITH PROSTAGLANDIN E(2) FOR CERVICAL RIPENING [Articolo su rivista]
Facchinetti, Fabio; Neri, Isabella; Genazzani, Ar
abstract

The aim of this study is the evaluation of predictive factors in the onset of labour after pre-induction cervical ripening with prostaglandins. We enrolled 112 consecutive singleton term pregnancies (37-42.3 weeks) with unfavourable cervix and intact membranes, requiring induction of labour because prolonged pregnancy (59%) or maternal/fetal complications (41%). Treatment consisted of the cervical application (once or twice, 12 h apart) of prostaglandin E(2) gel (Upjohn, Italy). Uterine activity was monitored by external cardio-tocography before and during the next 2 h. Two patients showed uterine hyperstimulation and acute fetal distress requiring caesarean section. Sixty percent of patients went to labour and delivered without further stimulations. In this group the rate of caesarean section (9.1%) was lower than in patients failing to onset labour (68.2%). According to the logistic regression three factors positively predicted the onset of labour: first-hour uterine contractility, basal uterine activity and gestational age. The first-hour contractility in particular, represents the myometrial sensitivity to prostaglandin E(2) and may become a practical marker of spontaneous onset of labour in patients undergoing cervical ripening.


1995 - Genetics: Expression of pro-opiomelanocortin gene in human ovarian tissue [Articolo su rivista]
Gallinelli, A.; Garuti, G.; Matteo, M. L.; Genazzani, A. R.; Facchinetti, F.
abstract

The high concentration of pro-opiomelanocortin (POMC)derived peptides in human follicular fluid, which is several times higher than in plasma, suggested a local expression of the POMC gene. This has previously been observed in the animal ovaries. Peripheral POMC-like mRNAs are not translated in POMC-derived peptides but recent evidence supports the presence of a small amount of full-length transcript in human testes and lymphocytes. The purpose of this study was to test two hypotheses: firstly, that there is a different pattern of POMC mRNA expression in the human ovary of fertile and post-menopausal women, and secondly that there is a tissue-specific localization of POMC transcript. Northern blot analysis showed that a potential relationship exists between POMC gene expression and the reproductive age of a woman, and that POMC mRNA has a tissue-specific localization. The expression of POMC messenger in the ovarian parenchyma collected from women of fertile age and in the germinative follicles appeared higher than that observed in samples from postmenopausal women. No signals were detected in corpora lutea. In conclusion, we believe that the physiological role of the POMC gene in the human ovary remains an unsolved problem, necessitating more sensitive methods of mRNA detection as well as further studies in vitro. © 1995 Oxford University Press.


1995 - IMMUNOCYTOCHEMICAL LOCALIZATION AND BIOCHEMICAL-CHARACTERIZATION OF MELANOTROPIN-LIKE PEPTIDES IN THE GONADS OF A PROTOCHORDATE [Articolo su rivista]
Pestarino, M; Facchinetti, Fabio
abstract

The compound gonads of the protochordate ascidian Styela plicata were investigated by immunocytochemistry HPLC, and radioimmunoassay to verify the presence of melanotropin-like peptides, alpha-MSH-like immunoreactivity is localized in the follicular cells and in the perinuclear cytoplasm of different types of ovaric follicles, as well as in the spermatogonia and spermatocytes of testicular lobules. The ascidian immuno-reactive peptides occurring in the gonads consist of alpha-MSH and ACTH(1-13)-NH2 and their amounts are higher in summer than in winter.


1995 - IMPACT OF THE L-ARGININE/NITRIC OXIDE SYSTEM IN PREGNANCY [Articolo su rivista]
Neri, Isabella; G. C., Di Renzo; G., Caserta; A., Gallinelli; Facchinetti, Fabio
abstract

..


1995 - [Non-specific pituitary responses in insulin-dependent diabetes mellitus in children and adolescents]. [Articolo su rivista]
Iughetti, Lorenzo; F., Petraglia; Facchinetti, Fabio; A. R., Genazzani; A., Cozzini; M., Vanelli; S., Bernasconi
abstract

OBJECTIVES: Several reports indicate a number of changes in the control of the release of PRL, LH, FSH, GH and beta-endorphin (B-EP) as a result of insulin-dependent diabetes mellitus (IDDM). In this study we evaluate the presence of non-specific pituitary responses to releasing hormones in IDDM children and adolescents.METHODS: The non-specific effects of TRH on plasma GH, LH and B-EP levels and of GnRH on plasma GH, PRL, TSH and B-EP levels were measured in 16 IDDM children and in 16 healthy children matched by age and sex. All subjects were tested with injection of TRH (200 micrograms i.v. bolus) and GnRH (50 micrograms i.v. bolus). GH, TSH, PRL, LH and B-EP levels were evaluated with radioimmunological methods on blood samples collected before and after stimulation by releasing hormones.RESULTS: GH and B-EP non-specific responses to TRH and GnRH were significantly more pronounced in IDDM patients than in controls. All patients showed at least one non-specific response to one of the two releasing hormones. No significant correlations were found between non-specific pituitary responses and the patient's age, the duration and onset of disease or the degree of metabolic control.CONCLUSIONS: These observations may indicate that: in IDDM hypothalamus-pituitary regulating mechanism is altered; the hormones whose levels are most often found to be abnormal in IDDM (other than insulin) are also hormones which respond non specifically to the neuropeptides TRH and GnRH.


1995 - THE EFFICACY AND SAFETY OF SUBCUTANEOUS SUMATRIPTAN IN THE ACUTE TREATMENT OF MENSTRUAL MIGRAINE. [Articolo su rivista]
Facchinetti, Fabio; Bonellie, G; Kangasniemi, P; Pascual, J; Shuaib, A.
abstract

OBJECTIVE:To compare the efficacy and safety of subcutaneous sumatriptan with placebo in the treatment of menstrual migraine.METHODS:A double-blind, placebo-controlled, parallel group study was conducted to assess the efficacy and safety of subcutaneous sumatriptan in the treatment of menstrual migraine over two attacks. A total of 179 subjects received sumatriptan or placebo to treat at least one menstrual migraine attack.RESULTS:The efficacy results were consistent for attacks one and two. Two hours after treatment in attacks one and two, 53 (73%) and 51 (81%) of the sumatriptan-treated subjects, respectively, reported headache relief (reduction of a severe or moderately severe headache to a mild or no headache), compared with 27 (31%) and 18 (29%) of the placebo-treated subjects (P < .001). Within 24 hours of treatment in attack one, 28 (53%) and 14 (52%) of the initial responders to sumatriptan and placebo, respectively, experienced headache recurrence. The incidence and nature of adverse events in this study were similar to that seen in previous studies.CONCLUSIONS:Subcutaneous sumatriptan is an effective and well-tolerated acute treatment for menstrual migraine.


1994 - Changes of opioid modulation of the hypothalamo-pituitary-adrenal axis in patients with severe premenstrual syndrome. [Articolo su rivista]
Facchinetti, Fabio; L., Fioroni; E., Martignoni; G., Sances; A., Costa; A. R., Genazzani
abstract

To assess the function of the hypothalamus-pituitary-adrenal axis in patients with severe premenstrual syndrome (PMS) 28 patients and 14 asymptomatic controls were studied during the mid- to late-luteal phase of the menstrual cycle. The response of plasma cortisol to both high-dose naloxone and corticotropin-releasing hormone (CRH) was assessed. Naloxone stimulated a significant cortisol release in controls whereas it was otherwise almost absent in patients. CRH stimulated a greater release of cortisol in patients than in controls. Fifteen patients met criteria for either current anxiety and/or mood disorders. The cortisol secretion after both naloxone and CRH stimulations was similar for PMS patients with or without psychiatric disorders. These data indicate that endogenous opioids modulate the activity of the hypothalamus-pituitary-adrenal axis. Irrespective of the concomitant presence of menstrual migraine or psychiatric disorder, such control is altered in patients with severe PMS because of the possible hyposensitivity of opiate receptors. The hyperresponsiveness to CRH may be the consequence of the reduced inhibition that endogenous opioids tonically exert on HPA axis.


1994 - Immunocytochemical evidence for the presence of Met-enkephalin and Leu-enkephalin in distinct neurons in the brain of the elasmobranch fish Scyliorhinus canicula. [Articolo su rivista]
M., Vallarino; C., Bucharles; Facchinetti, Fabio; H., Vaudry
abstract

Immunohistochemical methods have been used to investigate the distribution of various opioid peptides derived from mammalian proenkephalin in the central nervous system of Scyliorhinus canicula. The results indicate that both Leu- and Met-enkephalin-immunoreactive peptides are present in the dogfish brain. In contrast, enkephalin forms similar to Met-enkephalin-Arg-Phe or Met-enkephalin-Arg-Gly-Leu, and mammalian alpha-neo-endorphin, dynorphin A (1-8), dynorphin A (1-13), and dynorphin A (1-17) were not detected. Met- and Leu-enkephalin immunoreactivities were found in distinct neurons of the telencephalon and hypothalamus. In particular, cell bodies reacting only with the Met-enkephalin antiserum were localized in the preoptic nucleus and in the suprachiasmatic region of the hypothalamus. Conversely, cell bodies reacting only with the Leu-enkephalin antiserum were localized in the pallium and the nucleus lobi lateralis hypothalami. Several areas of the telencephalon and diencephalon exhibited both Met- and Leu-enkephalin-like immunoreactivity, but the two immunoreactive peptides were clearly contained in distinct perikarya. The overall distribution of Met-enkephalin-immunoreactive elements in the dogfish exhibited similarities to the distribution of proenkephalin-derived peptides previously reported for the brain of tetrapods. The fact that Met- and Leu-enkephalin-like peptides were detected in distinct neurons, together with the absence of dynorphin-related peptides, suggests the existence of a novel Leu-enkephalin-containing precursor in the dogfish brain.


1994 - Intracellular magnesium is reduced in patients at risk for developing pregnancy-induced hypertension [Relazione in Atti di Convegno]
C., Battaglia; Borella, Paola; F., Pianazzi; S., De Martis; F., Droghini; Facchinetti, Fabio
abstract

The aim of the present study was to correlate the maternal Mg levels with increased resistance of uterine arteries, in patients at risk of developing PIH.


1994 - Life events impact in patients with secondary amenorrhoea. [Articolo su rivista]
L., Fioroni; M., Fava; Genazzani, Alessandro; Facchinetti, Fabio; A. R., Genazzani
abstract

To evaluate the relationship between stressful life events and the onset of secondary amenorrhoea Paykel's semi-structured interview for Recent Life Events was administered to patients affected by secondary amenorrhea and also to healthy volunteers. The number, quality, and objective negative impact of life events were compared among different hormonal subtypes of secondary amenorrhoea and healthy normally menstruating women, as a control group. The number of life events in amenorrhoeic patients (N = 131) was significantly greater than those observed in the control group (N = 64) (45.9 vs 32.8\%). Moreover, where only hypothalamic hypogonadotrophic amenorrhoea was considered, the occurrence of life events was significantly higher (59.8\%) than in hyperandrogenic (26.6\%) or in normogonadotrophic (20.4\%) patients. The most prevalent events among hypothalamic hypogonadotrophic amenorrhoeic patients were those classified as 'undesirable', 'uncontrolled' and with 'Objective Negative Impact'. The present study supports the hypothesis of a cause-effect relationship between stressful personal life events and the onset of secondary amenorrhoea of hypogonadotrophic subtype.


1994 - Menstrual-related mood changes in patients with oligomenorrhea. [Articolo su rivista]
Facchinetti, Fabio; Neri, Isabella; M., Fava; A. R., Genazzani
abstract

In order to evaluate the role of negative anticipation on self-report of premenstrual symptoms, we studied 13 oligomenorrheic and 12 control women with regular menses. Both hormonal and psychological measures (using the Symptom Rating Test) were obtained once a week for 5-9 weeks. The presence of ovulatory cycles was confirmed by progesterone levels > or = 3.0 ng/ml. In both groups, there was a significant increase in the total Symptom Rating Test score during the premenstrual phase with respect to the intermenstrual period. As far as specific symptoms were concerned, MANOVA showed significant premenstrual fluctuations in anxiety, depression, somatic symptoms, and inadequacy in both groups. These results suggest that premenstrual discomfort may be unrelated to both cycle length and negative anticipation of one's menses.


1994 - Opioid peptide modulation of stress-induced plasma steroid changes in the frog Rana esculenta. [Articolo su rivista]
G., Mosconi; O., Carnevali; Facchinetti, Fabio; Neri, Isabella; A., Polzonetti Magni
abstract

The present paper aims to evaluate whether a neuroendocrine system including opioids accounts for the effects of stress in the frog, Rana esculenta. Using an acute-stress paradigm, the involvement of hypothalamic opioid peptides was investigated biochemically as well as by in vivo studies. HPLC and RIA investigations confirm the presence of beta-endorphin-like peptides in the brain of this frog. Several immunoreactive peaks are present, two of them coeluting with beta-endorphin and acetyl beta-endorphin reference peptides. Quantitative evaluation revealed that the beta-EP content of 24-hr captured animals was higher than that in fresh captured ones. The stress paradigm applied here was consistent with the measurement of plasma androgens and corticosterone levels in females after short-captivity confinement. In comparison with fresh-captured animals, a sharp decrease of these levels was found within 10-24 hr after capture. These effects were reversed by naltrexone, a long-acting opioid antagonist, after 24 hr of treatment. In fact, in the captive animals injected with 100 ng of naltrexone, the plasma androgen titers remained low at the 10th hour postcapture, but rose to the control levels within 24 hr. A similar effect was found for the plasma corticosterone levels. These data demonstrate that, in this anuran, endogenous opioids could mediate the stress-induced inhibition of gonadal function, and perhaps the inhibition of the hypothalamus-pituitary-adrenal axis.


1994 - Opioid peptides and testicular activity in the lizard Podarcis s. sicula Raf. [Articolo su rivista]
G., Ciarcia; Facchinetti, Fabio; M., Vallarino; M., Pestarino; M., Paolucci; A., Cardone; S., Fasano; R., Pierantoni; A. R., Genazzani
abstract

In mammals endorphinergic systems have been shown to modulate reproductive processes and beta-endorphin (beta-EP) has been found to influence sexual functions, acting at the hypothalamus-pituitary-gonadal axis level. Using immunocytochemical and in vitro studies, evidence for a diffuse pro-opiomelanocortin-related opioid system in the lizard Podarcis s. sicula was produced. In the testis, beta-EP immunoreactivity showed seasonal variation, being most pronounced in the interstitial cells of sexually quiescent lizards (December). Reverse-phase high-performance liquid chromatography, coupled with radioimmunoassay and immunocytochemistry, showed that beta-EP and acetyl beta-EP increased during December, while their concentrations were low during April, when the highest testicular activity occurred. Using in vivo studies, it was found that naltrexone treatment, blocking pituitary opioid receptor, increased androgen levels in the plasma and in the testis. It was also found with in vitro studies that the endogenous opioid system inhibits gonadotrophin release and therefore androgen production by the testis. The data reported here provide evidence for the physiological role played by opioid peptides at the pituitary level to regulate the seasonal reproductive activity of the lizard Podarcis s. sicula.


1994 - OVARIAN MELANOTROPIC PEPTIDES AND ADAPTATION IN 2 TELEOSTEAN SPECIES - SPARUS-AURATA L AND DICENTRARCHUS-LABRAX L [Articolo su rivista]
Mosconi, G; Carnevali, O; Facchinetti, Fabio; Radi, D; Pestarino, M; Vallarino, M; Polzonettimagni, Am
abstract

The ovarian tissue of Dicentrarchus labrax and Sparus aurata displays two immunoreactive peaks that correspond to the elution time of human des-acetyl alpha-MSH [ACTH(1-13)-amide] and human alpha-MSH. In view of the close identity between the primary structure of fish and human alpha-MSH, these data demonstrate that two MSH-related peptides are present both in sea bream and sea bass ovary. alpha-MSH-like immunoreactivity was found within both granulosa and thecal layers of mature follicles, as well as in the cytoplasm of oogonia of sea bream and sea bass ovary. Gonadal content of ACTH(1-13)-amide and alpha-MSH display differences with regard to season, showing the highest peptide levels in reproductive animals. Moreover, the alpha-MSH content is significantly higher in the ovary of fish farm animals, whereas that of ACTH(1-13)-amide prevails in wild fish ovary.


1994 - Pleural effusion in sarcoidosis: a case report. [Articolo su rivista]
A., Tommasini; G. D., Vittorio; Facchinetti, Fabio; G., Festi; V., Schito; A., Cipriani
abstract

Pleural effusion is a well-recognized clinical entity that can be associated with sarcoidosis. Nevertheless, the real prevalence of this phenomenon remains to be established. This study describes the case of a 57-year-old male sarcoid patient who presented with right exudative pleural effusion, dyspnea on exertion, and bilateral pulmonary interstitial infiltrates. Sarcoidosis was diagnosed more than 2 years prior to the onset of pleural involvement. Pleural biopsy revealed the presence of typical sarcoid non caseating granulomas. Sarcoid involvement of the pleura resolved following a 1-month course of high doses of steroids and did not recur during a 18-month follow up. When we retrospectively analyzed clinical data obtained from 624 consecutive sarcoid patients who were referred to our hospital between January 1980 and June 1993 and examined for the presence of pleural involvement, the only patient who showed pleural effusion and histologically proven sarcoidosis of the pleura was the case here described. The frequency of the phenomenon in our series is 0.16\%. We conclude that pleural effusion represents a rare event in sarcoidosis.


1994 - Presence and steroidogenetic activity of beta-endorphin in the ovary of the lizard, Podarcis s. sicula raf. [Articolo su rivista]
A., Polzonetti Magni; Facchinetti, Fabio; O., Carnevali; G., Mosconi; M., Pestarino; M., Vallarino; G., Ciarcia
abstract

In mammals, proopiomelanocortin (POMC)-related peptides are involved in reproductive processes at both the hypothalamopituitary and ovarian levels. Through immunocytochemical and physiological in vitro studies, evidence for a diffuse POMC-related opioid system in the lizard Podarcis s. sicula is provided. In the lizard ovary, beta-endorphin (beta-EP)-like immunoreactive cells were observed within the granulosa layer; the immunoresponse showed seasonal variation, being most pronounced in the winter ovary. HPLC followed by immunoassay showed that acetyl beta-EP is the main form of POMC-related peptide in both pituitary and ovary. In vitro studies showed that picomolar amounts of beta-EP stimulate follicular estrogen production during both the reproductive and winter phases; induction was found to be higher in the reproductive phase. The data reported here provide evidence for the physiological role played by beta-EP in the reproductive function of Podarcis s. sicula via induction of ovarian production of estradiol-17 beta, which is the main factor responsible for the vitellogenic process.


1994 - Recommendations about the use of leucocytes to assess magnesium status [Relazione in Atti di Convegno]
Borella, Paola; Facchinetti, Fabio; E., Rocchi; R., Lorini; Bargellini, Annalisa
abstract

The results of this study suggest that leucocytes are suitable for detecting magnesium deficiency, although modifications in magnesium content may differ according to the population studied.


1994 - The neuroendocrine effects of sumatriptan, a specific ligand for 5-HT1-like receptors. [Articolo su rivista]
Facchinetti, Fabio; R. E., Nappi; G., Sances; L., Fioroni; G., Nappi; A. R., Genazzani
abstract

A relationship between the serotoninergic and the opiatergic system in the pathogenesis of head pain is supported by several data. This study was carried out to investigate the neuroendocrine effects of sumatriptan, a specific serotonin agonist used in the treatment of migraine, on hypothalamic-pituitary-adrenal axis (PHA) hormones.Two consecutive studies were performed. In study A, eight subjects received a subcutaneous (s.c.) injection of sumatriptan (6 mg). In study B, a further six subjects were randomized to receive either sumatriptan or placebo.Healthy volunteers recruited within the staff (eight males and six females) were studied.In study A, plasma cortisol and PRL were measured by direct RIA and beta-endorphin after extraction and chromatography. Samples were collected from 60 minutes before to 120 minutes after the administration of the drug, at 15-minute intervals. According to the data of the first study, in study B, in addition to cortisol and beta-endorphin, ACTH was also measured.Significant increases in the mean beta-endorphin and cortisol concentrations were found in every subject receiving sumatriptan, while no significant changes were observed in prolactin plasma levels. Study B confirmed the activation of the pituitary-adrenal axis, additionally demonstrating the release of ACTH, and indicated that placebo has no effects.Acute s.c. stimulation with sumatriptan activates the pituitary-adrenal axis.


1994 - The premenstrual syndrome belongs in the diagnostic criteria for menstrual migraine. [Articolo su rivista]
Facchinetti, Fabio
abstract

..


1994 - THE PRO-OPIOMELANOCORTIN-DERIVED PEPTIDE, BETA-ENDORPHIN, REGULATES OVARIAN-FUNCTION IN THE REPRODUCTIVE LIZARD, PODARCIS S. SICULA RAF [Articolo su rivista]
Polzonettimagni, Am; Carnevali, O; Mosconi, G; Nabissi, M; Facchinetti, Fabio
abstract

By in vitro studies, it was found that beta-endorphin (beta-EP) stimulates estradiol-17 beta and progesterone secretion in the ovary of reproductive lizard Podarcis s. sicula; these effects were reversed by naloxone. In the post-ovulatory follicles no significant changes were observed in the progesterone titres, when the medium was supplemented by beta-EP and/or naloxone; conversely, estradiol-17 beta was stimulated by beta-EP and this effect was abolished by naloxone. The data reported here provide evidence for the tonic activity of an endogenous opioid system in the ovary of this lizard. The action exerted by homologous pituitary, moreover, has also been evaluated in order to compare the effects of beta-EP with these of pituitary gland, generally considered the physiological trigger of gonadal function.


1993 - Cefalea ed alterazioni neuroendocrine e cronobiologiche. [Articolo su rivista]
Genazzani, Alessandro; Gastaldi, M; Facchinetti, Fabio; Nappi, G; Martignoni, E; Micieli, G; Genazzani, Ar
abstract

..


1993 - Characteristics of headache at menopause: a clinico-epidemiologic study. [Articolo su rivista]
Neri, Isabella; F., Granella; R., Nappi; G. C., Manzoni; Facchinetti, Fabio; A. R., Genazzani
abstract

The prevalence and characteristics of primary headaches in a large sample of postmenopausal women were investigated. Seventy-six out of 556 women (13.7\%) were affected by headache of either the migraine or tension type. In 82\% of cases onset had preceded the menopause. The postmenopausal course of headaches with a premenopausal onset differed according to type of headache and type of menopause. Indeed, while migraine improved in almost two-thirds of cases, tension-type headache worsened or did not change in 70\% of cases. However, in women who had undergone surgical ovariectomy, the natural course of migraine was worse than in those who had a physiological menopause (P = 0.003). Among the symptoms covered by the Kuppermann Index, only anxiety and insomnia were correlated with headache. The favourable course of migraine in the postmenopausal period can be attributed primarily to the absence of variations in sex hormone levels although psychological factors also seem to play a fundamental role.


1993 - Correlazioni tra magnesio intra cellulare e variazioni pressorie circadiane in gravidanza [Relazione in Atti di Convegno]
Facchinetti, Fabio; F., Pianazzi; Borella, Paola; S., De Martis; Bargellini, Annalisa; A. R., Genazzani
abstract

In questo studio preliminare abbiamo voluto verificare le possibili correlazioni tra omeostasi del Mg e variazioni circadiane della pressione arteriosa. Sono state studiate, alla 20a settimana di gestazione, 8 gravide che presentavano fattori di rischio per lo sviluppo di PIH


1993 - DERANGEMENT OF LH EPISODIC SECRETION IN CLUSTER HEADACHE SUFFERERS [Articolo su rivista]
Genazzani, Alessandro; Micieli, G; Martignoni, E; Facchinetti, Fabio; Rodbard, D; Nappi, G.
abstract

In patients with cluster headache (CH) testosterone plasma levels have been consinstently reported to be lower than in normal males. Thus, we studied LH pulsatile secretory pattern in a group of 29 males suffering from CH. Ten of them were studied longitudinally, while 19 were studied cross-sectionally only during active (n=9) or attack free (n=10) phases. Nine healthy, age-matched males were studied as reference group. All subjects underwent a pulsatility study of 6 hours, sampling every 15 minutes. CH patients resulted to have a lower LH pulsatile release both during active (3.6+/-0.9 peaks/6h, p<0.0001) and attack free (4.1+/-0.9 peaks/6h, p<0.004) phases than normal males (5.2+/-0.6 peaks/6h). When longitudinally studied, CH patients (n=10) showed lower LH secretory episodes during the active than during the attack free phase (3.3+/-0.9 and 4.1+/-0.7 peaks/6h, p<0.05). Testosterone plasma levels did not differ between active and free phases (4.3+/-1 and 4.7+/-0.8 ng/ml, respectively), while, in patients they were significantly lower than in controls (6.8+/-0.9 ng/ml, p<0.01)). These data demonstrate an impaired function of the hypothalamo-pituitary axis possibly due to an overactivity of the opioid neuromodulation.


1993 - FSH SECRETORY PATTERN AND DEGREE OF CONCORDANCE WITH LH IN AMENORRHEIC, FERTILE, AND POSTMENOPAUSAL WOMEN. [Articolo su rivista]
Genazzani, Alessandro; F., Petraglia; C., Volpogni; G., D'Ambrogio; Facchinetti, Fabio; A. R., Genazzani
abstract

Pulsatile secretion of gonadotropin was investigated in amenorrheic patients and in fertile and postmenopausal women to assess both follicle-stimulating hormone (FSH) episodic secretion and its temporal coupling with luteinizing hormone (LH). Three groups of amenorrheic patients were studied: hyperandrogenic (n = 20), hypogonadotropic (n = 51), and normogonadotropic (n = 31). Nineteen fertile women (during the follicular and luteal phases of the cycle) and sixteen postmenopausal women were investigated as reference groups. All subjects demonstrated the presence of a distinct pulsatile pattern with LH and FSH pulses/4 h as follows: hyperandrogenic 3.95 +/- 0.26 and 3.85 +/- 0.2, hypogonadotropic 3.76 +/- 0.26 and 3.9 +/- 0.16, normogonadotropic 3.5 +/- 0.2 and 3.9 +/- 0.17 LH and FSH pulses/4 h, respectively (means +/- SE). Normal controls showed 4.1 +/- 0.2 and 3.1 +/- 0.2 pulses/4 h for LH (P < 0.05) and 3.2 +/- 0.1 and 3.6 +/- 0.3 pulses/4 h for FSH, during follicular and luteal phases, respectively. Postmenopausal women showed 3.6 +/- 0.2 and 3.0 +/- 0.3 pulses/4 h for LH and FSH, respectively. Specific concordance (SC) index demonstrated that LH and FSH were significantly and simultaneously secreted in all groups. Conversely, LH and FSH were not temporally related during the luteal phase. In conclusion, we report a distinct FSH episodic secretion and its temporal linkage with LH pulses irrespective of plasma concentrations of gonadal steroids in secondary amenorrhea


1993 - Immune and neuroendocrine response to restraint in male and female rats. [Articolo su rivista]
F., Farabollini; M. E., Albonetti; A. M., Aloisi; Facchinetti, Fabio; G., Grasso; L., Lodi; C., Lupo; M., Muscettola
abstract

A parallel study of the modification in the opioid and immunological systems induced by acute restraint (RT) was carried out in male and female rats 24 hr after the treatment. beta-Endorphin-like immunoreactivity (beta-ELI) was measured in two brain areas (ventral hypothalamus [HYP] and periaqueductal gray matter [PAG]) and in the pituitary (anterior and neurointermediate lobes), together with plasma corticosterone (C) and ACTH. Immune function was measured as mitogen-induced Interferon-gamma (IFN-gamma) production by splenocytes. RT reduced beta-ELI levels in the PAG in males and females. Plasma levels of C and ACTH did not differ from the basal levels in restrained animals. RT reduced IFN-gamma production in both sexes, but this effect was more marked in females than in males. The possible relationship between the immune and opioid system is discussed.


1993 - Letter to the editor [Articolo su rivista]
Facchinetti, Fabio
abstract


1993 - Neuroendocrine changes in luteal function in patients with premenstrual syndrome. [Articolo su rivista]
Facchinetti, Fabio; Genazzani, Alessandro; E., Martignoni; L., Fioroni; G., Nappi; A. R., Genazzani
abstract

The present study evaluates the luteal progesterone (P) and LH secretions in 14 patients affected by premenstrual syndrome (PMS) and in 14 asymptomatic controls through the evaluation of their episodic release. PMS was prospectively confirmed in two consecutive menstrual cycles using Moos' Menstrual Distress Questionnaire. A pulsatility study was performed during the luteal phase. Blood samples were drawn every 10 min for 12 h, beginning at 0800 h. Statistically significant pulses were detected using the Detect program, and the degree of concordance of LH and P pulses was estimated. Similar mean 12-h P levels were found in controls (mean +/- SD, 13.9 +/- 9.3 nmol/L) and patients (14.2 +/- 10.1). LH levels were also similar in the two groups. Patients showed a higher P pulse frequency (13.4 +/- 1.8 vs. 11.4 +/- 2.3; P < 0.02) and a reduced amplitude of secretory episodes (126.5 +/- 61.6\% vs. 187.1 +/- 126.7\%; P < 0.03) than controls. Similarly, PMS patients showed pulsatile LH release of increased frequency and reduced amplitude than controls. A significant degree of concordance between LH and P pulses was observed in both groups, with a time lag of 0-10 min; that is, P secretory episodes follow LH with a delay of 0-10 min. These findings demonstrate that despite the fact that integrated P levels in PMS patients are similar to those in control subjects, the episodic secretion of the hormone is characterized by pulses of increased frequency and reduced amplitude. This phenomenon is temporally related to LH secretion, thus reinforcing the concept of PMS as a neuroendocrine disorder.


1993 - Opioids and testicular activity in the frog, Rana esculenta. [Articolo su rivista]
Facchinetti, Fabio; A. R., Genazzani; M., Vallarino; M., Pestarino; A., Polzonetti Magni; O., Carnevali; G., Ciarcia; S., Fasano; M., D'Antonio; R., Pierantoni
abstract

The presence and activity of brain, pituitary and testicular beta-endorphin (beta-EP)-like material have been studied in the frog, Rana esculenta, using reverse-phase high-pressure liquid chromatography, coupled with radioimmunoassay and immunocytochemistry. In-vivo and in-vitro treatments with naltrexone were carried out to assess the putative physiological activity of opioid peptides. beta-EP(1-31) and (1-27), together with their acetylated forms, have been identified in brain, pituitary and testis. In particular, beta-EP(1-31) concentrations peaked during July in the brain and pituitary, whilst in testes maximum concentrations were found in April and November. beta-EP immunoreactivity was present in the brain within the nucleus preopticus and nucleus infundibularis ventralis while positive fibres in the retrochiasmatic regions projected to the median eminence. In the testis, interstitial cells, canaliculi of the efferent system, spermatogonia and spermatocytes showed positive immunostaining for beta-EP. In intact animals, naltrexone treatment increased plasma and testicular androgen levels and this effect was confirmed in in-vitro incubations of minced testes. Naltrexone also induced a significant increase in germ cell degeneration. Our results indicated that an opioid system modulates the hypothalamus-pituitary-gonadal axis in the frog, Rana esculenta and, for the first time, we have shown that the testicular activity of a non-mammalian species may be regulated by opiates locally.


1993 - Ovarian melanotropic peptides in two teleostean fishes. [Articolo su rivista]
Facchinetti, Fabio; A., Polzonetti Magni; Neri, Isabella; A., Gallinelli; G., Alessandrini; M., Vallarino
abstract

..


1993 - Stressful life events and affective disorders inhibit pulsatile LH secretion in hypothalamic amenorrhea. [Articolo su rivista]
Facchinetti, Fabio; M., Fava; L., Fioroni; Genazzani, Alessandro; A. R., Genazzani
abstract

The aim of this study was to evaluate relationships between emotional state and hypothalamic activity in patients with hypothalamic secondary amenorrhea. Sixty-seven normal weight patients with hypothalamic amenorrhea were submitted to concomitant psychological and LH pulsatility evaluation. Structured clinical interview for anxiety and depressive disorders (DSM III-R) as well as life events investigations (Paykel test) were performed. LH pulses (blood sampling every 10 min for 4 hr) were analyzed through DETECT program and Instantaneous Secretory Rate were computed. Twenty-one patients reporting life events associated to the onset of amenorrhea had LH pulse frequency (2.28 +/- 1.10 pulses/4 hr) lower than those without life events (3.40 +/- 1.46 p = .007). LH pulses amplitude was lower in patients meeting a DSM III-R (21 cases: 1.22 +/- 0.96 mIU/ml) diagnosis than in those without (1.99 +/- 1.20 p = .04) diagnosis. Plasma estradiol and FSH levels as well as duration of amenorrhea and Body Mass Index were similar among groups. It is concluded that psychogenic factors (namely the presence of life events related to the onset of menstrual disorder) are associated with significant and specific changes of hypothalamic activity which could be involved in determining hypogonadism.


1993 - The association of menstrual migraine with the premenstrual syndrome. [Articolo su rivista]
Facchinetti, Fabio; Neri, Isabella; E., Martignoni; L., Fioroni; G., Nappi; A. R., Genazzani
abstract

To investigate the comorbidity of premenstrual syndrome (PMS) and menstrual migraine, the Menstrual Distress Questionnaire (MDQ) was prospectively administered for two consecutive menstrual cycles to 22 patients with menstrual migraine, 12 cases with migraine without aura and 15 patients with PMS. MDQ scores varied throughout the menstrual cycle in each patient group, the wider changes being shown by patients with PMS. Fourteen menstrual migraine patients and 4 migraine without aura patients achieved diagnostic criteria for PMS over two menstrual cycles. In these patients MDQ scores did not differ from PMS sufferers at any stage of the menstrual cycle. The premenstrual increase of each cluster of PMS symptoms was identical in menstrual migraine and PMS subjects with the exception of negative affect. We suggest that PMS symptoms should be taken into account in the IHS diagnostic criteria for menstrual migraine.


1992 - Central changes of beta-endorphin-like immunoreactivity during rat tonic pain differ from those of purified beta-endorphin. [Articolo su rivista]
Facchinetti, Fabio; Tassinari, G.; Porro, Carlo Adolfo; Galetti, A.; Genazzani, Andrea Riccardo
abstract

Several studies have described changes in beta-endorphin-like immunoreactivity (beta-ELI) in the rat brain in response to pain and stress stimuli. In order to ascertain the components of beta-ELI, brain samples of rats experiencing acute prolonged (tonic) pain were evaluated for their beta-ELI and later submitted to a chromatographic purification allowing the measurement of beta-endorphin (beta-EP) and acetyl beta-EP. The chromatographic analysis of both ventromedial hypothalamus (VMH) and periaqueductal grey (PAG) homogenates indicates that beta-ELI is distributed in several fractions including shortened forms of beta-EP and their respective acetylated compounds. Quantitatively, while beta-ELI in formalin-injected animals was increased by 48\% in VMH and 45\% in PAG in respect to controls, the net increase of purified beta-EP was 1100\% and 470\%, respectively, for VMH and PAG. Moreover, the maximal increase of beta-ELI was evident at 120 min, in both tissues. In contrast, the beta-EP peak was reached at 30 min in VMH and at 60 min in PAG. Acetyl beta-EP was unchanged by treatment in both central areas. No correlation of beta-ELI and beta-EP was found in VMH. These data demonstrate that the evaluation of beta-ELI gives a poor estimate of beta-EP changes, due to several components of the endorphin family.


1992 - COMORBID ANXIETY AND DEPRESSION AMONG PATIENTS WITH LATE LUTEAL PHASE DYSPHORIC DISORDER [Articolo su rivista]
Fava, M; Pedrazzi, F; Guaraldi, Gian Paolo; Romano, G; Genazzani, Ar; Facchinetti, Fabio
abstract

The presence of current anxiety and mood disorders was evaluated with the Structured Clinical Interview for the DSM-M-Revised (SCID) in three groups: (a) a group of 32 women with prospectively confirmed Late Luteal Phase Dysphoric Disorder (LLPDD), (b) a group of 35 women with secondary amenorrhea, and (c) a group of 38 female healthy volunteers. Both LLPDD and secondary amenorrhea patients had a greater percentage of comorbid anxiety or mood disorders compared to healthy volunteers. Although patients with amenorrhea displayed mood disorders more often than LLPDD patients, 59% of the 32 women with LLPDD had current anxiety disorders either alone or with comorbid mood disorders, and this percentage was.significantly higher (p < 0.005) than that of amenorrheic patients (23%). Generalized anxiety, panic disorder, and social phobia were the most common diagnoses among LLPDD women. In conclusion, patients with prospectively confirmed LLPDD appear more likely to suffer from current anxiety or mood disorders than healthy controls and to have current anxiety disorders more often than women with secondary amenorrhea.


1992 - Evidence of alpha-N-acetyl beta-endorphin in human cerebrospinal fluid. [Articolo su rivista]
Facchinetti, Fabio; G., Sances; E., Martignoni; I., Pagani; G., Nappi; A. R., Genazzani
abstract

Alpha-N-acetyl-beta-endorphin (Ac-beta-EP) is a post-translational product of beta-endorphin (beta-EP) with no analgesic properties. Ac beta-EP is present in human fetal and adult pituitary gland and cross-reacts in all available beta-EP assays. This study evaluates levels of Ac-beta-EP in the cerebrospinal fluid (CSF) of 22 normal subjects and 15 chronic headache sufferers. Since dopamine may play a role in the acetylation process, homovanillic acid levels were also determined. After extraction and high performance liquid chromatographic (HPLC) fractionation of CSF, an immunoreactive Ac-beta-EP peak was detected coeluting with reference peptide. Ac-beta-EP was detectable in all but 5 normal subjects. In headache sufferers, Ac-beta-EP levels were always detectable and their mean value was significantly higher than that of healthy subjects (11.6 +/- 11.8 vs 3.9 +/- 3.6 fmol/ml; P less than 0.01). Conversely, CSF beta-endorphin (beta-EP) concentrations were decreased in headache patients (9.8 +/- 9.4 vs 15.7 +/- 9.7 fmol/ml; P less than 0.05), and as a consequence the beta-EP/Ac-beta-EP ratio was also markedly reduced (P less than 0.005). No difference was observed for CSF homovanillic acid concentrations. These data demonstrate that HPLC coupled to radioimmunoassay allows the identification of low but significant amounts of Ac beta-EP in human CSF. This compound represents a confounding factor when beta-EP immunoreactivity is assessed by conventional methods. In headache sufferers, Ac-beta-EP levels were higher than normal, whereas beta-EP concentrations were lower.(ABSTRACT TRUNCATED AT 250 WORDS)


1992 - Immunoreactive Met-enkephalin-like material in the testis of Rana esculenta: identification and localization. [Articolo su rivista]
M., Vallarino; M., Pestarino; M., D'Antonio; S., Fasano; Facchinetti, Fabio; R., Pierantoni
abstract

Methionine-enkephalin (Met-Enk) has been detected in the testis of the frog, Rana esculenta, using a reverse-phase high-performance liquid chromatography system coupled with a specific radioimmunoassay. By means of immunocytochemical techniques Met-Enk positive cells have been localized in interstitial and germinal compartments. Particularly, spermatogonia, spermatocytes, and spermatozoa were stained in seminiferous tubules, and numerous interstitial cells showed strong cytoplasmic immunoreactivity in summer animals. Variations in the concentration of Met-Enk immunoreactive material occurred during the annual cycle. Our data show that Met-Enk is present in testes of nonmammalian vertebrate species. These results suggest that autocrine and/or paracrine mechanisms may regulate testicular activity in amphibians.


1992 - Lactate infusion induces panic attacks in patients with premenstrual syndrome. [Articolo su rivista]
Facchinetti, Fabio; G., Romano; M., Fava; A. R., Genazzani
abstract

A sodium lactate test was performed during the premenstrual phase in 35 women suffering from prospectively confirmed premenstrual syndrome (PMS) and in 16 controls in order to assess whether these patients were sensitive to this test and whether this sensitivity was accounted for primarily by the presence of concomitant panic disorder. Patients with PMS also underwent the Structured Clinical Interview for the DSM-III-R (SCID) to determine the presence of co-morbid anxiety and/or mood disorders. Only 31\% of the PMS patients were free from a depressive/anxiety disorder, while nine patients met criteria for panic disorder, and the remaining 15 subjects were diagnosed as having anxiety and/or mood disorders. Lactate infusion induced panic attacks in 22 subjects (62.9\%) and two controls (12.5\%). Panickers were equally distributed among PMS patients with or without a concurrent anxiety/mood disorder. Although cardiovascular responses to lactate were similar among PMS patients regardless of the presence of concomitant anxiety/mood disorders, both plasma cortisol levels and panic and mood scores were higher during the test in those patients with concomitant panic disorder. These results suggest that PMS patients display an increased sensitivity to lactate, which is not primarily accounted for by the presence of co-morbid panic disorder.


1992 - Magnesium involvement in swinging mood and pain during menstrual cycle [Articolo su rivista]
Facchinetti, F.; Fioroni, L.; Nappi, G.; Genazzani, A. R.
abstract


1992 - Nutrients influence on beta-endorphin blood levels in lean and obese children. [Articolo su rivista]
S., Bernasconi; Iughetti, Lorenzo; L., Ghizzoni; Facchinetti, Fabio; C., Volta; A. R., Genazzani
abstract

The authors studied the influence of nutrients on opiod secretion


1992 - Occurrence of immunoreactive Met- and Leu-enkephalin-like peptides in the ovary of the green frog, Rana esculenta. [Articolo su rivista]
Pestarino, M; Vallarino, M; Polzonettimagni, A; Carnevali, O; Mosconi, G; Facchinetti, Fabio
abstract

In the present study, we have localized for the first time Met- and Leu-enkephalin-like material in the ovary of the anuran, Rana esculenta, using the indirect immunofluorescence method. The ovaries were sampled during the main representative phases of the annual reproductive cycle of the frog, living in a mountain pond (Colfiorito, Umbria at 820 m a.s.l.). Strong immunoreactivity to Met- and Leu-enkephalin antisera was observed in the follicle cells of the granulosa layer of vitellogenic oocytes; moreover, during this phase, immunofluorescent materials were also radially localized in the cytoplasm and in the perinuclear zone. The mature oocytes showed Met- and Leu-enkephalin-like immunostaining in the thecal layer and in several granules scattered in the peripheral zone of the yolk. The different pattern of Leu- and Met-enkephalin-like immunoreactivity in the frog ovary parallels and complements the changes occurring in the reproductive (May) and in the vitellogenetic (September) phases during the ovarian cycle. Consequently, these findings strongly support the hypothesis for a local synthesis of these peptides in the ovary and suggest their possible involvement in the control of ovarian function.


1992 - Opioid response to clonidine test as a predictor of effectiveness of antidepressant treatments in chronic headache [Articolo su rivista]
Martignoni, E.; Facchinetti, F.; Sances, G.; Costa, A.; Genazzani, A. R.; Nappi, G.
abstract

In this study we evaluated the opioid response to clonidine administration in headache sufferers with depressive symptoms, to test the hypothesis that such pharmacological tools may help characterize the profile of the different types of chronic headache. The plasma β-endorphin (β-EP) levels were evaluated before and after clonidine administration (0.075 mg IV) in 34 headache patients, 11 suffering from chronic tension headache (CTH) and 23 from migraine with coexisting chronic tension headache (MCTH), prior to starting an antidepressive treatment with amitriptyline or ritanserin. As controls, we examined eight age-matched healthy subjects. Patients as a whole and in the MCTH group, but not the CTH group, showed β-EP levels significantly lower than controls. In all patients and in both CTH and MCTH groups, a blunted response to clonidine administration was observed. Treatments with antidepressive drugs were both effective on pain severity and HRSD score. Moreover, the patients showing the largest increase in plasma β-EP levels following clonidine injection reported a more evident clinical response to the treatments. These findings suggest that the opioid response to the clonidine challenge in chronic headache may well predict the clinical effectiveness of the therapy.


1992 - Oral magnesium supplementation improves fetal circulation. [Articolo su rivista]
Facchinetti, Fabio; C., Battaglia; R., Benatti; Borella, Paola; A. R., Genazzani
abstract

It is well known that pregnancy is a condition in which plasma magnesium falls because of accumulation of the ion in the placenta and fetus. Magnesium (Mg) is therefore widely given as a supplement during pregnancy, particularly in cases of preterm labour. In our experience, the combination of oral Mg (magnesium pyrrolidone carboxylic acid) at a dose of 360 mg/day with conventional ritodrine treatment allows a reduction in ritodrine dosage, accompanied by a significant reduction in side effects. We therefore evaluated changes in fetal blood flow, using pulsed Doppler, in women submitted to combined magnesium and ritodrine treatment compared to those treated with ritodrine plus placebo. The Mg-treated group showed a decrease in vessel resistance both in the umbilical artery and in the fetal middle cerebral artery, indicating that fetal vasculature is sensitive to exogenous Mg. Measurement of plasma and mononuclear cell Mg showed an intracellular increase in the cation of about 10 per cent. We conclude that oral magnesium supplementation in pregnancy is safe and that it has a positive effect on the fetal circulation.


1992 - Ovarian opioids and the reproductive cycle of the frog Rana esculenta. [Articolo su rivista]
Facchinetti, Fabio; A. R., Genazzani; M., Pestarino; M., Vallarino; R., Pierantoni; S., Fasano; M., D'Antonio; O., Carnevali; G., Mosconi; A., Polzonetti Magni
abstract

In mammals, proopiomelanocortin-related peptides are involved in reproductive processes both at the hypothalamo-pituitary and ovarian levels. Using immunocytochemical, biochemical and physiological "in vitro" studies, we provide here evidence for a diffuse POMC-related opioid system in the frog Rana esculenta. Ovarian beta-endorphin (beta-EP) is expressed in thecal cells and changes during the reproductive cycle in an inverse relationship with follicular development. Seasonal changes in the ovary are different to those in the brain or in the pituitary. The ratio of acetylated vs native beta-EP in the ovary also changes over the reproductive period, affecting the biological activity of the peptide. During both the reproductive spring period and the summer post-reproductive phase pMol amounts of beta-EP stimulate follicular androgen secretion in vitro, in a naloxone-reversible way. In either period, an inhibition of estradiol, possibly mediated via other factors, is the result of opioid action. In conclusion, these data demonstrate for the first time the widespread presence of beta-EP-related peptides in the frog Rana esculenta. Both immunocytochemical and biochemical evidence, as well as in vitro responses, support a physiological role for beta-EP in ovarian seasonality during the reproductive cycle of this amphibian.


1992 - PLASMA BETA-ENDORPHIN, CORTISOL AND NOREPINEPHRINE RESPONSES TO PHYSICAL AND METABOLIC STRESSORS IN YOUNG AND ELDERLY HUMANS [Articolo su rivista]
Martignoni, E; Costa, A; Blandini, F; Petraglia, F; Facchinetti, Fabio; Deril, Gvm; Nappi, G; Genazzani, Ar
abstract

The aim of the present study was to evaluate the effects of ageing on the activity of both the hypothalamic pituitary-adrenal axis and the sympathetic system in response to physical and metabolic stimuli. Eight young and eight elderly healthy subjects were studied. Three different tests were performed: handgrip, cold pressor and insulin-induced hypoglycaemia. Plasma beta-endorphin (beta-END), cortisol and norepinephrine (NEpi) levels were measured before and during the tests. While the two physical tests, handgrip and cold pressor, did not induce significant changes in plasma beta-END and cortisol levels, plasma NEpi levels rose in both young and aged subjects. The response of plasma NEpi was significantly higher in elderly than in young men. During the insulin-induced hypoglycaemia, plasma beta-END, cortisol and NEpi values significantly increased in both young and elderly men, the group of elderly subjects showing an enhanced responsiveness of plasma NEpi levels. These data suggest that ageing is associated with an increased activity of the sympathetic system and a normal responsiveness of the hypothalamic-pituitary-adrenal axis to the hypoglycaemic stress.


1992 - Psychosomatic disorders related to gynecology. [Articolo su rivista]
Facchinetti, Fabio; K., Demyttenaere; L., Fioroni; Neri, Isabella; A. R., Genazzani
abstract

In this paper current issues on four psychosomatic disorders related to gynecology will be reviewed. The history, nosological problems and psychoneuroendocrine correlates of psychogenic amenorrhea have been summarized taking into account the important role of psychological factors in inducing loss of menses. Definition and diagnostic problems in assessing menstrually related disorders (formerly premenstrual syndrome) have been reviewed, looking at this syndrome as a disorder of adaptation to the cyclical changes of neuroendocrine functions. The impact of stress on fertility and, on the other hand, the effects of infertility on psychological well-being have been pointed out trying to ascertain the pathways involved in these mutual relationships. Finally, the issue of mood changes at menopause and the effects of steroid replacement on affective state have been discussed. As a whole, these evidences indicate the importance of a close cooperation between gynecologist and psychiatrist in the management of gynecological disorders.


1992 - The treatment of hyperandrogenism [Articolo su rivista]
Facchinetti, Fabio
abstract


1991 - Central beta-endorphin system involvement in the reaction to acute tonic pain. [Articolo su rivista]
Porro, C. A.; Tassinari, G.; Facchinetti, Fabio; Panerai, A. E.; Carli, G.
abstract

The involvement of the beta-endorphin (B-EP) system during acute prolonged (tonic) pain was investigated by biochemical and behavioral approaches in freely-moving rats after subcutaneous injection of a small amount of a dilute formaldehyde solution (0.08 ml, 5\%) in a forepaw. Beta-endorphin-like immunoreactivity levels were increased over the respective control groups in rats killed 30, 60 and 120 min after injection in discrete regions of the rat brain, namely ventro-medial hypothalamus, ventro-basal thalamus and periaqueductal gray matter, and at 30 and 60 min in postero-medial thalamus. In a separate group of experiments a small amount of anti-B-EP or normal rabbit serum was injected in the lateral ventricle; 6 h later rats received formalin injection as in previous groups and their behavior was scored over the following 2 h. A significant hyperalgesia (as expressed by an increase in the amount of time rats spent licking or chewing the injected paw) was observed 10-50 min and 70-80 min after formalin in the anti-B-EP icv-injected group. Other behavioral parameters such as general motor activity, grooming and limb flexion were not different in the two groups, nor was animal behavior prior to formalin injection. Altogether these data suggest that the central beta-endorphin system is triggered by prolonged noxious stimulation in freely-moving animals, and in turn plays a physiological role in the modulation of the reaction to, or perception of, tonic pain.


1991 - CSF LEVELS OF ALPHA-N-ACETYLATED AND DEACETYLATED BETA-ENDORPHIN IN CHRONIC MIGRAINE [Articolo su rivista]
Facchinetti, Fabio; Sances, G; Martignoni, E; Blandini, F; Pagani, I; Nappi, G.
abstract

..


1991 - Magnesium prophylaxis of menstrual migraine: effects on intracellular magnesium. [Articolo su rivista]
Facchinetti, Fabio; G., Sances; Borella, Paola; A. R., Genazzani; G., Nappi
abstract

The effects of oral Magnesium (Mg) pyrrolidone carboxylic acid were evaluated in 20 patients affected by menstrual migraine, in a double-blind, placebo controlled study. After a two cycles run-in period, the treatment (360 mg/day of Mg or placebo) started on the 15th day of the cycle and continued till the next menses, for two months. Oral Mg was then supplemented in an open design for the next two months. At the 2nd month, the Pain Total Index was decreased by both Placebo and Mg, with patients receiving active drug showing the lowest values (P less than 0.03). The number of days with headache was reduced only in the patients on active drug. Mg treatment also improved premenstrual complaints, as demonstrated by the significant reduction of Menstrual Distress Questionnaire (MDQ) scores. The reduction of PTI and MDQ scores was observed also at the 4th month of treatment, when Mg was supplemented in all the patients. Intracellular Mg++ levels in patients with menstrual migraine were reduced compared to controls. During oral Mg treatment, the Mg++ content of Lymphocytes (LC) and Polymorphonucleated cells (PMN) significantly increased, while no changes in plasma or Red Blood Cells were found. An inverse correlation between PTI and Mg++ content in PMN was demonstrated. These data point to magnesium supplementation as a further means for menstrual migraine prophylaxis, and support the possibility that a lower migraine threshold could be related to magnesium deficiency


1991 - Oral magnesium successfully relieves premenstrual mood changes [Articolo su rivista]
Facchinetti, Fabio; Borella, Paola; G., Sances; L., Fioroni; R. E., Nappi; A. R., Genazzani
abstract

Reduced magnesium (Mg) levels have been reported in women affected by premenstrual syndrome (PMS). To evaluate the effects of an oral Mg preparation on premenstrual symptoms, we studied, by a double-blind, randomized design, 32 women (24-39 years old) with PMS confirmed by the Moos Menstrual Distress Questionnaire. After 2 months of baseline recording, the subjects were randomly assigned to placebo or Mg for two cycles. In the next two cycles, both groups received Mg. Magnesium pyrrolidone carboxylic acid (360 mg Mg) or placebo was administered three times a day, from the 15th day of the menstrual cycle to the onset of menstrual flow. Blood samples for Mg measurement were drawn premenstrually, during the baseline period, and in the second and fourth months of treatment. The Menstrual Distress Questionnaire score of the cluster "pain" was significantly reduced during the second month in both groups, whereas Mg treatment significantly affected both the total Menstrual Distress Questionnaire score and the cluster "negative affect." In the second month, the women assigned to treatment showed a significant increase in Mg in lymphocytes and polymorphonuclear cells, whereas no changes were observed in plasma and erythrocytes. These data indicate that Mg supplementation could represent an effective treatment of premenstrual symptoms related to mood changes


1991 - Perimenstrual headache prophylaxis with dihydroergokriptine [Articolo su rivista]
Fioroni, L.; Sances, G.; Martignoni, E.; Facchinetti, F.; Nappi, G.; Genazzani, A. R.
abstract


1991 - Peripheral opioid secretory pattern in anorexia nervosa. [Articolo su rivista]
F., Brambilla; E., Ferrari; F., Petraglia; Facchinetti, Fabio; M., Catalano; A. R., Genazzani
abstract

The peripheral secretion of endogenous opioids was studied in 10 women with restrictive anorexia nervosa and 10 age- and sex-matched healthy controls. The circadian rhythm of beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH), and their responses to the administration of corticotropin releasing hormone (CRH, 1 micrograms/kg body weight, i.v.), clonidine (150 microgram, i.v.), domperidone (10 mg, i.v.), and 5-hydroxytryptophan (5-HTP, 200 mg, p.o.) were examined in patients and controls. The results revealed increased nocturnal secretion of beta-EP and diurnal-nocturnal secretion of beta-LPH with loss of circadian rhythmicity of both peptides, normal response to CRH stimulation, blunted response to clonidine and domperidine, and normal beta-EP and blunted beta-LPH response to 5-HTP stimulation. The data suggest a complex alteration of peripheral opioids and of central aminergic mechanisms that regulate proopiomelanocortin-derived peptide secretion and eating behavior.


1991 - PERSONALITY-TRAITS IN SECONDARY AMENORRHEA [Articolo su rivista]
Fioroni, L; Facchinetti, Fabio; Cerutti, G; Nappi, G; Genazzani, Andrea Riccardo
abstract

The personality traits in 61 consecutive patients affected by secondary amenorrhea requesting help for menstrual disorders were evaluated. Patients were administrated the reduced form of the Minnesota Multiphasic Personality Inventory (MMPI) and a semistructured interview. Clinical, instrumental and neuroendocrine examinations were done, including plasma estrogens, luteinizing hormone (LH) pulsatility study, thyrotropin releasing hormone (TRH) test. Nine patients were excluded because the endocrine evaluation did not show evidence of certain pathological changes. The remaining 52 patients were considered for this study and divided into two groups according to the presence (16 cases) or the absence (36 cases) of an acute life event temporally related to the onset of amenorrhea. MMPI profiles showed high levels in all scales of 'Neurotic area' and a reduction in the correction (K) and masculinity-femininity (Mf) scales in the group with a life event. With the neuroendocrine approach 87.5% of these patients showed hypogonadotropic hypogonadism with poor or absent LH pulsatility. The MMPI profile of these patients was similar to that described above with insecurity, anxiety conversion trait, hypochondria, depression, emotional lability and difficulty of adaptation to distress. This study indicated that in amenorrheic patients characterized by a life event concomitant to the onset of the menstrual disorder, a particular personality trait of the neurotic type could be demonstrated and may indicate an inadequate reaction to stress.


1991 - Pituitary and brain beta-endorphin in male and female rats: effects of shock and cues associated with shock. [Articolo su rivista]
F., Farabollini; R. P., Heinsbroek; Facchinetti, Fabio; N. E., Van
abstract

The present experiment was designed to study whether or not prior exposure to inescapable shock is accompanied by sex-dependent changes in pituitary and central levels of immunoreactive beta-endorphin, which is proposed to play an important role in opioid analgesia induced by aversive stimulation. Further, the effects of brief reexposure (5 min) to the chamber where inescapable shock was experienced earlier, were established in both sexes. Elevated levels of beta-endorphin were found 24 hours after inescapable shock, in the anterior pituitary of males and in the midbrain periaqueductal gray of both males and females. Reexposure to the experimental chamber only affected beta-endorphin levels if shock had been experienced in this chamber. Reexposure after inescapable shock reduced beta-endorphin content of the arcuate nucleus of males and beta-endorphin content of the periaqueductal gray of males and females. The present results are related to previous findings of sensitization and conditioning of analgesic reactions. The sex differences found in the present experiment are discussed with respect to sex-dependent behavioral consequences of inescapable shock.


1991 - PREVALENCE OF POSTMENOPAUSAL HEADACHE - A PROSPECTIVE-STUDY [Articolo su rivista]
Martignoni, E; Neri, Isabella; Granella, F; Manzoni, Gc; Facchinetti, Fabio; Genazzani, Ar
abstract

PREVALENCE OF POSTMENOPAUSAL HEADACHE - A PROSPECTIVE-STUDY


1991 - Unresponsiveness of the endorphinergic system to its physiological feedback in obesity. [Articolo su rivista]
C., Giovannini; E., Ciucci; M. R., Cassetta; P., Cugini; Facchinetti, Fabio
abstract

Beta-endorphin (beta-Ep) plasma levels are higher in obese patients than in normal subjects. To establish that this finding constitutes hyperendorphinemia, 28 obese patients aged 12-55 years, six males and 22 females, (weighing 61-117 kg) were investigated twice by an overnight 1-mg p.o. dose dexamethasone suppression test (DST) before and after weight loss. beta-Ep was measured by radioimmunoassay (RIA). Before body weight loss, beta-Ep was higher than normal and unresponsive to DST, whereas ACTH and cortisol were suppressible. After weight loss, beta-Ep was slightly reduced but still insensitive to DST. ACTH and cortisol were responsive as usual. Findings suggest a resistance to DST in obesity as far as beta-Ep is concerned. The disorder persists even after weight loss, indicating that hyperendorphinemia is not secondary to body weight excess. Accordingly, one can argue that the unresponsiveness of the endorphinergic system to its physiological feedback is a pathophysiological characteristic of obesity.


1991 - USE OF MECLOFENAMIC ACID IN GYNECOLOGY AND OBSTETRICS - EFFECTS ON POSTSURGICAL STRESS [Articolo su rivista]
Facchinetti, Fabio; Depietri, R; Giunchi, M; Genazzani, Ar
abstract

Meclofenamic acid has been successfully used in several obstetrical and gynecological disorders sustained by a prostaglandin overproduction. A brief review of meclofenamic acid use for primary dysmenorrhea, menorrhagia, and episiotomy pain is followed by an original study of this compound in postsurgical pain and stress. Thirty gynecological patients undergoing abdominal hysterectomy and 10 pregnant women submitted to cesarean section at term were considered. In gynecological patients, meclofenamic acid suppositories (200 mg) or placebo were given every 12 h during the immediate postsurgical period; pregnant women were given the active drug only. Subjective pain was evaluated [through visual analogue scale (VAS)] in basal conditions (2 h from the end of surgery) and 2, 4, 6, 24, and 28 h from the first drug dose. At the same time, blood was drawn for the evaluation of plasma cortisol levels (through coated-tube radioimmunoassay). A significant pain relief was obtained after only 4 h posttreatment both in gynecological patients and pregnant women. Meclofenamic acid was superior to placebo from 6 h after treatment and it almost suppressed subjective pain at the end of the observation period (28th h). Cortisol levels were already high at the basal evaluation and showed a further increase during the first postsurgery hours. Patients treated with meclofenamic acid had cortisol values lower than those who were treated with placebo. The former recovered normal levels after 24 h, whereas the latter already had increased values. These data demonstrate that meclofenamic acid is a safe, powerful and specific analgesic for the postsurgical period. The reduction of pain stimulation is also accompanied by a reduced activation of the neuroendocrine axis with a prompt recovery from postsurgical stress.


1990 - A new 5-HT2 antagonist (ritanserin) in the treatment of chronic headache with depression. A double-blind study vs amitriptyline. [Articolo su rivista]
G., Nappi; G., Sandrini; F., Granella; L., Ruiz; G., Cerutti; Facchinetti, Fabio; F., Blandini; G. C., Manzoni
abstract

The exact relationship between depression and chronic headache remains unclear. Considerable clinical and pharmacological evidence suggests the existence of a common biological terrain. Many antidepressant drugs are effective in the treatment of migraine and chronic headache disorders. Ritanserin, a new very selective serotonin-2 (5-HT2) antagonist, has recently shown both analgesic and antidepressant properties. The present study compares in a double-blind design, the effectiveness of ritanserin and amitriptyline, a well-known antidepressant extensively used in migraine prophylaxis. Thirty-eight patients (30 females and 8 males ranging in age from 20 to 50 yrs) were classified according to the International Headache Society criteria as: patients with chronic tension-type headache (CTH) (11 cases) and patients with coexisting migraine and CTH (MCTH) (27 cases). Only patients with a score equal to or higher than 18 on the Hamilton Rating Scale for Depression (HRSD) were included. Ritanserin was highly effective in reducing Pain Total Index and analgesic consumption in chronic headache, and its activity was similar to that observed during amitriptyline treatment. A significant improvement of HRSD and HRSA (Hamilton Rating Scale for Anxiety) scores was observed during both treatments. The main results of our study concern the demonstration of antiheadache and antidepressive properties of ritanserin. To better define the profile of the patients and their clinical responsiveness to the treatment, dexamethasone suppression test, clonidine test and nociceptive flexion reflex were investigated in our patients. Our data confirm the usefulness of these methods as markers of chronic headache with depression.


1990 - Abnormal dexamethasone suppression test in headaches: Effect of analgesic abuse [Articolo su rivista]
Martignoni, E.; Facchinetti, F.; Sances, G.; Rocchi, L.; Orlandi, R.; Genazzani, A. R.; Nappi, G.
abstract

The response to dexamethasone suppression test (DST) in 13 subjects suffering from migraine without aura with coexisting chronic tension type headache, and abusing of instant-relief drugs was studied before and after analgesic withdrawal. Seventy-six per cent of the subjects was found to be non suppressor when abuser and 36% of them maintained the same response to DST after analgesic wash-out. These latter subjects showed a mild degree of depression and a daily pattern of plasma cortisol similar to that reported for depressed patients. These results suggest that in some patients headache and mood disorders coexist, possibly linked to a common psychobiological trait.


1990 - Beta-Endorphin, Insulin, ACTH and Cortisol Plasma Levels during Oral Glucose Tolerance Test in Obesity after Weight Loss [Articolo su rivista]
C., Giovannini; E., Ciucci; R., Clementi; P., Cugini; Facchinetti, Fabio; M., Negri
abstract

..


1990 - Bromocriptine in the Rett syndrome. [Articolo su rivista]
M., Zappella; A., Genazzani; Facchinetti, Fabio; G., Hayek
abstract

Twelve typical cases of the Rett syndrome and one forme fruste were treated with bromocriptine for six months and then had a washout for two months followed by resumption of the bromocriptine treatment. During the first bromocriptine treatment there were improvements in communication and relaxation in some of the girls: a more regular sleep pattern was observed in 4 and a more varied facial expression in 8, and 4 girls began to utter a few words. The bouts of hyperpnea disappeared in 5 and grinding of the teeth in 3. There was also a reduction in stereotypic hand activities in 5 girls and signs of improved motor abilities in 3. The washout caused a general decrease in the positive effects of the previously administered bromocriptine and resumption of the treatment with this drug led to less marked improvement. Metoclopramide was tested in all the girls before the treatment, and it was noted that, while endorphins were hyporesponsive, prolactin was hyperresponsive. This test was repeated two months after the bromocriptine treatment had been performed and, while beta-lipotropin remained unchanged, beta-endorphin showed increased responsiveness.


1990 - Changes in beta-endorphin in fetal membranes and placenta in normal and pathological pregnancies. [Articolo su rivista]
Facchinetti, Fabio; G., Garuti; F., Petraglia; F., Mercantini; A. R., Genazzani
abstract

Several studies indicated that trophoblast tissue synthesizes pro-opiomelanocortin-related peptides. These peptides are also present in amniotic fluid, but their origin remains unknown. The present study evaluated the presence of and the possible changes in beta-endorphin (beta-EP) in amnion and chorion during pregnancy, at parturition and in spontaneous abortion. Amnion, chorion and placental tissues were isolated and homogenized from a total of 46 pregnant women between 4th and 42 th week of pregnancy. Beta-EP was separated on a Sephadex G-75 column and measured by RIA with specific antiserum. The identity of the endogenous opioid with its corresponding reference molecule was confirmed by high performance liquid chromatography. In all tissues, the concentration of beta-EP in the first trimester was significantly higher than in the second trimester. A negative correlation between opioid levels and gestational age was observed in the first two trimesters. At delivery, the beta-EP content of all tissues was greater than in the second trimester. In tissues collected at term, in the absence of labor, beta-EP levels were very low in comparison with those collected after vaginal delivery. Low beta-EP contents were found in membranes collected from spontaneous abortion in 1st trimester. From these data one can surmise the existence of a local endogenous opioid system in fetal adnexes. This system seems sensitive to the stress of vaginal delivery and could be involved in the mechanisms leading to spontaneous abortion.


1990 - β-Endorphin and consummatory behaviors: The case of hyperphagic obesity [Relazione in Atti di Convegno]
Facchinetti, Fabio
abstract

The hypersecretion of opioids is evaluated in hyperphagic obesity. The abnormal and persistent stimulation of β-Endorphin after glucose load (even after weight loss) suggests a direct involvement of endogenous opioids in the reward properties of food intake.


1990 - Erratum: Time-course of opioid and pituitary-adrenal hormone modifications during the immobility reaction in rabbits (Physiology and behavior 47(2) 337-341 (1990)) [Articolo su rivista]
Facchinetti, Fabio
abstract


1990 - Maternal plasma concentration of magnesium, calcium, zinc and copper in normal and patological pregnancies [Articolo su rivista]
Borella, Paola; A., Szilagyi; G., Than; I., Csaba; A., Giardino; Facchinetti, Fabio
abstract

In this study, plasma levels of magnesium, calcium, zinc and copper were simultaneously determined in pregnancies complicated by either abortion, intrauterine growth retardation (IUGR), diabetes or EPH (edema, proteinuria, hypertension) gestosis. The levels of the four cations in non-pregnant women and in healthy, pregnant women were also determined. Compared with controls, a significant decrease in magnesium, with increase of the Ca/Mg ratio, was found in spontaneous abortions, but not when patients had a successful continuation of pregnancy. In EPH gestosis, total calcium was reduced, with a significant decrease of the plasma Ca/Mg ratio. A slight, but significant, increase in plasma zinc was observed in women affected by either diabetes or IUGR, probably as a result of reduced zinc uptake by the fetus. In addition, higher copper levels were found in the pathologies studied, with the exception of missed abortions. The possible role of an altered Ca/Mg ratio homeostasis in relation to gestational pathologies is discussed.


1990 - Naproxen sodium in menstrual migraine prophylaxis: a double-blind placebo controlled study. [Articolo su rivista]
G., Sances; E., Martignoni; L., Fioroni; F., Blandini; Facchinetti, Fabio; G., Nappi
abstract

In this study, the efficacy of Naproxen sodium (Nxs) in the prophylaxis of Menstrual Migraine (MM) was tested, versus Placebo (PL). Forty women suffering from MM were admitted to a double-blind treatment protocol with Nxs 550 mg twice each day by mouth or Placebo (PL), for 3 months; in the next 3 months all the women were treated with the active drug in an open study. The headache intensity and duration, as well as the number of days of headache and the analgesic consumption, were significantly reduced with Nxs compared to PL. The efficacy of Nxs, shown also in improving premenstrual pain, and its good tolerability, support the use of this drug in the prophylactic therapy of MM.


1990 - [Neuroendocrine changes and affective disorders in patients with hyperphagic obesity]. [Articolo su rivista]
C., Giovannini; C., Barletta; F., Burla; E., Ciucci; D., Vagiri; Facchinetti, Fabio
abstract

Circulating levels of cortisol and beta-endorphin were evaluated in basal condition and following dexamethasone administration in 20 healthy subjects and in 60 subjects suffering from hyperphagic obesity. Moreover, mental tests were administered to these subjects in order to evaluate the affective state. Our data showed that in obese patients B-Ep plasma levels were significantly higher than those of the control group, while cortisol plasma levels were similar in the two groups. Dexamethasone administration decreased cortisol plasma levels in normal and obese subjects, while did not modify B-Ep plasma levels in obese subjects. However, after dexamethasone administration 16.6\% of the obese subjects did not show a complete decrease of cortisol level. This group of subjects obtained the highest scores for depression and hypochondria to MMPI.


1990 - Neuroendocrine correlates of premenstrual syndrome: changes in the pulsatile pattern of plasma LH. [Articolo su rivista]
Facchinetti, Fabio; Genazzani, Alessandro; E., Martignoni; L., Fioroni; G., Sances; A. R., Genazzani
abstract

Some studies suggest that patients suffering from premenstrual syndrome (PMS) may be affected by an endogenous opioid dysfunction. Since opioids are the main modulators of the pulsatile LH secretion, we evaluated plasma LH pulsatility in 13 patients with PMS (aged 33.1 yr) and in six asymptomatic control volunteers (aged 31.5 yr), in the late luteal phase (-7, -5 days before their next menses). The patients were prospectively evaluated for two menstrual cycles with the Menstrual Distress Questionnaire; the main symptoms which worsened during the premenstrual period were mood swings and water retention. The pulsatility of plasma LH secretion was studied by collecting blood samples every 10 min for 12 hr, starting at 0800h. The presence of LH pulses was estimated using the program DETECT on the raw data. This program also allows the computation of the instantaneous secretory rate (ISR). Ovulation was ascertained in all the controls and in nine PMS patients by means of urinary LH assay and luteal progesterone (P) determination. The remaining four patients did not ovulate. Both the ovulatory and the anovulatory PMS patients had an increased number of LH pulses/12 hr (10.3 +/- 2.4 and 11.5 +/- 4.4, mean +/- SD, respectively) in comparison with the controls (7.0 +/- 1.3 pulses, p less than 0.01), together with a reduced amplitude and duration. Similar findings were obtained with the ISR computation. Plasma P levels were similar in both the ovulatory patients and controls. The increased frequency and reduced amplitude of LH pulses in the PMS patients most likely reflect a dysfunction of hypothalamic Gn-RH release, possibly linked to a reduction of opioid inhibition.


1990 - Opioid control of the hypothalamus-pituitary-adrenal axis cyclically fails in menstrual migraine. [Articolo su rivista]
Facchinetti, Fabio; E., Martignoni; L., Fioroni; G., Sances; A. R., Genazzani
abstract

To assess the biological correlates of the precipitation of migraine attacks in the perimenstrual period, plasma beta-endorphin (beta-EP) and cortisol responses to naloxone (8 mg iv) and corticotropin releasing hormone (100 micrograms iv) were evaluated in both the follicular phase and the premenstrual period in 7 patients suffering from menstrual migraine and in 7 healthy, asymptomatic control volunteers. In the controls, naloxone evoked a significant release of both beta-EP (F = 5.86, p less than 0.002) and cortisol (F = 4.43, p less than 0.008), independently of the menstrual cycle phase (F = 0.31 and 1.04, for beta-EP and cortisol, respectively). Menstrual migraine patients, on the other hand, showed a significant hormone response only in the follicular phase, not in the premenstrual period. Corticotropin releasing hormone significantly increased beta-EP and cortisol in both the controls and the menstrual migraine patients, independently of the menstrual cycle phase. In both the naloxone and corticotropin releasing hormone testings, the basal beta-EP levels measured in the premenstrual period were lower than those observed in the follicular phase (p less than 0.02). These data demonstrate a cyclical, premenstrual dysfunction of the hypothalamic control exerted by opioids on the hypothalamus-pituitary-adrenal axis. Impairment of this fundamental adaptive mechanism (involved in stress responses and in pain control) could establish a causal relationship between menstrual-related migraine attacks and premenstrual opioid hyposensitivity.


1990 - [Plasma levels of beta-endorphin , ACTH and cortisol in obese patients subjected to several weight-loss treatments]. [Articolo su rivista]
C., Giovannini; E., Ciucci; Facchinetti, Fabio
abstract

It is now well-known that the plasmatic levels of beta-endorphin (B-Ep) in subjects suffering from hyperphagie obesity during childhood, adolescence and adult age, are higher than those of normal weight standard-wright. The causes are still unknown. In obese subjects, there is also a dissociation between plasmatic levels of B-Ep and of ACTH, in spite of the common origin of Proopiomelanocortin (POMC). On the basis of these observations we studied the plasmatic levels of B-Ep, ACTH and cortisol, basal and after DXM, before and after the reduction of body weight. With the aim of evaluating pharmacological interference, the obese subjects were treated with diet alone or diet associated with an anorectic and serotoninergic drug (fenfluramin). The results have shown that after slimming, obtained with diet alone or with the help of the serotoninergic drug, the hyperendorphinemia persists both in basal conditions and after the DXM test. The verification of such behaviour in some psychiatric diseases supports our assumption of a link between hyperendorphinemia, behaviour alterations, hyperphagy and obesity.


1990 - PLASMA ß-ENDORPHIN AND ß-LIPOTROPIN LEVELS INCREASE IN WELL TRAINED ATHLETES AFTER COMPETITION AND NON COMPETITIVE EXERCISE. [Articolo su rivista]
Petraglia, F; Bacchi Modena, A; Comitini, G; Scazzina, D; Facchinetti, Fabio; Fiaschetti, D; Genazzani, Alessandro; Barletta, C; Scavo, D; Genazzani, Ar
abstract

Plasma beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) levels were measured in 15 healthy trained marathon runners. These hormones were evaluated in two different conditions: 1-before (1h) and after a marathon race (n = 10); 2-before, during and after a prolonged (90 min) submaximal exercise (bicycle ergometer at 50% VO2 max) (n = 5). In these latter group plasma beta-EP and beta-LPH levels were measured every 15 min for 165 min. In all the athletes, both plasma beta-EP and beta-LPH levels were significantly higher after the end of the marathon race than in basal conditions (p less than 0.01). The prolonged exercise with bicycle ergometer significantly stimulated plasma beta-EP and beta-LPH levels. Starting 60 min after the beginning of the exercise, plasma beta-EP and beta-LPH levels resulted significantly higher than basal values until the end of the exercise (p less than 0.01 at 60, 75 and 90 min). These data confirming that marathon running is a potent stress stimulus, showed that the duration and related factors but not the work load may be considered critical in stimulating beta-EP and beta-LPH release during physical exercise


1990 - Post-operative increase of cerebrospinal fluid beta-endorphin-like immunoreactivity levels [Articolo su rivista]
Fusi, S.; Porro, C. A.; Facchinetti, F.; Casadei, E.; Pecchi, A.; Genazzani, A. R.
abstract


1990 - Reduction of monocyte magnesium in patients affected by premenstrual-syndrome. [Articolo su rivista]
Facchinetti, Fabio; Borella, Paola; L., Fioroni; T., Pironti; A. R., Genazzani
abstract

.


1990 - ß-ENDORPHIN PLASMA LEVELS AFTER MIXED MEAL IN OBESE CHILDREN [Articolo su rivista]
Iughetti, Lorenzo; Facchinetti, Fabio; A., Cozzini; A. R., Genazzani; S., Bernasconi
abstract

..


1990 - The endocrine effects of visual erotic stimuli in normal men. [Articolo su rivista]
Carani, Cesare; J., Bancroft; G., Del Rio; A. R. M., Granata; Facchinetti, Fabio; P., Marrama
abstract

not available


1990 - Time-course of opioid and pituitary-adrenal hormone modifications during the immobility reaction in rabbits. [Articolo su rivista]
F., Farabollini; Facchinetti, Fabio; C., Lupo; G., Carli
abstract

A series of experiments in male rabbits examined the influence of tonic immobility (animal hypnosis) on the opioid and pituitary-adrenal hormones. The aims of the experiments were to follow the temporal modifications in hormone parameters and to discriminate the effects of immobility from those of the manipulative procedure to induce the reaction. Results show that immobility elicits increases in plasma ACTH and beta-EP, but no modifications in pituitary beta-EP. The effects of induction procedure were dissociable from those of immobility, the most marked effect being a prolonged, sustained increase of corticosterone plasma levels. Results support the hypothesis of the opioid involvement in the physiological control of immobility reaction and indicate different mechanisms underlying the immobility response and the procedure of induction.


1989 - A 7-DAY I.V.C. INFUSION OF ACTH-(1-24), IN RATS, IS ASSOCIATED WITH THE DEVELOPMENT OF TOLERANCE TO ITS BEHAVIOURAL EFFECTS AND WITH INCREASED LEVELS OF HYPOTHALAMIC B-ENDORPHIN [Articolo su rivista]
Av, Vergogni; D., Marrama; R., Poggioli; C., Bazzani; Facchinetti, Fabio; A., Bertolini
abstract

..


1989 - Beta-Endorphin plasma levels after mixed meal in obese children. [Articolo su rivista]
Iughetti, Lorenzo; Facchinetti, Fabio; A., Cozzini; A. R., Genazzani; S., Bernasconi
abstract

N.A.


1989 - Chronic paroxysmal hemicrania: a chronobiological study (case report). [Articolo su rivista]
G., Micieli; A., Cavallini; Facchinetti, Fabio; G., Sances; G., Nappi
abstract

In this study the 24-h pattern of blood pressure (BP), heart rate (HR), plasma catecholamine (CA), beta-endorphin (beta-EP), beta-lipotropin (beta-LPH) and RIII threshold was investigated in a patient suffering from chronic paroxysmal hemicrania (CPH). The investigation was carried out before and during indomethacin therapy in order to assess the presence or otherwise of a disordered biorhythmic organization resembling that documented in cluster headache (CH). A severe alteration in the majority of the rhythms explored was found not only during the drug-free phase, but also in the indomethacin phase of the investigation. These data are similar to those obtained in CH studies and point to the possibility of a common pathophysiological mechanism.


1989 - Effect of oral contraceptives or dexamethasone on plasma beta-endorphin during the menstrual cycle. [Articolo su rivista]
G., Comitini; F., Petraglia; Facchinetti, Fabio; M., Monaco; Volpe, Annibale; A. R., Genazzani
abstract

Several studies have showed a significant increase of plasma beta-endorphin levels during the periovulatory days of the menstrual cycle. The aim of the present study was to investigate the origin of the periovulatory changes of plasma beta-endorphin, trying to discriminate between a possible ovarian and/or pituitary origin. Daily plasma beta-endorphin, luteinizing hormone (LH), and cortisol levels were measured from the 8th to the 20th day of the menstrual cycle in healthy normal-cycling women (10 cases) before and during dexamethasone (DEX; 6 cases) or estroprogestinic treatment with monophasic (5 cases) or triphasic (5 cases) pill. In the control menstrual cycle, during the preovulatory days, a significant increase of plasma beta-endorphin was found. While oral contraceptives abolished the midcycle increase of plasma beta-endorphin, the periovulatory plasma beta-endorphin peak was present during DEX treatment. Plasma cortisol levels did not show any significant change throughout the control menstrual cycle, while they were significantly lowered by the DEX administration and significantly increased during estroprogestinic treatment. These results suggest that the increase of plasma beta-endorphin during the periovulatory days is related to the ovulatory function, and suggest a possible ovarian origin.


1989 - Effects of bromocriptine on pituitary and adrenal cortex in pre-adrenarchal rabbits. [Articolo su rivista]
R., Pérez Fernandez; Facchinetti, Fabio; T. G., Caballero; A. R., Genazzani; J., Devesa
abstract

The effect of bromocriptine on the morphological picture and steroid content of the adrenal gland, and on certain pro-opiomelanocortin (C) peptides in the pituitary gland was evaluated in preadrenarchal rabbits. Eighteen immature male rabbits (5 weeks of age), were treated for 10 days with saline (n = 10,2 ml sc) or bromocriptine mesylate (n = 8, 3 mg/kg sc) two times/day. After the last administration all animals received dexamethasone (0.25 mg im) and the next morning, 60 min after ACTH injection (0.25 mg im), plasma was drawn and they were sacrificed. Adrenals and pituitaries were immediately removed. For each animal, one adrenal gland was fixed, dehydrated and embedded in paraffin for histology; the other one was stored in saline for determination of androstenedione (A), dehydroepiandrosterone (DHA), 17-OH progesterone (17 P), and cortisol. Steroids were analyzed by RIA after previous extraction and celite-ethyleneglycol chromatography, or directly (cortisol). The immunoreactivities (ir) related to beta-Endorphin (B-EP), ACTH and alpha-MSH were evaluated in pituitary homogenates using specific RIAs. The bromocriptine-treated rabbits showed a significant increase in the percentage of the adrenal zona reticularis (21.5 +/- 3.9\% of total cortex vs. 12.7 +/- 1.3\% in controls, p less than 0.05, mean +/- SE), and a decrease of the zona fasciculata (57.6 +/- 3.13\% vs. 67.7 +/- 2.05\% in controls, p less than 0.05). No significant changes were observed in the relative percentage of the zona glomerulosa.(ABSTRACT TRUNCATED AT 250 WORDS)


1989 - Fetal intermediate lobe is stimulated by parturition. [Articolo su rivista]
Facchinetti, Fabio; A., Lanzani; A. R., Genazzani
abstract

The fetal pituitary gland secretes beta-endorphin in blood in response to delivery. However, other forms of endorphin have recently been observed in the fetal pituitary, such as N-acetyl-beta-endorphin, which is devoid of opiate activity, and a desacetylated form of alpha-melanocyte-stimulating hormone. Both endorphins originate in the pituitary intermediate lobe. The sensitivity of this lobe to labor stress was assessed by the evaluation of beta-endorphin, N-acetyl-beta-endorphin, melanocyte-stimulating hormone, and desacetylated alpha-melanocyte-stimulating hormone in maternal plasma and cord blood in 11 cases of vaginal delivery and 10 cases of elective cesarean section without labor. Plasma peptide levels were determined by specific radioimmunoassays after extraction on Sep-Pak C-18 cartridges and high-performance liquid chromatography fractionation. Cord blood samples of infants delivered vaginally showed higher beta-endorphin (8.5 +/- 1.6 pmol/L, mean +/- SE) and desacetylated alpha-melanocyte-stimulating hormone (13.6 +/- 3.2 pmol/L) levels than those delivered by elective cesarean section (3.7 +/- 0.8 and 4.2 +/- 1.1 pmol/L, for beta-endorphin and desacetylated alpha-melanocyte-stimulating hormone, respectively). N-acetyl-beta-endorphin and alpha-melanocyte-stimulating hormone levels do not differ in relation to the mode of delivery. In maternal circulation beta-endorphin levels were higher in those delivered vaginally (5.2 pm 1) than in women who had cesarean sections (2.5 +/- 0.5 pmol/L), whereas no changes were found for the other peptides. In vaginal deliveries, the level of desacetylated alpha-melanocyte-stimulating hormone was higher in cord blood (13.6 +/- 3.2 pmol/L) than in maternal plasma (6.5 +/- 3 pmol/L); there were no significant differences with regard to the other peptides. Fetal and maternal levels of all the peptides were similar in cases of cesarean section. We conclude that parturition activates proopiomelanocortin peptide release from both the anterior and the intermediate pituitary lobe and that the fetus secretes the appropriate beta-endorphin molecule, that is, the peptide able to bind opiate receptors. Concomitant secretion of desacetylated alpha-melanocyte-stimulating hormone may occur with adrenal androgen activation at birth.


1989 - Fetal pituitary intermediate lobe response to parturition [Articolo su rivista]
Facchinetti, Fabio
abstract


1989 - Gastrin-releasing peptide-like immunoreactivity in porcine follicular fluid and ovary. [Articolo su rivista]
L., Gnessi; S., Altamura; M., Arizzi; C., Tei; C. L., Torre; V., Bonifacio; Facchinetti, Fabio; G., Spera
abstract

Porcine follicular fluid was found to contain gastrin-releasing peptide (GRP) by radioimmunoassay. High pressure liquid chromatography of the extracted material showed two peaks of GRP immunoreactivity that closely resembled the C-terminal fragments of GRP, GRP18-27 and GRP14-27. Immunohistochemical studies revealed specific staining for GRP in the granulosa cells of adult porcine ovary. These results demonstrate the presence of substances which behave like authentic GRP-like peptides in porcine ovary and follicular fluid and suggest that these peptides may play a paracrine and/or autocrine role in the regulation of the ovarian function.


1989 - Intra-uterine growth retardation is associated with increased levels of magnesium in amniotic fluid. [Articolo su rivista]
Facchinetti, Fabio; Borella, Paola; M., Valentini; A., Segre; C., Battaglia; A. R., Genazzani
abstract

Magnesium (Mg) and zinc (Zn) levels were measured in amniotic fluid of 30 normal pregnancies between the 16th and the 42nd week of amenorrhea and in 15 cases of intra-uterine growth retardation (IUGR) at 30-38th week of pregnancy. While Zn levels were stable throughout physiological pregnancy, the Mg concentration decreased progressively from 1.09 +/- 0.31 mg/100 ml (mean +/- SD) at the end of the second trimester to 0.75 +/- 0.20 (p less than 0.02) at term. In the case of IUGR, Mg levels (1.22 +/- 0.28) were higher than in controls (0.89 +/- 0.27, p less than 0.01) matched for gestational age. No differences in Zn levels were found between the two groups. Although the mechanisms leading to Mg accumulation in the amniotic fluid of growth-retarded fetuses remain unknown, these data support the role played by Mg in fetal growth.


1989 - Long-acting theophylline in the prevention of nocturnal asthma [Articolo su rivista]
Facchinetti, Fabio
abstract


1989 - Naproxen sodium in the treatment of premenstrual symptoms. A placebo-controlled study. [Articolo su rivista]
Facchinetti, Fabio; L., Fioroni; G., Sances; G., Romano; G., Nappi; A. R., Genazzani
abstract

The prostaglandin system is thought to play a role in the etiology of the premenstrual syndrome. Many authors describe that prostaglandins are involved in both central and peripheral symptoms. To test this hypothesis, we studied the effects of naproxen sodium treatment (550 mg twice daily, from day -7, in relation to next menses, to the 4th day of the cycle) in 34 patients suffering from premenstrual syndrome. Six cases dropped out. Fourteen women were given placebo for the first three cycles of the trial, followed by active drug. The other 14 patients were given naproxen sodium, beginning from the first cycle. In order to evaluate premenstrual symptoms, the Moos menstrual distress questionnaire was prospectively applied during the 2-month run-in period and at the 3rd and 6th cycles of treatment. During our double-blind naproxen sodium study, both menstrual and premenstrual 'pain' decreased during active drug treatment, while placebo was ineffective. We also obtained a significant improvement of premenstrual 'behavioral changes' which is probably related to the relief of painful symptomatology. In conclusion, this study indicates that naproxen sodium is a useful and safe drug in the treatment of premenstrual and menstrual pain related symptoms.


1989 - Neuroendocrine evidence of deranged noradrenergic activity in chronic migraine. [Articolo su rivista]
E., Martignoni; Facchinetti, Fabio; F., Rossi; G., Sances; A. R., Genazzani; G., Nappi
abstract

Migraine is a psychobiological disorder in which a recurrent failure of opioid and adrenergic systems might occur, as plasma and CSF studies suggest. In order to elucidate the relationship between noradrenergic and opioidergic functions, the plasma beta-endorphin (beta-EP) response to clonidine and the cortisol response to dexamethasone were evaluated together in 25 patients suffering from migraine without aura, and with chronic tension headache (MTH). Baseline beta-EP plasma levels and beta-EP response to clonidine were significantly lower in MTH subjects than in controls, suggesting a postsynaptic hypothalamo-pituitary impairment. Forty-four percent of the MTH subjects showed either a lack of suppression of plasma cortisol following dexamethasone administration, or basal cortisol concentrations higher than controls and suppressors, suggesting a disinhibition of the hypothalamopituitary-adrenal (HPA) axis. An inverse correlation was found between pain severity and beta-EP secretion induced by clonidine (delta max), and no relationship was found between beta-EP and mood. These data suggest a failure of central noradrenergic activity, or perhaps an impaired secretion of beta-EP not related to HPA axis hyperactivity or to affective state.


1989 - Oocyte fertilization in vitro is associated with high follicular immunoreactive beta-endorphin levels. [Articolo su rivista]
Facchinetti, Fabio; P. G., Artini; M., Monaco; Volpe, Annibale; A. R., Genazzani
abstract

Follicular fluid (FF) levels of immuno reactive beta-Endorphin (i.r. beta-EP), i.r. gamma-Endorphin (i.r. gamma-EP), i.r. alpha-melanocyte-stimulating hormone (i.r. alpha-MSH), androgens and estrogens were measured in 76 preovulatory follicles obtained, after gonadotropin stimulation from 19 women undergoing in vitro fertilization (IVF). The aim of the study was to investigate the relationships existing between peptide contents of FF and both oocyte-cumulus-corona-complex (OCCC) maturity and the success of IVF. Peptides and steroids were measured by RIA after FF extraction with liquid chromatography and ethyl-ether, respectively. Out of the total of 76 oocytes, 52 were fertilized in vitro and 35 of them underwent normal cleavage and were transferred. Among the three peptides, only i.r. beta-EP levels were higher in FF from follicles which contained oocytes that were subsequently fertilized (127.6 +/- 16.2 pmol/L mean +/- SE) than in FF from follicles which contained oocytes that did not subsequently fertilized (62.9 +/- 8.4, p less than 0.04). Independent of subsequent fertilization, i.r. alpha-MSH values in FF were 5 times higher than those of i.r. beta-EP and i.r. gamma-EP. In the presence of a morphologically mature oocyte, FF i.r. gamma-EP levels (165.2 +/- 45.3 pmol/L) were higher than in FF from follicles yielding immature (63.6 +/- 13.5, p less than 0.01) or luteinized (32.7 +/- 9.2, p less than 0.01) oocytes. Steroid levels in FF did not change in relation to oocyte maturity or subsequent oocyte fertilization.(ABSTRACT TRUNCATED AT 250 WORDS)


1989 - Plasma beta-endorphin levels in obese and non-obese patients with polycystic ovarian disease. [Articolo su rivista]
C., Nappi; F., Petraglia; V., Cudemo; Volpe, Annibale; Facchinetti, Fabio; A. R., Genazzani; U., Montemagno
abstract

Several reports have shown elevated circulating beta-endorphin (beta-EP) levels in patients with polycystic ovarian disease (PCOD). However, it is not yet clear whether these high beta-EP levels are linked to the etiopathogenesis of PCOD or are secondary to the obesity. In the present study we measured beta-EP plasma concentrations in 19 PCOD patients, 10 with normal weight (Group A) and 9 with excessive weight (Group B), and in 18 normally ovulating women, 10 with normal weight (Group C) and 9 with excessive weight (Group D). beta-EP values were similar in the two groups of non-obese patients and controls. beta-EP concentrations were also similar in the two groups of obese patients and controls, and they were significantly higher (p less than 0.05) than in non-obese patients. Our data indicate that in PCOD, elevated beta-EP values are related to obesity, suggesting that they are not linked to the pathogenesis of PCOD.


1989 - Premenstrual failure of alpha-adrenergic stimulation on hypothalamus-pituitary responses in menstrual migraine. [Articolo su rivista]
Facchinetti, Fabio; E., Martignoni; G., Nappi; L., Fioroni; G., Sances; A. R., Genazzani
abstract

In nine women suffering from menstrual migraine (MM), and in six healthy asymptomatic volunteers, plasma beta-endorphin (beta-EP), growth hormone (GH), norepinephrine (NE), and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) concentrations were measured in response to clonidine (0.075 mg, i.v.) stimulation. In MM patients clonidine testing was performed in both the early and the late luteal phases of the menstrual cycle. Premenstrual symptoms were prospectively evaluated in the actual cycle using the Moos Menstrual Distress Questionnaire. beta-EP (after gel chromatography) and GH were measured using radioimmunoassay. NE and MHPG were evaluated by HPLC using electrochemical detection. In both phases of the menstrual cycle clonidine significantly reduced NE and MHPG levels in MM patients and controls in a similar way. In MM patients beta-EP and GH plasma levels were stimulated by clonidine only in the early luteal phase, whereas they remained unchanged when they were stimulated in the premenstrual period. In controls the response of both hormones was not affected by the menstrual cycle. The lack of hormonal response to clonidine in MM may suggest a postsynaptic alpha 2-adrenoreceptor hyposensitivity during the premenstrual period. This demonstrates a transient vulnerability of the neuroendocrine/neurovegetative systems, and could thus be a factor facilitating the precipitation of both behavioral changes and migraine attacks.


1989 - Presence of acetylated and shortened endorphins in human fetal pituitary gland. [Articolo su rivista]
Facchinetti, Fabio; A. R., Storchi; F., Petraglia; A. R., Genazzani
abstract

A total of 21 human fetal pituitaries was collected from spontaneous abortions (11 cases) or prostaglandin (PG)-induced abortions at the second trimester. Pituitaries were homogenized, fractionated by HPLC, and the fractions were tested by specific RIA for alpha-endorphin (EP) (beta-EP 1-16), gamma-EP (beta-EP 1-17), beta-EP (beta-EP 1-31), and their alpha-N-acetylated derivatives. In the fetal pituitaries collected after spontaneous abortion, the contents of alpha-EP (23.4 +/- 7.5 pmol/mg protein, mean +/- SE) and gamma-EP (28.9 +/- 9.7) were similar to those of beta-EP (28.6 +/- 7.4). Both beta-EP/alpha-EP (1.2 +/- 0.3) and beta-EP/gamma-EP (1.1 +/- 0.3) ratios approached unity. Although 35.7 and 30.2\% of alpha-EP and gamma-EP were acetylated, acetyl-beta-EP was only 8.4\% of the total beta-EP immunoreactivity. In the five cases of PG-induced abortion that were more than 20 wk of pregnancy, the pituitary content of beta-EP (75.9 +/- 21.2) and gamma-EP (26.2 +/- 7.5) were significantly higher than in samples collected after spontaneous abortion (13.3 +/- 8.2 and 5.9 +/- 1.8, respectively, p less than 0.01). On the contrary, neither alpha-EP (31.3 +/- 5.2), acetyl-alpha-EP (0.94 +/- 0.28), acetyl-gamma-EP (0.65 +/- 0.07), acetyl-beta-EP (0.35 +/- 0.05) pituitary contents in PG-induced abortions differed from those measured after spontaneous abortion (alpha-EP: 25.6 +/- 6.6; acetyl-alpha-EP: 0.92 +/- 0.41; acetyl-gamma-EP: 0.82 +/- 0.30; acetyl-beta-EP: 0.96 +/- 0.44).(ABSTRACT TRUNCATED AT 250 WORDS)


1989 - Reduced cerebrospinal fluid B-endorphin levels in Rett syndrome. [Articolo su rivista]
A. R., Genazzani; M., Zappella; A., Nalin; Y., Hayek; Facchinetti, Fabio
abstract

Cerebrospinal fluid (CSF) levels of B-endorphin (B-EP), B-lipotropin (B-LPH) and ACTH were measured in nine girls with Rett syndrome with features of autistic behavior (3.7-12.1 years of age) and in ten children with chronic leukemia (control group). The peptides were measured by radioimmunoassay, either directly in the sample (ACTH) or after Sephadex G-75 column chromatography, in order to eliminate interfering substances (B-LPH and B-EP). The CSF B-EP patient levels (20.8 +/- 13.1 fmol/ml, means +/- SD) were significantly lower than in age-matched controls (69.1 +/- 32.6, P less than 0.01), whereas the B-LPH and ACTH levels were in the control range. No correlations were found between the clinical findings and CSF neuropeptide concentrations. These data demonstrate a decrease in central opiate activity in girls with Rett syndrome.


1989 - safety and efficacy of nitroprusside gel for cervical ripening [Abstract in Rivista]
Facchinetti, Fabio; Piccinini, F.; Fazio, M.; Volpe, Annibale
abstract

.


1989 - Stress and hormones in humans [Relazione in Atti di Convegno]
Genazzani, A. R.; Petraglia, F.; Monzani, A.; Fabbri, G.; De Ramundo, B.; Di Domenica, P.; Facchinetti, F.; Volpe, A.
abstract


1989 - Tolerance develops to the behavioural effects of ACTH-(1-24) during continuous i.c.v. infusion in rats, and is associated with increased hypothalamic levels of beta-endorphin. [Articolo su rivista]
A. V., Vergoni; R., Poggioli; Facchinetti, Fabio; C., Bazzani; D., Marrama; A., Bertolini
abstract

In rats, the continuous infusion of ACTH-(1-24) into a brain lateral ventricle (0.5 micrograms/h in the volume of 1.11 microliters, for 7 days) caused a significant inhibition of the subsequent behavioural response to the acute intracerebroventricular injection of the same peptide. Tolerance developed to all the most typical signs of the ACTH-induced behavioural syndrome (grooming, stretching, yawning, penile erection, inhibition of food intake), and was associated with a significant increase in the hypothalamic levels of beta-endorphin immunoreactivity.


1988 - Absent B-Endorphin response to Clonidine in obese children. [Articolo su rivista]
Facchinetti, Fabio; S., Bernasconi; F., Petraglia; C., Marcellini; Iughetti, Lorenzo; A. R., Genazzani
abstract

Plasma B-Endorphin (B-EP), Growth Hormone (GH) and cortisol response to 100 mcg/m2 b.s., i.v. clonidine (an alpha 2-adrenergic agonist) were evaluated in 17 normal weight children (8 prepubertal and 9 pubertal) and in 15 children with simple exogenous obesity (7 prepubertal and 8 pubertal, weight excess ranging from 29% to 97%). All the hormones were measured by radioimmunoassay either directly in the plasma (GH and cortisol) or after extraction and chromatography (B-EP). Obese prepubertal and pubertal children showed basal B-EP levels significantly higher than in controls and no differences were found in GH and cortisol levels. While in controls clonidine stimulated a significant release of plasma GH and B-EP in obese patients, irrespective of pubertal development, no changes were found. Cortisol levels decreased in both groups. These data suggest an impaired adrenergic control of GH and B-EP secretion in children with simple exogenous obesity.


1988 - Acetyl-L-carnitine acutely administered raises beta-endorphin and cortisol plasma levels in humans. [Articolo su rivista]
E., Martignoni; Facchinetti, Fabio; G., Sances; F., Petraglia; G., Nappi; A. R., Genazzani
abstract

Acetyl-L-carnitine acutely administered raises beta-endorphin and cortisol plasma levels in humans.


1988 - Acetyl-L-carnitine normalizes pituitary-adrenocortical hyperactivity in pathological ageing brain [Articolo su rivista]
Facchinetti, Fabio
abstract

The prevalence of glucocorticoid hypersecretion and the loss of hippocampal inhibition of hypothalamus-pituitary-adrenal (HPA) axis in Alzheimer type dementia (ATD) underlie the 'glucocorticoid cascade' hypothesis for a neuroendocrine definition of aging. Therefore we measured, in mild to moderate demented patients, plasma B-endorphin and cortisol levels, which, in 41% of the subjects were both higher than 2 SD of mean control values. The treatment with Acetyl-L-Carnitine (ALC) normalized the highest values, while piracetam did not. The possibilities that this effect is due to the cholinergic activity of ALC and/or its action in preventing the loss of hippocampal glucocorticoid receptors after cold stress are suggested.


1988 - Aging brain and dementias: changes in central opioids. [Articolo su rivista]
G., Nappi; E., Sinforiani; E., Martignoni; F., Petraglia; Facchinetti, Fabio; F., Rossi; A. R., Genazzani
abstract

We evaluated the CSF levels of beta-lipotropin (beta-LPH), beta-endorphin (beta-EP) and ACTH, which are three neuropeptides expressed by the same gene encoding for pro-opiomelanocortin, in various groups of demented patients including degenerative (presenile and senile Alzheimer-type dementia, ATD) and vascular (MID) forms. Twelve sex- and age-matched subjects were taken as controls. Our data indicate that ACTH levels are significantly reduced both in ATD and MID patients, while beta-EP and beta-LPH are significantly reduced only in ATD. The low CSF ACTH levels can be considered typical of all demented processes (both degenerative and vascular), while the reduction of beta-EP and beta-LPH in CSF could be due to a degenerative process of CNS.


1988 - Alteration of opioid peptide and receptor ontogeny in the brain of pre- and postnatally low-level lead-exposed rats. [Articolo su rivista]
M., Baraldi; P., Zanoli; T., Rossi; Facchinetti, Fabio
abstract

While the dopaminergic, the cholinergic and the GABAergic systems have been extensively studied in various models of lead intoxication, less attention has been devoted to the brain opiatergic system (opioid). We have recently reported that in rats pre- and postnatally exposed to a very low amount of lead (1 mg/kg/day) there was, at 40 days of age (behavioural anomalies such as hypermotility and decreased response to pain stimuli), an increased number of opiate receptors in the brain associated to a decrease of beta-endorphin and an increase of Met-enkephalin. The aim of the present study was to find out whether the above mentioned abnormalities of the opiatergic system (opioid) could be the result of a neurotoxic effect of lead exerted early in the development of the central nervous system of rats born from lead-poisoned parents. Here we report that the exposure to a low level of lead induces a decrease of beta-endorphin with a concomitant increase of opiate receptors measured at embryonic day 16 as well as at 7, 15, 40 and 60 days postnatally. On the other hand, an increased presence of Met-enkephalin was not detectable until postnatal day 7. Since endogenous opioid peptides, particularly beta-endorphin, have been recognized as important factors in central nervous system development, the described ability of lead to affect the ontogeny of the opiatergic system (opioid) might provide a new insight in understanding the complex mechanism of lead neurotoxicity.


1988 - CISAPRIDE (R 51619) HAS NO EFFECT ON ANTERIOR PITUITARY SECRETIONS [Abstract in Rivista]
E., Martignoni; Facchinetti, Fabio; G., Comitini; G., Sances; G., Nappi; A. R., Genazzani
abstract

The effects of a new prokinetic compound, cisapride (R51619), on anterior pituitary secretion were evaLuated in 20 heaLthy voLunteers (10 men and 10 fertiLe women) in a doubLe bLind crossover pLacebo study. Cisapride (5 mg tabLet) and pLacebo, were given oraLLy (3 times a day) for 5 days with one week intervaL. PLasma hormone determinations were done by RIAs. No changes in PRL, LH, FSH, GH, TSH, cortisoL, B-Lipotropin, B-endorphin, testosterone and estradioL pLasma LeveLs were found after both cisapride and pLacebo. These data indicate that cisapride is a safe drug as concerns neuroendocrine effects and its mechanisms of action do not incLude a dopaminergic mediation


1988 - DOPAMINE ACTS ON ACETYLATION OF PROOPIOMELANOCORTIN-DERIVED PRODUCTS IN DOG PITUITARY [Articolo su rivista]
Facchinetti, Fabio; Perez Fernandez, R; Toma, Mo; Gaudiero, Gj; Lechuga, Mj; Devesa, J; Genazzani, A. R.
abstract

The effect of chronic dopaminergic receptor blockade using domperidone (DOM) on the immature dog pituitary content of POMC-related peptides was evaluated. Six immature dogs were treated with DOM for 15 days, 3 times/day, po (3 mg/kg) together with DOM sc (0.6 mg/kg) at 21.00 h. Placebo was administered to six control animals with the same protocol. On the 16th day, the animals were killed, the whole pituitary removed, homogenized, and submitted to reverse-phase HPLC purification prior to radioimmunoassay (RIA) evaluation of beta-endorphin, ACTH and alpha-MSH immunoreactivities (ir). DOM-treated dogs showed a pituitary concentration of beta-EP and ACTH similar to the placebo-treated dogs. The total alpha-MSH ir was similar in both groups and distributed on two main peaks: one corresponding to alpha-MSH and another coeluting with des-acetyl-alpha-MSH [1-13(ACTH)NH2]. However, the percentage of alpha-MSH on total ir in DOM-treated dogs (15.4 +/- 2.6%) was lower than in controls (37.5 +/- 4.5%, P less than 0.01); the corresponding percentage of 1-13(ACTH)NH2 content was 63.0 +/- 3.8% vs 44.7 +/- 3.7%, (P less than 0.01). The alpha-MSH/1-13(ACTH)NH2 ratio was considerably decreased by the treatment (0.25 +/- 0.06 vs 0.89 + 0.15, P less than 0.01). Acetyl beta-EP-like ir was also lower in treated (38.4 + 5.4 fmol/mg) vs control (86.6 + 19.2 fmol/mg, P less than 0.05) animals. These data indicate that the dopaminergic system plays an important role in the control of acetylation processes of POMC-related peptides in the pituitary


1988 - Effectiveness of salmon calcitonin nasal spray preparation in migraine treatment. [Articolo su rivista]
G., Micieli; A., Cavallini; E., Martignoni; V., Covelli; Facchinetti, Fabio; G., Nappi
abstract

Effectiveness of salmon calcitonin nasal spray preparation in migraine treatment.


1988 - EVIDENCES FOR A DOPAMINE-REGULATED PERIPHERAL SOURCE OF CIRCULATING B-ENDORPHIN. [Articolo su rivista]
A. R., Genazzani; F., Petraglia; Facchinetti, Fabio; S., Golinelli; P., Oltramari; V., Santoro; A., Volpe
abstract

Circulating beta-endorphin (beta EP) and beta-lipotropin (beta LPH) concentrations increase after the administration of acetylcholine or serotonin agonist drugs. In this study we examined the effect of dopamine receptor agonists and/or antagonists on plasma beta EP, beta LPH, cortisol, and PRL levels in normal subjects. Neither direct dopamine (DA) agonist drugs, DA (1 microgram/kg min for 120 min), bromocriptine (2.5 mg po), L-dopa (500 mg po) or an indirect DA agonist, nomifensine (200 mg po), significantly altered plasma beta EP and beta LPH levels. The administration of metoclopramide, a DA antagonist (10 mg iv), significantly increased plasma beta EP, beta LPH, PRL, and cortisol levels. This effect was completely reversed by pretreatment with L-dopa (500 mg po) and only partially antagonized by DA infusion. Domperidone (10 mg iv), a DA antagonist which does not cross the blood brain barrier, increased only plasma beta EP levels, an effect inhibited both by L-dopa and DA. After dexamethasone (2 mg/day for 2 days) domperidone still increased plasma beta EP and PRL levels. The concomitant increase of beta EP, beta LPH, and cortisol after metoclopramide suggests that endogenous DA inhibits the secretion of proopiomelanocortin-related peptides. Moreover, since domperidone increases only beta EP and this effect is not altered by dexamethasone, there may be a corticotropin-releasing hormone-independent source of circulating beta EP in humans, which is inhibited by DA


1988 - EXPRESSION OF PROOPIOMELANOCORTIN RELATED PEPTIDES IN HUMAN FOLLICULAR FLUID [Articolo su rivista]
Facchinetti, Fabio; Ar, Storchi; F., Petraglia; A., Volpe; Ar, Genazzani
abstract

In order to evaluate the expression of the opioid precursor proopiomelanocortin (POMC) in the ovarian follicle, we measured 6 of its main end-products in 23 follicular fluids. We coupled high performance liquid chromatography (HPLC) to specific radioimmunoassays. Seven follicles were immature (diameter less than 9 mm), 10 were obtained from superovulated patients during an in vitro fertilization-embryo transfer program (greater than 22 mm) and six were persistent follicles, collected during the luteal phase [15-31 mm, luteinized unruptured follicles (LUF)]. Follicular fluids were extracted by mean of Sep-pak cartridges and then purified by HPLC with a reverse-phase C-18 column eluted in a linear gradient with acetonitrile/0.01 M hydrochloric acid (from 18:82 to 40:60). Fractions were tested with specific antisera for ACTH (1-39), alpha-MSH, beta-lipotropin (beta-LPH), beta-endorphin (beta-EP) and gamma-endorphin (gamma-EP) immunoreactivities. No presence of beta-LPH, beta-EP and ACTH was confirmed, while gamma-EP, alpha-MSH and des-alpha-MSH were detected for the first time in follicular fluid. In every class of follicles shorter chain peptides predominate over their longer chain precursor. Immature follicles are characterized by the highest amounts of gamma-EP, ACTH, alpha-MSH and des-alpha-MSH if compared to superovulated and LUF. On the contrary, beta-EP amount was highest after superovulation. Apart from this finding, peptide levels in superovulated patients and LUF are similar


1988 - Impaired beta-endorphin response to human corticotropin-releasing hormone in obese children. [Articolo su rivista]
S., Bernasconi; F., Petraglia; Iughetti, Lorenzo; C., Marcellini; A., Lamborghini; Facchinetti, Fabio; A. R., Genazzani
abstract

In order to evaluate the secretion of beta-endorphin in obese children and adolescents, we measured plasma beta-endorphin, ACTH and cortisol levels before and following administration of CRH (1 microgram/kg). Fourteen normal weight and 22 obese subjects (weight excess ranging from 30 to 98%) were studied. Plasma hormone levels were measured by radioimmunoassay directly in plasma (cortisol, ACTH) and after silicic acid extraction and Sephadex G-75 column chromatography (beta-endorphin). Basal beta-endorphin levels in obese children were significantly higher than in controls (14.7 +/- 1.8 vs 6.0 +/- 0.6 pmol/l; mean +/- SEM). No differences were found in basal ACTH and cortisol levels. CRH administration significantly increased beta-endorphin, ACTH and cortisol levels in normal subjects and ACTH and cortisol levels in obese subjects. Plasma beta-endorphin levels in obese children and adolescents did not show any significant increment. These data confirm the higher than normal beta-endorphin plasma levels in obese subjects in childhood and demonstrate that CRH is unable to increase beta-endorphin levels, suggesting an impairment of the hypothalamo-pituitary control mechanisms or an extra-anterior pituitary source.


1988 - IMPAIRMENT OF THE OPIOIDERGIC CONTROL OF LUTEINIZING HORMONE SECRETION IN TURNER'S SYNDROME: LACK OF EFFECT OF GONADAL STEROID THERAPY. [Articolo su rivista]
F., Petraglia; D., Larizza; M., Maghnie; Facchinetti, Fabio; Volpe, Annibale; S., Bernasconi; Ar, Genazzani; F., Severi
abstract

We studied the activity of endogenous opioid peptides in regulating LH secretion in patients with Turner's syndrome. To do so, we determined the LH secretory response to opiate receptor blockade by naloxone (0.08 mg/kg BW, iv) in 17 patients (age range, 9-23 yr). Eight patients were untreated (3 of whom had had spontaneous menarche), and 9 patients were taking ethinyl estradiol/medroxyprogesterone acetate treatment (5 of these patients were also studied before treatment). In addition, the plasma LH responses to GnRH (50 micrograms, iv) and placebo were determined in the patients as well as in 13 age-matched normal girls (6 prepubertal and 7 pubertal). Naloxone did not increase plasma LH levels in the amenorrheic untreated and treated patients with Turner's syndrome. However, in the 3 patients who had had spontaneous menarche and in normal pubertal girls naloxone increased plasma LH levels. GnRH was effective to the same extent in the patients and normal subjects. These results indicate that in patients with Turner's syndrome the opioidergic inhibition of LH secretion is impaired and is not restored by gonadal steroid replacement therapy. Moreover, the normal plasma LH responses to naloxone in the spontaneously menstruating patients with Turner's syndrome indicate both the clinical variability of this syndrome and the participation of endogenous opioid peptides in the regulation of normal menstrual function


1988 - Investigation on cerebrospinal fluid opioids and neurotransmitters related to spinal cord stimulation. [Articolo su rivista]
L., Tonelli; T., Setti; A., Falasca; E., Martignoni; E., Torcia; F. M., Calcaterra; G. A., Merli; Facchinetti, Fabio
abstract

The purpose of this study was to assess the biochemical mechanisms underlying spinal cord stimulation (SCS). Seventeen patients with chronic pain were investigated by measuring cerebrospinal fluid concentrations of endogenous opioids and biogenic amines before and during dorsal column stimulation. Basal cerebrospinal fluid beta-endorphin levels were below the normal range. No significant change of norepinephrine, epinephrine, dopamine, beta-endorphin, beta-lipotropin, or adrenocorticotropic hormone levels were found after SCS. A 50\% increase of cerebrospinal beta-endorphin and beta-lipotropin levels occurred in 6 out of 16 patients, namely those where SCS gave the major pain relief. These data confirm the derangement of the endogenous opioid system in chronic pain conditions and suggest that the beta-endorphin response to SCS could have clinical value in predicting the success of treatment.


1988 - Lack of clinical-EEG effects of naloxone injection on infantile spasms. [Articolo su rivista]
A., Nalin; F., Petraglia; A. R., Genazzani; G., Frigieri; Facchinetti, Fabio
abstract

In a previous study we found depressed ACTH and normal beta-endorphin values in the cerebrospinal fluid of patients with West's syndrome, whereas normal peptide levels were present in infants with secondary Infantile spasms. This prompted us to study the effects of naloxone administration in children with West's syndrome. After informed consent was obtained from the parents, the effects of naloxone administration on clinical and EEG findings were evaluated in five infants 5-9 months old (3 males, 2 females) with cryptogenic infantile spasms and hypsarrhythmia. The infants were studied at the onset of symptomatology before therapy. An average of 5-10 groups of spasms were present per day. Naloxone (12 micrograms/kg body weight) was administered as an intravenous bolus in two cases, as a slow venous drip in another two cases, and intramuscularly in the last case. EEG and polygraphic monitoring were performed for 2 h. Naloxone did not induce any acute behavioral changes and the number of seizures remained unchanged after treatment. These data reject the possibility that endogenous opioids tonically modulate infantile spasms. Further studies are required to ascertain the involvement of POMC peptides in West's syndrome.


1988 - Modificazioni delle concentrazioni plasmatiche di beta-endorfina e beta-lipotropina in corso di angor. [Abstract in Rivista]
Barbieri, Alberto; Facchinetti, Fabio; Porro, Ca; Genazzani, Ar; Mattioli, G.
abstract

Modificazioni delle concentrazioni plasmatiche di beta-endorfina e beta-lipotropina in corso di angor.


1988 - NEUROENDOCRINE EVALUATION OF CENTRAL OPIATE ACTIVITY IN PRIMARY HEADACHE DISORDERS [Articolo su rivista]
Facchinetti, Fabio; E., Martignoni; V., Gallai; G., Micieli; F., Petraglia; G., Nappi; Ar, Genazzani
abstract

The evaluation of central opiate activity could be of clinical value in the diagnosis and treatment of pain syndromes. The current approach via direct measurement of endogenous opioid peptides in cerebrospinal fluid (CSF) is not devoid of side effects and cannot be used in every-day practice. As an alternative to this method, we have studied the neuroendocrine response of plasma LH to an i.v. naloxone injection in 39 headache sufferers from different diagnostic subgroups, and in 12 age- and sex-matched healthy volunteers. Patients (19 females and 20 males) were affected by common migraine (CM, 11 cases), migraine with interparoxysmal headache (MIH, 9), classical migraine (CIM, 9), and chronic cluster headache (CH, 10). Headache lasted 3-36 years. Prior to naloxone challenge (4 mg i.v.), LH pulsatility was evaluated for 1 h. The next morning, the pituitary response to LH-RH (10 micrograms i.v.) was tested in 20 patients. Plasma LH was measured by RIA in every sample. The response to the tests was evaluated as secretion area of plasma LH minus the mean basal value. Controls (497.5 +/- 85.5 mIU/ml x 120 min), ClM (357.8 +/- 78.9) and CH (450.5 +/- 70.4) patients showed similar results, while in cases of CM (155.3 +/- 71.7, P less than 0.05) and MIH (104.1 +/- 53.7, P less than 0.01) the LH secretion after naloxone injection was significantly blunted. On the contrary, the response of LH to LH-RH was similar in controls and patient groups, thus excluding pituitary dysfunctions in this response


1988 - Neuroendocrine features of obese adolescents. [Capitolo/Saggio]
S., Bernasconi; Facchinetti, Fabio; Iughetti, Lorenzo; F., Petraglia; C., Marcellini; G., Guarneri; A. R., Genazzani
abstract

n.a


1988 - Nocturnal bronchospasm prevention by sustained release anhydrous theophylline in once a day bedtime administration [Articolo su rivista]
Facchinetti, Fabio
abstract


1988 - N-terminal ACTH fragments increase the CSF beta-EP content in Alzheimer type dementia. [Articolo su rivista]
G., Nappi; Facchinetti, Fabio; E., Martignoni; F., Petraglia; E., Sinforiani; G., Bono; A. R., Genazzani
abstract

Eleven patients with presenile Alzheimer type dementia (ATD) were treated with N-terminal ACTH fragments for 14 days. No change in cognitive functions was observed during the treatment. A significant increase in CSF beta-endorphin (beta-EP) levels was found, while ACTH and beta-lipoprotein remain unaffected. The possibility that ACTH and its moieties could interfere with beta-EP activities in CNS is discussed.


1988 - PITUITARY CHANGES OF DESACETYL-a-MELANOCYTE-STIMULATING HORMONE THROUGHOUT DEVELOPMENT. [Articolo su rivista]
Facchinetti, Fabio; Ar, Storchi; S., Furani; D., Radi; Ar, Genazzani
abstract

Adrenocorticotropin (ACTH), alpha-melanocyte-stimulating hormone (alpha-MSH) and desacetyl-alpha-MSH (des-alpha-MSH) concentrations were evaluated in 4 embryos and 18 fetal pituitaries collected after spontaneous (n = 9) and prostaglandin-induced abortion (n = 9) at 13-25 weeks of gestation. The peptides were measured by radioimmunoassays after a high-performance liquid chromatographic separation of the homogenates. In both embryonic and fetal pituitaries, des-alpha-MSH concentrations were 2-4 times higher than those of alpha-MSH and 1- to 50-fold increased in comparison to those of ACTH. Either melanotropin showed the highest pituitary content in the first part of the second trimester, while the ACTH content remained constant. In the oldest fetuses (over 20th week), the pituitaries collected after prostaglandin-induced abortion showed markedly increased values of both des-alpha-MSH and alpha-MSH in comparison to samples collected after spontaneous abortion. In conclusion, des-alpha-MSH, the typical melanotropic hormone of fetal pituitary, undergoes important changes during development. Des-alpha-MSH seems to be the end product of proopiomelanocortin cleavage and its pituitary content increases in concomitance with the fetal adrenal sprout. Moreover, these data indicate that the intermediate pituitary lobe could be activated by the stress of labor after the 20th week of pregnancy


1988 - Plasma beta-endorphin, free fatty acids and blood lipid changes in type 2 (non-insulin dependent) diabetic patients. [Articolo su rivista]
S. B., Solerte; M., Fioravanti; F., Petraglia; Facchinetti, Fabio; A. L., Patti; N., Schifino; A. R., Genazzani; E., Ferrari
abstract

A lipolytic activity for beta-endorphin (beta EP) has been recently suggested both in vitro and in vivo. In our study we evaluated the relationship between beta EP and blood lipid pattern in Type 2 (non-insulin dependent) diabetic patients. Plasma beta EP, together with plasma beta-lipotropin (beta LPH), ACTH, cortisol and plasma insulin (IRI), was measured by RIA after silicic acid plasma extraction and Sephedex G-75 column chromatography. Although reduced beta EP (7.12 +/- 3.8 fmol/ml) and increased beta LPH (9.3 +/- 3.7 fmol/ml) levels were found in diabetic patients, compared to controls (8.53 +/- 3.3 fmol/ml, p less than 0.05 and 8.34 +/- 2.6 fmol/ml, p less than 0.05, respectively), higher plasma beta EP concentrations were demonstrated in hyperlipidemic diabetic patients (10.3 +/- 3.9 fmol/ml) than in patients with normal blood lipid pattern (4.85 +/- 1.45 fmol/ml, p less than 0.001). Several positive correlations between beta EP, plasma free fatty acids (r = 0.75, p less than 0.001), triglycerides (r = 0.84, p less than 0.001) and VLDL (r = 0.80, p less than 0.001) were found in our patients independently of overweight, hypoglycemic treatment, plasma IRI levels and of the degree of metabolic control. A higher prevalence of micro- and macrovascular complications was demonstrated in hyperlipidemic than in normolipidemic patients. Blood lipid disorders might therefore be associated with increased plasma beta EP levels in Type 2 diabetes.


1988 - PLASMA ß-ENDORPHIN RESISTANCE TO DEXAMETHASONE SUPPRESSION IN OBESE PATIENTS [Articolo su rivista]
FACCHINETTI, Fabio; C., Giovanni; F., Petraglia; C., Barletta; G., Comitini; GENAZZANI, Andrea Riccardo
abstract

Patients with simple exogenous obesity are characterized by increased B-endorphin (B-EP) plasma levels, despite normal ACTH and B-Lipotropin (B-LPH). To evaluate the origin of such an hyperendorphinemia, 42 obese patients were submitted to a short overnight dexamethasone suppression test (DST: 1 mg at 23:00 h). Blood samples were taken in basal conditions and 9, and 17 h after DST. The same procedure was applied in 12 healthy, normal weight volunteers. In further five patients, 0.5 mg per 4/die were given. B-EP was measured by radioimmunoassay (RIA) after silicic acid extraction and Sephadex G-75 column chromatography. ACTH and Cortisol were measured by direct IRMA and RIA, respectively. Basal B-EP levels of patients (24.2 +/- 16.5, fmol/ml, M +/- SD) were double than in normal weight controls (10.8 +/- 4.6), while ACTH and cortisol fell in the normal range. ACTH and cortisol were significantly reduced by DST in both patients and controls, while B-EP in patients did not. Cortisol, however, was not suppressed in 7 patients (16%). At 08:00, the suppression of B-EP in controls was 49.0 +/- 18.4%, while in obese patients it was only 21.2 +/- 38.8% (p less than 0.01). However, patients with weight excess below 50% normally suppressed B-EP (41.6 +/- 15.3%), while those with weight excess over 75% did not (11.3 +/- 47.5%). The doubling of dexamethasone intake does not lead to a suppression of plasma B-EP in these last patients. These data indicate the existence of neuroendocrine abnormalities in the hypothalamus-pituitary-adrenal axis of obese patients and suggest that their hyperendorphinemia originates outside the anterior pituitary


1988 - Premenstrual increase of intracellular magnesium levels in women with ovulatory, asymptomatic menstrual cycles [Articolo su rivista]
Facchinetti, Fabio; Borella, Paola; M., Valentini; L., Fioroni; A. R., Genazzani
abstract

Intracellular magnesium (Mg) levels regulate several enzymatic reactions and the hypoactivity of Mg has been involved in different pathological states. In addition to other factors, gonadal hormones, too, have been found to interfere in Mg balance. This study evaluates the changes in Mg in women throughout the normal menstrual cycle and those measured at weekly intervals in males. Magnesium and potassium (K) levels were measured in the plasma, red blood cells (RBC), lymphocytes (LC) and polymorphonucleated cells (PMN) of 11 normal menstruating women, in different periods of their menstrual cycle. Blood samples were collected every 4th day. According to the time and LH, progesterone and estradiol levels, they were classed as follicular (Foll), periovulatory (OV), luteal (Lut) or premenstrual (PM). The Menstrual Distress Questionnaire completed by the subjects revealed that no significant symptomatology was present. Four blood samples were also collected from 4 normal males, at weekly intervals. Mg and K were determined by atomic absorption spectrophotometry. LC and PMN were purified by centrifugation on a Ficoll discontinuous gradient. No differences were found in males versus females in the Mg or K contents in the different compartments. In the 4 periods tested, the K levels were constant, in both females and males. The same applies for Mg contents in males. In females, Mg contents, as well as the Mg/K ratio in LC and PMN, showed a significant increase in the premenstrual period compared with the other periods of the cycle. On the contrary, plasma and RBC Mg levels were constant throughout the cycle


1988 - Presence of pro-opiomelanocortin-related peptides in dog adrenal gland [Articolo su rivista]
Facchinetti, Fabio
abstract

Coupling high performance liquid chromatography to specific radioimmunoassays, this study evaluates the presence of several pro-opiomelanocortin(POMC)-related peptides in dog adrenal gland. In addition to Met-enkephalin, adrenals contain β-lipotropin, β-endorphin, ACTH, α-MSH, des-acetyl-α-MSH and acetyl-gamma-EP. β-endorphin is the peptide more represented in the gland, and despite the presence of acetylated peptides, no acetyl-β-endorphin was detected. The content of both melanotropins prevails over that of ACTH suggesting an extensive processing of POMC, like that occurring in intermediate pituitary and brain. These data demonstrate that dog adrenal gland could be a source of POMC-derived opioid peptides. Their high contents (equal or even higher than those of pituitary) suggest a possible local function, i.e. modulating steroidogenesis.


1988 - Response of circulating adrenocorticotropin, beta-endorphin, beta-lipotropin and cortisol to athletic competition. [Articolo su rivista]
F., Petraglia; C., Barletta; Facchinetti, Fabio; F., Spinazzola; A., Monzani; D., Scavo; Ar, Genazzani
abstract

Acute physical exercise stimulates the activity of the hypothalamus-pituitary-adrenal axis in man. In the present study we measured plasma adrenocorticotropin, beta-endorphin, beta-lipotropin and cortisol levels in 27 male trained athletes in basal conditions, 60 min before and immediately after an official competition. The endocrine responses were evaluated in different groups of athletes participating in races (100 m, 1500 m, 10,000 m) or in the disc throw. The athletes competing for the runs showed a statistically significant increase in plasma adrenocorticotropin, beta-endorphin, beta-lipotropin and cortisol levels after the race (P less than 0.01), whereas the disc throwers showed no significant change in the hypothalamus-pituitary-adrenal axis hormones after the competition. The percent increase in plasma adrenocorticotropin, beta-endorphin, beta-lipotropin and cortisol was higher in the athletes who run 1500 m and 10,000 m than in those participating in the short distance race (100 m). The present results showed that plasma proopiomelanocortin-related peptides and cortisol levels increase in trained athletes following running competition and that this increase is related to the duration of the physical exercise


1988 - Serotoninergic and dopaminergic control of beta-endorphin secretion in obese children and adolescents. [Articolo su rivista]
S., Bernasconi; F., Petraglia; Iughetti, Lorenzo; Facchinetti, Fabio; C., Marcellini; S., Mari; A. R., Genazzani
abstract

N.A.


1988 - STEROID REPLACEMENT TREATMENT INCREASES BETA-ENDORPHIN AND BETA-LIPOTROPIN PLASMA LEVELS IN POSTMENOPAUSAL WOMEN. [Articolo su rivista]
Ar, Genazzani; F., Petraglia; Facchinetti, Fabio; A., Grasso; G., Alessandrini; Volpe, Annibale
abstract

The present study shows the effects of two different steroid replacement therapies, with conjugated estrogens or with a new synthetic steroid derivative, ORG OD14, on plasma beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) levels in postmenopausal subjects. Blood samples were collected before treatment and after 1, 2 and 4 months of treatment; a third group of patients was treated with placebo. After 2 months of treatment both groups of patients who underwent steroid supplementation showed circulating levels of beta-EP and beta-LPH higher than basal levels. ORG OD14 treatment increased beta-EP and beta-LPH levels more than conjugated estrogens at the 2nd month of therapy. No further change was found after 4 months. The two drugs were effective in reducing hot flushes and improving physical and psychological symptoms. These data indicate that sex steroids are able to increase beta-EP and beta-LPH secretion in postmenopausal women, with a concomitant relief of climacteric symptoms.


1988 - [Stress and postoperative analgesia]. [Articolo su rivista]
Stacca, R.; Porro, C. A.; Piccinini, P.; Petraglia, F.; Facchinetti, Fabio
abstract

..


1988 - The circadian rhythm of proopiomelanocortin-related peptides in aging [Articolo su rivista]
Facchinetti, Fabio
abstract

The circadian rhythm of POMC-related peptides and of pl.cortisol was well maintained in aged subjects. Pl.β-EP levels were not different in old and in young subjects, while pl.ACTH and cortisol levels were higher in old than in young subjects.


1988 - Tonic pain time-dependently affects β-endorphin-like immunoreactivity in the ventral periaqueductal gray matter of the rat brain [Articolo su rivista]
Porro, C. A.; Facchinetti, F.; Pozzo, P.; Benassi, C.; Biral, G. P.; Genazzani, A. R.
abstract

β-Endorphin-like immunoreactivity (B-EP-LI) levels have been investigated in the ventral periaqueductal gray matter (vPAG) of rats killed 30, 60 or 120 min after the subcutaneous injection of dilute formalin (0.08 ml, 5%) in one fore- or hindpaw, or comparable handling. B-EP-LI was estimated by radioimmunoassay, using an anti-camel B-EP serum directed against the C-terminal portion of B-EP molecule. In both fore- and hindlimb groups vPAG B-EP-LI values were significantly increased 60 and 120 min after the injection relative to controls. Values from animals killed 120 min after formalin injection were higher than the ones at 30 and 60 min, forelimb effects being quantitatively more pronounced. The increase in B-EP-LI appeared distributed along the whole rostrocaudal extent of the region. © 1988.


1988 - TONIC PAIN TIME-DEPENDENTLY AFFECTS ß-ENDORPHIN-LIKE IMMUNO-REACTIVITY IN THE VENTRAL PERIAQUEDUCTAL GREY MATTER OF THE RAT BRAIN [Articolo su rivista]
Porro, Ca; Facchinetti, Fabio; Pozzo, P.; Benassi, C.; Biral, Gp; Genazzani, Ar
abstract

beta-Endorphin-like immunoreactivity (B-EP-LI) levels have been investigated in the ventral periaqueductal gray matter (vPAG) of rats killed 30, 60 or 120 min after the subcutaneous injection of dilute formalin (0.08 ml, 5%) in one fore- or hindpaw, or comparable handling. B-EP-LI was estimated by radioimmunoassay, using an anti-camel B-EP serum directed against the C-terminal portion of B-EP molecule. In both fore- and hindlimb groups vPAG B-EP-LI values were significantly increased 60 and 120 min after the injection relative to controls. Values from animals killed 120 min after formalin injection were higher than the ones at 30 and 60 min, forelimb effects being quantitatively more pronounced. The increase in B-EP-LI appeared distributed along the whole rostrocaudal extent of the region


1988 - Transient failure of central opioid tonus and premenstrual symptoms. [Articolo su rivista]
Facchinetti, Fabio; E., Martignoni; D., Sola; F., Petraglia; G., Nappi; A. R., Genazzani
abstract

In order to evaluate the relationships between endogenous opioid activity and premenstrual complaints, we subjected three groups of patients in the mid (days 8-12 prior to menses) and late (days 1-5 prior to menses) luteal phases of the cycle to a naloxone test and some of the patients to a luteinizing-hormone-releasing hormone (LHRH) test. The premenstrual syndrome (PMS) group was composed of nine patients complaining of dizziness, irritability and depression close to menses for at least three years. The menstrually related migraine (MM) group was composed of 15 patients complaining of premenstrually related migraine. The common migraine (CM) group was made up of 16 women suffering from common migraine for years whose attacks occurred independently of menstrual cycle events. A group of seven fertile women served as controls. Every two days the patients filled out the Menstrual Distress Questionnaire for evaluation of their complaints. After the evaluation of spontaneous LH pulsatility for one hour, 4 mg of naloxone was injected as a bolus, and samples were collected every 15 minutes for 2 hours. Both estradiol (E2) and progesterone (P) were measured in basal samples from each naloxone test. LH responsiveness to LHRH was similar in the mid and late luteal phases and did not change between groups. In the mid luteal phase the LH response to naloxone in PMS and MM patients was similar to that in normal subjects, while CM patients had impaired LH secretion. In the premenstrual phase only the controls maintained an LH responsiveness similar to that observed in the mid luteal phase, while both PMS and MM lost the naloxone-induced LH release.(ABSTRACT TRUNCATED AT 250 WORDS)


1987 - Abnormal pro-opiomelanocortin processing in Alzheimer's disease. A case report. [Articolo su rivista]
Facchinetti, Fabio; A. R., Storchi; C., Pacchetti; E., Martignoni; A. R., Genazzani
abstract

Several authors have reported reduced levels of pro-opiomelanocortin (POMC)-related peptides in the cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD), but the mechanisms regulating the CSF content of these substances are still debated. In this case report the processing of POMC peptides has been investigated post-mortem (HPLC and RIA methods) at the pituitary and hypothalamic level in an AD patient and in a control subject. From the results obtained it seems likely that defects of axonal transport and/or secretion rather than synthesis could account for the abnormalities of POMC peptides in the CSF.


1987 - Adrenal steroid responses to naloxone in polycystic ovarian disease. [Articolo su rivista]
G., D'Ambrogio; Facchinetti, Fabio; S., Golinelli; T., Setti; F., Petraglia; A. R., Genazzani
abstract

In order to investigate the role of the adrenal gland in the pathogenesis of polycystic ovarian disease (PCOD), we evaluated the adrenal steroid response to an opiate receptor blockade. Six healthy menstruating volunteers and 6 patients with PCOD were given a saline or naloxone (4 mg i.v.) injection in the early follicular phase. Blood samples were taken prior to the injections and every 15-30 minutes in the following 2 hours. Cortisol, androstenedione (A) and dehydroepiandrosterone (DHA) plasma levels were determined by RIA after extraction (cortisol) and celite chromatography (A and DHA). While in controls naloxone increased only cortisol concentrations, in PCOD patients DHA plasma levels also were stimulated by the opiate receptor antagonist. In PCOD patients the increase of cortisol (p less than 0.05) and of DHA (p less than 0.001) levels resulted significantly higher than in controls. In both groups A plasma levels remained unchanged after naloxone administration. These data confirm that endogenous opioids exert an inhibitory control on the pituitary-adrenal axis. In PCOD patients the response to naloxone led to a hypersecretion of adrenal delta 5-androgens, which could account for the development of the syndrome.


1987 - Beta-lipotropin is the major component of the plasma opioid response to surgical stress in humans. [Articolo su rivista]
Porro, C. A.; Facchinetti, Fabio; Bertellini, E.; Petraglia, F.; Stacca, R.; Barbieri, G. C.; Genazzani, A. R.
abstract

There is growing experimental evidence that beta-endorphin immunoreactivity is raised by surgical stress in patients undergoing general anesthesia. As the assay methods employed to date did not allow to fully discriminate between beta-endorphin and its immediate precursor, beta-lipotropin, we have investigated in the present study plasma levels of these two peptides by separating them by chromatography on plasma extracts prior to radioimmunoassay in eighteen surgical patients under general anesthesia and eight under spinal anesthesia. Beta-lipotropin, but not beta-endorphin, plasma levels were found to be significantly elevated during surgery in the general anesthesia group, while no change was found in either peptide concentration in the spinal one. Cortisol plasma levels also increased significantly 90 minutes after the beginning of surgery, when they were positively correlated to beta-lipotropin ones. Although the sampling time we adopted may have prevented us from detecting an early peak of beta-endorphin during the first 30 minutes of surgery, the major component of the pituitary opioid response to surgical stress appears to be related to beta-lipotropin. This is in agreement with results of experimental work on various kinds of stress in animals and humans and seems to rule out a role for plasma beta-endorphin in post-operative analgesia.


1987 - CENTRAL AND PERIPHERAL OPIATES IN RETT SYNDROME [Abstract in Rivista]
Nalin, A; Facchinetti, Fabio; Hayek, G; Zappella, M; Genazzani, Ar
abstract

.


1987 - Circulating opioids and plasma renin activity in insulin-dependent diabetics with renal haemodynamic alterations. [Articolo su rivista]
S. B., Solerte; M., Fioravanti; F., Petraglia; Facchinetti, Fabio; C., Aprile; A. R., Genazzani; E., Ferrari
abstract

Circulating opioids were studied in insulin-dependent diabetics with renal haemodynamic alterations. Higher circulating beta-endorphin (beta-EP) and lower beta-lipotropin (beta-LPH) levels were found in patients with glomerular hyperfiltration than in diabetics with normal glomerular filtration rate (GFR) and controls. Moreover, significantly positive correlations between beta-EP and GFR, and between beta-EP and renal plasma flow were demonstrated in these patients. On the contrary, reduced beta-EP levels were observed in diabetics with impaired GFR and overt nephropathy. Plasma renin activity was increased in diabetics with glomerular hyperfiltration and reduced in diabetics with overt nephropathy. Circulating opioids might, therefore, play a role in renal haemodynamic alterations, both in patients with early and advanced glomerular changes.


1987 - Dexamethasone fails to suppress hyperendorphinaemia of obese children. [Articolo su rivista]
Facchinetti, Fabio; C., Livieri; F., Petraglia; L., Cortona; F., Severi; A. R., Genazzani
abstract

In order to evaluate the origin of hyperendorphinaemia in obese patients, plasma B-endorphin (B-EP), B-lipotropin (B-LPH) and cortisol levels were measured in basal conditions and after overnight treatment with 1 mg of dexamethasone. Thirteen obese children (weight excess ranging from 44 to 100\%) and 10 normal weight controls were studied. Weight gain started in prepuberty and could not be explained by concurrent diseases. Hormone levels were measured by RIA, either directly in the plasma (cortisol) or after silicic acid extraction and Sephadex G-75 column chromatography (B-EP and B-LPH). Basal B-EP levels in the obese children (19.4 +/- 4.9 pmol/l, mean +/- SEM) were significantly higher than in the controls (7.8 +/- 1.2, P less than 0.01), whereas B-LPH and cortisol was within normal range. In the controls, post-dexamethasone morning and afternoon hormone levels were significantly suppressed. In the obese children, B-EP concentrations remained unaffected by the treatment (14.6 +/- 5.3 and 14.9 +/- 5.2 at 08.00 and 16.00 h, respectively), whereas both B-LPH and cortisol values were significantly decreased. These data demonstrate that a short-term dexamethasone treatment is unable to correct the increased B-EP levels which characterize obese children, whereas it is effective on B-LPH and cortisol concentrations. It can be concluded that circulating B-EP in this condition loses the control of CRH. However, the origin of hyperendorphinaemia in obese patients still remains to be investigated.


1987 - Differences in the opioid control of luteinizing hormone secretion between pathological and iatrogenic hyperprolactinemic states. [Articolo su rivista]
F., Petraglia; V. D., Leo; C., Nappi; Facchinetti, Fabio; U., Montemagno; F., Brambilla; A. R., Genazzani
abstract

The cause of the amenorrhea that occurs in patients with hyperprolactinemia is unknown. The involvement of endogenous opioid peptides in the inhibition of GnRH release as a central factor leading to the hypogonadotropic state has been recently described. This study analyzed the LH response to opiate receptor blockade by naloxone (4 mg, iv) in groups of subjects with amenorrhea due to hyperprolactinemia of different etiologies. Patients presenting with a PRL-secreting pituitary adenoma (n = 7), idiopathic hyperprolactinemia (n = 9), or hyperprolactinemia during pharmacological treatment for schizophrenia (n = 5) were studied. Furthermore, to evaluate whether high circulating PRL levels influence the activity of the opioid system after the menopause, a group of seven postmenopausal subjects was tested before and 1 week after the administration of metoclopramide (10 mg, three times a day), a dopamine receptor antagonist. Normal premenopausal women (n = 6) served as controls. Naloxone significantly increased plasma LH levels in both prolactinoma and idiopathic hyperprolactinemic patients (P less than 0.01 vs. basal and placebo). In neither of those groups was a significant correlation found between the plasma LH response to naloxone and basal plasma PRL levels. In contrast to pathological hyperprolactinemia, blockade of opiate receptors did not significantly change LH secretion in either amenorrheic women with pharmacologically induced hyperprolactinemia or postmenopausal women. These results suggest that the effect of hyperprolactinemia on opioid modulation of LH secretion is related to the nature of the hyperprolactinemic state, supporting the existence of increased opioid inhibition of LH levels in pathological hyperprolactinemia.


1987 - Disordered pulsatile LH release in cluster headache [Articolo su rivista]
Facchinetti, Fabio
abstract


1987 - Effects of neuroleptic treatments on peripheral opioid secretion. [Articolo su rivista]
F., Brambilla; Facchinetti, Fabio; F., Petraglia; E., Smeraldi; L., Bellodi; V., Brancato; A. R., Genazzani
abstract

The effects of short- and long-term neuroleptic therapy on peripheral secretion of beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) were examined in 25 chronic schizophrenic patients. Haloperidol was given to 8 patients for 10 days (group A: 0.1 mg/kg b.w./day) and to another group of 8 patients for 30 days (group B: 10-18 mg/day). The other 9 patients were given a combination of haloperidol (6-30 mg/day) with either chlorpromazine (25-75 mg/day), clotiapine (40-60 mg/day), or fluphenazine decanoate (25-75 mg/month) for 14-18 months (group C). beta-EP and beta-LPH levels were assayed before and after each treatment. Haloperidol plasma levels were assayed in group B patients at the end of treatment. beta-EP mean basal levels were higher in patients than in controls; however, beta-LPH mean basal levels were higher only for group A patients. After treatment, the mean levels did not differ from those prior to therapy in groups A and B, while beta-LPH levels were significantly higher in group C. Level increases or decreases in single patients did not correlate with drug dose or duration of treatment, with baseline peptide levels or with the clinical effects of the various treatments.


1987 - Effects of Org OD 14 on pituitary and peripheral beta-endorphin in castrated rats and post-menopausal women. [Articolo su rivista]
A. R., Genazzani; F., Petraglia; Facchinetti, Fabio; Genazzani, Alessandro; M., Bergamaschi; A., Grasso; Volpe, Annibale
abstract

The aim of the first part of this study was to evaluate the effects of a new synthetic steroid (7 alpha,17 alpha)-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one (Org OD 14), on anterior pituitary (AP) and neurointermediate pituitary lobe (NIL) contents and on circulating levels of beta-endorphin (beta-EP) in rats. Three weeks after ovariectomy, groups of 9 rats were treated with either Org OD 14 (2 or 10 micrograms/day/rat for 14 days) or a placebo. In addition, 2 groups of ovariectomized rats were also treated with oestradiol benzoate (EB) (2 or 10 micrograms/day/rat for 14 days) to compare the effectiveness of the new steroid with that of a classical oestrogenic substance. beta-Ep concentrations were measured in plasma and in AP and NIL extracts by means of double-antibody radioimmunoassay (RIA), employing a specific anti-camel beta-EP (C-terminal fragment). Both doses of Org OD 14 induced a significant dose-related increase in plasma and pituitary lobe beta-EP concentrations as compared with the results on placebo treatment. By comparison, EB was active only at a dose of 10 micrograms/day. Despite the common stimulatory effects of EB and Org OD 14 on pituitary beta-EP, these findings suggest that the two steroids have different modes of action. The second part of the study investigated the changes in beta-EP and beta-lipotrophin (beta-LPH) plasma levels in a group of post-menopausal women treated for 6 months with Org OD 14 (2.5 mg/day) in comparison with the levels in a placebo-treated group. The clinical efficacy of Org OD 14 treatment in post-menopausal symptoms was confirmed, as well as its lack of or only transient effect on plasma lipids and lipoproteins. beta-EP and beta-LPH plasma levels were significantly higher in the Org OD 14-treated group than in the placebo group as from the second month until the end of the observation period.


1987 - Headache and reproductive life [Articolo su rivista]
Facchinetti, Fabio
abstract


1987 - INCREASE OF OPIATE RECEPTORS ANO OECREASE OF ENOOGENOUS OPIATE PEPTIDES IN POSTMENOPAUSALUTERUS [Articolo su rivista]
Giarre, G; Latorre, L; Santi, Mr; Facchinetti, Fabio
abstract

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1987 - Involvement of serotonin in the central control of opioid secretion [Articolo su rivista]
Facchinetti, Fabio
abstract


1987 - Localization and Expression of the Three Opioid Systems [Articolo su rivista]
Facchinetti, Fabio; M., D.; Felice, Petraglia; M., D.; A. R., Genazzani; M., D.
abstract

The various opioid peptides thus far isolated and characterized are derived from three different bio- synthetìc precursors (Fig. l). The aminoacid (AA) sequence of these proteins has been determined by recombinant DNA techniques, namely, determining the nucleotide sequence of DNA complementary to the mRNA encoding these precursors. The three precursors are pro-opiomelanocortin (POMC), pre- proenkephalin A, and preproenkephalin B. There are some similarities in the structural organization of these three precursors, suggesting a common evolu- tionary derivation.


1987 - Morphological and functional stimulation of adrenal reticularis zone by dopaminergic blockade in dogs. [Articolo su rivista]
R., Perez Fernandez; Facchinetti, Fabio; A., Beiras; L., Lima; G. J., Gaudiero; A. R., Genazzani; J., Devesa
abstract

In order to investigate factors affecting adrenal maturation leading to adrenarche, the effect of dopaminergic blockade on the morphology and function of the adrenal reticularis zone was studied in fourteen preadrenarchal dogs. Seven animals of 7 weeks of age (adrenarche at 11 weeks) were treated with domperidone (DOM) 3 times/day p.o. (3 mg/kg) at 09.00 h, 14.00 h, and 21.00 h, plus an additional injection of DOM s.c. (0.6 mg/kg) at 21.00 h for 15 days. Seven control animals received diluent. Twelve hours after the last injection, dogs received 0.25 mg ACTH i.m. and were sacrificed 60 min later. Blood was collected and adrenals removed. After histological evaluation, the percent of the reticularis, fasciculata, and glomerulosa zones with respect to the total cortex was calculated. Plasma androstenedione (A), dehydroepiandrosterone (DHA), 17-OH-progesterone (17P), and cortisol (F) levels in response to ACTH were also assessed. DOM-treated dogs show a significant development of the zona reticularis compared to control animals (19.2 +/- 0.6\% vs 8.8 +/- 2.09\% respectively, X +/- SE, P less than 0.01). In the same animals, the DHA response to ACTH (9.0 +/- 1.6 ng/dl) was significantly higher than in placebo-treated dogs (3.8 +/- 1.1 ng/dl, P less than 0.05) while no significant differences were found in F, A, and 17P levels between the two groups. Finally the post-ACTH A/DHA ratio of DOM-treated dogs (1.33 +/- 0.28) was significantly decreased in respect to the placebo-treated animals (5.49 +/- 2.54, P less than 0.01). These data demonstrate that the morphological and functional development of zona reticularis may be subject to dopaminergic control and this could represent an important step in the initiation of adrenarche. However, the cellular mechanism responsible remains to be clarified.


1987 - Naloxone test in primary headache sufferers [Articolo su rivista]
Facchinetti, Fabio
abstract


1987 - No gradient exists between lumbar and ventricular cerebrospinal fluid beta-endorphin. [Articolo su rivista]
Facchinetti, Fabio; F., Petraglia; S., Cicero; G., Nappi; M., Valentini; A. R., Genazzani
abstract

In 8 patients, beta-lipotropin (beta-LPH), beta-endorphin (beta-EP), ACTH, protein and chloride concentrations were measured in cerebrospinal fluid (CSF) samples obtained simultaneously from the lumbar space and lateral ventricle. Albumin and IgG levels were significantly higher in lumbar than in ventricular CSF samples while no craniocaudal gradient was observed for neuropeptide concentrations. The importance of molecular weight in determining such a regional distribution is supported also by the similar lumbar and ventricular levels of chlorides. These data would validate the CSF approach through lumbar puncture as a tool for exploring neuropeptides in the central nervous system.


1987 - Obesity: an example of the dissociation of beta-endorphin from ACTH [Articolo su rivista]
Facchinetti, Fabio
abstract


1987 - Ontogeny of pituitary beta-endorphin and related peptides in the human embryo and fetus. [Articolo su rivista]
Facchinetti, Fabio; A. R., Storchi; F., Petraglia; G., Garuti; A. R., Genazzani
abstract

In this study we evaluated the presence of proopiomelanocortin-related peptides (beta-lipotropin, beta-endorphin, and gamma-endorphin) in five embryos (5 to 10 weeks of pregnancy) and 11 fetal pituitaries (15 to 25 weeks) by means of high-performance liquid chromatography coupled with specific radioimmunoassays. Tissues were collected at laparotomy for ectopic pregnancy (five embryos) or after spontaneous (seven) or prostaglandin-induced (four) abortion. beta-Endorphin and beta-lipotropin were present starting at the seventh week of pregnancy while gamma-endorphin appeared only in the second trimester. During embryonic life opioid activity was limited to the cephalic portion. The three peptides, but little, if any, acetylated 1-31 beta-endorphin, were recognized in the fetal pituitary throughout the second trimester, at which time beta-lipotropin and beta-endorphin showed constant values in spite of increasing gamma-endorphin concentrations. beta-Lipotropin was the predominant peptide in both embryonic and fetal life. In conclusion, the three peptides related to proopiomelanocortin were expressed from the precursor at different times throughout development. By the beginning of the second trimester the pituitary processing of proopiomelanocortin is similar to that of adult life and the functional activity of the anterior lobe seems to prevail over that of the "fetus-related" neurointermediate lobe around the twenty-fifth week of pregnancy.


1987 - Opioid control of luteinizing hormone secretion in patients with hirsutism and hyperandrogenemia. [Articolo su rivista]
F., Petraglia; S., Golinelli; G., D'Ambrogio; G., Comitini; Facchinetti, Fabio; Volpe, Annibale; A. R., Genazzani
abstract

The present study was designed to evaluate the influence of hyperandrogenemia on the activity of the opioid system regulating LH secretion in menstruating women. Ten subjects presenting with hirsutism and hyperandrogenemia and 9 healthy normally cyclic subjects participated in the study. Naloxone or saline was administered on 2 different days both during the follicular (6-8 days after menstrual bleeding) and during the luteal phase of the menstrual cycle. Naloxone significantly increased plasma LH levels in the luteal, but not during the follicular phase of the cycle in both subject groups. It may be inferred from these observations that opioid-mediated inhibition of LH secretion is not altered in menstruating hyperandrogenic patients, suggesting that the circulating androgens are not an important determinant of the functional neuroendocrine activity of the opioid system.


1987 - Opioid plasma levels: a marker of impaired central control in psychiatric disorders? [Articolo su rivista]
F., Brambilla; Facchinetti, Fabio; F., Petraglia; E., Ferrari; M., Maggioni; A. R., Genazzani
abstract

Opioid plasma levels: a marker of impaired central control in psychiatric disorders?


1987 - Plasma beta-endorphin in response to oral glucose tolerance test in obese patients. [Articolo su rivista]
D., Scavo; FACCHINETTI, Fabio; C., Barletta; F., Petraglia; R., Buzzetti; M., Monaco; C., Giovannini; R., Genazzani
abstract

In order to clarify the possible interaction between endogenous opioids and glucose homeostasis in obesity we studied Beta-Endorphin (B-Ep), ACTH, cortisol and insulin plasma levels in response to an oral glucose tolerance test (OGTT) in 8 females suffering from uncomplicated obesity and in 6 healthy volunteers of normal weight. Results were evaluated in terms of secretion areas subtracted from basal value. Basal glucose, insulin and B-Ep levels were significantly higher in the obese patients compared to controls, cortisol levels and ACTH were not statistically different between obese and normal subjects. During OGTT total areas of insulin secretion were significantly higher in the obese patients; cortisol, ACTH, B-Ep plasma levels did not change in controls, whereas obese patients showed a response to B-Ep which reached a peak at 60 minutes. The area of B-Ep response to OGTT in obese patients was significantly higher than in controls. On the basis of these results we may suggest that the opioid system belongs to the chain of neuroendocrine and metabolic events responsible for the origin and the growth of overweight. But the possibility exists that obesity itself can enhance the B-Ep secretion above all through overeating. In this regard it is to stress that glucose ingestion induces in obese patients, differently from normal subjects, insulin hypersecretion and the B-Ep secretion, possibly from gastro-enteric tract and/or pancreatic isles.


1987 - Plasma β-endorphin Levels in Anovulatory States: Changes After Treatment for The Induction of Ovulation [Articolo su rivista]
Facchinetti, Fabio
abstract


1987 - Premenstrual fall of plasma beta-endorphin in patients with premenstrual syndrome. [Articolo su rivista]
Facchinetti, Fabio; E., Martignoni; F., Petraglia; M. G., Sances; G., Nappi; A. R., Genazzani
abstract

Plasma beta-endorphin (beta-EP), beta-lipotropin (beta-LPH), and cortisol concentrations were measured by perimenstrual period in 11 patients affected by premenstrual syndrome (PMS) and in 8 asymptomatic healthy volunteers. Blood samples were collected every 2 to 3 days, for 1 month, starting from midcycle. The Menstrual Distress Questionnaire (MDQ) was administered during the testing period. Plasma beta-LPH and cortisol levels remain stable during the perimenstrual period, in both controls and PMS patients. On the contrary, PMS patients showed a decrease of plasma beta-EP in the week preceding menses and during the first days of menstrual flow. Beta-EP values of PMS patients regain normal levels during the next follicular phase. No changes of beta-EP levels were recorded in asymptomatic women. MDQ scores revealed that PMS patients complained of water retention, pain discomfort, and mood swings. The transient and reversible decrease of plasma beta-EP in PMS patients near to and at menses remains to be clarified.


1987 - Progesterone and progestins modulate beta-endorphin concentrations in the hypothalamus and in the pituitary of castrated female rats. [Articolo su rivista]
A. R., Genazzani; F., Petraglia; M., Bergamaschi; Genazzani, Alessandro; Facchinetti, Fabio; Volpe, Annibale
abstract

Hypothalamic and pituitary beta-endorphin (B-EP) concentrations are modified by ovariectomy and estrogen treatments, supporting a direct interaction between this peptidergic system and gonadal steroids. Because the use of progestins is becoming even more diffuse in clinical practice, we evaluated the effect of progesterone and of the synthetic progestins medroxyprogesterone acetate (MPA), norethisterone acetate (NET) and desogestrel on the concentration of B-EP in the medial-basal hypothalamus and the anterior and neurointermediate pituitary lobes in ovariectomized rats (OVX), treated or untreated with estradiol benzoate (EB). B-EP concentrations were significantly increased by desogestrel in the anterior lobe and by progesterone, desogestrel and medroxyprogesterone acetate in the neurointermediate lobe. Progesterone and progestins significantly reduced B-EP increase induced by estradiol benzoate in the anterior lobe. Estradiol benzoate treatment did not modify the effect of progesterone and desogestrel on B-EP in the neuro-intermediate pituitary lobe. Norethisterone acetate and progesterone increased B-EP concentrations in the medial-basal hypothalamus, while the other steroids were inactive. In contrast, in the hypothalamus all progestins attenuated the increase of B-EP induced by estradiol benzoate (p less than 0.01). These data indicate that progesterone and progestins modulate the hypothalamic and pituitary B-EP concentrations in concert with estrogens. The capacity of progestins to modify the hypothalamic contents of B-EP may represent one of the mechanisms of action of these steroids in influencing brain function.


1987 - Proopiomelanocortin-related peptides and methionine enkephalin in human follicular fluid: changes during the menstrual cycle. [Articolo su rivista]
F., Petraglia; G. D., Meo; R., Storchi; A., Segre; Facchinetti, Fabio; S., Szalay; A., Volpe; A. R., Genazzani
abstract

Several studies indicate the presence of different pituitary hormones or neuropeptides in ovarian follicular fluid from various species. Recently our group showed that the ovarian follicular fluid of health women contains two of the endogenous opioid peptides, beta-endorphin and methionine enkephalin, in concentrations that are tenfold to twentyfold higher than in circulating plasma. The presence of immunoreactive beta-lipotropin was also shown. The aim of the present study was to evaluate whether adrenocorticotropic hormone, which in pituitary cells is synthesized from proopiomelanocortin such as beta-endorphin and beta-lipotropin, is also present in follicular fluid and the possible changes of proopiomelanocortin-related peptides during the menstrual cycle. Concentrations of beta-endorphin, methionine enkephalin, adrenocorticotropic hormone, and beta-lipotropin were measured in 60 healthy menstruating women at different periods of the menstrual cycle (20 during the follicular, 22 in the preovulatory days, and 18 during the luteal phase). Thirteen women participated in an in vitro fertilization program and thus received clomiphene citrate (100 mg/day from the fifth to the ninth day) plus 5000 IU human chorionic gonadotropin before starting the program. All samples were collected at laparoscopy under general anesthesia. In another eight patients fluid was collected from follicular cysts. Peptides were extracted on octadodecasilyl silica columns with 80\% methanol in 0.5 mol/L acetic acid. The identity of follicular fluid beta-endorphin, methionine enkephalin, adrenocorticotropic hormone, and beta-lipotropin and standard peptides was demonstrated with high-pressure liquid chromatography. Peptide concentrations were measured in extracts by radioimmunoassays either directly by (methionine enkephalin and adrenocorticotropic hormone) or after (beta-endorphin and beta-lipotropin) gel filtration on Sephadex G-75. The concentrations of methionine enkephalin, adrenocorticotropic hormone, and beta-lipotropin were similar in the different periods of the cycle. Conversely, beta-endorphin concentrations were significantly higher in preovulatory days than in the other periods; no differences were evident between spontaneous and stimulated cycles. These results indicate that proopiomelanocortin-related peptides are present in the follicular fluid and that beta-endorphin concentrations change during the menstrual cycle, with the highest values occurring in the preovulatory follicle.


1987 - PROOPIOMELANOCORTIN-RELATED PEPTIDES IN FETOPLACENTAL STRUCTURES THROUGHOUT PREGNANCY [Articolo su rivista]
Facchinetti, Fabio; A. E., Panerai; F., Petraglia; Radi, Daniele; T., Setti; A. R., Storchi; A. R., Genazzani
abstract

This study evaluates the presence of proopiomelanocortin(POMO).related peptides in four embryos and eight fetal pituitaries starting from 5 to 25 weeks of pregnancy. .Moreover, fetal membranes (amnion and chorion) were also investigated. Freshly collected samples were boiled in acetic acid to destroy enzymes, homogenized and aub- mitted to high performance liquid chromatography (linear gradient from 25 to 40% acetonitrile in 0.01 M HOI, in 15', 1.5 ml/min), The collected fractions were tested for the presence of p.lipotrophin (p.LPH), p.endorphin(p.EP), y.endorphin(y.EP) through: RIAs. p.EP and p•LPH were detected from 7 weeks of pregnancy while y.EP appeared later. Only the cephalic portion of the embryos contained the peptides where p.LPH predominates while no immunoreactivity was detected in the rostral one. In the fetal pituitary there is a progressive increase of y.EP according to the gestational age and both p.EP and p.LPH showed a trend toward constancy in the 15- 25 week range. Amnion and chorion contai n a significant amount of the three peptìdes. Their ontogenesis starts earlìerthan in the embryo; p.LPH or p.EP were detected at 5 weeks of pregnancy. In both tissues p.EP was higher in the first than in the second trimester. These data demonstrate a different pattern of POMO ontogeny and processing betweeri the con- ceptus and his environment. This suggests that the POMQ•related opiod system of the fetus and of fetal adnexes are independent of each other, possibly subserving to different functions,


1987 - Prostaglandin-induced mid-pregnancy abortion increases plasma and amniotic fluid levels of beta-lipotropin and beta-endorphin. [Articolo su rivista]
A. R., Genazzani; F., Petraglia; G. D., Meo; V., Santoro; Facchinetti, Fabio; A., Segre
abstract

The continuous and progressive rise of beta-endorphin (B-EP), beta-lipotropin (B-LPH) and cortisol plasma levels during labor in term-pregnant women represents one of the most relevant maternal hormonal responses to the stress of parturition. The aim of the present study was to evaluate the changes of these hormones, both in plasma and amniotic fluid (except cortisol), in a group of pregnant women undergoing prostaglandin-induced therapeutic abortion at the 2nd trimester of pregnancy. B-EP, B-LPH and cortisol were measured by radioimmunoassay. Both plasma and amniotic fluid samples were purified through extraction and chromatography (Sephadex G-75 columns). The prostaglandin derivative, 16-phenoxy-PGE2-methylsulfonylamide (sulprostone, Schering, Berlin) (500 micrograms, i.m., every 4 h), caused a rapid and significant rise of plasma B-EP, B-LPH and cortisol levels in all subjects. The relative increase of the 3 hormones was less relevant after the 2nd and absent after the 3rd injection of PGE2. The amniotic fluid concentrations of B-EP and B-LPH were also raised 2 h after the 1st injection. These data indicate that sulprostone-induced abortion activates both maternal and fetoplacental release of opioids independently of the trend of uterine contractions. The pattern of pro-opiomelanocortin-related labor differs from spontaneous labor and can probably be linked to a direct effect of the drug.


1987 - Ritanserin, a serotonin-S2 receptor antagonist, does not prevent 5-hydroxytryptophan-induced beta-EP, beta-LPH and cortisol secretion. [Articolo su rivista]
Facchinetti, Fabio; E., Martignoni; G., Nappi; S., Marini; F., Petraglia; G., Sandrini; A. R., Genazzani
abstract

Ritanserin, a new serotonin antagonist selective upon S2 receptor subclass is available. Thus, in order to better define the positive control of serotoninergic pathway on proopiomelanocortin (POMC)-related peptide release, a group of 7 healthy male volunteers has been submitted to a 5-hydroxytryptophane (5-OH-TP) test (200 mg p.o.) before and after 4 days Ritanserin pretreatment. Plasma beta-endorphin (beta-EP), beta-lipotropin (beta-LPH) and cortisol levels were measured hourly for 4 h after each 5-OH-TP loading. Hormonal levels were measured by specific RIAs on extracted (cortisol) and chromatographed (beta-EP and beta-LPH) plasma samples. Basal plasma concentrations of the three hormones were unchanged by Ritanserin pretreatment. Similarly, the integrated areas of beta-LPH, beta-EP and cortisol release in response to 5-OH-TP remained unaffected by the receptor blockade. These data confirm that serotonin-acting drugs are able to stimulate POMC-related peptide release and indicate that such interaction is not mediated through S2 receptor subclass.


1987 - Seminal fluid androgen levels in infertile patients. [Articolo su rivista]
Facchinetti, Fabio; G., Comitini; Genazzani, Alessandro; C., Bakalakis; A. R., Genazzani; S., Loche
abstract

Seminal fluid concentrations of testosterone (T), dihydrotestosterone (DHT), androstenedione (A), and 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol) were measured in 34 male patients of infertile couples. Patients were subdivided into oligospermic (less than 20 X 10(6)/mL) and asthenospermic (typical motility less than 20\%; total motility less than 40\%) groups. Steroids were measured by specific radioimmunoassay after ether extraction and celite column chromatography. 3 alpha-Diol was present in seminal fluid, and its concentration was significantly correlated with DHT (r = .49, P less than .05). In oligospermic patients, seminal levels of T (78 +/- 29 pg/mL, mean +/- SD) and DHT (323 +/- 132 pg/mL) were significantly reduced in comparison with normospermic men (T, 119 +/- 56, P less than .05; DHT, 557 +/- 255, P less than .01), while A and 3 alpha-diol concentrations were similar in the two groups. Seminal T and DHT levels were also reduced in asthenospermic specimens, which showed increased 3 alpha-diol concentrations (75 +/- 44 pg/mL) with respect to normokinetic samples (45 +/- 20, P less than .05). Finally, a positive linear relationship was observed between DHT and both sperm density (P less than .01) and total motility (P less than .01). These data demonstrate the existence of a significant amount of 3 alpha-diol in seminal plasma and suggest DHT as the androgen most closely related to sperm quality.


1987 - SIMULTANEOUS RIA OF HUMAN beta-ENDORPHIN e beta-LIPOTROPIN IN PLASMA EXTRACTS [Abstract in Rivista]
Facchinetti, Fabio; A. R., Genazzani
abstract

The identification of f)-endorphin (f)-EP) as part of the larger precurs~_ f)-lipotropin (f)-LPH) in pituitary cells and the importance of f)-E P in behaviour and endogenous analgesia dictate the need for a method of measur- ing the plasma or li.quour concentrations of them in physiological and path- ological conditions. The present study concerns the deve:.opment of RIA methods to measure f)-EP ~:Id f)-LPH after extraction and pu r i f i c a t i.o n . Synt:" etic f)-EP (Peninsular Inc., San Francisco) and h f)-LPH (Dr.C.H.Li, San Fra~ cisco) and h f)-EP antiserum (Dr.C.Pert NIH, Bethesda) were used. 8nth peptides were labelled with Il~5 using the chloramine T method, an then purified by gel filtration in a Sephadex G-25 culumn. The specific activity of f)-EP-I125 was lSOuC/ug and that of f)-LPH-I125 was 242uC/ug. The specificity of the antiserum using both labelled peptides was chec~ with the following substances: leu-enkephalin, Ret-enkephalin, substance P GIF, 1-39 ACTH, f)-MSH, 61-77 f)-LPH, 79-91 f)-LPH, f)-E P and f)-LPH. No cross reaction was found with leu and met-enkephalin, substance P, GIF and 1-39 ACTH, while in the f)-EP and f)-LPH RIAs, f)-LPH and f)-EP showe d a cross r e ac t-: ion of 54.7% and 196.2% respectively. Using f)-LPH as tracer, 7S-9l f)-LP H atd 61-77 f)-LPH cross reacted very s l i gh tI y (0.29% a nd 0.01% r e s p e c t i ve Ly) ; when f)-EP-I125 was used the cross reactions were 0.91% and 0.26%; and whe an equimolecular pool of both peptides was tested the cross reaction in- creased to 5.2%. After the addition of 4000 dpm labelled f)-EP and f)-LPH, 2.Sml plasma was extracted for l hr with 150me glass powder in il rotary mixer at room temp- erature. The glass powders were washed with distilled water'and then 2N HC: and the peptides removed in a l hr rotation with 2ml acetone-HCl 2N 4:1. After nitrogen drying the residue was dissolved in 0.4ml acetic acid O.lN, 0.1% BSA, applied to a Sephadex G-7S column and eluted with the same sol- ution. Two distinct peaks of elution were collected, lyophilised and redissolveè in phosphate buffer pH 7.4, O.OSM for assay; an aliquot was utilised to evaluate the recovery which was 61.1~ + 4.5 and SS.2% + 5.7 (M + SE) for f)-EP and f)-LPH respectively. Using different dilutions of the antiserum and of the labelled compounds, two different RIA systems were perfected; the first for f)-EP having a sensitivity of lSpg and the second for f)-LPH having a sensitivity of 4Spg. The RIAs were characterised by an lShr pre- incubation with the antiserum followed by the addition of tracer for an inc- ubation time of 4Shr (both at 4°C); the complcx was then precipitated with goat antirabbit y globulin (24hr). This study was supported by the CNR project "Biology of Reproduction"


1987 - Sympathergic/neuroendocrine reactivity as a marker of adaptive processes underlying migraine susceptibility [Articolo su rivista]
Facchinetti, Fabio
abstract


1987 - The full sequence is required for the Met-Enkephalin effects on granulosa cell progesterone production [Articolo su rivista]
Facchinetti, Fabio
abstract


1986 - Abnormal beta-endorphin and beta-lipotropin responses to TRH and LRH administration in primary and secondary affective disorders. [Articolo su rivista]
F., Brambilla; F., Petraglia; Facchinetti, Fabio; A. R., Genazzani
abstract

Anomalous anterior pituitary hormone responses to acute administration of TRH and LRH have previously been observed in patients with primary affective disorders (PAD), with TRH eliciting GH, FSH and LH rises, and LRH eliciting GH and Prl rises. We examined whether the same unusual responses were present also for beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) in 15 PAD patients, in 9 patients with secondary affective disorders (SAD), and in 7 controls. TRH (500 micrograms iv) elicited rises of beta-EP plasma levels in 5 PAD and 2 SAD patients, and of beta-LPH in 4 PAD and 3 SAD patients. LRH (150 micrograms iv) elicited rises of plasma beta-EP levels in 2 PAD and 2 SAD patients, and of beta-LPH in 5 PAD and 2 SAD patients. No rises of beta-EP and beta-LPH plasma levels were observed in PAD patients after saline administration, nor in the controls after TRH, LRH or saline administration.


1986 - Abnormal dexamethasone suppression test in daily chronic headache sufferers. [Articolo su rivista]
E., Martignoni; Facchinetti, Fabio; G. C., Manzoni; F., Petraglia; G., Nappi; A. R., Genazzani
abstract

The dexamethasone suppression test (DST) was administered in 48 daily chronic headache (DCH) sufferers, 37 of whom also suffered from mild to severe depression. In 14 of 48 subjects (29.2\%), cortisol values at 1600h were greater than 50 ng/ml, despite normal suppression at 0800h. The escapers showed basal cortisol values and (Depression scale) scores on the Minnesota Multiphasic Personality Inventory higher than suppressors. Thus, a group of DCH sufferers appeared to share a biochemical defect often seen in endogenous depression. The escape from dexamethasone suppression could be a psychobiological indicator of vulnerability to develop depressive disorder and/or chronic pain complaints.


1986 - Association of monooctanoin with cicloxilic acid in treatment of secondary common duct stones [Articolo su rivista]
Facchinetti, Fabio
abstract


1986 - Benefits and risks of different hormonal replacement therapies in post-menopausal women. [Articolo su rivista]
Volpe, Annibale; Facchinetti, Fabio; A., Grasso; F., Petraglia; D., Campanini; A. R., Genazzani
abstract

A total of 113 women who presented with climacteric symptoms participated in the study. They were randomly allocated to seven groups of 10-27 subjects, who received for 6 mth the following therapies, respectively: conjugated oestrogens (CE) 0.625 mg/day for 21 days + norethisterone (NET) 5 mg/day from day 12 to day 21; CE + cyproterone acetate (CPA) 12.5 mg/day from day 1 to day 10; oestradiol valerate (EV) 2 mg/day for 21 days + NET; EV + CPA; oestriol (E3) 2-4 mg/day; tibolone (ORG OD14) 2.5 mg/day; and placebo, one tablet/day. Hot flushes decreased significantly over the treatment period in all seven groups. However, E3 was less effective at the dose used than CE, EV or ORG OD 14. At the end of the 6 month treatment period histological examination revealed no changes in endometrial morphology in any of the patients treated. Indeed, the addition of a progestogen even induced regression of endometrial hyperplasia in 8 cases. No significant variation in the plasma levels of triglycerides, total cholesterol, high-density lipoprotein (HDL) or low-density lipoprotein (LDL) was observed after the second and sixth months of treatment with E3 or ORG OD 14. After 6 months, treatment with CE/EV + CPA produced a significant increase in HDL, while treatment with CE/EV + NET brought about a reduction in total cholesterol and HDL and an increase in LDL.


1986 - BETA ENDORPHIN (B-EP) and CORTISOL (C) RESPONSES TO CRF IN OBESE ADOLESCENTS [Abstract in Atti di Convegno]
S., Bernasconi1; Facchinetti, Fabio; C., Marcellini1; S., Mari1; L., Ghizzoni1; A. R., Genazzani
abstract

B-EP and C serum levels in response to CRF were studied in 10 obese adolescent subjects (4M,6F) 8-17 years of age. All patients were healthy with an overweight ranging from 35 to 95% and a mean duration of obesity of 10 years. Blood samples were drawn before and 15, 30, 60, 120, 240 minutes after i.v. injection of 1 ug/kg of CRF (CRF Bissendorf). The baseline B-EP and C levels were 12.9 ± 6.3 fmol/ml and 9.4 ± 4.7 ug%ml respectively, confirming the hyper B-EP previously reported. Among these subjects 2 different groups were identified, based on their responses to CRF: A) Responders with 100% increase of B-EP (Δ = 14.4 ± 5.9, n=4) and B Non-responders in which B-EP did not rise after CRF stimulation (maxΔ = 1.7, n=4). Furthermore, the mean baseline values of B-EP in group A were significant lower than those in group B (8.17±2.5 v.s. 19.3±4.3 p<0.01). No correlation was found between basal and stimulated levels of B-EP and C in the two groups. These data show that among obese patients 2 different population can be identified based on B-EP responses to CRF and that this distinction is independent from age, sex, % overweight, duration of obesity and C responses.


1986 - Central and peripheral beta-endorphin response to transcutaneous electrical nerve stimulation. [Capitolo/Saggio]
Facchinetti, Fabio; G., Sforza; M., Amidei; C., Cozza; F., Petraglia; C., Montanari; A. R., Genazzani
abstract

The effects of transcutaneous electrical nerve stimulation on plasma and cerebrospinal fluid (CSF) levels of beta-Endorphin (beta-EP) were studied in 6 groups of pain-free patients. Different modes of TENS were applied for 20 minutes. Regardless of mode and/or frequency of the stimulation plasma and/or CSF beta-EP levels were significantly increased. Plasma and CSF responses were not correlated suggesting that TENS activates different opiatergic pathways at central and peripheral level.


1986 - Changes in immunoreactive beta-endorphin, methionine-enkephalin and ACTH in bone marrow cells and fluid from leukemic children. [Articolo su rivista]
S., Sardelli; F., Petraglia; F., Massolo; A., Messori; V., Santoro; Facchinetti, Fabio; A. R., Genazzani
abstract

The present study demonstrates the presence of the endogenous opioid peptides, beta-endorphin (beta-EP) and methionine-enkephalin (MET-ENK), and of ACTH in cell homogenates and interstitial fluid from sternal biopsy of leukemic children. The peptides were identified by chromatography and radioimmunoassay. In leukemic children with lymphoblastic cells present in the sternal sample, concentrations of immunoreactive (ir) beta-EP in the cell homogenate, but not in the fluid, were significantly higher than in leukemic children with normal bone marrow. In contrast, ir MET-ENK and ir ACTH did not differ between the two study groups either in the cell homogenate or in the fluid. These data suggest the presence of a complex system of opioid peptides in the cells and interstitial fluid of bone marrow of leukemic children with the highest concentrations of ir beta-EP appearing in samples collected during the active phase of the disease, and may suggest a possible role of opioid peptides as immunomodulatory substances.


1986 - Circadian variations of human flexion reflex. [Articolo su rivista]
G., Sandrini; E., Alfonsi; G., Bono; Facchinetti, Fabio; L., Montalbetti; G., Nappi
abstract

We investigated 8 healthy male volunteers, evaluating RII and RIII thresholds every 6 h starting from noon, for a 24-h period. Both reflex responses exhibited a circadian rhythmicity: the lowest values were found in the early morning (9.1 +/- 3.0 and 13.1 +/- 4.4 mA, respectively), while the highest values were observed at midnight (13.1 +/- 3.5 and 18.5 +/- 5.3 mA). Also mean cosinor analysis indicated the existence of a significant rhythm with acrophase at 20:12 for RII and 22:29 for RIII. In 4 subjects, beta-endorphin plasma (beta-EP) level was tested during the day. No correlation was observed between circadian changes of beta-EP and RIII threshold. Other factors are likely to be involved in the circadian variation of nociceptive flexion reflex in man.


1986 - Circulating opioids during sexual maturation [Articolo su rivista]
Facchinetti, Fabio
abstract


1986 - CSF and plasma levels of pro-opiomelanocortin-related peptides in reversible ischaemic attacks and strokes. [Articolo su rivista]
G., Nappi; Facchinetti, Fabio; G., Bono; F., Petraglia; E., Sinforiani; A. R., Genazzani
abstract

Plasma and CSF beta-endorphin (beta-EP), beta-lipotropin (beta-LPH) and ACTH levels were studied in a group of 25 patients who underwent reversible ischaemic attacks or completed strokes. CSF beta-EP and beta-LPH in ischaemic patients were higher than those of the control population, independently of both clinical reversibility of the cerebral damage, and the time lapse sampling and the acute event. The presence of a CT demonstrable lesion was related to the highest CSF beta-EP levels. These data confirm an involvement of central opioid substances in the phenomena related to brain ischaemia. ACTH levels in the CSF did not differ from the controls; this finding further supports the concept of an independent central secretion of the different pro-opiomelanocortin-related peptides. The peripheral plasma concentrations of beta-EP, beta-LPH and ACTH, were, in contrast, within the normal range, confirming that CSF and plasma contents of pro-opiomelanocortin-related peptides are differently controlled and originate from different sources.


1986 - Cyclic reduction of plasma B-endorphin in premenstrual syndrome (PMS) [Articolo su rivista]
Facchinetti, Fabio
abstract


1986 - Dissociation between CSF and plasma B-endorphin in major depressive disorders: evidence for a different regulation. [Articolo su rivista]
Facchinetti, Fabio; F., Petraglia; G., Sances; C., Garuti; P., Tosca; G., Nappi; A. R., Genazzani
abstract

Plasma and cerebrospinal fluid (CSF) levels of ACTH, B-lipotropin (B-LPH) and B-endorphin (B-EP) were simultaneously measured in 10 patients with major depression (35-57 yr) with a disease history of 10-34 yr, 7 of them with recurrent episodes, and in 13 age-matched healthy controls. In patients, lumbar puncture was performed after a 10 days drug-free period. Plasma B-EP and B-LPH levels were measured by RIA after silicic acid plasma extraction and Sephadex G-75 column chromatography. Plasma ACTH concentrations were measured by IRMA. For CSF assays the extraction step was avoided. In depressed patients, plasma ACTH (16.2 +/- 6.9 fmol/ml, mean +/- SD), B-LPH (19.8 +/- 8.5) and B-EP (17.8 +/- 7.0) levels were significantly higher (p less than 0.01) than in controls. On the contrary, CSF levels of the three peptides were similar in the two groups. No correlations were found between plasma or CSF concentrations and duration of the disease or severity of the actual episode. These data add further evidence to the independent regulation between central and peripheral POMC-related peptides. They also reduce the possibility that peptides of pituitary origin, directly from the gland or through the peripheral circulation, could penetrate the CSF.


1986 - Dysregulation of plasma pro-opiomelanocortin-related peptides in neurotic depression. [Articolo su rivista]
A. R., Genazzani; F., Petraglia; E., Sinforiani; F., Brambilla; Facchinetti, Fabio; G., Nappi
abstract

In order to assess whether a central hypothalamic impairment could account for the pro-opiomelanocortin (POMC)-related peptide over-secretion in depressive disorders, plasma B-lipotropin (B-LPH), B-endorphin (B-EP) and cortisol concentrations were measured in 9 patients affected by neurotic depression: every 4 h over a 24-h period; in response to insulin-induced hypoglycaemia (0.1 IU/kg body weight), and during dexamethasone (DXM) administration (0.5 mg X 4/day for 2 days). Eight age-matched healthy volunteers (controls) were also studied. B-EP and B-LPH were determined by specific radioimmunoassays after plasma extraction and gel chromatography. Compared with the controls, the patients showed a 3 times higher plasma B-EP, twice the normal B-LPH levels, and a 20\% cortisol increase. The neurotic depressed patients showed and evening-related decrease in the levels of the 3 hormones, expressed as mean values, similar to that in the controls, whereas the single cosinor analysis revealed a significant circadian rhythm of B-LPH and B-EP only in 3 and 2 patients, respectively. Insulin-induced hypoglycaemia (ITT) stimulated the release of B-LPH and cortisol in both groups, whereas the B-EP increase was absent in the patients. DXM reduced plasma cortisol and B-LPH levels in controls and patients, but in the latter it failed to reduce the B-EP concentrations. The present data indicate that neurotic depressed patients are characterized by increased activity of the hypothalamic-pituitary-adrenal axis, with maintained circadian rhythmicity.(ABSTRACT TRUNCATED AT 250 WORDS)


1986 - Effects of L-5HTP with and without carbidopa on plasma beta-endorphin and pain perception. Possible implications in migraine prophylaxis. [Articolo su rivista]
A. R., Genazzani; G., Sandrini; Facchinetti, Fabio; V., Rizzo; E., Alfonsi; G., Sances; M., Calvani; G., Nappi
abstract

L-Tryptophan (L-TP) has been used in migraine and other pain conditions. The mechanism underlying the analgesic effect is still partly undefined. In this study the effects of subchronic administration of L-5-hydroxy-tryptophan (L-5HTP) (with and without carbidopa) on plasma beta-endorphin (beta-EP) levels and subjective pain threshold and tolerance were investigated in seven healthy volunteers. To measure also an objective indicator for pain, the nociceptive flexion reflex threshold was studied. L-5HTP treatment with and without carbidopa administration increased beta-EP levels significantly (p less than 0.05). L-5HTP plus carbidopa induced an increase in beta-EP significantly (p less than 0.05) higher than that after L-5HTP alone. Neither subjective pain threshold and tolerance nor RIII threshold was modified by either treatment. Our data seem to point to the existence of a complex linkage between plasma opioid levels and pain perception.


1986 - Effects of L-5HTP with and without carbidopa on plasma β-endorphin and pain perception: Possible implications in migraine prophylaxis [Articolo su rivista]
Genazzani, A. R.; Sandrini, G.; Facchinetti, F.; Rizzo, V.; Alfonsi, E.; Sances, G.; Calvani, M.; Nappi, G.
abstract


1986 - Effects of sodium valproate and diazepam on beta-endorphin, beta-lipotropin and cortisol secretion induced by hypoglycemic stress in humans. [Articolo su rivista]
F., Petraglia; S., Bakalakis; Facchinetti, Fabio; Volpe, Annibale; E. E., Muller; A. R., Genazzani
abstract

Evidence that gamma-aminobutyric acid (GABA) and benzodiazepine receptors play a role in the inhibition of ACTH-cortisol secretion in humans has until now been drawn only from data indicating that sodium valproate, a GABA mimetic, and diazepam, a benzodiazepine, decrease hypothalamus-pituitary-adrenal (HPA) axis secretion in patients affected by pathological hypersecretion of the axis. Therefore, the present study investigated the effects, in the same healthy subjects, of sodium valproate or diazepam, on both basal and stress-stimulated concentrations of beta-endorphin (beta-EP), beta-lipotropin (beta-LPH) and cortisol. A single maximal dose of sodium valproate (400 mg) or diazepam (10 mg) did not significantly modify basal concentrations of beta-EP, beta-LPH and cortisol. On the other hand, in the same subjects, pretreatment with sodium valproate (20 mg X 3) or diazepam (10 mg X 2) blocked the increases in these hormones produced by hypoglycemic stress in all patients tested (p less than 0.01 vs. placebo at 45, 60 and 90 min after insulin injection), without affecting the decrease in blood glucose levels. The present data show that sodium valproate and diazepam inhibit stress-induced beta-EP, beta-LPH and cortisol secretion in humans, suggesting that endogenous GABA and benzodiazepine receptors participate in physiological mechanisms regulating the activity of the HPA axis.


1986 - Endogenous opioid inhibitory tone on LH secretion in normal puberty and in several pubertal disturbances. [Articolo su rivista]
S., Bernasconi; F., Petraglia; Iughetti, Lorenzo; Facchinetti, Fabio; C., Marcellini; G., Giovannelli; A. R., Genazzani
abstract

N.A.


1986 - Endogenous opioid peptides in uterine fluid. [Articolo su rivista]
F., Petraglia; Facchinetti, Fabio; K., M'Futa; M., Ruspa; J. J., Bonavera; F., Gandolfi; A. R., Genazzani
abstract

The present study demonstrates the presence of the endogenous opioid peptides beta-endorphin (beta-EP) and methionine-enkephalin (MET-ENK), in the uterine fluid of fertile women and normally cycling and superovulated cows. The two peptides are undetectable in the uterine fluid of untreated postmenopausal women, whereas they are present following estrogen-progesterone treatment. Immunoreactive (IR) MET-ENK concentrations were higher in the secretory than in the proliferative phase of the menstrual cycle. IR beta-EP and IR MET-ENK are present also in the follicular, oviductal, and uterine fluid of cows, and in the uterine fluid, concentrations of IR MET-ENK are higher in the superovulated than in the control animals. Because opioids play important roles on endocrine and immune functions, the present data support the potential physiologic role of endometrial secretions.


1986 - Evidence for serotonin-S2 receptor involvement in analgesia in humans. [Articolo su rivista]
G., Sandrini; E., Alfonsi; C. D., Rysky; S., Marini; Facchinetti, Fabio; G., Nappi
abstract

The possible analgesic activity of ritanserin (a new very selective and potent serotonin-S2 antagonist) was studied (double-blind) in humans. A significant increase in nociceptive flexion reflex threshold and subjective pain threshold was observed after five days of treatment, while treatment with placebo did not induce any change. The effects of ritanserin were not reversed by either naloxone or saline (double-blind) administration. Our data suggest a possible role of serotonin-S2 receptors in analgesia.


1986 - Hyperendorphinemia in obese children and adolescents. [Articolo su rivista]
A. R., Genazzani; Facchinetti, Fabio; F., Petraglia; C., Pintor; R., Corda
abstract

To study the role of opioid peptides in human obesity, plasma beta-endorphin (beta EP), beta-lipotropin (beta LPH), and cortisol resting values, circadian rhythms, and responses to hypoglycemia were studied in 6 prepubertal and 6 pubertal obese adolescents (at least 40\% above ideal body weight) and in 10 normal subjects matched for age, sex, and pubertal development. Baseline plasma beta LPH and beta EP concentrations in both obese children and adolescents were twice as high as those in normal controls, while cortisol levels were not different. Cortisol, beta EP, and beta LPH levels had a clear circadian rhythmicity in all subjects, with the exception of obese pubertal boys whose plasma beta EP concentrations were constant throughout the day. After insulin administration, the fall in blood sugar was similar in all groups. Plasma cortisol and beta EP responses were similar in both obese and normal prepubertal subjects. In obese pubertal adolescents, beta EP did not increase significantly after hypoglycemia, although it did increase in normal weight pubertal subjects. In normal prepubertal subjects, the circadian rhythms of beta EP and beta LPH secretion and release induced by hypoglycemia suggest the presence of a well developed neuroendocrine control of proopiomelanocortin-related peptide secretion. In prepubertal obese children, the increased plasma beta EP and beta LPH levels with the maintenance of their circadian rhythm and responsivity to hypoglycemia suggest overactivity of anterior pituitary secretion. In obese adolescents, in spite of the normal rhythm of beta LPH and cortisol, beta EP levels did not change throughout the day, thus suggesting beta EP secretion from nonpituitary sources in these subjects. The present study indicates a possible direct role for hyperendorphinemia in the induction of overeating in obese children and adolescents.


1986 - Hyperendorphinemia in obesity and relationships to affective state. [Articolo su rivista]
Facchinetti, Fabio; C., Giovannini; C., Barletta; F., Petraglia; R., Buzzetti; F., Burla; R., Lazzari; A. R., Genazzani; D., Scavo
abstract

Eight obese patients (exceeding ideal body weight by 50\% or more) with no endocrinological or metabolic disorders and 8 healthy, age-matched, normal-weight volunteers were submitted to an overnight short dexamethasone (DXM) suppression test and to a psychological assessment through various psychometric scales. Plasma B-Endorphin (B-EP), B-Lipotropin (B-LPH), ACTH and cortisol concentrations were evaluated in basal conditions, as well as 9 and 17 hours after late night administration of 1 mg DXM in both groups. All hormones were measured by radioimmunoassay, either directly in the plasma (ACTH and cortisol) or after silicic acid extraction and Sephadex G-75 column chromatography (B-LPH and B-EP). In obese patients, plasma B-EP levels in basal conditions were three times higher than in normal weight controls and remained unaltered by DXM suppression. ACTH and B-LPH, in contrast, were within the normal range and were significantly reduced by DXM. In 3 of the 8 patients, plasma cortisol concentrations at 17 hours post-DXM were greater than 50 ng/ml indicating an early escape from the suppression. Psychometric evaluations revealed a prevalence of depressive personality in obese patients. These data indicate an hypersecretion of B-EP in obese patients, which is only partially dependent on hypothalamic control.


1986 - LH and Cortisol responses to Naloxone : relationship to normal and pathological puberal development. [Capitolo/Saggio]
Bernasconi, S.; Petraglia, F.; Iughetti, Lorenzo; Marcellini, C.; Romanini, F.; Facchinetti, F.; Genazzani, A. R.
abstract

n.a.


1986 - Met-enkephalin enhances follicle-stimulating hormone-dependent progesterone production from cultured granulosa cells. [Articolo su rivista]
Facchinetti, Fabio; M., Ruspa; A., Turci; F., Petraglia; A., Segre; A., Forabosco; A. R., Genazzani
abstract

beta-Endorphin (beta-EP) and methionine-enkephalin (Met-Enk) have been detected in human follicular fluid in concentrations several times higher than those in plasma. These data stimulated us to study the possible physiological role of ovarian opioids. We, therefore, determined the effects of both beta-EP and Met-Enk, alone or in combination with naloxone, on FSH-induced progesterone (P) secretion by cultured granulosa cells. Granulosa cells were collected from follicular fluid recovered at laparoscopy in seven superovulated women. The cells were preincubated with RPMI-1640 medium containing 20\% fetal calf serum in 5\% CO2 for 48 h, followed by the addition of 100 mU purified FSH and the various test substances for 48 more h. beta-EP (10 nM to 1 pM) had no effect on P secretion either alone or in combination with FSH and/or naloxone. Micro- to picomolar amounts of Met-Enk increased FSH-induced P secretion up to 186.9 +/- 35.1\% (+/- SEM). Met-Enk had no affect in the absence of FSH, and its action was significantly blunted by the concomitant addition of 10(-5) M naloxone. These data provide evidence for a dose-dependent naloxone-reversible synergistic action of Met-Enk and FSH on P secretion by cultured granulosa cells. This finding supports the hypothesis of the existence of an ovarian opioid system.


1986 -