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Biomedical subjects

S Ferrazzani

Publications and source records attributed to S Ferrazzani.

At least 19 recordsLinked to original sources

Low-molecular weight heparin induces in vitro trophoblast invasiveness: role of matrix metalloproteinases and tissue inhibitors.

Heparin is used widely for the prevention of pregnancy loss in pregnant women with thrombophilia. However, it is still unknown if heparin may be able to affect trophoblast functions. Therefore, we investigated the hypothesis that low-molecular weight heparin (LMWH) might regulate in vitro trophoblast invasiveness and placental production of matrix metalloproteinases (MMPs) and tissue inhibitors (TIMPs). In the first-trimester placental tissue, the MMP-9 expression was observed in both villous and extravillous cytotrophoblast cells, and MMP-2 mainly in villous cytotrophoblast. In human choriocarcinoma cells (JAR), MMP-2 was the dominant form. Heparin significantly enhanced both pro-MMPs and the active forms, and increased Matrigel invasiveness of extravillous trophoblast and choriocarcinoma cells. In choriocarcinoma cells the heparin effect was also indirect, inducing a significant decrease in TIMP-1 and TIMP-2 protein expressions and mRNAs. The present data suggest that the increase in trophoblast invasion by heparin is due to a specific protein playing a role in placental invasion. These observations may help in understanding the effects of heparin treatment during pregnancy.

Anticoagulants↗

[Postpartum hemorrhage].

Postpartum hemorrhage, frequently due to uterine atony, is an important cause of maternal death and morbidity. The knowledge of causes, of antenatal and intrapartum risk factors and of physiopathological changes in hemodynamics and coagulation during pregnancy are essential for the management of the condition. At the present time, many efforts are made to organize a multidisciplinary approach to this complication of delivery involving clinical and laboratory staffs, since the rapid correction of hypovolemia, the diagnosis and treatment of defective coagulation, the surgical and pharmacological control of bleeding are mandatory. Several medical options have been developed and the surgical management includes traditional and newer conservative procedures with variable success rates. The developments in the treatment of postpartum hemorrhage may reduce hysterectomy that is to be considered the last resort to resolve the hemorrhage in some cases. In the modern management of postpartum hemorrhage protocols and guidelines should be available in every delivery room.

Embolization, Therapeutic↗

Celiac disease and inflammatory bowel disease in pregnancy.

An adverse influence on reproductive life and obstetric complications are known to occur in women with celiac disease (clinical and subclinical disease) or inflammatory bowel diseases. Treatment can improve the pregnancy outcome; therefore, it is advisable that a clinical evaluation is performed by a joint team of obstetricians, internists and surgeons. The preconception clinical evaluation of the affected women is useful to focus on the different clinical aspects of the disease and to indicate specific therapeutic strategies. In this study a review of the literature regard to celiac disease and inflammatory bowel disease in pregnancy is presented.

Celiac Disease↗

[Therapy and prevention of obstetric hemorrhage by tamponade using a balloon catheter].

The aim of this study was to verify the possibility to use a balloon catheter as hemostatic method in pregnancies at high risk for hemorrhage as an alternative to less conservative surgical procedures. In 4 pregnancies at risk for hemorrhage, a compressive endouterine or endocervical method, consisting of a balloon catheter filled of warm saline solution, was used in order to stop or to prevent otherwise uncontrollable bleeding. In the cases treated the use of the balloon catheter was safe and effective both in the treatment of hemorrhage due to abnormal placentation and in the prevention of hemorrhagic complications due to abnormal implantation of pregnancy. Among novel medical and surgical approaches developed to control obstetric hemorrhage, tamponade using a balloon catheter could be considered a valid option. Moreover, this procedure, by avoiding radical surgical treatments, such as hysterectomy, which are frequently performed in unstable patients, could offer the advantage of preserving fertility.

Balloon Occlusion↗

There is poor agreement between manual auscultatory and automated oscillometric methods for the measurement of blood pressure in normotensive pregnant women.

OBJECTIVE: To assess the agreement between manual auscultatory arterial blood pressure values and the values obtained by an automated oscillometric device in normotensive pregnant patients. METHODS: Arterial blood pressure was determined concomitantly by a Dinamap 1846 sx/p device and by one observer (I, IV, V Korotkoff sounds) blinded to the Dinamap values. Agreement between methods was tested and graded according to the protocol of the British Hypertension Society. RESULTS: A total of 490 observations were performed. Differences were observed between the manual auscultatory method and the Dinamap method. In monitoring normotensive pregnant patients with a Dinamap device, an error was made of about 10 mmHg in 22% of the observations for systolic arterial blood pressure (BP); in 11% for diastolic arterial BP (IV sound); and in 15% for diastolic arterial BP (V sound). According to the British Hypertension Society protocol, the overall grade reached was 'C'. CONCLUSIONS: Although an underestimation of only 10 mmHg was shown, this can be of great importance in delaying a correct diagnosis of pre-eclampsia. The assessment of agreement of the Dinamap 1846 sx/p device in hypertensive pregnant patients should also be determined. A prospective study could be useful to determine the effectiveness of an automated device in detecting hypertensive disease in pregnancy.

Adult↗

Interleukin-3 and human trophoblast: in vitro explanations for the effect of interleukin in patients with antiphospholipid antibody syndrome.

OBJECTIVE: To examine the effect of interleukin (IL)-3 on in vitro trophoblast differentiation, hormone production, and invasiveness affected by antiphospholipid antibodies. DESIGN: Primary cytotrophoblast cell cultures. SETTING: Obstetrics and Gynecology Department of the Catholic University, Rome, Italy. PATIENT(S): Five normal pregnant women underwent uncomplicated vaginal delivery at 36 weeks of gestation. INTERVENTION(S): Immunoglobulin (Ig) G antibodies were isolated from the plasma of two patients with antiphospholipid syndrome and two normal control subjects with the use of protein-G Sepharose columns. Cytotrophoblast cells were dispersed in Ringer's bicarbonate buffer containing trypsin and DNAseI, filtered, and layered over a Percoll gradient in Hank's balanced salt solution. MAIN OUTCOME MEASURE(S): We investigated the effects of IL-3 and antiphospholipid antibodies on trophoblast cell invasiveness, differentiation, and hormone secretion. RESULT(S): IgG obtained from patients with antiphospholipid syndrome bound to trophoblast cells, with inhibitory effects on the cells' invasiveness, differentiation, and hCG secretion. IL-3 was able to restore in vitro placental functions. CONCLUSION(S): These results imply that IL-3 favorably affects human trophoblast implantation and development.

Antiphospholipid Syndrome↗

Birth weight in pre-eclamptic and normotensive twin pregnancies: an analysis of discordance and growth restriction.

The aim of this study was to verify whether twin pregnancies complicated by pre-eclampsia were associated with a higher rate of inter-twin weight discordance or an increased prevalence of small for gestational age (SGA) neonates than in normotensive twin pregnancies. A 17 year retrospective study was undertaken by examining 76 twin pregnancies complicated by pre-eclampsia and comparing them with 400 normotensive twin pregnancies. The case notes were reviewed in reference to birth weight differences, birth order, pregnancy outcome and inter-twin birth weight discordance. Statistical analyses were performed with t-test, contingency tables, regression curves, rank sum test and non-parametric survival plots. Power analysis was also carried out. Pre-eclamptic twin pregnancies were delivered at similar weeks of gestation to normotensive. They resulted in a smaller size for the second twin the earlier the delivery week, while in normotensive twin pregnancies no significant difference occurred at any week. Twin pregnancies complicated by pre-eclampsia showed higher rates of SGA neonates among second twins than those with normal pressure. The >25% discordance was associated with lower gestational age at delivery in each group [mean (range) 33 weeks (27-38) versus 37 (29-41), P < 0.005 pre-eclampsia and 35 weeks (25-41) versus 38 (25-42), P < 0.001 normotensive]. In pre-eclampsia the concomitant occurrence of SGA second twin and the discordance >25% was associated with shorter gestation while the presence of SGA second twin alone was not.

Adult↗

Emergency cerclage in the presence of protruding membranes: is pregnancy outcome predictable?

BACKGROUND: The aim of this retrospective study is to verify whether some maternal features are related to pregnancy outcome in cases of emergency mid-trimester cerclage when membranes are protruding through the dilated cervix. METHODS: Between 1988 and 1996 twenty-three pregnant patients with dilated cervix and protruding membranes were treated with emergency cerclage. At the time of cerclage, gestational age ranged from 17 to 27 weeks (median 22). RESULTS: Pregnancy was prolonged from 0 to 20 weeks (median 4). Eleven living infants were born (46%); median gestational age at delivery was 25 weeks (range 21-39) and median birth weight 700 g (range 350-3980 g). Obstetric histories, white blood cell count, and vaginal-cervical and urine cultures obtained on admission were analyzed in the two following groups: data from patients with good pregnancy outcome (live births) versus those from patients with poor outcome (stillbirths and neonatal deaths). No significant difference was found between the groups for the above mentioned maternal features. CONCLUSIONS: The possibility of 46% live births is considered a good result for mid-trimester emergency cerclage when the membranes are protruding. Success of the procedure remains unpredictable on the basis of the maternal features investigated.

Adult↗

Carbohydrate metabolism in gestational diabetes: effect of chronic hypertension.

OBJECTIVE: To evaluate whether the coexistence of chronic hypertension and gestational diabetes mellitus (GDM) is characterized by a greater impairment of carbohydrate metabolism than GDM alone. METHODS: Carbohydrate metabolism of eight women with chronic hypertensive GDM and 15 normotensive women with GDM was evaluated in the third trimester using the oral glucose tolerance test (GTT) and hyperinsulinemic-euglycemic clamp technique. Controls were ten normotensive, glucose-tolerant, pregnant women in the third trimester. RESULTS: Insulin sensitivity of women with chronic hypertension and GDM was approximately twofold lower than those with GDM only (1.54+/-0.35 versus 4.15+/-0.31, P < .001) and approximately fivefold lower than controls (1.54+/-0.35 versus 7.65+/-0.66, P < .001). Women with chronic hypertension and concomitant GDM had higher insulin levels in response to GTT than controls (P < .001 repeated measures analysis of variance). In all subjects, mean arterial pressure (MAP) had a strong negative correlation with maternal insulin sensitivity (r = -0.62, P < .001). Significant correlation was also found between percent of body fat and insulin sensitivity (r = -0.53, P < .002). Those regressions were still significant when adjusted for percent of body fat and MAP. CONCLUSION: Gravidas with chronic hypertension and GDM are more insulin resistant than those with GDM alone. Blood pressure, in a population of pregnant women with normal and abnormal carbohydrate metabolism, is a stronger predictor of insulin resistance than adiposity.

Adult↗

Gestational hypertension but not pre-eclampsia is associated with insulin resistance syndrome characteristics.

The aim of this study was to assess whether the metabolic characteristics of insulin resistance syndrome are present in pre-eclamptic (PE), gestational (GH) and chronic hypertensive (CH) pregnancies. Glucose and insulin serum concentrations, both fasting and after oral administration of a glucose tolerance test, were evaluated in 26 hypertensive pregnant women (10 PE, 10 GH and six CH patients) and in 10 healthy controls during the third trimester of gestation. Insulin sensitivity was assessed using the hyperinsulinaemic-euglycaemic clamp technique. The plasma concentrations of triglyceride (TG), high density (HDL), low density (LDL), and very low density (VLDL) lipoprotein cholesterol, apolipoproteins AI and B, and non-esterified fatty acid (NEFA) were also measured. Women with GH exhibited approximately 40% lower steady-state insulin sensitivity index (ISI) compared to controls (3.75 versus 6.34, P < 0.03), as well as approximately 33% higher mean plasma TG (3.57 versus 2.68 mmol/l, P < 0.01), and approximately 69% higher mean NEFA (0.59 versus 0.35 mmol/l, P < 0.01). Women with PE showed similar ISI but reduced insulin and glucose areas under curve compared to controls (P < 0.006, P < 0.0005 respectively). Women with PE also had higher HDL-cholesterol and apo-AI than controls. Patients with CH had similar lipid and carbohydrate metabolism to control subjects. In conclusion, women with GH exhibit metabolic features similar to those of patients with insulin resistance syndrome, suggesting that similar abnormalities could be involved in the pathogenesis of these disorders. In contrast, our data do not support an association between insulin resistance syndrome and hypertension in pregnant women with PE and chronic hypertension.

Adult↗

Low-molecular weight heparin restores in-vitro trophoblast invasiveness and differentiation in presence of immunoglobulin G fractions obtained from patients with antiphospholipid syndrome.

The present study was designed to investigate the effects of immunoglobulin G obtained from patients with antiphospholipid syndrome (APS) on in-vitro models of trophoblast invasiveness and differentiation. We tested the binding of affinity-purified immunoglobulin G to human primary trophoblast cells. These antibodies affected the invasiveness and differentiation of cytotrophoblast cells after binding to the cell surface. In addition, we determined whether the drugs used to treat APS might be able to restore the trophoblast functions. Low-molecular weight heparin, in a dose-dependent manner, significantly reduced the immunoglobulin G binding to trophoblast cells and restored in-vitro placental invasiveness and differentiation. No effect was observed in the presence of acetylsalicylic acid. These observations may help in understanding the role of these treatments in women with APS.

Adult↗

Effect of maternal carbohydrate metabolism on fetal growth.

OBJECTIVE: To determine the effect of maternal carbohydrate metabolism and anthropometric characteristics on fetal growth. METHODS: Eight pregnant women in the third trimester with unexplained fetal growth restriction (FGR) and 11 women with normal pregnancies in the third trimester were evaluated for maternal carbohydrate metabolism, using oral glucose tolerance tests and hyperinsulinemic-euglycemic clamps. These data and maternal anthropometric characteristics subsequently were related to relative birth weight, defined as observed birth weight x 100/50th percentile birth weight. RESULTS: The women with FGR pregnancies were more insulin sensitive than were controls (21.6+/-4.4 versus 16.7+/-4.8 micromol/kg x min, P < .05) and showed reduced insulin and glucose areas under the curve (96,293+/-25,870 versus 145,291+/-49,356 pmol/L, P < .03; 1057.0+/-184.7 versus 1210.1 +/-85.9 mmol/L, P < .05, respectively). No differences were seen in fasting plasma glucose, insulin and human placental lactogen samples, age, height, pregravid weight, weight gain, and parity. In all patients, maternal insulin sensitivity and weight gain correlated well with relative birth weight (r =-.65, P < .002; r=.68, P < .001, respectively). When the same analysis was computed separately in the groups, insulin sensitivity exhibited a strong negative correlation with relative birth weight in the FGR group but not in controls (r=-.84, P < .007; r=-.54, P=.08, respectively). Conversely, in control women the best correlation between relative birth weight and the other variables studied was seen with maternal weight gain (r=.82, P < .002). CONCLUSION: Women with unexplained FGR have a different glucose metabolic pattern than do normals. We speculate that increased insulin sensitivity leads to a reduction in metabolic substrates for fetal growth.

Adult↗

Endocrino-metabolic features in women with polycystic ovary syndrome during pregnancy.

To elucidate the mechanism of metabolic adaptation of women with polycystic ovary syndrome (PCOS) during pregnancy, the endocrino-metabolic features of a group of PCOS patients with or without gestational diabetes were studied longitudinally during the three trimesters of gestation. Oral glucose tolerance test (OGTT, 100 g) and hyperinsulinaemic-euglycaemic clamp were performed throughout the study. Plasma concentrations of insulin and glucose were determined by radioimmunoassay and glucose oxidase technique, respectively. Five of 13 PCOS patients developed gestational diabetes (GD) at the third trimester (PCOS-GD), while the other eight patients did not develop any alteration of glucose metabolism (PCOS-nGD). Both fasting glucose and insulin plasma concentrations did not change significantly during pregnancy and no difference was seen between the two groups. On the contrary PCOS-GD group early exhibited higher values of area under the curve (AUC) for glucose and insulin response to OGTT with respect to those found in PCOS-nGD group. This difference was already significant in the first gestational trimester. Moreover insulin sensitivity value (M) was significantly lower in the first trimester of gestation in PCOS-GD as compared with that found in PCOS-nGD group. However, as gestation proceeded, M value decreased in PCOS-nDG group and the difference from PCOS patients developing gestational diabetes was not sustained into the second and third trimesters. Both groups had similar body mass index values and AUC insulin increase from first to third trimester of gestation. It is concluded that early alteration of insulin sensitivity and secretion constitute specific risk factors in PCOS patients for the development of abnormalities of glucose tolerance.

Adult↗

Heparin and low-dose aspirin restore placental human chorionic gonadotrophin secretion abolished by antiphospholipid antibody-containing sera.

This study was conducted to determine whether drugs used for conventional treatments of pregnant women with antiphosholipid syndrome might be able to restore the gonadotrophin-releasing hormone (GnRH)-induced secretion of placental human chorionic gonadotrophin (HCG) in vitro. We tested this hypothesis using a modified enzyme-linked immunosorbent assay (ELISA) and an in-vitro placental culture system. Pharmacological dose of low molecular weight heparin (20 IU/ml) significantly (P < 0.02) reduced the antiphospholipid antibody (aPL) binding in the ELISA and was able to restore GnRH-induced HCG secretion (P < 0.05) in presence of aPL-containing sera. Low-dose aspirin (0.03 M) did not modify aPL binding in the ELISA, but partially restored HCG secretion (P < 0.05). These observations may help to explain the role of these treatments in antiphospholipid syndrome.

Anti-Inflammatory Agents↗

Chronic hypertension in pregnancy: color Doppler investigation of uterine arteries as a predictive test for superimposed preeclampsia and adverse perinatal outcome.

To determine if uterine artery Doppler velocimetry is useful in identifying chronic hypertensive pregnancies at risk for superimposed preeclampsia and adverse perinatal outcome. Resistance index (RI) was assessed by color velocimetry at the level of uterine arteries at 23-24 weeks of gestation in 42 women with chronic hypertension. The "lowest", the "highest" and the "average" values were compared to select the most predictive index for superimposed preeclampsia, intrauterine growth retardation (IUGR), birth weight lower than 2500 g and gestational age at delivery less than 36 weeks. Nine patients developed superimposed preeclampsia (21%) and 15 delivered before the 36th week of gestation (36%); 4 babies were IUGR (10%) and in 18 cases birth weights were below 2500 g (43%). Statistical analysis of Doppler findings showed that abnormal values of "lowest RI" were significantly correlated with adverse pregnancy outcome. Color Doppler analysis of uterine arteries is able to select chronic hypertensive pregnant women at risk of superimposed preeclampsia and poor perinatal outcome.

Adult↗

Term and postterm low-risk pregnancies: management schemes for the reduction of high rates of cesarean section.

BACKGROUND: We compare trends and current levels of cesarean section delivery by indication in some industrialized countries to help us understand factors underlying national differences in obstetric delivery practice and identify pathways to lower cesarean rates. STUDY DESIGN: In this report we describe the schemes employed at our Department for the management of low-risk at term and postterm pregnancies and list the most important motivations for increased cesarean section rate and remedies suggested to reduce high cesarean section rate. Moreover a randomized trial to assess the role of labor induction with PGE2 gel vs i.v. Oxytocin+Amniotomy in the management of prolonged pregnancy is being evaluated presently at our center. METHODS: To date, 75 postterm pregnancies have been followed. Patients are enrolled at > or = 287 days (41 weeks). Intracervical PGE2 gel (0.5 mg) is used for cervical ripening. Induction of labor is randomly performed using intravaginal PGE2 gel (2 mg) or i.v. Oxytocin+Amniotomy. RESULTS: Overall rates of 75% for spontaneous delivery, and 25% for cesarean section have been observed in our study group of prolonged pregnancies. CONCLUSIONS: The accurate labelling of low- and high-risk pregnancy and the appropriate management of term and postterm pregnancy are two important steps for the reduction of a high rate of cesarean section.

Adolescent↗