Giampiero Capobianco

Efficacy of low-dose intravaginal estriol on urogenital aging in postmenopausal women

Objective To assess the efficacy and safety of intravaginal estriol administration on urinary incontinence, urogenital atrophy, and recurrent urinary tract infections in postmenopausal women. Design Eighty-eight postmenopausal women with urogenital aging symptoms were enrolled in this prospective, randomized, placebo-controlled study. Participants were randomly divided into two groups, with each group consisting of 44 women. Women in the treatment group received intravaginal estriol ovules: 1 ovule (1 mg) once daily for 2 weeks and then 2 ovules once weekly for a total of 6 months as maintenance therapy. Women in the control group received inert placebo vaginal suppositories in a similar regimen. We evaluated urogenital symptomatology, urine cultures, colposcopic findings, urethral cytologic findings, urethral pressure profiles, and urethrocystometry before as well as after 6 months of treatment. Results After therapy, the symptoms and signs of urogenital atrophy significantly improved in the treatment group in comparison with the control group. Thirty (68%) of the treated participants, and only seven (16%) of the control participants registered a subjective improvement of their incontinence. In the treated participants, we observed significant improvements of colposcopic findings, and there were statistically significant increases in mean maximum urethral pressure, in mean urethral closure pressure as well as in the abdominal pressure transmission ratio to the proximal urethra. Urethrocystometry showed positive but not statistically significant modifications. Conclusions Our results show that intravaginal administration of estriol may represent a satisfactory therapeutic choice for those postmenopausal women with urogenital tract disturbances who have contraindications or refuse to undergo standard hormone therapy.

Postpartum ovarian vein thrombosis: an unpredictable event: two case reports and review of the literature

Abstract. Ovarian vein thrombosis (OVT) is a rare but serious postpartum complication that, in most cases, occurs in the right ovarian vein. Certain diagnosis, following clinical suspect because of lower quadrant tenderness and fever that alone does not respond to adequate broad-spectrum antibiotics, is now based on computed tomography (CT), although other imaging techniques, such as color Doppler ultrasonography and magnetic resonance (MR) imaging, are useful. Heparin and intravenous antibiotics are the mainstay of treatment so as to avoid laparotomy. We report on the management of two cases of postpartum OVT.

Update on Raloxifene: Mechanism of Action, Clinical Efficacy, Adverse Effects, and Contraindications

Raloxifene is the only selective estrogen receptor modulator approved for long-term treatment in the prevention of osteoporotic fractures and for the reduction of invasive breast cancer risk in postmenopausal women. The demonstrated beneficial effects on bone and mammalian tissue led clinical and molecular research to focus mainly on these organs, giving less attention to all other systemic effects. The aim of this review was to evaluate all described systemic effects of raloxifene, investigating its molecular and tissutal mechanism of action. A literature research was carried out in electronic databases MEDLINE, EMBASE, ScienceDirect, and the Cochrane Library in interval time between 2000 and 2012. Outcomes were considered in relation to positive/adverse effects concerning bone metabolism, lipid metabolism, coagulation pattern, menopausal symptoms, breast cancer onset, and endometrial cancer onset. Raloxifene acts as an estrogen agonist or antagonist depending on the tissue. This feature is related to specific actions on at least 2 distinct estrogen receptors, whose proportions vary according to tissue type. Raloxifene is a drug for the treatment of osteoporosis and for the prevention of estrogen receptor–positive breast cancer because it guarantees a safety profile on the endometrium. Raloxifene is furthermore an effective therapy in women with increased levels of plasma cholesterol. Raloxifene treatment shifts the coagulation pattern toward prothrombosis, and the patients should be exhaustively informed about the risks associated with therapy. Raloxifene does not show to affect memory and cognition. Finally, it is noteworthy that quality-of-life studies demonstrated some favorable effects of raloxifene. Target Audience: Obstetricians and gynecologists, family physicians Learning Objectives: After completing this CME activity, physicians should be better able to identify the mechanism of action of raloxifene, treat the adverse effects of raloxifene, prescribe raloxifene for patients with osteoporosis, to prevent estrogen receptor–positive breast cancer, as effective therapy in women with osteoporosis and concomitant increased levels of plasma cholesterol, and select the appropriate patients for raloxifene treatment using the patient’s medical history and risk of thromboembolism.

Akt downregulation by flavin oxidase–induced ROS generation mediates dose-dependent endothelial cell damage elicited by natural antioxidants

High intake of natural antioxidants (NA) from plant-derived foods and beverages is thought to provide cardiovascular benefits. The endothelium plays a pivotal role in cardiovascular homeostasis, and for this reason, the molecular events resulting from NA actions on endothelial cells (ECs) are actively investigated. Here, we show the direct impact of two NA, coumaric acid and resveratrol, on intracellular reactive oxygen species levels, protein carbonylation, and cell physiology in human ECs. While at lower doses, both NA promoted antioxidant effects, at moderately high doses, NA elicited a dose-dependent pro-oxidant effect, which was followed by apoptosis, cell damage, and phospho-Akt downregulation. NA-induced pro-oxidant effects were counteracted by N-acetyl cysteine and diphenyleneiodonium (DPI), suggesting a role for flavin oxidases in NA-induced toxicity. DPI also prevented NA-induced phospho-Akt downregulation indicating that Akt can work downstream of flavin oxidases in mediating cellular responses to NA. Stimulation of phospho-Akt by insulin dramatically counteracted NA-induced cell death, an effect abolished by Akt inhibition further suggesting that mechanistically Akt regulates cell survival in response to NA-induced stress. Although further studies are required to better characterize the molecular mechanism of NA-induced cell toxicity, our study is the first to show in a human vascular model that moderately high doses of NA can induce cell damage mediated by flavoproteins and the Akt pathway.

Determining the best catheter for sonohysterography

OBJECTIVE To compare the characteristics of six different catheters for performing sonohysterography (SHG) to identify those that offer the best compromise between reliability, tolerability, and cost. DESIGN Prospective study. SETTING University hospital. PATIENT(S) Six hundred ten women undergoing SHG. INTERVENTION(S) We performed SHG with six different types of catheters: Foleycath (Wembley Rubber Products, Sepang, Malaysia), Hysca Hysterosalpingography Catheter (GTA International Medical Devices S.A., La Caleta D.N., Dominican Republic), H/S Catheter Set (Ackrad Laboratories, Cranford, NJ), PBN Balloon Hystero-Salpingography Catheter (PBN Medicals, Stenloese, Denmark), ZUI-2.0 Catheter (Zinnanti Uterine Injection; BEI Medical System International, Gembloux, Belgium), and Goldstein Catheter (Cook, Spencer, IN). MAIN OUTCOME MEASURE(S) We assessed the reliability, the physicians ease of use, the time requested for the insertion of the catheter, the volume of contrast medium used, the tolerability for the patients, and the cost of the catheters. RESULT(S) In 568 (93%) correctly performed procedures, no statistically significant differences were found among the catheters. The Foleycath was the most difficult for the physician to use and required significantly more time to position correctly. The Goldstein catheter was the best tolerated by the patients. The Foleycath was the cheapest whereas the PBN Balloon was the most expensive. CONCLUSION(S) The choice of the catheter must be targeted to achieving a good balance between tolerability for the patients, efficacy, cost, and the personal preference of the operator.

A second hysterosalpingography reduces the use of selective technique for treatment of a proximal tubal obstruction

OBJECTIVE To assess whether a second hysterosalpingography (HSG) can permit tubal patency, reducing the use of selective salpingography in patients with proximal tubal obstruction. DESIGN Prospective study. SETTING University hospital. PATIENT(S) The study population consisted of 360 infertile women. INTERVENTION(S) In patients with unilateral or bilateral proximal tubal obstruction, a second HSG was performed after about 1 month. In those cases with persistent obstruction, an immediate selective salpingography and tubal catheterization were performed. MAIN OUTCOME MEASURE(S) Tubal opacification. RESULT(S) Forty patients underwent a second HSG procedure for proximal tubal occlusion. Among these, 24 achieved bilateral tubal patency. Thus, repetition of a conventional HSG after 1 month avoided unnecessary salpingography in 60% of patients. CONCLUSION(S) In infertile women with proximal tubal obstruction, we believe it is best to perform a second HSG. HSG is easy to carry out and subjects patients to a lower dosage of radiation and fewer risks than selective salpingography. The latter technique should be reserved for unsuccessful cases.

Human umbilical endothelial cells (HUVECs) have a sex: characterisation of the phenotype of male and female cells

BackgroundHuman umbilical endothelial cells (HUVECs) are widely used to study the endothelial physiology and pathology that might be involved in sex and gender differences detected at the cardiovascular level. This study evaluated whether HUVECs are sexually dimorphic in their morphological, proliferative and migratory properties and in the gene and protein expression of oestrogen and androgen receptors and nitric oxide synthase 3 (NOS3). Moreover, because autophagy is influenced by sex, its degree was analysed in male and female HUVECs (MHUVECs and FHUVECs).MethodsUmbilical cords from healthy, normal weight male and female neonates born to healthy non-obese and non-smoking women were studied. HUVEC morphology was analysed by electron microscopy, and their function was investigated by proliferation, viability, wound healing and chemotaxis assays. Gene and protein expression for oestrogen and androgen receptors and for NOS3 were evaluated by real-time PCR and Western blotting, respectively, and the expression of the primary molecules involved in autophagy regulation [protein kinase B (Akt), mammalian target of rapamycin (mTOR), beclin-1 and microtubule-associated protein 1 light chain 3 (LC3)] were detected by Western blotting.ResultsCell proliferation, migration NOS3 mRNA and protein expression were significantly higher in FHUVECs than in MHUVECs. Conversely, beclin-1 and the LC3-II/LC3-I ratio were higher in MHUVECs than in FHUVECs, indicating that male cells are more autophagic than female cells. The expression of oestrogen and androgen receptor genes and proteins, the protein expression of Akt and mTOR and cellular size and shape were not influenced by sex. Body weights of male and female neonates were not significantly different, but the weight of male babies positively correlated with the weight of the mother, suggesting that the mother’s weight may exert a different influence on male and female babies.ConclusionsThe results indicate that sex differences exist in prenatal life and are parameter-specific, suggesting that HUVECs of both sexes should be used as an in vitro model to increase the quality and the translational value of research. The sex differences observed in HUVECs could be relevant in explaining the diseases of adulthood because endothelial dysfunction has a crucial role in the pathogenesis of cardiovascular diseases, diabetes mellitus, neurodegeneration and immune disease.

Plasma levels of C-reactive protein, leptin and glycosaminoglycans during spontaneous menstrual cycle: differences between ovulatory and anovulatory cycles.

PurposeTo assess the plasma levels of the inflammatory markers such as C-reactive protein (CRP), leptin, and glycosaminoglycans (GAGs) during the menstrual cycle.MethodsEighteen healthy volunteers were divided into two groups according to the presence of ovulatory or anovulatory menstrual cycles. Blood samples were collected at different time points: at the menstrual phase (days 2–3), periovulatory phase (days 12–13), and luteal phase (days 23–24). CRP and leptin concentrations were measured by enzyme immunoassay. GAGs were isolated using ion-exchange chromatography on DEAE-Sephacel and quantified as hexuronate. The structural characterization of chondroitin sulfate (CS) isomers was performed by fluorophore-assisted carbohydrate electrophoresis (FACE).ResultsIn the women with ovulatory cycles, plasma GAG levels differed significantly during menstrual cycle, with increased values at the periovulatory with respect to the menstrual phase. No significant differences in CRP and leptin concentrations were observed through the menstrual cycle in both the examined cycles, but inter-group analysis revealed significant differences of CRP and leptin levels between the ovulatory and anovulatory cycles with higher values at periovulatory phase in the ovulatory cycles.ConclusionsThere are no fluctuations of both total GAG concentration and CS isomer content during menstrual cycle in the anovulatory cycles. A significant correlation between CRP and gonadotrophins was found. There is no significant difference in CRP across the menstrual cycle among ovulatory cycles, but there is a trend toward higher CRP at the periovulatory than the other phases, consistent with the significant difference in CRP between ovulatory and anovulatory cycles at the periovulatory phase. Both the trend and the significant result suggest an elevation in CRP with ovulation. These observations provide additional evidences to the hypothesis that the ovulation is an inflammatory-like phenomenon.

Perimortem cesarean delivery 30 minutes after a laboring patient jumped from a fourth-floor window: Baby survives and is normal at age 4 years

We describe the first case of a perimortem cesarean section on a patient who committed suicide during labor by jumping from the fourth-floor window of the labor ward. The cesarean section was performed 30 minutes after the death of the woman, and a child of 3037 g was born with an Apgar score of 0 at 1 minute. Today, 4 years later, the baby is well and has no apparent neurological problems.

Routine second trimester ultrasound screening for prenatal detection of fetal malformations in Sassari University Hospital, Italy: 23 years of experience in 42,256 pregnancies.

OBJECTIVE To establish, for a determined period of time, the effectiveness of a program of ultrasound screening in detecting fetal malformations in prenatal time. To assess the sensitivity, the specificity, the positive and the negative predictive value of the ultrasound screening. To examine the trend of such indexes of diagnostic accuracy in a long time period. STUDY DESIGN The patients admitted to the study had effected at least one ultrasound examination within the second trimester of pregnancy (< or =23 gestational weeks). The examined pregnant women were 42,256 and the period of reference ranged from January 1981 to December 2004. All patients delivered in Gynecologic and Obstetric Clinic of Sassari University, Sassari, Italy. RESULTS In the considered period were reported 1050/42,256 (2.48%) cases of fetal malformations, of which 974 single and 76 multiple malformations. The cases of malformations diagnosed in prenatal period were 578/1050 (55.05%), of which 65/578 (11.24%) multiple anomalies. The overall sensitivity was 55.05% (95% confidence interval: 52-58%), with a variability from the 32.95% (cardiovascular system) to 81.05% (central nervous system) in relationship to the typology of the examined apparatus. The overall specificity was 99.88% (95% confidence interval: 98-99.9%), the predictive positive value 91.89% (95% confidence interval: 89-93%) and the negative predictive value 98.87% (95% confidence interval: 95-99%). CONCLUSION The sensitivity of the ultrasound screening undoubtedly appeared to be satisfactory. We believe that, for the examination of some apparatuses, as for the cardiovascular apparatus, with the extension of the standard examination (four-chamber view) to further plans of scanning, sensitivity could subsequently be improved.