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Biomedical subjects

S Mancuso

Publications and source records attributed to S Mancuso.

At least 199 records · Page 11Linked to original sources
PubMed1996

Effect of follicular fluid on granulosa luteal cells from polycystic ovary.

Recent data suggest that follicular fluid may play an important role in the endocrine balance of polycystic ovary syndrome, probably by acting on the theca-granulosa cell relationship. The aim of this study was to evaluate the effect of steroid-free follicular fluid on steroidal response and cell proliferation of human granulosa luteal cells from polycystic (POGC) and normal ovary (NC). Granulosa cells (from both POGC and NC) were cultured for 48 h with or without increasing dilutions of follicular fluid (FF) obtained from polycystic (FFp) and normo-ovulating (FFc) patients. Both follicular fluids were able to elicit aromatase activity as well as progesterone production and thymidine incorporation. POGC, when incubated with FFp, showed a lower increase of aromatase activity and progesterone production with respect to NC. Furthermore, the proliferation rate was increased by incubation with either follicular fluid, but the increase was less with FFp compared to FFc. Aromatase/[3H]thymidine (A/T) and progesterone/ [3H]thymidine (P/T) ratios could be considered to be representative of the contribution of the single cell unit to steroidogenesis. Using high concentrations of either follicular fluids, POGC showed a higher A/T ratio compared with NC. Moreover, the same treatment strongly decreased P/T ration in POGC, while it was ineffective in NC. Our study show that an abnormal interaction between POGC and their own follicular fluid can be implicated in the pathogenesis of the altered steroidal response in these cells, and that in particular it could affect the proliferation rate.

Adult↗
PubMed1996

Preconceptional and gestational evaluation of insulin secretion in patients with polycystic ovary syndrome.

The relationship between insulinaemia and obesity and glucose tolerance and the impact of pregnancy as risk factor for carbohydrate abnormalities were investigated in 91 consecutive patients with polycystic ovary syndrome (PCOS) aged 26-32 years. Fifteen normoglycaemic patients became pregnant within 6 months of the pregestational study using pharmacological induction of ovulation. Plasma concentrations of insulin and glucose after an oral glucose tolerance test (OGTT) were determined by immunoradiometric assay and glucose oxidase technique respectively. OGTT patients were classified according to their response as normoinsulinaemic (n = 46) or hyperinsulinaemic (n = 45). Impairment of glucose metabolism occurred in 12.1% (n = 11, 10 obese and one lean) of all PCOS subjects. Based on insulin secretion, 6.5% of normoinsulinaemic and 13.3% of hyperinsulinaemic patients had an impaired glucose tolerance and 2.3 and 2.2% respectively a non-insulin-dependent diabetes mellitus. Obese patients had higher values for area under the curve for insulin response to OGTT (I-AUC values) than lean patients, and the percentage above ideal body weight was greater in hyperinsulinaemic than in normoinsulinaemic patients. All hyperinsulinaemic (7/15) subjects who became pregnant developed an impairment of glucose metabolism during pregnancy. It is concluded that the PCOS population was at higher risk of developing carbohydrate abnormalities than the normal population of a similar reproductive age. Furthermore, those with abnormal insulin secretion at the pregestational stage may, during pregnancy, develop an impaired gestational glucose tolerance or gestational diabetes.

Adult↗
PubMed1996

Influence of growth factors on proliferation and morphogenesis of rabbit ovarian mesothelial cells in vitro.

The ovarian mesothelium (OM) is the source of one of the most frequent and lethal types of common ovarian epithelial tumors, the so-called papillary serous carcinomas. Recent work from our laboratory indicates the existence of postovulatory luteal OM mitogens with variable affinity for heparin. To further investigate the paracrine regulation of this ovarian tissue, rabbit ovarian mesothelial cells (OMC) were cultured in serum-free, fibronectin-rich HL-1 medium with or without one of the following luteal growth factors (0.1, 1, and 10 ng/ml): basic (bFGF) and acidic (aFGF) fibroblastic growth factors, epidermal growth factor (EGF), transforming growth factors alpha (TGF alpha) and beta (TGF beta), tumor necrosis factor alpha, platelet-derived growth factor (PDGF-BB), and vascular endothelial growth factor. After 8 days of culture, OMC growth was stimulated 3-fold by all tested doses of bFGF, EGF, and TGF alpha and 2-2.5-fold by 10 ng/ml of PDGF-BB and aFGF; it was inhibited more than 60% by TGF beta (10 ng/ml). In addition to enhancing the formation of cohesive OMC monolayers, most factors enhanced 3- to 6-fold the aggregation of OMC into papillary processes. The finding of a growth and morphogenetic response to intraluteal growth factors is novel and suggests a role for postovulatory paracrine regulation of OM pathobiology.

Animals↗
PubMed1996

Distal fallopian tube occlusion: false diagnosis with hysterosalpingography in cases of tubal diverticula.

PURPOSE: To evaluate the accuracy of hysterosalpingography (HSG) in the diagnosis of distal fallopian tube occlusion in infertile patients who were candidates for laparoscopic surgery. MATERIALS AND METHODS: A retrospective review of charts was performed for 25 patients who were scheduled to undergo laparoscopic surgery. A preoperative diagnosis was made at HSG of bilateral (or unilateral in case of previous contralateral salpingectomy) distal tube occlusion. RESULTS: At laparoscopy, in three patients (12%) who were scheduled for salpingostomy, the diagnosis of distal tube occlusion made at HSG was incorrectly positive; in the three patients, a single tubal diverticulum was present in the distal ampulla in otherwise normal, patent tubes. CONCLUSION: Bilateral tubal diverticula appear to be often misdiagnosed at HSG as distal tube occlusion.

Adult↗
PubMed1996

Laparoscopically assisted vaginal hysterectomy as an alternative to abdominal hysterectomy. A pilot study.

Laparoscopically assisted vaginal hysterectomy (LAVH) allows for conversion of some abdominal hysterectomies to a vaginal route. LAVH may be particularly useful when adnexectomy is indicated. In this study the authors evaluate the results obtained in a series of 21 patients prospectively selected for LAVH. The mean operative time was 96 min (range 58-155), with an estimated blood loss of 218 ml (range 50-510). The mean uterine weight was 320 g (range 105-610). Intraoperative complications were limited to one case of bladder injury which occurred during the vaginal phase of the procedure. No patient required heterologous blood transfusion. No postoperative complications were observed. The average length of hospitalisation was 4.4 days (range 2-9). The authors conclude that LAVH allows for conversion of a significant number of abdominal hysterectomies to a vaginal route and that with respect to the former it is definitely less costly since it allows for earlier hospital discharge and resumal of a normal lifestyle.

Endometriosis↗
PubMed1996

Use of fibrin sealant for reproductive surgery: a randomized study in the rabbit model.

The present study was undertaken to compare adhesion formation and reproductive outcome after reproductive surgery with or without the application of fibrin sealant. At laparotomy, the ovaries and uterine horns of 20 rabbits were longitudinally incised on the antimesenteric side using a monopolar microneedle. At random, one ovary and the ipsilateral uterine horn were covered with fibrin sealant, while those on the contralateral side were left uncovered without application of sutures. The rabbits were then mated, and 2 weeks later a second-look laparotomy was performed by a blinded observer. No statistically significant differences were found in postoperative adhesions, number of corpora lutea in each ovary, number of embryos in the ipsilateral uterine horn, and nidation index for each side. Fibrin sealant for conservative surgery does not appear to significantly affect either postoperative adhesion formation or reproductive outcome.

Animals↗
PubMed1996

nm23 in ovarian cancer: correlation with clinical outcome and other clinicopathologic and biochemical prognostic parameters.

PURPOSE: The aim of the study was to define the prognostic role of the metastasis suppressor gene, nm23, in 106 primary ovarian cancer patients. PATIENTS AND METHODS: Northern and Western blotting analysis of nm23-H1 and nm23-H2 expression were performed in a subset of ovarian tumors. Immunohistochemical analysis was performed on formalin-fixed paraffin-embedded specimens from 106 primary ovarian carcinomas by the antihuman nm23 monoclonal antibody. RESULTS: Northern and Western blotting analysis demonstrated a direct association between nm23-H1 and nm23-H2 levels. Moreover, an overall concordance of 86.7% between Northern blotting and immunohistochemical data was observed. Sixty-six specimens (68%) showed a positive nm23-H1 immunoreaction. The percentage of nm23-H1 positivity was higher in lymph node-negative (70%) than in lymph node-positive cases (44%) (P = .049). Moreover, the percentage of complete/partial responses to chemotherapy was higher in nm23-H1-positive (69%) than in nm23-H1-negative (44%) patients (P = .03). The percentage of epidermal growth factor receptor (EGFR) positive cases was lower in nm23-H1-positive (44%) than in nm23-H1-negative immunostained (72%) samples (P = .012). Lower ras/p21 levels (median, 1.77 absorbance units) were found in nm23-H1-positive than in nm23-H1-negative samples (median, 2.63 absorbance units) (P = .03). The 6-year progression-free survival (PFS) rate of nm23-H1-positive cases was 50% (95% confidence interval [CI], 33 to 67) versus 12% (95% CI, -2 to 26) for nm23-H1-negative patients (P = .0056). In multivariate analysis, only stage, ascites, and nm23-H1 content retained independent prognostic roles. CONCLUSION: The assessment of nm23 content may provide useful information for prognostic characterization of ovarian cancer patients.

Blotting, Northern↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

[The use of hyperimmune anti-cytomegalovirus immunoglobulins in HIV infection].

Cytomegalovirus (CMV) is one of the most frequent opportunistic agents that affects HIV positive subjects. The prophylaxis and treatment of cytomegalovirus infection in HIV positive subjects represent difficult and controversial problems. In this study we evaluated efficacy of anti-CMV immunoglobulins (derived from plasma with a high titer of CMV anti-bodies) in primary and in secondary prophylaxis for CMV disease in adults with severe immunodeficiency caused by HIV infection. For primary prophylaxis, in 22 patients with CD4 < 200/mmc enrolled to receive a monthly infusion of intravenous immunoglobulins (IVIG) at 200 mg/kg we observed prophylactic effect for the prevention of CMV and bacterial infections. Concerning secondary prophylaxis, 7 patients with CMV manifestation treated after remission with anti-CMV IVIG at 200 mg/kg every two weeks, had a low frequency of relapse and a good clinical outcome. Because their tolerability, anti-CMV immunoglobulins are an interesting option particularly for the prevention of CMV and bacterial infection in HIV-positive adults in advanced stages of disease.

AIDS-Related Opportunistic Infections↗
PubMed1996

Evidence of a disturbance of the hypothalamic-pituitary-adrenal axis in polycystic ovary syndrome: effect of naloxone.

DESIGN: There are conflicting data on hypothalamic-pituitary-adrenal (HPA) axis function in women with polycystic ovary syndrome (PCOS). We have evaluated the HPA axis responses to naloxone in patients with PCOS compared to control subjects. PATIENTS: Twenty PCOS patients and 10 control women participated in the study. MEASUREMENTS: On days 5-6 of a spontaneous or progestin induced cycle each patient received an intravenous bolus (5 mg) of naloxone (time 0 min), followed by a 2-mg naloxone infusion in 100 ml of 0.9% saline over one hour. Samples were collected at -30, 0, 15, 30, 60, 90 and 120 minutes. ACTH and cortisol levels were measured in all plasma samples. RESULTS: PCOS patients showed significantly greater response than controls to naloxone of ACTH (peak value 261 vs 172% of basal value) and cortisol (peak value 237 vs 165% of basal value); also, ACTH and cortisol incremental areas were higher in PCOS patients (P < 0.05 and P < 0.04 respectively). The cortisol/ACTH ratio of AUCs percentage increase was found to be near unity for all patients without significant difference between PCOS and control groups, suggesting a direct correspondence between ACTH circulating levels and adrenal cortisol production. CONCLUSIONS: Polycystic ovary syndrome patients showed a hypothalamic-pituitary-adrenal axis hyper-responsiveness to naloxone infusion compared with control subjects. These data support the hypothesis that this disturbance could be central in origin.

Adolescent↗
PubMed1996

Operative laparoscopy for ovarian cysts. Excision vs. aspiration.

OBJECTIVE: To evaluate operative laparoscopy for excision vs. aspiration of ovarian cysts. STUDY DESIGN: From July 1, 1990, to June 30, 1993, 100 women under 40 years of age were subjected by the senior author to laparoscopic cyst excision, and 31 patients with similar characteristics underwent laparoscopic cyst aspiration by their attending physicians. Four-puncture laparoscopy was performed for laparoscopic cyst excision using the stripping technique, whereas two-puncture laparoscopy was employed for laparoscopic cyst aspiration. All patients underwent postoperative serial clinical examinations and ultrasound scans for the detection of recurrence. RESULTS: Four recurrences (4%) were observed in the group that underwent laparoscopic cyst excision, whereas 26 (84%) recurrences occurred in the group that underwent laparoscopic cyst aspiration (P < .0001). CONCLUSION: Provided that patients are carefully selected according to age and sonographic pattern, enucleation of adnexal masses at operative laparoscopy is the treatment of choice.

Adolescent↗
PubMed1995

Methyl-p-hydroxyphenyllactate-esterase activity and type-II estrogen-binding sites in ovarian cancer: correlation with biological and clinico-pathological parameters.

We examined the levels of activity of methyl-p-hydroxyphenyllactate esterase (MeHPLA-ase) and cytosolic Type-II-estrogen-binding sites (Type-II EBS) in 61 and 71 cases, respectively, of primary ovarian cancer. MeHPLA-ase activity and Type-II EBS were seen to by asymmetrically distributed, in that levels were skewed towards the lower values. A statistically significant direct correlation was found between MeHPLA-ase activity and Type-II EBS. MeHPLA-ase activity and Type-II EBS were inversely correlated with ER and PR levels and showed a trend towards inverse correlation with the percentage of cells in S-phase of the cell cycle. MeHPLA-ase activity and Type-II EBS did not correlate with clinico-pathological parameters. The median MeHPLA-ase activity tended to be higher in responders than in unresponsive patients, but statistical significance was not reached. Higher Type-II-EBS levels were found in cases showing complete and partial response to chemotherapy than in cases which did not respond. A statistically significant relationship was found between high MeHPLA-ase activity and longer overall survival.

Carboxylic Ester Hydrolases↗
PubMed1995

Interaction of tamoxifen with cytosolic and nuclear type II estrogen binding sites (type II EBS).

The aim of this study was to investigate the interaction of tamoxifen (TAM) with the so-called Type II estrogen binding sites (Type II EBS) in both the cytosolic and the nuclear fraction of the ER-negative A 2780 human ovarian cancer cell line and in an ER-negative ovarian cancer tissue. Although cytosolic and nuclear Type II EBS in A 2780 cells showed substantially similar binding characteristics in terms of ligand affinity and specificity, TAM, while exhibiting the ability to displace [3H]estradiol from cytosolic Type II EBS failed to interact with nuclear Type II EBS. The ability of TAM to interact only with cytosolic Type II EBS seems also to be a characteristic of ovarian cancer tissue and to be shared by several TAM metabolites. The hypothesis that the interaction of TAM with cytosolic Type II EBS could mobilize the true endogenous ligand of Type II EBS which would become available for binding to nuclear Type II EBS was tested by incubating the nuclear fraction with the cytosolic fraction. In the presence of cytosol, TAM acquires the ability to displace the tracer from nuclear Type II EBS but when the cytosolic fraction was DCC, stripped in order to remove the endogenous ligand, the competing activity of TAM for nuclear Type II EBS was abolished. Our results suggest that TAM does not interact with nuclear Type II EBS, but can favor the nuclear binding of endogenous ligand by displacing it from cytosolic Type II EBS.

Binding Sites↗
PubMed1995

Molecular alterations of the AKT2 oncogene in ovarian and breast carcinomas.

The AKT2 gene is one of the human homologues of v-akt, the transduced oncogene of the AKT8 virus, which induces lymphomas in mice. In previous studies, AKT2, which codes for a serine-threonine protein kinase, was shown to be amplified and overexpressed in some human ovarian carcinoma cell lines and amplified in primary tumors of the ovary. To confirm and extend these findings, we conducted a large-scale, multicenter study of AKT2 alterations in ovarian and breast cancer. Southern-blot analysis demonstrated AKT2 amplification in 16 of 132 (12.1%) ovarian carcinomas and in 3 of 106 (2.8%) breast carcinomas. No AKT2 alteration was detected in 24 benign or borderline tumors. Northern-blot analysis revealed overexpression of AKT2 in 3 of 25 fresh ovarian carcinomas which were negative for AKT2 amplification. The difference in the incidence of AKT2 alterations in ovarian and breast cancer suggests a specific role for this gene in ovarian oncogenesis. No significant association was found between AKT2 amplification and amplification of the proto-oncogenes MYC and ERBB2, suggesting that amplification of AKT2 defines an independent subset of breast and ovarian cancers. Ovarian cancer patients with AKT2 alterations appear to have a poor prognosis. Amplification of AKT2 was especially frequent in undifferentiated tumors (4 of 8, p = 0.019), suggesting that AKT2 alterations may be associated with tumor aggressiveness.

Adenocarcinoma↗
PubMed1995

Growth hormone-releasing factor stimulates meiotic maturation in follicle- and cumulus-enclosed rat oocyte.

This study was designed in order to assess the possible role of growth hormone-releasing factor (GRF) on oocyte maturation. This effect was analyzed in follicle-enclosed, cumulus-enclosed and denuded oocytes obtained from immature pregnant mare's serum gonadotropin-treated rats. The addition of GRF to the cultures significantly accelerated maturation in follicle- and cumulus-enclosed oocytes while no effect was seen on denuded oocytes. Also, the neuropeptide was able to induce maturation in follicle-enclosed oocytes obtained from immature untreated rats. The GRF action was probably not mediated by the vasoactive intestinal peptide (VIP) receptors since the two hormones had different effects on oocyte maturation and on cAMP production by granulosa cells. In addition the disappearance of the GRF effect observed in the presence of antibodies anti-GH suggested that GRF required the intermediacy of GH to accomplish its effect on oocyte maturation. Finally, GRF did not affect meiotic maturation when dbcAMP was added to the cultures. Our results demonstrate the ability of GRF to accelerate maturation in oocytes from both primed and unprimed rats. Since the presence and the involvement of GRF at the ovarian levels is now well established, the present data strongly suggest an important potential role of GRF in the ovarian physiology.

Animals↗
PubMed1995

Bisdioxopiperazine, (+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane (ICRF 187), enhances the antiproliferative effect of cisplatin on human ovarian cancer cells.

The bisdioxopiperazine ICRF 187 is a potent intracellular chelating agent which effectively diminishes Adriamycin cardiotoxicity without compromising its antitumor activity. Our study aimed at verifying whether ICRF 187 can modulate the cytotoxic action of cisplatin (CDDP) on ovarian cancer cells. We used the A2780 ovarian cancer cell line and a subline resistant to CDDP (A2780-CDDP) obtained in our laboratory by continuous exposure of the parenatal cells to progressively increasing CDDP doses. In both cell lines ICRF 187 (0.1-0.5 microgram/ml) used in combination with CDDP (0.01-1 microgram/ml) produced a dose-dependent reduction of CDDP IC50 (the concentration inhibiting 50% of cell growth). Moreover, when ICRF 187 was used in combination with CDDP, analysis of the data by the isobole method showed that the combination of the two drugs produced a synergistic antiproliferative activity in both cell lines, with a CDDP potentiation up to fivefold. Our in vitro data show that ICRF 187 can synergize with CDDP. Prospective clinical trials are now needed to verify whether the addition of ICRF 187 to CDDP-containing regimens will result in an improved clinical response in ovarian cancer.

Antineoplastic Agents↗