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S Mancuso

Publications and source records attributed to S Mancuso.

At least 127 records · Page 7Linked to original sources
PubMed1998

Endothelin-1: expression and role in human corpus luteum.

PROBLEM: Several recent data suggest an involvement of endothelin (ET)-1, a powerful vasoconstrictor peptide, in reproductive function. This study was designed to investigate the presence and role of ET-1 in human corpus luteum. METHOD OF STUDY: Purified luteal cells were incubated for different times with ET-1 or ET-3 alone or associated with human chorionic gonadotropin. In another set of experiments cells were treated with ET-1 and BQ485, an ET-A receptor antagonist, or with phorbol 12-myristate-13 acetate (PMA), an activator of protein kinase C. RESULTS: ET-1 reduced both basal and human chorionic gonadotropin-induced progesterone production at all examined times, similarly PMA inhibited basal progesterone synthesis. BQ485 prevented the inhibitory effect of ET-1, while no effect was observed with ET-3. Finally, ET-1 mRNA was detected in the luteal cells. CONCLUSION: ET-1 is expressed by human luteal cells and reduces basal and human chorionic gonadotropin-induced progesterone synthesis through the ET-A receptors and the protein kinase C pathway. Conversely, ET-3 does not affect luteal steroidogenesis.

Adult↗
PubMed1998

Treatment of obstetric and gynecologic infections with meropenem: comparison with imipenem/cilastatin.

The aim of this study was to compare the clinical and bacteriologic efficacy of meropenem with imipenem/cilastatin in the treatment of obstetric and gynecologic infections. This was a controlled, multicenter, randomized study with two parallel groups and a follow-up period of up to 4 weeks. A total of 105 hospital in-patients requiring antibacterial parenteral therapy were enrolled, 52 in the meropenem group and 53 in the imipenem/cilastatin group. Both drugs were administered at 0.5 g every 8 hours, by slow intravenous infusion over 20-30 minutes; for meropenem the administration by intravenous bolus injection (over approximately 5 minutes) was allowed. The mean duration of therapy was 5 days for both treatments. At the end of treatment, all 46 evaluable patients in the meropenem treatment group had a satisfactory clinical response, while in the imipenem/cilastatin group 5/49 patients were clinical failures. The difference between the treatment groups in clinical response was statistically significant (100% vs 89.8%; p=.026). A similar result was seen in the intention-to-treat analysis (98% vs 84.6%; p=0.017). Both treatments were well tolerated, but fewer meropenem patients experienced treatment-related adverse events in comparison with imipenem/cilastatin (11.5% vs 15.1%).

Adolescent↗
PubMed1998

Involvement of ovarian steroids in the opioid-mediated reduction of insulin secretion in hyperinsulinemic patients with polycystic ovary syndrome.

To evaluate the possible involvement of ovarian steroids on the opioid-mediated disorders of insulin in patients affected by polycystic ovary syndrome (PCOS), we studied 40 PCOS women. All patients underwent an oral glucose tolerance test (OGTT; 75 g) and basal hormone assay; based on the insulin response to OGTT, 26 women were classified as hyperinsulinemic and continued the study protocol. Patients were randomly divided into three groups characterized by different treatments: group A (nine patients) was treated with GnRH analog (one ampule every 28 days for 2 months), group B (eight patients) was treated with naltrexone (an oral opioid antagonist, 50 mg/day, orally) for 8 weeks, and group C (nine patients) was treated with GnRH analog plus naltrexone for 2 months. After continuation of treatment, all patients repeated the basal study in a second hospitalization. Naltrexone treatment significantly reduced the insulin response to OGTT, whereas GnRH analogue administration did not significantly change the insulin secretion after the glucose load. The GnRH analog/ naltrexone cotreatment was not able to influence the insulin secretory pattern; in fact, the insulin area under the curve was superimposable before and after therapy. These data could lead to the hypothesis that the opioidergic regulation of insulin secretion requires a normal steroidogenic pattern, thus suggesting that ovarian steroids modulate opioid activity also at peripheric districts.

Adult↗
PubMed1998

Antiproliferative activity of colchicine analogues on MDR-positive and MDR-negative human cancer cell lines.

In this study the in vitro antitumor activity of a series of 20 colchicine analogues was tested and compared with colchicine and thiocolchicine on three different human cancer cell lines, two of which express the multidrug-resistance (MDR) phenotype. At concentrations from 1 nM to 100 microM, all compounds tested inhibited cancer cell proliferation. The IC50 values indicate that the three fluorinated analogues were the most active compounds, with a similar decreasing order of potency (IDN 5005 > IDN 5079 > IDN 5080) on the two MDR-expressing cell lines, whereas thiocolchicine was the most effective compound on the MDR-negative MDA-MB 231 cells. A strong correlation (r = 0.94; P = 0.004) was found between IC50 values obtained using the two MDR-positive cell lines. Conversely, IC50 values obtained in MDA-MB 231 cells did not show a significant correlation with MDR-positive cell lines, thereby suggesting some difference in the antiproliferative mechanism(s) of colchicine analogues. Cell cycle analysis of the most active analogues in breast cancer cells showed a relationship between cell cycle blocking activity and growth inhibition. The most active agents on the MDR-positive MCF7 ADRr cell line, after 24 h of culture, in terms of cell cycle blocking activity were the three fluorinated analogues. Interestingly, after 72 h, when the cell cycle block subsided, a consistent amount of DNA fragmentation was evident. The extent of cell cycle block, measured as the G2/G1 ratio, was significantly correlated with the apoptosis rate expressed as a percentage of DNA fragmentation on both cell lines, thereby suggesting that a large number of blocked cells underwent the apoptotic pathway.

Antineoplastic Agents↗
PubMed1998

bcl-2, bax, bcl-XL, and bcl-XS expression in normal and neoplastic ovarian tissues.

The bcl-2 family of proteins includes some important regulators of apoptosis. Among these, bcl-2 and bcl-xL prevent cells from entering apoptosis, whereas bax and bcl-xS can induce cell death. Alterations in the control of this process can lead to a decrease in cell death, thus contributing to neoplastic growth. Diminished susceptibility to chemotherapy has also been attributed, in in vitro systems, to alterations in the levels of bcl-2, bax, or bcl-x. We analyzed the expression of bcl-2, bax, bcl-xL, and bcl-xS in normal and neoplastic ovarian tissues by reverse transcriptase-PCR and Western blotting. The RNA and protein levels were significantly correlated for all genes. Interestingly, the levels of these genes in normal and neoplastic tissues were significantly different: bcl-2 was higher in normal tissue (P < 0.002), whereas bax and bcl-xL were higher in carcinoma (P < 0.018 and P < 0.030, respectively). bcl-xS was present at low levels in 83% of neoplastic samples and was undetectable in normal tissue. Reverse transcriptase-PCR analysis of 74 tumors showed no major correlation with clinicopathological parameters or with response to chemotherapy. Only bax and bcl-xL were correlated with progesterone receptor levels (n = 29, r = +0.44, P < 0.0189, and r = -0.40, P < 0.035, respectively). No correlation was found with estrogen receptor levels or with p53 immunostaining. Our data indicate that the regulation of the bcl-2 family of proteins differs between normal and neoplastic ovarian tissues. Moreover, the modulation of these genes in ovarian carcinoma is different compared to other tissues; therefore, tissue specificity is very important in regulation of the bcl-2 family of proteins.

Female↗
PubMed1998

[Therapy of bacterial vaginosis. Prospective clinical study ot the efficacy and tolerability of quaternary ammonium salts vs. clindamycin].

BACKGROUND: To evaluate the efficacy and safety of intravaginal quaternary ammonium antimicrobial compounds (SQA) versus clindamycin 2% intravaginal cream (CL) in the treatment of bacterial vaginosis (VB). MATERIALS AND METHODS: One hundred-thirty-three patients affected by VB were enrolled in the study from January 1995 to October 1997. Patients were classified according to Amsel's criteria and/or to the indications of the Scandinavian Society of Bacterial Vaginosis. Twenty-three patients were initially excluded from the study, and 110 patients were randomized in two groups, SQA versus CL. Patients were reevaluated after 3 weeks, 3 months and 6 months from the end of therapy. The safety of treatment was also investigated. RESULTS: Of 110 patients, 59 were treated with SQA and 51 with CL. One hundred (90.9%) patients completed the therapy and were subjected to the first control after 3 weeks from the end of therapy. A significant reduction of most of the symptoms and all signs of VB was observed in the group treated with SQA. Similarly, a significant reduction of most of the symptoms (vaginal and urinary in particular) and all signs of VB was observed in the group treated with CL. The percentage of response was 86.7% for SQA group and 87.2% for CL group. Moreover, after 3 months from the end of therapy, 47.2% and 50% of the patients treated with SQA and CL, respectively, recurred, and after 6 months 78.5% and 75% of the patients recurred, respectively. CONCLUSIONS: SQA treatment conferred 86.7% of response after 3 weeks from the end of therapy, with poor side effects and a good compliance in good keeping with the results obtained with CL treatment.

Adolescent↗
PubMed1998

Management of cervical intraepithelial neoplasia of the uterine cervix: 110 cases treated by cold-knife conization.

PURPOSE OF INVESTIGATION: The purpose of this study was to evaluate treatment by cold-knife-conization in women carriers of cervical intraepithelial neoplasia (CIN). METHODS: The histologic findings of pre-clinical neoplasia of the cervix after conization were compared to the previous findings of cytology, colposcopy and punch-biopsy in 110 women examined between 1985 and 1995. The chi square test (chi2) was used for the statistical analysis. RESULTS AND CONCLUSIONS: A close correlation is clinically important where complementary roles of these three methods are used to identify lesions suitable for local ablative therapy. The Pap test alone is no longer sufficient for the screening of the pre-cancerous lesion of the cervix and colposcopy is compulsory each time the smear is inadequate or altered. Conization permitted us to single out 13 (11.8%) cases of carcinoma. After cold-knife conization we had six (5.4%) recurrences within two years and two (1.8%) within three years. Our data show that conservative therapy by conization in women with CIN reduces the risk of invasive cancer of the cervix but careful follow-up of these patients is essential.

Adult↗
PubMed1998

[Efficacy of estrogen therapy in urinary incontinence. A meta-analytic study].

OBJECTIVE: To analyze by meta-analysis the results of randomized controlled clinical trials on the efficacy of estrogen treatment in menopausal patients with urinary incontinence. STUDY DESIGN: Meta-analysis. MATERIALS AND METHODS: Randomized controlled clinical trials, published from January 1965 to December 1996, on estrogen therapy in patients with urinary incontinence, were selected. They included: trials with placebo vs estrogen therapy, studies on menopausal patients with confirmed diagnosis of urinary incontinence based on clinical and/or urodynamic tests, studies with sufficient statistical informations on the results obtained and with information about subjective and objective outcome. RESULTS: Out of 72 articles reviewed, 7 were selected and only 4 were considered on the basis of the requested criteria. Subjective outcome was statistically different in patients treated with estrogen therapy compared with patients treated with placebo. Objective clinical and urodynamic outcome was not statistically different in the two types of treatment (estrogen vs placebo treatment). CONCLUSIONS: There were few published randomized controlled studies on estrogen therapy in patients with urinary incontinence in medical literature. Different results between subjective and objective outcome showed by meta-analysis, could be explained either by an estrogen induced unperceivable improvement not registered by clinical and instrumental parameters or by insufficient systems used to collect subjective data. Therefore, it is suggested that, for future research, randomized controlled clinical trials on topical or transcutaneous systemic estrogen treatment with a more than 6 months follow-up will be carry out.

Estrogens↗
PubMed1998

Antitumor activity of paclitaxel (taxol) analogues on MDR-positive human cancer cells.

A series of newly developed paclitaxel analogues have been tested for their growth inhibitory activity on two human breast cancer cell lines, one of which expresses the MDR (multidrug resistance) phenotype. Paclitaxel (taxol) was used as a reference compound. Three new classes of taxanes were analyzed: the cephalomannine compounds, the pyrazoline derivatives and the seco-derivatives. Our results demonstrated an increased antiproliferative activity of pyrazoline derivatives on drug-resistant cancer cells with respect to paclitaxel. These compounds were able to block MDR-bearing MCF-7 ADRr cells in the G2/M phase of cell cycle and, consequently, induce programmed cell death. In keeping with the antiproliferative effects, cells treated with paclitaxel derivatives showed a more pronounced cell cycle arrest than the parent compound paclitaxel. Also, apoptotic cell death, calculated as a percent of DNA fragmentation, occurred to a greater extent in cells exposed to pyrazoline derivatives. The development of new paclitaxel analogues with greater antitumour activity on MDR-positive cells may be useful in selecting new taxanes effective on resistant tumors.

Antineoplastic Agents, Phytogenic↗
PubMed1997

Anti-proliferative activity of a new class of taxanes (14beta-hydroxy-10-deacetylbaccatin III derivatives) on multidrug-resistance-positive human cancer cells.

Paclitaxel, docetaxel and a series of new analogs synthesized from 14beta-hydroxy-10-deacetylbaccatin III (14-OH-DAB), a natural diterpene closely related to the core synthon of the 2 above prototypes, were tested in vitro for their growth-inhibitory activity on different human cancer cell lines, including some expressing the classic multidrug-resistant (MDR) phenotype (MCF-7 ADRr and CEM VBLr). The 14-OH-DAB derivatives showed enhanced anti-proliferative activity as compared to the parent compounds on the MDR-positive cancer cell lines. Particularly, IDN 5109 showed a 25- to 30-fold higher activity than paclitaxel. The fold change in activity between paclitaxel and analogs (IC50 paclitaxel/IC50 analogs) on the MDR-positive cell lines was calculated and a significant correlation observed. As far as the MDR-negative MDA-MB 231 cells are concerned, docetaxel and IDN 5109 exhibited a more potent activity than paclitaxel. On the basis of the data obtained on cell growth inhibition, we selected the most active compounds to study their effect on the cell cycle. Cell cycle analysis showed that all of the compounds tested were able to induce cell cycle block at G2/M in a concentration-dependent manner. The amount of cell block, measured as a G1/G2 ratio, was correlated significantly (p < 0.001) with apoptosis, as evaluated in the sub-G1 region (% of DNA fragmentation), thereby suggesting that the G2/M-blocked cells underwent apoptosis. To confirm the occurrence of apoptosis in this system, DNA gel agarose electrophoresis was performed and showed the typical ladder pattern.

Antineoplastic Agents, Phytogenic↗
PubMed1997

Altered expression of cyclin D1 and CDK4 genes in ovarian carcinomas.

We analyzed the expression and amplification of cyclin D1 and CDK4 genes in ovarian carcinomas. Northern blot analysis revealed overexpression of cyclin D1 in 12 of 65 (18%) ovarian carcinomas while CDK4 was overexpressed in 7 of 48 cases (14%). None of the tumors showed amplification of any of the 2 genes. Overexpression of cyclin D1 and CDK4 transcripts was correlated, suggesting a role of both genes in altered growth control of ovarian cancer cells. Elevated levels of cyclin D1 were significantly associated with a well-moderately differentiated grade (G1-G2) (p < 0.005). No significant association was found between cyclin D1 expression and estrogen receptor, progesterone and epidermal growth factor receptor content. Cyclin D1 expression does not appear to be associated with clinical outcome in human ovarian cancer, although a longer follow-up period and screening of other molecules involved in the same pathway would be necessary to assess this hypothesis.

Age Factors↗
PubMed1997

A randomized study comparing retroperitoneal drainage with no drainage after lymphadenectomy in gynecologic malignancies.

OBJECTIVE: To evaluate the clinical effectiveness of retroperitoneal drainage following lymphadenectomy in gynecologic surgery. METHODS: One hundred thirty-seven consecutive patients undergoing systematic lymphadenectomy for gynecologic malignancies were randomized to receive (Group A, 68) or not (Group B, 69) retroperitoneal drainage. The pelvic peritoneum and the paracolic gutters were not sutured after node dissection. Perioperative data and complications were recorded. RESULTS: Clinical and surgical parameters were comparable in the two groups. Postoperative hospital stay was significantly shorter in Group B (P < 0.001), whereas the complication rate was significantly higher in Group A (P = 0.01). This was mainly due to a significant increase in lymphocyst and lymphocyst-related morbidity. Sonographic monitoring for lymphocyst showed free abdominal fluid in 18% of drained and 36% of not-drained patients (P = 0.03). Symptomatic ascites developed in 2 drained (3%) and 3 not-drained (4%) patients (NS), respectively. CONCLUSIONS: Prophylactic drainage of the retroperitoneum seems to increase lymphadenectomy-related morbidity and postoperative stay. Therefore, routine drainage following lymphadenectomy seems to be no longer indicated when the retroperitoneum is left open.

Adolescent↗
PubMed1997

Control of human luteal steroidogenesis: role of growth hormone-releasing hormone, vasoactive intestinal peptide, and pituitary adenylate cyclase-activating peptide.

OBJECTIVE: To examine the possible effect of growth hormone-releasing hormone (GHRH), vasoactive intestinal peptide, and pituitary adenylate cyclase-activating peptide on basal and hCG-stimulated P production by human luteal cells. DESIGN: Cultures of human luteal cells from the early and midluteal phase. SETTING: All corpora lutea were obtained from the Obstetrics and Gynecology Department of the Università Cattolica, a public care center. PATIENT(S): Ten nonpregnant women between 35 and 47 years of age underwent surgery for various nonendocrine disorders, such as leiomyomatosis. INTERVENTION(S): Corpora lutea were obtained at the time of hysterectomy. MAIN OUTCOME MEASURE(S): Luteal cells were incubated with GHRH, vasoactive intestinal peptide, and pituitary adenylate cyclase-activating peptide with or without hCG at different concentrations. RESULT(S): Pituitary adenylate cyclase-activating peptide stimulated P production in a dose- and time-dependent manner, whereas GHRH and vasoactive intestinal peptide did not affect luteal steroidogenesis. None of the three peptides were found to synergize with hCG. CONCLUSION(S): Pituitary adenylate cyclase-activating peptide can influence human luteal steroidogenesis.

Adult↗
PubMed1997

Correlation between endometriosis-associated dysmenorrhea and the presence of typical or atypical lesions.

OBJECTIVE: To evaluate the correlation between the severity of endometriosis-associated dysmenorrhea and the extent of the disease assessed both with a current classification system and with the number and type of endometriosis lesions. DESIGN: Prospective, blinded study. SETTING: Tertiary care, university hospital. PATIENT(S): Sixty-five consecutive patients with endometriosis diagnosed at laparoscopy performed for pelvic pain, infertility, or adnexal mass. INTERVENTION(S): The patients were submitted preoperatively to a questionnaire including the assessment of the severity of dysmenorrhea by means of a 10-point linear analog scale. Evaluation of all visible signs of endometriosis at laparoscopy was performed by a surgeon not aware of the patients' symptoms. MAIN OUTCOME MEASURE(S): The correlation between the severity of dysmenorrhea and the total score for endometriosis and the partial scores for superficial, deep, and adhesion disease as assessed with a current classification system was evaluated. The severity of dysmenorrhea was also correlated with the total number of superficial implants and with the number of typical, pigmented versus atypical, nonpigmented lesions. RESULT(S): The linear analog score for dysmenorrhea correlated significantly with the total endometriosis score, the partial score for deep endometriosis, and the partial score for adhesions. There was no correlation between the pain score for dysmenorrhea and the partial score for superficial endometriosis, nor with the total number of endometriosis implants, the number of typical implants, or the number of atypical implants. CONCLUSION(S): The current classification system for endometriosis, devised primarily to formulate a prognosis in infertile patients, correlates significantly with endometriosis-associated dysmenorrhea. The present study does not support the suggested association between atypical implants and the severity of dysmenorrhea.

Adult↗
PubMed1997

Somatostatin treatment reduces the exaggerated response of adrenocorticotropin hormone and cortisol to corticotropin-releasing hormone in polycystic ovary syndrome.

OBJECTIVE: To evaluate the influence of somatostatin analogue (octreotide) in the function of hypothalamic-pituitary-adrenal (HPA) axis in women with polycystic ovary syndrome (PCOS). SETTING: Women referred to the Department of Obstetrics and Gynecology, Università Cattolica del Sacro Cuore. PATIENT(S): Twelve PCOS women and 12 normo-ovulatory controls. INTERVENTION(S): In early follicular phase, I microgram/kg human corticotrophin-releasing hormone (CRH) was injected at 9:00 A.M. and blood samples were collected for 90 minutes after stimulus; ACTH and cortisol plasma levels were measured. The following day at 8:00 A.M., PCOS patients received an ACTH test (250 micrograms IV) and samples were collected 60 minutes after injection. After 6 weeks of octreotide treatment (100 mg s.c. twice daily), PCOS patients repeated the same study. MAIN OUTCOME MEASURE(S): Plasma cortisol and ACTH concentrations. RESULT(S): The ACTH and cortisol baseline levels were similar in PCOS and control patients. The responses to human CRH of ACTH (incremental area = 437.86 +/- 188.7 versus 175.78 +/- 87.6 pmol/L; mean +/- SD) and cortisol (incremental area = 17,293.6 +/- 4,320.3 versus 5,885 (912.1 nmol/L) were significantly greater in PCOS with respect to control subjects. After octreotide treatment, ACTH response significantly decreased and no difference was observed with respect to controls (incremental area = 176.94 +/- 91.4). Cortisol responses were decreased by treatment. However, they remained significantly higher than in controls. Treatment did not modify adrenal response to IV ACTH. CONCLUSION(S): Data suggest that, in the HPA axis, hyperfunction of PCOS somatostatin could be involved partially.

Adolescent↗