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Biomedical subjects

S Mancuso

Publications and source records attributed to S Mancuso.

At least 271 records · Page 15Linked to original sources

Anatomical and pathological study of retroperitoneal nodes in epithelial ovarian cancer.

The pattern of lymphatic spread was evaluated in 81 previously untreated ovarian cancer patients (Stage I, 35; Stage II, 2; Stage III, 44) undergoing systematic aortic and pelvic lymphadenectomy. Positive nodes were found in 14% Stage I and 68% Stage III patients. Either pre- and paraaortic, or pre- and paracaval nodes were the only aortic node metastasis in 14% of patients. Common iliac nodes were the sole metastasis in pelvic area in 11%, external iliac in 14%, and obturator in 6% of patients. Therefore, the above node groups, which overall were the most frequently involved, may be considered those primarily invaded by the tumor. When data were analyzed according to stage, aortic nodes were the site of metastasis in 6% Stage I and 14% Stage III patients and pelvic nodes in 8% Stage I and 11% Stage III patients. Both aortic and pelvic areas were positive in 43% Stage III patients. The median number of positive nodes/patient was 2 (range, 1-3) and 4 (range 2-46) in Stages I and III, respectively. Lymphatic spread was ipsilateral to the tumor in all Stage I and in 40% Stage III patients. In Stage III metastases were also observed in intercavoaortic, retrocaval, retroaortic, internal iliac, and presacral nodes. In apparent Stage I, lymphatic metastasis seemed to be limited to one ipsilateral group, and the removal of the primary nodes ipsilateral to the tumor may be considered an adequate procedure. In Stage III, the presence of metastasis beyond the primary nodes and the frequent bilateral involvement suggest that all lymphatic tissue surround the aorta, the cava, and the pelvic vessels should be removed if a cytoreductive intent is pursued.

Adult↗

Expression of ras oncogene p21 protein in normal and neoplastic ovarian tissues: correlation with histopathologic features and receptors for estrogen, progesterone, and epidermal growth factor.

OBJECTIVE: The aim of the study was to investigate the biologic significance of p21 expression in normal and neoplastic ovarian tissues. STUDY DESIGN: Western blotting analysis of p21/ras oncoprotein was conducted in a group of 14 normal and cystic ovaries, six benign tumors, 42 primary ovarian cancers, and 15 omental metastases. RESULTS: Levels of p21 were similar in normal and cystic ovaries and in benign tumors, whereas they were significantly higher in malignant tumors than in control tissues (median 1.91, range 0.12 to 5.00 vs median 1.03, range 0.32 to 2.20; p = 0.023) and in omental metastases than in primary ovarian carcinomas (median 3.05, range 0.55 to 5.72 vs median 1.97, range 0.12 to 5.00; p = 0.14). We found no correlation between p21 expression and histopathologic or clinical characteristics. Estrogen receptor-positive and progesterone receptor-positive tumors expressed higher p21 levels than did estrogen receptor-negative and progesterone receptor-negative tumors (p < 0.05), but no correlation with epidermal growth factor receptor status was found. In the univariate analysis of survival p21 positivity showed a negative prognostic value. CONCLUSION: The enhancement of p21 protein is associated in the ovarian tissue with the malignant phenotype and the acquisition of metastatic potential.

Adult↗

Ovarian sensitivity to follicle-stimulating hormone during the follicular phase of the human menstrual cycle and in patients with polycystic ovarian syndrome.

OBJECTIVE: To investigate the existence of a different sensitivity of ovaries to follicle-stimulating hormone (FSH) during the follicular phase of the human menstrual cycle and in patients with polycystic ovarian syndrome (PCOS). DESIGN: Thirty-four normal subjects and 13 patients with PCOS were treated intravenously by FSH (75 or 225 IU) or saline at different stages of follicular phase. MAIN OUTCOME MEASURES: Plasma levels of luteinizing hormone (LH), FSH, estradiol (E2), and testosterone (T) in samples collected for a period of 26 hours after the injection. RESULTS: In patients at the early stages of follicular phase (baseline E2 < 50 pg/mL), FSH increased in dose-dependent manner E2 and E2:T-stimulated area under curve (AUC) in respect to saline experiments. In PCOS subjects, saline E2, and E2:T-stimulated AUC were significantly lower than normal women. Follicle-stimulating hormone (75 IU) dramatically increased these values, and no difference was seen in respect to 75 and 225 IU FSH-treated controls. In patients with E2 baseline plasma levels > 50 pg/mL, FSH (75 or 225 IU) failed to increase both E2 and E2:T-stimulated AUC in comparison with saline studies. CONCLUSIONS: Early stages of follicular phase in normal and polycystic ovaries are the most responsive to the elevation of circulating FSH levels, whereas the ovarian sensitivity spontaneously decreases as follicular maturation enhances.

Adult↗

Long-term naltrexone treatment normalizes the pituitary response to gonadotropin-releasing hormone in polycystic ovarian syndrome.

OBJECTIVE: To investigate the influence of opioid system on the exaggerated LH response to GnRH test in the polycystic ovarian syndrome (PCOS). DESIGN: Pituitary stimulation (GnRH 100 micrograms) in a group of PCOS patients under basal condition and after 4 weeks of treatment with naltrexone. RESULTS: In the PCOS group, the naltrexone treatment determines a significant reduction of the LH response (calculated as the area under curve) to GnRH test, with a similar significant decrease of the LH:FSH. CONCLUSION: Naltrexone normalizes in the PCOS group the pituitary response to GnRH test, abolishing every statistical differences with the control group.

Adolescent↗

Human growth hormone enhances progesterone production by human luteal cells in vitro. II. Evidence of a distinct effect on two luteal cell types.

OBJECTIVE: To examine the differential effect of human GH (hGH) on basal and hCG-stimulated production by cultured small and large human luteal cells. DESIGN: Distinct cultures of small and large luteal cells from early and midluteal phase. SETTING: All corpora lutea were obtained from the Obstetrics and Gynecology Department of the Catholic University, a public care center in Rome, Italy. PATIENTS, PARTICIPANTS: Ten nonpregnant women between 31 and 43 years of age underwent surgery for various nonendocrine disorders such as leiomyomatosis. INTERVENTIONS: Corpora lutea were obtained at the time of hysterectomy. MAIN OUTCOME MEASURES: Small and large luteal cells were incubated with or without hCG and/or hGH at different concentrations. RESULTS: Human GH neither at 250 nor at 500 micrograms/L increased basal P production by small luteal cells, whereas from 1,000 micrograms/L, P concentration in media was significantly increased. The concomitant treatment with ineffective doses of hCG (30 and 60 IU/L) and hGH (250 and 500 micrograms/L) enhanced P production to that obtained with the highest doses of hGH (1,000 micrograms/L or more) or hCG (125 to 250 IU/L) alone. Human GH addition did not change the amount of P release by large luteal cells at any concentration. CONCLUSIONS: These results indicate a distinct and differential effect of hGH on in vitro luteal steroidogenesis by the two luteal cell types.

Adult↗

Indomethacin in vivo inhibits the enhancement of the progesterone secretion in response to gonadotrophin-releasing hormone by human corpus luteum.

Different prostaglandins (PG) seem to have luteolytic or luteotrophic function in relation to the phases of life of the human corpus luteum and in-vitro studies demonstrate a luteotrophic function of PGE2, PGI2, PGD2. The present study evaluated the effect of an inhibitor of prostaglandin synthesis on the hypophyseal and luteal responses to gonadotrophin-releasing hormone (GnRH) in women during the mid-luteal phase. Twenty normal menstruating women participated in the study. Two different protocols were applied. After monitored ovulation (day 0), eight patients were treated with indomethacin for 7 days and 12 untreated patients served as controls. To evaluate luteal progesterone production, blood samples were taken every 15 min for 2 h basally and after a bolus of GnRH (25 micrograms i.v.); eight control patients were also treated with indomethacin for one day, and the endocrine study was repeated. The long-term administration of indomethacin significantly reduced basal as well as luteinizing hormone (LH)-stimulated progesterone production by the corpus luteum in respect to controls. Short-term administration failed to influence basal progesterone production, but abolished its secretory response to LH. A luteotrophic role for prostaglandins in human luteal function is suggested.

Adult↗

Pregnancy outcome in relation to uterine artery flow velocity waveforms and clinical characteristics in women with antiphospholipid syndrome.

OBJECTIVE: To determine whether uterine artery velocimetry is a useful tool for identifying pregnancies with antiphospholipid syndrome at risk for adverse outcome. METHODS: Twenty-four women with antiphospholipid syndrome, who had experienced 56 fetal losses in 63 previous pregnancies (88.9%), were treated with prednisone (40 mg/day) and aspirin (100 mg/day) during 28 pregnancies. Color Doppler ultrasound was performed at 18-24 weeks' gestation to investigate the resistance index of the uterine arteries. RESULTS: Treated women delivered 23 live infants in the 28 pregnancies (82.1%). Three infants weighed less than the tenth percentile (13%). Five pregnancies were complicated by preeclampsia and ten by nonproteinuric gestational hypertension. Positive results for all three assays for antiphospholipid antibodies (anticardiolipin antibodies, lupus anti-coagulant, VDRL) at conception identified pregnancies destined to have poor fetal outcome and a significantly lower birth weight compared to pregnancies not having all three assays positive. An abnormal resistance index of the uterine arteries predicted pregnancies with poor fetal outcome in terms of week of delivery, birth weight, and birth percentile, as well as four of five cases of preeclampsia. CONCLUSIONS: Three assays positive for antiphospholipid antibodies at conception and an abnormal resistance index of the uterine arteries at 18-24 weeks' gestation predicted pregnancies at major risk for obstetric complications. Future studies should determine whether treatment can be modulated based on the Doppler findings.

Adult↗

Evaluation of ovarian and adrenal sources of androgens in women with polycystic ovary syndrome. Dexamethasone and GnRH-agonist administration.

Ovarian and adrenal production of androgens was evaluated in 18 patients with polycystic ovary syndrome (PCOS) by administering a combination of short-term dexamethasone (DEX) and long-term gonadotropin-releasing hormone agonist (GnRH-A). At day 6 of the cycle, blood samples were collected at 7 A.M. (basal) and 11 P.M. At midnight, 2 mg DEX was given orally, and blood samples were collected at 7 A.M. the following day (DEX1). Blood samples were obtained for 6 weeks at the same time after administration of a potent GnRH-A (400 micrograms/day given subcutaneously). Eight normal subjects served as controls. The amounts of androgens and 17-hydroxyprogesterone (17-OHP) suppressed by using DEX (adrenal-source suppression) and GnRH-A (ovarian-source suppression) were greater in PCOS patients than in controls. We differentiated PCOS patients as having a normal or an exaggerated response to DEX or GnRH-A administration; threshold values were considered average +2SD of the suppressed androgen amounts of controls. Three patients had an exaggerated response to GnRH-A treatment for androstenedione, testosterone and 17-OHP, while DEX inhibition was similar to controls. The remaining 15 patients had an exaggerated response to DEX for all three androgens; seven also had an exaggerated response to GnRH-A. Thus, the combination of GnRH-A and DEX permitted us to selectively study and identify adrenal and ovarian sources of hyperandrogenemia.

Adrenal Glands↗

Long-term naltrexone treatment reduces the exaggerated insulin secretion in patients with polycystic ovary disease.

OBJECTIVE: To evaluate the involvement of endogenous opiates in the pathophysiology of the hyperinsulinism in patients affected by polycystic ovary disease by administering naloxone and naltrexone. We also studied the hormonal status following long-term opioid antagonist administration. METHODS: Twenty-one women affected by polycystic ovary disease participated in the study. An oral glucose tolerance test (GTT) was performed at baseline and repeated after short-term naloxone infusion and after 6 weeks of naltrexone administration. Plasma glucose and insulin levels were evaluated in all samples. Gonadotropins, sex hormone-binding globulin, and androgen levels were determined initially and after the naltrexone treatment. RESULTS: None of the patients showed any alteration of glucose tolerance. Based on the insulin response to the GTT, the patients were classified as normo- or hyperinsulinemic. Opioid antagonist administration significantly reduced the insulin response to the GTT in hyperinsulinemic patients, without affecting their glycemic levels. In normoinsulinemic patients, glucose plasma levels were increased whereas insulin levels were not modified by the treatments. Gonadotropin and androgen plasma concentrations were not modified after naltrexone administration. CONCLUSIONS: This work supports a role for the endogenous opiates in the regulation of exaggerated insulin secretion in patients with polycystic ovary disease. The reduction of insulin secretion failed to demonstrate any hormonal modification in such hyperandrogenized patients.

Adult↗

[The role of laparoscopy in the evaluation of chronic pelvic pain].

Chronic pelvic pain, defined as cyclic or acyclic pain reported for a minimum of six months, is one of the most common gynecological symptoms and one of the most important in terms of social costs. From January 1987 to December 1991, 127 patients suffering from chronic pelvic pain were submitted to diagnostic laparoscopy at the Department of Obstetrics and Gynecology of the Università Cattolica del Sacro Cuore in Rome. The mean age of the patients was 30 years, ranging from 14 to 46. All patients were submitted to bimanual pelvic examination upon hospital admission, and most of them (No. = 99, 78%) to pelvic ultrasonographic examination. In 117 patients (92%) samples for the isolation of Chlamydia trachomatis in 5-iodo-2-deoxiuridine treated McCoy cell cultures were obtained from the cervix, the endometrium and the cul-de-sac peritoneal fluid. At laparoscopy, in 25 patients (20%) the exam showed normal pelvic anatomy, whereas in 102 patients (80%) some pelvic pathology was found. The most frequent conditions observed were: pelvic adhesions in 55% (No. = 70), endometriosis in 29% of the cases (No. = 37), and other pathologies (non-endometriotic ovarian cysts, hydrosalpinges, myomas, etc.) in 25% of the cases (No. = 32). At the comparison of bimanual examination and laparoscopic findings, out of 71 patients with normal findings at bimanual examination, 75% (No. = 53) were found to have abnormal findings at laparoscopy; out of 55 patients with abnormal bimanual examination, 11% (No. = 6) were found to have normal laparoscopic findings.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cathepsin D in primary squamous laryngeal tumors: correlation with clinico-pathological parameters and receptor status.

Using an immunoradiometric assay, Cathepsin D (Cath D) levels were measured in the cytosol of 23 normal and 39 neoplastic human laryngeal tissues. Scattered Cath D levels (from 2.2 to 17.8 pM/mg protein; median = 7.6) were found in normal mucosa specimens. Cath D concentrations range from 2.0 to 29.3 pM/mg protein (median = 8.5) in laryngeal tumors. When a comparison between Cath D levels in normal and neoplastic tissue specimens from the same patient was done, Cath D levels were significantly higher in laryngeal cancers than in their normal counterparts (P = 0.03). No correlation with clinico-pathological parameters and steroid hormone and epidermal growth factor receptor status was found. Further studies should investigate whether the production of Cath D by laryngeal tumors could have a clinical relevance for this neoplasia.

Adult↗

Growth-inhibitory effect of quercetin and presence of type-II estrogen-binding sites in human colon-cancer cell lines and primary colorectal tumors.

We studied the effect of quercetin (Q) on the proliferation of HT-29, WiDr, COLO 201, and LS-174T human colon cancer cell lines. Q, between 10 nM and 10 microM, exerted a dose-dependent, reversible inhibition of cell proliferation. Cell-cycle analysis revealed that the growth-inhibitory effect of Q was due to a blocking action in the G0/G1 phase. Using a whole-cell assay with 17 beta-[3H]-estradiol as tracer, we demonstrated that all these cell lines contain type-II estrogen-binding sites (type-II EBS). By using Q and other chemically related flavonols (3,7-4'-trimethoxyquercetin, 3,7,3',4'-tetramethoxyquercetin, kaempferol, morin, and rutin), we observed that the affinities of these compounds for type-II EBS are correlated with their growth-inhibitory potential. Furthermore, the Q sensitivity of the colon cancer cell lines was correlated with the number of type-II EBS/cell. Then Q could regulate colon cancer cell growth through a binding interaction with type-II EBS. This mechanism could also be active in vivo as we have observed that cytosolic type-II EBS are present in primary colorectal cancers and that Q is effective in inhibiting the in vitro bromodeoxyuridine incorporated by neoplastic cells in these cancers.

Adenocarcinoma↗

Ultrasound diagnosis of fetal macrosomia.

Macrosomic infants and their mothers are at increased risk for intrapartum injury and perinatal morbidity and mortality. This study investigates the effectiveness of individual ultrasound fetal measurements, ponderal indices and estimated fetal weight in the identification of macrosomia in 732 pregnant patients who underwent ultrasound examination within 7 days of delivery. All the indices evaluated were compared for accuracy in predicting birth weight. Statistical comparison revealed that estimated fetal weight predicted macrosomia better than single ultrasound parameters and ponderal indices. The formulae tested yielded an accuracy of 94% and a positive predictive value of 90%. Abdominal diameter and abdominal circumference values above the 90th centile correctly predicted macrosomia in 82% and 72% of cases, respectively. Fetal length showed a sensitivity of 61% with a predictive positive test of 41%. Femur length-to-abdominal circumference ratio detected macrosomia with a sensitivity of 80% and an accuracy of 82%. The other single ultrasound parameters and ponderal indices were significantly less indicative of macrosomia. The combined use of four indices (growth profile) did not improve the effectiveness of ultrasound in detecting fetal macrosomia. We conclude that the optimal prediction of fetal macrosomia is obtained from mathematical formulae for fetal weight estimation, based on several fetal measurement parameters and adjusted for different gestational periods.

Journal Article↗

Effects of dexamethasone on the growth and epidermal growth factor receptor expression of the OVCA 433 ovarian cancer cells.

We studied the correlation between dexamethasone (Dex) induced growth effects and modulation of epidermal growth factor receptor (EGFR) expression in OVCA 433 ovarian cancer cells. These cells express specific high and low affinity 125I-EGF binding sites and are growth stimulated by EGF. Dex exhibits mitoinhibitory effects by recruiting OVCA 433 cells in the G0-G1 phase of the cycle, but increases the number of both the high and the low affinity EGFR in a dose dependent manner. The maximal EGFR expression increase occurs after 24 h of Dex treatment consistently with Northern blot studies. The mitogenic activity of EGF in OVCA 433 cells is not affected by the presence of Dex. Moreover Dex growth inhibition occurs in JA1 cells, an ovarian cancer cell line which expresses unfunctional EGFR and which is unresponsive to EGF. Our results indicate that the Dex induced growth effects occur independently of EGFR expression.

Antibodies, Monoclonal↗

Synergistic antiproliferative activity of tamoxifen and cisplatin on primary ovarian tumours.

We looked for the presence of the so-called type II oestrogen binding sites (EBS), in four oestrogen (ER) and progesterone (PR) receptor negative primary ovarian tumours. Moreover, the colony-forming assay was used to evaluate the response of ovarian cancer cells from these primary tumours to tamoxifen and cisplatin used alone or in combination. All tumours contained type II EBS, and tamoxifen was able to compete for [3H] oestradiol binding to these sites. Cisplatin and tamoxifen exhibited a dose-dependent inhibition of colony formation in a range of concentrations between 10 and 1000 micrograms/l and 37 and 3710 micrograms/l, respectively. The combination of the two drugs resulted in a synergistic antiproliferative activity, with a potentiation up to and beyond 50-fold. Our results show that in ovarian cancer tamoxifen interacts with type II EBS with an affinity consistent with the concentration effective both in inhibition of colony formation and in synergising cisplatin activity. Based on the experiments performed the action of tamoxifen on cell growth is independent of ER expression, and could be mediated by type II EBS. The possibility that the association of tamoxifen and cisplatin may result in an improved clinical response in ovarian cancer should be investigated.

Binding Sites↗

Oral condyloma lesions in patients with extensive genital human papillomavirus infection.

OBJECTIVES: The incidence, location, and morphologic appearances of human papillomavirus oral lesions in patients with genital condylomatosis were investigated with clinical, colposcopic, and histologic examination as diagnostic procedures. The human papillomavirus types were also evaluated with filter in situ hybridization. STUDY DESIGN: One hundred one patients, 66 female and 35 male, with genital condyloma underwent an oral cavity examination. Ninety-nine (99%) practiced orogenital sex, and all were asymptomatic for oral lesions. RESULTS: Ninety-one underwent biopsy; histologic studies gave a diagnosis of condyloma in 48% of 101 specimens collected. In 8 of 91 (9%) oral lesions were suspected by naked-eye examination; they were confirmed histologically in all eight. Of 83 patients suspected of having oral condyloma on colposcopic examination, 38 (46%) were confirmed histologically. Thus 38 of 46 patients (83%) had oral condyloma not visible to the naked eye. Colposcopically, oral lesions appeared filiform (50%), moruloid (26%), and mixed (24%). Twenty cytologic oral samples were also collected for deoxyribonucleic filter in situ hybridization analysis. Human papillomavirus deoxyribonucleic genital types were observed in 45% (9/20) of all oral scrapings collected, and all were histologically confirmed. CONCLUSION: Our data indicate that genital human papillomavirus types are capable of establishing a local infection in the oral cavity and demonstrate a high incidence of human papillomavirus oral lesions in patients with genital condyloma.

Adult↗

Human growth hormone enhances progesterone production by human luteal cells in vitro: evidence of a synergistic effect with human chorionic gonadotropin.

OBJECTIVE: To examine the possible direct effect of human growth hormone (hGH) on basal and human chorionic gonadodotropin (hCG)-stimulated progesterone (P) production by cultured human luteal cells. DESIGN: Cultures of human luteal cells from early and midluteal phase. SETTING: All corpora lutea were obtained from the Obstetrics and Gynecology Department of the Catholic University, a public care center. PATIENTS, PARTICIPANTS: Twelve nonpregnant women between 35 and 47 years of age underwent surgery for various nonendocrine disorders such as leiomyomatosis. INTERVENTIONS: Corpora lutea were obtained at the time of hysterectomy. MAIN OUTCOME MEASURE: Luteal cells were incubated with or without hCG and/or hGH at different concentrations. RESULTS: Human growth hormone neither at 250 nor at 500 ng/mL increased basal P production, whereas from 1,000 ng/mL P concentration in media was significantly increased (P less than 0.05). The concomitant treatment with uneffective doses of hCG (6 and 12 ng/mL) and hGH (250 and 500 ng/mL) enhanced P production similarly to that obtained with the highest doses of hGH (1,000 ng/mL or more) or hCG (25 to 50 ng/mL) alone. CONCLUSIONS: These results indicate a direct effect of hGH on the luteal steroidogenesis in vitro.

Adult↗