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Biomedical subjects

S Mancuso

Publications and source records attributed to S Mancuso.

At least 217 records · Page 12Linked to original sources

Significance of cathepsin-D expression in uterine tumours.

Cathepsin-D (Cath-D) expression was evaluated by an immunoradiometric assay in 67 primary endometrial carcinomas and 70 cervical cancers. In the endometrial tumours, an inverse correlation was observed between Cath-D levels and stage (P = 0.027) and myometrial invasion (P = 0.046). A significant correlation between Cath-D levels and hormone receptor status was demonstrated (P < 0.05). In cervical cancer, no differences in the distribution of Cath-D levels according to clinicopathological parameters and hormone receptors were observed. However, patients not responding to neoadjuvant chemotherapy had significantly lower Cath-D values than those showing complete or partial response (P = 0.011). As far as prognostic significance is concerned, it appears that Cath-D expression might have a different role in the two uterine neoplasias. While our preliminary data in endometrial cancer suggest that high Cath-D levels may be a favourable prognostic indicator, cervical cancer patients with Cath-D+ tumours had a shorter disease-free survival than those with Cath-D- tumors (P = 0.017).

Adult↗

Prognostic role of laparoscopic salpingoscopy of the only remaining tube after contralateral ectopic pregnancy.

OBJECTIVE: To evaluate the prognostic value of laparoscopic salpingoscopy in detecting patients who are at increased risk for a repeat ectopic pregnancy (EP). DESIGN: Patients with secondary infertility after a previous contralateral salpingectomy for EP were evaluated by laparoscopy with tubal perfusion and salpingoscopy of the only remaining tube. Subsequent reproductive outcome was evaluated and correlated to laparoscopic and salpingoscopic findings. SETTING: Department of Obstetrics and Gynecology of the Catholic University, a tertiary care university center in Rome, Italy. PATIENTS: Eighteen patients submitted to laparoscopy and salpingoscopy after a previous salpingectomy for EP. INTERVENTION: A two- to three-puncture laparoscopy with tubal perfusion and salpingoscopy. MAIN OUTCOME MEASURE: Reproductive outcome after a mean follow-up of 42.6 months. RESULTS: Salpingoscopy revealed a normal tubal mucosa in 13 patients (72%) and intra-ampullary adhesions in 5 patients (28%). Eight of the 13 patients with a normal mucosa conceived an intrauterine pregnancy. In the 5 patients with intra-ampullary adhesions, there were 3 repeat EPs, with one patient having first a term pregnancy and then a repeat EP. The presence of peritubal adhesions at laparoscopy was not of prognostic significance. CONCLUSION: Direct visualization of the ampullary mucosa by salpingoscopy can allow the detection of intraluminal adhesions that put the patient at increased risk for a repeat EP.

Adult↗

Corticotropin-releasing hormone induces an exaggerated response of adrenocorticotropic hormone and cortisol in polycystic ovary syndrome.

OBJECTIVE: To evaluate pituitary-adrenal responsive to corticotropin-releasing hormone (CRH) stimulus in polycystic ovary syndrome (PCOS). DESIGN: Controlled clinical study. PATIENTS: Twelve women aged 17 to 32 years, who had been diagnosed as having PCOS, were studied. Fifteen appropriately age- and weight-matched ovulatory patients served as the control. INTERVENTION: In the early follicular phase or after progestin-induced menses, human CRH was injected at 8:00 A.M. and blood samples were collected at 0, 15, 30, 60, and 90 minutes after stimulus. Plasma levels of ACTH and cortisol were measured. RESULTS: Baseline levels of ACTH and cortisol were similar in PCOS and control patients. Both ACTH and cortisol response to CRH were markedly greater in the PCOS population as compared with controls. Moreover, ACTH- and cortisol-stimulated secretion was prolonged for the whole period of the study in hyperandrogenic patients with respect to controls, where baseline levels were attained 60 minutes after the stimulus. CONCLUSIONS: Our results are consistent with the hypothesis that women with PCOS may demonstrate hyperfunction of the hypothalamic-pituitary-adrenal axis, which may be involved in the physiopathologic events leading to the complexity of the syndrome.

Adolescent↗

Effectiveness of a somatostatin analogue in lowering luteinizing hormone and insulin-stimulated secretion in hyperinsulinemic women with polycystic ovary disease.

OBJECTIVE: To analyze the action of a long-acting somatostatin analogue on circulating insulin levels and on pituitary sensitivity to GnRH in women affected by polycystic ovary disease (PCOD). DESIGN: Controlled clinical study. SETTING: Normal human volunteers in the Department of Obstetrics and Gynecology, Universita' Cattolica del Sacro Cuore. PATIENTS: Twenty euglycemic women affected by PCOD, aged 19 to 30 years, were studied in their early follicular phase. INTERVENTIONS: A long-acting somatostatin analogue (octreotide) was administered SC for 6 weeks; an oral glucose tolerance test (OGTT), a GnRH test, and plasma hormone determinations were performed at baseline and repeated after 6 weeks of treatment. A glucose load also was performed after 1 week of treatment. MAIN OUTCOME MEASURES: Insulin and glucose serum concentrations were measured in all samples under the oral glucose stimulus, LH and FSH were measured under GnRH test. Plasma levels of PRL, sex hormone-binding globulin, androstenedione (A), T, 17 beta-hydroxyprogesterone, DHEAS, and cortisol were measured. Steroids also were assayed after the octreotide administration. RESULTS: Based on the insulin response to OGTT, subjects were classified as hyperinsulinemic (n = 12) and normoinsulinemic (n = 8). Octreotide administration did not affect the glycemic levels in both groups. Octreotide significantly reduced insulin and LH exaggerated response to GnRH stimulus, as well as the A and T circulating levels, only in the hyperinsulinemic group. CONCLUSIONS: A functional linkage exists between exaggerated insulin and LH-stimulated secretion in a group of polycystic ovary patients. Octreotide may be useful in normalizing these alterations and in reducing ovarian androgen secretion of hyperinsulinemic subjects.

Adult↗

Correlation between the American Fertility Society classifications of adnexal adhesions and distal tubal occlusion, salpingoscopy, and reproductive outcome in tubal surgery.

OBJECTIVE: To compare the prognostic value of salpingoscopy with a current classification system of adnexal adhesions and distal tubal occlusion in patients with tubal infertility undergoing reconstructive tubal surgery. DESIGN: Prospective clinical study. SETTING: Department of Obstetrics and Gynecology of the Catholic University, a tertiary care University Center in Rome, Italy. PATIENTS: Fifty-five infertile patients with either adnexal adhesions (29 patients) or hydrosalpinx (26 patients) undergoing reconstructive tubal surgery. INTERVENTIONS: Salpingoscopy performed concomitantly to salpingo-ovariolysis or salpingoneostomy at the time of either operative laparoscopy or laparotomy using microsurgical techniques. MAIN OUTCOME MEASURES: Salpingoscopic findings were compared with a current classification system of adnexal adhesions and distal tubal occlusion. The patients were followed for a mean follow-up of 49 months; the pregnancy rates achieved were correlated with the salpingoscopic findings and the classification system used. RESULTS: There was a significant correlation between the salpingoscopic grade and the occurrence of a term pregnancy for both the salpingo-ovariolysis and salpingoneostomy groups of patients. There was no significant correlation between the classification system used and the occurrence of a term pregnancy for both groups of patients. CONCLUSION: Salpingoscopy plays an important role in selecting the patients who may benefit the most from reconstructive tubal surgery.

Adnexal Diseases↗

Epidermal growth factor, oestrogen and progesterone receptor expression in primary ovarian cancer: correlation with clinical outcome and response to chemotherapy.

The expression of epidermal growth factor receptor (EGFR), oestrogen receptor (ER) and progesterone receptor (PR) was assayed by a radioreceptor method in 117 primary ovarian cancers. EGFR was not significantly related to any of the clinicopathological parameters examined. In patients with stage II-IV disease who underwent second-look surgery after primary chemotherapy, a significant correlation between high EGFR levels and poor response to chemotherapy was demonstrated (P = 0.031). Moreover, post-operative residual tumour showed an independent role in predicting chemotherapy response (P = 0.0007) and EGFR status showed a borderline significance (P = 0.052) in the multivariate analysis. No correlation between steroid hormone receptors and clinicopathological parameters was observed. Whereas a significant relationship was shown between EGFR positivity and a shorter overall survival (OS) (P = 0.0022) and progression-free survival (PFS) (P = 0.0033), patient survival was not related to steroid hormone receptor status. Among the parameters tested only stage, ascites and EGFR status retained an independent prognostic value in the multivariate analysis.

Adult↗

Prognostic significance of interleukin 6 serum levels in patients with ovarian cancer.

High levels of IL-6 were found in 50% of 114 patients with primary ovarian cancer. IL-6 sensitivity was lower than that of CA 125, and the combination of both assays did not increase the sensitivity of CA 125 alone. However, elevated IL-6 serum levels were correlated with a poor prognosis since patients with low IL-6 levels had a better survival than patients with high IL-6 levels (P = 0.0009). Multivariate analysis revealed that IL-6 positivity has an independent value.

Adult↗

Laparoscopic findings after transvaginal ultrasound-guided aspiration of ovarian endometriomas.

From 1 July 1990 to 31 January 1994, 55 patients underwent operative laparoscopy for the excision of monolateral endometriomas. None of the patients had previously undergone surgery by laparotomy or laparoscopy. At the time of laparoscopy, the surgeon staged the disease according to the American Fertility Society classification of endometriosis. A second surgeon, blinded to the preoperative management of the patients, re-staged the disease based on a videotape review. Interobserver disagreement was between 0 and 12%. Total, endometriosis (deep and superficial) and adhesion scores were evaluated separately. These scores in patients who had previously undergone transvaginal ultrasound-guided aspiration of the cyst content (n = 13) were compared with those from patients who had not undergone this procedure (n = 42). The total and endometriosis scores were not significantly different between the two groups, whereas the adhesion score in patients who had undergone a transvaginal aspiration procedure was significantly higher than in patients who had not (mean +/- SD, 12.0 +/- 13.7 versus 5.9 +/- 4.6; P = 0.02). Therefore it is possible that transvaginal ultrasound-guided endometrioma aspiration may determine tissue trauma that enhances adhesion formation.

Adolescent↗

The growth hormone response to growth hormone-releasing hormone is blunted in polycystic ovary syndrome: relationship with obesity and hyperinsulinaemia.

This study was designed to investigate the growth hormone (GH) secretory response to the growth hormone-releasing hormone (GHRH) test in women with polycystic ovary syndrome (PCOS). A total of 25 patients with PCOS (13 obese and 12 non-obese) and 15 normal ovulatory women (seven obese and eight non-obese) were included in this study. In the follicular phase patients were subjected to an oral glucose tolerance test (OGTT); 2 days later they underwent a GHRH test. Basal plasma concentrations of gonadotrophins, steroids and sex hormone-binding globulin were measured. Insulin and GH were assayed under the OGTT and GHRH test respectively. Based on the insulin response to OGTT in the PCOS group, nine patients were classified as normoinsulinaemic and 16 as hyperinsulinaemic; none of the patients of the control group had a hyperinsulinaemic response to OGTT. Obese patients showed a trend towards a lower GH response to GHRH. Moreover, hyperinsulinaemic patients showed a significantly (P < 0.05) lower area under the curve for secretion of GH (AUC-GH) as compared to normo-insulinaemic patients. All PCOS patients exhibited a markedly decreased response of GH to GHRH compared with the control population. Obese and hyperinsulinaemic PCOS patients were both found to have a lower response of GH to GHRH than all other groups. Despite the fact that obesity and hyperinsulinaemia have an additive influence on the impairment of GH secretion, our results suggest that other factors may also negatively affect GH secretion in PCOS.

Adult↗

Epidermal growth factor receptors in placentae and fetal membranes from hypertension-complicated pregnancies.

Epidermal growth factor receptor concentrations (EGFR) in placentae and fetal membranes from 25 normal and 25 hypertension-complicated pregnancies were analysed by a radioreceptor technique. Higher EGFR concentrations were found in placentae from hypertension-complicated pregnancies than in those from normal pregnancies (median 125.0 fmol/mg protein, range: 33.4-190.7 versus median 50.3 fmol/mg protein, range 21.4-184.0) (P = 0.0002). EGFR concentrations were significantly lower in fetal membranes than in placental tissue, both in normal membranes (median 31.7, range 4.8-92.0 versus median 50.3, range 21.4-184.0) (P = 0.0004) and in hypertension-complicated pregnancies (median 65.0, range 16.8-125.0 versus median 125.0, range 33.4-190.7) (P = 0.0001). A statistically significant inverse correlation between EGFR concentrations and gestational age was found in placentae (r = 0.53, P = 0.0061) and fetal membranes (r = 0.56, P = 0.0032) from hypertension-complicated pregnancies. Multiple regression analyses demonstrated that hypertensive disease is more closely associated with EGFR concentrations than gestational age and fetal weight in placental tissue and fetal membranes. Our findings suggest that hypertensive disorders in pregnancy are associated with elevated EGFR concentrations in both the placenta and fetal membranes.

Epidermal Growth Factor↗

Somatostatin action on rat ovarian steroidogenesis.

To date, very few studies on the effect of somatostatin on female reproductive function have been reported. In our study, we examined the effects of somatostatin on (i) androgen biosynthesis using whole ovarian dispersates, and (ii) aromatase activity and progesterone production using granulosa cells. Whole ovarian dispersates obtained from immature rats were cultured for 96 h in serum-free medium with human chorionic gonadotrophin (HCG; 25 ng/ml) and insulin (10 micrograms/ml) in the presence or absence of an increasing concentration of somatostatin (0.03-3.00 ng/ml). HCG- and insulin-stimulated accumulation of androsterone by these cells was inhibited significantly by somatostatin. Granulosa cells from diethylstilbestrol-treated rats were cultured for 48 h in serum-free medium with follicle-stimulating hormone (FSH; 20 ng/ml) and FSH plus insulin (1 microgram/ml) with or without somatostatin (0.03-3.00 ng/ml). Both aromatase activity and progesterone production stimulated by FSH and FSH plus insulin were significantly inhibited by somatostatin. Somatostatin by itself (1 ng/ml) did not have an effect on any of the evaluated parameters. The action of somatostatin could be immunoneutralized and did not influence the plated viable cell mass. These findings indicate that somatostatin can regulate ovarian steroidogenesis by mediating gonadotrophin and growth factor action on different ovarian cell types.

Androgens↗

Effect of opioid blockade on insulin metabolism in polycystic ovarian disease.

A total of 17 women affected by polycystic ovarian disease (PCOD) were studied to evaluate the involvement of endogenous opioids in the pathophysiology of the hyperinsulinism in PCOD by administering naltrexone, an oral opioid antagonist. An oral glucose tolerance test (OGTT) was performed at baseline (on day 5 of the cycle) and repeated after 6 weeks of naltrexone administration. Plasma glucose, insulin and connecting peptide (c-peptide) concentrations were evaluated in all samples. Based on their insulinaemic response to OGTT, patients were classified as hyperinsulinaemic or normoinsulinaemic. Naltrexone treatment significantly (P < 0.007) reduced the insulin response to OGTT in the hyperinsulinaemic group without affecting the c-peptide incremental area; in the normoinsulinaemic group there was a slight, but not significant, increase in both c-peptide and insulin incremental areas. The two groups showed similar c-peptide incremental areas after naltrexone treatment. There was no significant difference in the c-peptide:insulin incremental areas molar ratio between the two groups; after treatment, a significant increase in this ratio was observed in both groups. When we considered the data as an expression of the fractional hepatic extraction of insulin, we found a lower value for hyperinsulinaemic in comparison with normoinsulinaemic patients (not significant), and a significant (P < 0.01) improvement of this parameter in the hyperinsulinaemic group after naltrexone administration. In conclusion, we suggest that the contribution to hyperinsulinaemia in PCOD patients may be at least in part due to both increased pancreatic secretion and reduced hepatic removal of insulin. Chronic pharmacological inhibition of opioid tone could improve the insulin plasma concentration by acting chiefly on the liver metabolism of insulin in hyperinsulinaemic patients.

Adolescent↗

False diagnosis of distal tubal occlusion in case of tubal diverticula.

A 28-year-old infertile patient with a diagnosis of bilateral distal tubal occlusion made at hysterosalpingography and laparoscopy was found at a second laparoscopy to have bilateral single diverticula in patient tubes. The patient conceived an intrauterine pregnancy 5 months after discharge. This report casts doubt on the suggested association between tubal diverticula and infertility.

Adult↗

Evidence of a distinct derangement of opioid tone in hyperinsulinemic patients with polycystic ovarian syndrome: relationship with insulin and luteinizing hormone secretion.

Recent data indicate that an altered opioid tone could be involved in the LH hypersecretion and metabolic alterations seen in polycystic ovary syndrome (PCOS). The aim of the present study was to investigate the presence of a common mechanism of action of opioids on altered insulin and gonadotropin release in patients suffering from PCOS. Twenty-eight women affected by PCOS and 8 normal ovulatory women were studied; an oral glucose tolerance test (OGTT) and GnRH tests were performed during the follicular phase before and after 6 weeks of naltrexone treatment (50 mg/day, orally). Plasma levels of sex hormone-binding globulin and steroids were assayed in the basal samples, whereas FSH and LH were analyzed during the GnRH stimulus. Insulin and glucose were assayed by the OGTT. Based on the insulinemic response to OGTT, 17 women were classified as hyperinsulinemic and 11 as normoinsulinemic. No difference in glucose and hormone plasma concentrations was observed before and after naltrexone treatment in both groups. Only basal sex hormone-binding globulin values were higher in normoinsulinemic compared to hyperinsulinemic subjects. Administration of the opioid antagonist significantly reduced the insulin response to OGTT only in the hyperinsulinemic group. No difference were found in the LH increment after the GnRH stimulus in both group of patients before treatment; on the contrary, naltrexone administration reduced the LH response to GnRH in hyperinsulinemic women but failed to be effective in normoinsulinemic subjects. Only 5 patients showed no concordance of drug-induced changes in insulin and LH secretion. In control subjects, naltrexone failed to have any effect on insulin or LH secretion. These data support the involvement of endogenous opioids in the regulation of insulin and LH secretion in a specific group of PCOS patients exhibiting an exaggerated insulin response to OGTT.

Adult↗

Guidelines for the use of zidovudine in pregnant women with HIV infection.

Zidovudine therapy seems to be effective for reducing vertical transmission of HIV infection and preventing paediatric AIDS. Besides those cases in which it is indicated, zidovudine plays an important role in safeguarding maternal well-being. Even though no data indicating teratogenic effect of this drug exist, its use during the first trimester should be limited to those cases where it is absolutely indicated. All undergoing this therapy should be informed that no information regarding the long term effects of this drug are available yet. Further controlled studies are necessary if this drug is to be used in those cases where it could actually be of benefit.

Female↗

High-dose chemotherapy with autologous peripheral stem cell support in advanced ovarian cancer.

Twenty patients with advanced (stage III-IV), previously untreated ovarian carcinoma were treated by: (a) induction chemotherapy (40 mg/m2 cisplatin, days 1-4; 1.5 g/m2 cyclophosphamide, day 4; every 4 weeks for two cycles) followed by (b) intensification chemotherapy (100 mg/m2 cisplatin, day 1; 650 mg/m2 etoposide, day 2; 1.8 g/m2 carboplatin, day 3). Eligibility criteria further included: age less than 55 years, moderately good to poor tumour grade, macroscopic (> 0.5 cm) residual tumour. Autologous peripheral stem cells were recruited after the induction cycles and, to ensure haematological support, autologous bone marrow harvesting was routinely performed in the first 14 cases. Haematological support consisted of autologous peripheral stem cells and autologous bone marrow transplant in 16 and four patients, respectively. All patients are evaluable for toxicity and 19 for pathological response, one being dead of systemic mycosis 35 days after the autologous bone marrow transplant. Severe extra-haematological toxicities were the following: gastrointestinal (100%), neurological (10%), hepatic (10%). Pathological response was detected in 84% of cases (CR 37%, microscopic PR 26%, macroscopic PR 21%). Median follow-up times of 48 and 41 months have been reached respectively from enrolment and second-look. Four-year 62% overall and 57% progression-free survivals have been reached. Ten patients are still alive with NED (six of seven with CR, three of five with microscopic PR, and one of four with macroscopic PR). Autologous peripheral stem cell transplant significantly reduced the duration of aplasia compared with autologous bone marrow transplant, and toxicity was proved to be manageable in those patients undergoing autologous peripheral stem cell transplant. The prolonged disease-free survival in patients showing CR and microscopic PR suggests that further investigation on this new approach is worthwhile.

Adult↗