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Biomedical subjects

S Mancuso

Publications and source records attributed to S Mancuso.

At least 325 records · Page 18Linked to original sources

Analysis of 138 consecutive ovarian cancer patients: incidence and characteristics of familial cases.

Eight families with two or more first-degree relatives affected with ovarian carcinoma were identified among a series of 138 consecutive ovarian cancer patients. History of breast cancer was reported in six of the eight families. Five of 19 patients with familial cancer developed ovarian cancer as a second primary tumor following breast carcinoma, whereas only 6/130 sporadic cases had a previous history of breast cancer. No significant difference was detected in clinical and pathological features between sporadic and familial cases. However, in three high-risk families ovarian cancer tended to develop at a younger age compared with other familial cases and with sporadic occurrences, and nulliparity was less frequent in the familial group. These observations emphasize the need to take into account multiple factors-in addition to positive family history-for the evaluation of genetic predisposition to ovarian carcinoma.

Carcinoma↗

Steroid hormone receptors in carcinoma of the cervix: lack of response to an antiestrogen.

Levels of estrogen (ER) and progesterone (PR) receptors were measured in 81 patients with primary cervical cancer. In 10 patients, receptor levels were evaluated before and after a short course of tamoxifen treatment. Fifty-six percent of cervical tumors contained ER, and 58%, PR. Receptor level and expression were not related to any clinical and histological characteristic. Moreover, both survival time and response to neoadjuvant chemotherapy did not correlate with the presence of ER and PR. Tamoxifen treatment did not influence ER and PR levels. Our results suggest that steroid hormone receptors are of little value in the management of cervical cancer, and that in this neoplasia, ER is probably not functional.

Antineoplastic Agents↗

High prevalence of silent chlamydia colonization of the tubal mucosa in infertile women.

Thirty-four asymptomatic infertile patients without distal tubal occlusion were prospectively evaluated at laparoscopy for C. trachomatis infection. Samples were collected from the urethra, the cervical canal, the endometrium, the cul-de-sac peritoneal fluid and the endosalpinx. In 8 patients (24%), C. trachomatis was isolated from at least one site. In 6 patients C. trachomatis was isolated from at least one tube, demonstrating the possibility of silent chlamydial colonization of the tubal mucosa in the absence of signs of active pelvic infection.

Chlamydia Infections↗

Serum CA-125 levels do not depend on ovarian steroidogenesis.

To investigate the relationship between CA-125 production and ovarian steroidogenesis, serum CA-125 levels were evaluated in patients with normal pelvis in different ovarian endocrine situations: (1) during the menstrual cycle, (2) during stimulatory treatment with gonadotropin for the induction of ovulation, and (3) during suppression treatment with gonadotropin-releasing hormone agonists. In spite of the spontaneous or the markedly induced variations of estradiol (E2) or ovarian volume, CA-125 levels remained unvaried in all patients. Moreover, CA-125 serum levels did not correlate with the increasing values of the plasma E2 or ovarian volume. In conclusion, steroidogenetic activity of the ovary is unlikely to affect CA-125 production.

Adult↗

Serum levels of tumour associated glycoprotein (TAG 72) in patients with gynaecological malignancies.

Serum levels of TAG 72 were measured in 726 serum samples from patients with benign and malignant gynaecological conditions in order to evaluate the clinical usefulness of TAG 72 alone or in combination with other tumour markers. Sixty-six per cent of patients with ovarian cancer showed abnormal concentrations of TAG 72 antigen. A good correlation was also found between serial TAG 72 values and the clinical course of disease during chemotherapy and follow-up. In cervical and endometrial cancer abnormal TAG 72 values occurred in 23% and 14% of cases, while none of the patients with breast cancer had abnormal TAG 72 levels. Among patients with benign disease only one out of 12 patients (8%) with benign ovarian tumours and one of 15 patients with uterine fibromyomatosis (7%) showed high TAG 72 serum levels. However, the determination of TAG 72 did not increase the sensitivity of CA 125 and squamous cell carcinoma antigen (SCC), in ovarian and cervical cancer, respectively. The systemic administration of recombinant interferon alpha-2b to 15 patients with ovarian cancer and different basal levels of TAG 72 did not increase serum levels of the antigen.

Adenocarcinoma↗

Inhibitory effect of quercetin on OVCA 433 cells and presence of type II oestrogen binding sites in primary ovarian tumours and cultured cells.

We investigated the effect of the flavonoid quercetin (Q) on the proliferation of the ovarian cancer cell line OVCA 433. Growth experiments demonstrated that Q exerted a reversible dose-dependent inhibition of cell proliferation in the range of concentrations between 10 nM and 10 microM. Two other flavonoids tested, rutin and hesperidin, were ineffective in inhibiting cell growth. Cell cycle analysis showed that the growth inhibitory effect of Q was due to a blocking effect in the GO/G1 phase. Using a whole cell assay with (6.7-3H) oestradiol (3H-E2) as tracer we demonstrated that OVCA 433 cells contain type II oestrogen binding sites (type II EBS). Competition analysis showed that Q competed for 3H-E2 binding to type II EBS while both rutin and hesperidin did not. Appreciable amounts of type II EBS were also detected in seven primary ovarian tumours. Our results suggest that Q may regulate ovarian cancer cell growth through a mechanism involving a binding interaction with type II EBS. This mechanism could also be active in vivo since primary ovarian tumours contain type II EBS.

Cell Division↗

Doppler assessment of fetal blood flow velocity waveforms during acute maternal oxygen administration as predictor of fetal outcome in post-term pregnancy.

The changes in fetal blood flow velocity waveforms during maternal administration of 60% humidified oxygen were assessed by Doppler ultrasonography in 45 post-term fetuses. During oxygen treatment, nine fetuses exhibited temporary increases (24.3 +/- 2.0% [1 standard deviation] above pretreatment values) in the pulsatility index at the level of internal carotid artery. Although no significant changes (2.9 +/- 5.1%) were found in the remaining 36 fetuses. In this former group a higher incidence of emergency cesarean delivery due to fetal distress and more neonatal complications were observed. Also, meconium staining of the amniotic fluid and low 1- and 5-minute Apgar scores occurred more frequently in the group of fetuses who responded to maternal oxygen administration. An increase of at least 20% in the pulsatility index of internal carotid artery during maternal hyperoxygenation may be a useful marker of adverse outcome in post-term fetuses.

Adolescent↗

Pefloxacin in the antibacterial treatment of immunodepressed patients.

Pefloxacin 800 to 1200 mg daily was given for 3 to 20 days, orally or intravenously, to 84 immunocompromised patients. Five patients dropped out because of side effects and 2 for other causes. Treatment efficacy was evaluated in 77 patients, 43 men and 34 women, aged 18 to 80 years. Immunodepression resulted from malignancy in 46 patients, LAS/ARC or AIDS in 28, and from unknown causes in 3. Fifty-eight patients had documented infections (respiratory-tract infections 29, urinary-tract infections 13, septicemia 10, other 6) and 19 had a fever of unknown origin (FUO). Cure or significant improvement of symptoms was achieved in 81% of patients with documented infections and in 74% of patients with FUO. Side effects (mainly gastrointestinal disturbances and skin rash) occurred in 7 patients (8.2%), including dropouts. These results suggest that pefloxacin may be useful for the antibacterial treatment of immunodepressed patients.

Acquired Immunodeficiency Syndrome↗

Antibiotic prophylaxis in gynecological surgery.

A randomized prospective study was undertaken at the Obstetrics and Gynecology Clinic of the Catholic University of Rome in order to evaluate the effectiveness of two wide spectrum antibiotics: mezlocillin and cefotetan. Both drugs were administered 2 g i.v. 15 to 20 minutes preoperatively to allow optimal serum and tissue levels of antibiotic at the moment of bacterial innoculation. 184 patients undergoing elective gynecological surgery for nonmalignant disease were considered eligible for the study (124 pts abdominal hysterectomy, 58 pts vaginal hysterectomy). We found no statistically significant differences between the results obtained with the two drugs.

Adult↗

Insulin secretion in polycystic ovarian disease: effect of ovarian suppression by GnRH agonist.

Nine obese and ten non-obese women with polycystic ovarian disease (PCO), and seven obese and eight non-obese normal women, had an oral glucose tolerance test (OGTT) before and after treatment with GnRH agonist (buserelin 400 micrograms/day s.c. for 8 weeks) in order to investigate the effect of ovarian suppression on their insulinaemic secretion. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), oestradiol (E2), androstenedione (A), testosterone (T), DHEAS, cortisol and insulin (I) were measured at time 0 of OGTT; in all samples of OGTT, E2, T, A and I were also assayed. PCO patients showed higher basal androgen levels than control patients. All subjects showed a normal glycaemic response to OGTT. The mean fasting and areas under the curve (ISA) of plasma I were significantly greater in the obese PCO women than in non-obese PCO, the normal obese and non-obese women. All PCO patients showed significantly higher fasting I and ISA values in respect to all control patients. Hyperinsulinaemic responses were 89% in PCO obese, 30% in non-obese PCO and 29% in obese control patients. After buserelin treatment, these values did not change significantly in respect to pretreatment in all groups, in spite of a significant decrease of androgen secretion. During OGTT, no variations of steroid plasma concentrations were seen in both normal or hyperinsulinaemic PCO patients. The data of this study show that hyperandrogenism, hyperinsulinism and obesity were associated with different modalities in PCO patients and that a marked decrease of androgen secretion did not restore a normal insulinaemic response to OGTT, suggesting that hyperandrogenism does not produce hyperinsulinism.

Adult↗

Synergistic antiproliferative activity of quercetin and cisplatin on ovarian cancer cell growth.

It has been demonstrated that the flavonoid quercetin (3,3',4',5-7-pentahydroxyflavone) (Q) inhibits the growth of several cancer cell lines and that the antiproliferative activity of this substance is mediated by a so-called type II estrogen binding site (type II EBS). We investigated the effects of quercetin and cisplatin (CDDP) alone and in combination on the proliferation of the ovarian cancer cell line OVCA 433. Both drugs exhibited a dose-related growth inhibition in a range of concentrations between 0.01 and 2.5 microM and 0.01 and 2.5 micrograms/ml for Q and CDDP respectively. The combination of the two drugs resulted in a synergistic antiproliferative activity. Two other flavonoids tested, i.e., rutin (3-rhamnosylglucoside of quercetin) and hesperidin [7-b rutinoside of hesperetin (3'-5-3-hydroxy-4-methoxyflavone)] were ineffective both alone and in combination with CDDP. Since both rutin and hesperidin do not bind to type II EBS it can be hypothesized that Q synergizes with CDDP by acting through an interaction with these binding sites.

Antineoplastic Combined Chemotherapy Protocols↗

Type II oestrogen binding sites in acute lymphoid and myeloid leukaemias: growth inhibitory effect of oestrogen and flavonoids.

The presence of oestrogen receptors (ER) and type II oestrogen binding sites (type II EBS) have been investigated by a whole cell assay in seven cases of acute lymphoid leukaemia (ALL) and 16 cases of acute myeloid leukaemia (AML). ER were detected in 6/7 ALL patients with values ranging between 133 and 2268 sites/cell and in 12/16 AML patients with values ranging between 274 and 4197 sites/cell. The apparent dissociation constant (KD) for ER was 0.6 +/- 0.3 nM (mean + SD of 20 cases). All blasts from ALL and AML patients expressed type II EBS at variable levels ranging between 3109 and 239450 sites/cell. The mean KD value for these sites was 18.3 +/- 5.6 nM (mean +/- SD of 23 cases). Specificity experiments demonstrated that type II EBS are oestrogen specific relative to the class of steroid hormones. In addition, the flavonol quercetin was able to compete for [3H]17 beta-oestradiol (E2) binding to type II EBS, the relative binding affinity (RBA) of quercetin being greater than that of diethylstillboestrol (DES). DES and quercetin exerted a dose-dependent inhibition of ALL and AML blast proliferation in the range of concentrations between 10(-8) and 10(-5) M. The RBA of DES and quercetin for type II EBS correlated well with their potency as cell growth inhibitors. Moreover, the flavonols rutin and hesperidin which compete slightly for [3H]E2 binding to type II EBS, were scarcely effective in inhibiting leukaemic cell proliferation. The inhibitory effect of DES and quercetin was not due to a non-specific cytotoxic action since after a 1 d culture period, cell viability did not vary between control and treated cells, being greater than 80%. Our results suggest that high oestrogen concentrations and the flavonol quercetin may inhibit leukaemic blast proliferation through a common mechanism involving a binding interaction with type II EBS.

Adolescent↗

Gonadotrophin releasing hormone agonist (buserelin) in the treatment of endometriosis: changes in the extent of the disease and in CA 125 serum levels after 6-month therapy.

Twenty-two women with endometriosis were treated with the luteinizing hormone-releasing hormone (LHRH) agonist buserelin for 6 months. At second-look laparoscopy the mean score of endometriosis had decreased from 23.1 (SD 17.0) to 17.2 (SD 20.2) (P less than 0.05). CA 125 serum levels decreased from 38.4 (SD 32.2) U/ml at diagnosis to 15.5 (SD 7.0) at second look (P less than 0.005). CA 125 levels correlated at diagnosis with total score of endometriosis (P less than 0.05) and with active score of endometriosis (P less than 0.05), but not with the adhesion score. CA 125 levels were not correlated with endometriosis scores at second look laparoscopy, thus suggesting that mechanisms other than the change in the extent of the disease may be involved in the CA 125 decrease during therapy. CA 125 levels may therefore not be a reliable indicator for monitoring the efficacy of LHRH agonist treatment of endometriosis.

Adult↗

Doppler echocardiographic assessment of time to peak velocity in the aorta and pulmonary artery of small for gestational age fetuses.

The time to peak velocity was measured at the level of the ascending aorta and pulmonary artery by Doppler echocardiography in 38 small-for-gestational age (SGA) fetuses before and during maternal hyperoxygenation. The values were compared to a reference range derived from the study of 142 appropriate-for-gestational age (AGA) fetuses. In the SGA fetuses the time to peak velocity at the level of pulmonary artery was significantly lower and at the level of the aorta significantly higher than in AGA fetuses. During maternal hyperoxygenation the aortic time to peak velocity decreased towards normal range but there was no significant change at the level of the pulmonary artery. These results may indicate variations of aortic and pulmonary pressures in SGA fetuses that can be partially modified by maternal hyperoxygenation and which may be associated with changes in the peripheral resistance of the cerebral circulation.

Aorta, Thoracic↗

Doxorubicin and cyclophosphamide, alternated with bleomycin and mitomycin C as a second-line regimen in advanced ovarian carcinoma resistant to cisplatin-based chemotherapy.

Fourteen patients with advanced ovarian carcinoma (FIGO stages III-IV) resistant to cisplatin were submitted to an alternating regimen with doxorubicin (A), cyclophosphamide (C), bleomycin (B) and mitomycin C (M). All patients had measurable disease on entry into the study. No responses were observed while 3 patients, previously showing no change in cisplatin, had disease stabilization lasting 3, 4 and 6 months, respectively. All but 1 patient died with a median survival from the start of ACBM therapy of 7 months (range 6-11). ACBM-induced toxicity was remarkable with 50% grade II-III myelotoxicity which required a dose reduction in 43%, treatment delays in 64% and treatment discontinuation in 14%. All patients suffered from mild to moderate nausea and vomiting while reversible alopecia was seen in 42.8%. The lack of response and the substantial toxicity observed suggest that the ACBM regimen in the doses and schedule employed is not beneficial in ovarian carcinoma resistant to cisplatin.

Adenocarcinoma↗

Effects of maternal hyperoxygenation on atrioventricular velocity waveforms in healthy and growth-retarded fetuses.

In order to assess whether maternal hyperoxygenation induces modifications of Doppler-measured velocity waveforms across atrioventricular valves, 15 healthy and 15 growth-retarded fetuses were studied in basal conditions and during the maternal administration of 60% humidified oxygen. Recordings were performed at 5-min intervals before, during and after maternal oxygen administration. In basal conditions, growth-retarded fetuses exhibited significantly lower ratios between the velocities during early passive ventricular filling and active ventricular filling (E/A ratio) at the level of both mitral and tricuspid valves when compared to healthy fetuses. Furthermore in healthy fetuses the velocity time integral across the tricuspid valve always slightly exceeded that across the mitral valve, whilst growth-retarded fetuses showed an inversed ratio between these velocities. During oxygen administration no changes were found between the two groups of fetuses with regard to the E/A ratios. Similarly the velocity time integrals were unaffected by oxygen administration in the healthy fetuses. Besides growth-retarded fetuses exhibited significant temporary modifications during oxygen administration as expressed by an increase in the velocity time integral across the mitral valve associated with a decrease of that across the tricuspid. These changes result in an inversion of the ratio between transtricuspid and transmitral velocity time integrals reaching values similar to those of healthy fetuses. Short-term oxygen administration affects the intracardiac flow redistribution present in growth-retarded fetuses bringing it to a pattern similar to that of healthy fetuses whereas the E/A ratios were not affected by the treatment.

Blood Circulation↗

Growth hormone and somatomedin-C secretion in patients with polycystic ovarian disease. Their relationships with hyperinsulinism and hyperandrogenism.

Nineteen women with polycystic ovarian disease (PCO; 9 obese) and 15 normal ovulatory women (7 obese) were studied at their follicular phase. All patients had an oral glucose tolerance test (OGTT) before and after treatment with gonadotropin-releasing hormone (GnRH) agonist (Buserelin 400 micrograms/die s.c. for 8 weeks) to investigate the relationship between ovarian steroidogenesis and insulin and growth hormone (GH) and insulin-like growth factor (SmC) secretion. Luteinizing hormone, follicle-stimulating, estradiol, androstenedione, testosterone, dehydroepiandrosterone sulfate, cortisol, insulin, GH and SmC were measured basally at the time of OGTT. PCO patients showed higher androgen basal levels than control patients. All subjects showed a normal glycemic response to OGTT. The mean fasting level and area under the curve of plasma insulin were also significantly greater in PCO than in control patients (p less than 0.05), while GH and SmC plasma concentrations did not differ between the groups. Despite a considerable decrease in androgens and the similar levels in both PCO and control women, buserelin treatment did not determine any significant changes of insulin and GH-SmC secretion. GH and SmC did not correlate with ideal body weight (IBW), insulin or androgens, whereas insulin correlated with both testosterone and androstenedione levels (p less than 0.05) and with IBW (p less than 0.01); after the buserelin regimen only IBW remained related to plasma insulin (p less than 0.01). In conclusion results of this study confirm that hyperinsulinism is a characteristic picture of PCO and is related in an unclear way with hyperandrogenism and obesity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Transvaginal ultrasound evaluation of myometrial invasion in endometrial carcinoma.

In 20 cases of histologically proved endometrial cancer the depth of myometrial invasion was ascertained by means of transvaginal ultrasound, using a high-frequency endocavitary probe. The sonographic findings were confirmed by histologic examination in 18 of the 20 patients evaluated (90.0%). Transvaginal ultrasound provides a fuller preoperative clinical picture and supplies additional diagnostic information which is invaluable in the choice of therapeutic approach.

Adult↗