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Biomedical subjects

S Mancuso

Publications and source records attributed to S Mancuso.

At least 289 records · Page 16Linked to original sources

Differential androgen response to adrenocorticotropic hormone stimulation in polycystic ovarian syndrome: relationship with insulin secretion.

OBJECTIVE: To investigate the relationship between insulin and adrenal androgens in patients with polycystic ovarian disease (PCOD). DESIGN: Patients with PCOD and a group of volunteers who attended the department during a period of 6 months were studied. SETTING: Department of Gynaecology and Obstetrics, Università Cattolica del Sacro Cuore, Roma, Italy. PARTICIPANTS: Healthy women with ovulatory cycles (hospital personnel, n = 8) and women affected by PCOD (n = 32) were studied on day 5 to 6 of their follicular phase. INTERVENTIONS: All women had an oral glucose tolerance test (OGTT) (75 g) on day 5 to 6 of the cycle. Then plasma samples were collected at 7.00 A.M.; at 11.00 P.M., 2 mg of dexamethasone (DEX) were orally administered with blood samples collected the day after at 7.00 A.M. (effect of DEX). Then adenocorticotropic hormone (ACTH, Synacten; Ciba-Geigy, Varese, Italy) 250 micrograms was injected intravenously (IV) and samples collected 60 minutes later (effect of ACTH). MAIN OUTCOME MEASURES: Plasma glucose and insulin concentration were assayed on OGTT samples collected at time 0, 30, 60, 90, 120, 180, and 240 minutes after glucose ingestion. Data are expressed as area under the curve. Cortisol, 17 alpha-hydroxyprogesterone (17-OHP), testosterone (T), androstenedione (A), and dehydroepiandrosterone sulphate (DHEAS) plasma levels were evaluated on the samples collected before and after DEX or ACTH administration. Data are expressed as absolute concentrations and percent increase in respect to values before the treatment. RESULTS: According to the OGTT response, 21 patients were classified as hyperinsulinemic and 11 as normoinsulinemic. The ideal body weight was greater in hyperinsulinemic patients. No differences in baseline hormone levels were found between the two groups. Only sex hormone binding globulin levels were significantly greater in normoinsulinemic patients (P less than 0.05). Also, the plasma concentration of all steroids after DEX were similar in both groups. Intravenous injection of ACTH significantly increased plasma androgens levels. Cortisol, DHEAS, and T enhancement did not differ in normoinsulinemic and hyperinsulinemic patients, whereas significantly greater A (P less than 0.01) and 17-OHP (P less than 0.05) plasma concentrations were observed after ACTH injection in hyperinsulinemic when compared with normoinsulinemic PCOD subjects. Control group after IV ACTH showed an increase of A and 17-OHP similar to those found in normoinsulinemic PCOD group. CONCLUSIONS: These data suggest that insulin could be involved in the androgen production by adrenal gland and it could influence the responsiveness of adrenal to its trophic hormones.

17-alpha-Hydroxyprogesterone↗

Mitomycin C and 5-fluorouracil salvage chemotherapy in platinum-resistant ovarian carcinoma.

Twenty-four patients with progressing or recurrent ovarian carcinoma, all pretreated with cisplatin, were evaluated for response and toxicity to mitomycin C (MMC) and 5-fluorouracil (5-FU) chemotherapy. Eligible patients had histologically proven intra-abdominal disease (67% clinically measurable; 33% nonmeasurable), and 67% of them had progressed on prior platinum-based chemotherapy. WHO response criteria were adopted in patients with measurable disease while those with nonmeasurable lesions were considered as responding in case of nonevident disease and CA-125 values less than 35 U/dl for at least 6 months. All patients received at least 2 treatment courses (median 6, range 2-10), and 5 patients (21%) could be considered as responding: 4/8 (50%) with nonmeasurable and 1/16 (6%) with measurable disease. The overall median survival was 12 months, range 7-30+ (median follow-up: 29.5 months, range 28-30). Progression-free survival was significantly different in responders (15 months) versus nonresponders (3 months) (p = 0.0001). Toxicity was mainly represented by myelosuppression (grade I 29%; II 8% and III 4%). MMC and 5-FU did not show significant activity against large tumor burden, while a relatively good activity was detected in patients with minimal disease. The limited toxicity and possible schedule modifications have to be taken into account for further investigation on selected patients.

Adult↗

Early prenatal diagnosis and therapy of fetal hypothyroid goiter.

We report a case of early diagnosis of iodide-induced fetal hypothyroidism at 22 weeks of gestation, confirmed at 29 weeks by cordocentesis and successfully treated intra-amniotically. The ultrasonographic feature was the presence of two echogenic masses in the fetal neck; polyhydramnios was absent. Mild hypothyroidism was diagnosed based on fetal serum obtained by percutaneous umbilical blood sampling at 29 weeks of gestation. The persistence of fetal hypothyroidism in spite of maternal thyroid improvement was confirmed by a second cordocentesis at 35 weeks of gestation, and a single injection of intra-amniotic levothyroxine (250 micrograms) was performed. The serial ultrasonographic examinations showed disappearance of the fetal goiter. A healthy female baby (3,630 g) was delivered at term. At birth, the thyroid gland was not enlarged, and neonatal thyroid hormones were within the normal range. This case suggests that cordocentesis is a reliable method to assess the fetal thyroid status; moreover a single injection of intra-amniotic thyroxine was effective in treating fetal hypothyroid goiter.

Adult↗

Significance of epidermal growth factor receptor in advanced ovarian cancer.

PURPOSE: The purpose of this study was to investigate the significance of epidermal growth factor receptor (EGF-R) expression in a group of advanced ovarian carcinomas. PATIENTS AND METHODS: The study was conducted on 72 previously untreated patients with International Federation of Gynecology and Obstetrics (FIGO) stage III-IV disease. The median follow-up was 24 months (range, 4 to 75 months). EGF-R was measured by a radioreceptorial assay. A cutoff of 1.5 fmol per milligram of protein was chosen to define EGF-R positivity. Medians and life tables obtained with the Kaplan and Meier method were analyzed by the log-rank test. The risk of progression was estimated by Cox's proportional hazards model. RESULTS: EGF-R was detected in 54% of primary tumors. When EGF-R was analyzed in different tissue specimens of the same tumor, consistent findings were noted in 88% (seven of eight) of cases. A lower concordance rate (nine of 15; 60%) was found between primary tumors and omental metastases, with a tendency toward higher EGF-R levels in the latter. The EGF-R expression did not significantly correlate with age, stage, grading, and residual tumor after primary surgery. In the univariate analysis, stage IV disease, postoperative residual tumor diameter greater than 2 cm, presence of ascites, and EGF-R positivity were found to be significantly associated with a greater risk of disease progression. In the multivariate analysis, only the postoperative residual tumor and the EGF-R expression remained significantly associated with a high risk of progression. CONCLUSION: Data reported here suggest that the presence of EGF-R in advanced ovarian tumor at the time of the primary surgery identifies a subset of patients with a particularly poor prognosis.

Analysis of Variance↗

Multiple serum marker assay in the diagnosis of endometriosis.

Serum levels of CA-125, CA-15-3 and TAG-72 were measured in 81 patients with endometriosis, diagnosed by laparoscopy, and staged according to the Revised American Fertility Society, and in 31 control subjects. The values of CA-125 and CA-15-3 were also determined in peritoneal fluid. The aim of the present study was to evaluate the clinical usefulness of these various markers in the diagnosis of endometriosis by using them either by themselves or combined. High serum levels of CA-125 were found in 43 of 81 patients with endometriosis (53%) and in five of 38 control subjects (13%). The values of serum CA-125 progressively increased in relation to the severity of the disease. High serum values of CA-15-3 and TAG-72 were also found in patients with endometriosis, but with a similar incidence also in control patients. High CA-125 and CA-15-3 values in peritoneal fluid were found in all patients investigated. These results suggest that measurement of serum CA-15-3 and TAG-72 in addition to CA-125, does not provide any advantage for the diagnosis of endometriosis.

Adult↗

Longitudinal evaluation of uterine myoma growth during pregnancy. A sonographic study.

Thirty-six pregnant women with a single uterine myoma were examined by ultrasonography at 2 to 4 week intervals. The initial diagnosis was made in 12 patients before pregnancy and in the other 24 patients between 9 and 12 weeks of gestation. Thirty-four women had a scan 4 weeks after delivery. A reduction in size was observed in puerperium, which may indicate a return to its initial volume. Myoma growth was analyzed in different periods of gestation. An increase in volume during pregnancy was observed in 31.6% of cases. A statistically significant change in volume was noted between the first and the third trimesters (P < 0.001). The greatest increase in volume of myomas occurred before the 10th week of gestation. The relationship between myoma volume and myoma growth in the different gestational periods considered was not statistically significant. On the other hand, when myoma volume was related to complications during pregnancy or at delivery, a statistically significant difference was observed. Myomas with volumes greater than 200 cm3 show a higher rate of complications than those with volumes equal to or less than 100 cm3.

Adult↗

[The US-guided positioning of intraprostatic metal spirals. Preliminary experience].

The authors report their preliminary experience with the insertion of intraprostatic spirals in the treatment of chronic urinary retention due to prostatic hypertrophy in 8 inoperable patients. The value is stressed of transrectal US guidance during spiral insertion together with the advantages of US over other positioning techniques (i.e., better visualization of prostatic urethra and urethral sphincter, real time visualization of spiral progression and correct positioning). All patients were successfully treated without complications; spiral positioning was easier in the patients with a Foley's catheter (22 CH). US-guided positioning of intraprostatic spirals appears an easy and safe treatment of chronic urinary retention in inoperable patients.

Aged↗

Ovulation induction with human menopausal gonadotropin versus follicle-stimulating hormone after pituitary suppression by gonadotropin releasing hormone agonist in polycystic ovary disease. A cross-over study.

Ten patients with polycystic ovary disease (PCOD) had ovulation induction after pituitary suppression by gonadotropin releasing hormone agonist (GnRHa) with GnRHa plus pure follicle-stimulating hormone (FSH) or plus human menopausal gonadotropin (hMG). Duration of the stimulation period and gonadotropin doses were superimposable. A multifollicular response was observed in both treatments. Bioassay and radioimmunoassay of luteinizing hormone, androstanedione and testosterone plasma levels were higher in hMG cycles compared to FSH-treated cycles. No differences was found in FSH and estradiol (E2) plasma concentrations, whereas in hMG-treated cycles the E2/number of follicles and E2/ovarian volume ratios were greater than in the FSH-treated cycles. Clinical results in terms of percentages of ovulation and pregnancies were the same in the two protocols. We conclude that the presence of luteinizing hormone in induction of ovulation in patients with PCOD does not seem to influence follicular recruitment and development, but it may have a role in the enhancement of steroid production.

Adult↗

[Salpingoscopy: a new method for the evaluation of the tubal factors in sterility].

Salpingoscopy is a new endoscopic procedure that allows the direct vision of the tubal mucosa. Therefore, it is able to identify and evaluate intraluminal lesions not detected by hysterosalpingography or laparoscopy. The endoscopic evaluation of the tubal mucosa can predict the possibility of an intrauterine pregnancy or laparoscopic tubal surgery, permitting the selection of patients with the most favourable prognosis. This technique may also have a role in identifying patients at risk for a repeat ectopic pregnancy and patients with silent endosalpingitis.

Endoscopy↗

Anatomical study of para-aortic and pelvic lymph nodes in gynecologic malignancies.

Between January 1986 and June 1990, systematic para-aortic and pelvic lymphadenectomy was performed in 208 women with untreated ovarian, endometrial, and cervical cancers. This study aimed to evaluate the median number of nodes collected from each pelvic and para-aortic group and to verify a new detailed nomenclature for the various lymph node groups. The para-aortic nodes were distinguished as paracaval, precaval, and retrocaval, depending on their relationship with the vena cava. Para-aortic, pre-aortic, and retro-aortic nodes were located close to the aorta. The nodes situated between the vena cava and aorta were designated intercavo-aortic. A median of 26 (range 15-48) para-aortic nodes were collected during ovarian or endometrial cancer operations. The lymphatic system of the pelvis was divided into six groups, depending on the relationship with the pelvic blood vessels. The pelvic nodes were distinguished as common, internal and external iliac, presacral, obturator, and parametrial. In cases of cervical cancer, the median number of pelvic nodes collected was 38 (range 20-88). Such anatomical study of the lymphatic system shows that a higher number of nodes than expected can be found in the retroperitoneum.

Aorta, Abdominal↗

The use of lyophilized collagen in gynaecology.

Collagen plays an important physiological role in the process of wound healing and the possibility of using lyophilized collagen has opened up prospects in surgery. The author reports his experience in gynaecological surgery: myomectomy, vaginal or abdominal hysterectomy and repair surgery for vaginal prolapse with hysterectomy and cystourethropexy. The results obtained suggest the use of lyophilized collagen in the above-mentioned cases and a possible wider application in gynaecological surgery.

Adult↗

Recombinant alpha-2b-interferon dynamic test as a potential tool in predicting disease status during second look in ovarian cancer. A preliminary report.

The circulating levels of a 90-kilodalton (KD) tumor-associated antigen were measured in the blood of 26 patients with ovarian cancer in clinical remission who received a short course of recombinant alpha-2b-interferon (rIFN-alpha-2b, 3 million U/m2/d intramuscularly for 3 days) before second-look procedures. The administration of rIFN-alpha-2b to 90-KD antigen-positive patients produced a slight increase of the marker. However, in patients without the marker but with evidence of disease, a remarkable increase above the cutoff level was observed. Less pronounced modifications of 90-KD antigen serum levels were found in patients with no disease at second look. Moreover, considering the 90-KD antigen mean percentage increase, the dynamic test with rIFN-alpha-2b was able to eliminate five of six false-negative results obtained with the 90-KD antigen basal assay alone. The sensitivity of the assay increased to 92% after IFN compared with 54% for the 90-KD antigen assay alone. An increase (greater than 100% above pretreatment titer) of 90-KD antigen levels during the test also was observed in four patients with no evidence of disease at second look. In two of these false-positive cases, recurrence of disease was observed 13 and 24 months later. At the time of this analysis, none of the patients with a negative second look and negative dynamic test had relapsed. These results suggest that the dynamic test with rIFN-alpha-2b might be a new tool to assess disease status in patients with ovarian cancer before second-look procedures.

Adult↗

Receptors for epidermal growth factor and steroid hormones in primary laryngeal tumors.

The authors investigated the presence of epidermal growth factor (EGF-R), estrogen (ER), progesterone (PR), and androgen (AR) receptors in 42 laryngeal squamous cell carcinomas and 20 normal laryngeal mucosa specimens. EGF-R were expressed in all tumor specimens analyzed, with significantly higher levels in tumor samples compared with normal mucosa (P less than 0.05). The immunohistochemical study demonstrated the presence of EGF-R in basal and parabasal cells of normal mucosa and in most of the cancer cells. There was no correlation between EGF-R and tumor localization or T classification. On the other hand, the authors did find an interesting correlation between EGF-R levels and grading, EGF-R levels being significantly higher in G3 than in G1-G2 tumors. Moreover, the three patients whose tumors expressed the highest EGF-R levels had disease recur within 8 months. Among tumor specimens, 9.5%, 35.7%, and 9.5% expressed very low but detectable ER, PR, and AR levels, respectively. No statistically significant difference was found between the levels of steroid receptors in the tumor and normal mucosa specimens, and neither was there any correlation of ER, PR, and AR with the pathologic findings. The authors' results suggest that the EGF-R system may play a role in regulating the growth of laryngeal cancer. Additional studies should demonstrate whether, as in other tumor types, EGF-R expression may have prognostic significance in human laryngeal cancer.

Adult↗

Quercetin inhibits the growth of a multidrug-resistant estrogen-receptor-negative MCF-7 human breast-cancer cell line expressing type II estrogen-binding sites.

It has been demonstrated that the flavonoid quercetin (3,3',4',5,7-pentahydroxyflavone; Q) inhibits the growth of several cancer cell lines. There is evidence suggesting that the antiproliferative activity of this substance is mediated by the so-called type II estrogen-binding site (type II EBS). We looked for the presence of type II EBS and the effect of Q on the proliferation of an Adriamycin-resistant estrogen-receptor-negative human breast-cancer cell line (MCF-7 ADRr). By whole-cell assay using estradiol labelled with 6,7-tritium [( 3H]-E2) as a tracer, we demonstrated that MCF-7 ADRr cells contain type II EBSs. Competition analysis revealed that diethylstilbestrol (DES) and Q competed with similar potency for [3H]-Es binding to type II EBSs. The antiestrogen tamoxifen (TAM) competed for type II EBSs, albeit to a lesser extent than either DES or Q. Growth experiments demonstrated that Q and DES exerted a dose-dependent inhibition of cell proliferation in the range of concentrations between 10 nM and 10 microM, whereas TAM was less effective. Q could also inhibit colony formation in a clonogenic assay. Our results indicate that multidrug-resistant estrogen-receptor-negative MCF-7 cells express type II EBSs and are sensitive to the inhibitory effect of Q. This substance could be the parent compound of a novel class of anticancer agents.

Binding Sites↗

Low-dose aspirin and vascular response in pregnant patients sensitive to angiotensin II.

The angiotensin sensitivity test was performed in 25 high risk pregnant women before and after administration of low-dose aspirin (100 mg/day for 7 days). After aspirin administration there was a significant decrease in AII sensitivity in sensitive patients with no change in nonsensitive patients. Low-dose aspirin favorably affects sensitivity to AII in sensitive patients, thus indicating a reduced vascular reactivity as a consequence of this regimen.

Angiotensin II↗

High-dose cisplatin and bleomycin neoadjuvant chemotherapy plus radical surgery in locally advanced cervical carcinoma: a preliminary report.

One course of chemotherapy containing cisplatin and bleomycin as a neoadjuvant treatment was given to 26 consecutive patients with previously untreated stage IB (bulky disease)-III cervical carcinoma and followed by radical surgery. After chemotherapy responses were detected in 23 patients (5 complete and 18 partial; overall, 88%) and permitted radical surgery in 21 cases (81%). Surgery consisted of type III-IV radical hysterectomy plus systematic para-aortic and pelvic lymphadenectomy. At histologic examination, complete responses were found in 5 (19%) and partial responses in 16 (62%) cases. The average number of lymph nodes removed was 61 (range, 38-118). A lower than expected incidence of lymph node metastases was detected (2/21, 9.5%). The chemotherapy-induced toxicity was mainly represented by nausea and vomiting. Chemotherapy did not seem to complicate surgery in these circumstances, even though moderate-degree postoperative complications occurred in 48% of cases. Eighteen months median follow-up time (range, 11-23) from hystological diagnosis has been reached in the operated patients, and no recurrences have been detected so far.

Adult↗

Effect of recombinant human interferon-alpha 2b on receptors for steroid hormones and epidermal growth factor in patients with endometrial cancer.

Interferons (IFNs) may modulate oestrogen (ER), progesterone (PR) and epidermal growth factor (EGFR) receptor expression in vitro. ER, PR and EGFR levels in tumour specimens taken from 13 patients with endometrial adenocarcinomas before and after 5 days' intramuscular treatment with 5 x 10(6) U per recombinant human leucocyte interferon-alpha 2b (rh IFN-alpha 2b). After treatment, ER (P less than 0.01) and PR (P less than 0.05) levels were significantly increased with a simultaneous reduction of EGFR content (P less than 0.05). Since the expression of ER and PR characterises more differentiated hormono-sensitive tumours, while EGFR are preferentially expressed in less differentiated tumours, the increase of steroid hormone receptor levels with the reduction of EGFR expression suggests that rh IFN-alpha 2b may induce endometrial cancer cell differentiation. Moreover, the decrease of EGFR levels may explain the antiproliferative effect of IFNs.

Adenocarcinoma↗