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Biomedical subjects

G Ambrosini

Publications and source records attributed to G Ambrosini.

At least 19 recordsLinked to original sources
PubMed2006

Mouse double minute antagonist Nutlin-3a enhances chemotherapy-induced apoptosis in cancer cells with mutant p53 by activating E2F1.

MDM2 is a critical negative regulator of the p53 tumor suppressor protein. Recently, small-molecule antagonists of MDM2, the Nutlins, have been developed to inhibit the p53-MDM2 interaction and activate p53 signaling. However, half of human cancers have mutated p53 and they are resistant to Nutlin treatment. Here, we report that treatment of the p53-mutant malignant peripheral nerve sheath (MPNST) and p53-null HCT116 cells with cisplatin (Cis) and Nutlin-3a induced a degree of apoptosis that was significantly greater than either drug alone. Nutlin-3a also increased the cytotoxicity of both carboplatin and doxorubicin in a series of p53-mutant human tumor cell lines. In the human dedifferentiated liposarcoma cell line (LS141) and the p53 wild-type HCT116 cells, Nutlin-3a induced downregulation of E2F1 and this effect appeared to be proteasome dependent. In contrast, in MPNST and HCTp53-/- cells, Nutlin-3a inhibited the binding of E2F1 to MDM2 and induced transcriptional activation of free E2F1 in the presence of Cis-induced DNA damage. Downregulation of E2F1 by small interfering RNA significantly decreased the level of apoptosis induced by Cis and Nutlin-3a treatment. Moreover, expression of a dominant-negative form of E2F1 rescued cells from apoptosis, whereas cells overexpressing wild-type E2F1 showed an increase in cell death. This correlated with the induction of the proapoptotic proteins p73alpha and Noxa, which are both regulated by E2F1. These results indicate that antagonism of MDM2 by Nutlin-3a in cells with mutant p53 enhances chemosensitivity in an E2F1-dependent manner. Nutlin-3a therefore may provide a therapeutic benefit in tumors with mutant p53 provided it is combined with chemotherapy.

Animals↗
PubMed2006

Oocytes cryopreservation: state of art.

In the present review article we sought to analyze, on the basis of a systematic review, the indications, rationale of oocytes cryopreservation, as well as the techniques that improved the aforementioned procedure in order to higher the pregnancy rate in women undergoing that procedure. Moreover, we pointed out the importance of oocytes cryopreservation in the research field as oocyte banking may be of utmost importance to increase the availability of oocytes for research applications such as genetic engineering or embryo cloning. Oocyte freezing has 25 year of history alternating successes and setbacks. Human oocytes have a delicate architecture but are freezable. Clinical efficiency remains low, but healthy children have been born, indicating that chromosomally normal embryos can originate from frozen oocytes. Freezing protocols are not yet optimal and it is now desirable to combine empirical and theoretical knowledge.

Cryopreservation↗
PubMed2006

Development of an interactive learning tool for teaching rheumatology--a simulated clinical case studies program.

OBJECTIVES: To promote independent self-study involving problem solving and decision analysis in the undergraduate medical curriculum, we have developed a series of interactive web-based clinical case studies. METHODS: An initial needs assessment was performed to determine students' attitudes to e-learning. From these results we designed a series of 30 interactive case studies for delivery from a web-server. RESULTS: A survey of 59 undergraduate students believed that online teaching resources were a useful supplement to existing teaching and they could see a positive use for e-learning. The interactive case studies program was well received by a broad range of respondents (n = 84) of different abilities and backgrounds who felt that the program was realistic and clearly presented in an intuitive manner. CONCLUSIONS: The recent increases in numbers of medical undergraduates, the trend towards student-centred learning and the emphasis on patient-related teaching means a great pressure on teachers and resources in medical schools. The case studies program we have developed was effective and well received by both biomedical and medical students. This approach may provide a way to increase the exposure of students to clinical cases involving interactive diagnostic and treatment procedures, that mimic real-world scenarios, but with fewer resource implications.

Computer Simulation↗
PubMed2005

Radiation dose exposure during cardiac and peripheral arteries catheterisation.

BACKGROUND: Ionising radiation carries an oncogenic risk which is linearly related to the dose. An estimation of the effective dose can be obtained from the measurements of the dose-area product (DAP), which is a measure of stochastic risk and a potential quality indicator. AIM: To assess radiation exposure of patients in a large volume cardiac cath-lab. METHODS: A retrospective analysis of adult cardiac and peripheral percutaneous procedures (April to December 2004) was carried out to determine the DAP and estimated risk of malignancy. We identified 6 groups: Group 1 (n=100, coronary angiography and ventriculography); Group 2 (n=50, carotid stenting); Group 3 (n=50, aortography+coronary angiography+ventriculography); Group 4 (n=100, inferior extremities angiography+predilatation and stenting); Group 5 (n=100, coronary angiography+ventriculography+direct coronary stenting); Group 6 (n=100, coronary angiography+ventriculography+coronary predilation and stenting). Dose-area product meter attached on the X-ray unit was used for the estimation of the radiation dose received by the patient during the procedures. RESULTS: DAP values (mean+/-S.D.) ranged from 41+/-30 Gy cm2 in Group 1 (lowest) to 118+/-89 Gy cm2 in Group 6 (highest). Within each group, individual radiation exposure varies substantially: from 11 to 200 Gy cm2 in Group 1, and from 30 to 733 Gy cm2 in Group 6 patients. Average exposure in a Group 6 patient corresponds to a risk of mortality from a malignancy of about 1 in 1000. CONCLUSION: The radiation dose varies substantially across different types of procedures and up to tenfold within the same procedure. The enhanced knowledge of radiation dose might help the cardiologist to implement radiation sparing procedures eventually minimizing patient and operator radiation hazards in invasive cardiology.

Adult↗
PubMed2005

Hysteroscopic permanent tubal sterilization using a nitinol-dacron intratubal device without anaesthesia in the outpatient setting: procedure feasibility and effectiveness.

BACKGROUND: Hysteroscopic permanent tubal sterilization has recently been introduced, resulting in a non-invasive, safe and effective technique. The aim of this study was to assess the feasibility of outpatient hysteroscopic tubal sterilization using a nitinol-dacron intratubal device without anaesthesia and to assess patient procedure compliance. MATERIALS AND METHODS: We untertook a prospective study of 36 consecutive cases of outpatient hysteroscopic tubal sterilization using a nitinol-dacron intratubal device without anaesthesia. Tubal sterilization was performed by placing the device with the aid of a 5.2-mm continuous-flow operative hysteroscope. At the end of the procedure women were asked to rate the pain experienced on a visual analogue scale (VAS) (0, no discomfort to 100, severe discomfort). Successful device placement was assessed after 3 months by hysterosalpingography and diagnostic hysteroscopy. RESULTS: Successful bilateral placement was obtained in 32 patients (88.9%); in one (2.8%) the placement was monolateral; and in three (8.3%) the procedure failed. Mean operating time was 8.6 +/- 5.3 min. A mean VAS of 36.1 +/- 23.9 was recorded. CONCLUSIONS: The nitinol-dacron intratubal device is safe, appears to be effective long-term, is non-invasive and can be used in the outpatient setting without anaesthesia. Low-level discomfort was experienced by the patients. Limitations of its use include that it is not effective immediately, it is irreversible, it requires special equipment and training, and it is difficult to use in cases of uterine anomalies. We conclude that this method may be offered to all woman asking for permanent tubal sterilization, particularly those who refuse or have contraindications for anaesthesia.

Adult↗
PubMed2005

High fetal urocortin levels at term and preterm labor.

CONTEXT: Placental urocortin has a role in the cascade of events leading to parturition by stimulating myometrial contractility and placental uterotonins secretion. OBJECTIVE: The objective of this study was to evaluate urocortin levels in maternal and fetal [umbilical cord artery (UCA) and vein (UCV)] plasma at term and preterm labor. DESIGN: The study design was a controlled cross-sectional study performed from November 2003 to June 2004. SETTING: This study was performed at the Division of Obstetrics and Gynecology, University of Siena (Siena, Italy). PATIENTS: Plasma samples were collected at term in the absence of labor (TNL; n = 27; 39.3 +/- 0.1 gestational weeks), at term spontaneous vaginal delivery (TL; n = 24; 40.1 +/- 0.2 gestational weeks), and at preterm labor (PTL; n = 19; 32.4 +/- 0.4 gestational weeks). Changes in urocortin mRNA expression were also evaluated in placentas collected from TNL (n = 11), TL (n = 11), and PTL (n = 10). INTERVENTION: Urocortin levels were measured by specific RIA. Changes in placental mRNA expression were determined by real-time quantitative RT-PCR analysis. RESULTS: Maternal and UCA plasma urocortin levels were significantly (P < 0.0001 for all) higher in TL and PTL than in TNL. Furthermore, UCA concentrations were significantly (P < 0.0001 for all) higher than and correlated with maternal concentrations (TNL: r = 0.45; P < 0.05; TL: r = 0.959; P < 0.0001; PTL: r = 0.7719; P < 0.0001). UCV levels were significantly (P < 0.001) higher in TL and PTL than in TNL and were significantly (P < 0.0001 for all) higher than and significantly (P < 0.0001 for all) correlated with maternal values, but were significantly (P < 0.0001 for all) lower than and correlated with UCA values (TNL: r = 0.9548; P < 0.0001; TL: r = 0.927; P < 0.0001; PTL: r = 0.838; P < 0.0001). Placental urocortin mRNA expression did not differ among TNL, TL, and PTL samples. CONCLUSIONS: Fetal urocortin secretion is increased in term and preterm labor. Whether these changes are a consequence rather than a cause of human parturition remains to be addressed.

Corticotropin-Releasing Hormone↗
PubMed2005

The additional risk of malignant mesothelioma in former workers and residents of Wittenoom with benign pleural disease or asbestosis.

AIMS: To examine the hypothesis that people with benign pleural disease or asbestosis have an increased risk of malignant mesothelioma beyond that attributable to their degree of asbestos exposure. METHODS: Former workers and residents of the crocidolite mining and milling town of Wittenoom are participating in a cancer prevention programme (n = 1988). The first plain chest radiograph taken at the time of recruitment into the cancer prevention programme was read for evidence of benign pleural disease and asbestosis, using the UICC classification. Crocidolite exposure of former workers was derived from employment records and records of dust measurements performed during the operation of the asbestos mine and mill between 1943 and 1966. Based on fibre counts, exposure for former residents was determined using duration of residence and period of residence (before and after a new mill was commissioned in 1957) and interpolation from periodic hygienic measures undertaken from personal monitors between 1966 and 1992. Cox proportional hazards modelling was used to relate benign pleural disease, asbestosis, asbestos exposure, and mesothelioma. RESULTS: Between 1990 and 2002, there were 76 cases of mesothelioma (56 of the pleura and 20 of the peritoneum). Cases had more radiographic evidence of (all) benign pleural disease, pleural thickening, blunt/obliterated costophrenic angle, and asbestosis than non-cases. Adjusting for time since first exposure (log years), cumulative exposure (log f/ml-years), and age at the start of the programme, pleural thickening (OR = 3.1, 95% CI 1.2 to 7.6) and asbestosis (OR = 3.3, 95% CI 1.3 to 8.6) were associated with an increased risk of peritoneal mesothelioma. There was no increased risk for pleural mesothelioma. CONCLUSION: The presence of benign pleural disease, in particular pleural thickening, and asbestosis appears to increase the risk of mesothelioma of the peritoneum, but not of the pleura beyond that attributable to indices of asbestos exposure in this cohort of subjects exposed to crocidolite.

Aged↗
PubMed2002

Multimodal treatment with primary single-agent epirubicin in operable breast cancer: 5-year experience of the Michelangelo Cooperative Group.

BACKGROUND: To assess the efficacy of primary single-agent epirubicin (120 mg/m(2) every 3 weeks for three cycles) in reducing tumor burden in operable breast cancer >or=2.5 cm in largest diameter at diagnosis and its effect on the rate of conservative surgery. PATIENTS AND METHODS: A total of 319 eligible patients, who were all candidates for mastectomy, were enrolled on to a multicenter prospective non-randomized study. Tumor response was assessed clinically and pathologically. Relapse-free and overall survival were assessed on major prognostic variables. RESULTS: After primary epirubicin, complete disappearance of invasive neoplastic cells accounted for only 2.6% of patients, but 40% of patients had their primary tumor downstaged to <or=2 cm in diameter. Conservative surgery was performed in 67% of patients. At a median follow-up of 5 years, both primary tumor size at diagnosis (P <0.01) and pathological nodal involvement (P <0.01) significantly influenced treatment outcome. After conserving surgery and breast irradiation, local recurrences accounted for approximately 4% of patients. CONCLUSIONS: This multicenter study confirms that three cycles of full-dose epirubicin can avoid mutilating surgery in a high proportion of patients with tumors not amenable to primary conservative surgery. This multimodal treatment can be safely administered outside of clinical trials in patients presenting with large tumors and with a desire to preserve their body integrity.

Adult↗
PubMed2002

Utility of bipolar electrocautery scissors for cervical conization.

OBJECTIVE: To evaluate the usefulness of bipolar electrocautery scissors for cervical conization. METHODS AND MATERIALS: Forty patients with severe dysplasia/in situ carcinoma of the uterine cervix underwent cervical conization: 20 randomly selected patients were operated on with the unipolar energy scalpel and the other 20 were operated on with bipolar electrocautery scissors. In both groups operating time, number of ligations, blood loss, duration of recovery, perioperative complications and adequacy of the margins of the lesion were assessed. Data were compared by analysis of variance. RESULTS: In the bipolar group the average operating time and duration of recovery were significantly reduced (halved), no ligations were needed and the amount of blood loss was significantly reduced. Regarding perioperative complications, in the bipolar group there were no hemorrhages nor need of a second operation or transfusion. Infections did not occur in either group. We found no difference between the two groups regarding adequacy of the margins of the lesion for a good pathologic examination. CONCLUSION: Bipolar electrocautery scissors were safe and useful in cervical conization by reducing the operating time and blood loss without increasing postoperative morbidity.

Adult↗
PubMed2002

Intracystic evaluation of tumor markers in benign and malignant ovarian pathology.

OBJECTIVE: To evaluate, in patients with benign and malignant ovarian cysts, serum samples and ovarian intracystic fluids for the presence of tumor markers such as CA 125, CA 15.3, tissue polypeptide antigen (TPA), CA 19.9 and the carcinoembryonic antigen (CEA). MATERIAL AND METHOD: We studied overall 64 patients with ovarian pathology. Sixteen patients were affected by functional cysts, 28 women by benign cystic tumors and 20 by cystoadenocarcinomas. RESULTS: Average serum levels of all but CA 15.3, TPA and CEA tumor markers of benign cystic ovarian tumors were higher than those of functional cysts. All but CA 19.9 mean intracystic fluid markers levels were more elevated in benign tumors than in functional cysts. In patients with malignant cystic tumors, all but CEA mean serum marker levels were higher than those of benign tumors; furthermore even all mean intracystic levels of markers were more elevated than those of benign tumors. CONCLUSION: This study confirmed the high positivity of tumor markers such as CA 125, CA 15.3, TPA, CA 19.9 and CEA in both the serum and intracystic fluid of patients with malignant epithelial ovarian tumors.

Adolescent↗
PubMed2001

Phase II study of sequential administration of docetaxel followed by doxorubicin and cyclophosphamide as first-line chemotherapy in metastatic breast cancer.

PURPOSE: To evaluate the feasibility and efficacy of a sequential administration of four cycles of docetaxel (100 mg/m(2) every 3 weeks) followed by four cycles of doxorubicin and cyclophosphamide (AC; 60/600 mg/m(2) every 3 weeks), with subsequent consolidation with docetaxel or AC, as first-line chemotherapy in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Forty-eight patients received 443 cycles of chemotherapy (median, 11 cycles/patient; range, 1 to 13 cycles). A total of 267 cycles of docetaxel (60.3%) and 176 of AC (39.7%) were given. Consolidation therapy was given to 33 patients (29 with docetaxel). RESULTS: Grade 4 neutropenia was the most frequent toxicity (83% of patients). This was not cumulative and was rarely complicated by febrile neutropenia or severe infection. The nonhematologic safety profile was favorable: there were no grade 4 adverse events, and grade 3 episodes were infrequent. Docetaxel-specific toxicities were generally not severe. With a median cumulative doxorubicin dose of 397 mg/m(2) (range, 150 to 543 mg/m(2)), two incidences of unrelated congestive heart failure after further treatment with anthracyclines and two of asymptomatic left ventricular ejection fraction decrease were observed. Among the 42 assessable patients, five (12%) had complete and 25 (60%) had partial responses, for an overall response rate of 71% (95% confidence interval, 55% to 84%). Median duration of response was 53 weeks (range, 12 to 72 weeks), and median time to progression was 46 weeks (range, 3 of 72 weeks). With a median follow-up of 40.4 months, median survival was 32 months (range, 2 to 55 months). CONCLUSION: This docetaxel-based sequential schedule is safe and effective in first-line therapy for MBC, without incurring cumulative toxicity, and provides a feasible chemotherapeutic option in this clinical setting.

Adult↗
PubMed2001

Evidence for local production of inhibin A and activin A in patients with ovarian endometriosis.

OBJECTIVE: To evaluate the expression of inhibin A and activin A in ovarian endometriosis. DESIGN: Uncontrolled cross-sectional study and controlled prospective in vitro study. SETTING: Academic health centers in Siena, Udine, Sassari, and Milan, Italy. PATIENT(S): A group of women (n = 19) who underwent laparoscopic excision of ovarian endometriotic cysts. INTERVENTION(S): Specimens of serum, peritoneal fluid, and cystic fluid, ovarian tissue for immunohistochemistry, and endometriotic cells for primary culture were collected. Cell cultures were also prepared from proliferative endometrium of women without endometriosis. MAIN OUTCOME MEASURES: Dimeric inhibin A and activin A concentrations in biological fluids; immunostaining of alpha and betaA subunits in ovarian endometrioma; alpha and betaA gene expression in cultured endometriotic cells compared with normal endometrium. RESULT(S): Inhibin A and activin A concentrations in the cystic fluid were slightly higher than in peritoneal fluid and significantly higher than in serum (P<.05). Immunoreactive alpha and betaA subunits were strongly expressed both in the epithelial and stromal components of ovarian endometrioma. The relative abundance of betaA mRNA was significantly decreased in endometriotic cells compared with eutopic stromal cells. CONCLUSION(S): The results of the present study provide evidence for a local production and secretion of inhibin A and activin A in ovarian endometriotic cysts.

Activins↗
PubMed2001

Determining the best catheter for sonohysterography.

OBJECTIVE: To compare the characteristics of six different catheters for performing sonohysterography (SHG) to identify those that offer the best compromise between reliability, tolerability, and cost. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): Six hundred ten women undergoing SHG. INTERVENTION(S): We performed SHG with six different types of catheters: Foleycath (Wembley Rubber Products, Sepang, Malaysia), Hysca Hysterosalpingography Catheter (GTA International Medical Devices S.A., La Caleta D.N., Dominican Republic), H/S Catheter Set (Ackrad Laboratories, Cranford, NJ), PBN Balloon Hystero-Salpingography Catheter (PBN Medicals, Stenloese, Denmark), ZUI-2.0 Catheter (Zinnanti Uterine Injection; BEI Medical System International, Gembloux, Belgium), and Goldstein Catheter (Cook, Spencer, IN). MAIN OUTCOME MEASURE(S): We assessed the reliability, the physician's ease of use, the time requested for the insertion of the catheter, the volume of contrast medium used, the tolerability for the patients, and the cost of the catheters. RESULT(S): In 568 (93%) correctly performed procedures, no statistically significant differences were found among the catheters. The Foleycath was the most difficult for the physician to use and required significantly more time to position correctly. The Goldstein catheter was the best tolerated by the patients. The Foleycath was the cheapest whereas the PBN Balloon was the most expensive. CONCLUSION(S): The choice of the catheter must be targeted to achieving a good balance between tolerability for the patients, efficacy, cost, and the personal preference of the operator.

Adult↗
PubMed2001

Ultrasound-guided mammotome vacuum biopsy for the diagnosis of impalpable breast lesions.

OBJECTIVES: To assess the diagnostic accuracy of ultrasound-guided mammotome vacuum biopsy in impalpable breast lesions. METHODS: Seventy-three patients who presented with impalpable breast lesions that were suspicious for malignancy at mammography and/or sonography were included in the study. In the first instance the women underwent ultrasound-guided fine-needle aspiration cytology, then, 3 days later, histological biopsy with an ultrasound-guided mammotome device. The patients with both cytological and histological diagnoses of malignancy underwent surgery; those with a negative (for malignancy) cytological diagnosis, but with a histological diagnosis of atypical hyperplasia or sclerosing adenosis, underwent surgical biopsy. RESULTS: The diagnostic accuracy of fine-needle aspiration cytology was 67.2%; the sensitivity was 86.7%, the specificity was 48.4%, the negative predictive value was 78.9% and the positive predictive value was 61.9%. In comparison, the diagnostic accuracy of histological sampling by mammotome vacuum biopsy was 97.3%; the sensitivity was 94.7%, the specificity was 100%, the negative predictive value was 94.6% and the positive predictive value was 100%. Thus there was a statistically significant difference in diagnostic accuracy between fine-needle aspiration cytology and mammotome vacuum biopsy (67.2% vs. 97.3%; chi2 test, P < 0.001). The 2.7% (2/73) failure rate of mammotome biopsy was likely to be due to an error in the positioning of the needle. The subsequent surgical biopsy proved that two cases, negative for malignancy by mammotome biopsy, were in fact malignant. CONCLUSIONS: Our data confirm the value of sonography for the diagnosis of breast carcinoma in the preclinical phase and the efficacy of ultrasound sampling using a mammotome device to confirm the diagnosis in impalpable breast lesions.

Adult↗
PubMed2001

Umbilical artery pulsatility index in pregnancies complicated by insulin-dependent diabetes mellitus without hypertension.

OBJECTIVE: In a group of diabetic pregnant women, the umbilical artery pulsatility index (PI) was compared with both pregnancy complications and perinatal outcomes. METHOD: We evaluated 67 women with pregnancies complicated by insulin-dependent diabetes mellitus (IDDM), without hypertension. For the study we took the last umbilical PI value before delivery into consideration. Doppler results were not used for patient management. Umbilical artery PI was correlated with the route of delivery and the following perinatal complications: intrauterine growth retardation; cesarean sections for acute fetal distress; respiratory distress syndrome (RDS); neonatal hyperbilirubinemia; hypocalcemia; hypoglycemia; macrosomia, and neonatal intensive care unit (NICU). RESULTS: Among the 67 diabetic patients enrolled in this study, 44 (66%) had umbilical PIs ranging from the 5th to the 95th percentile (PI mean +/- SD = 1.2 +/- 0.3), while 23 (34%) had PIs above the 95th percentile (PI mean +/- SD = 1.6 +/- 0.3). Among the group with pathologic umbilical PIs, analysis of the data revealed a significantly higher incidence of both cesarean sections for acute fetal distress and perinatal complications: RDS; hyperbilirubinemia; hypoglycemia, and the need for NICU, respectively. CONCLUSION: In 34% of the diabetic pregnant women without hypertension, we found increased vascular resistances. Among these patients the incidence of perinatal complications was higher, and both closer maternal metabolic control and stricter care of fetal conditions are needed.

Cesarean Section↗