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Biomedical subjects

G Bevilacqua

Publications and source records attributed to G Bevilacqua.

At least 19 recordsLinked to original sources

Methyl group metabolism gene polymorphisms as modifier of breast cancer risk in Italian BRCA1/2 carriers.

BRCA1 and 2 are major cancer susceptibility genes but their penetrance is highly variable. The folate metabolism plays an important role in DNA methylation and its alterated metabolism is associated with cancer risk. The role of allele variants 677T and 1298C (MTHFR gene) and 2756G (MS gene) has been investigated as potentially modifying factors of BRCA gene penetrance, evaluated as age at first diagnosis of cancer, in 484 BRCA1/BRCA2 carriers and in 108 sporadic breast cancer cases as a control group. The genotype analysis has been performed by means of PCR/RFLP's. The analysis of association between a particular genotype and disease risk was performed using Cox Regression with time to breast or ovarian cancer onset as the end-point. The presence of 677T allele confers an increased risk of breast cancer in BRCA1 carriers (P = 0.007) and the presence of 1298C allele confers an increased risk of breast cancer in sporadic cases (P = 0.015).

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

Large needle aspiration biopsy and galectin-3 determination in selected thyroid nodules with indeterminate FNA-cytology.

Thyroid fine-needle aspiration biopsy (FNA)-cytology is widely used for the preoperative characterisation of thyroid nodules but this task is difficult for follicular lesions, which often remain undefined. We propose a strategy for improving the preoperative characterisation of selected follicular thyroid proliferations, which is based on large needle aspiration biopsy (LNAB) and galectin-3 expression analysis. Eighty-five thyroid specimens were obtained by LNAB (20-gauge needles) from thyroid nodules with indeterminate follicular FNA-cytology. Aspirated material was processed as a tissue microbiopsy to obtain cell blocks for both cyto/histo-morphological evaluation and galectin-3 expression analysis, by using a purified monoclonal antibody to galectin-3 and a biotin-free immunoperoxidase staining method. Preoperative diagnosis was compared to the final histology. LNAB and cell-block technique allow a preliminary distinction between nodules with a homogeneous microfollicular/trabecular structure, as frequently observed in tumours, and lesions with mixed normo-micro-macrofollicular architecture, as observed in goitre. Furthermore, LNAB provides optimal substrates for galectin-3 expression analysis. Among 85 cases tested, 14 galectin-3-positive cases were discovered preoperatively (11 thyroid cancers and three adenomas confirmed at the final histology), whereas galectin-3-negative cases were 71 (one carcinoma and 70 benign proliferations at the final histology). Sensitivity, specificity and diagnostic accuracy of this integrated morphologic and phenotypic diagnostic approach were 91.6, 97.2 and 95.3%, respectively. In conclusion, LNAB plus galectin-3 expression analysis when applied preoperatively to selected thyroid nodules candidate to surgery can potentially reduce unnecessary thyroid resections.

Adult↗

MMTV-like sequences in human breast cancer: a fluorescent PCR/laser microdissection approach.

The hypothesis that a retrovirus homologous to the mouse mammary tumour virus (MMTV) is involved in human breast cancer aetiology has fascinated scientists from many years, but it has never been convincingly demonstrated. Renewed interest in this hypothesis developed when an MMTV env gene-like sequence was found in 38% of human breast cancer tissues. Whereas some subsequent studies confirmed these findings, others did not. The main reasons for this discrepancy, among others, are the different sensitivities and technical details of current molecular approaches to the detection of these sequences. This study is an attempt to find sensitive and reproducible conditions capable of detecting MMTV env-like sequence in human samples. To this end, we first developed a fluorescence nested-PCR (FN-PCR) method that was able to detect very low copies of the viral genome, and then screened a panel of 45 frozen breast cancer samples obtained by laser microdissection. The MMTV env gene-like sequence was found in 15 (33%) of the human breast cancers analysed, whereas the same sequence was detectable neither in normal tissues nor in other types of tumour. Sequence analysis revealed 96% homology with the MMTV genome, but no other significant similarities with the human genome. The combined use of frozen material, microdissected cell populations and FN-PCR provides a novel, sensitive, robust, non-radioactive and fast methodology for the molecular detection of human-MTV. This approach might be successfully used in large molecular studies that aim to investigate the hypothesis of a retroviral aetiology of human breast cancer.

Base Sequence↗

Small cell lung cancer.

Small cell lung cancer accounts for 13-15% of all lung cancer worldwide. There has been a decrease in the number of cases, with no clear explanation, except probably to changing in smoking habits in the last two decades. In the early eighties, it became clear that SCLC was an extremely sensitive tumor as to radiation as to chemotheraputic agents. With cisplatinum etoposide combinations or cyclophosphamide, anthracycline and vincristine/etyoposide regimens responses were observed in 50-70%, with 20-30% complete remissions in extensive disease. For limited stage patients chemotherapy associated with thoracic radiation was able to produce a cure rate of 10-20%. The addition of prophylactic brain irradiation to limited stage cases has reduced mortality by a factor of nearly 5%. But despite these early good results no breakthrough came later on, and in the last decade or so, we are still facing this plateau. New agents have recently been included in the therapeutic armamentarium, such as gemcitabine, irinotecan, paclitaxel. This fact has allowed many patients to receive a relatively active second line therapy, but the overall survival remains unchanged. Targeted therapies are undergoing some evaluations, but the data are too premature and so far quite discouraging. At the present time there is a urgent need to improve clinical research in this somehow forgotten disease.

Antineoplastic Agents↗

The sodium-iodide symporter expression in placental tissue at different gestational age: an immunohistochemical study.

BACKGROUND: Iodide (I(-)) is crucial for foetal thyroid function. Foetal iodide results from maternal circulating iodide and from deiodination of iodothyronines within the placenta. The Na(+)/I(-) symporter (NIS) localized in placental cells appears to be involved in iodide exchange. Low NIS expression has been reported in trophoblast cells from the first trimester and pregnancy at term. AIMS: The aim of this study was to examine NIS expression by immunohistochemistry in the major components of human ovular tissue and placenta. MATERIALS AND METHODS: Formalin-fixed and paraffin-embedded specimens of placental tissue from the first trimester and at term were analysed. NIS expression was quantified as percentage of NIS-positive cells/total cells. NIS expression was also evaluated by real-time polymerase chain reaction (RT-PCR) in five first-trimester and five at-term placental specimens. RESULTS: In the first-trimester specimens heterogeneous NIS immunoreactivity was found in cyto-syncytiotrophoblast cells, with a range of NIS-positive cells from 5% to 80% (mean +/- SD 21.85 +/- 23.95), in mesenchymal and endothelial cells from 1% to 40% (14.5 +/- 11.16), in decidual cells from 5% to 40% (10.38 +/- 11.98) and in endometrial glands from 3% to 40% (21.86 +/- 13.93). In specimens from placenta at term, NIS-positive cyto-syncytiotrophoblast cells were between 5% and 40% (mean 17.85 +/- 18.15), mesenchymal and endothelial cells between 1% and 40% (13.67 +/- 12.16), decidual tissue between 5% and 30% (16.43 +/- 9.08), and endometrial glands between 3% and 40% (16.67 +/- 15.27). No significant differences in NIS expression were observed between the first trimester and placenta at term. A similar level of mRNA expression for the NIS gene was obtained by RT-PCR both in ovular material of the first trimester and in placenta at term. CONCLUSIONS: We found NIS to be expressed in various placental and ovular components and its expression to remain constant during pregnancy.

Decidua↗

Reexamination of the Helfrich-Hurault effect in smectic-A liquid crystals.

The Helfrich-Hurault effect is a phase transition that occurs in samples of cholesteric or smectic liquid crystals subject to external electric or magnetic fields. In this paper we analyze the Helfrich-Hurault effect of smectic-A liquid crystals in an electrostatic field taking into account the complete electromechanical coupling. A comparison is made with the results already obtained for the partially coupled case where one takes into account only the effect of the field on the crystal configuration and considering that field unaffected.

Journal Article↗

Coherent population trapping spectra in presence of ac magnetic fields.

Experimental and theoretical investigations are reported on the effects induced by an alternating magnetic field on coherent population trapping resonances. We show that the ac magnetic field produces sidebands of these resonances in such a way that the spectrum observed is similar to those observed via the FM spectroscopic technique. Because of the very narrow linewidth of the resonances, sidebands are resolved even for ac field frequencies as low as a fraction of a kHz. The theoretical model developed, which takes into account a very simple atomic structure, fits the experimental data quite well.

Journal Article↗

Current concepts on the pulmonary surfactant in infants.

Surfactant has been a main topic of neonatology in the last 20 years. Many studies have been conducted since the discovery of its role in the pathogenesis of respiratory distress syndrome and the knowledge on its composition and metabolism has become complex. In this article we review the current concepts of its metabolism, ways of acting, properties of its proteins and activities other than the ability of reducing surface tension within the lung as a basis to understand the development of disease in case of its deficiency.

Fetal Organ Maturity↗

A longitudinal evaluation of the effect of two doses of tibolone on bone density and metabolism in early postmenopausal women.

Tibolone, a steroid with tissue-specific activities, can reduce the bone resorption that takes place after the menopause. The present calcium-controlled, 2-year study aimed to evaluate the effect of two doses of oral tibolone, 1.25 mg and 2.5 mg, on bone loss in early postmenopausal women. The subjects were randomly allocated to one of the three groups, namely tibolone 2.5 mg (n = 30), tibolone 1.25 mg (n = 30) and a control group (n = 30). All subjects received 1000 mg of calcium per day. In the control group, vertebral and femur bone mineral density (BMD) decreased significantly (p < 0.05) after 12 and 24 months. In both tibolone groups, vertebral and femur BMD increased significantly (p < 0.05) increased after 12 and 24 months. In the control group, bone turnover markers (urinary excretion of hydroxyproline/creatinine and plasma osteocalcin levels) remained constant, while in both tibolone groups these markers showed similar significant decreases (p < 0.05) after 12 and 24 months. After 24 months, body weight increased in the control group (p < 0.05), while smaller increments were evident in the tibolone groups. Symptom scores in the control group did not show any significant modification during the study. In contrast, the administration of 2.5 mg tibolone was significantly (p < 0.05) effective in reducing hot flushes and other symptoms. The tibolone 1.25 mg group yielded similar results (even if it was proportionally less efficient) to the higher dose. It is concluded that tibolone is effective, even at lower doses, in relieving climacteric symptoms and preventing a decrease in spine and femur BMD in early postmenopausal women.

Administration, Oral↗

The policy of antenatal corticosteroid administration in Italy vs. other European countries.

OBJECTIVE: To describe antenatal corticosteroid policies in Italy in comparison with other European countries, as inferred by the published data of the EURAIL Study Group (1999). METHODS: The results of a mail survey of departmental policies in Italy and Europe were compared. RESULTS: The survey response rate was similar in Italy and Europe (86% and 81%, respectively); 70.7% of the respondents in Italy and 84% in Europe started antenatal corticosteroids from 24 to 28 weeks' gestation; however, 5% of respondents in Italy started at a gestational age of >34 weeks. The use of multiple antenatal corticosteroid courses was observed in 81% of the units in Italy and 87% in Europe. Betamethasone was the more frequently used drug in Italy. CONCLUSIONS: Antenatal corticosteroids are used frequently in Italy and Europe in accordance with international recommendations, although many differences exist in the mode of administration. In 1999 almost all units used multiple courses, although this may not represent the rule 5 years later, following the publication of a prospective randomized trial that questioned the benefits of multiple courses of antenatal corticosteroids.

Betamethasone↗

Early diagnosis of bacterial infection in the neonate.

The diagnosis of neonatal bacterial infection remains one of the greatest and most tantalizing challenges to neonatologists. At birth it must be based on the history of pregnancy and take into account a number of now well-defined risk factors. In addition, if promptly started, antibiotic therapy can reduce its sequelae and improve the prognosis. However, the number of tests that obstetricians can rely on for the diagnosis of infection is quite limited. Tests of maternal inflammation indicators have a low specificity, culture tests are not immune from the risk of contamination, and the measurement of interleukins in the amniotic fluid and maternal blood serum is not yet routine. Observation of clinical signs therefore remains crucial to neonatologists, at the same time that new and more sophisticated laboratory tests enable them to establish a diagnosis of infection at an increasingly earlier stage. In recent years, several infection markers have been investigated, such as procalcitonin and especially C-reactive protein (CRP). Currently, the measurement of plasma concentrations of interleukins (IL), IL-6 and IL-8 in particular, appears to be one of the most sensitive and specific infection indicators in newborns. Cytokine levels are increased even before infants develop any clinical symptoms and routine laboratory tests turn positive. However, owing to their short half-life, their sensitivity decreases after 12-24 h from the onset of inflammation, increasing the risk of false negatives. Ideally, they should then be used in combination with other inflammation indicators, such as CRP. The measurement of cytokines and other new inflammatory markers might be helpful in the early diagnosis of both early-onset infection (assay in umbilical cord blood) and late-onset infection (serial assays performed during the stay in the neonatal intensive care unit). In spite of their time-consuming techniques, culture tests remain of the utmost importance to plan a targeted treatment; blood culture, in particular, is crucial to the diagnosis of sepsis.

Bacteremia↗

The web survey network of sudden infant death syndrome and apparent life-threatening events in the Emilia-Romagna region.

To survey epidemiology and to study the etiology of sudden infant death syndrome (SIDS) and apparent life threatening events (ALTE) in Emilia-Romagna, a web network was constituted. A regional supervisor and a steering committee plan the action of district and local co-ordinators. They keep contact with the Regional Office of Health Services. District and local co-ordinators collect clinical and laboratory and, in case of SIDS, also autopsy data. Records are communicated to the Regional Supervising Center by on-line software. From these data, future planning of care and of mass information as well as auditing of their efficacy can be carried out. The characteristics of the network that has just started to collect data, as well its future developmental aspects, are discussed.

Epidemiologic Methods↗

Neonatal seizures in preterm infants: clinical outcome and relationship with subsequent epilepsy.

OBJECTIVE: Neonatal seizures are considered an acute manifestation of disturbance of the neonatal brain. Some of them can be considered as neonatal epilepsy. Our goal was to evaluate perinatal risk factors, electroencephalogram (EEG) findings and ictal semeiological characteristics of our newborns with neonatal seizures in order to identify which clinical variables were the most early predictive factors of poor neurodevelopmental outcome and of epilepsy. METHODS: Among all preterm infants consecutively admitted to the neonatal intensive care unit (NICU) of the University Hospital of Parma in the period between January 1999 and June 2003, 28 preterm infants with gestational age<or=36 weeks were selected according to the presence of repetitive neonatal seizures, need of chronic anticonvulsant therapy, more than one EEG performed during the neonatal period, and at least one imaging examination (cerebral ultrasound and/or cerebral magnetic resonance imaging (MRI). These patients were prospectively followed up for at least 6 months to evaluate the clinical outcome. Independent variables considered for analysis included perinatal risk factors, etiology of convulsions, EEG activity and type of seizures. RESULTS: The background EEG activity was the strongest predictive factor of the neurodevelopmental outcome, but status epilepticus (SE) also represented a significant variable associated with poor prognosis and subsequent epilepsy. CONCLUSIONS: EEG activity was predictive of the developmental outcome and allowed identification of the infants with SE, a condition often related to neonatal epilepsy (71.4%, p<0.05).

Electroencephalography↗

Genetic alterations in hereditary breast cancer.

Genetic linkage studies have led to the identification of highly penetrant genes as the possible cause of inherited cancer risk in many cancer-prone families. Most women with a family history of breast/ovarian cancer have tumors characterized by alterations in particular genes, mainly BRCA1 and BRCA2, but also CHK2, ATM, STK11 and others. This paper examines the BRCA1 and BRCA2 genes, focusing on the Italian pattern of mutations. The function of these two genes, classified as tumor suppressors, is linked with key metabolic mechanisms such as DNA damage repair, regulation of gene expression and cell cycle control. The pathological BRCA allelic variants may cause alteration of protein function, transcriptional activity and DNA repair; accumulation of the defects leads to widespread chromosome instability that may be directly responsible for cancer formation. In fact, mutations in BRCA1 and BRCA2, conferring a highly increased susceptibility to breast and ovarian cancer, do not lead to cancer by themselves. The current consensus is that these are 'caretaker' genes, which, when inactivated, allow other genetic defects to accumulate. The nature of these other molecular events may define the pathway through which BRCA1 and BRCA2 act. The BRCA mutation spectrum is complex, and the significance of most nucleotide alterations is difficult to understand. Moreover, the mutation pattern seems to be related to ethnicity. The Italian Consortium of Hereditary Breast and Ovarian Cancer has reviewed 1758 families; 23% have been found to be carriers of pathogenetic mutations in BRCA1 or BRCA2. Founder mutations have been described in geographically restricted areas of Italy; a regional founder effect has been demonstrated in Italy for the mutations BRCA1 5083del19 and BRCA2 8765delAG, and a probable new founder mutation has been characterized in Tuscany. The presence of founder mutations has practical implications for genetic testing.

Adult↗

Inflammatory cells contribute to the generation of an angiogenic phenotype in pancreatic ductal adenocarcinoma.

BACKGROUND: Inflammatory cells contribute to the growth and spread of human malignancies by producing molecules that enhance tumour invasiveness. AIMS: To characterise the inflammatory infiltrate in pancreatic ductal adenocarcinoma and to analyse its contribution to angiogenesis and its prognostic relevance. METHODS: Immunohistochemistry was used to identify inflammatory cells and evaluate the expression of proangiogenic and prolymphangiogenic molecules (vascular endothelial growth factor A (VEGF-A), VEGF-C, and basic fibroblast growth factor (bFGF)) by inflammatory and cancer cells in 137 pancreatic cancers. Intratumorous microvessel density (IMD) was assessed using CD34 as an endothelial cell marker. RESULTS: There were significantly more mast cells and macrophages in pancreatic cancers than in normal pancreas and the number of mast cells directly correlated with the presence of lymph node metastases. However, there was no relation between numbers of infiltrating inflammatory cells and the presence of chronic pancreatitis (CP)-like changes in the parenchyma surrounding the tumour. Double immunostaining revealed that both pancreatic mast cells and macrophages express VEGF-A, VEGF-C, and bFGF. These factors were also expressed in the tumour cells in many cases. The numbers of VEGF-A expressing tumour cells and bFGF expressing tumour and inflammatory cells significantly correlated with IMD. Moreover, tumours with higher IMD had higher numbers of infiltrating mast cells and macrophages. CONCLUSIONS: Mononuclear inflammatory cells of the non-specific immune response are recruited to pancreatic cancer tissues independent of the presence of CP-like changes, may influence the metastatic capacity of the cancer cells, and may contribute to the development of tumours with high angiogenic activity.

Adult↗

An observational study of surfactant treatment in infants of 23-30 weeks' gestation: comparison of prophylaxis and early rescue.

OBJECTIVE: To test the clinical efficacy of exogenous surfactant for treatment of neonatal respiratory distress syndrome (RDS). METHODS: In a retrospective multicenter observational study, data were collected on 987 infants of 23-30 weeks' gestation given surfactant for respiratory problems within 3 h of birth. Obstetric, neonatal and short-term outcome data were retrieved from recording charts and analyzed after subdivision of the sample into two treatment groups: prophylaxis (surfactant within 15 min) and early rescue (surfactant at 16-180 min). RESULTS: A total of 965 infants were eligible for the study: 244 receiving prophylaxis and 721 receiving early rescue. The prophylaxis group had lower gestational ages and birth weights than the early rescue group (p = 0.0001), but were otherwise comparable. Natural surfactants were used in > 90% of infants in both groups. The rates of retreatments and the mean total doses of surfactant were similar in both groups. Babies receiving prophylaxis presented less grade 3-4 RDS than those receiving early rescue (32.4% vs. 53.8%, p = 0.0001). Those requiring prophylaxis also needed lower peak inspiratory pressure and had a shorter duration of oxygen therapy. Mortality and complications were similar between the groups, but babies receiving prophylaxis had less pulmonary interstitial emphysema (p = 0.0006) and periventricular leukomalacia (p = 0.0113) than infants receiving early rescue. CONCLUSIONS: In clinical practice, prophylaxis was preferred in babies with lower birth weights and gestational ages compared to early rescue treatment. Not surprisingly, infants treated with prophylactic surfactant had a lower rate of RDS than the infants treated by early rescue, even though they did not need less surfactant overall.

Biological Products↗