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Biomedical subjects

G Bevilacqua

Publications and source records attributed to G Bevilacqua.

At least 127 records · Page 7Linked to original sources
PubMed1993

Multiple endocrine neoplasia type 2A and cutaneous lichen amyloidosis: description of a new family.

Multiple endocrine neoplasia (MEN) 2A associated to cutaneous lichen amyloidosis is a variant of MEN 2A recently reported in few families. We describe an additional family with this syndrome. The skin lesion is a pruritic one, located over the upper back showing, at biopsy, cutaneous amyloid. The propositus of our family was a 35-year-old woman already treated with total thyroidectomy for medullary thyroid cancer and with bilateral adrenalectomy for pheochromocytoma. The patient referred that the skin lesion was present since childhood and increased with time. Skin biopsy showed negative staining for amyloid, for calcitonin and neuron-specific enolase. The paraspinal muscles corresponding to the area of affected skin showed slight neurogenic abnormalities. Ten other members of her family were affected by MEN 2A, three of whom (all females) had the same cutaneous alteration.

Adrenal Gland Neoplasms↗
PubMed1993

3'-Deamino-3'-(2-methoxy-4-morpholinyl)-doxorubicin (FCE 23762): a new anthracycline derivative with enhanced cytotoxicity and reduced cardiotoxicity.

The purpose of this study was to examine the cytotoxicity and cardiotoxicity of the new doxorubicin derivative, 3'-deamino-3'-(2-methoxy-4-morpholinyl)-doxorubicin (FEC 23762). The concentration of FCE 23762 that resulted in a 50% reduction in colony formation of DU 145, COLO 320DM, A549 and A2780 human cancer cell lines ranged from 1.1 and 3.2 nmol/l and was 3-9 times as low as doxorubicin. In the isolated perfused rat hearts, doxorubicin 10(-5) mol/l induced a significant prolongation of S alpha T segment and Q-Fmax interval, and reduction in dF/dtmax and coronary flow while only FCE 23762 10(-5) mol/l induced a widening of QRS complex. Anaesthetised rats given a single intravenous (i.v.) dose of doxorubicin 10 mg/kg showed significant changes in both ECG (S alpha T segment and QRS complex enlargement) and haemodynamic parameters (increase in mean arterial blood pressure and reduction in systemic arterial dP/dtmax), while animals given FCE 23762 (0.1 and 0.3 mg/kg) had a significant increase in QRS complex duration after the highest dose. In the chronic cardiotoxicity study animals receiving FCE 23762 (0.03 mg/kg i.v. once a week for 3 weeks) did not show any significant alteration of ECG and minor changes of cardiac histological picture; by contrast doxorubicin (3 mg/kg i.v. once a week for 3 weeks) induced a severe cardiomyopathy, characterised by progressive widening of S alpha T segment, increase in T wave and histological damage consisting of vacuolations and loss of myofibrils. These results indicate that FCE 23762 is more active in vitro than doxorubicin and markedly less cardiotoxic in vivo at the doses used in the present study.

Animals↗
PubMed1993

Randomized multicentre trial of treatment with porcine natural surfactant for moderately severe neonatal respiratory distress syndrome. The Collaborative European Multicentre Study Group.

A randomized trial comparing outcome of babies treated with a natural surfactant (Curosurf) for moderately severe respiratory distress syndrome (RDS) with corresponding data from babies treated at a more advanced stage of the disease is reported. A total of 182 newborn babies (mean gestational age 29.8 weeks) requiring mechanical ventilation and a fraction of inspired oxygen (FiO2) in the range of 0.40-0.59 for RDS were randomized to immediate ("early") treatment (No = 86) with surfactant (200 mg/kg), or to a control group (No = 96). According to the protocol 49 controls (51%) qualified for a "late" surfactant treatment at an FiO2 requirement of > or = 0.60. In both groups of treated patients administration of surfactant led to a rapid improvement of oxygenation, but the peak value for PaO2 and the variability of the response tended to be lower in babies given immediate treatment. In comparison with the total control group, babies treated immediately had lower incidence of grade III-IV intraventricular hemorrhage (7% vs 18%; p < 0.05), lower mortality (9% vs 23%; p < 0.05), and lower incidence of unfavourable outcome--defined as death or bronchopulmonary dysplasia--(18% vs 34%; p < 0.05) at 28 days. Also significant reductions of time in oxygen > 21% and time on mechanical ventilation were observed. Our data suggest that treatment with surfactant when RDS is moderately severe prevents or reverses the natural progression of the disease in at least 50% of the cases and lowers the risk of serious complications.

Animals↗
PubMed1993

Risk factors for respiratory distress syndrome in the newborn. A multicenter Italian survey. Study Group for Lung Maturity of the Italian Society of Perinatal Medicine.

Risk factors for respiratory distress syndrome (RDS) in the newborn have been evaluated using data from a large survey conducted between 1980 and 1989 in selected periods in eleven perinatal units placed in five Italian regions. A total of 1624 liveborn infants consecutively delivered at the collaborating centers, at delivery 26-37 weeks gestational age and without clinically evident congenital anomalies were included in the survey. All the newborns were followed up to the 28th day of life. A total of 131 newborns (7.8%) developed RDS. Overall 1st-7th and 1st-28th day of life infant mortality rates were 54.8 and 61.6/1,000 livebirths; the corresponding rates in babies who developed RDS were 419.8 and 465.6/1,000 livebirths. The frequency of RDS was higher in males than in females and the corresponding relative risk, RR, was 0.7, with 95% confidence interval, CI, ranging from 0.5 to 0.9. The risk of RDS markedly increased with decreasing birth weight: compared to babies weighing more than 2500 g at birth the RR estimates were respectively 1.4, 4.5, 8.8 and 39.3 in those weighing > 2000-2500 g, > 1500-2000 g, > 1000-1500 g and 1000 g or less. Likewise, compared to babies born between the 35th and the 37th week of gestation, the RR of RDS was 3.3 and 21.5 in those born between the 31st-34th or before the 31st week of gestation. Multiple pregnancy, gestational or chronic diabetes, pregnancy-induced or chronic hypertension and premature rupture of the membranes were not related to the risk of RDS.(ABSTRACT TRUNCATED AT 250 WORDS)

Apgar Score↗
PubMed1992

The NM23 gene maps to human chromosome band 17q22 and shows a restriction fragment length polymorphism with BglII.

The NM23-Hl gene is a putative tumor suppressor gene that may be important in the metastasic process. Recent genetic and immunological data indicate that the NM23-Hl gene encodes a protein with nucleoside diphosphate (NDP) kinase activity. The mapping of NM23-Hl by panels of rodent-human somatic cell hybrids and in situ hybridization showed that the gene is located in human chromosome band 17q22. A two-allele polymorphism with BglII was demonstrated.

Alleles↗
PubMed1992

Ocular myopathy without ophthalmoplegia can be a form of mitochondrial myopathy.

To characterize muscle pathology in 3 cases affected by ocular myopathy with eyelid ptosis and upper facial weakness, but without ophthalmoplegia, light microscopy and ultrastructural study were performed on levator palpebrae, orbicularis oculi and deltoid muscle biopsies. While levator palpebrae proved uninformative because of the massive fibrous degeneration of muscle, orbicularis oculi biopsies showed histochemical and ultrastructural alterations indicating a mitochondrial involvement, resembling that reported in ocular mitochondrial myopathies (OMM). On the other hand very mild aspecific findings were observed in deltoid. We suggest that these cases with ocular myopathy and without ophthalmoplegia should be considered a partial or initial form of OMM.

Adult↗
PubMed1992

Variability of the expression of muscle mitochondrial damage in ocular mitochondrial myopathy.

In this study we comparatively analysed deltoid histochemistry, biochemistry and mitochondrial DNA (mtDNA) in two groups of ten sporadic ocular mitochondrial myopathies (OMM), respectively with and without ragged red fibres (RRF). (1) All but one RRF--patients presented the mild form of OMM with blepharoptosis but without ophthalmoplegia; (2) the occurrence of cytochrome c oxidase deficient (COX-) fibres was significantly higher in the RRF+ group, but four RRF- cases also showed COX- fibres; (3) no difference was observed in biochemical findings between the groups; (4) two RRF- patients without COX- fibres showed mtDNA heteroplasmy; (5) in two RRF- patients without deltoid mtDNA deletion, biopsy of an eyelid muscle showed significant mitochondrial alterations. These results suggest that the expression of a mitochondrial defect can vary and that the absence of RRF in a skeletal muscle biopsy does not necessarily rule out the diagnosis of OMM, if other data support that.

Adolescent↗
PubMed1991

Neoadjuvant chemotherapy, surgery, and postoperative radiation therapy for invasive thymoma.

Between January 1988 and June 1990, seven previously untreated patients with histologically confirmed and clinically staged IIIa invasive thymoma (IT) were enrolled in a prospective, single treatment arm study of neoadjuvant chemotherapy (NC) followed by surgery and postoperative radiation therapy (4600 to 6000 cGy). The NC included three cycles of cisplatin (75 mg/m2 on day 1), epirubicin (100 mg/m2 on day 1), and etoposide (120 mg/m2 on days 1, 3, and 5), every 3 weeks. All patients showed a partial response (greater than 50%) and underwent complete (n = 4) or incomplete (gross [n = 1] or microscopic [n = 2] residual tumor) surgical resection. Histologic examination was negative for two completely resected patients. Projected 2-year survival was 80%; all patients but one currently are alive and disease-free. This approach appeared to be feasible and may be a new therapeutic choice in the management of IT, but its use on a regular basis should be reserved until a larger number of patients and longer follow-up are available.

Adult↗
PubMed1990

Cardiac toxicity and antitumor activity of 4'-deoxy-4'-iodo-doxorubicinol.

The acute and chronic cardiotoxicity as well as the cytotoxicity of 4'-deoxy-4'-iodo-doxorubicinol (I-DXRol), the major metabolite of the doxorubicin (DXR) derivative 4'-deoxy-4'-iodo-DXR (I-DXR), were compared with those of I-DXR and DXR. In the acute study, anesthetized rats received i.v. DXR (10 mg/kg), I-DXR (4 mg/kg), or I-DXRol (4 mg/kg) and were monitored for ECG (S alpha T segment and T wave), systolic (SBP) and diastolic (DBP) blood pressure, the first derivative of the systemic arterial pressure (SA dP/dtmax), and heart rate. Treatments induced a significant widening of the S alpha T segment, but I-DXRol was significantly less toxic than I-DXR or DXR. As compared with control values, DXR induced a marked increase in SBP and DBP and a decrease in SA dP/dtmax, whereas I-DXR and I-DXRol induced modest changes in hemodynamic parameters. In the chronic study, 3 mg/kg DXR given to rats by i.v. bolus once a week for 3 weeks resulted in severe chronic cardiotoxicity that lasted 6 weeks and was characterized by S alpha T-segment widening, T-wave flattening, and severe cardiac histological damage. Doses of 1.2 mg/kg I-DXR and 1.2 and 2.4 mg/kg I-DXRol, given i.v. once a week for 3 weeks, and 3.6 mg/kg I-DXRol given as a single dose were associated with a significant T-wave voltage reduction; I-DXR and 2.4 mg/kg I-DXRol induced significant histological alterations of cardiac tissue as compared with control values, whereas modest alterations of heart tissue were observed after injections of 1.2 and 3.6 mg/kg I-DXRol in three doses and in a single dose, respectively. The cytotoxicity of the three anthracyclines against one glioblastoma cell line and two human small-cell lung cancer lines was similar. Results indicate that the acute cardiotoxicity of I-DXRol is lower than that of I-DXR and DXR, whereas the chronic heart damage is similar to that induced by I-DXR and significantly lower compared than that caused by DXR. Moreover, the cytotoxicity of the metabolite appears to be similar to that of I-DXR and DXR. The lack of additional cardiac toxicity due to I-DXRol further supports the lower overall cardiac toxicity of I-DXR, which retains a cytotoxic activity similar to that of the parent drug.

Animals↗
PubMed1990

Phase II study of high-dose epirubicin in untreated patients with small-cell lung cancer.

Eighteen previously untreated patients with histologically confirmed small-cell lung cancer were treated with high-dose epirubicin (course 1, 100 mg/m2; courses 2-6, 140 mg/m2, day 1), every 3 weeks. Overall response rate was 33% (95% confidence limits, 14-52%), including two complete and four partial responses. The response rates for limited (n = 11) and extensive (n = 7) disease patients were 45% and 14%, respectively. With a median follow-up of 18 months, estimated 2-year survival of all patients was 29% and the median duration of response 18.5 months. The dose-limiting toxicity was myelosuppression, with a median granulocyte nadir of 1,150/mm3; 39% of patients had neutropenic fever. Nausea/vomiting, alopecia, and stomatitis were the most common nonhematological toxicities, usually mild to moderate. Acute cardiac toxicity was unusual and no episodes of congestive heart failure were observed. Cumulative doses of 800 mg/m2 were associated with moderate cardiotoxicity (grade 2), as assessed by endomyocardial biopsy and electron microscopy analysis. These results indicate that epirubicin, at the present doses and schedule, is an active single agent in patients with small-cell lung cancer, with acceptable general and moderate cardiac toxicity.

Aged↗
PubMed1989

Association of low nm23 RNA levels in human primary infiltrating ductal breast carcinomas with lymph node involvement and other histopathological indicators of high metastatic potential.

Expression of a recently identified murine gene, nm23, has been previously proposed to be inversely correlated to tumor metastatic potential in rodent model systems. The present study was designed to investigate whether nm23 RNA was detectable in human tumor tissue, and if it was differentially expressed. nm23 RNA levels in 27 human primary infiltrating ductal breast carcinomas were determined by using Northern blots or in situ hybridization. These data were compared to traditional histopathological indicators of metastatic potential, including the number of involved (tumor bearing) lymph nodes, grade of differentiation, and hormone receptor status. A striking consistency was observed in all tumors from patients with involved lymph nodes. Using Northern blot or in situ hybridizations, all of these tumors expressed low levels of nm23 RNA. Quantitative in situ hybridization on tumors from patients with 0 involved lymph nodes identified two groups: (a) approximately 75% contained high nm23 RNA levels, and (b) 25% contained significantly (alpha = 0.05) lower nm23 RNA levels. Low nm23 RNA levels in the 0 involved lymph node tumors were accompanied by two additional histopathological indicators of high metastatic potential, low nuclear and cytoplasmic estrogen receptor content, and poorly differentiated histological grade. In contrast, none of the high nm23 RNA level tumors were both receptor negative and poorly differentiated. We conclude that nm23 RNA levels are differentially expressed in human breast tumors, and that low nm23 RNA levels are associated with histopathological indication of high metastatic potential. Short term (median follow-up of 16 months) clinical course data were consistent with nm23 RNA levels, in that 2 of 11 low nm23 RNA content patients (including one from the 0 involved lymph node group) developed metastases, while none of the high nm23 RNA patients have experienced recurrent disease.

Biomarkers, Tumor↗