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Biomedical subjects

E Ferrazzi

Publications and source records attributed to E Ferrazzi.

At least 19 recordsLinked to original sources

Deflazacort and fluoximesterone in advanced, pretreated breast cancer.

A very simple, low dose, orally administered regime (10 to 15 mg of fluoximesterone + 6 mg of deflazacort daily for periods of 1 to several months) resulting in mild-acceptable toxicity (essentially some weight gain) determined subjective improvement in 2/3 of 34 evaluable patients (out of 36 treated) and an objective measurable tumor reduction in 1/3, although most patients had been previously treated with chemotherapy and hormone treatment and proved primarily or secondarily refractory. The receptor status at the beginning of fluoximesterone+deflazacort treatment was not known, except in one negative-receptor patient, who responded to the combination after becoming resistant to tamoxifen (see photo). In some patients the condition of hormone refractoriness would suggest a no-treatment policy, but a trial with this regime is always convenient as it may improve both duration and quality of life.

Adult

Doppler velocimetry: critical analysis of umbilical, cerebral and aortic reference values.

Cross-sectional reference standards of the umbilical flow velocity waveforms were investigated from 18 to 38 weeks of gestation on 482 normal pregnancies. A significant decrease in the pulsatility index (PI) and systolic/diastolic (SD) ratio was observed during gestation. This phenomenon was confirmed in a longitudinal study on 150 patients of the same population. The two slopes of cross-sectional and longitudinal data were not significantly different. A bimodal distribution of PI and S/D ratio was observed. Six per cent of data fell above the vast majority of cases. The dimension of the population studied allowed us to consider these findings not as outliers but as an interesting transient phenomenon of very low end-diastolic velocities which can occur in normal fetuses, without concomitant variations on the thoracic aorta and middle cerebral artery. Cross-sectional reference ranges were studied for these vessels on the same population from 26 to 38 weeks of gestation. A significant decrease in the PI of the middle cerebral artery was observed versus a significant increase in the PI of the thoracic aorta. These latter indices could be used to obtain indirect information on the normal redistribution of blood flow in the human fetus in the third trimester of gestation. However, the great variability observed should warn against the risks of a simplistic clinical use of these observations.

Aorta, Thoracic

DNA damage and cytotoxicity induced by metabolites of anthracycline antibiotics, doxorubicin and idarubicin.

This study assessed the ability of major metabolites of two types of anthracycline antibiotics, doxorubicin and idarubicin (4-demethoxydaunorubicin) to damage DNA in mouse fibrosarcoma 935.1 cells. Since DNA lesions by anthracyclines may be mediated by topoisomerase II, we also characterized the ability of the drugs to inhibit this enzyme. The C-13 alcohol and aglycone metabolites of doxorubicin and idarubicin were compared to the parent drugs in terms of induction of DNA single strand breaks measured by filter elution. In whole cells, the maximal DNA strand breakage induced by the C-13 alcohol metabolites was similar to that of their respective parent drugs. In isolated nuclei, however, the alcohol metabolites were two times more potent than the parent drugs. The aglycone metabolites produced very little damage in either whole cells or nuclei. The doxorubicin compounds differed markedly from idarubicin drugs in the way their ability to induce DNA breaks was related to cytotoxic activity. Doxorubicin and doxorubicinol cytotoxic effects (50% cell growth inhibition at 0.2 and 4 microM, respectively) coincided (in terms of drug concentrations) with the induction of significant breakage of cellular DNA. In contrast, the concentrations of idarubicin and idarubicinol needed to produce 50% growth inhibition (0.005 and 0.006 microM, respectively) were about 20 times lower than drug levels that induced significant DNA damage. All six compounds inhibited the catalytic activity of isolated topoisomerase II. While the alcohol metabolites produced this inhibition at concentrations similar to those of their parent drugs (5-10 microM), the aglycones were again much less active.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Role of umbilical Doppler velocimetry in the biophysical assessment of the growth-retarded fetus. Answers from neonatal morbidity and mortality.

We compared umbilical Doppler velocimetry with biophysical parameters, obstetrical management, and neonatal morbidity. The study of 85 pregnancies was prospective and blind both to the obstetric and pediatric staff. Our results show that under the same biophysical diagnosis, ie, abnormal fetal growth, oligohydramnios, and nonreactive cardiotocographics, the prevalence of neonatal morbidity was significantly higher in fetuses with associated abnormal umbilical pulsatility index (PI) in utero. Newborns with abnormal PI were delivered earlier, mostly for fetal indication, and were smaller and more asymmetrical than newborns with a normal PI in utero. The analysis of morbidity for homogeneous classes of weight showed that in the group of newborns between 1500 and 2500 g, newborns with normal umbilical PI did show only metabolic disturbances and one respiratory distress syndrome. On the contrary, newborns of the same gestational age and of the same weight with abnormal PI had more severe morbid episodes. In the class of weight between 1500 and 1000 g not only the severity but also the prevalence of neonatal morbidity was significantly higher in newborns with an abnormal PI in utero. None of the newborns delivered below 1000 g had a normal umbilical PI. Five died in the early neonatal period. Three suffered from mild neuromotor sequelae. Practical consequences of these findings on fetal management are the scheduled frequency of biophysical examinations, which must be closer and on an inpatient basis whenever abnormal, and the interpretation of other abnormal biophysical parameters, which must be considered as more severe whenever associated with an abnormal umbilical velocimetry.

Biophysical Phenomena

Lactate metabolism in normal and growth-retarded human fetuses.

Lactate concentration and oxygen content were measured in 21 normal (AGA) and 34 intrauterine growth-retarded (IUGR) infants at the time of elective cesarean section. Maternal lactate and umbilical arterial and venous lactate concentrations were significantly higher in IUGR infants compared with AGA infants. However, when IUGR patients were subdivided according to pulsatility index (PI) measurements of the umbilical artery, no differences were detected between AGA and IUGR patients with PI less than 4 SD, whereas IUGR patients with PI greater than 4 SD had higher lactate concentrations in maternal arterial blood and umbilical arterial and venous blood from both other groups. There was a significant inverse linear relationship between umbilical arterial lactate concentration and umbilical venoarterial differences for both lactate concentrations and for lactate/oxygen quotients. These relationships were significantly different in IUGR fetuses with PI greater than 4 SD compared with AGA and IUGR fetuses with PI less than 4 SD. AGA and IUGR fetuses with PI less than 4 SD have arterial lactate concentrations less than 2 mM even at low oxygen concentrations (O2 content less than 2 mM, O2 saturations less than 20%). At comparable levels of oxygenation, IUGR fetuses with PI greater than 4 SD have a marked lactacidemia. The data suggest that coupling Doppler assessment of flow velocimetry with biochemical analyses of fetal blood can be useful in identifying a subset of IUGR human fetuses at risk of intrauterine hypoxia.

Female

Umbilical flow waveforms versus fetal biophysical profile in hypertensive pregnancies.

The pulsatility index (PI) of the umbilical arteries was measured in 40 hypertensive pregnancies. Doppler-velocimetric data were kept unknown to the clinical staff. An abnormal PI was found in 79% of cases in which an abnormal fetal growth in utero had been diagnosed by ultrasonographic measurements. Serial PI findings showed worsening figures in most of the cases with an abnormal fetal growth, irrespective of the last absolute value. Amniotic fluid estimation and PI data were significantly correlated. PI values were markedly abnormal in fetuses with non-reactive heart-rate tracings. A high sensitivity and an optimal specificity were found for umbilical PI versus the diagnosis of fetal growth retardation made by the coexistence of different biophysical criteria. However, false normal results may occur. 62% of the newborns weighed below the 5th percentile. The sensitivity of abnormal PI values to detect these light fetuses resulted to be only 67%. However the prevalence of neonatal morbidity in fetuses with abnormal PI values was 74%, while morbidity occurred only in 14% of cases with normal PI values. In hypertensive pregnancies, this simple velocimetric parameter proved to correlate with abnormal biophysical monitoring and complicated neonatal outcomes.

Birth Weight

Spectral analysis of antepartum heart rate variability.

The present paper illustrates the basic methodological aspects of the power spectral analysis applied to fetal ECG starting from a gestational age around the 25th week of gestation until term. An abdominal ECG signal is recorded and fetal and maternal QRSs are recognised through selective digital filtering and averaging techniques. Power Spectral Density (PSD) of the discrete R-R series is then calculated through an autoregressive (AR) technique. In analogy with what happens in adult human subjects, fetuses manifest variability in correspondence to particular bands in the spectrum which are sensitive to the sympatho-vagal balance which controls many cardiovascular functions and respiration in different physiological conditions. Such a method is easily implemented on a personal computer and may be used to asses the development of the autonomic nervous system in fetuses as well as to show the physiopathological reasons which perturbate the relevant control mechanisms.

Cardiotocography

Power spectral analysis of the heart rate of the human fetus at 26 and 36 weeks of gestation.

The fetal electrocardiogram (ECG) was recorded from the maternal abdomen together with sonographic detection of fetal states in four pregnant patients at 26 and 36 weeks of gestation. Computerised algorithms obtained a good recognition of maternal ECG and fetal ECG. The corresponding power spectral density (PSD) was estimated during epochs of quiet or breathing movements for 256 consecutive heart beats. At 36 weeks of gestation the PSD analysis showed heart rate variability components similar to an adult heart. A low frequency component was observed together with a high frequency component in the range of fetal breathing movements. This high frequency component (0.6 - 0.9 Hz) disappeared from the PSD analysis during epochs of apnea. To our knowledge this is the first demonstration of such a mechanism in the human fetus in utero. At 26 weeks no respiratory component was observed in the PSD analysis. The maturation of control mechanisms could be responsible for this difference.

Electrocardiography

Prenatal diagnosis and management of congenital heart disease.

Thirty-two fetuses were diagnosed as having congenital heart disease (CHD). The major indications for level II echocardiography other than suspected cardiac abnormalities were fetal malformations, nonimmune hydrops and cardiac arrhythmia. Only three patients had a previous history of fetal CHD. No false-abnormal diagnosis of severe CHD was made. Aortic arch anomalies represented the major diagnostic problem among the six correct but incomplete diagnoses. Sixty-one percent of the fetuses were growth retarded, thus confirming the severity of their CHD. Chromosomal anomalies and extracardiac malformations were associated in 19% and 44% of the fetuses, respectively. Obstetric management and fetal prognosis in cases of extracardiac malformations were greatly influenced by the diagnosis of CHD. The poorest perinatal outcome was associated with heart failure. The only intrauterine deaths occurred in that group, and only one neonate survived. The outcome was more favorable in neonates without other malformations or heart failure. Four of ten (40%) of those neonates survived, while the overall perinatal survival rate was 24%.

Chromosome Aberrations

The correlation of biochemical monitoring versus umbilical flow velocity measurements of the human fetus.

The pulsatility index of the fetal umbilical arteries was evaluated in 14 high-risk pregnant patients delivered by cesarean section between 30 and 35 weeks of gestation. Transabdominal cord sampling by ultrasonic guidance was performed on 10 of these patients. Umbilical arterial and venous blood was obtained in all patients from the doubly clamped cord at the time of cesarean section. The blood samples were analyzed for respiratory gases, acid-base balance, and lactate concentrations. A significant relationship was found between the pulsatility index and pH, PCO2, and lactate concentrations measured on umbilical venous blood sampled in utero. The pulsatility index also correlated with the same variables measured on venous and arterial blood sampled at cesarean section. Umbilical venous blood obtained transabdominally had a significantly higher oxygen content than blood obtained at cesarean section. No significant correlation was found between umbilical venous oxygen content obtained at transabdominal cord sampling and the pulsatility index. At a pulsatility index greater than 1.5, lactate concentrations in umbilical venous blood increased sharply. There would appear to be a curvilinear relationship between umbilical blood flow and these indices of fetal oxygenation, such that moderate increases in pulsatility index were not associated with a significant increase in fetal lactate concentrations.

Acid-Base Equilibrium

The yolk sac in early pregnancy failure.

An attempt was made to visualize the yolk sac in 845 patients scheduled for chorionic villi sampling. The distribution of yolk sac diameters and the interpolating growth curve up to 11 weeks of development were analyzed in 239 pregnant women who were delivered of normal infants. The highest visualizing rate of the yolk sac in normal pregnancies was 97 at 7 weeks of gestation. A total of 130 miscarriages occurred before chorionic villi sampling. In these cases, the diameter of the yolk sac versus crown-rump length tended to be larger than found in normal pregnancies. The visualizing rate of the yolk sac in miscarriages after the embryo had been formed was significantly higher in those women who demonstrated fetal heart activity (82.1%) than in those who did not (54.5%). On the other hand, the yolk sac was observed in 44% of miscarriages without a visible embryo. These findings suggest different types of missed abortion. An abnormal karyotype was observed in 23 of 29 chromosomal analyses performed on aborted specimens. An abnormal karyotype was observed in all eight cases with only a yolk sac-like structure within the gestational sac.

Abortion, Spontaneous

The relationship of maternal and fetal glucose concentrations in the human from midgestation until term.

The relationship between maternal and fetal glucose concentrations was investigated in pregnant women at different gestational ages. Maternal and fetal blood samples were obtained during 14 fetoscopies (17 to 21 weeks), four umbilical cord samples (32 to 36 weeks), nine elective cesarean sections with appropriate for gestational age (AGA) fetuses (35 to 39 weeks) and nine elective cesarean sections with small for gestational age (SGA) fetuses (34 to 37 weeks). A significant linear relationship between maternal and fetal glucose concentrations was demonstrated at midgestation (P less than .001) and at late gestation (P less than .001). At equal maternal concentrations there were no significant differences in fetal glucose concentration between the cord samples obtained in late gestation and those obtained at cesarean section. At midgestation fetal glucose concentration is independent of and may exceed maternal concentration at maternal glucose levels less than 4.44 mmol/L. Furthermore, the relationship between maternal and fetal concentrations at maternal glucose concentrations greater than 4.44 mmol/L is significantly different at midgestation from that at late gestation (P less than .01); at equal maternal concentrations there were higher glucose concentrations in the mid trimester fetus. In late gestation as the maternal glucose concentration increases there is an increase in the maternal arterial-umbilical arterial glucose concentration difference and the umbilical glucose/oxygen quotient (P less than .003) reflecting increased glucose utilization by the fetus. There were no significant differences between AGA and SGA babies with respect to these relationships.

Blood Glucose

Ultrasonography in the differential diagnosis of "double" uteri.

A total of 43 infertile patients with hysterosalpingographic diagnosis of bifid uterus underwent sonography and subsequent laparoscopy/hysteroscopy to evaluate the capacity of ultrasound to demonstrate the peritoneal profile of the malformed uteri correctly. Sonographic visualization was adequate in 39 cases (90.7%) and the following were identified correctly: 1 of 2 didelphic uteri, all of 11 bicornuate uteri, all of 4 complete septate uteri, and all of 22 partial septate uteri. The sensitivity of ultrasound in detecting the presence of a perimetrial fundal notch was 92.3% and its specificity 100%. Thus, a precise differential diagnosis of "double" uteri was possible with this technique, which may in some clinical situations provide an alternative to laparoscopy.

Endoscopy

Fitting growth curves to head and abdomen measurements of the fetus: a multicentric study.

Three different mathematical models were fitted to ultrasonic measurements of the biparietal diameter, head circumference, and abdomen circumference obtained from 1,426 healthy fetuses. The linear cubic function gives coefficients comparable with most previous studies, but it does not thoroughly explain fetal growth throughout pregnancy. Both the exponential-power function and the logistic-logarithmic function fit the raw data well and theoretically reflect the biological phenomena of human fetal growth. The characteristics of each model are discussed.

Abdomen

Chorionic villus sampling: an analysis of the obstetric experience of 1,000 cases.

Chorionic villus sampling was performed between 7 and 12 weeks gestation in 1,000 patients, 935 of whom intended to continue after fetal diagnosis. Transcervical and Transabdominal aspiration techniques were used providing a sampling success rate of 99 per cent. Anatomical and clinical contraindications to transcervical aspiration were pointed out, and the complementary role of the transabdominal approach evaluated. In the 615 concluded pregnancies an overall abortion rate of 4.1 per cent was observed. A significant association between fetal loss and number of catheter insertions was demonstrated. Bacterial inoculation by catheter insertion and colonization of uterine cavity was suspected as the cause of chorionamnionitis diagnosed in two cases (0.2 per cent) after CVS. Bleeding was the most frequent early complication (12.0 per cent) following chorionic aspiration, but was not significantly related to pregnancy wastage. Late complications, i.e. premature rupture of membranes (0.8 per cent), preterm delivery (6.3 per cent), perinatal losses (1.2 per cent), placental disorders (1.6 per cent), and congenital defects (2.6 per cent) did not exceed the expected values. Normal intrauterine growth patterns were ultrasonically estimated by cross-sectional and longitudinal studies, while the weight at birth was normally distributed in the range of the general population.

Abortion, Missed

Cord sampling for the evaluation of oxygenation and acid-base balance in growth-retarded human fetuses.

In 14 pregnancies complicated by intrauterine growth retardation, the umbilical cord was sampled before delivery under ultrasonic guidance for rapid fetal karyotyping. Fetal blood was analyzed for respiratory gases, acid-base balance, and lactate concentrations. Two patients were excluded from the study because cord samples were diluted with amniotic fluid. In six patients (group 1), the clinical assessment warranted continuation of pregnancy. Cesarean sections were performed in the remaining eight patients (group 2) within 8 hours of cord sampling. The data from the two groups were compared with those obtained from umbilical venous blood at the time of elective repeat cesarean section in term appropriate for gestational age infants (controls). No significant difference in PO2 was found between groups 1 and 2 and controls. In contrast, there were significant differences in oxygen saturation and acid-base balance between groups 1 and 2. Lactate concentration was inversely correlated with pH and was elevated in five of six fetuses requiring a prompt cesarean section: In two of these five fetuses, nonstress fetal heart rate tracings were reactive. The results suggest that fetal blood biochemistry, and particularly lactate concentration, may represent an additional indicator of fetal well-being in pregnancies complicated by intrauterine growth retardation.

Acid-Base Equilibrium