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Biomedical subjects

T Todros

Publications and source records attributed to T Todros.

At least 19 recordsLinked to original sources
PubMed2006

Prenatal screening for congenital heart disease with four-chamber and outflow-tract views: a multicenter study.

OBJECTIVE: Congenital heart diseases (CHD) are the most common congenital anomalies, and most cases occur in the low-risk population. Prenatal ultrasound screening based on visualization of the four-chamber view has had disappointing results in detecting these anomalies thus far. The aim of this study was to evaluate the diagnostic accuracy of ultrasound screening based on the combination of the four-chamber and outflow-tract views. METHODS: We conducted a multicenter prospective observational study in 15 obstetric units in the Piedmont Region, Italy. All operators received specific training. Data were recorded regarding visualization of the four-chamber view and the outflow tracts at each routine scan in pregnancies without any risk factor. When an anomaly was suspected, the patient was sent to the referral center. We obtained the follow-up data of the newborns until discharge from hospital and calculated the diagnostic accuracy of the test. RESULTS: 9074 ultrasound scans were performed on 7041 women and complete follow-up information was available for 6368 of them. Fifty-eight cases of CHD were observed at birth or postmortem (prevalence 9.1 per thousand); 38 of them were diagnosed in utero. The sensitivity of the test was 65.5%, the specificity 99.7%, the positive predictive value 70.4% and the negative predictive value 99.7%. The sensitivity of the four-chamber view alone was 60.3%. CONCLUSIONS: The sensitivity was significantly higher than that in a similar study performed in 1997 in the same setting. This improvement can be attributed in part to extension of the examination to the outflow-tract view, but also to technological developments and better training of the operators.

Echocardiography↗
PubMed2006

Low incidence of hypertensive disorders of pregnancy in women treated with spiramycin for toxoplasma infection.

AIMS: Toxoplasma infection in pregnancy is usually treated with long-term administration of the macrolide spiramycin to prevent fetal malformations. We had empirically observed that treated patients seldom developed pregnancy-induced hypertension (PIH), a common and severe disorder of pregnancy whose aetiology and pathogenesis are still debated. Some clinical and experimental data suggest that infection could play a role in its development. METHODS: To test this hypothesis, we studied a cohort of 417 pregnant women treated with spiramycin because of seroconversion for Toxoplasma gondii and 353 low-risk women who did not take any antibiotic during pregnancy. PIH was defined as blood pressure>140/90 mmHg on two or more occasions, occurring after 20 weeks of gestational age. RESULTS: Seventeen (5.2%) women in the control group developed PIH compared with two (0.5%) in the case group. The odds of developing the disease were significantly lower in the treated subjects (odds ratio=0.092, 95% confidence interval 0.021, 0.399; P<0.001). CONCLUSIONS: Our results suggest that antibiotic treatment during pregnancy can reduce the incidence of PIH, thus opening new perspectives in its prevention and therapy.

Adult↗
PubMed2005

Fetal cerebral ventriculomegaly: outcome in 176 cases.

OBJECTIVE: To evaluate the outcome of fetuses affected by different degrees of ventriculomegaly. METHODS: We studied 176 fetuses with ventriculomegaly and evaluated the pregnancy outcome and the neurodevelopmental outcome at age > or = 24 months. The population was divided into three groups according to ventricular width: A (mild ventriculomegaly, 10 to 12 mm); B (moderate, 12.1 to 14.9 mm) and C (severe, > or = 15 mm). RESULTS: Ventriculomegaly was more often an isolated finding in Group A (44/75; 58.7%) than in Group B (10/41; 24.4%) and Group C (24/60; 40%). When the ventriculomegaly was an isolated finding, 97.7% of fetuses with mild, 80% with moderate and 33.3% of those with severe dilatation were alive at > or = 24 months. The neurodevelopmental outcome was normal in 93% of Group A, 75% of Group B and 62.5% of Group C. CONCLUSIONS: Our results suggest that the definition of borderline ventriculomegaly should be limited to ventricular width below 12 mm. Cases with measurements above this value are more often associated with malformations and have a normal neurodevelopmental outcome less frequently.

Abnormalities, Multiple↗
PubMed2005

A novel Mtd splice isoform is responsible for trophoblast cell death in pre-eclampsia.

Pre-eclampsia is a serious disorder of human pregnancy, characterized by decreased utero-placental perfusion and increased trophoblast cell death. Presently, the mechanisms regulating trophoblast cell death in pre-eclampsia are not fully elucidated. Herein, we have identified a novel Mtd/Bok splice isoform (Mtd-P) resulting from exon-II skipping. Mtd-P expression was unique to early-onset severe pre-eclamptic placentae as assessed by quantitative real-time-PCR and immunoblotting. Mtd-P overexpression in cell lines (BeWo: cytotrophoblast-derived; and CHO: ovary-derived) resulted in increased apoptotic cell death as assessed by caspase-3 cleavage, internucleosomal DNA laddering and mitochondrial depolarization. Moreover, Mtd-P expression increased under conditions of low oxygenation/oxidative stress in human villous explants. Antisense knockdown of Mtd under conditions of oxidative stress resulted in decreased caspase-3 cleavage. We conclude that under conditions of reduced oxygenation/oxidative stress, Mtd-P causes trophoblast cell death in pre-eclampsia and hence may contribute to the molecular events leading to the clinical manifestations of this disease.

Alternative Splicing↗
PubMed2005

Growth factors and their receptors: fundamental molecules for human placental development.

In this review we present data concerning the localization of some important growth factors and their receptors in the human placenta. We focus our attention on molecules playing a fundamental role in angiogenesis and morphologic processes as beta-FGF, EGF and TGF-beta. The distribution of these growth factors and their receptors in the placental villi during gestation suggests that these molecules play a pivotal role in growth and differentiation of the villous tree.

Chorionic Villi↗
PubMed2004

Rapid prenatal diagnosis of common chromosome aneuploidies by QF-PCR. Assessment on 18,000 consecutive clinical samples.

The quantitative fluorescent PCR (QF-PCR) assay, introduced during the last few years, allows prenatal diagnoses of common chromosome aneuploidies in a few hours after sampling. We report the first assessment of QF-PCR performed on a large cohort of 18,000 consecutive clinical specimens analysed in two different Centres. All samples were analysed by QF-PCR using several selected STR markers together with amelogenin and, occasionally, SRY for fetal sexing. Results were compared with those obtained by conventional cytogenetic analysis. In 17,129 tests, normal fetuses were detected by QF-PCR. No false positives were observed. All 732 cases of trisomy 21, 18, 13, triploidies, double trisomies as well as all but one fetuses with X and Y aneuploidies were correctly diagnosed. Chromosome mosaicism could also be suspected in several samples. In some cases of in vitro culture failures, QF-PCR was the only evidence of fetal X, Y, 21, 18 and 13 chromosome complement. QF-PCR proved to be efficient and reliable in detecting major numerical chromosome disorders. The main advantages of the molecular assay are its very low cost, speed and automation enabling a single operator to perform up to 40 assays per day. QF-PCR relieves anxiety of most parents within 24 h from sampling and accelerates therapeutic interventions in the case of an abnormal result. In countries where large scale conventional cytogenetics is hampered by its high cost and lack of technical expertise, QF-PCR may be used as the only prenatal diagnostic test.

Aneuploidy↗
PubMed2004

Economic evaluation of ultrasound screening options for structural fetal malformations.

OBJECTIVE: To perform a cost-effectiveness analysis comparing the current Italian situation of no organized screening program for structural fetal malformations with an organized screening model involving a scan at 19-21 weeks of gestation. METHODS: Assumptions were made about the number of pregnant women examined per year, the number of ultrasound examinations (screening and diagnostic) and amniocenteses, the prevalence of fetal anomalies, ultrasound sensitivity and specificity and the rates of termination of pregnancy and of fetal death. The costs included procedures performed during and after the diagnosis of malformations, and the resources required to organize the program. Data sources were a literature review, estimates and national tariffs. A sensitivity analysis considered variations in screening test sensitivity, number of private scans and costs of ultrasound, fetal echocardiography, amniocentesis, care for malformed infants and organization. RESULTS: An organized program would increase the number of diagnosed malformations (+10.7%) and decrease the number of malformed infants (-19.9%). It would also decrease the total cost of screening, from 505 billion to 400 billion euros (-20.7%), decrease the cost per woman examined from 971 to 770 euros (-20.7%) and decrease the cost per malformed fetus diagnosed from 79,085 to 56,637 euros (-28.4%). CONCLUSIONS: In all scenarios considered, an organized program would lead to increased detection of malformations at lower cost. Further cost analyses should provide a better representation of resources used, especially those related to the care of malformed infants, while cost-benefit assessments should include all the consequences of prenatal diagnosis, such as those deriving from false results and those for both the woman and society, including ethical issues.

Abortion, Induced↗
PubMed2004

Pregnancy after kidney transplantation: an evidence-based approach.

Despite the relatively little space for transplantation in most medical schools, this issue is considered interesting by the students both for its clinical and ethical implications. The students were asked to choose a particular aspect of nephrology for a 2-hour case discussion. They chose the case of a 35-year-old female, kidney transplant recipient now 1.5 years postoperatively, who was coming to seek advice about pregnancy. The aim of the present work is to report an integration between narrative and evidence-based medicine (EBM) approaches. The search strategy was developed within a multidisciplinary working group, two of whose members were also masters in the methodology of systematic revisions. The first step in the discussion was the identification of ethical and methodological problem. In a rapidly developing field, books are unlikely to be able to give updated information. One needs to interact with electronic databases. In this context, no randomized controlled trial on pregnancy is expected. The evidence is likely to be heterogeneous. Prenatal care delivery differs around the world in part related to attitudes toward pregnancy, which depend upon religion and traditions. The second step was the definition of the search strategy. The third step, was selecting and cataloging the evidence. The titles and abstracts retrieved by the search strategy (272 items) were examined to identify full papers to be retrieved. The evidence retrieved was screened for the type of paper (reviews, primary studies, case reports, case series) and for the authors to give an indirect idea of duplicate publication bias. Teaching a complex and ever-changing subject, such as kidney transplantation, is a difficult task. The case of a young woman seeking information on the probability to undergo a successful pregnancy was particularly likely to exemplify the importance of being aware of the biases of the book-based information and on the need to interact with the internet. The search strategy developed by the working group of postgraduate trainees allowed students to have a direct experience with the complexity of the field. This preliminary study, as the basis for development of a checklist informed consent form on pregnancy in kidney transplantation, may give a first rough quantification of the work needed by a physician who wants to have a direct idea of the odds and risks of pregnancy in kidney transplant patients.

Evidence-Based Medicine↗
PubMed2004

Temperature monitoring using ultrasound contrast agents: in vitro investigation on thermal stability.

Invasiveness of temperature monitoring devices is presently one of the most serious limitations to the application of oncological hyperthermia (HT). A promising approach aims at detecting temperature variations by monitoring the mean grey level (MGL) of the ultrasonographic image of the tissue. Gaseous ultrasound contrast agents (UCA), enhancing Ultrasonic (US) imaging, are expected to be sensitive to temperature, and are therefore a good candidate as temperature monitoring medium. The present study evaluates the 'in vitro' temporal and thermal stability and the correlation between temperature and MGL using a gaseous UCA (SonoVue) as phantom. No statistical differences were detected between the MGL value of the phantom kept at 43.5 degrees C before (215.2+/-3.5) and after 1 h (214.8+/-2.5), showing good stability at HT temperatures. Data of MGL image vs. temperature were obtained during both heating and cooling experiments in the HT range (30-43 degrees C). A good linearity of MGL vs. temperature (R2=0.976) was found with a good accuracy (2.5%) and a sensitivity of about 6.6 MGL/degrees C.

Analysis of Variance↗
PubMed2004

Assessment of the effect of vessel curvature on Doppler measurements in steady flow.

Blood vessel curvature is responsible for the appearance of nonaxial velocity components and for minor changes in the pattern of the axial flow. All the velocity components are expected to contribute to the Doppler signal produced by the ultrasound (US) backscattered by the insonated blood cells, the axial velocity, contributing to the actual volumetric blood flow, and the transverse velocity, causing the recirculating vortices. A detailed, separate analysis of the velocity components is, therefore, mandatory to quantify how vessel curvature can affect results and clinical diagnosis. Both experimental in vitro measures and numerical simulations were performed on a curved tube and the Doppler power spectra so obtained were compared. The satisfactorily agreement of the above spectra shows that the nonaxial velocity components are easily detectable with clinical equipment and that their amplitude, as expected, is not negligible and can bias Doppler measurements and resulting clinical diagnosis.

Blood Flow Velocity↗
PubMed2004

Fetal short femur length in the second trimester and the outcome of pregnancy.

We reviewed 86 consecutive cases with fetal femur length (FL) below the 10th centile of our reference ranges at midtrimester ultrasonography. Three groups were identified based on perinatal outcome: normal infants (n= 28), newborns with structural and/or chromosomal anomalies (n= 40), small-for-gestational age (SGA) newborns (n= 18). Fetuses with skeletal dysplasias (n= 13) had significantly shorter FL. Aneuploidies were only found in fetuses with malformations other than skeletal dysplasias. The diagnosis of SGA, based on ultrasound abdominal circumference measurement <10th centile, was made 9 weeks (range 5-14) after the finding of a short FL. Half of these cases also developed pre-eclampsia.

Abortion, Induced↗
PubMed2003

Pulmonary stenosis and atresia with intact ventricular septum during prenatal life.

AIM: To identify fetal echocardiographic characteristics predictive of perinatal outcome in cases with a prenatal diagnosis of pulmonary stenosis or pulmonary atresia. PATIENTS AND METHODS: We retrospectively reviewed the records and the videotapes of all the cases of pulmonary stenosis and pulmonary atresia diagnosed at our institutions between 1990 and 1999. The following measurements were obtained: diameters of right and left atria and ventricles and ventricular wall thickness; main pulmonary artery and aortic root diameter; direction of flow through the atrioventricular, aortic and pulmonary valves and through the ductus arteriosus. Perinatal outcome and follow-up of the survivors were available in each case. RESULTS: There were 21 cases of pulmonary atresia. Eleven were diagnosed before 24 weeks and nine of them (82%) underwent termination of pregnancy. The survival rate was 50% among the 12 fetuses born at term. None of the fetuses that survived had a large right ventricle, while this was a finding in 50% of those that died. Among the fetuses that died, 83% had a hypertrophic right ventricular wall compared to 33% of the survivors. There were 12 cases of pulmonary stenosis. Three cases were diagnosed before 24 weeks but none underwent termination of pregnancy. All the fetuses with pulmonary stenosis were born at term and four died in the perinatal period. The survival rate was thus 66.6% (8/12). Three (75%) of the fetuses that died had reversed flow in the ductus arteriosus compared with one of the fetuses that survived. CONCLUSION: Our data suggest that a grossly enlarged right ventricle and/or a hypertrophied right ventricular wall in cases of pulmonary atresia and reversed flow in the arterial duct in cases of pulmonary stenosis are likely indicators of a poor prognosis.

Cardiomyopathy, Dilated↗
PubMed2003

Investigation of placental stem villi arteries in fetally growth-restricted pregnancies: a multivariate analysis.

Thirteen placentas were studied from 5 normal pregnancies and 8 from pregnancies complicated by fetal growth restriction (4 with present, 3 with absent, and 1 with reversed end-diastolic velocities at Doppler interrogation of the umbilical arteries). On immunohistochemically stained slides, the diameter (d) and the wall thickness (t) of the arterial vasculature of the stem villi were measured for a total of approximately 10,000 vessels. A multivariate 'mixed effect model' statistical analysis was performed using d and t as dependent variables and gestational age, delivery mode, fetal and placental weight, the degree of vascular collapse and Doppler blood flow patterns as independent variables. Gestational age, Doppler pattern and the degree of vascular collapse significantly affected both d and t, the mode of delivery influenced d while fetal and placental weights scarcely affected the dependent variables. The above parameters should therefore be taken into account when investigating placental stem vessel morphometry.

Birth Weight↗
PubMed2002

Macrophage migration inhibitory factor in human pregnancy and labor.

PROBLEM: Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in reproduction. Presently there is no information on the possible involvement of MIF in the onset of labor. METHODS: Macrophage migration inhibitory factor was assayed, by enzyme-linked immunosorbent assay (ELISA), in maternal serum (MS) and amniotic fluid (AF) both, at midtrimester and at term, as well as in cord serum (CS) at birth. Extraembryonic membranes were analyzed by immunohistochemistry. RESULTS: Amniotic fluid MIF concentrations were significantly higher at term (median 62.10 ng/mL) than at midtrimester (median 20.07 ng/mL) and reached a peak in term labor (median 258.80 ng/mL). The AF/MS ratio varied from a median of 4.34 at midtrimester and 33.7 at term labor. The MS/CS ratio was 0.4. Migration inhibitory factor immunoreactivity was found in different cell layers of the extraembryonic membranes. CONCLUSIONS: The increased secretion of MIF in AF at term, particularly at term labor, suggests that MIF contributes to the inflammatory events leading to labor.

Adult↗
PubMed2002

PPARgamma expression in normal human placenta, hydatidiform mole and choriocarcinoma.

Peroxisome proliferator-activated receptor (PPAR) gamma belongs to a subclass of nuclear hormone receptors that execute their transcriptional functions as heterodimers with the retinoid X receptors (RXR). PPARgamma plays a pivotal role in cellular differentiation. This study investigated PPARgamma protein expression in normal human placentas, hydatidiform moles and choriocarcinoma, using immunohistochemical and Western blot analyses. In first trimester normal placenta, PPARgamma was mainly localized in the nuclei of the villous cytotrophoblastic cells, whereas at term it was mainly localized in the nuclei of the syncytiotrophoblast. Extravillous cytotrophoblast of cell islands and cell columns also showed nuclear PPARgamma immunostaining. A striking result was the altered expression patterns of PPARgamma in pathological tissues; PPARgamma showed a reduced immunostaining in the trophoblastic diseases. In hydatidiform moles, PPARgamma was mainly localized in the nuclei of the trophoblastic collections of the pathological villi and in the extravillous trophoblastic cells, whereas in the choriocarcinoma, only a few trophoblastic cells showed weak PPARgamma nuclear immunostaining. These findings suggest an involvement of PPARgamma in trophoblast differentiation during normal placental development. The down-regulation of PPARgamma expression in the gestational trophoblastic diseases analysed in this study provides a new insight into the progression of these pathologies.

Choriocarcinoma↗