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Biomedical subjects

P Volpe

Publications and source records attributed to P Volpe.

At least 19 recordsLinked to original sources
PubMed2006

Diagnosis, characterization and outcome of congenitally corrected transposition of the great arteries in the fetus: a multicenter series of 30 cases.

OBJECTIVE: To describe the anatomy, associated anomalies and outcome of 30 cases of congenitally corrected transposition of the great arteries (ccTGA) detected prenatally. METHODS: This was a retrospective observational study of the 30 cases of ccTGA confirmed at autopsy or postnatal echocardiography seen at one of three referral centers from 1994 to 2003. The following data were considered: gestational age at diagnosis, cardiac anatomy, associated cardiac and extracardiac anomalies and fetoneonatal outcome. All fetuses underwent fetal echocardiography and a detailed anomaly scan, with follow-up scans at 3-4-week intervals until delivery. The diagnosis was confirmed at autopsy or after delivery. Follow-up data were retrieved from the clinical files of the patients. RESULTS: The mean gestational age at diagnosis was 25.5 weeks. Intracardiac defects associated with the ccTGA included a ventricular septal defect in 21 cases, pulmonary outflow obstruction in 12 cases, an abnormal tricuspid valve in 10 cases, ventricular hypoplasia in five cases and dextro/mesocardia in five cases. The karyotype was normal in all 24 newborns, and unknown in the cases which resulted in termination of pregnancy (n = 5) or intrauterine death (n = 1). There were associated extracardiac anomalies in four cases only. Three of the four cases of atrioventricular block (AV block) developed in the third trimester, while the fourth appeared after birth. There were nine deaths (five terminations, two perinatal deaths and two infant deaths). The remaining 21 (70%) newborns were alive at a median follow-up time of 32 months, 11 of them after various surgical procedures. CONCLUSIONS: Our data suggest that in fetuses with ccTGA the risk of chromosomal and extracardiac anomalies is low, in accordance with postnatal data. The spectrum of associated cardiac lesions is consistent with that reported in the pediatric literature. These data may be of use during prenatal counseling since no figures regarding survival and/or outcome of ccTGA in the fetus have been reported so far.

Female↗
PubMed2006

Posterior fossa and vermian morphometry in the characterization of fetal cerebellar abnormalities: a prospective three-dimensional ultrasound study.

OBJECTIVES: To assess whether, by applying a predefined set of morphometric measurements to the posterior fossa and the cerebellar vermis, it is possible to detect and quantify the following parameters, which represent key features of abnormalities of the vermis and posterior fossa: 1) upward rotation of the vermis; 2) upward displacement of the tentorium; 3) underdevelopment of the vermis. Also to assess, in a small subset of cases, the correlation between ultrasound and magnetic resonance imaging (MRI) in the measurement of these three parameters. METHODS: This was a prospective observational trial. The study population included 51 normal fetuses and 20 abnormal fetuses with Dandy-Walker malformation (n = 5), Dandy-Walker variant (n = 8) or megacisterna magna (n = 7). Three-dimensional (3D) ultrasound volumes of the fetal head were acquired from the posterior fontanelle or the posterior part of the sagittal suture and processed offline with dedicated software. The following parameters were analyzed: tentorovermian angle; tentoroclivus angle; clivovermian angle; vermian diameter/biparietal diameter x 100 ratio (VD/BPD ratio). In seven cases, MRI performed on the same day as sonography was available for comparison. Non-parametric statistics were used to assess differences in means and correlations. RESULTS: The tentoroclivus angle was increased only in fetuses with Dandy-Walker malformation (P < 0.001). Upward rotation of the vermis was demonstrated both by the tentorovermian and the clivovermian angles in fetuses with Dandy-Walker variant (P < 0.001), while in those with Dandy-Walker malformation the difference was not statistically significant, probably due to the small number of cases. Finally, the VD/BPD ratio demonstrated that the degree of vermian hypoplasia was higher in Dandy-Walker malformation compared with Dandy-Walker variant (P < 0.001). CONCLUSIONS: Using 3D ultrasound, we have demonstrated in the fetus the key elements characterizing most anomalies of the posterior fossa, namely the upward displacement of the tentorium, the counterclockwise rotation and the significant hypoplasia of the cerebellar vermis. In addition, our observations in a small number of cases indicate that there is a good correlation between MRI- and 3D ultrasound-derived morphometric measurements of the vermis.

Case-Control Studies↗
PubMed2006

Characteristics, associations and outcome of partial agenesis of the corpus callosum in the fetus.

OBJECTIVES: To report, in a population of fetuses diagnosed with partial agenesis of the corpus callosum (PACC), the sonographic characterization, incidence of cerebral, extracerebral and chromosomal anomalies, and outcome. In addition, in some of our cases a comparison was made between findings on ultrasound and fetal magnetic resonance imaging (MRI). METHODS: This was a retrospective study of all cases of PACC seen at two referral centers for prenatal diagnosis of congenital anomalies over a 10-year period. The following variables were assessed: indication for referral, additional cerebral and extracerebral malformations, chromosomal abnormalities, and pregnancy and fetal/neonatal outcome. RESULTS: Among 54 cases of fetal agenesis of the corpus callosum detected in the referral centers during the observation period, PACC was diagnosed at prenatal sonography in 20 cases and confirmed at pre/postnatal MRI and necropsy examinations in 19 cases (35%). These 19 constituted the study group. The diagnosis was made in the sagittal planes and in 12 cases it was made prior to 24 weeks. In most cases the indication for referral was the presence of indirect signs of callosal anomalies, such as colpocephaly. In 10 cases PACC occurred in association with other anomalies and in nine it was isolated. MRI was particularly useful for demonstrating some additional cerebral anomalies such as late sulcation, migrational pathological conditions and heterotopia. Regarding pregnancy outcome, of those diagnosed before 24 weeks which had associated anomalies, all except two were terminated. Of the nine cases with isolated PACC, all were liveborn. Follow-up was available in eight, and two of these (25%) showed evidence of significant developmental delay. In our series the outcome of isolated PACC was not better than that of complete agenesis of the corpus callosum reported in other series. CONCLUSIONS: PACC can be diagnosed reliably and characterized in prenatal life. The sonographic sign present in most cases is colpocephaly. Prenatal MRI can be performed to confirm the diagnosis. It is particularly useful to demonstrate some additional cerebral anomalies such as late sulcation, migrational pathological conditions and heterotopia. The relatively poor survival rate is due to the high rate of terminations and associated major anomalies.

Abnormalities, Multiple↗
PubMed2006

Novel application of 4D sonography with B-flow imaging and spatio-temporal image correlation (STIC) in the assessment of the anatomy of pulmonary arteries in fetuses with pulmonary atresia and ventricular septal defect.

OBJECTIVES: To assess the reliability of two-dimensional gray-scale (2D) and color Doppler echocardiography in the study of the size and anatomy of the central pulmonary arteries and of the sources of pulmonary blood flow in a case series of fetuses with pulmonary atresia and ventricular septal defect (PA-VSD), and to evaluate whether the use of 4D ultrasound with B-flow imaging and spatio-temporal image correlation (STIC) can improve prenatal diagnostic accuracy. METHODS: The study population comprised a group of seven PA-VSD fetuses that had been examined by 2D and color Doppler echocardiography exclusively, and a group of five additional cases identified initially by conventional echocardiography and examined further by 4D ultrasound, for all of which a thorough postnatal or autopsy study of the size and anatomy of the pulmonary arteries and blood supply was available. RESULTS: 2D and color Doppler echocardiography failed to assess the anatomy of the central pulmonary arteries and the source of the pulmonary blood supply in 33% and 25% of the 12 cases, respectively. 4D ultrasound with B-flow imaging and STIC assessed successfully the anatomy of the pulmonary arteries and the source of pulmonary blood supply in all five fetuses examined. CONCLUSIONS: The prognosis of PA-VSD is influenced by the anatomy of the pulmonary arteries and the sources of the pulmonary blood supply, and by coexisting extracardiac and genetic anomalies. Our findings, although limited to a small sample size, suggest that 4D echocardiography with B-flow imaging and STIC, unlike 2D ultrasound, can provide thorough visualization of very small vessels and of the arterial blood supply to the lungs of fetuses with PA-VSD. 4D ultrasound may be used in the future to improve and help to detail the diagnosis of other fetal cardiac defects.

Adult↗
PubMed2006

[Varix of the extra-hepatic portion of the fetal intra-abdominal umbilical vein: pathogenesis, prenatal sonographic diagnosis, and perinatal outcome].

AIM: Aim of the study was to investigate pathogenesis, diagnosis, and prognosis of the fetal intra-abdominal umbilical vein varix (FIUVV). METHODS: We reviewed all cases of FIUVV diagnosed in our hospital from August 1999 to December 2002. The umbilical vein was considered dilated when the measurement was above 2 standard deviation of the mean for gestational age. In all cases prenatal echocardiography and post-natal karyotype were performed. Our cases were also considered in the light of all the cases of FIUVV reported in literature. RESULTS: FIUVV was diagnosed in 5 cases between 22 and 37 weeks' gestation, among an unselected population of pregnant woman. Karyotype was normal in all cases; an apparently isolated septal ventricular defect was present in one patient. No obstetrical complications due to the presence of FIUVV (i.e. thrombosis) were associated. CONCLUSIONS: In our case series no obstetrical complications, and only one mild fetal anomaly were present. In literature an high association has been reported between the presence of FIUVV and fetal anomalies and/or obstetrical complications. Fetal echocardiography and detailed US study of fetal anatomy is needed to exclude associated anomalies. Karyotype should be offered only when other fetal anomalies are present. In presence of FIUVV, a close fetal monitoring by serial color Doppler and ultrasonographic examinations should be performed.

Adult↗
PubMed2005

Severe ductal constriction in the third-trimester fetus following maternal self-medication with nimesulide.

OBJECTIVE: This was a multicenter series of 10 cases of constriction of the fetal ductus arteriosus occurring after maternal ingestion of one or two oral doses of nimesulide, which led to emergency delivery in four cases. METHODS: The computerized databases of three referral centers were searched for all cases of ductal constriction detected during the last 8 years in association with maternal ingestion of nimesulide. Ten cases were retrieved and represent the study population. The following variables were analyzed: gestational age at diagnosis, reason for nimesulide ingestion, total nimesulide dose, time interval between drug intake and ultrasound examination, indication for echocardiography, presence of right ventricular hypertrophy, presence of tricuspid valve regurgitation, ductal systolic and diastolic peak velocities, ductal pulsatility index, signs of fetal heart failure, pregnancy and feto-neonatal outcome, and ductal status at neonatal echocardiography. RESULTS: Nimesulide ingestion was the result of self-medication in all cases. The mean gestational age at diagnosis was 36.3 weeks and the mean time interval between nimesulide intake and echocardiographic examination was 2.9 days. The five cases with ductal peak velocities > 2.5 m/s showed right ventricular dysfunction with significant tricuspid regurgitation. At echocardiography performed immediately after birth, the ductus appeared closed in all cases and two neonates showed persistent pulmonary hypertension requiring intermittent positive pressure ventilation and nitric oxide therapy for 1 week. CONCLUSIONS: Although the true incidence of the adverse effect of nimesulide ingestion during pregnancy cannot be deduced, we believe that patients and their clinicians should be alerted to the possibility that clinically significant ductal constriction may follow maternal self-medication with just one or two oral doses of nimesulide, at least if the drug is taken near term.

Administration, Oral↗
PubMed2005

The language of methylation in genomics of eukaryotes.

Background studies have shown that 6-methylaminopurine (m6A) and 5-methylcytosine (m5C), detected in DNA, are products of its post-synthetic modification. At variance with bacterial genomes exhibiting both, eukaryotic genomes essentially carry only m5C in m5CpG doublets. This served to establish that, although a slight extra-S phase asymmetric methylation occurs de novo on 5'-CpC-3'/3'GpG-5', 5'-CpT-3'/3'-GpA-5', and 5'-CpA-3'/3'-GpT-5' dinucleotide pairs, a heavy methylation during S involves Okazaki fragments and thus semiconservatively newly made chains to guarantee genetic maintenance of -CH3 patterns in symmetrically dimethylated 5'-m5CpG-3'/3'-Gpm5C-5' dinucleotide pairs. On the other hand, whilst inverse correlation was observed between bulk DNA methylation, in S, and bulk RNA transcription, in G1 and G2, probes of methylated DNA helped to discover the presence of coding (exon) and uncoding (intron) sequences in the eukaryotic gene. These achievements led to the search for a language that genes regulated by methylation should have in common. Such a deciphering, initially providing restriction minimaps of hypermethylatable promoters and introns vs. hypomethylable exons, became feasible when bisulfite methodology allowed the direct sequencing of m5C. It emerged that, while in lymphocytes, where the transglutaminase gene (hTGc) is inactive, the promoter shows two fully methylated CpG-rich domains at 5 and one fully unmethylated CpG-rich domain at 3' (including the site +1 and a 5'-UTR), in HUVEC cells, where hTGc is active, in the first CpG-rich domain of its promoter four CpGs lack -CH3: a result suggesting new hypotheses on the mechanism of transcription, particularly in connection with radio-induced DNA demethylation.

Base Sequence↗
PubMed2005

[''Isolated'' single umbilical artery: incidence, cytogenetic abnormalities, malformation and perinatal outcome].

AIM: The aim of the study was to 1) evaluate the gestational age at diagnosis and the incidence of single umbilical artery in an unselected population of 3750 pregnant women; 2) identify its association with malformations and/or karyotype aberrations in pre/postnatal age; 3) evaluate the fetal-neonatal outcome; 4) investigate the likelihood that a fetus might be affected by a cytogenetic abnormality even in presence of an apparently ''isolated'' single umbilical artery. METHODS: Transabdominal ultrasound of the umbilical vessels and histological confirmation at birth. In presence of single umbilical artery an accurate prenatal ultrasound assessment, karyotyping (pre/postnatal), and clinical follow-up after birth were performed. RESULTS: The incidence of single umbilical artery in our population resulted 1.07% (40/3750), being ''isolated'' in 40% of cases. The diagnosis of chromosomal aberration associated with single umbilical artery was made in 6 cases (15%), while structural fetal abnormalities in absence of causal chromosomal anomalies were present in 9 cases (22.5%), with syndromic patterns in 3 of them. In 2 cases with chromosomal anomalies the single umbilical artery was apparently ''isolated'' at the ultrasound examination between the 17th and the 22nd week of gestation. Excluding 4 terminations of pregnancy, the perinatal mortality percentage resulted 25% (9/36); similarly, fetal growth retardation was present in 25% of cases (9/36). CONCLUSIONS: The incidence of single umbilical artery in our population confirms that this fetal vascular anomaly is frequently identified in pregnancy. In the light of our cases and data in the literature it is evident that diligent surveillance in prenatal age and accurate clinical follow-up after birth are mandatory when a single umbilical artery has been diagnosed. Finally, the possibility, even if rare, that even when the single umbilical artery is apparently ''isolated'', a chromosomal aberration might be present (1/24 of our ''isolated'' cases) should be considered when addressing correct counselling to the couples.

Chromosome Aberrations↗
PubMed2004

Characteristics, associations and outcome of absent pulmonary valve syndrome in the fetus.

OBJECTIVES: To assess in a population of 21 fetuses diagnosed with absent pulmonary valve syndrome (APVS) the accuracy of prenatal diagnosis, the incidence of extracardiac and chromosomal anomalies and the perinatal outcome. METHODS: This was a retrospective observational study of 21 fetuses with a confirmed diagnosis of APVS. All of them underwent fetal echocardiography and a detailed anatomical scan. Karyotyping was performed in 20/21 cases, with fluorescent in-situ hybridization analysis to detect the 22q11 microdeletion performed in 16/21 cases. The following variables were retrieved from databases and evaluated: indication for referral, gestational age at diagnosis, presence of cardiomegaly, branch pulmonary dilatation, associated anomalies or intrauterine growth restriction, and fetal/neonatal outcome. Autopsy reports and postnatal surgical/medical files were available for confirmation in all cases. RESULTS: Prenatal diagnosis of APVS proved correct in all cases, with only three cases occurring not in association with tetralogy of Fallot. Additional cardiovascular anomalies were present in five cases (24%). Extracardiac anomalies were found in nine cases (42.8%), and were associated with chromosomal anomalies in five cases (24%). The 22q11 microdeletion was present in 4/16 cases (25%). Fetal/neonatal outcome was as follows: nine terminations of pregnancy, three intrauterine deaths, six postnatal deaths. The remaining three (14.3%) neonates were alive after surgery. Cardiomegaly and marked branch pulmonary dilatation were present in 16 and 15 cases, respectively, and were associated with bronchomalacia in virtually all cases. CONCLUSIONS: APVS can be reliably diagnosed and characterized prenatally. The association with major chromosomal anomalies or 22q11 microdeletion is consistent with previous findings. The relatively poor survival rate is due to the high rate of terminations, associated genetic anomalies and bronchomalacia. Bronchomalacia is present in the overwhelming majority of cases featuring cardiomegaly and marked branch pulmonary dilatation.

Chromosome Disorders↗
PubMed2004

Characterization of two novel BRCA1 germ-line mutations involving splice donor sites.

Deleterious BRCA1 mutations have significant clinical implications for the patients that carry them. Point mutations in critical functional domains and frameshift mutations that lead to early termination of protein translation are associated with a 60-80% risk of breast cancer and a 20-40% risk of ovarian cancer. In contrast, the significance of mutations located in intronic regions of BRCA1, even in the setting of a family history of breast and ovarian cancer, is not always clear. Some of these mutations occur in splice donor/acceptor consensus sites. These mutations can affect heteronuclear RNA (hnRNA) processing, leading to the loss of functional BRCA1 protein and thus may be disease-associated. However, it is important to verify the effect of these mutations, because splicing alterations cannot be predicted from genomic sequence alone. We report here the characterization of two novel BRCA1 mutations identified in families seen in our cancer risk evaluation clinic that alter splice donor sites of BRCA1. We show that both mutations alter transcript splicing and result in truncated BRCA1. IVS17 + 1G --> T leads to inclusion of part of intron 17 after the coding sequence of exon 17, resulting in early termination of BRCA1 protein following codon 1692. 252del5insT abolishes the splice donor site in exon 3, leading to the skipping of exon 5 and BRCA1 protein truncation following codon 45. Thus, both mutations result in loss of BRCA1 function, and carriers of these mutations should be counseled in the same manner as carriers of other truncating BRCA1 mutations.

BRCA1 Protein↗
PubMed2004

Absence of BRAF mutations in UV-protected mucosal melanomas.

BACKGROUND: Mutations in BRAF have recently been identified in a significant percentage of primary and metastatic cutaneous malignant melanomas. As ultraviolet (UV) exposure may play a role in the development of cutaneous melanoma lesions with BRAF mutations, BRAF mutation frequency in melanomas arising in sites protected from sun exposure may be lower than those from sun-exposed areas. Thus, we determined the BRAF mutation frequency in a panel of 13 mucosal melanomas and compared those data with data from all currently published series of cutaneous melanomas. METHODS: BRAF exon 15 DNA from 13 archival primary mucosal melanomas (eight vulvar, four anorectal, and one laryngeal) was sequenced using intron-based primers. As archival DNA occasionally produces poor-quality template, results were confirmed with a TspRI restriction fragment length polymorphism (RFLP) that distinguishes wild-type BRAF from the common mutant form V599E. A binomial test was used to compare the mutation frequency in the mucosal melanomas with the published mutation frequency in cutaneous melanomas. RESULTS: None of the 13 mucosal melanomas in this series had an exon 15 BRAF mutation, as compared to 54/165 (33%) primary cutaneous melanomas with BRAF mutations in a compilation of all current published studies (p = 0.006). DISCUSSION: These data suggest that UV exposure, plays a role in the genesis of BRAF mutations in cutaneous melanoma, despite the absence of the characteristic C>T or CC>TT mutation signature associated with UV exposure, and suggests mechanisms other than pyrimidine dimer formation are important in UV-induced mutagenesis.

DNA Mutational Analysis↗
PubMed2003

FISH and cytogenetic characterization of a terminal chromosome 1q deletion: clinical case report and phenotypic implications.

We report a 24-year-old woman with minor facial anomalies, mental retardation, seizures, and partial agenesis of the corpus callosum. Cytogenetic analysis showed a de novo terminal chromosome 1 long arm deletion. FISH with a panel of chromosome 1q42-qter bands-specific BAC and YAC clones located the breakpoint at the 1q42-q43 junction, with monosomy restricted to the 1q43 and 1q44 bands. The changing craniofacial phenotype of this patient with age is described as part of the del(1)(q) syndrome natural history. The patient's features are compared with those of other patients with similar deletions, and variable phenotypic findings due to different deleted chromosomal segments are discussed.

Abnormalities, Multiple↗
PubMed2003

Common arterial trunk in the fetus: characteristics, associations, and outcome in a multicentre series of 23 cases.

OBJECTIVE: To assess the accuracy of prenatal diagnosis, the incidence of extracardiac and chromosomal anomalies, and the perinatal outcome in a population of fetuses with common arterial trunk (CAT). DESIGN: Observational study of 23 fetuses from three referral centres with a confirmed diagnosis of CAT. All underwent fetal echocardiography, detailed anatomical scanning, and karyotyping. In 19 cases, FISH analysis was done to detect 22q11 microdeletion. The following variables were evaluated: gestational age at diagnosis, anatomical variants of the CAT, presence of extracardiac and chromosomal anomalies, pregnancy, and fetal-neonatal outcome. Necropsy reports and postnatal files were available for confirmation of the prenatal diagnosis in all cases. RESULTS: The prenatal diagnosis proved correct in 23 of 24 cases, the last being pulmonary atresia with ventricular septal defect (PAVSD). A second cardiovascular anomaly was present in eight cases (34.8%); extracardiac anomalies were found in 10 (43.4%). FISH analysis showed 22q11 microdeletion in six of 19 cases (31.6%). Outcomes were as follows: eight terminations of pregnancy (34.8%), two intrauterine deaths (8.7%), five postnatal deaths (before or after surgery) (21.7%); the remaining eight neonates (34.8%) are alive and thriving after surgery (six) or awaiting surgery (two). CONCLUSIONS: CAT can be reliably diagnosed and characterised in prenatal life, although differentiation from PAVSD may be challenging. The association with chromosomal anomalies is consistent (8.7%), but there is a higher risk of 22q11 microdeletion (31.6%), in agreement with postnatal studies. The relatively poor survival rate (34.8%) reflects the high rate of terminations and the unfavourable cardiac anatomy in some cases.

Aorta, Thoracic↗
PubMed2002

Interrupted aortic arch type A with 22q11 deletion: prenatal detection of an unusual association.

Interrupted aortic arch is a rare, severe congenital heart defect subdivided into three types, A, B and C, according to the site of interruption. Type C is by far the least common form of interrupted aortic arch (less than 5% of cases), type A is commonly an isolated defect whereas type B is frequently associated with 22q11 deletion. Differentiation of interrupted aortic arch type A from type B by prenatal echocardiography is possible but difficult; it needs to be done on the basis of observation of reliable morphological indicators which point to the correct diagnosis. Here we report the first case of prenatal diagnosis of interrupted aortic arch type A associated with 22q11 deletion. The significance of this association is not yet clear, since 22q11 genes mainly affect embryonic cardiovascular morphogenesis of those regions whose development is critically dependent on neural crest cell migration and function, affected in type B defect but not in type A.

Adult↗