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Biomedical subjects

P Martinelli

Publications and source records attributed to P Martinelli.

At least 19 recordsLinked to original sources
PubMed2006

Cytoplasmic localization of NPM in myeloid leukemias is dictated by gain-of-function mutations that create a functional nuclear export signal.

Nucleophosmin (NPM) is a nucleus-cytoplasmic shuttling protein that is implicated in centrosome duplication, cell cycle progression and stress response. At the steady state, NPM localizes mainly in the nucleolus, where it forms a complex with different cellular proteins. One-third of acute myeloid leukemias (AML) are characterized by aberrant cytoplasmic localization of NPM, due to mutations within its last coding exon (exon 12) that cause a frameshift and the formation of novel C-termini. We report here our investigations on the molecular basis for the aberrant localization of mutated NPM. Alignment of the C-terminus of the various NPM mutants revealed the obligatory presence of four amino-acid residues that match a CRM1-dependent nuclear export signal (NES). Single alanine-substitutions at these sites provoked nuclear re-localization, while fusion of the mutated C-terminus to a heterologous nuclear protein induced CRM1-dependent cytoplasmic localization. Molecular characterization of one exceptional AML carrying cytoplasmic NPM and germ line exon 12 revealed a somatic mutation in the splicing donor site of exon 9 that caused the formation of a functional NES. It appears, therefore, that AMLs are frequently characterized by gain-of-function mutations of NPM that create functional NES, suggesting that alterations of nuclear export might represent a general mechanism of leukemogenesis and a novel target for therapeutic intervention.

Acute Disease↗
PubMed2006

Early prenatal diagnosis of concordant posterior urethral valves in male monochorionic twins.

The association between monozygotic twins and posterior urethral valves (PUV) in postnatal life has been thoroughly described. In the fetus, the prenatal recognition of PUV is feasible. However, it has been repeatedly reported in singletons but never in monochorionic twins. We describe two cases of early prenatal diagnosis of concordant PUVs in monochorionic twins. In one of the sets, the expression of the disease was different for each twin.

Adult↗
PubMed2006

The role of spatio-temporal image correlation (STIC) with tomographic ultrasound imaging (TUI) in the sequential analysis of fetal congenital heart disease.

OBJECTIVE: Spatio-temporal image correlation associated with the tomographic ultrasound imaging mode (TUI-STIC) is a new modality that allows a complete sequential analysis of cardiac structures to be displayed on a single panel by showing all echocardiographic transverse views at the same time. The aims of this study were to identify the best settings for displaying the classic echocardiographic views at different gestational ages and to investigate the role of TUI-STIC in the sequential segmental analysis of complex congenital heart disease (CHD). METHODS: Four-dimensional volumes from 103 cases of confirmed fetal CHD diagnosed and managed at our referral center were evaluated using TUI-STIC. To select the best interslice distance for adequate display of the central cardiovascular connections, each volume was opened and the TUI mode activated, having as a reference the apical four-chamber view. The number of slices was set at nine. The volume was then scrolled until the most significant echocardiographic views were displayed on the screen windows. Then, if too many windows showed intermediate non-diagnostic views, the slice distance was adjusted finely until all key echocardiographic views showed up in the various windows. The interslice distance was regressed against gestational age and the best-fitting curve was identified. RESULTS: A sequential segmental analysis could be shown with TUI-STIC in all cases. A linear regression equation best fitted the correlation between interslice distance and advancing gestational age (r(2) = 0.9042), with the mean interslice distance being 2.7 (SD, 0.3) mm at 19-23 gestational weeks, and 4.0 (SD, 0.4) mm at 30-33 weeks. These settings allowed a complete sequential analysis in all cases. CONCLUSIONS: TUI-STIC allows a complete sequential analysis of CHD in the fetus. The most suitable interslice distances for all gestational ages could be identified. These data may be used while adopting this imaging modality in the four-dimensional evaluation of fetal CHD.

Echocardiography, Four-Dimensional↗
PubMed2006

Parkinsonism in Caplan's syndrome.

Parkinsonism is a rare feature of immunological diseases. We describe a 67-year-old man with Caplan's syndrome (CS) and parkinsonism. CS is an immunologic disease characterised by the presence of rheumatoid arthritis associated with a specific form of pneumoconiosis. Parkinsonism as a manifestation of involvement of the central nervous system in this condition has never been reported. Following immunosuppressive treatment both the CS and the parkinsonian signs and symptoms showed a marked improvement. The role of immune mechanisms in these parkinsonian syndromes is discussed.

Aged↗
PubMed2005

Split notochord syndrome variant: prenatal findings and neonatal management.

Spilt notochord syndrome is an extremely rare form of spinal dysraphism characterized by a complete cleft of the spine and a persistent communication between endoderm and ectoderm. A variant of split notochord syndrome was diagnosed in a 25-week-old fetus showing a prolapsed congenital colostomy and a spinal cystic lesion. The final diagnosis included protruding colon segment, imperforate anus with a rectourethral fistula and lipomyelomeningocele. The ultrasound features of the condition and the post-natal management are discussed. The neonate was successfully treated with a posterior sagittal anorectoplasty, while the lipomyelomeningocele was resected at a later stage.

Abnormalities, Multiple↗
PubMed2005

Hypoplastic left heart syndrome associated with left ventricle-coronary artery-pulmonary artery fistula: prenatal diagnosis and histological correlation.

We describe an unusual case of left ventricle-left coronary artery-pulmonary artery fistula associated with hypoplastic left heart syndrome (HLHS) and a ventricular septal defect, in which findings on echocardiography and histological analysis were correlated. The diagnosis was made at 22 weeks of gestation. We speculated that the presence of the fistula was the primary cause of the HLHS due to the existence of the ventricular septal defect that nullified the intraventricular pressure gradient, which is typical of hypoplastic ventricles and thought to be responsible for the secondary development of fistulas in other cases.

Abortion, Therapeutic↗
PubMed2005

REM sleep behaviour disorder in Parkinson's disease: a questionnaire-based study.

The aim of the study was to determine the clinical frequency and features of REM sleep behaviour disorder (RBD) in a large population of Parkinson's disease (PD) patients using defined diagnostic criteria both for RBD and PD. Six trained neurologists used a semistructured questionnaire based on ICSD-R diagnostic criteria for RBD to evaluate 200 PD patients and their caregivers. Interobserver reliability for the diagnosis of RBD was "substantial" (Kappa 0.65). Five patients were excluded from the study because of an MMSE lower than 25. The demographic and PD clinical features were compared in the clinically defined RBD group and in those without RBD (NRBD). Then the RBD features during the last year were analysed in the affected group. Out of 195 patients, 66 fulfilled the ICSD-R criteria for RBD; 62 patients reported RBD during the last year (frequency 31.8%). RBD features: two or more episodes per week in 35.5%; upper limb movements in 87%; lower limb movements in 79%; vocalisations during events in 85%. RBD onset was before PD in 27% of patients; 69% of the RBD group had injured themselves or their caregivers during sleep. According to multivariate analysis, RBD was associated with male gender, age and PD duration. Brief training and the use of a semistructured questionnaire may help the neurologist in dealing with sleep disturbances in PD patients. The search for RBD symptoms in PD is highly recommended, especially in patients with a long disease duration, the risk of sleep-related injuries being high.

Aged↗
PubMed2005

Prenatal diagnosis of placental chorioangioma: our experience.

Placental chorioangioma is the most common benign tumor of placenta. The relationship of vascularized chorioangiomas to adverse pregnancy outcome is well recognized. We report 3 cases of placental chorioangioma. Hypervascularization of the lesions in all patients and the immune hydrops with adverse fetal outcome in 2 cases are the complications of our mini-series. Ultrasonography and Doppler ultrasonography findings were useful in establishing the prenatal diagnosis and the prognosis.

Adult↗
PubMed2004

Congenital constriction band of the upper arm: the role of three-dimensional ultrasound in diagnosis, counseling and multidisciplinary consultation.

Constriction band syndrome represents a sporadic condition that may result in amputations, constrictions and other deformities of the fetal limbs and body. Prenatal diagnosis by two-dimensional ultrasound has been reported. We present a case of constriction band involving the upper arm in which the assessment by three-dimensional ultrasound significantly contributed to the diagnosis and the multidisciplinary counseling. In fact, multiplanar imaging and surface rendering allowed a clear depiction of the extent of the constriction, the club-hand deformity and the relationship between the amniotic band, the cord and the fetal limb. This case represents a unique and effective application of three-dimensional ultrasound in prenatal diagnosis.

Amniotic Band Syndrome↗
PubMed2004

Prenatal diagnosis of hemifacial microsomia and ipsilateral cerebellar hypoplasia in a fetus with oculoauriculovertebral spectrum.

Oculoauriculovertebral spectrum, or Goldenhar syndrome, is characterized by varying degrees of prevalently unilateral underdevelopment of craniofacial structures (orbit, ear, mandible) and spinal anomalies. We report the prenatal ultrasonographic diagnosis made at 24 weeks' gestation in a family with a negative history. The prenatal diagnosis was suspected due to the presence of marked hemifacial microsomia and moderate ipsilateral cerebellar hemisphere hypoplasia in the absence of facial clefting.

Adult↗
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

The role of tissue harmonic imaging in fetal echocardiography.

OBJECTIVE: To define the role of tissue harmonic imaging (THI) in fetal echocardiography. METHOD: Three trials were conducted in a tertiary referral center: Study A was a prospective randomized trial including 50 women referred for fetal echocardiography. Those allocated to Arm 1 underwent conventional fundamental frequency ultrasound (FFU) and those allocated to Arm 2 underwent THI. Study B was conducted in 21 patients who were obese or overweight with significant weight gain in pregnancy. In these patients, both THI and FFU echocardiography were performed and compared. In Study C, THI was employed as a second-line rescue technique in cases of inadequate or incomplete examination by FFU. A subjective scoring system was used by a reviewer who had not performed the examinations to assess the comprehensiveness of the examination and the image resolution. The reviewer was blinded to the image modality. RESULTS: In Study A, no difference was found in the diagnostic accuracy between THI and FFU echocardiography but the resolution was significantly poorer in the THI arm. In studies B and C, THI performed significantly better than FFU (P < 0.001). CONCLUSIONS: THI echocardiography seems to be the best technique to employ in obese women and in those in whom FFU fails to provide diagnostic information. However, due its poorer resolution in women of average weight, FFU echocardiography should remain the technique of choice.

Echocardiography↗
PubMed2004

Genetic prenatal RET testing and pregnancy management of multiple endocrine neoplasia Type II A (MEN2A): a case report.

Multiple endocrine neoplasia 2A (MEN 2A) is an inherited dominant syndrome characterised by medullary thyroid carcinoma, adrenal pheochromocytoma and hyperparathyroidism due to specific RET proto-oncogene mutations. Fertile MEN 2A women are at risk of complicated pregnancy because of unrecognised pheochromocytoma and transmission of RET mutation to the progeny. This condition may cause psychological distress in affected pregnant patients and their families. Here we describe the genetic prenatal testing, the pregnancy management and obstetric outcome in a MEN 2A patient with a right side adrenal hyperplasia and elevated calcitonin levels, a condition suspicious for possible recurrence of pheochromocytoma. We confirm that maternal or fetal complications are rare when MEN 2A diagnosis is made before pregnancy and an accurate monitoring is instituted. Furthermore, our results indicate that prenatal testing for RET mutations is highly recommended in making decisions and assuring parents on the lifelong risk of tumors. This will avoid the psychological distress that can further complicate the pregnancy of affected women.

Adrenal Hyperplasia, Congenital↗
PubMed2004

Undiagnosed coeliac disease does not appear to be associated with unfavourable outcome of pregnancy.

BACKGROUND: In a previous hospital based study, we suggested that undiagnosed coeliac disease has a prevalence, among pregnant women, of 1:80, and is a cause of unfavourable outcome of pregnancy. AIMS: In order to confirm or dismiss this hypothesis, which has significant public health implications, we carried out a large population based study on a stratified sample from the whole Campania region. PATIENTS: During the period of the study, 5345 women were admitted to the OBS-GYN wards regional network: 5055 (95%) were enrolled in the study. METHODS: Antihuman IgA class antitissue transglutaminase (TGASE) antibodies were tested by an ELISA method. Endomysial antibodies (EMA) were investigated on thin sections of human cord blood by an immunofluorescence test. The HLA class II DQA1*0501/DQB1*02 and DQA1*0301/DQB1*0302 haplotypes were assessed using the Eurospital Eu-DQ kit. Duodenal biopsy was not considered feasible by the ethics committee for pregnant women near delivery. RESULTS: Fifty one of 5055 patients had confirmed positive results. We added to these 12 women with known coeliac disease, giving a prevalence rate for coeliac disease of 1:80 (exactly the value observed during the first study). Comparing the 51 TGASE positive with 4997 negative women, we did not observe an excess risk of abortion, premature delivery, small birth weight, or intrauterine growth retardation. Anaemia was more frequent in cases than controls. CONCLUSIONS: Undiagnosed coeliac disease is frequent among pregnant women (>1%) but is not associated with an unfavourable outcome of pregnancy.

Adult↗
PubMed2003

Prenatal ultrasound diagnosis of Nager syndrome.

Nager syndrome, or acrofacial dysostosis, is a rare malformation complex characterized by facial anomalies (external ear abnormalities and micrognathia) and limb defects (radial hypoplasia and absence of the thumb and/or other digits). Since its first description in 1948, more than 80 cases have been reported in the pediatric literature. However, there is only one previous report on the prenatal recognition of the syndrome, which was at 30 weeks of gestation. We report here a further case of Nager syndrome, prospectively diagnosed at 23 weeks of gestation.

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↗