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PubMed2002

Interobserver and intraobserver variability in detection of patent foramen ovale and atrial septal aneurysm with transesophageal echocardiography.

BACKGROUND: An accurate diagnosis of patent foramen ovale (PFO) and atrial septal aneurysm (ASA) may be of decisional importance in the management of patients with ischemic stroke. Very few studies have been devoted to observer agreement in the diagnosis of these atrial septum abnormalities using contrast transesophageal echocardiography, which is considered as the method of choice for the diagnosis. The aim of this study was to assess interobserver and intraobserver variability in the diagnosis of PFO and ASA with contrast echocardiography. METHODS: Three sonographers independently reviewed 100 contrast studies stored on videotape on 2 occasions each. The interobserver and intraobserver variability was assessed by calculating kappa statistics. RESULTS: The overall interobserver and intraobserver kappa values for the assessment of degree of shunting through a PFO were 0.77 (first and second reading) and 0.82, respectively. The best kappa statistics were obtained when no and small shunts (less than 10 microbubbles) were pooled and compared with larger shunts. For the diagnosis of ASA, the overall interobserver kappa value was 0.45 for the first reading and 0.71 for the second reading, whereas the overall intraobserver kappa value was 0.74. CONCLUSION: Interobserver and intraobserver agreements for the diagnosis of PFO and ASA by transesophageal echocardiography are not perfect and need to be improved, particularly for ASA. This variability has to be taken into account when deciding on a potential risky treatment to prevent recurrent strokes.

Adult↗
PubMed2002

Comprehensive assessment of patent ductus arteriosus by echocardiography before transcatheter closure.

BACKGROUND: Anatomic type and angiographic measurements of patent ductus arteriosus (PDA) are used to determine the suitability of transcatheter closure (TCC). The purpose of this study is to evaluate whether these PDA features can be obtained by 2-dimensional echocardiography (2DE). METHODS: We retrospectively compared PDA measurements and type from 36 patients submitted to TCC between November 1995 and October 2000. RESULTS: The patient age ranged between 2 months to 10.5 years (median = 1.2 years). A significant correlation was found between measurements of PDA minimal diameter (R(2) = 0.88) and diameter at aortic ostium (R(2) = 0.72); whereas a poor correlation existed between measurements of the ampulla length. The 2DE and angiographic PDA classification were concordant in 31 of 36 (86%) patients. CONCLUSION: Our data support the use of 2DE measurements of PDA minimal diameter and PDA diameter at the aortic end to assess suitability for TCC. In the majority of cases, PDA type can be diagnosed by 2DE.

Age Factors↗
PubMed2002

Evaluation of shunt flow by multiplane transesophageal echocardiography in adult patients with isolated patent ductus arteriosus.

The role of multiplane (M) transesophageal echocardiography (TEE) in the diagnosis of isolated patent ductus arteriosus (PDA) in adults and its effectiveness in the assessment of the pulmonary to systemic flow ratio were evaluated and compared with those obtained from cardiac catheterization examination. Eleven consecutive patients, ranging from 17 to 56 years old (mean of 29.5 +/- 12.0), with clinically suspected PDA were subjects of this study. A complete transthoracic echocardiographic study was performed in each patient before MTEE. MTEE with Doppler color flow mapping showed clear visualization of a ductal structure between the descending aorta and pulmonary artery with a continuous turbulent mosaic flow suggestive of PDA in all 11 patients. The pulmonary/systemic flow and vascular resistance ratios obtained by echocardiography and cardiac catheterization correlated well (r = 0.8732, P =.0004; r = 0.623, P =.04, respectively). This study demonstrated that MTEE combined with transthoracic echocardiography examination is an accurate noninvasive means in the diagnosis of PDA and assessment of the pulmonary to systemic flow and vascular resistance ratios in adult patients.

Adolescent↗
PubMed2002

The effect of in utero exposure to indomethacin on the need for surgical closure of a patent ductus arteriosus in the neonate.

OBJECTIVE: Our purpose was to determine the effect of in utero exposure to indomethacin on the need for surgical closure of a patent ductus arteriosus (PDA). STUDY DESIGN: Perinatal variables were compared between infants at <32 weeks who required surgical closure of PDA after failed medical management and those who did not. Statistical analysis was performed by Student t, Mann-Whitney, chi(2), and multiple logistic regression tests. RESULTS: Eight of 77 infants with PDA failed therapy and required surgery. Maternal demographics, gestational age, birth weight, and delivery route were similar in both groups. In utero exposure to indomethacin was more common in neonates requiring surgery versus those who did not, particularly when exposure was for >72 hours (50.0% vs 8.7%, odds ratio 10.5, 95% CI 1.6-72.1, P =.008). CONCLUSION: Need for surgical closure of PDA appears to be increased by in utero indomethacin exposure. These findings should be considered in the overall context of the risk versus benefits of tocolysis.

Adult↗
PubMed2001

Early versus late indomethacin treatment for patent ductus arteriosus in premature infants with respiratory distress syndrome.

OBJECTIVE: To compare efficacy and side effects of early versus late indomethacin treatment for patent ductus arteriosus (PDA) in premature infants. METHODS: One hundred twenty-seven neonates receiving ventilatory assistance (gestational age: 26-31 weeks) with PDA confirmed by echocardiography were randomly assigned in a prospective multicenter trial to either early (day 3, n = 64) or late (day 7, n = 63) intravenous indomethacin treatment (3 x 0.2 mg/kg every 12 hours). Treatment history and side effects were registered. RESULTS: The PDA closure rate was higher in the early treatment group at both 6 (73% vs 44%, P =.0008) and 9 days of age (91% vs 78%, P =.047). However, there was no significant difference in PDA ligation. Urine output was significantly lower (P <.0001), serum creatinine level was higher (P =.016), and more indomethacin courses were administered in the early treatment group (70 vs 26). Respiratory support, number of deaths, and intraventricular hemorrhages were similar in both groups. However, on the whole, major adverse events (death, necrotizing enterocolitis, and/or localized perforation, extension of hemorrhage, or cystic leukomalacia) occurred more frequently in the early treatment group (P =.017). CONCLUSION: Early indomethacin treatment improves PDA closure but is associated with increased renal side effects and more severe complications and has no respiratory advantage over late indomethacin administration in ventilated, surfactant-treated, preterm infants <32 weeks' gestational age.

Ductus Arteriosus, Patent↗
PubMed2003

Indomethacin responsiveness of patent ductus arteriosus and renal abnormalities in preterm infants treated with indomethacin.

OBJECTIVES: We evaluated the factors related to indomethacin responsiveness of the patent ductus arteriosus (PDA) and subsequent renal and electrolyte abnormalities in a large number of low birth weight infants. METHODS: The ductus was evaluated by Doppler echocardiogram or clinical signs after the last administration of indomethacin for 2538 low birth weight infants, through the use of postmarketing surveillance data. RESULTS: Multivariate logistic regression analyses demonstrated that clinical closure of PDA was significantly associated with pregnancy-induced hypertension and respiratory distress syndrome. In contrast, a 1-point increase of cardiovascular dysfunction score or a 1-day increase in postnatal age at the first indomethacin treatment decreased the responsiveness of the ductus to indomethacin. Clinical ductal reopening was significantly less likely to occur for each week of increased gestational age. Ductal reopening was more likely for each day of postnatal life at the first administration of indomethacin. Infants with preexisting renal and electrolyte abnormalities and infants whose mothers had received indomethacin tocolysis or who had chorioamnionitis were at increased risk of development of renal impairment. CONCLUSIONS: Both antenatal and postnatal factors predict good or poor response to indomethacin therapy for PDA.

Cardiovascular Agents↗
PubMed2005

Syndromic patent ductus arteriosus: evidence for haploinsufficient TFAP2B mutations and identification of a linked sleep disorder.

Patent ductus arteriosus (PDA) is a common congenital heart disease that results when the ductus arteriosus, a muscular artery, fails to remodel and close after birth. A syndromic form of this disorder, Char syndrome, is caused by mutation in TFAP2B, the gene encoding a neural crest-derived transcription factor. Established features of the syndrome are PDA, facial dysmorphology, and fifth-finger clinodactyly. Disease-causing mutations are missense and are proposed to be dominant negative. Because only a small number of families have been reported, there is limited information on the spectrum of mutations and resulting phenotypes. We report the characterization of two kindreds (K144 and K145) with Char syndrome containing 22 and 5 affected members, respectively. Genotyping revealed linkage to TFAP2B in both families. Sequencing of TFAP2B demonstrated mutations in both kindreds that were not found among control chromosomes. Both mutations altered highly conserved bases in introns required for normal splicing as demonstrated by biochemical studies in mammalian cells. The abnormal splicing results in mRNAs containing frameshift mutations that are expected to be degraded by nonsense-mediated mRNA decay, resulting in haploinsufficiency; even if produced, the protein in K144 would lack DNA binding and dimerization motifs and would likely result in haploinsufficiency. Examination of these two kindreds for phenotypes that segregate with TFAP2B mutations identified several phenotypes not previously linked to Char syndrome. These include parasomnia and dental and occipital-bone abnormalities. The striking sleep disorder in these kindreds implicates TFAP2B-dependent functions in the normal regulation of sleep.

Abnormalities, Multiple↗
PubMed2002

Finding genetic contributions to sporadic disease: a recessive locus at 12q24 commonly contributes to patent ductus arteriosus.

The causes of many sporadic diseases are unexplained; the contribution of recessive loci with reduced penetrance is one possibility that has been difficult to explore. We describe an approach to this problem by first searching for diseases with higher prevalence in populations with high rates of consanguinity, then determining whether disease cases are more commonly the product of consanguinous union than controls in such populations, followed by analysis of genetic linkage in consanguinous cases. We demonstrate the utility of this approach by investigation of congenital heart disease in Iran. We found that patent ductus arteriosus (PDA), a common congenital heart disease, accounts for a higher fraction of congenital heart disease in Iran (15%) than in the United States (2-7%). Moreover, Iranian PDA cases demonstrated a marked increase of parental consanguinity (63%), compared with the general Iranian population (25%) or control cases with tetralogy of Fallot (30%). The recurrence of PDA among siblings was 5%. A genomewide analysis of linkage in 21 unrelated consanguinous PDA cases demonstrated a multipoint logarithm of odds score of 6.27 in favor of linkage of PDA to a 3-centimorgan interval of chromosome 12q24, with 53% of kindreds linked. These findings together establish a recessive component to PDA and implicate a single locus, PDA1, in one third or more of all PDA cases in Iran; they further suggest a role for this locus in PDA worldwide. Finally, these results suggest a general approach to the identification of recessive contributions to sporadic diseases.

Chromosome Mapping↗
PubMed2004

Patent ductus venosus and dioxin resistance in mice harboring a hypomorphic Arnt allele.

The Ah receptor nuclear translocator (ARNT) is the dimeric partner of hypoxia-inducible factors and thus plays a pivotal role in cellular adaptation to low oxygen environments. ARNT is also a dimeric partner for the Ah receptor (AHR), and this complex is essential in regulating the adaptive metabolic response to polycyclic aromatic hydrocarbons. Because of the essential role of ARNT in hypoxia-driven developmental events, it has been difficult to study the physiological significance of AHR.ARNT heterodimers in vivo. To address this issue, we developed a hypomorphic Arnt allele that displayed normal development and allowed the examination of the role of ARNT in AHR biology. In this regard, the AHR is also known to mediate two additional biological processes: the toxicological response to compounds such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) and the developmental closure of a fetal vascular structure known as the ductus venosus. Although the mechanism of the adaptive pathway has been well described, the mechanism of AHR-mediated signal transduction in the toxic and developmental pathways is not well understood. Liver perfusion studies demonstrated that ARNT hypomorphs have a patent ductus venosus, identical to that observed in the Ahr null mice. Parallel dioxin toxicity studies demonstrated that the ARNT hypomorphs exhibited resistance to the end points of dioxin exposure. Moreover, we observed that toxicity could be segregated from the classical adaptive responses such as P4501A induction. Taken in sum, these experiments demonstrate that ARNT is an essential component of AHR developmental signaling and shed light on the mechanism of dioxin toxicity.

Alleles↗
PubMed1998

The patentability of human genes: an ethical debate in the European Community.

The European Parliament rejected in 1995 the European Commission proposal to harmonize legal protection of biotechnological inventions. Although it did not seem initially the most contentious of the many issues involved in the current legal and ethical debate around biomedicine and genetics, patenting is now focusing bioethics in Europe.

Bioethics↗
PubMed2001

Commercialization, patents and moral assessment of biotechnology products.

The biotechnology patent debates have revealed deep moral concerns about basic genetics research, R&D and specific biotechnological products, concerns that are seldom taken into consideration in Technology Assessment. In this paper important moral concerns are examined which appear at the various stages of development of a specific genetic product: a predictive genetic test. The purpose is to illustrate the need for a more contextual approach in technology assessment, which integrates the various forms of interaction between bio-technology and society or societal segments. Such an approach will generate greater insight in the moral issues at all stages of a product's life-cycle and this will facilitate decision-making on the 'morality' of a specific biotechnological product.

Biotechnology↗
PubMed1999

Cephalad renal ectopia, duplication of pelvicalyceal system and patent ductus arteriosus in an adult female.

An unusual cause for a shadow in the plain CX-ray of a female with uncomplicated patent ductus arteriosus is presented herein. The chest CT scan and IVU revealed the presence of a high (cephalad) right kidney in an eventrated hemidiaphragm. A bifid ureter and duplication of the pelvis were found in the contralateral kidney. This constellation of anomalies is exceedingly rare.

Adult↗
PubMed1992

Preterm infants with patent ductus arteriosus: treatment with an enteral preparation of indomethacin.

Forty-one preterm infants with a mean gestational age and birthweight of 29.7 weeks and 1322 g, respectively, were treated with an enteral preparation of indomethacin for the closure of haemodynamically significant patent ductus arteriosus. The indomethacin was prepared by diluting the content of the commercially available 25-mg indomethacin capsule with lactose by the method of trituration. The mixture was suspended in solution form just prior to administration to the infants. The ductus arteriosus was successfully closed in 29 infants, giving an overall success rate of 71%. The response to treatment was considered satisfactory, except for infants whose birthweights were less than 750 g. Only two infants (5%) developed major complications, both in the form of ileal perforation. As the outcome of treatment with this enteral preparation of indomethacin was comparable with that of the intravenous preparation reported in previous studies, it would be an acceptable alternative to the intravenous preparation in areas where the latter is not available or considered expensive.

Administration, Oral↗
PubMed2000

Prophylaxis of patent ductus arteriosus with ibuprofen in preterm infants.

UNLABELLED: The aim of our study was to evaluate whether the prophylactic use of ibuprofen would reduce the incidence of significant patent ductus arteriosus (PDA) and to confirm the effectiveness of ibuprofen as rescue treatment in closing PDA. Eighty preterm infants with gestational age less than 34 wk with infant respiratory distress syndrome (iRDS) were randomized to receive intravenous ibuprofen lysine (10 mg/kg, followed by 5 mg/kg after 24 and 48 h) either within 24 h of life (group A) or after echocardiographic diagnosis of PDA (group B). To evaluate the severity of RDS in each patient, we calculated the initial and highest values of Oxygenation Index (O.I. = mean airway pressure x FiO2 x 100/PaO2) and Ventilatory Index (V.I. = O.I. x mechanical respiratory rate). Other studied variables were ventilatory support, renal function, biochemical and haematological profiles, frequency of bronchopulmonary dysplasia (BPD), intraventricular haemorrhage (IVH), necrotizing enterocolitis (NEC) and retinopathy of prematurity (ROP). On the 3rd day of life, 8% (3/40) of patients of group A and 53% of patients (21/40) of group B (p < 0.0001) developed a significant PDA. Between patients of group B who presented PDA at 3 d of life 90% (19/21) had a closure of ductus arteriosus after ibuprofen treatment. Initial and highest values of O.I. and V.I. were similar in both groups A and B. No significant differences between the groups were observed in regard to respiratory support, renal function and frequency of BPD, IVH, NEC and ROP. Ibuprofen was not associated with adverse effects. CONCLUSION: Prophylactic treatment with ibuprofen reduces PDA occurrence in preterm infants with iRDS at 3 d of life in comparison with rescue treatment, but both modes are effective in closing the ductus without significant adverse effects.

Age Factors↗
PubMed2001

Plasma levels of natriuretic peptides and hemodynamic assessment of patent ductus arteriosus in preterm infants.

UNLABELLED: The main purpose of this study was to investigate whether circulating natriuretic peptides in premature infants reflect the hemodynamic significance of a patent ductus arteriosus (PDA). The study comprises 120 examinations in 55 premature infants with a mean gestational age of 27.2 wk and a mean birthweight of 933 g. Based on clinical and echocardiographic findings, the hemodynamic influence of ductal shunting was classified as small, moderate or large. Blood samples for N-terminal proatrial natriuretic peptide (Nt-proANP) and brain natriuretic peptide (BNP) were analysed after completion of the clinical part of the study. Linear regression indicated a very strong association between Nt-proANP and BNP (adjusted R = 0.89). The mean levels of Nt-proANP and BNP increased with the size of the shunt through a PDA, and peptide values followed hemodynamic alterations. The size of PDA accounted for 50% and 47% of the total variation in the plasma values of Nt-proANP and BNP, respectively. In detecting an echocardiographically significant PDA, the area under a ROC curve was 0.94 for Nt-proANP and 0.90 for BNP. CONCLUSION: The magnitude of shunting through a PDA is the main determinant of plasma levels of natriuretic peptides in premature infants. Nt-proANP and BNP seem to have the same pattern of secretion. Our findings indicate that measurements of natriuretic peptides may provide clinically relevant information in the hemodynamic assessment of premature infants.

Atrial Natriuretic Factor↗
PubMed2004

Necrosis of the epididymis in a premature infant with patent ductus arteriosus and diastolic aortic steal: ischemia or torsion?

UNLABELLED: We describe a case of isolated ischemic necrosis of the epididymis in a premature newborn with aortic steal syndrome, secondary to a large patent ductus arteriosus (PDA). Neither this finding nor the possible underlying pathogenesis has been previously described. CONCLUSION: In this report our knowledge of the potential complications of PDA in the premature neonate is extended.

Adult↗
PubMed2006

Patent ductus arteriosus in extremely preterm infants receiving phototherapy: does shielding the chest make a difference? A randomized, controlled trial.

BACKGROUND: Patent ductus arteriosus (PDA), a common complication in extremely preterm infants, is associated with increased mortality and morbidity. Phototherapy has been associated with PDA, and one randomized, control trial has shown that shielding of the chest may decrease the risk of PDA. AIM: To examine if chest shielding reduces the incidence and severity of PDA in extremely preterm infants. STUDY DESIGN: Randomized clinical trial of infants < 29 wk gestation (stratified into two groups: < 27 wk gestation and 27-28 wk gestation). METHODS: Following written parental consent, eligible infants were randomized to receive phototherapy, with or without a chest shield. Ductal parameters were assessed by Doppler echocardiogram in all infants prior to starting phototherapy and at 48 h after initiation, or earlier if phototherapy was discontinued. RESULTS: 54 infants were enrolled in the study. The incidence of PDA (shield 19/27 vs no shield 21/27), ductal size (1.4 vs 1.0 mm) and left atrial/aortic root (LA/Ao) ratio (1.2 vs 1.3) were similar in the two groups pre-phototherapy. There was no difference between the groups post-phototherapy in incidence (shield 12/27 vs no shield 13/27), ductal size (1.4 vs 1.5 mm) or LA/Ao ratio (1.1 vs 1.3). CONCLUSION: Chest shielding did not alter the incidence or severity of PDA in our population of extremely preterm infants.

Ductus Arteriosus, Patent↗
PubMed2004

Association of patent ductus arteriosus and severe hypothyroidism in term newborns: coincidence or causal?

We report on 3 term newborns with the association of patent ductus arteriosus (PDA) and severe hypothyroidism attributed to thyroid agenesis (n = 2) or feto-maternal pit-1 deficiency (n = 1). This association suggests that sufficient thyroid hormone availability is among the prerequisites for normal postnatal ductal closure. Unravelling the maturational effects of thyroid hormone on the ductus arteriosus might also be relevant in preterm infants as further studies of the perinatal thyroid axis may clarify the potential role of thyroid hormone in PDA closure in preterm infants. Based on our observation, hypothyroidism should be considered in term infants with PDA.

Ductus Arteriosus, Patent↗