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Neurogenic chronic idiopathic intestinal pseudo-obstruction, patent ductus arteriosus, and thrombocytopenia segregating as an X linked recessive disorder.

We present a family with three affected males in two generations with congenital neurogenic chronic idiopathic intestinal pseudo-obstruction (CIIP), patent ductus arteriosus, and large platelet thrombocytopenia apparently segregating as an X linked recessive disorder. The pattern of segregation of DNA markers within the family is consistent with linkage to the previously described neurogenic CIIP (CIIPX) locus at Xq28. This combination may represent a new contiguous gene disorder and appears to have a good prognosis with supportive therapy.

Abnormalities, Multiple↗

Pulmonary hypertension accompanying ventricular septal defect and patent ductus arteriosus. Management in infancy and early childhood.

Forty-one infants and children with the combination of patent ductus arteriosus (PDA) and ventricular septal defect (VSD) were encountered over 20 years. Twenty-four presented in infancy with congestive cardiac failure. Pulmonary hypertension was present in 32, the cause in 19 being increased pulmonary blood flow. Increased pulmonary vascular resistance (PVR) was detected in 13 (indicated by a pulmonary to systemic resistance ratio (Rp : RS) greater than 0.24:1 and PVR greater than 4 units). Thus 22% had a pulmonary artery systolic pressure less than 30 mmHg and 68% had a pulmonary vascular resistance below four units, indicating an unusually mild form of the combined condition in these patients. Surgical management is discussed, and in particular the question of simultaneous closure of the defects during infancy. Cardiac failure, resistant to drug treatment, and increased PVR are indications of operation. The PDA should be closed and only if there is no substantial fall in pulmonary artery pressure is the VSD repaired.

Child↗

Use of a balloon occlusion catheter to facilitate transarterial coil embolisation of a patent ductus arteriosus in two dogs.

Two dogs with a history of coughing and exercise intolerance were suspected to have a patent ductus arteriosus (PDA), and the presence of a type III PDA was confirmed by radiography, electrocardiography, ultrasonography and angiography. Transarterial coil embolisation was carried out by using a modified technique. An occlusion balloon catheter was inserted through a femoral vein and placed at the pulmonary side of the ductus before the embolisation coils were put in place. Both dogs remained healthy during a follow-up period of nine months.

Animals↗

Patent ductus arteriosus in preterm infants with idiopathic respiratory distress syndrome. Radiographic and echocardiographic evaluation.

Clinical, radiographic, echocardiographic and operative findings were evaluated in 55 preterm infants with idiopathic respiratory distress syndrome (IRDS) complicated by patent ductus arteriosus (PDA). Pulmonary plethora was detected prior to age seven days in 52 infants, and prior to murmur detection in 42 infants. In those with large shunts, only 35% had cardiomegaly while 78% had a significant increase in cardiothoracic ratio (C/T) on sequential radiographs. Moreover, within 48 hours after ligation, 91% of infants had a significant decrease in C/T. Echocardiographic left atrial to aortic ratio (LA/Ao) was elevated in 71% with large shunts. In one patient with a large shunt there was neither a sequential increase in C/T nor an increased LA/Ao. Severity of left-to-right shunting across a PDA in the newborn was reliably gauged by combined radiographic and echocardiographic evaluation. Either modality alone failed to reflect the presence of a large volume shunt in a number of infants.

Ductus Arteriosus, Patent↗

Differential shunting in the diagnosis of patent ductus arteriosus with Eisenmenger physiology by radionuclide angiography.

Radionuclide angiography and static whole body imaging performed with technetium-99m-labeled particulates can clearly demonstrate differential shunting in patients with patent ductus arteriosus (PDA) with Eisenmenger physiology. The anatomic arterial relationships in this condition which direct deoxygenated blood into the lower body (differential cyanosis) produce specific radionuclide images characterized by differential shunting of the technetium-99m-labeled particulates into the abdomen and lower extremity.

Adult↗

Assessment of patent ductus arteriosus in preterm infants by single lateral film aortography.

Differentiation of a hemodynamically significant cardiovascular abnormality from lung disease in the newborn infant may remain problematic after clinical, radiographic, and echocardiographic evaluation. Single-view aortography was performed in 38 preterm and one full term infant in the neonatal special care nursery. Special lateral views were obtained consisting of either a horizontal x-ray beam with oblique angulation of the supine patient or a vertical bean with 30 degree head-up angulation of the patient. These views projected the ductus caudal to the aortic arch and enabled visualization of the entire length of the ductus and focal constrictions of the ductus. The severity of patent ductus arteriosus was judged by anatomic (diameter of the ductus compared to the descending aorta) and physiologic (preferential opacification of the aortic arch or pulmonary circulation) criteria.

Aortography↗

Patent ductus arteriosus: transcatheter closure with a transvenous technique.

Transvenous closure is described of the patent ductus arteriosus with a conical device that consists of polyurethane foam mounted on a stainless steel frame. Since 1981, the procedure has been performed in 273 patients in Russia. Permanent complete ductus closure was achieved in 258 (95%) patients. In eight cases (3%), the occlusion was incomplete. Complications occurred in 10 patients (4%), seven of whom required emergency surgery. The new technique combines certain advantages of both alternative methods. The conical shape of the occlusion device is well suited for the anatomic structure of the ductus. The possibility of selecting the size of the device permits reduction in the rate of incomplete closure while still taking advantage of transvenous delivery to avoid entry-site problems. In the initial 10 years of experience, the described technique proved effective, safe, and applicable in the vast majority of patients older than 2 years.

Adolescent↗

Respiratory effects of a patent ductus arteriosus in premature newborn lambs.

We examined the respiratory effects of a patent ductus arteriosus in 29 premature lambs (131-135 days gestational age) after infiltrating the ductal wall with formaldehyde solution (Formalin) and placing a snare around the ductus to regulate its patency. The lambs were given sheep surfactant, paralyzed, and mechanically ventilated at birth. We first compared 8 lambs with open ductus and 13 lambs with closed ductus during the 12 h after birth. Although lambs with open ductus had greater pulmonary blood flow (301 +/- 36 vs. 188 +/- 11 ml.min-1.kg-1, mean +/- SE, at 12 h of age) and mean pulmonary arterial (44 +/- 3 vs. 33 +/- 2 mmHg) and left ventricular end-diastolic (6 +/- 0.6 vs 4 +/- 0.7 mmHg) pressures, we found no differences in dynamic respiratory compliance (Cdyn = 0.55 +/- 0.07 vs. 0.55 +/- 0.03 ml.cmH2O-1.kg-1), midtidal volume resistance (62 +/- 5 X 10(-3) vs. 62 +/- 7 X 10(-3) cmH2O.ml-1.s), or functional residual capacity (FRC = 27 +/- 3 vs. 26 +/- 2 ml.kg-1). Alveolar-arterial PO2 difference was lower in the lambs with open ductus (238 +/- 65 vs. 362 +/- 37 Torr). Next, we challenged eight lambs with two separate saline infusions (50 ml.kg-1 over 3 min), each given with the ductus alternately closed or open. When the ductus was closed, FRC was unchanged, but Cdyn increased by 18% immediately after the infusion. When the ductus was open, FRC decreased by 16% and Cdyn decreased by 12%. We conclude that the premature lamb is surprisingly resistant to changes in respiratory function from ductal patency during the immediate neonatal period.

Animals↗

[Ibuprofen versus indomethacin in the treatment of patent ductus arteriosus in preterm infants].

INTRODUCTION: Persistent patent ductus arteriosus (PDA) is a common entity in preterm infants. The most commonly used pharmacological treatment to close the ductus is indomethacin but it can affect cerebral, renal and mesenteric blood flow. Ibuprofen has recently been shown to be effective in closing PDA with fewer hemodynamic effects. In this study we compared the safety and efficacy of ibuprofen and indomethacin in the treatment of PDA in preterm infants. MATERIAL AND METHODS: A randomized trial was performed. Premature infants with symptomatic PDA confirmed by echocardiography in the first week of life and who required respiratory support were included. The patients were randomly assigned to receive either intravenous indomethacin or ibuprofen. The rate of ductal closure, need for additional treatment, complications, and clinical course were evaluated. RESULTS: Twenty-four patients were treated with indomethacin and 23 with ibuprofen. The clinical characteristics before treatment were similar in both groups. Both treatments were effective in closing PDA (87.5% in the indomethacin group and 82.6% in the ibuprofen group). The two cohorts did not differ in the rate of reopening, need for a second pharmacologic treatment, or surgical ductal ligation. No patient in the ibuprofen group developed gastrointestinal adverse effects, but two infants in the indomethacin group had isolated bowel perforation and one had necrotizing enterocolitis. Transient renal dysfunction developed in seven patients (29%) in the indomethacin group versus two (9%) in the ibuprofen group. Transient renal insufficiency was found in one patient in the indomethacin group and in none in the ibuprofen group. The rate of other complications was similar in both groups. CONCLUSIONS: In our trial ibuprofen was as effective as indomethacin in closing PDA. No significant differences were found in the incidence of complications but fewer renal complications and no gastrointestinal complications were found in the ibuprofen group.

Anti-Inflammatory Agents, Non-Steroidal↗

Mechanics of breathing after surgical ligation of patent ductus arteriosus in newborns with respiratory distress syndrome.

The aim of the study was to detect changes in pulmonary function following ligation of a patent ductus arteriosus (PDA). Pulmonary function was recorded in 16 newborns (birth weight 1,081 +/- 166 g, gestational age 27.6 +/- 1.7 weeks) before and after ligation. No change in resistance of airways or mean airway pressure was observed. We found an increase in dynamic compliance (Cdyn) of 77% (p < 0.01), in tidal volume (TV) of 29% (p = 0.004), and in minute ventilation (MV) of 17% (p < 0.01) after the procedure. We demonstrated that pulmonary function improves after surgical ligation of the PDA. Because of considerable variation in intubated and spontaneously breathing premature newborns, we recommend the analysis of three main parameters: Cdyn, TV and MV for estimation of pulmonary mechanics in these infants.

Airway Resistance↗

Moyamoya angiopathy with dolichoectatic internal carotid arteries, patent ductus arteriosus and pupillary dysfunction: a new genetic syndrome?

We report on 2 children with moyamoya angiopathy and bilateral dolichoectatic internal carotid arteries in combination with iris hypoplasia with bilateral fixed dilated pupils and a history of patent ductus arteriosus. Both were symptomatic with moyamoya angiopathy and underwent bilateral extracranial-intracranial (EC-IC) bypass operations for cerebral revascularization. This is the first report on moyamoya angiopathy and bilateral dolichoectatic internal carotid arteries with simultaneous occurrence of ocular and cardiovascular malformations. There have been descriptions of cerebral vascular abnormalities in combination with either congenital heart disease or ocular abnormalities but not with both presenting together. The combination of these separate congenital developmental defects may not be purely coincidental: we propose that the 2 probands are affected with a not yet recognized clinical syndrome of probably genetic etiology.

Carotid Artery, Internal↗

Patent ductus arteriosus and respiratory outcome in premature infants.

A persistent ductus arteriosus is a common event in preterm infants. The systemic-to-pulmonary shunting that occurs as the pulmonary vascular resistance decreases after birth can have significant cardiovascular and respiratory consequences. Acute pulmonary effects include pulmonary edema and hemorrhage, worsened lung mechanics and deterioration in gas exchange with hypoxemia and hypercapnia. The increased pulmonary blood flow can also produce damage to the capillary endothelium and trigger an inflammatory cascade. This, plus the need for longer and more aggressive mechanical ventilation, can explain the association between patent ductus arteriosus and an increased risk for bronchopulmonary dysplasia in extremely premature infants.

Bronchopulmonary Dysplasia↗

Effects of ibuprofen and indomethacin on urinary antidiuretic hormone excretion in preterm infants treated for patent ductus arteriosus.

OBJECTIVE: To compare the effects of intravenous ibuprofen and indomethacin for treatment of patent ductus arteriosus (PDA) on urinary antidiuretic hormone (ADH) excretion, as a cause of oliguria. STUDY DESIGN: Forty-four respiratory distress syndrome prematures (<or=34 weeks' gestation) with PDA received either ibuprofen (n = 22) in an initial dose of 10 mg/kg followed by two doses of 5 mg/kg each after 24 and 48 h or three doses at 12-hour intervals of indomethacin (n = 24), 0.2 mg/kg, both infused continuously over a period of 15 min. Urinary ADH excretion, diuresis, serum creatinine, urinary sodium, fractional excretion of sodium, and urinary osmolality were measured before and after treatment. RESULTS: Indomethacin treatment caused a significant decrease in urinary ADH excretion (21.8 +/- 20.8 vs. 13.8 +/- 12.9 pg/ml; p < 0.05), along with a significant reduction in urinary sodium (92.1 +/- 36.1 vs. 64.8 +/- 35.6; p < 0.05), fractional excretion of sodium (68.5 +/- 37.1 vs. 45.6 +/- 37.1; p < 0.05), and urinary osmolality (276.2 +/- 103.9 vs. 226.4 +/- 60.3; p < 0.05). Ibuprofen treatment did not modify urinary ADH excretion and caused a statistically insignificant decrease in urinary sodium and in fractional excretion of sodium. CONCLUSIONS: Compared with ibuprofen, indomethacin caused a significant reduction in urinary ADH excretion and a significant decrease in urinary sodium and osmolality.

Cyclooxygenase Inhibitors↗

Lung compliance in newborns with patent ductus arteriosus before and after surgical ligation.

Pressure volume curves of the lungs were determined in 10 premature infants (mean gestational age 31.4 weeks, mean birth weight 1,260 g) before and after surgical ligation of a patent ductus arteriosus (PDA). 7 infants who had low compliance initially showed a significant improvement in lung compliance after surgery, while 3 infants whose compliance was close to normal before surgery had a decrease after ligation. In conclusion, a PDA with left to right shunt is frequently associated with a decrease in lung compliance that improves after ligation. Measurement of lung compliance in infants with PDA can be helpful in predicting the degree of improvement in lung function that may result from the closure of the ductus.

Ductus Arteriosus, Patent↗

Symptomatic patent ductus arteriosus following prophylactic indomethacin. A clinical and biochemical appraisal.

Seven of 36 premature infants with birth weight less than 1,250 g who had been randomly assigned to either high-frequency ventilatory ventilation or conventional mechanical ventilation developed symptomatic patent ductus arteriosus (PDA) after receiving prophylactic indomethacin, 0.2 mg/kg, i.v. 24 h after birth. Infants who developed symptomatic PDA were more likely to be white and male and have more severe pulmonary insufficiency than infants who did not develop symptomatic PDA. Serum indomethacin levels were similar in both groups of patients. There was no difference in the degree of suppression or subsequent recovery of endogenous eicosanoid biosynthesis between infants who did and did not develop symptomatic PDA. Compared to conventional mechanical ventilation, high-frequency oscillatory ventilation had no significant effect on endogenous eicosanoid biosynthesis. The susceptibility of white male infants to symptomatic PDA following prophylactic indomethacin may represent the influence of maturational factors on ductus patency. Cyclooxygenase products do not appear to be involved in mediating ductus patency when symptomatic PDA occurs immediately following administration of prophylactic indomethacin.

Dinoprostone↗

Closure of patent ductus arteriosus decreases pulmonary myeloperoxidase in premature infants with respiratory distress syndrome.

The aim of the study was to determine whether in premature infants with respiratory distress syndrome (RDS), an interrelationship existed between patent ductus arteriosus (PDA) and pulmonary neutrophil content. Thirteen premature infants with PDA (gestational age 26.9 +/- 2.4 weeks, birth weight 903 +/- 300 g) were pair-matched with infants without PDA (gestations age 27.1 +/- 2.5 weeks, birth weight 1,041 +/- 430 g) with regard to gestational age, birth weight and severity of RDS. The myeloperoxidase (MPO) contents of tracheal aspirates were analyzed before (age 2.8 +/- 1.7 days, MPO I) and after closure of PDA with indomethacin (5.5 +/- 1.9 days, MPO II), and at corresponding time points in controls (2.6 +/- 1.6 and 4.8 +/- 1.8 days). In PDA patients closure of PDA decreased MPO from 14.7 (range 2.1-27.4) to 4.6 (1.2-8.0) micrograms/mg protein (p = 0.0008), whereas in controls it remained unchanged: 5.4 (2.9-7.8) and 5.3 (2.9-7.8; p = 0.58). A significant difference existed in the change in MPO contents between the infants with PDA and the controls. In premature infants with RDS, closure of PDA decreases the neutrophil content of the lungs. The effect may be caused by closure of PDA as such, or by indomethacin. The high pulmonary neutrophil content in PDA may exacerbate inflammatory processes and contribute to the development of chronic pulmonary disease.

Birth Weight↗

Indomethacin therapy in premature infants with patent ductus arteriosus and oliguria.

Simultaneous administration of one dose of indomethacin (0.3 mg/kg, i.v.) and furosemide (1 mg/kg, i.v.) was given to 8 consecutive premature infants who had patent ductus arteriosus (PDA), and oliguria because of prerenal failure. Four infants responded with ductus closure and 2 infants showed improvement in echocardiogram and clinical distress. There was a significant increase in U/O, GFR, FENa and FECl following drug administration. This study suggests that simultaneous administration of indomethacin and furosemide can be safely used in infants with PDA and oliguria.

Anuria↗