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DuctOcclud--implant for transcatheter closure of patent ductus arteriosus.

The DuctOcclud implant is a metal coil device designed for transcatheter closure of small to moderate size patent ductus arteriosus, a Congenital Heart Disease in which a vessel-like communication between the aorta and the pulmonary artery persists after birth. The paper describes the design of the device, its delivery system, and the implant procedure. It also reviews and reports the experimental and the clinical experiences accumulated utilizing the device for occlusion of patent ductus arteriosus.

Animals↗

Randomized trial of prolonged low-dose versus conventional-dose indomethacin for treating patent ductus arteriosus in very low birth weight infants.

OBJECTIVE: Indomethacin is used for closing the patent ductus arteriosus in premature infants. Prolonged low-dose indomethacin given over 6 days could potentially improve closure rates because ductal constriction is maintained long enough for more effective anatomic closure. We compared the efficacy of this regimen to conventional dosing in a cohort of very low birth weight infants. METHODS: In a 2-arm clinical trial, 140 infants were randomized to either conventional dose (0.2 mg/kg/dose every 12 hours for 3 doses) or prolonged low-dose indomethacin (0.1 mg/kg/dose daily for 6 doses). The primary outcome measure was ductal closure rate, and the secondary outcomes were the need for a second course of treatment, surgical ligation rates, and side effects. RESULTS: Ductal closure after 1 course of indomethacin was similar between the 2 groups: 68% for the conventional dose group and 72% for the prolonged low dose (mean difference -4%; 95% confidence interval: -19% to 11%). The incidence of transient oliguria was higher in the conventional dose group, 31% versus 9%. There was a trend toward more necrotizing enterocolitis in the prolonged low-dose group, 7.0% versus 1.4%. CONCLUSIONS: There was no difference in efficacy between the 2 dosing regimens. In view of this and with its higher incidence of necrotizing enterocolitis, we do not recommend using prolonged low-dose indomethacin for closing the patent ductus arteriosus in very low birth weight infants.

Anti-Inflammatory Agents, Non-Steroidal↗

Transcatheter closure of patent ductus arteriosus.

More than three decades have passed since the introduction of transcatheter devices for closure of patent ductus arteriosus, and many occluders have been made available since then. The ideal requirements of any procedure are a user-friendly technique, optimum success rate, no residual anomaly, minimal morbidity/mortality, and comparability or superiority to the existing conventional modality of treatment. With various advancements in device design, delivery and assisted systems, the tremendous procedural safety and effectiveness, along with low cost and widespread availability of these devices makes transcatheter closure of patent ductus arteriosus a preferred therapeutic modality in all age groups, with decreasing demographic trends of surgical management.

Adult↗

Amplatzer Duct Occluder device: a new technology for the closure of the moderate-to-large-sized patent ductus arteriosus.

The Amplatzer Duct Occluder is a novel device designed to allow for the transcatheter closure of virtually all sized patent ductus arteriosuses. Prior technologies have been cumbersome and challenging to deploy with somewhat less than ideal closure rates associated with their use. This article summarizes the present knowledge about the Amplatzer Duct Occluder device and its various indications. With the introduction of this device as well as the use of embolization coils, all but the neonatal patent ductus arteriosuses can now be safely, consistently and successfully closed in the cardiac catheterization laboratory.

Biotechnology↗

Comparative tolerability of pharmacological treatments for patent ductus arteriosus.

The ductus arteriosus is a vascular channel which, although vital to the fetal circulation, rapidly becomes unnecessary and even deleterious after birth. As such, it is 'preprogrammed' to constrict within the first few hours of life. In infants born prematurely this natural closure is often delayed and/or ineffective. In this review, we summarise the current knowledge of the delicately orchestrated control of normal ductal closure, with emphasis on the role of various biochemical mediators. The major focus of this review, however, is on pharmacological approaches designed to prevent and/or treat the persistently patent ductus arteriosus (PDA) which often fails to constrict spontaneously in the premature infant. The standard treatment regimen is based on the administration of 3 doses of the nonselective cyclo-oxygenase inhibitor, indomethacin. We begin by examining, from the vantage point of the ductus, the use of this indomethacin as a tocolytic. It seems that antenatal administration of indomethacin can cause transient, reversible ductus constriction which renders the post-treatment ductus resistant to subsequent closure, both natural and therapeutic. We then review some of the pros and cons associated with the prophylactic administration of indomethacin. Although prophylactic indomethacin is aimed primarily at preventing intraventricular haemorrhages in premature neonates, it does tend to reduce the risk of PDA as well. We then describe some novel therapeutic approaches to effect ductal closure with indomethacin, including the use of continuous infusions to minimise toxic vasoconstrictive phenomena and the use of prolonged maintenance dose to prevent PDA recurrences. Finally we discuss some of the newer agents described more recently which play a role in closing the persistently patent ductus over the next decade. Most prominent of these is ibuprofen which some studies have shown to have less undesirable vasoconstrictive adverse effects. Studies which compare the use of ibuprofen to indomethacin are summarised.

Cyclooxygenase Inhibitors↗

Pharmaceuticals, patents, and politics: Canada and Bill C-22.

In response to high drug prices, the Canadian government amended the country's patent act in 1969 to allow for compulsory licensing to import pharmaceuticals. As a result of the legislation, by 1983 drug costs in Canada were over $200 million lower than they would otherwise have been. The multinational drug industry was strongly opposed to compulsory licensing, despite any evidence that its economic position had been harmed. Restoration of patent protection for drugs was one of the key U.S. demands during free-trade negotiations between Canada and the United States in 1985-1987. The result was Bill C-22, which gave new drugs protection from compulsory licensing for seven to ten years. This article analyzes the impact of Bill C-22 on the generic industry, the creation of jobs in research and development, drug prices, and research and development expenditures. It concludes with an examination of future demands from the pharmaceutical industry.

Canada↗

Radiographic and echocardiographic evaluation of newborns treated with indomethacin for patent ductus arteriosus.

A series of 33 consecutive preterm newborns who were treated with indomethacin, a drug which acts to close the patent ductus arteriosus, were studied retrospectively to examine the efficacy of chest radiography and echocardiography in diagnosing the presence of a significant patent ductus arteriosus. Radiographic changes in pulmonary vascular engorgement, pulmonary edema, and cardiac size on the anteroposterior film tended to precede the clinical changes of shunt appearance and resolution. The echocardiographic left atrial to aortic ratio (LA/Ao) supplemented the radiographic findings. The time of disappearance of the ductus arteriosus shunt, as judged by clinical findings, was identified accurately by radiographic and echocardiographic findings in the majority of cases; errors of under- and overestimation occurred in a minority of patients. In assessing both the presence and the resolution of the shunt, greater reliability was possible by using both radiographic and echocardiographic findings than by using either method alone.

Diagnostic Errors↗

Bronchial compression by a patent ductus arteriosus associated with pulmonary atresia.

Two infants with pulmonary atresia are presented, wherein a large, vertically oriented patent ductus arteriosus, acting as the only source of pulmonary blood supply, compressed the left bronchus, causing significant respiratory distress. Hyperinflation of the left lung was the clue to this circumstance. After bronchographic confirmation, surgical repair was accomplished by placement of aortopulmonary shunts and division of the patent ductus. Other causes of airway compression in congenital heart disease are briefly reviewed. The embryology of the ductus arteriosus is discussed, emphasizing its anatomic configuration and physiologic role in pulmonary atresia.

Airway Obstruction↗

Incidental finding on MDCT of patent ductus arteriosus: use of CT and MRI to assess clinical importance.

OBJECTIVE: The purpose of this article is to describe the imaging features of patent ductus arteriosus (PDA) identified on chest MDCT performed for other indications and to describe the additional functional information that cardiac MRI can provide about these lesions. CONCLUSION: The daily use of MDCT studies for the evaluation of pulmonary embolic disease or aortic abnormalities can reveal incidental PDAs. Small incidental PDAs can be identified on chest MDCT angiography timed for either the pulmonary arteries or the aorta. Using multiplanar reformations, one can assess PDA location, caliber, length, and presence of calcifications. The presence of a "positive" or a "negative contrast jet" verifies a patent shunt. Cardiac MRI shows the detailed anatomic and morphologic features of a PDA. Hemodynamic information revealing the presence and severity of a significant shunt is obtainable using velocity-encoded MRI, allowing accurate shunt calculation. Using MDCT and MRI, information regarding the clinical significance of an incidental PDA can influence management decisions. The imaging information was used to determine that one PDA required intervention.

Aged↗

Transcatheter treatment of perimembranous ventricular septal defect, secundum atrial septal defect and patent ductus arteriosus in a child.

A 4-year-old child with patent ductus arteriosus, perimembranous ventricular septal defect and ostium secundum atrial septal defect was successfully treated with the use of a simultaneous transcatheter for all of the anomalies present. The patent ductus arteriosus was closed first by using a coil, then the perimembranous ventricular septal defect was closed by using a 10-mm Amplatzer eccentric device. Finally, a 10-mm Amplatzer atrial septal defect device was implanted to treat the atrial septal defect.

Abnormalities, Multiple↗

[A 66-year-old woman with a patent ductus arteriosus and no significant progression of pulmonary arterial pressure over 17 years].

We report the case of a 66-year-old woman with a patent ductus arteriosus and no significant progression of pulmonary arterial pressure over 17 years. She was admitted to our hospital in 1978 because of palpitations on exertion and chest discomfort. Cardiac catheterization was done, and she was given a diagnosis of patent ductus arteriosus. Because the left-to-right shunt was small (15%) and because there was no evidence of pulmonary hypertension (38/18 mmHg), she was treated medically. In 1995 she was admitted again, to determine the cause of a cerebral infarction. The cerebral infarction was believed to have been caused by an embolism due to atrial fibrillation. She underwent cardiac catheterization again. The left-to-right shunt had increased to 41%, but the pulmonary artery pressure had not changed (27/14 mmHg). Intravascular ultrasound imaging was used to evaluate the ductus arteriosus. The diameter of the ductus was 4.4 mm and calcification was not observed. During the 17 years of follow-up, heart size increased slightly, but pulmonary artery pressure did not change. In addition, intravascular ultrasound was very useful for evaluating the condition of the ductus arteriosus.

Aged↗

The patenting of medical treatment.

The Full Federal Court of Australia recently held, in a decisive break with long-established legal principle, that methods of medical treatment are patentable inventions. The judgment signals the advent of monopolies and therefore monopoly prices on new therapeutic procedures until now made freely available to the medical profession. It also heralds delays in the dissemination of information about discoveries of such procedures through teaching and publication until a patent application can be prepared for and made.

Australia↗

Left ventricular systolic dysfunction after transcatheter closure of a large patent ductus arteriosus.

A 12-year-old boy reported in outpatient department with history of shortness of breath and dyspnoea on moderate exertion. Physical examination was significant for bounding pulses and for a continuous murmur III/VI, best heard at the left upper sternal border. Echocardiography confirmed a large patent arterial duct with shortening fraction of 33%. He underwent successful transcatheter closure of the patent arterial, using Amplatzer duct occluder 12/10. Few hours later echocardiography revealed an unexpected, yet important depression of left ventricular systolic function with shortening fraction decreasing to 24% and then two weeks later decreasing further to 20%. At a follow-up after four months, he had improved clinically but left ventricular dysfunction still persisted with shortening fraction of 24%.

Cardiac Catheterization↗

Indigenous self-determination in an age of genetic patenting: recognizing an emerging human rights norm.

This Note explores how the law can help indigenous people obtain meaningful control of their genetic material. Part I will briefly discuss the background of genetics, life patents, and indigenous groups. Part II sets out the domestic common law and international human rights law and demonstrates that neither currently provide adequate protection for indigenous peoples. Part III considers the human right of self-determination in the context of indigenous research and patenting, and illustrates that an emerging international norm recognizes an indigenous people's right to control their genetic material. Part IV argues that Congress should pass legislation to adequately meet the human rights needs of indigenous peoples generated by the rapid advancement of biotechnology. This Note concludes that congressional action to protect indigenous peoples is consistent with domestic and international law, and is a natural advancement of human rights and responsible state action.

Asia↗

Patenting life forms and preserving human values.

Utilitarian, pragmatic, and legal considerations, while valid, must not overshadow Catholic moral theology's concern about patenting life in view of natural law. The fundamental issues remain: Does technology diminish human values? Does the patent system's own monopolistic power pose its own risk?

Bioethics↗

[Transcatheter occlusion of patent ductus arteriosus].

Percutaneous closure of a patent arterial duct was performed in 58 patients. A Rashkind double umbrella was inserted in 20 patients. A supplementary double umbrella or coils were implanted in four who had residual leaks after 12 months. Three complications: embolization, haemolysis and late bacteriaemia were managed successfully without surgery. A detachable PDA coil was inserted in 38 patients. Three coils embolized and one could not be retrieved. At complete follow-up of 28 patients the duct was closed in all. Median procedure duration and fluoroscopy time was 60 min. and 12 min. respectively for double umbrella implantation, and 20 min. and 5 min. for coil insertion. Transcatheter occlusion of the patent duct is effective and carries little morbidity.

Cardiac Catheterization↗