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[Online patent searching--rapid responses to critical questions].

Online searching in publically available patent files opens up interesting possibilities to provide a rapid response to critical questions. A computerized analysis of all patents of leading German pharmaceutical companies over the last decade in important indication areas is described. Supported by subsequent manual processing of individual patents it is shown that duplicate experiments on animals practically never occur.

Chemical Phenomena↗

Gigantic patent ductus arteriosus--report of a newborn cadaver dissection and review of the literature.

During the gross anatomical dissection of the thoracic region in a newborn, a gigantic patent ductus arteriosus was found. This vessel had a diameter as large as the pulmonary trunk and a longer length. The brachiocephalic a. and the left common carotid a. originated from the aortic arch in close proximity with each other. The descending aorta showed a dilatation at the junction of this large-bored patent ductus arteriosus. We were unable to find any similar case in the published literature. Knowing that the anatomical variations of the great vessels may cause confusion during surgery or evaluation of CT and MRI scans, this rare case with a huge patent ductus arteriosus is presented.

Ductus Arteriosus↗

Patenting of hybridomas and genetically engineered microorganisms.

Many new technologies arrived at through basic research have practical applications. Two recent breakthroughs in microbiology, recombinant DNA techniques and hybridoma techniques, will permit designing cells for specific practical purposes resulting in new products or functions of commercial significance. The unique cell or its usefulness, or both, may satisfy the requirements of a patentable invention, i.e. an inventive act having utility and novelty. Ownership of such patents permits recovery of expenses incurred in the invention process and investment for all concerned in additional research. An integral part of the patenting process is submission of the new cell to an official repository, an outstanding example of which is The American Type Culture Collection.

DNA, Recombinant↗

A neonate with mitral stenosis due to accessory mitral valve, ventricular septal defect, and patent ductus arteriosus: changes in echocardiographical findings during the neonatal period.

A female neonate with mitral stenosis due to accessory mitral valve with ventricular septal defect and patent ductus arteriosus is described. She was referred to our hospital because of neonatal asphyxia. Asphyxia was improved by ventilator support, but rapid deterioration of respiration with pulmonary congestion and hemorrhage appeared 8 days after birth. Echocardiography revealed an accessory mitral valve attached to the anterior mitral leaflet with a perimembranous ventricular septal defect and patent ductus arteriosus. Although there were no echocardiographical findings indicating mitral stenosis on admission, the mitral stenosis blood flow patterns were detected by color and pulsed Doppler examination performed on the eighth day after admission. Transaortic resection of accessory mitral valve tissue was performed with patch closure of the ventricular septal defect and ligation of the ductus arteriosus 35 days after birth. After operation, pulmonary congestion and hemorrhage were improved. Postoperative echocardiography showed complete resection of the accessory mitral valve and no mitral insufficiency. We concluded that the combination of the accessory mitral valve and left-to-right shunt due to ventricular septal defect or patent ducturs arteriosus might have led to a critical hemodynamic condition due to relative mitral stenosis in the neonatal period with the decrease in pulmonary vascular resistance.

Cardiac Surgical Procedures↗

Radiographic characteristics of Cook detachable and Gianturco coils as well as clinical results of transcatheter closure of the patent ductus arteriosus.

PURPOSE: To describe the radiographic appearance of the Gianturco and the Cook detachable coils and present the clinical results in patients who underwent transcatheter closure of patent ductus arteriosus. MATERIALS AND METHODS: Between January 1994 and June 1997, eighty-two patients underwent closure of patent ductus arteriosus (PDA) using either Gianturco or Cook detachable coils. The chest x-ray and echocardiography of all patients were reviewed and the following parameters were evaluated: 1) the size of the heart (cardiothoracic ratio), 2) the position and the type of the coils in the postero-anterior and the lateral projection, 3) the number of coils used, 4) the existence of residual ductal flow, 5) Doppler velocity in the left pulmonary artery. RESULTS: Complete occlusion was achieved in 94%, and cardio-thoracic ratio regressed from 0.57 to 0.53 (p < 0.01), after a mean follow-up of 1.2 years. The identification of the different coils on the chest radiograph was successful in only 47% of cases, difficulties arising especially, when multiple coils were used. In 55 patients (67%) the coil position was judged to be optimal, in 27 patients (33%) suboptimal. The latter correlates with the presence of residual shunt. Multiple coils correlated more with a left pulmonary artery flow velocity exceeding 1.5 m/s. CONCLUSION: Coil-occlusion of patent ductus arteriosus is effective and leads to reduced cardio-thoracic ratio. Radiographic coil identification is possible but may be difficult if multiple coils are deployed. Suboptimal coil position led more often to residual PDA shunt. Multiple coils are more commonly associated with increased LPA velocities, but hemodynamic significant obstruction to flow is rare.

Adolescent↗

Safety and efficacy of interventional occlusion of patent ductus arteriosus with detachable coils: a multicentre experience.

UNLABELLED: In order to define the safety and efficacy of Cook detachable coils for interventional closure of patent ductus arteriosus, we performed a retrospective analysis of all patients who underwent cardiac catheterization in seven centres for intended interventional occlusion of patent arterial duct. From January 1995 until March 1998, cardiac catheterization for intended interventional occlusion of patent arterial duct was performed in 317 consecutive children. Successful placement of at least one coil was achieved in 282 children (89%). The mean diameter of the ductus in children treated with Cook detachable coils was 1.65 mm, mean fluoroscopy time was 10.7 min. Occlusion rates were 62% 10 min after the procedure, 82% at the time of discharge, 91% at 4 months and 95% at late follow-up (2 years). In children with a ductus diameter of < or = 2.5 mm the rate of successful coil deployment was 94% with a 98% occlusion rate at late follow-up. Complications occurred in 11 procedures (3.5%) including haemolysis (3 patients), embolization of a coil to the pulmonary artery (7 patients, 2.3%) and inability to release a coil (1 patient). CONCLUSION: In our opinion, Cook detachable coils are safe and effective especially in the treatment of persistent ductus arteriosus with a diameter < or = 2.5 mm. Due to the low costs these coils appear to be superior to other devices in this subgroup of patients.

Adolescent↗

Patenting humans: clones, chimeras, and biological artifacts.

The momentum of advances in biology is evident in the history of patents on life forms. As we proceed forward with greater understanding and technological control of developmental biology there will be many new and challenging dilemmas related to patenting of human parts and partial trajectories of human development. These dilemmas are already evident in the current conflict over the moral status of the early human embryo. In this essay, recent evidence from embryological studies is considered and the unbroken continuity of organismal development initiated at fertilization is asserted as clear and reasonable grounds for moral standing. Within this frame of analysis, it is proposed that through a technique of Altered Nuclear Transfer, non-organismal entities might be created from which embryonic stem cells could be morally procured. Criteria for patenting of such non-organismal entities are considered.

Bioethics↗

Noninvasive diagnosis of coarctation of the aorta in the presence of a patent ductus arteriosus.

Although the diagnosis of coarctation of the aorta in the full-term neonate is straightforward when no ductus arteriosus is present, identification of coarctation of the aorta when a ductus arteriosus is patent can be difficult. A patent ductus arteriosus is frequently found in association with coarctation of the aorta, and it may remain open for many days. Thus a reliable method to rapidly identify coarctation of the aorta would obviate the need for cardiac catheterization or an in-hospital observation period until the ductus arteriosus closes spontaneously. Echocardiographic/Doppler examination of 19 consecutive full-term neonates with a birth weight of > 2.9 kg, who subsequently underwent surgical repair of coarctation of the aorta, were reviewed. Fourteen patients with similar weights, a patent ductus arteriosus, and a normal aortic arch were matched for comparison. Based on the findings, the following diagnostic criteria for coarctation of the aorta are suggested: isthmic diameter less than or equal to 3 mm or isthmus equal to 4 mm together with the Doppler finding of continuous antegrade flow in the isthmal segment. Coarctation of the aorta in the full-term neonate can be ruled out when the flow within the ductus arteriosus is exclusively from aorta to pulmonary artery or when the isthmic diameter is equal to or greater than 5 mm.

Aorta, Thoracic↗

Utility of transesophageal echocardiography in the examination of adult patients with patent ductus arteriosus.

Thirteen patients with clinical suspicion of patent ductus arteriosus were evaluated by transthoracic and transesophageal echocardiographic studies. Findings were corroborated during corrective surgery in 8 patients and by cardiac catheterization in 5. Transthoracic echocardiography confirmed the diagnosis in 7 patients; in 2 of the patients endarteritis of the pulmonary artery was demonstrated, and in one infective vegetations in aortic and mitral valves. With transesophageal echocardiography, patent ductus arteriosus was established in all 8 patients and endarteritis of the pulmonary artery was shown in 3, including 1 not discovered by transthoracic technique. In 1 of these patients, vegetations were also found on the pulmonic valve. Both techniques demonstrated significant pulmonary hypertension in 5 cases; contrast studies showed the venoarterial shunt between the pulmonary artery and the aorta with particular clarity in transesophageal images. On the basis of these findings it may be concluded that transesophageal echocardiography complements the information provided by transthoracic recordings in adult patients with patent ductus arteriosus, especially when it is associated with pulmonary hypertension or pulmonary endarteritis.

Adolescent↗

Prolonged rupture of fetal membranes and decreased frequency of respiratory distress syndrome and patent ductus arteriosus in preterm infants.

Observations were made on 153 preterm infants (25 to 34 weeks' gestation) in an attempt to answer the following questions: dose prolonged rupture of the fetal membranes (ROM) correlate with a decreased frequency of respiratory distress syndrome (RDS) and patent ductus arteriosus, and, if so, what is the duration of ROM required? An analysis of the data indicates that as the duration of ROM is lengthened the incidence of RDS and patent ductus arteriosus decreases. In fact, after 48 hours of prolonged ROM (PROM), there is a virtual absence of RDS. In addition, after 72 hours of PROM, the frequency of patient ductus arteriosus was markedly reduced to only 12 per cent (three of 25 infants). PROM beyond 24 hours was also associated with a significant decrease in deaths (p less than 0.05). Amnionitis occurred in 33 per cent of pregnancies with PROM greater than 48 hours; however, only one infant died of sepsis. These findings support the hypothesis put forth by the others 1-5 that PROM is indeed associated with a decreased frequenct of RDS in preterm infants. Moreover, our findings suggest that PROM greater than 72 hours is associated with a relatively low frequency of patent ductus arteriosus. The question is then raised that perhaps pregnancies less than or equal to 34 weeks' gestation with PROM should be allowed to continue for 72 hours in the absence of amnionitis.

Birth Weight↗

Operative closure of patent ductus arteriosus in premature infants in the neonatal intensive care unit.

Fifty-two premature infants underwent hemoclip closure of patent ductus arteriosus in the neonatal intensive care unit after a brief trial of fluid restriction and diuretics. Indomethacin was used in only four patients. The median time from diagnosis to operation was 3 days. There were no deaths directly attributable to operation. Nine operative complications developed in nine patients (17 percent). There were no surgical infections. Complications related to prematurity resulted in 20 deaths (38 percent). Patent ductus arteriosus closure in the neonatal intensive care unit prevented the complications of hypothermia, inadvertent extubation, and interruption of vascular access and monitoring. Early operative closure in the neonatal intensive care unit is the treatment of choice in most premature infants with patent ductus arteriosus.

Ductus Arteriosus, Patent↗

Safety of patent ductus arteriosus closure in premature infants without tube thoracostomy.

During a 30-month period, 34 premature infants underwent surgical closure of a patent ductus arteriosus. The mean gestational age at birth was 25 +/- 0.3 weeks and the mean age at the time of operation was 3 +/- 0.3 weeks (mean weight, 829 +/- 54 g). Indomethacin therapy had failed in 32 patients, and 2 had contraindications to its use. The initial 8 patients had parascapular incision and ligation of the patent ductus arteriosus; the last 26 patients had a short transaxillary incision and clipping. The average duration of the operation from the time of incision to skin closure was 36 +/- 2 minutes (range, 15 to 65 minutes). One patient (3%) needed chest tube insertion intraoperatively because of visceral pleura disruption. Two patients (5.8%) had a "small pneumothorax" (< 10% of the lung field) that resolved within 24 hours. There was no morbidity or mortality directly related to the operative procedure, although 3 patients (8.8%) ultimately died from problems related to their severe prematurity. We conclude that surgical closure of patent ductus arteriosus without chest tube drainage can be accomplished safely in premature infants. Postoperative nursing care is simplified and the cost is reduced because the need for the chest tube and drainage system is eliminated and the number of chest radiograms needed postoperatively is reduced.

Blood Loss, Surgical↗

Thoracoscopic clipping and ligation of a patent ductus arteriosus.

Several techniques of patent ductus arteriosus occlusion primarily by thoracotomy have been practiced. They have shown to be more reliable than nonsurgical procedures. Videothoracoscopy has been useful in several intrathoracic surgical procedures with faster recovery and minimal mortality and morbidity. We report 2 patients with clipping and ligation of a patent ductus arteriosus by a thoracoscopic approach. This technique may be useful in children with a noncomplicated patent ductus arteriosus. It allows an easier recovery and causes less pain.

Child↗

Patent ductus arteriosus ligation: are we doing better?

Limitation on health care resource use is stimulating critical evaluation of previous preoperative standards. We retrospectively reviewed the clinical and hospital financial records of all children admitted for patent ductus arteriosus ligation from July 1984 to April 1994 for age, perioperative length of stay, readmissions for postoperative surgical problem, and hospital charges adjusted to 1994 dollars. Patients with an isolated patent ductus arteriosus, greater than 3 months of age, without preoperative or postoperative complications were included in this study and stratified into two groups based on date of operation. Group I had operation before January 1, 1991, and group II had operation on or after January 1, 1991. Comparison of these two groups revealed a significant difference in perioperative length of stay (group I, 3.9 +/- 1.2 days [mean +/- standard deviation]; group II, 2.7 +/- 0.9 days; p < 0.0001) and in hospital charges (group I, $8,700 +/- $2,100; group II, $6,600 +/- $1,000; p < 0.0001). These data support the premise that children older than 3 months undergoing elective ligation of a patent ductus arteriosus have been treated with improved efficiency and less charge without an increase in postdischarge morbidity. Health care policy decisions have forced us to evaluate the standards of perioperative care more critically.

Adolescent↗

Successful transcatheter closure of patent arterial duct six years after balloon dilatation of coarctation of the aorta.

A boy underwent total transcatheter occlusion of a patent arterial duct six years after successful balloon angioplasty of a native coarctation of the aorta. After successful implantation of a 12 mm device in the patent arterial duct there was no gradient across the descending aorta and five hours later there was no residual leak across the occluded patent arterial duct as judged by color Doppler.

Angioplasty, Balloon, Coronary↗

Transfemoral closure of patent ductus arteriosus in adult patients.

Patent ductus arteriosus is an uncommon anomaly in adult patients. Surgical closure of patent ductus arteriosus in this age group presents difficult problems to the surgeon. We report our experience of 21 adult patients (19-62 years of age, mean 40 years) who underwent closure of the ductus by transfemoral implantation of a Rashkind double umbrella device. The patients came to light because of atrial fibrillation, congestive heart failure, residual flow after surgical ligation of the duct or because of incidental diagnosis made during physical examination or chest X-ray. In ten patients the pulmonary arterial pressure was normal (systolic pressure < 30 mmHg), in eleven it was elevated (systolic pressure from 30 to 100 mmHg, mean 50 mmHg). In seven patients the duct was clearly calcified and the size of the duct varied from 3 to 9 mm (mean 4.3 mm). In 16 patients the ductus resulted perfectly closed after implantation of the first double umbrella device, two patients had minimal residual aortopulmonary flow, whereas in three patients the residual shunt was significant; two of these also developed haemolysis and went to surgery, in the latter the shunt was completely abolished after implantation of a second 17-mm device 16 months later. In conclusion transcatheter closure of patent ductus arteriosus in adults is feasible, even in the presence of calcifications and/or pulmonary hypertension; taking into account the significant surgical risk, PDA umbrella closure should be considered the first choice procedure in this group of patients.

Adult↗

Follow-up of coil occlusion of patent ductus arteriosus.

OBJECTIVE: We sought to determine the prevalence and fate of residual ductal shunting following coil occlusion of patent ductus arteriosus. BACKGROUND: Although transcatheter coil occlusion of patent ductus arteriosus has gained popularity, few follow-up data have been reported. METHODS: A review of 75 patients who underwent coil occlusion was performed. Residual shunting was investigated by Doppler echocardiography in follow-up. Angiograms were reviewed to obtain minimal ductal diameter and ductal angiographic type. RESULTS: Residual shunts were found in 31 patients (41%) on the day of the procedure, and of these, spontaneous closure was noted in 17 (55%) at 2 weeks to 20 months of follow-up. Of the 75 patients studied, 5 (7%) required a second coil procedure, and 10 (13%) remained with persistent residual shunts at most recent follow-up. Actuarial analysis estimated a 6 +/- 5% prevalence of residual shunts 20 months after a single coil procedure and 3 +/- 3% after all coil procedures. Minimal ductal diameter was associated with immediate complete ductal occlusion by a single coil. These patients had significantly smaller (p = 0.003) minimal ductal diameters (1.2 +/- 0.7 mm) than those who required two coils during their initial procedure to achieve immediate occlusion (1.9 +/- 0.7 mm), those who required a second coil procedure (2.0 +/- 0.9 mm), those who had spontaneous closure of residual shunts (1.9 +/- 0.7 mm) and those with persistent residual shunts (2.0 +/- 0.9 mm). No association was identified between ductal angiographic type and outcome of coil occlusion. No late adverse clinical events of coil occlusion or evidence of recanalization was found. CONCLUSIONS: Small residual shunts are common after coil embolization of patent ductus arteriosus, but most close spontaneously. Actuarial analysis estimates complete closure in 94% at 20 months, and reintervention was required in only 7% of patients.

Actuarial Analysis↗

Patentability of life and ethics.

Patent law has relied in part on ethical considerations since its inception in Europe. Such considerations have been introduced more recently in the United States. Whereas the EU Directive on the protection on the occasion of the Human Genome Project of biotechnological inventions was intended to foster economic development in Europe, its implementation is outweighted by controversy about patenting life and commercialization of science. The confusion created must be cleared at the international level through harmonization of patent office policies preventing abusive commercial practices in the absence of inventiveness.

Biotechnology↗