First reported long-term two- and three-dimensional echocardiographic follow-up with histopathological analysis of a transcatheter pulmonary valve implantation in a pet dog.

Transcatheter pulmonary valve implantation (TPVI) is indicated for use in the management of failing pulmonary valves in humans. We report here the long-term follow-up of the first documented transcatheter pulmonary valve implanted in a client-owned dog. A one-year-old Beagle dog with severe congenital type A valvular pulmonic stenosis first underwent percutaneous balloon pulmonary valvuloplasty, leading two years later to severe pulmonary regurgitation. A TPVI using a Melody™ bioprosthetic valve was then successfully performed, with normalization of the right heart cavities. Repeated two- and three-dimensional transthoracic echocardiographic examinations combined with Doppler modes confirmed the appropriate position and function of the valve for four years. Mitral myxomatous valvular degeneration led to refractory left-sided congestive heart failure, and the dog was humanely euthanized. After postmortem examination, X-ray imaging and histopathological evaluation of the stent and the valve were performed. Ex-vivo imaging of the implanted valve using a Faxitron® Path radiography system and microscopic evaluation of the implanted stent and bioprosthetic leaflets did not show any relevant leaflet or stent alterations. This case provides a proof of concept in interventional veterinary cardiology, showing that TPVI can be performed in dogs with subsequent long-term maintaining normal pulmonary valve function.

The variety of phenotypes behind 'double outlet right ventricle': clinical and imaging presentations in four dogs and a cat.

This report describes five cases of double outlet right ventricle (DORV) in four dogs (aged 3-18 months, two males and two females) and a domestic shorthair cat (aged 6 months, female) who presented with various clinical signs including tachypnea (n = 5), exercise intolerance (n = 5), mucous cyanosis (n = 3), delayed growth (n = 2), and/or lethargy (n = 2). The represented canine breeds were poodle, Yorkshire terrier, Samoyed, and Shetland sheepdog. For all animals, echocardiography revealed marked aortic dextroposition with both arterial trunks totally arising from the right ventricle, associated with a ventricular septal defect and various other congenital abnormalities, including subvalvular aortic stenosis (n = 2), minor aortic insufficiency (n = 5), subvalvular pulmonic stenosis with pulmonary trunk hypoplasia (n = 1), patent ductus arteriosus (n = 1), minor mitral and/or tricuspid dysplasia (n = 3). Subsequent cardiac remodeling was characterized by marked right ventricular hypertrophy for all patients, associated with right ventricular and right atrial dilation for most of them (4/5). Two dogs died soon after the initial DORV diagnosis (i.e. after 24 h and two months). A surgical correction attempted for another dog confirmed the presence of a DORV associated with patent ductus arteriosus, but the animal died during the procedure from sudden cardiac arrest. The fourth dog underwent a contrast-enhanced retrospective electrocardiogram-gated multidetector computed tomography angiography under general anesthesia, which confirmed the conotruncal malformation. Despite episodes of exercise intolerance, this dog is still alive, at the age of 53 months, as is the cat at the age of 21 months.

Successful transcatheter pulmonary valve implantation in a dog: first clinical report.

Transcatheter pulmonary valve (TPV) implantation is a therapeutic approach approved by the United States Food and Drug Administration for human patients with failing pulmonary conduits in 2010 and for failing bioprosthetic surgical pulmonary valves in 2017. We report here the first successful transcatheter implantation of a stented valve in a pulmonary position in a dog with congenital pulmonary valve disease. A 3-year-old, 10.9 kg, client-owned Beagle dog was referred for a follow-up visit after a percutaneous balloon valvuloplasty performed 22 months before for treatment of a severe type A valvular pulmonary stenosis. The Doppler-derived peak pressure gradient was 348 mmHg before the procedure and 66 mmHg 24 h after. The dog was lethargic. Echocardiography revealed a mild pulmonary stenosis (pressure gradient-43 mmHg), severe pulmonary regurgitation, and secondary severe right ventricular and right atrial dilation. Worsening of right heart dilation was observed 2 months later despite medical therapy. A TPV implantation was performed using a prestented Melody bovine jugular bioprosthetic valve. The dog recovered uneventfully and was discharged 10 days after the procedure. Right heart dilation resolved within 15 days. The dog was doing well 7 months after valve implantation. This case demonstrates that TPV implantation with a stented valve is technically feasible in dogs with severe pulmonary valve disease. Stringent postoperative care, with particular attention to thrombosis and infectious endocarditis, and appropriate sizing and positioning of the valve stent are keys to the success of this procedure.

Comparative anatomy and angiography of the cardiac coronary venous system in four species: human, ovine, porcine, and canine.

INTRODUCTION: The coronary arterial system has been the subject of greater investigation than its venous system due to the importance of human coronary artery disease. With the advent of new percutaneous treatments, the anatomy of the coronary venous system has increasing relevancy. We compared the organization of the coronary venous circulation in three species commonly used in research and compared these to normal humans using both macroscopic anatomic and angiographic studies. ANIMALS: The anatomy of five explanted hearts from healthy dogs, pigs, and sheep were studied macroscopically, and 10 explanted hearts per animal species and 10 clinically normal human were examined by angiography. METHODS: Animal hearts were injected with latex and dissected macroscopically. The coronary venous system of humans was evaluated from clinical angiographic studies. In the animal hearts, a retrograde angiographic study was performed via a Foley catheter in the coronary sinus. RESULTS: The general organization of the coronary venous circulation was similar among humans, dogs, sheep, and pigs. Despite overall similarities to humans, animal hearts demonstrated the absence of the oblique vein of the left atrium and differences in position and organization of venous valves; venous diameters; number of tributary veins; and presence of an anastomosis between the left and right (human anterior and posterior) venous tree. The left azygos of the pig and sheep joined the coronary sinus. CONCLUSIONS: Anatomical differences must be considered when planning biomedical and veterinary studies incorporating cardiac veins. This study provides baseline data regarding structure and organization of the cardiac venous system.

Successful transcatheter retrieval of embolized Amplatz Canine Duct Occluders in two dogs.

Transcatheter occlusion of patent ductus arteriosus (PDA) using an Amplatz® Canine Duct Occluder (ACDO) is routinely performed in dogs. Pulmonary embolization of the device is a rarely reported complication of this procedure. We report here the first two cases of successful transcatheter retrieval of an embolized ACDO. An 8-month-old, 21-kg, German shepherd (case 1) was referred for pulmonary edema secondary to a large PDA with left-to-right shunting. After medical stabilization, an emergency procedure for PDA closure was recommended. An 8-mm ACDO was deployed under general anesthesia. The device was released after confirming its stability with a gentle tug test but migrated into the pulmonary trunk. A 10-mm ACDO was subsequently successfully deployed and released. Vascular access was then obtained from the right jugular vein so that a vascular snare could be used to capture the ACDO waist and pull it back toward the right ventricle and then the right atrium. It was then removed through the jugular vein. The dog recovered uneventfully and was discharged after confirmation of complete ductal occlusion. The same complication occurred in a second case (case 2, asymptomatic 6-month-old, 7.9-kg, cocker spaniel), and a similar procedure was used to successfully retrieve the embolized device. Both dogs are still doing well 9 and 21 months, respectively, after the procedure. These cases illustrate that transcatheter retrieval of ACDO devices embolized in the pulmonary artery using vascular snares is technically feasible in the dog.

Intracardiac echocardiography: use during transcatheter device closure of a patent ductus arteriosus in a dog.

Intracardiac echocardiography (ICE) is used in humans for percutaneous interventional procedures, such as transcatheter device closures. Intracardiac echocardiography provides high-resolution imaging of cardiac structures with two-dimensional, M-mode, Doppler, and also three-dimensional modalities. The present report describes application of ICE during transcatheter occlusion of patent ductus arteriosus using a canine ductal occluder in a dog for which transesophageal echocardiography could not provide an optimal acoustic window.

Experimental study of urodynamic changes after ovariectomy in 10 dogs.

The urodynamic changes in 10 bitches up to 18 months after they had undergone ovariectomy were investigated. There were significant decreases in the maximum urethral closure pressure, the functional urethral length and the total integrated pressure profile 18 months after spaying, resulting in a caudal shift of the urethral profile, and a deterioration of urethral closure function. Each urethral pressure profile was divided into three equal sections; the mean cranial and middle integrated pressure decreased significantly and consistently over the 18-month observation period whereas the caudal integrated pressure increased.

The Mom1AKR intestinal tumor resistance region consists of Pla2g2a and a locus distal to D4Mit64.

The Mom1 (Modifier of Min-1) region of distal chromosome 4 was identified during a screen for polymorphic modifiers of intestinal tumorigenesis in ApcMin/+ mice. Here, we demonstrate that the Mom1AKR allele consists of two genetic components. These include the secretory phospholipase Pla2g2a, whose candidacy as a Mom1 resistance modifier has now been tested with several transgenic lines. A second region, distal to Pla2g2a, has also been identified using fine structure recombinants. Pla2g2aAKR transgenic mice demonstrate a modest resistance to tumorigenesis in the small intestine and a very robust resistance in the large intestine. Moreover, the tumor resistance in the colon of Pla2g2aAKR animals is dosage-dependent, a finding that is consistent with our observation that Pla2g2a is expressed in goblet cells. By contrast, mice carrying the distal Mom1 modifier demonstrate a modest tumor resistance that is confined to the small intestine. Thus, the phenotypes of these two modifier loci are complementary, both in their quantitative and regional effects. The additive effects and tight linkage of these modifiers may have been necessary for the initial identification of the Mom1 region.

Late oligodendrocyte progenitors coincide with the developmental window of vulnerability for human perinatal white matter injury.

Hypoxic-ischemic injury to the periventricular cerebral white matter [periventricular leukomalacia (PVL)] results in cerebral palsy and is the leading cause of brain injury in premature infants. The principal feature of PVL is a chronic disturbance of myelination and suggests that oligodendrocyte (OL) lineage progression is disrupted by ischemic injury. We determined the OL lineage stages at risk for injury during the developmental window of vulnerability for PVL (23-32 weeks, postconceptional age). In 26 normal control autopsy human brains, OL lineage progression was defined in parietal white matter, a region of predilection for PVL. Three successive OL stages, the late OL progenitor, the immature OL, and the mature OL, were characterized between 18 and 41 weeks with anti-NG2 proteoglycan, O4, O1, and anti-myelin basic protein (anti-MBP) antibodies. NG2+O4+ late OL progenitors were the predominant stage throughout the latter half of gestation. Between 18 and 27 weeks, O4+O1+ immature OLs were a minor population (9.9 +/- 2.1% of total OLs; n = 9). Between 28 and 41 weeks, an increase in immature OLs to 30.9 +/- 2.1% of total OLs (n = 9) was accompanied by a progressive increase in MBP+ myelin sheaths that were restricted to the periventricular white matter. The developmental window of high risk for PVL thus precedes the onset of myelination and identifies the late OL progenitor as the major potential target. Moreover, the decline in incidence of PVL at approximately 32 weeks coincides with the onset of myelination in the periventricular white matter and suggests that the risk for PVL is related to the presence of late OL progenitors in the periventricular white matter.

Mom1 is a semi-dominant modifier of intestinal adenoma size and multiplicity in Min/+ mice.

The intestinal tumor multiplicity in mice heterozygous for ApcMin is strongly modulated by genetic background. On the sensitive C57BL/6J (B6) background, mice develop large numbers of intestinal adenomas. The AKR/J (AKR) strain carries alleles that correlate with a strong reduction in tumor multiplicity. To study the effect of one of these modifiers, Mom1, we have generated a mouse line in which the AKR allele of Mom1 is carried on the sensitive B6 genetic background. This strain was produced by using a marker-assisted selection method to eliminate unlinked AKR alleles more rapidly. The application and efficiency of this method are discussed. We used this strain to determine that Mom1 affects both tumor multiplicity and tumor size in a semi-dominant fashion.

Genetic evaluation of candidate genes for the Mom1 modifier of intestinal neoplasia in mice.

As genetic mapping of quantitative trait loci (QTL) becomes routine, the challenge is to identify the underlying genes. This paper develops rigorous genetic tests for evaluation of candidate genes for a QTL, involving determination of allelic status in inbred strains and fine-structure genetic mapping. For the Mom1 modifier of intestinal adenomas caused by ApcMin, these tests are used to evaluate two candidate genes: Pla2g2a, a secretory phospholipase, and Rap1GAP, a GTPase activating protein. Rap1GAP passes the first test but is excluded by a single fine-structure recombinant. Pla2g2a passes both tests and is a strong candidate for Mom1. Significantly, we also find that ApcMin-induced adenomas remain heterozygous for the Mom1 region, consistent with Mom1 acting outside the tumor lineage and encoding a secreted product.

Efficient transformation and frequent single-site, single-copy insertion of DNA can be obtained in mouse erythroleukemia cells transformed by electroporation.

Electroporation has recently been shown to have advantages over the commonly used method of calcium phosphate precipitation for obtaining DNA-mediated transformation of certain types of cells. Although mouse erythroleukemia cells and other cells of hematopoietic origin are not transformed at useful frequencies by calcium phosphate-DNA precipitation methods, we obtained high frequencies of transformation (approximately 10(-5)) of these cells with electroporation. Even higher transformation frequencies (approximately 10(-3)) were obtained with human fibroblasts. Another advantage of electroporation was found when analysis of Southern blots of DNA from 243 transformed erythroleukemia cell colonies indicated that, under appropriate conditions, about 79% of the transformed cells had the exogenous DNA integrated in single copies at single sites. Under conditions of higher DNA and lower cell concentrations using fibroblasts, cotransformation was obtained with two plasmids that confer HAT or G418 resistance when integrated into cellular DNA. About 23% of the transformed cells developed both types of resistance. We describe a simple, inexpensive apparatus for carrying out electroporation.

Medicine court, II: Rivers in practice.

The authors conducted a retrospective study of the initial impact (1986-1987) of the Rivers v. Katz decision involving patients' right to refuse treatment at New York State's largest forensic psychiatric hospital. Of 18 petitions submitted, 15 cases were adjudicated. All 15 patients were found incompetent, and all treatment plans submitted were approved by the court. Most patients selected for Rivers hearings were diagnosed as having chronic schizophrenia and/or were older than the hospital population. A comparison of the implementation of the Rivers decision with that of Rogers v. Commissioner of Mental Health in Massachusetts showed Rogers to be significantly more expensive in human resources, time, and money.

Minimization and management of wastes from biomedical research.

Several committees were established by the National Association of Physicians for the Environment to investigate and report on various topics at the National Leadership Conference on Biomedical Research and the Environment held at the 1--2 November 1999 at the National Institutes of Health in Bethesda, Maryland. This is the report of the Committee on Minimization and Management of Wastes from Biomedical Research. Biomedical research facilities contribute a small fraction of the total amount of wastes generated in the United States, and the rate of generation appears to be decreasing. Significant reductions in generation of hazardous, radioactive, and mixed wastes have recently been reported, even at facilities with rapidly expanding research programs. Changes in the focus of research, improvements in laboratory techniques, and greater emphasis on waste minimization (volume and toxicity reduction) explain the declining trend in generation. The potential for uncontrolled releases of wastes from biomedical research facilities and adverse impacts on the general environment from these wastes appears to be low. Wastes are subject to numerous regulatory requirements and are contained and managed in a manner protective of the environment. Most biohazardous agents, chemicals, and radionuclides that find significant use in research are not likely to be persistent, bioaccumulative, or toxic if they are released. Today, the primary motivations for the ongoing efforts by facilities to improve minimization and management of wastes are regulatory compliance and avoidance of the high disposal costs and liabilities associated with generation of regulated wastes. The committee concluded that there was no evidence suggesting that the anticipated increases in biomedical research will significantly increase generation of hazardous wastes or have adverse impacts on the general environment. This conclusion assumes the positive, countervailing trends of enhanced pollution prevention efforts by facilities and reductions in waste generation resulting from improvements in research methods will continue.

Convulsive attacks due to antidepressant drug overdoses: case reports and discussion.

Antidepressant drug overdoses have been reported to induce seizures, but the etiology of this phenomenon is still unclear. Recently we treated three patients who suffered from epileptic seizures after acute overdoses of three antidepressant drugs: (a) Dibenzepin HCl (Noveril), (b) Maprotiline HCl (Ludiomil), and (c) Clorimipramine (Anafranil). After a review of the pertinent literature, the possible role of antidepressant drugs in the genesis of epileptic seizures is discussed.

Development of an ultrasonically activated trocar system.

BACKGROUND: Although rare, visceral and vascular injuries related to the insertion of conventional laparoscopic trocars may have disastrous consequences. Most of these injuries are due to the high puncture force applied to the trocar. We present the results of an animal laboratory evaluation of a newly developed ultrasonically activated trocar. METHODS: A total of 40 punctures were made in four pigs with an average weight of 53 kg. An 11-mmHg pneumoperitoneum was created through a Veress needle. A 10-mm diameter trocar was inserted in the midline for a laparoscope. A series of five trocars were then inserted on each lateral wall under laparoscopic control. Twenty punctures were made with a conventional reusable 11-mm trocar (CT) whose tip was sharp and conical. Twenty punctures were made with an 11-mm ultrasonically activated trocar (UT), whose fequency was 23.5 KHz and amplitude 150 mm. The cutaneous incision was made large enough so that the skin did not interfere with the trocar insertion. The force applied to the trocar was measured with a push-pull gauge connected to a computer. The following data were recorded: maximal force applied to the trocar to obtain insertion of the tip through the abdominal wall, maximum abdominal pressure increase during trocar insertion, and time for abdominal penetration. RESULTS: The average time needed for trocar penetration was 12.8 s with CT and 4.5 s with UT (p < 0.001). The average maximal force was 6.8 kgF with CT and 0.4 kgF with UT (p < 0.001). The average abdominal pressure increase was 7.6 mmHg with CT and 0.8 mmHg with UT (p < 0.001). At 30 days, no necrosis was found. Pathological findings were similar in both groups. CONCLUSION: Ultrasonically activated trocars required less time and much less force to be inserted. This may be a breakthrough in the safety of trocar insertion.

Families, murder, and insanity: a psychiatric review of paternal neonaticide.

Neonaticide is the killing of a newborn within the first 24 h of life. Although relatively uncommon, numerous cases of maternal neonaticide have been reported. To date, only two cases of paternal neonaticide have appeared in the literature. The authors review neonaticide and present two new case reports of paternal neonaticide. A psychodynamic explanation of paternal neonaticide is formulated. A new definition for neonaticide, more consistent with biological and psychological determinants, is suggested.

[Percutaneous artificial heart valves: from animal experimentation to the first human implantation in a case of calcified aortic stenosis]. / Valves cardiaques artificielles percutanées: de l'expérimentation animale à la première implantation humaine dans un cas de rétrécissement aortique calcifié.

The development of artificial cardiac valves capable of being positioned by catheter has become an important subject for research, with the objective of treating valvular patients who are not operable or at very high surgical risk. We tested an artificial valve implantable by the percutaneous route, consisting of three leaflets of bovine pericardium sutured to the inside of a stainless steel stent, deployable by inflating a balloon. Following laboratory evaluation, this valve was implanted with success in animals, then for the first time in man, in a case of calcified aortic stenosis. The patient, a 57 year old male in cardiogenic shock, had associated multiple non-cardiac pathology and could not be operated on. Implantation was carried out by the trans-septal anterograde route, the only route available due to severe end stage arteritis. The artificial valve was deposited in the centre of the native aortic valve, without obstructing the coronaries nor reaching the mitral valve. The result was spectacular with instantaneous haemodynamic improvement and excellent valvular function confirmed by transoesophageal echocardiography every 15 days after implantation. Non-cardiac complications marred the progress, dominated by aggravation of pre-existing leg ischaemia, necessitating amputation for which the consequences were fatal at 4 months. This case demonstrates that implantation of a cardiac valve by the percutaneous route is possible in calcified aortic stenosis, and that it brings rapid clinical improvement. This technique could in future constitute an important alternative therapeutic approach for selected patients.

[Exploration of a third degree atrioventricular block by standard echocardiography, tissue Doppler imaging, and treatment with a cardiac pacemaker in a German wire-haired pointer]. / Exploration d'un bloc atrio-ventriculaire du 3ème degré par échocardiographie conventionnelle, Doppler tissulaire, biopsie endomyocardique et traitement par pacemaker chez un Drathaar.

A nine-year-old intact male Drathaar was evaluated for syncope and extreme weakness, and was found to have a third degree atrioventricular (AV) block. As there were no biochemic, serologic, organic (thoracic radiographs, abdominal echography, standard and tissue Doppler echocardiographies) and histologic (interventricular septum biopsy) anomalies, the dog was treated with a permanently implanted cardiac pacemaker.

[Pacemaker implantation in dogs: results of the last 30 years]. / La pose de pacemaker chez le chien: le point sur les 30 dernières années.

Pacemaker implantation in veterinary practice is still not well known and remains uncommon. However, this technique is the only possible way to cure animals suffering from symptomatic bradycardia whose state does not improve with a medical treatment. In most cases, the use of pacemakers in veterinary medicine leads to the disappearance of the clinical and electrocardiographic signs. This retrospective study concerning the last 30 years draws up an evaluation of the improvements, advantages and drawbacks of this method. Moreover, this study allows the understanding of the evolution of pacemakers' use in veterinary cardiology.