Karim A. Diab

Ceramide generation by two distinct pathways in tumor necrosis factor α‐induced cell death

Ceramide accumulation in the cell can occur from either hydrolysis of sphingomyelin or by de novo synthesis. In this study, we found that blocking de novo ceramide synthesis significantly inhibits ceramide accumulation and subsequent cell death in response to tumor necrosis factor α. When cells were pre‐treated with glutathione, a proposed cellular regulator of neutral sphingomyelinase, inhibition of ceramide accumulation at early time points was achieved with attenuation of cell death. Inhibition of both pathways achieved near‐complete inhibition of ceramide accumulation and cell death indicating that both pathways of ceramide generation are stimulated. This illustrates the complexity of ceramide generation in cytokine action.

Device closure of muscular ventricular septal defects in infants less than one year of age using the Amplatzer devices: Feasibility and outcome

In this study, we evaluated the feasibility, safety, and outcome of device closure of muscular ventricular septal defects (mVSD) in infants less than 1 year of age using the Amplatzer devices.

Erosions, erosions, and erosions! Device closure of atrial septal defects: how safe is safe?

Secundum atrial septal defect (ASD) accounts for approximately 6 to 10% of all CHD in children and 30% in adult patients [1,2]. Although surgical closure of ASDs is associated with very low mortality (0–3%), the use of transcatheter device techniques has become widely accepted as an alternative therapy to surgery. Device closure is considered safe and offers many intuitive advantages over surgical closure. Such advantages may include avoidance of cardiopulmonary bypass (CPB) and its potential adverse neurologic sequelae, avoidance of sternotomy scar, a potentially lower incidence of post-procedure complications, and a shorter hospital stay [3,4]. Currently, there are two devices approved by the United States Food and Drug Administration (FDA) for ASD closure: the Amplatzer Septal Occluder (ASO) (AGA/St. Jude Medical Corporation, St. Paul, Minnesota), approved in December 2001 [5]; and the Gore Helex Septal Occluder (HSO) (W.L. Gore & Associates, Flagstaff, Arizona), approved in August 2006 [6]. Lately, there has been an increasing concern regarding device erosion with the ASO. Although this is a very rare complication, it presents particular concerns. First, it is potentially fatal if not promptly recognized; second, it can unpredictably occur early or late (days to years) after the procedure making close follow-up difficult; third, there are no definite identifiable risk factors and the etiology is multifactorial (patients factors, device size, rim deficiency, septal malalignment). Recently at the PICS AICS 2012 meeting, there was a special session on this topic with a panel of experts including interventional cardiologists, cardiac surgeons, and FDA representative. In addition, the FDA held a panel meeting on May 24, 2012 to discuss this issue and came up with some recommendations that may help identify the true incidence of erosions and may shed some light as to the mechanism of erosions. Below is an overview on this life-threatening complication as well as a review of the available data and an update on the latest recommendations provided by the advisory panel to the FDA in order to assist in further understanding the causes and incidence of erosion and subsequently how to avoid/minimize its occurrence.

Hybrid pulmonary artery plication followed by transcatheter pulmonary valve replacement: Comparison with surgical PVR

Objective/Background

Left Hemitruncus Associated with Tetralogy of Fallot: Fetal Diagnosis and Postnatal Echocardiographic and Cardiac Computed Tomographic Confirmation

Anomalous origin of one pulmonary artery from the aorta, or hemitruncus, is a rare cardiac malformation. We report a case of left hemitruncus (aortic origin of the left pulmonary artery) associated with tetralogy of Fallot diagnosed in utero. To the authors’ knowledge, this is the first such case diagnosed by fetal echocardiography to be described in the literature. The condition was documented by postnatal echocardiogram and cardiac computed tomography. Prompt recognition of this lesion is essential for early repair to improve outcome.

Device Closure of Congenital Ventricular Septal Defects

Ventricular septal defect is the most common congenital heart malformation. Surgical closure, when indicated, has been practiced for over 50 years with good results; however, surgical closure is still associated with significant morbidity and mortality. Over the past decade, several occluding devices have been developed that made catheter device closure an attractive alternative to surgery with widely satisfactory results. In this article, a comprehensive review of percutaneous and perventricular (hybrid) device closure of each type of ventricular septal defect is presented.

Coronary artery bypass grafting after pneumonectomy

The need to perform coronary artery bypass grafting in patients who have a single lung is not uncommon. To date, the safety of such procedures has not been well documented. In this article, we review the literature using the Medline 1966 to September 2000 database to identify patients with pneumonectomy who underwent coronary artery grafting and we provide a compilation of all reported cases. We also present an additional case in whom the use of nasal bilevel positive airway pressure was beneficial in preventing postoperative pulmonary complications.

Development of Quality Metrics in Ambulatory Pediatric Cardiology

The American College of Cardiology Adult Congenital and Pediatric Cardiology (ACPC) Section had attempted to create quality metrics (QM) for ambulatory pediatric practice, but limited evidence made the process difficult. The ACPC sought to develop QMs for ambulatory pediatric cardiology practice. Five areas of interest were identified, and QMs were developed in a 2-step review process. In the first step, an expert panel, using the modified RAND-UCLA methodology, rated each QM for feasibility and validity. The second step sought input from ACPC Section members; final approval was by a vote of the ACPC Council. Work groups proposed a total of 44 QMs. Thirty-one metrics passed the RAND process and, after the open comment period, the ACPC council approved 18 metrics. The project resulted in successful development of QMs in ambulatory pediatric cardiology for a range of ambulatory domains.

Lack of apoptosis in the hypoxic brain of a rat model mimicking cyanotic heart disease

Objective : To assess the effect of chronic hypoxia on brain neuronal apoptosis, an animal model mimicking cyanotic heart disease was utilized. Methods : Rats were placed in an hypoxic environment at birth and oxygen levels were maintained at 10% in an air-tight Plexiglass chamber. Controls remained in room air. Animals were sacrificed and the brains were harvested at 1 and 4 weeks, respectively. Results : Significant polycythemia developed in the hypoxic rats at 1 and 4 weeks. Indexed brain mass to body weight was significantly increased in the hypoxic groups by 18% ( p < 0.01) and 38% ( p < 0.01) as compared to controls at 1 and 4 weeks, respectively. There was no difference in the number of apoptotic neurons between the chronically hypoxic rats and controls, as assayed by TUNEL labelling and Hoechst staining. The role of the sphingolipid ceramide was then examined because of its reported role in stress response, growth suppression and apoptosis. It was found that the brain ceramide accumulation was not significantly different in the hypoxic and control groups at 1 and 4 weeks. Conclusion : A protective adaptive response to chronic hypoxia in the neonatal brain may exist.

Cerebral mycotic aneurysm in a child with Down's syndrome: a unique association.

Mycotic aneurysms are rare complications in patients with infective endocarditis, particularly in the pediatric population. We report a case of mycotic aneurysm of the middle cerebral artery complicating bacterial endocarditis in a child with Downs syndrome. The patient was successfully treated medically without the need for surgical intervention. (J Child Neurol 2001;16:868—870).