Acyanotic and Cyanotic Congenital Heart Diseases

There has been tremendous progress in treatment of heart disease in children. Device therapy is increasingly being used in acyanotic congenital heart disease, while surgical results have improved significantly to give smile to many cyanotic heart disease children and their parents. This article makes an attempt to increase awareness of general pediatricians about common congenital heart diseases.     

Hepatocellular carcinoma: Where there is unmet need

Hepatocellular carcinoma (HCC) is a complex and heterogeneous tumor most commonly associated with underlying chronic liver disease, especially hepatitis. It is a growing problem in the United States and worldwide. There are two potential ways to prevent HCC. Primary prevention which is based on vaccination or secondary prevention involving agents that slow down carcinogenesis. Several pathways have been thought to play a role in the development of HCC; specifically, those involving vascular endothelial growth factor (VEGF)‐mediated angiogenesis, WNT, phosphatidylinositol 3‐kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR), AMP‐activated protein kinase (AMPK), and c‐MET. Currently, there are only a limited number of drugs which have been proven as effective treatment options for HCC and several clinical trials are testing drugs which target aberrations in the pathways mentioned above. In this review, we discuss currently approved therapies, monotherapies and combination therapy for the treatment of HCC.     

Transcatheter closure of aortopulmonary window

Aortopulmonary window is an uncommon congenital cardiac defect. Most infants presenting with aortopulmonary window will require conventional surgical repair. Experience with transcatheter closure of aortopulmonary window is limited. We report the case of a 9-year-old girl with aortopulmonary window, in whom transcatheter closure was performed successfully using Amplatzer ductal occluder device.     

Chondroitin sulfate proteoglycan but not hyaluronic acid is the receptor for the adherence of Plasmodium falciparum-infected erythrocytes in human placenta, and infected red blood cell adherence up-regulates the receptor expression

A low-sulfated chondroitin sulfate proteoglycan (CSPG) has been shown to be the receptor for the adherence of Plasmodium falciparum-infected red blood cells (IRBCs) in human placenta. Recently, hyaluronic acid (HA) has been suggested as an additional receptor even though IRBC binding to HA and the presence of HA at locations where IRBCs adhere in the placenta have not been established. In this study, we investigated whether HA is also a receptor for IRBC binding. IRBCs from infected placentas as well as those from different laboratory strains could bind to CSPG but not to HA. In a cell depletion assay, IRBCs from infected placentas could bind quantitatively to CSPG. Although CSPG is present both in the intervillous space and on the syncytiotrophoblast surface, HA is absent in these locations. These data conclusively demonstrate that CSPG, but not HA, is a receptor for IRBC adherence in the placenta. Our data also show, for the first time, that the IRBC-binding CSPG in the placenta is of fetal origin and that, in P. falciparum-infected placentas, the CSPG level is significantly increased, which could exacerbate IRBC adherence and placental pathogenesis. These results have important implications for the development of anti-IRBC adhesion-based vaccine for pregnancy-associated malaria.     

Carotid intima-media thickness in children with Kawasaki disease

Kawasaki disease (KD) is an acute medium vessel vasculitis seen in children. The most significant long-term complication is related to coronary artery abnormalities. Use of intravenous immunoglobulins, however, has led to significant reduction in incidence of coronary aneurysms. What is more alarming is the fact that higher risk of cardiovascular disease is seen in even those children who do not have coronary artery aneurysms during subacute phase. Various factors like abnormal lipid profiles, abnormal vessel wall reactivity and endothelial dysfunction have been implicated for this. Carotid intima-media thickness (cIMT) has been used as a surrogate marker for atherosclerosis. This study was planned to evaluate cIMT in children with KD. Twenty-seven children with diagnosis of KD at least 1 year prior to enrolment were evaluated for cIMT at enrolment and then after 3 months. Fasting lipid profile was done for all patients. Mean cIMT was significantly higher in children with KD compared to controls. In lipid profiles, undesirable HDL-C and triglyceride levels were seen in 2 and 3 children, respectively. Undesirable and borderline LDL-C levels were seen in 1 and 2 patients, respectively. Undesirable and borderline total cholesterol levels were seen in 1 and 3 patients, respectively. Higher cIMTs were seen in our cohort of KD patients. Proatherogenic abnormalities in lipid profile were seen in a few patients. Both abnormalities may predict a higher risk of atherosclerosis in future. The results of this study need to be replicated on a larger study sample and over longer follow-up periods.     

Feasibility of integrating high-spatial-resolution 3D breath-hold coronary MR angiography with myocardial perfusion and viability examinations

The study was institutional review board approved and Health Insurance Portability and Accountability Act compliant. All subjects provided informed consent. Three-dimensional breath-hold coronary magnetic resonance (MR) angiography with use of steady-state free precession was performed in 12 patients up to 20 minutes after 0.2 mmol gadolinium-based contrast material per kilogram of body weight was administered. Within 24 heartbeats, a spatial resolution of up to 1.0 x 1.2 x 2.0 mm was achieved. Sixty-five (82%) of the 79 visualized coronary artery segments had a grade of 3 or 4 on a four-point scale of depiction in which grade 4 indicated excellent depiction. Twenty-seven percent (n = 21) of the 79 segments were assigned a grade of 4; 56% (n = 44), a grade of 3; 16% (n = 13), a grade of 2; and 1% (n = 1), a grade of 1. Coronary MR angiography performed as part of a first-pass myocardial perfusion and viability assessment MR imaging examination is feasible and does not involve additional imaging time.     

Recombinant paraoxonase 1 protects against sarin and soman toxicity following microinstillation inhalation exposure in guinea pigs

To explore the efficacy of paraoxonase 1 (PON1) as a catalytic bioscavenger, we evaluated human recombinant PON1 (rePON1) expressed in Trichoplusia ni larvae against sarin and soman toxicity using microinstillation inhalation exposure in guinea pigs. Animals were pretreated intravenously with catalytically active rePON1, followed by exposure to 1.2 X LCt₅₀ sarin or soman. Administration of 5 units of rePON1 showed mild increase in the blood activity of the enzyme after 30 min, but protected the animals with a significant increase in survival rate along with minimal signs of nerve agent toxicity. Recombinant PON1 pretreated animals exposed to sarin or soman prevented the reduction of blood O₂ saturation and pulse rate observed after nerve agent exposure. In addition, rePON1 pretreated animals showed significantly higher blood PON1, acetylcholinesterase (AChE), and butyrylcholinesterase activity after nerve agent exposure compared to the respective controls without treatments. AChE activity in different brain regions of rePON1 pretreated animals exposed to sarin or soman were also significantly higher than respective controls. The remaining activity of blood PON1, cholinesterases and brain AChE in PON1 pretreated animals after nerve agent exposure correlated with the survival rate. In summary, these data suggest that human rePON1 protects against sarin and soman exposure in guinea pigs.     

Elective laparoscopic cholecystectomy in the presence of common bile duct stent

Background  

Endoscopic retrograde cholangiopancreatography (ERCP) is a common procedure done in patients with common bile duct (CBD) stones. Some clinicians insert a CBD stent at the time of ERCP. Such patients may then present for laparoscopic cholecystectomy (LC) with CBD stents in situ. The aim of this study was to examine the impact of the presence of a CBD stent on the outcome of elective LC.     

Large field-of-view real-time MRI with a 32-channel system.

The emergence of parallel MRI techniques and new applications for real-time interactive MRI underscores the need to evaluate performance gained by increasing the capability of MRI phased-array systems beyond the standard four to eight high-bandwidth channels. Therefore, to explore the advantages of highly parallel MRI a 32-channel 1.5 T MRI system and 32-element torso phased arrays were designed and constructed for real-time interactive MRI. The system was assembled from multiple synchronized scanner-receiver subsystems. Software was developed to coordinate across subsystems the real-time acquisition, reconstruction, and display of 32-channel images. Real-time, large field-of-view (FOV) body-survey imaging was performed using interleaved echo-planar and single-shot fast-spin-echo pulse sequences. A new method is demonstrated for augmenting parallel image acquisition by independently offsetting the frequency of different array elements (FASSET) to variably shift their FOV. When combined with conventional parallel imaging techniques, image acceleration factors of up to 4 were investigated. The use of a large number of coils allowed the FOV to be doubled in two dimensions during rapid imaging, with no degradation of imaging time or spatial resolution. The system provides a platform for evaluating the applications of many-channel real-time MRI, and for understanding the factors that optimize the choice of array size.