Vascular endothelial growth factor and basic fibroblast growth factor in children with cyanotic congenital heart disease

OBJECTIVE: Vascular endothelial growth factor and basic fibroblast growth factor are potent stimulators of angiogenesis. Children with cyanotic congenital heart disease often experience the development of widespread formation of collateral blood vessels, which may represent a form of abnormal angiogenesis. We undertook the present study to determine whether children with cyanotic congenital heart disease have elevated serum levels of vascular endothelial growth factor and basic fibroblast growth factor. METHODS: Serum was obtained from 22 children with cyanotic congenital heart disease and 19 children with acyanotic heart disease during cardiac catheterization. Samples were taken from the superior vena cava, inferior vena cava, and a systemic artery. Vascular endothelial growth factor and basic fibroblast growth factor levels were measured in the serum from each of these sites by enzyme-linked immunosorbent assay. RESULTS: Vascular endothelial growth factor was significantly elevated in the superior vena cava (P =.04) and systemic artery (P =.02) but not in the inferior vena cava (P =.2) of children with cyanotic congenital heart disease compared to children with acyanotic heart disease. The mean vascular endothelial growth factor level, determined by averaging the means of all 3 sites, was also significantly elevated (P =.03). Basic fibroblast growth factor was only significantly elevated in the systemic artery (P =.02). CONCLUSION: Children with cyanotic congenital heart disease have elevated systemic levels of vascular endothelial growth factor. These findings suggest that the widespread formation of collateral vessels in these children may be mediated by vascular endothelial growth factor.     

Circadian and seasonal variation of malignant arrhythmias in a pediatric and congenital heart disease population

INTRODUCTION: Recent studies in adult populations have revealed seasonal variation in the frequency of acute cardiovascular events, including life-threatening arrhythmias, demonstrating increased events during winter and early spring. Trends in the time of day that arrhythmias occur also were noted. We sought to establish whether pediatric and young adult congenital heart disease implantable cardioverter defibrillator (ICD) recipients have circadian or seasonal variability in shock frequency, similar to adult populations. METHODS AND RESULTS: Data from ICD patients at six pediatric centers in North America were analyzed to assess the timing of life-threatening arrhythmias. The populations consisted of children and adults with congenital heart disease and ICDs placed for malignant arrhythmias. Data were considered in 46 patients who received appropriate therapy (total 139 episodes) for ventricular tachycardia or ventricular fibrillation. Multiple variables were analyzed, including time of day, day of week, and month of year. In contrast to previously studied adult patients, fewer events occurred in the early morning (7.5%), with the most therapies occurring between 6 P.M. and midnight (35%). An increased frequency of therapies was observed in the fall and winter (September-January), representing 60% of all appropriate shocks. Unlike adult populations, Mondays did not have an increased frequency of malignant arrhythmias. CONCLUSION: Pediatric and adult congenital heart disease populations have moderate seasonal and 24-hour variation in ICD event rate, with some distinctly different peaks than those seen in typical adult ICD populations. These findings suggest circadian variation in arrhythmia vulnerability that may differ from conventional occupational, physical, or emotional stressors. (J Cardiovasc Electrophysiol, Vol. 13, pp.     

The Medical and Endovascular Treatment of Atherosclerotic Renal Artery Stenosis (METRAS) study: rationale and study design

It is unclear whether revascularization of renal artery stenosis (RAS) by means of percutaneous renal angioplasty and stenting (PTRAS) is advantageous over optimal medical therapy. Hence, we designed a randomized clinical trial based on an optimized patient selection strategy and hard experimental endpoints. Primary objective of this study is to determine whether PTRAS is superior or equivalent to optimal medical treatment for preserving glomerular filtration rate (GFR) in the ischemic kidney as assessed by 99mTcDTPA sequential renal scintiscan. Secondary objectives of this study are to establish whether the two treatments are equivalent in lowering blood pressure, preserving overall renal function and regressing target organ damage, preventing cardiovascular events and improving quality of life. The study is designed as a prospective multicentre randomized, un-blinded two-arm study. Eligible patients will have clinical and angio-CT evidence of RAS. Inclusion criteria is RAS affecting the main renal artery or its major branches either >70% or, if <70, with post-stenotic dilatation. Renal function will be assessed with 99mTc-DTPA renal scintigraphy. Patients will be randomized to either arms considering both resistance index value in the ischemic kidney and the presence of unilateral/bilateral stenosis. Primary experimental endpoint will be the GFR of the ischemic kidney, assessed as quantitative variable by 99TcDTPA, and the loss of ischemic kidney defined as a categorical variable.     

T2-weighted,apparent diffusion coefficient and 18F-FDG PET histogram analysis of rectal cancer after preoperative chemoradiotherapy

Techniques in Coloproctology - The aim of our study was to investigate the correlation among T2-weighted (T2w) images, apparent diffusion coefficient (ADC) maps, 18F-fluorodeoxyglucose (18F-FDG)...     

Torulopsis glabrata peritonitis complicating continuous ambulatory peritoneal dialysis: successful management with oral 5-fluorocytosine

We report two cases of fungal peritonitis caused by Torulopsis glabrata, an uncommon opportunistic pathogen, in patients with end-stage renal disease receiving continuous ambulatory peritoneal dialysis (CAPD). The general clinical characteristic of T glabrata peritonitis was comparable to previously reported cases of Candida peritonitis. Although appropriate therapy of fungal peritonitis in patients undergoing CAPD still remains controversial, both for the drug of choice and for the dosage to be used, our study indicates that a 5-week course of oral 5-fluorocytosine (5-FC) may obviate the need to remove the peritoneal catheter during the management of peritonitis caused by susceptible strains of T glabrata.     

Inability to Cannulate the Coronary Sinus in Patients with Supraventricular Arrhythmias: Congenital and Acquired Coronary Sinus Atresia

We report 4 cases of congenital and acquired coronary sinus ostial atresia incidentally found during electrophysiologic assessment for supraventricular arrhythmias. Congenital variants consisted of coronary sinus drainage predominantly via persistent left superior vena cavae and partial coronary sinus unroofing into the left atrium. The acquired variant was inadvertently produced during surgery for cor triatriatum. A variety of electrophysiologic substrates including right and left-sided accessory pathways and both typical and atypical AV nodal reciprocating tachycardia were identified. Approaches to imaging and accessing the coronary sinus when the os cannot be cannulated are discussed, including a search for right atrial accessory venous collaterals, venography to rule-out a persistent left superior vena cava, and coronary angiography.     

Satoyoshi syndrome in a Caucasian girl improved with glucocorticoids--a clinical report

Satoyoshi syndrome (OMIM 600705) is a rare disorder of unknown cause characterized by progressive painful intermittent muscle spasms, amenorrhea, alopecia, malabsorption, and skeletal abnormalities mimicking a skeletal dysplasia. In this report, we describe a Caucasian 12-year-old girl that presented with characteristic manifestations, including alopecia, muscle cramps, and short stature with onset at age 7. Prednisone 60 mg/m(2) every other day and amytriptiline 25 mg QD were administered. After 2 months, alopecia had significantly improved and muscle cramps had almost disappeared, so that glucocorticoid treatment was tapered. Follow-up, 9 months later, showed a normal looking and asymptomatic girl.     

Pharmacogenetics of irinotecan

Pharmacogenetics focuses on intersubjects variation in therapeutic drug effects and toxicity depending on genetic polymorphisms. This is particularly interesting in oncology since anticancer drugs usually have a narrow margin of safety. Irinotecan [7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin] is used in cancer chemotherapy as a topoisomerase I inhibitor and it is characterised by a sometimes unpredictable severe toxicity. It is mostly intestinal with nausea, vomit and diarrhoea or haematologic with leuko-thrombocytopenia. Its complex metabolism involves many proteins. Human carboxylesterase isoforms 1 and 2 (hCE1, hCE2) activate irinotecan to its metabolite SN-38 (7-ethyl-10-hydroxycamptothecin); cytochrome P450 isoforms 3A4 and 3A5 (CYP3A4, CYP3A5) mediate the oxidation of the parental compound to irinotecan; uridino-glucuronosil transferase isoform 1A1 (UGT1A1) catalyses glucuronidation of SN-38; the multi-resistance protein isoform 2 (MRP2) allows the cellular excretion of the SN-38 glucuronide (SN-38G) and the multi-drug resistance gene (MDR1), encoding for P-glycoprotein, is responsible for the excretion of irinotecan from the cell. Polymorphic structures in the genes encoding for all these proteins have been described. In particular, the UGT1A1*28 allele has been associated with an increased toxicity after irinotecan chemotherapy. Classical parameters used in the clinic, such as body-surface area, have no longer a meaningful correlation with clinical outcome. Hence it emerges the importance of studying the individual genotype to predict the toxicity and efficacy of irinotecan and to individualise therapy. In this review, we summarise the new developments on the study of the pharmacogenetics of irinotecan, stressing its importance in drug cytotoxic effect.