High resolution analysis of follicular lymphoma genomes reveals somatic recurrent sites of copy‐neutral loss of heterozygosity and copy number alterations that target single genes

A multiplatform approach, including conventional cytogenetic techniques, BAC array comparative genomic hybridization, and Affymetrix 500K SNP arrays, was applied to the study of the tumor genomes of 25 follicular lymphoma biopsy samples with paired normal DNA samples to characterize balanced translocations, copy number imbalances, and copy‐neutral loss of heterozygosity (cnLOH). In addition to the t(14;18), eight unique balanced translocations were found. Commonly reported FL‐associated copy number regions were revealed including losses of 1p32‐36, 6q, and 10q, and gains of 1q, 6p, 7, 12, 18, and X. The most frequent regions affected by copy‐neutral loss of heterozygosity were 1p36.33 (28%), 6p21.3 (20%), 12q21.2‐q24.33 (16%), and 16p13.3 (24%). We also identified by SNP analysis, 45 aberrant regions that each affected one gene, including CDKN2A, CDKN2B, FHIT, KIT, PEX14, and PTPRD, which were associated with canonical pathways involved in tumor development. This study illustrates the power of using complementary high‐resolution platforms on paired tumor/normal specimens and computational analysis to provide potential insights into the significance of single‐gene somatic aberrations in FL tumorigenesis. © 2010 Wiley‐Liss,Inc.     

Effect of sildenafil on haemodynamic response to exercise and exercise capacity in Fontan patients

Giardini et al.¹ reported on the increase of peak oxygen uptakeat a cardiopulmonary exercise test in Fontan patients aftera single dose of sildenafil. This is an excellent study     

Determining lung volume with three-dimensional reconstructions of CT scan data: A pilot study to evaluate the effects of expansion thoracoplasty on children with severe spinal deformities

A retrospective review of a cohort of five patients who had been treated with a new technique for expansion thoracoplasty was performed. This study was designed to demonstrate that measurement of the volume of the lungs by three-dimensional reconstruction of CT scan data from children with complex spinal and thoracic deformities is a useful method for determining lung volumes in children who are too young to cooperate with pulmonary function testing. The authors' results indicate that lung volume by analysis of CT scan data is also a means of evaluating and quantifying the effects of expansion thoracoplasty. The authors were able to show that expansion thoracoplasty and stabilization with a titanium rib was able to increase the volume of lung parenchyma in the five patients in the study group by approximately 25% to 90% after surgical intervention.     

A therapeutic approach to wean total parenteral nutrition in the management of short bowel syndrome: three cases using nocturnal enteral rehydration

Short bowel syndrome is characterized by severe dehydration and malnutrition and requires total parenteral nutrition (TPN). Prolonged TPN has serious complications. Caloric requirements can be met orally but oral fluid replacement is problematic. Noncompliance and an inability to discontinue TPN earlier increase the likelihood of complications. Discontinuation of parenteral support requires an assessment of gastrointestinal anatomy and absorption capacity. Fluids must be replaced independently of feedings because the osmotic gradients decrease fluid absorption. Nocturnal enteral rehydration is an intervention using oral rehydration solutions through percutaneous endoscopic gastrostomy tubes at night. Patients given nocturnal enteral rehydration discontinued TPN earlier and had improved fluid absorption.     

New support for branched-chain amino acid supplementation in advanced hepatic failure

Nutritional supplementation with branched-chain amino acids (BCAA) has been a topic of considerable debate for more than two decades. Several studies have demonstrated that supplementation with BCAA is associated with improvement of the catabolic state commonly seen in people with cirrhosis, whereas other studies have showed an improvement in portosystemic encephalopathy in patients with liver disease. Some studies have also shown there to be no benefit in BCAA supplementation in advanced cirrhosis. A recent large clinical trial showed that long-term BCAA supplementation may be useful in preventing progressive hepatic failure and improving liver function in some patients.     

Hearts late after fontan operation have normal mass,normal volume,and reduced systolic function: a magnetic resonance imaging study

OBJECTIVES: The purpose of this study was to assess ventricular mass, volume, and systolic function in patients late after Fontan operation by cardiac magnetic resonance imaging. BACKGROUND: An assessment of determinants for ventricular function in post-Fontan patients was intended. METHODS: Twenty-three unselected patients (9 female, 14 male) at a median age of 19.4 years (range, 7.8 to 31.3 years), at a median time of 10.5 years (range, 4.1 to 18 years) after Fontan operation were studied. A standard 1.5-T scanner was used, and analysis was performed using dedicated software. Ten healthy volunteers (median age 26.4, range 18 to 39.3 years) served as the control group. RESULTS: Median end-systolic mass index was 72.2 g/m(2) (range, 43 to 138 g/m(2)) and 86.6 g/m(2) (range, 52 to 123 g/m(2)) in the control group (p = NS). Median end-diastolic ventricular volume was 64 ml/m(2) (range, 32 to 117 ml/m(2)) compared with 67.7 ml/m(2) (range, 59 to 75 ml/m(2)) in the control group (p = NS). Median ejection fraction was 49.3% (range, 20% to 63%) compared with 64.8% (range, 57% to 79%) in normals (p = 0.00001). CONCLUSIONS: We conclude that long-term survivors of a Fontan operation have normal ventricular mass, normal volume, but reduced systolic ventricular function.     

Emergency hospital admissions and three-year survival of adults with and without cardiovascular surgery for congenital cardiac disease

OBJECTIVE: This study determined the quantity and nature of emergencies leading to unscheduled hospital admissions of adults with congenital cardiac disease and their mid-term survival. RESULTS: During 1 year, 429 adults with congenital cardiac diseases were admitted 571 times, and 124 admissions (22%) of 95 patients (22%) were emergency admissions. Fifteen of the 95 patients were seen for the first time in 1 of the participating centers. The underlying anomalies were Fallot's tetralogy and pulmonary atresia (n = 26/7), univentricular heart after Fontan procedure (n = 25), atrial septal defect (n = 18), Eisenmenger syndrome (n = 12), complete transposition (n = 11), and others (n = 25). Indications for admission were cardiovascular complications (n = 103; 83%) (arrhythmia, cardiac failure, syncope, pacemaker problems, pericardial tamponade, and sudden death), infections (n = 8, 6%) (endocarditis, pacemaker infection, pneumonia, and cerebral abscess), acute chest pain (n = 7; 6%), and acute abdominal pain (n = 4; 3%). All patients required immediate emergency care, and 16 patients (17%) required urgent cardiovascular or abdominal surgery. Six patients died during the hospital stay. During a follow-up of 2.9 years (SD 0.8), 16 (18%) of the discharged patients died, and 2 additional patients underwent heart or heart-lung transplantation. CONCLUSION: Adults with congenital cardiac disease often experience serious emergency situations with a high in-hospital and mid-term post-hospital mortality. Care given by physicians with special expertise is important in this specific group of patients.     

Pulmonary blood pressure, not flow, is associated with net endothelin-1 production in the lungs of patients with congenital heart disease and normal pulmonary vascular resistance

OBJECTIVE: Endothelin-1 concentrations are increased in patients with increased mean pulmonary arterial pressure, pulmonary blood flow, and pulmonary vascular resistance. However, endothelin-1 concentrations have not been well characterized in patients with congenital heart disease and normal pulmonary vascular resistance. In particular, it is unclear whether pressure or flow is the key regulator of endothelin- 1 in this setting. We tested the hypothesis that pulmonary blood pressure and not flow is associated with net endothelin-1 production in patients with congenital heart disease and normal pulmonary vascular resistance. METHODS: With a commercially available immunoassay, we measured endothelin-1 concentrations in pulmonary arterial and pulmonary venous plasma of 56 consecutive patients with congenital heart disease and pulmonary vascular resistance less than 2 U. m(2) undergoing cardiac catheterization. We used multiple linear regression to analyze the effect of demographic and hemodynamic variables on pulmonary arterial and venous endothelin-1 concentrations and on the change of endothelin-1 concentration over the pulmonary vascular bed. RESULTS: Multiple linear regression revealed that of all the hemodynamic variables tested, mean pulmonary arterial pressure had the greatest effect on increasing the change of endothelin-1 concentration over the pulmonary vascular bed (P <.0001). Pulmonary blood flow did not have any effect on endothelin-1 concentrations or on the change of endothelin-1 concentration over the pulmonary vascular bed. CONCLUSIONS: This study shows that pulmonary blood pressure and not flow is associated with net endothelin-1 production in patients with congenital heart disease and normal pulmonary vascular resistance.     

A critical interaction: leptin and ghrelin

Continuing research has increased our understanding of regulatory factors involving appetite, food intake, and energy metabolism. There appears to be a complex interaction among insulin, leptin, and ghrelin. A new study explored these interactions and indicates that leptin may regulate ghrelin levels and affect body weight changes.