Chemokine expression in hepatocellular carcinoma versus colorectal liver metastases

INTRODUCTION Chemokines represent a family of small chemotactic cytokines, initially identified as mediators of leucocyte trafficking and homing. In the last few years, chemokines have been shown to participate also in tumor growth and the lymphatic and e…     

Exercise testing three days after onset of acute myocardial infarction

To determine the feasibility and predictive value of early exercise testing 72 hours after acute myocardial infarction, 109 consecutive patients who received reperfusion therapy were prospectively evaluated. In the group studied, in 87 (80%) the course was uncomplicated 3 days after admission, as defined by a lack of congestive heart failure, arrhythmias and angina, and 53 patients (49%) performed heart rate-limited (140 beats/min) treadmill exercise. These patients exercised for 7.9 +/- 3.4 minutes, achieving a heart rate of 129 +/- 11 beats/min and a systolic blood pressure of 151 +/- 27 mm Hg. The exercise test was not accompanied by any protracted ischemia, infarction or significant arrhythmias. Accompanying tomographic thallium-201 scintigraphy demonstrated a reversible perfusion defect in 14 patients (26%), no evidence for ischemia in 36 patients (69%) and an equivocal result in 3 patients (6%). Of the 14 patients with a positive exercise-thallium test result, 4 had an adverse clinical outcome of either reinfarction, postinfarction angina or ventricular tachycardia during hospital days 4 to 10; an adverse in-hospital outcome was not seen in the 40 patients with a negative exercise-thallium test result (p = 0.009). Thus, early exercise testing after acute myocardial infarction is safe in selected patients with an uncomplicated course and the test is predictive of in-hospital clinical outcomes.     

Severe Hypertriglyceridemia‐Related Acute Pancreatitis

Acute pancreatitis is a potentially life‐threatening complication of severe hypertriglyceridemia. In some cases, inborn errors of metabolism such as lipoprotein lipase deficiency, apoprotein C‐II deficiency, and familial hypertriglyceridemia have been reported as causes of severe hypertriglyceridemia. More often, severe hypertriglyceridemia describes various clinical conditions characterized by high plasma levels of triglycerides (>1000 mg/dL), chylomicron remnants, or intermediate density lipoprotein like particles, and/or chylomicrons. International guidelines on the management of acute pancreatitis are currently available. Standard therapeutic measures are based on the use of lipid‐lowering agents (fenofibrate, gemfibrozil, niacin, Ω‐3 fatty acids), low molecular weight heparin, and insulin in diabetic patients. However, when standard medical therapies have failed, non‐pharmacological approaches based upon the removal of triglycerides with therapeutic plasma exchange can also provide benefit to patients with severe hypertriglyceridemia and acute pancreatitis. Plasma exchange could be very helpful in reducing triglycerides levels during the acute phase of hyperlipidemic pancreatitis, and in the prevention of recurrence. The current evidence on management of acute pancreatitis and severe hypertriglyceridemia, focusing on symptoms, treatment and potential complications is reviewed herein.     

Array comparative genomic hybridization reveals similarities between nodular lymphocyte predominant Hodgkin lymphoma and T cell/histiocyte rich large B cell lymphoma

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and T cell/histiocyte rich large B cell lymphoma (THRLBCL) usually affect middle‐aged men, show tumour cells with a B cell phenotype and a low tumour cell content. Whereas the clinical behaviour of NLPHL is indolent, THRLBCL presents with advanced stage disease and an aggressive behaviour. In the present study, array comparative genomic hybridization was performed in seven typical NLPHL, four THRLBCL‐like NLPHL variants, six THRLBCL and four diffuse large B cell lymphomas (DLBCL) derived from NLPHL. The number of genomic aberrations was higher in THRLBCL compared with typical and THRLBCL‐like variant of NLPHL. Gains of 2p16.1 and losses of 2p11.2 and 9p11.2 were commonly observed in typical and THRLBCL‐like variants of NLPHL as well as THRLBCL. Gains of 2p16.1, affecting the REL locus were confirmed in an independent cohort. Expression of the REL protein was observed at similar frequencies in typical and THRLBCL‐like variant of NLPHL as well as THRLBCL (33–38%). In conclusion, the present study reveals further similarities between NLPHL and THRLBCL on the genomic level, confirming that these entities are part of a pathobiological spectrum with common molecular features, but varying clinical presentations.     

Impact of rhinoviruses on pediatric community-acquired pneumonia

This study of 592 children seen in our Emergency Department with radiographically confirmed community-acquired pneumonia (CAP) was designed to evaluate the role of rhinoviruses (RVs) in the disease. The respiratory secretions of each child were assayed using RVP Fast in order to detect 17 respiratory viruses, and the RV-positive samples were characterised by means of real-time polymerase chain reaction and sequencing. RVs were identified in 172 cases (29.0%): 48/132 children aged<1 year (36.3%), 80/293 aged 1-3 years (27.3%), and 44/167 aged≥4 years (26.3%). Sequencing demonstrated that 82 RVs (49.1%) were group A, 17 (10.1%) group B, and 52 (31.1%) group C; 21 (12.2%) were untyped. RVs were found as single agents in 99 cases, and together with two or more other viruses in 73 (40.7%). There were only marginal differences between the different RV groups and between single RV infection and RV co-infections. RV CAP is frequent not only in younger but also in older children, and RV-A is the most common strain associated with it. The clinical relevance of RV CAP seems to be mild to moderate without any major differences between the A and B strains and the recently identified RV C.     

A circular mitochondrial plasmid incites hypovirulence in some strains of Cryphonectria parasitica

In the chestnut-blight fungus Cryphonectria parasitica, a plasmid, pCRY1, occurs in the mitochondria of several strains isolated at various locations in the northeastern United States and Canada. The monomer of this plasmid is a 4.2-kb circular double-stranded DNA that has no detectable sequence homology with the 160–kb mitochondrial DNA of Ep155, a standard virulent laboratory strain of C. parasitica. The circular nature and oligomeric characteristics of the plasmid were deduced from the heterogeneous size of plasmid DNA molecules as detected by one- and two-dimensional gel-electrophoresis, the nature and alignment of restriction fragments, and the lack of detectable termini in the nucleotide sequence. The cytoplasmic location of the plasmid was deduced from its co-purification with mitochondria, uniparental (maternal) transmission in sexual crosses, dissociation from the nuclei of the donor strain during its horizontal transfer between vegetatively compatible strains through hyphal anastomoses, and mitochondrial codon usage (UGA=Try). The pCRY1 plasmid contains a long open reading frame that is transcribed and potentially encodes a unique 1214 amino-acid, B-family DNA polymerase similar to those encoded by the LaBelle and Fiji circular mitochondrial plasmids of Neurospora. In this subgroup of proteins, the DTD motif characteristic of B-family DNA polymerases is replaced by TTD. Amino-acid motifs related to those that are characteristic of the 3′→5′ exonuclease domains of B-family DNA polymerases have been located in the amino-terminal portion of the proteins. A comparison of isogenic plasmid-free and plasmid-containing cultures indicates that pCRY1 is an infectious agent that effects a reduction in the pathogenicity of some, but not all, strains of C. parasitica. Received: 12 August / 9 December 1999     

A common haplotype at the CD36 locus is associated with high free fatty acid levels and increased cardiovascular risk in Caucasians

CD36 is a class B scavenger receptor recognizing a variety of ligands including long-chain fatty acids and modified LDL. We investigated whether genetic variability at this locus is a determinant of free fatty acid (FFA) plasma levels and risk of coronary artery disease (CAD) in Caucasians. Typing of 21 polymorphic markers, evenly spanning the CD36 gene, revealed two linkage disequilibrium (LD) blocks that could be tagged by five polymorphisms (-33137A>G, -31118G>A, 25444G>A, 27645del>ins and 30294G>C). In 585 non-diabetic individuals of Caucasian origin, the 30294G>C polymorphism was significantly associated with FFA levels (P = 0.02)--an effect that was especially visible among men (P = 0.009). A similar association was observed in this gender at -33137 (P = 0.008) and -31118 (P = 0.028). When the five tag polymorphisms were considered together, men carrying the AGGIG haplotype had 31% higher FFA (P = 0.0002) and 20% higher triglycerides (P = 0.025) than non-carriers. The same haplotype was associated with increased risk of CAD in 197 type 2 diabetic individuals from the US (OR = 2.3, 95% CI 1.2-4.2). A similar tendency was observed in a group of 321 type 2 diabetic individuals from Italy (OR = 1.4, 0.9-2.3), resulting in an overall relative risk of 1.6 (1.1-2.3, P = 0.015) in the two populations considered together. By targeted resequencing, we identified a common variant in the CD36 promoter that is in strong LD with the AGGIG haplotype and could be partly responsible for these findings. In conclusion, this comprehensive study of CD36 variability indicates that the common polymorphisms at this locus modulate lipid metabolism and cardiovascular risk in Caucasians.