Pseudoprominent aorta: radiographic findings and CT correlation

The presence of a persistent left-sided superior vena cava (LSVC) in the absence of a right-sided superior vena cava (RSVC) may be suspected on a posteroanterior (PA) chest radiograph because of a prominent-appearing ascending aorta, which results from the absence of the RSVC. In the absence of an RSVC, the right upper lobe abuts and outlines the course of the ascending aorta, allowing better demonstration of its profile. This report describes a patient with this finding on a PA chest radiograph. Computed tomographic correlation is presented.     

Peripheral blood stem cell collection and use in Hodgkin''s disease. Comparison with marrow in autologous transplantation

Hematopoietic progenitor cells can be collected from blood by cytapheresis; the clinical use of these cells may offer such advantages over marrow as the avoidance of general anesthesia, collection on an outpatient basis, and use when marrow is involved with malignancy. Since Hodgkin's disease rarely spreads hematogenously, postchemotherapy marrow transplantation with autologous peripheral blood stem cells (PBSCs) was compared to that with marrow transplantation in patients with this disorder. Seven patients were treated with PBSCs and 19 with marrow. Five to nine collections of PBSC were performed per patient. There was a rebound increase in circulating committed progenitors when PBSC were collected during the marrow rebound after cyclic chemotherapy. After intensification and cellular rescue, quicker recovery of circulating white cells (p less than 0.05) and a shorter hospital stay (not significant) were seen in the PBSC patients than in those treated with autologous marrow. There was no difference in the duration of red cell or platelet transfusion required after transplant. Of six patients whose marrows were previously involved by Hodgkin's, recurrent or progressive disease has occurred in five. PBSC may be a viable alternative to marrow in selected patients.     

Predictive value of signs and symptoms for colorectal cancer in patients with rectal bleeding in general practice

The aim of the study is to determine the diagnostic value of(combinations of) signs, symptoms and simple laboratory testresults for colorectal cancer in patients with rectal bleedingpresenting in general practice. Initial complaints and findingswere compared with the final diagnoses based on clinical follow-upafter at least 1 year. Patients studied were those presentingovert rectal bleeding to the general practitioner (83 GPs inthe South of the Netherlands). Outcome measures are sensitivity,specificity, predictive values, odds ratios and a predicitionmodel derived from multiple logistic regression analysis. Age,change in bowel habit and blood mixed with or on stool showa statistically significant independent value in the discriminationbetween patients with a low and those with a high probabilityof colorectal cancer. Many other variables did not show predictivevalue. The prediction model has a sensitivity of 100% and aspecificity of 90%. Although the number of patients with colorectalcancer is small (n=9) it was possible to identify three characteristicswhich can be helpful in the prediction of presence or absenceof colorectal cancer in general practice. Application of themodel presented might prevent 90% of ‘unnecessary’invasive diagnostic procedures for patients with rectal bleedingwho do not have colorectal cancer (true negative). Testing theperformance of the model in other general practice populationsis recommended.     

Reanalysis of mGWAS results and in vitro validation show that lactate dehydrogenase interacts with branched-chain amino acid metabolism

The assignment of causative genes to noncoding variants identified in genome-wide association studies (GWASs) is challenging. We show how combination of knowledge from gene and pathway databases and chromatin interaction data leads to reinterpretation of published quantitative trait loci for blood metabolites. We describe a previously unidentified link between the rs2403254 locus, which is associated with the ratio of 3-methyl-2-oxobutanoate and alpha-hydroxyisovalerate levels, and the distal LDHA gene. We confirmed that lactate dehydrogenase can catalyze the conversion between these metabolites in vitro, suggesting that it has a role in branched-chain amino acid metabolism. Examining datasets from the ENCODE project we found evidence that the locus and LDHA promoter physically interact, showing that LDHA expression is likely under control of distal regulatory elements. Importantly, this discovery demonstrates that bioinformatic workflows for data integration can have a vital role in the interpretation of GWAS results.     

Altered interface adhesion molecules in oral lichen planus

OBJECTIVE: To evaluate expression of key epithelial-connective tissue interface adhesion molecules (basal keratinocyte integrins and extracellular matrix receptors) in oral lichen planus (LP).
DESIGN: Integrins α3, α6, β1, β4 and basement membrane proteins laminin 1, laminin 5, collagen IV, and collagen VII were immunohistochemically identified in frozen biopsy specimens (14 oral LP and 11 matched controls) using a standard avidin-biotin-peroxidase technique.
RESULTS: An increased staining intensity of all antigens in LP was shown, as compared to controls. Integrin expression by LP keratinocytes was generally more intense and appeared on more upper level cells. Staining for basement membrane-associated extra-cellular matrix proteins was also generally more intense, although fragmentation and gaps were typically seen. Reactions for α6, β4, laminin 5, and collagen VII stains were particularly intense along the basement membrane. In LP, strands of laminin 5, collagen IV, and collagen VII appeared in the submucosa approximating or duplicating the basement membrane.
CONCLUSIONS: The apparent increased expression of the interface-associated adhesion molecules may be reflective of a keratinocyte compensatory response (due to lymphocyte-mediated damage) that would functionally help resist epithelial separation (ulceration). Expression of α3β1 and α6β4 would also assist in epithelial migration associated with wound repair. We interpret the submucosal extensions and deposits of basement membrane proteins as representing remnants of basement membrane, indicating recent remodeling or atrophy of epithelial rate ridges.