Wilms tumor: ultrasonic features, pathologic correlation, and diagnostic pitfalls

The gray-scale ultrasonic features of Wilms tumor are reported with pathologic comparison. The most consistent ultrasonic features are large size, sharp margination, and echogenic heterogeneity. The frequently observed anechoic areas correlated with hemorrhage and necrosis. A rare case of mesoblastic nephroma is included for comparison. Pitfalls in diagnosis are discussed.     

Dystroglycan is essential for early embryonic development: disruption of Reichert's membrane in Dag1-null mice

Dystroglycan is a central component of the dystrophin-glycoprotein complex (DGC), a protein assembly that plays a critical role in a variety of muscular dystrophies. In order to better understand the function of dystroglycan in development and disease, we have generated a null allele of dystroglycan (Dag1neo2) in mice. Heterozygous Dag1neo2 mice are viable and fertile. In contrast, homozygous Dag1neo2 embryos exhibit gross developmental abnormalities beginning around 6.5 days of gestation. Analysis of the mutant phenotype indicates that an early defect in the development of homozygous Dag1neo2 embryos is a disruption of Reichert's membrane, an extra-embryonic basement membrane. Consistent with the functional defects observed in Reichert's membrane, dystroglycan protein is localized in apposition to this structure in normal egg cylinder stage embryos. We also show that the localization of two critical structural elements of Reichert's membrane- -laminin and collagen IV--are specifically disrupted in the homozygous Dag1neo2 embryos. Taken together, the data indicate that dystroglycan is required for the development of Reichert's membrane. Furthermore, these results suggest that disruption of basement membrane organization might be a common feature of muscular dystrophies linked to the DGC.      

Neutrophil labeling with indium-111: tropolone vs. oxine

This study was undertaken to compare tropolone with oxine (8-hydroxy-quinoline) for labeling human neutrophils with In-111. Exposure of neutrophils to tropolone at concentrations required for efficient labeling resulted in a marked impairment of chemotaxis. In contrast, no impairment of neutrophil chemotaxis was observed using In-111 oxine. Labeling efficiencies obtained with In-111 tropolone under optimal conditions were consistently less than those obtained with In-111 oxine. We evaluated cells labeled by the two methods using chemotaxis radioassay to assess the chemotatic potential of labeled cells. The results led to the conclusion that the oxine technique is preferable to tropolone for labeling human neutrophils with In-111.     

Hydroxyurea increases fetal hemoglobin in cultured erythroid cells derived from normal individuals and patients with sickle cell anemia or beta-thalassemia

Hydroxyurea (HU), an inhibitor of DNA synthesis, has been shown to increase fetal hemoglobin (HbF) levels in patients with sickle cell anemia and in some patients with beta-thalassemia. However, until now there have not been good in vitro model systems that simulate this effect for study of the molecular and cellular mechanism(s) involved in perturbing the normal ontogeny of the globin genes. We analyzed the cellular effects of HU using a two-phase liquid culture procedure (Fibach et al: Blood 73:100, 1989) in which human peripheral blood- derived progenitor cells undergo proliferation and differentiation. HU was found to have multiple effects on these cultured cells: (1) an increase in the proportion of HbF produced; (2) a decrease in cell number due to inhibition of cell proliferation; (3) an increase in hemoglobin content per cell (mean corpuscular hemoglobin [MCH]); and (4) an increase in cell size (mean corpuscular volume). The extent of these effects was related to the HU dose and time of addition. When added to cell cultures from normal individuals, 4 days following their exposure to erythropoietin (EPO), 100 mumol/L HU caused a 1.3- to 3.5- fold increase in the proportion of HbF, from 0.4% to 5.2% (mean 1.6) in untreated to 1.5% to 8.2% (mean 3.1) in HU-treated cultures and a 45% +/- 10% increase in MCH but only a 25% +/- 7% decrease in cell number on day 13. Cultures of cells derived from five patients with sickle cell anemia have shown a twofold to fivefold increase in the percentage of Hb F following addition of HU while four patients with beta- thalassemia showed a 1.3- to 6.2-fold increase. We believe that this primary cell culture procedure should prove useful in studying the cellular and molecular mechanisms of pharmacologic induction of HbF and might provide a valuable predictive assay system for evaluation of the response of individual patients with hemoglobinopathies to HU and similar agents.     

Non-invasive splenic parameters of portal hypertension: Assessment and utility

BACKGROUNDPortal hypertension is a major complication of cirrhosis that is associated with significant morbidity and mortality. The present gold-standard method to risk stratify and observe cirrhosis patients with portal hypertension is hepatic venous pressure gradient measurement or esophagogastroduodenoscopy. However, these methods are invasive, carry a risk of complications and are associated with significant patient discomfort. Therefore, non-invasive splenic parameters are of clinical interest as potential useful markers in determining the presence of portal hypertension. However, diagnostic accuracy and reproducibility remains unvalidated.AIMTo assess the diagnostic accuracy of spleen stiffness, area and diameter in predicting the presence of portal hypertension.METHODSOf 50 patients with varying liver disease pathologies were prospectively recruited from the St. Mary’s Hospital Liver Unit in London; 25 with evidence of portal hypertension and 25 with no evidence of portal hypertension. Liver stiffness, spleen stiffness, spleen diameter and spleen area were measured using the Philips Affiniti 70 elastography point quantification point shear wave elastography system. The aspartate aminotransferase-to-platelet-ratio-index (APRI) score was also calculated. Performance measures, univariate and multivariate logistic regression were used to evaluate demographic, clinical and elastography variables. Interclass correlation coefficient was used to determine the reproducibility of splenic area and diameter.RESULTSOn univariate and individual performance, platelet count [area under the receiver operating characteristic (AUROC) 0.846, P value < 0.001], spleen area (AUROC 0.828, P value = 0.002) and APRI score (AUROC 0.827, P value < 0.001) were the most accurate variables in identifying the presence of portal hypertension. On multivariate logistic regression models constructed, the combination of spleen area greater than 57.90 cm² and platelet count less than 126 × 10⁹ had 63.2% sensitivity and 100% specificity, 100% positive predictive value and 100% negative predictive value. An alternative combination of spleen stiffness greater than 29.99 kPa and platelet count less than 126 × 10⁹ had 88% sensitivity, 75% specificity, 78.6% positive predictive value and 85.7% negative predictive value. An interclass correlation coefficient value of 0.98 (95%CI: 0.94-0.99, P value < 0.001) and 0.96 (95%CI: 0.91-0.99, P value < 0.001) were determined for inter-operator variability for spleen area and diameter respectively.CONCLUSIONSpleen area, spleen stiffness and platelet count may be useful markers to assess the presence of portal hypertension in patients of various etiologies.