Nodular pattern of bone marrow infiltration: frequent finding in immunosuppression-related EBV-associated large B-cell lymphomas

Different patterns of bone marrow (BM) infiltration by diffuse large B cell lymphomas (DLBCL) have been described. A pure nodular pattern is uncommon, and the pathologic features, as well as the clinical correlates of DLBCL manifesting this pattern in the BM have not been well characterized. We evaluated BM biopsies involved by large B cell lymphomas diagnosed at our institute over an 11-year period to assess the morphology, phenotype, cytogenetic abnormalities, and clinical features of cases associated with a nodular pattern. A distinct nodular pattern of BM involvement was noted in 14 out of 55 (25%) cases. Although both EBV+ and EBV− DLBCL with this pattern were identified, a pure nodular pattern was significantly more common in EBV+ DLBCL compared to EBV− DLBCL (8/9, 89% versus 6/46, 13%; P = 0.00002). The majority of EBV+ DLBCL associated with a nodular pattern had distinctive morphologic features (polymorphic cellular infiltrate and pleomorphic cytology), and CD30 expression was more commonly observed in this group (P = 0.0163). All EBV+ DLBCL and two out of six (33%) EBV− DLBCL had nongerminal center phenotypes. No recurrent cytogenetic abnormalities were detected in either group. Importantly, all EBV+ DLBCL occurred in individuals with immune dysfunction (organ transplant recipients, HIV infection) or in those >50 years of age. Our study indicates a much higher predilection for EBV+ DLBCL to involve the marrow in a nodular pattern compared to EBV− cases and highlights similarities in the morphologic pattern of BM involvement by previously recognized subsets of immunodeficiency-related EBV + lymphomas and the newer entity of “EBV+ DLBCL of the elderly.”     

Hereditary haemorrhagic telangiectasia (Osler–Weber–Rendu syndrome): otorhinolaryngological manifestations

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder affecting blood vessels of the skin, mucous membrane and viscera. The otorhinolaryngologist is the commonest clinician involved in management as epistaxis occurs in 93% of the patients. ¹ As marked advances have recently been made regarding the pathogenesis and management of the condition, the otorhinolaryngological perspective is reviewed.     

Child demographics and DSM diagnosis: A multiaxis study

Using all five axes of the DSM-III, this study explored variations by gender, race age, and socioeconomic status in diagnoses given to children at an outpatient child guidance clinic. Overall, boys, minorities, and low income children were more likely to receive the more serious diagnoses on the DSM-III and to be given the diagnoses that are least likely to go into remission with the passage of time. Alternative explanations for these findings of differences are discussed, and implications for practice and research are identified.Research for this article was supported by a faculty research grant from The George Warren Brown School of Social Work, Washington University in St. Louis.     

Calcium channel agonist/antagonist effects on cholinergic stimulation of the diabetic rat bladder.

The in vitro effects of a calcium channel agonist (BAY K8644) and antagonist (nifedipine) on the cholinergic responses of the streptozotocin-induced diabetic rat bladder were investigated. the bladder body and bladder base were studied separately. There were significant differences in contractile responses to acetylcholine stimulation in the diabetic bladder body compared to the control body. Similarly, the diabetic bladder base demonstrated significantly increased contractile responses compared to the control base. Contractile responses in the diabetic bladder body and base were significantly increased from the control in the absence of extracellular calcium. Differences were found in the effects on maximum responses between diabetic and control tissues treated with nifedipine and BAY K8644. BAY K8644 did not completely reverse the effect of nifedipine on the contractile responses. Rates of contractile response were significantly different between controls and diabetics and between body and base. Alterations in calcium channel activity in diabetic bladder smooth muscle may be responsible at least in part for the nonspecific pharmacologic responses found in smooth muscle strips.     

Effect of covalently bound fatty acids and associated lipids on the viscosity of gastric mucus glycoprotein in cystic fibrosis

The contribution of associated and covalently bound lipids to the viscosity of gastric mucus glycoprotein in healthy and cystic fibrosis (CF) individuals was investigated. While both preparations exhibited similar contents of protein and carbohydrate, the CF glycoprotein contained 1.3 times more associated lipids and 6 times more covalently bound fatty acids. The viscosity of CF mucus glycoprotein was about 1.8 times higher than that of normal glycoprotein. Extraction of associated lipids lead to 3-fold drop in the viscosity of CF glycoprotein and 5-fold drop in the case of normal glycoprotein. Removal of covalently bound fatty acids caused further 1.6-fold reduction in the viscosity of normal mucus glycoprotein and 6-fold in CF glycoprotein. The viscosity of the delipidated and deacylated CF mucus glycoprotein was only about 10% higher than that of the similarly treated normal glycoprotein. The results suggest that the elevated level of covalently bound and associated lipids is responsible for the increased viscosity of CF mucin.     

STAT3 pathway regulates lung-derived brain metastasis initiating cell capacity through miR-21 activation

Brain metastases (BM) represent the most common tumor to affect the adult central nervous system. Despite the increasing incidence of BM, likely due to consistently improving treatment of primary cancers, BM remain severely understudied. In this study, we utilized patient-derived stem cell lines from lung-to-brain metastases to examine the regulatory role of STAT3 in brain metastasis initiating cells (BMICs). Annotation of our previously described BMIC regulatory genes with protein-protein interaction network mapping identified STAT3 as a novel protein interactor. STAT3 knockdown showed a reduction in BMIC self-renewal and migration, and decreased tumor size in vivo. Screening of BMIC lines with a library of STAT3 inhibitors identified one inhibitor to significantly reduce tumor formation. Meta-analysis identified the oncomir microRNA-21 (miR-21) as a target of STAT3 activity. Inhibition of miR-21 displayed similar reductions in BMIC self-renewal and migration as STAT3 knockdown. Knockdown of STAT3 also reduced expression of known downstream targets of miR-21. Our studies have thus identified STAT3 and miR-21 as cooperative regulators of stemness, migration and tumor initiation in lung-derived BM. Therefore, STAT3 represents a potential therapeutic target in the treatment of lung-to-brain metastases.     

Thrombus in Right Ventricular Outflow Tract: Unique Cause of Refractory Cyanotic Spell

Iron deficiency state in patients with cyanotic congenital heart disease can mimic as well as aggravate hyperviscosity symptoms. Correction of iron deficiency in these cases is expected to improve symptoms. We report an unexpected occurrence of refractory cyanotic spell in a child with tetralogy of Fallot due to thrombus in right ventricular outflow tract following intravenous iron sucrose therapy.