Addisalem T. Makuria

Lipoprotein-Associated Phospholipase A2 Protein Expression in the Natural Progression of Human Coronary Atherosclerosis

Objective—Although lipoprotein-associated phospholipase A2 (Lp-PLA2) has received recent attention as a biomarker of inflammation and risk for acute coronary events, its relative expression in coronary plaque phenotypes, including unstable lesions, has not been established. Methods and Results—Coronary segments (n=30) were prospectively collected from 25 sudden coronary death patients for immunolocalization of Lp-PLA2. Lesion morphologies were classified as pathologic intimal thickening, fibroatheromas, thin-cap fibroatheromas (fibrous cap thicknesses <65 &mgr;m), and rupture. The expression of Lp-PLA2 was detected using a specific monoclonal antibody. Apoptosis was identified by DNA end-labeling using terminal deoxynucleotidyl transferase (TdT). Lp-PLA2 staining in early plaques was absent or minimally detected. In contrast, thin-cap fibroatheromas and ruptured plaques showed intense Lp-PLA2 expression within necrotic cores and surrounding macrophages including those in the fibrous cap. The degree of macrophage apoptosis was greater in thin-cap fibroatheroma and ruptures compared with less advanced plaques with additional double labeling studies showing Lp-PLA2 present in apoptotic cells in regions of high macrophage density. Conclusions—Lp-PLA2 is strongly expressed within the necrotic core and surrounding macrophages of vulnerable and ruptured plaques, with relatively weak staining in less advanced lesions. These findings together with the association of Lp-PLA2 in apoptotic macrophages suggest a potential role in promoting plaque instability.

Oligodendroglioma with neurocytic differentiation versus atypical extraventricular neurocytoma: a case report of unusual pathologic findings of a spinal cord tumor

Differentiating oligodendroglioma from extraventricular neurocytoma by conventional light microscopy alone can present a diagnostic challenge. We report pathologic findings of an unusual spinal cord tumor from a 33-year-old male patient which showed hybrid features of oligodendroglioma and extraventricular neurocytoma. Magnetic resonance imaging (MRI) showed an enhancing intramedullary mass in the cervicothoracic region (C7 through T6). Histologic examination revealed a clear cell neoplasm containing ganglion-like cells and calcifications, prompting the differential diagnosis of oligodendroglioma and extraventricular neurocytoma. The immunohistochemical analysis disclosed neural differentiation of the neoplastic cells with strong synaptophysin and neurofilament staining consistent with extraventricular neurocytoma, as well as strong S-100 and glial fibrillary acidic protein (GFAP) expression. Molecular studies with fluorescent in situ hybridization (FISH) revealed chromosome 1p/(partial) 19q deletions, a finding commonly observed in oligodendroglioma. The proliferation index (using antibody MIB1) of the tumor was ∼30%. The morphologic findings and these results strengthen the hypothesis that these tumors may share a common progenitor cell, which has also been observed by others. Because there are differences in patient management and long-term prognosis, it is important to attempt to distinguish between oligodendroglioma and neurocytoma. This unusual case and similar rare reported cases support the need to reclassify tumors showing pathologic features common to both neurocytoma and oligodendroglioma as a unique entity, while the effort continues to identify the cell of origin.

The clinical relevance of persistent recombinant immunoblot assay–indeterminate reactions: insights into the natural history of hepatitis C virus infection and implications for donor counseling

BACKGROUND: Recombinant immunoblot assay (RIBA) is used to determine the specificity of antibody to hepatitis C virus (anti‐HCV). The RIBA result is recorded as positive, negative, or indeterminate. The interpretation and significance of RIBA‐indeterminate reactions are unclear. We addressed the clinical relevance of these reactions in the context of the natural history of HCV infection in a prospectively followed cohort of anti‐HCV–positive blood donors.

Beta radiation for renal nerve denervation: initial feasibility and safety

AIMS In small clinical trials, sympathetic renal denervation using radiofrequency (RF) energy shows promise in treating resistant hypertension. However, the RF procedure is lengthy and is associated with pain during ablation. Vascular brachytherapy, a proven treatment for in-stent restenosis, has the potential to cause nerve fibrosis. The purpose of the present study was to assess the safety and feasibility of renal artery brachytherapy for sympathetic renal denervation. METHODS AND RESULTS A total of 10 normotensive domestic swine underwent vascular brachytherapy to left and right renal arteries using the Beta-Cath 3.5 Fr delivery system at doses of 25 Gy (n=8) and 50 Gy (n=8) at 2 mm from the source centre. These groups were compared to untreated arteries that served as control (n=4). Follow-up obtained at one or two months included angiogram, intravascular ultrasound, and histopathology analysis. The vascular brachytherapy procedure was safe and no apparent angiographic or ultrasound injuries to the vessel were seen. Histology showed a varying degree of thermal injury more pronounced in the 50 Gy group. The majority of examined nerves showed some degree of injury; there was a dose-related effect on nerve injury severity. There were varying degrees of arteriolar changes in the examined sections, with most showing a 2-20% degree of endothelial cell loss. CONCLUSIONS This initial feasibility and safety study of renal nerve denervation, mediated by low and intermediate β-radiation dosages, indicates that this approach can cause nerve fibrosis while avoiding significant damage to the renal artery.

The Clinical Relevance of Persistent RIBA Indeterminate Reactions: Insights into the Natural History of HCV infection and Implications for Donor Counseling

BACKGROUND: Recombinant immunoblot assay (RIBA) is used to determine the specificity of antibody to hepatitis C virus (anti‐HCV). The RIBA result is recorded as positive, negative, or indeterminate. The interpretation and significance of RIBA‐indeterminate reactions are unclear. We addressed the clinical relevance of these reactions in the context of the natural history of HCV infection in a prospectively followed cohort of anti‐HCV–positive blood donors.

The clinical relevance of persistent recombinant immunoblot assay-indeterminate reactions: insights into the natural history of hepatitis C virus infection and implications for donor counseling: RIBA-INDETERMINATE REACTIVITY

BACKGROUND: Recombinant immunoblot assay (RIBA) is used to determine the specificity of antibody to hepatitis C virus (anti‐HCV). The RIBA result is recorded as positive, negative, or indeterminate. The interpretation and significance of RIBA‐indeterminate reactions are unclear. We addressed the clinical relevance of these reactions in the context of the natural history of HCV infection in a prospectively followed cohort of anti‐HCV–positive blood donors.

Spinal Cord Tumor Oligodendroglioma: Diagnosis

Oligodendrogliomas arise throughout the central nervous system (CNS), primarily affecting the cerebral hemispheres of adults, and sometimes disseminating as intraspinal drop metastasis. Primary spinal cord oligodendrogliomas are rare, constituting less than 2% of spinal cord tumors. Clinically, patients present with sensorimotor deficits such as weakness and pain, genitourinary dysfunction or scoliosis, depending on location. Radiographically, the characteristic finding is that of a hypodense, well-demarcated mass lesion, sometimes with calcifications on CT. With MRI the expansile, masses appear hypointense on T1-weighted images and show signal hyperintensity on T2 and FLAIR sequences. The classic microscopic appearance is that of an infiltrating glial neoplasm composed of monotonous clear cells with perinuclear halos embedded in a scaffolding of “chicken wire” vessels. Occasionally, the neoplastic cells possess round, eccentric nuclei with more abundant eosinophilic cytoplasm (gliofibrillary oligodendrocytes and minigemistocytes). Tumors lack the expression of markers of mature oligodendrocytes; although, there may be focal expression of GFAP, especially in gliofibrillary oligodendrocytes and minigemistocytes. In adult oligodendrogliomas, approximately 80% contain characteristic 1p36 and 19q13 co-deletions, due to an unbalanced t(1,19) (q10; p10) translocation, which appears to correlate with chemosensitivity. Rarely, spinal cord oligodendrogliomas present as primary leptomeningeal oligodendrogliomas (PLO)/primary leptomeningeal gliomatosis (PLG) or “holocord” oligodendrogliomas. The age group, clinical features and MRI findings of these patients are different than the localized spinal cord parenchymal oligodendrogliomas. Accordingly, a high index of suspicion is required for the timely diagnosis of these tumors. Distinction from other spinal cord tumors is crucial due to differences in patient management and long-term prognosis.