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. STUDY DESIGN AND METHODS: Donor demographics, exposure history, and humoral and cell-mediated immunity (CMI) were compared in 15 RIBA-indeterminate subjects, nine chronic HCV carriers, and eight spontaneously recovered subjects. Serum samples were tested for anti-HCV by a quantitative, liquid luciferase immunoprecipitation system (LIPS). CMI was assessed by interferon-γ enzyme-linked immunosorbent spot assay. RESULTS: In the LIPS assay, the sum of antibody responses to six HCV antigens showed significant (p < 0.001) stepwise diminution progressing from chronic carriers to spontaneously recovered to RIBA-indeterminate subjects. CMI responses in RIBA-indeterminate subjects were similar to spontaneously recovered subjects and greater than chronic carriers and controls (p < 0.008). A parenteral risk factor was identified in only 13% of RIBA-indeterminate subjects compared to 89% of chronic carriers and 87% of spontaneously recovered subjects. RIBA-indeterminate donors were older than the other groups. CONCLUSION: The CMI and LIPS results suggest that persistent RIBA-indeterminate reactions represent waning anti-HCV responses in persons who have recovered from a remote HCV infection. In such cases, detectable antibody may ultimately disappear leaving no residual serologic evidence of prior HCV infection, as reported in a minority of long-term HCV-recovered subjects.

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 ß-radiation dosages, indicates that this approach can cause nerve fibrosis while avoiding significant damage to the renal artery.

Atypical teratoid rhabdoid tumor (AT/RT) in adults: review of four cases.

Atypical teratoid/rhabdoid (AT/RT) tumor is a rare, highly malignant tumor of the central nervous system (CNS) most commonly found in children less than 5 years of age. Although the vast majority of cases are diagnosed in young children, there have been isolated case reports in adults. Since its histological appearance can be confused with other tumors, especially in adults, separating AT/RT from other neoplasms may be difficult. In many instances, a reliable diagnosis is not possible without demonstrating the lack of nuclear INI1 protein expression by immunohistochemical methods. The patients (three males and one female) ranged in age from 23 to 42 years (mean age, 32 years). Radiographically, two tumors were localized in the right fronto-parietal region, one was frontal and the other was found in the left temporal lobe. Varying degrees of hydrocephalus and heterogeneous enhancement were present on MRI. In all cases, diagnosis during intraoperative consultation and preliminary diagnosis was different from the final diagnosis after immunohistochemical analysis. Immunohistochemical staining showed that the tumor cells were positive for vimentin and reacted variably for keratin, epithelial membrane antigen (EMA), synaptophysin, neurofilament protein, CD34, and smooth muscle actin (SMA). All were negative for GFAP, S-100, desmin and CD99. Three of the four cases lacked nuclear expression of INI1. One patient is alive with no evidence of disease 17 years after the diagnosis. In adult examples of AT/RT, the diagnosis requires a high index of suspicion, with early tissue diagnosis and a low threshold for investigation with INI1 immunohistochemistry to differentiate this entity from other morphologically similar tumors. Although the prognosis is dismal in pediatric population, long term survival is possible in adult AT/RT cases after surgery and adjuvant radiotherapy and chemotherapy.

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 approximately 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.