A Systematic Molecular Pathology Study of a Laboratory Confirmed H5N1 Human Case

Autopsy studies have shown that human highly pathogenic avian influenza virus (H5N1) can infect multiple human organs other than just the lungs, and that possible causes of organ damage are either viral replication and/or dysregulation of cytokines and chemokines. Uncertainty still exists, partly because of the limited number of cases analysed. In this study, a full autopsy including 5 organ systems was conducted on a confirmed H5N1 human fatal case (male, 42 years old) within 18 hours of death. In addition to the respiratory system (lungs, bronchus and trachea), virus was isolated from cerebral cortex, cerebral medullary substance, cerebellum, brain stem, hippocampus ileum, colon, rectum, ureter, aortopulmonary vessel and lymph-node. Real time RT-PCR evidence showed that matrix and hemagglutinin genes were positive in liver and spleen in addition to positive tissues with virus isolation. Immunohistochemistry and in-situ hybridization stains showed accordant evidence of viral infection with real time RT-PCR except bronchus. Quantitative RT-PCR suggested that a high viral load was associated with increased host responses, though the viral load was significantly different in various organs. Cells of the immunologic system could also be a target for virus infection. Overall, the pathogenesis of HPAI H5N1 virus was associated both with virus replication and with immunopathologic lesions. In addition, immune cells cannot be excluded from playing a role in dissemination of the virus in vivo

Generation of candidate human influenza vaccine strains in cell culture: rehearsing the European response to an H7N1 pandemic threat

Background: Although H5N1 avian influenza viruses pose the most obvious imminent pandemic threat, there have been several recent zoonotic incidents involving transmission of H7 viruses to humans. Vaccines are the primary public health defense against pandemics, but reliance on embryonated chickens eggs to propagate vaccine and logistic problems posed by the use of new technology may slow our ability to respond rapidly in a pandemic situation. Objectives: We sought to generate an H7 candidate vaccine virus suitable for administration to humans whose generation and amplification avoided the use of eggs. Methods: We generated a suitable H7 vaccine virus by reverse genetics. This virus, known as RD3, comprises the internal genes of A/Puerto Rico/8/34 with surface antigens of the highly pathogenic avian strain A/Chicken/Italy/13474/99 (H7N1). The multi-basic amino acid site in the HA gene, associated with high pathogenicity in chickens, was removed. Results: The HA modification did not alter the antigenicity of the virus and the resultant single basic motif was stably retained following several passages in Vero and PER. C6 cells. RD3 was attenuated for growth in embryonated eggs, chickens, and ferrets. RD3 induced an antibody response in infected animals reactive against both the homologous virus and other H7 influenza viruses associated with recent infection by H7 viruses in humans. Conclusions: This is the first report of a candidate H7 vaccine virus for use in humans generated by reverse genetics and propagated entirely in mammalian tissue culture. The vaccine has potential use against a wide range of H7 strains

Radial artery complications occurring after transradial coronary procedures using long hydrophilic-coated introducer sheath: a frequency domain-optical coherence tomography study

This study was performed to analyze the impact of transradial intervention (TRI), performed by long (25-cm) hydrophilic-coated radial introducer sheath (HRS), on radial artery (RA). Both acute damages and chronic intimal modifications, occurring in RA, were assessed using frequency domain-optical coherence tomography (FD-OCT). FD-OCT evaluation of RA was performed in 51 consecutive patients, undergoing TRI by long (25-cm) HRS. FD-OCT was performed from RA ostium to the puncture site. Acute damages such as intimal tears and medial dissections together with chronic intimal modifications, assessed as intimal hyperplasia indexes, were observed and compared between proximal and distal RA segments. Intimal tears were detected in 37\ua0% of patients, especially located in proximal RA segment (p\ua0=\ua00.09). Medial dissections were imaged in 9.8\ua0% of patients with no significant difference between proximal and distal RA segments. Intimal hyperplasia indexes were higher in distal RA segment, with no significant association with a previous history of TRI. In the setting of TRI, performed by long HRS, intimal tears represented the main RA injury occurring in about one-third of patients, while medial dissections only occurred in a small proportion of patients. Distal RA segment was more prone to intimal thickening, although this phenomenon was not associated with repeated transradial procedures