Enhancement of the lymphatic system following intravenous administration of ferumoxytol.

BACKGROUND: Lymphatic imaging is becoming increasingly important in the management of patients with congenital heart disease. However, the influence of the intravenous contrast agent ferumoxytol on lymphatic imaging is not well understood. OBJECTIVE: To evaluate the impact of intravenous ferumoxytol on T1-weighted and T2-weighted lymphatic imaging in patients with congenital heart disease. MATERIALS AND METHODS: We included consecutive patients receiving ferumoxytol-enhanced 3D angiography for congenital heart disease evaluation. The visibility of the thoracic duct was reviewed on the T1-weighted 3D inversion recovery balanced-steady-state free precession (SSFP) with respiratory navigator gating sequence which is routinely used for angiography and the heavily T2-weighted turbo spin echo sequence which is employed for lymphatic imaging. Data on demographics and time interval between contrast administration and imaging were collected. Statistical analyses were performed using t-tests for continuous variables and chi-squared tests for categorical variables. RESULTS: One hundred nineteen consecutive patients with a mean age of 12.46 years±7.7 years were included. Of these, 45 cases underwent both T1-weighted and T2-weighted imaging; the other 74 underwent only T1-weighted imaging. Of the 45 patients, 20 had thoracic duct enhancement on T1-weighted imaging; among the 26 sedated, only 2 showed enhancement, while 18 of 19 non-sedated patients showed enhancement (P<0.001), indicating a strong association between sedation and reduced thoracic duct visibility. If T2-weighted imaging was performed after contrast administration, the thoracic duct was not visible on those images. For all 45 cases of visible thoracic duct in the entire cohort, the time from contrast administration to imaging ranged from 8 min up to 75 min. CONCLUSION: The enhancement of the thoracic lymphatic duct on T1-weighted imaging, coupled with degradation observed on T2-weighted imaging, suggests that intravenously administered ferumoxytol rapidly enters the lymphatic fluid. To prevent T2 shortening from degrading the imaging results, T2-weighted imaging for lymphatic evaluation should be performed prior to the administration of ferumoxytol. Sedation and, by inference, fasting may influence this property and warrant further investigation in future studies.

Stability of the parainfluenza virus 5 genome revealed by deep sequencing of strains isolated from different hosts and following passage in cell culture.

UNLABELLED: The strain diversity of a rubulavirus, parainfluenza virus 5 (PIV5), was investigated by comparing 11 newly determined and 6 previously published genome sequences. These sequences represent 15 PIV5 strains, of which 6 were isolated from humans, 1 was from monkeys, 2 were from pigs, and 6 were from dogs. Strain diversity is remarkably low, regardless of host, year of isolation, or geographical origin; a total of 7.8% of nucleotides are variable, and the average pairwise difference between strains is 2.1%. Variation is distributed unevenly across the PIV5 genome, but no convincing evidence of selection for antibody-mediated evasion in hemagglutinin-neuraminidase was found. The finding that some canine and porcine, but not primate, strains are mutated in the SH gene, and do not produce SH, raised the possibility that dogs (or pigs) may not be the natural host of PIV5. The genetic stability of PIV5 was also demonstrated during serial passage of one strain (W3) in Vero cells at a high multiplicity of infection, under conditions of competition with large proportions of defective interfering genomes. A similar observation was made for a strain W3 mutant (PIV5VΔC) lacking V gene function, in which the dominant changes were related to pseudoreversion in this gene. The mutations detected in PIV5VΔC during pseudoreversion, and also those characterizing the SH gene in canine and porcine strains, predominantly involved U-to-C transitions. This suggests an important role for biased hypermutation via an adenosine deaminase, RNA-specific (ADAR)-like activity. IMPORTANCE: Here we report the sequence variation of 16 different isolates of parainfluenza virus 5 (PIV5) that were isolated from a number of species, including humans, monkeys, dogs, and pigs, over 4 decades. Surprisingly, strain diversity was remarkably low, regardless of host, year of isolation, or geographical origin. Variation was distributed unevenly across the PIV5 genome, but no convincing evidence of immune or host selection was found. This overall genome stability of PIV5 was also observed when the virus was grown in the laboratory, and the genome stayed remarkably constant even during the selection of virus mutants. Some of the canine isolates had lost their ability to encode one of the viral proteins, termed SH, suggesting that although PIV5 commonly infects dogs, dogs may not be the natural host for PIV5.

Analysis of the pH requirement for membrane fusion of different isolates of the paramyxovirus parainfluenza virus 5.

Paramyxoviruses enter cells by fusing their envelopes with the plasma membrane, a process that occurs at neutral pH. Recently, it has been found that there is an exception to this dogma in that a porcine isolate of the paramyxovirus parainfluenza virus 5 (PIV5), known as SER, requires a low-pH step for fusion (S. Seth, A. Vincent, and R. W. Compans, J. Virol. 77: 6520-6527, 2003). As a low-pH activation mechanism for fusion would greatly facilitate biophysical studies of paramyxovirus-mediated membrane fusion, we have reexamined the triggering of the PIV5 SER fusion protein. Using multiple assays, we could not find a requirement for low-pH triggering of PIV5 SER fusion. The challenge of discovering how the paramyxovirus receptor binding protein (HN, H, or G) activates the metastable fusion protein to cause membrane fusion at neutral pH remains.