Fiberoptic Endoscopic Documentation of the High Incidence of Aspiration following Extubation in Critically Ill Trauma Patients

The purpose of this study was to investigate the incidence of aspiration following extubation in critically ill trauma patients. This prospective pilot study included 20 consecutive trauma patients who required orotracheal intubation for at least 48 hours. All subjects underwent a bedside transnasal fiberoptic endoscopic evaluation of swallowing at 24 ± 2 hr after extubation to determine objectively aspiration status. Aspiration was defined as the entry of a blue dyed material into the airway below the level of the true vocal folds, with silent aspiration occurring in the absence of any external behavioral signs such as coughing or choking. Aspiration was identified in 9 of 20 (45%) subjects and 4 of these 9 (44%) were silent aspirators. Therefore, silent aspiration occurred in 20% of the study population. Eight of the 9 (89%) aspirating subjects resumed an oral diet from 2–10 days (mean, 5 days) following extubation. All subjects had no evidence of pulmonary complications. It was concluded that trauma patients after orotracheal intubation and prolonged mechanical ventilation have an increased risk of aspiration. An objective assessment of dysphagia to identify aspiration may reduce the likelihood of pulmonary complications after extubation.     

A deletion within the murine Werner syndrome helicase induces sensitivity to inhibitors of topoisomerase and loss of cellular proliferative capacity

Werner syndrome (WS) is an autosomal recessive disorder characterized by genomic instability and the premature onset of a number of age-related diseases. The gene responsible for WS encodes a member of the RecQ-like subfamily of DNA helicases. Here we show that its murine homologue maps to murine chromosome 8 in a region syntenic with the human WRN gene. We have deleted a segment of this gene and created Wrn-deficient embryonic stem (ES) cells and WS mice. While displaying reduced embryonic survival, live-born WS mice otherwise appear normal during their first year of life. Nonetheless, although several DNA repair systems are apparently intact in homozygous WS ES cells, such cells display a higher mutation rate and are significantly more sensitive to topoisomerase inhibitors (especially camptothecin) than are wild-type ES cells. Furthermore, mouse embryo fibroblasts derived from homozygous WS embryos show premature loss of proliferative capacity. At the molecular level, wild-type, but not mutant, WS protein copurifies through a series of centrifugation and chromatography steps with a multiprotein DNA replication complex.     

Demonstration of antibodies to human T-cell lymphotropic virus-I tax in patients with the cutaneous T-cell lymphoma, mycosis fungoides, who are seronegative for antibodies to the structural proteins of the virus

Although most patients with the cutaneous T-cell lymphoma, mycosis fungoides (MF), are seronegative for human T-cell lymphotropic virus-I or -II (HTLV-I/II) when tested by assays that measure only antibodies to the viral structural proteins, the majority of such patients harbor HTLV-I-related pol and tax proviral sequences that encode proteins not included in routinely used serologic tests. Tax mRNA has also been detected in their peripheral blood mononuclear cells (PBMC). Therefore, it seemed possible that these patients have antibodies to the tax protein. To investigate this, enzyme-linked immunosorbent assays (ELI- SAs) and Western blot assays were set up, using as antigens the full- length HTLV-I tax cloned from the prototypic HTLV-I-infected cell line, C91PL, and from PBMC of a MF patient, as well as a synthetic peptide made to the carboxy-terminal 20 amino acids of tax-I. Of 60 MF patients whose PBMC were shown to be positive for tax proviral DNA and mRNA, 50 (83%) were shown to have tax antibodies. The antigen derived from the MF patient was most useful in detecting such antibodies. These results demonstrate the need for including other HTLV-related antigens in addition to gag and env in serologic tests used to identify HTLV- infected individuals. The findings underscore the fact that individuals considered seronegative on the basis of currently used tests can be infected with HTLV.     

TRANSLOCATION OF MRNA CODONS, II. PROPERTIES OF AN ANTI-TRANSLOCASE ANTIBODY

A purified preparation of translocase, one of several enzymes required for protein biosynthesis, has been used to prepare a specific anti-translocase antibody. This antibody provides an extremely useful tool not only for detecting the enzyme independent of its activity, but for inhibiting the translocase-mediated reaction and, thus, protein biosynthesis. Though the antibody very rapidly inhibits elongation of the peptide chain, it fails to effect initiation, binding, or peptide bond formation, which strongly suggests that translocase is not a direct participant in these reactions. It also arrests translation of the defined tricodon AUG(U(6)) at the second codon, permitting formation only of the dipeptide, fMet-Phe, rather than the tripeptide, fMetPhe-(Phe)(2), which is formed in the presence of control serum. We have shown previously that the third codon becomes available only in the presence of translocase, thereby defining the site of action of the antibody. The antibody also has been used to demonstrate that translocase is antigenically distinct from the other proteins required for initiation and protein synthesis in E. coli.