ObjectiveTo determine the likelihood that head injured patients on Warfarin with a negative initial head CT will have a positive repeat head CT. A retrospective chart review of our institution’s trauma registry was performed for all patients admitted for blunt head trauma and on Warfarin anti-coagulation from January 2009 to April 2014. Inclusion criteria included patients over 18 years of age with initial GCS ≥ 13, INR greater than 1.5 and negative initial head CT. Initial CT findings, repeat CT findings and INR were recorded. Interventions performed on patients with a delayed bleed were also investigated.Results394 patients met the study inclusion criteria. 121 (31%) of these patients did not receive a second CT while 273 patients (69%) underwent a second CT. The mean INR was 2.74. Six patients developed a delayed bleed, of which two were clinically significant. No patients had any neurosurgical intervention. Our results demonstrate a low rate of delayed bleeding. The utility of repeat head CT in the neurologically stable patient is thus questioned. Patients who have an abnormal baseline neurological status and those with INR >3 may represent a subgroup of patients in whom repeat head CT should be performed.
DNA adenine methyltransferase (Dam) methylates GATC sites and is important for mismatch repair and the expression of pathogenic genes in Escherichia coli (E. coli). The three base pairs flanking each GATC site influence the methylation efficiency of Dam for that site. In vitro and in vivo studies have demonstrated that methylation of GATC sites with A/T rich flanking sequences are less efficiently methylated (“bad” sites) than those with G/C rich flanking sequences (“good” sites). Our goal is to determine how the structure of Dam contributes to this preference for certain GATC sites and what residues are involved. R116 and N126 are conserved Dam residues that lie within close proximity to the GATC flanking sequences. These residues were independently mutated to alanine, forming Dam mutants R116A and N126A. We hypothesize that disruption of the hydrogen bonds between the GATC flanking sequences and the amino acid side chains of R116 or N126 will affect the methylation efficiency of Dam at “good” and “bad” GATC sites. An in vivo analysis of methylation efficiency of the mutants at various GATC sites was performed. Our preliminary results reveal that both mutants show a difference in GATC site preference compared to the wildtype, suggesting the importance of these residues in specificity. Analysis of the mutants will illuminate an alternate route for the control of bacterial DNA methylation that is crucial for pathogenesis.
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