Publications (38) View all
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Article: The role of microRNAs in hepatocyte nuclear factor-4alpha expression and transactivation.
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ABSTRACT: Hepatocyte nuclear factor (HNF)-4α is a key member of the transcription factor network regulating hepatocyte differentiation and function. Genetic and molecular evidence suggests that expression of HNF-4α is mainly regulated at the transcriptional level. Activation of HNF-4A gene involves the interaction of distinct sets of transcription factors and co-transcription factors within enhancer and promoter regions. Here we study the inhibitory effect of microRNAs (miRNA) on the 3'-untranslated region (3'-UTR) of HNF-4A mRNA. The potential recognition elements of a set of miRNAs were identified utilizing bioinformatics analysis. The family members of miR-34 and miR-449, including miR-34a, miR-34c-5p and miR-449a, share the same target elements located at two distinct locations within the 3'-UTR of HNF-4A. The over-expression of miR-34a, miR-34c-5p or miR-449a in HepG2 cells led to a significant decrease in the activity of luciferase reporter carrying 3'-UTR of HNF-4A. The repressive effect on reporter activity was partially or fully eliminated when one or two of the binding site(s) for miR-34a/miR-34c-5p/miR-449a were deleted within the 3'-UTR. The protein level of HNF-4α was dramatically reduced by over-expression of miR-34a, miR-34c-5p and miR-449a, which correlates with a decrease in the binding activity of HNF-4α and transactivation of HNF-4α target genes. These results suggest that the recognition sites of miR-34a, miR-34c-5p and miR-449a within 3'-UTR of HNF-4A are functional. The mechanism of down-regulation of the binding activity and transactivation of HNF-4α by the miRNAs involves the decrease in HNF-4α protein level via miRNAs selectively targeting HNF-4A 3'-UTR, leading to the translational repression of HNF-4α expression.Biochimica et Biophysica Acta 01/2013; · 4.66 Impact Factor -
Article: Evidence-based guidelines are equivalent to a liberal computed tomography scan protocol for initial patient evaluation but are associated with decreased computed tomography scan use, cost, and radiation exposure.
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ABSTRACT: We hypothesized that trauma patient evaluations using evidence-based treatment guidelines (evidence-based group [EBG]), which include serial examinations and limited computed tomography (CT) scans in an established trauma center, would be associated with equivalent outcomes but with decreased CT scan usage, decreased cost, and less radiation exposure compared with a liberal CT scan approach (conventional group [CONV]). Fifteen evidence-based treatment guidelines were developed using published literature and in collaboration with other institutional departments. These were implemented on July 1, 2010. Prospectively collected data during a 4-month period were compared with a similar period in 2008 when CONV was used. In 2010 (EBG), there were 611 patients compared with 612 in 2008 (CONV). Their average Injury Severity Score was 11.93 versus 8.77 (p < 0.0001), and the total CT scans were 757 and 1194, respectively (p < 0.001). The average APACHE II and hospital length of stay did not significantly vary. No missed or delayed injuries were identified. Estimated CT scan charges were $1,842,534 versus $2,935,024. The average number of scans per patient were 1.2 (EBG) versus 1.9 (CONV). Regarding radiation dosimetry, the estimated average computed tomography dose index (CTDI) per patient were 36.7 versus 53.31 mGy, and the estimated average dose-length product per patient were 889.91 versus 1364.11 mGy·cm. EBG, including serial examinations, provided equivalent diagnostic data to CONV for initial workup but reduced CT scan usage, CT scan charges, and average radiation exposure per patient. This strategy may be beneficial in institutions where serial monitoring can be assiduously provided. Case management study, level IV.The journal of trauma and acute care surgery. 09/2012; 73(3):573-8; discussion 578-9. -
Article: Successful nonoperative management of the most severe blunt liver injuries: a multicenter study of the research consortium of new England centers for trauma.
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ABSTRACT: Grade 4 and grade 5 blunt liver injuries can be safely treated by nonoperative management (NOM). Retrospective case series. Eleven level I and level II trauma centers in New England. Three hundred ninety-three adult patients with grade 4 or grade 5 blunt liver injury who were admitted between January 1, 2000, and January 31, 2010. Failure of NOM (f-NOM), defined as the need for a delayed operation. One hundred thirty-one patients (33.3%) were operated on immediately, typically because of hemodynamic instability. Among 262 patients (66.7%) who were offered a trial of NOM, treatment failed in 23 patients (8.8%) (attributed to the liver in 17, with recurrent liver bleeding in 7 patients and biliary peritonitis in 10 patients). Multivariate analysis identified the following 2 independent predictors of f-NOM: systolic blood pressure on admission of 100 mm Hg or less and the presence of other abdominal organ injury. Failure of NOM was observed in 23% of patients with both independent predictors and in 4% of those with neither of the 2 independent predictors. No patients in the f-NOM group experienced life-threatening events because of f-NOM, and mortality was similar between patients with successful NOM (5.4%) and patients with f-NOM (8.7%) (P = .52). Among patients with successful NOM, liver-specific complications developed in 10.0% and were managed definitively without major sequelae. Nonoperative management was offered safely in two-thirds of grade 4 and grade 5 blunt liver injuries, with a 91.3% success rate. Only 6.5% of patients with NOM required a delayed operation because of liver-specific issues, and none experienced life-threatening complications because of the delay.Archives of surgery (Chicago, Ill.: 1960) 05/2012; 147(5):423-8. · 4.32 Impact Factor -
Article: A massive transfusion protocol incorporating a higher FFP/RBC ratio is associated with decreased use of recombinant activated factor VII in trauma patients.
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ABSTRACT: We implemented a protocol incorporating a higher fresh frozen plasma (FFP)/RBC ratio for the management of trauma patients requiring massive transfusion in 2007. This study aims to identify issues that affected the effective deployment of the massive transfusion protocol (MTP) and compare outcome variables with a historic cohort. Data from 49 trauma patients who received at least 10 units of packed RBCs within 24 hours were analyzed and compared with a historic massively transfused cohort who had received recombinant activated factor VII (rFVIIa). Of the patients, 28 received an FFP/RBC ratio of 1:1 to 1:2; 12 received a lower ratio of 1:2 to 1:4; 3 received more than 1:1 and 6 had less than 1:4. Compared with the historic cohort, the 1:1-1:2 group received significantly fewer blood components and did not require rescue rFVIIa. An MTP incorporating a higher FFP/RBC ratio of 1:1 to 1:2 is associated with decreased use of blood components and may obviate the need for rFVII.American Journal of Clinical Pathology 04/2012; 137(4):566-71. · 2.60 Impact Factor -
Article: Chest X-ray after tracheostomy is not necessary unless clinically indicated.
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ABSTRACT: Chest radiography is routinely used post-tracheostomy to evaluate for complications. Often, the chest X-ray findings do not change clinical management. The present study was conducted to evaluate the utility of post-tracheostomy X-rays. This retrospective review of 255 patients was performed at a single-center, university, level I trauma center. All patients underwent tracheostomy and were evaluated for postprocedure complications. Of the 255 patients, 95.7% had no change in postprocedure chest X-ray findings. New significant chest X-ray findings were found in 4.3% of patients, including subcutaneous emphysema, pneumothorax, and new significant consolidation. Only three of these patients required change in clinical management, and all changes were based on clinical presentation alone. Routine chest X-ray following tracheostomy fails to provide additional information beyond clinical examination. Therefore radiographic examination should be performed only after technically difficult procedures or if the patient experiences clinical deterioration. Significant cost savings and minimization of radiation exposure can be achieved when chest radiography after tracheostomy is performed exclusively for clinical indications.World Journal of Surgery 12/2011; 36(2):266-9. · 2.36 Impact Factor
