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Manjoo A.,00 Commissioners Road East | Sanders D.,00 Commissioners Road East | Lawendy A.,00 Commissioners Road East | Gladwell M.,00 Commissioners Road East | And 3 more authors.
Journal of Orthopaedic Trauma | Year: 2010

Introduction: Indomethacin may preserve tissue viability in compartment syndrome. The mechanism of improved tissue viability is unclear, but the anti-inflammatory effects may alter the relative contribution of tissue necrosis versus apoptosis to cellular injury. Existing studies have only considered indomethacin administration before induction of elevated intracompartment pressure. The purpose of this study was to determine the effect of timing of indomethacin administration on muscle damage in elevated intracompartment pressure and to assess apoptosis as a cause of tissue demise. Methods: Twenty-four Wistar rats were randomized to elevated intracompartmental pressure (EICP) for either 45 or 90 minutes (30 mmHg). In the 45-minute cohort, indomethacin was withheld in Group 1 (CS45), given before induction of EICP in Group 2 (CS45Indo0), or given after 30 minutes of EICP/15 minutes before fasciotomy in Group 3 (CS45Indo30). In the 90-minute cohort, indomethacin was withheld in Group 4 (CS90) or given after 30 or 60 minutes of EICP in Groups 5 (CS90Indo30) and 6 (CS90Indo60). Intravital microscopy and fluorescent staining assessed capillary perfusion, cell damage, and inflammatory activation within extensor digitorum longus muscle. Apoptosis was assessed using spectrophotometric assessment of caspase levels. Groups 1 to 3 and 4 to 6 were compared using analysis of variance with P < 0.05 deemed significant. Results: Perfusion and tissue viability improved in indomethacin-treated groups. Nonperfused capillaries decreased from Group 1 (CS45) (50.1 ± 2.5) to Group 2 (CS45Indo0) (38.4 ± 1.8) and Group 3 (CS45Indo30) (14.13 ± 1.73) (P < 0.05). Similarly, Group 5 (CS90Indo30) and Group 6 (CS90Indo60) had 25% fewer nonperfused capillaries compared with Group 4 (CS90) (P < 0.0001). Group 2 (CS45Indo0) and Group 3 (CS45Indo30) showed fewer damaged cells (1% ± 0.5% and 8.7% ± 2%) compared with Group 1 (CS45) (20% ± 14%) (P < 0.0001). Group 5 (CS90Indo30) showed decreased cell damage (13% ± 1%) compared with Group 4 (CS90) (18% ± 1%) (P < 0.01). Group 6 (CS90Indo60) also showed decreased cell damage (11% ± 1%) compared with Group 4 (CS90) (18% ± 1%); however, this difference was not significant (P > 0.05). Apoptotic activity was present with elevated intracompartment pressure. At 30 minutes, there were elevated caspase levels in Group 4 and Group 6 EICP groups (0.47 ± 0.08) compared with control subjects (0.19 ± 0.02) (P < 0.003). However, indomethacin-treated groups did not differ from control subjects with regard to caspase levels (P > 0.05). Conclusion: Indomethacin decreased cell damage and improved perfusion in elevated intracompartment pressure. The benefits of indomethacin were partially time-dependent; some improvement in tissue viability occurred regardless of timing of administration. Although apoptosis was common in elevated intracompartment pressure, the protective effect of indomethacin does not appear to be related to apoptosis. Clinical Relevance: Adjuvant treatment with indomethacin may improve outcome in compartment syndrome. © 2010 by Lippincott Williams & Wilkins.

Kernohan K.D.,00 Commissioners Road East | Kernohan K.D.,Childrens Health Research Institute | Jiang Y.,00 Commissioners Road East | Jiang Y.,Childrens Health Research Institute | And 11 more authors.
Developmental Cell | Year: 2010

Human developmental disorders caused by chromatin dysfunction often display overlapping clinical manifestations, such as cognitive deficits, but the underlying molecular links are poorly defined. Here, we show that ATRX, MeCP2, and cohesin, chromatin regulators implicated in ATR-X, RTT, and CdLS syndromes, respectively, interact in the brain and colocalize at the H19 imprinting control region (ICR) with preferential binding on the maternal allele. Importantly, we show that ATRX loss of function alters enrichment of cohesin, CTCF, and histone modifications at the H19 ICR, without affecting DNA methylation on the paternal allele. ATRX also affects cohesin, CTCF, and MeCP2 occupancy within the Gtl2/Dlk1 imprinted domain. Finally, we show that loss of ATRX interferes with the postnatal silencing of the maternal H19 gene along with a larger network of imprinted genes. We propose that ATRX, cohesin, and MeCP2 cooperate to silence a subset of imprinted genes in the postnatal mouse brain. © 2010 Elsevier Inc. All rights reserved.

Bax K.C.,00 Commissioners Road East | Norozi K.,00 Commissioners Road East | Sharma A.P.,00 Commissioners Road East | Filler G.,00 Commissioners Road East
Health Economics Review | Year: 2011

Background: Electronic medical records (EMR) are considered the best solution to improved dissemination of health information for patients. The associated transcription caused a significant cost increase in an academic pediatric center. An educational campaign was implemented to achieve cost-effective transcriptions without compromising the number of EMR transcriptions. Methods: We analyzed the effect of seniority on transcription times over a 4-month period. We also compared the dictation volume before and 4 months after educational interventions. This study was performed in a pediatric academic center with both inpatient and outpatient transcription utilization analyzed. All clinicians providing pediatric care and utilizing the hospital-based transcription over the study time period were analyzed. Interventions included targeted education about efficiencies in transcription, time-based dictation costs, avoidance of lengthy pauses and unnecessary detail, shortening of total transcriptions, superfluous phrases as well as structured templates. Level of training by postgraduate year of training and seniority within faculty were measured for impact on dictation time and effect of education to improve times. Results: Learners in year one had an average dictation time of 7.5 ± 2.2 minutes, which decreased with seniority to an average of 4.1 ± 2.2 minutes for senior faculty (0.0007, ANOVA). After educational initiatives were implemented, there was progressive decline in dictation utilization. The total dictation time decreased from 8,750 minutes per month in August 2009 to 4,296 minutes in December of 2009 (p = 0.0045, unpaired t-test). Conclusion: We identified a substantial need for education in dictation utilization and demonstrated that relatively simple interventions can result in substantial costs savings. © 2011 Bax et al; licensee Springer.

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