Michael A Gordon

Publications (2)6.55 Total impact

• Article: Nerve stimulator versus ultrasound guidance for placement of popliteal catheters for foot and ankle surgery.

  Daniel Maalouf, Spencer S Liu, Rana Movahedi, Enrique Goytizolo, Stavros G Memstoudis, Jacques T Yadeau, Michael A Gordon, Michael Urban, Yan Ma, Barbara Wukovits, Dorothy Marcello, Shane Reid, Amanda Cook
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  ABSTRACT: To determine whether ultrasound guidance improves the quality of continuous popliteal block when compared with a nerve stimulator after major foot and ankle surgery. Prospective, randomized, double-blinded clinical trial. Operating room, Postanesthesia Care Unit (PACU), and hospital wards of a university-affiliated hospital. 45 ASA physical status 1, 2, and 3 patients undergoing elective major foot and ankle surgery. Placement of a popliteal sciactic nerve catheter using either nerve stimulator or ultrasound guidance. In the PACU, a continuous infusion of ropivacaine 0.2% was started at a basal rate of 4 mL/hr and adjusted in a standardized fashion to maintain visual analog scale (VAS) pain scores < 4. All patients also received intravenous (IV) patient-controlled analgesia with hydromorphone and oral opioids. VAS pain scores at rest and with physical therapy, ropivacaine use, opioid use, and opioid-related side effects were recorded. Cummulative ropivacaine use was lower in patients whose catheter was placed by ultrasound than by nerve stimulator guidance (mean 50 vs 197 mL, P < 0.001). Pain scores at rest and during activity were similar between groups. Cumulative opioid consumption (mean 858 vs 809 mg oral morphine equivalents) and daily frequencies of nausea (5% to 33% vs 0 to 24%) and pruritus (0 to 21% vs 0 to 24%) were similar between groups. Length of hospital stay was similar between groups (3.5 vs 3.7 days). Ultrasound guidance was associated with less local anesthetic consumption than with the nerve stimulator; however, there was little clinical benefit, as all other outcomes were similar between groups.
  Journal of clinical anesthesia 02/2012; 24(1):44-50. · 1.32 Impact Factor
• Article: A systems biology approach identifies SART1 as a novel determinant of both 5-fluorouracil and SN38 drug resistance in colorectal cancer.

  Wendy L Allen, Leanne Stevenson, Vicky M Coyle, Puthen V Jithesh, Irina Proutski, Gail Carson, Michael A Gordon, Heinz-Josef D Lenz, Sandra Van Schaeybroeck, Daniel B Longley, Patrick G Johnston
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  ABSTRACT: Chemotherapy response rates for advanced colorectal cancer remain disappointingly low, primarily because of drug resistance, so there is an urgent need to improve current treatment strategies. To identify novel determinants of resistance to the clinically relevant drugs 5-fluorouracil (5-FU) and SN38 (the active metabolite of irinotecan), transcriptional profiling experiments were carried out on pretreatment metastatic colorectal cancer biopsies and HCT116 parental and chemotherapy-resistant cell line models using a disease-specific DNA microarray. To enrich for potential chemoresistance-determining genes, an unsupervised bioinformatics approach was used, and 50 genes were selected and then functionally assessed using custom-designed short interfering RNA (siRNA) screens. In the primary siRNA screen, silencing of 21 genes sensitized HCT116 cells to either 5-FU or SN38 treatment. Three genes (RAPGEF2, PTRF, and SART1) were selected for further analysis in a panel of 5 colorectal cancer cell lines. Silencing SART1 sensitized all 5 cell lines to 5-FU treatment and 4/5 cell lines to SN38 treatment. However, silencing of RAPGEF2 or PTRF had no significant effect on 5-FU or SN38 sensitivity in the wider cell line panel. Further functional analysis of SART1 showed that its silencing induced apoptosis that was caspase-8 dependent. Furthermore, silencing of SART1 led to a downregulation of the caspase-8 inhibitor, c-FLIP, which we have previously shown is a key determinant of drug resistance in colorectal cancer. This study shows the power of systems biology approaches for identifying novel genes that regulate drug resistance and identifies SART1 as a previously unidentified regulator of c-FLIP and drug-induced activation of caspase-8.
  Molecular Cancer Therapeutics 01/2012; 11(1):119-31. · 5.23 Impact Factor