S M Opal

Summary

Affiliation: Brown University
Country: USA

Publications

  1. ncbi Sepsis: time to reconsider the concept
    Jean Carlet
    Intensive Care Unit, Infectious Diseases Department, Groupe Hospitalier Paris Saint Joseph, Paris, France
    Crit Care Med 36:964-6. 2008
  2. ncbi Effect of eritoran, an antagonist of MD2-TLR4, on mortality in patients with severe sepsis: the ACCESS randomized trial
    Steven M Opal
    Alpert Medical School of Brown University, Providence, Rhode Island, USA
    JAMA 309:1154-62. 2013
  3. ncbi Clinical review: the role of biomarkers in the diagnosis and management of community-acquired pneumonia
    Mirjam Christ-Crain
    Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital Basel, Petersgraben 4, CH 4031 Basel, Switzerland
    Crit Care 14:203. 2010
  4. ncbi Inhibition of the RAGE products increases survival in experimental models of severe sepsis and systemic infection
    Emily C Lutterloh
    Division of Infectious Diseases, Memorial Hospital of Rhode Island, 111 Brewster St, Pawtucket, RI 02860, USA
    Crit Care 11:R122. 2007
  5. ncbi A clinical evaluation committee assessment of recombinant human tissue factor pathway inhibitor (tifacogin) in patients with severe community-acquired pneumonia
    Pierre Francois Laterre
    St Luc University Hospital, Universite Catholique de Louvain, Avenue Hippocrate 10, 1200 Brussels, Belgium
    Crit Care 13:R36. 2009
  6. ncbi Bench-to-bedside review: Quorum sensing and the role of cell-to-cell communication during invasive bacterial infection
    Shadaba Asad
    Infectious Disease Division, Warren Alpert Medical School of Brown University, Memorial Hospital of Rhode Island, 111 Brewster Street, Pawtucket, RI 02860, USA
    Crit Care 12:236. 2008
  7. ncbi Coagulation abnormalities in critically ill patients
    Marcel Levi
    Department of Vascular Medicine and Internal Medicine, Academic Medical Centre, University of Amsterdam, The Netherlands
    Crit Care 10:222. 2006
  8. ncbi Severe sepsis and septic shock: defining the clinical problem
    Steven M Opal
    Infectious Disease Division, Brown Medical School, Providence, Rhode Island, USA
    Scand J Infect Dis 35:529-34. 2003
  9. ncbi Clinical trial design and outcomes in patients with severe sepsis
    Steven M Opal
    Medicine Infectious Disease Division, Brown University School of Medicine, Pawtucket, Rhode Island 02860, USA
    Shock 20:295-302. 2003
  10. ncbi Systemic host responses in severe sepsis analyzed by causative microorganism and treatment effects of drotrecogin alfa (activated)
    Steven M Opal
    Brown University School of Medicine, Providence, RI, USA
    Clin Infect Dis 37:50-8. 2003

Research Grants

  1. Role of Inter-alpha Inhibitors in Anthrax Intoxication
    Steven Opal; Fiscal Year: 2007

Collaborators

Detail Information

Publications86

  1. ncbi Sepsis: time to reconsider the concept
    Jean Carlet
    Intensive Care Unit, Infectious Diseases Department, Groupe Hospitalier Paris Saint Joseph, Paris, France
    Crit Care Med 36:964-6. 2008
    ..To discuss the difficulty in using the concept of sepsis for clinical trials and propose new ways for designing future trials for severe infections...
  2. ncbi Effect of eritoran, an antagonist of MD2-TLR4, on mortality in patients with severe sepsis: the ACCESS randomized trial
    Steven M Opal
    Alpert Medical School of Brown University, Providence, Rhode Island, USA
    JAMA 309:1154-62. 2013
    ..LPS is a major component of the outer membrane of gram-negative bacteria and is a potent activator of the acute inflammatory response...
  3. ncbi Clinical review: the role of biomarkers in the diagnosis and management of community-acquired pneumonia
    Mirjam Christ-Crain
    Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital Basel, Petersgraben 4, CH 4031 Basel, Switzerland
    Crit Care 14:203. 2010
    ..None should be used on its own; and none is anything more than an aid in the exercise of clinical judgment based upon a synthesis of available clinical, physiologic and laboratory features in each patient...
  4. ncbi Inhibition of the RAGE products increases survival in experimental models of severe sepsis and systemic infection
    Emily C Lutterloh
    Division of Infectious Diseases, Memorial Hospital of Rhode Island, 111 Brewster St, Pawtucket, RI 02860, USA
    Crit Care 11:R122. 2007
    ..The receptor for advanced glycation end products (RAGE), a multi-ligand member of the immunoglobulin superfamily, contributes to acute and chronic disease processes, including sepsis...
  5. ncbi A clinical evaluation committee assessment of recombinant human tissue factor pathway inhibitor (tifacogin) in patients with severe community-acquired pneumonia
    Pierre Francois Laterre
    St Luc University Hospital, Universite Catholique de Louvain, Avenue Hippocrate 10, 1200 Brussels, Belgium
    Crit Care 13:R36. 2009
    ....
  6. ncbi Bench-to-bedside review: Quorum sensing and the role of cell-to-cell communication during invasive bacterial infection
    Shadaba Asad
    Infectious Disease Division, Warren Alpert Medical School of Brown University, Memorial Hospital of Rhode Island, 111 Brewster Street, Pawtucket, RI 02860, USA
    Crit Care 12:236. 2008
    ..These rather sophisticated, microbial communication systems may prove to be a liability to pathogens as they make convenient targets for therapeutic intervention in our continuing struggle to control microbial pathogens...
  7. ncbi Coagulation abnormalities in critically ill patients
    Marcel Levi
    Department of Vascular Medicine and Internal Medicine, Academic Medical Centre, University of Amsterdam, The Netherlands
    Crit Care 10:222. 2006
    ....
  8. ncbi Severe sepsis and septic shock: defining the clinical problem
    Steven M Opal
    Infectious Disease Division, Brown Medical School, Providence, Rhode Island, USA
    Scand J Infect Dis 35:529-34. 2003
    ..Further refinements in the definitions and predisposing factors of severe sepsis should improve the understanding and management of severe sepsis and septic shock in the near future...
  9. ncbi Clinical trial design and outcomes in patients with severe sepsis
    Steven M Opal
    Medicine Infectious Disease Division, Brown University School of Medicine, Pawtucket, Rhode Island 02860, USA
    Shock 20:295-302. 2003
    ....
  10. ncbi Systemic host responses in severe sepsis analyzed by causative microorganism and treatment effects of drotrecogin alfa (activated)
    Steven M Opal
    Brown University School of Medicine, Providence, RI, USA
    Clin Infect Dis 37:50-8. 2003
    ..Results demonstrate that DrotAA, administered as an adjunct to standard anti-infective therapy, can improve the rate of survival for patients who develop severe sepsis regardless of causative microorganism...
  11. ncbi The clinical relevance of endotoxin in human sepsis: a critical analysis
    Steven M Opal
    Infectious Disease Division, Brown Medical School, Memorial Hospital of Rhode Island, Pawtucket 02860, USA
    J Endotoxin Res 8:473-6. 2002
    ..Several clinical studies have associated high levels of LPS with an excess risk of morbidity and mortality in sepsis that is largely independent of the nature of the micro-organism responsible for the septic episode...
  12. ncbi Coming soon to an ICU near you: severe pandemic influenza in ICU patients in Spain
    Steven M Opal
    Infectious Disease Division, Warren Alpert Medical School of Brown University, Memorial Hospital of Rhode Island, 111 Brewster Street, Pawtucket, RI 02860, USA
    Crit Care 13:196. 2009
    ..This initial report of ventilatory needs for patients with severe influenza pneumonia in Spanish intensive care units provides a useful guide of what to expect and how to respond to the challenge of pandemic influenza...
  13. ncbi The evolution of the understanding of sepsis, infection, and the host response: a brief history
    Steven M Opal
    The Warren Alpert School of Medicine of Brown University, Biomed Center, Providence, RI 02912, USA
    Crit Care Clin 25:637-63, vii. 2009
    ..This article focuses on the evolution of understanding about the fundamental nature of infection and the host response that leads to sepsis...
  14. ncbi Translational research in the development of novel sepsis therapeutics: logical deductive reasoning or mission impossible?
    Steven M Opal
    Infectious Disease Division SMO, Memorial Hospital of Rhode Island, Pawtucket, RI, USA
    Crit Care Med 37:S10-5. 2009
    ..It is abundantly clear that sepsis researchers need to do a better job informing clinicians about the possible benefits and potential risks of new treatment interventions as they traverse the gap between the bench and the bedside...
  15. ncbi Active immunization with a detoxified endotoxin vaccine protects against lethal polymicrobial sepsis: its use with CpG adjuvant and potential mechanisms
    Steven M Opal
    Infectious Disease Division, Brown Medical School, Providence, RI 02860, USA
    J Infect Dis 192:2074-80. 2005
    ....
  16. ncbi Interactions between coagulation and inflammation
    Steven M Opal
    Infectious Disease Division, Brown Medical School, Providence, Rhode Island, USA
    Scand J Infect Dis 35:545-54. 2003
    ..Optimal use of this and other anticoagulant agents in sepsis will necessitate further basic research into the critical linkage between coagulation and innate immunity...
  17. ncbi The nexus between systemic inflammation and disordered coagulation in sepsis
    Steven M Opal
    Infectious Disease Division, Brown Medical School, Providence, Rhode Island, USA
    J Endotoxin Res 10:125-9. 2004
    ..Further advances in the management of severe infections may accrue with a better understanding of the integral link between coagulation and innate immunity...
  18. ncbi The immunopathogenesis of sepsis in elderly patients
    Steven M Opal
    Infectious Disease Division, Brown University School of Medicine, Providence, Rhode Island, USA
    Clin Infect Dis 41:S504-12. 2005
    ..This immune dysregulation is accompanied by a more pronounced procoagulant state in older patients. These molecular events function in concert to render elderly patients at excess risk for mortality from severe sepsis and septic shock...
  19. ncbi Inter-alpha-inhibitor proteins are endogenous furin inhibitors and provide protection against experimental anthrax intoxication
    Steven M Opal
    Center for Biodefense and Emerging Pathogens, Memorial Hospital of RI, 111 Brewster Street, Pawtucket, RI 02860, USA
    Infect Immun 73:5101-5. 2005
    ..001). We conclude that human IalphaIp may be an effective preventative or therapeutic agent against anthrax intoxication...
  20. ncbi The use of immunocompromised animals as models for human septic shock
    Steven M Opal
    Infectious Disease Division, Brown Medical School, Providence, RI 02860, USA
    Shock 24:64-70. 2005
    ..Greater emphasis should be placed on preclinical models of immunocompromised animals in the future to assess the potential clinical utility of novel drugs for human septic shock...
  21. ncbi The activity of pathway-selective estrogen receptor ligands in experimental septic shock
    Steven M Opal
    Memorial Hospital of Rhode Island, Brown Medical School, Providence, Rhode Island 02860, USA
    Shock 24:535-40. 2005
    ..These agents may prove to be useful clinically as a novel treatment strategy for severe sepsis...
  22. ncbi Can we RESOLVE the treatment of sepsis?
    Steven M Opal
    Department of Medicine, Brown Medical School, Memorial Hospital of Rhode Island, Pawtucket, RI 02860, USA
    Lancet 369:803-4. 2007
  23. ncbi The host response to endotoxin, antilipopolysaccharide strategies, and the management of severe sepsis
    Steven M Opal
    Infectious Disease Division, Brown Medical School, Memorial Hospital of RI, 111 Brewster Street, Pawtucket, RI 02860, USA
    Int J Med Microbiol 297:365-77. 2007
    ..This information should provide the necessary insights to specifically target anti-LPS interventions in the ongoing effort to improve the management of sepsis...
  24. ncbi Endotoxin and cytokine detection systems as biomarkers for sepsis-induced renal injury
    Steven M Opal
    Infectious Disease Division, Brown Medical School, Providence, and Memorial Hospital of Rhode Island, Pawtucket RI 02860, USA
    Contrib Nephrol 156:220-6. 2007
    ..A reliable biomarker as an indicator of the presence of severe sepsis is an unmet medical need...
  25. ncbi Communal living by bacteria and the pathogenesis of urinary tract infections
    Steven M Opal
    Warren Alpert Medical School of Brown University, Infectious Disease Division, Memorial Hospital of Rhode Island, Pawtucket, Rhode Island, United States of America
    PLoS Med 4:e349. 2007
  26. ncbi Effect of anti-CD14 monoclonal antibody on clearance of Escherichia coli bacteremia and endotoxemia
    Steven M Opal
    Brown University School of Medicine, Infectious Disease Division, Pawtucket, RI, USA
    Crit Care Med 31:929-32. 2003
    ..To determine the effects of an anti-CD14 monoclonal antibody on the clearance of a bacteremic Escherichia coli challenge in the presence or absence of antimicrobial agents...
  27. ncbi Bench-to-bedside review: functional relationships between coagulation and the innate immune response and their respective roles in the pathogenesis of sepsis
    Steven M Opal
    Infectious Disease Division, Brown University School of Medicine, Providence, Rhode Island, USA
    Crit Care 7:23-38. 2003
    ..The mechanisms by which these highly complex and coregulated defense strategies are linked together are the focus of the present review...
  28. ncbi Recombinant human interleukin-11 has anti-inflammatory actions yet does not exacerbate systemic Listeria infection
    S M Opal
    Division of Infectious Diseases, Brown University School of Medicine, Memorial Hospital of Rhode Island, Pawtucket, RI 02860, USA
    J Infect Dis 181:754-6. 2000
    ..The results indicate that IL-11 down-regulates cytokine production but does not exacerbate systemic infection in the murine Listeria infection model...
  29. ncbi Anti-inflammatory cytokines
    S M Opal
    Infectious Disease Division, Brown University School of Medicine, Providence, RI, USA
    Chest 117:1162-72. 2000
    ..The nature of anti-inflammatory cytokines and soluble cytokine receptors is the focus of this review. The current and future therapeutic uses of these anti-inflammatory cytokines are also reviewed...
  30. ncbi Therapeutic rationale for antithrombin III in sepsis
    S M Opal
    Brown University School of Medicine, Infectious Disease Division, Memorial Hospital of Rhode Island, Providence 02860, USA
    Crit Care Med 28:S34-7. 2000
    ..To review the preclinical evidence that provides the therapeutic rationale for antithrombin as a novel treatment for human sepsis...
  31. ncbi Phylogenetic and functional relationships between coagulation and the innate immune response
    S M Opal
    Brown University School of Medicine, Providence, RI 02860, USA
    Crit Care Med 28:S77-80. 2000
    ..The complex and highly integrated linkage between systemic inflammation and coagulation are reviewed in this article...
  32. ncbi Clinical gram-positive sepsis: does it fundamentally differ from gram-negative bacterial sepsis?
    S M Opal
    Brown University School of Medicine, Povidence, RI, USA
    Crit Care Med 27:1608-16. 1999
    ..To review the basic differences between gram-positive and gram-negative sepsis and to assess the effect of these differences on current and future therapeutic strategies for sepsis...
  33. ncbi Lipopolyamines as a therapeutic strategy in experimental Gram-negative bacterial sepsis
    S M Opal
    Brown University School of Medicine, Infectious Disease Division, Memorial Hospital of Rhode Island, Pawtucket, RI, USA
    J Endotoxin Res 7:35-8. 2001
    ..05) but had no significant effect on bacteremia and bacterial concentrations of P. aeruginosa in liver or spleen tissue. Lipopolyamines may be potentially valuable as a therapeutic adjunct in treatment of Gram-negative bacterial sepsis...
  34. ncbi Antiendotoxin strategies for the prevention and treatment of septic shock. New approaches and future directions
    S M Opal
    Infectious Disease Division, Brown University School of Medicine, Providence, Rhode Island, USA
    Drugs 55:497-508. 1998
    ..It will require focused efforts by basic scientists, continued support by industry and enlightened study designs by clinical investigators to successfully develop antiendotoxin in therapies for use in septic patients in the future...
  35. ncbi Clinical impact of novel anticoagulation strategies in sepsis
    S M Opal
    Brown University School of Medicine, and Director, Infectious Disease Division, Memorial Hospital of Rhode Island, Pawtucket 02860, Rhode Island, USA
    Curr Opin Crit Care 7:347-53. 2001
    ..Anticoagulants such as recombinant human activated protein C and related agents may become the mainstay of adjuvant therapies for severe sepsis in the near future...
  36. ncbi Year in review 2008: Critical Care--sepsis
    Steven M Opal
    Department of Medicine, Infectious Disease Division, Memorial Hospital of RI, The Warren Alpert Medical School of Brown University, 111 Brewster Street, Pawtucket, RI 02860, USA
    Crit Care 13:224. 2009
    ....
  37. ncbi Immunologic alterations and the pathogenesis of organ failure in the ICU
    Steven M Opal
    Department of Medicine, The Alpert Medical School of Brown University, Providence, Rhode Island, USA
    Semin Respir Crit Care Med 32:569-80. 2011
    ..This brief review summarizes the current understanding of the fundamental immune alterations in critical illness that lead to organ failure in critical illness...
  38. ncbi Orally administered recombinant human interleukin-11 is protective in experimental neutropenic sepsis
    Steven M Opal
    Infectious Disease Division and Department of Pathology, Memorial Hospital of Rhode Island and Brown University School of Medicine, Providence 02860, USA
    J Infect Dis 187:70-6. 2003
    ..These results indicate that orally administered IL-11 may preserve epithelial cell integrity in the presence of cytoreductive chemotherapy. This may represent a new treatment strategy for the prevention of infection in neutropenic hosts...
  39. ncbi Endotoxins and other sepsis triggers
    Steven M Opal
    Infectious Disease Division, Memorial Hospital of Rhode Island, Pawtucket, RI 02860, USA
    Contrib Nephrol 167:14-24. 2010
    ..This information is providing novel interventions in the continuing effots to improve the care of septic patients...
  40. ncbi Inter-α inhibitor proteins: a novel therapeutic strategy for experimental anthrax infection
    Steven M Opal
    Infectious Disease Research Laboratory, Memorial Hospital of Rhode Island, Pawtucket, RI 02860, USA
    Shock 35:42-4. 2011
    ..Inter-α inhibitor proteins could represent a novel adjuvant therapy for the treatment of established anthrax infection...
  41. ncbi The evolution of the understanding of sepsis, infection, and the host response: a brief history
    Steven M Opal
    The Warren Alpert School of Medicine of Brown University, Biomed Center, Providence, RI 02912, USA
    Crit Care Nurs Clin North Am 23:1-27. 2011
    ..Much work remains before the benefits of these discoveries can be thoughtfully applied to the management of severe sepsis and septic shock worldwide...
  42. ncbi Relationship between plasma levels of lipopolysaccharide (LPS) and LPS-binding protein in patients with severe sepsis and septic shock
    S M Opal
    Infectious Disease Division, Brown University School of Medicine and Memorial Hospital of Rhode Island, Providence, Rhode Island 02860, USA
    J Infect Dis 180:1584-9. 1999
    ..05) in nonsurvivors than survivors over the 28-day study period. No correlation was found between endotoxin and LBP levels. The quantitative level of both endotoxin and LBP may have prognostic significance in patients with severe sepsis...
  43. ncbi Antithrombin, heparin, and heparan sulfate
    Steven M Opal
    Infectious Disease Division, Brown Medical School, Providence, RI 02860, USA
    Crit Care Med 30:S325-31. 2002
    ..The interaction between antithrombin and specific polysulfated, acidic oligosaccharide moieties found on heparin and related proteoglycan molecules within the circulation and on endothelial surfaces will also be examined...
  44. ncbi Bench-to-bedside review: Toll-like receptors and their role in septic shock
    Steven M Opal
    Professor of Medicine, Infectious Disease Division, Brown University Medical School, Providence, Rhode Island, USA
    Crit Care 6:125-36. 2002
    ..The potential clinical implications of therapeutic modulation of these recently characterized receptors of innate immunity are also discussed...
  45. ncbi The activity of tissue factor pathway inhibitor in experimental models of superantigen-induced shock and polymicrobial intra-abdominal sepsis
    S M Opal
    Brown University School of Medicine, Providence, RI, USA
    Crit Care Med 29:13-7. 2001
    ..To study recombinant human tissue factor pathway inhibitor (rhTFPI) in a superantigen-induced shock model and in a cecal ligation and puncture (CLP) model of peritonitis in mice...
  46. ncbi Recombinant human interleukin-11 in experimental Pseudomonas aeruginosa sepsis in immunocompromised animals
    S M Opal
    Division of Infectious Diseases, University School of Medicine, Providence, Rhode Island, USA
    J Infect Dis 178:1205-8. 1998
    ..05). These results indicate that rhIL-11 supports mucous membrane integrity of the alimentary tract and decreases the systemic inflammatory response to experimental gram-negative infection in immunocompromised animals...
  47. ncbi Active immunization with a detoxified Escherichia coli J5 lipopolysaccharide group B meningococcal outer membrane protein complex vaccine protects animals from experimental sepsis
    A S Cross
    Division of Infectious Diseases, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA
    J Infect Dis 183:1079-86. 2001
    ..Active immunization with this vaccine merits further investigation...
  48. ncbi Evaluation of the safety of recombinant P-selectin glycoprotein ligand-immunoglobulin G fusion protein in experimental models of localized and systemic infection
    S M Opal
    Infectious Disease Division, Brown University School of Medicine, Providence, Rhode Island, USA
    Shock 15:285-90. 2001
    ..The results indicate that rPSGL-Ig did not exacerbate infection in these experimental sepsis models...
  49. ncbi Detoxified endotoxin vaccine (J5dLPS/OMP) protects mice against lethal respiratory challenge with Francisella tularensis SchuS4
    Stephen H Gregory
    Department of Medicine, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, 55 Claverick Street, Providence, RI 02903, USA
    Vaccine 28:2908-15. 2010
    ..tularensis. The efficacy of J5dLPS/OMP vaccine suggests its potential utility in immunizing the general population against several different gram-negative select agents concurrently...
  50. ncbi Phase I study of detoxified Escherichia coli J5 lipopolysaccharide (J5dLPS)/group B meningococcal outer membrane protein (OMP) complex vaccine in human subjects
    Alan S Cross
    Department of Medicine, Center for Vaccine Development, University of Maryland School of Medicine, 685 W Baltimore Street, HSF 480, Baltimore, MD 21201, USA
    Vaccine 21:4576-87. 2003
    ..We conclude that this J5dLPS/OMP vaccine was safe and well-tolerated with transient, local pain at the injection site. Vaccine formulations with different adjuvants are currently under investigation...
  51. ncbi WAY-202196, a selective estrogen receptor-beta agonist, protects against death in experimental septic shock
    Patricia A Cristofaro
    Infectious Disease Division, Memorial Hospital of Rhode Island, Brown Medical School, Providence, RI, USA
    Crit Care Med 34:2188-93. 2006
    ..To determine the effect of an estrogen receptor-beta selective agent in experimental models of systemic infection and sepsis...
  52. ncbi Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial
    B L Warren
    Brown University School of Medicine, Infectious Disease Division, Memorial Hospital of Rhode Island, 111 Brewster St, Pawtucket, RI 02860, USA
    JAMA 286:1869-78. 2001
    ..There was some evidence to suggest a treatment benefit of antithrombin III in the subgroup of patients not receiving concomitant heparin...
  53. ncbi Sepsis strategies in development
    Steven P Larosa
    Warren Alpert School of Medicine, Brown University, Providence, RI, USA
    Clin Chest Med 29:735-47, x-xi. 2008
    ..Molecules with pluripotent activity, such as interalpha inhibitor proteins and estrogen-receptor ligands, are also being investigated...
  54. ncbi Decreased protein C, protein S, and antithrombin levels are predictive of poor outcome in Gram-negative sepsis caused by Burkholderia pseudomallei
    Steven P Larosa
    Division of Infectious Disease, Rhode Island Hospital, Gerry House 113, 593 Eddy Street, and Infectious Diseases and Microbiologic Divisions of Brown University School of Medicine, Providence, Rhode Island 02903, USA
    Int J Infect Dis 10:25-31. 2006
    ..Excessive release of these cytokines may lead to endothelial injury, depletion of naturally occurring endothelial modulators, microvascular thrombosis, organ failure, and death...
  55. ncbi Efficacy of antilipopolysaccharide and anti-tumor necrosis factor monoclonal antibodies in a neutropenic rat model of Pseudomonas sepsis
    S M Opal
    Infectious Disease Division, Memorial Hospital of Rhode Island, Providence
    J Clin Invest 88:885-90. 1991
    ..This immunotherapeutic approach may be of potential utility in the management of serious, gram-negative bacterial infection in neutropenic patients...
  56. ncbi Failure of ciprofloxacin to eradicate convalescent fecal excretion after acute salmonellosis: experience during an outbreak in health care workers
    M A Neill
    Brown University Program in Medicine, Providence, Rhode Island
    Ann Intern Med 114:195-9. 1991
    ..To determine the efficacy of ciprofloxacin therapy in eradicating convalescent fecal excretion of salmonellae after acute salmonellosis...
  57. ncbi Bioterrorism and physicians
    Andrew W Artenstein
    Infectious Disease Division, Memorial Hospital of R.I, 11 Brewster St, Pawtucket, RI 02860, USA
    Med Health R I 85:74-6. 2002
  58. ncbi Correlation between mortality and the levels of inter-alpha inhibitors in the plasma of patients with severe sepsis
    Yow Pin Lim
    Brown Medical School, Division of Medical Oncology Department of Medicine, Rhode Island Hospital, Providence, Rhode Island, USA
    J Infect Dis 188:919-26. 2003
    ..Thus, human IalphaIp may be a useful predictive marker and potential therapeutic agent in sepsis...
  59. ncbi 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference
    Mitchell M Levy
    Rhode Island Hospital, 593 Eddy Street, MICU Main 7, Providence RI 02903, USA
    Intensive Care Med 29:530-8. 2003
    ..Nevertheless, there has been an impetus from experts in the field to modify these definitions to reflect our current understanding of the pathophysiology of these syndromes...
  60. ncbi Tissue factor pathway inhibitor and antithrombin trial results
    Steven P Larosa
    Infectious Disease Division, Rhode Island Hospital, Gerry House 113, 593 Eddy Street, Providence, RI 02903, USA
    Crit Care Clin 21:433-48. 2005
    ..Drug-drug interactions and dosing issues were observed in both trials. The similarities and differences of each anticoagulant and the lessons learned from the recent phase III clinical trials are examined in this review...
  61. ncbi Chloroquine enhances survival in Bacillus anthracis intoxication
    Andrew W Artenstein
    Center for Biodefense and Emerging Pathogens, Division of Infectious Diseases, Memorial Hospital of Rhode Island, Pawtucket 02860, USA
    J Infect Dis 190:1655-60. 2004
    ..CQ significantly enhanced survival and may augment current treatment and prophylaxis options for this otherwise lethal infection...
  62. ncbi New perspectives on immunomodulatory therapy for bacteraemia and sepsis
    Steven M Opal
    The Alpert Medical School of Brown University, Providence, RI, USA steven
    Int J Antimicrob Agents 36:S70-3. 2010
    ..The intelligent use of immunomodulatory agents in sepsis will necessitate a personalised medicine approach to treat each patient at the appropriate time and with the optimal therapy...
  63. ncbi Role of Toll-like receptors in infection and immunity: clinical implications
    Patricia Cristofaro
    Infectious Disease Division, Brown Medical School, Providence, Rhode Island, USA
    Drugs 66:15-29. 2006
    ..Their role as potential targets for therapeutic intervention is just beginning to be appreciated, and the current status of these treatment strategies is reviewed in this article...
  64. ncbi The Toll-like receptors and their role in septic shock
    Patricia Cristofaro
    Infectious Disease Division, Memorial Hospital of Rhode Island, 111 Brewster Street, Pawtucket, RI 02860, USA
    Expert Opin Ther Targets 7:603-12. 2003
    ..This review covers the events responsible for TLR activation in detail, with an emphasis on possible points of pharmacological intervention...
  65. ncbi 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference
    Mitchell M Levy
    Rhode Island Hospital, Brown University School of Medicine, 593 Eddy Street, Providence, RI 02903, USA
    Crit Care Med 31:1250-6. 2003
    ..This lack of evidence serves to underscore the challenge still present in diagnosing sepsis in 2003 for clinicians and researchers and also provides the basis for introducing PIRO as a hypothesis-generating model for future research...
  66. ncbi Unintended bias, clinical trial results, and the heparin post hoc crossover fallacy
    Steven M Opal
    ID Division, Brown Medical School, Memorial Hospital of Rhode Island, Pawtucket, RI, USA
    Crit Care Med 32:874-5. 2004
    ..This will obviate the unavoidable selection bias and allocation bias intrinsic to postrandomization events in clinical trials with a high early mortality rate such as severe sepsis and septic shock...
  67. ncbi Endotoxin as a drug target
    Steven M Opal
    Infectious Disease Division, Brown Medical School, Providence, RI, USA
    Crit Care Med 31:S57-64. 2003
    ..Ongoing clinical trials with specific endotoxin inhibitors should determine the potential value of this therapeutic approach to the management of septic shock...
  68. ncbi Longitudinal studies of inter-alpha inhibitor proteins in severely septic patients: a potential clinical marker and mediator of severe sepsis
    Steven M Opal
    Infectious Disease Division, Brown Medical School, ProThera Biologics, LLC, East Providence, RI, USA
    Crit Care Med 35:387-92. 2007
    ..To determine the clinical relevance and prognostic significance of serial measurement of inter-alpha inhibitor proteins (IalphaIp) in severely septic patients...
  69. ncbi History of U.S. military contributions to the study of vaccines against infectious diseases
    Andrew W Artenstein
    Center for Biodefense and Emerging Pathogens, Memorial Hospital of Rhode Island, Pawtucket, RI 02860, USA
    Mil Med 170:3-11. 2005
    ..Through the efforts of military researchers, numerous serious threats to the health of American troops and their families have been mitigated...
  70. ncbi Estrogen receptor beta agonism increases survival in experimentally induced sepsis and ameliorates the genomic sepsis signature: a pharmacogenomic study
    Eirini Christaki
    Infectious Disease Division, Memorial Hospital of Rhode Island, Warren Alpert School of Medicine of Brown University, Providence, Rhode Island, USA
    J Infect Dis 201:1250-7. 2010
    ..Work reported elsewhere has demonstrated that ERbeta agonists have beneficial effects in multiple (but not all) models of inflammatory diseases and also increase survival in experimentally induced sepsis...
  71. ncbi A new paradigm for the treatment of sepsis: is it time to consider combination therapy?
    Alan S Cross
    Department of Medicine, Center for Vaccine Development, University of Maryland School of Medicine, 685 West Baltimore Street, HSF 480, Baltimore, Maryland 21201, USA
    Ann Intern Med 138:502-5. 2003
    ..It is now time to test a new therapeutic paradigm based on an improved understanding of the pathophysiology of the septic process and the recognition that we may have reached the limits of adjunctive monotherapy...
  72. ncbi Concept of PIRO as a new conceptual framework to understand sepsis
    Steven M Opal
    Department of Medicine, Brown Medical School, Providence, RI, USA
    Pediatr Crit Care Med 6:S55-60. 2005
    ..The PIRO model should be directly tested in both the research laboratory and in clinical trial designs to determine the practical value and clinical relevance of this new classification scheme for sepsis...
  73. ncbi Is the mortality rate for septic shock really decreasing?
    Eirini Christaki
    The Infectious Disease Division, The Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA
    Curr Opin Crit Care 14:580-6. 2008
    ..To critically examine the mortality rates of septic shock over the last 25 years to determine if significant improvements have been accomplished...
  74. ncbi Advances in sepsis therapy
    Thomas Gluck
    Klinik und Poliklinik für Innere Medizin I, Universitatsklinikum Regensburg, Regensburg, Germany
    Drugs 64:837-59. 2004
    ..How these new and often expensive regimens will fit into the standard treatment approach to sepsis remains to be defined by future clinical investigations...
  75. ncbi High-dose antithrombin III in the treatment of severe sepsis in patients with a high risk of death: efficacy and safety
    Christian J Wiedermann
    Department of Medicine, Central Hospital of the Province of Bolzano, Bolzano, Italy
    Crit Care Med 34:285-92. 2006
    ..CONCLUSIONS: Treatment with high-dose antithrombin III may increase survival time up to 90 days in patients with severe sepsis and high risk of death. This benefit may even be stronger when concomitant heparin is avoided...
  76. ncbi Benefit/risk profile of high-dose antithrombin in patients with severe sepsis treated with and without concomitant heparin
    Johannes N Hoffmann
    Department of Surgery, Ludwig-Maximilian University of Munich, Munich, Germany
    Thromb Haemost 95:850-6. 2006
    ..Combined administration of the two increases bleeding risk and probably abolishes efficacy of antithrombin...
  77. ncbi Sepsis associated with immunosuppressive medications: an evidence-based review
    Juan C Gea-Banacloche
    National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
    Crit Care Med 32:S578-90. 2004
    ....
  78. ncbi Antibodies against RAGE in sepsis and inflammation: implications for therapy
    Emily C Lutterloh
    Expert Opin Pharmacother 8:1193-6. 2007
    ..The pathophysiology of sepsis and inflammation is incompletely understood. The complicated nature of these processes may make new techniques, such as computer simulation and genomics, vital in understanding how to target therapies...
  79. ncbi The duration of hypotension before the initiation of antibiotic treatment is a critical determinant of survival in a murine model of Escherichia coli septic shock: association with serum lactate and inflammatory cytokine levels
    Anand Kumar
    Division of Cardiovascular Diseases and Critical Care Medicine, Cooper Hospital University Medical Center, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Camden, New Jersey
    J Infect Dis 193:251-8. 2006
    ..This study was designed to examine the relationship between the timing of antibiotic treatment and both survival rates and hemodynamic/inflammatory correlates of survival in a murine model of Escherichia coli septic shock...
  80. ncbi Coagulation in sepsis
    Andre Amaral
    Dept of Intensive Care, Erasme Hospital, Free University of Brussels, Belgium
    Intensive Care Med 30:1032-40. 2004
    ..In this article, we explore the complex relationship between inflammation and coagulation and how improved understanding of this interaction has led to the development of new therapeutic agents for patients with severe sepsis...
  81. ncbi Host-pathogen interactions in sepsis
    Tom van der Poll
    Academic Medical Centre, University of Amsterdam, Centre for Infection and Immunity Amsterdam, Netherlands
    Lancet Infect Dis 8:32-43. 2008
    ..This Review summarises current knowledge of microbial pathogenesis and host-pathogen interactions during sepsis and the ensuing development of potential therapeutics...
  82. ncbi Intraabdominal infections in infants and children: descriptions and definitions
    Ann E Thompson
    Critical Care Medicine and Pediatrics, University of Pittsburgh School of Medicine, PA, USA
    Pediatr Crit Care Med 6:S30-5. 2005
    ..CONCLUSIONS: Criteria defining intraabdominal infection are proposed based on reports in the pediatric literature and expert opinion. Additional study of individual disorders, diagnostic criteria, and approach to management is warranted...
  83. ncbi Corticosteroids for patients with septic shock
    Steven M Opal
    JAMA 289:41-2; author reply 43-4. 2003
  84. ncbi Bioterrorism and physicians
    Andrew W Artenstein
    Ann Intern Med 137:626. 2002
  85. ncbi Quality of life effects of antithrombin III in sepsis survivors: results from the KyberSept trial [ISRCTN22931023]
    Dale Rublee
    Aventis Behring L, L, C, King of Prussia, Pennsylvania, USA
    Crit Care 6:349-56. 2002
    ..Treatment of sepsis is aimed at increasing both the duration and quality of survival. A long-term focus on quality of life (QoL) in clinical trial evaluations of sepsis care should be a priority...
  86. ncbi Insights into severe sepsis in older patients: from epidemiology to evidence-based management
    Timothy D Girard
    Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    Clin Infect Dis 40:719-27. 2005
    ..Clinicians must be aware of the level of evidence in support of various interventions and must keenly screen older survivors for ongoing deficits that will limit their functional recovery...

Research Grants1

  1. Role of Inter-alpha Inhibitors in Anthrax Intoxication
    Steven Opal; Fiscal Year: 2007
    ..Our research is focused on the development of a new and safe treatment based on the ability of inter-alpha proteins to prevent the fatal consequences of anthrax infection. ..