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Biomedical subjects

R C Bone

Publications and source records attributed to R C Bone.

At least 19 recordsLinked to original sources
PubMed1992

Modulators of coagulation. A critical appraisal of their role in sepsis.

Widespread intravascular coagulation is common in patients with sepsis. Coagulation abnormalities may result from exposure to endotoxin, from tumor necrosis factor alpha or interleukin 1 release, or from the actions of a more specific mediator, such as vascular permeability factor. The result is marked activation of the contact and coagulation systems; simultaneously, there is decreased fibrinolysis and depressed levels of the inhibitors of the contact and coagulation systems. Multiple agents are being studied to correct these abnormalities. Antithrombin III holds promise because it inhibits a number of factors important in contact and coagulation activation, not just thrombin. Plasminogen activators may prove helpful in increasing fibrinolysis during sepsis; because they have been associated with rebound thrombin generation, however, plasminogen activators may be most effective if used in conjunction with hirudin or a synthetic hirudin analogue. Bradykinin may offset hypotension in sepsis. Protein C may inhibit thrombin formation and also complex with plasminogen activator inhibitor 1, thereby promoting fibrinolysis. Other agents that may prove effective include alpha 1-antitrypsin Pittsburgh, C1-esterase inhibitor, monoclonal antibodies to contact factors, soybean trypsin inhibitors, thrombomodulin, prostaglandin I2, and aprotinin. There are no data to support the use of heparin or fibronectin, except in limited circumstances.

Animals↗
PubMed1992

Patients' preferences for intensive care.

OBJECTIVES: To determine patients' preferences for intensive care and to evaluate the influence of a recent ICU experience on preferences for future ICU treatment. DESIGN: Survey of nonrandomized patient sample using structured interviews. SETTING: Large, urban, tertiary academic medical center. PATIENTS: Eighty-four adult inpatients discharged from the medical ICU between June and August 1990. MEASUREMENTS: Agreement with life-supportive care under each of four potential outcome scenarios was assessed on a 5-point scale. An overall preference score was created by summing scores for the four items. Patients were also asked about their recent experiences in the ICU. RESULTS: Patients identified sources of stress associated with their ICU stay, yet most (76%) rated their ICU experience positively. Preferences for future intensive care varied with perceived outcome, and were strongest for health restoration and weakest for persistent vegetative states. No significant relationships were found between ICU preferences and any demographic or clinical variable except race. CONCLUSIONS: Patients tolerate intensive care well and desire it to restore health. Most patients modify their desire for intensive care if less favorable outcomes are likely. Patients' preferences for intensive care cannot be predicted from demographic features or previous ICU experiences.

Academic Medical Centers↗
PubMed1992

Hypothermia in the sepsis syndrome and clinical outcome. The Methylprednisolone Severe Sepsis Study Group.

OBJECTIVE: To evaluate the consequences of clinical hypothermia associated with sepsis syndrome and septic shock. DESIGN: Analysis of data from a multi-institutional, randomized, placebo-controlled, prospective study with predetermined end-point analysis of development of shock, recovery from shock, hospital length of stay, and death. SETTING: Multi-institutional medical and surgical ICUs. PATIENTS: Patients meeting predetermined criteria for severe sepsis syndrome. INTERVENTIONS: Appropriate sepsis and shock care with 50% of patients receiving methylprednisolone and 50% receiving placebo. MEASUREMENTS AND MAIN RESULTS: The occurrence rate of hypothermia (< 35.5 degrees C) is 9% in this population. When compared with febrile patients, hypothermic patients had a higher frequency of central nervous system dysfunction (88% vs. 60%), increased serum bilirubin concentration (35% vs. 15%), prolonged prothrombin times (50% vs. 23%), shock (94% vs. 61%), failure to recover from shock (66% vs. 26%), and death (62% vs. 26%). The hypothermic patients were also more likely to be classified as having a rapidly or ultimately fatal disease upon study admission. CONCLUSIONS: This prospective study confirms that hypothermia associated with sepsis syndrome has a significant relationship to outcome manifest by increased frequency of shock and death from shock. This finding is in sharp contrast to the protective effects of induced hypothermia in septic animals and perhaps man.

Adolescent↗
PubMed1992

Adult respiratory distress syndrome. Sequence and importance of development of multiple organ failure. The Prostaglandin E1 Study Group.

STUDY OBJECTIVE: To determine the epidemiology of multiple organ failure (MOF) in patients with the adult respiratory distress syndrome. PATIENTS: We followed up 50 patients with serial determinations of respiratory and nonrespiratory organ function for seven days after diagnosis. DESIGN: Data were stratified between patients who died and those who survived (defined as hospital discharge). MEASUREMENTS AND RESULTS: Values that did not differ at any time between the two groups of patients included oxygen availability, oxygen consumption, oxygen extraction, PaCO2, respiratory rate, heart rate, systolic blood pressure, cardiac output, stroke index, systemic vascular resistance, and temperature. Patients who died had greater defects in oxygenation (from day 1 through day 7). They also exhibited decreased arterial oxygen content (from day 1 to day 4), decreased mixed venous oxygen content (day 1), increased peak inspiratory pressure (present on day 2, persisted to day 5, reappeared on day 7), decreased diastolic blood pressure (seen on days 1 through 3, reappeared on day 7), and increased mean pulmonary artery pressure (seen on days 2 and 3). Nonsurvivors also exhibited greater degrees of thrombocytopenia (from day 1 to day 4). Decreases in pH (seen on day 1, reappeared from days 4 to 7), abnormalities in liver function (seen only on day 1), and increases in serum creatinine levels (appeared on day 7) were also observed. CONCLUSIONS: Multiorgan dysfunction (MOD) was frequently observed in both groups of patients. Alterations in organ function and the pattern of abnormalities were often subtle and would not be characterized as significant organ dysfunction by most available organ scoring systems. Adult respiratory distress syndrome is a manifestation of systemic disease produced by widespread increases in endothelial permeability; lung dysfunction dominates the early clinical course. When respiratory function is supported, it becomes evident that alterations occur in other organs. Multiorgan failure is really a misnomer; the term emphasizes end-stage changes. Multiorgan dysfunction is common and often resolves without progressing to MOF. Alternatively, MOD can progress to MOF.

Blood Pressure↗
PubMed1992

Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine.

An American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference was held in Northbrook in August 1991 with the goal of agreeing on a set of definitions that could be applied to patients with sepsis and its sequelae. New definitions were offered for some terms, while others were discarded. Broad definitions of sepsis and the systemic inflammatory response syndrome were proposed, along with detailed physiologic parameters by which a patient may be categorized. Definitions for severe sepsis, septic shock, hypotension, and multiple organ dysfunction syndrome were also offered. The use of severity scoring methods when dealing with septic patients was recommended as an adjunctive tool to assess mortality. Appropriate methods and applications for the use and testing of new therapies were recommended. The use of these terms and techniques should assist clinicians and researchers who deal with sepsis and its sequelae.

Critical Care↗
PubMed1992

The effects of prostaglandin E1 on non-pulmonary organ function during clinical acute respiratory failure. The Prostaglandin E1 Study Group.

The effects of prostaglandin E1 (PGE1) on non-pulmonary vital organs in critically ill patients are not well defined. This study evaluated the role of exogenous PGE1 in systemic homeostasis during the adult respiratory distress syndrome (ARDS). Indicators of end-organ function were analyzed retrospectively in 146 septic or post-trauma patients with ARDS who received PGE1 (30/ng/kg/min) or placebo IV for up to 7 days in a randomized, double-blind clinical trial. Hemodynamic variables and serum levels of creatinine, bilirubin, and SGOT, platelet count, and changes in the white blood cell count were measured daily. Our results indicate that mean arterial pressure, pulmonary artery pressure, and systemic and pulmonary vascular resistance indices were significantly lower in the PGE1 group versus the placebo-treated group. Cardiac index, stroke index, and oxygen delivery index were significantly increased in the PGE1 group. Serum bilirubin and SGOT were decreased significantly among PGE1-treated patients compared with placebo-treated patients, while the white blood cell count increased more significantly from baseline values with PGE1 treatment. Intergroup differences in platelet count and serum creatinine levels were not statistically significant. The results indicate that PGE1 improves cardiovascular performance, hepatic function, and leukocyte availability during clinical ARDS. Prostaglandin E1 did not affect platelet counts and renal function in this study.

Acute Disease↗
PubMed1992

Phospholipids and their inhibitors: a critical evaluation of their role in the treatment of sepsis.

OBJECTIVE: The clinical condition sepsis and its sequelae are caused by numerous mediators that are released by various cell types. The purpose of this review is to describe the results of various studies performed with agents that either inhibited or stimulated the synthesis of, or affected the receptor-binding characteristics of a specific class of these mediators, the phospholipids. DESIGN: Antagonists to platelet-activating factor and thromboxane A2 receptors, monoclonal antibodies to phospholipase A2, agents which increased levels of prostaglandins, and cyclooxygenase, lipoxygenase, and other specific pathway inhibitors, which block the production of leukotrienes and thromboxane A2, were used in the studies described to affect the physiologic correlates of sepsis animal models and human studies. DATA SOURCES: The matters discussed in this paper come from a wide variety of sources, including many broad-based clinical studies of humans with inflammatory disease. Many animal studies are discussed, along with some in vitro cell culture studies and work in molecular genetics. STUDY SELECTION: This article reviews a subject that is rapidly evolving, with frequent discoveries. Thus, much of the article discusses research in basic science, particularly the use of experimental drugs in animals. Clinical studies are generally of large numbers of patients showing overt signs of sepsis. DATA EXTRACTION: Most cited literature was found in reputable, peer review journals, including such major basic science journals as Science, and clinical journals such as the Journal of the American Medical Association, New England Journal of Medicine, and Critical Care Medicine. DATA SYNTHESIS: Occasionally, contradictions do occur in the results of various studies. These contradictions are discussed in this review, and may often be due to the use of different protocols and definitions of the various clinical states. CONCLUSIONS: Increases of some mediators, such as platelet-activating factor, thromboxane A2, and the leukotrienes are associated with animal models of sepsis and seem to have a negative effect on the course of sepsis. Antagonists and blockers of these mediators increased survival in these studies. More research is needed to identify how these mediators of inflammation are associated with sepsis, and what the effects of blocking their actions will have on sepsis.

Animals↗
PubMed1992

Inhibitors of complement and neutrophils: a critical evaluation of their role in the treatment of sepsis.

OBJECTIVE: Damage to the vascular system is a major finding of sepsis and its sequelae. This damage is caused, in part, by the recruitment and adhesion of neutrophils to the endothelium and their release of destructive molecules. Mediators released by various cell types, including the neutrophil itself, control these destructive actions of the neutrophil. The complement system is one such group of mediators. Through the use of medications that decrease neutrophil activation and adherence and block complement activation, it may be possible to control the course of sepsis. DATA SOURCES: The issues discussed in this paper come from a wide variety of sources, including several broad-based clinical studies of humans with inflammatory disease. Many animal studies are discussed, along with some in vitro cell culture studies and work in molecular genetics. STUDY SELECTION: This article reviews a subject that is rapidly evolving, with frequent new discoveries. Thus, much of the article discusses research in basic science, particularly the use of experimental drugs in animals. Few clinical studies have been performed using these agents. DATA EXTRACTION: Most cited literature was found in reputable, peer review journals, including important basic science and clinical journals such as Science, Journal of the American Medical Association, New England Journal of Medicine, and Critical Care Medicine. DATA SYNTHESIS: Occasionally, contradictions do occur in the results of various studies. These contradictions are discussed and may often be due to different protocols and different definitions of the various clinical states. CONCLUSIONS: Pentoxifylline has been shown to decrease neutrophil adhesion and provides increased survival rate in various animal models of sepsis. Early studies regarding monoclonal antibodies to adhesion molecules are exciting. However, the possible effects of these agents in sepsis has yet to be studied. Drugs have been discovered that show potential to block the numerous destructive agents released by degranulating neutrophils.

Animals↗
PubMed1991

A critical evaluation of new agents for the treatment of sepsis.

OBJECTIVE - To evaluate new treatments directed against endotoxin, tumor necrosis factor alpha, and interleukin 1 for use in sepsis and related disorders (sepsis syndrome and septic shock). DATA SOURCES - Investigations of these treatments in animal models, healthy human volunteers, and patients with sepsis and related disorders. STUDY SELECTION - Particular attention was paid to studies of patients with sepsis and related disorders, especially randomized, double-blind, controlled trials. DATA EXTRACTION - Animal studies and investigations with human volunteers were judged by how closely the experimental model replicated the clinical disorder (sepsis). Patient trials were assessed by sample size and design. Results of all studies were used to evaluate the likelihood that a given treatment would reduce mortality. DATA SYNTHESIS - Direct comparison of E5 and HA-1A antibody studies is difficult because of differences in their design, definitions of shock, and methods of subgroup analysis. However, both antibodies improve outcome in some subgroups: E5 benefits patients with gram-negative infection (bacteremic or focal) who do not have refractory shock, and HA-1A benefits those with gram-negative bacteremia (regardless of whether shock is present) but not those with focal gram-negative infection. Two agents that may be beneficial in gram-positive and gram-negative infection are monoclonal antibodies to tumor necrosis factor alpha and receptor antagonists to interleukin 1. Preliminary results with both are reviewed. CONCLUSIONS - All three types of treatment may improve outcome in sepsis. The best results will probably be obtained with combination therapy that interrupts multiple points of the inflammatory cascade underlying sepsis.

Endotoxins↗
PubMed1991

The pathogenesis of sepsis.

Sepsis and its sequelae (sepsis syndrome and septic shock) are increasingly common and are still potentially lethal diagnoses. Many mediators of the pathogenesis of sepsis have recently been described. These include tumor necrosis factor alpha (TNF alpha), interleukins, platelet activating factor, leukotrienes, thromboxane A2, and activators of the complement cascade. Neutrophil and platelet activation may also play a role. Other agents that may participate in the sepsis cascade include adhesion molecules, kinins, thrombin, myocardial depressant substance, beta-endorphin, and heat shock proteins. Endothelium-derived relaxing factor and endothelin-1 are released from the endothelium and seem to exert a regulatory effect, counterbalancing each other. A central mediator of sepsis does not seem to exist, although TNF alpha has been commonly proposed for this role. Animal studies are difficult to extrapolate to the clinical setting because of cross-species differences and variations in experimental design. Rather than being caused by any single pathogenic mechanism, it is more likely that sepsis is related to the state of activation of the target cell, the nearby presence of other mediators, and the ability of the target cell to release other mediators. Also important is the downregulation or negative feedback of these mediators or the generation of natural inflammation inhibitors, such as interleukin-4 and interleukin-8. Endothelial damage in sepsis probably results from persistent and repetitive inflammatory insults. Eventually, these insults produce sufficient damage that downregulation can no longer occur; this leads to a state of metabolic anarchy in which the body can no longer control its own inflammatory response.

Animals↗