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A P Wheeler

Publications and source records attributed to A P Wheeler.

At least 19 recordsLinked to original sources
PubMed2001

New ways to reduce unnecessary variation and improve outcomes in the intensive care unit.

The care of critically ill patients and the advent of the modern day intensive care unit (ICU) present a large person power and cost burden to society. The high cost of critical care is attributed to high overhead expenses (eg, experienced staff and equipment), high resource utilization (eg, pharmaceutical resources, lab testing, imaging procedures), and high demand for services. Pathways to standardize numerous facets of patient care have been shown to improve the efficiency of delivery of care and to reduce resource utilization, and are becoming the most sought-after means of improving patient outcomes and reducing overall ICU expenditures. A number of large, randomized, prospective trials have demonstrated that protocol-based strategies can not only reduce variation and cost of ICU medicine but also improve morbidity and mortality of critically ill patients requiring ICU support. In this article, we discuss examples of these trials investigating four major areas of modern ICU medicine: ventilator management, ventilator weaning, sedation and analgesia, and blood transfusions.

Humans↗
PubMed2000

Determination of apparent thermodynamic parameters for adsorption of a midchain peptidyl residue onto a glass surface.

Protein adsorption onto the surface of an implanted material is widely recognized as an important factor controlling the biological response. Although numerous studies have been conducted to investigate protein adsorption behavior, very little is actually understood regarding the specific molecular events involved in protein-surface adsorption processes. As a basic science approach to investigate protein-surface interactions, an experimental method is developed and applied to determine apparent thermodynamic parameters for the adsorption of a single midchain peptidyl residue onto a glass surface. This article presents the results of adsorption studies for four molecular weight ranges of poly-L-lysine onto glass microspheres in physiologic saline at four temperatures. Isotherm data plots are constructed and the apparent changes in enthalpy (DeltaH degrees ), entropy (DeltaS degrees ), and Gibbs' free energy (DeltaG degrees ) are calculated assuming a Langmuir-like model for adsorption. Estimates of apparent DeltaH degrees, DeltaS degrees, and DeltaG degrees for the adsorption of a single midchain lysine residue are determined from the initial slopes of the plots of the apparent thermodynamic parameters versus the degree of polymerization of the adsorbed poly-L-lysine. It is proposed that the generation of such molecular-level adsorption data is a necessary step toward the goal of understanding, predicting, and controlling protein-surface interactions.

Adsorption↗
PubMed2000

Hypoproteinemia predicts acute respiratory distress syndrome development, weight gain, and death in patients with sepsis. Ibuprofen in Sepsis Study Group.

OBJECTIVE: Starling's equation indicates that reduced oncotic pressure gradients will favor edema formation, and the current consensus definition of acute respiratory distress syndrome (ARDS) excludes only the hydrostatic pressure contribution. We hypothesized that low serum total protein levels might correlate with the likelihood of ARDS in at-risk patients because serum total protein is the chief determinant of oncotic pressure in humans. DESIGN: Regression analysis to compare outcomes in patients with low serum total protein levels with outcomes in patients with normal serum total protein levels with respect to weight change, development of ARDS, and mortality. SETTING: Intensive care units (ICUs) of seven clinical centers in North America. PATIENTS: A total of 455 ICU patients who met consensus criteria for severe sepsis (178 of whom developed ARDS) from a recently completed prospective clinical trial. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We found that 92% of the patients developing ARDS had low or borderline serum total protein levels (<6 g/dL). Logistic and multiple regression analyses confirmed that of 18 clinical variables, initial serum total protein level and protein change over time were the most statistically significant predictors of weight gain, prolonged mechanical ventilation, ARDS development, and mortality in the study population. This correlation remained significant after adjustment for the other major predictors of outcome present at baseline (ie, Acute Physiology and Chronic Health Evaluation II score). CONCLUSIONS: Hypoproteinemia is significantly correlated with fluid retention and weight gain, development of ARDS and poor respiratory outcome, and mortality in patients with sepsis. Prospective, randomized trials of serum protein manipulation are needed to establish whether there is a cause-effect relationship to this association.

Adult↗
PubMed2000

Nucleation and growth of calcite on native versus pyrolyzed oyster shell folia.

The thin sheets of calcite, termed folia, that make up much of the shell of an oyster are covered by a layer of discrete globules that has been proposed to consist of agglomerations of protein and mineral. Foliar fragments, treated at 475 degrees C for 36 h to remove organic matter, were imaged by atomic force microscopy (AFM) as crystals grew on the foliar surfaces in artificial seawater at calcite supersaturations up to 52-fold. Crystals were also viewed later by scanning electron microscopy. After pyrolysis, the foliar globules persisted only as fragile remnants that were quickly washed away during AFM imaging, revealing an underlying morphology on the foliar laths of a tightly packed continuum of nanometer-scale protrusions. At intermediate supersaturations, crystal formation was seen immediately almost everywhere on these surfaces, each crystal having the same distinctive shape and orientation, even at the outset with crystals as small as a few nanometers. In contrast, nucleation did not occur readily on non-pyrolyzed foliar surfaces, and the crystals that did grow, although slowly at intermediate supersaturations, had irregular shapes. Possible crystallographic features of foliar laths are considered on the basis of the morphology of ectopic crystals and the atomic patterns of various surfaces. A model for foliar lath formation is presented that includes cycles of pulsed secretion of shell protein, removal of the protein from the mineralizing solution upon binding to mineral, and mineral growth at relatively high supersaturation over a time frame of about 1 h for each turn of the cycle.

Animals↗
PubMed1999

Effects of ibuprofen on the physiology and survival of hypothermic sepsis. Ibuprofen in Sepsis Study Group.

OBJECTIVES: The objective was to compare the clinical and physiologic characteristics of febrile septic patients with hypothermic septic patients; and to examine plasma levels of cytokines tumor necrosis factor alpha (TNF-alpha and interleukin 6 (IL-6) and the lipid mediators thromboxane B2 (TxB2) and prostacyclin in hypothermic septic patients in comparison with febrile patients. Most importantly, we wanted to report the effect of ibuprofen treatment on vital signs, organ failure, and mortality in hypothermic sepsis. SETTING: The study was performed in the intensive care units (ICUs) of seven clinical centers in the United States and Canada. PATIENTS: Four hundred fifty-five patients admitted to the ICU who met defined criteria for severe sepsis and were suspected of having a serious infection. INTERVENTION: Ibuprofen at a dose of 10 mg/kg (maximum 800 mg) was administered intravenously over 30 to 60 mins every 6 hrs for eight doses vs. placebo (glycine buffer vehicle). MEASUREMENTS AND MAIN RESULTS: Forty-four (10%) septic patients met criteria for hypothermia and 409 were febrile. The mortality rate was significantly higher in hypothermic patients, 70% vs. 35% for febrile patients. At study entry, urinary metabolites of TxB2, prostacyclin, and serum levels of TNF-alpha and IL-6 were significantly elevated in hypothermic patients compared with febrile patients. In hypothermic patients treated with ibuprofen, there was a trend toward an increased number of days free of major organ system failures and a significant reduction in the 30-day mortality rate from 90% (18/20 placebo-treated patients) to 54% (13/24 ibuprofen-treated patients). CONCLUSIONS: Hypothermic sepsis has an incidence of approximately 10% and an untreated mortality twice that of severe sepsis presenting with fever. When compared with febrile patients, the hypothermic group has an amplified response with respect to cytokines TNF-alpha and IL-6 and lipid mediators TxB2 and prostacyclin. Treatment with ibuprofen may decrease mortality in this select group of septic patients.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

Use of pulse oximetry to recognize severity of airflow obstruction in obstructive airway disease: correlation with pulsus paradoxus.

STUDY OBJECTIVES: The purpose of this cross-sectional study was to confirm the observation that pulse oximetry tracing correlates with pulsus paradoxus, and is therefore a measure of the severity of air trapping in obstructive airway disease. DESIGN: Cross-sectional survey. SETTING: The ICU in a tertiary care academic hospital. PATIENTS: Twenty-six patients consecutively admitted to the ICU with obstructive airway disease, either asthma or COPD. MEASUREMENTS AND RESULTS: Forty-six percent of the study patients required mechanical ventilation, and 69% had an elevated pulsus paradoxus. We defined the altered pulse oximetry baseline tracing as the respiratory waveform variation (RWV). The RWV was measured in numerical form as the change in millimeters from the baseline. Pulsus paradoxus was significantly correlated with the RWV of the pulse oximetry tracing (p < 0.0001). An analysis of the respiratory variations in the pulse oximetry waveforms in obstructive lung disease patients reflects the presence and degree of auto-positive end-expiratory pressure (auto-PEEP; p < 0.0001). CONCLUSIONS: We describe the characteristic alterations in the pulse oximetry tracings that occur in the presence of pulsus paradoxus and auto-PEEP. Since pulse oximetry is available universally in ICUs and emergency departments, it may be a useful noninvasive means of continually assessing pulsus paradoxus and air trapping severity in obstructive airway disease patients.

Adult↗
PubMed1997

The effects of ibuprofen on the physiology and survival of patients with sepsis. The Ibuprofen in Sepsis Study Group.

BACKGROUND: In patients with sepsis the production of arachidonic acid metabolites by cyclooxygenase increases, but the pathophysiologic role of these prostaglandins is unclear. In animal models, inhibition of cyclooxygenase by treatment with ibuprofen before the onset of sepsis reduces physiologic abnormalities and improves survival. In pilot studies of patients with sepsis, treatment with ibuprofen led to improvements in gas exchange and airway mechanics. METHODS: From October 1989 to March 1995, we conducted a randomized, double-blind, placebo-controlled trial of intravenous ibuprofen (10 mg per kilogram of body weight [maximal dose, 800 mg], given every six hours for eight doses) in 455 patients who had sepsis, defined as fever, tachycardia, tachypnea, and acute failure of at least one organ system. RESULTS: In the ibuprofen group, but not the placebo group, there were significant declines in urinary levels of prostacyclin and thromboxane, temperature, heart rate, oxygen consumption, and lactic acidosis. With ibuprofen therapy there was no increased incidence of renal dysfunction, gastrointestinal bleeding, or other adverse events. However, treatment with ibuprofen did not reduce the incidence or duration of shock or the acute respiratory distress syndrome and did not significantly improve the rate of survival at 30 days (mortality, 37 percent with ibuprofen vs 40 percent with placebo). CONCLUSIONS: In patients with sepsis, treatment with ibuprofen reduces levels of prostacyclin and thromboxane and decreases fever, tachycardia, oxygen consumption, and lactic acidosis, but it does not prevent the development of shock or the acute respiratory distress syndrome and does not improve survival.

Acidosis, Lactic↗
PubMed1997

A trial of antioxidants N-acetylcysteine and procysteine in ARDS. The Antioxidant in ARDS Study Group.

OBJECTIVE: To determine the levels of glutathione and cysteine in patients with ARDS and examine the effect of treatment with N-acetylcysteine (NAC) and L-2-oxothiazolidine-4-carboxylate (Procysteine; Clintec Technologies Inc; Chicago [OTZ]) on these levels and on common physiologic abnormalities, and organ dysfunction associated with ARDS. DESIGN: Randomized, double-blind, placebo-controlled, prospective clinical trial. SETTING: ICUs in five clinical centers in the United States and Canada. PATIENTS: Patients meeting a predetermined definition of ARDS and requiring mechanical ventilation. INTERVENTION: Standard care for ARDS and I.V. infusion, every 8 h for 10 days, of one of the following: NAC (70 mg/kg, n=14), OTZ (63 mg/kg, n=17), or placebo (n=15). MAIN RESULTS: Both antioxidants effectively repleted RBC glutathione gradually over the 10-day treatment period (47% and 49% increases from baseline values for NAC and OTZ, respectively). There was no difference in mortality among groups (placebo, 40%; NAC, 36%; OTZ, 35%). However, the number of days of acute lung injury was decreased and there was also a significant increase in cardiac index in both treatment groups (NAC/OTZ [+]14%; placebo [-]6%). CONCLUSIONS: Our findings suggest that repletion of glutathione may safely be accomplished with NAC or OTZ in patients with acute lung injury/ARDS. Such treatment may shorten the duration of acute lung injury, but larger studies are needed to confirm this.

Acetylcysteine↗
PubMed1996

Diagnosis and therapy of acute respiratory distress syndrome in adults: an international survey.

In an attempt to identify the range of opinions influencing the diagnosis and therapy of patients with the adult respiratory distress syndrome (ARDS), a postal survey was mailed to 3,164 physician members of the American Thoracic Society Critical Care Assembly. The questionnaire asked opinions regarding the factors important in the diagnosis of ARDS and its treatment. Thirty-one percent of physicians surveyed responded within 4 weeks, the vast majority of which were board certified or eligible in Internal Medicine, Pulmonary Disease, and/or Critical Care Medicine. A known predisposing cause, measure of oxygenation efficiency, and a chest radiograph depicting pulmonary edema were reported to be the most important criteria for a clinical and research diagnosis of ARDS. Lung compliance and bronchoalveolar lavage neutrophil or protein content were reportedly less important. The initial treatment of patients with ARDS was reported to be most commonly accomplished using volume-cycled ventilation in the assist/control mode. Nearly half the responders reported using lower tidal volumes (5 to 9 mL/kg) than the traditionally recommended 10 to 15 mL/kg. Most respondents indicated they have intentionally allowed CO2 retention. On average, oxygen toxicity was thought to begin at an FIO2 between 0.5 and 0.6. It was reported that modest levels of positive end-expiratory pressure (PEEP) were used in incremental fashion as FiO2 requirements increased. Perceived indications for insertion of pulmonary artery catheters and compensation of the effects of PEEP on the pulmonary artery occlusion pressure varied widely among the responders. We conclude that reported practice patterns regarding the care of ARDS patients vary widely even within a relatively homogenous group of critical care practitioners.

Adult↗
PubMed1996

Applications of molecular biology and biotechnology: antibody therapy of sepsis.

The use of antibody therapy for the treatment of infections and inflammatory disease is well established. Unfortunately, clinical studies of antiendotoxin and anti-TNF monoclonal antibodies have failed to show clear physiological or survival benefit. Little information is available regarding the effect of antibodies to cytokines other than TNF in human sepsis. Limited pre-clinical data indicate that IL-6 antibodies may abrogate the effects of endotoxin infusion, but no human studies have been performed. Although both monoclonal and polyclonal antibodies have the potential to protect septic humans, at this time it is the polyclonal antibodies that have shown the greatest promise. Each type of antibody possesses specific advantages and limitations, the ultimate effectiveness of which will need to be proven in large randomized clinical trials.

Animals↗
PubMed1995

Escherichia coli endotoxin-mediated endothelial injury is modulated by glutathione ethyl ester.

The mechanisms involved in endotoxin-induced endothelial injury are not fully understood. Oxidant stress is thought to play a role in cell damage after endotoxin exposure. Glutathione may ameliorate these affects. Glutathione ethyl ester (GSE) was used in bovine pulmonary artery endothelial cell (BPAEC) cultures to determine the potential for attenuation of endotoxin-induced injury. GSE (0.05-25 mM) was preincubated with BPAEC for 4 h before endotoxin exposure. Fresh media containing GSE and Escherichia coli endotoxin (0.05 microgram/mL) were then placed on the BPAEC and incubated for 18 h. GSE, at doses of 5 and 25 mM, attenuated endotoxin-induced injury, as reflected by a significant reduction in lactate dehydrogenase release. This was paralleled by a significant increase in endotoxin-stimulated prostaglandin E2 and prostacyclin release. Thus, GSE attenuates endotoxin-induced injury of BPAEC in culture and alters BPAEC prostaglandin metabolism.

Animals↗
PubMed1995

Pivot/Remote: a distributed database for remote data entry in multi-center clinical trials.

1. INTRODUCTION. Data collection is a critical component of multi-center clinical trials. Clinical trials conducted in intensive care units (ICU) are even more difficult because the acute nature of illnesses in ICU settings requires that masses of data be collected in a short time. More than a thousand data points are routinely collected for each study patient. The majority of clinical trials are still "paper-based," even if a remote data entry (RDE) system is utilized. The typical RDE system consists of a computer housed in the CC office and connected by modem to a centralized data coordinating center (DCC). Study data must first be recorded on a paper case report form (CRF), transcribed into the RDE system, and transmitted to the DCC. This approach requires additional monitoring since both the paper CRF and study database must be verified. The paper-based RDE system cannot take full advantage of automatic data checking routines. Much of the effort (and expense) of a clinical trial is ensuring that study data matches the original patient data. 2. METHODS. We have developed an RDE system, Pivot/Remote, that eliminates the need for paper-based CRFs. It creates an innovative, distributed database. The database resides partially at the study clinical centers (CC) and at the DCC. Pivot/Remote is descended from technology introduced with Pivot [1]. Study data is collected at the bedside with laptop computers. A graphical user interface (GUI) allows the display of electronic CRFs that closely mimic the normal paper-based forms. Data entry time is the same as for paper CRFs. Pull-down menus, displaying the possible responses, simplify the process of entering data. Edit checks are performed on most data items. For example, entered dates must conform to some temporal logic imposed by the study. Data must conform to some acceptable range of values. Calculations, such as computing the subject's age or the APACHE II score, are automatically made as the data is entered. Data that is collected serially (BP, HR, etc.) can be displayed graphically in a trend form along with other related variables. An audit trail is created that automatically tracks all changes to the original data, making it possible to reconstruct the CRF to any point in time. On-line help provides information on the study protocol as well as assistance with the use of the system. Electronic security makes it possible to lock certain parts of the CRF once it has been monitored. Completed CRFs are transmitted to the DCC via electronic mail where it is reviewed and merged into the study database. Questions about subject data are transmitted back to the CC via electronic mail. This approach to maintaining the study database is unique in that the study data files are distributed among the CC and DCC. Until a subject's CRF is monitored (verified against the original patient data residing in the hospital record), it logically resides at the CC where it was collected. Copies are transmitted to the DCC and are only read there. Any pre-monitoring changes must be made to the data at the CC. Once the subject's CRF is monitored, it logically moves to the DCC, and any subsequent changes are made at the DCC with copies of the CRF flowing back to the CC. 3. DISCUSSION. Pivot/Remote eliminates the need for paper forms by utilizing portable computers that can be used at the patient bedside. A GUI makes it possible to quickly enter data. Because the user gets instant feedback on possible error conditions, time is saved because the original data is close at hand. The ability to display trended data or variables in the context of other data allows detection of erroneous conditions beyond simple range checks. The logical construction of the database minimizes the problem of managing dual databases (at the CC and DCC) and keeps CC personnel in the loop until all changes are made.

Computer Communication Networks↗
PubMed1993

Radiographic issues in adult respiratory distress syndrome.

Despite significant technical limitations, the portable chest radiograph remains the primary tool for radiographic evaluation of patients with the acute respiratory distress syndrome (ARDS). Using good-quality films, experienced observers usually can distinguish permeability-induced from nonpermeability-induced pulmonary edema. In patients with ARDS, the chest radiograph typically shows rapid dramatic deterioration within 24 hrs, as indicated by the development of patchy peripheral infiltrates. Radiographic density may increase in severity for 5 to 7 days, after which time, further deterioration usually signals the occurrence of another process (e.g., infection, fluid overload). In the period beyond 1 wk, where the radiograph usually remains relatively stable, the chest radiograph is most useful in detecting complications of therapy, predominantly barotrauma. The vast majority of survivors of ARDS show improvement in their radiographs within the first 10 to 14 days after the onset of illness. Failure to show improvement during this time is a poor prognostic factor. Computed tomography is a useful modality in patients with questionable chest radiograph findings, provided that the patients are stable enough to leave the ICU for evaluation.

Capillary Permeability↗