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Biomedical subjects

S B Higgins

Publications and source records attributed to S B Higgins.

18 recordsLinked to original sources
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↗
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↗
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↗
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↗
PubMed1991

A generic algorithm for finding restriction sites within DNA sequences.

This paper describes a generic algorithm for finding restriction sites within DNA sequences. The 'genericity' of the algorithm is made possible through the use of set theory. Basic elements of DNA sequences, i.e. nucleotides (bases), are represented in sets, and DNA sequences, whether specific, ambiguous or even protein-coding, are represented as sequences of those sets. The set intersection operation demonstrates its ability to perform pattern-matching correctly on various DNA sequences. The performance analysis showed that the degree of complexity of the pattern matching is reduced from exponential to linear. An example is given to show the actual and potential restriction sites, derived by the generic algorithm, in the DNA sequence template coding for a synthetic calmodulin.

Algorithms↗
PubMed1991

Prostacyclin and thromboxane A2 formation is increased in human sepsis syndrome. Effects of cyclooxygenase inhibition.

Arachidonic acid metabolites, especially thromboxane-A2 and prostacyclin, have been shown to be increased in experimental models of sepsis and the adult respiratory distress syndrome (ARDS) and play a major pathophysiologic role. This study was designed to determine if these metabolites are increased in human sepsis syndrome and if inhibition of fatty acid cyclooxygenase affects their formation and their pathophysiologic sequelae. We conducted a double-blind, placebo-controlled trial of ibuprofen (800 mg given rectally every 4 h for three doses) in 30 patients with sepsis syndrome defined by abnormal vital signs, the appearance of serious infection, and at least one major organ failure. Urinary concentrations of the metabolite of thromboxane-A2, 2,3-dinor-TxB2, and prostacyclin, 2,3-dinor-6-keto-prostaglandin F2 alpha, were elevated 10 to 20 times normal and declined to four to five times normal by 12 h after entry in the ibuprofen-treated group and remained elevated in the placebo-treated patients. The urinary concentration of TxB2 and 6-keto-prostaglandin F1 alpha, which reflect renal production of TxA2 and prostacyclin, respectively, were also increased approximately 10-fold over normal and were subsequently decreased by ibuprofen. Coincident with the reduction in metabolite levels, the ibuprofen-treated group, but not the placebo-treated group, experienced a significant decline in temperature, heart rate, and peak airway pressure, and a trend towards more rapid reversal of shock (p = 0.12).(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclooxygenase Inhibitors↗
PubMed1991

A graphical ICU workstation.

A workstation designed to facilitate electronic charting in the intensive care unit is described. The system design incorporates a graphical, windows-based user interface. The system captures all data formerly recorded on the paper flowsheet including direct patient measurements, nursing assessment, patient care procedures, and nursing notes. It has the ability to represent charted data in a variety of graphical formats, thereby providing additional insights to facilitate the management of the critically ill patient. Initial nursing evaluation is described.

Attitude of Health Personnel↗
PubMed1990

A knowledge-based experimental design system for nucleic acid engineering.

Presented in this paper is a knowledge-based experimental design system that incorporates the domain expertise used in nucleic acid engineering, thus automating the processing of error-prone, laborious low-level work, and many decision-making steps, and guiding the biologist toward a workable plan. This allows the biologist to work at a higher abstraction level, concentrating on more fundamental, difficult and challenging problems directly related to protein structure - function relationships. Cassette-based site-directed mutagenesis and synthetic gene designs are used as examples to illustrate the utility of the knowledge-based system approach to experimental design.

Algorithms↗
PubMed1990

Lung microvascular transport properties measured by multiple indicator dilution methods in patients with adult respiratory distress syndrome. A comparison between patients reversing respiratory failure and those failing to reverse.

We conducted indicator dilution studies on the lungs of patients in the early phases of adult respiratory distress syndrome (ARDS) to test the hypothesis that capillary permeability was increased in patients with respiratory failure. Indicator dilution studies were performed using 51Cr-erythrocytes, 125I-albumin, 14C-urea, and 3H-water as tracers. The injectate was infused as a bolus into a central venous line. Peripheral arterial blood was collected and counted for radioactivity. Mathematical analysis of the indicator curves yielded cardiac output, measures of the product of capillary permeability and surface area for urea (PS and D1/2S), the intravascular lung volume (Vv), and the extravascular lung water volume (Ve). Permeability was separated from surface area by normalizing PS and D1/2S to Vv. Patients could be divided into 16 in whom blood gas determinations and radiologic criteria for ARDS were reversed and 23 in whom they were not. We examined indicator dilution and other measures of lung function in the two groups to determine whether significant differences in microvascular function existed. PS and PS/Vv were significantly higher in the nonreversal patients. Ve was above normal, but not different between groups. Linear regression analysis showed significant correlations for all of the following in the nonreversal group: Ve and all measures of permeability, pulmonary vascular resistance (PVR), and the inverse of permeability-surface area measures and AaDO2 and PVR. Only measures of Ve and PS correlated in the reversal group. These results support the hypothesis that capillary permeability is increased in patients with early ARDS and continuing respiratory failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Transport↗
PubMed1988

A knowledge-based system for cassette mutagenesis experimental design.

A knowledge-based system for the design and planning of cassette mutagenesis experiments has been developed for scientists working in the field of structural biology and protein engineering. The system applies domain-specific knowledge to manage the menial details and automate most of the decision-making steps involved in the design process. This allows scientists to work at a high abstraction level, and results in significant time savings and increased productivity. The system also includes an automated documentation facility to improve the efficiency and accuracy of record keeping.

Artificial Intelligence↗
PubMed1981

Comparison of radionuclide and contrast ventriculography for detection and quantitation of regions of myocardial ischemia in dogs.

Radionuclide and contrast ventriculography were evaluated for their ability to estimate myocardial ischemia. In 14 closed-chest, sedated dogs, a small and larger region of ischemia were produced by inflating balloon occluders on the left anterior descending coronary artery. The systemic arterial pressure, atrial-paced heart rate, global ejection fraction by radionuclide and contrast ventriculography, regional wall-motion abnormalities (as the percentage of abnormally contracting segments), and regional myocardial blood flow (using the microsphere technique) were measured during an initial control period, two separate ischemic periods, and a final control period. The regional ischemic weights based on myocardial blood flow ranged from 0 to 38.5 g and were grouped as zero, small (range 0 to less than 10 g, mean 3.40 g), and large regions of ischemia (greater than 10 g, mean 24.8 g). Regional wall-motion abnormalities were sensitive qualitative indicators of ischemia. Receiver operating characteristic analysis showed that both ventriculographic methods were highly sensitive, specific, and accurate for detecting regional ischemia. Contrast ventriculography was slightly superior for detecting small regions less than 4 g, but the methods were equal for regions greater than 4 g. The arterial pressure and heart rate were unchanged during ischemia. For small regions of ischemia, the global ejection fraction did not fall using either the contrast or radionuclide technique, but it fell significantly when large regions were produced. There was a quantitative relationship between the percentage of abnormally contracting segments and the grams of myocardial ischemia (for radionuclide ventriculography, r = 0.65, P = 0.003, and for contrast ventriculography, r = 0.75, P less than 0.001), but for many small regions of ischemia, wall-motion changes were greater than anticipated, suggesting hypofunction of the continguous normal tissue. This study demonstrated that both radionuclide and contrast ventriculography were quite sensitive and specific for detecting measured amounts of regional ischemia. The functional changes resulting from ischemia are quantitatively related to the extent of regional ischemia, small areas resulting in regional wall motion abnormalities, and large areas producing both reduced global ejection fraction and wall motion changes.

Animals↗
PubMed1980

Total suppression of ventricular arrhythmias by encainide. Pharmacokinetic and electrocardiographic characteristics.

We studied the antiarrhythmic effect of a range of oral doses of encainide in 11 patients with stable high-frequency ventricular arrhythmias. Total suppression of arrhythmia was documented in 10 patients at a wide range of doses and plasma concentrations, and the suppression was subsequently verified in a placebo-controlled crossover study. Drug elimination was rapid (the half-life was 1.9 to 3.8 hours), but the margin between efficacy and side effects was sufficiently wide for therapy every six to 12 hours to be feasible in all 10 patients, with continuing outpatient treatment at six to 12 months. Marked prolongation of PR (mean, 44 per cent) and QRS (mean, 47 per cent) durations coincided with abolition of arrhythmia, but no evidence that these effects were detrimental was observed in radionuclide ventriculograms, exercise testing, or prolonged monitoring. A single patient whose arrhythmia and electrocardiogram were unchanged during therapy eliminated the drug much more slowly than the others and was the only patient in whom no O-demethyl form could be detected in plasma, suggesting that this metabolite may be active. In this study, encainide was a highly effective, well-tolerated antiarrhythmic agent.

Adult↗
PubMed1980

Tocainide therapy for refractory ventricular arrhythmias.

Tocainide, a congener of lidocaine, was used to treat symptomatic ventricular arrhythmias in 19 patients resistant to or unable to tolerate conventional agents. In this highly selected group, 15 showed good initial responses to oral therapy. Ventricular tachycardia was suppressed to a greater extent than isolated ventricular ectopic depolarizations at any plasma concentration, and upward dose-ranging showed progressive suppression of both. Arrhythmia responsiveness to lidocaine was found to be an excellent predictor of tocainide response. Of the 15 responders, one died 24 hours after stopping therapy, three died while receiving tocainide, nine stopped because of adverse reactions (five allergic), and two continue on therapy at 1 and 4 years. We conclude that tocainide is an effective agent for the short-term suppression of ventricular arrhythmias, particularly ventricular tachycardia sensitive to lidocaine, but a high incidence of adverse effects limits its application to chronic therapy in many patients.

Adult↗
PubMed1980

Antiarrhythmic efficacy, pharmacokinetics and safety of N-acetylprocainamide in human subjects: comparison with procainamide.

The antiarrhythmic efficacy and pharmacokinetics of N-acetylprocainamide (NAPA), the major metabolite of procainamide, were investigated in 23 patients with chronic, high frequency ventricular ectopic depolarizations. An extensive trial design incorporated the approaches of (1) generation of dose-response relations, (2) randomized crossover, and (3) prolonged electrocardiographic monitoring. Seven patients with reproducible suppression of arrhythmias (70 percent or greater reduction in frequency) were thus identified. The mean plasma concentration of acecainide associated with efficacy was 14.3 micrograms/ml (range 9.4 to 19.5) and with side effects (primarily gastrointestinal) was 22.5 micrograms/ml (10.6 to 37.9). The antiarrhythmic response to procainamide did not predict response to acecainide; this finding implies that estimates of the antiarrhythmic contribution of acecainide concentrations achieved during long-term procainamide therapy are unlikely to be meaningful in a given person. The mean half-life of elimination after a single 500 mg dose of acecainide was 7.5 hours; this had prolonged significantly (p < 0.05) to 10.3 hours after higher dosages. No variable examined (including acetylator phenotype) was found to be a predictor of responsiveness to acecainide. Outpatient therapy (2 to 20 months) was not associated with the development of antinculear antibodies or the lupus syndrome; one patient's procainamide-induced arthritis resolved during therapy. Acecainide, unlike procainamide, is an agent whose pharmacokinetics allow long-term therapy on a practical schedule. It is effective in a subset of patients with ventricular arrhythmias yet appears much less likely to induce the lupus syndrome seen with the parent compound.

Acecainide↗
PubMed1979

Suppression of chronic ventricular arrhythmias with propranolol.

The antiarrhythmic efficacy of propranolol was evaluated in 32 patients with chronic high frequency ventricular arrhythmias in a placebo-controlled protocol. After a placebo control period, propranolol was begun and the dosage increased sequentially until arrhythmia suppression was achieved, side effects appeared, or a maximum dosage of 960 mg/day was reached. Computerized analysis of ambulatory recordings was used to quantify the arrhythmias. Twenty-four patients had 70--100% arrhythmia suppression at plasma levels ranging from 12--1100 ng/ml (end of dosing interval). Eight patients in this group had frequent episodes of ventricular tachycardia that were totally suppressed at or below the dosage that produced greater than or equal to 70% suppression of ventricular ectopic depolarizations (VEDs). A biphasic dose-response curve was seen in five patients who responded with a decrease in arrhythmia frequency in the lower ranges of dosages but had increased frequency of ectopic rhythms as the dosage was increased above the optimal level. Only one-third of patients responded at doses less than or equal to 160 mg/day. However, with dosages of 200--640 mg/day, an additional 40% responded. Propranolol appears to control ventricular arrhythmias safely and effectively in many patients. The finding that the antiarrhythmic effect in many patients required plasma concentrations greater than those that produce substantial beta-adrenergic blockage raises a question whether blockade of cardiac beta receptors can directly account for all of the antiarrhythmic actions of propranolol.

Adult↗
PubMed1979

Scintigraphic characteristics of experimental myocardial infarct extension.

Technetium-99m-stannous pyrophosphate scintiphotos were evaluated for diagnosing and quantitating myocardial infarct (MI) extension in sedated dogs. Infarction and extension were produced by serial left anterior descending coronary artery ligations at 0 and 48 hours. We compared serial scintiphoto data with regional myocardial blood flow (MBF) (microsphere technique) and infarct histopathology. In eight control dogs, the scintigraphic MI area was stable at 24, 48, and 72 hours. In each of 11 dogs undergoing extension, the MI area increased after the 48-hour occlusion, averaging a 48.9% increase (p less than 0.001). Grossly, most extensions were mixtures of confluent necrosis and moderate (patchy) necrosis. MBF to confluent infarct tissue decreased significantly, allowing the documentation of extension by totaling the grams of newly flow-deprived tissue, but patchy infarct tissue had little flow deprivation, making it difficult to quantitate this type of extension accurately by flow criteria alone. Rarely, extension could be diagnosed using conventional histologic criteria. We concluded that the scintiphoto MI area was related quantitatively to infarct weight in both control and extension. However, it was not possible to determine that an increase in the MI scintiphoto area was an accurate predictor of the degree of extension using independent flow or pathologic criteria.

Acute Disease↗
PubMedDate not supplied

Patient monitoring systems: criteria for evaluation & selection.

Patient monitoring is more than just the acquisition and accumulation of physiological data. In order for it to be efficacious in patient diagnosis and treatment, the professional staff must be continuously involved in protocol development, evaluation, and modification. Given the constraints of these tasks, of cost limitations, and of staff interest and expertise, the clinical engineer should develop a rationale for making judgments about patient monitoring systems at his particular site. This rationale should include: evaluation of design criteria from medical, nursing, and engineering standpoints; consideration of the considerable and increasing effect of computers on monitoring; and the intelligent appraisal of technique and system development performed at other sites.

Bibliographies as Topic↗