bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytomegalovirus
Authors: Papazian Laurent , Fraisse Alain , Garbe Louise , Zandotti Christine , Thomas Pascal , Saux Pierre , Perrin Gilles , Gouin Francois 
Published: November 2003

Background
Cytomegalovirus (CMV) frequently is observed in immunocompromised hosts. The aim of this study was to report cases of ventilator-associated CMV pneumonia diagnosed by pathologic examination in intensive care patients without acquired immunodeficiency syndrome or hematologic malignancy or who were not receiving immunosuppressive agents.

Methods
From June 1, 1989, to May 31, 1994, 2,785 patients were hospitalized. During the study period, 60 autopsies and 26 open-lung biopsies were performed in nonimmunocompromised patients who were seen with acute respiratory failure and/or symptoms suggestive of ventilator-associated pneumonia. Cytomegalovirus pneumonia was diagnosed using pulmonary samples by the identification of large cells with large nuclei containing a basophilic or eosinophilic inclusion surrounded by a light halo. These typical findings always were associated with a diffuse interstitial pneumonitis.

Results
Cytomegalovirus pneumonia was diagnosed after histologic examination in 25 patients. The reason for admission to the intensive care unit was major surgery in 13 patients and medical problems in 12 patients. Ventilator-associated CMV pneumonia was diagnosed by histologic examination 22.4 +/- 8.8 days after admission to the intensive care unit (median 18 days; range 10-40 days). The clinical description was similar with the 25 patients who were seen with ventilator associated CMV pneumonia and the 61 patients without ventilator-associated CMV pneumonia. However, there was a more severe hypoxemia 72 +/- 16 vs. 95 +/- 41 mmHg, P < 0.05) and a higher Weinberg's radiologic score (9.2 +/- 1.9 vs. 7.4. +/- 2.7, P < 0.05) in the ventilator-associated CMV pneumonia group. Diagnosis of ventilator-associated CMV pneumonia was made for 9 of 17 patients when shell-vial culture technique using fluorescein-labelled antibody E 13 was performed on bronchoalveolar lavage products. Four of the eight patients treated by ganciclovir therapy died of multiple organ dysfunction syndrome.

Conclusions
The diagnosis of ventilator-associated CMV pneumonia should not be excluded in intensive care patients, even those without acquired immunodeficiency syndrome, hematologic malignancy, or immunosuppressive agents on admission.
Pharmacodynamic Interaction between Propofol and Alfentanil When Given for Induction of Anesthesia
Authors: Vuyk Jaap , Engbers Frank H. M. , Burm Anton G. L. , Vletter Arie A. , Griever Gerard E. R. , Olofsen Erik , Bovill James G. 
Published: November 2003

Background
Propofol and alfentanil often are combined during induction of anesthesia. However, the interaction between these agents during induction has not been studied in detail. The influence of alfentanil on the propofol concentration-effect relationships was studied for loss of eyelash reflex, loss of consciousness, and hemodynamic function in 20 unpremedicated ASA physical status 1 patients aged 20-55 yr.

Methods
Patients were randomly divided into four groups to receive a computer- controlled infusion of alfentanil with target concentrations of 0, 50, 200, or 400 ng/ml (groups A, B, C, and D, respectively). While the target concentration of alfentanil was maintained constant, patients received a computer- controlled infusion of propofol, with an initial target concentration of 0.5-1 microgram/ml, that was increased every 12 min by 0.5-1 microgram/ml. Every 3 min, the eyelash reflex and state of consciousness were tested an an arterial blood sample was taken for blood propofol and plasma alfentanil determination. The propofol-alfentanil concentration-response relationships for loss of eyelash reflex and loss of consciousness were determined by nonlinear regression, and for the percentage of change in systolic blood pressure and heart rate by logistic regression.

Results
The patient characteristics did not differ significantly among the four groups. The patients in groups A and B continued to breathe adequately, whereas all patients in groups C and D required assisted ventilation. End-tidal carbon dioxide partial pressure remained less than 46 mmHg in all patients. With plasma alfentanil concentrations increasing from 0 to 500 ng/ml, the EC(50) of propofol decreased from 2.07 to 0.83 microgram/ml for loss of eyelash reflex and from 3.62 to 1.55 microgram/ml for loss of consciousness. With plasma alfentanil concentrations increasing from 0 to 500 ng/ml, the blood propofol concentrations associated with a 10% decrease in systolic blood pressure and heart rate decreased from 1.68 to 0.17 microgram/ml and from 2.36 to 0.04 microgram/ml, respectively.

Conclusions
Alfentanil significantly reduces blood propofol concentrations required for loss of eyelash reflex and loss of consciousness. In addition, alfentanil enhances the depressant effects of propofol on systolic blood pressure and heart rate. Hemodynamic stability, therefore, does not increase in patients receiving propofol in combination with alfentanil compared to those receiving propofol as the sole agent for induction of anesthesia.
Mechanical Significance of Respiratory Muscle Activity in Humans during Halothane Anesthesia
Authors: Warner David O. , Warner Mark A. , Ritman Erik L. 
Published: November 2003

Background
Prior human studies have shown that halothane attenuates activity in the parasternal intercostal muscle and enhances phasic activity in respiratory muscles with expiratory actions. This expiratory muscle activity could contribute to reductions in the functional residual capacity produced by anesthesia. Termination of this activity could contribute to the maintenance of inspiratory rib cage expansion. The purpose of this study was to estimate in humans the mechanical significance of expiratory muscle activity during halothane anesthesia and to search for the presence of scalene muscle activity during halothane anesthesia that might contribute to inspiratory rib cage expansion.

Methods
Six subjects (3 males, 3 females) were studied while awake and during 1.2 MAC halothane anesthesia, both during quiet breathing and during carbon dioxide rebreathing. Respiratory muscle activity was measured using fine-wire electromyography electrodes. Chest wall configuration was determined using images of the thorax obtained by three-dimensional, fast computed tomography and respiratory impedance plethysmography. Functional residual capacity was measured by a nitrogen dilution technique. Measurements were obtained after paralysis with 0.1 mg/kg vecuronium and mechanical ventilation.

Results
Phasic inspiratory activity was present in the scalene muscle of four anesthetized subjects during quiet breathing and all anesthetized subjects during rebreathing. Phasic inspiratory activity was present in the parasternal intercostal muscle during halothane anesthesia in only the three female subjects and was enhanced by rebreathing; parasternal intercostal muscle activity was never present in anesthetized males. During anesthesia with quiet breathing, phasic expiratory activity was observed in the transversus abdominis muscles of only the three male subjects. Despite these differences in the pattern of respiratory muscle use, the pattern of chest wall responses to rebreathing was similar between males and females. When expiratory muscle activity was present, paralysis increased the end-expiratory thoracic volume by expanding the rib cage, demonstrating that this activity reduced thoracic volume in these subjects. Changes in thoracic blood volume were significant determinants of the change in functional residual capacity produced by paralysis.

Conclusions
In humans anesthetized with 1.2 MAC end-tidal halothane, there are marked interindividual differences in respiratory muscle use during quiet breathing that may be related to sex; phasic inspiratory scalene muscle and parasternal intercostal muscle activity may contribute to inspiratory rib cage expansion in some subjects; and when present, expiratory muscle activity significantly constricts the rib cage and contributes to reductions in functional residual capacity caused by halothane anesthesia.
Theoretical Assessment of Normobaric Oxygen Therapy to Treat Pneumocephalus
Authors: Dexter Franklin , Reasoner Daniel K. 
Published: November 2003

Background
Pneumocephalus has been linked to several clinical conditions, including headache, lethargy, and even brain herniation or death. The effects of different normobaric oxygen concentrations and durations of therapy on the rate of air absorption were examined.

Methods
An existing mathematical model of inert gas absorption was used. The model accounts for the major phenomena that determine absorption of bubbles, including surface tension, pressure dependence of bubble size, and removal of gases to the surrounding tissue. Sensitivity analysis tested reliability of our results.

Results
Times for a 50-ml air collection to have been absorbed were 5.8, 1.9, and 0.6 weeks at an FIO2 of 0.21, 0.4, and 1.0 respectively. Thirty percent and 72% of the air was absorbed in 2 days at an FIO2 of 0.4 and 1.0, respectively. The percent decrease in time for absorption achieved by increasing the FIO2 from 0.21 was nearly identical for different volumes of air. The benefit of increasing the FIO2 decreased with progressive increases in the FIO2. Increasing the FIO2 from 0.21 to 0.4 caused the time to total air absorption to decrease by 67%. In contrast, increasing the FIO2 from 0.8 to 1.0 caused the time to total air absorption to decrease by an additional 3%.

Conclusions
Based on mathematical model predictions, an FIO2 of 0.4 or 1.0 for at least 1 week or 2 days, respectively, will significantly decrease the time for absorption of a pneumocephalus.
Semilinear Canonical Correlation Applied to the Measurement of the Electroencephalographic Effects of Midazolam and Flumazenil Reversal
Authors: Schnider Thomas W. , Minto Charles F. , Fiset Pierre , Gregg Keith M. , Shafer Steven L. 
Published: November 2003

Background
The electroencephalographic (EEG) effect of benzodiazepines, and midazolam in particular, has been described using simple measures such as total power in the beta band, waves.s(-1) in the beta band and total power from aperiodic analysis. All these parameters failed to consistently describe the EEG effect of midazolam in a study in which large doses of midazolam were infused, and the effect subsequently reversed with flumazenil. Using a technique called semilinear correlation it is possible to extract a parameter from the EEG that is statistically optimally correlated with the apparent concentration of the benzodiazepine in the effect site. This method has been used to develop new univariate measures of the effects of opioids on the EEG but has not previously been applied to the EEG effects of benzodiazepines.

Methods
Data from ten subjects who received an infusion of midazolam were analyzed. The data were divided into "learning" and "test" sets. The learning set consisted of ten studies in which the volunteers received an infusion of 2.5 mg.min(-1) midazolam. Semilinear canonical correlation was used to extract an univariate descriptor of the EEG effect by weighting the different frequency bands of the EEG power spectrum. The test set comprised the same subjects on subsequent visits, in which the subjects received a continuous infusion of midazolam to maintain 20% or 80% of the peak drug effect for 3h. Twenty minutes after start of the midazolam infusion, the patient received an infusion of flumazenil to acutely reverse the benzodiazepine drug effect. The weights obtained from the learning set were tested prospectively in the test set, based on the coefficient of multiple determination, R(2), obtained by fitting the EEG effect to a sigmoid Emax model.

Results
The canonical univariate parameter of benzodiazepine drug effect on the EEG, when applied to the test set receiving the midazolam infusion with flumazenil reversal, yielded a median R(2) of 0.78. The median R(2) of six commonly used empirical EEG measures of drug effect ranged from 0.18 to 0.55.

Conclusions
The canonical univariate parameter for benzodiazepine drug effect on the EEG correlates more accurately and consistently with the predicted EEG effects of midazolam and its reversal than previously reported EEG measures of benzodiazepine effect.
Pharmacodynamics and Pharmacokinetics of Cisatracurium in Geriatric Surgical Patients
Authors: Ornstein Eugene , Lien Cynthia A , Matteo Richard S. , Ostapkovich Noeleen D. , Diaz Jaime , Wolf Karen B. 
Published: November 2003

Background
Cisatracurium, one of ten stereoisomers that comprise atracurium, is more potent than atracurium and has less propensity to release histamine. This study compares the pharmacokinetics and pharmacodynamics of cisatracurium in elderly and young patients.

Methods
Twelve elderly (aged 65-82 yr) and 12 younger patients (aged 30-49 yr) were anesthetized with nitrous oxide, fentanyl, and isoflurane (0.7%, end-tidal). The mechanomyographic response to train-of-four stimulation was assessed every 15 s after the administration of cisatracurium (0.1 mg/kg). Arterial samples were obtained over 6 h. Plasma cisatracurium concentration versus time data were fit to compartmental models. Pharmacokinetic parameters were determined assuming that elimination occurred from the central compartment only. This provides accurate clearance and half-life estimates but underestimates V(ss) (reported herein as V(ss). The pharmacodynamic response was described by the neuromuscular blocking profile.

Results
Onset to 90% paralysis (mean +/- SD) was delayed in the elderly (3.4 +/- 1.0 vs. 2.5 +/- 0.6 min). Recovery profiles were the same for both groups. Elimination half-life was minimally prolonged in the elderly (25.5 +/- 3.7 vs. 21.5 +/- 2.4 min). The Vss was larger in the elderly (126 +/- 16 vs. 108 +/- 13 ml/kg), although the clearances were the same for the two groups (5.0 +/- 0.9 vs. 4.6 +/- 0.8 ml.kg(-1).min(-1).

Conclusions
There are minor differences in the pharmacokinetics of cisatracurium between elderly and young patients. These differences are not associated with changes in recovery profile after a single bolus dose, although the mean time to onset was approximately 1 min longer in elderly patients.
Propofol Inhibits Cardiac L-Type Calcium Current in Guinea Pig Ventricular Myocytes
Authors: Yang Ching-Yue , Wong Chih-Shung , Yu Chuan-Cheng , Luk Hsiang-Ning , Lin Cheng-I 
Published: November 2003

Background
Propofol may exert negative inotropic and chronotropic actions in the heart. Single-channel studies show that propofol affects the kinetics of opening and closing of cardiac L-type calcium channels (ICa(L)) without altering channel conductance. The aim of this study was to investigate the mechanisms of depressant effects of propofol on cardiac whole-cell ICa(L).

Methods
Single ventricular myocytes were freshly dissciated from guinea pig hearts using enzymatic isolation. One-suction electrode voltage-clamp technique (whole-cell mode) was used. LCa(L) was separated from other contaminated ionic currents. Propofol was applied in the commercial 10% Intralipid emulsion formula (Zeneca, UK).

Results
In isolated cardiomyocytes, propofol significantly inhibited whole-cell ICa(L) in a concentration-dependent manner (K D = 52.0 microM; Hill coefficient = 1.3). The solvent (Intralipid) did not affect ICa(L). Propofol decreased ICa(L) at all potentials tested along the voltage axis and reduced the slope conductance. The threshold potential for activation and the peak potential of the current-voltage relationship were not changed by propofol. The steady-state activation curves overlapped in the absence and the presence of 56 microM propofol. In contrast, the steady-state inactivation curve was shifted in the hyperpolarizing direction. The time course of the recovery from inactivation was delayed by 56 microM propofol. The blocking action on ICa(L) of propofol shows marked resting block and use-dependent block. Propofol caused more pronounced inhibition at a higher stimulation frequency. The effect of propofol on the inactivation process was even more clear on ICa(L).

Conclusions
The authors conclude tha propofol, at supratherapeutic concentrations, inhibits cardiac ICa(L). This inhibition is mainly due to a shift of inactivation curve and a reduction in slope conductance.
Ventilation with Constant Versus Decelerating Inspiratory Flow in Experimentally Induced Acute Respiratory Failure
Authors: Markstrom Agneta M. , Lichtwarck-Aschoff Michael , Svensson Bjorn A. , Nordgren K. Anders , Sjostrand Ulf H. 
Published: November 2003

Background
Recognition of the potential for ventilator-associated lung injury has renewed the debate on the importance of the inspiratory flow pattern. The aim of this study was to determine whether a ventilatory pattern with decelerating inspiratory flow, with the major part of the tidal volume delivered early, would increase functional residual capacity at unchanged (or even reduced) inspiratory airway pressures and improve gas exchange at different positive end-expiratory pressure levels.

Methods
Surfactant depletion was induced by repeated bronchoalveolar lavage in 13 anesthetized piglets. Decelerating and constant inspiratory flow ventilation was applied at positive end-expiratory pressure levels of 22, 17, 13, 9, and 4 cm H(2)O. Tidal volume, inspiration-to-expiration ratio, and ventilatory frequency were kept constant. Airway pressures, gas exchange, functional residual capacity (using a wash-in/washout method with sulfurhexafluoride), central hemodynamics, and extravascular lung water (using the thermo-dye-indicator dilution technique) were measured.

Results
Decelerating inspiratory flow yielded a lower arterial carbon dioxide tension compared to constant flow, that is, it improved alveolar ventilation. There were no differences between the flow patterns regarding end-inspiratory occlusion airway pressure, end-inspiratory lung volume, static compliance, or arterial oxygen tension. No differences were seen in hemodynamics and oxygen delivery.

Conclusions
The decelerating inspiratory flow pattern increased carbon dioxide elimination, without any reduction of inspiratory airway pressure or apparent improvement in arterial oxygen tension. It remains to be established whether these differences are sufficiently pronounced to justify therapeutic consideration.
Pseudocholinesterase-mediated Hydrolysis Is Superior to Neostigmine for Reversal of Mivacurium-induced Paralysis In Vitro
Authors: Yang H. S. , Goudsouzian N. , Martyn J. A. J. 
Published: November 2003

Background
The metabolic hydrolysis of mivacurium (and succinylcholine) is markedly impaired in the presence of hereditary or acquired defects of pseudocholinesterase. Clinical reports are conflicting as to the utility of anticholinesterases, in the reversal of mivacurium paralysis. In the current study, the role of exogenous cholinesterases and/or of anticholinesterase, neostigmine, in the reversal of deep mivacurium-induced paralysis, was studied. The rat phrenic-diaphragm preparation, in a fixed volume of Krebs solution, was chosen to eliminate the confounding effects on the dissipation of neuromuscular effects caused by hydrolysis, elimination, and redistribution of the drug.

Methods
In the phrenic-diaphragm preparation, mivacurium was administered to obtain >90% single twitch inhibition. Single twitch responses (0.1 Hz) were monitored for 60 min, after which the response to train-of-four stimulation was tested. The reversal of mivacurium by 0.5, 1.0, or 2.0 units/ml of (true) acetylcholinesterase, bovine pseudocholinesterase, or human plasma cholinesterase and by neostigmine, 0.1, 1.0, or 10.0 micrograms/ml tested. The efficacy of human plasma cholinesterase, 1 unit/ml in combination with each of the above neostigmine concentrations, also was examined. The reversal of succinylcholine-induced paralysis by the acetylcholinesterase, bovine pseudocholinesterase, or human plasma cholinesterase (1 unit/ml) alone and in the presence of neostigmine (10.0 micrograms/ml) was additionally tested as a positive control. A train-of-four ratio > 0.75 was considered adequate reversal.

Results
Acetylcholinesterase was a poor hydrolyzer of mivacurium, as bioassayed by reversal of paralysis. Bovine pseudocholinesterase in concentrations of 0.5 and 1.0 units/ml did not effectively reverse single twitch and train-of-four responses by 60 min, but bovine pseudocholinesterase (2 units/ml) and all concentrations of human plasma cholinesterase did. Neostigmine alone, tested at all concentrations, was an incomplete reversal drug. Clinical or therapeutic concentrations (0.1 and 1.0 micrograms/ml) of neostigmine did not, but pharmacologic concentrations (10 micrograms/ml) interfere with the efficacy of human plasma cholinesterase (1 unit/ml). Bovine pseudocholinesterase and human plasma cholinesterase equally reversed the effects of succinylcholine but acetylcholinesterase did not, whereas the addition of 10 micrograms/ml neostigmine to the enzymes inhibited the reversal of succinylcholine.

Conclusions
Human plasma cholinesterase will reverse mivacurium more effectively than bovine pseudocholinesterase, but both will effectively reverse succinylcholine. Acetylcholinesterase has no effects on either relaxant. The anticholinesterase neostigmine was an incomplete reversal drug. Pharmacologic concentrations of anticholinesterases do, while clinical or therapeutic concentrations do not, completely inhibit the metabolic activity of pseudocholinesterases.