Carotid intima-medial thickness measured on multiple ultrasound frames: evaluation of a DICOM-based software system

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Human physiologically based pharmacokinetic model for propofol

BACKGROUND: Propofol is widely used for both short-term anesthesia and long-term sedation. It has unusual pharmacokinetics because of its high lipid solubility. The standard approach to describing the pharmacokinetics is by a multi-compartmental model. This paper presents the first detailed human physiologically based pharmacokinetic (PBPK) model for propofol. METHODS: PKQuest, a freely distributed software routine , was used for all the calculations. The "standard human" PBPK parameters developed in previous applications is used. It is assumed that the blood and tissue binding is determined by simple partition into the tissue lipid, which is characterized by two previously determined set of parameters: 1) the value of the propofol oil/water partition coefficient; 2) the lipid fraction in the blood and tissues. The model was fit to the individual experimental data of Schnider et. al., Anesthesiology, 1998; 88:1170 in which an initial bolus dose was followed 60 minutes later by a one hour constant infusion. RESULTS: The PBPK model provides a good description of the experimental data over a large range of input dosage, subject age and fat fraction. Only one adjustable parameter (the liver clearance) is required to describe the constant infusion phase for each individual subject. In order to fit the bolus injection phase, for 10 or the 24 subjects it was necessary to assume that a fraction of the bolus dose was sequestered and then slowly released from the lungs (characterized by two additional parameters). The average weighted residual error (WRE) of the PBPK model fit to the both the bolus and infusion phases was 15%; similar to the WRE for just the constant infusion phase obtained by Schnider et. al. using a 6-parameter NONMEM compartmental model. CONCLUSION: A PBPK model using standard human parameters and a simple description of tissue binding provides a good description of human propofol kinetics. The major advantage of a PBPK model is that it can be used to predict the changes in kinetics produced by variations in physiological parameters. As one example, the model simulation of the changes in pharmacokinetics for morbidly obese subjects is discussed

Impact of the frequency of online verifications on the patient set-up accuracy and set-up margins

<p>Abstract</p> <p>Purpose</p> <p>The purpose of the study was to evaluate the patient set-up error of different anatomical sites, to estimate the effect of different frequencies of online verifications on the patient set-up accuracy, and to calculate margins to accommodate for the patient set-up error (ICRU set-up margin, SM).</p> <p>Methods and materials</p> <p>Alignment data of 148 patients treated with inversed planned intensity modulated radiotherapy (IMRT) or three-dimensional conformal radiotherapy (3D-CRT) of the head and neck (n = 31), chest (n = 72), abdomen (n = 15), and pelvis (n = 30) were evaluated. The patient set-up accuracy was assessed using orthogonal megavoltage electronic portal images of 2328 fractions of 173 planning target volumes (PTV). In 25 patients, two PTVs were analyzed where the PTVs were located in different anatomical sites and treated in two different radiotherapy courses. The patient set-up error and the corresponding SM were retrospectively determined assuming no online verification, online verification once a week and online verification every other day.</p> <p>Results</p> <p>The SM could be effectively reduced with increasing frequency of online verifications. However, a significant frequency of relevant set-up errors remained even after online verification every other day. For example, residual set-up errors larger than 5 mm were observed on average in 18% to 27% of all fractions of patients treated in the chest, abdomen and pelvis, and in 10% of fractions of patients treated in the head and neck after online verification every other day.</p> <p>Conclusion</p> <p>In patients where high set-up accuracy is desired, daily online verification is highly recommended.</p

Understanding Novel Superconductors with Ab Initio Calculations

This chapter gives an overview of the progress in the field of computational superconductivity. Following the MgB2 discovery (2001), there has been an impressive acceleration in the development of methods based on Density Functional Theory to compute the critical temperature and other physical properties of actual superconductors from first-principles. State-of-the-art ab-initio methods have reached predictive accuracy for conventional (phonon-mediated) superconductors, and substantial progress is being made also for unconventional superconductors. The aim of this chapter is to give an overview of the existing computational methods for superconductivity, and present selected examples of material discoveries that exemplify the main advancements.Comment: 38 pages, 10 figures, Contribution to Springer Handbook of Materials Modellin

Cerebral cortical effects of desflurane in sheep: comparison with isoflurane, sevoflurane and enflurane

The definitive version is available at www.blackwell-synergy.comBackground:  Different volatile anesthetic agents have differing propensities for inducing seizures. A measure of the predilection to develop seizures is the presence of interictal spike discharges (spikes) on the electrocorticogram (ECoG). In this study, we investigated the propensity of desflurane to induce cortical spikes and made a direct objective comparison with enflurane, isoflurane, and sevoflurane. The ECoG effects of desflurane have not been previously reported. Methods:  After establishment of invasive monitoring and a parasagittal array of eight electrodes to record the ECoG; eight adult merino sheep were given a series of short inhalational anesthetics (using desflurane, enflurane, sevoflurane and isoflurane); each titrated to ECoG burst suppression. Anesthetic effect was estimated by the effects on the approximate entropy of the ECoG. The effect of anesthetic on the spike-rate in the ECoG was analyzed using a non-linear mixed-effect method with a sigmoid Emax model. Results:  A similar `depth of anesthesia' was achieved for each agent, as estimated by the approximate entropy. The mean (SD) values of Emax for the spike-rate vs. approximate entropy relationship were desflurane 0.5 (0.9), enflurane 17.2 (4.0), isoflurane 0.7 (1.2), and sevoflurane 5.3 (1.2) spikes/min. The spike rate caused by desflurane was similar to isoflurane and significantly lower than that of enflurane (P > sevoflurane > isoflurane = desflurane.Voss, L.J.; Ludbrook, G.; Grant, C.; Sleigh, J.W. and Barnard, J.P.M

Progression of cardiovascular and endocrine dysfunction in a rabbit model of obesity

In rabbits, mean arterial pressure (MAP) increases in response to fat feeding, but does not increase further with progressive weight gain. We documented the progression of adiposity and the alterations in endocrine/cardiovascular function in response to fat feeding in rabbits, to determine whether stabilization of MAP after 3 weeks could be explained by stabilization of neurohormonal factors. Rabbits were fed a control diet or high-fat diet for 9 weeks (n&frac14;23). Fat feeding progressively increased body mass and adiposity. Heart rate (HR) was elevated by week 3 (15&plusmn;3%) but changed little thereafter. The effects of fat feeding on MAP were dependent on baseline MAP and peaked at 3 weeks. From baseline, MAP p80mmHg, MAP had increased by 8.1&plusmn;1.3, 4.7&plusmn;1.7 and 5.6&plusmn;1.2mmHg, respectively, 3, 6 and 9 weeks after commencing the high-fat diet, but by only 2.6&plusmn;1.5, 3.0&plusmn;1.7 and 3.9&plusmn;1.4mmHg, respectively, in control rabbits. Fat feeding did not increase MAP from a baseline 480mmHg. Plasma concentrations of leptin and insulin increased during the first 3&ndash;6 weeks of fat feeding and then stabilized (increasing by 111&plusmn;17% and 731&plusmn;302% by week 9, respectively), coinciding with the pattern of changes in MAP and HR. Plasma total cholesterol, triglycerides, renin activity, aldosterone and atrial natriuretic peptide were not significantly altered by fat feeding. Given that the changes in plasma leptin and insulin mirrored the changes in MAP and HR, leptin and insulin may be important factors in the development of hypertensionand tachycardia in the rabbit model of obesity