An evaluation of remifentanil-sevoflurane response surface models in patients emerging from anesthesia: model improvement using effect-site sevoflurane concentrations.

INTRODUCTION: We previously reported models that characterized the synergistic interaction between remifentanil and sevoflurane in blunting responses to verbal and painful stimuli. This preliminary study evaluated the ability of these models to predict a return of responsiveness during emergence from anesthesia and a response to tibial pressure when patients required analgesics in the recovery room. We hypothesized that model predictions would be consistent with observed responses. We also hypothesized that under non-steady-state conditions, accounting for the lag time between sevoflurane effect-site concentration (Ce) and end-tidal (ET) concentration would improve predictions. METHODS: Twenty patients received a sevoflurane, remifentanil, and fentanyl anesthetic. Two model predictions of responsiveness were recorded at emergence: an ET-based and a Ce-based prediction. Similarly, 2 predictions of a response to noxious stimuli were recorded when patients first required analgesics in the recovery room. Model predictions were compared with observations with graphical and temporal analyses. RESULTS: While patients were anesthetized, model predictions indicated a high likelihood that patients would be unresponsive (> or = 99%). However, after termination of the anesthetic, models exhibited a wide range of predictions at emergence (1%-97%). Although wide, the Ce-based predictions of responsiveness were better distributed over a percentage ranking of observations than the ET-based predictions. For the ET-based model, 45% of the patients awoke within 2 min of the 50% model predicted probability of unresponsiveness and 65% awoke within 4 min. For the Ce-based model, 45% of the patients awoke within 1 min of the 50% model predicted probability of unresponsiveness and 85% awoke within 3.2 min. Predictions of a response to a painful stimulus in the recovery room were similar for the Ce- and ET-based models. DISCUSSION: Results confirmed, in part, our study hypothesis; accounting for the lag time between Ce and ET sevoflurane concentrations improved model predictions of responsiveness but had no effect on predicting a response to a noxious stimulus in the recovery room. These models may be useful in predicting events of clinical interest but large-scale evaluations with numerous patients are needed to better characterize model performance.

Application of particle swarm optimisation to evaluation of polymer cure kinetics models

A particle swarm optimisation approach is used to determine the accuracy and experimental relevance of six disparate cure kinetics models. The cure processes of two commercially available thermosetting polymer materials utilised in microelectronics manufacturing applications have been studied using a differential scanning calorimetry system. Numerical models have been fitted to the experimental data using a particle swarm optimisation algorithm which enables the ultimate accuracy of each of the models to be determined. The particle swarm optimisation approach to model fitting proves to be relatively rapid and effective in determining the optimal coefficient set for the cure kinetics models. Results indicate that the singlestep autocatalytic model is able to represent the curing process more accurately than more complex model, with ultimate accuracy likely to be limited by inaccuracies in the processing of the experimental data.

Evaluation of glycated glucagon-like peptide-1(7-36)amide in intestinal tissue of normal and diabetic animal models

Glucagon-like peptide-1(7-36)amide (tGLP-1) is an important insulin-releasing hormone of the enteroinsular axis which is secreted by endocrine L-cells of the small intestine following nutrient ingestion. The present study has evaluated tGLP-1 in the intestines of normal and diabetic animal models and estimated the proportion present in glycated form. Total immunoreactive tGLP-1 levels in the intestines of hyperglycaemic hydrocortisone-treated rats, streptozotocin-treated mice and ob/ob mice were similar to age-matched controls. Affinity chromatographic separation of glycated and non-glycated proteins in intestinal extracts followed by radioimmunoassay using a fully crossreacting anti-serum demonstrated the presence of glycated tGLP-1 within the intestinal extracts of all control animals (approximately 19%., of total tGLP-1 content). Chemically induced and spontaneous animal models of diabetes were found to possess significantly greater levels of glycated tGLP-1 than controls, corresponding to between 24-71% of the total content. These observations suggest that glycated tGLP-1 may be of physiological significance given that such N-terminal modification confers resistance to DPP IV inactivation and degradation, extending the very short half-life (

Pharmacological evaluation of selective α2c-adrenergic agonists in experimental animal models of nasal congestion

Nasal congestion is one of the most troublesome symptoms of many upper airways diseases. We characterized the effect of selective α2c-adrenergic agonists in animal models of nasal congestion. In porcine mucosa tissue, compound A and compound B contracted nasal veins with only modest effects on arteries. In in vivo experiments, we examined the nasal decongestant dose-response characteristics, pharmacokinetic/pharmacodynamic relationship, duration of action, potential development of tolerance, and topical efficacy of α2c-adrenergic agonists. Acoustic rhinometry was used to determine nasal cavity dimensions following intranasal compound 48/80 (1%, 75 µl). In feline experiments, compound 48/80 decreased nasal cavity volume and minimum cross-sectional areas by 77% and 40%, respectively. Oral administration of compound A (0.1-3.0 mg/kg), compound B (0.3-5.0 mg/kg), and d-pseudoephedrine (0.3 and 1.0 mg/kg) produced dose-dependent decongestion. Unlike d-pseudoephedrine, compounds A and B did not alter systolic blood pressure. The plasma exposure of compound A to produce a robust decongestion (EC(80)) was 500 nM, which related well to the duration of action of approximately 4.0 hours. No tolerance to the decongestant effect of compound A (1.0 mg/kg p.o.) was observed. To study the topical efficacies of compounds A and B, the drugs were given topically 30 minutes after compound 48/80 (a therapeutic paradigm) where both agents reversed nasal congestion. Finally, nasal-decongestive activity was confirmed in the dog. We demonstrate that α2c-adrenergic agonists behave as nasal decongestants without cardiovascular actions in animal models of upper airway congestion.

An experimental evaluation of prediction models for the mechanical behavior of unreinforced, lime-mortar masonry under compression

This paper contributes to the understanding of lime-mortar masonry strength and deformation (which determine durability and allowable stresses/stiffness in design codes) by measuring the mechanical properties of brick bound with lime and lime-cement mortars. Based on the regression analysis of experimental results, models to estimate lime-mortar masonry compressive strength are proposed (less accurate for hydrated lime (CL90s) masonry due to the disparity between mortar and brick strengths). Also, three relationships between masonry elastic modulus and its compressive strength are proposed for cement-lime; hydraulic lime (NHL3.5 and 5); and hydrated/feebly hydraulic lime masonries respectively.

Disagreement between the experimental results and former mathematical prediction models (proposed primarily for cement masonry) is caused by a lack of provision for the significant deformation of lime masonry and the relative changes in strength and stiffness between mortar and brick over time (at 6 months and 1 year, the NHL 3.5 and 5 mortars are often stronger than the brick). Eurocode 6 provided the best predictions for the compressive strength of lime and cement-lime masonry based on the strength of their components. All models vastly overestimated the strength of CL90s masonry at 28 days however, Eurocode 6 became an accurate predictor after 6 months, when the mortar had acquired most of its final strength and stiffness.

The experimental results agreed with former stress-strain curves. It was evidenced that mortar strongly impacts masonry deformation, and that the masonry stress/strain relationship becomes increasingly non-linear as mortar strength lowers. It was also noted that, the influence of masonry stiffness on its compressive strength becomes smaller as the mortar hydraulicity increases.