Articles: biological-models.
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Development of effect compartment model theory has greatly enhanced our understanding of the relationship between pharmacokinetics and pharmacodynamics. When effect versus concentration in serum (usually total concentration) is plotted and counterclockwise hysteresis is observed, an initial disequilibrium between receptor(s) and serum is generally presumed and an effect compartment model is used; alternatively, clockwise hysteresis may infer tolerance, which may be characterized by an adaptation model. In this simulation study, the influence of time-dependent binding to serum protein on the relationship between effect and concentration in serum was investigated. ⋯ Clockwise hysteresis, consistent with tolerance, occurred with a time-dependent increase in binding to serum protein. For both sets of simulations, no hysteresis was observed when response was plotted against concentration of free drug in serum. These results indicate that, when response is related to concentration of free drug, measurement of concentration of free drug may allow a clearer interpretation of the pharmacokinetic-pharmacodynamic relationship.
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Acta Anaesthesiol Scand · Jan 1992
A new ventilator converter with the Siemens Servo Ventilator--evaluation in a lung model.
A ventilator converter device (Anmedic) for connecting a non-rebreathing ventilator (Servo Ventilator 900 B; Siemens-Elema) to a circle anaesthesia system was evaluated in a lung model. Recorded minute ventilation was slightly lower than dialled in most cases. We furthermore found inadequate expiratory expansion of the ventilator converter bellows, with progressive loss of tidal volume and consequently recorded minute volume, when fresh gas flow to the circle system was low (1 l.min-1), expiratory time was short (less than 40%) and respiratory obstruction was present.
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Pediatric pulmonology · Jan 1992
Comparative StudyHigh-frequency oscillatory ventilation compared with conventional mechanical ventilation in newborn lambs: effects of increasing airway pressure on intracranial pressures.
We tested the hypothesis that intracranial pressures and cerebral perfusion pressure in the newborn are more seriously affected by increasing airway pressure during high-frequency oscillatory ventilation (HFOV) than during conventional mechanical ventilation (CMV). Mean airway pressure was acutely elevated in stepwise fashion to 25 cm H2O in six anesthetized, paralyzed newborn lambs. Pressure (mean +/- SE) increased similarly during HFOV and CMV in the jugular vein (7 +/- 1 and 8 +/- 1 cm H2O, respectively), the sagittal sinus (6 +/- 1 and 7 +/- 1 cm H2O), and the cerebrospinal fluid of the lateral ventricle (4 +/- 1 and 6 +/- 1 cm H2O). ⋯ Intracranial pressure-volume curves were generated by incrementing cerebrospinal fluid volume in eight lambs. Curves generated during HFOV and CMV were similar, reflecting a similar intracranial compliance during the two ventilatory modes. These data indicate that intracranial compliance and the effects of increasing airway pressure upon intracranial pressures are not significantly different between HFOV and CMV.
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J Pharmacokinet Biopharm · Dec 1991
Reversal of neuromuscular blockade in humans by neostigmine and edrophonium: a mathematical model.
Generalizations of the integrated model describing the interaction of nondepolarizing neuromuscular blocking drugs with reversible anticholinesterase drugs described in Unadkat et al. (1) are reported. The models can deal with possible incomplete reversal (irreversible block) and/or noninstantaneous anticholinesterase kinetics. Experimental data were obtained from 22 human volunteers. ⋯ In the case of neostigmine we find a nondistributional delay in its action. We relate this delay to the slow decarbamylation rate of the (neostigmine-induced) carbamylated anticholinesterase observed in vitro, and are able to model such noninstantaneous anticholinesterase kinetic processes. For both edrophonium and neostigmine we detect an inverse relationship between the (induced) level of initial block and maximal percentage recovery.
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Clin. Orthop. Relat. Res. · Nov 1991
Longitudinal crack propagation in bone around femoral prosthesis.
Intraoperative femoral fracture is a well-recognized technical complication of cementless total hip arthroplasty. This study was designed to establish an in vitro model for initiation and propagation of fractures of the proximal femur in cementless THA and to assess the effect of fracture fixation in the form of cerclage wiring and drilling a hole in the distal extent of the fracture line. ⋯ A drill hole at the tip of a longitudinal crack does not prevent crack propagation. However, cerclage wiring has a statistically significant effect (p less than 0.025) on the ability of the fractured femur to withstand increased load.