A new multidimensional movement analysis system was used to record limb tremor over six degrees-of-freedom, and signal processing techniques were explored to develop a suitable classification method to distinguish between different types of tremor. The specific aims were to investigate the ability of the system to screen for differences between normal subjects and a group of neurological patients, and then to differentiate between three diagnostic groups of patients.
Postural tremor at the hand was recorded in normal subjects (n=24) and patients with essential tremor (n=21), multiple sclerosis (n=17) and parkinsonism (n=19). Data were collected using a 3Space Fastrak® (Polhemus, Inc.) over six degrees-of-freedom (three translational directions and three rotations). Spectral estimates produced measures of tremor frequency and amplitude. Mathematical models of the data, using autoregressive modelling and K-nearest neighbour classification, produced parameters used to classify, (1) the normal subjects and 24 patients (using the three rotational movements), and (2) the three patient groups (using all six movement directions). Results were given in terms of the probability of each subject belonging to the groups being classified.
Tremor frequency and amplitude showed large overlap between the groups. The screening classification produced high probabilities of correctly classifying normal subjects (>70%) and patients (>70%). The diagnostic classification produced clear differences between the patient groups (60% for essential tremor, 80% for multiple sclerosis and 60% for parkinsonism).
The ability of this assessment technique to distinguish between postural tremor in normal subjects and neurological patients suggests that it could be developed as a screening tool. Classification of tremors between the patients groups, with a high degree of sensitivity, indicates the potential for further development of the system as a diagnostic aid. 相似文献
Summary After perfusion of mouse livers with A14-125I-insulin for designated intervals, an acid-wash technique was employed to separately measure the surface-bound (Xs) and intracellular (Xi) A14-125I-insulin, as well as intracellular degradation products (Xdeg) of labelled insulin. From the perfusate concentrations (Cp) of A14-125I-insulin, the apparent intrinsic hepatic clearance of labelled insulin at a high dose (0.2 nmol/l) was shown to be 60% smaller than that at a low dose (0.018 nmol/l), indicating that the cellular uptake of insulin is remarkably nonlinear at the concentration range examined. From the time courses of Cp, Xs, Xi and Xdeg, the hepatic insulin disposition was shown to be largely accounted for by the receptor-mediated endocytosis. The observed data at the low dose were analysed to estimate biochemical parameters, (i.e., total receptor number, endocytotic rate constant and intracellular degradation rate constant) according to receptor-recycling and non-receptor-recycling models, using a computer-aided optimization procedure. The receptor-recycling model could not only adequately explain the Cp, Xs, Xi and Xdeg at the low dose, but also predict the Cp at the high dose. On the other hand, a non-receptor-recycling model, in which recycling of receptors was not assumed, could also explain the observed data at the low dose, but failed to predict the Cp at the high dose, indicating that the receptor recycling process is necessary to explain the hepatic insulin clearance at high insulin concentrations, at which hepatic insulin clearance should be limited by the rate of receptor recycling. However, the applicability of our model might be limited within the physiologic insulin concentrations, because of the negative co-operativity of insulin-receptor interaction and a high-capacity, non-degradative and more rapidly recycling pathway for receptors that may occur at high concentrations of insulin. In conclusion, we have developed a mathematical model of hepatic insulin clearance and distribution under physiological conditions, including receptor binding, receptor-mediated endocytosis and receptor recycling, which has been so far demonstrated using isolated hepatocytes. 相似文献
In animal models, liposomal formulations of paclitaxel possess lower toxicity and equal antitumor efficacy compared with the clinical formulation, Taxol. The goal of this study was to determine the formulation dependence of paclitaxel pharmacokinetics in rats, in order to test the hypothesis that altered biodistribution of paclitaxel modifies the exposure of critical normal tissues. Paclitaxel was administered intravenously in either multilamellar (MLV) liposomes composed of phosphatidylglycerol/phosphatidylcholine (L-pac) or in the Cremophor EL/ethanol vehicle used for the Taxol formulation (Cre-pac). The dose was 40 mg/kg, and the infusion time was 8 to 9 minutes. Animals were killed at various times, and pharmacokinetic parameters were determined from the blood and tissue distribution of paclitaxel. The area under the concentration vs time curve (AUC) for blood was similar for the 2 formulations (L-pac: 38.1±3.32 μg-h/mL; Cre-pac: 34.5±0.994 μg-h/mL), however, the AUC for various tissues was formulation-dependent. For bone marrow, skin, kidney, brain, adipose, and muscle tissue, the AUC was statistically higher for Cre-pac. For spleen, a tissue of the reticuloendothelial system that is important in the clearance of liposomes, the AUC was statistically higher for L-pac. Apparent tissue partition coefficients (Kp) also were calculated. For bone marrow, a tissue in which paclitaxel exerts significant toxicity, Kp was 5-fold greater for paclitaxel in Cre-pac. The data are consistent with paclitaxel release from circulating liposomes, but with efflux delayed sufficiently to retain drug to a greater extent in the central (blood) compartment and reduce penetration into peripheral tissues. These effects may contribute to the reduced toxicity of liposomal formulations of paclitaxel. 相似文献