Spectral characteristics of visually induced postural sway in healthy elderly and healthy young subjects.

Spectral analysis and time-frequency analysis were applied to anterior-posterior (A-P) center-of-pressure (COP) data collected during quiet stance and sinusoidal (0.25 Hz) moving visual scene perturbations from sixteen healthy elderly subjects and thirteen healthy young subjects. While the total energy of COP was larger in the elderly subjects than in the young subjects, energy-normalized spectra of the entire COP time series were similar between the two populations. Further time-dependent analysis of the spectral characteristics showed that the time-varying spectra were also similar, as revealed by time-frequency analysis, although some differences were observed. Specifically, time-dependent mean frequency and bandwidth responses to the stimulus showed similar increases in both young and elderly subjects with the introduction of the stimulus. Furthermore, time-frequency analysis showed that both groups exhibited an initial increase in sway at the stimulus frequency that then declined as the sinusoidal scene movement progressed. This reduction in sway during visual stimulation may indicate an "adaptation" to constant frequency visual perturbation that is invariant with age. This finding is in contrast to results reported recently for patients with vestibular impairments, who appear to lack such adaptation.

Efficacy, safety and tolerability of combined administration of lithium and selective serotonin reuptake inhibitors: a review of the current evidence. Hertfordshire Neuroscience Research Group.

Several case reports have engendered concern about the safety of coadministering lithium and selective serotonin reuptake inhibitor (SSRI) antidepressants and there are theoretical reasons to suppose that lithium and serotonergic antidepressants may be associated with dangerous interactions. Systematic reports regarding combination therapy with lithium and SSRI antidepressants were assimilated for the purpose of this review. Although there are many publications, few are directly informative as to safety and tolerability. A total of 503 patients are considered in systematic reports and, among these, no serious or life-threatening adverse events can be identified. Such data as there are demonstrate little potential for toxic interactions between lithium and SSRIs, although new, non-serious, adverse events do frequently arise. The evidence for the efficacy of addition of lithium to SSRIs in treatment refractory depression is only provisional.

Compensating for window effects in the calculation of spectrographic instantaneous bandwidth.

Exact results derived by Cohen and Lee are used to study the distortion induced by the window in the computation of instantaneous bandwidth via the spectrogram. These concepts have been recently used in an interesting study regarding lesion-induced blood flow disturbances, where an approximation was made to compensate for the window effects. We show that this compensation is accurate for stationary signals, but becomes increasingly poorer as the signal becomes less stationary (e.g., large frequency modulations). We propose an alternative technique to reduce the window distortions, and point out the use of other time-frequency distributions that do not suffer such distortions.

Resistance-modifying agents. Part 7: 2,6-disubstituted-4,8-dibenzylaminopyrimido[5,4-d]pyrimidines that inhibit nucleoside transport in the presence of alpha1-acid glycoprotein (AGP).

The synthesis and biological evaluation of potent 4,8-dibenzylaminopyrimidopyrimidine nucleoside transport inhibitors, with reduced binding to alpha1-acid glycoprotein, is reported.

Potentiation of the cytotoxicity of thymidylate synthase (TS) inhibitors by dipyridamole analogues with reduced alpha1-acid glycoprotein binding.

Dipyridamole has been shown to enhance the in vitro activity of antimetabolite anticancer drugs through the inhibition of nucleoside transport. However, the clinical potential of dipyridamole has not been realized because of the avid binding of the drug to the plasma protein alpha1-acid glycoprotein (AGP). Dipyridamole analogues that retain potent nucleoside transport inhibitory activity in the presence of AGP are described and their ability to enhance the growth inhibitory and cytotoxic effects of thymidylate synthase (TS) inhibitors has been evaluated. Three dipyridamole analogues (NU3026, NU3059 and NU3060) were shown to enhance the growth inhibitory activity of the TS inhibitor CB3717 and block thymidine rescue in L1210 cells. The extent of potentiation at a fixed analogue concentration (10 microM) was related to the potency of inhibition of thymidine uptake. A further analogue, NU3076, was identified, which was more potent than dipyridamole with a Ki value for inhibition of thymidine uptake of 0.1 microM compared to 0.28 microM for dipyridamole. In marked contrast to dipyridamole, inhibition of thymidine uptake by NU3076 was not significantly affected by the presence of AGP (5 mg ml(-1)). NU3076 and dipyridamole produced equivalent potentiation of the cytotoxicity of the non-classical antifolate TS inhibitor, nolatrexed, in L1210 cells with both compounds significantly reducing the LC90, by > threefold in the absence of salvageable thymidine. Thymidine rescue of L1210 cells from nolatrexed cytotoxicity was partially blocked by both 1 microM NU3076 and 1 microM dipyridamole. NU3076 also caused a significant potentiation of FU cytotoxicity in L1210 cells. These studies demonstrate that nucleoside transport inhibition can be maintained in the absence of AGP binding with the dipyridamole pharmacophore and that such analogues can enhance the cytotoxicity of TS inhibitors.

Time-varying characteristics of visually induced postural sway.

To study potential time-varying dynamics of postural sway as measured via center-of-pressure (COP) under the feet, we applied time-frequency analysis to COP data from ten vestibularly impaired subjects and 13 nonimpaired controls, during quiet stance and in response to visual perturbation. This analysis revealed that 1) the spectral characteristics of COP change over time; 2) there are time-dependent and frequency-dependent differences in COP between impaired and nonimpaired populations during visual perturbation, and 3) there is no difference in COP during quiet stance (eyes opne) between impaired and nonimpaired populations for the parameters investigated. A novel finding of this research is that controls appear to adapt to constant frequency visual perturbation, while vestibularly impaired subjects do not. This difference could not have been observed with conventional Fourier analysis, which is commonly used in COP data analysis, because time is not a parameter of the spectrum and adaptation is, by nature, a time-varying process. These results suggest that time-frequency analysis of COP data is useful for studying temporal dynamics of postural control, and in particular the differences between vestibularly impaired subjects and healthy controls during visual perturbation.

An oil-based model of inhalation anesthetic uptake and elimination.

An oil-based model was developed as a physical simulation of inhalation anesthetic uptake and elimination. It provides an alternative to animal models in testing the performance of anesthesia equipment. A 7.5-1 water-filled manometer simulates pulmonary mechanics. Nitrogen and carbon dioxide flowing into the manometer simulate oxygen consumption and carbon dioxide production. Oil-filled chambers (180 ml and 900 ml) simulate the uptake and washout of halothane by the vessel-rich and muscle tissue groups. A 17.2-1 air-filled chamber simulates uptake by the lung group. Gas circulates through the chambers (3.7, 13.8, and 25 l/min) to simulate the transport of anesthetic to the tissues by the circulatory system. Results show that during induction and washout, the rate of rise in endtidal halothane fraction simulated by the model parallels that measured in patients. The model's end-tidal fraction changes correctly with changes in cardiac output and alveolar ventilation. The model has been used to test anesthetic controllers and to evaluate gas sensors, and should be useful in teaching principles underlying volatile anesthetic uptake.