Community assessment.
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Biomedical subjects
Publications and source records attributed to K Muir.
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Although discriminable changes in stimulus energy or overall duration may accompany the silent temporal gap, there is little evidence that these extraneous cues confound the measurement of temporal gap detection threshold. In this report we show that (1) under conditions where gap detection thresholds are large in relation to the duration of the standard, extraneous cues may confound gap detection leading to underestimates of the true threshold, and (2) randomization of overall stimulus level and duration can successfully remove confounding energy and duration cues without distracting the listener's attention from the temporal-gap cue.
Modulation detection thresholds (as a function of sinusoidal amplitude modulation frequency) and temporal gap detection thresholds were measured for three low-pass-filtered noise signals (fc = 1000, 2000, and 4000 Hz), a high-pass-filtered noise signal (fc = 4000 Hz), and a broadband signal. The two latter noise signals were effectively low-pass filtered (fc = 6500 Hz) by the earphone. Each of the filtered signals was presented with a complementary filtered noise masker. Modulation and gap detection thresholds were lowest for the broadband and high-pass signals. Thresholds were significantly higher for the low-pass signals than for the broadband and high-pass signals. For these tasks and conditions, the high-frequency content of the noise signal was more important than was the signal bandwidth. Sensitivity (s) and time constant (tau) indices were derived from functions fitted to the modulation detection data. These indices were compared with gap detection thresholds for corresponding signals. The gap detection thresholds were correlated inversely (rho = -1.0, p less than 0.05) with s (i.e., smaller gap detection thresholds were correlated with greater sensitivity to modulation), but were not correlated significantly with tau, which was relatively invariant across signal conditions.
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The plasma concentrations of pindolol have been examined following the administration of single doses of 15 mg tablets to eight healthy male subjects. The apparent half-life of elimination in plasma (t1/2 = 4.05 h) and in urine (t1/2 = 3.21 h) was calculated using conventional pharmacokinetic methods. The renal clearance was estimated by plotting urinary excretion rates versus plasma concentrations; for all subjects these plots were curved. In addition to these graphical estimations, the plasma concentrations of pindolol and the urinary excretion data for each volunteer were simultaneously fitted using a one or two-compartment open body model; a computer program using non-linear regression algorithms was used. This procedure did not give an adequate fit to the data. Another type of data analysis, using a population - based model, permitted us to show that the renal elimination of pindolol in man comprises of two separate processes - tubular secretion and reabsorption, which was partially saturable under the experimental conditions. The theoretical relevance and clinical significance of these findings are discussed.
In order to assess the clinical impact of dose-dependent kinetics for theophylline, the relationship between serum concentration and daily dosage among patients under the care of the University of Iowa Pediatric Allergy and Pulmonary Service was examined. Dosage was titrated clinically, with the final adjustment based on a serum theophylline measurement. Of 200 charts initially reviewed, 42 patients were found in whom at least two peak serum concentrations had been measured at different doses of the same theophylline preparation. In 30 (15% of initial 200) of these 42 patients, the percent change in serum concentration exceeded the percent change in dose by at least 50%. Subsequently, 300 additional charts were reviewed to identify a total of 26 patients with three steady-state serum concentrations at three different doses. Only five of these patients demonstrated a linear relationship between dose and serum concentration; the other 21 demonstrated disproportionate changes compatible with parallel first-order and dose-dependent kinetics. Thus, clinically important dose-dependent kinetics for theophylline occur in at least 15% of children, and theophylline dosage therefore must be adjusted in small increments in order to avoid disproportionately large changes in serum concentration with consequent risks of toxicity during continuous therapy.
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