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R J Stubbs

Publications and source records attributed to R J Stubbs.

69 records · Page 4Linked to original sources
PubMed1990

Strengths and weaknesses of procedures for separating simultaneous voices.

Two signal-processing procedures for separating the continuously-voiced speech of competing talkers are described and evaluated. With competing sentences, each spoken on a monotone, the procedures improved the intelligibility of the target talker both for listeners with normal hearing and for listeners with moderate-to-severe hearing losses of cochlear origin. However, with intoned sentences, benefits were smaller for normal-hearing listeners and were inconsistent for impaired listeners. It is argued that smaller benefits arise with intoned sentences because harmonics of the two voices are blurred together during spectral analysis, limiting the extent to which spectral contrast can be recovered in the processed signal. This is particularly disadvantageous to impaired listeners who have reduced spectro-temporal resolution. This paper discusses other substantial problems to be overcome before the feasibility of the procedures as components of a speech-enhancement system for hearing-impaired listeners could be demonstrated.

Audiometry, Pure-Tone↗
PubMed1989

Animal safety and toxicology of simvastatin and related hydroxy-methylglutaryl-coenzyme A reductase inhibitors.

Simvastatin, a hydroxy-methylglutaryl-coenzyme A reductase inhibitor intended for use as a hypocholesterolemic agent, has undergone a thorough preclinical toxicology evaluation. This review describes preclinical toxicology findings associated with simvastatin administration in animals and provides the rationale for our conclusion that these changes are not indicative of potential human toxicity. Although it was not surprising to find that a potent inhibitor of this key biochemical pathway produces toxicity at high dosages in animals, none of the observed changes poses a significant risk to humans at clinical dosages. Many of the toxicities produced by high dosage levels of simvastatin in animals are directly related to the drug's biochemical mechanism of action and are the result of a profound, sustained inhibition of the target enzyme that is not anticipated at clinical dosages. Furthermore, several of the simvastatin-induced changes are species-specific responses to this agent and are not relevant to human risk assessment. Of the treatment-related changes reported for simvastatin, the development of cataracts in dogs has received considerable attention. The available data demonstrate a wide margin of safety in terms of dosage levels required to elicit this response as well as the plasma concentrations associated with the development of these ocular lesions. The data suggest that the development of lenticular opacities at clinical doses of simvastatin is highly improbable. Overall, simvastatin is highly improbable. Overall, simvastatin was well-tolerated by animals in preclinical toxicology studies, and no findings contraindicating its use in humans were identified.

Animals↗
PubMed1989

Toxicity of the HMG-coenzyme A reductase inhibitor, lovastatin, to rabbits.

Lovastatin, a specific inhibitor of the rate-limiting enzyme in cholesterol biosynthesis, HMG-CoA reductase, has been shown to be highly effective in lowering serum cholesterol in animals and humans and thus represents a promising approach to the treatment and prevention of cardiovascular disease. During the preclinical safety assessment of lovastatin, oral doses that were tolerated by dogs, rats and mice were found to be lethal to rabbits in subacute studies. Postmortem findings in rabbits consisted of centrilobular hepatic necrosis, frequently accompanied by renal tubular necrosis and occasionally gallbladder necrosis. The liver lesions were associated with up to 300-fold elevations in serum aspartate and alanine aminotransferase activities, whereas the kidney lesions resulted in accumulations of serum urea nitrogen and creatinine. The organ damage was preceded by a progressive decline in food consumption and loss of body weight. All histopathological and serum biochemical changes induced by lovastatin were completely prevented by coadministration of mevalonate, the product of the inhibited HMG-CoA reductase enzyme. In addition, administration of mevalonate after the onset of lovastatin-induced hepatotoxicity effectively reversed the toxicity despite continued drug treatment. These findings indicated that the toxicity of high doses of lovastatin to rabbits is a consequence of a highly exaggerated pharmacologic action in blocking mevalonate synthesis. However, supplementation of lovastatin-treated rabbits with oral doses of the major product of mevalonate metabolism, cholesterol, paradoxically enhanced the liver and kidney damage, which suggested that the toxicity of lovastatin stemmed from depletion of a nonsterol metabolite(s) of mevalonate critical for cell viability.

Animals↗
PubMed1988

Evaluation of two voice-separation algorithms using normal-hearing and hearing-impaired listeners.

Two signal-processing algorithms, designed to separate the voiced speech of two talkers speaking simultaneously at similar intensities in a single channel, were compared and evaluated. Both algorithms exploit the harmonic structure of voiced speech and require a difference in fundamental frequency (F0) between the voices to operate successfully. One attenuates the interfering voice by filtering the cepstrum of the combined signal. The other uses the method of harmonic selection [T. W. Parsons, J. Acoust. Soc. Am. 60, 911-918 (1976)] to resynthesize the target voice from fragmentary spectral information. Two perceptual evaluations were carried out. One involved the separation of pairs of vowels synthesized on static F0's; the other involved the recovery of consonant-vowel (CV) words masked by a synthesized vowel. Normal-hearing listeners and four listeners with moderate-to-severe, bilateral, symmetrical, sensorineural hearing impairments were tested. All listeners showed increased accuracy of identification when the target voice was enhanced by processing. The vowel-identification data show that intelligibility enhancement is possible over a range of F0 separations between the target and interfering voice. The recovery of CV words demonstrates that the processing is valid not only for spectrally static vowels but also for less intense time-varying voiced consonants. The results for the impaired listeners suggest that the algorithms may be applicable as components of a noise-reduction system in future digital signal-processing hearing aids. The vowel-separation test, and subjective listening, suggest that harmonic selection, which is the more computationally expensive method, produces the more effective voice separation.

Algorithms↗
PubMed1987

Analysis of sulindac and metabolites in plasma and urine by high-performance liquid chromatography.

A reversed-phase high-performance liquid chromatographic method with ultraviolet detection is described for the quantification of sulindac, sulindac sulfone and sulindac sulfide in plasma and sulindac, trans-sulindac, sulindac sulfone and sulindac sulfide in urine. Plasma samples are de-proteinized with acetonitrile and urine samples are injected directly following enzymatic hydrolysis of glucuronide metabolites. The resulting chromatograms are essentially free from endogenous interference and the limits of detection are 0.1 microgram/ml for plasma and 0.2 microgram/ml for urine for all of the above compounds.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Peripheral signals affecting food intake.

Peripheral signals arise from the sequence involving location, selection, ingestion, digestion, and absorption of food. These signals can be anatomically localized to gastrointestinal signals, circulating factors, metabolic signals, nutrient stores, and the sensory capabilities of the nervous system. Since many of the physiologic signals thought to affect feeding are triggered by nutrient ingestion and feeding behavior is influenced by diet composition, it is useful to consider peripheral appetite signals in the context of energy and nutrient balance. Evidence suggests that nutrient metabolism is (directly or indirectly) related to postingestive satiety. Protein is the most satiating macronutrient and has the greatest detectable effect on qualitative intake. Carbohydrates (CHOs) exert potent effects on satiety. Inhibition of CHO metabolism stimulates intake, as do transient declines in plasma glucose. Inhibition of fat metabolism also stimulates intake, but fat is the least readily metabolized macronutrient, and therefore, joule for joule, is less satiating than CHO or protein. High-fat, energy-dense diets lead to excess energy intakes (EIs) and weight gain relative to lower-fat, less energy-dense diets, and fat intake is a risk factor for subsequent weight gain. Earlier models viewed peripheral control of feeding as due to one or more simple negative feedback loops. More recently research has focused on the multiple signalling systems involved in the maintenance of nutrient and energy balance (EB). While protein influences satiety at several levels, relatively little is known about "aminostatic" mechanisms. CHO status appears to be monitored in both the central nervous system (CNS) and periphery; signals relating to fat status largely appear to arise in the periphery. More progress has been made in identifying peripheral signals and some of their connections to the brain than in understanding their quantitative importance for normal feeding.

Animals↗
PubMedDate not supplied

Interrelationship between circulating leptin concentrations, hunger, and energy intake in healthy subjects receiving tube feeding.

BACKGROUND: Tube feeding is an unphysiological route of nutrient delivery, and yet there is a lack of controlled trials examining its effects on appetite, food intake, and factors involved in their control. This study aimed to investigate the relationship between diurnal tube feeding, hunger, food intake, and circulating concentrations of leptin (a putative satiety factor). METHODS: Six healthy lean men received a continuous nasogastric infusion (9:00 AM to 9:00 PM) of colored water (2 days), liquid feeding (4.2 kJ/mL, energy provision 1 x the initial predicted basal metabolic rate; 3 days), and colored water (2 days). Measurements of hunger (visual analog scales), weighed food intake, and fasting circulating leptin concentrations were made while the subjects were allowed free access to isoenergetically dense food items. RESULTS: Three days of diurnal nasogastric feeding (mean, 6.9 MJ/d) significantly increased total energy intake (to 19.4 MJ/d; p < .001; analysis of variance [ANOVA]), suppressing oral energy intake by only 17%, with no significant effect on mean daily hunger. Higher levels of energy intake led to a universal rise in circulating leptin concentrations (2.82 to 4.23 ng/mL; p < .004; ANOVA) that was not significantly related to subsequent breakfast energy intake, first rated hunger of the day, timing of morning food consumption, or subsequent mean daily oral energy intake or hunger. CONCLUSIONS: This study suggests that 3 days of diurnal tube feeding (equivalent to basal metabolic rate) failed to suppress hunger and reduced food intake by only 17%. The rise in circulating leptin concentrations, associated with tube feeding and the increase in total energy intake, failed to predict subsequent hunger or oral energy intake.

Adult↗
PubMedDate not supplied

The physiological disposition of lovastatin.

Lovastatin is a pro-drug lactone whose open chain beta-hydroxy-acid (HA) is a potent inhibitor of hydroxymethylglutaryl-CoA-reductase and thus of cholesterol synthesis. Because the liver is the major site of cholesterolgenesis, it is the principal target organ for agents of this class. In animals, lovastatin is not as well absorbed as HA given per se, but that fraction that is absorbed reaches the portal circulation largely unchanged and is more efficiently extracted by the liver, after which it is reversibly biotransformed to HA and irreversibly to other enzymatically active products. These, like HA, maintain high hepatic gradients relative to all tissues examined. The minimal systemic burden for HA is attributable in part to the metabolic equilibrium, lovastatin in equilibrium HA, the opposing reactions for which appear to be present in most tissues. Excretion is very largely biliary in all species. Detailed comparisons of absorption, distribution, metabolism, and excretion profiles presented here and elsewhere indicate dogs to be the most appropriate paradigm for humans for study of lovastatin disposition.

Animals↗