Two-state compression of spectral tilt: individual differences and psychoacoustical limitations to the benefit from compression

A psychoacoustic rationale was developed for a hearing aid design in which compression of spectral tilt was incorporated without any instantaneous nonlinear distortion. This involved switching between a 'flat' and a 'rising' frequency response; the switching was done slowly to avoid audible transients and was controlled by feedback derived from comparison of output levels in low- and high-frequency channels, approximating voiced/unvoiced detection. The effect of this switching process was to narrow the distribution of spectral tilt values compared with the input. Asynchrony between the switching and the triggering speech structures was avoided by also delaying the signal path. Unfortunately, hearing-impaired listeners performed more poorly on the switching system than on either of the control 'flat' or 'rising' frequency-responses. An explanation is offered (on the basis of growing evidence from perceptual experiments) of the perceptual importance of temporal envelope contours within individual frequency bands. It was possible, in part, to predict individuals' results in the switching condition from age and audiometric or psychoacoustic characteristics. The results suggest a modification to the switching design, and they point to an intrinsic limit to the ability of all hearing aids of the compression type to enhance intelligibility.     

Inhibitory effects of AH 21-132 in guinea-pig isolated ileum and taenia caeci.

1. AH 21-132 is being investigated as a potential chemotherapeutic agent for bronchial asthma. The present experiments were designed to determine whether AH 21-132 shares the activity of theophylline as an antagonist at adenosine A1 receptors and to assess its potency as a relaxant in intestinal smooth muscle. 2. In the transmurally-stimulated guinea-pig ileum, theophylline (1 mM), but not AH 21-132 (1 and 10 microM), antagonized twitch depression induced by adenosine. Higher concentrations (100 microM and 1 mM) of AH 21-132 themselves had a depressant effect. Neither theophylline (1 mM) nor AH 21-132 (1 and 10 microM) antagonized twitch depression induced by noradrenaline. 3. AH 21-132 (100 microM and 1 mM) depressed maximum contractions of ileum induced by both acetylcholine (ACh) and histamine. 4. In ileum treated with hyoscine (1 microM), AH 21-132 (greater than 10 microM) caused a concentration-dependent depression of the log concentration-effect curve for potassium chloride. 5. Simultaneous extracellular electrophysiological and mechanical recording from taenia caeci showed that AH 21-132 (100 microM-1 mM) inhibited spontaneous tension waves and their associated bursts of electrical spike activity. 6. Intracellular electrophysiological recording from taenia caeci showed that the mechano-inhibitory effect of 1 mM AH 21-132 was accompanied by abolition of spontaneous spike activity. Following spike abolition, the membrane potential assumed a value very close to that observed during periods of electrical quiescence prior to drug exposure. 7. AH 21-132 inhibited the activity of cyclic AMP-dependent and cyclic GMP-dependent phosphodiesterases derived from homogenates of ileal smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pre-clinical pharmacology of ICI D2138, a potent orally-active non-redox inhibitor of 5-lipoxygenase.

1. This paper describes the pre-clinical pharmacology of ICI D2138, a potent orally-active non-redox inhibitor of 5-lipoxygenase which is undergoing clinical evaluation. 2. ICI D2138 potently inhibited leukotriene synthesis in murine peritoneal macrophages (IC50 = 3 nM) and human blood (IC50 = 20 nM). In human and dog blood, ICI D2138 did not inhibit thromboxane B2 synthesis at a concentration of 500 microM, thus the selectivity ratio (cyclo-oxygenase: 5-lipoxygenase) was greater than 20,000. In contrast, zileuton (a 5-lipoxygenase inhibitor also undergoing clinical evaluation) exhibited a selectivity ratio of 15-100. 3. ICI D2138 potently and dose-dependently inhibited ex vivo leukotriene B4 (LTB4) synthesis by rat blood with ED50 values of 0.9, 4.0 and 80.0 mg kg-1 p.o. at 3, 10 and 20 h respectively after dosing. Similar activity was observed for inhibition of LTB4 production in a zymosan-inflamed rat air pouch model. Zileuton produced ED50 values of 5 and 20 mg kg-1 at 3 and 10 h respectively. 4. Oral administration of 1, 3 or 10 mg kg-1 ICI D2138 to dogs produced maximal inhibition of ex vivo LTB4 synthesis by blood for 5, 9 and 31 h respectively. A dose of 5 mg kg-1 p.o. of zileuton caused maximal inhibition of LTB4 for 24 h. 5. Oral administration of 10 mg kg-1 ICI D2138 caused total inhibition of LTB4 production in zymosan-inflamed rabbit knee joint. 6. Topical administration of ICI D2138 to rabbit skin caused a dose-related inhibition of arachidonic acid-induced plasma extravasation with an ID30 of 1.08 nmol per site.(ABSTRACT TRUNCATED AT 250 WORDS)     

An outbreak of watermelon-borne pesticide toxicity.

The largest reported United States outbreak of illness caused by a foodborne pesticide was due to aldicarb-contaminated watermelons. In Oregon, where the first episodes of toxicity were reported, 264 reports were received, and 61 definite cases were identified. Residues of aldicarb, a cholinesterase inhibitor, were found in 10 of 16 tested melons which had been eaten by persons meeting the case definition. The outbreak demonstrates the need for enhanced physician vigilance with respect to anticholinesterase intoxication. It also demonstrates the value of an established system for reporting of unusual illness to public health officials.     

Skin cancer in the North Solomons

The Melanesians of the North Solomons are exposed to intense equatorial sunlight and yet have a very low incidence of skin cancer. This study reveals no proven cases of basal cell carcinoma in these people, and demonstrates the rarity of squamous cell carcinoma and melanoma arising in normal pigmented skin. Most, if not all squamous cell carcinomas, arise in skin damaged by tropical ulceration, burns or osteomyelitis. Melanoma arises from the unpigmented skin of the sole of the foot. North Solomon Islanders are very deeply pigmented. Presumably, dense cutaneous melanin in normal undamaged skin provides the highly effective protection against solar carcinogenesis which these people enjoy. Chronic or recurrent skin ulceration with subsequent repair, scarring and loss of pigment is the precursor to almost all non-melanoma skin cancer in these people. Most of these cancers could be prevented by split thickness skin grafting of chronic ulcers, and protection of ulcerated, depigmented and scarred skin from solar radiation.