Covert manipulation of dietary fat and energy density: effect on substrate flux and food intake in men eating ad libitum.

This study assessed whether human food intake is regulated by negative feedback, directly or indirectly, from carbohydrate stores (glycogenostatic model). Six men were studied on three occasions during 7 d of whole-body indirect calorimetry, throughout which they had ad libitum access to one of three covertly manipulated diets: low fat (20% of energy as fat, 67% of energy as carbohydrate, and 13% of energy as protein; 4.80 kJ/g; LF), medium fat (40% of energy as fat, 47% of energy as carbohydrate, and 13% of energy as protein; 5.

Alterations in fuel selection and voluntary food intake in response to isoenergetic manipulation of glycogen stores in humans.

This study investigated the relative importance of alterations in carbohydrate intake or oxidation as mechanisms for rectifying extreme perturbations of glycogen stores. Six lean men were studied on three occasions in which a stabilization period (days 1 and 2) was immediately followed by whole-body indirect calorimetry (days 3-5). Glycogen stores were manipulated on days 3 and 4 by using isoenergetic diets providing carbohydrate at 79% (HC), 48% (MC), or 9% (LC) of energy.

Carbohydrate balance and the regulation of day-to-day food intake in humans.

The hypothesis that carbohydrate stores are an important determinant of voluntary food intake was tested by covert dietary manipulation of carbohydrate stores in nine men during 2 d of continuous whole-body calorimetry that provided half-hourly monitoring of energy and fuel balance. On day 1 subjects were fed diets intended to maintain energy balance but containing carbohydrate at either 3% (depletion) or 47% (control) energy. Average carbohydrate balance changed by 153 +/- 42 g (mean +/- SD).

Single-dose pharmacokinetics of 14C-lovastatin in chronic renal failure.

An open study on the pharmacokinetics of lovastatin was conducted in six patients with chronic renal failure (mean creatinine clearance, 0.40 ml/sec; range, 0.20 to 0.

Enhancement of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor efficacy through administration of a controlled-porosity osmotic pump dosage form.

An extended-release osmotic dosage form was designed for gastrointestinal delivery of the water-soluble tromethamine salt of the beta-hydroxyacid form of simvastatin, a potent HMG-CoA reductase inhibitor and cholesterol lowering agent. The cholesterol lowering efficacy and systemic plasma drug levels resulting from peroral administration of this dosage form, relative to a powder-filled capsule oral bolus, were evaluated in dogs. A twofold improvement in cholesterol lowering efficacy was realized with the controlled-release dosage form that was accompanied by a drug AUC and Cmax that were 67 and 16%, respectively, of those achieved with the bolus dosage form.

HMG-CoA reductase inhibitor-induced myopathy in the rat: cyclosporine A interaction and mechanism studies.

Recent clinical evidence indicates a potential for skeletal muscle toxicity after therapy with HMG-CoA reductase inhibitors (HMGRIs) in man. Although the incidence of drug-induced skeletal muscle toxicity is very low (0.1-0.

Effects of signal-to-noise ratio, signal periodicity, and degree of hearing impairment on the performance of voice-separation algorithms.

Procedures for enhancing the intelligibility of a target talker in the presence of a co-channel competing talker were evaluated in tests involving (i) continuously voiced sentences spoken on a monotone, (ii) continuously voiced sentences with time-varying intonation, and (iii) noncontinuously voiced sentences produced with natural intonation. The procedures were based on the methods of harmonic selection and cepstral filtering [R.J.

Bedside and field methods for assessing body composition: comparison with the deuterium dilution technique.

Estimates of body composition by the deuterium dilution technique were made in 55 healthy subjects (38 men and 17 women) with a mean age of 28.4 years, weight 65.5 kg and height 173.

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.

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.

Algorithms for separating the speech of interfering talkers: evaluations with voiced sentences, and normal-hearing and hearing-impaired listeners.

Two signal-processing algorithms, derived from those described by Stubbs and Summerfield [R.J. Stubbs and Q.

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.

Papillary cystadenocarcinoma of the appendiceal stump with mucocele and peritoneal metastases.

A 54-year-old Polynesian male developed a mucocele of the appendiceal stump 25 years after appendicectomy. Scattered peritoneal deposits up to 0.4 cm in diameter were also identified at laparotomy, and these were confined to the right iliac fossa.

External septorhinoplasty--exposure for the difficult nose.

External septorhinoplasty affords direct exposure, which allows both the novice and the expert surgeon to treat the most challenging noses with a higher degree of assurance. Criticism of the external columellar scar is unwarranted. The technique is reviewed in detail, and complex cases are illustrated.

Psittacosis pneumonia.

A 57-year-old man with symptoms and signs consistent with atypical pneumonia had epidemiologic and later serologic evidence of psittacosis pneumonia. Therapy with tetracycline resulted in rapid resolution.

Inhibition of the stimulated canine exocrine pancreas by amino acids and fat.

To investigate the possible exocrine pancreatic inhibitory actions of amino acids and fat, pancreatic fistula outputs and plasma concentrations of glucagon, somatostatin, and pancreatic polypeptide were measured for response to intravenous (IV) and intraduodenal nutrient administration in six dogs submaximally stimulated with cholecystokinin. Intravenous amino acids caused abrupt and significant 45% to 73% reductions in stimulated pancreatic protein, bicarbonate, and volume outputs. There were no significant associated changes in plasma hormone concentrations and no similar immediate pancreatic inhibition with IV mannitol, thus suggesting a possible direct inhibitory effect of amino acids.

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.

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.

Choledochal cyst: case reports and current concepts.

Choledochal cyst is an unusual but serious condition which most commonly affects Oriental people. Recent experience of three patients with this condition in whom diagnosis was made by ultrasound examination is reported. Cholangiography (ERCP or PTC) was performed in two of the cases to define the anatomy.

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.

Pressure changes in canine gall-bladder associated with emptying.

1. For decades it has been supposed that emptying of the gall-bladder follows a rise in gall-bladder pressure of some 10-15 mmHg and relaxation of the sphincter of Oddi. 2.