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Biomedical subjects

K Bailey

Publications and source records attributed to K Bailey.

At least 91 records · Page 5Linked to original sources

The relation between resource limitations and optional conceptual processing by children and adults.

In some situations children fail to perform optional conceptual processing that they are able to perform. The purpose of the 4 experiments was to determine if the difficulty of word identification affects optional conceptual processing by second/third graders, fifth graders, and college students in a cued recall task. Conceptual processing was manipulated by presenting Hard (e.g., hawk eagle canary) or Easy (river lake canary) word triplets that varied in the contrastive processing necessary to identify the "odd" target word (canary). The orienting activity also varied: for the Oddity Choice activity, contrastive processing was obligatory because the subject had to identify the target; for the Read activity, contrastive processing was optional because the experimenter identified the target. A recall advantage for the Hard over the Easy triplets was the measure of contrastive processing. Finally, the difficulty of word identification varied in that the subjects read the stimuli or the experimenter read the stimuli, and all the words were degraded, only the nontarget words were degraded, or all the words were intact. The results established that contrastive processing facilitates recall, and that word identification difficulty may limit the extent of optional contrastive processing.

Adolescent↗

Change in physician perspective on cholesterol and heart disease. Results from two national surveys.

The National Heart, Lung, and Blood Institute sponsored national telephone surveys of practicing physicians in 1983 (N = 1610) and 1986 (N = 1277) to assess attitudes and practices regarding elevated serum cholesterol levels. The 1983 survey was conducted just before the release of the results of the Lipid Research Clinics Coronary Primary Prevention Trial, which showed that a reduction in the blood cholesterol level reduced coronary heart disease. In 1986, 64% of physicians thought that reducing high blood cholesterol levels would have a large effect on heart disease, up considerably from 39% in 1983. Whereas in 1983, physicians attributed considerably less preventive value to reducing the cholesterol level than to reducing blood pressure or smoking, this disparity was substantially smaller in 1986. The median range of blood cholesterol at which diet therapy was initiated was 6.21 to 6.70 mmol/L (240 to 259 mg/dL) in 1986, down from 6.72 to 7.21 mmol/L (260 to 279 mg/dL) in 1983; the median for drug therapy was 7.76 to 8.25 mmol/L. (300 to 319 mg/dL) in 1986 and 8.79 to 9.28 mmol/L (340 to 359 mg/dL) in 1983. In 1986, 87% of physicians surveyed felt that medical evidence warranted the recommended treatment levels set forth in the 1984 National Institutes of Health Consensus Conference on Lowering Blood Cholesterol. These changes indicate that by 1986, physicians were more convinced of the benefit of lowering high blood cholesterol levels and were treating patients accordingly. The data also suggest areas for continued educational initiatives.

Adult↗

Change in public perspective on cholesterol and heart disease. Results from two national surveys.

The National Heart, Lung and Blood Institute, Bethesda, Md, and the Food and Drug Administration, Washington, DC, sponsored two national probability telephone surveys (N = 4000) of adults to assess attitudes and knowledge about heart disease risk from high blood cholesterol levels and the public's efforts to lower blood cholesterol levels. The first survey was conducted in 1983, before release of the results from the Lipid Research Clinics Coronary Primary Prevention Trial, which showed that a reduction in the blood cholesterol level reduced coronary heart disease; the second survey was conducted in 1986. The percentage of adults who believed that reducing high blood cholesterol levels would have a large effect on heart disease increased from 64% in 1983 to 72% in 1986, so that the importance attached to reducing high blood cholesterol levels approached that attributed to reducing smoking and high blood pressure. In 1983, 35% of adults reported that they had their cholesterol level checked vs 46% in 1986. In both years, diet changes were most frequently chosen (greater than 60%) as ways to control the blood cholesterol level; reducing dietary fat was believed to be as important as reducing dietary cholesterol. By 1986, 23% of adults reported that they made dietary changes specifically to lower their blood cholesterol level, up from 14% in 1983. These comparative data show gains in public awareness and action relating to high blood cholesterol level risk. The data can be used to develop education programs.

Attitude to Health↗

Synthesis and antilipolytic activities of quinolyl carbanilates and related analogues.

A series of quinolyl carbanilates was prepared and tested as antilipolytic agents. These compounds inhibited production of glycerol from rat adipocytes and inhibited liberation of free fatty acids from triolein by canine cardiac triglyceride lipases. An extensive structure-activity relationship study indicated that 8-quinolyl 4-methoxycarbanilate (1) contained features necessary for maximum potency in vitro. Substituting a benzofuranyl group for the quinolyl group of 1 provided the most interesting compound on the basis of both potency and structural novelty. 7-Benzofuranyl 4-methoxycarbanilate (44) has IC50's of 16 and 0.3 microM in the myocardial lipase and rat adipocyte assays, respectively. In vivo, compound 44 was orally active as an inhibitor (97% at 25 mg/kg) of lipolysis in the rat.

Adipose Tissue↗

Synthesis and antiallergic activities of 1,3-oxazolo[4,5-h]quinolines.

A series of new 1,3-oxazolo[4,5-h]quinolines has been prepared. These compounds were tested as inhibitors of antigen-induced release of histamine (AIR) in vitro from rat peritoneal mast cells (RMC) and as inhibitors of IgE-mediated passive cutaneous anaphylaxis in the rat (PCA). After several modifications of the original lead, the most potent compound of the series was determined to be 5-chloro-1,3-oxazolo[4,5-h]quinoline-2-carboxylic acid methyl ester (4a). It has an IC50 of 0.3 microM in the RMC assay and an ED50 (intraperitoneal) of 0.1 mg/kg in the PCA test, which is 10 times and 60 times more potent than disodium cromoglycate (DSCG), respectively. Of greater importance, it is orally active (ED50 = 0.5 mg/kg) as an inhibitor of the PCA test.

Animals↗

Functional aspects of T-lymphocyte subsets in pregnancy.

Several recent reports have suggested that a decrease in circulating T helper cells may contribute to the relative immunodeficiency of pregnancy. To investigate the significance of these findings, 90 pregnant women were evaluated. The results of this study indicate that although pregnant women have a decreased proportion of T helper cells, they do have adequate T helper cell function as determined by an in vitro immunoglobulin synthesis assay and a T-lymphocyte colony-forming assay. Based on these studies it is unlikely that decreased numbers of T helper cells are primarily responsible for the immunodeficiency of pregnancy.

Adult↗

Synthesis of 2-(2,3-dihydro-2-oxo-1,3,4-oxadiazol-5-yl) benzo heterocycles. A novel series of orally active antiallergic agents.

A series of new 2-(2,3-dihydro-2-oxo-1,3,4-oxadiazol-5-yl) benzo heterocycles has been prepared. These compounds were tested as inhibitors of antigen-induced release of histamine (AIR) in vitro from rat peritoneal mast cells (RMC) and as inhibitors of IgE-mediated rat passive cutaneous anaphylaxis in the rat (PCA). Most of this new class of antiallergic agents showed good activity in the RMC assay. The most potent compound, 3-chloro-2-(2,3-dihydro-2-oxo-1,3,4-oxadiazol-5-yl)benzo[b]thiophe ne (6t), with an I50 value of 0.2 microM, is 15 times more potent than disodium cromoglycate (DSCG) in the RMC assay. Many compounds were orally active in the PCA test, and several of these compounds showed higher potency when given in this way to that shown by DSCG when given intraperitoneally.

Animals↗

Structure of the isonicotinyl hydrazone of norethindrone.

The contraceptive steroid norethindrone reacts with isoniazid both in vivo and in vitro to give the corresponding hydrazone, which exists as syn and anti (with respect to C-4) isomers. These isomers rapidly interconvert, with the anti form predominating in solution. The identification of the isomers was based on an interpretation of 1H- and 13C-NMR spectroscopic data and corroborated by high-performance liquid chromatographic UV spectrophotometric evidence. 1H- and 13C-NMR spectroscopic data for other derivatives of norethindrone hydrazone are presented and interpreted.

Chemical Phenomena↗

Physiological factors affecting drug toxicity.

Physiological factors that affect the fate of drugs in the body and thereby have effects on their pharmacology and toxicology involve the systems that control absorption, distribution, metabolism, and excretion. The main factors are disease, genetics, and age. Nutritional status, sex, hormonal status (e.g., the effects of pregnancy), and circadian rhythm have important influences. Maternal toxicity will affect the fetus. The absorption and excretion of drugs are frequently reduced by diseases. Excretion is reduced by impaired renal function, often found in the elderly, which may increase the toxic response. Distribution is affected by body weight and build, for example, the proportion of fat. The disposition of many drugs has been shown to be significantly influenced by circadian rhythms such that therapeutic doses may exhibit toxicity if administered at an inappropriate time of day. Metabolism is modified by environmental influences including previous food and drug experience, and various factors such as age, sex, and disease. Intersubject variations in drug disposition can be very great with possibly severe consequences for the individual; in this regard, knowledge of genetic polymorphism in drug metabolizing enzymes is rapidly increasing. The toxicology of a drug may be profoundly affected by a particular disease state, for example, the administration of a drug that might be a tumor promoter when a cancerous or precancerous condition exists. These effects are illustrated with examples from the literature and recent studies undertaken in the Bureau of Drug Research.

Acetylation↗

The metabolism of 3-methoxyamphetamine in dog, monkey and man.

1. The metabolism of 3-methoxyamphetamine in vivo was examined in dog, monkey and man. 2. The metabolites identified in all three species were 3-O-methyl-alpha-methyldopamine, 1-(3-methoxy-4-hydroxyphenyl)propan-2-ol, 3-hydroxyamphetamine, 1-(3-hydroxyphenyl)propan-2-one, 1-(3-hydroxyphenyl)propan-2-ol, 1-(3-methoxyphenyl)propan-2-ol and 1-(3-methoxyphenyl)propane-1,2-diol. 3. 1-Hydroxyl-1(3-hydroxyphenyl)propan-2-one was tentatively identified in the urine of all three species. 4. 4-O-Methyl-alpha-methyldopamine was also found in the urine of dog and monkey but not in human urine.

Ammonium Hydroxide↗

Metabolic O-demethylation of 3,4-dimethoxyamphetamine in vivo in dog and monkey.

1. The disposition of the hallucinogen 3,4-dimethoxyamphetamine in vivo was examined in dogs and monkeys. 2. O-Demethylation is important since 3-O-methyl-alpha-methyldopamine (3-methoxy-alpha-methyltyramine) was found in the urine of both species, and traces of alpha-methyldopamine were found in the urine of dogs. 3. Also found in the urine of dogs were 1-(3,4-dihydroxyphenyl)propan-2-one and 3,4-dihydroxybenzoic acid, which are side-chain modified metabolites of alpha-methyldopamine. 4. 1-(3-Methoxy-4-hydroxyphenyl)propan-2-one, a side-chain modified metabolite of 3-O-methyl-alpha-methyldopamine, was present in the urine of both dogs and monkeys. 5. The 3-O-demethylated isomers 4-O-methyldopamine and 1-(3-hydroxy-4-methoxyphenyl)propan-2-one were not detected.

Amphetamines↗