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Biomedical subjects

K A Hale

Publications and source records attributed to K A Hale.

12 recordsLinked to original sources
PubMed1995

High-performance liquid chromatographic assay of plasma thalidomide: stabilization of specimens and determination of a tentative therapeutic range for chronic graft-versus-host disease.

Thalidomide is now widely used to treat chronic graft-versus-host disease, but its use is associated with non-teratogenic side effects such as peripheral neuropathy. To examine the value of monitoring plasma concentrations of the drug in such patients, we have developed a high-performance liquid chromatographic (HPLC) assay. The method uses 0.5 mL plasma, is linear to 10 mg/L and had a detection limit of 0.2 mg/L. Thalidomide in plasma specimens was unstable at physiological pH but could be stabilized for several weeks by simple acidification. We describe a protocol for monitoring patients treated with thalidomide which permits convenient transportation and storage of specimens and report, provisionally, that plasma concentrations in the range 1-7 mg/L are therapeutically effective in chronic graft-versus-host disease without adverse side effects.

Chromatography, High Pressure Liquid↗
PubMed1994

Lack of effect of H2-receptor antagonists on the pharmacokinetics of alcohol consumed after food at lunchtime.

The possibility of a pharmacokinetic interaction between H2-receptor antagonists and alcohol consumed at lunchtime, was investigated in 24 healthy non-alcoholic male subjects, each receiving ranitidine 150 mg four times daily, cimetidine 400 mg four times daily, famotidine 20 mg four times daily and placebo in an open, four-way cross-over study. The subjects consumed 50 g alcohol after a standard lunch on the eighth day of dosing with study medication. Blood samples taken during the 6 h after alcohol consumption were analysed for alcohol concentrations by gas liquid chromatography using head space analysis. None of the H2-receptor antagonists had any statistically significant effects on any of the pharmacokinetic parameters for alcohol. Mean Cmax (95% CI) results for ranitidine were 547 (516, 580), cimetidine 531 (501, 563), famotidine 563 (530, 598) and placebo 529 (499, 561) mg l-1.

Adult↗
PubMed1992

The suitability of the urinary metabolite 1-hydroxypyrene as an index of poly nuclear aromatic hydrocarbon bioavailability from workers exposed to carbon black.

Levels of airborne dust have been measured in the breathing zone of five warehouse packers in a carbon black manufacturing plant on consecutive days over 1 week. Post-shift urine samples were collected on individuals over the week and the concentration of the pyrene metabolite 1-hydroxypyrene have been measured. A questionnaire was used to assess the likelihood of potential confounding factors, such as direct exposure to feedstock oil, as well as smoking and diet. The arithmetic mean both of airborne dust and of excreted 1-hydroxypyrene for each individual have been correlated (a) with the constraint that the regression line pass through the origin, and (b) without this constraint. The slope of the regression through the origin was significant and that of the second regression (not through the origin) was not. The statistical test to determine whether excretion on days after Monday was higher than that on Monday itself proved highly significant. The results suggest that 1-hydroxypyrene may be a useful indicator of exposure to the PNAs adsorbed onto carbon black.

Biological Availability↗
PubMed1992

Caffeine or theophylline for neonatal apnoea?

Caffeine, in the dose usually recommended (12.5 mg/kg loading dose and 3 mg/kg daily maintenance), and a higher dose regimen (25 mg/kg loading and 6 mg/kg daily maintenance), was compared with theophylline (7.5 mg/kg loading and 3 mg/kg thrice daily maintenance). The study was a randomised controlled trial in the treatment of a group of 44 infants of less than 31 weeks' gestation (mean gestational age 28.3 weeks) who were suffering from frequent apnoeic attacks. All three regimens produced a significant reduction in apnoeic attacks within 24 hours, but only the higher dose caffeine and theophylline groups showed a significant improvement in apnoea within eight hours. The use of caffeine for the treatment of neonatal apnoea is recommended, because a once daily dose is more easily administered, and because it was found that plasma concentrations were more predictable than those of theophylline. If used in very preterm infants, however, its is suggested that a higher dose regimen than that previously recommended be used to achieve a faster response.

Apnea↗
PubMed1984

Lung disease in long-term cigarette smokers with and without chronic air-flow obstruction.

Despite the established role of cigarette smoking in the causation of chronic air-flow obstruction (CAO), only a small proportion of regular cigarette smokers develop significant clinical disease. We compared emphysema severity as well as pathologic and morphometric features of the peripheral conducting airways and the muscular pulmonary arteries among 3 groups of older subjects. These groups included lifelong nonsmokers (NSM), regular smokers without severe disease (SM), and smokers with an established diagnosis of CAO (SM-CAO). For most pathologic features examined there was an orderly progression in severity when comparing SM to NSM and SM-CAO to SM. Emphysema severity and scores for peripheral airways disease, except for goblet cell metaplasia, better distinguished SM-CAO from SM than did measures of bronchiole lumenal caliber. Within the SM-CAO group, the premortem percent predicted forced expiratory volume in one second (FEV1) correlated significantly with emphysema severity (r = 0.74), with average bronchiole diameter (r = 0.54), with the proportion of bronchioles with diameters less than 400 mu (r = 0.51), but not with any of the scores for bronchiolar disease. However, within this group no morphologic or pathologic feature of the small airways was an independent predictor of ventilatory function beyond that of emphysema alone. When compared with those from NSM, histological sections from SM-CAO lungs contained approximately twice as many fully muscularized artery profiles 0 to 300 mu in diameter, the arterial medial muscle layer was doubled in thickness, and the amount of arterial intimal fibrosis was tripled.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1983

Chronic airflow obstruction. Two-pronged approach to outpatient management.

The goal of outpatient management of chronic airflow obstruction is to relieve symptoms, which can be accomplished by smoking cessation and by use of bronchodilators. The inhaled beta agonists are the first choice for bronchodilator therapy, followed by oral theophylline if beta agonists alone are ineffective. If symptoms persist, corticosteroids should be tried. Because of the serious side effects of steroids, however, objective evidence of improvement must be documented before long-term use can be justified.

Adrenal Cortex Hormones↗
PubMed1980

Morphologic and morphometric effects of prolonged cigarette smoking on the small airways.

We studied lungs from 25 smokers and 14 lifelong nonsmokers, all over 40 yr of age, to examine the relationship of long-term cigarette smoking to histopathologic changes in the small airways. Despite considerable overlap between the 2 groups, smokers had a significantly higher score (p < 0.01) for small airway disease. The specific morphologic features separating smokers from nonsmokers were increases in goblet cell metaplasia (p < 0.001), smooth muscle hypertrophy (p < 0.05), inflammation in the walls of bronchioles (p < 0.01), and respiratory bronchiolitis (p < 0.001). The average bronchiolar diameter was not significantly different in smokers compared with nonsmokers; however, smokers had an excess of airways less than 400 microns in diameter (p < 0.03). Among smokers, the severity of small airway disease correlated with the percentage of airways that are less than 400 microns in diameter (rs = 0.63) and with the extent of centrilobular emphysema (r = 0.53). Smokers also had an increase in the proportion of bronchial gland mass (p < 0.05), but this pathologic feature was not related to the severity of either small airway disease or centrilobular emphysema. We concluded that prolonged cigarette smoking is associated with progressive pathologic changes in the small airways that may be an important cause of airflow obstruction and that may predispose to the development of centrilobular emphysema.

Adult↗
PubMed1980

Morphologic changes in the muscular pulmonary arteries: relationship to cigarette smoking, airway disease, and emphysema.

The muscular pulmonary arteries were studied by morphometric methods in 25 long-term cigarette smokers and were compared with those of 14 lifelong nonsmokers. Muscular pulmonary arteries < 500 microns in external diameter were identified and counted. The external diameter, medial thickness, and intimal thickness were measured in each of these arteries. Smokers had an increased number of transected muscular arteries < 200 microns in diameter (p < 0.03), increased medial smooth muscle (p < 0.02), and more intimal thickening (p < 0.04). Among smokers, these vascular changes correlated significantly with the severity of small airway disease and with the degree of emphysema, but not with bronchial mucous gland enlargement. We conclude that regular cigarette smoking is associated with morphologic changes in the muscular pulmonary arteries that evolve in parallel with small airway disease and emphysema. Although the functional significance of these findings is unknown, they may be important in the eventual development of pulmonary hypertension and cor pulmonale.

Adult↗