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Biomedical subjects

J R Foster

Publications and source records attributed to J R Foster.

At least 73 records · Page 4Linked to original sources
PubMed1989

Influence of rifampin on tocainide pharmacokinetics in humans.

The effects of metabolic enzyme induction by rifampin on the pharmacokinetics of tocainide were studied in eight healthy volunteers. In an open, unrandomized fashion, volunteers received tocainide hydrochloride 600 mg orally. Blood samples were obtained immediately before and at various time intervals up to 48 hours after the dose. Urine samples were collected before and at various intervals up to 72 hours after the dose. Serum and urine samples were assayed for tocainide content by high-performance liquid chromatography. After a four-week washout period, volunteers ingested 300 mg of rifampin by mouth every 12 hours. After 10 doses, subjects received a second oral dose of tocainide hydrochloride 600 mg, and blood and urine samples were collected as before. During the sampling period, subjects continued to ingest rifampin 300 mg orally every 12 hours. Significant differences in elimination rate constant (average increase, 0.0545 to 0.0748 hr-1), elimination half-life (average reduction, 13.2 to 9.4 hours), oral clearance, and area under the concentration-time curve (average reduction, 76.8 to 55.0 mg.hr/L) between the control and rifampin treatment phases were observed. Volume of distribution and renal clearance of tocainide were not significantly different after rifampin treatment. Tocainide appears to be susceptible to significant drug-drug interactions mediated by metabolic enzyme induction.

Adult↗
PubMed1988

Use dependence of amiodarone during the sinus tachycardia of exercise in coronary artery disease.

The QRS duration at rest and during exercise was studied in 19 patients with coronary artery disease before and after oral amiodarone therapy to determine if this drug produces detectable rate-dependent conduction slowing during physiologic increases in heart rate. QRS duration did not change significantly during exercise in the absence of the drug. However, after amiodarone, QRS duration at rest increased from 99 to 114 ms (p less than 0.001), and increased further from 114 to 127 ms (p less than 0.001) during the 45 beats/min mean increase in heart rate produced by exercise. The magnitude of this effect was related to the resting QRS duration. After amiodarone therapy, the QRS increased during exercise by only 6% in 8 patients with QRS less than 110 ms, while in 12 patients with QRS greater than or equal to 110 ms, the QRS increased by 15% (p less than 0.05). Rate-dependent conduction slowing occurs during the sinus tachycardia of exercise in patients treated with amiodarone, presumbably due to use-dependent sodium channel blockade. This result is most pronounced in patients with abnormal ventricular conduction at rest.

Administration, Oral↗
PubMed1988

Thresholds, refractory periods, and conduction times of the normal and diseased human atrium.

In order to better understand the electrophysiology of the diseased human atrium, we measured high right atrial refractory periods, threshold, and conduction times of 61 patients undergoing routine electrophysiologic study. Refractory periods and conduction times of patients with apparently normal atria were compared to those of patients with a history of persistent sinus bradycardia, atrial fibrillation, or other forms of primary atrial tachyarrhythmia. Refractory periods and thresholds were derived from strength-interval curves. Conduction times were measured for all premature beats induced. Threshold, refractory periods, and conduction times of premature beats induced late in the cardiac cycle did not distinguish patients with normal atria from patients with bradycardia or tachycardia. In contrast, increases in conduction time of early cycle premature beats separated patients with these abnormalities from patients with normal atria. The increases in interatrial and intraatrial conduction time of early cycle premature beats were the strongest correlates of primary atrial tachyarrhythmia (r = 0.52, p = 0.0065 and r = 0.274, p = 0.041, respectively) and induction of repetitive atrial firing (r = 0.65, p = 0.002, and r = 0.59, p = 0.0001, respectively). This increase in conduction time of early cycle premature beats may predispose these patients to primary atrial tachyarrhythmias.

Atrial Fibrillation↗
PubMed1988

The role of trichloracetic acid and peroxisome proliferation in the differences in carcinogenicity of perchloroethylene in the mouse and rat.

Fischer 344 rats and B6C3F1 mice of both sexes were exposed to 400 ppm perchloroethylene (PER) by inhalation, 6 hr/day for 14, 21, or 28 days or to 200 ppm for 28 days. Increased numbers of peroxisomes were seen under the electron microscope and increased peroxisomal cyanide-insensitive palmitoyl CoA oxidation was measured (3.6-fold increase in males and 2.1-fold increase in females) in the livers of mice exposed to PER. Hepatic catalase was not increased. Peroxisome proliferation was not observed in rat liver or in the kidneys of either species. Trichloracetic acid (TCA), a known carcinogen and hepatic peroxisome proliferating agent, was found to be a major metabolite of PER. Blood levels of this metabolite measured in mice and rats during and for 48 hr after a single 6-hr exposure to 400 ppm PER showed that peak blood levels in mice were 13 times higher than those seen in rats. Comparison of areas under the curves over the time course of the experiment showed that mice were exposed to 6.7 times more TCA than rats. The difference in metabolism of PER to TCA in mice and rats leads to the species difference in hepatic peroxisome proliferation which is believed to be the basis of the species difference in hepatocarcinogenicity. Peroxisome proliferation does not appear to play a role in the apparent carcinogenicity of PER in the rat kidney.

Administration, Inhalation↗
PubMed1988

A curriculum for education in geriatric psychiatry.

The authors present recommendations for educating medical students and psychiatric residents in geropsychiatry. They are primarily concerned with the objectives and methods rather than the content of training. Proposals are structured in terms of training objectives and educational settings in which such training takes place. The proposals are intended to be specific enough to be truly useful and at the same time sufficiently generalizable to adapt to geropsychiatric training in a variety of institutions. Priority is given to integrating knowledge of normal and abnormal aging with the clinical skills and empathy necessary to approach patients with competence and understanding.

Aged↗
PubMed1987

Enhancement of procainamide-induced rate-dependent conduction slowing by elevated myocardial extracellular potassium concentration in vivo.

Procainamide, a type 1A antiarrhythmic drug, blocks sodium channels and reduces the maximum rate of rise of the cardiac action potential (Vmax) in a rate-dependent fashion. In vitro, the magnitude of this rate-dependent reduction in Vmax is greater in tissue that is partially depolarized at rest than in tissue with a normal resting potential. Reductions in Vmax produced by drugs that block sodium channels are also directly related to the reductions in longitudinal conduction velocity of action potential propagation in papillary muscle preparations. We therefore sought to determine whether the rate-dependent conduction slowing induced by procainamide in the intact canine heart is enhanced in myocardial tissue abnormally depolarized by an elevated myocardial extracellular potassium concentration, [K+]o. QRS duration and epicardial activation times were measured as indexes of myocardial conduction. QRS duration and epicardial activation times were measured at control (4.0 mM) and at intermediate (6.5 mM) and high (9.2 mM) myocardial [K+]o in the presence or absence of a clinically relevant procainamide concentration (12.2 +/- 2.6 g/ml) at the longest obtainable interstimulus interval of 440 msec and at 330, 280, and 250 msec. Intermediate and high myocardial [K+]o alone induced rate-dependent conduction slowing as the frequency of stimulation increased (cycle length 440 msec to 330, 280, and 250 msec). In the presence of procainamide, rate-dependent conduction slowing was observed at all levels of myocardial [K+]o, and the amount of rate-dependent change in conduction time increased as the myocardial [K+]o was increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1987

The four alternative auditory feature test (FAAF)--linguistic and psychometric properties of the material with normative data in noise.

The linguistic properties of the FAAF test material are expounded in relation to its objectives. It is shown from reference data that there are lexical effects inherent in the use of real-word minimal pairs rather than nonsense syllables. These are word-frequency effects upon phonemes in initial position and effects of imageability upon phonemes in final position. However, those effects are not large enough to undermine the use of the FAAF as an acoustical phonetically structured material reflecting the analysis of auditory information. Normative data on a range of signal-to-noise ratios are presented. These data have helped to delimit the subsets of items that best reflect variations in performance under easy and under difficult conditions. This offers a mapping of the percentage correct from scores at one or two fixed S/N ratios required for a given level of performance and hence permits comparison with SRT(N) measures.

Humans↗
PubMed1987

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.

Adult↗
PubMed1986

Immunocytochemical localization of cytochrome P-450 in hepatic and extra-hepatic tissues of the rat with a monoclonal antibody against cytochrome P-450 c.

The cellular distribution of cytochrome P-450 has been studied in the liver and a number of extrahepatic tissues in the rat by immunocytochemistry, using an antibody raised against cytochrome P-450 form c. Immunoreactive cytochrome P-450, most probably form c, was found in the proximal tubules of the kidney, in the Clara cells of the lung, and in the olfactory epithelium and Bowman's glands of the olfactory tissue, in addition to its location in the liver. Immunoreactive cytochrome P-450 was not found in the small intestine, the testes or the adrenal gland, although these organs are known to contain isoenzymes of cytochrome P-450. The use of antibody titration enabled the effects of phenobarbitone, beta-naphthoflavone and clofibrate on the content and distribution of immunoreactive cytochrome P-450 to be studied in both the liver and in the other organs discussed. Phenobarbitone induces epitope-specific cytochrome P-450 in the centrilobular cells of the liver but has no effect in any of the other tissues studied. Clofibrate is without effect on the levels of immunoreactive cytochrome P-450 in any of the tissues studied. In contrast, beta-naphthoflavone induces immunoreactive cytochrome P-450 in the periportal region of the liver, and also in the Clara cells of the lung, in the enterocytes of the small intestine and in the proximal tubules of the kidney. Of all of the tissues studied, in which immunoreactive cytochrome P-450 could be detected, only the olfactory epithelium failed to undergo enzyme induction following treatment with beta-naphthoflavone.

Adrenal Glands↗
PubMed1986

Alpha 2U-globulin: measurement in rat kidney and relationship to hyaline droplets.

The concentration of renal alpha 2U-globulin increased in a dose-dependent manner in adult male but not female rats which received a single dose of 2,2,4-trimethylpentane (TMP). After administration of a single dose of 12 mmol TMP/kg to adult male rats, the renal concentration of alpha 2U-globulin reached a peak at 48 hours and returned to near background level after 7 days. These changes in renal alpha 2U-globulin concentration were closely paralleled by changes in renal hyaline droplet formation. Renal alpha 2U-globulin and hyaline droplets were absent in normal pre-puberty male rats, and neither could be stimulated by a single dose of TMP. alpha 2U-Globulin was localised in the renal cortex of adult male rats, in particular the S2 segment of the proximal tubule. A greater staining intensity due to alpha 2U-globulin was seen in the S2 and adjacent segments after a single dose of TMP. A strong association is suggested between the presence of renal hyaline droplets and the occurrence of alpha 2U-globulin.

Alpha-Globulins↗
PubMed1986

Alpha 2U-globulin: measurement in rat kidney following administration of 2,2,4-trimethylpentane.

Hyaline droplet formation was stimulated markedly in the kidneys of post-puberty male rats 24-48 h after a single oral dose of 12/24 mmol/kg 2,2,4-trimethylpentane [TMP]. Renal hyaline droplet formation could not be detected in female rats or in pre-puberty male rats following similar doses of TMP. A dose-dependent increase in the renal concentration of the androgen-dependent low molecular weight protein, alpha 2U-globulin was observed in post-puberty male rats 24 h after a single oral dose of TMP, over the range 0.3-12.0 mmol/kg. After administration of a single dose of 12 mmol/kg TMP to male rats, the renal concentration of alpha 2U-globulin rose steadily up to a peak after 48 h and then returned slowly to near normal after 7 days. Renal alpha 2U-globulin could not be detected in female rats and in pre-puberty male rats. An immunocytochemical assay was developed to examine the distribution of alpha 2U-globulin within the kidney. alpha 2U-Globulin was localised primarily in the S2 segment of renal proximal tubules in untreated male rats. Rats which received a single dose of 12 mmol TMP/kg showed not only a greater staining intensity, due to the presence of a higher concentration of alpha 2U-globulin, but also staining in adjacent segments of the renal cortex. Several urinary biochemical indicators of nephrotoxicity were measured daily in male rats for up to 72 h following a single dose of 12 mmol TMP/kg. Renal proximal tubular function was unimpaired by TMP treatment. On the basis of studies in untreated and TMP-treated rats, a strong association has been found between the presence of renal hyaline droplets and the occurrence of renal alpha 2U-globulin. The findings in the present study provide an explanation for the occurrence of renal hyaline droplets only in adult male rats, but do not, as yet, establish the toxicological significance of increases in renal hyaline droplet formation.

Alpha-Globulins↗
PubMed1986

Psychoacoustical and audiometric prediction of auditory disability for different frequency responses at listener-adjusted presentation levels.

Audiometric prediction of word identification scores has typically used one fixed presentation level for all subjects in the sample, with presentation in quiet and a wide range of hearing impairment among the listeners; under such conditions it is hardly surprising that moderate to good predictions are found. To see if prediction is possible under clinically relevant conditions, that is, on a homogeneous clinical sample of new hearing-aid candidates and to listener-adjusted levels, as would obtain in use of a hearing aid. In addition to audiometric variables, we employed a clinical approximation to the psychoacoustic tuning curve. We tested speech identification (FAAF) performance both with a 'rising'(+9 dB/octave) and with a 'flat' frequency response. Prediction of performance in the 'flat' condition was only good when a full set of audiometric frequencies entered the multiple-regression formula, each with its own weighting. Audiometric prediction for the 'rising' frequency response was particularly poor. Thus, the fairly good predictability from thresholds found traditionally for word identification scores or other disability measures appears to be a special case, depending partly on the wide range of hearing levels employed. Within our clinical sample the predictive power of formulae based on the mean of all thresholds or of mid-frequency thresholds alone (as used in compensation schemes) or on a priori combinations of thresholds (such as slopes) was generally poor. However, a three-parameter model taking account separately of low (0.25 kHz) and high-frequency (greater than 2.0 kHz) thresholds was effective. This and other audiometric descriptions were valuably supplemented by a psychoacoustic measure of frequency resolution at 2 kHz. In particular, such supplementation here allowed a satisfactory level of prediction to be achieved for speech heard with a +9 dB/octave frequency response, which the audiogram alone did not. The limitations of the prediction paradigm are discussed and several conceptual and statistical problems not previously emphasised in the audiological literature are illustrated in relation to the data.

Adult↗
PubMed1985

Efficacy of verapamil in exercise-induced ventricular tachycardia.

The antiarrhythmic efficacy of verapamil was determined by serial treadmill testing in 16 patients with reproducible exercise-induced ventricular tachycardia (VT). Twelve of the 16 patients responded to verapamil, 0.2 mg/kg intravenously; in 8 of these 12 responders, an oral verapamil regimen of 160 to 320 mg given every 8 hours also prevented exercise-induced VT. Plasma verapamil concentration was significantly higher in the responders than in the nonresponders to intravenous verapamil, but levels were similar in responders and nonresponders to oral therapy. The 8 responders to the oral drug were followed up while receiving verapamil therapy for 6 to 22 months (mean 15), and exercise-induced VT did not recur in any patient. Five of the 8 responders also had concomitant spontaneous VT unrelated to exercise which verapamil suppressed initially as well: 4 remained free of spontaneous VT, while 1 patient had recurrence of spontaneous VT. Thus, in patients with exercise-induced VT, verapamil is a promising alternative therapy to beta-adrenergic blocking agents. The effectiveness of verapamil is consistent with a mechanism of arrhythmogenesis involving calcium channels.

Administration, Oral↗
PubMed1985

A comparative study of the pulmonary effects of NO2 in the rat and hamster.

A study of the response of rat and hamster to nitrogen dioxide (NO2) under identical conditions has been undertaken. Exposure to 20 parts/IO6 NO2 for 24 h produced a mild cytotoxic effect on the terminal bronchiole and proximal alveoli in the rat, whereas the hamster developed a moderate to severe bronchiolitis and alveolitis. Electron microscopic examination of tissue sections showed accumulation of surfactant in lamellar bodies of the alveolar type II cell in the rat but not in the hamster, whereas in the hamster Clara cells were observed in mitosis. Increased levels of surfactant isolated from whole lung homogenates by sucrose gradient centrifugation were found in both rat and hamster. In contrast surfactant isolated from bronchiolo-alveolar lavage was increased only in the hamster. The results suggest that caution must be exercised in the choice of animal model in investigations aimed at the understanding of the toxicological effects of nitrogen dioxide in man.

Animals↗