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Biomedical subjects

E Harman

Publications and source records attributed to E Harman.

At least 19 recordsLinked to original sources
PubMed1992

The effect of inhaled gallopamil, a potent calcium channel blocker, on the late-phase response in subjects with allergic asthma.

The effect of gallopamil on the late-phase response to inhaled allergen was evaluated in six young adults with allergic asthma in a crossover manner. During 2 study days, subjects received 20 mg of inhaled gallopamil or placebo 30 minutes before challenge with the same dose of allergen. In addition, a histamine challenge was performed 1 1/2 hours before and 24 hours after allergen challenge. On 2 additional study days, in the absence of allergen, basal airway responsiveness to histamine was measured before and after gallopamil or placebo administration. During the early phase, the mean +/- SD decrease in FEV1 was 28.0% +/- 11.3% after placebo and 25.1% +/- 8.4% after gallopamil administration (p greater than 0.05; beta = 0.14). During the late phase, the maximum decrease in FEV1 was 26.9% +/- 11.9% after placebo and 25.3% +/- 10.3% after gallopamil administration (p greater than 0.05; beta = 0.21). Airway reactivity to histamine 24 hours after allergen challenge could not be measured in three subjects after gallopamil administration and in one subject after placebo administration because of persistent bronchospasm. In contrast, basal responsiveness to histamine in the absence of allergen was modestly decreased by gallopamil. Since gallopamil is one of the most potent calcium channel blockers when it is administered by the inhaled route, it is unlikely that this group of drugs will be clinically useful for allergic asthma.

Administration, Inhalation↗
PubMed1992

Relative amount of albuterol delivered to lung receptors from a metered-dose inhaler and nebulizer solution. Bioassay by histamine bronchoprovocation.

The results of previous studies comparing bronchodilatation from beta agonists administered by metered-dose inhaler (MDI) and nebulizer solution have been conflicting. We therefore evaluated a range of albuterol doses administered by these two methods, using histamine bronchoprovocation as a bioassay for the amount of drug reaching the beta 2 receptors in the lung. Twelve stable asthmatic volunteers received, in a double-blind, randomized, crossover design on different days, placebo or one, two, four, or six puffs from an MDI attached to an InspirEase device (90 micrograms per puff) or 0.625, 1.25, 2.5, or 5.0 mg of solution delivered in 2 ml of buffered saline through a Hudson Updraft II nebulizer. The histamine concentration required to decrease FEV1 by 20 percent (PC20) was measured 1 h before and 30 min after administration of each treatment and expressed as the increase in PC20 from baseline. The dose-response curves for change in PC20 indicated that the higher doses of the nebulizer solution delivered more drug to beta 2 receptors in the lung than the lower doses from the MDI. For example, the geometric mean increase in PC20 was 1.1 +/- 1.6 (SD) after placebo, 7.5 +/- 2.7 after two puffs from the MDI, and 20.0 +/- 2.1 after 2.5 mg of nebulizer solution (p less than 0.05). Using this bioassay method and administration technique, we estimated that ten puffs from the MDI (0.9 mg) would deliver approximately the same amount of albuterol to lung receptors as 2.5 mg of the nebulizer solution. Taking into account previously published reports and the results of the present study, we conclude that differences in dose, administration technique, nebulizer system efficiency, and severity of airway obstruction can alter the amount of drug reaching the beta 2 receptors in the lungs and, thus, the clinical response.

Adult↗
PubMed1992

Evaluation of a generic albuterol metered-dose inhaler: importance of priming the MDI.

Since the patent on albuterol metered-dose inhalers (MDI) expired in 1989, several manufacturers have developed generic products. In order to determine whether one generic albuterol MDI is equivalent to a reference product (Ventolin MDI), we compared the relative efficacy of two puffs (180 micrograms) of each inhaler in 17 intermittent or mild chronic adult asthmatics (FEV1 48% to 77% predicted) in a randomized, single-blind, crossover manner. The test dose was the first two puffs out of each canister. Pulmonary function was measured before each test dose and at frequent intervals over eight hours. Baseline FEV1 values on both study days were within 20%. The mean +/- SD peak effect was 80.5 +/- 15.5% of maximum achievable improvement in FEV1 after the generic compared with 92.2 +/- 8.8% after Ventolin (P = .006). The area under the curve (AUC) for this same measurement during the first four hours was 242 +/- 75%.hr-1 after the generic compared with 297 +/- 40%.hr-1 after Ventolin, a mean difference of 19% (P = .002). The study was then repeated with the MDI primed prior to the test dose (ie, two puffs were first discharged into a waste basket) in subjects willing to return for re-study (n = 11). There was no significant difference in AUC in the second study: 215 +/- 77%.hr-1 after generic and 228 +/- 82%.hr-1 after Ventolin (P = .65); however, there was only a 35% chance of detecting a 20% difference in AUC with this sample size. These data indicate that, without priming, an MDI may deliver less drug, and thereby less therapeutic effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1991

Endogenous anabolic hormonal and growth factor responses to heavy resistance exercise in males and females.

To examine endogenous anabolic hormonal responses to two different types of heavy resistance exercise protocols (HREPs), eight male and eight female subjects performed two randomly assigned protocols (i.e. P-1 and P-2) on separate days. Each protocol consisted of eight identically ordered exercises carefully designed to control for load, rest period length, and total work (J) effects. P-1 utilized a 5 RM load, 3-min rest periods and had lower total work than P-2. P-2 utilized a 10 RM load, 1-min rest periods and had a higher total work than P-1. Whole blood lactate and serum glucose, human growth hormone (hGH), testosterone (T), and somatomedin-C [SM-C] (i.e. insulin-like growth factor 1, IGF-1) were determined pre-exercise, mid-exercise (i.e. after 4 of the 8 exercises), and at 0, 5, 15, 30, and 60 min post-exercise. Males demonstrated significant (p less than 0.05) increases above rest in serum T values, and all serum concentrations were greater than corresponding female values. Growth hormone increases in both males and females following the P-2 HREP were significantly greater at all time points than corresponding P-1 values. Females exhibited significantly higher pre-exercise hGH levels compared to males. The P-1 exercise protocol did not result in any hGH increases in females. SM-C demonstrated random significant increases above rest in both males and females in response to both HREPs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1991

Inhaled verapamil-induced bronchoconstriction in mild asthma.

Methacholine challenges were performed in ten subjects with mild asthma at 2 h before and 20 min after placebo or 5, 10, 20, 40, 80, and 160 mg of inhaled verapamil given in a single-blind randomized crossover manner on different days. While verapamil did not have a bronchodilator effect, the 10-mg dose modestly increased the concentration of methacholine required to decrease FEV1 by 20 percent (PC20). The mean (+/- SEM) increase in PC20 from baseline was 2.1 +/- 0.2 times baseline after 10 mg of verapamil, compared to 1.1 +/- 0.1 times baseline after placebo (p less than 0.001). Unexpectedly, bronchoconstriction (greater than 10 percent decrease in FEV1) associated with cough or wheezing was observed in seven of ten subjects at doses of 20 mg or more. This adverse effect was not related to the osmolarity of the nebulized solutions. Thirty minutes before a standardized exercise challenge, 13 subjects inhaled placebo, 10 mg, or the highest dose of verapamil tolerated during the methacholine study (20 to 160 mg) in a double-blind randomized crossover manner. The exercise challenge was aborted in three subjects because of bronchospasm that occurred after administration of the higher dose. The mean (+/- SEM) maximum change in FEV1 after exercise in the ten subjects completing all three regimens of treatment was -17.1 +/- 4.0 percent after placebo, -12.7 +/- 4.3 percent after 10 mg (p less than 0.05), and -6.4 +/- 3.6 percent after the highest dose (p less than 0.05). We conclude that increasing the dose of verapamil above 10 mg did not provide greater benefit but, paradoxically, induced bronchoconstriction in most of the subjects. Because of this potential bronchoconstrictor effect, high doses of oral or intravenous verapamil should be used with caution in asthmatic subjects.

Administration, Inhalation↗
PubMed1990

Pentamidine-induced torsades de pointes in a renal transplant recipient with Pneumocystis carinii pneumonia.

Pentamidine isethionate, an important agent used to treat Pneumocystis carinii pneumonia, has been shown to be associated with the development of torsades de pointes in patients with AIDS. We have described a case of pentamidine-induced polymorphous ventricular tachycardia in a renal transplant recipient whose renal insufficiency may have prolonged the duration of arrhythmias. Careful ECG monitoring should be done during pentamidine administration, especially in patients with renal insufficiency. Physicians should be aware that this variety of polymorphous ventricular tachycardia can occur well within the recommended dose of pentamidine. More data are needed to define the relationship between renal dysfunction, plasma levels, and pentamidine cardiotoxicity.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Hormonal and growth factor responses to heavy resistance exercise protocols.

To examine endogenous anabolic hormone and growth factor responses to various heavy resistance exercise protocols (HREPs), nine male subjects performed each of six randomly assigned HREPs, which consisted of identically ordered exercises carefully designed to control for load [5 vs. 10 repetitions maximum (RM)], rest period length (1 vs. 3 min), and total work effects. Serum human growth hormone (hGH), testosterone (T), somatomedin-C (SM-C), glucose, and whole blood lactate (HLa) concentrations were determined preexercise, midexercise (i.e., after 4 of 8 exercises), and at 0, 5, 15, 30, 60, 90, and 120 min postexercise. All HREPs produced significant (P less than 0.05) temporal increases in serum T concentrations, although the magnitude and time point of occurrence above resting values varied across HREPs. No differences were observed for T when integrated areas under the curve (AUCs) were compared. Although not all HREPs produced increases in serum hGH, the highest responses were observed consequent to the H10/1 exercise protocol (high total work, 1 min rest, 10-RM load) for both temporal and time integrated (AUC) responses. The pattern of SM-C increases varied among HREPs and did not consistently follow hGH changes. Whereas temporal changes were observed, no integrated time (AUC) differences between exercise protocols occurred. These data indicate that the release patterns (temporal or time integrated) observed are complex functions of the type of HREPs utilized and the physiological mechanisms involved with determining peripheral circulatory concentrations (e.g., clearance rates, transport, receptor binding). All HREPs may not affect muscle and connective tissue growth in the same manner because of possible differences in hormonal and growth factor release.

Adult↗
PubMed1989

Hypothalamic-pituitary-adrenal responses to short-duration high-intensity cycle exercise.

beta-Endorphin (beta-EP), adrenocorticotropin (ACTH), and cortisol plasma concentrations were examined before and after maximal exercise at four intensities [36, 55, 73, and 100% of maximal leg power (MLP)] by means of a computerized cycle ergometer. All intensities were greater than those eliciting peak O2 uptake for the individual subjects. Blood samples were collected at rest, immediately after exercise, and at 5 and 15 min postexercise. Significant (P less than 0.05) increases were observed at 36% MLP for beta-EP and ACTH immediately after exercise and at 5 and 15 min postexercise. Plasma cortisol increased at 36% MLP at 15 min postexercise. Blood lactate significantly increased at all postexercise collection points for exercise intensities of 36, 55, and 73% MLP and at 5 min postexercise for 100% MLP. beta-EP concentrations at 36% MLP were significantly correlated (r = 0.75) with capillary density (mm-2), and cortisol concentrations at 36% MLP were significantly correlated (r = 0.89) with percentage of type II muscle fibers. No other significant relationships were observed. These data show that brief, high-intensity exercise up to maximal power production results in a nonlinear response pattern in peripheral blood hormone concentrations. Furthermore, blood lactate levels do not appear to be related to hypothalamic-pituitary-adrenal hormone plasma concentrations at high exercise intensities.

Adrenocorticotropic Hormone↗
PubMed1989

Clinical relevance of the interaction of theophylline with diltiazem or nifedipine.

The results of previously published studies indicate that calcium channel blockers are capable of competitively inhibiting cytochrome P-450 activity in hepatic microsomes, the pathway of theophylline metabolism. In addition, case reports have suggested that theophylline serum concentrations change when a calcium channel blocker has been added to or deleted from a stable theophylline regimen. To determine the clinical relevance of this potential interaction in patients with chronic asthma, we measured a peak steady-state theophylline serum concentration in 21 subjects while receiving theophylline alone (400 to 1,500 mg/day), and again, at least seven days later, after the addition of continuous therapy with maximally tolerated doses of either diltiazem (n = 18) or nifedipine (n = 16). The diltiazem dose was increased in 120 mg/day increments, as tolerated, to a maximum of 240 to 480 mg/day, while the nifedipine dose was increased in increments of 40 mg/day, to a maximum dose of 80 to 160 mg/day. The mean +/- SEM theophylline serum concentrations were 13.6 +/- 1.4 micrograms/ml before and 14.0 +/- 1.2 micrograms/ml during concurrent diltiazem therapy, and 12.6 +/- 1.0 micrograms/ml before and 12.2 +/- 1.1 micrograms/ml during nifedipine (p greater than 0.05). With this sample size there is a 5 percent chance that we missed a 20 percent change in serum concentration (type II error). Thus, maximum tolerated doses of diltiazem or nifedipine do not impair the metabolism of theophylline to a clinically relevant degree and adjustment of theophylline dosage is not required after the addition or discontinuation of diltiazem or nifedipine. In addition, these data suggest that currently available in vitro techniques for evaluating drug interactions in the hepatocyte do not predict the clinical relevance of such an interaction in patients who might require both drugs for different therapeutic indications.

Adolescent↗
PubMed1988

Duration of effect of gallopamil, a calcium channel blocker, on methacholine-induced bronchoconstriction.

We previously demonstrated a modest but significant protective effect of inhaled gallopamil (D600), the methoxy derivative of verapamil, against methacholine-induced bronchoconstriction; however, the duration of the protective effect of this and other calcium channel blockers is unknown. We therefore evaluated the duration of this protective effect in 15 asthmatic subjects in a prospective, placebo-controlled trial. Methacholine challenges (Cockcroft method) were performed 2 hours before and 30 minutes after the administration of placebo, and 1 mg and 10 mg of inhaled gallopamil. Gallopamil did not alter resting airway caliber, but significantly increased the concentration of methacholine required to decrease the FEV1 20% 30 minutes after the dose. Results with both the 10-mg and 1-mg doses were significantly different from placebo, but not from each other. The duration of this protective effect was transient in the group as a whole; the mean drug activity ratios were not significantly different with this sample 2.5 hours after the dose. Thus the short duration of effect limits the potential clinical usefulness of gallopamil in suppressing the signs and symptoms of chronic asthma.

Adolescent↗
PubMed1988

Duration of protection of calcium channel blockers against exercise-induced bronchospasm: comparison of oral diltiazem and inhaled gallopamil.

The present study was conducted to determine the duration of the positive effect of oral diltiazem and inhaled gallopamil in mild asthmatic volunteers, ages 18-37 years, with a history of exercise-induced asthma and a 25-56% decrease in FEV1 after a standardized exercise challenge. Oral diltiazem 120 mg, inhaled gallopamil 10 mg, and placebo were administered in a double blind, randomized, crossover manner on different days 48 h apart. Diltiazem was administered 90 min and gallopamil 30 min before the first exercise challenge. Challenges were then repeated 3 and 6 h later. Neither diltiazem nor gallopamil significantly altered baseline FVC, FEV1, or FEF25-75. The mean maximum decrease in FEV1 after the first challenge was 16.8% after gallopamil, 25.2% after diltiazem and 30.1% after placebo. The mean post-exercise decrease in FEV1 after gallopamil was significantly smaller than after placebo. There were no significant differences in the post-exercise decreases in FEV1 between the three treatment regimens 3 and 6 h later. Thus, inhaled gallopamil provided significant protection against exercise-induced bronchospasm, but the beneficial effect was modest and short in duration.

Administration, Inhalation↗
PubMed1988

Maximal aerobic capacity for repetitive lifting: comparison with three standard exercise testing modes.

A multi-stage, repetitive lifting maximal oxygen uptake (VO2max) test was developed to be used as an occupational research tool which would parallel standard ergometric VO2max testing procedures. The repetitive lifting VO2max test was administered to 18 men using an automatic repetitive lifting device. An intraclass reliability coefficient of 0.91 was obtained with data from repeated tests on seven subjects. Repetitive lifting VO2max test responses were compared to those for treadmill, cycle ergometer and arm crank ergometer. The mean +/- SD repetitive lifting VO2max of 3.20 +/- 0.42 l.min-1 was significantly (p less than 0.01) less than treadmill VO2max (delta = 0.92 l.min-1) and cycle ergometer VO2max (delta = 0.43 l.min-1) and significantly greater than arm crank ergometer VO2max (delta = 0.63 l.min-1). The correlation between repetitive lifting oxygen uptake and power output was r = 0.65. VO2max correlated highly among exercise modes, but maximum power output did not. The efficiency of repetitive lifting exercise was significantly greater than that for arm cranking and less than that for leg cycling. The repetitive lifting VO2max test has an important advantage over treadmill or cycle ergometer tests in the determination of relative repetitive lifting intensities. The individual curves of VO2 vs. power output established during the multi-stage lifting VO2max test can be used to accurately select work loads required to elicit given percentages of maximal oxygen uptake.

Adult↗
PubMed1988

The effects of nalmefene, a potent oral opiate antagonist, on exercise-induced bronchospasm.

Endogenous opioids are released during exercise and have been demonstrated to induce mast cell degranulation when they are administered intradermally. Thus, these peptides may play a role in the pathogenesis of exercise-induced bronchospasm (EIB). However, in two previous studies, intravenous naloxone did not provide significant protection from EIB. To determine if these failures were due to inadequate dosage (pharmacokinetic failure) or lack of an inherent pharmacologic effect (pharmacodynamic failure), the present study was conducted with nalmefene (Key Pharmaceuticals, Inc., Miami, Fla.), a slowly metabolized, orally bioavailable opiate antagonist, with 30 times the potency of naloxone. Ten subjects with mild intermittent asthma and a greater than or equal to 20% decrease in FEV1 after a standardized exercise test were studied. nalmefene, 20 mg, and identically appearing placebo tablets were administered orally in a double-blind, randomized, crossover design 2 hours before bronchoprovocation. Treadmill exercise was performed for 6 minutes at a minute ventilation of 55% to 66% of the calculated maximum voluntary ventilation and not exceeding 75% to 85% maximal heart rate for age. Spirometry was performed before and 3, 5, 8, 10, and 15 minutes after exercise. The mean decrease in FEV1 after exercise was 28.6 +/- 4.5% with placebo and 30.3 +/- 4.5% with Nalmefene (p = 0.6; beta = 0.04 for a 15% difference). Thus, we conclude that narcotic antagonists do not alter airway reactivity to exercise. In addition, these data suggest that endogenous opioids probably do not play an important role in the pathogenesis of EIB.

Administration, Oral↗
PubMed1988

Dose response of inhaled gallopamil (D600), a calcium channel blocker, in attenuating airway reactivity to methacholine and exercise.

To determine if there is a dose-response relationship for calcium channel blockers in preventing experimentally induced bronchoconstriction, we evaluated the effects of inhaled gallopamil (D600), a potent methoxy derivative of verapamil, on airway reactivity to methacholine and exercise in volunteers with mild asthma. Methacholine challenges were completed by 11 subjects 2 hours before and 20 minutes after placebo, and 1, 2, 5, 10, and 20 mg of inhaled gallopamil administered in a single-blind, randomized manner on different days. Gallopamil did not significantly alter FVC, FEV1, or forced expiratory flow rate between 25% and 75% of FVC, but increased the dose of methacholine required to produce a 20% decrease in FEV1 from baseline (p less than 0.0001). The mean +/- SEM fold increase in the dose of methacholine required to produce a 20% decrease in FEV1 from baseline was 1.0 +/- 0.1 after placebo, 2.4 +/- 0.2 after 1 mg, 2.2 +/- 0.2 after 2 mg, 2.5 +/- 0.2 after 5 mg, 2.5 +/- 0.3 after 10 mg, and 2.3 +/- 0.2 after 20 mg. Thirty minutes before a standardized exercise challenge, 10 subjects inhaled 1 and 10 mg of gallopamil or placebo in a randomized, double-blind, crossover manner. The mean +/- SEM maximum decrease in FEV1 after exercise was 25.1 +/- 5% after 10 mg of gallopamil (p less than 0.01), 34.4 +/- 5% after 1 mg (p greater than 0.05), and 39.0 +/- 6% after placebo. We conclude that inhaled gallopamil only modestly alters airway reactivity to methacholine; increasing the dose greater than 1 mg did not provide greater benefit.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Dose-response of inhaled diltiazem on airway reactivity to methacholine and exercise in subjects with mild asthma.

Methacholine challenges were performed by 10 asthmatic subjects, 2 hours before and 15 minutes after placebo (diluent alone) and 5, 10, 15, 30, and 60 mg inhaled diltiazem given in a single-blind crossover manner. There was no significant change from placebo in the dose of methacholine required to produce a 20% decrease in forced expiratory volume in the first second (FEV1) (PD20); the fold increase in PD20 from baseline was 1.1 +/- 0.1 after placebo, 1.4 +/- 0.2 after 5 mg, 1.8 +/- 0.3 after 10 mg, 1.4 +/- 0.2 after 15 mg, 1.6 +/- 0.2 after 30 mg, and 1.2 +/- 0.1 after 60 mg. There was a 1% chance that we missed a twofold difference between placebo and the 10 mg dose because of inadequate sample size. Fifteen minutes before a standardized exercise challenge, 10 subjects received placebo, 10 mg, and the highest dose tolerated during the methacholine study (20 to 45 mg) in a randomized double-blind crossover design. The mean +/- SE maximum postexercise decrease in FEV1 was 28.8% +/- 5.7% after placebo, 23.4% +/- 4.6% after 10 mg, and 20.8% +/- 3.0% after high-dose diltiazem (P greater than 0.05). There was a 12% chance that we missed a 15% difference between placebo and the high-dose regimen because of inadequate sample size. We conclude that diltiazem does not attenuate airway reactivity to methacholine or exercise even when high concentrations are delivered to the lungs.

Adult↗
PubMed1987

Automated data collection and processing for a cycle ergometer.

A system is described for collection and processing of data from a cycle ergometer. Cycle pedals, specially made to withstand the extremely high forces exerted during maximal power cycling, contain transducers to measure pedal angle relative to the crank and foot forces both perpendicular and parallel to the pedal surface. An additional transducer monitors crank position. Output signals are conditioned, amplified, digitized by a 12-bit analog-to-digital converter, fed into a computer at 100 Hz/channel, and mathematically smoothed to attenuate noise. For each sample interval, foot force components perpendicular and parallel to the crank arm are calculated. Power generated on each crank revolution is determined from transducer information. Computer graphics display pedaling parameters vs. crank angle in both rectangular and circular format. Data files containing variables descriptive of pedaling force curves are produced to enable computerized statistical analysis of cycling performance.

Computer Graphics↗