Nominal resistive power loads of cycle ergometers.
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Equipment Design↗
Biomedical subjects
E Harman
Publications and source records attributed to E Harman.
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↗
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↗
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↗
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↗
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↗
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↗
Should we abandon the notion that calcium channel blockers are potentially useful for asthma?
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Asthma↗
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↗
The effect of oral diltiazem on airway reactivity to methacholine and exercise in subjects with mild intermittent asthma.
The effect of increasing doses of oral diltiazem on airway reactivity to methacholine was evaluated in 10 volunteers with mild asthma. Then the highest tolerated dose was compared with placebo in preventing exercise-induced bronchoconstriction. Methacholine challenges were performed 1 h before and 100 min after placebo or after 30, 60, 90, 120, or 180 mg of oral diltiazem, given in a single-blind, crossover manner on different days within 2 wk. Diltiazem, at doses above 60 mg prolonged the P-R interval of the electrocardiograph but had no significant effect on FVC, FEV1, or FEF25-75. The mean +/- SEM ratio of the dose of methacholine required to produce a 20% decrease in FEV1 (PD20) after diltiazem to the PD20 before diltiazem, i.e., the fold increase in PD20, was not significantly different from placebo at any dose: 0.93 +/- 0.11 after placebo, 1.2 +/- 0.1 after 30 mg, 1.3 +/- 0.3 after 60 mg, 1.2 +/- 0.2 after 90 mg, 1.1 +/- 0.1 after 120 mg, and 1.0 +/- 0.1 after 180 mg. One hundred minutes before a standardized exercise challenge, 120 to 180 mg of oral diltiazem and identically appearing placebo tablets were administered in a randomized, double-blind, crossover design on separate days at least 48 h apart. The mean +/- SEM maximal postexercise decrease in FEV1 was 25.5 +/- 3.3% after placebo and 17.0 +/- 4.8% after diltiazem (p less than 0.01). There was no correlation between change in FEV1 and serum concentrations of diltiazem or its active metabolite desacetyldiltiazem.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Short-term outcome among patients with leukemia and lymphoma admitted to a medical intensive care unit.
We report here the short-term outcome of medical intensive care unit (MICU) admissions of patients with leukemia or lymphoma. We reviewed the charts of 29 such patients. Of 21 patients with acute leukemia admitted to the MICU, seven survived to leave the hospital; of eight patients with lymphoma, two survived to leave the hospital. The acute physiologic score (APS) (a system in which 0 to 4 points are given for the degree of deviation from normal for several organ systems) was used to score each patient on day 1 of their MICU stay. The APS for all patients with leukemia and lymphoma admitted to MICU was 28 +/- 11. The mortality was 69%, which is not significantly different from the predicted mortality of 56% for patients with the same APS but no underlying malignant disease. Among the survivors, young age and early stage of disease were predictors of favorable outcome.
Adolescent↗
Evaluation of the asthmogenicity of propafenone, a new antiarrhythmic drug. Comparison of spirometry with methacholine challenge.
Propafenone is a new membrane-stabilizing antiarrhythmic agent that structurally resembles the beta-adrenergic receptor antagonist, propranolol. To determine the potential asthmogenicity of this new drug, pulmonary function, airway reactivity to methacholine, blood pressure, the electrocardiogram, and plasma concentrations were measured in 12 patients with mild intermittent asthma after 48 to 72 hours of treatment with placebo and with oral propafenone in low dosage (150 mg every eight hours) and high dosage (300 mg every eight hours) in a double-blind crossover manner. The forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory flow over the middle half of the FVC (FEF25-75%), heart rate, and blood pressure during the three regimens of treatment were not significantly different; however, the QRS interval on the ECG was significantly widened with both dosages of active drug, and the mean provocative dose of methacholine (+/- SE) required to reduce FEV1 by 20 percent (PD20) decreased from 3.0 +/- 0.6 mg/ml with placebo to 2.1 +/- 0.7 mg/ml with the high dosage of propafenone (p less than 0.01). The mean PD20 on the low-dose regimen was not significantly different from placebo or high-dose therapy. A potentially relevant increase in airway reactivity, as measured by a ratio of less than 0.5 for PD20 after treatment to PD20 after placebo, occurred in seven subjects with high-dose and in one subject during low-dose treatment (p less than 0.01). These data suggest that propafenone should be used with caution in patients with asthma and that bronchial provocation will provide a more sensitive measure of the asthmogenicity of a drug with beta-adrenergic receptor antagonist activity than pulmonary function tests. Moreover, use of bronchial provocation allows the selection of subjects with mild disease, thus reducing the risk of potentially severe bronchospasm.
Adult↗
Sleep-disordered breathing and oxygen desaturation in obese patients.
Fourteen morbidly obese subjects, referred to our institution for bypass surgery for obesity, were studied with regard to pulmonary function and respiratory patterns during sleep. The seven female patients experienced no episodes of desaturation or disordered breathing during sleep. Six of the seven male patients experienced desaturation or disordered breathing. The one who did not had hypogonadism, suggesting that testosterone may have a role in the regulation of breathing during sleep. The two patients with the most frequent episodes of apnea and lowest oxygen saturation had a clinical picture consistent with the pickwickian syndrome. This supports the relationship previously noted between the degree of hypoxia and the presence of hypersomnolence.
Adult↗
Pulmonary risk factors in surgery.
The altered pattern of ventilation and the diminution in lung vol-mes after general anesthesia and surgery predispose the postoperative patient to develop serious pulmonary complications. Many additional risk factors are readily identifiable and often reversible. Careful attention to these allows the institution of therapy which can greatly diminish the incidence of serious postoperative pulmonary complications. In patients for whom thoracic surgery is contemplated, the identification and quantification of risk factor helps identify those individuals in whom surgical risk is prohibitively great, or who will not likely tolerate lung resections of major or minor extent.
Humans↗
Sarcoidosis presenting as multiple pulmonary nodules.
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Adult↗
Miliary tuberculosis presenting as acute respiratory failure: treatment by membrane oxygenator and ventricle pump.
A 58-year-old woman with high fever, dyspnea, rapidly progressive hypoxemia and opacification of the lung fields presented the clinical picture of catastrophic respiratory failure. Extracorporeal support of oxygenation using a membrane oxygenator and a new ventricle pump was initially successful. At autopsy, miliary tuberculosis was found to be the cause of this "shock lung like" syndrome.
Assisted Circulation↗
Criteria for selecting textbooks.
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Books↗
Therapeutic equivalence of a generic slow-release theophylline tablet.
STUDY OBJECTIVE: To evaluate the relative bioavailability and clinical efficacy of two slow-release theophylline products. DESIGN: Randomized, double-blind, crossover trial. SETTING: A university-affiliated clinical research center. PATIENTS: Fourteen adults with asthma. INTERVENTIONS: The patients received a generic slow-release theophylline tablet or Theo-Dur at bedtime for 5 nights. MEASUREMENTS AND MAIN RESULTS: Serum drug concentrations were measured after the last dose. Attenuation of exercise-induced bronchospasm (EIB) was included as a surrogate for efficacy. There was no significant difference in extent of absorption. The mean differences between the generic product and Theo-Dur in area under the curve was -13.9 micrograms/ml.hr-1 (95% CI -41 to 12.9, p = 0.3) and in peak concentration (Cmax), -0.5 microgram/ml (95% CI -1.7 to 2.7, p = 0.6). In contrast, the generic product was absorbed more rapidly; the mean differences in the time to peak concentration (Tmax) was -3.0 hours (95% CI -4.3 to -1.7, p = 0.0003), in trough concentration (Cmin), -0.9 microgram/ml (95% CI -1.9 to -0.01, p = 0.05), and in fluctuation between Cmax and Cmin, +128% (95% CI 40 to 217, p = 0.008). Neither product effectively attenuated EIB, since mean serum concentrations during the exercise challenges were unexpectedly below 10 micrograms/ml after both products. CONCLUSION: These two products are not bioequivalent, but the difference in absorption rates is unlikely to be clinically important in most patients (i.e., they are therapeutic equivalents).
Absorption↗