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Biomedical subjects

E Harman

Publications and source records attributed to E Harman.

At least 19 recordsLinked to original sources
PubMed2000

Complete remission of pulmonary spindle cell carcinoma after treatment with oral germanium sesquioxide.

Spindle cell carcinoma (SCC) is a rare form of lung cancer representing 0.2 to 0.3% of all primary pulmonary malignancies. Even with combined surgery, chemotherapy, and radiation therapy, these tumors are associated with a poor prognosis and only 10% of patients survive 2 years after diagnosis. We describe a patient with an unresectable SCC who, following no response to conventional treatment with combined modality therapy, chose to medicate herself with daily doses of germanium obtained in a health food store. She noted prompt symptomatic improvement and remains clinically and radiographically free of disease 42 months after starting her alternative therapy.

Antineoplastic Agents↗
PubMed1999

The effect of Cys LT1 receptor blockade on airway responses to allergen.

STUDY OBJECTIVE: To evaluate the effect of a potent experimental leukotriene receptor antagonist, MK-571, on airway responses to inhaled allergen. DESIGN: Randomized, double-blind, placebo-controlled, crossover trial. SETTING: Clinical research center. SUBJECTS: Eight male volunteers with allergic asthma. INTERVENTIONS: An intravenous loading dose was followed by an 8-hour infusion of MK-571 or placebo, with a 7- to 14-day washout between treatments. Allergen challenge was performed after the loading dose and a histamine challenge was performed before and 24 hours after allergen. MEASUREMENTS AND MAIN RESULTS: Forced expiratory volume in 1 second was measured serially. MK-571 provided about 50% protection during maximum early and late responses compared with placebo (p=0.005), but airway obstruction persisted 8-24 hours after allergen on both treatment days. Airway responsiveness to histamine was not significantly attenuated at 24 hours. CONCLUSION: Blocking Cys LT1 receptors for 8 hours attenuated the early and late responses but did not interrupt the cascade of events leading to subsequent allergen-induced airway obstruction and hyperreactivity.

Adult↗
PubMed1997

Increased urinary excretion of LTE4 after exercise and attenuation of exercise-induced bronchospasm by montelukast, a cysteinyl leukotriene receptor antagonist.

BACKGROUND: A study was undertaken to determine whether montelukast, a new potent cysteinyl leukotriene receptor antagonist, attenuates exercise-induced bronchoconstriction. The relationship between the urinary excretion of LTE4 and exercise-induced bronchoconstriction was also investigated. METHODS: Nineteen non-smoking asthmatic patients with a forced expiratory volume in one second (FEV1) of > or = 65% of the predicted value and a reproducible fall in FEV1 after exercise of at least 20% were enrolled. Subjects received placebo and montelukast 100 mg once daily in the evening or 50 mg twice daily, each for two days, in a three-period, randomised, double blind, crossover design. In the evening, approximately 20-24 hours after the once daily dose or 12 hours after the twice daily dose, a standardised exercise challenge was performed. Data from 14 patients were available for complete analysis. RESULTS: The mean (SD) maximal percentage decrease in FEV1 after exercise was 29.6 (16.0), 17.1 (8.2), and 14.0 (9.4) for placebo, once daily, and twice daily regimens, respectively. The mean (95% CI) percentage protection was 37 (15 to 59) for the group who received 50 mg twice daily and 50 (31 to 69) for those who received 100 mg once daily. Active treatments were not different from each other. The mean (SD) plasma concentrations of montelukast were higher after the twice daily regimen (1.27 (0.81) microgram/ml) than after the once daily regimen (0.12 (0.09) microgram/ml); there was no correlation between the percentage protection against exercise-induced bronchoconstriction and plasma concentrations. After exercise urinary excretion of LTE4 increased significantly during placebo treatment (from 34.3 to 73.7 pg/mg creatinine; p < 0.05) but did not correlate with the extent of exercise-induced bronchoconstriction. CONCLUSIONS: Montelukast protects similarly against exercise-induced bronchoconstriction between plasma concentrations of 0.12 and 1.27 micrograms/ml. The increase in the urinary excretion of LTE4 after exercise and the protection from exercise-induced bronchoconstriction with a cysteinyl leukotriene receptor antagonist provide further evidence of the role of leukotrienes in the pathogenesis of exercise-induced bronchoconstriction.

Acetates↗
PubMed1997

Valproate-associated carnitine deficiency and malignant cerebral edema in the absence of hepatic failure.

We describe a 27-year-old woman who developed encephalopathy and cerebral edema during treatment of refractory complex partial seizures that included acute administration of valproate (VPA) at a dosage of 35 mg/kg per day. Multiple random VPA levels were within therapeutic range, and results of liver function studies did not show evidence of hepatic failure. Cerebral computerized tomography (CT) showed evidence of massive cerebral edema with central herniation. Just prior to death, plasma levels of free and acyl carnitines were markedly decreased. Analysis of urinary organic acids showed increased excretion of lactate, but a normal distribution of VPA metabolites. Carnitine deficiency may predispose patients to the development of coma and life-threatening cerebral edema associated with acute administration of VPA, even in the absence of concomitant hepatic failure. We suggest specific guidelines for the evaluation and management of altered consciousness in patients with seizures receiving VPA.

Adult↗
PubMed1996

Load carriage using packs: a review of physiological, biomechanical and medical aspects.

This paper reviews the biomedical aspects of transporting loads in packs and offers suggestions for improving load-carriage capability. Locating the load mass as close as possible to the body center of gravity appears to result in the lowest energy cost when carrying a pack. Thus, the double pack (half the load on the front of the body and half the load on the back) has a lower energy cost than the backpack. However, backpacks provide greater versatility in most situations. The energy cost of walking with backpack loads increases progressively with increases in load mass, body mass, walking speed or grade; type of terrain also influences energy cost. Predictive equations have been developed for estimating the energy cost of carrying loads during locomotion but these may not be accurate for prolonged (>2 h) or downhill carriage. Training with loads can result in greater energy efficiency since walking with backpack loads over several weeks decreases energy cost. Load-carriage speed can be increased with physical training that involves regular running and resistance training. Erector spinae electrical activity (EMG) is lower during load carriage than in unloaded walking until loads exceed 30-40 kg, at which point erector spinae EMG activity is higher than during unloaded walking. EMGs of the quadriceps and gastrocnemius, but not the tibialis anterior or hamstrings, increase with load. Framed packs with hip belts reduce the electrical activity of the trapezius muscles, presumably by shifting forces from the shoulders to the hips. Increases in the backpack load mass result in increases in forces exerted on the grounds, amount of knee flexion and the forward inclination of the trunk. Compared to backpacks, double packs produce fewer deviations from normal walking. Common injuries associated with prolonged load carriage include foot blisters, stress fractures, back strains, metatarsalgia (foot pain), rucksack palsy (shoulder traction injury) and knee pain. Closed-cell neoprene insoles and use of an acrylic or nylon sock, combined with a wool sock, reduce blister incidence. A framed pack with a hip belt reduces the incidence of rucksack palsy. Backpack load carriage can be facilitated by lightening loads, optimizing equipment, improving load distribution and by preventive action aimed at reducing the incidence of injury.

Journal Article↗
PubMed1995

Theophylline attenuation of airway responses to allergen: comparison with cromolyn metered-dose inhaler.

BACKGROUND: The purpose of this study was to compare the protection afforded by individualized doses of theophylline and a cromolyn metered-dose inhaler (MDI) during allergen challenge. METHODS: The study design was randomized, double-blind, and crossover. Responses to inhaled allergen were measured in 16 subjects with allergic asthma (age range, 18 to 35 years) after 7 days of treatment with either placebo, once daily slow-release theophylline producing a mean +/- SD serum concentration of 16 +/- 5 micrograms/ml during the late phase, or 2 mg of cromolyn administered by MDI four times daily. Forced expiratory volume in 1 second was measured at frequent intervals, and airway responsiveness to histamine was measured before and 3 hours after allergen challenge. RESULTS: The mean +/- SD maximum decrease in forced expiratory volume in 1 second during the late phase was 30% +/- 14% during placebo treatment, 16% +/- 13% during theophylline treatment, and 13% +/- 14% during cromolyn treatment (placebo vs theophylline and cromolyn, p = 0.0001; theophylline vs cromolyn, p = 0.1). The geometric mean fold increase in airway responsiveness was 3.0 +/- 1.7 during placebo treatment, 1.7 +/- 1.7 during theophylline treatment, and 1.5 +/- 1.6 during cromolyn treatment (placebo vs theophylline and cromolyn, p = 0.0001; theophylline vs cromolyn, p = 0.1). CONCLUSIONS: Theophylline, when administered once daily as a slow-release formulation, was as effective as cromolyn, administered four times daily through an MDI, in attenuating airway responses to inhaled allergen. The protection afforded by both treatments, however, was modest when compared with the results of similar studies with inhaled corticosteroids or other cromolyn formulations that deliver more drug to the lungs than the MDI available in the United States.

Adolescent↗
PubMed1993

Does aminophylline benefit adults admitted to the hospital for an acute exacerbation of asthma?

OBJECTIVE: To determine the effect of adding intravenous theophylline (administered as aminophylline) to nebulizations of albuterol and intravenous methylprednisolone in adults hospitalized for acute asthma. DESIGN: Randomized, placebo-controlled, double-blind study. SETTING: Inpatient service of a tertiary-care, university teaching hospital. PATIENTS: 21 adults (22 to 48 years old)--10 in the aminophylline group and 11 in the placebo group. INTERVENTIONS: Nebulized albuterol, 2.5 or 5.0 mg every 0.5 to 4 hours; intravenous methylprednisolone, 60 mg every 6 hours; and either individualized doses of aminophylline or placebo for 48 hours. MEASUREMENTS: Forced expiratory volume in 1 second (FEV1), the number of "as needed" albuterol nebulizations and total dose, asthma symptom scores, and adverse effects. RESULTS: At admission from the emergency department, the mean +/- SD baseline FEV1 was 49% +/- 19% of the predicted value in the aminophylline group and 43% +/- 13% of the predicted value in the placebo group. The improvement in FEV1 at 3 hours was greater in the aminophylline group (29% +/- 23% compared with 10% +/- 10% in the placebo group; mean difference, 19 percentage points; 95% CI, 3 to 35 percentage points; P = 0.023). At 48 hours, FEV1 was 75% +/- 19% of the predicted value in the aminophylline group and 58% +/- 15% of the predicted value in the placebo group (mean difference, 17 percentage points; CI, 0.2 to 34.8 percentage points; P = 0.048). Aminophylline-treated patients required fewer nebulizations of albuterol (10.3 +/- 3.8 compared with 16.4 +/- 5.3; mean difference, -6.1; CI, -10.3 to -1.8) and less total dosage (34 +/- 16 mg compared with 70 +/- 34 mg; mean difference, -36 mg; CI, -60.6 to -11.3 mg P = 0.02). No statistical differences were observed in asthma symptom scores or frequency of adverse effects. CONCLUSIONS: Individualized doses of intravenous theophylline added to frequent nebulizations of albuterol and intravenous methylprednisolone appear to benefit adults admitted to the hospital with acute asthma and are well tolerated when serum concentrations are maintained in the therapeutic range.

Acute Disease↗
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↗