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Biomedical subjects

R W Weber

Publications and source records attributed to R W Weber.

At least 55 records · Page 3Linked to original sources
PubMed1989

Comparison of PEFR and FEV1 in patients with varying degrees of airway obstruction. Effect of modest altitude.

Measurements of FEV1 and PEFR performed on a Jones Pulmonor Spirometer (JPF) were compared with PEFR obtained with a mini-Wright peak flow meter (WPF) in 102 patients. Data were converted to percent predicted. Standard deviations of triplicate measurements were: FEV1, 3.01 percent; JPF, 7.22 percent; and WPF, 5.12 percent. Correlation of best of three measurements was FEV1-JPF r = .758; FEV1-WPF r = .744; and JPF-WPF r = .846. The mean percent predicted of the best of three values of FEV1 was 74.8 percent, JPF 91.4 percent, and WPF 94 percent. These higher values for percent predicted PEFR were obtained throughout the range of FEV1 values. Studies on nine normal volunteers in an atmospheric chamber suggested that higher altitudes may account for higher PEFR values. We conclude that PEFR, measured by either waterless spirometer or mini-Wright peak flow meter, has greater intrasubject variability than FEV1, and it tends to underestimate the degree of pulmonary impairment.

Adolescent↗
PubMed1988

The development of subsensitivity to atropine methylnitrate. A double-blind, placebo-controlled crossover study.

This is a double-blind, placebo-controlled crossover study designed to assess the effectiveness of nebulized atropine methylnitrate (AMN) with chronic use. We studied 22 patients with asthma, 10 receiving theophylline and inhaled beta-agonists and 12 who were receiving corticosteroids as well. All had demonstrated at least a 15% change in FEV1 either spontaneously or after bronchodilator. Bronchodilator effect was measured serially for 4 h after inhalation of the initial dose and again after 2 wk of four-times-daily use. Significant bronchodilator effect was seen initially with AMN when compared to placebo (p less than 0.01). After 2 wk of use, the bronchodilator effect of AMN was significantly diminished as compared to the initial effect (p less than 0.01) but was still better than placebo (p less than 0.05). Subsensitivity did develop to varying degrees in the patients, but we were unable to identify any clinical parameters that would allow prediction of subsequent subsensitivity. We conclude that the development of subsensitivity to AMN occurs in certain patients with chronic administration but does not reflect a total loss of bronchodilator effect.

Adult↗
PubMed1987

Allergens.

The environment contains a huge array of allergens, primarily proteins or glycoproteins, to which the atopic individual may become sensitized. In situations of high exposure and highly reactive substances, even nonatopic individuals may develop allergic antibodies. The individual's response depends on the underlying immune responsiveness, the dosage, frequency, route, and possibly the chemical nature of the allergen. Most allergenic sources contain multiple allergenic determinants, as demonstrated by characterization of pollen and mold extracts. Major allergens are acidic proteins with weights in the 20,000 to 40,000 dalton range, and pIs in the 4 to 6 range. Minor allergens may be larger or smaller and either acidic or basic. These conclusions are based on the isolation of a relatively small number of allergens. Cross-reactivity data, especially with the pollens, are useful in the rational formulation of immunotherapy extracts. Considering the wealth of allergenic pollens, information available to date is very scanty. Data on molds, epidermals, and mites are even more preliminary or conflicting. As further research proceeds on purifying and characterizing allergens, a number of these questions and conflicts will be resolved.

Bronchial Provocation Tests↗
PubMed1986

Addition of terbutaline to optimal theophylline therapy. Double blind crossover study in asthmatic patients.

The efficacy and side effects of oral or inhaled terbutaline were examined in 13 mild-to-moderate asthmatic patients (ages 12 to 71 years) on maintenance theophylline (levels 10 to 25 micrograms/ml). In a crossover design, each patient received for two weeks oral terbutaline, 5 mg qid, inhaled terbutaline, 400 micrograms qid, or identical placebo tablets or metered-dose inhalers. Prior to each double-blind period, terbutaline was given for two weeks to ensure development of beta-adrenergic subsensitivity. Home-monitored peak flows and need for supplementary bronchodilators were significantly improved with both oral and inhaled terbutaline, but only the inhaled drug significantly decreased symptoms. Long-term terbutaline, either oral or inhaled, added to maintenance theophylline improved the patients' pulmonary function. The inhaled drug also improved the patients' clinical status as reflected by asthma symptom scores and need for extra bronchodilator. Combining terbutaline with theophylline did not produce evidence of cardiotoxicity.

Administration, Intranasal↗
PubMed1984

Structural features of the quinidine and quinine molecules necessary for binding of drug-induced antibodies to human platelets.

Although most quinidine- and quinine-induced platelet antibodies react only in the presence of the drug that provoked sensitization, some are active with either quinidine or its stereoisomer, quinine; that is, they are "cross-reactive." This suggests that the activity of drug-dependent antibodies is dependent on different structural features of the quinidine or quinine molecules. To investigate this possibility, we studied reactions of 16 quinidine- and quinine-induced antibodies with quinidine, quinine, and analogues of these drugs modified at the quinoline ring (desmethoxy-derivative), the quinuclidine ring (dihydro-derivative), or the asymmetric C(9)-hydroxyl position. It was found that the antibodies could be classified into three groups on the basis of their reactions with platelets in the presence of these compounds. Eight antibodies (group 1) reacted only in the presence of the sensitizing drug or its dihydro- or desmethoxy-derivative. Three antibodies (group 2) differed from those in group 1 only in that their reactions were markedly weakened when the primary desmethoxy-derivative was used. Five antibodies (group 3) reacted in the presence of the sensitizing drug, its stereoisomer, and one or more of the analogues tested, including at least one of the C(9)-derivatives. Antibodies in this group gave stronger reactions with the sensitizing drug than with its stereoisomer. These results provide further evidence for heterogeneity among drug-induced platelet antibodies by demonstrating that noncross-reactive antibodies (groups 1 and 2) are dependent for their activity on a specific configuration at the optically active C(9)-hydroxyl position, and that some of these (group 2) also require the methoxy group for full reactivity. In contrast, cross-reactive antibodies (group 3) appear to be dependent on the quinoline ring common to all the analogues tested but also require a specific configuration at C(9) for full reactivity.

Adult↗
PubMed1982

Aerosolized terbutaline in asthmatics: development of subsensitivity with long-term administration.

The peak response and the duration of bronchodilator effect were measured after four inhalations at 20 min intervals of 250 micrograms of aerosolized terbutaline in 13 patients with bronchial asthma. Patients were initially studied after strict avoidance of all adrenergic agents for 2 wk; they were then studied at 2 wk intervals for 12 wk while receiving 500 micrograms of aerosolized terbutaline q.i.d. The initial testing (TI) and the testing at the end of 12 wk (TII) were double blind. Both peak response and duration of action decreased significantly between TI and TII. Cumulative dose-response curves showed that further improvement occurred after each inhalation during TI but that there was significant improvement only after the first inhalation during TII.

Adrenal Cortex Hormones↗
PubMed1982

Beta-carbolines: synthesis and neurochemical and pharmacological actions on brain benzodiazepine receptors.

We have prepared a series of tetrahydro-beta-carbolines (TH beta C), beta-carbolines (beta-C), and other nitrogen heterocycles and evaluated them in vitro with respect to their ability to bind to benzodiazepine receptors. The fully aromatic beta-C's were more potent than their corresponding TH beta C derivatives. When substituents possessing a carbonyl (CO2Me, COCH3, CHO) were introduced at the beta-C 3-position the in vitro potency was augmented. Alcohol substituents (CH2OH, CHOHCH3) demonstrated decreased in vitro potency. The importance of the carbonyl moiety was further demonstrated when beta-carboline-3-carboxylic acid was shown to bind tighter to benzodiazepine receptors at lower pH. A lower pH increases the concentration of the acid and decreases the concentration of the anion. 3-(Hydroxymethyl)-beta-carboline (24), 3-formyl-beta-carboline (25) and 3-acetyl-beta-carboline (27) were benzodiazepine antagonists in vivo. Methyl isoquinoline-3-carboxylate (31a) also had in vitro activity. The same structure-activity relationships seen in beta-C's were also observed for isoquinolines.

Animals↗
PubMed1980

Theophylline and aerosolized terbutaline in the treatment of bronchial asthma. Double-blind comparison of optimal doses.

The bronchodilator response to aerosolized terbutaline and optimal doses of theophylline, given singly and in combination, was studied in ten patients with perennial asthma. Optimal doses of theophylline were determined (mean peak theophylline level of 20.9 micrograms/ml). Patients then received this theophylline dose plus 500 micrograms aerosolized terbutaline by metered-dose nebulizer qid for one week. Placebo was then substituted for one of the active agents for two weeks, followed by both active agents again for one week, and finally, placebo substituted for the second agent for a two-week period. The therapeutic response was determined by measurement of peak expiratory flow rate four times daily at different intervals following medication and the patient's subjective assessment of each period. The combination was found to be superior to either theophylline or terbutaline alone (P < .05). Theophylline alone and aerosolized terbutaline alone were equally effective. No side effects were encountered with any of the treatment regimens.

Adult↗
PubMed1980

The effect of theophylline on the lower esophageal sphincter pressure.

The effects of theophylline on lower esophageal sphincter pressure (LESP) were studied on four normal volunteers and six asthmatics with symptoms of gastroesophageal reflux (GER). Manometric evaluations of LESP were obtained before and after an intravenous dose of aminophylline. All subjects had therapeutic theophylline levels at the time of the second measurement of LESP and a significant decrease in LESP occurred in normal and asthmatic volunteers.

Aminophylline↗