Considerations of the estimation of plasmodesmatal frequencies.
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Biometry↗
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The immobilization period for fractures of the mandibular body.
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Adolescent↗
The internal structure of an insect virus.
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In Vitro Techniques↗
Standardization of inhalation provocation tests: influence of nebulizer output, particle size, and method of inhalation.
Standardization of inhalation tests requires a knowledge of factors that will affect the response. We measured the output and particle size of six types of nebulizers used for inhalation tests. Output varied considerably between nebulizers of different types (0.12 to 1.59 ml/min) and to a lesser extent between nebulizers of the same type. Particle size varied between 0.8 and 5.2 micrometer aerodynamic mass median diameter (AMMD). The influence of these two properties on bronchial response to inhaled methacholine was examined. Nebulizer output but not particle size (between 1.3 and 3.6 micrometer AMMD) altered the response. We also examined the effect of change in inspiratory time during inhalation from residual volume to total lung capacity on lung deposition of radiolabeled aerosol and on the provocative concentration of histamine required to reduce the 1-sec forced expiratory volume (FEV1) by 20% (PC20). A reduction in inspiratory time from 8 to 2 sec resulted in a lower total lung dose, relatively more aerosol deposited in central airways, and a higher PC20. The results emphasize the importance of keeping nebulizer output and pattern of breathing constant when performing inhalation provocation tests if consistent results are to be obtained.
Aerosols↗
Bronchial responsiveness to histamine or methacholine in asthma: measurement and clinical significance.
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Aerosols↗
Effect of beclomethasone dipropionate on bronchial responsiveness to histamine in controlled nonsteroid-dependent asthma.
We investigated the possibility that corticosteroids can reduce bronchial responsiveness to histamine by mechanisms other than change in airway caliber. Ten adult asthmatic subjects were selected because their symptoms were controlled by bronchodilators alone, they had no recent respiratory infection or allergen exposure that might have temporarily altered responsiveness, their spirometry was more than 70% predicted, and they had a range of histamine bronchial hyperresponsiveness. They received, in random order and double-blind manner, beclomethasone dipropionate (400 micrograms daily) or placebo for 4 wk and then, after a 2-week washout period, they crossed over to the other treatment for 4 wk. Treatment with beclomethasone induced a small but significant reduction in bronchial responsiveness to histamine (p = 0.014). Although the improvement was too small to be considered of clinical significance, its importance lies in the mechanisms by which it was produced. Part of the improvement was related to improvement in airway caliber, but, even when the data was adjusted for this, there was still a significant difference between beclomethasone and placebo treatment (p = 0.018). The results suggest that regular treatment with corticosteroids can alter bronchial responsiveness through mechanisms other than change in airway caliber.
Adult↗
Polyethylene glycol-modified ragweed pollen extract in rhinoconjunctivitis.
Sixty-two ragweed-sensitive adult subjects volunteered to take part in a 2-year, placebo-controlled efficacy study of polyethylene glycol (PEG)-modified ragweed extract, in ragweed pollen-induced rhinoconjunctivitis. At the beginning of the study, subjects were stratified according to skin sensitivity to ragweed extract and PEG-modified ragweed and the severity of hay fever in the previous year. There was random allocation of half to active treatment and half to placebo treatment. Before the first ragweed pollen season the 36 most sensitive subjects received 10 weekly injections (group 1), and the remaining 26 received six injections (group 2). Before the second season all subjects received 10 injections. Doses increased by half a log concentration each week unless there were adverse reactions. The mean total dose received by group 1 in year 1 was 385 micrograms of protein (28.9 micrograms AgE) and received by group 2 was 218 micrograms of protein (16.4 micrograms AgE). In year 2 the mean total dose was 1829 micrograms (137.2 micrograms AgE). Sixty-six percent of injections elicited no reaction or a mild local reaction; the remaining injections produced local redness and swelling more than 2 inches in diameter. Four percent of injections produced systemic symptoms. PEG-modified ragweed stimulated increases in ragweed specific IgG antibody both years, but increases in ragweed specific IgE antibody were significant only in group 1 in year 1. The magnitude of the IgG antibody changes was directly related to the total dose injected. At the beginning of the second year, PEG-modified ragweed-treated subjects still had elevated IgG antibody levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Airway responses to hyperventilation of cold dry air: duration of protection by cromolyn sodium.
The magnitude and duration of the inhibitory effect of three doses of cromolyn sodium on the airway response to hyperventilation of cold dry air was examined in a double-blind, randomized controlled trial. Eight subjects with well controlled asthma were studied. On 4 separate days, doses of either 2 mg, 10 mg, 20 mg, or placebo were administered by metered-dose inhaler. Twenty minutes, 2 hours, and 4 hours after each medication, airway responsiveness to isocapnic hyperventilation of cold dry air was measured by use of a standardized dose-response method. At 20 minutes, all three doses inhibited bronchoconstriction, and there was no evidence of any difference in the magnitude of the inhibition between the doses. All three doses progressively provided less protection with time. By 2 hours, the inhibition induced by 2 mg was no longer different from placebo, and by 4 hours, only 20 mg still provided significant protection. The results demonstrate that, although the initial magnitude of inhibition may not be different between 2 mg and 20 mg, the rate at which the protective effect wears off is dose related.
Adolescent↗
Polyethylene glycol-modified ragweed extract: comparison of two treatment regimens.
Fifty ragweed-sensitive subjects were each administered a course of 12 injections of polyethylene glycol-modified ragweed extract. To investigate the effect of two treatment regimens, subjects were paired according to their skin sensitivity to ragweed extract and the severity of their rhinoconjunctivitis the previous year. One of each pair was randomly allocated to receive injections at weekly intervals, and the other subject was to receive injections daily until a local or systemic adverse reaction occurred and then to switch to a weekly schedule for the rest of the course. Blood was obtained immediately before each injection and at the end of the study to examine the rates of change of ragweed-specific IgE and IgG antibody levels and to evaluate whether these or other variables could be used to predict the occurrence of adverse reactions. Immediate reactions were minimal in both groups, but more late reactions occurred in subjects receiving the modified rush regimen; therefore, although the total number of injections received by the two groups was similar, the total dose of protein injected in the rush group was only half that achieved in the weekly group. Treatment induced increases in ragweed-specific IgE and IgG antibodies in both groups; the increase in IgE was similar in the two groups, but the increase in IgG was higher in the weekly group. There was a marked decrease in skin sensitivity to ragweed extract after treatment that was directly related to the IgG antibody response, and therefore, these changes were greater in the weekly group.(ABSTRACT TRUNCATED AT 250 WORDS)
Allergens↗
A comparison of budesonide and beclomethasone dipropionate nasal aerosols in ragweed-induced rhinitis.
The clinical potency of budesonide, a new glucocorticosteroid, was compared in a randomized double-blind study with beclomethasone dipropionate in the treatment of seasonal allergic rhinitis during the ragweed-pollen season. Sixty-one subjects were matched according to their skin sensitivity to ragweed-pollen extract and the severity of ragweed-induced rhinitis during the previous season. Thirty subjects received budesonide, and 31 received beclomethasone dipropionate, 50 micrograms per actuation. A double-dummy technique was used to achieve blinding, since the aerosol canisters and adaptors were dissimilar. Subjects were instructed to keep rhinitis well controlled by starting intranasal trial medication as soon as symptoms became troublesome, two puffs into each nostril, when it was needed, up to four times per day. If this became inadequate, subjects received supplementary chlorpheniramine maleate, 4 mg. Nasal symptoms (none = 0, mild = 1, moderate = 2, and severe = 3) and all medication use were recorded daily in a diary. Budesonide demonstrated better clinical potency than beclomethasone in that less was needed to maintain good control of nasal symptoms. Side effects were mild and transient for both groups.
Administration, Inhalation↗
Efficacy of continuous treatment with astemizole (Hismanal) and terfenadine (Seldane) in ragweed pollen-induced rhinoconjunctivitis.
Astemizole (Hismanal; Janssen Pharmaceutica Inc., Mississauga, Ontario, Canada) and terfenadine (Seldane; Merrell Dow Pharmaceuticals [Canada], Inc., Concord, Ontario, Canada) were compared for clinical efficacy in a double-blind randomized trial during the ragweed pollen season. Sixty adults, with a history of ragweed-induced rhinoconjunctivitis, were matched according to sensitivity to ragweed pollen. Half took astemizole, 10 mg/day, and the rest took terfenadine, 60 mg twice daily. Medications were started 1 week before and continued daily until 1 week after the ragweed pollen season (7 weeks). If the trial medication was insufficient to keep symptoms well controlled, a steroid nasal spray and/or eye drops were used in the minimum dose that would ensure symptoms were not troublesome. Subjects completed a diary of nocturnal and daytime nasal and eye symptoms and recorded the amount of concomitant medications used. Astemizole showed greater efficacy than terfenadine in controlling rhinorrhea; in addition, the astemizole group used less nasal spray. Other nasal symptoms, eye symptoms, and use of eye drops were similar in the two groups. Skin test sensitivity to serial dilutions of histamine and ragweed extract was determined 1 and 7 weeks after the start of the trial medication. More tachyphylaxis to histamine was shown by the subjects taking terfenadine, as demonstrated by a larger increase in skin sensitivity over the study period. However, a similar change was not observed for ragweed skin sensitivity. These results suggest that when the medication is started before and continued daily throughout the pollen season, astemizole is more efficacious than terfenadine in controlling nasal symptoms, but there is little difference for eye symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Comparison of beclomethasone dipropionate aqueous nasal spray, astemizole, and the combination in the prophylactic treatment of ragweed pollen-induced rhinoconjunctivitis.
The clinical efficacy and side effect of (1) beclomethasone dipropionate aqueous nasal spray, 400 micrograms daily, (2) astemizole, 10 mg daily, and (3) beclomethasone, 400 micrograms, plus astemizole, 10 mg daily, were compared in a double-blind, randomized, parallel-group trial. Ninety adults were matched into groups of three according to sensitivity to ragweed pollen. One of each of the three subjects was assigned to nasal spray alone, one was assigned to astemizole alone, and one subject was assigned to both medications. Medications were started 1 week before and continued daily until 1 week after the ragweed-pollen season (6 weeks). If rhinoconjunctivitis was inadequately controlled with the trial medications, pressurized steroid nasal spray and/or antihistamine-decongestant eye drops were used in the minimum dose that would ensure relief. Nose and eye symptoms and concomitant medication use were recorded daily in a diary. Sneezing, nasal obstruction, and rhinorrhea were significantly better, and less additional nasal spray was used in subjects taking beclomethasone alone than in subjects taking astemizole alone. Beclomethasone plus astemizole provided no better control of rhinitis than beclomethasone alone. Eye symptoms and eye drop use tended to be less in subjects taking astemizole alone than in subjects taking beclomethasone alone, but the best control of eye symptoms was recorded in the subjects taking both trial medications. Side effects were mild or transient.
Administration, Intranasal↗
Comparison of the efficacy and side effects of aqueous steroid nasal spray (budesonide) and allergen-injection therapy (Pollinex-R) in the treatment of seasonal allergic rhinoconjunctivitis.
The efficacy and side effects of two approaches to the treatment of ragweed pollen-induced rhinoconjunctivitis were compared in a double-blind, parallel-group trial. Sixty ragweed-sensitive adults were randomized either to a course of four Pollinex-R hyposensitization injections during the 6 weeks before the ragweed-pollen season, or to budesonide aqueous nasal steroid spray, 400 micrograms daily, throughout the season. A double-dummy technique was used to achieve blinding. During the ragweed-pollen season, troublesome nasal symptoms were treated with terfenadine, 60 mg, when treatment was needed, up to 240 mg daily, and eye symptoms were treated with naphazoline eye drops, when treatment was needed, up to four times daily. Every day, subjects recorded the severity of nasal and eye symptoms and medication use in a diary. Fourteen of the subjects receiving Pollinex-R were unable to complete the course of injections because of systemic or large local reactions. Eight subjects withdrew during the pollen season because of severe rhinitis; all subjects had received Pollinex-R. Subjects in the budesonide-treated group had minimal nasal symptoms and used very little terfenadine, compared with subjects in the Pollinex-R-treated group (p less than 0.0001). Eye symptoms and eye drop use were similar in the two treatment groups. No clinically important side effects were reported by the subjects receiving budesonide. The results of this study suggest that aqueous budesonide nasal spray is markedly more effective than Pollinex-R in controlling symptoms of seasonal rhinitis while the side effects and inconvenience of immunotherapy are avoided.
Aldehydes↗
Reduction of budesonide after a year of increased use: a randomized controlled trial to evaluate whether improvements in airway responsiveness and clinical asthma are maintained.
We have demonstrated recently that 1 year of regular inhaled budesonide use can produce substantial improvements in airway responsiveness accompanied by significant improvements in clinical asthma severity. The present study was designed to evaluate whether these improvements are maintained when the dose of budesonide is reduced. At the end of the original study, 28 subjects with asthma, who had been in the active-treatment arm of the study were randomized either to continue taking the dose of budesonide taken in the original study or to have the dose reduced. Airway responsiveness to methacholine, bronchodilator requirements, symptoms, and spirometry were assessed after 6 weeks and 3 months. During the 3 months, no subject experienced an asthma exacerbation, and there was no evidence of change in airway responsiveness in subjects who had their steroids reduced (provocative concentration causing a 20% drop in FEV1; initial, 2.03 mg/ml; final, 1.91 mg/ml), and this change was not different from change in subjects maintained with a higher dose (initial, 3.02 mg/ml; final, 3.12 mg/ml) (p = 0.39). Similarly, there was no evidence of any change in bronchodilator requirements (p = 0.89). However, after 3 months of reduced steroid use, there was a small decline in spirometry (FEV1 percent predicted: initial, 84.4%; final, 81.5%), and this change was significantly different from change in subjects in whom steroids were not reduced (initial, 90.2%; final, 90.2%) (p = 0.002). At 3 months, symptoms (predominantly sputum production) were also beginning to redevelop in the reduced budesonide group (p = 0.056).(ABSTRACT TRUNCATED AT 250 WORDS)
Asthma↗
In re: Van Bever HP, Stevens WJ. (JACI 1990;86: 141-6)
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Animals↗
Aqueous beclomethasone dipropionate in the treatment of ragweed pollen-induced rhinitis: further exploration of "as needed" use.
BACKGROUND: The objective of this study was to compare regular and "as required" (prn) use of aqueous beclomethasone dipropionate nasal spray (Beconase AQ nasal spray) in the treatment of ragweed pollen-induced rhinitis and to examine possible predictors of unsatisfactory symptom control in the group of patients who used it on a prn basis. METHODS: Sixty adults with ragweed pollen-induced rhinitis, who had participated in previous hay fever studies or who responded to media notices, were enrolled in the study. The study design was a randomized, unblinded, parallel group comparison between regular use (400 micrograms daily) and prn use of Beconase AQ spray during the 6 weeks of the ragweed pollen season. Patients recorded daily symptoms and medication use in diaries. The Rhinoconjunctivitis Quality of Life Questionnaire was administered, and patient satisfaction with symptom control was assessed at clinic visits. RESULTS: Symptoms and quality of life tended to be better in the regular group, but differences were not statistically significant. Twenty-seven percent of patients in the prn group reported unsatisfactory control of symptoms; they experienced significantly worse symptoms and quality of life than the remainder of the prn group and used significantly more Beconase. No obvious predictors of unsatisfactory control were identified. Patients who achieved satisfactory control in the prn group had symptom and quality of life scores that were very similar to those of the regular group. CONCLUSIONS: Most patients can use Beconase AQ as needed successfully for the treatment of hay fever, but there may be an apparently unpredictable minority who do not achieve satisfactory symptom control or quality of life with this approach and who require regular treatment.
Adolescent↗
Sodium cromoglycate eye drops: regular versus "as needed" use in the treatment of seasonal allergic conjunctivitis.
OBJECTIVE: The objective of this study was to compare the efficacy and side effects of sodium cromoglycate eye drops (Opticrom 2%) used regularly versus as needed in the treatment of seasonal (ragweed) allergic conjunctivitis. METHODS: A randomized, unblinded, parallel group comparison was performed during the 6 weeks of the ragweed pollen season. Sixty-two adults with ragweed pollen-induced conjunctivitis were recruited for the study from previous ragweed studies and notices in the local media. Two drops of sodium cromoglycate were placed in each eye either four times daily (regular treatment group) or when needed, up to four times daily (prn group), from 1 week before and throughout the ragweed pollen season. Uncontrolled eye symptoms were treated with terfenadine 60 mg as needed, up to 120 mg daily. Subjects kept daily diaries for symptoms and medication requirements throughout the 6 weeks of treatment. The Rhinoconjunctivitis Quality of Life Questionnaire was administered and adverse experiences were reported after 1, 3, and 6 weeks of treatment. RESULTS: Diary eye symptoms were similar in the two treatment groups, but quality of life was better in the regular treatment group. There was a trend for the prn group to require more terfenadine for uncontrolled eye symptoms. CONCLUSIONS: There may be some additional therapeutic benefit from using sodium cromoglycate eye drops regularly throughout the ragweed pollen season.
Adolescent↗
Assessment of quality of life in adolescents with allergic rhinoconjunctivitis: development and testing of a questionnaire for clinical trials.
BACKGROUND: The objectives of the study were to evaluate impairment in quality of life in 12- to 17-year-old patients with seasonal allergic rhinoconjunctivitis and to develop and test a questionnaire suitable for evaluating change in quality of life during clinical trials. METHODS: Patients were asked to identify physical and emotional impairments associated with allergic rhinoconjunctivitis. The resultant questionnaire was tested for responsiveness and validity in a clinical trial in which fluticasone nasal spray and loratadine were compared for treatment of ragweed pollen-induced rhinoconjunctivitis. Eighty-three patients, 12 to 17 years of age, with grass- or ragweed-induced hayfever participated in the instrument development phase. They were recruited for the study from an allergy clinic and local schools and recreational organizations. Two hundred forty patients with ragweed hayfever participated in the clinical trial and provided quality of life data. RESULTS: The survey showed that in addition to local symptoms, patients experienced impairment of quality of life because of systemic symptoms, activity limitations, and emotional and practical problems. The resultant questionnaire has 25 items in six domains. In the clinical trial responsiveness was demonstrated by the questionnaire's ability to detect change over time and differences between treatments. Construct validity was demonstrated by moderate to strong relationships between changes in diary symptom scores and quality of life. CONCLUSIONS: The items identified by 12- to 17-year-old patients were not identical to those previously identified by adults. This suggests that impairment of quality of life may not be the same in the two groups and that it is appropriate to have a questionnaire specifically designed for adolescent rhinoconjunctivitis clinical trials.
Activities of Daily Living↗