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Biomedical subjects

G Rachelefsky

Publications and source records attributed to G Rachelefsky.

At least 19 recordsLinked to original sources
PubMed1999

Onset and duration of action of levocabastine nasal spray in atopic patients under nasal challenge conditions.

BACKGROUND: Although prior studies have documented the rapid onset of action of topical intranasal levocabastine (LEV), little is known about its duration of action under nasal challenge conditions. OBJECTIVES: We sought to assess the onset and duration of action of escalating doses of LEV nasal spray by using a nasal allergen challenge (NAC) model. METHODS: Eighteen asymptomatic subjects with histories of seasonal allergic rhinitis were enrolled into a randomized, single-blind, placebo-controlled, dose-ranging crossover study. Each patient was randomly assigned to receive single doses of placebo and intranasal LEV 0.1, 0.2, and 0.4 mg during 2 parts of the study. In part 1 (onset of action), NAC consisted of a single dose of allergen administered 5 minutes after study drug treatment. In part 2 (duration of action), NAC consisted of increasing doses of allergen administered 0.5, 6, 12, and 24 hours on separate days after study drug treatment. Nasal symptom scores (NSSs) and nasal peak expiratory flow rates were measured after NAC in both phases of the study. Blood samples for plasma LEV concentrations were drawn after each NAC. RESULTS: In part 1, NSSs were significantly lower after the administration of LEV 0.1, 0.2, and 0.4 mg compared with placebo (P <.05). In part 2, NSSs were significantly lower after LEV doses of 0.2 and 0.4 mg compared with placebo at 0.5, 6, 12, and 24 hours after treatment (P <.05). The mean provocative dose of allergen required to elicit a positive nasal reaction was increased after LEV doses of 0.2 and 0.4 mg at 0.5, 6, and 12 hours after treatment. Nasal peak expiratory flow rates demonstrated no significant differences between LEV and placebo for any doses at any time points. Mean plasma LEV concentrations were low (range, 0 to 3. 7 ng/mL) after all doses and did not correlate with drug efficacy. CONCLUSIONS: Single intranasal LEV doses of 0.1, 0.2, and 0.4 mg significantly reduced the severity of the immediate nasal response to allergen when administered 5 minutes before NAC. This protective effect against NAC continued to be present 24 hours after administration of LEV doses of 0.2 and 0.4 mg. Efficacy in blocking the reaction to NAC did not correlate with plasma LEV levels, suggesting that the inhibitory effect was due largely to topical rather than systemic effects.

Administration, Intranasal↗
PubMed1999

Dose-ranging study of a new steroid for asthma: mometasone furoate dry powder inhaler.

A new formulation of mometasone furoate (MF) for administration by dry powder inhaler (DPI) was evaluated for the treatment of asthma. A 12-week, double-blind, placebo-controlled dose-ranging study compared the efficacy and safety of three doses of MF DPI (100, 200 and 400 mcg b.i.d) with beclomethasone dipropionate (BDP) 168 mcg b.i.d. administered by metered dose inhaler in 365 adult or adolescent patients being treated with inhaled glucocorticoids. The mean change from baseline to endpoint (last treatment visit) for forced expiratory volume in 1 sec (FEV1) was the primary efficacy variable. Secondary efficacy variables included other objective measures of pulmonary function [forced vital capacity (FVC), forced expiratory flow 25-75% (FEV25-75%.) and peak expiratory flow rate (PEFR)] as well as subjective measures of therapeutic response (patients' daily evaluation of asthma symptoms and physicians' evaluation). At endpoint, all four active treatments were significantly more effective than placebo (P < 0.01) in improving FEV1 (MF DPI 5 to 7%, BDP 3%, placebo -6.6%) and all other measures of pulmonary function (FVC: MF DPI 4 to 5%, BDP 2%, placebo -4.7%; FEF25-75%: MF DPI 6 to 18%, BDP 7.5%, placebo -9.5%; PEFR (AM): MF DPI 5 to 10%, BDP 5.7%, placebo -7%). A consistent trend was observed for better improvement in patients treated with MF DPI 200 mcg b.i.d. than with MF DPI 100 mcg b.i.d., with no apparent additional benefit of MF DPI 400 mcg b.i.d. Results for the MF DPI 100 mcg b.i.d. and BDP 168 mcg b.i.d. treatment groups were similar. Patients' and physicians' subjective evaluations of symptoms found similar improvement in the MF DPI 200 and 400 mcg b.i.d. treatment groups, which were slightly better than that in the MF DPI 100 mcg b.i.d. group. Symptoms tended to worsen in the placebo group. MF DPI was well tolerated at all dose levels and the most frequently reported treatment-related adverse effects were headache, pharyngitis and oral candidiasis. No evidence of HPA-axis suppression was detected in any treatment group. In summary, all doses of MF DPI were well tolerated and significantly improved lung function and MF DPI 400 mcg (200 mcg b.i.d.) was the optimal dose in this study of patients with moderate persistent asthma.

Adolescent↗
PubMed1998

A comparison of triamcinolone acetonide MDI with a built-in tube extender and beclomethasone dipropionate MDI in adult asthmatics.

STUDY OBJECTIVE: In this study, the efficacy and safety of triamcinolone acetonide (TA) metered-dose inhaler with a built-in tube extender and beclomethasone dipropionate (BDP) metered-dose inhaler without a spacer device were compared. Both treatments were dosed at their most commonly used daily doses (within labeling). DESIGN: A 56-day, randomized, double-blind, double-dummy, placebo-controlled trial. SETTING: Seventeen asthma/allergy centers. PATIENTS: We enrolled 339 patients 18 to 65 years of age, with a documented history of bronchial asthma (FEV1, 50 to 90% of predicted value) for > or = 2 years who required inhaled corticosteroid therapy. INTERVENTIONS: Patients were randomized to receive BDP 336 microg/d (4 puffs bid) plus TA placebo (4 puffs bid), TA 800 microg/d (4 puffs bid) plus BDP placebo (4 puffs bid), or TA and BDP placebos (4 puffs of each bid). The only other asthma medication permitted was inhaled albuterol that was used as a rescue medication. All medications were administered via the closed-mouth inhalation technique. MEASUREMENTS AND RESULTS: At 8 weeks and at study end point, both active treatment groups had statistically significant and comparable improvements in FEV1 relative to baseline, and statistically significant increases relative to placebo. At study end point, improvements in forced expiratory flow (FEF25.75%), clinic peak expiratory flow (PEFR), and FVC were statistically significant for the active treatment groups compared with placebo. At end point, the mean difference between BDP and TA for mean change in FEV1 from baseline in the efficacy population was 0.02 and the 95% confidence interval was -0.11, 0.15. Asthma symptoms recorded at clinic visits showed statistically significant improvements for the BDP and TA groups compared with the placebo group. Treatment-related adverse events occurred with similar frequency in all patient groups-25.5% of placebo-treated patients, 22.3% of BDP patients, and 20.4% of TA patients. The incidence of oropharyngeal adverse events, including cough, thrush, and dysphonia, was not statistically different between the two active treatment groups. CONCLUSION: In this randomized, double-blind, placebo-controlled study of adult asthmatics treated with either BDP without a spacer or TA with its built-in tube extender, BDP and TA were comparable in efficacy as measured by FEV1 and other pulmonary function tests, and by improvement in asthma symptoms. Both active treatments were significantly more effective than placebo. All treatment groups were comparable in safety as measured by the incidence of adverse events.

Administration, Inhalation↗
PubMed1997

Childhood asthma and allergic rhinitis: the role of leukotrienes.

Research in the past two decades has shown that patients with asthma and rhinitis have inflammation of the involved tissues. This perception has been reflected in recent treatment guidelines, which stress the decreased use of symptom-based therapy and increased use of antiinflammatory therapies to control underlying inflammation. Corticosteroids are the most effective drugs currently in use; however, their use may be limited by potential problems with safety and patient/family adherence, which includes the "fear factor." In addition, the use of high doses of topical corticosteroids (especially when used in both the nose and airways) may have adverse effects when used continuously for long periods. The inflammatory response is complex, involving numerous inflammatory mediators and cells that interact in complicated and interrelated pathways. This provides researchers with numerous interactions at which molecular intervention may result in the attenuation of inflammation, and thus clinical disease. The leukotrienes, a group of important inflammatory mediators, cause vascular leakage and tissue edema; they also promote mucus secretion and a potent bronchoconstriction in patients with asthma. Currently a number of antileukotriene drugs have been developed and preliminary research indicates that they may provide clinicians with a non-steroidal antiinflammatory therapy that may provide steroid-sparing effects. This review examines the leukotrienes and the effects of antileukotriene agents in patients with asthma and allergic rhinitis.

Adrenal Cortex Hormones↗
PubMed1996

Organizing the community to target poor Latino children with asthma.

A community-university partnership to improve outcomes of care for poor Latino children (aged 6-14 years) with asthma in East Los Angeles was based on development of a community infrastructure. A family-centered educational program involved over 500 families. The Association of Latinos with Asthma and Allergy Symptoms (ALAAS) was formed. Parents report reductions in hospitalizations, emergency room, and acute care visits. Survival of the infrastructure following the end of grant funds is unlikely unless other resources offset the costs of volunteerism among poor families. Block grants to community agencies from established fund-raising groups might reduce dependency-producing practices currently employed to "help" the poor.

Adolescent↗
PubMed1994

The termination of a randomized clinical trial for poor Hispanic children.

OBJECTIVE: To conduct a randomized clinical trial of the Spanish version of an educational program designed to be an adjuvant to adequate medical care of children with asthma. DESIGN: Randomized, clinical trial. SETTING: Los Angeles County, Calif. PARTICIPANTS: One hundred thirty-eight Hispanic children, ages 7 to 12 years, from disadvantaged families. All had used emergency facilities of major local hospitals in the previous year. MEASUREMENT/MAIN RESULTS: As the study proceeded, it became apparent that subjects were receiving inadequate medical and nursing care and had numerous barriers to applying knowledge and self-care skills gained from the program. Realizing this, we considered it unethical to allow the control children to suffer for the duration of the trial (1 year). Therefore, all children received "adequate" care from the research staff, and the randomized clinical trial, as originally designed, was ended. The emergency department/hospital use by both groups was significantly reduced compared with previous experience. CONCLUSION: Those researchers conducting randomized trials involving poor children should be aware of the potential ethical problems inherent in such ventures.

Asthma↗
PubMed1993

Validity and reproducibility of multi-test skin test device.

Thirty patients were skin tested by Multi-Test and Morrow Brown needle using antigens, histamine, glycerosaline, and blank controls to examine reproducibility and influence of positive reactions on adjacent negative controls. There was no evidence that histamine or strongly positive antigen reactions affected adjacent negative controls. Multi-Test was more reproducible, and preferred by patients over Morrow Brown.

Adolescent↗
PubMed1993

An update on the diagnosis and management of pediatric asthma. Based on the National Heart, Lung and Blood Institute expert panel report.

Asthma morbidity and mortality are increasing despite the availability of antiasthma medicines and a broader understanding of the pathology of the disease. In an attempt to enhance the understanding of asthma and to aid in appropriate asthma management, the National Heart, Lung and Blood Institute assembled an expert panel, which developed a report titled "Guidelines for the Diagnosis and Management of Asthma." These guidelines are designed to facilitate patient and health-care-provider education, and diagnosis and management of asthma. Proper diagnosis of the disease is a frequent problem in children and adults. For proper diagnosis of asthma, a complete patient history, physical examination and specific laboratory tests are required. Health care providers who educate patients and their families about common symptom triggers, encourage avoidance techniques and who incorporate state-of-the-art treatment for acute and chronic asthma management may reduce the recent increases in asthma morbidity and mortality while maintaining normal growth and development of the child.

Academies and Institutes↗
PubMed1992

Immediate and delayed type hypersensitivity to malathion.

Between December 1989 and June 1990, 1,874 reports of alleged malathion application related illness from repeated spraying of a mixture of malathion corn syrup bait to eradicate a Mediterranean fruit fly infestation in Southern California were received by the Toxics Epidemiology Program of Los Angeles County. Among these complaints were 47 reports of urticaria, 38 reports of angioedema and 213 reports of a nonspecific skin rash. In order to determine whether these alleged skin reactions were the result of an immediate or delayed type of hypersensitivity reaction to malathion or to the corn syrup bait we studied ten subjects referred for testing by the local health department. All ten subjects had no reaction on patch testing. One child exhibited a positive reaction to the bait and one child had irritant reactions to malathion and to the bait. This study documented one case of a possible immediate IgE reaction to malathion bait. Due to the low participation rates in this study, no specific conclusions concerning the rate of sensitivity in the population can be drawn, although it appears that such reactions are uncommon.

Adult↗
PubMed1992

Effect of terfenadine in asthmatic patients.

The bronchodilator effect of terfenadine, 60-mg or 120-mg single dose, and 1 week twice daily dosing, was evaluated in 12 allergic asthmatic patients. When compared with baseline, FEV1 rose significantly for single dose 120 mg terfenadine at one, one and one-half, three, five and one-half, and six hours and for 60 mg terfenadine at three, five and one-half, six, and eight hours postdose. Variations in patient response were observed. At steady state, 120 mg terfenadine b.i.d. showed consistent improvement over placebo from three to 12 hours postdosing but no improvement in FEV1 was noted for terfenadine, 60 mg b.i.d. There no longer was a statistically significant difference in mean FEV1 or percent change from baseline. Thus, terfenadine proved to be a safe and a mild bronchodilator; however, tachyphylaxis might develop to the bronchodilator effect after 1 week of continuous b.i.d. dosing.

Asthma↗
PubMed1990

The use of reservoir devices for the simultaneous delivery of two metered-dose aerosols.

Many patients benefit from using metered-dose inhalers (MDIs) with spacer or reservoir devices. Concomitant therapy with separate MDI doses of cromolyn sodium and a beta-agonist is common practice. If two puffs from each drug could be placed into a chamber, the patient could administer both medications at once, enhancing compliance. A multistage liquid impinger (a four-stage inertial impaction device incorporating an inlet bend and an absolute filter, which separates an aerosol cloud into six fractions) was used to investigate such a possibility. Cromolyn sodium and albuterol MDIs were used with an Aerochamber (Monaghan Medical Corp., Plattsburgh, N.Y.) and an Inspirease (Schering Corp., Kenilworth, N.J.). Results are reported by analyzing milligrams of cromolyn sodium per actuation retrieved. With the Aerochamber, two puffs of cromolyn sodium followed by two puffs of albuterol resulted in the total "dose to patient" being reduced by 75% (0.19 versus 0.05 mg) and the effective dose of fine particles (less than 6.5 microns) being reduced by 80% (0.13 versus 0.03 mg) compared to two puffs of cromolyn sodium alone. With the Inspirease, total dose was decreased by 80% (0.32 versus 0.06 mg), whereas the effective dose of fine particles was reduced by 60% (0.19 versus 0.05 mg) compared to one puff of cromolyn sodium alone. The use of cromolyn sodium and albuterol MDIs in a multipuff combination with the Aerochamber or the Inspirease is not recommended because this leads to a loss of the dose delivered compared to a single administration.

Aerosols↗
PubMed1987

ACT-asthma control y tratamiento para niños: a progress report.

A randomized clinical trial is in progress to evaluate an asthma educational program for Latino children and their parents. The intervention, "ACT-Asma Control y Tratamiento Para Niños," was adapted from ACT for Kids, an asthma self-management program for English-speaking families. Results of a pilot study indicated that socioeconomic status was a critical variable to be considered in the design of such programs. Latino children and parents encounter significant barriers to access and continuity of medical care. Therefore, the intervention was redesigned to include "linkages" using a nurse to reduce barriers and to coordinate care. The lesson plans emphasize concrete, experimental learning experiences, with repetition of key points in each session.

Asthma↗
PubMed1986

Sustained-release theophylline preparations in asthmatic children. A short-term comparison of two products and the relationship of serum theophylline levels and pulmonary function changes.

In a four-week study, 20 children with chronic asthma were treated in a randomized, double-blind, crossover manner with two sustained-release theophylline preparations (Theo-Dur and Uniphyl) to compare their drug concentrations and clinical efficacy. In addition, the effects of serum theophylline concentration on results of pulmonary function tests (PFTs) were evaluated. Twelve-hour doses (to achieve serum concentrations between 10 and 20 mg/L) of each drug were given for two weeks. Diaries of asthma symptoms and peak flows were kept daily. After 14 days of each treatment, children returned for measurement of theophylline levels and PFTs over a 12-hour period. The two drugs were equally effective in clinically controlling asthma over the two weeks of treatment. Serum theophylline levels obtained over the 12-hour dosing periods were not significantly different. Uniphyl provided less (but not significantly) deviation between peak and trough levels. Analysis of individual patient data did not reveal a predictable relationship between serum theophylline concentrations and results of PFTs.

Adolescent↗
PubMed1984

A randomized trial of A.C.T. (asthma care training) for kids.

A randomized control trial of a curriculum, A.C.T. (Asthma Care Training) for Kids, was conducted. Seventy-six children between the ages of 8 and 12 years, whose asthma required treatment with medications at least 25% of the days per month, were randomly assigned to control and experimental groups. The control group received 4 1/2 hours of lecture presentations on asthma and its management. The experimental groups (consisting of four to seven children and their parents) received five 1-hour sessions comprising "the treatment." Children and their parents were interviewed before the sessions and 3, 6, and 12 months after the completion of the experimental treatment. Use of emergency rooms and hospitals was determined by reviewing the records of these patients (all members of the Los Angeles Kaiser Permanente health care system) for the period of 1 year before and 1 year after the treatment. Results include (1) equivalent increases in knowledge and changes in beliefs in both groups, (2) significant changes in the self-reported compliance behaviors of the experimental group only, and (3) significant reductions in emergency room visits and days of hospitalization among those receiving the experimental treatment, compared with the control group. These changes represent an estimated savings of approximately $180 per child per year for those in the experimental group.

Asthma↗
PubMed1978

Treatment of chronic childhood asthma with beclomethasone dipropionate aerosols: II. Effect on pituitary-adrenal function after substitution for oral corticosteroids.

The effects of beclomethasone, dipropionate aerosol (DBA) (400 microgram/day) on clinical course, pulmonary function, and pituitary-adrenal function was studied in 34 steroid-dependent asthmatic children. Asthma severity was assessed by daily symptom and medication scores, peak flow measured three times a day, and weekly spirometry. Pituitary-adrenal function was evaluated by diurnal cortisol levels, cortisol responses to intravenous (IV) corticotropin (ACTH), and steroid responses to IV metyrapone. After 12 weeks of BDA therapy, 30 of 34 patients no longer required prednisone. Mean weekly symptom and medication scores and the number of attacks decreased significantly (P less than .01)). A significant improvement was demonstrated in the patients' peak flow (P less than .01), forced expiratory volume in one second, and maximum midexpiratory flow rates (P less than .01). Thirty of the 34 patients initially had abnormal metyrapone responses, 28 had abnormal diurnal cortisol levels, whereas only 14 had abnormal IV ACTH response tests. Although significant improvement was noted in the mean metyrapone and diurnal cortisol tests, only partial recovery of pituitary-adrenal function was observed in 20 patients, complete recovery in 5, and no change in 9. BDA was found to be therapeutically superior to oral steroids in the group of steroid-dependent asthmatic children and produced no serious adverse effects.

Administration, Oral↗
PubMed1977

Comparison of aerosolized atropine sulfate and SCH 1000 on exercise-induced bronchospasm in children.

The new anticholinergic compound Sch 1000 (ipratropium bromide) has been reported to be an effective bronchodilator without significant atropine-like side effects. We evaluated the effectiveness of different doses of nebulized Sch 1000 (40 microgram and 80 microgram) aerosolized atropine sulfate (1 mg) and placebo in the prevention of exercise-induced bronchospasm (EIB) in 20 children with atopic bronchial asthma. A random, crossover double-blind protocol was used. Standard exercise on a cycloergometer was used to induce EIB. Pulmonary function was determined before and after drug administration and exercise. Following no treatment or placebo, exercise resulted in average reductions of 33% to 43% in plethysmographic specific airway conductance (SGaw), of 20% to 25% in forced expiratory volume in 1 sec (FEV1), and of 25% to 32% in maximal midexpiratory flow rate. Exercise following no treatment or placebo resulted in average increases of 23% to 30% in thoracic gas volume (Vtg). Prior to exercise atropine and either dose of Sch 1000 caused significant increases in SGaw (48% to 59%). After pretreatment with Sch 1000 or atropine, exercise caused SGaw to fall to values that were not significantly different from pretreatment medication values, but were significantly higher than values following exercise without pretreatment or after pretreatment with placebo. No significant differences were noted between the effects of atropine and Sch 1000 on EIB. We conclude that at the doses used atropine and Sch 1000 cause equivalent degrees of bronchodilation but neither drug specifically inhibits EIB.

Adolescent↗