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Biomedical subjects

J Portnoy

Publications and source records attributed to J Portnoy.

At least 19 recordsLinked to original sources

A double monoclonal antibody assay for the Alternaria allergen GP70.

A double monoclonal antibody-based assay for the 70-kD Alternaria allergen GP70 is described. The assay is sensitive to GP70 concentrations as low as 0.2 microgram/mL and is highly specific for this allergen. The glycoprotein detected by this assay is shown to bind to human IgE from Alternaria-sensitive patients, proving that it is an allergen. Two of three commercial Alternaria preparations tested contained no detectable GP70. Several related fungi were shown to contain detectable concentrations of GP70, but the most abundant source was a commercial preparation of house dust. Further measurement of GP70 in biologic materials should increase our knowledge of the distribution and importance of this Alternaria allergen in the environment and in the development of allergic diseases.

Allergens

Chest pain in otherwise healthy children and adolescents is frequently caused by exercise-induced asthma.

Chest pain in children and adolescents, unlike in adults, is rarely of cardiac origin and its etiology is frequently unknown. In this age group, chest pain can limit normal activity and sports participation. The reported incidence of exercise-induced asthma in children with chest pain is less than 20%. For this study, 88 otherwise healthy children and adolescents with chest pain followed a treadmill protocol without a warm-up period designed to obtain a target heart rate of 180 or greater during the first several minutes of exercise. Patients maintained this workload for 6 to 8 minutes. Pulmonary function tests performed prior to exercise and at 2, 5, 10, 15, 20, and 25 minutes revealed a decrease in forced expiratory volume in 1 second or peak expiratory flow rate of greater than or equal to 15% in 64 (72.7%) children. Inhaled albuterol resulted in subjective improvement in 97% (35/36) and objective improvement in 70% (25/36) of patients. In otherwise healthy children and adolescents with chest pain, the incidence of exercise-induced asthma seems greater than previously reported. Treatment with bronchodilators may help these patients lead a more active life-style.

Adolescent

Methotrexate treatment of severe asthma in children.

Seven children from 3 to 14 years old with chronic steroid-dependent asthma were treated with methotrexate (MTX). Asthma in all of the patients had been poorly controlled for at least 2 years despite the use of oral theophylline and inhaled corticosteroids, cromolyn and albuterol. All presented with significant side effects as a result of chronic systemic steroid therapy. Five patients were atopic and had been unable to tolerate immunotherapy because of systemic reactions. Forced expiratory volume in 1 second and forced expiratory flow, mid-expiratory phase, improved in four patients after 4 to 6 months of treatment with doses of MTX ranging from 7.5 to 17.5 mg/wk. Three patients were able to discontinue their systemic corticosteroids. Laboratory values including complete blood cell count with differential and liver enzymes remained at baseline in all except one patient, who had transient elevation in alanine aminotransferase and aspartate aminotransferase. One patient experienced side effects sufficient to require discontinuation of MTX. It is concluded that MTX is effective for reducing the need for systemic corticosteroids and for improving pulmonary functions in some individuals. The benefits of MTX in this group of severe asthmatics appear to justify the potential risks involved in its use.

Adolescent

Incidence of systemic reactions during rush immunotherapy.

Rush immunotherapy (RIT) was administered on an outpatient basis to 11 patients. Of these, nine had asthma and four were steroid-dependent. All patients received extracts containing a mixture of antigens to which they were prick-sensitive. FEV1s were greater than 80% predicted before starting RIT. Four patients each required a 1 week steroid "burst" to accomplish this. A series of 8 subcutaneous injections were given starting with 0.3 mL of 1:100,000 (wt/vol) and ending with 0.10 mL of 1:100 (wt/vol) 1.5 days later. A dose of 0.15 mL of 1:100 was given weekly after that. All patients but one completed the RIT. Four had sore arms, four had pruritus and/or sneezing, four developed wheezing, and one experienced anaphylaxis with hypotension. Systemic reactions tended to occur at the higher doses and usually more than 30 minutes after a previous injection. Subsequent weekly injections were tolerated without reactions by seven of the patients. Rush immunotherapy is an effective method for administering a high dose of allergen in a very short time period. Due to the risk of systemic reactions it needs to be given under carefully controlled conditions.

Adolescent

Continuous nebulization for status asthmaticus.

Continuous nebulization of beta 2 agonists is now recognized as a useful treatment for severe exacerbations of asthma. This mode of administration has been described both for adults and children in the emergency room and in the intensive care unit. It has been suggested that early use of continuous inhalation therapy may reduce or prevent the need for intensive care unit admissions and potentially toxic treatments such as intravenous beta agonists and mechanical ventilation. A number of methods have been proposed for continuous administration of beta agonists, however, there is no concensus as to the best one. The lack of controlled studies clearly demonstrating superior outcomes in patients who receive this treatment leaves many questions unanswered. In addition, differences in efficacy and safety between frequent and continuous nebulization, if any, are unclear. Adverse effects primarily consist of muscle cramps, hypokalemia, and hyperglycemia. It is suggested that use of this treatment should be considered for the asthmatic patient who demonstrates progression towards significant obstruction before institution of the more toxic treatments listed above. While continuous nebulization has not been proven to prevent the need for them, it is clearly safer. Should population studies eventually fail to demonstrate its superior efficacy, continuously nebulized beta 2 agonist therapy may still be beneficial for individual patients.

Adolescent

Separation of Alternaria into protein and carbohydrate fractions with phenyl sepharose.

To evaluate the contribution of high carbohydrate-containing fractions to the allergen content of Alternaria, samples of an Alternaria extract were bound to a phenyl Sepharose column and eluted with Tris buffer containing 4, 2, and 1 mol/L of NaCl and then distilled water. The fractions were dialyzed and lyophilized. The 4 mol/L fraction accounted for 79% of the dry weight and most of the carbohydrate content. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the fractions demonstrated significant interfraction differences with the largest number of silver-stained bands in the H2O fraction. Although individual differences in skin reactivity to the fractions were present, geometric means of histamine equivalent pricks were approximately the same with only a 0.5 log dilution higher potency for the 1 mol/L and H2O fractions. The 50% IgE ELISA-inhibition concentration was 100 micrograms/ml for the 1 mol/L and distilled water fractions and 10 micrograms/ml for the other fractions. Since the 4 mol/L fraction accounted for most of the dry weight and had the highest carbohydrate to protein ratio (5.8), purification of Alternaria extracts by removal of carbohydrate fractions may result in significant loss of allergenic material.

Adolescent

Restriction endonuclease patterns of herpes simplex virus DNA: subtyping of HSV-1 and HSV-2 strains from genital and nongenital lesions.

Herpes simplex type 1 (HSV-1) and type 2 (HSV-2) isolates from genital and nongenital infections were submitted to restriction endonuclease analysis for possible genomic changes in relation with the adaptation of the virus to a new site on the body. HSV-1 and HSV-2 strains were successfully divided into two subgroups using the Hin c II restriction enzyme. No correlation was found, however, between the proposed genomic subtypes H1A, H1B, H2A and H2B, and the genital or nongenital origin of the HSV strains.

Animals

Affinity purification of a major Alternaria allergen using a monoclonal antibody.

An extract of Alternaria (ALT) was passed through an affinity column containing a monoclonal antibody directed to ALT. After washing the column, a single glycoprotein was eluted using 0.1 M glycine (pH 3.0). This glycoprotein accounted for 13% of the dry weight of our ALT preparation and had a carbohydrate to protein ratio of 0.35 as compared with 3.2 for the whole ALT extract. Its molecular weight was 70 kD by SDS-PAGE and isoelectric point was 3.5 by IEF. Though individual sensitivities varied, 14/16 patients skin reactive to ALT were also reactive to this glycoprotein. Quantitative skin tests of extracts adjusted to the same dry weight per volume showed that it required about a four times greater concentration of the purified glycoprotein to give a wheal size equal to whole Alternaria. The ability to purify large amounts of this allergen with affinity chromatography should make its complete characterization possible.

Adolescent

Diagnosis of herpes simplex virus infection in a clinical setting by a direct antigen detection enzyme immunoassay kit.

A commercial 4-h direct herpes simplex virus (HSV) antigen detection enzyme immunoassay (EIA) kit (Du Pont Herpchek) was evaluated by using 273 clinical specimens obtained in a hospital-based infectious disease practice. The EIA was compared with a standard culture method in which WI38 cells were inoculated within 20 min of sample collection. Cultures were observed for 2 weeks, and positive findings were confirmed by fluorescein-labeled monoclonal antibody (FA) staining. The values for the overall HSV detection rate were 40.7% by the standard culture method and 41.4% by EIA. In eight cases, the EIA was positive, while the culture method was negative; however, clinical data and confirmatory blocking EIA suggested that a true HSV infection was present. For six FA-confirmed, culture-positive samples, the direct EIA was negative; however, an EIA performed on the supernatants of these cultures was positive, suggesting that the failure of the EIA to detect these samples was not due to lack of strain specificity of the test. After confirmatory tests of standard culture and EIA discrepant results, the overall sensitivity of the test was 95.0% (113 of 119) and the specificity was 100% (154 of 154).

Acyclovir

One-year suppression of frequent recurrences of genital herpes with oral acyclovir.

A double-blind, placebo-controlled study was undertaken to evaluate the long-term efficacy and safety of oral acyclovir suppressive therapy over a 1-year period. Results from the multicenter trials, based on a total of 261 patients with frequently recurring genital herpes, were analyzed. Of the patients enrolled in the study, 131 received oral acyclovir capsules (800 mg) daily and 130 received placebo capsules. Medication was taken twice daily. Analysis of data from patients who completed a full year of therapy demonstrated that only 5% of patients receiving placebo were free from recurrences, as compared with 46% of acyclovir recipients. The mean number of recurrences for patients on acyclovir therapy was 1.8, as compared with a rate of 8.7 recurrences for the placebo group over the course of the year. The mean time to the first recurrent herpes outbreaks was 19 days for the placebo group and 274 days for the acyclovir-treated patients. There were no significant differences between the two groups in laboratory data or in the frequency or nature of side effects reported. Daily administration of acyclovir capsules for 1 year is a safe and effective therapy for control of frequent recurrences of genital herpes.

Acyclovir

Efficacy and safety of foscarnet for recurrent orolabial herpes: a multicentre randomized double-blind study.

Foscarnet sodium (trisodium phosphonoformate hexahydrate) has been shown to inhibit herpes simplex virus (HSV) in vitro and to be efficacious for topical treatment of experimental HSV infection in animals. To assess its clinical efficacy in the treatment of recurrent orolabial herpes a multicentre collaborative, double-blind, placebo-controlled trial was conducted. The study patients were randomly assigned to receive either 3% foscarnet cream (78 patients) or placebo (cream vehicle) (75 patients) and were asked to start treatment at the earliest indication of a recurrence. Efficacy was evaluated in 143 patients (74 in the foscarnet group and 69 in the placebo group). There was no significant difference in time to healing or duration of virus shedding between the two groups. However, in the subgroup of patients who started treatment before vesicles appeared, the duration of virus shedding was shorter in the foscarnet group than in the placebo group (p = 0.04), and the proportion of lesions that evolved to the vesicular stage was smaller (p = 0.03). No significant difference in the incidence of local or systemic adverse effects was noted between the two groups. We conclude that the beneficial effect of foscarnet was limited to a subgroup of patients who started treatment in the prevesicular stage.

Administration, Topical

Pilot study of recombinant interferon alpha-2a for treatment of infants with bronchiolitis induced by respiratory syncytial virus.

Eleven children with bronchiolitis induced by respiratory syncytial virus received 10,000 to 70,000 U of recombinant interferon alpha-2a per kg of body weight per day. None developed signs of toxicity, and all but one developed an antiviral state following treatment. Interferon alpha-2a appears to be safe for infants with bronchiolitis. Its efficacy for the treatment of this condition remains to be determined.

Antibodies

Continuous terbutaline nebulization for the treatment of severe exacerbations of asthma in children.

Twelve children with severe asthma were treated in an intensive care unit with continuously nebulized terbutaline at doses between 1.0 and 12.0 mg/hour. All patients showed improvement in blood gases, pulse, and respiratory rates. None experience significant side effects. The duration of therapy ranged from 1 to 24 hours (mean = 8.3 hours), and all were able to leave the intensive care unit within one day. The use of continuously nebulized terbutaline appears to be safe and effective for the treatment of severe asthma in children in this limited experience.

Administration, Inhalation