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Biomedical subjects

J Portnoy

Publications and source records attributed to J Portnoy.

At least 37 records · Page 2Linked to original sources
PubMed1994

Premedication reduces the incidence of systemic reactions during inhalant rush immunotherapy with mixtures of allergenic extracts.

BACKGROUND: Rush immunotherapy, while having many potential benefits, is associated with an increased incidence of systemic reactions. OBJECTIVE: To determine whether pretreatment with medications reduces the rate of systemic reactions during rush immunotherapy and to identify predictors of such reactions if possible. METHODS: We conducted a double-blind, placebo-controlled study of 22 allergic children ages 6 to 18 years who received rush immunotherapy. Active treatment consisted of a combination of H1 and H2 histamine antagonists and a corticosteroid in gelatin capsules given prior to administration of rush immunotherapy whereas placebo patients received lactose. Rush immunotherapy consisted of eight injections of increasing doses of a mixture of allergens to which each patient was skin-reactive over 1 1/2 days. Serial skin tests and peak expiratory flow rate measurements were performed during the procedure. Following the initial series of injections, patients were followed for 8 weeks and had blood drawn at 2-week intervals for measurements of specific IgG and IgE. RESULTS: Systemic reactions were observed in 3 (27%) active and 8 (73%) placebo patients (Fisher's exact test: P = .047). The mean time for systemic reactions was 63 minutes after a previous injection. The most common dose causing a systemic reaction was 0.3 mL of 1:1000 (wt/vol). The best predictors of development of a systemic reaction were degrees of skin sensitivity to the extract before and after premedication. Local reactions were not associated with subsequent systemic reactions. Specific IgG rose by 2 weeks while specific IgE did not change significantly during the 8-week follow-up period. Pretreatment did not change the number of systemic reactions seen with subsequent injections. CONCLUSIONS: Premedication significantly reduces the incidence of systemic reactions during rush immunotherapy and is therefore recommended. Degree of skin sensitivity to the injected extract may eventually prove to be a clinically useful predictor for the development of systemic reactions.

Adolescent↗
PubMed1993

Enhanced sensitivity of immunoblotting with peroxidase-conjugated antibodies using an adsorbed substrate method.

Immunoblots probed with immunoglobulin E (IgE)-containing sera from allergic patients are frequently used in allergy research. Current techniques for detection of specific IgE include radiolabeled and enzyme-linked methods. Although radiolabeled methods are very sensitive, many research groups prefer non-radioactive procedures with equal or greater sensitivity. Alkaline phosphatase (AP) and horse radish peroxidase (HRP) are the most frequently used conjugating enzymes for immunoblotting with the former generally recognized as more sensitive. We describe a method of immunoblot detection using HRP-conjugated immunochemicals with sensitivity equal to and for some systems greater than that of AP conjugates. An adsorbed substrate method for developing immunoblots probed with HRP immunochemical conjugates is compared with traditional AP and HRP methods. The adsorbed substrate system, when used to detect IgE binding to allergic proteins, gives high resolution and delineates bands not otherwise seen. The system has advantages of high sensitivity, rapid development and conservation of immunochemicals. Problems of fading, sensitivity to heat and light, and high background can be solved with increased washing, prompt photography and computer scanning.

Adsorption↗
PubMed1993

Selection of representative Alternaria strain groups on the basis of morphology, enzyme profile, and allergen content.

In an attempt to identify representative strains, 12 strains of Alternaria alternata were contributed by four different research groups. Each was grown on two types of solid media and characterized with descriptions of pigmentation and morphology. Enzyme profiles were determined on both the cellular antigen and the culture filtrate material with use of a commercial kit. Concentrations of a previously described Alt a 1 and a 70 kd allergen, GP70, were measured by a two-antibody "sandwich" ELISA. Allergenic proteins were visualized by IgE immunoblots. With use of these criteria, four separate strains were identified that might serve as representative of Alternaria for further research.

Alkaline Phosphatase↗
PubMed1993

The effect of time and extraction buffers on residual protein and allergen content of extracts derived from four strains of Alternaria.

BACKGROUND: A series of studies was performed to identify optimal elution conditions for production of desired Alternaria allergens with simultaneous reduction of undesired ones. METHODS: Proteins and allergens from four strains of Alternaria extracted for differing time intervals and in different buffers were analyzed by one- and two-dimensional electrophoresis, as well as by immunoglobulin E enzyme-linked immunosorbent assay inhibition and immunoblotting. RESULTS: The amount of protein and carbohydrate released varied with each time interval but was consistent between buffers. Extracts from longer time intervals tended to contain more carbohydrate. Electrophoresis of the four strains demonstrated many similar proteins; however, the concentrations of these proteins showed considerable interstrain difference. Comparison of extraction times for single strains by immunoblotting showed that certain allergens are preferentially released during specific time intervals. Some allergens were seen to be most prevalent in a 24-hour extract, whereas others were most prevalent in a 1-hour extract. Two-dimensional electrophoresis resolved bands into discrete spots. The major shared elements of the four strains could be easily identified. The appearance and disappearance of individual protein elements with time was seen. CONCLUSIONS: Elution conditions have a significant impact on quantities of specific glycoproteins contained in extracts of Alternaria and must be controlled and optimized when such extracts are produced for allergen purification.

Allergens↗
PubMed1993

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1988

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↗
PubMed1988

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↗