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Biomedical subjects

P Lieberman

Publications and source records attributed to P Lieberman.

At least 19 recordsLinked to original sources
PubMed2001

Efficacy of azelastine nasal spray in the treatment of vasomotor (perennial nonallergic) rhinitis.

BACKGROUND: Azelastine hydrochloride is an antihistamine with anti-inflammatory properties that is available in the United States in a nasal spray formulation for the treatment of seasonal allergic rhinitis. Vasomotor (perennial nonallergic) rhinitis (VMR) is a noninfectious, chronic rhinitis usually not associated with inflammatory cell infiltration. OBJECTIVE: Two multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trials were conducted to determine whether patients with symptoms of VMR (rhinorrhea, sneezing, postnasal drip, and nasal congestion) could be effectively treated with azelastine nasal spray. METHODS: All of the patients who participated in the trials had a diagnosis of VMR, symptoms for at least 1 year, negative skin tests for a mixed panel of seasonal and perennial allergens, and a nasal cytology examination negative for eosinophils. After a 1-week, single-blind, placebo lead-in period, patients who met the symptom severity qualification criteria were randomized to receive either azelastine nasal spray (two sprays per nostril twice daily, 1.1 mg/day) or placebo nasal spray for 21 days. Patients recorded the severity of their VMR symptoms on diary cards each morning and evening of the trial using a four-point symptom rating scale (0 = none to 3 = severe). The primary efficacy variable was the overall reduction from baseline in the total vasomotor rhinitis symptom score (TVRSS) over the 21-day, double-blind treatment period. RESULTS: In both studies, azelastine nasal spray significantly (study 1, P = .002; study 2, P = .005) reduced the TVRSS from baseline when compared with placebo. Significant improvement was observed within the first week and improvement in all symptoms favored treatment with azelastine nasal spray. No serious or unexpected adverse events were reported in either study. Bitter taste (19% vs 2%) was the only adverse experience that occurred with a statistically significantly greater incidence in the azelastine group than in the placebo group. CONCLUSIONS: This is the first demonstration of the efficacy of an antihistamine in the therapy of VMR in two double-blind, placebo-controlled clinical trials.

Administration, Intranasal↗
PubMed2001

Update on nonallergic rhinitis.

BACKGROUND: Although nonallergic rhinitis is a well recognized entity, its incidence and therapy have not been definitively studied. Recent epidemiologic studies and treatment trials have furthered our knowledge regarding the frequency of occurrence of this disorder and effective treatment modalities. OBJECTIVE: To review and put into perspective recent advances in our knowledge regarding the incidence and significance as well as therapy of chronic nonallergic rhinitis. In addition, based upon these data, to propose a classification of this disorder. DATA SOURCES: The MEDLINE database and the results of a national survey of allergists (National Rhinitis Task Force) conducted in 15 allergy practices involving 975 patients. CONCLUSIONS: Nonallergic rhinitis is a common disease that probably affects as many as 17 million Americans. Of equal importance is that, based on available data, approximately 22 million people suffer with a combination of nonallergic rhinitis and allergic diseases (mixed rhinitis). Both nonallergic and mixed rhinitis occur more frequently in adults than in children, may be more common in female patients than in male patients, and are more likely to be perennial than seasonal. Agents demonstrating efficacy (based on controlled trials or having approval by the FDA) for the therapy of nonallergic rhinitis are azelastine and topical nasal steroids.

Adrenal Cortex Hormones↗
PubMed2001

Pulmonary remodeling in asthma.

For many years it was assumed that all asthmatics had an at least potentially reversible disease. It is now clear both from longitudinal studies of FEV1 and biopsy data that some asthmatics develop permanent obstructive lung disease. Some adults exhibit an accelerated decline in lung function, and some children never reach normal lung volume. The most likely histologic changes accounting for this phenomena are the deposition of collagen and glycoprotein beneath the basement membrane and in the extracellular matrix, and the destruction of elastic tissue. This permanent obstruction does not occur in all asthmatics. Factors that place patients at increased risk appear to be related to the severity and the duration of the disease and the degree of bronchial hyperresponsiveness. It is unclear, based upon present data, as to whether or not inhaled corticosteroids can favorably affect the process of remodeling, but evidence seems to favor this hypothesis. Inhaled corticosteroids, in some studies, have been shown to decrease the thickness of the lamina reticularis and retard the decline in FEV1. In addition, removal of the source of asthma, as demonstrated in occupational asthma due to toluene diisocyanate, can have a beneficial effect in this regard.

Adrenal Cortex Hormones↗
PubMed2001

57th AAAAI. Oligodeoxynucleotides.

This meeting was notable for its eclectic approach to the field of Allergy and Clinical Immunology. There were plenary sessions on the management of asthma, anaphylaxis, and rhinitis, and workshops that dealt with each of these fields in depth. In addition, a number of sessions were devoted to the management of anaphylaxis, food allergy, urticaria, angioedema, and atopic dermatitis. There were research reports and clinical trials of antihistamines, corticosteroids, beta-adrenergic agents, leukotriene antagonists, and combination agents. For example, there were over 20 reported trials on inhaled corticosteroids either for rhinitis or asthma, and a similar amount presented regarding antihistamine therapy, antileukotriene therapy, and beta-adrenergic therapy. Emphasis was placed on the utilization of combination agents specifically montelukast (Merck) and loratadine (Schering-Plough) for the treatment of rhinitis, and formoterol/budesonide (AstraZeneca) and salmeterol/fluticasone (GlaxoSmithKline) for the therapy of asthma. Meetings were held from early morning (6.30) until the late evening (22.00).

Journal Article↗
PubMed1999

Management of allergic rhinitis with a combination antihistamine/anti-inflammatory agent.

Azelastine nasal spray is a topical antihistamine treatment for the symptoms of seasonal allergic rhinitis. Besides histamine antagonism, azelastine affects other chemical mediators of the inflammatory response including leukotrienes and kinins. This article reviews and discusses the antihistaminic and anti-inflammatory properties of azelastine and the results of pharmacokinetic studies and controlled clinical trials.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

Double-blind trials of azelastine nasal spray monotherapy versus combination therapy with loratadine tablets and beclomethasone nasal spray in patients with seasonal allergic rhinitis. Rhinitis Study Groups.

BACKGROUND: Azelastine hydrochloride is an H1-receptor antagonist with antiinflammatory properties that is available in the US as Astelin Nasal Spray for the treatment of seasonal allergic rhinitis. The symptoms of seasonal allergic rhinitis can initially be treated with monotherapy using either an antihistamine or an intranasal corticosteroid. Patients whose symptoms do not respond adequately are often prescribed a combination of both an antihistamine and an intranasal corticosteroid. OBJECTIVE: Three multicenter, randomized, double-blind studies were conducted to determine whether patients with moderate-to-severe symptoms of seasonal allergic rhinitis who had responded inadequately to monotherapy with either an oral antihistamine or an intranasal corticosteroid, and who were candidates for combination therapy with both an oral antihistamine and an intranasal corticosteroid, could be effectively treated with azelastine nasal spray monotherapy. METHODS: Following a 1- to 2-week washout period, patients were randomized to 7 days of double-blind treatment with either azelastine nasal spray (2 sprays per nostril bid, 1.1 mg/day) monotherapy or combination therapy with oral loratadine (Claritin, one 10-mg tablet/day) plus intranasal beclomethasone dipropionate monohydrate (Beconase AQ, 2 sprays per nostril bid, 336 microg/day). Efficacy was determined at the end of the study by both a physician assessment of the need for additional anti-rhinitis medication and a patient global evaluation of therapeutic effectiveness. The three studies were conducted at 71 investigational sites during the 1998 spring allergy season. Three separate studies were conducted to verify the reproducibility of the new study design. RESULTS: In all three studies a total of 1,070 patients were randomized to double-blind treatment. There were no statistically significant differences in the percentage of patients treated with azelastine nasal spray versus patients treated with a combination of loratadine tablets and beclomethasone nasal spray who did not require additional anti-rhinitis medication (32% to 45% and 39% to 46%, respectively). The patient global evaluation indicated that 77% to 84% of the patients treated with azelastine nasal spray had symptomatic improvement and 85% to 90% of the patients treated with loratadine tablets and beclomethasone nasal spray had symptomatic improvement. The most commonly reported adverse experience with azelastine nasal spray was a transient aftertaste (8%), while the most commonly reported adverse experience with loratadine tablets and beclomethasone nasal spray in combination was headache (6%). CONCLUSIONS: Based on the percentage of patients not requiring additional antirhinitis medication and the patient assessment of efficacy, azelastine nasal spray monotherapy was as effective as the combination of oral loratadine plus intranasal beclomethasone in treating moderate-to-severe symptoms of seasonal allergic rhinitis.

Administration, Intranasal↗
PubMed1999

Intradermal injection of granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with metastatic melanoma recruits dendritic cells.

Dendritic cells (DCs) are the main antigen-presenting cells in the skin. We hypothesized that intradermal (i.d.) injection of granulocyte-macrophage colony-stimulating factor (GM-CSF) would recruit DCs into melanoma skin metastases and enhance autologous melanoma antigen presentation to host T cells. Sixteen patients with cutaneous or subcutaneous melanoma metastases were treated with GM-CSF injected i.d. into a single dermal metastasis and into a normal skin site for 10 consecutive days at one of four dose levels (10, 20, 40, or 80 microg/injection). Pretreatment and post-treatment skin and tumor biopsies were stained for a panel of T-cell, B-cell, macrophage, and DC immunohistochemical markers. Positive cells were quantitated in a blinded fashion. There was a significant increase in the number of DCs (HLA-DR+, S100+, factor XIIIa+) and CD45R0+ T cells in the skin and in the tumors Injected with GM-CSF at all dose levels. Uninjected control tumors showed no increase in HLA-DR+ cells or T-cell infiltrate, but did show an Increase in S100+ and factor XIIIa+ cells, suggesting a non-DC population. ID GM-CSF administered in this manner recruited DCs into melanoma tumors and normal skin. Although no antitumor effects were seen, this represents a potential method of preparing skin sites for vaccine delivery.

Antigen Presentation↗
PubMed1999

American Academy of Asthma, Allergy and Immunology--55th annual meeting. 26 February-3 March 1999, Orlando, FL, USA.

This was a particularly comprehensive gathering of investigators and clinicians interested in the field of allergy, asthma and immunology. The meeting presented information ranging from basic immunological research to the clinical trials of drugs already available for treatment in the US today. There were 984 original oral and poster presentations and over 100 symposia, seminars and workshops. The plenary sessions involved sections on allergic inflammation, immune modulation, chemokine receptors, the origins of asthma, the diagnosis and management of food and drug reactions, the environmental influences on allergic diseases, and dermatological diseases. There were approximately 500 faculty members who presented new data or participated in lectures, seminars or workshops.

Journal Article↗
PubMed1998

Selective speech motor, syntax and cognitive deficits associated with bilateral damage to the putamen and the head of the caudate nucleus: a case study.

Deficits in speech production, sentence comprehension and abstract reasoning occurred in a subject having profound bilateral damage to the putamen and the caudate nucleus. Acoustic analyses indicated that the subject's speech was degraded due to inappropriate sequencing of articulatory gestures that involve different articulatory structures. Transitions between sounds were slow and often did not achieve target configurations. The subject had a 14% error rate comprehending distinctions in meaning conveyed by syntax in English sentences; normal controls make virtually no errors in this test. Cognitive deficits involving impaired sequencing occurred: the subject had a 70% error rate on the Odd Man Out test when making decisions within a single category. Cognitive perseveration occurred when the subject was asked to shift categories. In contrast, performance was within normal ranges in tests of lexical access and memory. The pattern of deficits provides evidence for basal ganglia involvement in the regulation of sequencing across modalities.

Adult↗
PubMed1998

Simian virus 40 large T antigen stabilizes the TATA-binding protein-TFIIA complex on the TATA element.

Large T antigen (T antigen), the early gene product of simian virus 40 (SV40), is a potent transcriptional activator of both cellular and viral genes. Recently we have shown that T antigen is tightly associated with TFIID and, in this position, performs a TATA-binding protein (TBP)-associated factor (TAF)-like function. Based on this observation, we asked whether T antigen affected steps in preinitiation complex assembly. Using purified components in in vitro complex assembly assays, we found that T antigen specifically enhances the formation of the TBP-TFIIA complex on the TATA element. T antigen accomplishes this by increasing the rate of formation of the TBP-TFIIA complex on the TATA element and by stabilizing the complexes after they are formed on the promoter. In addition, DNA immunoprecipitation experiments indicate that T antigen is associated with the stabilized TBP-TFIIA complexes bound to the DNA. In this regard, it has previously been shown that T antigen interacts with TBP; in the present study, we show that T antigen also interacts with TFIIA in vitro. In testing the ability of T antigen to stabilize the TBP-TFIIA complex, we found that stabilization is highly sensitive to the specific sequence context of the TATA element. Previous studies showed that T antigen could activate simple promoters containing the TATA elements from the hsp70 and c-fos gene promoters but failed to significantly activate similar promoters containing the TATA elements from the promoters of the SV40 early and adenovirus E2a genes. We find that the ability to stabilize the TBP-TFIIA complex on the hsp70 and c-fos TATA elements, and not on the SV40 early and E2A TATA elements, correlates with the ability or inability to activate promoters containing these TATA elements.

Adenovirus E2 Proteins↗
PubMed1997

Fundamental frequency of phonation and perceived emotional stress.

Nonlinguistic information about the speaker's emotional state is conveyed in spoken utterances by means of several acoustic characteristics and listeners can often reliably identify such information. In this study we investigated the effect of short- and long-term F0 measures on perceived emotional stress using stimuli synthesized with the LPC coefficients of a steady vowel and varying F0 tracks. The original F0 tracks were taken from naturally occurring speech in highly stressful (contingent on terror) and nonstressful conditions. Stimuli with more jitter were rated as sounding more hoarse but not more stressed, i.e., a demonstrably perceptible amount of jitter did not seem to play a role in perceived emotional stress. Reversing the temporal pattern of F0 did not affect the stress ratings, suggesting that the directionality of variations in F0 does not convey emotional stress information. Mean and maximum F0 within an utterance correlated highly with stress ratings, but the range of F0 did not correlate significantly with the stress ratings, especially after the effect of maximum F0 was removed in stepwise regression. It is concluded that the range of F0 per se does not contribute to the perception of emotional stress, whereas maximum F0 constitutes the primary indicator. The observed effects held across several voices that were found to sound natural (three male voices and one of two female ones). An effect of the formant frequencies was also observed in the stimuli with the lowest F0; it is hypothesized that formant frequency structure dominated the F0 effect in the one voice that gave discrepant results.

Affect↗
PubMed1996

Idiopathic anaphylaxis: a purely internal reaction.

Episodes are clinically identical to classic anaphylaxis, yet no external allergen or psychological disorder can be identified as the cause of the patient's symptoms and signs. Combinations of a corticosteroid, an H1-histamine receptor blocker, and a sympathomimetic amine are highly effective at inducing control and can often achieve a remission.

Albuterol↗