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Biomedical subjects

R Naclerio

Publications and source records attributed to R Naclerio.

At least 19 recordsLinked to original sources

Pharmacologic and anti-IgE treatment of allergic rhinitis ARIA update (in collaboration with GA2LEN).

The pharmacologic treatment of allergic rhinitis proposed by ARIA is an evidence-based and step-wise approach based on the classification of the symptoms. The ARIA workshop, held in December 1999, published a report in 2001 and new information has subsequently been published. The initial ARIA document lacked some important information on several issues. This document updates the ARIA sections on the pharmacologic and anti-IgE treatments of allergic rhinitis. Literature published between January 2000 and December 2004 has been included. Only a few studies assessing nasal and non-nasal symptoms are presented as these will be discussed in a separate document.

Animals↗

Location and gross morphology of the nasopalatine duct in human adults.

OBJECTIVE: To characterize the nasal opening of the human nasopalatine duct (NPD; a major duct of the vomeronasal system used in animals for chemical communication) by identifying its location, categorizing variations in physical characteristics, and assessing frequency of detection. DESIGN: Two studies: (1) general study incorporating endoscopic examinations documented by videotapes and photographs, and an investigation of detection bias in terms of method of visualization and defining criteria for NPD identification; and (2) cadaver dissections examining NPD gross anatomy and proximity to the putative vomeronasal organ (VNO), the second major duct of the vomeronasal system. SETTING: Department of Otolaryngology, University of Chicago Hospitals, Chicago, Ill. SUBJECTS: A total of 125 university community volunteers, with a mean age of 23 years. RESULTS: (1) General study: NPD was located 1.9+/-0.02 cm (mean+/-SEM) dorsal to the columella nasi, and 0.2+/-0.01 cm above the nasal floor/septum junction, in both nostrils (90% bilateral), and was symmetrical in shape. An NPD was detected in 94% of 221 nostrils unobstructed in the region of interest. Fossa shapes were oval (57%), round (18%), spindle-shaped (18%), and tubular (7%). A small, round aperture was visualized in 30% of fossae. Among 3 observers, NPD detection frequency ranged from 94% to 40%, with the disparity due to inclusion of different defining characteristics. (2) Cadaver dissection study: bilateral nasal NPD fossae were found in every specimen probed to maximum approximate depth of 8 mm. No buccal pits associated with patent NPD were detected. Putative VNOs superior and just anterior to NPD fossae were detected in fewer than half the specimens. CONCLUSIONS: The nasal opening of the NPD is bilateral and symmetrical, located at the base of the nasal septum. Unusually contradictory anatomical descriptions in the human putative VNO literature may be attributable to inexact descriptions or misidentification of structures. The function of NPD remains controversial.

Adolescent↗

As-needed use of fluticasone propionate nasal spray reduces symptoms of seasonal allergic rhinitis.

BACKGROUND: The daily use of intranasal corticosteroids is approved for the treatment of seasonal allergic rhinitis. OBJECTIVE: Our objective was to test the effectiveness of as-needed use of intranasal corticosteroids in the treatment of seasonal allergic rhinitis. METHODS: A double-blind, placebo-controlled, randomized, parallel-group study of the as-needed usage of fluticasone propionate nasal spray in the management of seasonal allergic rhinitis was performed. Outcome measures were symptom score, Rhinitis Quality of Life Questionnaire (RQLQ), and the number of eosinophils and the level of eosinophilic cationic protein (ECP) in nasal lavage. RESULTS: Twenty-six subjects in each group completed the 4-week study. The median symptom score over the duration of the study in the placebo group was 8.5 versus 4.5 in the active group. The active group had significant improvement on the interim visit in the sleep, non-nose/eye, activities, nasal, practical, and overall domains (P <.05) of the RQLQ and on the final visit in the nasal symptom domain. The number of eosinophils was significantly lower in the active than in the placebo group at the final visit. Changes in ECP were not significant. CONCLUSION: As-needed fluticasone propionate nasal spray is efficacious in the treatment of seasonal allergic rhinitis.

Administration, Intranasal↗

Bactrim reduces the inflammatory response in a murine model of acute rhinosinusitis.

OBJECTIVE: To determine whether treatment with an antibiotic (trimethoprim-sulfamethoxazole) reduced the inflammatory response in a murine form of Streptococcus pneumoniae-induced rhinosinusitis. DESIGN: We randomized 18 C57BL/6 mice to either treatment with intraperitoneal trimethoprim-sulfamethoxazole (Bactrim, 30 mg/kg) or no treatment (control). After 2 days, we inoculated all C57BL/6 mice intranasally with a Bactrim-susceptible strain of Streptococcus pneumoniae, ATCC 49619, suspended in Trypticase soy broth. At day 5 after bacterial inoculation, we sacrificed the mice and prepared histopathologic sections of their sinuses after culturing their nasal cavities by lavage. SETTING: Animal care facility at a tertiary, academic institution. METHODS: The histopathologic sections of the sinuses were examined in a blind manner for the percent of sinus cavity area occupied by neutrophil clusters, and for the number of neutrophils per square millimeter of sinus mucosa. RESULTS: The Bactrim group had a significantly smaller sinus area occupied by neutrophil clusters (1.58% +/- 1.13 vs 4.38% +/- 3.41; P < 0.05), significantly fewer neutrophils infiltrating the mucosa (58.81 +/- 29.63/mm2 vs 105.85 +/- 48.49/mm2; P < 0.05), and significantly less growth of Streptococcus pneumoniae colonies in the intranasal cultures (8 few and 1 moderate vs 3 few, 3 moderate, and 1 many; P = 0.05) compared to the control group. CONCLUSION: In our murine model of acute rhinosinusitis, Bactrim decreased the number of neutrophil clusters in the sinus cavities, the number of neutrophils infiltrating the sinus mucosa, and the growth of Streptococcus pneumoniae. We propose that our murine model can be used for the study of the pathophysiology and treatment of acute rhinosinusitis.

Animals↗

Rhinitis and inhalant allergens.

Allergic rhinitis affects about 20% of the US population. The diagnosis is based on patterns of symptoms, physical examination, and assessment of IgE antibodies by skin or in vitro testing. The most common offending allergens are pollens of grasses, trees, and weeds; fungi; animal allergens; and dust mites. In an individual with nasal allergy, exposure leads to rapid release of mast cell-derived mediators. This immediate response is followed by a cell-dominated response, including eosinophils and lymphocytes. Cytokines from T(H)2 lymphocytes, such as interleukin 4 and interleukin 5, orchestrate allergic inflammation. Resulting tissue changes produce symptoms of the disease and augment responses on subsequent exposure to allergens and irritants. Strategies for avoiding offending agents are important in management. In intermittent disease, antihistamines and/or decongestants are first prescribed. More continuous symptoms may mandate intranasal steroids. Immunotherapy is often helpful for patients who respond poorly to pharmacotherapy and avoidance.

Allergens↗

Sinusitis: bench to bedside. Current findings, future directions.

Sinusitis, an inflammatory disease of the sinus, is one of the most commonly reported diseases in the United States, affecting an estimated 14% of the population. The prevalence of sinusitis is rising. Between 1990 and 1992, persons with sinusitis reported approximately 73 million restricted activity days-an increase from the 50 million restricted activity days reported between 1986 and 1988. Because critical questions remain unanswered about its cause, pathophysiology, and optimal treatment, sinusitis continues to generate significant health care costs and affects the quality of life of a large segment of the U.S. population. To identify critical directions for research on sinus disease, the American Academy of Allergy, Asthma and Immunology and the American Academy of Otolaryngology-Head and Neck Surgery Foundation, Inc., convened a meeting in January 1996 in collaboration with the National Institutes of Allergy and Infectious Disease. This document summarizes the proceedings of that meeting and presents what is intended to be the background for future investigation of the many unanswered questions related to sinusitis.

Acute Disease↗

Sinusitis: bench to bedside. Current findings, future directions.

Sinusitis, an inflammatory disease of the sinus, is one of the most commonly reported diseases in the United States, affecting an estimated 14% of the population. The prevalence of sinusitis is rising. Between 1990 and 1992, persons with sinusitis reported approximately 73 million restricted activity days--an increase from the 50 million restricted activity days reported between 1986 and 1988. Because critical questions remain unanswered about its cause, pathophysiology, and optimal treatment, sinusitis continues to generate significant health care costs and affects the quality of life of a large segment of the U.S. population. To identify critical directions for research on sinus disease, the American Academy of Allergy, Asthma and Immunology and the American Academy of Otolaryngology-Head and Neck Surgery Foundation, Inc., convened a meeting in January 1996 in collaboration with the National Institutes of Allergy and Infectious Disease. This document summarizes the proceedings of that meeting and presents what is intended to be the background for future investigation of the many unanswered questions related to sinusitis.

Acute Disease↗

Effect of terfenadine on nasal provocation.

The effect of premedication with terfenadine, an H1 antagonist, on nasal challenge with antigen, histamine and methacholine was evaluated. A single dose of terfenadine had no effect on the response to a localized challenge with methacholine but completely blocked the secretory response to histamine on both the ipsilateral and contralateral sides. These results suggest that terfenadine has no anticholinergic activity and that the direct and reflex secretory response to challenge with histamine is mediated by the H1 receptor. A single dose of terfenadine significantly reduced sneezing and nasal secretion after challenge with antigen but had no effect on nasal congestion. A double-blind placebo-controlled clinical trial was undertaken to compare the effects of pretreatment with terfenadine for 1 week on the response to sequential nasal challenge with antigen and histamine. Terfenadine significantly reduced the number of sneezes and the levels of kinins, albumin and TAME esterase activity following challenge with antigen. The levels of histamine were also significantly reduced, suggesting inhibition of the degranulation of mast cells. The number of sneezes and the levels of albumin were also significantly reduced by terfenadine following challenge with histamine.

Humans↗

Demonstration of bilateral cholinergic secretory response after unilateral nasal cold, dry air challenge.

Cold, dry air (CDA) causes rhinorrhoea and nasal congestion in some individuals. This response can be mimicked in the laboratory by exposing susceptible individuals to cold, dry air nasal breathing. One of the characteristics of this response is that nasal secretions are produced by both nostrils after a unilateral challenge. This study evaluated the role of cholinergic innervation on the ipsi- and contralateral responses to unilateral CDA challenge. Twelve individuals participated in a randomized, double-blind, placebo-controlled, 3-way crossover study where local atropine and placebo were alternated ipsilateral and the contralateral to the CDA challenge. The reproducibility of the model, assessed by the response after pre-treating with placebo, was excellent; after placebo, the ipsilateral response was double the size of the contralateral. Regardless of the site of application, atropine significantly reduced the secretory response to CDA by 60-70%. However, significant secretions were still induced by CDA, even after atropine treatment. We conclude that cholinergically-mediated neuronal pathways play a major role in the nasal secretory response to CDA. Additional neuronal pathways may, however, be involved. This method is a tool to understand the different components of the mucosal response to a cold and dry environment.

Adult↗

Preinduction of anesthesia in children with rectally administered midazolam.

The authors evaluated the efficacy of rectally administered midazolam for preinduction (i.e., premedication/induction) of anesthesia in 67 pediatric patients, ASA physical status 1 or 2, undergoing a variety of elective surgical procedures. In phase 1, 41 children weighing 12 +/- 3 kg (range 7-20 kg) and 31 +/- 16 months (range 8-67 months) of age (mean +/- SD) received midazolam, 0.4-5.0 mg.kg-1, in an attempt to produce unconsciousness. Only one child lost consciousness (4.5 mg.kg-1). However, at all doses, inhalational induction of anesthesia was facilitated because children were tranquil and calmly separated from their parent(s). There were no clinically significant changes in arterial blood pressure, heart rate, oxyhemoglobin saturation, and end-tidal carbon dioxide concentration, 10 min after drug administration. In phase 2, 26 children weighing 17 +/- 4 kg (range 10-26 kg) and 44 +/- 19 months (range 17-84 months) months of age undergoing tonsil and/or adenoid surgery were studied to determine the optimal sedative dose of rectally administered midazolam. Patients received 0.3, 1.0, 2.0, or 3.0 mg.kg-1 of midazolam in a randomized, double-blind fashion. One third (3 of 9) of patients receiving 0.3 mg.kg-1 struggled during mask induction. All patients receiving greater than or equal to 1.0 mg.kg-1 were adequately sedated (P less than 0.008). Discharge from the postanesthesia care unit (PACU), however, was delayed (greater than 60 min) in children receiving greater than or equal to 2.0 mg.kg-1 (P less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Rectal↗

Comparison of the in-vivo and in-vitro response to ragweed immunotherapy in children and adults with ragweed-induced rhinitis.

In order to compare results of allergen immunotherapy in paediatric and adult populations, 22 children with a history of ragweed hay fever were matched with an equal number of adults for skin sensitivity to ragweed and all were given a 1-year course of immunotherapy with a partially purified ragweed extract. Biological responses were measured by nasal challenges with ragweed before therapy was started, after 12 weekly injections and when the maintenance dose had been reached and also by methacholine bronchoprovocation tests before and after 12 months of therapy. Skin-test sensitivity to ragweed and control allergens, and ragweed-specific IgE and IgG antibody responses were measured at the same intervals as the challenges and at the end of the study. The effect of the therapy on clinical symptoms was not evaluated. Before therapy the groups of adults and children were comparable by all indices, except for TAME esterase activity in nasal washes during ragweed nasal challenge which was significantly lower in children. During treatment, mediators released during sequential nasal challenges declined to undetectable levels in most patients and changes in nasal ragweed sensitivity were comparable in both groups. Ragweed IgE increases after 12 weeks of therapy and IgG levels at maintenance therapy tended to be higher in the children, but neither difference was statistically significant. At the end of the study IgE and IgG antibody levels were comparable in both groups. Results of methacholine inhalation tests did not change significantly in either group. The decrease in skin sensitivity to ragweed was similar in both groups. We conclude that ragweed immunotherapy leads to immunological and biological consequences that are comparable in children and adults.

Adolescent↗

Ragweed IgE and IgG4 antibody in nasal secretions during immunotherapy.

We have developed sensitive amplified immunoassays for measurement of IgE and IgG4 ragweed (RW) antibodies in unconcentrated nasal washes. IgE to Amb a I (formerly antigen E) can be assayed to less than 0.1 ng/ml using IgE capture by anti-IgE on microtitre plates and an alkaline phosphatase-conjugated Amb a I with an amplification substrate technique. IgG4 to whole RW extract was assayed to less than 0.01 ng/ml by amplification ELISA using monoclonal anti-IgG4. Nasal washes (NW) (10 ml) and serum were obtained in December from 22 RW-sensitive patients before and after 1 and 2 yr of RW immunotherapy (IT), and assayed for Amb a I IgE or RW IgE and RW IgG4 antibodies Amb a I IgE could be measured in the NW of 15/22 pre IT, 19/22 at 1 yr IT, but only 3/10 at 2 yr IT (compared with pre-IT, P less than 0.05). Mean Amb a I IgE in NW was 0.66, 0.36 and 0.21 ng/ml at pre, 1 yr and 2 yr IT (P-values greater than 0.05). Mean serum RW IgE, was 76, 55 and 27 ng/ml at pre, 1 yr and 2 yr IT (P-values greater than 0.05). Amb a I IgE in nasal washes was correlated with RW IgE in serum (r = 0.56, P less than 0.001, n = 44). RW IgG4 was detectable in NW of 15/22 pre-IT, 18/22 at 1 yr IT and 9/10 at 2 yr IT (P-values greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Attenuation of allergen sensitivity early in the course of ragweed immunotherapy.

During the course of an open immunotherapy (IT) study of ragweed (RW)-allergic patients, nasal mediator release was studied by provocation testing. All subjects had a history of seasonal RW rhinitis, positive skin puncture test to RW, and RW-specific IgE by RAST. Nasal challenge was performed with serial dilutions of RW extract, before and after 12 weekly injections, providing a cumulative dose of 0.22 microgram of Amb a I. Serum IgE and IgG and basophil histamine release with RW were also measured. By 12 weeks of IT, when only 1% of the usual maintenance level dose had been administered, mean histamine release and TAME-esterase activity in nasal washes decreased significantly (p less than 0.05 and p less than 0.01). Prostaglandin D2 release did not change. Skin sensitivity decreased (p less than 0.05), whereas RW-specific IgE increased (p less than 0.05). No significant change in basophil histamine release was observed for RW or a control antigen. Only six of 40 subjects had an RW-specific IgG rise greater than 0.05 microgram/ml. Changes in nasal sensitivity did not correlate with the increases in IgE or IgG or with the change in skin test sensitivity. These present data indicate that there is a significant decline in nasal sensitivity to inhaled RW very early in the course of IT. There is, however, no indication of a relationship between the decreased nasal sensitivity and the production of RW-specific IgG antibodies.

Adolescent↗

In vivo release of inflammatory mediators by hyperosmolar solutions.

Hyperosmolar environments induce histamine release from mast cells and basophils in vitro. To assess whether the same stimulus induces mediator release in vivo, 15 healthy human volunteers underwent nasal challenges with instilled solutions of differing osmolalities: lactated Ringer's solution (257 +/- 3 mOsm/kg), isosmolar mannitol (277 +/- 6 mOsm/kg), and hyperosmolar mannitol (869 +/- 8 mOsm/kg). The effect of these challenges on the volume, osmolality, and inflammatory mediator content of subsequent 5-ml isosmolar lavages was determined. The volumes of lavages returned after hyperosmolar challenges were significantly greater than those after isosmolar challenges (5.5 +/- 0.2 ml versus 4.2 +/- 0.1 ml; p less than 0.01) and these lavage solutions had higher osmolalities. Even when corrected for increased volumes, the lavages after hyperosmolar challenges contained significantly higher quantities of inflammatory mediators such as histamine (29.0 versus 10.1 ng; p less than 0.01), TAME-esterase activity (32.7 versus 11.1 cpm x 10(-3); p less than 0.01), and immunoreactive leukotrienes (9.9 versus 3.4 ng; p less than 0.01). The changes in mediators were dose dependent in that incremental increase in challenge osmolality were associated with incremental increases in histamine release. Therefore, when exposed to hyperosmolar stimuli in vivo, the nasal respiratory airway releases inflammatory mediators and fluid rapidly shifts into the airway lumen. It has been suggested that the mediator release observed on breathing cold and dry air is due to increased osmolality of airway secretions; the present data confirm that osmotic variations at the airway surface can provide an adequate stimulus for cell activation.

Adult↗

The effect of a topical tricyclic antihistamine on the response of the nasal mucosa to challenge with cold, dry air and histamine.

We have previously demonstrated that azatadine, a tricyclic antihistamine, known also to inhibit mediator release from mast cells and basophils in vitro, inhibits the early release of histamine and other mediators after nasal challenge with antigen. In this article, we studied the effect of azatadine on preventing the release of histamine after nasal challenge with cold, dry air (CDA) and its effect on antagonizing nasal challenge with histamine. With histamine challenge, azatadine inhibited symptoms (sneezing, nasal congestion, and rhinorrhea) and the increase in the level of albumin in nasal secretions (p less than 0.01 all). With challenge with CDA, the drug had no effect on either symptoms or histamine and N-tosyl-L-arginine methyl ester-esterase release. Although the patterns of mediator release after CDA and after the early reaction to antigen are similar, the pharmacologic control differs, suggesting different mechanisms of induction of histamine release from mast cells.

Administration, Topical↗