Nathan D. Schwade

Characteristics of Bony Erosion in Allergic Fungal Rhinosinusitis

OBJECTIVES: Erosion of bone with or without extension of disease into adjacent anatomic spaces is observed among some patients with allergic fungal rhinosinusitis (AFRS). The objective of this report is to further define these findings as they relate to this disease. STUDY DESIGN: Retrospective chart review of 142 patients with AFRS diagnosed using the Bent-Kuhn criteria. All patients were treated at a single institution. RESULTS: Approximately 20% of patients with AFRS demonstrated bone erosion on CT scan. The ethmoid sinus was the most commonly eroded site. The orbit and anterior cranial fossa were the most common adjacent anatomic spaces to exhibit disease extension. Sinus expansion, not the specific organism identified, was associated with the presence of bone erosion. Surgical management with endoscopic techniques was successful for all patients without any major perioperative complications. CONCLUSION: Bone erosion can be related to AFR. Recognition of this possibility is important because bone erosion can be interpreted as an indication of invasive pathosis. In the presence of bone erosion or disease extension, endoscopic techniques can be used to surgically manage this disease.

Skull base cerebrospinal fluid fistulas: A comprehensive diagnostic algorithm

OBJECTIVE: Our goal was to assess the efficacy of current diagnostic modalities in the management of skull base cerebrospinal fluid (CSF) fistulas. METHODS: We conducted a retrospective review of all patients presenting to our institution over the past 6 years with skull base CSF fistulas. RESULTS: Fifty-two patients were included in the study. β2-Transferrin analysis of collected specimen was the most efficacious means of confirming a CSF leak. High-resolution computed tomography was the most informative radiographic study, yielding a sensitivity and an accuracy of 87%. Magnetic resonance cisternography, yielding a sensitivity and an accuracy of 78%, was instrumental in localizing the site of leak for a few cases but was most commonly corroborative. Using a graduated diagnostic approach, successful repair was attained in 88% of cases after 1 attempt and 98% after 1 or 2 attempts. CONCLUSION: For patients with skull base CSF fistulas, a graduated diagnostic approach with emphasis on confirmation of leak by β2-transferrin analysis and precise localization by high-resolution computed tomography is both efficacious and cost effective.

Natural history of allergic fungal rhinosinusitis: a 4- to 10-year follow-up.

BACKGROUND: Numerous studies have noted the high rate of recidivism after the initial treatment of allergic fungal rhinosinusitis (AFS). Short–term studies have revealed varying recurrence rates based on therapy; however, little is currently known about the long–term natural history of the disease. OBJECTIVE: Our goal was to address the question of long–term outcomes in AFS patients and make observations about the natural history of the disease. PATIENTS AND METHODS: Seventeen patients with follow–up ranging from 46 to 138 months were examined and interviewed, and their charts were reviewed. A quality–of–life survey was completed, and blood was drawn to measure immunoglobulin levels. RESULTS: All patients initially underwent treatment with a combination of surgery, systemic and/or topical corticosteroids, and immunotherapy to pertinent fungal and nonfungal antigens. Normalization of sinonasal mucosa (Kupferberg stage 0) was seen in 5 (29%) of 17 patients, whereas 76% demonstrated either normal or slight mucosal edema (Kupferberg stage 0 or 1). Serologic testing revealed fungus-specific IgE significantly elevated in all 17 patients. CONCLUSION: The initial choice of therapy did not appear to affect the long–term outcome, and patients tended to be doing well overall. These results suggest that after successful initial treatment and control of AFS, many patients can achieve a quiescent disease state.

Clinical Presentation of Allergic Fungal Sinusitis in Children

Objective To compare the differences in the clinical and radiographic presentation of allergic fungal sinusitis in children and adults.

Use of immunotherapy in previously treated patients with allergic fungal sinusitis

OBJECTIVE: Sixty patients with a diagnosis of allergic fungal sinusitis were studied. The objective was to show whether, after initial surgical removal of allergic mucin and polyps, immunotherapy decreases re-operation rates and office visits that require medical intervention. STUDY DESIGN AND SETTING: Sixty patients with adequate follow-up for at least 1 year were evaluated: 24 patients who did not receive immunotherapy and 36 patients whose treatment included postoperative immunotherapy. RESULTS: The re-operation rates were 33.0% in those not receiving immunotherapy versus 11.1% in the treated group. Furthermore, the total number of postoperative office visits that required medical therapy decreased from 4.79 per patient to 3.17 with the addition of immunotherapy. CONCLUSION/SIGNIFICANCE: These results indicate that immunotherapy is a beneficial part of the overall treatment regimen for allergic fungal sinusitis.

Structured drug-loaded bioresorbable films for support structures

Bioresorbable films can serve simultaneously as anatomic support structures and as drug delivery platforms. In the present study, bioresorbable PLLA films containing dexamethasone were developed through solution processing. The effect of processing parameters on the film morphology and the resulting mechanical properties was studied. A model describing the structuring of these films is suggested. Generally, the solvent evaporation rate determines the kinetics of drug and polymer crystallization and thus, both the mode of drug dispersion in the polymer and the resulting mechanical properties. Two types of structured films were studied: (1) a polymer film with drug located on its surface, obtained due to drug skin formation accompanied by a later polymer core formation; and (2) a polymer film with small drug particles and crystals distributed within the bulk, obtained by parallel solidification of the two components. A prototypical application of these films is an expandable biodegradable support structure (stent), which we have developed. This stent demonstrated good initial mechanical properties. The film structure has only a minor effect on the stent radial compression strength, but more significantly affects the tensile mechanical properties.

In vitro study of drug-loaded bioresorbable films and support structures

Bioresorbable films can serve simultaneously as anatomic support structures and as drug delivery platforms. In the present study, bioresorbable poly(L-lactic acid) (PLLA) films containing dexamethasone were prepared by solution processing methods. Their in vitro studies focused on the mechanical properties with respect to morphology and degradation and erosion processes. Novel expandable support devices (stents) developed from these films were studied. Such a stent would support conduits, such as the neonatal trachea to treat tracheal malacia, until the airway matures, and would then be totally resorbed, obviating the need for a removal operation. The PLLA films showed good initial mechanical properties. They can accommodate drug incorporation on the film surface and also in the bulk. Water incubation of the films results in a decrease in their tensile mechanical properties, due to chain scission and morphological changes. These changes can vary from degradation and small changes in morphological features to erosion, leading to a microporous structure, depending on the polymer. The cumulative release of dexamethasone from the films is linear. The rate of release is determined by the films structure (drug location/dispersion). The stents demonstrated good mechanical properties. The initial radial compression strength of the stent is determined mainly by the polymer structure. Drug incorporation has a minor effect on the initial stent strength. Exposure to radial compression stress results in elastic reversible deformation or a sudden brittle fracture, depending on the polymer. A 20-week in vitro study of the stents showed that they are applicable for supporting body conduits, such as the trachea.

Fosfomycin does not inhibit the tumoricidal efficacy of cisplatinum.

Objectives: This study investigates the effect of fosfomycin on the tumoricidal efficacy of cisplatinum.

Diazepam Tolerance Effects on Vestibular Function Testing, Part I: Saccadic Parameters during Electronystagmography

Objectives: Benzodiazepines, particularly diazepam (DZ), are used in clinical practice to suppress acute vestibular symptoms. There have been limited studies looking at the effects of tolerance to DZ on parameters designed to measure the integrity of the vestibular system and its interaction with the oculomotor and balance systems. Methods: In a double-blinded, repeated-measures design, we randomized 30 young healthy men into one of two treatment groups (diazepam and placebo) and assessed with electro-oculography the effects of clinical divided doses of DZ on saccadic eye movements and sedation over 16 days. Results: Only sedation and saccadic latency were significant (p < .05) for treatment group, indicating selective effects on different central nervous system mechanisms. No significant effect for time was seen in any of the variables measured. Bonferroni t-test comparisons of the DZ group among 3 days were significant (p < .017) between baseline and day 3 for saccadic latency and accuracy and between day 3 and day 16 for self-ratings of sedation. Conclusions: Saccadic latency and accuracy and sedation ratings appear to be more sensitive to changes over time and less affected by subject variability than saccadic eye velocity. It remains questionable whether patients who have been on DZ for acute or extended periods of time need to discontinue the drug 48 hours before testing.

Hyaluronic acid effect on postoperative wound healing following antrostomy in rabbit

Problem Addressed: The nose functions to warm and humidify inspired air. We have developed a method to reproducibly measure the temperature (T) and relative humidity (RH) of inspired air at the nasal inlet and in the nasopharynx, after conditioning by the nasal mucosa. From these measurements, we calculate the water content (WC) of the air and compute the difference between the WC of air prior to entry into the nose and that in the nasopharynx (NP). This calculation represents the water gradient (WG) across the nose, a measure of nasal conditioning capacity. The purpose of this experiment was to study the effect of allergic inflammation on the conditioning capacity of the nose. Methods/Measures: We enrolled 7 subjects (average age 28.0 years) with seasonal allergic rhinitis, as documented by history and skin-prick testing, who were outside of their allergy season. They underwent a baseline challenge with cold, dry air (CDA) at increasing flow rates (5, 10, and 20 L/minute) via nasal mask. This was followed, at least 48 hours later, by an antigen challenge with 2 increasing dilutions of either grass or ragweed extracts. Sixteen to 20 hours after the antigen challenge, the subjects underwent an identical CDA challenge. The WC of inspired air was calculated for the CDA challenges, and the number of sneezes and the number of eosinophils in nasal lavage after antigen challenge were used to monitor allergic inflammation. Results: Antigen challenge led to an allergic reaction as indicated by a significant increase in sneezes after the highest dose of antigen compared with the diluent challenge (0 0 vs 9.7 • 1.3, P < 0.02) and a significant increase in eosinophils in nasal lavages 24 hours after antigen challenge (2587 • 2087 vs 22794 • 8040, P < 0.05). These data show that allergic inflammation increases the ability of the nose to condition inspired air.