Ankona Ghosh

Cellular Adaptive Inflammation Mediates Airway Granulation in a Murine Model of Subglottic Stenosis

Objective. To determine the contribution of B- and T-cell–mediated inflammation in a murine airway granulation model. Study Design. Pilot study in a modified murine model. Setting. Philadelphia VA Medical Center Research Building. Subjects and Methods. Laryngotracheal complexes (LTCs) from 54 donor C57BL/6 mice were harvested and divided into 3 groups: (1) uninjured, (2) mechanically injured using a wire brush, and (3) chemically injured using hydrochloric acid. One donor LTC from each group was placed in deep dorsal subcutaneous pockets of either severe combined immunodeficiency (SCID)– or C57BL-recipient mice, for a total of 3 transplanted tracheas per recipient mouse. After 3 weeks, the transplanted LTCs were harvested from both C57BL- and SCID-recipient mice. Tissues were fixed, sectioned, and stained with hematoxylin and eosin. Representative slides were reviewed by a blinded pathologist to determine the formation of granulation tissue and graded as to the degree of formation of granulation tissue. Results. Despite significant granulation formation in C57BL-recipient mice, direct airway injury did not induce the formation of granulation tissue under the disrupted epithelium of airway mucosa in SCID mice 3 weeks after injury. Conclusion. The data indicate that the immune response that results in the formation of granulation tissue is mediated by circulating B- and/or T-cell processes rather than resident airway immune cells. Further studies focusing on cellular adaptive immune processes in response to airway injury may provide a novel treatment modality for subglottic stenosis.

Pulse Steroid Therapy Inhibits Murine Subglottic Granulation

Objective Using a functional model of airway granulation tissue in subglottic stenosis, we investigated changes in inflammatory markers within granulation tissue in response to intraperitoneal dexamethasone injections. Changes in inflammatory markers will allow us to identify potential targets for immunological therapy. Study Design Institutional Animal Care and Use Committee–approved animal study. Setting Philadelphia Veterans Administration Medical Center animal research facility. Subjects and Methods Laryngotracheal complexes of donor mice underwent direct airway injury and were transplanted into subcutaneous tissue of 19 recipient mice in 2 groups: steroid treated and untreated, with sample sizes of 10 and 9, respectively. The steroid-treated arm received intraperitoneal injection of dexamethasone for 3 weeks. Laryngotracheal complexes were then harvested, and granulation formation was measured. The messenger RNA (mRNA) expression of transforming growth factor (TGF)–β1 and interleukin (IL)–1 was quantified. Results At 3 weeks posttransplantation, there were statistically significant differences in observable granulation formation as well as mRNA expression of TGF-β1 and IL-1β in all groups within the steroid treated arm as compared with the untreated arm. Conclusions Systemic steroids have been used to prevent formation of granulation tissue and subglottic stenosis. However, the study of the immunologic markers and the corresponding changes with steroid treatment has not been well studied in animal models. Using a previously described novel murine model, we begin to delineate inflammatory markers that can be applied for potential therapeutic targets.

Inflammatory Protein Expression in Human Subglottic Stenosis Tissue Mirrors That in a Murine Model

Objectives: We undertook to describe the genetic and protein composition of subglottic stenosis (SGS) by measuring an array of protein expression and messenger RNA levels within human SGS tissue. We also sought to compare this human array to cytokine expression from a murine model of SGS in order to confirm the effective translational nature of our animal model. Methods: Human granulation tissue from 10 patients with early symptomatic SGS was compared to control bronchus. The expression levels of 24 different cytokines were measured by a Luminex protein assay and real-time polymerase chain reaction. Results: The protein expression in human SGS mirrors that seen in murine SGS. Transforming growth factor β1, interleukin 1β, and matrix metalloproteinase 9 were markedly elevated in both human and mouse SGS tissues. The protein array showed a statistically significant elevation in the proinflammatory cytokines tumor necrosis factor α, interleukin 1, granulocyte macrophage colony-stimulating factor, and interferon γ. Conclusions: This is the first study, to our knowledge, to measure an array of protein expression within human SGS tissue. The expression profile suggests that symptomatic tracheal granulation tissue is mostly within the early inflammatory phase of wound healing and has only begun fibrotic and angiogenic remodeling. This study validates our murine model of SGS, and also helps to define the exact pathways of tissue injury, in the hope of leading to new treatments for this difficult condition.

First bite syndrome: Our experience with intraparotid injections with botulinum toxin type A

First bite syndrome is the sudden onset of acute and severe pain in the parotid region at the initiation of mastication. Although it generally lasts less than a minute, it is disabling for these individuals and leads to a fear of oral intake. It is typically seen after parapharyngeal or deep parotid space surgery. Intraparotid injection of botulinum toxin A (BTA) has been suggested as a treatment for this condition, but there is little supporting literature to this effect. The purpose of this study is to document our experience using this treatment method for first bite syndrome.

You can't pay me to quit: the failure of financial incentives for smoking cessation in head and neck cancer patients.

OBJECTIVE A prospective randomised study was conducted at a tertiary care hospital to evaluate the effects of financial incentives for smoking cessation targeted at a high-risk population. METHODS Patients with a past history of head and neck cancer were voluntarily enrolled over a two-year period. They were randomised to a cash incentives or no incentive group. Subjects were offered enrolment in smoking cessation courses. Smoking by-product levels were assessed at 30 days, 3 months and 6 months. Subjects in the incentive group received

Surgical Treatment of Nasal Obstruction in Rhinoplasty

150 if smoking cessation was confirmed. RESULTS Over 2 years, 114 patients with an established diagnosis of head and neck cancer were offered enrolment. Twenty-four enrolled and 14 attended the smoking cessation classes. Only two successfully quit smoking at six months. Both these patients were in the financially incentivised group and received

Pediatric nasoseptal flap reconstruction for suprasellar approaches

150 at each test visit. CONCLUSION Providing a financial incentive for smoking cessation to a population already carrying a diagnosis of head and neck cancer in order to promote a positive behaviour change was unsuccessful.

IL-1 Receptor Antagonist Inhibits Early Granulation Formation

The key to a successful septorhinoplasty includes an understanding of nasal anatomy and physiology. This allows the surgeon the ability to properly address both form and function during the operation. History and physical examination are paramount in diagnosing and subsequently treating the epicenter of obstruction, which is commonly found among the internal and external nasal valve, the septum, or the turbinates. Treatment of each of these areas is nuanced and multiple approaches are discussed to provide an understanding of the current surgical techniques that allow for excellent functional and cosmetic rhinoplasty results.

Temporal patterns of 18F‐fluorodeoxyglucose positron emission tomography/computed tomography sinonasal uptake after treatment of sinonasal malignancy

To determine the pediatric age groups viable for nasoseptal flap (NSF) reconstruction of endoscopic endonasal approaches (EEA) to intracranial pathology of suprasella neoplasms.

A murine model of subglottic granulation.

Purpose: Using a functional model of airway granulation tissue in laryngotracheal stenosis, we investigated changes in histopathology and inflammatory markers within granulation tissue in response to an interleukin-1 receptor antagonist (IL-1Ra). This study allows us to further delineate the immune response to wound healing and potentially identify treatment markers. Methods: Laryngotracheal complexes (LTCs) of donor mice underwent direct airway injury. The LTCs were transplanted into subcutaneous tissue of recipient mice in 2 groups: IL-1Ra treated and untreated. The IL-1Ra–treated arm received daily intraperitoneal injections of IL-1Ra for 3 weeks. The LTCs were then harvested. Granulation formation was measured. The mRNA expression of transforming growth factor (TGF) beta and IL-1 was quantified using real-time reverse transcript polymerase chain reaction. Results: There were statistically significant differences in lamina propria thickness. There were no statistically significant changes in mRNA expression of TGF-β and IL-1β between the treated and untreated specimens. Conclusions: Using a previously described murine model, we delineate inflammatory markers that can be targeted for potential therapy. While the levels of inflammatory markers do not change significantly, the lamina propria thickness shows that the effects of IL-1 have been inhibited. The early use of the IL-1Ra will inhibit the efficacy of IL-1 in the inflammatory cascade and can prevent early granulation formation.