Terence M. Davidson

Clinical study and literature review of nasal irrigation.

Objectives/Hypothesis Nasal disease, including chronic rhinosinusitis and allergic rhinitis, is a significant source of morbidity. Nasal irrigation has been used as an adjunctive treatment of sinonasal disease. However, despite an abundance of anecdotal reports, there has been little statistical evidence to support its efficacy. The objective of this study was to determine the efficacy of the use of pulsatile hypertonic saline nasal irrigation in the treatment of sinonasal disease.

Bcl6 and Maf Cooperate To Instruct Human Follicular Helper CD4 T Cell Differentiation

Follicular helper CD4 T (Tfh) cells provide B cells with signals that are important for the generation of high-affinity Abs and immunological memory and, therefore, are critical for the protective immunity elicited by most human vaccines. Transcriptional regulators of human Tfh cell differentiation are poorly understood. In this article, we demonstrate that Bcl6 controls specific gene modules for human Tfh cell differentiation. The introduction of Bcl6 expression in primary human CD4 T cells resulted in the regulation of a core set of migration genes that enable trafficking to germinal centers: CXCR4, CXCR5, CCR7, and EBI2. Bcl6 expression also induced a module of protein expression critical for T–B interactions, including SAP, CD40L, PD-1, ICOS, and CXCL13. This constitutes direct evidence for Bcl6 control of most of these functions and includes three genes known to be loci of severe human genetic immunodeficiencies (CD40L, SH2D1A, and ICOS). Introduction of Bcl6 did not alter the expression of IL-21 or IL-4, the primary cytokines of human Tfh cells. We show in this article that introduction of Maf (c-Maf) does induce the capacity to express IL-21. Surprisingly, Maf also induced CXCR5 expression. Coexpression of Bcl6 and Maf revealed that Bcl6 and Maf cooperate in the induction of CXCR4, PD-1, and ICOS. Altogether, these findings reveal that Bcl6 and Maf collaborate to orchestrate a suite of genes that define core characteristics of human Tfh cell biology.

Gender differences in obstructive sleep apnea and treatment implications

Obstructive sleep apnea (OSA) is a common cause of daytime sleepiness for millions of Americans. It is also a disease associated with an increased likelihood of hypertension, cardiovascular disease, stroke, daytime sleepiness, motor vehicle accidents, and diminished quality of life. A number of population-based studies have shown that OSA is more common in men than in women and this discrepancy is often evident in the clinical setting. There are a number of pathophysiological differences to suggest why men are more prone to the disease than women. Although the exact mechanisms are unknown, differences in obesity, upper airway anatomy, breathing control, hormones, and aging are all thought to play a role. The purpose of this review was to examine the literature on gender differences in OSA and to analyze whether or not these differences in pathogenic mechanisms affect diagnosis or treatment.

Scar management: prevention and treatment strategies.

Purpose of reviewAberrant wound healing results in unsightly scar, hypertrophic scar, and keloid formation, causing functional and cosmetic deformities, discomfort, psychological stress, and patient dissatisfaction. Scar prevention and management, both surgical and nonsurgical, continue to be important issues for the otolaryngologist. Recent findingsBoth animal and human models continue to point to the integral role of transforming growth factor-β in aberrant healing. Multiple extracts have promising results as therapies for scarring and are widely marketed but need to be further investigated. Scar prevention advancements include refinements in surgical technique, nutritional supplementation, and optimal wound care. Steroid injections continue to play a major role in the regression of scars and keloids. Dermatography assists in the minimization of scar appearance. Dermatography, laser therapies, intralesional 5-fluorouracil, and adjuvant radiotherapy are emerging therapies. Topical vitamin E utility is revisited. New surgical scar revision techniques include modified excision techniques and skin grafting. SummaryDespite optimal efforts to avoid scar formation, aberrant wound healing may occur. The use of topical agents and intralesional steroid injections can minimize early scar formation. Strategies for prevention and management of keloids and hypertrophic scars continue to develop, as the basic science mechanisms underlying aberrant wound healing are elucidated.

Management of chronic sinusitis in cystic fibrosis.

Chronic rhinosinusitis is extremely common in patients with cystic fibrosis. It causes numerous problems in these patients and can put them at risk for life‐threatening illness. Potential problems include nasal obstruction, congestion, sinus pain and pressure, infection (usually with Pseudomonas organisms), hyposmia or anosmia, and the seeding of bacteria into the lower respiratory tract. Cystic fibrosis patients with chronically infected sinuses are at increased risk for pneumonia following lung transplantation. A prophylactic protocol has been developed for the management of chronic sinusitis in patients with cystic fibrosis. These patients are fully evaluated at the Nasal Dysfunction Clinic of the University of California, San Diego (UCSD), Medical Center. Based on the results of the evaluation, they are treated with endoscopic sinus surgery, partial middle turbinectomy, septoplasty, and a large middle meatal maxillary antrostomy. Surgery is followed by a rigorous regimen of pulsatile hypotonic saline nasal irrigation to wash away tenacious cystic secretions. Tobramycin (Nebcin®) is given once daily in the nasal irrigant to inhibit the growth of Pseudomonas organisms. At the USCD Nasal Dysfunction Clinic, this prepulmonary transplantation protocol is now used in all cystic fibrosis patients with chronic sinusitis.

The Great Leap Forward: the anatomic basis for the acquisition of speech and obstructive sleep apnea

Obstructive sleep apnea is an anatomic illness caused by evolutionary changes in the human upper respiratory tract. These changes include shortening of the maxillary, ethmoid, palatal and mandibular bones, acute oral cavity-skull base angulation, pharyngeal collapse with anterior migration of the foramen magnum, posterior migration of the tongue into the pharynx, descent of the larynx and shortening of the soft palate with loss of the epiglottic-soft palate lock-up. While it is commonly believed that some of these changes had positive selection pressures for bipedalism, binocular vision and locomotion, development of voice, speech and language ultimately became a substantial contributing factor. Here it is shown that these changes are the anatomic basis of obstructive sleep apnea.

Lingual fat at autopsy.

Objectives/Hypothesis: Obesity as measured by body mass index (BMI) has been shown to correlate with incidence and severity of sleep disordered breathing (SDB), but the actual mechanism underlying this relationship has not been defined. Pharyngeal obstruction from posterior displacement of a large, fat laden tongue is one mechanism that may explain this link. The objective of this study is to characterize the fat content within the tongue and then to determine whether tongue weight and percent of fat correlate with BMI and other metrics of obesity.

Efficacy of Intranasal Bevacizumab (Avastin) Treatment in Patients with Hereditary Hemorrhagic Telangiectasia-Associated Epistaxis

Intranasal Bevacizumab is an effective therapy for epistaxis in patients with hereditary hemorrhagic telangiectasia (HHT).

Waist circumference and sleep disordered breathing.

Objectives/Hypothesis: To explore how the different metrics of obesity, specifically body mass index (BMI), Mallampati, neck circumference, waist circumference, and waist‐hip ratio, correlate with metrics of sleep disordered breathing (SDB), specifically the apnea/hypopnea index (AHI), and which is/are the most likely to predict and correlate with SDB.

The effect of bevacizumab (Avastin) treatment on epistaxis in hereditary hemorrhagic telangiectasia.

Determine the effectiveness of treating epistaxis in hereditary hemorrhagic telangiectasia (HHT) with potassium titanyl phosphate (KTP) laser cautery combined with submucosal injection of 100 mg of bevacizumab.