Publications by authors named "Thomas H Alexander"

27 Publications

  • Page 1 of 1

Increased peripheral blood neutrophil activation phenotypes and NETosis in critically ill COVID-19 patients: a case series and review of the literature.

Clin Infect Dis 2021 May 14. Epub 2021 May 14.

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California San Diego (UCSD), La Jolla, CA 92093, USA.

Background: Increased inflammation has been well defined in COVID-19, while definitive pathways driving severe forms of this disease remain uncertain. Neutrophils are known to contribute to immunopathology in infections, inflammatory diseases and acute respiratory distress syndrome (ARDS), a primary cause of morbidity and mortality in COVID-19. Changes in neutrophil function in COVID-19 may give insight into disease pathogenesis and identify therapeutic targets.

Methods: Blood was obtained serially from critically ill COVID-19 patients for eleven days. Neutrophil extracellular trap formation (NETosis), oxidative burst, phagocytosis and cytokine levels were assessed. Lung tissue was obtained immediately post-mortem for immunostaining. Pubmed searches for neutrophils, lung and COVID-19 yielded ten peer-reviewed research articles in English.

Results: Elevations in neutrophil-associated cytokines IL-8 and IL-6, and general inflammatory cytokines IP-10, GM-CSF, IL-1b, IL-10 and TNF, were identified both at first measurement and across hospitalization (p<0.0001). COVID neutrophils had exaggerated oxidative burst (p<0.0001), NETosis (p<0.0001) and phagocytosis (p<0.0001) relative to controls. Increased NETosis correlated with leukocytosis and neutrophilia, and neutrophils and NETs were identified within airways and alveoli in lung parenchyma of 40% of SARS-CoV-2 infected lungs available for examination (2 out of 5). While elevations in IL-8 and ANC correlated with disease severity, plasma IL-8 levels alone correlated with death.

Conclusions: Literature to date demonstrates compelling evidence of increased neutrophils in the circulation and lungs of COVID-19 patients. importantly, neutrophil quantity and activation correlates with severity of disease. Similarly, our data shows that circulating neutrophils in COVID-19 exhibit an activated phenotype with enhanced NETosis and oxidative burst.
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http://dx.doi.org/10.1093/cid/ciab437DOI Listing
May 2021

Delayed Facial Palsy After Resection of Vestibular Schwannoma: An Analysis of Long-term Facial Nerve Outcomes.

Otol Neurotol 2021 07;42(6):e764-e770

University of California, San Diego, Kaiser Permanente Southern California Medical Group, San Diego, California, USA.

Objectives: 1) Identify clinical factors associated with delayed facial palsy (DFP) after microsurgical resection of vestibular schwannoma. 2) Determine whether DFP predicts worse facial nerve (FN) outcomes.

Methods: Adult patients (≥18 yrs) who underwent vestibular schwannoma resection between February 2008 and December 2017 were retrospectively reviewed. Postoperative House-Brackmann (HB) FN function was assessed on the day of surgery, daily during patients' inpatient admissions, and at postoperative clinic visits. Follow-up exceeded ≥12 months for all patients. DFP was defined as a decline (≥1 HB grade) in FN function (relative to the preoperative state) occurring between postoperative days 1 and 30.

Results: Two hundred ninety-one patients were analyzed. Mean age was 51.5 years (±12.3) and mean tumor size 20.6 mm (±10.8). Immediate FP occurred in 61 (21%) patients, and DFP occurred in 112 (38%) patients. Tumor size was largest in patients with immediate FP (p < 0.0001). On univariate analysis, DFP was associated with better final FN outcomes (OR 0.447, p = 0.0101) compared with immediate FP. Multivariate analysis, however, showed that timing of FP was no longer significant, whereas larger tumor size and preoperative HB2 function predicted worse FN outcomes (OR 2.718, p < 0.0001 and OR 9.196, p = 0.0039, respectively). In patients with DFP, longer time to onset of palsy predicted more favorable FN outcomes.

Conclusions: When accounting for tumor size, the timing of onset of postoperative facial palsy does not predict final FN outcomes. In patients who develop DFP, the longer the interval between surgery and onset of weakness, the better the chances of good long-term FN function.
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http://dx.doi.org/10.1097/MAO.0000000000003158DOI Listing
July 2021

Preoperative Sudden Hearing Loss May Predict Hearing Preservation After Retrosigmoid Resection of Vestibular Schwannoma.

Otol Neurotol 2021 07;42(6):923-930

University of California San Diego.

Objectives: Describe the effect of preoperative sudden hearing loss (SHL) on likelihood of hearing preservation (HP) after surgical resection of vestibular schwannoma (VS).

Study Design: Retrospective chart review.

Setting: Tertiary referral center.

Patients: Adult patients (≥18 years) who underwent retrosigmoid VS resection for HP between February 2008 and December 2018 were reviewed. All patients had preoperative word recognition score (WRS) of at least 50%. Similarly, HP was defined as postoperative WRS of more than or equal to 50%. Regression analysis was used to describe the effect of SHL on HP, accounting for tumor size, and preoperative hearing quality.

Interventions: All patients underwent retrosigmoid VS resection for HP.

Main Outcome Measures: WRS of at least 50%.

Results: Of 160 patients who underwent retrosigmoid VS resection during the study period, 153 met inclusion criteria. Mean tumor size was 14.0 (±6) mm. Hearing was preserved in 41.8% (n = 64). Forty patients (26.1%) had a history of preoperative SHL. Among 138 patients (90.2%) in whom the cochlear nerve was anatomically preserved during surgery, HP was achieved in 61.8% of those with SHL (21 of 34) and 41.3% of those without SHL (43 of 104) (p = 0.0480). On univariate and multivariate analysis (accounting for tumor size and preoperative hearing quality), SHL was a significant positive predictor of HP (odds ratio 2.292, p = 0.0407 and odds ratio 2.778, p = 0.0032, respectively).

Conclusion: In patients with VS and retained serviceable hearing, SHL is an independent predictor of HP after retrosigmoid microsurgical resection when the cochlear nerve is preserved.
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http://dx.doi.org/10.1097/MAO.0000000000003088DOI Listing
July 2021

The Effect of Tumor Size on Likelihood of Hearing Preservation After Retrosigmoid Vestibular Schwannoma Resection.

Otol Neurotol 2020 12;41(10):e1333-e1339

Kaiser Permanente Southern California Medical Group, University of California, San Diego, San Diego, California.

Objectives: 1) Describe the effect of tumor size on the likelihood of hearing preservation after retrosigmoid approach for resection of vestibular schwannoma (VS).2) Describe the effect of preoperative hearing status on the likelihood of hearing preservation.

Study Design: Retrospective chart review.

Setting: Tertiary referral center.

Patients: Adult (18 years or older) patients underwent retrosigmoid VS resection and postoperative audiometry between 2008 and 2018 and had a preoperative word recognition score (WRS) of at least 50%. Patients with a history of neurofibromatosis 2, radiation, or previous resection were excluded.

Interventions: All patients underwent retrosigmoid VS resection with attempted hearing preservation.

Main Outcome Measures: WRS of at least 50%.

Results: Data from 153 patients were analyzed. Mean age was 50.8 (±11.3) years and mean tumor size 14 (±6) mm. Hearing was preserved and lost in 64 (41.8%) and 89 (58.2%) patients, respectively. Hearing preservation rates were higher for intrameatal tumors than for tumors with extrameatal extension (57.6% versus 29.4%, p = 0.0005). On univariate and multivariate regression analysis, tumor size (per mm increase) was a negative predictor of hearing preservation (odds ratio [OR] 0.893, p = 0.0002 and 0.841, p = 0.0005, respectively). Preoperative American Academy of Otolaryngology-Head & Neck Surgery Hearing Class was also predictive of hearing preservation (p = 0.0044). Class A hearing (compared with class B hearing) was the strongest positive risk factor for hearing preservation (OR 3.149, p = 0.0048 and 1.236, p = 0.0005, respectively).

Conclusion: Small tumor size and preoperative class A hearing are positive predictors of hearing preservation in patients undergoing the retrosigmoid approach for VS resection.
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http://dx.doi.org/10.1097/MAO.0000000000002882DOI Listing
December 2020

Predicting Long-Term Facial Nerve Outcomes After Resection of Vestibular Schwannoma.

Otol Neurotol 2020 12;41(10):e1328-e1332

Kaiser Permanente Southern California Medical Group, University of California, San Diego, San Diego, California.

Objectives: 1) Describe the effect of tumor size on facial nerve (FN) outcomes after microsurgical resection of vestibular schwannoma (VS).2) Describe the effect of surgical approach, preoperative radiation, and early postoperative facial function on long-term FN outcomes.

Study Design: Retrospective analysis.

Setting: Tertiary referral center.

Patients: Adult (≥18 yr) patients underwent translabyrinthine or retrosigmoid VS resection by a single neurotologist and single neurosurgeon between February 2008 and December 2017.

Main Outcome Measures: Long-term FN outcomes (≥12 mo) according to House-Brackmann (HB) grade.

Results: During the study period, 350 patients underwent VS resection, of whom 290 met inclusion criteria. Translabyrinthine surgery was performed in 54% (n = 158) and retrosigmoid in 45% (n = 131). One patient underwent a combined approach. Among patients who underwent retrosigmoid approach, none had a tumor more than 30 mm. Gross total resection was achieved in 98% (n = 283). Long-term HB1-2 function was achieved in 90% (n = 261). On univariate analysis, tumor size (per cm increase), history of preoperative radiation, and worse HB score at discharge predicted worse FN function. Multivariate analysis showed that tumor size (per cm increase) and history of radiation were independent predictors of FN function. For patients with tumors less than 30 mm, multivariate analysis of tumor size and surgical approach was performed; tumor size remained predictive of worse FN function (odds ratio [OR] 2.362, p = 0.0035), whereas surgical approach was not significantly predictive (p = 0.7569).

Conclusion: Tumor size and history of radiation predict long-term FN function after VS resection. When accounting for tumor size, the translabyrinthine and retrosigmoid approaches yield equivalent FN results.
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http://dx.doi.org/10.1097/MAO.0000000000002883DOI Listing
December 2020

Factors That Affect Length of Hospital Stay After Vestibular Schwannoma Surgery.

Otol Neurotol 2018 10;39(9):1203-1209

Southern California Permanente Medical Group, Pasadena.

Objective: To identify perioperative factors that influence hospital length of stay (LOS) after resection of vestibular schwannoma (VS).

Study Design: Retrospective case review.

Setting: Tertiary skull base referral center.

Patients: Patients who underwent acoustic neuroma resection between January 1, 2007 and January 1, 2014.

Interventions: Approaches used for VS resection included translabyrinthine and retrosigmoid.

Main Outcome Measures: LOS and several perioperative factors that may delay hospital discharge were examined. Factors included were patient demographics (age and sex), tumor characteristics (size), surgical factors (operative time, approach, revision surgery, date of surgery), and immediate postoperative factors (presence of vertigo or immediate postoperative complications).

Results: Two hundred eighty-eight patients underwent VS resection during the study period. Two hundred fifty-five patients had complete charts available for review. LOS ranged from 1 to 10 days with an average of 2.66 days and mode of 2 days. One hundred thirty-one patients were admitted for ≤2 days and 124 patients stayed longer. Of the perioperative factors examined with univariate analysis, female gender (p = 0.0266) and presence of postoperative vertigo (p < 0.0001) were statistically significant factors associated with LOS >2 days. On multivariate logistic regression analysis with odds ratios (OR), older patient age (OR = 1.028, p = 0.0177), female gender (OR = 1.810, p = 0.0314), longer operative time (OR = 1.424, p = 0.0007), and presence of postoperative vertigo (OR = 4.904, p < 0.0001) carried a statistically significant increased odds toward a LOS >2 days.

Conclusions: VS surgery and postoperative care can be carried out efficiently with a minimal LOS. Identifying factors that may prolong LOS may help the operative team anticipate and address needs to optimize LOS.
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http://dx.doi.org/10.1097/MAO.0000000000001960DOI Listing
October 2018

Otolaryngology in Critical Care.

Ann Am Thorac Soc 2018 06;15(6):643-654

1 Pulmonary and Critical Care Section, Department of Medicine, Veterans Affairs San Diego Healthcare System, San Diego, California; and.

Diseases affecting the ear, nose, and throat are prevalent in intensive care settings and often require combined medical and surgical management. Upper airway occlusion can occur as a result of malignant tumor growth, allergic reactions, and bleeding events and may require close monitoring and interventions by intensivists, sometimes necessitating surgical management. With the increased prevalence of immunocompromised patients, aggressive infections of the head and neck likewise require prompt recognition and treatment. In addition, procedure-specific complications of major otolaryngologic procedures can be highly morbid, necessitating vigilant postoperative monitoring. For optimal outcomes, intensivists need a broad understanding of the pathophysiology and management of life-threatening otolaryngologic disease.
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http://dx.doi.org/10.1513/AnnalsATS.201708-695FRDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6207134PMC
June 2018

Treatment of OSA with CPAP Is Associated with Improvement in PTSD Symptoms among Veterans.

J Clin Sleep Med 2017 01 15;13(1):57-63. Epub 2017 Jan 15.

Division of Pulmonary and Critical Care Medicine, University of California San Diego, San Diego, CA.

Study Objectives: Posttraumatic stress disorder (PTSD) is common among veterans of the military, with sleep disturbance as a hallmark manifestation. A growing body of research has suggested a link between obstructive sleep apnea and PTSD, potentially due to obstructive sleep apnea (OSA) related sleep disruption, or via other mechanisms. We examined the hypothesis that treatment of OSA with positive airway pressure would reduce PTSD symptoms over 6 months.

Methods: A prospective study of Veterans with confirmed PTSD and new diagnosis of OSA not yet using PAP therapy were recruited from a Veteran's Affairs sleep medicine clinic. All subjects were instructed to use PAP each night. Assessments were performed at 3 and 6 months. The primary outcome was a reduction in PTSD symptoms at 6 months.

Results: Fifty-nine subjects were enrolled; 32 remained in the study at 6 months. A significant reduction in PTSD symptoms, measured by PCL-S score was observed over the course of the study (60.6 ± 2.7 versus 52.3 ± 3.2 points; p < 0.001). Improvement was also seen in measures of sleepiness, sleep quality, and daytime functioning, as well as depression and quality of life. Percentage of nights in which PAP was used, but not mean hours used per night, was predictive of improvement.

Conclusions: Treatment of OSA with PAP therapy is associated with improvement in PTSD symptoms, although the mechanism is unclear. Nonetheless, PAP should be considered an important component of PTSD treatment for those with concurrent OSA. Improving PAP compliance is a challenge in this patient population warranting further investigation.

Clinical Trial Registration: ClinicalTrials.gov, ID: NCT02019914.

Commentary: A commentary on this article appears in this issue on page 5.
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http://dx.doi.org/10.5664/jcsm.6388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5181615PMC
January 2017

Primary treatment of idiopathic sudden sensorineural hearing loss with intratympanic dexamethasone.

Curr Opin Otolaryngol Head Neck Surg 2016 Oct;24(5):407-12

Division of Otolaryngology - Head and Neck Surgery, University of California San Diego, San Diego, California, USA.

Purpose Of Review: Systemic corticosteroids have been the mainstay of treatment of idiopathic sudden sensorineural hearing loss (ISSNHL) for over 30 years. Recently, intratympanic steroids have risen in popularity; however, there is no consensus regarding the details of their application. The purpose of this article is to review the current literature and share our opinion that intratympanic dexamethasone (alone or with systemic steroids) should be offered as primary treatment of ISSNHL.

Recent Findings: Intratympanic steroids have been shown to result in higher inner ear concentrations than systemic steroids in animal and human studies. Primary treatment of ISSNHL with intratympanic steroids in combination with systemic steroids has been demonstrated to result in better hearing outcomes than systemic steroids alone. Recent evidence has revealed these hearing outcomes to be dependent on the dose of intratympanic steroid. Dexamethasone may be better absorbed than methylprednisolone, and potentially offer a greater benefit. Furthermore, intratympanic steroids provide an effective alternative for patients who cannot tolerate systemic steroids.

Summary: Intratympanic dexamethasone alone, or in combination with systemic steroids, provides effective treatment of ISSNHL and should be utilized as primary treatment. Further investigation is required to determine the optimal choice, concentration, and administration schedule of intratympanic steroids.
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http://dx.doi.org/10.1097/MOO.0000000000000288DOI Listing
October 2016

Re: Meniere's disease: Importance of socioeconomic and environmental factors.

Am J Otolaryngol 2016 Jul-Aug;37(4):387-8. Epub 2016 Jan 21.

Program Director, Neurotology Fellowship UC San Diego School of Medicine. Electronic address:

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http://dx.doi.org/10.1016/j.amjoto.2015.11.006DOI Listing
October 2017

Dose Effect of Intratympanic Dexamethasone for Idiopathic Sudden Sensorineural Hearing Loss: 24 mg/mL Is Superior to 10 mg/mL.

Otol Neurotol 2015 Sep;36(8):1321-7

*University of California, San Diego Division of Otolaryngology Head and Neck Surgery; and †Veterans Affairs Medical Center San Diego, San Diego, California, U.S.A.

Objective: To compare outcomes in patients with idiopathic sudden sensorineural hearing loss (ISSNHL) treated with intratympanic (IT) dexamethasone (DEX) at either 10 mg/mL or 24 mg/mL.

Study Design: Retrospective case series.

Setting: Tertiary referral center.

Patients: Thirty-seven adults with ISSNHL.

Interventions: In addition to concurrent prednisone taper, patients received a series of IT DEX injections for 2 weeks with either 10 mg/mL or 24 mg/mL.

Main Outcome Measure: Greater than 30-dB improvement in pure-tone average (PTA).

Results: Baseline characteristics were similar between groups. Mean follow-up was 10 weeks. Ten (53%) of 19 patients treated with 24 mg/mL had greater than 30-dB improvement in PTA compared with 3 (17%) of 18 treated with 10 mg/mL (p = 0.0382, Fisher's exact test). There was a trend toward improved word recognition score outcome with 24 mg/mL. The interval between onset and initiation of IT DEX significantly affected outcome, with earlier treatment resulting in greater improvement in PTA and word recognition score. Multivariate logistic regression confirmed that IT DEX dose and interval to starting treatment were both independent predictors of PTA outcome. Change in PTA was not significantly affected by age, sex, pretreatment hearing levels, or concurrent treatment with hyperbaric oxygen.

Conclusion: To our knowledge, this is the first demonstration of superiority of IT DEX at 24 mg/mL for the treatment of ISSNHL, with significantly better recovery of PTA. Our data suggest that treatment should be initiated as soon as possible. A prospective randomized trial to confirm the optimal dose is warranted.
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http://dx.doi.org/10.1097/MAO.0000000000000834DOI Listing
September 2015

Is Inferior Turbinate Lateralization Effective?

Plast Reconstr Surg 2015 Nov;136(5):710e-711e

Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of California, San Diego, San Diego, Calif.

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http://dx.doi.org/10.1097/PRS.0000000000001687DOI Listing
November 2015

Imaging Characteristics of Cerebellopontine Angle Chloroma.

Otol Neurotol 2016 08;37(7):e241-3

*Division of Otolaryngology-Head & Neck Surgery †Department of Radiology, University of California, San Diego, California.

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http://dx.doi.org/10.1097/MAO.0000000000000784DOI Listing
August 2016

Hearing preservation and vestibular schwannoma: intracochlear FLAIR signal relates to hearing level.

Otol Neurotol 2014 Feb;35(2):348-52

*University of California at San Francisco Medical Center, San Francisco, CA, U.S.A.; †University of California at San Diego Medical Center, San Diego, CA, U.S.A.; ‡Kaiser Permanente, Los Angeles, CA, U.S.A.; and §Kaiser Permanente San Diego, CA, U.S.A.

Objectives: This study aimed to evaluate the relationship between cochlear signal on fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) sequences and hearing in patients undergoing hearing preservation surgery for vestibular schwannoma (VS) and to demonstrate a new classification system to be used in imaging evaluation of patients with VS.

Methods: A search of archived surgical cases at a single institution between January 1, 2006, and January 1, 2012, revealed 51 patients who underwent hearing preservation surgery for VS. Tumor size, patient age and sex, and preoperative and postoperative pure-tone average (PTA) and speech discrimination score (SDS) were recorded. Cochleae on the affected side were examined on preoperative FLAIR sequences and classified as limited hyperintensity (LH) or extensive hyperintensity (EH).

Results: Mean patient age was 51 years, and mean tumor size was 1.3 cm. Preoperative FLAIR sequences were classified into LH (n = 36) and EH (n = 15) categories. Preoperative PTA and SDS were 29.5 dB (SD, 16.7), 90% (SD, 14) and 40.6 dB (SD, 13.8), 80% (SD, 25) for LH and EH, respectively. On univariate analysis, preoperative PTA was superior in the LH group (p = 0.04). There was a trend toward superior preoperative SDS and postoperative PTA in the LH group, but these differences were not statistically significant (p = 0.08 and p = 0.06, respectively).

Conclusion: The current study is the first to demonstrate a distinct association between cochlear FLAIR signal and pretreatment hearing levels in patients with VS. A new classification system for evaluating cochlear FLAIR signal is proposed. Improvement in FLAIR sequences will allow further investigation of this association.
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http://dx.doi.org/10.1097/MAO.0000000000000191DOI Listing
February 2014

Incidence of sudden sensorineural hearing loss.

Otol Neurotol 2013 Dec;34(9):1586-9

Division of Otolaryngology-Head and Neck Surgery, University of California-San Diego; and VA Medical Center, San Diego, California, U.S.A.

Objective: Recent data regarding the incidence of sudden sensorineural hearing loss (SSNHL) in the United States is lacking. The objective of this study was to assess the current day incidence of SSNHL in the United States using data from a medical and pharmaceutical claims database containing information for more than 60 million unique patients.

Study Design: Population-based cross-sectional analysis.

Setting: Inpatient and outpatient.

Patients: Patients in the database are reported to be representative of the national, commercially insured population on a variety of demographic measures including age, sex, health plan type, and geographic location.

Results: During 2006 and 2007, the annual incidence of SSNHL was 27 per 100,000 in the United States. The incidence increased with increasing age, ranging from 11 per 100,000 for patients younger than 18 years to 77 per 100,000 for patients 65 years and older. There was an overall slight male preponderance with a male-to-female ratio of 1.07:1. This was more pronounced in patients 65 years and older, with a ratio of 1.30:1.

Conclusion: More than 66,000 new cases of SSNHL are seen annually in the United States. The disorder is more common in men and the elderly.
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http://dx.doi.org/10.1097/MAO.0000000000000222DOI Listing
December 2013

Pulmonary langerhans cell histiocytosis diagnosed in a cervical lymph node: a case report.

Acta Cytol 2010 Jul-Aug;54(4):618-22

Department of Pathology, University of California, San Diego, California 92103, USA.

Background: Pulmonary Langerhans cell histiocytosis (PLCH) is usually confined to the lungs and is therefore an unexpected finding in a cervical lymph node.

Case: A 52-year-old male with a 40-pack-year smoking history presented to our clinic with cough, fever and cervical lymphadenopathy. Chest computed tomography (CT) showed bilateral pulmonary nodules and enlarged mediastinal lymph nodes, worrisome for an infectious or malignant process. Bronchioloalveolar lavage was nondiagnostic. Fine needle aspiration cytology of the enlarged cervical lymph node revealed atypical histiocytoid cells, suspicious for malignancy. Immunohistochemistry revealed CD1a- and S-100-positive Langerhans cells. These findings, along with the patient's extensive smoking history and characteristic radiographic nodules, favored a diagnosis of PLCH with cervical lymph node involvement. The patient was advised to cease smoking, and no therapy was administered. Months later, follow-up chest CT showed spontaneous resolution of the lung nodules.

Conclusion: The demonstration of Langerhans cells by immunohistochemical staining of CD1a and S-100 on a fine needle aspiration cell block is a useful diagnostic adjunct. In this case, definitive cytology for Langerhans cells in the appropriate clinical and radiologic setting allowed us to arrive at the correct diagnosis of PLCH in a minimally invasive manner.
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http://dx.doi.org/10.1159/000325188DOI Listing
September 2010

Current epidemiology of Meniere's syndrome.

Otolaryngol Clin North Am 2010 Oct;43(5):965-70

Division of Otolaryngology-Head & Neck Surgery, University of California San Diego, 200 West Arbor Drive, Mail Code 8895, San Diego, CA 92103, USA.

The burden of Ménière syndrome (MS) is substantial, especially when considering the significant impact on the quality of life of those affected. Reported estimates of incidence and prevalence have varied widely due to methodological differences between studies, changes in criteria for diagnosis of MS, and differences in populations studied. Reported prevalence rates for MS range from 3.5 per 100,000 to 513 per 100,000. A recent study using health claims data for more than 60 million patients in the United States found prevalence of 190 per 100,000 with a female:male ratio of 1.89:1. The prevalence of MS increases with increasing age.
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http://dx.doi.org/10.1016/j.otc.2010.05.001DOI Listing
October 2010

Insulin-like growth factor-I and growth differentiation factor-5 promote the formation of tissue-engineered human nasal septal cartilage.

Tissue Eng Part C Methods 2010 Oct;16(5):1213-21

Division of Otolaryngology-Head and Neck Surgery, University of California-San Diego, San Diego, CA 92103, USA.

Introduction: Tissue engineering of human nasal septal chondrocytes offers the potential to create large quantities of autologous material for use in reconstructive surgery of the head and neck. Culture with recombinant human growth factors may improve the biochemical and biomechanical properties of engineered tissue. The objectives of this study were to (1) perform a high-throughput screen to assess multiple combinations of growth factors and (2) perform more detailed testing of candidates identified in part I.

Methods: In part I, human nasal septal chondrocytes from three donors were expanded in monolayer with pooled human serum (HS). Cells were then embedded in alginate beads for 2 weeks of culture in medium supplemented with 2% or 10% HS and 1 of 90 different growth factor combinations. Combinations of insulin-like growth factor-I (IGF-1), bone morphogenetic protein (BMP)-2, BMP-7, BMP-13, growth differentiation factor-5 (GDF-5), transforming growth factor β (TGFβ)-2, insulin, and dexamethasone were evaluated. Glycosaminoglycan (GAG) accumulation was measured. A combination of IGF-1 and GDF-5 was selected for further testing based on the results of part I. Chondrocytes from four donors underwent expansion followed by three-dimensional alginate culture for 2 weeks in medium supplemented with 2% or 10% HS with or without IGF-1 and GDF-5. Chondrocytes and their associated matrix were then recovered and cultured for 4 weeks in 12 mm transwells in medium supplemented with 2% or 10% HS with or without IGF-1 and GDF-5 (the same medium used for alginate culture). Biochemical and biomechanical properties of the neocartilage were measured.

Results: In part I, GAG accumulation was highest for growth factor combinations including both IGF-1 and GDF-5. In part II, the addition of IGF-1 and GDF-5 to 2% HS resulted in a 12-fold increase in construct thickness compared with 2% HS alone (p < 0.0001). GAG and type II collagen accumulation was significantly higher with IGF-1 and GDF-5. Confined compression modulus was greatest with 2% HS, IGF-1, and GDF-5.

Conclusion: Supplementation of medium with IGF-1 and GDF-5 during creation of neocartilage constructs results in increased accumulation of GAG and type II collagen and improved biomechanical properties compared with constructs created without the growth factors.
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http://dx.doi.org/10.1089/ten.TEC.2009.0396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2943402PMC
October 2010

Current-day prevalence of Ménière's syndrome.

Audiol Neurootol 2010 18;15(5):318-22. Epub 2010 Feb 18.

Division of Otolaryngology-Head and Neck Surgery, University of California, San Diego, San Diego, Calif. 92103, USA.

Previously reported prevalence rates of Ménière's syndrome (MS) have ranged from 3.5 per 100000 to 513 per 100000. Recent data regarding the prevalence in the United States are lacking. To further assess the current-day prevalence of MS in the US, data from a medical and pharmaceutical claims database containing information for over 60 million unique patients were analyzed. Patients in the database are representative of the national, commercially insured population on a variety of demographic measures including age, gender, health plan type, and geographic location. A 3-year period from 2005 to 2007 was analyzed. The prevalence of MS was 190 per 100000 with a female:male ratio of 1.89:1. The prevalence increased with increasing age, ranging from 9 per 100000 for patients under age 18 to 440 per 100000 for patients 65 years and older.
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http://dx.doi.org/10.1159/000286213DOI Listing
October 2010

Laterality of exostosis in surfers due to evaporative cooling effect.

Otol Neurotol 2010 Feb;31(2):345-51

Division of Otolaryngology-Head and Neck Surgery, University of California San Diego, La Jolla, California 92103, USA.

Objectives: 1. To correlate exostosis severity with ear canal evaporative cooling. 2. To assess hearing and complications after canalplasty.

Study Design: Retrospective chart review.

Subjects And Method: A retrospective chart review from 1990 to 2007 at a university tertiary referral center.

Results: Surfers from the west coast of the United States were twice as likely to have severe exostoses in the right ear compared with the left. Evaporative cooling from a predominant northerly wind direction during the coldest water temperature months in this region may contribute to this lateral bias because surfers on this coast spend most of their time facing west. Few postoperative complications were identified. No cases of facial nerve injury or entry into the temporomandibular joint occurred. Differences in preoperative versus postoperative pure-tone hearing thresholds were not significant.

Conclusion: Exostosis severity seems to correspond to the ear that is more exposed to the predominant coastal wind. We propose that evaporative cooling in a cold water environment contributes to greater progression of exostoses in the ear with more exposure to the predominant wind. Exostosis removal using the postauricular approach carries a low complication rate.
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http://dx.doi.org/10.1097/MAO.0b013e3181be6b2dDOI Listing
February 2010

Safety of high-dose corticosteroids for the treatment of autoimmune inner ear disease.

Otol Neurotol 2009 Jun;30(4):443-8

Division of Otolaryngology-Head and Neck Surgery, University of California San Diego, San Diego, CA 92103, USA.

Objective: To report the adverse effects associated with prolonged high-dose prednisone for the treatment of autoimmune inner ear disease (AIED).

Study Design: Prospective data collected as part of a multicenter, randomized, controlled trial for the treatment of corticosteroid-responsive AIED with methotrexate.

Setting: Tertiary referral centers.

Patients: One hundred sixteen patients with rapidly progressive, bilateral sensorineural hearing loss.

Intervention: All patients completed a 1-month course of prednisone (60 mg/d). In Phase 2, 67 patients with improvement in hearing underwent a monitored 18-week prednisone taper, resulting in 22 weeks of prednisone therapy at an average dose of 30 mg per day. Thirty-three patients were randomized to receive methotrexate in Phase 2. Thirty-four patients received prednisone and placebo.

Main Outcome Measure: Adverse events (AE) in patients treated with prednisone only.

Results: Of 116 patients, 7 had to stop prednisone therapy during the 1-month challenge phase due to AE. Of 34 patients, 5 were unable to complete the full 22-week course of prednisone due to AE. The most common AE was hyperglycemia, which occurred in 17.6% of patients participating in Phase 2. Weight gain was also common, with a mean increase in body mass index of 1.6 kg/m2 (95% confidence interval, 0.77-2.3) during the 22-week steroid course. Patients entering Phase 2 were followed for a mean of 66 weeks. No fractures or osteonecrosis were reported.

Conclusion: Although high-dose corticosteroids are associated with known serious side effects, prospective data in the literature are limited. The present study suggests that with appropriate patient selection, monitoring, and patient education, high-dose corticosteroids are a safe and effective treatment of AIED.
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http://dx.doi.org/10.1097/MAO.0b013e3181a52773DOI Listing
June 2009

Vestibular schwannoma quantitative polymerase chain reaction expression of estrogen and progesterone receptors.

Laryngoscope 2008 Aug;118(8):1458-63

Department of Surgery, Division of Otolaryngology, Head and Neck Surgery, University of California, San Diego School of Medicine and Veterans Affairs Medical Center, La Jolla, California, USA.

Objectives/hypothesis: Determine the role of estrogen receptor (ER) and progesterone receptor (PR) expression in sporadic and neurofibromatosis 2 (NF2)-related vestibular schwannomas (VS). Growth and proliferation signaling in human VS tumorigenesis may play a key role in molecular therapeutic targeting. VS carry mutations of the NF2 gene encoding the tumor suppressor, merlin, which interacts with ErbB2 in Schwann cells, implicating ErbB receptors in VS tumorigenesis. ErbB receptor family members are overexpressed or constitutively activated in many human tumors, and are effective therapeutic targets in some human cancers. VS occur more frequently in women and are larger, more vascular, and demonstrate increased growth rates during pregnancy. ER and PR may play a role in ErbB pathway activation and VS progression.

Study Design: Quantitative real-time polymerase chain reaction (qRT-PCR) for ER and PR messenger RNA was performed using greater auricular and vestibular nerve controls (n = 8), sporadic VS (n = 23), and NF2-related VS (n = 16) tissues.

Methods: The qRT-PCR data were normalized with standardization to a single constitutively expressed control gene, human cyclophylin.

Results: Reverse transcription of messenger RNA from control and tumor specimens followed by RT Q-PCR demonstrated differences in ER and PR gene expression between sporadic and NF2-related VS.

Conclusions: ER and PR expression in VS might have implications for development of a VS-specific drug delivery system using antihormone and ErbB pathway small molecule inhibitors, due to crosstalk between these receptors. These signals may be critical for re-establishing ErbB-mediated cell density dependent growth inhibition.
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http://dx.doi.org/10.1097/MLG.0b013e318177e20bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570025PMC
August 2008

Human serum for tissue engineering of human nasal septal cartilage.

Otolaryngol Head Neck Surg 2006 Sep;135(3):397-403

Division of Otolaryngology-Head and Neck Surgery, University of California-San Diego, 200 W. Arbor Drive, San Diego, CA 92103, USA.

Objective: To compare the chondrogenic and proliferative effects of pooled human serum (HS) and fetal bovine serum (FBS) on tissue-engineered human nasal septal chondrocytes.

Study Design And Setting: Human chondrocytes were expanded for one passage in monolayer in medium supplemented with 10% FBS, 2% HS, 10% HS, or 20% HS. Cells were then suspended in alginate beads for 3D culture for 2 weeks with 10% FBS, 2% HS, 10% HS, or 20% HS.

Results: Monolayer cell yields were greater with HS than FBS. In alginate, cellular proliferation, glycosaminoglycan production per cell, and type II collagen were significantly higher with 10% HS compared to 10% FBS controls.

Conclusion: HS results in increased proliferation and production of cartilaginous extracellular matrix by tissue-engineered human nasal septal chondrocytes, compared to FBS controls.

Significance: Culture with human serum may facilitate creation of neocartilage constructs that more closely resemble native tissue.
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http://dx.doi.org/10.1016/j.otohns.2006.05.029DOI Listing
September 2006

Twice-recurrent primary hyperparathyroidism due to parathyroid hyperplasia in an ectopic supernumerary gland.

Endocr Pract 2006 Mar-Apr;12(2):165-9

Division of Otolaryngology/Head and Neck Surgery, University of California at San Diego, San Diego, California 94115, USA.

Objective: To describe a patient with multiple recurrences of primary hyperparathyroidism during a 24-year period.

Methods: We present the long-term history, including clinical and laboratory evaluations as well as findings on surgical interventions, in a 42-year-old man with recurrent hyperparathyroidism. In addition, the relevant literature is briefly reviewed.

Results: At initial surgical exploration when the patient was 18 years old, a single enlarged parathyroid gland and a normal-appearing ipsilateral gland were found. After more than a decade without symptoms, the patient experienced recurrent symptomatic hypercalcemia. Surgical exploration revealed symmetric multiglandular disease that was treated by resection of 3 enlarged parathyroid glands and implantation of a portion of 1 gland in the forearm. After another 6-year asymptomatic period, the patient had recurrent symptoms and was found to have recurrent hypercalcemia. Surgical intervention revealed an enlarged supernumerary gland in an ectopic location. A preoperative technetium Tc 99m sestamibi scan and intravenous administration of methylene blue were helpful in identifying the ectopic parathyroid gland in the left carotid sheath.

Conclusion: This case illustrates the difficulty of determining which of a patient's parathyroid glands may become hyperfunctioning and the importance of considering whether supernumerary glands may be present. The case also demonstrates the need for long-term follow-up before a patient is considered "cured" of hyperparathyroidism.
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http://dx.doi.org/10.4158/EP.12.2.165DOI Listing
June 2006

Intranasal zinc and anosmia: the zinc-induced anosmia syndrome.

Laryngoscope 2006 Feb;116(2):217-20

Department of Surgery, Head and Neck Surgery and Continuing Medical Education, University of California, San Diego School of Medicine, VA San Diego Healthcare System, San Diego, CA 92103, USA.

Objective: Commercial preparations of intranasal zinc gluconate gel are marketed as a remedy for the common cold. However, intranasal zinc has been reported as a cause of anosmia in humans and animals. Seventeen patients presenting with anosmia after the use of intranasal zinc gluconate are described.

Methods: The authors conducted a retrospective case series of patients presenting to a nasal dysfunction clinic and conducted complete history and physical examination on all patients, including nasal endoscopy. All patients underwent detailed odor threshold and identification testing.

Results: Threshold and identification testing revealed impaired olfaction in all patients. Inflammatory and traumatic causes of anosmia were excluded based on history, physical examination, and imaging. All patients diagnosed with zinc-induced anosmia or hyposmia reported sniffing deeply when applying the gel. This was followed by an immediate sensation of burning lasting minutes to hours. Loss of sense of smell was then perceived within 48 hours. Seven of 17 patients never developed symptoms of an upper respiratory infection.

Conclusions: The zinc-induced anosmia syndrome, characterized by squirt, sniff, burn, and anosmia, occurs after the exposure of olfactory epithelium to zinc cation. It can be distinguished from postviral anosmia based on history.
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http://dx.doi.org/10.1097/01.mlg.0000191549.17796.13DOI Listing
February 2006

Changes in CD4+ T-cell differentiation phenotype during structured treatment interruption in patients with chronic HIV-1 infection.

J Acquir Immune Defic Syndr 2003 Dec;34(5):475-81

Duke University Medical Center, Durham, NC 27705, USA.

Markers of maturation and activation were measured on peripheral CD4+ T cells in chronically HIV-1-infected patients in a randomized, controlled pilot study of structured treatment interruption (STI). Eight subjects underwent 2 cycles of 1 month off and 1 month on highly active antiretroviral therapy (HAART), followed by a final 3-month interruption. During STI, CD4+ T-cell percentage remained relatively stable in 4 of 8 subjects. The remaining 4 STI subjects had significant rapid decline in CD4+ T-cell percentage during STI, followed by return to pre-STI baseline while on HAART. Changes in overall CD4+ T-cell percentage corresponded with fluctuations in the CD45RA+CCR7+ naive and CD45RA-CCR7+ central memory subsets. Subjects with variable CD4+ T-cell percentages tended to have higher pre-HAART plasma HIV-1 RNA set-points and experienced higher levels of plasma HIV-1 RNA rebound during STI. These results suggest that interruptions should be avoided whenever possible in patients on HAART with high plasma HIV-1 RNA set-points.
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http://dx.doi.org/10.1097/00126334-200312150-00005DOI Listing
December 2003

Inhibition of prolactin secretion from the male rat anterior pituitary by cryptic sequences of prothyrotropin releasing hormone, ProTRH178-199 and ProTRH186-199.

Endocrine 2002 Dec;19(3):313-8

Department of Psychology, San Diego State University, CA 92120, USA.

Previous studies have shown that intronic peptide sequences in the prohormone for thyrotropin-releasing hormone (TRH) have physiological actions on pituitary hormone secretion. The aim of this investigation was to examine the effect of the cryptic peptides, prothyrotropin- releasing hormone(178-199) (ProTRH(178-199)) and ProTRH(186-199), on prolactin (PRL) release from the anterior pituitary. Perifusion studies were performed with anterior pituitaries obtained from individual adult male Sprague Dawley rats at 70 90 d of age. Perifusate was collected in 5-min fractions for 25 min prior to peptide administration and for 60 min afterward. Pituitaries were perifused with a single 5 min pulse of either 2, 10, or 40 nM concentrations (peak pulse) of each peptide or the vehicle. Sixty minutes after peptide administration, a 200 mM pulse of potassium chloride was delivered to check tissue viability. Prolactin was measured in the perifusate by radioimmunoassay. Results showed that both peptides induced a significant long-term suppression of prolactin secretion that was still evident at 60 min after peptide exposure. ProTRH(186-199) was similar to ProTRH(178-199) in suppressing prolactin release at the 2 and 40 nM dose, suggesting that the amino acid sequence necessary for prolactin inhibition is contained within the smaller peptide fragment. These data indicate that a cryptic sequence within the proTRH peptide can have biological activity at the level of the anterior pituitary gland in regulating prolactin secretion.
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http://dx.doi.org/10.1385/ENDO:19:3:313DOI Listing
December 2002