bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune Mediators in Allergic Rhinitis and Sleep
Authors: Krouse Helene J. , Davis Jean E. , Krouse John H.
Published: February 2003

OBJECTIVE

Our study goal was to examine polysomnography, indices of sleep and allergy, and serum and nasal cytokines in allergic and nonallergic subjects.

STUDY DESIGN AND SETTING

In this descriptive, exploratory study, 4 allergic and 4 nonallergic subjects underwent 2 nights of polysomnographic recording with serial measurements of cytokines and completed measures of sleep quality and allergic symptoms.

RESULTS

Three serum cytokines (interleukin (IL)‐1β, IL‐4, and IL‐10) were higher in allergic subjects and were termed proallergic. Three serum cytokines (IL‐1ra, IL‐2, and IL‐12) were higher in nonallergic subjects and were termed allergy inhibitory. Proallergic serum cytokines correlated with increased latency to rapid eye movement sleep, decreased time in rapid eye movement sleep, and decreased latency to sleep onset. Low levels of allergy‐inhibitory serum cytokines were associated with increased allergic symptoms.

CONCLUSIONS

Differences in serum cytokines between allergic and nonallergic individuals are associated with variations in polysomnography and allergic symptoms.

SIGNIFICANCE

Understanding these mechanisms may suggest novel approaches to alleviating drowsiness and other symptoms in allergic patients.
Expression of p63 and 14‐3‐3σ in Normal and Hyperdifferentiated Mucosa of the Upper Aerodigestive Tract
Authors: Sniezek Joseph C. , Matheny Keith E. , Burkey Brian B. , Netterville James L. , Pietenpol Jennifer A.
Published: February 2003

OBJECTIVE

Our goal was to analyze p63 and 14‐3‐3σ expression in normal and hyperdifferentiated head and neck mucosa.

STUDY DESIGN

Compare the in vivo expression of p63 and 14‐3‐3σ by immunohistochemistry in normal mucosa and oral lichen planus, a benign mucosal lesion marked by hyperdifferentiation and apoptosis.

RESULTS AND CONCLUSION

p63 is underexpressed and 14‐3‐3σ is overexpressed in lichen planus on immunohistochemical analysis.

SIGNIFICANCE

The findings support the hypothesis that p63 plays an antidifferentiation role, whereas 14‐3‐3σ plays a prodifferentiation role in the upper aerodigestive tract epithelium. Lichen planus is a valuable model for the study of p63, 14‐3‐3σ, and mucosal differentiation. p63 and 14‐3‐3σ may be molecular markers for oral lichen planus.
Adenotonsillar Enlargement in Pediatric Organ Transplant Recipients: A Cross‐Sectional Analysis
Authors: Chiang Scott , Chau Vu Minh , Nguyen Mychelle , Strocker Ali , Horvath Stefan , Shapiro Nina
Published: February 2003

OBJECTIVE

Our goal was to statistically correlate adenotonsillar hypertrophy (ATH) in the pediatric posttransplant population with potential risk factors and to monitor the progression of ATH over time.

STUDY DESIGN AND SETTING

Participants were evaluated for ATH through a standardized 65‐point questionnaire and an 8‐point physical examination. They were also evaluated for current age, age at time of transplantation, type of organ transplant, gender, tacrolimus use, history of transplant rejection, Epstein‐Barr virus (EBV) serology, and cytomegalovirus (CMV) serology. We evaluated 243 pediatric solid organ transplant recipients, with 116 patients undergoing repeat evaluation.

RESULTS

A statistically significant negative correlation was noted between age at time of transplantation and both questionnaire scores (P = 0.0075) and examination scores (P = 0.013). A significant negative correlation was also seen between age at time of evaluation and questionnaire score (P = 0.028) but not examination score (P = 0.49). Recipient EBV seronegativity significantly increased questionnaire score (P = 0.05). Liver transplant recipients also had a significantly higher questionnaire score than did kidney transplant recipients (P = 0.0048). Gender, CMV recipient status, and tacrolimus (immunosuppressant) use did not significantly impact questionnaire or examination scores. Repeat evaluation of 116 patients after a 2‐to 9‐month interval did not demonstrate any significant increases in questionnaire scores. A statistically significant drop in examination scores was noted (P = 0.003).

CONCLUSIONS AND SIGNIFICANCE

These findings support previous reports in the literature that correlate EBV seronegativity, younger age at transplant, and liver versus kidney transplantation with increased incidence of PTLD.
Clinical Staging for Sleep‐Disordered Breathing
Authors: Friedman Michael , Ibrahim Hani , Bass Lee
Published: February 2003

OBJECTIVE

The purpose of this study was to identify prognostic indicators that would lead to stratification of patients likely to have successful surgery for sleep‐disordered breathing (SDB) versus those destined to fail.

STUDY DESIGN

We retrospectively reviewed 134 patients to correlate palate position and tonsil size to the success of the UPPP as based on postoperative polysomnography results. Similar to our previously published data on the Friedman Score as a predictor of the presence and severity of SDB, the palate position was determined on physical examination of the oral cavity and was graded for each patient. This grade combined with tonsil size was used to stage the patients. Stage I was defined as having palate position 1 or 2 combined with tonsil size 3 or 4. Stage II was defined as having palate position 3 or 4 and tonsil size 3 or 4. Stage III patients had palate position 3 or 4 and tonsil size 0, 1, or 2. Any patient with body mass index of greater than 40 was placed in the stage III group. The results of uvulopalatopharyngoplasty (UPPP) were then graded as success or failure and success rates were compared by stage.

SETTING

Academically affiliated tertiary care referral center.

RESULTS

Stage I patients who underwent UPPP had a success rate of 80.6%, stage II patients had a success rate of 37.9%, and stage III patients had a success rate of 8.1%.

CONCLUSION

A clinical staging system for SDB based on palate position, tonsil size, and body mass index is presented. It appears to be a valuable predictor of the success of UPPP. Additional studies and wider use of the staging system will ultimately define its role in the treatment of SDB.
Virtual Temporal Bone Dissection: An Interactive Surgical Simulator
Authors: Wiet Gregory J. , Stredney Don , Sessanna Dennis , Bryan Jason A. , Welling D. Bradley , Schmalbrock Petra
Published: February 2003

OBJECTIVE

Our goal was to integrate current and emerging technology in virtual systems to provide a temporal bone dissection simulator that allows the user interactivity and realism similar to the cadaver laboratory.

STUDY DESIGN

Iterative design and validation of a virtual environment for simulating temporal bone dissection.

SETTING

University otolaryngology training program with interdisciplinary interaction in a high‐performance computer facility.

RESULTS

The system provides visual, force feedback (haptic), and aural interfaces. Unlike previous “fly through” virtual systems, this environment provides a richer emulation of surgical experience.

CONCLUSION

The system provides a high level of functional utility and, through initial evaluations, demonstrates promise in adding to traditional training methods.

SIGNIFICANCE

The system provides an environment to learn temporal bone surgery in a way similar to the experience with cadaver material where the subject is able to interact with the data without constraints (nondeterministic). Eventually, it may provide the “front end” to a large repository of various temporal bone pathologies that can be accessed through the Internet.
Fungus‐Specific IgG and IgE in Allergic Fungal Rhinosinusitis
Authors: Stewart Alexander E. , Hunsaker Darrell H.
Published: February 2003

OBJECTIVE

Our study goal was to study fungus‐specific immunoglobulins G (sIgG) and E (sIgE) in polypoid rhinosinusitis with and without evidence of allergic fungal rhinosinusitis (AFS).

STUDY DESIGN AND SETTING

A prospective analysis was conducted of fungal sIgG and sIgE using a 9‐mold RAST panel in 13 AFS, 11 AFS‐like, and 27 non‐AFS polypoid rhinosinusitis patients. Nonpolyp controls included 17 volunteers with allergic rhinitis and 11 with no atopic history.

RESULTS

All groups had elevated fungal sIgG levels. Polyps, increasing polyp severity, and AFS were associated with elevated fungal sIgG to a greater number of molds. The AFS group had sIgE elevations (≥class II) to an average of 5 molds versus only 0.1 in the non‐AFS polyp group. Total IgE was 971 U/mL versus 64 U/mL, respectively.

CONCLUSIONS

Multiple elevations of fungal sIgE are adequate diagnostic evidence of these fungi when fungal cultures and histologic examinations are negative in diagnosing AFS. The significance of increased fungal sIgG remains unclear.

SIGNIFICANCE

Early recognition of AFS may be facilitated by screening polypoid rhinosinusitis patients with total serum IgE and RAST testing.
Transoral Radiofrequency Treatment of Snoring
Authors: Johnson Jonas T. , Pollack Gabrielle L. , Wagner Robin L.
Published: February 2003

OBJECTIVES/HYPOTHESIS

Radiofrequency ablation (RFA) may effectively treat snoring with acceptable patient tolerance.

STUDY DESIGN

A cohort of patients with unacceptable snoring underwent RFA to the soft palate between October 1997 and May 2000. Before the therapy, a family member or significant other person was interviewed to rate snoring loudness.

METHODS

Snoring was rated on a visual analog scale of 0 to 10 (in which 0 was no snoring and 10 was horrific snoring) before and after therapy. All patients were treated with transoral RFA administered under local anesthesia at 6‐week intervals.

RESULTS

Complete data were available for 60 of the 75 treated patients. The average number of treatment sessions per patient was 1.8. These patients received an average energy of 1845 J. Overall the average snoring score was 8.9 before therapy and 3.5 after therapy. Fifty‐one patients (85%) were considered to have major improvement in snoring loudness. A total of 9 patients (15%) were nonresponders.

CONCLUSIONS

RFA to the soft palate is a viable option to treat socially unacceptable snoring. Inadequate response to therapy may reflect misdiagnosis or delivery of an insufficient amount of energy.
Temperature‐Controlled Radiofrequency Tongue Base Reduction for Sleep‐Disordered Breathing: Long‐Term Outcomes
Authors: Li Kasey K. , Powell Nelson B. , Riley Robert W. , Guilleminault Christian
Published: February 2003

OBJECTIVE

Our goal was to evaluate the long‐term outcomes of temperature‐controlled radiofrequency reduction of the tongue base in sleep‐disordered breathing.

METHODS

The 18 patients from our initial pilot study were reevaluated. Clinical examinations, polysomnography (PSG), questionnaires, visual analog scales, and a comparative SF‐36 were used to assess long‐term outcomes.

RESULTS

Sixteen of the original 18 patients completed this study; 2 patients were lost to follow‐up. The mean follow‐up was 28 months. There was a mean weight increase of 3.1 ± 7.9 kg. The original pretreatment Respiratory Disturbance Index (RDI) was a mean of 39.5 with a mean mean oxygen saturation nadir (LSAT) of 81.9%, and the posttreatment RDI was a mean of 17.8 with a mean LSAT of 88.3%. Follow‐up PSG data showed a persistent improvement of the mean Apnea Index compared with pretreatment (5.4 vs 22.1) without significant changes compared with posttreatment (4.1). However, there were changes in the follow‐up Hypopnea Index (HI) of 22.9 compared with the pretreatment and posttreatment HI values of 17.4 and 13.6, respectively. This resulted in a relapse of the RDI from a posttreatment value of 17.8 to 28.7. The LSAT also worsened from 88.3% to 85.8%. However, there was no significant deterioration in the quality‐of‐life measurements by SF‐36 or in daytime sleepiness by Epworth Sleepiness Scale.

CONCLUSION

The success of temperature‐controlled radiofrequency tongue base reduction for sleep‐disordered breathing may reduce with time. PSG demonstrated that long‐term relapse is primarily reflected in the HI without significant detrimental effects on the patient's quality of life (SF‐36) and sleepiness (Epworth Sleepiness Scale). Continual evaluation of this treatment modality is warranted.
DNA Microarrays in Otolaryngology‐Head and Neck Surgery
Authors: Whipple Mark Eliot , Kuo Winston Patrick
Published: February 2003

OBJECTIVES

Our goal was to review the technologies underlying DNA microarrays and to explore their use in otolaryngology‐head and neck surgery.

STUDY DESIGN

The current literature relating to microarray technology and methodology is reviewed, specifically the use of DNA microarrays to characterize gene expression. Bioinformatics involves computational and statistical methods to extract, organize, and analyze the huge amounts of data produced by microarray experiments. The means by which these techniques are being applied to otolaryngology‐head and neck surgery are outlined.

RESULTS

Microarray technologies are having a substantial impact on biomedical research, including many areas relevant to otolaryngology‐head and neck surgery.

CONCLUSIONS

DNA microarrays allow for the simultaneous investigationof thousands of individual genes in a single experiment. In the coming years, the application of these technologies to clinical medicine should allow for unprecedented methods ofdiagnosis and treatment.

SIGNIFICANCE

These highly parallel experimental techniques promise to revolutionize gene discovery, disease characterization, and drug development.
Cough and Paradoxical Vocal Fold Motion
Authors: Altman Kenneth W. , Simpson C. Blake , Amin Milan R. , Abaza Mona , Balkissoon Ron , Casiano Roy R.
Published: February 2003

OBJECTIVES

The differential diagnosis and treatment of patients with chronic cough, paradoxical vocal fold motion, and disordered breathing can be a challenge to most practicing otolaryngologists. Tracheobronchial (ie, asthma, bronchitis, and tracheal stenosis), laryngeal (ie, vocal fold paralysis and neoplasms), and rhinologic (ie, allergies and rhinosinusitis) etiologies are commonly diagnosed and treated effectively. However, occasionally one is faced with patients who are refractory to medical treatment and have no obvious rhinologic, laryngeal or pulmonary cause.

STUDY DESIGN AND SETTING

We conducted a review of the literature.

METHODS

We present a thorough review of the current medical literature exploring the complex neurologic mechanisms involved in the production of cough and the relationship between gastroesophageal reflux disease, vagal neurapathy, and paradoxical vocal fold motion.

RESULTS

The diagnosis and successful treatment of chronic cough can be complex. It requires a thorough understanding of the neurologic mechanisms behind cough excitation and suppression. Successful treatment strategies include aggressive management of the patient's reactive airway disease, gastroesophageal reflux disease, and, in select cases, paradoxical vocal fold motion. This may involve a well‐coordinated effort among pulmonologists, otolaryngologists, gastroenterologists, and speech pathologists.

CONCLUSION

Gastroesophageal reflux disease, vagal neuropathy, and paradoxical vocal fold motion are additional causes of chronic cough and disordered breathing that need to be considered, in the absence of obvious laryngotracheal and/or rhinologic pathology. A high index of suspicion is essential in making the diagnosis and formulating an effective multidisciplinary treatment plan for these patients.
Prognostic Value of the Blink Reflex in Acoustic Neuroma Surgery
Authors: Darrouzet Vincent , Hilton Malcolm , Pinder Darren , Wang Jio‐Ling , Guerin Jean , Bebear Jean‐Pierre
Published: February 2003

OBJECTIVE

The study goal was to demonstrate that blink reflex analysis can predict postoperative facial nerve outcome in cerebellopontine angle tumor surgery.

STUDY DESIGN, SETTING, AND PATIENTS

In an open and prospective study conducted at a single tertiary care center over 3 years, 91 subjects with a vestibular schwannoma filling the internal auditory meatus were enrolled and operated on via a translabyrinthine approach. The difference in latency of the early response (δR1) of the blink reflex between the pathologic side and the healthy side was calculated in every patient during a complete electrophysiologic examination of the facial nerve performed on the day before surgery.

MAIN OUTCOME MEASURES

δR1 was compared with the other preoperative data (tumor volume, facial function), with the perioperative observations (difficulties with the dissection of the facial nerve), and especially with the postoperative status after 1 year. The statistical study was conducted using polynomial regression.

RESULTS

Patients with a negative or zero δR1 have normal facial function at 1 year. For those with a positive δR1 the outcome is not favorable unless the tumor is small. For patients presenting with an immediate complete facial paralysis, the value of δR1 is also indicative of facial function outcome.

CONCLUSION

Statistical analysis shows that the blink reflex, through δR1, has an excellent prognostic value in anticipating the difficulties with facial nerve dissection and postoperative facial function after 1 year.
Cystic Cervical Metastases: Incidence and Diagnosis using Fine Needle Aspiration Biopsy
Authors: Sheahan Patrick , O'Leary Gerard , Lee Gary , Fitzgibbon Jim
Published: February 2003

BACKGROUND

Seventeen patients presenting with a cystic cervical metastasis were identified after either having undergone excision of a cyst, initially diagnosed as a branchial cyst but subsequently found to be malignant, or after having had fluid aspirated from a neck mass that ultimately proved to be malignant while undergoing fine needle aspiration biopsy.

METHODS

Patients had primary cancer documented at a variety of primary sites, including hypopharynx (3 patients), oropharynx (2 patients), lower lip (2 patients), nasopharynx, supraglottis, oral cavity, and prostate (1 patient each). Six cases (35%) remained occult.

RESULTS

In nearly half of the cases (8 of 17), there was no evidence of the primary cancer at presentation. In the same period, 25 branchial cysts were encountered, giving an incidence of unsuspected carcinoma in cervical cysts of 24% (8 of 33).

CONCLUSION

In contrast to previous studies in which smaller numbers of patients underwent the procedure, we found fine needle aspiration to be very helpful in the assessment of these lesions, having a sensitivity of 73% in diagnosing malignancy.
Efficacy of Selective Lymph Node Dissection in Clinically Negative Neck
Authors: Mira Eugenio , Benazzo Marco , Rossi Vanessa , Zanoletti Elisabetta
Published: February 2003

OBJECTIVE

The purpose of this study was to evaluate the efficacy of selective neck dissection (SND) for elective treatment of the clinically negative neck in head and neck squamous cell carcinoma (SCC).

METHODS

A retrospective review was undertaken on 91 previously untreated patients with T1–4 SCC of oral cavity (23), oropharynx (5), hypopharynx (7), larynx (56), and clinically negative neck (NO), undergoing 126 SND from January 1990 to March 1999 at a single institution. Twenty‐five patients received postoperative radiation therapy on the basis of histologic evidence of >2 positive nodes, extracapsular spread (ECS), and/or the presence of advanced primary lesion.

RESULTS

On pathologic examination the average number of lymph nodes was 20.5 per neck, occult disease was detected in 14 (11.11%) of 126 necks; of necks with positive nodes, 6 (42.85%) of 14 had ECS. The median follow‐up was 36 months. Overall recurrence rate (local, regional, and distant) was 12.8% (11 of 91). Recurrent disease developed in the neck of one patient, outside the dissected field. There was no difference in recurrence rate between pN0 and pN+ patients, as well as between pN+ with or without ECS. Overall survival rate was 84% (77 of 91), with a statistically significant difference between pN0 and pN+ necks.

CONCLUSION

SND seems to be a pragmatic approach that is as effective as comprehensive procedures for staging and treating the clinically negative neck.
Muscle Tension Dysphonia as a Sign of Underlying Glottal Insufficiency
Authors: Belafsky Peter C. , Postma Gregory N. , Reulbach Todd R. , Holland Bradford W. , Koufman James A.
Published: February 2003

BACKGROUND

Hyperkinetic vocal function (muscle tension dysphonia) may be an indication of underlying glottal insufficiency. In the face of an organic voice disorder such as presbylaryngis or vocal fold paresis. Hyperkinetic laryngeal behaviors may be used to achieve glottal closure. Such compensatory laryngeal behaviors may mask the correct underlying diagnosis.

OBJECTIVE

We sought to evaluate the association between vocal fold bowing due to presbylaryngis and abnormal muscle tension patterns (MTPs).

METHODS

One hundred consecutive volunteers >40 years old were prospectively evaluated. All underwent a comprehensive head and neck examination that included transnasal fiberoptic laryngoscopy with videostroboscopy. Abnormal MTPs were compared in subjects with and without vocal fold bowing.

RESULTS

The mean age of the cohort was 61 years. Eighty‐four percent (42 of 50) of the male subjects and 60% (30 of 50) of female subjects had evidence of vocal fold bowing. Of the 72 patients with bowing, 94% (68 of 72) had abnormal MTPs. Compared with subjects without vocal fold bowing, persons with bowing were 17 times more likely to exhibit abnormal MTPs (P < 0.001).

CONCLUSIONS

Abnormal MTPs are common in persons with underlying glottal insufficiency. Patients with vocal fold bowing are 17 times more likely to exhibit abnormal MTPs (95% confidence interval, 4.9 to 59.4). Clinicians should be aware that compensatory hyperkinetic laryngeal behaviors may mask an underlying organic condition.
Neuroendocrine Adenoma of the Middle Ear
Authors: Aquino Benjamin F. , Chandra Rakesh K. , Haines G. Kenneth , Micco Alan G.
Published: February 2003

Middle ear adenoma is a recently described pathologic entity, first reported by Derlacki and Barney1 in 1976. Since that time, these tumors have been established as the most common “non‐glomus tumors” of the middle ear, but they are still extremely rare occurrences.2 We add the description of a new case to the literature and note the changing categorization of these tumors.
Squamous Cell Carcinoma Arising in a Dentigerous Cyst in a 16‐Month‐Old Girl
Authors: Gulbranson Scott H. , Wolfrey Jeffrey D. , Raines John M. , McNally Brian P.
Published: February 2003

Squamous cell carcinoma arising in a dentigerous cyst is a rare lesion with distinct histopathology and stringent criteria for diagnosis.1,2 During the past century, <60 cases have been reported.3 Of the previously documented cases, all have occurred in adults. We present the case of a squamous cell carcinoma arising in a dentigerous cyst in a 16‐month‐old girl. This case poses interesting questions regarding the pathophysiology of these tumors and highlights the importance of maintaining a high index of suspicion regardless of age when evaluating cystic lesions of the mandible and maxilla.
Robot‐Assisted Stapedotomy: Micropick Fenestration of the Stapes Footplate
Authors: Rothbaum Daniel L. , Roy Jaydeep , Stoianovici Dan , Berkelman Peter , Hager Gregory D. , Taylor Russell H. , Whitcomb Louis L. , Francis Howard W. , Niparko John K.
Published: February 2003

OBJECTIVE

Micropick fenestration of the stapes footplate, a difficult step in stapedotomy, was selected for trials evaluating the potential for robotic assistance (RA) to improve clinical measures of surgical performance.

STUDY DESIGN

In a surgical model of stapedotomy, we measured accuracy of fenestration to a desired point location and force applied to the stapes footplate. Performance variables were measured for 3 experienced and 3 less–experienced surgeons.

RESULTS

RA significantly reduced the maximum force applied to the stapes footplate. For fenestration targeting, RA significantly improved accuracy for less–experienced surgeons and significantly worsened targeting for more‐experienced surgeons.

CONCLUSIONS

RA significantly improves performance for micropick fenestration in a surgical model of stapedotomy. For certain tasks, RA differentially affects performance for users of different experience levels.

CLINICAL SIGNIFICANCE

These are the first results showing quantitative improvements in performance during simulated ear surgery using RA and differential effects of RA on performance for users of different experience levels.
The Effect of Ankyloglossia on Speech in Children
Authors: Messner Anna H. , Lalakea M. Lauren
Published: February 2003

OBJECTIVE

We wanted to determine whether ankyloglossia is associated with articulation problems and the effect of frenuloplasty on speech and tongue mobility.

STUDY DESIGN

We conducted a prospective study of 30 children aged 1 to 12 years with ankyloglossia undergoing frenuloplasty. Outcomes were assessed by measurements of tongue mobility, speech evaluation, and parent questionnaires.

RESULTS

Mean tongue protrusion improved from 14.2 mm preoperatively to 25.8 mm postoperatively (P < 0.01). Similarly, mean tongue elevation improved from 5.2 to 22 mm (P < 0.01). Preoperative speech pathology evaluation documented articulation problems thought due to ankyloglossia in 15 of 21 children. Postoperative evaluation in 15 of these children showed improvement in articulation in 9, no change in 4 who had normal speech preoperatively, and an ongoing articulation disorder in 2. Parent perception of speech intelligibility on a scale of 1 to 5 improved from 3.4 to 4.2 (P < 0.01).

CONCLUSION

Tongue mobility and speech improve significantly after frenuloplasty in children with ankyloglossia who have articulation problems.
A Comparison of Screening Methods in School‐Aged Children
Authors: Krueger Wesley W. O. , Ferguson Ladonna
Published: February 2003

OBJECTIVE

We sought to compare the findings of 3 different hearing screening methods in school‐aged children.

STUDY DESIGN AND SETTING

Prospective testing of second‐ and third‐grade students in their schools was carried out.

METHODS

Three hundred children (599 ears) were screened by using 3 test modalities, pure‐tone audiometry, distortion product otoacoustic emissions (DPOAE), and tympanometry.

RESULTS

All of the tests were normal in 532 ears (89%), and all were abnormal in 12 ears (2%). Tympanometry yielded the most abnormalities (8.3%), and pure‐tone testing demonstrated the fewest (3.3%), with a positive rate of 6.3% for DPOAE testing. False‐positive rates were 1.2%, 4.2%, and 6.4% for pure tones, DPOAE, and tympanometry, respectively, when normal results on pure‐tones or DPOAE were taken to represent true hearing.

CONCLUSION/SIGNIFICANCE

We continue to recommend pure‐tone testing as an effective screening method, with follow‐up by using otoacoustic emissions in those who fail the pure‐tone test.
Pleomorphic Adenoma of the Lateral Nasal Wall
Authors: Jackson Lance E. , Rosenberg Seth I.
Published: February 2003

Few cases of intranasal pleomorphic adenoma have been reported in the English literature. Of those observed in the nose, the vast majority of tumors originate from the septum and <10% originate from the lateral nasal wall.1 We present the case of a man with a unilateral nasal mass arising from the lateral nasal wall confirmed to be a pleomorphic adenoma on pathologic examination.
Multichannel Cochlear Implantation in Radical Mastoidectomy Cavities
Authors: Pasanisi Enrico , Vincenti Vincenzo , Bacciu Andrea , Guida Maurizio , Berghenti Teresa , Barbot Anna , Zini Carlo , Bacciu Salvatore
Published: February 2003

OBJECTIVE

We report on our experience in cochlear implantation in patients with radical mastoidectomy cavities.

STUDY DESIGN, SETTING, AND METHODS

Retrospectively, records of patients from the Department of Otolaryngology, University of Parma between December 1991 and March 2000 were reviewed, and 6 postlingually deafened adults who received a cochlear implant in a radical cavity were identified. Speech performances were evaluated in terms of bisyllabic word and sentence recognition and common phrase comprehension.

RESULTS

To date, with a follow‐up of 1 to 9 years, no patient has experienced extrusion of electrodes or other local or intracranial complications. Mean bisyllabic word and sentence recognition scores were 74% and 80%, respectively. Mean comprehension score for common phrases was 86%.

CONCLUSION

By obliterating and isolating the radical mastoidectomy cavity from the outer environment, patients who previously had undergone radical surgery of the middle ear can be safely implanted with satisfactory hearing results.

Multichannel cochlear implantation (CI) is a treatment accepted worldwide for patients with total or profound deafness. In the presence of normal temporal bone anatomy, CI surgery is a safe and relatively simple procedure with a low complication rate.1–3 However, some conditions, such as malformations of the middle or inner ear, cochlear ossification, chronic otitis media, and previous middle ear surgery, represent a technical challenge to CI surgeons.

Patients with a bilateral radical mastoidectomy cavity who are otherwise suitable for implantation represent a certainly more problematic group to manage than the “standard” CI patients. Under these circumstances, various potential problems must be considered: extrusion of the electrode array by breakdown of the thin epithelial lining of the mastoid cavity, risk of recurrent cholesteatoma, and possibility of spreading of inflammation to the implant with potential labyrinthitis and meningitis.

During recent years various surgical strategies have been proposed in the literature to avoid such complications. Many surgeons suggested overcoming these problems by performing an obliterative technique,4–6 whereas others preferred to maintain the benefits of an open technique7 or to rehabilitate the cavity8; it has also been suggested that the cavity be bypassed via a middle cranial fossa approach.9

We describe the experience at the CI Center of the University of Parma in managing 6 CI patients with radical mastoidectomy cavities.
Determination of the energetics governing the regulatory step in growth hormone-induced receptor homodimerization
Authors: Bernat Bryan , Pal Gabor , Sun Miao , Kossiakoff Anthony A.
Published: February 2003

Signaling in the human growth hormone (hGH)–human GH receptor system is initiated by a controlled sequential two-step hormone-induced dimerization of two hGH receptors via their extracellular domains (ECDs). Little is currently known about the energetics governing the important regulatory step in receptor signaling (step 2) because of previously existing experimental barriers in characterizing the binding of the second receptor (ECD2). A further complication is that ECD2 binds through contacts from two spatially distinct sites: through its N-terminal domain to hGH, and to ECD1 through its C-terminal domain, which forms a pseudo-2-fold symmetrical interaction between the stems of the two receptors. We report here a detailed evaluation of the energetics of step 2 binding using a modified surface plasmon resonance method that is able to measure accurately the kinetics of the trimolecular binding process and separate the effects of the two binding sites. The binding kinetics of 23 single and 126 ECD1-ECD2 pair-wise alanine mutations was measured. Although both of the ECD2 binding interfaces were found to be important, the ECD1-ECD2 stem–stem contact is the stronger of the two. It was determined that most residues in the binding interfaces act in additive fashion, and that the six residues common in both ECDs contribute very differently to homodimerization depending on which ECD they reside in. This interface is characterized by a binding “hot-spot” consisting of a core of three residues in ECD1 and two in ECD2. There is no similar hot-spot in the N-terminal domain of ECD2 binding to Site2 of hGH. This study suggests ways to engineer ECD molecules that will bind specifically to either Site1 or Site2 of hGH, providing novel reagents for biophysical and biological studies.
Determination of the transcriptome of
Vibrio cholerae
during intraintestinal growth and midexponential phase
in vitro
Authors: Xu Qing , Dziejman Michelle , Mekalanos John J.
Published: February 2003

Vibrio cholerae
is the etiologic bacterial agent of cholera, a severe diarrheal disease endemic in much of the developing world. The
V. cholerae
genome contains 3,890 genes distributed between a large and a small chromosome. Although the large chromosome encodes the majority of recognizable gene products and virulence determinants, the small chromosome carries a disproportionate number of hypothetical genes. Thus, little is known about the role of the small chromosome in the biology of this organism or other
Vibrio
species. We have used the rabbit ileal loop model of
V. cholerae
infection to obtain
in vivo
-grown cells under near midexponential conditions in the small-intestinal environment. We compared the global transcriptional pattern of these
in vivo
-grown cells to those grown to midexponential phase in rich medium under aerobic conditions. Under both conditions, the genes showing the highest levels of expression reside primarily on the large chromosome. However, a shift occurs
in vivo
that results in many more small chromosomal genes being expressed during growth in the intestine. Our analysis further suggests that nutrient limitation (particularly iron) and anaerobiosis are major stresses experienced by
V. cholerae
during growth in the rabbit upper intestine. Finally, relative to
in vitro
growth, the intestinal environment significantly enhanced expression of several virulence genes, including those involved in phenotypes such as motility, chemotaxis, intestinal colonization, and toxin production.
Regulation of Lymphocyte Apoptosis by Interferon Regulatory Factor 4 (IRF-4)
Authors: Fanzo Jessica C. , Hu Chuan-Min , Jang So Young , Pernis Alessandra B.
Published: February 2003

To ensure that homeostasis of the immune system is maintained, the sensitivity of lymphocytes to Fas-mediated apoptosis is differentially regulated during their activation. The molecular mechanisms that link the activation program of lymphocytes to changes in sensitivity to Fas-mediated apoptosis have, however, not been fully characterized. In these studies, we have investigated whether Fas-mediated apoptosis can be regulated by interferon regulatory factor 4 (IRF-4), a lymphoid-restricted member of the IRF family of transcription factors. IRF-4 expression is upregulated during lymphocyte activation and IRF-4–deficient mice have defects in both lymphocyte activation and homeostasis. Here, we show that stable expression of IRF-4 in a human lymphoid cell line that normally lacks IRF-4 leads to a significantly enhanced apoptotic response on Fas receptor engagement. A systematic examination of the downstream effectors of Fas signaling in IRF-4–transfected cells demonstrates an increased activation of caspase-8, as well as an increase in Fas receptor polarization. We demonstrate that IRF-4–deficient mice display defects in activation-induced cell death, as well as superantigen-induced deletion, and that these defects are accompanied by impairments in Fas receptor polarization. These data suggest that IRF-4, by modulating the efficiency of the Fas-mediated death signal, is a novel participant in the regulation of lymphoid cell apoptosis.
GATA-1 as a Regulator of Mast Cell Differentiation Revealed by the Phenotype of the GATA-1low Mouse Mutant
Authors: Migliaccio Anna Rita , Rana Rosa Alba , Sanchez Massimo , Lorenzini Rodolfo , Centurione Lucia , Bianchi Lucia , Vannucchi Alessandro Maria , Migliaccio Giovanni , Orkin Stuart H.
Published: February 2003

Here it is shown that the phenotype of adult mice lacking the first enhancer (DNA hypersensitive site I) and the distal promoter of the GATA-1 gene (neoΔHS or GATA-1low mutants) reveals defects in mast cell development. These include the presence of morphologically abnormal alcian blue+ mast cells and apoptotic metachromatic− mast cell precursors in connective tissues and peritoneal lavage and numerous (60–70% of all the progenitors) “unique” trilineage cells committed to erythroid, megakaryocytic, and mast pathways in the bone marrow and spleen. These abnormalities, which were mirrored by impaired mast differentiation in vitro, were reversed by retroviral-mediated expression of GATA-1 cDNA. These data indicate an essential role for GATA-1 in mast cell differentiation.
G-CSF–stimulated Neutrophils Are a Prominent Source of Functional BLyS
Authors: Scapini Patrizia , Nardelli Bernardetta , Nadali Gianpaolo , Calzetti Federica , Pizzolo Giovanni , Montecucco Cesare , Cassatella Marco A.
Published: February 2003

B lymphocyte stimulator (BLyS) is a novel member of the TNF ligand superfamily that is important in B cell maturation and survival. We demonstrate that human neutrophils, after incubation with G-CSF or, less efficiently, IFNγ, express high levels of BLyS mRNA and release elevated amounts of biologically active BLyS. In contrast, surface expression of the membrane-bound BLyS was not detected in activated neutrophils. Indeed, in neutrophils, uniquely among other myeloid cells, soluble BLyS is processed intracellularly by a furin-type convertase. Worthy of note, the absolute capacity of G-CSF–stimulated neutrophils to release BLyS was similar to that of activated monocytes or dendritic cells, suggesting that neutrophils might represent an important source of BLyS. In this regard, we show that BLyS serum levels as well as neutrophil-associated BLyS are significantly enhanced after in vivo administration of G-CSF in patients. In addition, serum obtained from two of these patients induced a remarkable accumulation of neutrophil-associated BLyS in vitro. This effect was neutralized by anti–G-CSF antibodies, indicating that G-CSF, present in the serum, stimulated neutrophils to produce BLyS. Collectively, our findings suggest that neutrophils, through the production of BLyS, might play an unsuspected role in the regulation of B cell homeostasis.
Dynamic Changes During the Immune Response in T Cell–Antigen-presenting Cell Clusters Isolated from Lymph Nodes
Authors: Hommel Mirja , Kyewski Bruno
Published: February 2003

Activation of antigen-specific T cells by mature dendritic cells in secondary lymphoid organs is a key control point of the adaptive immune response. Here we describe the ex vivo isolation of preformed multicellular clusters between T cells and antigen-presenting cells. Adoptively transferred, antigen-specific T cells segregated into individual clusters where their activation and proliferation was initiated in vivo. Transit of the T cell cohort through the cluster compartment required 32–36 h. The precise timing of the response to agonistic epitopes was remarkably invariant regardless of the T cell lineage, the major histocompatibility complex haplotype, and the antigen dose. Interestingly, initiation of cell division of T cells specific for a subdominant epitope and a weak agonist was delayed by 6 h. The results provide a basis for the analysis of short range, mutual cell–cell interactions within such confined microenvironments.
Integrin-dependence of Lymphocyte Entry into the Splenic White Pulp
Authors: Lo Charles G. , Lu Theresa T. , Cyster Jason G.
Published: February 2003

The steps involved in lymphocyte homing to the white pulp cords of the spleen are poorly understood. We demonstrate here that the integrins lymphocyte function associated (LFA)-1 and α4β1 make essential and mostly overlapping contributions necessary for B cell migration into white pulp cords. T cell entry to the white pulp is also reduced by blockade of LFA-1 and α4β1. The LFA-1 ligand, intercellular adhesion molecule 1 is critical for lymphocyte entry and both hematopoietic cells and radiation-resistant cells contribute to this requirement. Vascular cell adhesion molecule 1 contributes to the α4β1 ligand requirement and a second ligand, possibly fibronectin, also plays a role. By contrast with the entry requirements, antigen-induced movement of B cells from follicles to the outer T zone is not prevented by integrin blocking antibodies. Comparison of the distribution of integrin-blocked B cells and B cells treated with the Gαi inhibitor, pertussis toxin, early after transfer reveals in both cases reduced accumulation in the inner marginal zone. These observations suggest that chemokine receptor signaling and the integrins LFA-1 and α4β1 function together to promote lymphocyte transit from the marginal zone into white pulp cords.
Extrathymic T Cell Lymphopoiesis
Authors: Guy-Grand Delphine , Azogui Orly , Celli Susanna , Darche Sylvie , Nussenzweig Michel C. , Kourilsky Philippe , Vassalli Pierre
Published: February 2003

In the absence of thymopoiesis, T lymphocytes are nevertheless present, mainly in the gut epithelium. Ontogeny of the extrathymic pathway and the extent of its involvement in euthymic mice are controversial. These questions have been addressed by assessing the expression of recombinase activating gene (RAG) through the use of green fluorescent protein RAG2 transgenic mouse models. In athymic mice, T lymphopoiesis occurs mainly in the mesenteric lymph node and less in the Peyer's patches. Ontogenic steps of this lymphopoiesis resemble those of thymopoiesis, but with an apparent bias toward γδ T cell production and with a paucity of oligoclonal αβ T cells possibly resulting from a deficit in positive selection. Whether in athymic or euthymic mice, neither T intraepithelial lymphocytes (IEL) nor cryptopatch cells (reported to contain precursors of IEL) displayed fluorescence indicating recent RAG protein synthesis. Newly made T cells migrate from the mesenteric node into the thoracic duct lymph to reach the gut mucosa. In euthymic mice, this extrathymic pathway is totally repressed, except in conditions of severe lymphocytic depletion. Thus, in normal animals, all gut T IEL, including CD8αα+ cells, are of thymic origin, CD8αα+ TCRαβ+ IEL being the likely progeny of double negative NK1-1− thymocytes, which show polyclonal Vα and Vβ repertoires.
The Poxvirus Protein A52R Targets Toll-like Receptor Signaling Complexes to Suppress Host Defense
Authors: Harte Mary T. , Haga Ismar R. , Maloney Geraldine , Gray Pearl , Reading Patrick C. , Bartlett Nathan W. , Smith Geoffrey L. , Bowie Andrew , O'Neill Luke A.J.
Published: February 2003

Toll-like receptors (TLRs) are crucial in the innate immune response to pathogens, in that they recognize and respond to pathogen associated molecular patterns, which leads to activation of intracellular signaling pathways and altered gene expression. Vaccinia virus (VV), the poxvirus used to vaccinate against smallpox, encodes proteins that antagonize important components of host antiviral defense. Here we show that the VV protein A52R blocks the activation of the transcription factor nuclear factor κB (NF-κB) by multiple TLRs, including TLR3, a recently identified receptor for viral RNA. A52R associates with both interleukin 1 receptor–associated kinase 2 (IRAK2) and tumor necrosis factor receptor–associated factor 6 (TRAF6), two key proteins important in TLR signal transduction. Further, A52R could disrupt signaling complexes containing these proteins. A virus deletion mutant lacking the A52R gene was attenuated compared with wild-type and revertant controls in a murine intranasal model of infection. This study reveals a novel mechanism used by VV to suppress the host immunity. We demonstrate viral disabling of TLRs, providing further evidence for an important role for this family of receptors in the antiviral response.
Immunotherapy of Cytotoxic T Cell–resistant Tumors by T Helper 2 Cells
Authors: Mattes Joerg , Hulett Mark , Xie Wei , Hogan Simon , Rothenberg Marc E. , Foster Paul , Parish Christopher
Published: February 2003

Currently most attempts at cancer immunotherapy involve the generation of CD8+ cytotoxic T lymphocytes (CTLs) against tumor-associated antigens. Many tumors, however, have been immunoselected to evade recognition by CTLs and thus alternative approaches to cancer immunotherapy are urgently needed. Here we demonstrate that CD4+ T cells that recognize a secreted tumor-specific antigen and exhibit a cytokine secretion profile characteristic of Th2 cells, are capable of clearing established lung and visceral metastases of a CTL-resistant melanoma. Clearance of lung metastases by the Th2 cells was found to be totally dependent on the eosinophil chemokine, eotaxin, and partially dependent on the transcription activator signal transducer and activator of transcription 6 (STAT6), with degranulating eosinophils within the tumors inducing tumor regression. In contrast, tumor-specific CD4+ Th1 cells, that recruited macrophages into the tumors, had no effect on tumor growth. This work provides the basis for a new approach to adoptive T cell immunotherapy of cancer.
Restricting Zap70 Expression to CD4+CD8+ Thymocytes Reveals a T Cell Receptor–dependent Proofreading Mechanism Controlling the Completion of Positive Selection
Authors: Liu Xiaolong , Adams Anthony , Wildt Kathryn F. , Aronow Bruce , Feigenbaum Lionel , Bosselut Rémy
Published: February 2003

Although T cell receptor (TCR) signals are essential for intrathymic T cell–positive selection, it remains controversial whether they only serve to initiate this process, or whether they are required throughout to promote thymocyte differentiation and survival. To address this issue, we have devised a novel approach to interfere with thymocyte TCR signaling in a developmental stage-specific manner in vivo. We have reconstituted mice deficient for Zap70, a tyrosine kinase required for TCR signaling and normally expressed throughout T cell development, with a Zap70 transgene driven by the adenosine deaminase (ADA) gene enhancer, which is active in CD4+CD8+ thymocytes but inactive in CD4+ or CD8+ single-positive (SP) thymocytes. In such mice, termination of Zap70 expression impaired TCR signal transduction and arrested thymocyte development after the initiation, but before the completion, of positive selection. Arrested thymocytes had terminated Rag gene expression and up-regulated TCR and Bcl-2 expression, but failed to differentiate into mature CD4 or CD8 SP thymocytes, to be rescued from death by neglect or to sustain interleukin 7Rα expression. These observations identify a TCR-dependent proofreading mechanism that verifies thymocyte TCR specificity and differentiation choices before the completion of positive selection.
Activation of Dendritic Cells through the Interleukin 1 Receptor 1 Is Critical for the Induction of Autoimmune Myocarditis
Authors: Eriksson Urs , Kurrer Michael O. , Sonderegger Ivo , Iezzi Giandomenica , Tafuri Anna , Hunziker Lukas , Suzuki Shinobu , Bachmaier Kurt , Bingisser Roland M. , Penninger Josef M. , Kopf Manfred
Published: February 2003

Dilated cardiomyopathy, resulting from myocarditis, is the most common cause of heart failure in young patients. We here show that interleukin (IL)-1 receptor type 1–deficient (IL-1R1−/−) mice are protected from development of autoimmune myocarditis after immunization with α-myosin-peptide(614–629). CD4+ T cells from immunized IL-1R1−/− mice proliferated poorly and failed to transfer disease after injection into naive severe combined immunodeficiency (SCID) mice. In vitro stimulation experiments suggested that the function of IL-1R1−/−CD4+ T cells was not intrinsically defect, but their activation by dendritic cells was impaired in IL-1R1−/− mice. Accordingly, production of tumor necrosis factor (TNF)-α, IL-1, IL-6, and IL-12p70 was reduced in dendritic cells lacking the IL-1 receptor type 1. In fact, injection of immature, antigen-loaded IL-1R1+/+ but not IL-1R1−/− dendritic cells into IL-1R1−/− mice fully restored disease susceptibility by rendering IL-1R1−/− CD4+ T cells pathogenic. Thus, IL-1R1 triggering is required for efficient activation of dendritic cells, which is in turn a prerequisite for induction of autoreactive CD4+ T cells and autoimmunity.