bluuebunny/crossref_metadata_2025 huggingface dataset:
How Does Endotoxin Trigger Inflammation in Otitis Media With Effusion?
Authors: Schousboe Lars Peter , Ovesen Therese , Eckhardt Lars , Rasmussen Lars Melholt , Pedersen Christian Brahe
Published: November 2003

Objectives The relationship among microorganisms, endotoxin, and inflammatory mediators in otitis media with effusion (OME) was examined.

Study Design Analysis of 152 middle ear effusions aspirated at the time of ventilation tube insertion from children with OME.

Methods Effusion samples were cultured for pathogenic bacteria. The two primary cytokines, interleukin‐1β (IL1β) and tumor necrosis factor (TNFα), and the adhesion molecules, intercellular and vascular adhesion molecule (ICAM‐1 and VCAM‐1), were quantified using the enzyme‐linked immunosorbent assay (ELISA) technique. Endotoxin concentration was measured with a limulus amebocyte lysate assay, and total protein concentration was quantified using the Biorad microassay.

Results The cultures of pathogenic bacteria were positive in 33 of the 152 effusions (22%), which contained more endotoxin and more of the primary cytokines than the 119 culture‐negative effusions. Endotoxin and the primary cytokines were positively correlated, both in the whole material and in the sterile effusions alone. The adhesion molecules were positively correlated with each other, but not with endotoxin or the primary cytokines.

Conclusions We found a positive correlation between endotoxin and the primary cytokines TNFα and IL1β in culture‐positive OME effusions as well as in culture‐negative ones, suggesting endotoxin‐induced local production of TNFα and IL1β in the middle ear. ICAM‐1 and VCAM‐1 were also present in the middle ear, but their concentrations were not directly correlated to endotoxin or the primary cytokines.
Nitric Oxide Contributes to Control of Effusion in Experimental Otitis Media
Authors: Ryan Allen F. , Bennett Thecla
Published: November 2003

Objectives/Hypothesis Nitric oxide (NO) is a small, short‐lived free radical involved in cellular signaling and known to play a role in inflammation. It is generated on demand by the enzyme nitric oxide synthase (NOS) on arginine. We have previously found that mRNA encoding NOS is produced in the middle ear during otitis media. The role of NO was therefore explored in an experimental model of immune‐mediated otitis media.

Study Design and Methods Guinea pigs were systemically immunized and later challenged in the middle ear with the same antigen. One ear of each animal was challenged with antigen alone. In the opposite ear, antigen was combined with a potent inhibitor of NOS, NG‐amino‐L‐arginine (L‐NAA). After survival for 24, 48, or 72 hours, the middle ears were evaluated for otitis media.

Results Inhibition of NOS resulted in significantly increased middle ear effusion at all three time periods. This increase was blocked by the addition of excess l‐arginine, which bypasses the inhibitory effects of L‐NAA. The infiltration of cells into the middle ear lumen and the hyperplasia of the middle ear mucosa were unaffected by L‐NAA administration.

Conclusions The results suggest that NO is involved in regulating the permeability of the middle ear vascular, the transudation of serum into the middle ear mucosa, and/or the movement of extracellular fluid across the middle ear mucosal epithelium.
Alternative Voice After Laryngectomy Using a Sound‐Producing Voice Prosthesis
Authors: van der Torn M. , de Vries M. P. , Festen J. M. , Verdonck‐de Leeuw I. M. , Mahieu H. F.
Published: November 2003

Objective To improve the voice quality of female laryngectomees and/or laryngectomees with a hypotonic pharyngoesophageal (PE) segment by means of a pneumatic artificial source of voice incorporated in a regular tracheoesophageal (TE) shunt valve.

Study Design Experimental, randomized, crossover trial.

Methods The new sound source consists of a single silicone lip, which performs an oscillatory movement driven by expired pulmonary air flowing along the outward‐striking lip through the TE shunt valve. A prototype of this pneumatic sound source is evaluated in vitro and in six laryngectomees. In vivo evaluation includes speech rate, maximal phonation time, perceptual voice evaluation of read‐aloud prose by an expert listener, speech intelligibility measurements with 12 listeners, and self‐assessment by the patients. Moreover, extensive acoustical and aerodynamic in vivo registrations are performed using a newly developed data acquisition system.

Results The current prototype seems beneficial in female laryngectomees with a hypotonic PE segment only. For them the sound‐producing voice prosthesis improves voice quality and increases the average pitch of voice, without decreasing intelligibility or necessitating other pressure and airflow rates than regular TE shunt speech. Pitch regulation of this prosthetic voice is possible, yet limited.

Conclusions The mechanism is feasible and does not result in unacceptable airflow resistance. For this new mechanism of alaryngeal voice to become an established technique for postlaryngectomy voice restoration, a voice suitably pitched for male laryngectomees has to be generated and a large part of the melodic and dynamic range of the sound source has to be attainable within physiological airflow rates.
Submandibular Gland Transfer: A New Method of Preventing Radiation‐Induced Xerostomia
Authors: Seikaly Hadi , Jha Naresh , McGaw Timothy , Coulter Linda , Liu Richard , Oldring Derald
Published: November 2003

Objective Radiation‐induced xerostomia is a significant morbidity of radiation therapy in the management of patients with head and neck cancers. We have recently reported a method of transfer of one submandibular gland to the submental space in a small pilot series of eligible surgical patients. The submental space was shielded during postoperative radiation therapy. The transferred gland continued to function after the completion of radiation therapy and none of the patients developed xerostomia. The purpose of this article is to present the technique of submandibular gland transfer in detail and to evaluate the postoperative survival and function of the transferred submandibular glands.

Design Prospective clinical trial.

Methods The submandibular gland was transferred on eligible patients as part of their surgical intervention. The patients were followed clinically, with salivary flow and radioisotope studies.

Results We performed the surgical transfer of the submandibular salivary gland in 24 of 25 patients placed on the protocol. All the glands survived transfer and functioned well postoperatively as demonstrated on the salivary flow and the radioisotope studies. The surgical transfer was relatively simple and added 45 minutes to the surgical procedure. There were no complications attributed to the submandibular gland transfer.

Conclusions We have successfully demonstrated that the submandibular gland can be surgically transferred to the submental space with its function preserved. The gland seems to continue functioning even after radiation therapy with the appropriate shielding. This surgical transfer procedure has the potential to change the way we currently manage patients with head and neck cancer.
Technetium 99m Single Positron Emission Computed Tomography Scanning for Assessing Mandible Invasion in Oral Cavity Cancer
Authors: Imola Mario J. , Gapany Markus , Grund Frank , Djalilian Hamid , Fehling Sharon , Adams George
Published: November 2003

Objectives To study the accuracy of single positron emission computed tomography (SPECT) scanning and compare its results to clinical examination, Panorex, and computed tomography (CT) scanning with respect to determining mandibular invasion by oral cavity and oropharyngeal cancer, and to define the role of SPECT scanning in the preoperative assessment of oromandibular cancer.

Study Design Prospective study of 38 patients who underwent technetium 99m SPECT scanning as part of their preoperative clinical assessment for cancer at risk of invading the mandible. All patients underwent partial or segmental mandibulectomy as part of their surgical management.

Methods A data protocol was used to tabulate patient demographics, tumor characteristics and results of preoperative tests as patients were enrolled into the study. Following surgical treatment, these data were correlated with histopathological findings. Detailed analysis was performed to assess the tabulated data.

Results The SPECT scanning demonstrated an 87% overall accuracy in predicting bone invasion compared with 71% for clinical examination, CT scanning, and Panorex x‐rays. The SPECT scanning was significantly more sensitive (95%) than either CT scans (55%) or Panorex x‐rays (50%). Notably SPECT scanning demonstrated a considerable improvement in specificity (72%) compared with conventional radionuclide scanning. Although not as specific as CT scanning or plain films, SPECT scanning was significantly more effective in ruling out disease than was clinical examination.

Conclusions Preoperative SPECT scanning used in combination with clinical examination, CT scanning, and Panorex x‐rays to assess patients at risk for mandible involvement by oral cavity cancer can improve the accuracy of predicting bone invasion and help in appropriate treatment planning so as to safely reduce the proportion of disease‐free jaws resected.
Pretreatment With Portal Venous Ultraviolet B Irradiated Donor Alloantigen Promotes Donor‐Specific Tolerance to Rat Nerve Allografts
Authors: Genden Eric M. , Mackinnon Susan E. , Yu Samuel , Hunter Daniel A. , Flye M. Wayne
Published: November 2003

Objective To determine if a single intraportal inoculation of ultraviolet B‐irradiated (UVB) donor splenocytes can prevent nerve allograft rejection and confer donor‐specific immunotolerance to rat nerve allograft segments.

Methods Age‐matched, class I and class II major histocompatibility complex (MHC) mismatched Buffalo (RT1b) rats were transplanted with a syngeneic nerve isograft, a Lewis (RT1l) nerve allograft, or a Brown‐Norway (RT1n) rat nerve allograft segment. Control Buffalo rats in group I received a 3.0‐cm Lewis (RT11) sciatic‐posterior tibial interposition nerve allograft without pretreatment;group II Buffalo rats received a syngeneic Buffalo nerve isograft without pretreatment. Group III Buffalo recipients were inoculated with 2.5 × 107 UVB‐irradiated Lewis donor splenocyte cells by portal venous administration 7 days before transplantation with a 3.0‐cm sciatic‐posterior tibial nerve allograft from a Lewis (RT11) or a third party Brown‐Norway rat (RT1n) donor (group IV). Nerve graft regeneration was assessed with walking track analysis, nerve conduction studies, retrograde neural tracing, nerve graft histology, and morphometry. Recipient immune tolerance was assessed through in vitro immunological assessment.

Results Pretreatment with UVB‐irradiated donor splenocytes 7 days before transplantation prevented nerve allograft rejection. Pretreated animals receiving a nerve allograft recovered limb function, and demonstrated morphological, histological, and electrophysiologic parameters of nerve regeneration similar to that measured in rats receiving a nerve isograft. In vitro immunological assessment by mixed lymphocyte culture (MLC), cytotoxic T lymphocyte (CTL) assay, limiting dilution analysis (LDA) of helper (pTH) and cytotoxic (pCTL) precursor frequencies, and IL‐2 production demonstrated a marked donor‐specific suppression in allografted animals pretreated with intraportal UVB‐irradiated donor splenocytes. These assessments correlated with indefinite acceptance of donor nerve allografts.

Conclusions A single pretreatment with a single intraportal dose of UVB‐modified donor antigen specifically induces tolerance to peripheral nerve allografts in rats.
The Expression of Apoptosis‐Related Proteins in the Aged Cochlea of Mongolian Gerbils
Authors: Alam Shaheen Ara , Oshima Takeshi , Suzuki Masaaki , Kawase Tetsuaki , Takasaka Tomonori , Ikeda Katsuhisa
Published: November 2003

Objective Apoptotic changes have been reported in the aged gerbil cochlea and are speculated to be one of the principal causes of presbyacusis. The objective of the study was to determine the underlying mechanism of apoptotic change in the aged gerbil cochlea.

Study Design Prospective controlled animal study.

Methods We examined the tissue distribution of bcl‐2, bax, caspase‐3p20, and caspase‐3p32 using immunohistochemical techniques in the young and aged gerbil cochlea, together with the measurement of the distortion product of otoacoustic emission (DPOAE).

Results Aged gerbils showed a significant reduction of the DPOAE amplitude as compared with that of the young gerbils, suggesting a disturbance of the auditory function in the aged cochlea. There was a significant decrease in the number of bcl‐2–positive cells in the aged gerbils. The expression of bax in the aged group was slightly increased but did not significantly differ from that in the young gerbils. A significantly increased number of caspase‐3p20–positive cells was observed in the organ of Corti, spiral ganglion, and lateral wall of cochlea in the aged gerbils as compared with those of the young gerbils. There was no significant difference in the expression levels of caspase‐3p32 between the young and aged groups. In the aged cochlea, the degree of deterioration of DPOAE responses was compatible with those of both the reduction of bcl‐2 and the activation of caspase‐3p20.

Conclusion These data suggest that the suppression of bcl‐2 protein expression may lead to apoptosis‐induced presbyacusis through activation of caspase‐3 in the aged gerbil cochlea.
Expression of p75NTR and Its Associated Protein NADE in the Rat Cochlea
Authors: Sano Hajime , Mukai Jun , Monoo Katsumi , Close Lanny G. , Sato Taka‐Aki
Published: November 2003

Objectives/Hypothesis To investigate the expression of the low‐affinity neurotrophin receptor p75 (p75NTR) and its associated protein NADE in the cochlea of the developing and the adult rat. Studies such as this one will help to predict the functional role of p75NTR and NADE in cochlear development.

Study Design Histochemical evaluation of p75NTR and NADE in the rat cochlea was performed.

Methods Immunohistochemical analysis was used to localize p75NTR and NADE in the rat cochlea at postnatal (PN) days PN0, PN2, PN4, PN6, PN8, PN10, and PN13 and in the adult. Confocal laser scanning microscopy was used to analyze whole‐mount specimens.

Results Immunoreactivity of both p75NTR and NADE was observed in pillar cells. However, these proteins displayed reciprocal expression patterns. Expression of p75NTR was detected at PN0 and PN2, but disappeared after PN4. In contrast, NADE expression was initially detected at PN2 and persisted into adulthood.

Conclusions The neurotrophin receptor p75NTR and NADE have distinct and independent roles in developing and mature cochlea.
Unilateral or Localized Reinke's Edema (Pseudocyst) as a Manifestation of Vocal Fold Paresis: The Paresis Podule
Authors: Koufman James A. , Belafsky Peter C.
Published: November 2003

Background The nosology of free‐edge vocal fold lesions remains imprecise. In particular, the lesion termed pseudocyst remains enigmatic, because its histology is poorly defined and because its etiology is unknown. We define pseudocyst as a discrete, unilateral, localized area of Reinke's edema (without a capsule), usually occurring at the midportion of the free‐edge striking zone.

Objective To report the demographic and clinical findings, as well as discuss our diagnostic and therapeutic strategies, in patients with unilateral Reinke's edema or pseudocyst.

Methodology All patients diagnosed with unilateral Reinke's edema or pseudocyst over a 2‐year period (1998–1999) were identified from the clinical database of the Center for Voice Disorders of Wake Forest University, Winston‐Salem, North Carolina. The record of each patient was retrospectively reviewed.

Results Thirteen patients were identified, 12 of whom were female. The mean age was 36 years. Sixty‐nine percent (9 of 13) had unilateral pseudocyst and 31% (4 of 13) had unilateral Reinke's edema. All patients had documented vocal fold paresis on laryngeal electromyography. The 9 patients with pseudocyst underwent excision of their lesions; 7 had bilateral medialization laryngoplasties, 1 had lipoinjection, and 3 did not have surgical intervention. Significant improvement was noted postoperatively on a self‐administered glottal insufficiency (symptom) index (P <.001).

Conclusion Unilateral Reinke's edema and localized Reinke's edema (pseudocyst) are distinct clinical entities, occurring most frequently in women in their fourth decade. The finding of unilateral Reinke's edema or pseudocyst should alert the clinician to the likelihood of vocal cord paresis. Surgical intervention with medialization laryngoplasty appears to be beneficial.
Classification of Cilio‐Inhibiting Effects of Nasal Drugs
Authors: Merkus Paul , Romeijn Stefan G. , Verhoef J. Coos , Merkus Frans W. H. M. , Schouwenburg Paul F.
Published: November 2003

Objective/Hypothesis Nasal drug formulations are widely used for a local therapeutic effect, but are also used for systemic drug delivery. In the development of new nasal drugs, the toxic effects on the mucociliary clearance and therefore on the ciliated tissue is of importance. In this study, the effect of nasal drugs and their excipients on the ciliary beat frequency (CBF) is investigated.

Study Design Experimental, in vitro.

Methods CBF is measured by a photograph–electric registration method. Excised ciliated chicken trachea tissue is incubated for 15 minutes in the formulation, followed by a reversibility test. To estimate the ciliostatic potential, a classification is given of all tested formulations. According to the CBF, after 60 minutes every drug or excipient could be classified as follows:cilio‐friendly: after 60 minutes the CBF has regained 75% or more of its initial frequency;cilio‐inhibiting: after 60 minutes the CBF has regained between 25% and 75% of its initial frequency; or ciliostatic: after 60 minutes the CBF has regained 25% or less of its initial frequency.

Results Most formulations used are cilio‐friendly or cilio‐inhibiting. Only some are ciliostatic. Preservatives have a major role in the cilio‐inhibiting effect of the drug. Also, other additives can contribute to the toxicity profile of nasal drug formulations.

Conclusion This classification of the cilio‐inhibiting potential of nasal drug formulations is a valuable tool in the design of safe nasal drugs. The number of animal studies in vivo can be reduced substantially by using this in vitro screening technique. This study demonstrates that the effect on ciliary movement of most drug formulations is due to the preservatives and/or additives and mostly not to the drug itself.
Differentiation of Recurrent Nasopharyngeal Carcinoma and Skull Base Osteoradionecrosis by Epstein‐Barr Virus‐Derived Latent Membrane Protein‐1 Gene
Authors: Hao Sheng‐Po , Tsang Ngan‐Ming , Chang Kai‐Ping
Published: November 2003

Objectives In patients with nasopharyngeal carcinoma (NPC), the differentiation between recurrent primary cancer and osteoradionecrosis (ORN) is clinically difficult. Epstein‐Barr virus (EBV)‐derived latent membrane protein‐1 (LMP‐1) has been demonstrated to be highly associated with NPC. The objective of this study is to define the role of the LMP‐1 gene in the differential diagnosis of recurrent NPC and ORN.

Study Design Prospective.

Methods From July 1998 to June 2000, 15 postirradiated patients with NPC who were initially diagnosed to have skull base ORN underwent endoscopic sequestrectomy. The sequestra were examined for the presence of the LMP‐1 gene and cancer.

Results Two of 15 patients had recurrent cancer and only these two patients demonstrated a positive LMP‐1 gene in their surgically removed sequestra. The presence of the LMP‐1 gene in the sequestrum coincided with biopsy‐proven local recurrence.

Conclusions The LMP‐1 gene is a potential marker to differentiate between recurrent NPC and ORN. The presence of the LMP‐1 gene in patients with ORN may indicate local recurrence.
Tracheal Transplantation: Cytological Changes Studied by Scanning and Transmission Electron Microscopy in the Rabbit
Authors: Zagalo Carlos , Grande Nuno R. , dos Santos José Martins , Monteiro Emanuel , Brito José , Aguas Artur P.
Published: November 2003

Objectives Our goal was to offer a comprehensive cytological study of the changes in the trachea after experimental transplantation of the organ.

Study Design Autografting of four tracheal rings was done in rabbits and tracheal samples were observed by electron microscopy from 1 week to 6 months after the surgery was performed.

Methods Transmission and scanning electron microscopy were used to investigate the fine structure of tracheal samples of rabbits submitted to autotransplantation, and quantitative methods were used to compare several cytological parameters of the different groups of animals.

Results We found that tracheal autografting was associated with acute injury of ciliated cells expressed by loss of more than 90% of cilia density on the tracheal epithelium 1 week after the transplantation was performed. The loss of cilia was balanced by an increase in mucous cells present on the tracheal lumen. Recovery of ciliated cells was observed 1 month after the tracheal autografting was performed. In contrast, only mild cytological modifications were seen in the cartilage tissue of the autografted trachea during the first weeks of transplantation; the structural alterations of the cartilage progressed up to the third month after transplantation, resulting in a moderate tracheal stenosis.

Conclusions The data indicate that 1) autotransplantation of four tracheal rings is a viable surgical procedure; 2) tracheal grafting causes severe acute changes of the epithelium that are, however, reversible in nature; whereas 3) the initial mild alterations induced by the autografting in the cartilage may evolve into tracheal stenosis.

* Although the authors carried out the study they planned, it appears that their experiment was not well thought out from the onset. The clinical goal is to be able to transplant segments of trachea of two or more tracheal rings. In this procedure, as in most true transplants, one must expect some element of ischemia time, temperature changes (usually hypothermia), alterations in the dynamics of blood flow resulting from the inevitable sympathectomy, and the significant effects of lymphatic disruption. Virtually none of these effects were simulated in the “autotransplantation” carried out in this study. Thus, the study provides us with little practical clinical information and is useful primarily as a preliminary step in studying the effects of true transplantation.—Reviewer's Commentary
Two‐Step External Ear Canal Construction in Atresia as Part of Auricular Reconstruction
Authors: Siegert Ralf , Weerda Hilko
Published: November 2003

Objectives One of the common complications of atresia surgery is restenosis of the surgically constructed external ear canal. To avoid this complication, a new two‐step technique of creating an external ear canal was developed and evaluated.

Study Design Prospective clinical evaluation.

Patients and Methods Thirty‐six patients with third‐degree microtia and aural atresia have been treated this way. In the first step, the canal is drilled into the petrous bone, a Silastic cylinder is inserted and wrapped into pieces of cartilage and bone dust. In the second step several months later, the implant is removed and a slightly smaller tube covered with a split thickness skin graft is inserted.

Results E‐cept the first three patients operated with a slightly different technique, none of the following 33 patients showed a severe restenosis. Instead, all had a nice, smooth e‐ternal ear canal.

Conclusion With this two‐step technique of creating a new e‐ternal ear canal in atresia, we could avoid one of the major complications of this kind of surgery. The e‐ternal ear canal is either necessary for the reconstructed middle ear or it can be used to adapt a (behind or in the ear) hearing aid. By integrating this technique into a three‐step concept for auricular reconstruction, the patient does not need any additional operation, and his or her rehabilitation from ear malformation can be enhanced.
Single‐Stage Adult Laryngotracheal Reconstruction Without Stenting
Authors: Rhee John S. , Toohill Robert J.
Published: November 2003

Objectives/Hypothesis To present the indications, surgical technique, and results of single‐stage laryngotracheal reconstruction (SSLTR) without stenting for laryngotracheal stenosis (LTS) in adults. Various open surgical techniques have been previously described for LTS in adults; however, these techniques usually involve placement of intraluminal stents. The practice of early extubation without stenting is common for pediatric SSLTR. The success of this technique in the pediatric population has led to a trial of the same technique in selected cases of adult LTS.

Study Design Retrospective review.

Methods A retrospective review was conducted on 15 patients with glottic, subglottic, or tracheal stenosis or a combination of these, who underwent SSLTR with composite nasal septal grafts or costal cartilage grafts without stenting.

Results All patients were extubated or decannulated 1 to 7 days after surgery. Three of the 15 patients had no further procedures. Three patients had a second SSLTR to repair stenosis at a different level with no further difficulties. Eight patients had additional endoscopic airway procedures after extubation or decannulation, and one patient died in the immediate postoperative period. All 14 surviving patients are decannulated and well at the time of writing.

Conclusion For LTS in selected adult cases, SSLTR without stenting is a viable option. Indications, surgical technique, and complications are presented.
Labyrinthine Fistula: An Unreported Complication of the Grote Prosthesis
Authors: Gadre Arun K. , Hammerschlag Paul E.
Published: November 2003

Objectives To alert the otological surgeon that labyrinthine fistula is a rare and avoidable complication of the Grote hydroxyapatite ceramic external auditory canal (EAC) prosthesis. The reasons for its causation and strategies to prevent its formation are discussed.

Study Design Case study and retrospective review of the literature.

Methods Labyrinthine fistula that occurred after the use of the Grote hydroxyapatite ceramic EAC prosthesis is presented. The literature is reviewed retrospectively for various methods of reconstruction of the EAC following canal wall down mastoidectomy. Strategies and principles are outlined to avoid complications associated with reconstruction of the mastoid and EAC.

Results The Grote hydroxyapatite (HA) prosthesis is a reliable prosthesis for reconstruction of the external auditory canal (EAC) in the absence of a draining mastoid cavity or cholesteatoma and with adequate soft tissue cover. Contact of the medial end of the prosthesis with the lateral semicircular canal must be avoided. Immobilization or rigid fixation and avoidance of infection are essential for optimal prosthesis stability and osseointegration. Covering the prosthesis with vascularized soft tissue appears to be important for the achievement of a successful reconstruction.

Conclusion The Grote prosthesis is safe and effective provided it does not contact the lateral semicircular canal, is stabilized, and covered by vesicular tissue, in the absence of infection.
Radial Forearm Free Flap Pharyngoesophageal Reconstruction
Authors: Azizzadeh Babak , Yafai Sherry , Rawnsley Jeffrey D. , Abemayor Elliot , Sercarz Joel A. , Calcaterra Thomas C. , Berke Gerald S. , Blackwell Keith E.
Published: November 2003

Objectives This study evaluates the outcome of pharyngoesophageal reconstruction using radial forearm free flaps with regard to primary wound healing, speech, and swallowing in patients requiring laryngopharyngectomy.

Study Design Retrospective review in the setting of a tertiary, referral, and academic center.

Patients and Methods Twenty patients underwent reconstruction of the pharyngoesophageal segment using fasciocutaneous radial forearm free flaps.

Results All free flap transfers were successful. An oral diet was resumed in 85% of the patients after surgery. Postoperative pharyngocutaneous fistulas occurred in 4 patients (20%) with 3 resolving spontaneously. Distal strictures also occurred in 20% of the patients. Five patients who underwent tracheoesophageal puncture achieved useful speech.

Conclusions Advantages of radial forearm free flaps for microvascular pharyngoesophageal function include high flap reliability, limited donor site morbidity, larger vascular pedicle caliber, and the ability to achieve good quality tracheoesophageal speech. The swallowing outcome is similar to that achieved after jejunal flap pharyngoesophageal reconstruction. The main disadvantage of this technique relates to a moderately high incidence of pharyngocutaneous fistulas, which contributes to delayed oral intake in affected patients.
Combination Nonviral Cytokine Gene Therapy for Head and Neck Cancer
Authors: Li Daqing , Zeiders Jacob W. , Liu Shixi , Guo Ming , Xu Yun , Bishop Jeffrey S. , O'Malley Bert W.
Published: November 2003

Objective To establish the feasibility and efficacy of combination nonviral murine interferon‐α (mIFN‐α) and murine interleukin‐2 (mIL‐2) or murine interleukin‐12 (mIL‐12) gene therapy for head and neck squamous cell carcinoma in a murine model.

Study Design Randomized controlled studies in a murine head and neck cancer model were performed to assess antitumor responses, secondary cytokine expression, and both natural killer (NK) cell and cytolytic T‐cell (CTL) activity.

Methods Tumors were established in the floor of mouth in C3H/HeJ immunocompetent mice. Established tumors were directly injected with polymer‐formulated murine interferon‐α (mIFN‐α), lipid‐formulated mIL‐2, and polymer‐formulated mIL‐12 alone or in combination. Primary and secondary cytokine expression, NK cell activity, and CTL activity were assayed.

Results The use of mIFN‐α gene therapy in combination with either mIL‐2 or mIL‐12 resulted in significant antitumor effects as compared with each of the single cytokine and control treatment groups (P = .002). Increased levels of NK cell activity and tumor specific CD8+ cytotoxic T‐lymphocyte activity were found in the combination mIFN‐α and mIL‐2 or mIL‐12 groups. Augmented immune responses correlated with clinical antitumor effects.

Conclusions The present study demonstrates that mIL‐2 or mIL‐12 augments tumor inhibition from mIFN‐α and increases activation of NK and CD8+ T cells. These data support further investigation of polymer and lipid mediated delivery of cytokine genes for head and neck cancer.
Endolymphatic Hydrops in Asymptomatic Ears in Unilateral Ménière's Disease
Authors: Friedrichs Ilka , D. Thornton Arthur R.
Published: November 2003

Objectives/Hypothesis The aim of our study was the objective assessment of endolymphatic hydrops in asymptomatic ears in unilateral Ménière's disease with a noninvasive electrophysiological test and investigation of significant clinical signs. The null hypothesis was that there would be no signs of endolymphatic hydrops in the asymptomatic ear.

Study Design Prospective study using the traveling wave velocity test for endolymphatic hydrops.

Methods The traveling wave velocity test was used in conjunction with standard audiological tests to investigate both ears of 181 Ménière's patients attending the Medical Research Council Institute of Hearing Research in Southampton, United Kingdom. The test uses derived auditory brainstem responses to estimate the velocity of the cochlear traveling wave that is altered in endolymphatic hydrops. Ménière's disease was assessed using Arenberg's five staging criteria. Significant correlations were evaluated using standard statistical methods.

Results Of 100 patients with clinically unilateral Ménière's disease, 27% showed evidence of endolymphatic hydrops in their asymptomatic ear. There was a significant correlation between signs of hydrops and the mean air‐conduction threshold at 500 Hz.

Conclusions We recommend that a full assessment of incipient disease in the asymptomatic ear in unilateral Ménière's disease should be undertaken before offering any treatment options to patients. Any suspicion of early disease in the asymptomatic ear in unilateral Ménière's disease should lead to full electrophysiological assessment to assess the evidence of endolymphatic hydrops in that ear.
Growth Factors Influence Growth and Differentiation of the Middle Ear Mucosa
Authors: Palacios Sean D. , Oehl Heinz J. , Rivkin Alexander Z. , Aletsee Christoph , Pak Kwang , Ryan Allen F.
Published: November 2003

Objective Otitis media is a major cause of morbidity in pediatric and adult patients. This inflammatory condition is characterized by mucosal hyperplasia that is thought to be mediated by the complex actions of growth factors and their respective receptors. It was the purpose of this study to determine which growth factors might be responsible for the growth and differentiation of the middle ear epithelium during otitis media.

Study Design The effect of several growth factors on the expansion and differentiation of normal middle ear mucosa was evaluated in tissue culture.

Materials and Methods Explants of normal rat middle ear mucosa were exposed in vitro to six different growth factors known to influence epithelial cells in other tissues: epidermal growth factor, amphiregulin, betacellulin, heregulin‐α, keratinocyte growth factor, and hepatocyte growth factor.

Results After 12 days, the growth and level of cytokeratin expression were analyzed for each of the explant outgrowths. Each factor appeared to have a significant, concentration‐dependent effect on either the growth or differentiation of the cultured middle ear epithelial cells.

Conclusion The results suggest that several of the tested growth factors may play a significant role in controlling hyperplasia of the middle ear mucosa during otitis media.
Rise of Medical Specialization and Organizations Affecting Otolaryngology
Authors: Goldstein Jerome C.
Published: November 2003

As we enter the third millennium, there are in the United States 24 medical specialties recognized by the American Board of Medical Specialties. The majority of the members of each of these specialties have their education, training, and knowledge “certified” by an examining board unique to their specialty. One hundred years ago virtually none of the foregoing existed. At the turn of the 20th century, nearly all physicians practiced all of medicine. How and why did this evolution occur and what controls evolved to contain this? The goal of this presentation is to review the rise of medical specialties and the board examination system and describe some of the many organizations, often known by acronyms, which deal with this now complex architecture.
Combined External and Endoscopic Frontal Sinusotomy With Stent Placement: A Retrospective Review
Authors: Benoit Craig M. , Duncavage James A.
Published: November 2003

Objectives To examine the long‐term results of combined external and endoscopic frontal sinusotomy using frontal sinus stents and to compare our results with those reported for the endoscopic Lothrop procedure.

Study Design We performed a retrospective review of 40 patients with chronic frontal sinusitis refractory to medical management who underwent a total of 62 combined external and endoscopic frontal sinusotomies with stent placement. All procedures were performed by the senior author at Vanderbilt University Medical Center.

Main Outcome Measures Postoperative nasofrontal duct patency and subjective patient improvement based on the last clinical examination.

Results The overall patency rate of the nasofrontal duct was 79% (95% confidence interval [CI] of ±10%.) The overall subjective patient improvement rate was 78% (95% CI of ±14%.). The average length of stent placement was 5 weeks. The mean patient follow‐up time was 12 months. There were no surgical complications. The nasofrontal duct patency rate and patient improvement rate from our study did not differ statistically from results reported by other authors using the endoscopic Lothrop procedure.

Conclusion We have found endoscopic frontal sinusotomy, in conjunction with external frontal sinusotomy and placement of frontal sinus stents, to be as effective in obtaining frontal sinus patency rates and overall patient improvement rates as the endoscopic Lothrop procedure.
Intratemporal Facial Nerve Neuroma: Anatomical Location and Radiological Features
Authors: Kertesz Thomas R. , Shelton Clough , Wiggins Richard H. , Salzman Karen L. , Glastonbury Christine M. , Harnsberger Ric
Published: November 2003

Objectives To present the imaging findings and anatomical locations of a series of 88 facial nerve neuromas from two centers over a 30‐year period. We describe the salient radiological features of neuromas in each anatomical location and outline the ways in which modern imaging techniques have altered our perception of this entity.

Study Design A retrospective review of tumors presenting to two tertiary care referral institutions since 1970.

Methods The charts and available imaging of patients with the diagnosis of facial neuroma were reviewed. These patients presented to the House Ear Clinic between 1970 and 1994 and to the University of Utah Medical Center (Salt Lake City, UT) between 1986 and August 2000. We examined anatomical location to determine patterns of tumor presentation and compared the findings before and after the era of magnetic resonance imaging (MRI).

Results All segments of the facial nerve were represented. Overall, multiple‐segment tumors were almost twice as common (63.6%) as single‐segment tumors (36.4%). Before the advent of MRI, all segments of the nerve from the cerebellopontine angle to the tympanic portion were almost equally represented (29.5%–36.3%). After MRI, the geniculate ganglion (68.2%) and labyrinthine portion (52.3%) were by far the most commonly affected areas. Before MRI, there were, on average, 1.89 segments involved per tumor. After MRI, this average number increased to 2.57 segments per tumor. Radiologically, the high‐resolution computed tomography and MRI features cannot be generalized. Rather, the imaging features depend on which segments are involved. This is because of the variation in the surrounding anatomical landscape of the facial nerve in its course through the temporal bone.

Conclusion The more sensitive imaging provided by newer radiological techniques has altered our perception of facial neuroma. It has provided us with an increased ability to diagnose and fully evaluate this neoplasm preoperatively, allowing improved patient counseling and surgical planning.
Bone‐Anchored Hearing Aid Quality of Life Assessed by Glasgow Benefit Inventory
Authors: Arunachalam Perumkulam S. , Kilby David , Meikle David , Davison Tom , Johnson Ian J. M.
Published: November 2003

Objective/Hypothesis The bone‐anchored hearing aid (BAHA) is a well established mode of treatment and many studies show the audiological benefit, but none has assessed the benefit to the quality of life of patients. This study uses the validated Glasgow Benefit Inventory to quantify the changes in quality of life.

Study Design Retrospective questionnaire study.

Methods Sixty consecutive patients receiving treatment with BAHA were enrolled in the study. The male/female ratio was 1.26 to 1; mean patient age was 45 years. The most common indication was hearing loss secondary to mastoid disease and surgery followed by congenital atresia and chronic discharge from the ear.

Results The response rate was 85%, which is high and adds weight to the results. The general benefit score was +34 (range, +27–+48), which is comparable to middle ear surgery but just below benefit from cochlear implantation. The social benefit was +21 (range, +12–+37) with only +10 (range, +2–+26) for the physical score. This pattern mirrors that reported for other ear interventions. Maximum benefit was noted in patients with congenital atresias followed by discharging mastoid cavities.

Conclusion This study is the first to demonstrate significant quality of life benefit from BAHA surgical intervention as measured by the Glasgow Benefit Inventory.
Degranulation of Mast Cells Provokes a Massive Inflammatory Reaction in the Tympanic Membrane
Authors: Eriksson Per Olof , Hellström Sten
Published: November 2003

Objective The pars flaccida is extremely rich in mast cells. On stimulation the mast cells release preformed and de novo synthesized inflammatory substances. The purpose of this study was to examine how these mast cell substances provoke inflammatory changes in the tympanic membrane.

Study Design In vivo, murine model.

Methods In a rat model, the mast cell secretagogue compound 48/80 was applied locally to the tympanic membrane on 4 consecutive days and the ensuing inflammatory changes were evaluated by otological, light, and electron microscopy 3, 6, 9, 12, 18, 24, 36, and 48 hours and 4, 6, and 8 days later.

Results Degranulation of the mast cells occurred within 3 hours of applying compound 48/80. Release of the mast cell substances coincided with an inflammatory event characterized by a two‐stage reaction: an edema stage, peaking 6 hours after application, followed by a massive invasion of inflammatory cells, peaking at 24 and 48 hours. Pars flaccida and pars tensa were both involved, pars flaccida showing the earliest changes. Pars tensa exhibited the same biphasic reaction as pars flaccida, but approximately 6 hours later.

Conclusions The mast cells of the pars flaccida have the capacity to elicit an intense inflammation of the tympanic membrane. The biphasic reaction pattern resembles that observed in experimental otitis media, suggesting involvement of the mast cells in this inflammatory condition of the middle ear.
Comparison of Antral Tap With Endoscopically Directed Nasal Culture
Authors: Casiano Roy R. , Cohn Stephen , Villasuso Eloy , Brown Margaret , Memari Faramarz , Barquist Erik , Namias Nicholas
Published: November 2003

Objectives/Hypothesis The diagnosis of acute bacterial rhinosinusitis continues to generate controversy in critically ill patients. The efficacy of endoscopically directed cultures in these patients is unknown. We compared antral tap (AT) with endoscopic tissue culture (ETC) of the osteomeatal complex in an intensive care unit (ICU) setting.

Methods Twenty patients admitted to a surgical/trauma ICU were evaluated by AT and ENB for the presence of rhinosinusitis. All patients had 1) a fever of unknown origin without resolution on empiric antibiotic therapy for ≥48 hrs; 2) other sources of fever ruled out; 3) computed tomography scan evidence of mucoperiosteal thickening ± sinus air/fluid levels; and 4) attempt at conservative treatment with topical decongestants and removal of all nasal intubation. Microbiologic data were collected and analyzed for any statistical difference between groups.

Results A total of 29 sides underwent simultaneous tap and endoscopically directed tissue culture. The mean age was 40 years (range, 23–77 y) with 85% being males. Fifteen of 20 (75%) patients in the AT group were culture‐positive. Of the 49 isolates from the AT, 55% yielded Gram‐negative bacilli (Acinetobacter sp. 37%) and 45% yielded Gram‐positive cocci. The ETC group was culture‐positive in 18 of 20 (90%) patients. Of the 52 isolates from the ETC, Gram‐negative bacilli were found in 58% (Acinetobacter sp. 33%) and 42% yielded Gram‐positive cocci. The ETCs were culture‐positive in all but 1 patient with positive taps. There appeared to be a concordance between AT and ETC in 60% of the patients. In five instances (25%), results of the AT or ETC changed ICU management. Two patients ultimately required sinus surgery.

Conclusions Sinus taps and/or endoscopically directed tissue cultures led to a change in ICU care in 25% of ICU patients studied. In patients with fever of unknown origin and computed tomography evidence of sinusitis, an antral tap continues to provide important information concerning maxillary sinusitis. However, ETC may give as good a representation of the microbiology and secondary inflammatory changes responsible for bacterial ICU rhinosinusitis causing fever of unknown origin. Further study on a larger group of patients is needed.
Sinusitis Complicated by Meningitis: Current Management
Authors: Younis Ramzi T. , Anand Vinod K. , Childress Curt
Published: November 2003

Objectives Meningitis is the most common intracranial complication of sinusitis. We review the incidence, current management, outcomes, and complications of this serious infection. Our study also examines the evolving roles of endoscopic sinus surgery and other new therapeutic and diagnostic modalities in our armamentarium.

Study Design A retrospective chart review was performed at a tertiary academic medical center of all patients diagnosed with sinusitis with complications between January 1985 and December 1999.

Methods The patients were divided into two main groups: intracranial versus orbital complications. Meningitis was the most common intracranial complication. Data on patients with sinusitis and meningitis were collected and analyzed.

Results Intracranial complications were present in 39 of 82 patients whereas orbital complications were noted in 43 patients. Twenty‐one of the 39 intracranial complications were meningitis. The most common computed tomography finding in adults (54%) was sphenoid sinusitis. All patients with AIDS (6 of 21) had unique cryptococcus meningitis. In patients without AIDS, the most common organism was Streptococcus pneumoniae (10 of 21). The most common sequela was seizure disorder (4 of 21). Endoscopic sinus surgery was performed on 7 of 21 patients. One patient with AIDS who had sinusitis and meningitis died.

Conclusions Meningitis as a complication of sinusitis may still pose a serious threat. Although outcomes are encouraging, sequelae such as seizure disorders and hearing loss are common complications. The introduction of high‐resolution computed tomography scans and magnetic resonance imaging and the availability of wide‐spectrum antibiotics have improved our management significantly.