OBJECTIVES/HYPOTHESIS:Although many proinflammatory cytokines have been identified in nasal polyp tissue, the initial trigger that causes this inflammation characterized by edema, lymphocytosis, and eosinophilia, is still unknown. The purpose of the present study is to identify the presence of genetic polymorphisms in proinflammatory, anti-inflammatory, and chemokine genes that might contribute to genetic susceptibility to chronic hyperplastic sinusitis with nasal polyposis (CHSwNP).STUDY DESIGN:Case control study.METHODS:Buccal swabs were taken from the left and right oral mucosal surfaces from 179 patients with CHSwNP and 153 nonpolyposis controls with the Purgene DNA purification protocol (Gentra). Genotyping assays for cytokine gene loci were performed on 14 cytokine genes using the iPlex Gold and the Mass Array Compact system (Sequenom, San Diego, CA). Tests of Hardy-Weinberg equilibrium proportions were performed separately in the cases and controls. Tests for evidence of association between alleles at each single-nucleotide polymorphism (SNP) and case-control status were performed using unconditional logistic regression.RESULTS:The frequency of the A allele in a SNP located in tumor necrosis factor (TNF)-alpha (rs1800629) is significantly different in patients with nasal polyposis versus controls without nasal polyposis, 18.6% and 11.5%, respectively with an individuals' odds of susceptibility to nasal polyps increasing almost two-fold (odds ratio, 1.86; confidence interval, 1.4-3.09) given at least one copy of the A allele at this SNP. All other cytokine gene polymorphisms of both inflammatory, anti-inflammatory, and chemokine genes were not statistically different between the two groups.CONCLUSIONS:TNF-alpha-308, a SNP in the promoter region of this cytokine gene is associated with increased odds of developing nasal polyposis. TNF-alpha is a potent immuno-mediator and proinflammatory cytokine that has been implicated in the pathogenesis of a large number of human diseases. The location of this gene on the short arm of chromosome 6, with the major histocompatibility complex genes and complement, has raised the probability that polymorphism within this locus may contribute to a genetic association of this region of the genome with a wide variety of infectious and autoimmune diseases.

We conducted a prospective observational study of tracheostomy tubes with three primary goals: (1) to identify the presence and location of bacterial biofilms on adult tubes, (2) to determine how soon after insertion of a tube the presence of a biofilm could be identified, and (3) to identify the bacterial organisms that formed the biofilms on these tubes. Our study materials consisted of 7 adult tracheostomy tubes that had been changed during a routine outpatient clinic visit or hospital consultation. The tubes were examined for the presence of biofilms on the posterior aspect of the outer cannula; also, specimens were obtained from the posterosuperior aspect of the cuff on the 3 tubes that had a cuff Samples of 2 to 3 mm were taken from each site and analyzed by scanning electron microscopy. Bacterial biofilms were found on 4 of the 7 tubes; they were present on the outer cannula of 3 cuffless tubes that had been inserted 14 days, 4 months, and 2 years previously and on the cuff of 1 tube that had been inserted 10 days previously. The biofilms were composed of gram-positive cocci in pairs that were likely consistent with Staphylococcus epidermidis.

Dear Editor: We are writing this letter in response to the article entitled “Vocal Cord Paralysis After Laryngeal Mask Airway Ventilation” (2005;115:1436–1439) by Teresa Chan, MD, and Gregory Grillone, MD. We thought the subject was interesting, but we noted that in the authors' review of the literature, they pointed to 11 similar cases and neglected to refer to an almost identical case published 8 years earlier.1 In this article, a case of vocal fold fixation secondary to a laryngeal mask anesthetic during an orthopedic procedure was treated by injection of botulinum toxin with restoration of normal vocal fold mobility and function. It was postulated that the tip of the laryngeal mask airway (LMA) tube dislocated the arytenoid cartilage. In the case article described by Drs. Chan and Grillone, their hypothesis centered on the possibility that the vocal cord fixation was secondary to a vocal fold paralysis. The crux of their argument that this patient had paralysis was based on electromyographic evidence. They proceeded to offer a detailed explanation of their theory of the etiology of vocal fold fixation. A mention was made of the possibility of subluxation of the arytenoid, but no further discussion ensued. In terms of clinical presentation, there is a close similarity between subluxation of the arytenoid cartilage and a paralyzed vocal fold after LMA anesthesia. Typically, in subluxation, the arytenoid is anteriorly rotated, and there may be a bowed and foreshortened vocal fold. Electromyography can be helpful in making the distinction between paralysis and dislocation, but it is not universally reliable.2 We have found that injection with botulinum toxin into the adductor musculature will reduce these subluxations in a majority of cases.3, 4 We are not contending that the authors' hypothesis is incorrect. We want merely to point out that there are alternative mechanisms of fixation, theories of how this fixation can occur, and methods of treatment. Certainly, a case such as ours that is as closely related to their study should have been mentioned for comparison and analysis.

5184 Treatment decisions for patients with squamous cell carcinoma of the head and neck (SCCHN) rely heavily on TNM-classification. However, we have earlier shown that expression profiles can predict chemosensitivity. The aim of the present study was to evaluate potential genetic markers for prediction of response to radiotherapy in patients with SCCHN. Material&Methods : Fresh frozen pre-treatment biopsies were obtained from 37 patients with SCCHN at the following sub-sites: oropharynx (n=22), hypopharynx (n=6) and other (oral cavity (n=7), larynx (n=2). They all received radiotherapy with intention to cure. cDNA micro array analysis was performed using slides containing 21,632 sequence validated human cDNAs, generally with insert sizes of 0.25-2.5 kb. For each experiment, mRNA of each cell line was analyzed using equally mixed mRNAs from the normal mucous membranes of nasopharynx, oropharynx, tongue, bucca, submaxillary gland, and base of tongue as a reference. Results: Supervised clustering revealed a genetic profile of 72 genes (e.g. caveolin 1, VEGF, Bcl-2 and INH being upregulated in radioresistent cases) that significantly distinguished patients that responded with Complete Response to radiotherapy from those with Partial response/No Response (p Conclusions : We identified mRNA expression patterns, as analyzed by cDNA micro array analysis, that distinguished radiotherapy responders from non-responders. These findings, along with previously reported chemosensitivity profiles could facilitate individualization of treatment of SCCHN based on the biological properties of the tumors, rather than TNM classification alone.

The clinical picture of a paralyzed vocal fold often has the same appearance as a subluxated arytenoid, with anterior and medial displacement of the arytenoid and a foreshortened and lax vocal fold. Previous work by the authors has shown that a subluxated arytenoid may be permanently repositioned by reduction and selective injection of the intrinsic laryngeal musculature with botulinum toxin. The injection changes the forces within the larynx, allowing the arytenoid to be brought back to proper position on the cricoid cartilage. This concept has been extended to the paralyzed vocal fold. It has been noted that even a clinically paralyzed vocal fold has voluntary motor units that may still act on the arytenoid through residual action from the interarytenoid and synkinesis. These forces are significant enough to manipulate the arytenoid and, thus, the vocal fold, into its correct, adducted position. In this paper, the arytenoid is mobilized to free any fibrosis. The thyroarytenoid and lateral cricoarytenoid muscles are then injected to prevent any forward synkinetic pull on the arytenoid. Next, a Gelfoam injection medializes the vocal fold to create glottic closure. This rebalancing sufficiently positions the arytenoid, so that valvular function is permanently restored. In the ten patients studied for over 1 year, there was a 90% success rate as measured by videostroboscopy, phonation time, and V-RQOL analysis. There were no untoward complications. All the materials used are nonpermanent. The procedure does not limit other techniques from being performed at a later time.

Botulinum toxin has been demonstrated clinically to be an effective treatment for a variety of laryngeal problems, most notably spasmodic dysphonia. As in other movement disorders, the theory behind the injection of this substance in the larynx has been a weakening of the vocal fold musculature to relieve uncoordinated and spasmodic movement of the vocal folds, presumably rebalancing the forces within the intralaryngeal musculature. Recently, this concept was applied to help reposition the arytenoid cartilage in acute and longstanding anteromedial cricoarytenoid dislocations. This same concept may apply to the paralyzed vocal fold. In support of this idea, a number of investigators have shown that immobile, clinically paralyzed vocal folds may still have partial voluntary motor unit activity. This voluntary activation may not produce clinically evident movement but may be sufficient to produce tone within the fold. If the voluntary motor units in the abductor musculature of the paralyzed fold are weakened with botulinum toxin, the continued pull of the functioning adductor musculature may be sufficient to medialize the paralyzed fold. This idea has been supported by animal experiments, which have shown that botulinum toxin may affect the ability of the fold to rebalance itself. With this evidence in mind, a patient with fold immobility secondary to multiple sclerosis was treated in an attempt at laryngeal rebalancing, using botulinum toxin to medialize the fold. However, instead of simply having the fold return fixed to the midline, the patient regained normal laryngeal mobility and voice. While it is unclear whether the botulinum toxin alone was responsible, the coincidence of this occurrence certainly requires reporting. This paper is a report of the first successful treatment of vocal fold paralysis using botulinum toxin to treat vocal fold fixation in a patient with multiple sclerosis.

Arytenoid dislocation is one of the most vexing problems facing the laryngologist. The sliding nature of the joint and the small ligaments that hold it in place make stabilization a difficult task without an easy solution. To make matters worse, the disruption of this joint may be more common than previously recognized, especially in view of the increased number of anesthetic and manipulative techniques used in the operating room and in pulmonary intensive care units.1, 2 Part of the inability to diagnosis this condition may come from the distinction between a fixed cord from joint involvement and a paralyzed cord secondary to nerve disruption. To be certain, the differentiation between these two conditions can be extremely important in developing a proper therapeutic regime. Yet despite newer techniques of radiographic imaging and electrophysiologic testing, the diagnosis frequently remains obscure.3-5 In the final analysis it is usually the laryngologist who must rely on his clinical judgment to make the correct diagnosis. To this end, Jackson's treatise on the subject in 1937 remains the benchmark description of the clinical presentation.6 In this book he noted two main findings: the arytenoid is usually tilted forward, possibly with a line of demarcation where it is separated from the cricoid; and there is evidence of a flaccid vocal fold. Although there is no reported autopsy description of arytenoid dislocation, the positioning of this cartilage is presumed to be due to disruption of the posterior cricoarytenoid ligament. Standard surgical approaches to correct this problem have generally involved a manual reduction of the arytenoid.4 This technique utilizes a bronchoscope or other instrument to push the arytenoid back in place. Although commonly performed, the results from this type of reduction have not been uniformly successful. It is the authors' view that the cases that have failed are usually a result of an inability to control the unbalanced forces of the intrinsic laryngeal musculature. In the case of the anteromedial dislocation it would be the pull of the adductor musculature and the disruption of the posterior cricoarytenoid ligament that form the basis of the persistent deformity. If these forces can be controlled, then theoretically, the arytenoid should be able to be reduced, almost in the same way that an orthopedic surgeon splints muscles to keep fractures and dislocations in proper position.7 To translate this technical possibility into reality, the authors have devised a procedure to weaken or unbalance the distractive forces of the intrinsic laryngeal musculature with botulinum toxin. By injecting the laryngeal adductors on the side of the dislocation with this toxin, the arytenoid cartilage remains in its reduced position, freed from the unrestricted pull of the posterior cricoarytenoid muscle. The diagnosis of arytenoid dislocation is made by a combination of electromyographic readings, computed tomography scanning, and, most importantly, the clinical findings. Electromyographic studies are performed using a Caldwell 5200 electromyography unit (Kennewick, WA). The vocal fold recordings are carried out with a gain of 1000, band bypass filter setting of 100 to 10,000 Hz, and sweep duration of 100 ms. The presence of voluntary electrical activity in the muscles of the membranous vocal fold on the immobile side and evidence of recruitment indicates innervation. The computed tomography scanning will show anteromedial displacement of the arytenoid cartilage. Clinical findings will be that of an anteromedial displaced arytenoid with a bowed and foreshortened vocal cord. Once the diagnosis is made, the patient is taken to the operating room, where the larynx is examined under general anesthesia using jet ventilation. General anesthesia is chosen because of the need to both mobilize the arytenoid and inject the adductor laryngeal muscle groups. Jet ventilation is preferred because it allows a more complete visualization of the posterior commissure. Utilizing a 4-mm bronchoscope, the arytenoid is pushed in a posterolateral direction to a position on top of the cricoid cartilage. Whether or not this maneuver creates as stable and reduced arytenoid, botulinum toxin is injected. This injection is accomplished by using a tuberculin syringe and a disposable 5-inch 25-gauge spinal needle to prevent leakage at the tip or a 26-gauge offset laryngeal injection needle. The dose selected is similar to that used for individual muscle group injection in the treatment of spasmodic dysphoria. The actual injection consists of 2.5 units each into the thyroarytenoid muscle (TA) and lateral cricoarytenoid muscle (LCA) on the affected side and 2.5 units into the interarytenoid muscle (IA) on the side opposite the dislocation (Fig. 1). The volume of each injection was 0.1 mL of solution. The interarytenoid is injected on the side opposite the immobilized cord to prevent the possibility of spread into the posterior cricoarytenoid muscles (PCA) on the side of the fixation. The location of the injection is determined by the anatomic position of the various muscles and not with electromyography because of the use of general anesthesia. Initially after the surgery, the appearance of the arytenoid will be no different from in the preoperative examination. After 1 week some motion becomes noticeable in the cord (Fig. 2A and B). Follow-up is done at weekly intervals. Usually, a month after the surgery the cartilage has assumed its proper position on the cricoid and the patient's voice returns to normal (Fig. 2C). Cross-section of the larynx at the level of the vocal cords showing the three injection sites of 2.5 units each of botulinum toxin: 1) thyroarytenoid, 2) lateral cricoarytenoid, and 3) interarytenoid on the side opposite the fixation. A. Preoperative view showing the anteromedial dislocation and foreshortening of the vocal cord. B. One week after endoscopic manipulation and injection of botulinum toxin into the adductor musculature. The arytenoid cartilage is still in the anteromedial dislocated position. C. One month after injection of botulinum toxin into the adductor musculature. The arytenoid cartilage is now in proper position. The patient's voice has returned to normal. Like other orthopedic dislocations, anteromedial dislocation of the arytenoid cartilage is a derangement of the muscular and ligamentous forces that apply themselves to the joint. It begins with a tear of the posterior cricoarytenoid ligament and is perpetuated by the subsequent unopposed pull of the adductor musculature, keeping the arytenoid in its anteromedial position. Establishing the correct diagnosis of an arytenoid dislocation can be difficult because of the lack of definitive testing. Computed tomography scanning is not always correct and even electromyographic tracings can be hard to interpret since a paralyzed cord can have voluntary motor units.8, 9 In many cases a reliance on clinical evaluation of the patient is paramount to the correct diagnosis. However, once the diagnosis is made, conventional treatment has focused on endoscopic manipulation. Alternatively, in some cases, open procedures with a tracheotomy have been proposed. Whichever procedure is recommended, in order to maintain reduction of the arytenoid, the distracting forces of the adductor musculature must be overcome.6 Botulinum toxin is a substance that can achieve this result. This toxin weakens muscles; and, if selectively injected in certain intrinsic muscles of the larynx, it can effectively "splint" the arytenoid, allowing the cartilage to heal in the proper position. Care must be taken when injecting these muscles, especially the LCA. Shaari et al. have reported that up to 25% of the toxin injected can be found in adjacent muscles, having crossed the muscle fascia.10 To avoid this, the needle must be angled forward and lateral to inject only the membranous vocal fold. In addition, the smallest volume should be used to discourage seepage and spread of the effect into the PCA. In the cases presented here injection of the adductor musculature did not appear to affect the abductors. Botulinum toxin alters the balance of forces within the larynx. In the cases reported here this alteration comes in the form of weakening the adductor musculature to allow the abductors to function unopposed.6 However, it must be noted that it is still unclear whether the toxin alone is sufficient to reduce the arytenoid cartilage or whether it acts only as an adjunct to the endoscopic manipulation. Whichever the case, botulinum toxin is a valuable addition in the reduction of anteromedial arytenoid dislocation. By manipulation of the various distractive forces within the larynx, an effective, endoscopic approach can be utilized without the need for internal or external fixation and without the necessity for tracheotomy.6 To date, the authors have performed the procedure on 10 patients, eight of whom had an acute anteromedial dislocation of 2 months or less. In each of these cases, the rebalancing technique has allowed the arytenoid cartilage to reposition itself correctly on the cricoid. Voice quality has returned to normal as confirmed by objective speech analysis including voice spectrography and perturbation analysis in each of these patients. There have been no complications relating to the procedure other than the minor complaints of any other laryngoscopy. This technique is only for anteromedial dislocations. Posterior dislocation of the arytenoid is a more unusual injury with a different mechanism of derangement and a different set of parameters in terms of correction. Further studies are needed to determine whether this technique is successful in this type of derangement.

This study addresses the bacterial flora of chronic rhinosinusitis at the time of endoscopic sinus surgery. We used the consensus definition of chronic rhinosinusitis as the presence of paranasal sinus inflammation present for greater than 12 weeks. In our patient study group, all cases of chronic rhinosinusitis had failed to respond to antibiotic therapy and had not been treated previously with surgery. By microscopic examination, chronic inflammatory changes were confirmed in the resected sinus lining of all study patients. Intraoperative cultures were obtained from the nasal vestibule, the middle meatus, ethmoid lining, and peripheral blood during and after the endoscopic procedure. We found approximately 30% of the patients with sterile sinuses, 50% with coagulase-negative staphylococci, and the remainder with a mixed group of "nonpathogenic" organisms. Anaerobes were conspicuously rare. The blood cultures were positive in 7% of cases and were consistent with an organism of the operative site. This is the first time bacteremia has been reported in association with endoscopic sinus surgery. The results suggest that chronic rhinosinusitis is not a bacterial disease, but rather the result of chronic inflammation produced by a previous acute inflammation. The incidence of positive blood cultures, while relatively low and cleared quickly, should alert the physician for the possible need for prophylactic antibiotics in patients with cardiac, prosthetic, or systemic conditions that could lead to metastatic infection.

In almost every type of functional laryngeal operation a successfulresult hinges on the surgeon's ability to control the muscular and ligamentous forces that act upon the vocal folds. Most of the time these forces are small in relation to the manipulations and resections performed. Occasionally, the forces are significant relative to the problem encountered, resulting in a failed surgery. Of all the many conditions that fit in to this latter description, perhaps the best example in arytenoid dislocation. Dislocation of the arytenoid is usually secondary to trauma with the majorityof reported cases resulting from some type of anesthetic misadventure. Two types of dislocation have been described, anteromedial and posterolateral, each with a different mechanism of causation. This paper concerns itself with the more common anteromedial variety and its treatment using botulinum toxin.

This is a review of the innervation of the midface and nose as a guide to anesthesia in this region. Through an understanding of the embryologic development, better predictions of nerve coverage are possible. The variables encountered during surgery can be appreciated, and in a practical sense this leads to anesthetic approaches that allow comfortable and controlled surgery in this area.

Sore throat and hoarseness after laryngoscopy and short-term endotracheal intubation is not uncommon. The incidence ranges from 16% to 100% (1,2). The cause of postintubation hoarseness is multifactoral including pharyngeal and laryngeal trauma, hematoma and edema, vocal cord paralysis, and arytenoid cartilage dislocation (3-5). As of 1994 there were only 57 cases of arytenoid dislocation or subluxation reported in the world literature (6).The laryngeal mask airway (LMA) is an airway management device which was introduced in 1988 (7). It is an alternative to endotracheal intubation for certain routine anesthetics and is an adjunct in emergency airway management (8). The LMA does not necessitate direct laryngoscopy for insertion and, therefore, should limit the airway trauma sometimes caused by instrumentation with rigid laryngoscopes.We present the first report of arytenoid cartilage dislocation secondary to LMA insertion. Treatment was by mechanical reduction and chemical splinting.

Computer-assisted image guidance during endoscopic sinus surgery allows for safer and more thorough sinus surgery. We have previously reviewed our experience with the ISG Intraoperative Viewing Wand system. This article describes our current technique and indications for use of the system. Several new technological advances, including the development of a curved operative probe for use in the frontal recess, as well as the introduction of a free-hand infrared localizer, are also described. Computer-assisted image guidance during endoscopic sinus surgery allows for safer and more thorough sinus surgery. We have previously reviewed our experience with the ISG Intraoperative Viewing Wand system. This article describes our current technique and indications for use of the system. Several new technological advances, including the development of a curved operative probe for use in the frontal recess, as well as the introduction of a free-hand infrared localizer, are also described.

Educational objectives: To understand the adult normal paranasal sinus anatomy and the embryology that led to the development of these structures to understand the variations in the normal anatomy through a developmental approach.

As experience has increased in the treatment of bilateral vocal cord fixation, a significant and fundamental refinement in the concept of repair has evolved. By the use of selective tenotomy of the interarytenoid and thyroarytenoid muscles, the arytenoid and the vocal cord can be made to move away from the midline and thus open the glottis. This has allowed a drastic reduction in the amount of arytenoid that must be removed and prevents both aspiration and arthritis of the joint with subsequent stiffness. The procedure can be performed as an endoscopic or microscopic open procedure. All eight patients treated by this method have been decannulated by 6 weeks postoperation, have returned to full function, have not had aspiration, and have no worsening of their voices. The use of this concept and technique has led to a relatively safe and reliable method of rehabilitating patients with bilateral midline vocal cord paralysis.

With newer techniques for laryngeal intervention, it becomes a practical necessity to understand whether an immobile cord is due to neurogenic dysfunction or cricoarytenoid fixation. An objective test for this differentiation is laryngeal electromyography, which can be done as an office procedure with a minimum of discomfort. Our experience in a clinical setting has shown laryngeal electromyography to be efficient in accurately assessing the neuromuscular status of the intrinsic laryngeal musculature.

The treatment of adductor spasmodic dysphonia using botulinum toxin A was conducted in 13 patients as a double-blind, placebo-controlled study. Patients were diagnosed independently by an interdisciplinary team consisting of speech pathologists, an otolaryngologist, and a neurologist. The toxin or saline was injected into each thyroarytenoid muscle under electromyographic and laryngoscopic guidance. Botulinum toxin A markedly reduced perturbation, decreased fundamental frequency range, and improved the spectrographic characteristics of the voice. Fundamental frequency and phonation time remained unchanged. Patients injected with botulinum toxin A noticed significant improvement in their voices in comparison with the placebo-treated group. Excessive breathiness of the voice occurred in two patients, and mild bleeding in one patient in the botulinum toxin A-treated group. Injection with saline resulted in edema of the vocal cord in one patient. Botulinum toxin A proved to be an effective and safe treatment of adductor spasmodic dysphonia.

A preliminary technical report of the effective treatment of abductor spasmodic dysphonia with botulinum toxin is presented. Our technique attempts to place the toxin close to the posterior cricoarytenoid muscle to allow diffusion of the material to the PCA. Our pilot study demonstrates that botulinum toxin is an effective approach for reducing or eliminating the abductor glottal spasms during phonation and, thereby, providing functional speech communication.

Endoscopic techniques for paranasal sinus surgery have allowed detailed and complete removal of sinus disease while promising minimum distress to the patient. The telescopic view of the operative field shows detail of the sinus anatomy and its disease, not possible in earlier transnasal techniques. Several articles document the serious complications seen with the endoscopic surgery. To understand the paranasal sinuses and their relationships to the orbit and cribriform plate, blocks of cadaver heads that included the orbit and paranasal sinuses were whole sectioned. It has been possible to see areas of the cribriform and orbital wall that are at risk to produce cerebrospinal fluid rhinorrhea and orbital complications. At the same time, landmarks for avoiding these complications can be defined to guide the surgeon during this dissection as seen through the endoscope.