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In recent years endoscopically controlled laser-induced thermal therapy (LITT) has been increasingly accepted as a minimally invasive method for palliation of advanced or recurrent head and neck or gastrointestinal cancer. Previous studies have shown that adjuvant chemotherapy can potentiate endoscopic laser thermal ablation of obstructing tumors leading to improved palliation in advanced cancer patients. Eight patients with recurrent head and neck tumors volunteered to enroll as part of an ongoing phase II LITT clinical trial, and also elected to be treated with systemic chemotherapy (cisplatin, 80 mg/m2) followed 24 h later by palliative laser thermal ablation. Laser treatments were repeated in patients with residual disease or recurrence for a total of 27 LITT sessions. Four of the 8 patients treated with laser thermal chemotherapy remained alive after a median follow-up of 12 months. Of the 12 tumor sites treated, complete responses were located in the oral cavity (3), oropharynx (1), hypopharynx (1), maxillary sinus (1), and median survival for these patients was 9.5 months. This initial experience with cisplatinum-based laser chemotherapy indicates both safety and therapeutic potential for palliation of advanced head and neck cancer but this must be confirmed by longer follow-up in a larger cohort of patients.

Objective: To characterize the otolaryngologic manifestations of amyloidosis; classify patients with amyloidosis by specific location and type of underlying disease; and compare disease presentation and long-term outcome in these patients. Design: Retrospective review of biopsy specimens recorded as amyloidosis. Setting: Tertiary care referral center serving a diverse patient base. Patients: Of 141 patients with biopsy-verified amyloidosis who met the inclusion criterion for the study, 27 (19%) had head and neck manifestations. Outcome Measures: Good functional outcome and survival of patients with amyloidosis. Results: The tongue was the most commonly affected site of the head and neck. Distinct differences exist in functional outcome and long-term survival in patients with the localized form of amyloidosis when compared with patients with systemic amyloidosis. Conclusion: Because amyloidosis often affects the head and neck, otolaryngologists need to be familiar with this disease. (Arch Otolaryngol Head Neck Surg. 1995;121:778-782)

Although the experts acknowledge that there is no conclusive evidence linking secondhand smoke to head and neck cancer, a recent report by the Environmental Protection Agency classifies secondhand smoke as a group A carcinogen. There is strong evidence linking it to carcinoma of the lung. Whereas you may not be able to tell your patient that the same cause and effect is present for head and neck cancer, it is the editor's belief that this will one day be proven. Three experts agreed to treat this patient with surgery followed by full-course radiotherapy, although the surgical approaches differed. They included a marginal mandibulectomy, radical neck dissection, and plating of the remaining mandible (Dr. Strome) and a composite resection (Drs. Ward and Johnson). For reconstruction, options included a modified FAMM flap or a split-thickness skin graft (Dr. Strome), tongue flap or pectoralis major myocutaneous flap (Dr. Ward), or a split-thickness skin graft (Dr. Johnson). One consultant suggested resecting the neck mass and treating the primary tumor and neck with radiotherapy. A dental consultation is in order prior to radiotherapy (Dr. Goepfert). With regard to this woman's mental status, all the experts called for counseling. The husband should be included in the discussions (Dr. Strome and Ward) and consideration should be given to the Women's Right Advocacy Group (Dr. Johnson).

Rhodamine-123 is a specific dye with an absorption maxima at 511 nm which was tested as a potential chemosensitizing agent for laser treatment of tumor cells. Because Rhodamine, at high doses, has direct cytotoxic effects on human cells in the absence of laser exposure, we tested the human squamous P 3 carcinoma cell line and two normal fibroblast cell lines for sensitivity to various levels of this dye. These cells were exposed to Rhodamine-123 at concentrations of 1, 3, 6, and 10 mug/ml for 1, 8, and 24 hours. The results indicate that Rhodamine-123 is nontoxic to human P 3 carcinoma cells and normal fibroblast cultures at concentrations equal or lower than 1 mug/ml. However, at concentrations equal or higher than 3 mug/ml, a significant immediate and/or delayed inhibition of cell duplication was demonstrated. The results show that Rhodamine-123 at 1 mug/ml can be used to sensitize tumor cells for targeting by monochromatic 514.5 nm Argon lasers.

In this report we demonstrate the pattern of calcitonin gene-related peptide (CGRP) mRNA and immunoreactivity in the central and peripheral vestibular system of the rat, using a CGRP cRNA probe and a polyclonal CGRP antiserum. We present evidence that somata in all regions of efferent vestibular neurons contain CGRP based on the correspondence between in situ hybridization (mRNA) and immunohistochemistry (mRNA translation product). CGRP immunohistochemistry (CGRPi) and in situ hybridization confirm that CGRPi axons and terminals present in the vestibular neuroepithelium are efferent in origin. Immunoelectron microscopy revealed an extensive innervation of the afferent vestibular pathway by CGRPi terminals that was not limited to the primary afferent chalice, as previously reported by Tanaka et al. (Brain Res 1989;504:31-5). An efferent neuromodulatory role of CGRP can be inferred from the distribution of terminals found on the primary afferent fibers, and type I and type II hair cells. In addition, we present evidence that nicotinic acetylcholine receptor (nAChR) subunit mRNA is expressed by primary afferent cell bodies. On the basis of these data, a hypothetical molecular mechanism of vestibular efferent modulation of the primary afferent pathway is proposed.

Molecular biology of the vestibular system has been limited by a number of technical difficulties including fixation, decalcification of the temporal bone and the small size of specific structures relative to their surroundings. In situ hybridization histochemistry and immunoelectron microscopy allow the subcellular study of gene expression and gene products, respectively. We developed the methodologies necessary to apply these techniques to the central and peripheral vestibular systems. The central and temporal bone distributions of the neuropeptide calcitonin gene-related peptide (CGRP) mRNA and two genes coding for gap junction proteins, connexin C32 and C43 mRNA, were studied. The cellular distributions of these mRNAs are presented. In addition, examples of pre-embedding and postembedding immunoelectron microscopy are presented demonstrating the usefulness of these techniques in studying the subcellular localization of specific antigens. The ultrastructural innervation of the vestibular periphery by the efferent neuropeptide CGRP and ultrastructural evidence of glycoprotein secretion by the human endolymphatic sac is presented.

A surgical technique is presented to obtain the entire vestibular aqueduct, containing the endolymphatic duct and sac as well as the vestibular epithelia, from the maculae and cristae during labyrinthectomy. The inner ear tissue was fixed in 3% glutaraldehyde, decalcified in 0.1 mol/L Na-EDTA, and routinely processed for transmission electron microscopy, including post-fixation with osmium tetroxide. Postembedding protein A-colloidal gold immunoelectron microscopy was performed after exposure of cellular antigenic sites by sodium metaperiodate. To validate this technique, thin sections from the crista ampullaris and the endolymphatic sac were incubated with antibodies raised against S-100, a protein present in specific types of neural tissue. Specific immunoreactivity was observed in the crista ampullaris, but not in the endolymphatic sac. The surgical biopsy technique described provides a means for the neuro-otologist to collect inner ear tissue from surgical patients that can be used for pathological studies using immunohistochemistry and electron microscopy.

Rhodamine 123 has been shown to be an efficient photosensitizer for the argon laser treatment of a human squamous carcinoma and a melanoma cell line in vitro. Rhodamine 123 laser phototherapy also eradicates these human squamous cell carcinomas when grown as subcutaneous tumor transplants in athymic mice. This study extends these observations by testing a panel of 19 human tumor cell lines of various histologic origins for in vitro sensitivity to rhodamine 123 and the argon laser. Rhodamine 123 with an absorption maxima of 502 nm in water was found to undergo a redshift to 516 nm after uptake by the mitochondria of human tumor cells. Rhodamine 123-sensitized brain tumor cells were inhibited by over 80% after 15 seconds and by 98% after 60 seconds of laser exposure (514.5 nm, 4 W, T max = 39°C), as measured by reduced [ 3 H]thymidine incorporation into cellular DNA. Laser or rhodamine 123 alone did not significantly inhibit (>20%) tumor cell [ 3 H]thymidine uptake. Sensitization with 20 μg rhodamine 123 for 1 hour before 45 seconds of laser illumination decreased cell [ 3 H]thymidine uptake by 40% to 99% in four melanoma lines, five carcinomas, five leukemias, and four of five other human tumor lines. Two melanomas, two leukemias, and a lymphoma cell line also exhibited a 70% to 80% reduction in [ 3 H]thymidine uptake after sensitization in vitro with 1 μg/mL rhodamine 123 and laser illumination. Rhodamine 123-sensitized tumor cells were inhibited even more strongly by fractional dose laser irradiation at nonthermal temperatures. These results provide evidence that rhodamine 123 is an effective tumor targetting reagent in the laser photodynamic treatment of many types of malignant human cells in vitro, and suggest that cationic rhodamine laser dyes may be a useful new class of photosensitizers in the treatment of cancer.

The role of endolymphatic sac (ES) dysfunction in the etiopathogenesis of Meniere's disease has remained controversial since the early 1900s. The first reports of the ultrastructural (transmission electron microscopy, TEM) pathology of the human ES in Meniere's disease have been published only in the last decade. These studies have been based on biopsies of the extraosseous (intradural) ES and in no cases has the TEM appearance of the intraosseous ES been described. Likewise the control material used has been from biopsies of extraosseous ES taken from patients with acoustic schwannomas. To date, no reports have compared the ultrastructure of the intrasosseous ES from normal control patients to patients with Meniere's disease. Since the intraosseous ES is believed to be the most active portion of the entire ES, studies were made of the ultrastructure of ten normal interosseous human ESs fixed immediately after death and obtained at autopsy (control material). Fourteen patients undergoing translabyrinthine (TL) neurotologic procedures (10, TL resection of acoustic schwannoma; 4, TL eighth cranial nerve section for Meniere's disease) had the entire vestibular aqueduct, containing the endolymphatic duct and the intraosseous ES, removed and processed for TEM. The roles of the epithelium, subepithelial space, and vasculature were morphologically studied to evaluate possible ES pathology in Meniere's disease and in patients with acoustic schwannoma. Wide anatomic variation in the distribution and density of the subepithelial connective tissue was observed in all groups. There was no difference in the TEM appearance of the intraosseous ES from normal controls and patients with eighth nerve schwannoma, nor was there any difference in the ES collagen deposition in patients with Meniere's disease. The ESs from two patients with Meniere's disease showed evidence of abnormal glycoprotein metabolism; one with possible hypersecretion and one with possible alteration of degradation of resorbed glycoprotein. The results of this preliminary study suggest that "perisaccular fibrosis" of the intraosseous ES was not a pathologic feature in these four cases of Meniere's disease and that alteration of ES glycoprotein secretion/resorption may be of etiopathologic significance.

Evaluating the extent of tumor invasion of the mandible is clinically important in the management of mandibular tumors. Conventional imaging studies including panoramic radiography, bone scans, and computed tomography, as well as clinical evaluation can be unreliable in defining the extent of neoplastic marrow invasion. This study presents the initial UCLA, Los Angeles, Calif, experience with magnetic resonance imaging in evaluating mandibular invasion by benign and malignant neoplasms. Magnetic resonance imaging, using T1 and T2 images, was compared with conventional imaging methods in 11 patients with malignant lesions and nine patients with benign lesions. In all cases, magnetic resonance imaging most accurately determined the full extent of tumor invasion in the mandibular marrow spaces. Magnetic resonance imaging appears to be superior to offer clear benefits over conventional imaging methods, including computed tomography, for the evaluation of tumor invasion of the mandible.

Tonsillectomy using local anesthesia (local tonsillectomy) is a safe and effective alternative to general anesthesia in the healthy cooperative teenage or adult patient. This retrospective analysis involved 64 local tonsillectomies performed over the past 7 years in a minor operating room using only local anesthesia with intravenous sedation. Operations were performed by residents in training as well as by experienced head and neck surgeons. Blood loss, morbidity, complications, and patient satisfaction were reviewed and compared with tonsillectomies done under general anesthesia. The average blood loss was 42 mL in the local tonsillectomy group with no cases of postoperative hemorrhage, compared with 198 mL in the general anesthesia group with two cases of postoperative hemorrhage. There was one major complication related to postoperative antibiotic use in the local anesthesia group, and follow-up interviews revealed that patients were satisfied with the procedure and would recommend and choose local anesthesia again. We conclude that local tonsillectomies have high patient acceptance and are associated with minimal morbidity and complications. Furthermore, they are cost-effective.

Objectives: Laser therapy is becoming a more precise, minimally invasive alternative for tumor ablation. Recent reports confirm successful palliation of pain and functional disabilities in patients with advanced deep carcinoma of the head and neck using interstitial laser phototherapy (ILT). Study Design, Patients, and Methods: The current study describes an ongoing Phase II trial of neodymium/yttrium-aluminum-garnet (Nd:YAG) laser therapy for palliation of advanced head and neck cancer. A total of 40 advanced cancer patients have been entered into this protocol (25 men and 15 women). Results: Nineteen of these patients had no evidence of recurrence after ILT with an average follow-up of 11 months (range, 2 to 24 mo). Currently, 19 of these patients are alive, 14 with tumor remission and six with persistent disease. A total of 79 tumor sites received ILT with 43 (54.5%) completely ablated. Stratified by tumor site, ILT led to a complete response in 21 of 24 in the oral cavity, eight of 28 neck tumors, four of 10 in skin, and 10 of 17 in other sites. The procedure was well tolerated in most cases and was repeated at intervals in patients with residual disease or recurrences for a total of 118 laser treatments (average, 2.95 treatments per patient). Conclusions: The results suggest that ILT can be performed safely and repeated as needed, and may be less costly than conventional surgery for head and neck cancer. However, additional follow-up is needed to obtain convincing evidence of long-term therapeutic benefits.

The usual differential diagnosis of a lateral cystic neck mass places emphasis on benign entities. This is particularly true in the evaluation of patients under the age of 40. Generally included in the differential are branchial cleft cyst, lymphangioma, hemangioma, laryngocele, pharyngeal diverticulum, and infectious adenopathy or abcess. While metastatic cervical adenopathy is also included in the differential, it is generally placed quite low on the list. Metastasis from thyroid carcinoma is often not mentioned at all. Delayed or missed diagnosis can occur if malignancy is not considered in the differential. This report reviews the historical evolution of scientific thinking regarding thyroid gland embryology and the origin of lateral neck masses of thyroid histology. An illustrative case is described in which metastatic papillary thyroid carcinoma presented in the typical manner of a branchial cleft cyst. The preoperative evaluation and management of such patients is discussed.

Imaging-guided palliative therapy of recurrent and/or inaccessible head and neck tumors may soon become clinically practical since sensitive and noninvasive monitoring techniques of energy deposition in tissues are now available. Interstitial tumor therapy (ITT) is a technique whereby a source of energy (laser, radiofrequency, ultrasonic, cryoenergy, etc.) is directly applied into tumors at various depths. Recent studies have demonstrated the efficiency of ultrasound (UTZ) and magnetic resonance imaging (MRI) for real and/or "near" real time tumor and vessel identification as well as monitoring and quantifying energy-induced tissue damage. We now report our initial clinical experience with patients in which UTZ and/or MRI-guided ITT techniques were successfully applied for the treatment of recurrent, nonresectable, local, and/or metastatic head and neck carcinomas. Patients were treated on an outpatient basis either in the operating room or in an upgraded specially equipped SIGNA 1.5T MR suite. Most patients tolerated these procedures well and were successfully palliated for periods ranging from 3 months to 5 years posttreatment. The upgrades introduced in a standard MRI suite, the clinical experience, and future perspectives will be reviewed.

Interstitial laser phototherapy (ILP) is a technique whereby laser energy is directly applied into tumors at variable depths. This technique is attractive, since it is minimally invasive and carries a low morbidity. It may allow treatment of deep and difficult to reach tumors in the head and neck and other areas when improved noninvasive monitoring techniques of laser-tissue interactions are developed. Recent studies demonstrate, respectively, the efficiency of ultrasound (UTZ) and magnetic resonance imaging (MRI) for real time interstitial needle placement in tumors, identification of vessels, monitoring and quantifying laser-induced tissue damages. We present a case in which a patient with recurrent, metastatic base of skull carcinoma has managed successfully with repeat ILP using MRI and UTZ guidance. Under heavy sedation, needles were placed in the tumor using MRI or UTZ guidance. Tumors were treated with a 600 mum flexible Nd:YAG laser fiberoptic passed through the needles. Laser-induced tissue photoablation was monitored using real time color flow Doppler UTZ or near real time fast spin-echo T2-weighted MRI. Posttreatment fine needle aspiration cytologic study demonstrated the presence of cellular debris and no viable cancer cells. Posttreatment follow-up MRI scans showed significant reduction of tumor size, and positron emission tomography (PET) revealed interval decrease in tumor metabolism. Treatments were accompanied by pain relief and improved functional abilities. ILP has now evolved into minimally invasive outpatient surgical procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Intralaryngeal injections of botulinum toxin (Botox), under electromyographic guidance, have emerged as an effective treatment for adductor spasmodic dysphonia. To remain effective, these injections must be repeated every 3 to 9 months as the symptoms recur. One drawback to the current method is the need for electromyographic confirmation of needle placement into the thyroarytenoid muscle. This report describes an anatomic approach to Botox injection that requires only flexible nasopharyngeal endoscopy and careful evaluation of the anatomic landmarks. This technique has been used successfully on 13 patients, and objective pretreatment and posttreatment measures are reported.

One hundred three patients with nasopharyngeal carcinoma were treated with radiotherapy at UCLA Medical Center from January 1955 to December 1990. Overall survival, disease-free survival, and local control rates were analyzed. In addition, survival from 1955 to 1978 and from 1979 to 1990 were evaluated. Overall 5- and 10-year actuarial survival rates for all patients were 58% and 47%, respectively. Disease-free survival rates at 3 and 5 years were 45% and 30%, respectively. Local, persistent, or recurrent disease in the nasopharynx was the primary cause of failure, occurring in 32% of patients and correlating with the initial tumor size (T stage). Twenty-four percent of patients developed distant metastases, which correlated with nodal status but not with T stage. Seventy-nine percent of patients failed either locally or distally by 4 years. Sex, race, age, and T and N stage categories were evaluated as prognostic variables in terms of survival. Control of primary disease is important in determining long-term outcome. Modern imaging techniques have greatly assisted in the evaluation of disease extent and treatment options.

Rhodamine-123 uptake and release was determined in nu/nu mice heterotransplanted with P3 human squamous carcinomas to assess its value as an in vivo laser photosensitizer for treatment of solid tumors. Following intraperitoneal injection of Rh-123 (1 micrograms/g of body weight), mice were killed at 2, 4, 6 and 24 hours, and 3 and 7 days postinjection. The peak concentrations of Rh-123 per milligram of tissue measured by fluorescence spectrophotometry was distributed as follows: kidneys greater than spleen greater than intestine greater than stomach greater than liver greater than tumor greater than skin greater than skeletal muscles greater than lung greater than heart greater than blood greater than brain. No preferential uptake or retention of Rh-123 by tumors was observed. However, a longer retention with higher concentrations of the dye was seen in normal skin as opposed to P3 tumors from 4 hours to 7 days postinjection with Rh-123. The elimination of Rh-123 was rapid, with the dye falling to less than 2% of peak concentration at 7 days postinjection. Knowledge of Rh-123 biodistribution in tumors and other tissues suggests that optimal timing after injection of this dye may allow selective photodiagnosis and photodynamic therapy of tumors with the argon laser.

The mitochondrial dye Rhodamine 123 (Rh-123) has been shown to be an effective photosensitizer for argon-laser irradiation of some types of human cancer cells in vitro. We reported that 514.5-nm laser illumination of Rh-123 sensitized human melanoma, and squamous carcinoma cells strongly inhibited tumor-cell proliferation as measured by decreased 3H-thymidine (3H-T) uptake in vitro and may eradicate some tumors when grown as transplants in nude mice. However, several other human tumors were resistant to Rh-123 laser therapy in vitro and in vivo. In the current study, it was possible to obtain 100- to 1000-fold increased sensitivity to 514.5-nm laser illumination by replacement of Rh-123 with the cationic rhodamine dyes Rh-3G and Rh-6G. Cell viability was decreased over 95% and 3H-T incorporation reduced at least 80% by laser phototherapy after sensitizing tumor cells with 1 micrograms/mL Rh-123, 0.01 microgram/mL Rh-3G, or 0.001 microgram/mL Rh-6G. However, Rh-123 alone did not decrease 3H-T uptake significantly unless present at over 10- to 100-fold higher levels than Rh-3G, respectively. The tumor cell dye uptake level was measured by N-butanol extraction and absorption scans at 400 to 600 nm. The results revealed that dye uptake was more rapid, and retention of Rh-3G and Rh-6G was 5- to 10-fold higher than for Rh-123 in the human tumor cells. The data suggest that Rh-3G and Rh-6G may be highly sensitive chromophores for laser phototherapy of human cancer cells.

A new and highly promising adjunctive modality for the diagnosis and therapy of malignancies is under development using lasers and tumor targeting dyes. To reach the eventual goal of clinical treatment, several current "fantasies and fallacies" regarding laser applications in medicine must be identified and their problems clearly outlined. A multidisciplinary scientific approach is also required to enable the clinical practicality of this laser targeting approach. Many new dyes and laser wavelengths are being tested to improve specific tumor uptake and/or retention, lower systemic toxicity, increase tissue penetration, and identify fluorochromes with synergistic properties to further enhance laser tumoricidal effects. Rapid technological advancements in magnetic resonance imaging may now provide an extremely sensitive way to detect and monitor laser-tissue effects, and allow efficient interstitial laser phototherapy of deep and sometimes inaccessible tumors. The current and future prospectives of the emerging field of laser phototherapy are described.

There are a variety of methods for treating unilateral vocal cord paralysis, but to date there have been few studies that compare these phonosurgical techniques by using objective measures of voice improvement. Vocal efficiency is an objective voice measure that is defined as the ratio of the acoustic power produced by the larynx to the subglottic air power. Vocal efficiency has been found to decrease with glottic disorders such as vocal cord paralysis and carcinoma. This study compared the effects of vocal fold medialization by surgical augmentation to those of arytenoid adduction on the vocal efficiency, videostroboscopy, and acoustics (jitter, shimmer, and signal-to-noise ratio) of a simulated unilateral vocal cord paralysis in an in vivo canine model. Arytenoid adduction was superior to surgical augmentation in vocal efficiency, traveling wave motion, and acoustics.

Flexible Nd:YAG endoscopic laser surgery may become an effective new modality for palliation in patients with obstructive endotracheal metastatic malignancies. We report the results of the treatment of two patients with severely obstructing intraluminal tracheal metastatic melanoma and medullary thyroid carcinoma, using the neodymium-YAG laser via the flexible fiberoptic bronchoscope. Both patients complained of significant dyspnea, orthopnea, cough, and hemoptysis and were not candidates for rigid bronchoscopy because of underlying medical contraindications and anatomical problems. Multiple treatment sessions were used with treatment intervals of 1 to 2 weeks. All treatments were performed in the operating room under sedation, without intubation, with topical lidocaine and standard superior laryngeal nerve block. Successful relief of airway obstruction with complete regression of the endotracheal masses was achieved and no recurrences were seen after 9 months' follow-up. Flexible Nd:YAG laser bronchoscopy offered an alternative for the relief of obstructing endotracheal or bronchial malignancies in patients in whom the rigid bronchoscope could not be passed. it seemed to prolong survival in selected cases, and provided definite improvement in quality of life.

In situ hybridization histochemistry technology was developed for future application to neuro-otologic research. This method allowed the detection of cellular mRNA in tissue sections from the temporal bone or brainstem after cRNA/mRNA hybridization. To produce specific cRNA, single-stranded 35S-labeled cRNA (complimentary to target mRNA) is transcribed from commercially available plasmid vectors. These vectors contain promotor sequences for specific synthesis of RNA, and polylinker regions that will accept cloned DNA inserts for virtually any target nucleic acid sequence of interest. The protocol used in this research was optimized for studies that included concomitant immunohistochemical evaluation. The combination of in situ hybridization and immunohistochemistry provides the only method to correlate molecular information (gene expression) with biochemical or molecular markers, such as peptides or proteins (mRNA translation products) on individual cells in the temporal bone or brainstem. Using these techniques, we examined the distribution of the neuropeptide calcitonin gene-related peptide in rat temporal bone and brainstem sections using calcitonin gene-related peptide (CGRP) antisera and CGRP cRNA probes. We used in situ hybridization histochemistry with a cRNA probe complementary to the 3'-end noncoding sequence of the alpha CGRP mRNA and immunohistochemistry with a polyclonal antibody to the (TYR)CGRP23-37 to study the distribution of CGRP mRNA and CGRP-like immunoreactivity in the central and peripheral facial nerve. Numerous motoneuron cell bodies in the facial nucleus and accessory seventh nucleus and cell bodies in the gustatory geniculate ganglion were found to contain CGRP mRNA and the CGRP peptide.(ABSTRACT TRUNCATED AT 250 WORDS)

The immediate fixation required for satisfactory morphologic preservation of the human inner ear has not only limited the ultrastructural study of this region, but has also limited the application of immunohistochemistry. The technique of postembedding protein A-colloidal gold immunoelectron microscopy was used on human inner ear tissue taken at operation and on celloidin-embedded temporal bone sections from a traditional temporal bone bank. We describe the utility of postembedding immunoelectron microscopy for studying the localization of a wide variety of antigens including type I collagen, S-100, and calcitonin gene-related peptide. The use of this method in material available in temporal bone banks or that has been routinely processed for transmission electron microscopy provides the potential for broad application to collections of otologic material.

Vocal cord paralysis or paresis as the initial presenting symptom for intracranial tumors in children are rare. Recently, two pediatric patients who were later diagnosed as having intracranial tumors presented with the symptom of voice changes and stridor. Telescopic examination revealed bilateral vocal cord paresis and paralysis as demonstrated by video recordings. The majority of pediatric brain tumors present with both generalized and localized complaints; however, by discussing these two rare cases, we hope to underscore the importance of a thorough workup of the paralyzed or paretic vocal cords.

Positron emission tomography (PET) has been shown to be effective in detecting intracranial malignancies based on cerebral glucose metabolism. To evaluate the ability of PET to detect extracranial head and neck neoplasms and cervical metastases, 16 patients with primary squamous cell carcinomas were examined. All patients received preoperative computerized tomography (CT) and magnetic resonance imaging (MRI) scans and underwent PET evaluation using intravenous 18F-2-fluoro-2-deoxy-D-glucose (FDG). Histopathologic analysis compared tumor invasion and positive lymph nodes with findings on MRI, CT, and PET images. All primary tumors were delineated by PET, while MRI and CT failed to detect one superficial tumor involving the anterior tongue. Ten nodes were detected by CT and MRI versus 12 nodes demonstrated by PET. PET is highly effective in detecting head and neck carcinomas as well as metastatic cervical lymph nodes. In addition, PET may be useful in evaluating postsurgery and postradiotherapy patients for recurrent and new primary tumors.

Early reports of a percutaneous dilatational technique for tracheotomy tube placement have been encouraging. This method uses a needle for placement into the trachea, a J-tipped guidewire, and progressively larger dilators to widen the stoma for insertion of a tracheotomy tube. A prospective study was undertaken to assess the efficacy of this percutaneous tracheotomy technique. Serious complications were encountered, including difficulty with dilatation, excessive bleeding, false passage of the tracheotomy tube, and death. Because of this unacceptable morbidity, the study was terminated after enrollment of only seven patients. Percutaneous tracheotomy is a dangerous procedure with potential for catastrophic complications. These complications were encountered by third-and fourth-year surgical residents performing the procedure under close supervision. If the puncture technique is further popularized and attempted by untrained physicians, these authors predict many disasters.

Interstitial laser phototherapy (ILP) guided by magnetic resonance imaging (MRI) may become an attractive adjunctive modality for the treatment of deep and surgically inaccessible tumors of the head and neck when accurate methods of laser dosimetry and "real-time" monitoring techniques with the MRI are introduced. We recently demonstrated in ex vivo and in vivo models, a linear relationship between levels of laser energies, thermal profiles, MR signal intensity changes, and histopathological tissue damage. Results of treatment in a patient with an unresectable large right jugulodigastric metastatic squamous carcinoma using new approach of MRI guided ILP are now reported. The patient complained of significant right-sided neck pain and headaches secondary to a rapidly growing metastatic lymphadenopathy which recurred after previous surgery, radiation, and chemotherapy. Two treatment sessions were used at an interval of 2 weeks. Each treatment was performed in the MRI suite under heavy sedation. Using a 600-microns bare fiber of the Nd:YAG laser implanted interstitially under MR guidance, the metastatic node was treated at three sites. T1- and T2-weighted images were performed prior to, immediately after, 24 and 48 hours, and 4, 5, 7, 9, 16, and 25 days post-treatment. Successful relief of pain and growth arrest of this node was observed after the second treatment and at the 3-month follow-up. These results demonstrate that this technique of ILP guided by MRI may be feasible in humans, and will become clinically practical when appropriate methods of dosimetry and instrumentation are developed.

Rhodamine-123 (Rh-123) has been tested recently as a new laser dye for photodynamic therapy of human tumors in vitro and in vivo. Prior to initiation of clinical studies of this technique, we evaluated the biodistribution, metabolism, and pathological changes of Rh-123 in rabbits after systemic, repetitive injections of the dye in escalating doses. At doses between 0.1 to 1 mg/kg of Rh-123 injected intramuscularly (IM) daily for 5 days, no local or systemic toxicity was observed during the 4 weeks of follow-up. The peak concentrations of Rh-123 in micrograms/g of tissue was distributed as follows: kidney (3.24) greater than heart (2.24) greater than spleen (1.77) greater than lung (0.61) greater than liver (0.38) greater than skin (0.30) greater than skeletal muscle (0.17) greater than genitals (0.13) greater than brain (0.04). The elimination of Rh-123 was very rapid, with the dye falling to 2.7% of peak concentration at 72 hours in the kidneys, and to undetectable levels at 240 hours postinjection in all organs, except the skin, which retained 3% of the peak level at 240 hours. The low toxicity and rapid metabolism of Rh-123 in this preclinical model suggests that the dye and Argon laser may represent an effective combination for treatment of superficial malignancies.

Recent studies demonstrated that the cationic, mitochondrial-specific dye Rhodamine-123 (Rh-123), is an efficient tumor photosensitizer for Argon laser treatment of human cancer cells both in vitro and in tumors grown as xenografts in athymic mice. To demonstrate the photodynamic mechanism of action of this reaction, the intracellular role of oxygen and temperature changes in treated cells have to be defined. In the current study, a large panel of human tumor cell lines of diverse histologic origin were tested for in vitro sensitivity to Rh-123 and the Argon laser (514.5 nm) in oxygen, deuterium oxide (D2O), and nitrogen (N2) environment. Tumor cells in suspension were first sensitized to Rh-123 (1 or 20 micrograms/ml for 1 hour), cooled on ice to 4 degrees C, and then exposed to the Argon laser (delta T = 14 +/- 1 degree C). Cell proliferation measured by (3H)-thymidine uptake 24 hours after sensitization with Rh-123 and laser treatment was significantly decreased in tumor cells kept in oxygen and D2O atmospheres. No decrease in DNA synthesis was seen in Rh-123 and laser treated cells kept in an N2 environment. Control tumor cells treated with Rh-123 or the Argon laser separately did not show any decreased (3H)-thymidine uptakemore » in oxygen, D2O or N2 environment. These results provide evidence of a photodynamic process since Rh-123 sensitization and Argon laser activation occur at nonthermal levels of energy and are oxygen dependent. The high effectiveness of this technique of photodynamic therapy with the Argon laser, and low toxicity of Rh-123 could make its clinical use very attractive for the treatment of superficial malignancies.« less

The rapid technological advances of magnetic resonance imaging, laser fiberoptics, and compatible probes may allow treatment of deep and sometimes surgically unreachable tumors of the head and neck with minimal morbidity through interstitial laser phototherapy. In this study, a new application of magnetic resonance imaging was developed to monitor and quantify laser-induced tissue damages. Pig skin was exposed to increased levels of argon laser (514.5 nm) at energy densities between 62.5 and 375 J/cm2 as determined by an accurate and reproducible method of dosimetry. Thermal profiles were recorded using an infrared sensor and T1- and T2-weighted magnetic resonance images were taken; afterward, biopsies were performed to quantitate the level of tissue damage. Our results demonstrate that above a certain threshold of laser energy, the magnetic resonance imaging findings are temperature dependent. Appropriate development of a scale matching laser energies, temperature profiles, T1- and T2-weighted magnetic resonance images, and histological quantitation of tissue destruction will allow us to optimize the three-dimensional control and monitoring of laser-tissue interactions.

A series of 238 patients with laryngeal paralysis seen during a six-year period (1976–1982) were studied with serial 16-mm motion picture filmstrips. There were 39 cases in which no etiological disease process could be found responsible for the paralysis; these were called “idiopathic.” In all 39 cases, both the superior and recurrent laryngeal nerves were paralyzed indicating that the lesion involved the central (nuclear) lower motor neurons of the dorsal and ventral nucleus ambiguus. The high incidence of upper respiratory infections suggests a viral etiology in many cases. The ability to separate a pure recurrent from a combined superior and recurrent laryngeal paralysis on morphological indirect endoscopic appearance has significant diagnostic and therapeutic implications.

Tracheostomy during infancy often results in serious complications and even death. The current policy in many medical centers is to recommend extended hospitalization of an infant whenever tracheostomy is necessary. Almost all obstructing diseases of the infant larynx are treated by tracheostomy because of the concern that surgical intervention of the larynx may result in impaired laryngeal growth inadequate for airway or phonation. Since no applicable clinical or experimental reports could be found in the literature, a study was designed to determine the effect of laryngofissure on laryngeal development and function. Six five-week-old dogs underwent an anterior laryngofissure, three of which had placement of a Teflon® keel. The keels were removed six weeks later. Four five-week-old dogs served as controls. At maturity eight months later the ten animals were sacrificed just after direct laryngoscopy. Full vocal cord mobility was found, and the glottic aperture, including the anterior commissure, appeared to be normal. The larynges were excised and found to have the same dimensions and weight as did the controls. Microscopic studies revealed little scarring at the anterior commissure, and the thyroid lamina were bridged by fibrous and cartilaginous tissue with minimal displacement of the lamina. The results of this study suggest that the infant larynx may be divided by a midline vertical thyrotomy without impairment of laryngeal development or function.

Voice dysfunction is associated with neuromuscular impairment of laryngeal control and is often difficult to diagnose by indirect examination of the larynx. The newer techniques, currently used in the UCLA—Veterans Administration Medical Center Laboratories, provide some methods that aid in the diagnosis of voice impairment by providing documented objective data. Illustrative case reports of disorders of neuromuscular dysfunction of the larynx are presented and future research needs and direction are discussed.

This article discusses the importance of the evaluation and diagnosis of objective tinnitus (tinnitus heard by the patient and the physician). Intracranial arteriovenous communications and vascular anomalies are most frequently responsible for the tinnitus and auscultable bruits and are highly amenable to current surgical treatment. While the otolaryngologists may initially see these patients and be responsible for the diagnosis of their problem, the surgical correction of the intracranial lesions is usually the province of the neurosurgeon. Illustrative cases of extracranial causes are presented. Particular emphasis is placed on the diagnosis and treatment of venous hum. Formerly called cephalic bruit and essential objective tinnitus, venous hum is now a recognized nosological entity that is amenable to treatment by ligation of the internal jugular vein.

The space program and medicine's need for additional information in order to better understand, prevent and treat disorders of the vestibular system have stimulated widespread renewed interest in the study of this complex system. Despite the significant contributions by a number of investigators, much has yet to be learned in order to understand clearly the interrelationships and complexities of the vestibulo-ocular system and the associated peripheral and central subsystems. Because of the functional interdependence of each portion of the vestibulo-ocular reflex complex, a thorough study of the various parts is essential. After review and utilization of a number of available approaches for studying this complex system and its subsystems, it is apparent that the development of some new testing techniques along with improved data storing, retrieval, and analysis methods are needed. The concept, implementation, and activation of new experimental techniques are difficult and laborious as will be seen in this thesis. Better data storage, retrieval and analysis, likewise, require the use of modern technology as well as the extended efforts, assistance and cooperation of experts from other disciplines. This has been accomplished with the use of newly developed computer programs which make possible quantitative measurements, graphical display and correlative studies of massive amounts of information which would otherwise be humanly impossible. The general organization of this thesis is oriented toward reviewing the previous work by other investigators upon which any such endeavor must build. Particular emphasis is then given to the methods which are explained in detail so that they can be utilized by others without retracing the many pitfalls experienced in their development. Quantitative analysis of recordings of the behavior of the VIth cranial nerve fibers of cats in response to optokinetic and rotatory stimulation is presented and discussed. Comments on interesting observations made during the conduct of these experiments are presented. The significance and future plans of application of these new approaches to the study of the vestibulo-ocular systems are discussed.

The juvenile nasopharyngeal angiofibroma, a rare neoplasm of adolescent males, is histologically benign but often clinically malignant. Although spontaneous regression of this tumour has been reported (Dane, 1954; Martin, Erhlich and Abels, 1948), this is not the usual clinical course and aggressive treatment is necessary to control symptomatic lesions. Surgical resection has been generally regarded to be the treatment of choice (Pressman, 1962; Rodriguez, 1966, English, Hemenway and Cundy, 1972). However, it has been our experience (Kadin, 1974), as well as that of others (Patterson, 1965), that results of attempted resection of angiofibromas which have extended widely beyond the nasopharynx have been poor. Because of this experience, a patient with an extensive nasopharyngeal angiofibroma was treated with radiation therapy with pre-and post-arteriographic studies to evaluate the extent of the tumour and the results of therapy. A 14-year-old Japanese-American male presented with a four-month history of n...

Experiences with tracheoesophageal puncture are presented that confirm the beneficial experience of others in providing a superior means of voice rehabilitation. As with all surgical procedures, there is a short-term and long-term price to pay in terms of complications. The complications include allergy to tape, esophageal perforation, enlarging fistula, stomal stenosis, fistula migration, cellulitis, esophageal stenosis, pneumonia, and death from aspiration pneumonia. Careful selection of patients lessens the chances for complications and failure. Simultaneous laryngectomy and creation of a speaking fistula have been abandoned because of long-term, serious healing problems. In spite of the complications encountered, the authors feel that the tracheoesophageal voice fistula provides a superior means for vocal rehabilitation in total laryngectomy patients who do not develop esophageal speech.

• Angioblastic lymphoid hyperplasia with eosinophilia, or Kimura's disease, is a clinically and histopathologically recognized entity that is characterized by cutaneous nodules, proliferating blood vessels with atypical histiocyte-like endothelial cells, and numerous eosinophils. It has been treated with steroids and by surgical excision, irradiation, cryotherapy, and electrodesiccation. Persistent residual disease and local recurrence are frequent. We review the literature and report two cases that involve the ear. We present the histopathologic and clinical results of laser removal of a conchal and external canal lesion. (Arch Otolaryngol1981;107:316-319)

• Neuromuscular dysfunction of the cricopharyngeus muscle is becoming increasingly recognized as a cause of dysphagia, particularly in the growing geriatric population. The disorder may occur primarily, or as part of a generalized neurologic syndrome. This debilitating and potentially lethal type of dysphagia, formerly managed by nasogastric tube or gastrostomy feeding, is usually correctable by simple section of the cricopharyngeus muscle. We report a series of six successfully managed patients to illustrate important aspects of diagnosis and treatment. ( Arch Otolaryngol 101:726-729, 1975)

A grantsman is usually considered to be a person who successfully writes grant applications. The term carries a connotation that the writer of the grant has some particular ability or inside track on the method needed to apply for and successfully acquire funds to support a project. There is also a negative aura that surrounds the term grantsmanship, which has been built up primarily by those unsuccessful in competing for funds. This negative connotation has been promulgated in the form of myths that are untrue stories without a base of reality. The purpose of this article is to dispel some of these misconceptions and untruths that are counterproductive in the preparation of a quality research grant application. In the preparation of this article, discussions have been held with a number of persons including grant applicants, former study section members, council members, and members of the National Institute of Neurological and

Thirty-one patients referred to the Craniofacial Anomalies Clinic for speech evaluation were evaluated by endoscopy and cineradiographic examination (lateral and submentovertical projection). Movement of the velar and lateral walls was examined by both procedures in order to determine the accuracy of the endoscopy in assessing velopharyngeal movement. Cineradiography confirmed endoscopic observation in a large percentage of patients. In a second study, lateral wall motion was assessed in 20 cleft palate patients with repaired hard and soft palate but with velopharyngeal inadequacy. Four categories of closure defined in a previous study on normal subjects were used to classify lateral wall movement in the cleft palate patients. Mesial lateral motion past the sides of the velum during phonation occurred less frequently in patients with velopharyngeal inadequacy than in persons with normal structures. The absence of lateral wall motion was observed more often in the cleft palate patients, although in over half of these patients the lateral walls moved mesially and filled Rosenmuller’s fossa (lateral recesses). Degree of lateral wall movement, which varies among cleft palate patients, should be estimated before construction of a prosthesis or pharyngeal flap in order to determine whether occlusion of the lateral gutters will occur during phonation.

This study was conducted specifically to determine and document the various possible causes of postoperative aspiration. Such information may assist in better selection of candidates as well as provide insights that facilitate improvement of operative techniques for conservation surgery for cancer of the larynx. The major significant information derived from this study is the recognition and delineation of the part played by paralysis of the superior and recurrent laryngeal nerves as causes for aspiration following conservation laryngeal surgery.