Faculty Bibliography

OBJECTIVE: To evaluate the long-term hearing outcomes of neurofibromatosis type 2 (NF2) patients with cochlear implants. METHODS: Retrospective analysis of cochlear implant performance in NF2 patients using open- and closed-set speech perception testing. RESULTS: Patients with NF2-associated bilateral vestibular schwannomas frequently become profoundly deaf. The aim of surgical resection should be to preserve serviceable hearing in at least one ear; however, this goal can be difficult to achieve. Frequently, tumor size or poor preoperative hearing status can require a surgical approach that leaves the patient with a profound, bilateral sensorineural hearing loss. If the cochlear nerve is preserved anatomically after vestibular schwannoma surgery, and if promontory stimulation confirms the functionality of the cochlear nerve, then cochlear implantation is an excellent option to restore hearing. We present six cochlear implant patients with NF2 who attained a significant improvement in open- and closed-set speech understanding with a mean follow-up of 7.9 (range: 5-13) years after surgery. In all but one case, the hearing results did not deteriorate over the follow-up period. CONCLUSION: Early surgical intervention for vestibular schwannomas in NF2 patients when the cochlear nerve can be spared is an important consideration to allow for possible cochlear implantation. A 6- to 8-week recovery period for the anatomically intact cochlear nerve may be necessary to obtain a positive promontory stimulation response following tumor resection and should be performed prior to cochlear implantation

Noncoplanar polychlorinated biphenyls (PCBs) are widely dispersed in human environment and tissues. Here, an exemplar noncoplanar PCB was fed to rat dams during gestation and throughout three subsequent nursing weeks. Although the hearing sensitivity and brainstem auditory responses of pups were normal, exposure resulted in the abnormal development of the primary auditory cortex (A1). A1 was irregularly shaped and marked by internal nonresponsive zones, its topographic organization was grossly abnormal or reversed in about half of the exposed pups, the balance of neuronal inhibition to excitation for A1 neurons was disturbed, and the critical period plasticity that underlies normal postnatal auditory system development was significantly altered. These findings demonstrate that developmental exposure to this class of environmental contaminant alters cortical development. It is proposed that exposure to noncoplanar PCBs may contribute to common developmental disorders, especially in populations with heritable imbalances in neurotransmitter systems that regulate the ratio of inhibition and excitation in the brain. We conclude that the health implications associated with exposure to noncoplanar PCBs in human populations merit a more careful examination

The incidence of eating disorders has progressively increased over the last several years, mainly affecting both the health and quality of life of young women. Such disorders are primarily an outlet for manifest psychic suffering and secondarily, they jeopardize the integrity and function of multiple organ systems resulting in significant morbidity and sometimes, life-threatening outcomes. The complex emerging interplay of etiopathogenetic factors poses many challenges in their prevention and management, which is further complicated by a reluctance by patients with eating disorders to seek medical evaluation and treatment. Recognition of the oral manifestations is important because these signs and symptoms can provide insights about disease progression and parallel general health and psychic status. Oral health care providers may be one of the few providers contacted by this patient population seeking recall prophylaxis or urgent dental care. Thus, improving understanding and knowledge of both general medical aspects of eating disorders and their oral manifestations could be of great impact in elevating the attention of health providers towards this group of very debilitating disorders and, consequently, improving their overall prognosis. In this paper we will review and discuss all these aspects.

The treatment of laryngeal cancer has evolved through several phases, starting with wide extirpative surgical resection, and evolving through an era of conservation surgery and, finally, planned treatment using modalities of irradiation, chemotherapy and surgery in various combinations. Attempts to extirpate laryngeal cancer date to the nineteenth century, but only by the mid-twentieth century did advances in anesthesia, blood transfusion and antibiotics, make this surgery safe and reliable. Techniques of partial laryngectomy by external approach developed in the second half of the twentieth century, and endoscopic use of the laser refined the concept and provided a new paradigm for surgical treatment, particularly for early lesions. During most of this era, radiation was employed as an alternative method of treatment, with surgery reserved for salvage of radiation failure. By the last decade of the twentieth century, and to the present time, the value of combined modality therapy, using planned combinations of irradiation, chemotherapy and surgery became the standard of care for advanced laryngeal cancer, permitting maximal laryngeal preservation with the highest attainable cure rates.

Recent studies have demonstrated that delivery of genes to the inner ear can achieve a variety of effects ranging from support of auditory neuron survival to protection and restoration of hair cells, demonstrating the utility of vector based gene delivery. Translation of these findings to useful experimental systems or even clinical applications requires a detailed understanding of the pharmacokinetics of gene delivery in the inner ear. Ideal gene delivery systems will employ a well tolerated vector which efficiently transduces the appropriate target cells within a tissue, but spare non-target structures. Adenovectors based on serotype 5 (Ad 5) are commonly used vectors, are easy to construct and have a long track record of efficacious gene transfer in the inner ear. In this study we demonstrate that distribution of Ad5 vector occurs in a basal to apical gradient with rapid distribution of vector to the vestibule after delivery via a round window cochleostomy. Transduction of the vector and expression of the delivered transgene occurs by 10 min post vector delivery. At 24 h post delivery only 16% of vector that was initially detectable within the inner ear by quantitative PCR remained. Perilymph sampling was used to determine that vector concentrations in perilymph peaked at 30 min post delivery and then declined rapidly. Understanding these basic distribution patterns and parameters for delivery are important for the design of gene delivery vectors and vital for modeling dose responses to achieve safe efficacious delivery of a therapeutic agent.

In this study we investigated the role of endothelin-1 (ET-1) and its peripheral receptor (ET-A) in carcinoma-induced pain in a mouse cancer pain model. Tumors were induced in the hind paw of female mice by local injection of cells derived from a human oral squamous cell carcinoma (SCC). Significant pain, as indicated by reduction in withdrawal thresholds in response to mechanical stimulation, began at four days after SCC inoculation and lasted to 28 days, the last day of measurement. Intra-tumor expression of both ET-1 mRNA and ET-1 protein were significantly upregulated compared to normal tissue, and local administration of the ET-A receptor selective antagonist, BQ-123 (100 microM) significantly elevated withdrawal thresholds, indicating the induction of an antinociceptive effect. These findings support the suggestion that ET-1 and ET-A receptors contribute to the severity of carcinoma-induced soft tissue cancer pain

This study assessed the effects of age at implantation on the speech intelligibility of congenitally, profoundly deaf pediatric cochlear implant users. The children received implants during the first eight years of life and were divided into subgroups based on their age at implantation. The children's tape recordings of standard sentences were digitized and played back to normal-hearing listeners who were unfamiliar with deaf speech. Intelligibility was measured as the number of words correctly identified averaged across all listeners. The data showed that earlier implantation had a positive and significant effect on the speech intelligibility of cochlear implant users. The results also suggested that a gradual decline in the ability to acquire spoken language skills may occur over time and, furthermore, cochlear implantation before the age of two years may yield significantly better speech intelligibility outcomes than later implantation. (journal abstract)

OBJECTIVES: We describe the clinical features of granuloma of the membranous vocal fold (as opposed to granuloma of the vocal process, or 'contact granuloma'), a poorly recognized sequela of microlaryngoscopic surgery. Membranous vocal fold granuloma may mimic the initial lesion in appearance, and thus be mistaken for recurrence. METHODS: We performed a retrospective review of cases from 2 institutions. RESULTS: Fifteen cases of membranous vocal fold granuloma from 2 institutions were identified. In all but 1 case, granuloma developed in the early postoperative period, within 8 weeks. Of the 15 cases, 10 followed laser resection of carcinoma. Five were noted following cold steel resection of benign lesions (2 papillomas, 2 cysts, 1 Reinke's edema). Technical aspects of these cases suggest that membranous vocal fold granulomas result from surgical violation of deep tissue planes and/or epithelial defects. All patients were treated with proton pump inhibitors. In 12 cases, the granulomas proved self-limited, resolving over weeks to months following surgery. Three patients underwent surgical removal of the lesion, which confirmed the diagnosis. One of these cases recurred and was treated nonsurgically. CONCLUSIONS: Granuloma should be suspected when a mass lesion appears at the surgical site early in the postoperative course. Surgical excision is generally not necessary and may provoke further growth of granulation tissue

OBJECTIVE: We performed a systematic review of 97 patients in whom an entirely endoscopic modified Lothrop procedure (EMLP) was performed. We studied the safety, efficacy, need for revision surgery, and rate of complication following an EMLP. STUDY DESIGN: The study design was a retrospective chart analysis. METHODS: We performed a retrospective chart review and patient survey of 97 patients who underwent an EMLP at our institution from January 1999 to March 2006. Main outcomes measured were the need for revision surgery including an osteoplastic flap (OPF), improvement in patients' symptoms, and rate of cerebrospinal fluid (CSF) leak. RESULTS: The most common indication for the procedure was chronic frontal sinusitis and/or formation of mucocele. The frontal recess and floor of the frontal sinus were the most common areas of persistent disease. CSF leak rate was 1% (1/97) and was managed successfully at the time of surgery without any long-term sequelae. Twenty-two (23%) patients required revision surgery. Three (3%) patients required revision with an OPF. Some degree of symptomatic clinical improvement was reported by 98% (95/97) of patients. CONCLUSION: EMLP is a safe and effective surgical alternative to OPF for patients with recalcitrant frontal sinus disease. Major complications are rare. A large percentage of patients may require revision surgery.