Faculty Bibliography

We have studied interactions of tenascin with two chondroitin sulfate proteoglycans, neurocan and phosphacan. Neurocan is a multi-domain proteoglycan with a 136-kDa core protein that is synthesized by neurons and binds to hyaluronic acid, whereas the 173-kDa core protein of phosphacan, which is synthesized by glia, represents an extracellular variant of the receptor-type protein tyrosine phosphatase RPTP zeta/beta. Keratan sulfate-containing glycoforms of phosphacan (designated phosphacan-KS) are also present in brain. Immunocytochemical studies of early postnatal rat cerebellum demonstrated that the localization of neurocan, phosphacan, and phosphacan-KS all overlap extensively with that of tenascin, an extracellular matrix protein that modulates cell adhesion and migration. Binding studies using purified proteins covalently attached to fluorescent microbeads demonstrated that proteoglycan-coated beads co-aggregated with differently fluorescing beads coated with tenascin. The co-aggregation was specifically inhibited by Fab' fragments of antibodies against tenascin or the proteoglycans and by soluble neurocan, phosphacan, and tenascin. A solid phase radioligand binding assay confirmed that neurocan, phosphacan, and phosphacan-KS bind to tenascin but not to laminin and fibronectin. Chondroitinase treatment of the proteoglycans or addition of free chondroitin sulfate had no significant effect, indicating that the binding activity is mediated largely via the core glycoproteins. Scatchard analysis demonstrated high affinity binding of 125I-phosphacan, phosphacan-KS, and neurocan to a single site in tenascin, and neurocan and various glycoforms of phosphacan all inhibited binding of 125I-phosphacan to tenascin. In studies of cell adhesion to proteins adsorbed to Petri dishes, phosphacan inhibited adhesion of C6 glioma cells to tenascin whereas neurocan had no effect. Our results suggest that tenascin binds phosphacan and neurocan in vivo and that interactions between chondroitin sulfate proteoglycans and tenascin may play important roles in nervous tissue histogenesis, possibly by modulating signal transduction across the plasma membrane

Carcinoma in situ (CIS) is part of the histopathologic spectrum of laryngeal disorders where invasive squamous cell carcinoma is the endpoint of cellular disarray. Few reports consider prognostic indicators that predict which lesions become invasive. Forty-one patients with CIS of the glottic larynx were analyzed for risk factors that would predict invasive cancer. Anterior commissure involvement by CIS resulted in 92% conversion to invasive squamous cell cancer compared to 17% of lesions limited to the mobile fold. Epidermal growth factor receptors were also analyzed and were found not to be helpful in predicting invasion. Lesions of the mobile fold should be removed endoscopically and the patient should be observed closely for recurrence. Anterior commissure involvement that is inaccessible to complete laser ablation should be radiated, and the patient should be observed carefully

OBJECTIVE: A new modification of vertical dome division (VDD) in rhinoplasty using cartilage overlap and suturing to reestablish the integrity of the alar cartilages is analyzed and compared with the more standard technique of cartilage resection and suturing. DESIGN: Retrospective before-and-after trial. SETTING: Private patients of one of the authors (P.A.A.) undergoing surgery in the Department of Otolaryngology of the University of Toronto (Ontario). PATIENTS: A consecutive sample of 116 patients having undergone open rhinoplasty with VDD between 1981 and 1990 were evaluated. Seventy-five had VDD before 1987, when a cartilage resection and suturing technique was used (P.A.A.); 41 had their surgery after 1987, with the cartilage overlap and suturing technique. All patients were available for follow-up. The mean follow-up time was 15.2 months, with a range of 6 to 63 months. INTERVENTION: Indications for VDD were lobule asymmetry (47%), retrodisplacement (24%), wide domal arch (22%), hanging infratip lobule (6%), and rotation (1%). Prior to 1987, VDD was performed by dividing the alar cartilages, resecting certain portions, and then suturing the cartilages together again to recreate the alar margin. After 1987, VDD was revised by overlapping the portions of cartilage that would have been previously resected and suturing the overlapping portions to recreate the alar margin. MAIN OUTCOME MEASURES: Patient satisfaction; physician evaluation; physical examination; blinded comparison of preoperative and postoperative photographs; need for revision surgery. RESULTS: Overall, six (5.0%) of 116 patients required revision surgery or had photographic and/or physical evidence of nasal tip irregularities. Three (4.0%) of 75 patients from the cartilage excision group and one (2.4%) of 41 patients from the overlap group required revision surgery. The other two patients, one in each group, had minor tip irregularities not requiring surgery. The tip irregularities were due to nasal bossae in four patients and lobule asymmetries in two. There was no alar notching or lower nasal third pinching. Tip irregularities were three times as likely to occur in patients presenting for revision rhinoplasty than in those for primary rhinoplasty. CONCLUSIONS: Vertical dome division is a powerful tool in rhinoplasty, allowing for complex manipulations of alar cartilages to selectively enhance projection, rotation, and domal arch width. It also allows for correction of lobule asymmetries and elongation or hanging of the infratip lobule. The cartilage overlap technique reduces the occurrence of several common postoperative tip abnormalities and lowers the need for revision surgery when compared with cartilage resection VDD. The reported results can only be considered trends, as sample sizes in the series were too small to allow for statistical significance

The accuracy with which behavioral comfort levels could be predicted by the electrically elicited acoustic reflex threshold (EART) was examined in 35 Nucleus Cochlear Implant patients (16 adults and 19 children). EARTs were obtained by stimulating bipolar pairs of electrodes through the Nucleus Diagnostic Programming System and monitoring the change in middle ear admittance in the ear contralateral to the implanted ear. EARTs were successfully elicited in 24 patients. EARTs differed from behavioral comfort levels by a mean of 19.4 stimulus level units for adults and 9.6 stimulus level units for children. While EARTs were found to be acceptably close to behavioral comfort levels in four adults and eight children, EARTs significantly overestimated or underestimated comfort levels in the rest. The results of this study suggested that while the EART does not accurately predict comfort levels in all cases, it may provide valuable information regarding levels which should not be exceeded when programming the cochlear implant. Cautious use of information available from the EART may prove useful for programming the cochlear implant in children or adults who are unable to make reliable psychophysical judgments.

Two cases of pediatric isolated cervical emphysema caused by foreign bodies are presented. This report emphasizes the need for roentgenograms, flexible nasolaryngoscopy, and situational barium swallows to identify the exact location of a tear and to determine whether the situation requires direct laryngoscopy and esophagoscopy to remove a foreign body, or an open surgical repair of a mucosal disruption. The treatment of this self-limited condition usually requires only antibiotics, fasting, intravenous fluid, and most importantly, close observation for signs of perforation

The medial superior olive (MSO) functions as a coincidence detector for interaural time and phase differences by integrating excitatory synaptic inputs. Recent studies demonstrating glycinergic projections to MSO neurons suggest that coincidence detection results from the temporal integration of both EPSPs and IPSPs. We examined the impact of synaptic inhibition on the temporal coding properties of gerbil MSO neurons in vitro with intracellular recordings and electrical stimulation. For low-level bilateral electric stimulation, the EPSPs summated to produce an action potential in 73% of MSO neurons if they occurred within 50-500 microseconds of one another. Synaptic inhibition became more prominent at higher stimulus amplitudes in 73% of MSO neurons, and could block an evoked action potential if the stimuli to each pathway were delivered within 250 microseconds of one another. The glycine receptor antagonist strychnine influenced the response to simulated interaural time differences. In the presence of strychnine, interstimulus delays that originally resulted in full action potential suppression were sufficient to evoke an action potential. For trains of stimuli, as stimulus intensity increased (spatial summation), or as stimulus repetition rate increased to 100-500 Hz (temporal summation), there was a decrease in the number of stimulus pulses that evoked an action potential. In the presence of strychnine, MSO neurons generated a greater percentage of action potentials to the stimulus trains. When stimulus trains were delivered bilaterally, MSO neurons fired a greater number of action potentials at specific interstimulus time differences, and were selectively inhibited at other time differences.(ABSTRACT TRUNCATED AT 250 WORDS)

Cavernous malformations are congenital abnormalities of the cerebral vessels that affect 0.5% to 0.7% of the population. They occur in two forms: a sporadic form characterized by isolated lesions, and a familial form characterized by multiple lesions with an autosomal dominant mode of inheritance. The management of patients with cavernous malformations, particularly those with the familial form of the disease, remains a challenge because little is known regarding the natural history. The authors report the results of an ongoing study in which six families afflicted by familial cavernous malformations have been prospectively followed with serial interviews, physical examinations, and magnetic resonance (MR) imaging at 6- to 12-month intervals. A total of 59 members of these six families were screened for protocol enrollment; 31 (53%) had MR evidence of familial cavernous malformations. Nineteen (61%) of these 31 patients were symptomatic, with seizures in 12 (39%), recurrent headaches in 16 (52%), focal sensory/motor deficits in three (10%), and visual field deficits in two (6%). Twenty-one of these 31 patients underwent at least two serial clinical and MR imaging examinations. A total of 128 individual cavernous malformations (mean 6.5 +/- 3.8 lesions/patient) were identified and followed radiographically. During a mean follow-up period of 2.2 years (range 1 to 5.5 years), serial MR images demonstrated 17 new lesions in six (29%) of the 21 patients; 13 lesions (10%) showed changes in signal characteristics, and five lesions (3.9%) changed significantly in size. The incidence of symptomatic hemorrhage was 1.1% per lesion per year. The results of this study demonstrate that the familial form of cavernous malformations is a dynamic disease; serial MR images revealed changes in the number, size, and imaging characteristics of lesions consistent with acute or resolving hemorrhage. It is believed that the de novo development of new lesions in this disease has not been previously reported. These findings suggest that patients with familial cavernous malformations require careful follow-up monitoring, and that significant changes in neurological symptoms warrant repeat MR imaging. Surgery should be considered only for lesions that produce repetitive or progressive symptoms. Prophylactic resection of asymptomatic lesions does not appear to be indicated