Faculty Bibliography

Although previous efficacy studies have reported high compliance rates among children treated by private physicians with prophylactic antibiotics for prevention of otitis media, compliance rates in a lower socioeconomic, urban clinic population have not been well described. Eighty children who were placed on daily low dose antibiotics in the Pediatric Otolaryngology Clinic at Bellevue Hospital were prospectively followed in order to estimate compliance in this population. Compliance was estimated by the parent's stated word alone. Of the 77 patients with records adequate for analysis, only 36 (46.8%) families claimed compliance, 18 (23.4%) admitted non-compliance, and 23 (29.9%) did not reliably return for follow-up clinic visits. Statistical analysis revealed that no single characteristic of the patient population or the treatment regimen strongly influenced compliance. The factors examined included: the child's age, sex, race and otologic diagnosis, the type of prophylaxis prescribed, the parent's ability to speak English, national origin, consistency of follow-up, and method of payment. Based on these results, less than half of the children attending an inner city clinic compiled with maintenance medication. The clinician should consider alternate treatment modalities, such as the insertion of middle ear ventilation tubes, if poor compliance with prolonged antibiotic treatment is suspected

Phosphacan is a chondroitin sulfate proteoglycan produced by glial cells in the central nervous system, and represents the extracellular domain of a receptor-type protein tyrosine phosphatase (RPTP zeta/beta). We previously demonstrated that soluble phosphacan inhibited the aggregation of microbeads coated with N-CAM or Ng-CAM, and have now found that soluble 125I-phosphacan bound reversibly to these neural cell adhesion molecules, but not to a number of other cell surface and extracellular matrix proteins. The binding was saturable, and Scatchard plots indicated a single high affinity binding site with a Kd of approximately 0.1 nM. Binding was reduced by approximately 15% after chondroitinase treatment, and free chondroitin sulfate was only moderately inhibitory, indicating that the phosphacan core glycoprotein accounts for most of the binding activity. Immunocytochemical studies of embryonic rat spinal phosphacan, Ng-CAM, and N-CAM have overlapping distributions. When dissociated neurons were incubated on dishes coated with combinations of phosphacan and Ng-CAM, neuronal adhesion and neurite growth were inhibited. 125I-phosphacan bound to neurons, and the binding was inhibited by antibodies against Ng-CAM and N-CAM, suggesting that these CAMs are major receptors for phosphacan on neurons. C6 glioma cells, which express phosphacan, adhered to dishes coated with Ng-CAM, and low concentrations of phosphacan inhibited adhesion to Ng-CAM but not to laminin and fibronectin. Our studies suggest that by binding to neural cell adhesion molecules, and possibly also by competing for ligands of the transmembrane phosphatase, phosphacan may play a major role in modulating neuronal and glial adhesion, neurite growth, and signal transduction during the development of the central nervous system

We have previously shown that aggregation of microbeads coated with N-CAM and Ng-CAM is inhibited by incubation with soluble neurocan, a chondroitin sulfate proteoglycan of brain, suggesting that neurocan binds to these cell adhesion molecules (Grumet, M., A. Flaccus, and R. U. Margolis. 1993. J. Cell Biol. 120:815). To investigate these interactions more directly, we have tested binding of soluble 125I-neurocan to microwells coated with different glycoproteins. Neurocan bound at high levels to Ng-CAM and N-CAM, but little or no binding was detected to myelin-associated glycoprotein, EGF receptor, fibronectin, laminin, and collagen IV. The binding to Ng-CAM and N-CAM was saturable and in each case Scatchard plots indicated a high affinity binding site with a dissociation constant of approximately 1 nM. Binding was significantly reduced after treatment of neurocan with chondroitinase, and free chondroitin sulfate inhibited binding of neurocan to Ng-CAM and N-CAM. These results indicate a role for chondroitin sulfate in this process, although the core glycoprotein also has binding activity. The COOH-terminal half of neurocan was shown to have binding properties essentially identical to those of the full-length proteoglycan. To study the potential biological functions of neurocan, its effects on neuronal adhesion and neurite growth were analyzed. When neurons were incubated on dishes coated with different combinations of neurocan and Ng-CAM, neuronal adhesion and neurite extension were inhibited. Experiments using anti-Ng-CAM antibodies as a substrate also indicate that neurocan has a direct inhibitory effect on neuronal adhesion and neurite growth. Immunoperoxidase staining of tissue sections showed that neurocan, Ng-CAM, and N-CAM are all present at highest concentration in the molecular layer and fiber tracts of developing cerebellum. The overlapping localization in vivo, the molecular binding studies, and the striking effects on neuronal adhesion and neurite growth support the view that neurocan may modulate neuronal adhesion and neurite growth during development by binding to neural cell adhesion molecules

The clinical courses of children with acquired immunodeficiency syndrome (AIDS) who underwent diagnostic flexible bronchoscopy at Bellevue Hospital from 1987-1992 were reviewed to determine the value of the procedure in patient management. Twenty-eight children (age 13 days to 12 years) underwent 31 bronchoscopies for indications including respiratory distress, fever and abnormal chest radiograph. Procedures were well tolerated. Complications were limited to transient hypoxia and epistaxis. Although 58% of bronchoscopies yielded a diagnosis (Pneumocystis carinii, Streptococcus viridans, Pseudomonas aeruginosa, Cytomegalovirus, atypical mycobacterium, giant cell pneumonia, and mechanical obstruction), empiric medical therapy was altered in only 16% of cases. Bronchoscopic diagnoses are correlated with Centers for Disease Control (CDC) classification, immune status, treatment and outcome

Massive skull base injuries require detailed preoperative neurological and neurovascular assessment prior to undertaking surgical repair of isolated cranial nerve deficits. We present the management of a patient with traumatic facial paralysis, cerebrospinal fluid leak, and carotid artery cavernous sinus fistula as the result of a gunshot wound to the skull base. The carotid artery cavernous sinus fistula was ultimately controlled with super-selective embolization via the vertebral artery. The facial nerve injury was then safely treated with mobilization of the labyrinthine and vertical segments to allow a primary anastomosis

Endoscopic instruments have revolutionized surgical diagnosis and treatment. Recently, a high resolution microfiberoptic endoscope has been developed that has vast potential for otologic use. This microfiberoptic endoscope was used in cadaver and human studies to visualize the middle ear cavity. The technique used involved placing a 1.0-mm or smaller microfiberoptic scope into the middle ear via a tympanic membrane perforation, through a myringotomy tube or up the eustachian tube. Using the scope, the mesotympanum and hypotympanum can be well visualized. Similarly, the round window, oval window, ossicular chain, and related structures can be clearly demonstrated and recorded photographically. This technique has great potential to enhance diagnosis without open surgery

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

The potential influence of auditory information in the production of /s/ and /integral of/ was explored for postlingually deafened adults with four-channel Ineraid cochlear implants. Analyses of the spectra of the sibilant sounds were compared for speech obtained prior to implant activation, after early implant use and after 6 months of use. In addition, the output of the Ineraid device (measured at each of the four electrodes) was analyzed with pre- and postactivation speech samples to explore whether the speech production changes were potentially audible to the cochlear-implant user. Results indicated that subjects who showed abnormally low or incorrect contrast between /s/ and /integral of/ preactivation, and who received significant auditory benefit from their implants were able to increase the distinctiveness of their productions of the two speech sounds