Faculty Bibliography

The aim of this study was to investigate whether glial-associated molecules exhibit a pattern of expression that could influence oriented dendrite outgrowth in the gerbil lateral superior olive (LSO). In particular, we have previously noted that axon fascicles are oriented parallel to isofrequency laminae in the medial limb of the LSO, as are LSO dendrites, a phenotype that emerges postnatally. Therefore, we examined the immunocytochemical staining pattern of antibodies directed against three proteins that are found along axons: myelin basic protein (MBP), myelin-associated glycoprotein (MAG), and neuron-glia cell adhesion molecule (L1). MAG staining was first observed at postnatal day (P) 4 on the axon fibers surrounding the LSO. By P7 there was a differential pattern of MAG staining within the LSO, and immunopositive fibers were observed solely in the medial limb (e.g., high frequency projection region). Between P7 and P12, MAG staining was restricted largely to fascicles in the medial limb, and these were oriented parallel to the isofrequency axes. Few positive fibers of irregular orientation were observed in the lateral limb (e.g., low frequency projection region). Significant MAG-staining was not observed in the lateral limb until P15. The MAG immunoreactivity extended throughout the LSO by P21, although it was no longer restricted to axon fascicles. In contrast, MBP-positive fibers were uniformly distributed within the LSO by P12. Finally, L1 was found on oriented axon fascicles at P0, but became sparsely distributed throughout the LSO neuropil after P7, and was restricted to neuron cell bodies in the adult. Taken together, the results suggest that oriented axon fascicles bearing MAG and L1 may contribute to the developmental refinement of dendrite and axon arbors within the LSO

Neuron survival and axonal regeneration become severely limited during early postnatal development. In conjunction with our recent organotypic analysis of regeneration in the auditory midbrain, we wished to determine whether neurotrophins could serve as a trophic substance during the postnatal period. Therefore, the current study examines the development of three neurotrophin receptor tyrosine kinases (TrkA, TrkB, and TrkC) in the gerbil auditory brainstem. Immunoreactivity to TrkA, the nerve growth-factor receptor, was observed in nonneuronal cells during the first two postnatal weeks. In the cochlear nucleus of mature animals, however, there was a TrkA-positive neuronal subpopulation. In contrast, immunoreactivity to TrkB and TrkC (the receptors for brain-derived neurotrophic factor and neurotrophin-3, respectively) displayed a widespread distribution in the auditory brainstem. At postnatal day 0, TrkB and TrkC staining was virtually absent from auditory nuclei, although immunopositive neurons were present in the mesencephalic trigeminal nucleus. By postnatal day 7, TrkB- and TrkC-positive neurons were present in most brainstem auditory nuclei. At postnatal day 15, TrkB immunoreactivity was observed throughout the inferior colliculus (IC), the cochlear nucleus, the medial and lateral nuclei of the trapezoid body, and the lateral superior olive, whereas TrkC labeled only a subpopulation of neurons within the central nucleus of the IC. The TrkB immunoreactivity was present on both neuronal somata and dendrites, whereas TrkC was generally restricted to cell bodies. At postnatal day 30, TrkB immunostaining was observed on most neurons of the IC. The medial and lateral nuclei of the trapezoid body displayed extremely strong TrkB staining, followed by the cochlear nucleus. In contrast, the TrkC immunostaining was decreased dramatically by postnatal day 21. Observations at the ultrastructural level confirmed a neuronal localization of TrkB and TrkC. Immunostaining for both receptors was restricted largely to the postsynaptic density of synaptic profiles in both dendrites and somata. In summary, this study illustrates a differential pattern of immunoreactivity between three neurotrophin receptors during development. The general increase of TrkB expression is well correlated with the onset of sound-evoked activity in this system, and its synaptic localization suggests that it may be involved in the modulation or maintenance of postsynaptic physiology

The influence of excitatory transmission on postsynaptic structure is well established in developing animals, but little is known about the role of synaptic inhibition. We addressed this issue in developing gerbils with two manipulations designed to decrease glycinergic transmission in an auditory nucleus, the lateral superior olive (LSO), before the onset of sound-evoked activity. First, contralateral cochlear ablation functionally denervated the glycinergic pathway from the medial nucleus of the trapezoid body (MNTB) to the LSO, while leaving the excitatory pathway intact. Second, continuous release of a glycine receptor antagonist, strychnine (SN), was used to decrease transmission. The strength of excitatory and inhibitory synapses was examined with whole-cell recordings from LSO neurons in a brain-slice preparation. The percentage of LSO neurons exhibiting MNTB-evoked IPSPs was reduced in both ablated and SN-treated animals. In those neurons displaying IPSPs, the amplitude was significantly reduced. This decrease was accompanied by an 8 mV depolarization in the IPSP equilibrium potential. In contrast, the ipsilaterally evoked EPSPs were of unusually long duration in experimental animals. These long-duration EPSPs were significantly shortened by hyperpolarizing the neuron to -90 mV or exposing them to aminophosphonopentanoic acid (AP-5), an NMDA receptor antagonist. Membrane hyperpolarization and AP-5 had little effect in control neurons. In addition, LSO neurons from ablated or SN-treated animals displayed broad rebound depolarizations after membrane hyperpolarization, and these were abolished in the presence of Ni2+. Because both cochlear ablation and SN-rearing were initiated before the onset of sound-evoked activity, the results suggest that spontaneous glycinergic transmission influences the development of postsynaptic properties, including the IPSP reversal potential, NMDA receptor function, and a Ca2+ conductance

Anterior rerouting of the intratemporal facial nerve in the infratemporal fossa approach is employed to access to the jugular bulb, hypotympanum, and lateral skull base, whereas posterior rerouting of the facial nerve, as employed in the transcochlear craniotomy, is most frequently used for surgery of the posterior fossa, cerebellopontine angle, prepontine region, and petrous apex. Facial nerve rerouting may lead to facial paresis or paralysis. This review of the literature is intended to define the physiologic 'cost' of these procedures, so that the neurotologic surgeon can determine if the morbidity incurred in these techniques is worth the resultant exposure. Inconsistencies in reporting facial function places into question the validity of some of the cumulative data reported. Postoperatively, grades I-II facial nerve function was seen in 91% of patients undergoing short anterior rerouting, 74% of patients undergoing long anterior rerouting, and 26% of patients undergoing posterior complete rerouting. Although facial nerve rerouting allows unhindered exposure to previously inaccessible regions, it is achieved at the cost of facial nerve function. Facial nerve dysfunction increases with the length of facial nerve rerouted

Although root fractures are among the less common oral injuries (6 percent), a careful diagnostic evaluation of such injuries is required to arrive at an appropriate treatment plan. The position of the fracture in the root will determine the proper management. The problem of luxation due to trauma often involves the use of dental splints, which, if not properly designed, may cause root resorption, loss of alveolar bone, pulpal necrosis and pulp canal obliteration. The guidelines for the type of splint to use and conditions under which it should be placed are presented

Spontaneous cerebrospinal fluid (CSF) leaks of temporal bone origin are more prevalent than once believed. Twenty-eight of the 61 cases documented in the world literature have been reported since 1992. All but four of these cases involved unilateral defects. The authors have previously reported experiences with 12 cases, with the vast majority of defects localized to the tegmen tympani. These patients also had demonstrated a single area of bone and dural dehiscence. We report two additional cases of spontaneous CSF leak originating from multiple/distant skull base defects. As in previously reported multisite cases, one of our patients demonstrated an elevated opening pressure on lumbar puncture. Significant time intervals existed between leak site presentations, which emphasizes the importance of careful follow-up for treated patients. Potential etiologies and associated factors are also discussed. This patient subset contributes another dimension to the evolving natural history of spontaneous CSF leakage

During the past 25 years, the Radiation Therapy Oncology Group (RTOG) has played a major role in head and neck cancer clinical research. The major research themes for recent and currently active trials have been: (a) combined modality therapy, (b) altered fractionation radiotherapy, (c) hypoxic cell sensitizers, (d) organ preservation, (e) chemoprevention, and (f) clinical/laboratory correlations. For advanced operable disease, the RTOG showed improved local-regional control with postoperative radiotherapy as compared to preoperative radiotherapy for carcinoma of the supraglottic larynx and hypopharynx. This established the use of surgery followed by postoperative radiotherapy as the standard treatment in subsequent RTOG and Intergroup trials for operable disease. For advanced inoperable disease, the RTOG demonstrated the feasibility of testing altered fractionation radiotherapy in a multiinstitutional clinical trials setting. A Phase III trial comparing hyperfractionation and accelerated fractionation to conventional fractionation is now in progress. Phase I/II combined modality studies established the efficacy of concurrent high-dose cisplatin and radiotherapy in the treatment of advanced disease and provided the basis for further testing in Phase III trials for nasopharyngeal carcinoma, larynx preservation, and high-risk advanced operable disease. Analysis of the extensive RTOG Head and Neck Cancer database established the incidence of second malignancies and their adverse impact on patients whose initial tumors were cured by radiotherapy, and provided the basis for chemoprevention trials. Recursive partitioning analysis identified 6 distinct prognostically homogeneous patient groups based on pretreatment tumor or patient characteristics and/or treatment variables. Retrospective analysis identified tumor p105 antigen density as an independent prognostic indicator in patients irradiated for head and neck cancer. Future trials will continue to focus on the reduction of morbidity and mortality, and improvement of the quality of life of head and neck cancer patients through innovative radiotherapy delivery, multimodality approaches, use of chemical and biological modifiers, and other novel therapies, identification of clinical and biological prognostic indicators, and prevention or diminution of acute morbidity and late complications of the disease and its treatment

PURPOSE/OBJECTIVE:There are little data available on the prevalence of human immunodeficiency virus (HIV) disease and its relationship to postoperative infection in patients presenting with mandibular fractures. This retrospective study assesses these parameters. PATIENTS/METHODS:The study population consisted of 251 patients treated for mandibular fractures at San Francisco General Hospital (SFGH) between January 1990 and December 1993. Group 1 (n = 20) was composed of patients with documented HIV infection and group 2 (n = 231) served as controls. The groups were comparable with regard to age, sex, etiology, and number and types of fractures. RESULTS:HIV prevalence for this population was 7.9%, and was consistent with previously documented prevalence studies in SFGH surgical patients. In the HIV-positive group, 6 of 20 patients (30%) developed postoperative infection: 2 soft tissue (10%) and 4 bone-related (20%). In the control group, 22 of 231 patients (9.5%) developed postoperative infections: 16 soft tissue (6.9%) and 6 bone-related (2.6%). Statistical analysis showed a significant difference between the two groups with regard to overall (P = .016) and to bone-related (P = .001) infection rates. There was no statistically significant difference in soft tissue infections between the two groups (P = .953). The rate of postoperative infection was significantly higher in those patients (both HIV-positive and controls) who had open reduction and internal fixation (ORIF; 25/155; 16%) versus those who had closed reduction and maxillomandibular fixation (3/96; 3.1%; P = .003). The postoperative infection rate after ORIF was significantly higher in the HIV-positive (5/11; 45%) compared with the control group (20/144; 13.9%; P = .02). CONCLUSIONS:The results of this study indicate that the overall rate of postoperative infection after treatment of mandibular fractures is significantly higher in HIV-positive than in HIV-negative patients. Specifically, the use of ORIF in HIV-positive patients represents a significant risk.

PURPOSE/OBJECTIVE:This study evaluated the relationship of the mandibular third molar to the lingual nerve. MATERIALS AND METHODS/METHODS:An anatomic dissection of the lingual nerve in the third molar region was done on 20 cadavers (40 sides). RESULTS:The position of the nerve on one side bore no statistical relationship to the position of the nerve on the opposite side. The position of the lingual nerve was variable in both the sagittal and coronal planes. In two specimens the nerve lay superior to the lingual plate and in another the superior surface of the nerve was level with the crest of the lingual plate. CONCLUSION/CONCLUSIONS:These findings have implications for the avoidance of lingual nerve damage during surgery in the third molar and retromolar region of the mandible.

A 61-year-old woman was examined because of unilateral nonpulsatile tinnitus involving the right ear. CT scanning showed a soft-tissue mass in the hypotypanum. Angiographically, the mass was identified as a fenestrated or duplicated internal carotid artery associated with persistence of the stapedial artery. Embryologic considerations are discussed.