Mark Wake

Carboplatin ototoxicity: an animal model

A new animal model of ototoxicity is presented using intravenous carboplatin in adult chinchillas. A range of physiological and morphological effects was produced using doses calculated from the recommended therapeutic range (200-400 mg/m2). Auditory thresholds to tone pips stimuli were monitored using brain stem evoked responses (ABR). Cochlear histopathology was studied by light microscopy (LM) and ultrastructural hair cell abnormalities investigated with scanning electronmicroscopy (SEM). Carboplatin in this animal model predominantly affected the inner hair cells. This may provide an important model for the study of selective loss of the main afferent input in the auditory system.

Selective inner hair cell ototoxicity induced by carboplatin

Carboplatin is a second‐generation platinum antineoplastic agent. It has biological activity similar to cisplatin and is currently recommended for the treatment of ovarian cancer. In clinical use, carboplatin appears less ototoxic than cisplatin. This paper reports the ototoxic effects of carboplatin, in doses equivalent to the clinical use of the drug, in the chinchilla. Intravenous carboplatin 200 to 400 mg/m2 by bolus injection caused significant ototoxicity in this model as revealed by brainstem evoked responses (ABR audiometry). The cochlear pathology as seen by scanning electron microscopy revealed predominantly inner hair cell (IHC) stereocilia damage. Furthermore, the extent (grade) of the morphological lesions appears to be well correlated with the auditory brainstem response pattern of threshold elevation.

Recording from the Inferior Colliculus Following Cochlear Inner Hair Cell Damage

The anti-cancer drug carboplatin has been used to generate inner hair cell (IHC) lesions in the cochleae of chinchilla. This model has provided a valuable physiological tool for the study of the auditory system, particularly concerning the relative roles of IHCs and outer hair cells (OHCs). We recorded responses to contralateral sound stimuli of single units (SU) in the central nucleus (CN) of the inferior colliculus (IC) from normal and carboplatin treated animals. Normal single unit thresholds and frequency tuning curves (FTCs) were found, despite gross IHC damage within the cochleae of carboplatin treated animals. No evoked afferent responses could be detected in CN regions which represented cochlear loci where total IHC loss had occurred. Normal frequency selectivity in the auditory system is possible with small numbers of surviving IHCs provided OHCs remain normal.

The uncinate process: a histological and morphological study.

The uncinate process (UP) has become a familiar anatomical landmark to otolaryngologists due to the increasing popularity of functional endoscopic sinus surgery (FESS) in recent years. This study examines the histological and morphological features of UPs removed from a group of patients undergoing FESS operations for chronic sinusitis. The structure of the UP by light microscopy (LM) is reported. A relatively high proportion of goblet cells and seromucous glands was noted. Scanning electron microscopy (SEM) identified four surface cell types on the UP. Furthermore, four categories of surface morphology were noted. The most common appearance was of predominantly ciliated cells. A nonciliated surface ultrastructure is associated with a longer history of sinonasal symptoms and a higher incidence of surgical intervention.

The early development of sino‐nasal mucosa

The development of human nasal mucosa was studied in 20 fetal heads between 8 and 24 weeks of gestation. Initially the nasal cavity is lined by a single layer of flattened cells, which produces two to three layers of undifferentiated spherical cells. Olfactory epithelium lines the cranial portion of the human fetal nasal cavity at 8 weeks of gestation. Pseudostratified ciliated cuboidal or columnar epithelium appears at 9 weeks of gestation in the nasal cavity and between 14 and 16 weeks of gestation in the primitive ethmoid sinuses and maxillary sinus infundibulum. Goblet cells and glandular acini appear between 12 and 14 weeks of gestation. Initially these goblet cells/glands are found predominantly in the anterior nasal cavity but are more evenly distributed at 24 weeks of gestation. The epithelial development of the nasal septum generally precedes that of the lateral nasal wall. This study documents nasal mucosal maturation and associated anatomic development in the human fetus.

Ectopic production of Beta-Human chorionic Gonadotrop by inverted papilloma of the nose

A series of 19 inverted papillomas (transitional type or Schneiderian papillomas) of the nose were examined using an immunogold-silver (IGS) technique and an indirect immunoperoxidase technique. We demonstrated beta-HCG production in all 19 specimens with both methods. The staining demonstrated by the IGS technique was of a greater intensity and in a larger number of cells than that observed by the indirect immunoperoxidase method.