Squamous metaplasia and chronic rhinosinusitis: a clinicopathological study.

BACKGROUND: The significance of squamous metaplasia (SM) in chronic rhinosinusitis (CRS) is unknown. The objectives of this study were to determine the prevalence of SM in histopathological specimens from patients with CRS and to correlate these histological findings with clinical features. METHODS: We reviewed the clinical records and pathological slides from 87 consecutive patients who underwent endoscopic sinus surgery for CRS. Demographic and clinical data, preoperative Chronic Sinusitis Survey (CSS) scores, and sinus CT stage were evaluated. Pathological slides were graded by a pathologist to characterize the degree of inflammation and SM, when present. CRS patients with and without SM were compared using student's t-test and chi2 test. RESULTS: Evaluation of the pathology slides revealed that 18.4% of specimens had SM present, whereas only 2.2% of pathology reports noted this. Histological grading of chronic inflammation showed significantly greater severity in specimens with SM (n = 16) when compared with the cohort without SM (n = 75; 100.0% versus 77.5%, respectively; p = 0.016). There was no difference in preoperative CT stage or the presence of hyperostosis on imaging, CSS scores, duration of CRS symptoms, or other clinical features between those with SM and those without SM (p > 0.05). Immunodeficiency was the only comorbidity more prevalent in the metaplastic group (12.5% versus 0%, respectively; p = 0.003). CONCLUSION: SM is present in approximately 18% of routine CRS specimens. It has a positive correlation with the severity of inflammation noted histologically in CRS but does not correlate with disease severity or chronicity, clinically.

Concentration gradient along the scala tympani after local application of gentamicin to the round window membrane.

OBJECTIVES: The distribution of gentamicin along the fluid spaces of the cochlea after local applications has never previously been demonstrated. Computer simulations have predicted that significant basal-apical concentration gradients might be expected, and histologic studies indicate that hair cell damage is greater at the base than at the apex after local gentamicin application. In the present study, gradients of gentamicin along the cochlea were measured. METHODS: A recently developed method of sampling perilymph from the cochlear apex of guinea pigs was used in which the samples represent fluid originating from different regions along the scala tympani. Gentamicin concentration was determined in sequential apical samples that were taken after up to 3 hours of local application to the round window niche. RESULTS: Substantial gradients of gentamicin along the length of the scala tympani were demonstrated and quantified, averaging more than 4,000 times greater concentration at the base compared with the apex at the time of sampling. Peak concentrations and gradients for gentamicin varied considerably between animals, likely resulting from variations in round window membrane permeability and rates of perilymph flow. CONCLUSIONS: The large gradients for gentamicin demonstrated here in guinea pigs account for how it is possible to suppress vestibular function in some patients with a local application of gentamicin without damaging auditory function. Variations in round window membrane permeability and in perilymph flow could account for why hearing losses are observed in some patients.

Demonstration of a longitudinal concentration gradient along scala tympani by sequential sampling of perilymph from the cochlear apex.

Local applications of drugs to the inner ear are increasingly being used to treat patients' inner ear disorders. Knowledge of the pharmacokinetics of drugs in the inner ear fluids is essential for a scientific basis for such treatments. When auditory function is of primary interest, the drug's kinetics in scala tympani (ST) must be established. Measurement of drug levels in ST is technically difficult because of the known contamination of perilymph samples taken from the basal cochlear turn with cerebrospinal fluid (CSF). Recently, we reported a technique in which perilymph was sampled from the cochlear apex to minimize the influence of CSF contamination (J. Neurosci. Methods, doi: 10.1016/j.jneumeth.2005.10.008 ). This technique has now been extended by taking smaller fluid samples sequentially from the cochlear apex, which can be used to quantify drug gradients along ST. The sampling and analysis methods were evaluated using an ionic marker, trimethylphenylammonium (TMPA), that was applied to the round window membrane. After loading perilymph with TMPA, 10 1-muL samples were taken from the cochlear apex. The TMPA content of the samples was consistent with the first sample containing perilymph from apical regions and the fourth or fifth sample containing perilymph from the basal turn. TMPA concentration decreased in subsequent samples, as they increasingly contained CSF that had passed through ST. Sample concentration curves were interpreted quantitatively by simulation of the experiment with a finite element model and by an automated curve-fitting method by which the apical-basal gradient was estimated. The study demonstrates that sequential apical sampling provides drug gradient data for ST perilymph while avoiding the major distortions of sample composition associated with basal turn sampling. The method can be used for any substance for which a sensitive assay is available and is therefore of high relevance for the development of preclinical and clinical strategies for local drug delivery to the inner ear.