Evaluation of procedures to reduce fluid flow in the fistulized guinea-pig cochlea.

The rate of longitudinal flow of fluid in scala tympani (ST) has been quantified under a number of experimental conditions. The method used to measure flow involved using a tracer ion (trimethylphenylammonium: TMPA) as a volume flow marker. Movement of marked perilymph was monitored by ion-selective microelectrodes which were capable of detecting exceedingly low concentrations of TMPA. Our results show that when the cochlea is perforated at the apex, flow rates of 400-500 nl/min are induced in ST, compared to the normal very slow rate of 2 nl/min when the cochlea is sealed. This artifactual flow of CSF through the perforated cochlea can be reduced to 6.9 nl/min by releasing the hydrostatic pressure of cerebrospinal fluid (CSF) or further reduced to 1.8 nl/min by surgically obstructing the cochlear aqueduct. In addition, we observed no basally-directed flow in ST when the round window (RW) was perforated, demonstrating that perilymph is not produced in volume as previously assumed. This study demonstrates the importance of separating artifactual flows, induced by the experimental procedures required to access the cochlear fluids, from the low flow rates which occur in normal, physiologic conditions.

Alcohol, tobacco and paan use and understanding of oral cancer risk among Asian males in Leicester.

OBJECTIVES: To determine use of alcohol, tobacco and paan among males from the various Asian communities in Leicester; and assess their knowledge and attitudes towards oral cancer risk factors and prevention. Also, to determine any differences regarding habits and attitudes between first and second generation Asians. DESIGN: Volunteers completed a confidential, bilingual questionnaire regarding alcohol, tobacco and paan use and also knowledge about oral cancer risk factors and preventive measures. SETTING: Participants were recruited from sources that included GPs' surgeries, sixth form colleges and places of worship. SUBJECTS: Asian males, i.e. those of Indian, Pakistani, Bangladeshi or Sri Lankan origin; over the age of 16 years and resident in Leicester. MAIN OUTCOME MEASURES: Quantitative figures were obtained from the questionnaires as to the frequency of alcohol, tobacco and paan use and responses regarding oral cancer knowledge, risk factors and preventive measures. RESULTS: The principal Asian community groups in Leicester were Hindu, Sikh, Muslim and Jain. Significant differences were found in males from these groups with regards to habits and oral cancer awareness. Muslim males use tobacco and paan more than the other groups but avoid alcohol. Sikh males drink more alcohol (especially spirits) than the other groups but their use of tobacco and paan is low. Habits of Hindu and Jain males are variable. However, approximately 10% of both 1st and 2nd generation Hindu males combine all three habits of alcohol, tobacco and paan; and are thus considered to be at high risk of developing oral cancer. Seven percent of 1st generation Hindu males were found to chew paans containing tobacco which are strongly associated with oral cancer. More 2nd generation Jains drank alcohol than the 1st generation, and a greater proportion of Hindu, Sikh and Jain 2nd generation males drink spirits than their older counterparts. Knowledge of oral cancer risk factors and preventive measures were variable, the lowest level of knowledge being among the 1st generation Sikh group. Few volunteers realised the risk of alcohol drinking in the aetiology of oral cancer. CONCLUSION: The 'Asian' community in Leicester is not homogeneous, but consists of distinct community groups; each with their own cultural beliefs, habits and attitudes. Knowledge of these differences can be used to provide appropriate health education programmes suitably targeted to reduce the use of the known risk factors for oral cancer.

Cochlear threshold assessment using tone-derived action potentials.

An evoked-potential technique has been evaluated which detects whether the cochlea responds to a continuous, low level tone. The technique involves recording the cochlear action potential (AP) response to a suprathreshold probe tone, first in the absence and then in the presence of a continuous masking tone at the same frequency. Subtraction of the masked AP waveform from the unmasked AP yields a 'derived' potential, provided the continuous tone is above the threshold of cochlear sensitivity. Derived AP responses may be recorded with continuous masking tones over 10 dB below the threshold to the probe stimulus. In normally hearing guinea pigs, the mean best derived threshold using a 10-microV response criterion was 7.1 dB SPL, compared to 18.9 dB for conventional AP thresholds. The tone-derived response appears to provide a more sensitive and frequency-specific method for determining cochlear thresholds.

An immunohistochemical study of altered immunomodulatory molecule expression in head and neck squamous cell carcinoma.

For the presentation of peptide antigens to cytotoxic CD8+ T lymphocytes of the immune system, the expression of human leukocyte antigen (HLA) class I molecules on the cell surface is necessary. There is increasing evidence that surface HLA class I antigen expression is altered in a variety of human tumours by either loss or down-regulation of these molecules, which may be a strategy for evasion of immunosurveillance by malignant cells. This study has examined the expression of HLA class I molecules in head and neck squamous cell carcinoma (HNSCC) specimens by immunohistochemistry, using a wide panel of antibodies directed against allele-specific as well as monomorphic determinants of these molecules. The expression of TAP proteins, HLA-DR and the co-stimulatory molecule ICAM-1 were also studied. In addition, the expression of the tumour-associated antigens (TAA) p53 and MAGE genes was determined. Aberrant allelic expression of HLA class I antigens was detected in 17 out of 34 (50%) of the specimens stained, whereas HLA class I expression determined by W6/32 staining was found to be heterogeneous in only 2 out of 34 (6%) cases. Decreased expression of ICAM-1 was observed in 12 out of 34 (35%) tumour specimens and de novo expression of HLA-DR (HLA class II) by carcinoma cells in 13 out of 34 (38%) cases. Aberrant expression of HLA class I antigens was frequently observed in cases in which MAGE genes and p53 overexpression were detected. The altered expression of these immunomodulatory molecules in HNSCC may affect prognosis and has important implications for peptide-based immunotherapy strategies for these patients.