It appears that uvulopalatopharyngoplasty (UVPP) is a reliable procedure for reducing snoring, but much less reliable when used as a treatment for OSAS. This is thought to be because of poor patient selection in that the site of the problem is not always the site of the operation. We present the technique of sleep nasendoscopy which allows direct visualization of the site or sites of obstruction in a sleeping patient. Our study has shown that there are patients with obstructive sleep apnoea syndrome (OSAS) in whom the only site of pharyngeal obstruction is at the velopharynx. These patients should do well with the relatively simple procedure of UVPP. This is not true for many other OSAS patients in whom we found that obstruction was multisegmental. This helps to explain the frequently poor results of UVPP in OSAS patients. We feel that this form of preoperative assessment will avoid unnecessary surgery.

Alternate forms of the PolII transcription initiation machinery have been proposed to play a role in selective activation of cell-type-specific gene expression programs during cellular differentiation. The cannonball(can) gene of Drosophila encodes a homolog of a TBP-associated factor (dTAF5) protein expressed only in spermatocytes, where it is required for normal transcription of genes required for spermatid differentiation. We show that Drosophila primary spermatocytes also express four additional tissue-specific TAFs: nht (homolog of dTAF4), mia (homolog of dTAF6), sa (homolog of dTAF8) and rye (homolog of dTAF12). Mutations in nht, mia and sa have similar effects in primary spermatocytes on transcription of several target genes involved in spermatid differentiation, and cause the same phenotypes as mutations in can, blocking both meiotic cell cycle progression and spermatid differentiation. The nht, mia, sa and rye proteins contain histone fold domain dimerization motifs. The nht and rye proteins interact structurally when co-expressed in bacteria, similarly to their generally expressed homologs TAF4 and TAF12,which heterodimerize. Strikingly, the structural interaction is tissue specific: nht did not interact with dTAF12 and dTAF4 did not interact with rye in a bacterial co-expression assay. We propose that the products of the five Drosophila genes encoding testis TAF homologs collaborate in an alternative TAF-containing protein complex to regulate a testis-specific gene expression program in primary spermatocytes required for terminal differentiation of male germ cells.

It appears that uvulopalatopharyngoplasty (UVPP) is a reliable procedure for reducing snoring, but much less reliable when used as a treatment for OSAS. This is thought to be because of poor patient selection in that the site of the problem is not always the site of the operation. We present the technique of sleep nasendoscopy which allows direct visualization of the site or sites of obstruction in a sleeping patient. Our study has shown that there are patients with obstructive sleep apnoea syndrome (OSAS) in whom the only site of pharyngeal obstruction is at the velopharynx. These patients should do well with the relatively simple procedure of UVPP. This is not true for many other OSAS patients in whom we found that obstruction was multisegmental. This helps to explain the frequently poor results of UVPP in OSAS patients. We feel that this form of preoperative assessment will avoid unnecessary surgery.

SummaryThe pleuromutilin antibiotic tiamulin binds to the ribosomal peptidyl transferase centre. Three groups of Brachyspira spp. isolates with reduced tiamulin susceptibility were analysed to define resistance mechanisms to the drug. Mutations were identified in genes encoding ribosomal protein L3 and 23S rRNA at positions proximal to the peptidyl transferase centre. In two groups of laboratory-selected mutants, mutations were found at nucleotide positions 2032, 2055, 2447, 2499, 2504 and 2572 of 23S rRNA ( Escherichia coli numbering) and at amino acid positions 148 and 149 of ribosomal protein L3 ( Brachyspira pilosicoli numbering). In a third group of clinical B. hyodysenteriae isolates, only a single mutation at amino acid 148 of ribosomal protein L3 was detected. Chemical footprinting experiments show a reduced binding of tiamulin to ribosomal subunits from mutants with decreased susceptibility to the drug. This reduction in drug binding is likely the resistance mechanism for these strains. Hence, the identified mutations located near the tiamulin binding site are predicted to be responsible for the resistance phenotype. The positions of the mutated residues relative to the bound drug advocate a model where the mutations affect tiamulin binding indirectly through perturbation of nucleotide U2504.

Adult users of unilateral Nucleus CI24 cochlear implants with the SPEAK processing strategy were randomised either to receive a second identical implant in the contralateral ear immediately, or to wait 12 months while they acted as controls for late-emerging benefits of the first implant. Twenty four subjects, twelve from each group, completed the study. Receipt of a second implant led to improvements in self-reported abilities in spatial hearing, quality of hearing, and hearing for speech, but to generally non-significant changes in measures of quality of life. Multivariate analyses showed that positive changes in quality of life were associated with improvements in hearing, but were offset by negative changes associated with worsening tinnitus. Even in a best-case scenario, in which no worsening of tinnitus was assumed to occur, the gain in quality of life was too small to achieve an acceptable cost-effectiveness ratio. The most promising strategies for improving the cost-effectiveness of bilateral implantation are to increase effectiveness through enhanced signal processing in binaural processors, and to reduce the cost of implant hardware.