The sense of smell, its signalling pathways, and the dichotomy of cilia and microvilli in olfactory sensory cells

Smell is often regarded as an ancillary perception in primates, who seem so dominated by their sense of vision. In this paper, we will portray some aspects of the significance of olfaction to human life and speculate on what evolutionary factors contribute to keeping it alive. We then outline the functional architecture of olfactory sensory neurons and their signal transduction pathways, which are the primary detectors that render olfactory perception possible. Throughout the phylogenetic tree, olfactory neurons, at their apical tip, are either decorated with cilia or with microvilli. The significance of this dichotomy is unknown. It is generally assumed that mammalian olfactory neurons are of the ciliary type only. The existance of so-called olfactory microvillar cells in mammals, however, is well documented, but their nature remains unclear and their function orphaned. This paper discusses the possibility, that in the main olfactory epithelium of mammals ciliated and microvillar sensory cells exist concurrently. We review evidence related to this hypothesis and ask, what function olfactory microvillar cells might have and what signalling mechanisms they use

Upper aerodigestive tract cancer: summary of the National Institute for Health and Care Excellence guidelines for England and Wales.

The cancers of the upper aerodigestive tract (CUADT) considered in this guideline document include the oral cavity, oropharynx, nasopharynx, hypopharynx, larynx and paranasal sinus. Squamous cell carcinomas (SCC) are the predominant (91%) histological type of malignancies seen at these sites,with approximately 8500 people per annum being diagnosed with CUADT in England and Wales. This guideline deals with SCC and mucosal melanoma and applies to 94% of CUADT cancers. Between 1990 and 2006, the incidence of oropharyngeal cancer has doubled, oral cavity cancer showed a slight increase, whilst cases of larynx cancer have declined.1 Although the age and sex distribution varies across primary sites, SCCs are commoner in men with incidence starting at the age of 40, and peaking after the age of 60. The aetiologic factors associated with CUADT are smoking, alcohol, human papillomavirus (oropharynx only) and certain occupations.</p

A cost-utility study of the use of pregabalin in treatment-refractory neuropathic pain

ObjectivesA small but significant proportion of patients with peripheral neuropathic pain (NeP) are refractory to the typical treatments applied in clinical practice, including amitriptyline and gabapentin. Thus, they continue to suffer the debilitating effects of NeP. This study aimed to evaluate the cost-effectiveness of pregabalin in comparison to usual care, in patients with refractory NeP, from a third party payer's perspective (NHS).MethodsA stochastic simulation model was constructed, using clinical data from four non-randomized studies, to generate pain pathways of patients receiving usual care and pregabalin. Treatment effect (pain reduction) was converted to quality-of-life (QoL) data, using a regression analysis based on new utility data, collected from a survey of refractory NeP patients presenting to pain clinics in Cardiff, Wales. All relevant direct costs were estimated using resource use from the survey data (where available) and unit costs from the British National Formulary (BNF). The analysis was run over a 5-year time horizon, with costs and benefits discounted at 3.5%.Study limitationsThe use of non-randomized (observational) data to characterize the effectiveness of treatments for NeP. Exclusion of productivity costs and consequences from the analysis.ResultsIn the base case analysis, an incremental cost-effectiveness ratio (ICER) of £10,803 per quality adjusted life year (QALY) was attained. This result was found to be reasonably insensitive to variations in the key input parameters, with ICERs ranging from £8505 to £22,845 per QALY gained.ConclusionsThe analysis shows that pregabalin is a cost-effective alternative to usual care in patients with refractory NeP, with an ICER well below the threshold typically adopted by UK health technology assessment groups, such as NICE.Jason Gordon, Steven Lister, Matthew Prettyjohns, Phil McEwan, Anthony Tetlow, Zahava Gabrie