Dr Mussadiq Shah (Essex Centre for Neurological Science, Oldchurch Hospital, Romford, Essex, RM7 0BE )

There has been gradual increase of interest in olfaction since it was realised that anosmia was a common feature of idiopathic Parkinson’s disease (IPD) and Alzheimer-type dementia. In this review the following observation can be made:

We assessed olfaction in Essential tremor (ET) as it may be confused with IPD. We evaluated 60 patients with ET, 62 with IPD and 70 controls. The UPSIT and OERP results show that IPD patients have reduced or absent smell sense whereas most ET patients are normal. Olfaction has not been systematically examined in drug-induced Parkinsonism but our preliminary results suggest that those with reduced olfaction develop permanent Parkinsonism.

Dr Charles Evans (Glasgow Caledonian University)

Accessory Olfaction arises from the vomeronasal chemosensory input which integrates the neuroendocrine and chemical-signalling mechanisms of lower => higher Vertebrates. An overview of this neglected system (the AOS) reveals many characteristics not shared with the main olfactory sense (the MOS), ranging from gross morphology to genomic constituents.

The main criterion for a functional AOS is a physiologically competent vomeronasal neuroepithelium linked to a distinct primary processing centre - the accessory olfactory bulb. This exists in amphibians and in most major terrestrial groups. Exceptions occur amongst reptiles (crocodilians, chameleons) and mammals (some bats & primates) where there is a near vestigial status. The nature of AOS-specific responses, mediated by nonvolatile protein <> odourant semiochemical complexes, points to a selective importance for individual, gender and group identity, which is largely linked to reproductive events. However, the relevance of vomerolfaction in relation to the processing function(s) exerted by the MOS remains enigmatic. Both variously contribute to the social/neurocrine dynamics involved with intra- & inter-species signalling. The former will be illustrated by communicative practices in elephants. Particular questions are posed by the occurrence in several diosmic taxa of (secondary ?) sexual differentiation within the AOS, a unique property for any mammalian, let alone primate, sensory system.

An analysis of the likely explanations for the particular evolutionary and developmental characteristics of vomeronasal chemoreception will be attempted.

Dr Christopher Hawkes, FRCP, (Essex Neuroscience Centre, Oldchurch Hospital, Romford, Essex, RM7 0BE)

This review will deal mainly with the effects of aging, Alzheimer’s disease (AD) and cerebellar ataxia.

Olfaction in Aging.
Although it is well recognised that smell sense declines with age there are few studies analysing the components that are affected. We used our database of 211 UPSIT-40 healthy controls aged 17-90 (132 female, 79 male; mean age 49y). It was noted that there was significant decline in olfactory score after the age of 36y and that the rate of decline increased with age. We used the component analysis of Doty et al (1984) to determine the ratings for pleasantness, intensity, irritation, warmth and familiarity. There was significant decline in all ratings with age using 50y as a cut off point. Intensity followed by hedonic score were the best predictors of age. Some low intensity rated odours were identified irrespective of age and these included: chocolate, liquorice, leather, grass, coconut, strawberry, rose, watermelon. In testing for olfactory defects in the elderly it is important to use odours that are relatively preserved and these 8 odours are compliant with this.

Alzheimer’s disease.
Pathological studies suggest that the earliest change is in the transentorhinal cortex which is a boundary zone between the sensory association areas and their input to entorhinal cortex. Non-specific pathological changes occur in the nasal neuroepithelium. The olfactory bulb is significantly damaged in all regions including the anterior olfactory nucleus but it is not clear whether the bulb changes precede those of the transentorhinal cortex. Clinically there is claimed to be impairment of identification, memory, discrimination, detection threshold or semantic categorisation. Limited information regarding olfactory evoked potentials gives an unclear picture.

Cerebellar Ataxia.
Recent work suggests that the cerebellum may be involved in sniffing and perhaps olfactory processing. Two studies suggest that in some inherited ataxias there is smell impairment i.e. Friedreich’s ataxia and SCA 2. This is thought to support the involvement of the cerebellum in olfactory processing but there are no pathological studies of the major olfactory pathways in either of these conditions, hence the involvement of the cerebellum in smelling is not established.

Dr Glenis Scadding (The Royal National Throat, Nose & Ear Hospital, London)

Barbara A. Sommerville¹, John Church², Donald M. Broom¹ and Hywel Williams³

Physicians have long been aware that their sense of smell can be useful in the diagnosis of human and animal disease. The area for olfactory reception in a dog's nose is about 1000 fold as large as man's. The volume of dog brain devoted to analysing odour, pattern matching and olfactory memory is much larger than that of man. These facts form the basis for using dogs in a wide variety of tasks, for instance, law enforcement, disabled human support and even perhaps disease diagnosis. This paper will review the evidence that dogs can detect malignant changes in tumours and present the initial results from training them to do so using human urine to monitor prostate tumours.

Two letters in The Lancet [Williams, H.; Pembroke, A., 1989 and Church, J.; Williams, H. 2001] described how pet dogs saved the life of their owners by alerting them to a malignant change in a long established mole and another skin lesion. Since then we have recorded 14 similar cases, several clinically substantiated and the rest anecdotal. All these cases have concerned pet dogs reacting spontaneously to a member of their family and probably depended upon a high degree of human/dog bonding.

Our new research project seeks to find out how useful a dog with specific training can be in detecting odorous malignant changes in prostate and skin cancers. These carcinomas tend to develop insidiously from long-standing benign conditions and therefore present a diagnostic challenge. The conventional methods of diagnosis are too demanding and invasive to be carried out in routine screening.

Prostate carcinoma is the second most common cause of premature male death after heart disease (Moyad 1999). The major problem for prognosis and medical advice for the patient is that this disease presents continuum of pathology from benign hypertrophy, which affects most of the male population above the age of 60 (Neal et al, 2000), through to malignant carcinoma. If dogs can be trained to detect early malignant changes and do this more dependably than existing methods, they have a huge potential for rapid non-invasive screening which will lead to a swift medical response and save many lives.

Dr John Church Abney Court, Bourne End, Bucks SL8 5DL UK

Since the 1920s maggots have been used as agents of wound cleansing, now generally known as Maggot Débridement Therapy (MDT). With the advent of antibiotics, MDT virtually disappeared. But in the past fifteen years it has been revived, firstly in the United States, then, in 1995, in the UK, Israel and beyond. The past ten years has seen a dramatic development of MDT, particularly in Europe. We estimate that some 30,000 patients have now been treated this way. Maggots not only digest and remove necrotic material, but they destroy bacteria, and actively enhance wound healing. In many centres, MDT has now become an integral part of modern wound care. It is safe and low cost, applicable as much in hospital as in the community, in the ‘West’ as in the ‘Tropics’.

Being a living organism the maggot is as fickle and unpredictable in its behaviour as any other living organism. Study of the behaviour of maggots in the wild, in the laboratory, and in the human wound, indicates a ‘purposefulness’, which we presume to be a response to signals from the immediate environment. The fly species that we culture for clinical use of the maggots, is the blowfly Lucilia sericata (Greenbottle). These maggots are naturally dynamic, actively moving around a food source. They are air-breathing, through their posterior spiracles, but semi-aquatic in their feeding.

This presentation will ask more questions than it answers. What are the signals to which these maggots respond? Are these signals air-borne, water-borne or both? If we knew more about these signals, could we better control the behaviour of our ‘clinical’ maggots?

Dr Krishna Persaud DIAS, UMIST, PO Box 88, Sackville Street, Manchester M60 1QD

EMAIL: kcpersaud@umist.ac.uk

Many diseases and intoxications are accompanied by characteristic odours, and their recognition can provide diagnostic clues, guide the laboratory evaluation, and affect the choice of immediate therapy. The realisation that "electronic nose" technologies may be a useful diagnostic aid has spurred activity in many research laboratories and companies. This presentation reviews major activity in the field, and provides a perspective on measurement and sampling requirements for applications of "electronic noses" in clinical measurements and diagnosis. Examples are given of the identification of pathogens that cause infectious disease of the upper respiratory tract and ears; the classification of cyanobacteria, Microcystis aeruginosa, in water that may produce toxins that are poisonous to cattle; the diagnosis of pneumonia in humans and detection of lung cancer.

Dr Alan Cork University of Greenwich, Central Avenue, Chatham Maritime, Kent ME4 4TB, UK.

The lecture will provide a rapid review of our understanding of the chemistry that underlies the uncanny ability of female mosquitoes to select and locate unwary hosts. For mosquitoes this is a dangerous task, if caught she risks being killed by the potential host. For the host the consequences can be equally severe if the mosquito is carrying one of the many diseases that rely on such vectors for transmission. Some of the more efficient vectors of human diseases are highly anthropophilic. In order for them to successfully blood-feed they need to be able to recognise and respond to host-specific cues. Early work demonstrated that heat, humidity and carbon dioxide were important cues for mosquitoes but they are not host-specific. 1-Octen-3-ol, ammonia and a range of saturated aliphatic carboxylic acids have laterally been highlighted for their ability to attract mosquito species, at least in wind-tunnel bioassays, but again they are not human-specific.

Costantini et al. (2001) found that components of axillary odours, 7-octenoic acid, (E)- and (Z)-3-methyl-2-hexenoic acid, identified by Zeng et al. (1992) elicited behavioural responses from Anopheles gambiae s. l. in the presence of carbon dioxide, although in the latter case the effect was to reduce trap catch. L-Lactic acid is also known to affect the behaviour of the related Aedes aegypti but only in the presence of carbon dioxide. Recent work undertaken in partnership with Tim Healy and colleagues (2002) demonstrated that landing responses were elicited from female Anopheles gambiae in wind tunnel bioassays by human-specific 2-oxocarboxylic acids. The results of this work and implications for developing an odour-bait that could be utilised for monitoring purposes in malaria and dengue endemic areas will be discussed.

Selected references

Sara Jackson (Clinical Veterinary Science, Bristol University)

People have used dogs for thousands of years to locate useful objects. This is no less true in the 21st centaury where they are used to locate objects that are vital to human safety, such as firearms, drugs and explosives. The common factor in the location of these objects is the reliance on airborne scent as there is rarely an odour trail leading to them. Surprisingly, there has been no behavioural research into the strategies that dogs use to do this.

This research focuses on the fundamental questions as to when and why a dog changes its search strategy during source location. First, a set of behavioural descriptors was created, and then dogs were filmed as they located a hidden object to quantify the key behaviour patterns during source location. Check Pace, a slight pause in movement with a distinct change in direction, has been shown to be a strong indicator that the scent has been detected. Gait, head carriage and ear carriage are all significantly different before and after Check Pace.

This work was funded by the MOD Corporate Research Programme and contains Crown copyright.

Patrick Dunphy, Ian Butler and Ingmar Qvist Danisco (UK) Ltd., Wellingborough, Northants., England.

The development of chemical ionisation technique such as PTR-MS have made the continuous monitoring of fast formation and release of volatile organic compounds (VOC’s) a facile process. The technique is simple to operate and requires essentially no work up procedure. Quantification of VOC’s in the gas phase in the range pptv-ppmv is readily achievable and complex mixtures of aroma compounds, including flavour cocktails, can be simultaneously monitored both in vitro and in nose in view of the generally relative simplicity of the spectra associated with the soft ionisation procedure employed. The method is primarily employed for monitoring compounds and mixtures in vitro and in nose and not for identification purposes (1). An insight into the formation and release behaviour of flavour compounds in different matrices can be monitored by this fast processing method.

In a simple fabricated liquid drink and a solid food it was possible to monitor quantitatively the release of flavour compounds in real-time under the temporally demanding dynamic conditions of the mouth when the product is chewed and swallowed. Knowledge of the physiological/anatomical parameters involved in food consumption as well as the functional role of ingredients can play a defining role in the release and retention characteristics of flavour compounds (2,3).

Dr David Kelly (University of Cardiff)

A review of the current state of semiochemistry, the emerging trends and possibilities for the future.
(No abstract)

Tristram D. Wyatt Zoology Department, University of Oxford, South Parks Rd, Oxford OX1 3PS, UK

email: tristram.wyatt@zoo.ox.ac.uk Link

Responses to pheromones and olfactory cues are key elements of behaviour in animals from every part of the animal kingdom. Hormones mediate the action of many pheromones in vertebrates and invertebrates (reviewed in Wyatt 2003). Studies of pheromones, hormones and the brain reveal numerous mutual influences and feedback loops between them. By influencing either the olfactory sensory cells (peripheral effects) or the neurons in the CNS involved in processing olfactory information, hormones also help to orchestrate appropriate responses to pheromone signals, according to social status, reproductive maturity, sex and environmental variables such as day length or temperature. Indeed in some aquatic species, leaking hormones have evolved into pheromones.

Classically pheromones have been divided into releasers (which 'release' a specific reaction or behaviour) and primers (which cause a developmental process by signals to the brain to release the hormones of the endocrine system). However, reality may be more complex: many pheromones have both actions and some hormone-mediated reactions can be rapid.

In social insects and social mammals, such as honey bees and the common marmoset (a New World primate), only one female reproduces. Queen pheromone signals, mediated by hormones in the receiving subordinates, may be honest cooperative signals, not control.

Mechanisms of olfactory memory in vertebrates have been clarified by studies of how the mother sheep (ewe) learns the odour of her lamb, via the main olfactory system. The female mouse's learning of her mate's odour, which is the basis of the Bruce effect of pregnancy block, is similar but via the vomeronasal olfactory system. Both model systems require simultaneous appropriate odour stimulation and noradrenaline release in the olfactory bulbs by nerves stimulated by birth or mating, respectively.

Reference

Wyatt, T.D. (2003) Pheromones and animal behaviour: communication by smell and taste. Cambridge: Cambridge University Press.

Kevin R. Elliker, Barbara A. Sommerville and Donald M. Broom. Department of Veterinary Medicine, University of Cambridge, UK

As early diagnosis of prostate cancer is crucial, any method of mass screening males over the age of 50 would be valuable. Common screening methods require significant technology, expertise and invasiveness, so are inappropriate for mass screening. We aim to train dogs to discriminate urine samples from males with benign prostatic hyperplasia (BH) and malignant prostatic adenocarcinoma (MC) in order to develop an improved system for mass screening and early diagnosis.

Urine samples were presented in a floor-mounted array which had 6 holes for the dogs to sniff. Initially, dogs were trained to locate a single MC sample, (placed randomly in 1 of the 6 positions) sit, and nose point at the hole. Dogs were then trained to discriminate a single MC sample from 5 BH samples. The position of samples varied randomly each trial. Where possible, urine was pooled from several donors. To avoid influencing the dogs, the trainer was not informed of the sample positions.

Training is in its early stages. However, 1 dog has responded correctly when a novel MC sample was used in each trial (4/5 trials correct, p<0.01, 2-tailed binomial test). During these trials the 5 BH samples were familiar. This dog also responded correctly to novel pools of familiar MC samples when a novel BH sample was present in the array (3/4 trials correct, p<0.05, 2-tailed binomial test). Several other dogs can currently locate and respond to a lone MC sample.

These preliminary results suggest that dogs can discriminate BH and MC urine. Carefully controlled trials using a large number of novel samples are now needed. We further hope to test whether trained dogs can discriminate BH samples from samples from males with early prostate cancer (prostatic intraepithelial neoplasia, PIN). The success of the dogs in relation to existing screening methods will also be determined.