bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic Daily Headache with Migrainous Features due to Papilledema-Negative Idiopathic Intracranial Hypertension
Authors: Huff AL , Hupp SL , Rothrock JF
Published: March 2003

Patients with the syndrome of chronic daily headache often report migrainous symptoms and consequently are diagnosed as having a primary headache syndrome. We report two cases of idiopathic intracranial hypertension causing chronic daily headache with migrainous features in the absence of associated papilledema.
Acetylsalicylic Acid in the Treatment of Headache
Authors: Limmroth V , Katsarava Z , Diener H-C
Published: March 2003

Acetylsalicylic acid (ASA) is used to treat a broad range of symptoms and disorders. Since its discovery in 1897, it has been used to treat fever and rheumatic pain, to inhibit the formation of thrombocytes, to prevent myocardial ischemia and strokes, and as preventive medication against neoplasms. ASA is best known, however, as a headache medication. For this function alone, ASA underwent an evolution: from powder to tablet to effervescent and chewable tablets. In addition to these oral formulations, an injectable form was developed in the 1970s for intravenous and intramuscular application. Furthermore, coated (slow-releasing) tablets are now used in the prophylactic treatment of migraine. The various forms of ASA used to treat headache are discussed and the controlled studies conducted to evaluate ASA's efficacy in headache treatment are summarized.
Hybrid cyst: case reports and review of 15 cases in Japan
Authors: Takeda H , Miura A , Katagata Y , Mitsuhashi Y , Kondo S
Published: March 2003

Hybrid cyst is a rare cystic lesion that includes more than two components of the pilosebaceous units. To clarify the clinical and pathological features of hybrid cysts, we report two cases and review 15 cases of hybrid cyst in Japan.

On the whole, the age range was 12–73 years with a 2.95 : 1 female predominance and predilection for the scalp and face (46.7%). Most of the tumours presented as a solitary lesion and the size range was 2–45 mm. The most frequent histological type was the combination of infundibular and trichilemmal cysts (60.0%). Studying the clinicopathological features of hybrid cysts helps us in understanding the pathogenesis of diseases arising from pilosebaceous units.
Use of specialist occupational therapists within residential learning disabilities: a justified case?
Authors: Adams Jo
Published: March 2003

The principles of ‘social role valorization’ ( Wolfensberger 1983) advocate access to general primary health and social care facilities for individuals with learning disabilities alongside the rest of the population. Throughout the UK, there has been a variety of responses to employing specialist staff for people with a learning disability. Specialist learning disability occupational therapists with specific experience and skills in learning disabilities are employed by some National Health Service (NHS) trusts, whereas generalist occupational therapists with skills in assessing and providing intervention for issues concerning physical disability are employed by other trusts and social services departments. This article presents the findings of a small‐scale study of the use of specialist occupational therapists in residential homes within one NHS trust. It presents the views of community staff regarding their clients' needs in relation to specialist and generalist occupational therapy input. Recommendations are provided for the possible use of specialist and generalist occupational therapists for the clients and staff within community learning disability residential health and social care homes.
Diminished men and dangerous women: representations of gender and learning disability in early‐ and mid‐nineteenth‐century Britain
Authors: McDonagh Patrick
Published: March 2003

The present article explores the relationship of gender and learning disabilities in early‐ and mid‐nineteenth‐century literary representations of people with learning disabilities. Literary texts are useful historical documents because these often foreground how learning disabilities worked symbolically in a social context and enable us to examine the ideological forces shaping notions of learning disabilities. The images explored in the present study suggest some common cultural themes. Men with learning disabilities were understood as being diminished, somehow lacking an essential component of masculine identity. Women, on the other hand, were often reduced to the essential, yet disruptive element of feminine sexuality, or later in the century, were conceived as deviant from the feminine norm in their carnality.
Vocabulary needs in augmentative and alternative communication: a sample of conversational topics between staff providing services to adults with learning difficulties and their service users
Authors: Graves Judy
Published: March 2003

This paper describes an attempt to gather information about the vocabulary needs of a sample of people with learning difficulties in order to inform the content of local augmentative and alternative communication (AAC) resources and training programmes. The participants were staff members working in a range of local day care and residential services who were asked to record topics of conversation in diaries. The results were analysed in terms of the frequency of topic areas similar to those described by Maslow's model of human need. The influences on the development of vocabularies for AAC programmes and philosophies current in services for adults with learning difficulties are briefly discussed. The approaches of two of perhaps the most widely used resources (i.e. Makaton and Signalong) are described in the context of their rationale for vocabulary content. The results of the present study suggest that Physical Needs and Function were the most frequent topic areas for conversation. There were far fewer conversations recorded for Social and Emotional topics. Flexible topic‐based frameworks for AAC programmes are suggested as a model that might be able to respond to individual and local vocabulary needs more readily than any one prescribed vocabulary.
Impact of group training on emotion recognition in individuals with a learning disability
Authors: McKenzie Karen , Matheson Edith , McKaskie Kerry , Hamilton Lucie , Murray George C.
Published: March 2003

The present paper outlines the impact of group training on the emotion recognition of six individuals with a moderate learning disability. The accuracy of identifying emotions depicted by line drawings and photographs with and without an emotional context was examined before and after group training. The results indicated that there was a significant overall increase in accuracy in identifying emotions following group training. In addition, a significant increase was found in the ability to correctly label emotions depicted by line drawings typically used in symbol‐based communication systems. The implications of the results are discussed.
A psychotherapy service for children, adolescents and adults with learning disabilities at the Tavistock Clinic, London, UK
Authors: Hernadez‐Halton Isabel , Hodges Sally , Miller Lynda , Simpson David
Published: March 2003

In 1995, a new team was specifically created at the Tavistock Clinic, London, UK, to work with people with learning disability of all ages using psychodynamic ideas, principles and methods. This was a new organization, born out of the growing interest and work in this field, work that had been going on at the Tavistock Clinic for many years. The present paper describes the work of the organization, and provides two case examples to illustrate the team's way of working.
Making connections: the relevance of the social model of disability for people with learning difficulties
Authors: Chappell Anne Louise , Goodley Dan , Lawthom Rebecca
Published: March 2003

The present paper explores the social model of disability and its significance for people with learning difficulties. The authors argue that, while the social model has been adopted as an explicit framework for analysis by many people with physical and sensory impairments, its impact on people with learning difficulties, and the non‐disabled people who write about them or research with them has been much less marked. In the first part of the present paper, the authors examine why the social model appears to have neglected learning difficulty and why learning difficulty researchers have not utilized the social model as a means for understanding the experiences of people with learning difficulties. Drawing on research with self‐advocates, the second part of this paper discusses the way that many people with learning difficulties can be seen to engage with ideas inherent to the social model. However, the political nature of many of the everyday actions of people with learning difficulties, which impinges on the social model, is not recognized. Consequently, it has not been theorized.
From engagement to participation: How do we bridge the gap?
Authors: Joyce Theresa , Shuttleworth Lorraine
Published: March 2003

Supporting and developing choice has often been seen as an aim for community services, but is difficult to achieve for individuals with severe learning and communication difficulties. Measures of service quality have tended to look more at the activities which individuals engage in, although there is now an increasing emphasis on trying to access user views. The aims of the present study were to examine staff judgements about clients' responses to the daily routines organized for them and to examine the extent to which it appeared that service users were engaging in activities which they preferred. The results suggest that staff are able to ascribe meaning to the different behaviours of clients, but that they do not always agree amongst themselves as to what the behaviour means. They are also aware that service users do not enjoy all the activities in their daily routine. Service providers and commissioners need to make the development of choice and preferences for service users as much of a priority as engagement in activities.
Enabling young people with a learning disability to make choices at a time of transition
Authors: Cameron Lois , Murphy Joan
Published: March 2003

Transition times, such as leaving school and moving to and from college or day centre, are highly significant for young people with a learning disability, but it can be particularly difficult to ensure that their voice is heard when making choices. The pilot study described in the present paper examined whether Talking Mats, a light‐technology augmentative framework, could be used successfully with young adults with a learning and communication disability. The participants were able to indicate their likes and dislikes, and to express views about the choices available to them. Some expressed opinions not previously known to their carers, and some raised sensitive topics, such as where they wanted to live and who they wished to spend time with. The ‘mats’ allowed differences of opinion to be explored and were used as a vehicle for further, deeper discussion. Talking Mats has proved to be a powerful tool in allowing young people with a learning disability to communicate their views.
Consultation with children with autistic spectrum disorders about their experience of short‐term residential care
Authors: Preece David
Published: March 2003

Consultation with children receiving services from social services departments is required by international and national legislation. Research has been undertaken examining the experience of children with disabilities receiving short‐term care. However, none of these studies has focused on autistic spectrum disorders (ASDs). The present paper suggests that this condition's characteristics affect the ability of children with ASDs to participate in consultation. Case studies were undertaken investigating the impact of the characteristics of autism upon researchers' abilities to elicit children's opinions about their experience of short‐term residential care. Factors which maximized the children's input and the accuracy of results are identified.
The emotional lives of people with learning disability
Authors: Arthur Andrew R.
Published: March 2003

The emotional lives and difficulties of people with learning disabilities are much neglected. This paper reviews accounts of research and therapy and makes an assessment of the current state of knowledge. Very little research actually exists when compared to the non‐learning disabled, and so, studies of psychotherapy, child development, parent‐infant bonding, psychological assessment and emotional disturbance in people with learning disability are examined. The review finds that there is evidence to suggest the presence of a significantly higher level of emotional developmental problems and disturbance in people with learning disability. This problem requires multidisciplinary attention if progress in improving quality of life is to be maintained.
How far are people with learning disabilities involved in funeral rites?
Authors: Raji Oyepeju , Hollins Sheila , Drinnan Ange
Published: March 2003

Many referrals to specialist learning disability services follow bereavement and loss experiences. Research and clinical experience both suggest that people who have not been fully involved in funeral rituals have delayed and/or prolonged grief reactions. This study in a multicultural inner London borough examined local religious and cultural practices following bereavement of people with learning disabilities. Interviews were sought with funeral directors and representatives from six religious groups to build up a picture of local practice, resources and knowledge, particularly with regard to how people with learning disabilities are involved in the process. It was found that most of the local funeral directors had little direct experience of people with learning disabilities. The religious group representatives who were interviewed also spoke of a lack of involvement of people with learning disabilities. A pamphlet has been designed for funeral directors and religious groups to give to families or friends of people with learning disabilities who have been bereaved.
A comparison of the acceptability to student consumers of three food products retailed at three ‘quality’ levels
Authors: Mann Tracy , Reeve William G. , Creed Philip G.
Published: March 2003

This study aimed to determine whether the range of ‘quality’ levels offered by UK food retailers in the form of nationally advertised and retailers’ own label products which are differentiated by price, provides a corresponding range of sensory qual‐ities which can be detected by consumers. Under blind testing conditions, student consumers assessed three food products (bread, bacon and orange juice) at three ‘quality’ levels (own‐label economy; own‐label premium and national products) purchased from four major U.K. food retailers (Asda, Sainsbury, Co‐operative and Tesco). Fifty students (aged 18–25) assessed the hedonic liking of odour, texture, flavour, overall acceptability, colour, and acceptability based on appearance and purchase intent. The results demonstrated significant differences between ‘quality’ levels and retailers. For all three products, colour was generally less liked for own‐label economy and own‐label premium products than for national products, but there was no significant difference (P > 0.05) between the ‘quality’ levels for flavour and overall acceptability. Regarding purchase intent and acceptability based on appearance, national branded bread was preferred to own‐label brands; for bacon, there were no significant differences; and for orange juice, own‐label economy was significantly less acceptable and less likely to be purchased than own‐label premium and national brands. There were some significant differences between retailers for some product attributes, leading to the purchase intent for Co‐operative bread and Tesco orange juice being lower than from other retailers. Overall, it can be concluded that student consumers found few differences based solely on their liking of the products’ sensory attributes that would justify the price differentials between the retail ‘quality’ levels.
Sous vide processing of seasoned spinach soup
Authors: Kim Gi‐Tae , Koo Kyoung‐Mo , Paik Hyun‐Dong , Lyu Eun Soon , Lee Dong Sun
Published: March 2003

Spinach soup seasoned with fermented soybean paste, red pepper paste and other minor ingredients was processed into 600 g plastic pouch package by the sous vide method. The process involved hot filling, pasteurization based on the inactivation of psychrotropic Clostridium botulinum, and rapid chilling. The processed products were stored at 3 and 10°C with periodic sampling for quality measurements. The seasoned spinach soup processed by the sous vide method exhibited a sensory quality comparable to that of fresh soup. The pasteurized product showed a high microbial load of total aerobic bacterial count greater than 5 log CFU/g in the soup brine and 2 log CFU/g in the vegetable solids, caused by the use of fermented soybean and red pepper pastes in the seasoned brine. However, coliform bacteria, lactic acid bacteria and yeasts/moulds were not detected in the product. The product was stable in microbial quality during storage for 35 days at 3°C, while it was so only up to 10 days at 10°C. The surface colour, total chlorophyll, ascorbic acid content and texture of the spinach in the soup showed gradual changes toward less green colour, lower nutrient retention and softer vegetables with their changes being faster at higher temperature. The seasoned spinach soup may be stored for appropriate time periods under chilled conditions and used in the food service industry with good quality characteristics.
Recovery ofBanksiaandHakeacommunities after fire in mediterranean Australia—the role of species identity and functional attributes
Authors: Lamont Byron B. , Groom Philip K. , Richards Michael B. , Witkowski E. T. F.
Published: March 2003

Up to thirteen demographic, four morphological and four ecophysiological attributes were assessed in each of three studies of postfire recruitment patterns in mediterranean southwestern Australia. Three to seven of the most prominent, congeneric shrub species in each of five communities were monitored following a total of six fires, and numbers of individuals prefire were compared with those over two to four winters postfire. The proportion of individuals in each species only sometimes reflected the proportion at an earlier time. At least one species differed from the rest for twenty‐six of a total of twenty‐seven demographic steps assessed. Initial seedlings/parent, which was largely a function of seeds available, and, to a lesser extent, level of germination, were the most important attributes in accounting for the recruitment patterns. There was a trend for the faster growing, drought avoiding species to increase at the expense of the others. In the most comprehensive study, life form (four nonsproutingHakeaspp.v.four resproutingHakeaspp.) was the best predictor of the recovery pattern. This was through its association with seed availability and level of germination and, to a lesser extent, drought survival (all higher for nonsprouters). Leaf type, as an indicator of drought tolerance, had inconsistent predictive power between studies. The least summer stressed species, in terms of survival and water relations, tended to have the largest seedlings derived from the largest seeds, but there were notable exceptions. Within each life form category, species behaviour varied widely, making most predictions of postfire community dynamics based on relative prefire numbers little more than conjectural. However, in only one of the three studies were the trends sufficiently clear to show that postfire densities would never mirror those prefire.
A fine‐scaled predictive model for changes in species distribution patterns of high mountain plants induced by climate warming
Authors: Gottfried Michael , Pauli Harald , Reiter Karl , Grabherr Georg
Published: March 2003

Induced by global warming, mountain plant species are migrating upwards. Species inhabiting the nival zone of today are threatened by competitors which move from the alpine zone towards the summits. The manner in which species move depends on their abilities to cope with microtopographical situations. We present a spatially explicit predictive model which draws scenarios of future species distribution patterns at a typical high mountain of the European Alps. The altitudinal temperature gradient is examined. Based on the lapse rate and on definitions of topographical niches of species, a +1 °C‐ and a +2 °C‐warming scenario are modelled using a fine‐scaled digital elevation model. Nival species will lose area and become restricted to specific topographical situations. Alpine and subnival grassland species are predicted to expand their area, mainly along stable surface situations. Whether the migration will take place as a filling or a moving process is specific to the particular species. Overall, biodiversity is apparently not threatened on the decadal scale. In special cases, however, genetic losses are likely both on a local and on a regional scale.
Using an artificial neural network to characterize the relative suitability of environments for forest types in a complex tropical vegetation mosaic
Authors: Hilbert David W. , Van Den Muyzenberg Jeroen
Published: March 2003

A predictive understanding of the environmental controls on forest distributions is essential for the conservation of biodiversity and management of landscapes in the tropics. This is particularly true now because of potentially rapid climate change. The floristic complexity of tropical forests and the lack or absence of data severely limits the applicability of modelling methods based on the ecology or distribution of individual species. Here we present an artificial neural network (ANN) model using the information available in the humid tropics of North Queensland: a structural classification of forest types, maps of the forest mosaic, and estimates of spatial environmental variables.

The ANN model characterizes the relative suitabilities of environments for 15 forest classes defined by their physiognomy and canopy structure. Inputs include seven climate variables, nine soil parent‐material classes, and seven terrain variables. The data used to train the model consisted of a stratified random sample of 75000 points. Output of the model is used to measure the dissimilarity between the environment at each location and the environment that would be most suitable for the forest type that is mapped there.

The model is highly successful at distinguishing the relative suitability of environments for the forest classes with 75% of the region's forest mosaic accurately predicted by the model at a one hectare resolution. In contrast, a comparable maximum likelihood classification has an accuracy of only 38%. In the remaining 25% of the region the environments are quite dissimilar to what would be expected for the forest types present there. This is especially the case at boundaries between forest classes and for a transitional forest class. Areas mapped as this disturbed, transitional class are generally classified by the model as having environments suitable to the forest type they are most likely to become.

The approach has high potential for the analysis of climate change impacts as well as inferring vegetation patterns in the past and should be applicable wherever vegetation maps and spatial estimates of climate variables are available.
Allozyme diversity and geographic variation in the widespread coastal sedge, Carex arenaria
Authors: Jonsson B. Olle. , Prentice Honor C.
Published: March 2003

Abstract. Allozyme electrophoresis was used to investigate the structure of genetic variation in the rhizomatous coastal sedge, Carex arenaria, throughout its European range — from the SW Iberian peninsula to the Baltic region. Material was sampled from 77 sites in five geographic regions. Nine of the 13 investigated loci were polymorphic in the total material and there were interregional differences in the number of polymorphic loci per site and the percentage of variable sites. In the Scandinavia/Baltic region only 61% of the sites contained at least one locus with more than one allele, whereas all the British and SW Iberian sites were variable. There was a general tendency for the regional frequencies of the less common alleles at individual loci to decline from SW to NE. The mean (over loci and sites) within‐site gene diversity (H
site) was 0.064 (in calculations based on the number of observed multilocus allozyme genotypes within each sampling site). Although there was considerable variation between geographically adjacent sites, within‐site diversity showed a general decrease from SW to NE in Europe. There were significant differences in within‐region gene diversity (Hreg) for the four most variable loci between the five regions. Hreg generally decreased from SW to NE Europe and most loci showed the highest diversity in the SW Iberian peninsula and the Bay of Biscay regions. The mean (over loci) gene diversity in the total material (Htot) was 0.070 and the levels of diversity in Carex arenaria are substantially lower than is usual in rhizomatous sedges. The within‐site, between‐site and between‐regional components of the total diversity were 92.4%, 2.5% and 5.1%, respectively. The low levels of overall gene diversity in C. arenaria and the successive decrease in diversity from SW to NE are interpreted in terms of the species’ history of postglacial spread into northern Europe. Despite the overall northwards decrease in diversity, the widespread occurrence of less common alleles and the lack of regional deviations from Hardy–Weinberg genotype frequency expectations suggest that C. arenaria is not predominantly self‐fertilized.
Thrushes now largely restricted to the built environment in eastern England
Authors: Mason Christopher F.
Published: March 2003

Abstract.  I studied the distribution and density of three thrush populations, blackbird Turdus merula, song thrush T. philomelos and mistle thrush T. viscivorus, in an urban and contiguous rural area, totalling 2636 ha, in eastern England. Populations of these species are declining and I found 826, 85 and 30 territories of blackbird, song thrush and mistle thrush, respectively. Significantly more territories of all species than expected were within the urban boundary. Significantly more territories than expected were found of all three species in the built environment (residential housing, factories, schools, etc. with their associated gardens and green‐space), urban and rural areas combined. Farmland occupied 67% of the study area but held significantly fewer blackbird and mistle thrush territories than expected, associated mainly with the small amount of grass; song thrushes were not recorded on farmland. Rural woodland and scrub held more blackbird and song thrush territories than expected. Song thrush was significantly associated with scrub within the urban boundary. With all three species largely absent from farmland, residential habitats can be considered as habitat refuges. The consequences of this for conservation and planning are discussed.
Priority areas for the conservation of South African vegetation: a coarse‐filter approach
Authors: Reyers B. , Fairbanks D. H. K. , Van Jaarsveld A. S. , Thompson M.
Published: March 2003

South Africa has an important responsibility to global biodiversity conservation, but a largely inadequate conservation area network for addressing this responsibility. This study employs a coarse‐filter approach based on 68 potential vegetation units to identify areas that are largely transformed, degraded or impacted upon by road‐effects. The assessment highlights broad vegetation types that face high biodiversity losses currently or in the near future due to human impacts. Most vegetation types contain large tracts of natural vegetation, with little degradation, transformation or impacts from road networks. Regions in the grasslands, fynbos and forest biomes are worst affected. Very few of the vegetation types are adequately protected according to the IUCN’s 10% protected area conservation target, with the fynbos and savanna biomes containing a few vegetation types that do achieve this arbitrary goal. This investigation identifies areas where limited conservation resources should be concentrated by identifying vegetation types with high levels of anthropogenic land use threats and associated current and potential biodiversity loss.
Mutualism as a constraint on invasion success for legumes and rhizobia
Authors: Parker Matthew A.
Published: March 2003

Because hereditary symbiont transmission is normally absent in the mutualism of legume plants and root‐nodule bacteria (rhizobia), dispersing plants may often arrive at new habitats where mutualist partners are too rare to provide full benefits. Factors governing invasion success were explored by analysing a system of two coupled pairwise competition models: a legume invader competing with a resident non‐mutualistic plant, and a rhizobial population competing with a resident population of nonsymbiotic bacteria. The non‐linear dependence of benefits on partner abundance in this mutualism creates the possibility of two alternative population size equilibria, so that a threshold density can exist for invasion. If legumes and rhizobia exceed a critical population size, both species achieve rapid population growth, while if initial densities of both species are below their respective thresholds, they remain rare and are thus vulnerable to extinction in the presence of competitors. Overall, the results indicate that legumes may often fail at colonization attempts within habitats where mutualist partners are scarce. Data on legume prevalence in island floras and rates of geographical spread by legume weeds are consistent with this inference. Predictive insights about invasiveness may emerge from comparative research on key traits identified by the model, especially the shape of the function determining the number of nodules formed at low rhizobial density.
Biogeographical patterns of endemic terrestrial Afrotropical birds
Authors: De Klerk H. M. , Crowe T. M. , Fjeldså J. , Burgess N. D.
Published: March 2003

Biogeographical zones are described for terrestrial bird species endemic to the Afrotropics using up‐to‐date distributional data and multivariate statistical techniques. This provides an objective basis for a hierarchy of subregions, provinces and districts, based on a set of rules. Results are compared to previous studies at continental and regional scales. Biogeographical zones for passerines and non‐passerines are compared and found to be similar. Peaks of species richness and narrow endemism are described for the six major subdivisions (subregions) identified by the cluster analysis. Coincidence of peaks of species richness and narrow endemism is found to be low, such that areas selected to represent high species richness tallies will often fail to represent narrow endemics. Strong regionalization of Afrotropical birds indicates the need to use a biogeographical framework in conservation priority setting exercises to ensure that unique, but species‐poor, avifaunas are not neglected.
Amphibian declines: future directions
Authors: Storfer Andrew
Published: March 2003

Abstract.The amphibian decline problem is complex, and there is no easy solution. I highlight four major areas of future research that should increase our ability to detect declines, elucidate their underlying mechanisms, and advance our capacity to manage and conserve amphibian populations. First, a statistically sensitive monitoring approach is necessary to determine the distribution and abundance of amphibian populations, to assess whether they are declining, and to quantify the extent of declines. Most amphibian populations characteristically fluctuate, detection probabilities may be low for many species and populations tend to decline in numbers between years more often than they increase. These traits make establishing monitoring programmes difficult and distinguishing declines from natural fluctuations challenging. It is thus necessary to determine the best monitoring techniques based on their statistical power and to use appropriate statistical methods for detecting population trends. Secondly, although amphibian population studies occur most commonly at single or few breeding sites, research should occur often at the landscape level, and conservation efforts should focus on suitable habitat (whether or not it is occupied) and dispersal capabilities of species. Metapopulation dynamics are probably important for many species, but we must be cautious how we define metapopulations. That is, the term ‘metapopulation’ is currently used to define a wide range of demographic situations in amphibian populations, each with different management implications. Thirdly, recent advances in molecular genetic techniques make it possible to infer demographic events such as effects of recent fragmentation, bottlenecks or hybridization. Molecular techniques can be used in conjunction with census surveys to bolster knowledge about demographic processes such as declines. Alternatively, in the absence of long‐term census data, molecular data can be used to infer population trends. New genomic approaches may make estimating adaptive genetic variation more feasible. Fourthly, multi‐factorial studies are needed to disentangle the complexity of the several putative causes that probably interact to cause amphibian declines. Recent studies demonstrate the value of a multi‐factorial approach, and more work is needed to elucidate the synergistic effects of multiple environmental factors affecting amphibian populations simultaneously worldwide.
Infectious disease and amphibian population declines
Authors: Daszak Peter , Cunningham Andrew A. , Hyatt Alex D.
Published: March 2003

Abstract.A series of recent papers have implicated pathogens and parasites in amphibian population declines. Here, we review evidence on the link between infectious disease and amphibian population declines. We conclude that available data provide the clearest link for the fungal disease amphibian chytridiomycosis, although other pathogens are also implicated. We suggest additional experimental and observational data that need to be collected to provide further support that these other pathogens are associated with declines. We suggest that, in common with many emerging infectious diseases (EIDs) of humans, domestic animals and other wildlife species, emergence of chytridiomycosis may be driven by anthropogenic introduction (pathogen pollution). Finally, we review a number of recent advances in the host–parasite ecology of chytridiomycosis that help explain its emergence and impact.
Aphrodisiac evaluation in non‐copulator male rats after chronic administration of Eurycoma longifolia Jack*
Authors: Ang H. H. , Ngai T. H.
Published: March 2003

The aphrodisiac effect of Eurycoma longifolia Jack (0.5 g/kg) was evaluated in noncopulator male rats using an electrical cage. Fractions of E. longifolia Jack decreased the hesitation time of noncopulator male rats, throughout the investigation period. Furthermore, it possessed a transient increase in the percentage of the male rats responding to the right choice, more than 50% of the male rats scored ‘right choice’ after 3 weeks post‐treatment and the effect became more prominent after 8 weeks post‐treatment (only 40–50% of the control male rats responded to the right choice) using the electrical copulation cage. Hence, this study lends further support to the use of the plant by indigenous populations as a traditional medicine for it’s aphrodisiac property.
Quality management of pharmacology and safety pharmacology studies
Authors: Spindler Per , Seiler Jürg P.
Published: March 2003

Pharmacology has traditionally been excluded from the mandatory application of good laboratory practice (GLP) principles. Consensus has been reached through the process of the International Conference on Harmonisation (ICH, Topic S7A) with regard to the definitions of the different types of pharmacology studies (ICH S7A): primary pharmacodynamic, secondary pharmacodynamic and safety pharmacology studies, and guidance on the quality standards (expectations for GLP conformity) for these study types have been provided. Primary pharmacodynamic studies are the only study types that are fully exempt from GLP requirements. Secondary pharmacodynamic and safety pharmacology studies are expected to be conducted to GLP quality standards – preferably to full, formal GLP compliance, when results are used for human safety assessment.

At the present time, regulatory authorities will most likely be prepared to exercise flexibility in their requirement for GLP compliance, however, if non‐clinical studies used in human safety assessment are not formally in compliance with the principles of GLP, regulatory acceptance may not be guaranteed.

Historically, the application of formal GLP standards in safety pharmacology studies appears to vary between test facilities, and a number of study components in safety pharmacology studies, e.g. ECG monitoring, may not always conform to formal GLP standards. Apparently, however, formal GLP standards for these study components can be implemented for a relatively low additional cost. Based on the guidance given in the ICH S7A guideline, it thus appears logical to recommend that test facilities and sponsors consider their organisation of safety pharmacology studies in view of sound study management and formal implementation of GLP, where needed.

Organisation of study management should facilitate collaboration across scientific disciplines because a plethora of data, originating from basic pharmacodynamics, toxicology, kinetics, and metabolism, as well as from clinical investigations, are involved in a safety pharmacology assessment. Applying formal GLP standards to safety pharmacology studies, and, when indicated, to secondary pharmacodynamic studies, does not influence the scientific standards of studies. However, applying formal GLP standards will ensure the quality, reliability and integrity of studies, which reflect sound study management. It is important to encourage a positive attitude among researchers and academics towards these lines, whenever possible. GLP principles applied to the management of non‐clinical safety studies are appropriate quality standards when studies are used in the context of protecting public health, and these quality standards are therefore obviously pivotal for regulatory acceptance of non‐clinical safety studies in general, and of safety pharmacology studies in particular.
Application of pharmacokinetic modelling to the routine therapeutic drug monitoring of anticancer drugs
Authors: Rousseau Annick , Marquet Pierre
Published: March 2003

Over the last 10 years, proofs of the clinical interest of therapeutic drug monitoring (TDM) of certain anticancer drugs have been established. Numerous studies have shown that TDM is an efficient tool for controlling the toxicity of therapeutic drugs, and a few trials have even demonstrated that it can improve their efficacy. This article critically reviews TDM tools based on pharmacokinetic modelling of anticancer drugs. The administered dose of anticancer drugs is sometimes adjusted individually using either a priori or a posteriori methods. The most frequent clinical application of a priori formulae concerns carboplatin and allows the computation of the first dose based on biometrical and biological data such as weight, age, gender, creatinine clearance and glomerular filtration rate. A posteriori methods use drug plasma concentrations to adjust the subsequent dose(s). Thus, nomograms allowing dose adjustment on the basis of blood concentration are routinely used for 5‐fluorouracil given as long continuous infusions. Multilinear regression models have been developed, for example for etoposide, doxorubicin, carboplatin, cyclophosphamide and irinotecan, to predict a single exposure variable [such as area under concentration–time curve (AUC)] from a small number of plasma concentrations obtained at predetermined times after a standard dose. These models can only be applied by using the same dose and schedule as the original study. Bayesian estimation offers more flexibility in blood sampling times and, owing to its precision and to the amount of information provided, is the method of choice for ensuring that a given patient benefits from the desired systemic exposure. Unlike the other a posteriori methods, Bayesian estimation is based on population pharmacokinetic studies and can take into account the effects of different individual factors on the pharmacokinetics of the drug. Bayesian estimators have been used to determine maximum tolerated systemic exposure thresholds (e.g. for topotecan or teniposide) as well as for the routine monitoring of drugs characterized by a very high interindividual pharmacokinetic variability such as methotrexate or carboplatin. The development of these methods has contributed to improving cancer chemotherapy in terms of patient outcome and survival and should be pursued.
α2‐adrenoceptor ligands inhibit α1‐adrenoceptor‐mediated contraction of isolated rat arteries
Authors: Artigues‐Varin Cécile , Richard Vincent , Varin Rémi , Mulder Paul , Thuillez Christian
Published: March 2003

The experiments in this study were designed to investigate the potential relaxing effects of different compounds known as α2‐imidazoline ligands (either agonists or antagonists) in isolated rat arteries, and to test the role of nitric oxide (NO) and prostaglandins, in addition to the influence of the nature of the contracting agent in these responses. Segments of mesenteric arteries were isolated and mounted in a small vessel myograph (JP Trading, Aarhus, Denmark) for isometric tension recording, while segments of gracilis muscle arteries were cannulated and studied in the pressurized state using an arteriograph (Living Systems Instrumentation, Burlington, VT, USA).

In phenylephrine precontracted mesenteric arteries, the agonists clonidine, BHT920, UK 14304, and rilmenidine, as well as the antagonists idazoxan, yohimbine and rauwolscine, all induced marked relaxations. Similarly, clonidine and idazoxan, both induced marked dilatations of phenylephrine preconstricted gracilis muscle arteries. In both mesenteric and gracilis muscle arteries, the responses to clonidine and idazoxan were not affected by the NO synthase inhibitor Nω‐nitro‐L‐arginine (L‐NA, 10−5 M) or the cyclooxygenase inhibitor diclofenac (10−5 M). In mesenteric arteries, the responses to clonidine or idazoxan were similar when the arteries were precontracted by different α1‐adrenoceptor agonists (phenylephrine, methoxamine or norepinephrine). In contrast, in arteries precontracted by PGF2α or endothelin, clonidine induced contractions while idazoxan induced very modest relaxations.

Thus, α2‐adrenoceptor/imidazoline ligands (whether agonists and antagonists) induce paradoxical relaxation of small mesenteric or gracilis muscle arteries of rats, which are not affected by NO‐synthase or cyclooxygenase inhibition, and appear related to direct non specific interactions of the α2‐imidazoline ligands with α1‐adrenergic receptors in vascular smooth muscle.
Effect of amitriptyline on gastric ulceration
Authors: Sen T. , Abdulsalam C. A. , Pal S. , Sen S. , Karmakar S. , Saravanan K. S. , Nag Chaudhuri A. K.
Published: March 2003

Amitriptyline significantly inhibited alcohol, aspirin, indomethacin and cold‐restraint stress‐induced ulceration. Secretory studies conducted in pyloric‐ligated rats revealed that the drug, at the doses employed, significantly reduced total acidity and protein content. However, significant reductions of the gastric volume were only observed at the highest dose of the drug. In another set of experiments, when 50% alcohol (v/v) was administered to the pyloric‐ligated rats pretreated with amitriptyline, it was observed that the drug significantly reduced the pH, total acidity and protein content.
Sphingosine modulation of cAMP levels and beating rate in rat heart
Authors: Benediktsdóttir V. Edda , Jónsdóttir Anna M. , Skúladóttir Bergthóra H. , Grynberg Alain , Skarphéðinsson Jón Ó. , Helgason Jóhannes , Gudbjarnason Sigmundur
Published: March 2003

Sphingolipids, especially as elements of the sphingomyelin signal transduction cycle, are thought to play a significant role as second messengers and modulators of events in heart muscle cells. A possible modulatory role of sphingosine in signal transduction in the β‐adrenergic pathway in the heart was examined. Neonatal rat cardiomyocytes were incubated with sphingosine and/or other agents after which cAMP levels and contraction rates were measured. Heart rate in anaesthetized rats was also measured before and after sphingosine injection in the jugular vein. Sphingosine caused a decrease in basal cAMP levels and diminished isoproterenol‐induced increase in cAMP levels. These changes were dose‐ and time‐dependent and showed a significant negative effect on signal transmission in the β‐adrenergic pathway in cardiomyocytes. Increase in cAMP intracellular levels by forskolin, which activates adenylcyclase, was not inhibited by sphingosine. A phosphodiesterase inhibitor was used in all experiments in which cAMP was measured excluding effects on cAMP breakdown. It was also demonstrated that sphingosine caused reduction in the beating rate of cultured cardiomyocytes and a dose‐dependent reduction in heart rate of anaesthetized rats. The sphingosine‐induced inhibition of bradycardic response of anaesthetized rats reached a maximum about 5–10 min after the onset of sphingosine administration and returned to normal within 60 min. Sphingosine may modulate the signal transmission of the β‐adrenoceptor pathway upstream of adenylcyclase in rat cardiomyocytes. This may contribute to the sphingosine‐induced decrease in heart rate of rats in vivo.
Nitric oxide: therapeutic opportunities
Authors: Vallance Patrick
Published: March 2003

Fifteen years after the discovery of nitric oxide as a biological mediator how close are new therapies? This article describes the roles of nitric oxide, illustrates how its discovery is altering the way in which certain established drugs are being used and reviews new therapeutic developments.
Effects of central sympathetic inhibition on heart rate variability during steady‐state exercise in healthy humans
Authors: De Vito G. , Galloway S.D.R. , Nimmo M.A. , Maas P. , McMurray J.J.V.
Published: March 2003

The profound reduction in heart rate variability (HRV) that occurs during exercise is thought to be, at least in part, the result of sympathetic nervous system activation. Moxonidine is a centrally acting anti‐sympathetic drug, which suppresses sympathetic nervous system outflow by stimulation of central imidazoline receptors located in the rostral ventro‐lateral medulla. This study was designed to investigate the combined effects of central sympathetic inhibition with moxonidine and steady‐state dynamic exercise on HRV. Ten normal males participated in a double‐blind cross‐over study, taking either placebo or 0·4 mg of moxonidine. The subjects were studied at rest and during steady‐state exercise. HRV was measured considering both time and frequency domain parameters. As a non‐linear measure, the Poincaré scatter‐plot was measured and analysed quantitatively. Ventilation and gas exchange were also measured during exercise. In addition, plasma catecholamines were measured at rest and during exercise. The only parameter changed, at rest, by moxonidine was the blood pressure which was reduced. During exercise, moxonidine reduced plasma noradrenaline (NA), compared with the placebo (P<0·01). The only change observed in HRV during exercise was a significant reduction of the continuous long‐term standard deviation (SD2) of the Poincaré scatter‐plot of the R‐R interval (P<0·05). However, the potential and prognostic significance of this result needs to be further assessed.