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Biomedical subjects

S Paterson

Publications and source records attributed to S Paterson.

At least 19 recordsLinked to original sources

The contribution of nitric oxide to vestibular compensation: are there species differences?

Nitric oxide (NO) has been implicated in the processes by which animals recover from peripheral vestibular damage ("vestibular compensation"). However, there is little systematic data available on the effects of NO inhibition on the vestibular compensation process. In the present study we administered the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) using a subcutaneous osmotic minipump and examined its effects on the compensation of spontaneous nystagmus (SN), yaw head tilt (YHT) and roll head tilt (RHT) in guinea pigs. Following unilateral labyrinthectomy (UL), treatment with 5, 10, 50 or 100 mM L-NAME had no effect on the expression of any of these symptoms or their rate of compensation. By contrast, pre-UL treatment with 100 mM L-NAME resulted in a decrease in SN frequency at 10 h post-UL and an increase in its rate of compensation. Lower concentrations had no effect on SN. Pre-UL treatment with L-NAME had no significant effect on YHT or RHT at any particular time point. Analysis of NOS activity demonstrated that the highest concentration of L-NAME inhibited NOS activity in the contralateral vestibular nucleus complex, bilateral cerebellum and bilateral cortices. These results suggest that L-NAME may have different effects on vestibular compensation in guinea pigs compared to other species, such as the rat and frog.

Animals↗

Qualitative screening for drugs of abuse in hair using GC-MS.

A previously described method for the analysis of hair has been modified to include analysis for amphetamines, benzodiazepines, cocaine and its metabolites, methadone and its metabolite, and phencyclidine in addition to opiates on a sample of hair. The samples of hair were washed twice with dichloromethane and cut into 1-mm segments prior to extraction with methanol at 45 degrees C for 18 h. The extracts were split into two parts; both were evaporated to dryness. One half of the extract was derivatized using MBTFA for analysis of amphetamines, and the other half was derivatized using MTBSTFA for analysis of the remaining drugs. The extracts were analyzed using electron impact gas chromatography-mass spectrometry operating in selected ion monitoring mode. In total, 18 drugs of abuse/metabolites could be detected. The method was used to screen 20 hair samples from patients attending a methadone-maintenance clinic.

Gas Chromatography-Mass Spectrometry↗

Use of repeated measure linear modeling to analyze longitudinal data from experimental parasite infections.

Here the use of repeated measure linear modeling to analyze experimental infections is demonstrated. This method of analysis makes full use of serial measurements on the same host throughout the course of an infection while taking into account correlations between measures within the same host. As an example, repeated measure linear modeling is used to analyze worm output from an experimental infection of Strongyloides ratti, a nematode parasite of rats. This analysis allows differences in the temporal dynamics of infection of two lines of S. ratti to be dissected.

Animals↗

Language and number in Down syndrome: the complex developmental trajectory from infancy to adulthood.

This paper examines language and number understanding in infants with Down syndrome and Williams syndrome and compares infant performance to that of adults. The cross-syndrome/cross-domain studies demonstrate that the pattern of performance of infants with Down syndrome and Williams syndrome on two tasks assessing language and number cannot be derived from the pattern of proficiencies and impairments in the adult phenotypic outcome. Single word comprehension was assessed using a visual preference paradigm. All groups (Williams syndrome, Down syndrome, chronological age and mental age-matched controls) looked longer at the stimuli which matched the verbal label but the infants with Down syndrome and Williams syndrome were equally delayed (equivalent to their mental age controls). The similarity between the infants with Down syndrome and those with Williams syndrome did not parallel the difference present in the adult phenotypes, where vocabulary skill in Down syndrome is significantly lower than that in Williams syndrome. Number was assessed using a novelty preference paradigm, in which infants were familiarised with displays of 2 objects and then presented with 2 versus 3 objects. Infants with Williams syndrome discriminated between the familiar and novel numerosities. Infants with Down syndrome did not. Again, the difference between the Down syndrome and Williams syndrome infant groups did not parallel the pattern seen in the adult phenotypes, where individuals with Down syndrome performed better than those with Williams syndrome. It is therefore crucial to characterise the infant state, in order to understand fully the developmental trajectories of atypical groups.

Adolescent↗

The effects of L-NAME on vestibular compensation and NOS activity in the vestibular nucleus, cerebellum and cortex of the guinea pig.

Nitric oxide (NO) has been implicated in the processes by which animals recover from peripheral vestibular damage ('vestibular compensation'). However, few data exist on the dose-response effects of systemic administration of the nitric oxide synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), on the vestibular compensation process. The aim of this study was to investigate the effects on compensation of 5, 10, 50 or 100 mM L-NAME administered by s.c osmotic minipump for 50 h following unilateral vestibular deafferentation (UVD) in guinea pig, either commencing the drug treatment at 4 h pre-UVD or at the time of the UVD (i.e., post-UVD). Post-UVD treatment with L-NAME, at any of the four concentrations used, had no effect on the compensation of spontaneous nystagmus (SN), yaw head tilt (YHT) or roll head tilt (RHT). By contrast, pre-UVD treatment with 100 mM L-NAME resulted in a significant decrease in SN frequency (P<0.05) and a change in the rate of its compensation (P<0.0005). Pre-UVD L-NAME resulted in a significant increase in the overall magnitude of YHT (P<0.005); however, post-hoc comparisons revealed no significant differences between any specific L-NAME and vehicle groups. Pre-UVD L-NAME had no effect on RHT at any concentration. Analysis of NOS activity in the pre-UVD L-NAME treatment groups at 50 h post-UVD showed that only 100 mM L-NAME resulted in a significant decrease in NOS activity in the contralateral medial vestibular nucleus (MVN)/prepositus hypoglossi (PH) (P<0.05) and that NOS activity in the ipsilateral MVN/PH was not significantly affected. However, NOS activity was significantly inhibited in the bilateral cerebellum and cortices for several concentrations of L-NAME. These results suggest that pre-UVD systemic administration of L-NAME can significantly increase the rate of SN compensation in guinea pig and that this effect is correlated with inhibition of NOS activity in several regions of the CNS.

Animals↗

The interface between epidemiology and population genetics.

Modern biology increasingly integrates disparate disciplines. Here, Steve Paterson and Mark Viney examine the interface between epidemiology and population genetics. They argue that infection and inheritance can be considered as analogous processes, and that epidemiology and population genetics share many common features. They consider the potential for existing population genetic theory to dissect epidemiological patterns in field studies and they consider other relationships between genetics and epidemiology that provide a research challenge for the future.

Alleles↗

Inferring infection processes of a parasitic nematode using population genetics.

The distribution of genetic differentiation in a population of the parasitic nematode Strongyloides ratti divided between rat hosts was determined. We applied population genetic theory to these data to determine the source of new infections. We estimate the rate at which a rat acquires a new infection from (a) the existing subpopulation of parasites within that rat ('self-reinfection') versus (b) the wider environment ('immigration'). We find that the observed levels of genetic diversity and differentiation in the study population are consistent with low to moderate rates of self-reinfection and inconsistent with high rates of self-reinfection.

Animals↗

Analysis of urine for drugs of abuse using mixed-mode solid-phase extraction and gas chromatography-mass spectrometry.

A method for the simultaneous analysis of urine for the major drugs of abuse is described. The analytical procedure uses solid-phase extraction (SPE), gas chromatography-mass spectrometry (GC-MS) and a semi-automated identification process. It allows simultaneous extraction, derivatization and analysis of acidic, neutral and basic drugs from urine. Urine samples were subjected to enzymatic hydrolysis followed by SPE using Bakerbond narc-2 columns. The eluant was selectively derivatized with N-methyl-bis-trifluoroacetamide (MBTFA) and N-methyl-N-trimethylsilyltrifluoroacetamide + 1% trimethylchlorosilane. Analysis was performed using a GC-MS system operating in full scan mode. A simple macro programme was written to enhance the mass spectra identification capabilities of the MS software by producing extracted ion chromatograms (EIC) for the drugs of interest. Once a suspect compound was indicated by EIC, the mass spectrum of the compound was searched manually against reference libraries for positive identification and the retention time checked against that of the standard. This procedure has increased both the amount and the reliability of information given to clinicians without increasing the cost per sample. The system has been in routine operation for 24 months, processing up to 40 urine samples per day, with a usual turn-around time of 48 h.

Evaluation Studies as Topic↗

Clindamycin hydrochloride and clavulanate-amoxycillin in the treatment of canine superficial pyoderma.

A masked, randomised, controlled clinical trial for the treatment of canine superficial pyoderma was undertaken. Dogs with a clinical diagnosis of superficial pyoderma, supported by bacterial culture were admitted to the trial and randomly assigned to treatment with either clindamycin hydrochloride at 5.5 mg/kg twice daily or clavulanate-amoxycillin at 12.5 mg/kg twice daily. After 21 days the animals were re-assessed, and therapy was continued for a further 21 days in the dogs with persistent lesions if bacterial culture demonstrated continued sensitivity. Twenty-nine dogs were treated with clindamycin hydrochloride and 27 with clavulanate-amoxycillin. Complete cure was obtained after three weeks in 17 (59 per cent) of the clindamycin-treated cases, but in only eight (30 per cent) of the clavulanate-amoxycillin treated group. Clindamycin was significantly more effective than clavulanate-amoxycillin for the treatment of superficial pyoderma in dogs.

Amoxicillin↗

Heterogeneity in the distribution of Strongyloides ratti infective stages among the faecal pellets of rats.

The distribution of helminth parasites within their host population is usually overdispersed and can be described by the negative binomial distribution. The causes of this overdispersion are poorly understood, but heterogeneity in the distribution of infective stages within the environment has been implicated as a possible factor. Here we describe the distribution of infective stages of the rat intestinal nematode parasite Strongyloides ratti among the faecal pellets of its host. The distribution of infective stages between faecal pellets is overdispersed and well described by the negative binomial distribution. This overdispersion increases during the course of infection and occurs over a range of infection intensities. Overdispersion of nematode infective stages among faecal pellets may result in increased spatial heterogeneity of the infective stages in the environment and thus may contribute to the generation of overdispersion of adult parasitic stages. In addition, these findings raise important issues regarding the accurate quantification of helminth egg counts from faecal samples.

Animals↗

Genetic characterization of heather (Calluna vulgaris (L.) hull) subject to different management regimes across great britain

Heather plants were collected from 34 populations in Great Britain, which differed according to their geographical location and associated management histories. Comparisons of differential grazing regimes were made across 10 sites in the first year of study, whereas the influence of differential burning regimes was considered at four sites during the second year. The extent of genetic variation, both within and between the selected heather populations, was examined using polymerase chain reaction (PCR)-based DNA fingerprinting methodologies. Initially, high genetic variation within populations obscured differences between populations. Heather stands that were geographically close proved to be genetically similar. Site latitude and longitude were strongly associated with genetic differences between heather populations; however, a range of grazing and burning management treatments had no consistent effect upon genetic diversity. The results represent the first national survey of genetic variation at the DNA level within UK populations of this important heathland species. They provided insights into the genetic structure of heather-dominated heathlands, revealing a lack of clonal dominance within populations, but rather a much more varied genetic makeup than might have been expected given the species' ability to propagate vegetatively. The processes that influence genetic diversity in heather populations are discussed, and the potential role of molecular techniques in heathland conservation is considered.

Journal Article↗

Miconazole/chlorhexidine shampoo as an adjunct to systemic therapy in controlling dermatophytosis in cats.

A 2 per cent miconazole/2 per cent chlorhexidine shampoo was used in two groups of Persian cats infected with Microsporum canis. In the first group, the cats were treated with griseofulvin alone while, in the second, griseofulvin was used with the shampoo. The clinical signs of the cats were scored on a scale of 1 to 4 for seborrhoea, ease of epilation of hair and the extent of primary lesions, to try to give an overall impression of hair coat condition. The speed of resolution of the infection was assessed in terms of time to mycological cure. Samples were taken from the environment of both groups to assess the degree of environmental contamination at the end of treatment. No statistically significant difference was found between the two groups for time to mycological cure, although the lesion scores in the second group decreased significantly more quickly than those of the first group. Additionally, no dermatophytes were cultured from the environment in the second group at the end of the study.

Administration, Topical↗

Major histocompatibility complex variation associated with juvenile survival and parasite resistance in a large unmanaged ungulate population.

Antagonistic coevolution between hosts and parasites has been proposed as a mechanism maintaining genetic diversity in both host and parasite populations. In particular, the high levels of genetic diversity widely observed at the major histocompatibility complex (MHC) of vertebrate hosts are consistent with the hypothesis of parasite-driven balancing selection acting to maintain MHC genetic diversity. To date, however, empirical evidence in support of this hypothesis, especially from natural populations, has been lacking. A large unmanaged population of Soay sheep (Ovis aries L.) is used to investigate associations between MHC variation, juvenile survival, and parasite resistance. We show in an unmanaged, nonhuman population that allelic variation within the MHC is significantly associated with differences in both juvenile survival and resistance to intestinal nematodes. Certain MHC alleles are associated with low survivorship probabilities and high levels of parasitism or vice versa. We conclude that parasites are likely to play a major role in the maintenance of MHC diversity in this population.

Alleles↗

No evidence for major histocompatibility complex-dependent mating patterns in a free-living ruminant population.

Conventionally, the extraordinary diversity of the vertebrate major histocompatibility complex (MHC is thought to have evolved in response to parasites and pathogens affecting fitness. More recently, reproductive mechanisms such as disassortative mating have been suggested as alternative mechanisms maintaining MHC diversity. A large unmanaged population of Soay sheep (Ovis aries L.) was used to investigate reproductive mechanisms in the maintenance of MHC diversity. Animals were sampled as new-born lambs and between 887 and 1209 individuals were typed at each of five microsatellite markers located either within or flanking the ovine MHC. All loci were in Hardy-Weinberg proportions. A novel likelihood-based approach was developed to analyse mating patterns using paternity data. No evidence for non-random mating with respect to MHC markers was found using this technique. We conclude that MHC diversity in the St Kildan Soay sheep population is unlikely to be maintained by mating preferences and that, in contrast with evidence from experimental mice populations, MHC variation plays no role in the mating structure of this population.

Animals↗

Treatment of superficial ulcerative squamous cell carcinoma in three horses with topical 5-fluorouracil.

Three horses with superficial ulcerative squamous cell carcinoma were successfully treated with topical 5-fluorouracil. Two of them remain in remission after a single course of treatment and the third case is controlled by the application of the cream for seven days every six weeks. No systemic side-effects were observed but there was a localised inflammatory reaction in the skin in each case.

Administration, Topical↗