Biomedical subjects

S Paterson

Publications and source records attributed to S Paterson.

At least 19 recordsLinked to original sources

PubMed2005

No evidence for specificity between host and parasite genotypes in experimental Strongyloides ratti (Nematoda) infections.

A key requirement for several theories involving the evolution of sex and sexual selection is a specificity between host and parasite genotypes, i.e. the resistance of particular host genotypes to particular parasite genotypes and the infectivity of particular parasite genotypes for particular host genotypes. Determining the scope and nature of any such specificity is also of applied relevance, since any specificity for different parasite genotypes to infect particular host genotypes may affect the level of protection afforded by vaccination, the efficacy of selective breeding of livestock for parasite resistance and the long-term evolution of parasite populations in response to these control measures. Whereas we have some evidence for the role of specificity between host and pathogen genotypes in viral and bacterial infections, its role in macroparasitic infections is seldom considered. The first empirical test of this specificity for a vertebrate-nematode system is provided here using clonal lines of parasite and inbred and congenic strains of rat that differ either across the genome or only at the major histocompatibility complex. Although significant differences between the resistance of host genotypes to infection and between the fitness of different parasite genotypes are found, there is no evidence for an interaction between host and parasite genotypes. It is concluded that a specificity between host and parasite genotypes is unlikely in this system.

Animals↗

PubMed2005

Calcitonin gene-related peptide-induced suppression of luteinizing hormone pulses in the rat: the role of endogenous opioid peptides.

Calcitonin gene-related peptide (CGRP) is involved in a variety of stress responses in the rat. Central administration of CGRP activates the hypothalamo-pituitary-adrenal axis resulting in increased corticosterone secretion. We have previously shown that central CGRP suppresses the gonadotrophin-releasing hormone (GnRH) pulse generator, specifically LH pulses. Endogenous opioid peptides (EOPs) have been shown to play an important role in stress-induced suppression of the reproductive axis. The aim of the present study was to test the hypothesis that EOPs mediate CGRP-induced suppression of pulsatile LH secretion. Ovariectomized rats were implanted with intracerebroventricular (i.c.v.) and i.v. cannulae. Intravenous administration of the opioid antagonist naloxone (250 microg) completely blocked the suppression of LH pulses induced by 1.5 microg i.c.v. CGRP and significantly attenuated the suppression of pulsatile LH secretion induced by 5 microg i.c.v. CGRP. Furthermore, intravenous administration of naloxone was found to immediately restore normal LH pulse frequency in animals treated 90 min earlier with 1.5 microg i.c.v. CGRP. Co-administration (i.c.v.) of CGRP (1.5 microg) with the mu and kappa opioid receptor-specific antagonists naloxone (10 microg) and norbinaltorphimine (5 microg), respectively, blocked the CGRP-induced suppression of LH pulses, whilst i.c.v. co-administration of CGRP (1.5 microg) with the delta opioid receptor-specific antagonist naltrindole (5 microg) did not. These data provide evidence that EOPs play a pivotal role in mediating the inhibitory effects of CGRP on pulsatile LH secretion in the rat. They also suggest that the mu and kappa, but not the delta, opioid receptors may be responsible for mediating the effects of CGRP on LH pulses.

Animals↗

PubMed2005

Validation of techniques to detect illicit heroin use in patients prescribed pharmaceutical heroin for the management of opioid dependence.

BACKGROUND: The clinical implementation and evaluation of heroin substitution programmes have been confounded by the lack of objective and validated biomarkers for illicit heroin use in patients prescribed pharmaceutical heroin. This study examined the capacity to detect illicit heroin use by gas chromatography-mass spectrometry (GC-MS) analysis of urine samples for the presence of opium impurities common to illicit, but not pharmaceutical heroin. AIMS: To characterize the diagnostic properties of the metabolites of noscapine and papaverine in comparison to morphine as a gold-standard marker of illicit heroin use; and to examine the relationships between the self-reported time since most recent heroin use and the detection of these opioids in urine. DESIGN: A cross-sectional study of 52 opioid-dependent patients in treatment (not prescribed heroin), who self-reported illicit heroin use within the preceding 2 weeks. Self-report data regarding recent drug use and a urine sample were collected. GC-MS analyses of urines were conducted and reported by laboratory staff blinded to self-report data. FINDINGS: The metabolites of papaverine (hydroxypapaverine and dihydroxypapeverine) were found to have high sensitivity, specificity and negative predictive values as markers for illicit heroin use compared to the 'gold-standard' morphine. Other opioids, including 6-mono-acetylmorphine (6-MAM), codeine and noscapine metabolites (e.g. meconine) were less adequate in detecting heroin use. CONCLUSIONS: GC-MS detection of papaverine metabolites in urine appears to be suitable method of identifying illicit heroin use for clinical and research purposes.

Adult↗

PubMed2004

The effect of the host immune response on the parasitic nematode Strongyloides ratti.

The host immune response has profound effects on parasitic nematode infections. Here we have investigated how a range of infection parameters are affected by host immune responses and by their suppression and enhancement. The infection parameters considered were the number of parasitic females, their size, per capita fecundity and intestinal position. We found that in immunosuppressive treatments worms persist in the gut, sometimes with a greater per capita fecundity, maintain their size and have a more anterior gut position, compared with worms from control animals. In immunization treatments there are fewer worms in the gut, sometimes with a lower per capita fecundity and they are shorter and have a more posterior gut position, compared with worms from control animals. Worms from animals immunosuppressed by corticosteroid treatment reverse their changes in size and gut position. This description of these phenomena pave the way for a molecular biological analysis of how these changes in infection parameters are brought about by the host immune response.

Animals↗

PubMed2004

Effect of deception of distance on prolonged cycling performance.

This study examined the effect of deception of distance end-point on prolonged cycling performance. 21 subjects were randomly allocated to three groups (n = 7 per group). Each group completed three self-paced time-trials separated by one day. Subjects were told that each trial was a 30-km time-trial and were required to complete the distance in the fastest time possible. Following the initial trial of 30 km, one group completed Trial 2 with a longer distance (long distance group; 36 km), another group with a shorter distance (24 km; short distance group), and the third group as control (30 km; control). Each group then completed a third time-trial of 30 km. At no time was the deception of distance in Trial 2 disclosed to the subjects, and all sources of physiological and mechanical feedback were withheld during the trials. Data from Trials 1 and 3 were analysed by repeated-measures analysis of covariance. Time to complete Trial 1 was similar among groups (approximately 65 min.). Following the deception in Trial 2 the time to complete the 30 km in Trial 3 was increased for the short distance group, decreased for the long distance group, whilst the time for the control group remained unchanged. The times to complete the 30 km on Trials 1 and 3 were matched by changes in power output throughout the trials. It is concluded that subjects deceived of the actual distance completed will complete the subsequent performance trial based on perceived effort rather than on actual distance.

Adult↗

PubMed2004

Cot-nursing using a heated, water-filled mattress and incubator care: a randomized clinical trial.

AIMS: To evaluate the thermal responses and weight gain in preterm infants nursed in a cot on a heated, water-filled mattress (HWM) compared with infants receiving care in an air-heated incubator and to compare mothers' stress, anxiety levels and perceptions of their infants in the two groups. METHODS: Stable preterm infants weighing 1300 to 1500 g were enrolled, being randomly allocated to either the study group (n = 41) receiving care in a cot on an HWM, or the control group (n = 33) receiving incubator care. The mean daily body temperature and episodes of cold stress and hyperthermia were recorded. Weight gain (g kg(-1) body weight d(-1)) was also calculated. The mothers completed questionnaires on their perceptions of their infants, and their anxiety and stress levels before randomization, and 2-3 wk later during the trial. RESULTS: The mean body temperature was similar for the first week of the trial (study group 36.9 degrees C vs controls 36.9 degrees C). There were no significant differences in the incidence of cold stress, while more hyperthermic episodes were seen in the study group (p = 0.03). There were no significant differences in weight gain during the first (study group 21.4 g vs controls 19.6 g) or second weeks of the trial (study group 20.5 g vs controls 19.2 g). Neonatal morbidity did not differ between the groups. There were no differences in mothers' perceptions of their babies, or feelings of stress or anxiety. CONCLUSION: There were no differences between infants cot-nursed on an HWM and those receiving incubator care, with the exception of episodes of high temperature. The results suggest that the HWM may be used safely for low-weight preterm infants.

Beds↗

PubMed2003

Functional consequences of genetic diversity in Strongyloides ratti infections.

Parasitic nematodes show levels of genetic diversity comparable to other taxa, but the functional consequences of this are not understood. Thus, a large body of theoretical work highlights the potential consequences of parasite genetic diversity for the epidemiology of parasite infections and its possible implications for the evolution of host and parasite populations. However, few relevant empirical data are available from parasites in general and none from parasitic nematodes in particular. Here, we test two hypotheses. First, that different parasitic nematode genotypes vary in life-history traits, such as survivorship and fecundity, which may cause variation in infection dynamics. Second, that different parasitic nematode genotypes interact within the host (either directly or via the host immune system) to increase the mean reproductive output of mixed-genotype infections compared with single-genotype infections. We test these hypotheses in laboratory infections using genetically homogeneous lines of Strongyloides ratti. We find that nematode genotypes do vary in their survivorship and fecundity and, consequently, in their dynamics of infection. However, we find little evidence of interactions between genotypes within hosts under a variety of trickle- and single-infected infection regimes.

Animals↗

PubMed2003

Comorbidity of substance misuse and mental illness in community mental health and substance misuse services.

BACKGROUND: Improved management of mental illness and substance misuse comorbidity is a National Health Service priority, but little is known about its prevalence and current management. AIMS: To measure the prevalence of comorbidity among patients of community mental health teams (CMHTs) and substance misuse services, and to assess the potential for joint management. METHOD: Cross-sectional prevalence survey in four urban UK centres. RESULTS: Of CMHT patients, 44% (95% CI 38.1-49.9) reported past-year problem drug use and/or harmful alcohol use; 75% (95% CI 68.2-80.2) of drug service and 85% of alcohol service patients (95% CI 74.2-93.1) had a past-year psychiatric disorder. Most comorbidity patients appear ineligible for cross-referral between services. Large proportions are not identified by services and receive no specialist intervention. CONCLUSIONS: Comorbidity is highly prevalent in CMHT, drug and alcohol treatment populations, but may be difficult to manage by cross-referral psychiatric and substance misuse services as currently configured and resourced.

Adult↗

PubMed2002

Host immune responses are necessary for density dependence in nematode infections.

Nematode infections are subject to density-dependent effects on their establishment, survivorship and fecundity within a host. These effects act to regulate and stabilize the size of nematode populations. Understanding how these density-dependent effects occur is important to guide the development of control strategies against parasitic nematodes and the diseases that they cause. These density-dependent effects have been hypothesized to result from intraspecific competition between parasites for limited resources or from the action of host immune responses. However, no specific evidence exists to distinguish between these two hypotheses. We find that in nematode (Strongyloides ratti) infections, density-dependent effects on parasite establishment, survivorship and fecundity are mediated by the host immune response. These density-dependent effects are only observed late in primary infections and no density-dependent effects are observed in infections in immuno-compromised animals. We find no evidence for intraspecific competition between parasites in experimental infections over a range of doses that encompasses all that is observed in natural infections. We conclude that density-dependent effects due to the immune response will act to regulate S. ratti infections before competition for space or nutrients within the host gut ever occurs.

Animals↗

PubMed2002

The impact of sporadic campylobacter and salmonella infection on health and health related behaviour: a case control study.

The aim of the work was to explore the impact on general and psychological health of those with a proven bacterial gastrointestinal infection and to compare this with controls from whom no bacterial pathogen was identified. A case control study was conducted using an interviewer-administered questionnaire. Thirty-nine cases from whose faeces salmonella or campylobacter had been cultured were compared with matched controls. Reported gastrointestinal symptoms, general health and self-reported hygiene practices were compared. At the time of acute illness the General Household Questionnaire suggested similar levels of morbidity, though by follow up the controls were substantially more likely to be distressed. Cases were more likely to have changed their food preparation practices, to avoid certain eating places and to have been given advice about food preparation. In this small study a positive diagnosis of salmonella or campylobacter seems to have had a reassuring effect when compared with those for whom no diagnosis was made.

Acute Disease↗

PubMed2001

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↗

PubMed2001

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↗

PubMed2001

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↗

PubMed2001

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↗

PubMed2000

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↗

PubMed2000

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↗

PubMed2000

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↗

PubMed2000

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↗