PubMed Health⌕ Search

Biomedical subjects

G Smith

Publications and source records attributed to G Smith.

At least 19 recordsLinked to original sources
PubMed2006

A computer model to simulate control of parasitic gastroenteritis in sheep on UK farms.

A computer model that simulates the population dynamics and epidemiology of three major species of parasitic nematodes of sheep found in the UK (Telodorsagia [Ostertagia] spp., Haemonchus spp. and Trichostrongylus spp.) is described. The model has been developed as a tool for veterinarians and advisors to aid in the implementation of integrated parasite control strategies designed to optimise anthelmintic usage and delay the development of resistance on UK farms. The model represents the parasite life cycle, flock dynamics and the response of individuals with different susceptible and resistant genotypes to the major broad-spectrum classes of anthelmintic available in the UK. Where possible, UK data have been used for the model parameters. The model allows worm control simulations on individual UK farms. Inputs include environmental and farm management variables which impact on the epidemiology of the disease, e.g. regional weather data; flock stocking rates; initial pasture larval contamination levels and species proportions; lambing dates; timing of flock movements to clean pastures; and removal of lambs during the year. Farm management data, as well as nematode egg outputs and grass larval counts, were collected from eight UK farms over a 1-year period for initial validation of the model outputs. The management data for each farm were used as inputs for each model run and model outputs for nematode egg counts from ewes and lambs were compared to the observed data for each farm. Statistical analysis of results shows a positive correlation for observed and simulated counts and regression analysis suggests an acceptable fit between the data. Comparison of observed and simulated outputs for resistance were possible for only one farm due to low numbers of worms developing in the laboratory tests. Additional studies will be necessary before resistance data can be reliably compared. Further validation studies are proposed to ensure that the model is robust and applicable across a diverse range of farm types. The model will be used to demonstrate the advantage, in terms of delaying resistance development, of current guidelines for anthelmintic use and management practices for worm control in sheep.

Animals↗
PubMed2006

Pregnancy-induced hypertension is associated with lower infant mortality in preterm singletons.

OBJECTIVE: To assess the association between pregnancy-induced hypertension (PIH) and infant mortality. DESIGN: Retrospective cohort study. SETTING: Birth and infant death registration dataset of the USA. POPULATION: A total of 17,432,987 eligible, liveborn singleton births in 1995-2000. METHODS: Multivariate logistic regression was applied to evaluate the association between PIH and infant mortality, with adjustment of potential confounders. MAIN OUTCOME MEASURES: Infant death (0-364 days) and its three components: early neonatal death (0-6 days), late neonatal death (7-27 days), and postneonatal death (28-364 days). RESULTS: There was a significant reduction in infant mortality associated with PIH in early preterm infants (OR = 0.59, 95% CI: 0.56-0.63) and in late preterm infants (OR = 0.80, 95% CI: 0.73-0.87), but a significant increase in term infants (OR = 1.08, 95% CI: 1.02-1.14). Both in early preterm and late preterm births, early neonatal mortality (OR = 0.38, 95% CI: 0.34-0.42; OR = 0.68, 95% CI: 0.61-0.77) and late neonatal mortality (OR = 0.59, 95% CI: 0.50-0.70; OR = 0.76, 95% CI: 0.61-0.96) were decreased in infants born to mothers with PIH compared with those born to mothers with normal blood pressure. The PIH-associated reduction in neonatal mortality among preterm singletons was stronger in small-for-gestational-age infants than in normal growth infants and stronger in infants born to nulliparous women than in those born to multiparous women. CONCLUSIONS: PIH is associated with lower risk of infant death in preterm births but higher risk in term births.

Adult↗
PubMed2006

Coral diversity and disease in Mexico.

Field studies and empirical tests of the 'diversity-disease hypothesis' demonstrate the effects of species richness on disease transmission and severity in plant systems. Yet the converse, i.e. effects of disease on diversity, is rarely considered in either relatively well-studied plant systems or marine ecosystems. We investigated these effects along the Mexican Yucatan Peninsula to (1) quantify the relationship between disease prevalence and coral diversity, (2) test the hypothesis that octocoral and scleractinian disease prevalence are associated with one another, and (3) establish a long-term dataset. Aspergillosis of sea fans and 6 scleractinian diseases were documented. Prevalence of aspergillosis declined from 12.85% in 2002 to 5.26% in 2004, while prevalence of scleractinian diseases remained relatively constant at 5.7 +/- 0.8% in 2002 and 7.96 +/- 0.7% in 2004. Sites were relatively rich (71 species of octocoral and scleractinian corals) and even (E5 > 0.5). Sea fan disease prevalence was not associated with scleractinian disease prevalence, nor were there consistent associations between disease and measures of diversity. However, the most abundant octocoral and scleractinian species are susceptible to infection with several diseases, and disease may alter coral diversity in complex ways. These data represent the first in what will become a long-term dataset monitoring disease prevalence and associated changes in coral diversity.

Analysis of Variance↗
PubMed2006

Behavioural and hypothalamic molecular effects of the anti-cancer agent cisplatin in the rat: A model of chemotherapy-related malaise?

Many cancer patients receiving chemotherapy experience fatigue, disturbed circadian rhythms, anorexia and a variety of dyspeptic symptoms including nausea. There is no animal model for this 'chemotherapy-related malaise' so we investigated the behavioural and molecular effects of a potent chemotherapeutic agent, cisplatin (CP, 6 mg/kg, i.p.) in rats. Dark-phase horizontal locomotor activity declined post-CP reaching a nadir on day 3 (P < 0.001), before recovering after 7 days. CP's effect was most marked in the late part (05.00-07.00) of the dark-phase. Food intake reached a nadir (P > 0.001) at 2 days, coincident with an increase in gastric contents (cisplatin 9.04+/-0.8 vs. saline 2.32+/-0.3 g; P < 0.001). No changes occurred in hypothalamic mRNA expression for AGRP, NPY, HCRT, CRH, IL-1, IL-6, TNFalpha, ABCG1, SLC6A4, PPIA and HPRT mRNA but tryptophan hydroxylase (TPH) mRNA was decreased (47%, P < 0.05) at day 21 post-CP. This shows that despite marked behavioural effects of cisplatin, only a discrete change (TPH) was found in hypothalamic mRNA expression and that occurred when the animals' behaviour had recovered. Findings are discussed in relation to the neuropharmacology of chemotherapy-induced malaise.

Animals↗
PubMed2006

Regulation of cutaneous drug-metabolizing enzymes and cytoprotective gene expression by topical drugs in human skin in vivo.

BACKGROUND: Individuality in the expression and regulation of hepatic drug-metabolizing enzymes (DMEs) and cytoprotective (CP) genes is an important determinant of treatment response. There is increasing evidence that many DMEs and CP genes are also expressed in human skin. Responses to topical drugs used to treat common skin diseases, such as psoriasis, are unpredictable and may potentially be rationalized, at least in part, by interindividual differences in cutaneous DME and CP gene expression. OBJECTIVES: We investigated whether three topical drugs [coal tar, all-trans retinoic acid (atRA) and clobetasol 17-propionate] used in routine clinical practice modulated the expression of a variety of DME and CP genes [cytochrome P450s, glutathione S-transferases (GSTs) and drug transporters] in healthy human skin in vivo. METHODS: Healthy adult volunteers (n = 30) were invited to participate in the study. Each subject was randomly allocated to receive two of the three study chemicals and one control site application. Crude coal tar (n = 13), atRA (n = 14) or clobetasol 17-propionate (n = 10) was applied under occlusion to photoprotected buttock skin for 96 h. A vehicle control (white soft paraffin) was also applied under the same conditions at an adjacent site in all subjects. Full-thickness punch biopsies (4-mm diameter) were then taken from treated and control sites. Total RNA was extracted and reverse transcribed into cDNA, which was used as a template in subsequent real-time polymerase chain reaction analysis, where fluorescent output was directly proportional to input cDNA concentration. Triplicate measurements of skin mRNA expression were made from each sample, and the arithmetic mean values taken. After logarithmic transformation, the paired t-test was used to compare values between treated and control skin. RESULTS: Cytochrome P450s CYP1A1, CYP1A2, CYP1B1, CYP2C18, quinone reductase (NQO-1), GSTP1, gamma-glutamyl cysteine synthetase (gamma-GCS), glutathione peroxidase-1 (GPx-1), cyclooxygenase-2 (COX-2) and haem oxygenase-1 (HO-1) were induced by coal tar; CYP26, NADPH P450 reductase (CPR), GSTP1 and HO-1 by atRA; and CYP3A5 by clobetasol 17-propionate. In contrast, CYP1A1 and CYP1A2 expression was suppressed by atRA, and gamma-GCS and MRP1 by clobetasol 17-propionate. Marked interindividual variation in gene regulation by topical drugs was seen for the majority of genes examined. CONCLUSIONS: These data demonstrate that topical drugs can modulate DME gene expression in human skin in vivo and indicate that variation in the expression and regulation of these genes may be a determinant of individuality in response to topical therapies for common skin diseases.

Administration, Cutaneous↗
PubMed2006

Thyroid hormone resistance: the role of mutational analysis.

The finding of increased thyroxine (T4) and tri-iodothyronine (T3) levels in a patient with normal or increased thyroid-stimulating hormone is unexpected and presents a differential diagnosis between a thyroid-stimulating hormone-secreting pituitary adenoma, generalized resistance to thyroid hormone (RTH) and laboratory artefact. Without careful clinical and biochemical evaluation, errors may occur in patient diagnosis and treatment. In the case of RTH, mutation of the thyroid hormone receptor beta gene results in generalized tissue resistance to thyroid hormone. As the pituitary gland shares in this tissue resistance, euthyroidism with a normal thyroid-stimulating hormone is usually maintained by increased thyroid hormones. To date, we have identified eight pedigrees in New Zealand with mutations in the thyroid hormone receptor beta gene, including two novel mutations. Mutational analysis of the thyroid hormone receptor beta gene allows definitive diagnosis of RTH, potentially avoiding the need for protracted and expensive pituitary function testing and imaging. Mutational analysis also enables family screening and may help to avoid potential misdiagnosis and inappropriate treatment.

DNA Mutational Analysis↗
PubMed2006

The Canadian National Outcomes Measurement Study in Schizophrenia: overview of the patient sample and methodology.

OBJECTIVE: The Canadian National Outcomes Measurement Study in Schizophrenia (CNOMSS) is a prospective survey of routine clinical practice. METHOD: Patients with schizophrenia or a related disorder were consecutively enrolled from all regions of Canada. Both academic and community psychiatric clinics were included and patients were followed up for 2 years. Clinical and functional status, quality of life, medication and economic costs were assessed at enrollment and monitored throughout the follow-up period. RESULTS: Patients attending an academic clinic tended to be younger and more severely ill than those from community clinics. Both types of sites prescribed atypical neuroleptics to more than three-quarters of the patients. The majority of those enrolled were unemployed and living in poverty. Poor clinical status was associated with poverty. CONCLUSION: The CNOMSS provides demographic, clinical and treatment-related information about a large Canada-wide sample of psychiatric patients. The following three articles in this issue of Acta Psychiatrica Scandinavica explore issues related to medication, quality of life and resource utilization.

Academic Medical Centers↗
PubMed2006

Medication decisions and clinical outcomes in the Canadian National Outcomes Measurement Study in Schizophrenia.

OBJECTIVE: To evaluate over a 2-year period, patients from academic/non-academic centres, from each region of Canada, to determine whether location or other variables such as medication type, gender or income was associated with outcome as defined by non-hospitalization and persistence on original treatment. METHOD: A total of 448 patients were recruited from academic and non-academic centres across all provinces of Canada and followed up for 2 years. RESULTS: Patients from British Columbia had significantly lower rates of hospitalization than patients from other provinces. Male patients showed greater symptomatic improvement at 2 years from initial assessment compared to females. Patients on clozapine, risperidone and olanzapine were least likely to be hospitalized. CONCLUSION: There were some regional differences noted in both utilization of types of antipsychotic medications and hospitalization rates. In this sample of stable out-patients over 70% who started on monotherapy with clozapine, risperidone, olanzapine and quetiapine remained on the same medication over the 2-year study period.

Academic Medical Centers↗
PubMed2006

Outcome on quality of life in a Canadian national sample of patients with schizophrenia and related psychotic disorders.

OBJECTIVE: To examine changes in subjective and objective dimensions of quality of life (QoL) in a large Canadian sample of patients with diagnosis of schizophrenia or schizoaffective disorder treated in academic and non-academic settings over a 2-year period. METHOD: Patients recruited in the study across the country were assessed for QoL and functioning using the Client and Provider versions of the Wisconsin Quality of Life Questionnaire (WQoL) and the Short Form-36 (SF-36) at baseline (n = 448), 1 year (n = 308-353) and 2 years (188-297). Data were analyzed to examine change across time using multivariate analyses controlling for potential influence of variables such as age, regional variation, gender, duration of illness, type of treatment taken and baseline measures of symptoms and QoL. RESULTS: The weighted quality of life index (W-QoL-I) showed a significant change on both the client and the provider versions of the WQoL while the physical and mental composites of the SF-36 showed change only at 2 years. These changes were influenced significantly by baseline scores on W-QoL-I and in the case of provider version of the WQoL by baseline Brief Psychiatric Rating Scale (BPRS) scores. Regional variation or type of medication had no impact on improvement in QoL. CONCLUSION: Within a naturalistic sample of schizophrenia patients treated and followed in routine care the overall QoL showed an improvement over time but this improvement was not influenced by the type of medication prescribed.

Academic Medical Centers↗
PubMed2006

Resource utilization in a Canadian national study of people with schizophrenia and related psychotic disorders.

OBJECTIVE: To determine how the use of the newer, so called atypical antipsychotic medications, effects the pharmacoeconomic treatment burden of schizophrenia and related conditions and to provide a clear comparison of the costs and risks associated with these atypical drugs. METHOD: In this 2-year, open-label, prospective study, resource utilization (RU) data were collected on 160 patients with these conditions. A comparison between risks and costs was performed by combining the generalized CNOMSS data on both economic factors and risk assessments. RESULTS: The main findings of the study were that the total adjusted 1- and 2-year costs were lowest for quetiapine. Drug acquisition costs were lowest for risperidone for both the 1- and 2-year cohorts. Clozapine use was predictably associated with the highest overall and medication costs at both 1 and 2 years. CONCLUSION: Treatment with risperidone or quetiapine was associated with the lowest overall costs when compared with olanzapine or clozapine.

Adult↗
PubMed2005

Evaluation of syndromic surveillance based on National Health Service Direct derived data--England and Wales.

INTRODUCTION: Syndromic surveillance systems might serve as an early warning to detect outbreaks of infectious diseases and chemical poisoning, including those caused by deliberate release. In England and Wales, data from National Health Service (NHS) Direct, a national telephone health advice service, were used for surveillance of 10 syndromes commonly occurring in the community. OBJECTIVES: The objective of this study was to evaluate NHS Direct syndromic surveillance using the "Framework for Evaluating Public Health Surveillance Systems for Early Detection of Outbreaks", published by CDC. METHODS: Quantitative and qualitative assessments were performed. Examination of daily data flow was used to determine the timeliness and data quality. Validity was determined by comparing NHS Direct surveillance with a well-established clinical-based surveillance system using a time series analysis. Semistructured interviews of main stakeholders were conducted to determine usefulness, flexibility, acceptability, portability, stability, and system costs. RESULTS: NHS Direct syndromic surveillance has representative national coverage, provides near real-time recording and data analysis, and can potentially detect high-risk, large-scale events. Direct costs are low and variable costs are unpredictable. Flexibility depends on urgency of the need for change, and portability relies on the existence of infrastructure similar to NHS Direct. Statistically significant correlation exists between NHS Direct surveillance and a surveillance system based on the Royal College of General Practitioners data for influenza-like illness. CONCLUSION: The CDC framework is a useful tool to standardize the evaluation of syndromic surveillance. NHS Direct syndromic surveillance is timely, representative, useful, and acceptable with low marginal costs and borderline flexibility and portability. Cross-correlation time series modeling might represent an appropriate method in the evaluation of syndromic surveillance validity.

Disease Outbreaks↗
PubMed2005

Use of contaminated well water, example reference biospheres 1 and 2A.

The BIOMASS programme's Theme 1 evaluated a number of scenarios, which assisted in the development of practical guidance. A total of four Example Reference Biospheres were fully developed, with the assumptions, data, and models thoroughly documented. These Examples display both the practicality and the transparency available through the use of the Reference Biosphere Methodology. While the methodology is designed to promote transparency and traceability, proper documentation and justification is still the responsibility of the user. The Examples can also be used as generic analyses in some situations. Although it is anticipated that each of the Reference Biospheres explored within BIOMASS Theme 1 should be a useful practical example, the quantitative results of the model calculations are not intended to be understood as prescribed biosphere 'conversion factors'. In choosing to implement an Example, careful consideration would need to be given to their relevance (including associated data) to the particular assessment context at hand. In general, the more complex the model is, the more limited applicability it has for generic purposes. For example, ERB1A (direct use of well water for drinking) can be used straightforwardly, with minor or no adjustments, at a number of generic sites. Example 2A, however, for which climatic conditions and agricultural practices need to be specified, would need to be implemented for each specific situation.

Environmental Exposure↗
PubMed2005

The prognostic significance of K-ras, p53, and APC mutations in colorectal carcinoma.

BACKGROUND: Accumulation of molecular alterations, including mutations in Kirsten-ras (K-ras), p53, and adenomatous polyposis coli (APC), contribute to colorectal carcinogenesis. Our group has previously characterised a panel of sporadic colorectal adenocarcinomas for mutations in these three genes and has shown that p53 and K-ras mutations rarely occur in the same colorectal tumour. This suggests that mutations in these genes are on separate pathways to colorectal cancer development and may influence patient prognosis independently. AIMS: To correlate the presence or absence of mutations in K-ras, p53, and APC with survival in a cohort of colorectal cancer patients. PATIENTS: A series of 107 inpatients treated surgically for colorectal cancer in Tayside, Scotland between November 1997 and December 1999. METHODS: Colorectal tumours were characterised for mutations in K-ras, p53, and APC. Kaplan-Meier survival curves were constructed using overall survival and disease specific survival as the primary end points. Patient survival was analysed using the log rank test and Cox proportional hazards model. RESULTS: Patients with K-ras mutations had significantly poorer overall survival than patients without K-ras mutations (p = 0.0098). Multivariate analysis correcting for Dukes' stage, age, and sex confirmed this (hazard ratio 2.9 (95% confidence interval 1.4-6.2); p = 0.0040). K-ras mutations were also significantly associated with poorer disease specific survival. The presence of APC and p53 mutations did not affect survival in this cohort of patients (p = 0.9034 and p = 0.8290, respectively). CONCLUSIONS: Our data indicate that the presence of K-ras mutations predicts poor patient prognosis in colorectal cancer, independently of tumour stage.

Adenocarcinoma↗
PubMed2005

Genetic background regulates semaphorin gene expression and epileptogenesis in mouse brain after kainic acid status epilepticus.

The host response to neural injury, which can include axonal sprouting and synaptic reorganization is likely to be under tight genetic regulatory control at the level of the genome and may be implicated in epileptogenesis. Despite its importance, however, the molecular basis of synaptic reorganization is unclear. We have studied the development of synaptic reorganization, semaphorin gene expression, and epileptogenesis in hippocampus of epileptogenic sensitive (FVB/NJ) and epileptogenic resistant (C57BL/6J) mice (i.e. distinct genetic backgrounds) after kainic acid-induced status epilepticus. Our results support the hypothesis that disruption of transcriptional regulation of axon guidance genes leads to a differential loss of tonic neuropilin-2 dependent activation of semaphorin 3F receptors on hippocampal neurons on distinct genetic backgrounds. This results in rearranged synaptic circuitry and thus promotes epileptogenesis. These findings may define biologic principles underlying the role of semaphorin signaling which may broadly apply to other systems undergoing neural regeneration.

Animals↗