PubMed Health⌕ Search

Biomedical subjects

T Smith

Publications and source records attributed to T Smith.

At least 37 records · Page 2Linked to original sources
PubMed2005

Latent period for symptomatic sensitization in bakeries.

AIM: To describe the latent period for symptomatic sensitization in bread bakery workers. METHODS: Data on the latent period for symptomatic sensitization, resulting in either asthma or rhinitis, were obtained from an in-house health surveillance programme in a single large organization. RESULTS: Over a period of 10 years, 90 employees were identified with symptoms attributable to sensitization. The mean latent period was 7.3 years, with three employees describing the onset of symptoms in their first year of exposure. CONCLUSIONS: The long latent period, typically more than 1 year, suggests that health surveillance on appointment and then at annual intervals thereafter should be adequate to identify affected individuals in a bakery environment.

Asthma↗
PubMed2005

Spatial effects of the social marketing of insecticide-treated nets on malaria morbidity.

Randomized controlled trials have shown that insecticide-treated nets (ITNs) have an impact on both malaria morbidity and mortality. Uniformly high coverage of ITNs characterized these trials and this resulted in some protection of nearby non-users of ITNs. We have now assessed the coverage, distribution pattern and resultant spatial effects in one village in Tanzania where ITNs were distributed in a social marketing programme. The prevalence of parasitaemia, mild anaemia (Hb <11 g/dl) and moderate/severe anaemia (Hb <8 g/dl) in children under five was assessed cross-sectionally. Data on ownership of ITNs were collected and inhabitants' houses were mapped. One year after the start of the social marketing programme, 52% of the children were using a net which had been treated at least once. The ITNs were rather homogeneously distributed throughout the village at an average density of about 118 ITNs per thousand population. There was no evidence of a pattern in the distribution of parasitaemia and anaemia cases, but children living in areas of moderately high ITN coverage were about half as likely to have moderate/severe anaemia (OR 0.5, 95% CI: 0.2, 0.9) and had lower prevalence of splenomegaly, irrespective of their net use. No protective effects of coverage were found for prevalence of mild anaemia nor for parasitaemia. The use of untreated nets had neither coverage nor short distance effects. More efforts should be made to ensure high coverage in ITNs programmes to achieve maximum benefit.

Anemia↗
PubMed2005

Towards empirical description of malaria seasonality in southern Africa: the example of Zimbabwe.

BACKGROUND: Quantitative description and mapping of malaria seasonality is important for timely spatial targeting of interventions and for modelling malaria risk. There is a need for seasonality models that predict quantitative variation in transmission between months. METHODS: We use Zimbabwe as an example for developing an empirical map of malaria seasonality. We describe the relationship between seasonality in malaria and environmental covariates for the period 1988--1999, by fitting a spatial-temporal regression model within a Bayesian framework to provide smoothed maps of the seasonal trend. We adapt a seasonality concentration index used previously for rainfall to quantify malaria case load during the peak transmission season based on monthly values. RESULTS: Combinations of mean monthly temperature (range 28--32 degrees C), maximum temperature (24--28 degrees C) and high rainfall provide suitable conditions for seasonal transmission. High monthly maximum and mean monthly minimum temperatures limit months of high transmission. The intensity of seasonal transmission was highest in the north western part of the country from February to May with the peak in April and lowest in the whole country from July to December. The north western lowlands had the highest concentration of malaria cases (>25%) followed by some districts in the north central and eastern part with a moderate concentration of cases (20-25%). The central highlands and south eastern part of the country had the lowest concentration of malaria cases (<20%). This pattern was closely associated to the geographic variation in the seasonality of climatic covariates particularly rainfall and temperature. Conclusions Our modelling approach quantifies the geographical variation in seasonal trend and the concentration of cases during the peak transmission season and therefore has potential application in malaria control. The use of a covariate adjusted empirical model may prove useful for predicting the seasonal risk pattern across southern Africa.

Humans↗
PubMed2004

Vanishing contrast enhancement in malignant glioma after corticosteroid treatment.

Malignant gliomas of the brain typically exhibit on CT or MRI a strong peripheral contrast enhancement area with a variable central zone of necrosis. These tumours are not known to change their radiological appearance and contrast enhancement pattern under systemic steroid treatment--a feature usually associated with primary CNS lymphoma. We report two cases of adult patients with glioblastoma multiforme and atypical hemispherical contrast enhancement initially demonstrated on MRI or CT, which disappeared after dexamethasone administration. At the same time, however, another tumour focus became visible, in both cases localised in the corpus callosum. Histological diagnosis was confirmed by stereotactic biopsy in both cases. This unusual changing pattern of contrast enhancement seems to be associated with multifocal malignant glioma with partial blood-brain barrier disruption modified by dexamethasone, and may present diagnostic difficulties in respect to neuroimaging and selection of target areas for tumour biopsy.

Administration, Oral↗
PubMed2004

Spatial patterns of infant mortality in Mali: the effect of malaria endemicity.

A spatial analysis was carried out to identify factors related to geographic differences in infant mortality risk in Mali by linking data from two spatially structured databases: the Demographic and Health Surveys of 1995-1996 and the Mapping Malaria Risk in Africa database for Mali. Socioeconomic factors measured directly at the individual level and site-specific malaria prevalence predicted for the Demographic and Health Surveys' locations by a spatial model fitted to the Mapping Malaria Risk in Africa database were examined as possible risk factors. The analysis was carried out by fitting a Bayesian hierarchical geostatistical logistic model to infant mortality risk, by Markov chain Monte Carlo simulation. It confirmed that mother's education, birth order and interval, infant's sex, residence, and mother's age at infant's birth had a strong impact on infant mortality risk in Mali. The residual spatial pattern of infant mortality showed a clear relation to well-known foci of malaria transmission, especially the inland delta of the Niger River. No effect of estimated parasite prevalence could be demonstrated. Possible explanations include confounding by unmeasured covariates and sparsity of the source malaria data. Spatial statistical models of malaria prevalence are useful for indicating approximate levels of endemicity over wide areas and, hence, for guiding intervention strategies. However, at points very remote from those sampled, it is important to consider prediction error.

Adult↗
PubMed2004

A prospective study of Plasmodium falciparum multiplicity of infection and morbidity in Tanzanian children.

Several studies suggest that in individuals with substantial previous exposure to malaria, co-infection with multiple clones of Plasmodium falciparum can protect against subsequent clinical malaria attacks. Other studies, mainly of individuals with little previous exposure, found the converse relationship. To test whether acquisition of such cross-protection tracks the acquisition of clinical immunity in general, 610 Tanzanian children aged 0-6 years were enrolled in a nine-month prospective study of the risk of morbidity in relation to parasitological status and merozoite surface protein 2 genotypes on enrolment. Prevalence of parasitaemia and multiplicity of infection increased with age. In the first year of life, the incidence of clinical malaria was almost three times higher in children with parasites at baseline than in those without. In older children, baseline P. falciparum infections appeared to protect against both parasitaemic and non-parasitaemic fever episodes. In children aged less than three years, baseline multiple infection tended to be associated with higher prospective risk of clinical malaria than single infection while in children aged more than three years the converse was found, but these effects were not statistically significant. These results provide further evidence that relationships between asymptomatic malaria infections and clinical malaria change with cumulative exposure.

Age Distribution↗
PubMed2004

An update of recent evidence of the relationship between objective and self-report measures of the physical environment and physical activity behaviours.

The physical environment has the potential to influence the physical behaviours of large numbers of people; hence creating supportive environments has the potential to increase physical activity (PA). During the last decade, there has been growing interest in how the physical environment shapes PA behaviour. This area of research is important given that levels of PA participation are declining globally. Literature was reviewed that examined the association between physical environmental attributes and PA behaviours. The environmental attributes were grouped into four categories based on a conceptual framework of environmental factors that might influence PA and included functionality, safety, aesthetics and destinations. Positive associations were found between both perceived and objectively measured environmental factors and PA behaviour. The availability, accessibility and convenience of destinations and facilities, as well as the general functionality of the neighbourhood (eg, the presence of sidewalks, traffic conditions) and aesthetics were positively associated with various levels of PA. The review highlights the need for future studies: to examine behaviour-specific environmental attributes, to collect objectively-measured environmental data and to include both objective and perceived environmental data in the same studies, and to adopt prospective study designs to allow causal relationships to be established.

Environment↗
PubMed2004

Bayesian age-stage modelling of Plasmodium falciparum sequestered parasite loads in severe malaria patients.

A discrete-time age-stage model is proposed for estimating the number of sequestered parasites in severe malaria patients. A Bayesian Markov chain Monte Carlo (MCMC) approach is used to model the dynamics of Plasmodium falciparum parasitaemia in 107 paediatric patients in a randomized controlled trial of quinine and artemether in Kenya, in whom 4-hourly peripheral parasitaemia determinations were made. The MCMC approach allows the model to be fitted simultaneously to the entire dataset, providing point and interval estimates for both population and individual patient parameters. Analysis of a simulated dataset indicated that the models gave good estimates of the distribution of parasites between different stages on enrolment, for patients with a wide range of initial states. The analysis of the Kenyan patients suggested that there is considerable variation between patients within the same centre, in both the proportion of sequestered parasites and the intrinsic rate of increase of the parasite population in the absence of treatment. The resulting models should prove a useful tool for cross-validating biochemical approaches for estimating the sequestered load.

Animals↗
PubMed2004

Outcomes of autologous stem cell transplantation in patients with multiple myeloma who received dexamethasone-based nonmyelosuppressive induction therapy.

High-dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT) improves survival in myeloma (MM). The role of induction therapy on outcomes of ASCT in MM has not been systematically studied. Nonmyelosuppressive (NMS) steroid-based induction can be used in MM, with the potential of reducing neutropenias and other toxic effects prior to ASCT. NMS induction however could be associated with poorer outcomes if disease control or stem cell collection were inadequate. We studied outcomes of 136 MM patients who underwent HDC and ASCT as part of their initial therapy between March 1998 and December 2000. Of these, 46 received HDC and ASCT without any exposure to myelosuppressive agents, 39 received myelosuppressive therapy for disease control and/or stem cell collection, and 51 received alkylating agent-based initial treatment. We compared OS and EFS rates, stem cell collectability, and contamination of the grafts with monoclonal plasma cells. After a median of 33 months, response rates, EFS and OS rates were comparable in the three groups of patients. Adequacy of stem cell collection and plasma cell contamination were similar. Our data support the hypothesis that NMS induction for patients with MM is safe and effective and does not compromise the results of HDC.

Dexamethasone↗
PubMed2004

Relationships between the outcome of Plasmodium falciparum infection and the intensity of transmission in Africa.

Establishing the relationship between transmission intensity and health outcomes is crucial for the planning of long-term malaria control programs. Unfortunately this is fraught with methodologic difficulties. In this report, we address some of these problems by considering some important parameters that have previously been ignored. One important consideration is that the incidence of infection for Plasmodium falciparum malaria is much lower than entomologic inoculation rates (EIRs), especially at higher transmission levels. Moreover, biting rates of malaria vectors per host depend on his or her biomass and thus age. We propose an algorithm for estimating human infection rates from the EIR with allowance for these two factors. We then re-analyzed 1) data on EIR and age-specific incidence of clinical malaria in two villages in Senegal and 2) a survey of infant and child mortality rates across Africa. In each case, we review analyses of incidence in relation to the EIR and carry out a new analysis of morbidity and mortality rates in relation to the estimated incidence of infection (h). Reduction in malaria transmission may result in a shift of acute malaria attacks to older ages, and thus have little impact on life-time risk of clinical attacks. However, our analysis of the Senegalese data indicates that the peak incidence rate of disease relative to infection rates is in the youngest age groups in both the villages of Dielmo (EIR = 200 infectious bites per year) and Ndiop (EIR = 20). This suggests that simple models of acquired clinical immunity can explain age-incidence profiles better when incidence is expressed in relation to h, than when expressed in relation to the EIR. Relationships of malaria transmission intensity (in endemic areas) with overall mortality are very different from those with acute morbidity. Infant mortality rates (IMRs) decrease substantially when the EIR is reduced, probably largely because of prevention of indirect mortality. However, we were are not yet able to draw strong conclusions about the shape of relationships between the IMR and h because many of the available data points have similar values of h. The effects of transmission reduction on mortality rates in older age groups are also uncertain. However, it is clear that reduction of exposure during infancy is not reflected in increased mortality at older ages.

Adolescent↗
PubMed2003

Yttrium90 synovectomy in the management of chronic knee arthritis: a single institution experience.

Radiation synovectomy (RS) has been used to treat chronically inflamed joints refractory to treatment using conventional agents. In RS, the radioactive isotope is concentrated in the synovial membrane from the injected colloid suspension, where it exerts its activity. However, despite numerous reports confirming its safety and efficacy, this procedure is not widely practised. In the Singleton Hospital NHS Trust, yttrium(90) (Y(90)) RS has been practised since 1990 for refractory synovitis. In this study, we analyse the results of therapy and complications in 38 joints so treated. Doses of 10 mCi were used in the majority of patients. Most responses were apparent by 6 months following the procedure. Altogether, 68% of the treated joints showed satisfactory response at 3 years, with 29% having all symptoms under control beyond 3 years. In three patients, there was evidence of minor pigmentation at the injection site. Two patients had extravasation of the isotope and needle track ulcers, which were recorded as major toxicity. We find Y(90) radiosynovectomy to be safe, quick, and effective in the management of patients with refractory synovitis. The efficacy of RS should be tested in randomised clinical trials involving large numbers of patients.

Adult↗
PubMed2003

Evaluation of the pharmacokinetic profiles of the new testosterone topical gel formulation, Testim, compared to AndroGel.

A two-period, randomized, complete crossover study was performed to evaluate the pharmacokinetic profiles of Testim (AA2500), a new 1% testosterone topical gel formulation, compared to AndroGel, an already available 1% testosterone topical gel. Twenty-nine hypogonadal subjects received a single dose (50 mg testosterone) of each formulation seven days apart. C(max) estimates for total testosterone, dihydrotestosterone and free testosterone were greater (30, 19 and 38%, respectively) following the application of Testim compared to AndroGel. Similarly, AUC(0-24) estimates for total testosterone, dihydrotestosterone, and free testosterone were greater (30, 11 and 47%, respectively) following the application of Testim compared to AndroGel. Confidence intervals for C(max) and AUC(0-24) were not wholly contained within the bioequivalence limits for testosterone, therefore Testim trade mark and AndroGel are not bioequivalent with Testim providing higher serum levels and greater bioavailability than AndroGel.

Administration, Topical↗
PubMed2003

Cystic fibrosis mutation frequencies in an Irish population.

The incidence of cystic fibrosis (CF) at birth in Ireland is 1/1461. Neonate CF genetic testing is not routinely performed in Ireland. Currently, screening is only carried out where there is clinical evidence or a family history to suggest disease. Here we report the frequencies of common CF mutations occurring in an Irish population composed of samples collected from western, mid-western and southern regions of Ireland. Rarer CF mutations were also identified in a selected number of CF patients. In addition, a number of polymorphisms were identified, some of which are reported to be functionally and phenotypically important.

Cystic Fibrosis↗
PubMed2003

The RAD30 cancer susceptibility gene.

The human skin cancer-prone disease xeroderma pigmentosum variant (XPV) results from a mutation in RAD30, which encodes the novel lesion bypass DNA polymerase eta. XPV cells are characterized by delayed completion of DNA replication and increased mutagenesis following UV irradiation. In cell-free extracts of XPV lymphoblasts, functional DNA polymerase eta is required for the complete replication of a double-stranded plasmid containing either a single (6-4) photoproduct or a cyclobutane pyrimidine dime(CPD), the major mutagenic UV-induced lesion. In cultured XPV cells, replication arrest activates downstream signalling pathways, leading to hyperphosphorylation of the 34-kDa subunit of the trimeric single-stranded DNA-binding protein, RPA (replication protein A). Many of the RAD30 mutations identified in XPV cells result in truncation and inactivation of DNA polymerase eta. To examine whether polymorphisms in the RAD30 gene that result in altered polymerase eta function, rather than enzyme inactivation, might contribute to individual susceptibility to skin cancer, methods to screen for sequence changes in the RAD30 gene in human genomic DNAhave been developed.

Animals↗
PubMed2003

Transient optical elements: application to near-field microscopy.

We report methods of near-field infrared microscopy with transient optically induced probes. The first technique - a transient aperture (TA) - uses photoinduced reflectivity in semiconductors to generate a relatively large transient mirror (TM) with a small aperture at its centre. We report the optical properties of the TM and TA and experiments performed on near-field imaging with the TA. The second technique is based on solid immersion microscopy, in which high resolution is achieved when light is focused inside a solid with a high refractive index. By creating a transient Fresnel lens on the surface of a semiconductor wafer via photoinduction, we were able to form a solid immersion lens (SIL) for use as a near-field probe. The use of transient probes eliminates the need for mechanical scanning of the lens or sample, and thus provides a much faster scanning rate and the possibility to work with soft and liquid objects.

Journal Article↗
PubMed2003

HFE alleles in an Irish cystic fibrosis population.

The variable clinical manifestations of cystic fibrosis (CF) suggest the influence of modifier genes. Genetic and environmental factors that determine whether an individual will develop associated complications are still being determined. It has been proposed that the gene for hemochromatosis, HFE, may be a modifier locus for CF disease phenotype. Recent research has suggested a relationship between mutations to the HFE gene and the development of meconium ileus (MI) and liver disease in CF. This study aims to expand our knowledge of the HFE mutations C282Y and H63D carrier rate in an Irish population of CF allele carriers. PCR restriction enzyme analysis was performed on blood samples from CF patients to identify the C282Y and H63D mutations. HFE status of CF allele carriers and CF patients (Delta F508) homozygotes with and without meconium ileus was determined. The carrier frequency for C282Y was 30.8% for the Delta F508 homozygote MI positive group, as compared to 12.5% for the non-Delta F508 MI positive group but did not reach statistical significance (p = 0.27). Interestingly, no Delta F508 homozygote patients were homozygous for the C282Y mutation.

Alleles↗
PubMed2003

A phase I-II study of rituximab, ifosfamide, mitoxantrone and etoposide (R-IME) for B cell non-Hodgkin's lymphoma prior to and after high-dose chemotherapy and autologous stem cell transplantation (HDC-ASCT).

This phase I-II study describes the safety of rituximab, ifosfamide, mitoxantrone and etoposide (R-IME) as an induction regimen prior to high-dose chemotherapy and autologous stem cell transplantation (HDC-ASCT), and rituximab given post-HDC-ASCT for B cell non-Hodgkins's lymphoma. This study also measured the effect on disease burden and stem cell contamination. Patients with relapsed, refractory or poor risk B cell lymphomas were eligible. Patients were treated with two cycles of R-IME; all non-progressing patients under-went a third cycle and peripheral blood stem cell (PBSC) collection. Patients underwent HDC-ASCT and those patients in remission after HDC-ASCT were treated with four additional doses of rituximab. Tumor cell contamination was measured at baseline and in the PBSC. Serial immunoglobulin levels were measured. Patients were followed for time to treatment failure (TTF) and overall survival (OS). Thirty-two patients were enrolled. Thirty patients had at least stable disease after two cycles of R-IME. Twenty-nine underwent stem cell collection. The response rate to R-IME induction was 77% (20/26) with 35% (9/26) complete response(CR). Stem cell mobilization was successful in 93% (27/29) of patients. The response rate to R-IME induction and HDC-ASCT was 95% with a confirmed CR of 68%. Median follow-up was 28 months; the median TTFand OS have not been reached. There was a significant decline in stem cell tumor cell contamination and a significant decline in IgG without an increase in infections. Forty-three per cent of patients had transient neutropenia after post-transplant rituximab. R-IME is an effective cytoreductive and mobilization regimen. There appears to be a reduction in the number of lymphoma cells in the stem cell product and the toxicity is manageable.

Adult↗