Search PubMed⌕ Search

Biomedical subjects

R Thompson

Publications and source records attributed to R Thompson.

At least 19 recordsLinked to original sources
PubMed2007

Safety and immunogenicity of the RTS,S/AS02A candidate malaria vaccine in children aged 1-4 in Mozambique.

BACKGROUND: The development of a malaria vaccine remains a public health priority for sub-Saharan Africa. RTS,S/AS02A candidate malaria vaccine has been shown to be safe and immunogenic in previous studies in adults and staggered dose-escalation studies in children in The Gambia. However, genetic features and the intensity of malaria transmission may modify the safety and immune response of a vaccine. OBJECTIVE: We carried out a phase I, double-blind randomized controlled trial in 60 children aged 1-4 in Mozambique to evaluate the safety, reactogenicity and immunogenicity of the paediatric vaccine dose (fixed 25 microg RTS,S in 0.25 ml) of RTS,S/AS02A, prior to undertaking a planned larger phase IIb proof-of-concept of efficacy study in the same population. METHOD: Children were randomized to receive either RTS,S/AS02A or Engerix-B vaccine. Monitoring of safety and reactogenicity included detailed clinical and laboratory analyses and assessment of adverse events (AEs). RESULTS: The RTS,S/AS02A was found to be safe and well tolerated. Serious adverse events were balanced between both groups and none was related to vaccination. The frequency of adverse events reported with RTS, S/AS02A was comparable to previous studies in children. Grade 3 AEs were infrequent (one case of pain, one of fever in each group and some swelling greater than 20 mm in diameter), transient and resolved without sequelae. RTS,S/AS02A was highly immunogenic for anti-circumsporozoite protein antibody response and induced a strong anti-hepatitis-B surface antigen response.

Alanine Transaminase↗
PubMed2007

A stepwise approach to the laboratory diagnosis of Buruli ulcer disease.

OBJECTIVE: In view of technical and financial limitations in areas of endemicity, the current practice and recommendations for the laboratory diagnosis of Buruli ulcer disease (BUD) may have to be reconsidered. We reviewed diagnostic results in order to explore options for a modified, more practicable, cost-effective and timely approach to the laboratory diagnosis of BUD. METHODS: Diagnostic specimens from 161 clinically diagnosed BUD patients from four different treatment centres in Ghana were subjected to laboratory analysis. The positivity rates of the laboratory assays were compared. RESULTS: The number of laboratory-confirmed clinically diagnosed BUD cases with one positive confirmative test was 20% higher than that with two positive confirmative tests. The specificity of microscopy (MIC) and PCR was 96.6% and 100%, respectively. Subsequent analysis of specimens from surgically excised pre-ulcerative tissue-by-tissue MIC and tissue PCR rendered 65% laboratory-confirmed BUD cases. Subsequent analysis of diagnostic swabs from ulcerative lesions by swab smear MIC and swab PCR rendered 70% of laboratory-confirmed BUD cases. CONCLUSIONS: The specificity of the diagnostic tests used in this study suggests that one positive diagnostic test may be considered sufficient for the laboratory confirmation of BUD. Subsequent application of different diagnostic tests rendered a laboratory confirmation of 65% pre-ulcerative and of 70% ulcerative lesions. Implementation of a stepwise, subsequent analysis of diagnostic specimens will result in considerable cost saving compared with simultaneous testing of specimens by several diagnostic assays.

Cost-Benefit Analysis↗
PubMed2006

Clinical findings in 33 subjects with large supernumerary marker(15) chromosomes and 3 subjects with triplication of 15q11-q13.

We present clinical data on 33 subjects with additional copies of the Prader-Willi-Angelman critical region (PWACR) contained in a supernumerary marker chromosome (SMC). Twenty-three subjects had a typical large non-mosaic SMC(15) containing two copies of the PWACR. They showed a variable but generally severe phenotype of learning disability and autism, with seizures in approximately two-thirds. The other 10 differed from this typical pattern in respect of mosaicism, variation in copy number, or arrangement of the PWACR within the SMC or number of SMC per cell. Clinical severity increased with the number of additional copies of the PWACR and decreased with mosaicism for a normal cell line. There was a trend for a larger number of seizures to be associated with more severe learning disability. Three subjects with interstitial triplications of 15q11-q13 showed a range of phenotypes similar to those of the typical large SMC(15). All additional copies of the PWACR in this series were maternally-derived. FISH and molecular data localizing the breakpoints of the rearrangements have been previously published or are included in this report. No correlations were found between specific clinical features and variations in breakpoints proximal and distal to the PWACR.

Abnormalities, Multiple↗
PubMed2006

Spatio-temporal modelling and assessment of within-species phenological variability using thermal time methods.

Phenological observations of flowering date, budding date or senescence provide very valuable time series. They hold out the prospect for relating plant growth to environmental and climatic factors and hence for engendering a better understanding of plant physiology under natural conditions. The statistical establishment of associations between time series of phenological data and climatic factors provides a means of aiding forecasts of the biological impacts of future climatic change. However, it must be kept in mind that plant growth and behaviour vary spatially as well as temporally. Environmental, climatic and genetic diversity can give rise to spatially structured variation on a range of scales. The variations extend from large-scale geographical (clinal) trends, through medium-scale population and sub-population fluctuations, to micro-scale differentiation among neighbouring plants, where spatially close individuals are found to be genetically more alike than those some distance apart. We developed spatio-temporal phenological models that allow observations from multiple locations to be analysed simultaneously. We applied the models to the first-flowering dates of Prunus padus and Tilia cordata from localities as far apart as Norway and the Caucasus. Our growing-degree-day approach yielded a good fit to the available phenological data and yet involved only a small number of model parameters. It indicated that plants should display different sensitivities to temperature change according to their geographical location and the time of year at which they flower. For spring-flowering plants, we found strong temperature sensitivities for islands and archipelagos with oceanic climates, and low sensitivities in the interiors of continents.

Climate↗
PubMed2006

Oxygen sensing in neuroepithelial and adrenal chromaffin cells.

Oxygen sensing and initiation of appropriate physiological responses to hypoxia are crucial for survival. The molecular identity of the sensor has generally sparked considerable interest and controversy in O2-sensitive cells. In mammals, pulmonary neuroepithelial bodies (NEBs) and adrenal chromaffin cells (AMCs) are O2 sensitive, particularly during the transition from intrauterine to air-breathing life. In NEBs, there is good evidence that the O2 sensor is a plasma membrane-bound NADPH oxidase which during hypoxia, signals K+ channel inhibition, membrane depolarization and neurosecretion via changes in reactive oxygen species (ROS) (e.g. H2O2). Accordingly, hypoxic sensitivity is lost in NEBs from transgenic mice deficient in the gp91(phox) subunit of NADPH oxidase; it is, however, retained in neonatal AMCs from these transgenic mice. A search for the O2 sensor in neonatal rat AMCs suggests a role for the mitochondrial electron transport chain. For example, the complex I blocker, rotenone (1 microM), mimics hypoxia in causing K+ channel inhibition and ATP secretion, and occludes hypoxic sensitivity. The evidence is consistent with hypoxia and rotenone acting via a decrease in ROS. In contrast, the complex IV blocker cyanide (2 mM) did not mimic the effects of hypoxia. We propose thatchanges in ROS serve as a common link between the O2 sensor and secretion in perinatal NEBs and chromaffin cells. However, the subcellular localization of the O2 sensor appears to be different between these two cell types.

Adrenal Glands↗
PubMed2006

Tumour necrosis factor-alpha production stimulated by heat shock protein 70 and its inhibition in circulating dendritic cells and cells eluted from mucosal tissues in Crohn's disease.

Summaryand interleukin (IL)-12 by dendritic cells (DC) from patients with Crohn's disease. TNF-alpha concentration was increased significantly when DC from Crohn's disease were stimulated with HSP70 or CD40L and this was associated with signalling by the extracellular signal regulated kinase (ERK) 1/2 and p38 mitogen activated protein (MAP) kinase pathway. IL-12 production was also increased when DC were stimulated with HSP70. Cells eluted from inflamed intestinal mucosa from Crohn's disease, stimulated with HSP70, CD40L or lipopolysaccharide produced significantly greater TNF-alpha and IL-12 concentrations than cells from uninflamed mucosa. Significant inhibition of TNF-alpha production was demonstrated when DC from peripheral blood mononuclear cells or cells eluted from intestinal mucosa of Crohn's disease were treated with either the HSP70 inhibitory peptide (aa 457-496) or peptides derived from CD40 and CD40L. These inhibitory peptides target the CD40-CD40L and the emerging CD40-HSP70 co-stimulatory pathway. Our findings offer a novel strategy to prevent excessive production of TNF-alpha in Crohn's disease.

CD40 Antigens↗
PubMed2006

Community incidences of respiratory infections in an actively followed cohort of children <1 year of age in Manhiça, a rural area of southern Mozambique.

OBJECTIVE: To estimate the community incidence-rates of respiratory infections among infants in Manhiça, southern Mozambique, and to determine risk factors associated with these infections. METHODS: A cohort of children <1 year of age were visited at home every week until they turned one. During the visits, field workers recorded signs/symptoms of respiratory infections and tested the children for malaria parasites when they had fever. RESULTS: Between 1 July 1998 and 30 June 1999, 1,044 children contributed with 23,726 weeks at risk. Children met the criteria for acute respiratory infection in 19.2% of the visits, for lower respiratory infection in 0.9% and for severe lower respiratory infection in 0.2%. The crude incidence rate measured for acute respiratory infections was 23.0, that for lower respiratory infection was 0.9 and that for severe lower respiratory infection was 0.2 per 100-person-week-at-risk. The risk of acute and lower respiratory infection was inversely related to age. Females were at significantly lower risk for all three conditions than males. A trend of increased risk of severe lower respiratory infection was noted among children born during the rainy season (adjusted rate ratio = 1.95, P = 0.122 in only 47 episodes). Malaria was strongly associated with an increased risk of all three respiratory infections [rate ratio of 2.35, 10.90 and 13.82 (P < 0.001) in the adjusted analysis, respectively]. Thirty-five children died during the follow-up period; 20% of them from lower respiratory infection. Conclusions Respiratory infections are a major cause of morbidity and mortality among infants in rural Mozambique. Our study provides a better understanding of the associated determinants.

Acute Disease↗
PubMed2006

External quality assurance for the laboratory diagnosis of Buruli ulcer disease in Ghana.

OBJECTIVE: To assure the quality of the laboratory diagnosis of Buruli ulcer disease; microscopy and PCR were subjected to external quality assurance (EQA). METHODS: Slides were read by test laboratory staff, followed by blinded re-reading by the controller. Parallel testing of PCR specimens was carried out at the local and external reference laboratory. Slides and PCR specimens with discordant results were subjected to a second reading/testing by the controller to determine the final result. For training purposes, slides and PCR specimens with discrepant results were subsequently re-read/re-tested under supervision at the test laboratory. RESULTS: Microscopy. First reading: concordance rate 82.9%, discordance rate 17.1%, percentage false negatives 27.1% (sensitivity 72.9%), percentage false positives 10.1% (specificity 89.9%). Second reading: concordance rate 97.9%, discordance rate 2.1%, percentage false negatives 4.2% (sensitivity 95.8%), percentage false positives 0.6% (specificity 99.4%). PCR. First testing: concordance rate 87.9%, discordance rate 12.1%, percentage false negatives 8.2% (sensitivity 91.8%), percentage false positives 19.1% (specificity 80.9%). Second testing: concordance rate 96.2%, discordance rate 3.8%, percentage false negatives 4.7% (sensitivity 95.3%), percentage false-positives 2.1% (specificity 97.9%). CONCLUSIONS: EQA identified deficiencies in the laboratory performance. Corrective action consisted in on-site training and reduced the number of false-negative and false-positive microscopy and PCR results.

Clinical Laboratory Techniques↗
PubMed2005

1,2,4-trichlorobenzene marine risk assessment with special emphasis on the Osparcom region North Sea.

A risk assessment on 1,2,4-trichlorobenzene was carried out specifically for the marine environment according to the methodology laid down in the EU Risk Assessment Regulation 1488/94 and the Guidance Documents of the EU Existing Substances Regulation 793/93. The study consists of the collection and evaluation of data on effects and environmental concentrations from analytical monitoring programs in large rivers and estuaries in the North Sea area. The risk is indicated by comparing the predicted environmental concentration (PEC) with the predicted no-effect concentrations (PNEC) for the marine aquatic environment. A PNECwater) value of 0.3 microg/l and a PNECsed value of 38 microg/kgdw were derived from the results of toxicological studies in organisms representing three trophic levels, i.e. aquatic plants, invertebrates and fish. Based on monitoring data two situations are distinguished: a typical case and a worst case with a PECwater of <0.047 and 0.1 microg/l, respectively, and a PECsed of 40 and 90 microg/kgdw, respectively. The calculated PEC/PNEC ratios were 0.16 and 0.3 for water and 1 and 2.4 for sediment, respectively. It was concluded that no risks are expected for aquatic organisms. Based on the combination of worst-case assumptions risks to benthic organisms could not be fully excluded, but since all open uses of 1,2,4-trichlorobenzene will be ended following the EU risk assessment outcome of 2001 any potential risk is expected to be reduced accordingly. 1,2,4-trichlorobenzene is not considered toxic according to the EU criteria and the available data on persistence of 1,2,4-trichlorobenzene indicate a half-life in water of a few days and a significant biodegradation potential. The bioaccumulation potential is low to moderate with most BCF ratios for fish ranging from 600 to 1400 and one highest of 2020. Based on an extensive evaluation of persistence, biodegradation and bioaccumulation data it is concluded that 1,2,4-trichlorobenzene is not a PBT, since it does not fulfill any of the EU criteria. Biomagnification in the food chain is not expected due to the relatively high elimination rate constants.

Animals↗
PubMed2005

In situ expression of two storage protein genes in relation to histo-differentiation at mid-embryogenesis in Medicago truncatula and Pisum sativum seeds.

The seed consists of several layers of specialized cell-types that divide and differentiate following a highly regulated programme in time and space. A cytological approach was undertaken in order to study the histo-differentiation at mid-embryogenesis in Medicago truncatula as a model legume, and in Pisum sativum using serial sections of embedded immature seed. Little published information is available about seed development in Medicago species. The observations from this study revealed a number of distinctive features of Medicago seed development and differentiation. Transfer cells, involved in nutrient transfer to the embryo, were clearly identified in the thin-walled parenchyma of the innermost integument. Histological Schiff-naphthol enabled carbohydrate accumulation to be followed in the different seed compartments, and revealed the storage protein bodies. Non-radioactive mRNA in situ hybridization, was carried out using mRNA probes from two highly expressed genes encoding the major vicilin and legumin A storage protein types. The timing of mRNA expression was related to that of the corresponding proteins already identified.

Cell Differentiation↗
PubMed2005

Modality-specific aspects of sustained and divided attentional performance in multiple sclerosis.

While the prevalence of cognitive impairment in multiple sclerosis is well documented, few studies have systematically investigated the profile of attentional abilities. In the current study, 30 MS participants were assessed on measures of sustained and divided attention and compared to a sample of 30 neurologically intact healthy controls. Performance on visual and auditory unimodal and bimodal trials were conducted for measures of both forms of attention. A three-factor mixed measures analysis of variance (groupxtaskxmodality) was conducted. MS participants were impaired relative to controls on all measures of speed and accuracy across unimodal and bimodal trials and more impaired on measures of divided attention than on sustained attention measures. Performance on the bimodal trials was also significantly compromised relative to the unimodal trials especially on the divided attention task. The theoretical and clinical implications of these findings are discussed.

Acoustic Stimulation↗
PubMed2005

Reduced response of insecticide-resistant aphids and attraction of parasitoids to aphid alarm pheromone; a potential fitness trade-off.

Response to the alarm pheromone, (E)-beta-farnesene, produced by many species of aphids, was assessed in laboratory bioassays using an aphid pest, Myzus persicae (Sulzer), and its primary endoparasitoid, Diaeretiella rapae (McIntosh). This was done in three separate studies, the first investigating responses of a large number of M. persicae clones carrying different combinations of metabolic (carboxylesterase) and target site (kdr) insecticide resistance mechanisms, and the other two investigating the responses of young virgin female adult parasitoids. In M. persicae, both insecticide resistance mechanisms were associated with reduced repellence suggesting that each has a pleiotropic effect on aphid behaviour. In contrast, D. rapae females were attracted to the alarm pheromone source. The implications of this apparent fitness trade-off for the evolution and dynamics of insecticide resistance, and the potential for using beneficial insects to combat resistance development are discussed.

Animals↗
PubMed2005

Trichuris suis therapy in Crohn's disease.

BACKGROUND: Crohn's disease is common in highly industrialised Western countries where helminths are rare and uncommon in less developed areas of the world where most people carry worms. Helminths diminish immune responsiveness in naturally colonised humans and reduce inflammation in experimental colitis. Thus exposure to helminths may help prevent or even ameliorate Crohn's disease. AIMS: The aim of the study was to determine the safety and possible efficacy of the intestinal helminth Trichuris suis in the treatment of patients with active Crohn's disease. PATIENTS: Twenty nine patients with active Crohn's disease, defined by a Crohn's disease activity index (CDAI) > or =220 were enrolled in this open label study. METHODS: All patients ingested 2500 live T suis ova every three weeks for 24 weeks, and disease activity was monitored by CDAI. Remission was defined as a decrease in CDAI to less than 150 while a response was defined as a decrease in CDAI of greater than 100. RESULTS: At week 24, 23 patients (79.3%) responded (decrease in CDAI >100 points or CDAI <150) and 21/29 (72.4%) remitted (CDAI <150). Mean CDAI of responders decreased 177.1 points below baseline. Analysis at week 12 yielded similar results. There were no adverse events. CONCLUSIONS: This new therapy may offer a unique, safe, and efficacious alternative for Crohn's disease management. These findings also support the premise that natural exposure to helminths such as T suis affords protection from immunological diseases like Crohn's disease.

Adolescent↗
PubMed2005

Genetic parameters for a maternal breeding goal in beef production.

New maternal breeding values have been developed for use in UK beef evaluations. To undertake multitrait BLUP evaluations, it is necessary to have a full covariance matrix. This study outlines the approach taken to construct the full covariance matrices for the four beef breeds that most widely contribute to suckler beef cows in the United Kingdom. The maternal traits investigated were age at first calving, calving interval, lifespan, mature cow weight, 200-d weight, and calving difficulty. Three terminal sire traits (weight at 400 d, ultrasonic fat depth, and muscle score) were included to estimate covariances between the new and existing traits. A sire-maternal-grandsire model was used for the estimation procedure in a series of bivariate and multivariate models. A weighted bending procedure was employed to construct positive definite covariance matrices. Parameter estimates broadly agreed with literature values, although for some traits, literature information was very scarce. Some differences between parameters for different breeds were evident.

Animals↗
PubMed2004

The effects of vasopressin on human facial responses related to social communication.

Arginine vasopressin (AVP) and arginine vasotocin (AVT) influence social behaviors in a number of species from diverse taxonomic groups, therefore suggesting a conservation of social functions for these homologous neuropeptides during vertebrate evolution. However, whether or not AVP has the ability to directly influence social behavior in humans has not yet been determined. Because influences of AVT/AVP on behaviors related to social communication, particularly in aggressive contexts, are among the most consistently observed across species from diverse vertebrate groups, the present study was designed to determine if AVP administration would influence cognitive, autonomic and/or somatic responses to species-specific social stimuli important for agonistic communication in humans. Specifically, we tested the effects of intranasal AVP administration on attention towards emotionally expressive facial expressions, as well as on heart rate (HR), skin conductance (SC) and corrugator supercilii electromyograms (corrugator EMG) in response to these social stimuli. AVP did not affect attention toward, nor autonomic arousal in response to, emotionally neutral, happy or angry facial expressions, but it did selectively enhance the corrugator EMG responses evoked by emotionally neutral facial expressions, making them similar in magnitude to responses evoked by angry facial expressions in control subjects. Because this muscle group is involved in agonistic communication, these results suggest that AVP may influence aggression in human males by biasing individuals to respond to emotionally ambiguous social stimuli as if they were threatening/aggressive.

Adolescent↗
PubMed2004

Efficacy of chloroquine, amodiaquine, sulphadoxine-pyrimethamine and combination therapy with artesunate in Mozambican children with non-complicated malaria.

This paper reports a two-phase study in Manhiça district, Mozambique: first we assessed the clinical efficacy and parasitological response of Plasmodium falciparum to chloroquine (CQ), sulphadoxine-pyrimethamine (SP) and amodiaquine (AQ), then we tested the safety and efficacy in the treatment of uncomplicated malaria, of three combinations: AQ + SP, artesunate (AR) + SP and AQ + AR. Based on the WHO (1996, WHO/MAL/96.1077) in vivo protocol, we conducted two open, randomized, clinical trials. Children aged 6-59 months with axillary body temperature > or = 37.5 degrees C and non-complicated malaria were randomly allocated to treatment groups and followed up for 21 days (first and second trial) and 28 days (first trial). The therapeutic efficacy of AQ (91.6%) was better than that of SP (82.7%) and CQ (47.1%). After 14 days, 69% of the strains were parasitologically resistant to CQ, 21.4% to SP and 26% to AQ. Co-administration of AQ + SP, AR + SP and AQ + AR was safe and had 100% clinical efficacy at 14-day follow-up. The combination therapies affected rapid fever clearance time and reduced the incidence of gametocytaemia during follow-up.

Amodiaquine↗