Neutron spectrometry in mixed fields: multisphere spectrometers.
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Calibration↗
Biomedical subjects
D J Thomas
Publications and source records attributed to D J Thomas.
Transient ischaemic attacks are associated with increased rates of global cerebral atrophy.
OBJECTIVES: To determine whether patients presenting with a first transient ischaemic attack (TIA) subsequently show increased rates of brain atrophy compared with age matched controls; and to assess potential risk factors for brain atrophy in this group. METHODS: 60 patients with a first, isolated TIA and 26 age and sex matched controls were recruited. None had evidence of cognitive impairment. Vascular risk factors were treated appropriately. All subjects had volumetric imaging at the start of the study and one year later, when they were clinically reassessed. TIA patients also had serial dual echo brain imaging. Rates of whole brain atrophy were calculated from the registered volumetric scans, as was the incidence of new ischaemic lesions. In the TIA group, the degree of white matter disease was assessed. Atrophy rates and blood pressure were compared between patients and controls. RESULTS: 22 patients (37%) developed new "clinically silent" infarcts during follow up. The mean (SD) annualised percentage atrophy rate in the TIA group was significantly higher than in the controls, at 0.82 (0.39)% v 0.33 (0.3)% (p < 0.0001). In the TIA group, diastolic blood pressure (p = 0.004) and white matter disease severity (p < 0.001) were correlated with cerebral atrophy rate. Increased white matter disease was found in patients in whom new ischaemic lesions developed (p < 0.001). CONCLUSIONS: Patients presenting with a first TIA have excess global brain atrophy compared with age matched controls over the subsequent year. Increased atrophy rates following a TIA may be directly or indirectly related to increasing white matter disease and diastolic hypertension. Future studies should assess whether this atrophy inevitably leads to cognitive decline, and whether aggressive treatment of risk factors for cerebrovascular disease (particularly hypertension) after a TIA can influence outcome.
Aged↗
Treatment of asymptomatic arteriosclerotic carotid artery disease.
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Age Factors↗
The Asymptomatic Carotid Stenosis and Risk of Stroke (ACSRS) study. Aims and results of quality control.
AIM: The results of the Asymptomatic Carotid Atherosclerosis Study (ACAS) study have provided the first scientific evidence that in patients with asymptomatic carotid stenosis greater than 60% carotid endarterectomy reduces the risk of stroke from 2% to 1% per year. The implications are that approximately 20 operations need to be performed in order to prevent 1 stroke in 5 years. The aims of the Asymptomatic Carotid Stenosis and Risk of Stroke (ACSRS) study are to identify a subgroup or subgroups at a risk for stroke higher than 4% and a group at a risk for stroke less than 1% per year using systemic and local risk factors (plaque characterization) in addition to the degree of stenosis. The aim of this paper is to present the protocol and the results of the quality control. METHODS: The ACSRS is a multicentre natural history study of patients with asymptomatic internal carotid diameter stenosis greater than 50% in relation to the bulb. The degree of stenosis is graded using multiple established ultrasonic duplex criteria. In addition, ultrasonic plaque characterization is performed and clinical risk factors and medications are recorded. Training is provided centrally. All carotid ultrasound examinations are recorded on video-tape which together with CT-brain scans and ECG are analysed at the coordinating centre with feedback information to partner centres. RESULTS: The video recordings and analysis of data centrally with feed back information have provided quality control with a significant improvement not only in the completion of data forms but also in the grading of internal carotid stenosis and plaque recordings using ultrasound. CONCLUSION: The high level of quality of data collected will add credibility to the results of the ACSRS study and may eventually promote the development of international standards of plaque imaging and characterization.
Carotid Artery, Internal↗
Longitudinal study of intracellular T cell cytokine production in infants compared to adults.
Intracellular cytokine production in lymphocytes obtained longitudinally from 325 healthy infants aged 2-12 months was compared with adult lymphocytes using four-colour flow cytometry. Peripheral blood samples (180 microlitres) were stimulated with phorbol 12-myristate 13-acetate, ionomycin and brefeldin A to induce production and intracellular accumulation of cytokines. The method was validated by assessing reproducibility, repeatibility, ruggedness (i.e. fresh versus day-old blood samples), precision, linearity and sensitivity. Among infants, the number and percentage of T lymphocytes (helper/inducer T cell subsets and cytotoxic/suppressor T cell subsets) producing IFN-gamma (type 1) and IL4 (type 2) increased over the first year of life but remained significantly lower than levels found in adults. In both infants and adults more CD4- T cells than CD4+ T cells were induced to make IFN-gamma. Infant Th1/Th2 ratios revealed modest Th1-skewed (predominant) profiles compared to adults, which were 5-10 times higher. Infant Tc1/Tc2 ratios revealed Tc1-skewed responses which were equal to adult ratios by age 12 months. At 12 months infant Th2 responses were closer to adult levels than were Th1 cells. Intracellular cytokine detection by flow cytometry is a rapid, sensitive, rugged and precise method to characterize immune status changes over time.
Adult↗
The evaluation and use of a portable TEPC system for measuring in-flight exposure to cosmic radiation.
A recent EC directive has called for all member states to introduce legislation covering the assessment and restriction of air crew exposure to cosmic radiation. In the UK the Civil Aviation Authority, in conjunction with the Department of the Environment. Transport and the Regions issued guidelines suggesting the use of a predictive code such as CARI for this purpose. In order to validate the use of calculated route doses, an extensive programme of measurements is being carried out on long haul routes in conjunction with Virgin Atlantic Airways, using a prototype HAWK TEPC developed by Far West Technology. This programme began in January 2000 and by the end of February 2001 had resulted in the accumulation of data from 74 flights. In this paper the instrument design is discussed, together with the calibration programme. An overview of the in-flight results is also presented, including comparisons between measurements and calculations, which indicates that CARI under-predicts the route doses by approximately 20%.
Calibration↗
Blocks of limited haplotype diversity revealed by high-resolution scanning of human chromosome 21.
Global patterns of human DNA sequence variation (haplotypes) defined by common single nucleotide polymorphisms (SNPs) have important implications for identifying disease associations and human traits. We have used high-density oligonucleotide arrays, in combination with somatic cell genetics, to identify a large fraction of all common human chromosome 21 SNPs and to directly observe the haplotype structure defined by these SNPs. This structure reveals blocks of limited haplotype diversity in which more than 80% of a global human sample can typically be characterized by only three common haplotypes.
Algorithms↗
The cellular metabolism and systemic toxicity of arsenic.
Although it has been known for decades that humans and many other species convert inorganic arsenic to mono- and dimethylated metabolites, relatively little attention has been given to the biological effects of these methylated products. It has been widely held that inorganic arsenicals were the species that accounted for the toxic and carcinogenic effects of this metalloid and that methylation was properly regarded as a mechanism for detoxification of arsenic. Elucidation of the metabolic pathway for arsenic has changed our understanding of the significance of methylation. Both methylated and dimethylated arsenicals that contain arsenic in the trivalent oxidation state have been identified as intermediates in the metabolic pathway. These compounds have been detected in human cells cultured in the presence of inorganic arsenic and in urine of individuals who were chronically exposed to inorganic arsenic. Methylated and dimethylated arsenicals that contain arsenic in the trivalent oxidation state are more cytotoxic, more genotoxic, and more potent inhibitors of the activities of some enzymes than are inorganic arsenicals that contain arsenic in the trivalent oxidation state. Hence, it is reasonable to describe the methylation of arsenic as a pathway for its activation, not as a mode of detoxification. This review summarizes the current knowledge of the processes that control the formation and fate of the methylated metabolites of arsenic and of the biological effects of these compounds. Given the considerable interest in the dose-response relationships for arsenic as a toxin and a carcinogen, understanding the metabolism of arsenic may be critical to assessing the risk associated with chronic exposure to this element.
Animals↗
Determination of trivalent methylated arsenicals in biological matrices.
The enzymatically catalyzed oxidative methylation of As yields methylated arsenicals that contain pentavalent As (As(V)). Because trivalent As (As(III)) is the favored substrate for this methyltransferase, methylated arsenicals containing As(V) are reduced to trivalency in cells. Methylated arsenicals that contain As(III) are extremely potent inhibitors of NADPH-dependent flavoprotein oxidoreductases and potent cytotoxins in many cell types. Therefore, the formation of methylated arsenicals that contain As(III) may be properly regarded as an activation step, rather than a means of detoxification. Recognition of the role of methylated arsenicals that contain As(III) in the toxicity and metabolism of As emphasizes the need for analytical methods to detect and quantify these species in biological samples. Hence, a method was developed to exploit pH-dependent differences in the generation of arsines from inorganic and methylated arsenicals that contain either As(V) or As(III). Reduction with borohydride at pH 6 generated arsines from inorganic As(III), methyl As(III), and dimethyl As(III), but not from inorganic As(V), methyl As(V), and dimethyl As(V). Reduction with borohydride at pH 2 or lower generated arsines from arsenicals that contained either As(V) or As(III). Arsines are trapped in a liquid nitrogen-cooled gas chromatographic trap, which is subsequently warmed to allow separation of the hydrides by their boiling points. Atomic absorption spectrophotometry is used to detect and quantify the arsines. The detection limits (ng As ml(-1)) for inorganic As(III), methyl As(III), and dimethyl As(III) are 1.1, 1.2, and 6.5, respectively. This method has been applied to the analysis of arsenicals in water, human urine, and cultured cells. Both methyl As(III) and dimethyl As(III) are detected in urine samples from individuals who chronically consumed inorganic As-contaminated water and in human cells exposed in vitro to inorganic As(III). The reliable quantitation of inorganic and methylated arsenicals that contain As(III) in biological samples will aid the study of the toxicity of these species and may provide a new biomarker of the effects of chronic exposure to As.
Arsenicals↗
What's causing that gas?
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Abdominal Pain↗
Selenium modifies the metabolism and toxicity of arsenic in primary rat hepatocytes.
Arsenic and selenium are metalloids with similar chemical properties and metabolic fates. Inorganic arsenic (iAs) has been shown to modify metabolism and toxicity of inorganic and organic selenium compounds. However, little is known about effects of selenium on metabolism and toxicity of iAs. The present work examines the effects of selenite (Se(IV)) on the cellular retention, methylation, and cytotoxicity of trivalent iAs, arsenite (iAs(III)), in primary cultures of rat hepatocytes. The concurrent exposure to Se(IV) (0.1 to 6 microM) inhibited methylation and/or significantly increased cellular retention of iAs(III) in cultured cells. The ratio of the methylated metabolites produced from iAs(III), dimethylarsenic (DMAs) to methylarsenic (MAs), decreased considerably in cells treated with Se(IV), suggesting that synthesis of DMAs from MAs may be more susceptible to inhibition by Se(IV) than is the production of MAs from iAs(III). The 24-h preexposure to 2 microM Se(IV) had a similar but less pronounced inhibitory effect on the methylation of iAs(III) in cultured cells. The exposure to 2 microM Se(IV) alone for up to 24 h had no effect on the viability of cultured hepatocytes. However, concurrent exposure to 2 microM Se(IV) increased the cytotoxicity of iAs(III) and its mono- and dimethylated metabolites that contain trivalent arsenic, MAs(III) and DMAs(III). These data suggest that pre- or coexposure to inorganic selenium may enhance the toxic effects of iAs, increasing its retention in tissues and suppressing its methylation, which may be a pathway for detoxification of iAs.
Animals↗
Arsenicals inhibit thioredoxin reductase in cultured rat hepatocytes.
Thioredoxin reductase (TR), an NADPH-dependent flavoenzyme that catalyzes the reduction of many disulfide-containing substrates, plays an important role in the cellular response to oxidative stress. Trivalent arsenicals, especially methyl As that contains trivalent arsenic (MAs(III)), are potent noncompetitive inhibitors of TR purified from mouse liver. Because MAs(III) is produced in the biomethylation of As, it was postulated that the extent of inhibition of TR in cultured rat hepatocytes would correlate with the intracellular concentration of methyl As. Exposure of cultured hepatocytes to inorganic As(III) (iAs(III)), MAs(III), or aurothioglucose (ATG, a competitive inhibitor of TR activity) for 30 min caused a concentration-dependent reduction in TR activity. The estimated IC(50) was >>100 microM for iAs(III), approximately 10 microM for ATG, and approximately 3 microM for MAs(III). In hepatocytes exposed to 1 microM MAs(III) for up to 24 h, the inhibition of TR activity was maximal ( approximately 40%) after exposure for 15 min. After exposure for 3 h [when most MAs(III) has been converted to dimethyl As (DMAs)], TR activity in these cells had returned to control levels. Notably, exposure of the cell to 50 microM DMAs(III) did not affect TR activity. In hepatocytes exposed to 10 microM iAs(III) for up to 24 h, the inhibition of TR activity was progressive; at 24 h, activity was reduced approximately 35%. Following exposure to iAs(III) or MAs(III), the extent of inhibition of TR activity correlated strongly with the intracellular concentration of MAs. Taken together, these results suggest that arsenicals formed in the course of cellular metabolism of As are potent inhibitors of TR activity. In particular, MAs(III), an intermediate in the metabolic pathway, is an especially potent inhibitor of TR. Hence, the capacity of cells to produce or consume the intermediates in the pathway for As methylation may be an important determinant of susceptibility to the toxic effects of As.
Animals↗
Methylated trivalent arsenic species are genotoxic.
The reactivities of methyloxoarsine (MAs(III)) and iododimethylarsine (DMAs(III)), two methylated trivalent arsenicals, toward supercoiled phiX174 RFI DNA were assessed using a DNA nicking assay. The induction of DNA damage by these compounds in vitro in human peripheral lymphocytes was assessed using a single-cell gel (SCG, "comet") assay. Both methylated trivalent arsenicals were able to nick and/or completely degrade phiX174 DNA in vitro in 2 h incubations at 37 degrees C (pH 7.4) depending on concentration. MAs(III) was effective at nicking phiX174 DNA at 30 mM; however, at 150 microM DMAs(III), nicking could be observed. Exposure of phiX174 DNA to sodium arsenite (iAs(III); from 1 nM up to 300 mM), sodium arsenate (from 1 microM to 1 M), and the pentavalent arsenicals, monomethylarsonic acid (from 1 microM to 3 M) and dimethylarsinic acid (from 0.1 to 300 mM), did not nick or degrade phiX174 DNA under these conditions. In the SCG assay in human lymphocytes, methylated trivalent arsenicals were much more potent than any other arsenicals that were tested. On the basis of the slopes of the concentration-response curve for the tail moment in the SCG assay, MAs(III) and DMAs(III) were 77 and 386 times more potent than iAs(III), respectively. Because methylated trivalent arsenicals were the only arsenic compounds that were observed to damage naked DNA and required no exogenously added enzymatic or chemical activation systems, they are considered here to be direct-acting forms of arsenic that are genotoxic, though they are not, necessarily, the only genotoxic species of arsenic that could exist.
Arsenic↗
Photoinhibition and light-induced cyclic electron transport in ndhB(-) and psaE(-) mutants of Synechocystis sp. PCC 6803.
The ndhB(-) and psaE(-) mutants of the cyanobacterium Synechocystis sp. PCC 6803 are partly deficient in PSI-driven cyclic electron transport. We compared photoinhibition in these mutants to the wild type to test the hypothesis that PSI cyclic electron transport protects against photoinhibition. Photoinhibitory treatment greatly accelerated PSI cyclic electron transport in the wild type and also in both the mutants. The psaE(-) mutant showed rates of PSI cyclic electron transport similar to the wild type under all conditions tested. The ndhB(-) mutant showed much lower rates of PSI cyclic electron transport than the wild type following brief dark adaptation but exceeded wild type rates after exposure to photoinhibitory light. The wild type and both mutants showed similar rates of photoinhibition damage and photoinhibition repair at PSII. Photoinhibition at PSI was much slower than at PSII and was also similar between the wild type and both mutants, despite the known instability of PSI in the psaE(-) mutant. We conclude that photoinhibitory light induces sufficient PSI-driven cyclic electron transport in both the ndhB(-) and psaE(-) mutants to fulfill any role that cyclic electron transport plays in protection against photoinhibition.
Adaptation, Physiological↗
Fibrous ankylosis after distraction osteogenesis of a costochondral neomandible in a patient with grade III hemifacial microsomia.
Distraction osteogenesis has recently become a mainstay for treatment of craniofacial syndromes with mandibular hypoplasia. This article presents the difficult case of a patient with a previous costochondral rib graft who underwent mandibular distraction and developed a fibrous pseudoarthrosis at the distraction site. This was attributed in part to an associated temporomandibular joint ankylosis. Resorption of the pseudoarthrosis occurred once the distractor was removed. It appears that distraction osteogenesis of a mandible with an ankylosed temporomandibular joint can result in healing with a fibrous union, presumably because of movement at the distraction site when masticating. This can result in a pseudo "temporomandibular joint" at the distraction site. A temporomandibular joint arthroplasty was performed, followed by repeat distraction. We conclude that if there is an ankylosed temporomandibular joint or a stiff temporomandibular joint that may ankylose during the course of the distraction process, then a temporomandibular joint arthroplasty should be performed before or at the time the distractor is placed.
Adolescent↗
Plasmid transfer between Bacillus thuringiensis subsp. israelensis strains in laboratory culture, river water, and dipteran larvae.
Plasmid transfer between strains of Bacillus thuringiensis subsp. israelensis was studied under a range of environmentally relevant laboratory conditions in vitro, in river water, and in mosquito larvae. Mobilization of pBC16 was detected in vitro at a range of temperatures, pH values, and available water conditions, and the maximum transfer ratio was 10(-3) transconjugant per recipient under optimal conditions. Transfer of conjugative plasmid pXO16::Tn5401 was also detected under this range of conditions. However, a maximum transfer ratio of 1.0 transconjugant per recipient was attained, and every recipient became a transconjugant. In river water, transfer of pBC16 was not detected, probably as a result of the low transfer frequency for this plasmid and the formation of spores by the introduced donor and recipient strains. In contrast, transfer of plasmid pXO16::Tn5401 was detected in water, but at a lower transfer ratio (ca. 10(-2) transconjugant per donor). The number of transconjugants increased over the first 7 days, probably as a result of new transfer events between cells, since growth of both donor and recipient cells in water was not detected. Mobilization of pBC16 was not detected in killed mosquito larvae, but transfer of plasmid pXO16::Tn5401 was evident, with a maximum rate of 10(-3) transconjugant per donor. The reduced transfer rate in insects compared to broth cultures may be accounted for by competition from the background bacterial population present in the mosquito gut and diet or by the maintenance of a large population of B. thuringiensis spores in the insects.
Aedes↗
Haemodialysis and cerebral oedema.
BACKGROUND: Haemodialysis may cause neurological symptoms ranging from inconvenient feelings of disequilibrium to life-threatening neurological complications. There are animal data to suggest cerebral swelling may accompany haemodialysis and contribute symptomatically to dialysis disequilibrium. However, MR images acquired following haemodialysis often fail to demonstrate evidence of cerebral oedema. We wished to quantify any potential cerebral volume change which is caused by haemodialysis treatment. METHOD: Five renal patients and 5 control subjects had a two volumetric T1-weighted MRI scans on the same day. The patients were imaged immediately before and after haemodialysis. None were taking steroids. Precise positional matching (registration) was used to quantify cerebral volume change. RESULTS: Patients had an increase in cerebral volume following dialysis which averaged 32.8 ml (SE 7.4 ml, 3% brain volume). The change in the controls was 1.4 ml (SE 0.6 ml), p < 0.001. No patient had significant neurological symptoms. CONCLUSION: Cerebral oedema developed in the patients following dialysis. There is a good biological model for these observations. Modifications to dialysis may help. Common problems which increase cerebral volume, e.g. acute stroke, require careful appraisal in these patients. These observations need consideration when quantifying atrophy in dialysis patients.
Adult↗
An evaluation of attitudes of Midlands female dentists to general dental practice: will it impact upon the future delivery of primary dental care?
INTRODUCTION: Both anecdotal evidence and research indicate that there is a developing manpower shortage in the delivery of dental care in the UK. With the predicted increase in registered female dentists, it is possible that future changes in work patterns might occur. If they are occurring, it is important to understand the needs of these female dentists in order to maximise efficient delivery of dental care. The aim of the study was to identify any gender differences that might exist in attitudes to the delivery of primary dental care within general dental practice in the Midlands. METHOD: A Likert-style questionnaire was sent to all private and registered NHS GDPs who worked within the areas covered by three Midland health authorities. RESULTS: The results indicated that the clinical practice of female GDPs appears to involve less private work than their male counterparts and they seem less inclined than male GDPs to proactive development of private practise. Females were less likely than males to be principals and also less likely than males to employ other dentists. Female GDP attitudes towards management, net income and stress at work appears to differ to those of their male counterparts. There was little difference in gender attitude towards professional ethics and maintenance of clinical standards.
Adult↗