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Biomedical subjects

R Stevens

Publications and source records attributed to R Stevens.

At least 19 recordsLinked to original sources

The comparative sealing ability of hydroxyapatite cement, mineral trioxide aggregate, and super ethoxybenzoic acid as root-end filling materials.

A comparison was made of the ability of hydroxyapatite cement, mineral trioxide aggregate, and super ethoxybenzoic acid to prevent the leakage of bacteria from root canals, when used as root-end filling materials. The materials were tested in a double-chamber device in which a root segment connects the upper (delivery) chamber and the lower (receiving) chamber. The root segment was prepared by having the root canal instrumented to a #45 file, and a 3-mm-deep, root-end preparation placed at the apical foramen. The canal of each root segment was filled with gutta-percha, and the root-end preparation was filled with one of three test materials, mixed according to the manufacturer's directions. Negative controls were constructed with sticky wax sealing the apical foramen. A titered suspension of radioactively (3H-thymidine)-labeled bacteria (Enterococcus fecalis) was placed into the delivery chamber, and sterile saline was placed into the receiving chamber such that the apical third of each root section was immersed. At various time points, samples were taken from the receiving chamber, and measured for 3H activity. The results indicated that (a) all the test materials leaked significantly compared with the negative controls; and (b) there was no significant difference found between the leakage rates of the three materials tested.

Aluminum Compounds↗

A methodology to migrate the gene ontology to a description logic environment using DAML+OIL.

The Gene Ontology Next Generation Project (GONG) is developing a staged methodology to evolve the current representation of the Gene Ontology into DAML+OIL in order to take advantage of the richer formal expressiveness and the reasoning capabilities of the underlying description logic. Each stage provides a step level increase in formal explicit semantic content with a view to supporting validation, extension and multiple classification of the Gene Ontology. The paper introduces DAML+OIL and demonstrates the activity within each stage of the methodology and the functionality gained.

Classification↗

AtE2F-a and AtDP-a, members of the E2F family of transcription factors, induce Arabidopsis leaf cells to re-enter S phase.

In eukaryotes, transcription factors of the E2F family, in addition to having a role in cell proliferation, participate in regulating apoptosis, differentiation and development. In Arabidopsis thaliana, eight gene sequences have been identified as encoding E2F or DP homologues. DP proteins form heterodimers with E2Fs. The aim of this work was to characterize the functions of three of these factors: AtE2F-a, AtE2F-b and AtDP-a. Here we report that AtE2F-a and AtE2F-b transactivate a reporter gene via an E2F consensus cis-acting element in Arabidopsis protoplasts. AtE2F-a is a more potent activator than AtE2F-b. Furthermore, co-expression of the E2F partner AtDP-a, or the DNA binding protein AtPur alpha, modulates the activation of AtE2F-a. Taken together, these results suggest that AtE2F-a, AtE2F-b and AtDP-a share features characteristic of members of the E2F family of transcription factors. Moreover, over-expression of AtE2F-a and AtDP-a can induce differentiated, non-dividing, leaf cells to re-enter S-phase. We conclude that the transcription factor AtE2F-a plays an important role in progression into S phase, which probably correlates with its capacity to stimulate transcription.

Arabidopsis↗

Interactions of 3T3 fibroblasts and endothelial cells with defined pore features.

The colonization of biodegradable polymer scaffolds with cell populations has been established as the foundation for the engineering of a number of tissues, including cartilage, liver, and bone. Within these scaffolds, the cells encounter a porous environment in which they must migrate across the convoluted polymer surface to generate a homogenous cell distribution. Predicting the interactions between cells and pores is important if scaffold characteristics are to be optimized. Therefore, we investigated the behavior of two model cell types over a range of defined pore features. These pore features range from 5 to 90 microm in diameter and have been fabricated by photolithographic techniques. Quantitatively, the behavior of the cells is dependent on three factors: 1) percentage cell coverage of the surface; 2) pore size; and 3) cell type. Fibroblast cells displayed a co-operative pattern of cell spreading in which pores with diameters greater than the cell dimensions were bridged by groups of cells using their neighbors as supports. Endothelial cells were unable to use neighbors as support structures and failed to bridge pores greater than the cell diameter.

3T3 Cells↗

Identification of dynamically distinct subpopulations of T lymphocytes that are differentially affected by HIV.

We examined the effects of human immunodeficiency virus infection on the turnover of CD4 and CD8 T lymphocytes in 17 HIV-infected patients by 30 min in vivo pulse labeling with bromodeoxyuridine (BrdU). The percentage of labeled CD4 and CD8 T lymphocytes was initially higher in lymph nodes than in blood. Labeled cells equilibrated between the two compartments within 24 h. Based on mathematical modeling of the dynamics of BrdU-labeled cells in the blood, we identified rapidly and slowly proliferating subpopulations of CD4 and CD8 T lymphocytes. The percentage, but not the decay rate, of labeled CD4 or CD8 cells in the rapidly proliferating pool correlated significantly with plasma HIV RNA levels for both CD4 (r = 0.77, P < 0.001) and CD8 (r = 0.81, P < 0.001) T cells. In six patients there was a geometric mean decrease of greater than 2 logs in HIV levels within 2 to 6 mo after the initiation of highly active antiretroviral therapy; this was associated with a significant decrease in the percentage (but not the decay rate) of labeled cells in the rapidly proliferating pool for both CD4 (P = 0.03) and CD8 (P < 0.001) T lymphocytes. Neither plasma viral levels nor therapy had an effect on the decay rate constants or the percentage of labeled cells in the slowly proliferating pool. Monocyte production was inversely related to viral load (r = -0.56, P = 0.003) and increased with therapy (P = 0.01). These findings demonstrate that HIV does not impair CD4 T cell production but does increase CD4 and CD8 lymphocyte proliferation and death by inducing entry into a rapidly proliferating subpopulation of cells.

Adult↗

CD4 T cell expansions are associated with increased apoptosis rates of T lymphocytes during IL-2 cycles in HIV infected patients.

OBJECTIVE AND DESIGN: In an attempt to determine the mechanisms underlying the CD4 T cell expansions in patients receiving intermittent interleukin (IL)-2, a cohort of 10 HIV infected patients were studied during a 5-day cycle of IL-2 to measure rates of apoptosis, the expression of activation markers in CD4 and CD8 T cell subsets and the serum levels of proinflammatory cytokines. All patients were receiving highly active antiretroviral therapy. METHODS: Peripheral blood mononuclear cells were tested pre- and at the completion of IL-2 treatment with annexin V/7-AAD for the measurement of apoptosis. Phenotypic analyses of T lymphocytes were performed in parallel. Serum levels of interferon (IFN)gamma, granulocyte-macrophage colony stimulating factor, IL-6 and tumor necrosis factor (TNF)alpha were tested by enzyme-linked immunosorbent assay. RESULTS: IL-2 increased the spontaneous apoptosis rates of CD4 and CD8 T lymphocytes (P = 0.003). Expression of HLA-DR, CD38 and CD95 increased on both CD4 and CD8 T lymphocytes whereas CD25 induction was observed exclusively on CD4 T cells. Significant increases of serum IL-6 and TNFalpha levels were noted in all patients whereas viral loads remained unchanged. CONCLUSION: Administration of IL-2 for 5 days in HIV infected patients leads to enhanced apoptosis of both CD4 and CD8 T cells despite an eventual increase of the CD4 T cell count. A profound activation state with induction of activation markers on T cells and high levels of TNFalpha and IL-6 accompanies the increased apoptosis during the IL-2 cycle. These data suggest that the CD4 expansions seen in the context of intermittent IL-2 therapy are the net result of increases in both cell proliferation and cell death.

Antiretroviral Therapy, Highly Active↗

Interleukin-2 induced immune effects in human immunodeficiency virus-infected patients receiving intermittent interleukin-2 immunotherapy.

To characterize the immunological effects of intermittent IL-2 therapy, which leads to selective increases in CD4+ T lymphocytes in HIV-infected patients, 11 patients underwent extensive immunological evaluation. While IL-2 induced changes in both CD4+ and CD8+ cell number acutely, only CD4+ cells showed sustained increases following discontinuation of IL-2. Transient increases in expression of the activation markers CD38 and HLA-DR were seen on both CD4+ and CD8+ cells, but CD25 (a chain of the IL-2 receptor) increased exclusively on CD4+ cells. This increase in CD25 expression was sustained for months following discontinuation of IL-2, and was seen in naive as well as memory cells. IL-2 induced cell proliferation, but tachyphylaxis to these proliferative effects developed after 1 week despite continued IL-2 administration. It thus appears that sustained CD25 expression selectively on CD4+ cells is a critical component of the immunological response to IL-2, and that intermittent administration of IL-2 is necessary to overcome the tachyphylaxis to IL-2-induced proliferation.

ADP-ribosyl Cyclase↗

Effects of pre- and postnatal corticosterone exposure on the rat hippocampal GABA system.

Several lines of evidence have implicated prenatal stress and the hippocampal GABA system in the pathophysiology of schizophrenia, and prenatal stress is believed to increase the risk for schizophrenia through alterations of this neurotransmitter. To explore this hypothesis, we treated male rats pre- and/or postnatally (P48 and P60) with either corticosterone (CORT) or vehicle to establish three study groups: VVV, receiving vehicle at all three time points; VCC, receiving vehicle prenatally and CORT at both postnatal timepoints; and CCC, receiving CORT at all three timepoints. Animals were sacrificed at either 24 h or 5 days after final injection and examined for mRNA levels of GAD65, GAD67, and the GABA(A) receptor subunits alpha2 and gamma2. At 24 h, GAD65 mRNA was decreased in CA1, CA2, CA4, and dentate gyrus (DG) of VCC rats; this effect was either decreased or reversed in CCC-treated animals. No effect was detected in GAD67 mRNA at 24 h. At 5 days, CORT treatment increased GAD67 mRNA levels in CA1, CA3, and DG. Prenatal treatment with CORT was associated with increased responsiveness only in CA3 and DG. For the GABAA receptor, alpha2 subunit mRNA did not show any change in response to CORT treatment, while that for the gamma2 subunit was decreased in CA2 of both VCC- and CCC-treated animals. Consistent with gamma2 subunit mRNA decreases, benzodiazepine (BZ) receptor binding activity was decreased in CA2 with CORT treatment. Prenatal CORT exposure neither increased nor decreased this effect. These results demonstrate that CORT administration is associated with a complex regulation of mRNA expression for pre- and postnatal aspects of the hippocampal GABA system. Under these conditions, prenatal exposure to CORT may sensitize some of these effects, but does not fundamentally alter the nature of this response.

Animals↗

Cost-effectiveness analysis of intensive blood-glucose control with metformin in overweight patients with type II diabetes (UKPDS No. 51).

AIMS/HYPOTHESIS: To estimate the economic efficiency of intensive blood-glucose control with metformin compared with conventional therapy primarily with diet in overweight patients with Type II (non-insulin-dependent) diabetes mellitus. METHODS: Cost-effectiveness analysis based on patient level data from a randomised clinical controlled trial involving 753 overweight (> 120% ideal body weight) patients with newly diagnosed Type II diabetes conducted in 15 hospital-based clinics in England, Scotland and Northern Ireland as part of the UK Prospective Diabetes Study. Subjects were allocated at random to an intensive blood-glucose control policy with metformin (n = 342) or a conventional policy primarily with diet (n = 411). The analysis was based on the cost of health care resources associated with metformin and conventional therapy and the estimated effectiveness in terms of life expectancy gained from within-trial effects. RESULTS: Intensive blood-glucose control with metformin produced a net saving of 258 Pounds per patient (1997 United Kingdom prices) over the trial period (median duration of 10.7 years) due to lower complication costs, and increased life expectancy by 0.4 years (costs and benefits discounted at 6%). CONCLUSIONS/INTERPRETATION: As metformin is both cost-saving in the United Kingdom and extends life expectancy when used as first line pharmacological therapy in overweight Type II diabetic patients, its use should be attractive to clinicians and health care managers alike.

Adult↗

An on-belt elemental analyser for the cement industry.

On-line control of raw mill feed composition is a key factor in the improved control of cement plants. A new and improved on-conveyor belt elemental analyser for cement raw mill feed based on neutron inelastic scatter and capture techniques has been developed and tested successfully in Adelaide Brighton's Birkenhead cement plant on highly segregated material with a depth range of 100 to 180 mm. Dynamic tests in the plant have shown analyser RMS total errors of 0.49, 0.52, 0.38 and 0.23 wt% (on a loss free basis) for CaO, SiO2, Al2O3 and Fe2O3 respectively, when 10-minute counting periods are used.

Aluminum Oxide↗

Gentamicin pharmacokinetics in preterm infants with a patent and a closed ductus arteriosus.

BACKGROUND AND AIM: A patent ductus arteriosus (PDA) may influence renal and hepatic blood flow and hence pharmacokinetics of drugs in neonates compared to neonates with a closed ductus arteriosus (CDA). A 10-percent difference of gentamicin pharmacokinetic parameters between PDA and CDA has been reported; but its implications are unclear. The relevance of this difference relative to the variability within the neonatal population was investigated. METHODS: Twenty-four neonates (12 with a PDA and 12 with a CDA) treated with gentamicin were retrospectively included. Before closing treatment of the PDA, serum levels were drawn and analysed for regular therapeutic drug monitoring of gentamicin. Data were analysed using the standard two-stage approach (STS) and an iterative 2-stage Bayesian population analysis approach (It2B). RESULTS: Both types of analysis showed no significant differences between both populations for gentamicin total body clearance per kg bodyweight (CL/kg). Volume of distribution per kg bodyweight (Vd/kg) tended to be larger and elimination rate (Kel) tended to be smaller in neonates with PDA. Multiple regression analysis showed for both populations highly significant correlations between total body clearance and body weight (p < 0.0001) or gestational age (p < 0.0001), and between volume of distribution and body weight (p < 0.0001) or gestational age (p < 0.0001). CONCLUSION: Although neonates with a PDA may have small differences in gentamicin pharmacokinetics compared to neonates with a CDA, this is not relevant for clinical practice taking the variability within that population into account.

Anti-Bacterial Agents↗

An economic evaluation of atenolol vs. captopril in patients with Type 2 diabetes (UKPDS 54).

AIMS: To compare the net cost of a tight blood pressure control policy with an angiotensin converting enzyme inhibitor (captopril) or beta blocker (atenolol) in patients with Type 2 diabetes. DESIGN: A cost-effectiveness analysis based on outcomes and resources used in a randomized controlled trial and assumptions regarding the use of these therapies in a general practice setting. SETTING: Twenty United Kingdom Prospective Diabetes Study Hospital-based clinics in England, Scotland and Northern Ireland. SUBJECTS: Hypertensive patients (n = 758) with Type 2 diabetes (mean age 56 years, mean blood pressure 159/94 mmHg), 400 of whom were allocated to the angiotensin converting enzyme inhibitor captopril and 358 to the beta blocker atenolol. MAIN OUTCOME MEASURES: Life expectancy and mean cost per patient. RESULTS: There was no statistically significant difference in life expectancy between groups. The cost per patient over the trial period was 6485 UK pounds in the captopril group, compared with 5550 UK pounds in the atenolol group, an average cost difference of 935 UK pounds (95% confidence interval 188 UK pounds, 1682 UK pounds). This 14% reduction arose partly because of lower drug prices, and also because of significantly fewer and shorter hospitalizations in the atenolol group, and despite higher antidiabetic drug costs in the atenolol group. CONCLUSIONS: Treatment of hypertensive patients with Type 2 diabetes using atenolol or captopril was equally effective. However, total costs were significantly lower in the atenolol group. Diabet. Med. 18, 438-444 (2001)

Adrenergic beta-Antagonists↗

A classification of tasks in bioinformatics.

MOTIVATION: This paper reports on a survey of bioinformatics tasks currently undertaken by working biologists. The aim was to find the range of tasks that need to be supported and the components needed to do this in a general query system. This enabled a set of evaluation criteria to be used to assess both the biology and mechanical nature of general query systems. RESULTS: A classification of the biological content of the tasks gathered offers a checklist for those tasks (and their specialisations) that should be offered in a general bioinformatics query system. This semantic analysis was contrasted with a syntactic analysis that revealed the small number of components required to describe all bioinformatics questions. Both the range of biological tasks and syntactic task components can be seen to provide a set of bioinformatics requirements for general query systems. These requirements were used to evaluate two bioinformatics query systems.

Computational Biology↗

The contributions of managed care plans to public health practice: evidence from the nation's largest local health departments.

OBJECTIVE: The authors examine the extent and nature of managed care plans participating in local public health activities. METHODS: In 1998, the authors surveyed the directors of all US local health departments serving jurisdictions of at least 100,000 residents to collect information about public health activities performed in their jurisdictions and about organizations participating in the activities. Multivariate logistic and linear regression models were used to examine organizational and market characteristics associated with managed care plan participation in public health activities. RESULTS: Managed care plans were reported to participate in public health activities in 164 (46%) of the jurisdictions surveyed, and to contribute to 13% of the public health activities performed in the average jurisdiction. Plans appeared most likely to participate in public health activities involving the delivery or management of personal health services and the exchange of health-related information. Managed care participation was more likely to occur in jurisdictions with higher HMO penetration, fewer competing plans, and larger proportions of plans enrolling Medicaid recipients. Participation was positively associated with the overall scope and perceived effectiveness of local public health activities. CONCLUSIONS: Although plans participate in a narrow range of activities, these contributions may complement the work of public health agencies.

Administrative Personnel↗

From concept to application: the impact of a community-wide intervention to improve the delivery of preventive services to children.

OBJECTIVE: To improve health outcomes of children, the US Maternal and Child Health Bureau has recommended more effective organization of preventive services within primary care practices and more coordination between practices and community-based agencies. However, applying these recommendations in communities is challenging because they require both more complex systems of care delivery within organizations and more complex interactions between them. To improve the way that preventive health care services are organized and delivered in 1 community, we designed, implemented, and assessed the impact of a health care system-level approach, which involved addressing multiple care delivery processes, at multiple levels in the community, the practice, and the family. Our objective was to improve the processes of preventive services delivery to all children in a defined geographic community, with particular attention to health outcomes for low-income mothers and infants. DESIGN: Observational intervention study in 1 North Carolina county (population 182 000) involving low- income pregnant mothers and their infants, primary care practices, and departments of health and mental health. An interrupted time-series design was used to assess rates of preventive services in office practices before and after the intervention, and a historical cohort design was used to compare maternal and child health outcomes for women enrolled in an intensive home visiting program with women who sought prenatal care during the 9 months before the program's initiation. Outcomes were assessed when the infants reached 12 months of age. INTERVENTIONS: Our primary objective was to achieve changes in the process of care delivery at the level of the clinical interaction between care providers and patients that would lead to improved health and developmental outcomes for families. We selected interventions that were directed toward major risk factors (eg, poverty, ineffective care systems for preventive care in office practices) and for which there was existing evidence of efficacy. The interventions involved community-, practice-, and family-level strategies to improve processes of care delivery to families and children. The objectives of the community-level intervention were: 1) to achieve policy level changes that would result in changes in resources available at the level of clinical care, 2) to engage multiple practice organizations in the intervention to achieve an effect on most, if not all, families in the community, and 3) to enhance communication between, among, and within public and private practice organizations to improve coordination and avoid duplication of services. The objective of the practice-level interventions was to overcome specific barriers in the process of care delivery so that preventive services could be effectively delivered. To assist the health department in implementing the family-level intervention, we provided assistance in hiring and training staff and ongoing consultation on staff supervision, including the use of structured protocols for care delivery, and regular feedback data about implementation of the program. Interventions with primary care practices focused on the design of the delivery system within the office and the use of teamwork and data in an "office systems" approach to improving clinical preventive care. All practices (N = 8) that enrolled at least 5 infants/month received help in assessing performance and developing systems (eg, preventive services flow sheets) for preventive services delivery. Family-level interventions addressed the process of care delivery to high-risk pregnant women (<100% poverty) and their infants. Mothers were recruited for the home visiting intervention when they first sought prenatal care at the community health center, the county's largest provider of prenatal care to underserved women. The home visiting intervention involved teams of nurses and educators and involved 2 to 4 visits per month through the infant's first year of life to provide parental education on fetal and infant health and development, enhance parents' informal support systems, and link parents with needed health and human services. We included training in injury prevention and discipline, and home visitors assisted mothers in obtaining care from one of the primary care offices. RESULTS: There were high levels of participation, changes in the organization of the delivery system, and improvements in preventive health outcomes. Agencies cooperated in joint contracting, staff training, and defining program eligibility. All 8 eligible practices agreed to participate and 7/8 implemented at least 1 new office system element. Of eligible women, 89% agreed to participate, and outcome data were available on 80% (180/225). After adjusting for differences in baseline characteristics, intervention group women were significantly more likely than comparison group women to use contraceptives (69% vs 47%), not smoke tobacco (27% vs 54%) and have a safe and stimulating home environment for their children. Intervention group children were more likely to have had an appropriate number of well-child care visits (57% vs 37%) and less likely to be injured (2% vs 7%). Intervention mothers also received Aid to Families with Dependent Children for fewer months after the birth of their child (7.7 months vs 11.3 months). CONCLUSIONS: We observed a number of positive effects at all 3 levels of intervention. Policy-level changes at the state and community led to lasting changes in the organization and financing of care, which enabled changes in clinical services to take place. These changes have now been expanded beyond this community to other communities in the state. We were also able to engage multiple practice organizations, reduce duplication, and improve the coordination of care. Changes in the process of preventive services delivery were noted in participating practices. Finally, the outcomes of the family-level intervention were comparable in direction and magnitude to the outcomes of previous randomized trials of the intervention. All the changes were achieved over a relatively brief 3-year study period, and many have been sustained since the project was completed. Tiered, interrelated interventions directed at an entire population of mothers and children hold promise to improve the effectiveness and outcomes of health care for families and children.

Adult↗

The effects of Myxobolus cerebralis myxospore dose on triactinomyxon production and biology of Tubifex tubifex from two geographic regions.

The aquatic oligochaete Tubifex tubifex is an obligate host of Myxobolus cerebralis, the causative agent of salmonid whirling disease. Tubifex tubifex can become infected by ingesting myxospores of M. cerebralis that have been released into sediments upon death and decomposition of infected salmonids. Infected worms release triactinomyxons into the water column that then infect salmonids. How the dose of myxospores ingested by T. tubifex influences parasite proliferation and the worm host are not well understood. Using replicated laboratory experiments, we examined how differing doses of myxospores (50, 500, 1,000 per worm) influenced triactinomyxon production and biomass, abundance, and individual weight of 2 geographically distinct populations of T. tubifex. Worm populations produced differing numbers of triactinomyxons, but, within a population, the production did not differ among myxospore doses. At the lowest myxospore dose, 1 worm population produced 45 times more triactinomyxons than myxospores received, whereas the other produced only 6 times more triactinomyxons than myxospores. Moreover, total T. tubifex biomass, abundance, and individual weight were lower among worms receiving myxospores than in myxospore-free controls. Thus, T. tubifex populations differ in ability to support the replication of M. cerebralis, and infection has measurable consequences on fitness of the worm host. These results suggest that variability in whirling disease severity observed in wild salmonid populations may partially be attributed to differences in T. tubifex populations.

Animals↗

Ultrasensitive magnetic biosensor for homogeneous immunoassay.

A technique is described for specific, sensitive, quantitative, and rapid detection of biological targets by using superparamagnetic nanoparticles and a "microscope" based on a high-transition temperature dc superconducting quantum interference device (SQUID). In this technique, a mylar film to which the targets have been bound is placed on the microscope. The film, at room temperature and atmospheric pressure, is typically 40 micrometer from the SQUID, which is at 77 K in a vacuum. A suspension of magnetic nanoparticles carrying antibodies directed against the target is added to the mixture in the well, and 1-s pulses of magnetic field are applied parallel to the SQUID. In the presence of this aligning field the nanoparticles develop a net magnetization, which relaxes when the field is turned off. Unbound nanoparticles relax rapidly by Brownian rotation and contribute no measurable signal. Nanoparticles that are bound to the target on the film are immobilized and undergo Néel relaxation, producing a slowly decaying magnetic flux, which is detected by the SQUID. The ability to distinguish between bound and unbound labels allows one to run homogeneous assays, which do not require separation and removal of unbound magnetic particles. The technique has been demonstrated with a model system of liposomes carrying the FLAG epitope. The SQUID microscope requires no more than (5 +/- 2) x 10(4) magnetic nanoparticles to register a reproducible signal.

Biosensing Techniques↗