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Biomedical subjects

R Thomas

Publications and source records attributed to R Thomas.

At least 145 records · Page 8Linked to original sources

Changing provider behavior: an overview of systematic reviews of interventions.

BACKGROUND: Increasing recognition of the failure to translate research findings into practice has led to greater awareness of the importance of using active dissemination and implementation strategies. Although there is a growing body of research evidence about the effectiveness of different strategies, this is not easily accessible to policy makers and professionals. OBJECTIVES: To identify, appraise, and synthesize systematic reviews of professional educational or quality assurance interventions to improve quality of care. RESEARCH DESIGN: An overview was made of systematic reviews of professional behavior change interventions published between 1966 and 1998. RESULTS: Forty-one reviews were identified covering a wide range of interventions and behaviors. In general, passive approaches are generally ineffective and unlikely to result in behavior change. Most other interventions are effective under some circumstances; none are effective under all circumstances. Promising approaches include educational outreach (for prescribing) and reminders. Multifaceted interventions targeting different barriers to change are more likely to be effective than single interventions. CONCLUSIONS: Although the current evidence base is incomplete, it provides valuable insights into the likely effectiveness of different interventions. Future quality improvement or educational activities should be informed by the findings of systematic reviews of professional behavior change interventions.

Education, Medical, Continuing↗

Knowledge of epidemiology and statistics for an ophthalmic practitioner.

Ophthalmologists are frequently confronted with treatment options that claim to be better than those currently in use. Statistically significant P values are invariably provided by way of proof. For many ophthalmologists a simple look at this revered P value is enough evidence that a statistically significant result has indeed been obtained. Unfortunately, traditional interpretation of a study based on the P value at an arbitrary cut-off (P<0.05 or any other value) limits the ability to fully appreciate clinical implications. In this article the authors introduce the reader to and illustrate the use of "confidence intervals" as opposed to P values in examining the applicability of study results. Further, what is statistically significant may not necessarily be clinically significant; perhaps not enough for the practitioner to change from the currently preferred method of treatment. To resolve this, the authors have also used common ophthalmic examples to introduce the "number needed to treat", as a simple clinical approach for the practising ophthalmologist wishing to assess the clinical significance of treatment options.

Clinical Trials as Topic↗

Interpreting automated perimetry.

Visual field testing is mandatory for many ophthalmic conditions including glaucoma. The current gold standard for visual field testing is automated perimetry. In this article we familiarize the reader with the components of an automated perimetry printout. We describe a systematic approach that leads to a thorough interpretation of the printout. With the help of examples the reader should be able to learn to identify a normal field, detect the presence of a field defect, determine whether it is due to glaucoma, and establish progression, if any.

Humans↗

Dynamics of three-body breakup in dissociative recombination: H(2)O(+).

To better understand the propensity for the three-body breakup in dissociative recombination (DR) of dihydrides ( H(3)(+), NH(2)(+), CH(2)(+), and H(2)O(+)), we undertook a study of the dynamics of this process. A study of DR of H(2)O(+) to give O + H + H was carried out at the CRYRING Heavy-Ion Storage Ring in Stockholm. With the stored beam energy of 4.5 MeV, we separated the O signal from the H signals with a differential absorber, thus reducing the problem to a sum of two two-body problems. Results included (1) the ratio of O((3)P) to O((1)D) product, (2) the distribution of recoil-kinetic energy between the two hydrogen atoms, (3) the angular distribution between the hydrogen atoms in the O((3)P) channel and in the O((1)D) channel.

Journal Article↗

Candidate inhibitor of the volume-sensitive kinase regulating K-Cl cotransport: the myosin light chain kinase inhibitor ML-7.

K-Cl cotransport, KCC, is activated by swelling in many cells types, and promotes volume regulation by a KCl efflux osmotically coupled to water efflux. KCC is probably activated by swelling-inhibition of a kinase, permitting dephosphorylation, and activation of the cotransporter by a phosphatase. The myosin light chain kinase (MLCK) inhibitor ML-7 inhibits transporters activated by shrinkage. In red blood cells from three mammalian species, ML-7 stimulated KCC in a volume-dependent manner. Relative stimulation was greatest in more shrunken cells. Stimulation was reduced by moderate cell swelling and abolished by further swelling. The half-maximal stimulation is at approximately 20 microm ML-7, 50-fold greater than the IC(50) for inhibition of MLCK in vitro. Stimulation of KCC by ML-7 did not require cell Ca, while MLCK does. Therefore the target of ML-7 in stimulating KCC in red cells is probably not MLCK. The evidence favors stimulation of KCC by ML-7 by inhibiting the volume-sensitive kinase. Qualitatively similar effects of ML-7 on KCC in red cells from three mammalian species suggest a general mechanism.

Adult↗

RelB nuclear translocation regulates B cell MHC molecule, CD40 expression, and antigen-presenting cell function.

Mice with targeted RelB mutations demonstrated an essential role for RelB in immune responses and in myeloid dendritic cell differentiation. Human studies suggested a more global transcriptional role in antigen presentation. Burkitt lymphoma cell lines were used as a model to examine the role of RelB in antigen presentation. After transient transfection of BJAB with RelB, strong nuclear expression of RelB-p50 heterodimers was associated with increased APC function and expression of CD40 and MHC class I. Antisense RelB in DG75 reduced antigen-presenting capacity and CD40-mediated up-regulation of MHC molecules. The data indicate that RelB transcriptional activity directly affects antigen presentation and CD40 synthesis. Stimulation of RelB transcriptional activity may provide a positive feedback loop for facilitating productive APC/T cell interactions.

Antigen-Presenting Cells↗

Changes in Greenland ice sheet elevation attributed primarily to snow accumulation variability

The response of grounded ice sheets to a changing climate critically influences possible future changes in sea level. Recent satellite surveys over southern Greenland show little overall elevation change at higher elevations, but large spatial variability. Using satellite studies alone, it is not possible to determine the geophysical processes responsible for the observed elevation changes and to decide if recent rates of change exceed the natural variability. Here we derive changes in ice-sheet elevation in southern Greenland, for the years 1978-88, using a physically based model of firn densification and records of annual snow accumulation reconstructed from 12 ice cores at high elevation. Our patterns of accumulation-driven elevation change agree closely with contemporaneous satellite measurements of ice-sheet elevation change, and we therefore attribute the changes observed in 1978-88 to variability in snow accumulation. Similar analyses of longer ice-core records show that in this decade the Greenland ice sheet exhibited typical variability at high elevations, well within the long-term natural variability. Our results indicate that a better understanding of ice-sheet mass changes will require long-term measurements of both surface elevation and snow accumulation.

Journal Article↗

Mass Balance of the Greenland Ice Sheet at High Elevations.

Comparison of ice discharge from higher elevation areas of the entire Greenland Ice Sheet with total snow accumulation gives estimates of ice thickening rates over the past few decades. On average, the region has been in balance, but with thickening of 21 centimeters per year in the southwest and thinning of 30 centimeters per year in the southeast. The north of the ice sheet shows less variability, with average thickening of 2 centimeters per year in the northeast and thinning of about 5 centimeters per year in the northwest. These results agree well with those from repeated altimeter surveys, except in the extreme south, where we find substantially higher rates of both thickening and thinning.

Journal Article↗

Greenland Ice Sheet: High-Elevation Balance and Peripheral Thinning.

Aircraft laser-altimeter surveys over northern Greenland in 1994 and 1999 have been coupled with previously reported data from southern Greenland to analyze the recent mass-balance of the Greenland Ice Sheet. Above 2000 meters elevation, the ice sheet is in balance on average but has some regions of local thickening or thinning. Thinning predominates at lower elevations, with rates exceeding 1 meter per year close to the coast. Interpolation of our results between flight lines indicates a net loss of about 51 cubic kilometers of ice per year from the entire ice sheet, sufficient to raise sea level by 0.13 millimeter per year-approximately 7% of the observed rise.

Journal Article↗

Melting of the Earth's lithospheric mantle inferred from protactinium-thorium-uranium isotopic data

The processes responsible for the generation of partial melt in the Earth's lithospheric mantle and the movement of this melt to the Earth's surface remain enigmatic, owing to the perceived difficulties in generating large-degree partial melts at depth and in transporting small-degree melts through a static lithosphere. Here we present a method of placing constraints on melting in the lithospheric mantle using 231Pa-235U data obtained from continental basalts in the southwestern United States and Mexico. Combined with 230Th-238U data, the 231Pa-235U data allow us to constrain the source mineralogy and thus the depth of melting of these basalts. Our analysis indicates that it is possible to transport small melt fractions--of the order of 0.1%--through the lithosphere, as might result from the coalescence of melt by compaction owing to melting-induced deformation. The large observed 231Pa excesses require that the timescale of melt generation and transport within the lithosphere is small compared to the half-life of 231Pa (approximately 32.7 kyr). The 231Pa-230Th data also constrain the thorium and uranium distribution coefficients for clinopyroxene in the source regions of these basalts to be within 2% of one another, indicating that in this setting 230Th excesses are not expected during melting at depths shallower than 85 km.

Journal Article↗

Incidence of and risk factors for hallucinations and delusions in patients with probable AD.

OBJECTIVE: To examine the incidence of and risk factors for hallucinations and delusions associated with patients clinically diagnosed with probable AD. BACKGROUND: Estimates of the incidence of psychosis in AD range widely from 10% to 75%. The risk factors for psychosis of AD are not known, although multiple studies indicate that AD patients with psychosis demonstrate greater cognitive and functional impairment. METHODS: The authors conducted psychiatric evaluations of 329 patients with probable AD from the University of California at San Diego Alzheimer's Disease Research Center to determine the incidence of hallucinations and delusions. They examined data from annual clinical and neuropsychological evaluations to determine whether there were specific risk factors for the development of hallucinations and delusions. RESULTS: Using Cox survival analyses, the cumulative incidence of hallucinations and delusions was 20.1% at 1 year, 36.1% at 2, 49.5% at 3, and 51.3% at 4 years. Parkinsonian gait, bradyphrenia, exaggerated general cognitive decline, and exaggerated semantic memory decline were significant predictors. Age, education, and gender were not significant predictors. CONCLUSIONS: The authors found a relatively high incidence of hallucinations and delusions in patients diagnosed with probable AD and suggest that specific neurologic signs, cognitive abilities, and accelerated decline may be predictive markers for their occurrence.

Alzheimer Disease↗

Allelic frequencies of host genetic variants influencing susceptibility to HIV-1 infection and disease in South African populations.

OBJECTIVES: Limited information is available on the prevalence in African populations of host genetic polymorphisms conferring resistance to HIV-1 infection and disease. The objective of this study was to determine the allelic frequencies in South African populations of the chemokine receptor gene variants CCR5delta32, CCR5m303 and CCR2b-641 and the CXCR4 ligand gene variant SDF1-3'A. METHOD: Cross-sectional study to determine the prevalence of these gene variants in South African subjects of African and European descent. RESULTS: The CCR5delta32 genetic variant is rare in individuals of African origin, having an allelic frequency of 0.1% (n = 1247) compared with 9.8% (n = 144) in Caucasians. The CCR5m303 mutation was not detected in Africans (n = 687), whereas an allelic frequency of 0.9% (n = 145) was identified in Caucasians. The frequency of CCR2b-641 allele was 13.1% (n = 180) in Africans, which was significantly higher that the 7.2% (n = 146) detected in Caucasians. Finally the allelic frequency of the SDF1-3'A gene variant was only 1.0% (n = 198) in Africans compared with 19.8% (n = 145) in Caucasians. CONCLUSIONS: These results indicate that genetic polymorphisms conferring resistance to HIV-1 infection are rare in the South African Black population. Except for the CCR2b-641 gene variant, individuals of African origin also had a much lower prevalence of genetic variants associated with prolonged disease progression.

Alleles↗

Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease: a randomized controlled trial. Alzheimer's Disease Cooperative Study.

CONTEXT: Several reports from small clinical trials have suggested that estrogen replacement therapy may be useful for the treatment of Alzheimer disease (AD) in women. OBJECTIVE: To determine whether estrogen replacement therapy affects global, cognitive, or functional decline in women with mild to moderate AD. DESIGN: The Alzheimer's Disease Cooperative Study, a randomized, double-blind, placebo-controlled clinical trial conducted between October 1995 and January 1999. SETTING: Thirty-two study sites in the United States. PARTICIPANTS: A total of 120 women with mild to moderate AD and a Mini-Mental State Examination score between 12 and 28 who had had a hysterectomy. INTERVENTIONS: Participants were randomized to estrogen, 0.625 mg/d (n = 42), or 1.25 mg/d (n = 39), or to identically appearing placebo (n = 39). One subject withdrew after randomization but before receiving medication; 97 subjects completed the trial. MAIN OUTCOME MEASURES: The primary outcome measure was change on the Clinical Global Impression of Change (CGIC) 7-point scale, analyzed by intent to treat; secondary outcome measures included other global measures as well as measures of mood, specific cognitive domains (memory, attention, and language), motor function, and activities of daily living; compared by the combined estrogen groups vs the placebo group at 2, 6, 12, and 15 months of follow-up. RESULTS: The CGIC score for estrogen vs placebo was 5.1 vs 5.0 (P = .43); 80% of participants taking estrogen vs 74% of participants taking placebo worsened (P = .48). Secondary outcome measures also showed no significant differences, with the exception of the Clinical Dementia Rating Scale, which suggested worsening among patients taking estrogen (mean posttreatment change in score for estrogen, 0.5 vs 0.2 for placebo; P = .01). CONCLUSIONS: Estrogen replacement therapy for 1 year did not slow disease progression nor did it improve global, cognitive, or functional outcomes in women with mild to moderate AD. The study does not support the role of estrogen for the treatment of this disease. The potential role of estrogen in the prevention of AD, however, requires further research.

Aged↗

Differentiated dendritic cells expressing nuclear RelB are predominantly located in rheumatoid synovial tissue perivascular mononuclear cell aggregates.

OBJECTIVE: Differentiated dendritic cells (DC) and other antigen-presenting cells are characterized by the nuclear location of RelB, a member of the nuclear factor kappaB/Rel family. To characterize and enumerate differentiated DC in rheumatoid arthritis (RA) peripheral blood (PB), synovial fluid (SF), and synovial tissue (ST), the expression and location of RelB were examined. METHODS: RelB protein expression and cellular location were determined in RA PB, SF, and ST by flow cytometry and immunohistochemical analysis of purified cells or formalin-fixed tissue. DNA-binding activity of RelB was determined by electrophoretic mobility shift-Western immunoblotting assays. RESULTS: Circulating RA PBDC resembled normal immature PBDC in that they did not express intracellular RelB protein. In RA ST serial sections, cells containing nuclear RelB (nRelB) were enriched in perivascular regions. A mean +/- SD of 84 +/- 10% of these cells were DC. The remaining nRelB+,HLA-DR+ cells comprised B cells and macrophages. Only 3% of sorted SFDC contained nRelB. However, RelB present in the nucleus of these SFDC was capable of binding DNA, and therefore capable of transcriptional activity. CONCLUSION: Circulating DC precursors differentiate and express RelB after entry into rheumatoid ST. Differentiated DC can thus be identified by immunohistochemistry in formalin-fixed ST. Signals for DC maturation may differ between RA ST and SF, resulting in nuclear location of RelB predominantly in ST. This is likely to have functional consequences for the DC in these sites.

Antigen-Presenting Cells↗

Subtrochanteric corrective osteotomy for the endoprosthetic treatment of high hip dislocation. Treatment and mid-term results with a cementless straight stem.

Total hip arthroplasty is problematical in the case of high dislocation. To reposition the hip, a femoral shortening osteotomy is necessary in order to prevent damage to the neurovascular structures. This paper describes the implantation of a cementless straight stem in 15 patients using a simple technique with a simultaneous, derotating and shortening osteotomy. Femur fractures, pseudoarthroses, stem loosening, paresis and deep infections were not found. One socket loosening was revised. Fourteen patients had good or very good results in the Merle d'Aubigne score after a median of 4.3 (range 2-5.6) years of follow-up. The surgical technique described enables the initial stable fixation of a standard prosthesis without additional osteosynthesis. Additional advantages include a shorter duration of surgery, a lower complication rate and a more rapid consolidation of the osteotomy.

Adolescent↗

Immunology of DNA vaccines: CpG motifs and antigen presentation.

DNA vaccines elicit high levels of specific cytotoxic T lymphocytes and antibody production in numerous animal models. However, the specific immunological events which lead to this effective immune response remain unclear. Presentation of DNA-encoded antigens is particularly intriguing as there is now evidence to suggest that this occurs via both endogenous intracellular and cross-presentation. Further, it has been observed that many plasmid DNA vectors used in DNA vaccination contain CpG motifs--sequences of bacterial DNA which induce pro-inflammatory cytokines in various cells--and which thus provide a novel adjuvant for injected antigens. In this review we will discuss the effects these bacterial DNA sequences have on cells of the immune system, the immune response generated after DNA vaccination and the mechanisms by which DNA-encoded antigens are likely to be presented.

Animals↗

Procalcitonin: a valuable indicator of infection in a medical ICU?

OBJECTIVE: To assess the use of procalcitonin (PCT) for the diagnosis of infection in a medical ICU. DESIGN: Prospective, observational study. PATIENTS: Seventy-seven infected patients and 24 patients with systemic inflammatory response syndrome (SIRS) due to other causes. Seventy-five patients could be classified into sepsis (n = 24), severe sepsis (n = 27) and septic shock (n = 24), and 20 SIRS patients remained free from infection during the study. Plasma PCT and C-reactive protein (CRP) levels were evaluated within 48 h of admission (day 0), at day 2 and day 4. RESULTS: As compared with SIRS, PCT and CRP levels at day 0 were higher in infected patients, regardless of the severity of sepsis (25.2 +/- 54.2 ng/ml vs 4.8 +/- 8.7 ng/ml; 159 +/- 92 mg/l vs 71 +/- 58 mg/l, respectively). At cut-off values of 2 ng/ml (PCT) and 100 mg/l (CRP), sensitivity and specificity were 65% and 70% (PCT), 74% and 74% (CRP). PCT and CRP levels were significantly more elevated in septic shock (38.5 +/- 59.1 ng/ml and 173 +/- 98 mg/l) than in SIRS (3.8 +/- 6.9 ng/ml and 70 +/- 48 mg/l), sepsis (1.3 +/- 2.7 ng/ml and 98 +/- 76 mg/l) and severe sepsis (9.1 +/- 18. 2 ng/ml and 145 +/- 70 mg/l) (all p = 0.005). CRP, but not PCT, levels were more elevated in severe sepsis than in SIRS (p<0.0001). Higher PCT levels in the patients with four dysfunctional organs and higher PCT and CRP levels in nonsurvivors may only reflect the marked inflammatory response to septic shock. CONCLUSION: In this study, PCT and CRP had poor sensitivity and specificity for the diagnosis of infection. PCT did not clearly discriminate SIRS from sepsis or severe sepsis.

Analysis of Variance↗