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Biomedical subjects

B Williams

Publications and source records attributed to B Williams.

At least 217 records · Page 12Linked to original sources

Longitudinal analysis of quantitative virologic measures in human immunodeficiency virus-infected subjects with > or = 400 CD4 lymphocytes: implications for applying measurements to individual patients. National Institute of Allergy and Infectious Diseases AIDS Vaccine Evaluation Group.

The natural variability of quantitative virologic measures among human immunodeficiency virus (HIV) type 1-infected persons was prospectively studied in 29 untreated persons with >600 CD4 cells/microL and in 15 persons receiving zidovudine monotherapy who had 400-550 CD4 cells/microL at study entry. Cell- and plasma-associated infectious HIV-1, provirus, and virion RNA were determined monthly as were numbers of CD4 and CD8 cells. HIV-1 replication varied widely among subjects with similar CD4 cell counts. The within-individual variability was significantly less than the variability between subjects for all virologic measures. Plasma virion HIV-1 RNA levels had the least variability. A mathematical model was devised to assess whether a potential therapeutic intervention significantly alters peripheral HIV-1 load. The model indicated that three measurements of plasma RNA would be outside the 95th percentile for the expected change in an individual due to natural variability. This approach can be used to accurately assess a therapeutic intervention among persons with low plasma HIV-1 titers.

Adult↗

Assessing compliance to antihypertensive medications using computer-based pharmacy records.

Systematic approaches for compliance problem detection and intervention are needed if the benefits of prescribed drug therapy in chronic disease management are to be optimized. As with all measures of compliance, computer algorithms based on refill patterns have advantages and disadvantages. They are unobtrusive and easily determined, but they measure the timeliness of prescription refills, not actual drug-taking. Computer-generated algorithms for assessing compliance based on refill patterns should be used by practitioners with caution, because they are not only markers for potential drug taking compliance problems, but also for discrepancies between the medical chart, pharmacy records and verbal advice given to the patient. Because patients may obtain refills before depleting their supply, compliance rates using this methodology are best determined across several refills. In particular, we urge caution in applying them over time periods of less than 60 days. Longer minimum time periods further decrease the likelihood of "false positives" but limit the number of patients for whom a compliance measure can be computed. For the health professional (eg, the pharmacist) responsible for monitoring drug-taking compliance of patients, the message seems clear: when reviewing computer-generated noncompliance "flags," the first task is to fully explore the possibility of discrepancies in drug records before initiating compliance-related interventions.

Algorithms↗

Bleaching of a discoloured non-vital tooth: use of a sodium perborate/water paste as the bleaching agent.

Bleaching materials containing hydrogen peroxide have been used successfully for the treatment of discoloured non-vital teeth; however, their use has occasionally been associated with external root resorption. Some evidence exists that sodium perborate mixed with water is as effective as sodium perborate mixed with hydrogen peroxide. A case is presented which supports this and a step-by-step technique is described.

Adolescent↗

Univariate analysis of tsetse habitat in the common fly belt of southern Africa using climate and remotely sensed vegetation data.

Tsetse are vectors of trypanosomes that cause diseases both in humans and livestock. Traditional tsetse surveys, using sampling methods such as Epsilon traps and black screen fly rounds, are often logistically difficult, costly and time-consuming. The distribution of tsetse, as revealed by such survey methods, is strongly influenced by environmental conditions, such as climate and vegetation cover, which may be readily mapped using satellite data. These data may be used to make predictions of the probable distribution of tsetse in unsurveyed areas by determining the environmental characteristics of areas of tsetse presence and absence in surveyed areas. The same methods may also be used to characterize differences between tsetse species and subspecies. In this paper we analyse the distribution of Glossina morsitans centralis, Glossina morsitans morsitans and Glossina pallidipes in southern Africa with respect to single environmental variables. For G.m.centralis the best predictions were made using the average NDVI (75% correct predictions; range > 0.37) and the average of the maximum temperature (70% correct predictions; 27.0-29.2 degrees C). For G.m.morsitans the best prediction was given by the maximum of the minimum temperature (84% correct predictions; range > 18.8 degrees C), and for G.pallidipes, also by the maximum of the minimum temperature (86% correct predictions; range > 19.6 degrees C). The following paper compares a range of multivariate techniques for making predictions about the distribution of these species in the same region.

Africa, Southern↗

Mapping tsetse habitat suitability in the common fly belt of southern Africa using multivariate analysis of climate and remotely sensed vegetation data.

The distribution of Glossina morsitans centralis, Glossina morsitans morsitans and Glossina pallidipes are described in part of southern Africa, using a range of multivariate techniques applied to climate and remotely sensed vegetation data. Linear discriminant analysis is limited in its predictive power by the assumption of common covariances in the classes within multivariate environment space. Maximum likelihood classification is one of a variety of alternative methods that do not have this constraint, and produce a better prediction, particularly when a priori probabilities of presence and absence are taken into account. The best predictions are obtained when the habitat is subdivided, prior to classification, on the basis of a bimodality detected on the third component axis of a principal component analysis. The results of the predictions were good, particularly for G.m.centralis and G.m.morsitans, which gave overall correct predictions of 92.8% and 85.1%, with a Kappa index of agreement between the prediction and the training data of 0.7305 and 0.641 respectively. For G.pallidipes, 91.7% of predictions were correct but the value of Kappa was only 0.549. Very clear differences are demonstrated between the habitats of the two subspecies G.m.centralis and G.m.morsitans.

Africa, Southern↗

Glucose-induced protein kinase C activation regulates vascular permeability factor mRNA expression and peptide production by human vascular smooth muscle cells in vitro.

Hyperglycemia is an independent risk factor for the development of diabetic microvascular disease. Vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF) is a potent cytokine family that induces angiogenesis and markedly increases endothelial permeability. VPF is produced by many cell types, including vascular smooth muscle (VSM) cells, and has been implicated in the pathogenesis of neovascularization and endothelial dysfunction in diabetes. This study used cultured human VSM cells to study the regulation of VPF production and determine whether elevated glucose concentrations, per se, are a sufficient stimulus for increased VPF production by human cells. In human VSM cells, high extracellular glucose concentrations (20 mmol/l) increased VPF mRNA expression within 3 h (3-fold vs. glucose 5 mmol/l) and significantly increased VPF peptide production within 24 h (1.5-fold) in a time- and glucose concentration-dependent manner. The high glucose-induced increase in VPF mRNA expression was rapidly reversed after normalizing the extracellular glucose concentration and was specific for a high D-glucose concentration, as these effects were not reproduced by osmotic control media containing elevated concentrations of mannitol or L-glucose. High glucose concentrations activate protein kinase C (PKC) in human VSM cells, and PKC inhibitors (H-7 or chelerythrine chloride) or PKC downregulation each prevented the glucose-induced increases in VPF mRNA expression by human VSM cells. In conclusion, high glucose concentrations directly increase VPF mRNA expression and peptide production by human VSM cells via a PKC-dependent mechanism. These results demonstrate a cellular mechanism, whereby hyperglycemia could directly contribute to the development of endothelial dysfunction and neovascularization in diabetes.

Cells, Cultured↗

Quiescence, cycling, and turnover in the primitive hematopoietic stem cell compartment.

Continuous oral bromodeoxyuridine (BrdU) administration was used for the non-invasive measurement of the in vivo cell cycling characteristics of hematopoietic stem and progenitor cell populations of increasing maturity, isolated on the basis of their relative levels of Rhodamine 123 (Rh) and Hoechst 33342 (Ho) fluorescence. The results showed that whereas primitive hematopoietic stem cells (PHSCs) are hierarchically ordered on the basis of quiescence, the most primitive of these, characterized by their Rh/Ho(dull) phenotype and their capacity for long-term hematopoietic reconstitution, are not dormant, but cycle slowly in normal steady-state bone marrow (BM). Cell cycle analysis showed that 30 +/- 7% of Rh/Ho(dull) PHSCs had cycled and incorporated BrdU following continuous administration over 1 week, whereas 60 +/- 14% and 89 +/- 3% of these cells were BrdU positive at 4 and 12 weeks, respectively. Linear regression analysis of these data showed that Rh/Ho(dull) PHSCs cycle with an average turnover time of 4.3 weeks (30 days), and a t1/2 (time to 50% cycled) of 2.75 weeks (19 days).

Animals↗

Assessment of behavioral symptoms in community-dwelling dementia patients.

The authors compared the CERAD Behavior Rating Scale for Dementia (CBRSD) with the Cohen-Mansfield Agitation Inventory (CMAI) for their ability to detect behavioral symptoms in community-dwelling dementia patients with mild-to-moderate global impairment. Both instruments were administered to caregivers of 33 cognitively impaired patients seen in a dementia clinic at initial evaluation or follow-up visit. Endorsement of a higher percentage of items on the CBRSD than the CMAI suggests greater sensitivity of this instrument to the behavioral symptoms seen in community-dwelling patients. There was good correlation between the number of items endorsed on both scales but not between subscales of the CMAI and factors of the CBRSD that appeared related to agitation. Thus, the CBRSD and CMAI both seem to measure behaviors that occur in dementia patients, but the CBRSD's two agitation-related factors do not appear to measure agitation as defined by the CMAI.

Activities of Daily Living↗

Attendance versus compliance with tuberculosis treatment in an occupational setting--a pilot study.

AIM: To determine the prevalence of non-compliance with tuberculosis treatment at Freegold Mines. OBJECTIVES: 1. To establish the rates of attendance and collection of anti-tuberculosis drugs. 2. To determine prevalence of non-compliance by means of urine tests. DESIGN: A cross-sectional study conducted over 2 weeks at mine medical stations. METHOD: Urine samples were collected from tuberculosis patients 3 hours after drug ingestion. Non-compliance was established by testing these samples for rifampicin and/or isoniazid (INH) metabolites. Non-compliance was defined as a negative urine test result for these drugs in participants whose treatment regimens included one or both. Daily attendance and collection of drugs statistics are recorded in the medical station tuberculosis register. The patient rate of adherence was calculated as the observed number of days on which medication had been collected over the expected treatment days in a given period. RESULTS: Urine test results showed an overall prevalence of non-compliance of 14.6 +/- 3.3%. The study showed that non-compliance with tuberculosis treatment was underestimated by the surveillance data. The rate of non-adherence with treatment established from the formal surveillance procedure was 0.2%. The poor response rate of patients was found to be a major problem and fewer than 40% per day returned to bring urine specimens. The mean prevalences of non-compliance established by rifampicin and INH tests were 19.5 +/- 5.3% and 9.8 +/- 3.9%, respectively, and these were significantly different (Chi 2 = 7.44; P < 0.05). The proportion of false-positive results for INH and rifampicin urine tests were 21% (11/53) and 35% (17/48), respectively, showing that some patients were taking the wrong treatment. CONCLUSIONS: It is clear that attendance at the clinics does not accurately reflect compliance. Both programme compliance (dispensing of the correct treatment) and patient compliance need to be improved. This has important implications for the new national tuberculosis control policy adopted by the South African government that stresses the importance of directly observed therapy, short-course (DOTS) and a patient-centred approach.

Antibiotics, Antitubercular↗

Combination of SCF, IL-6, IL-3, and GM-CSF increases the mitotic index in short term bone marrow cultures from acute promyelocytic leukemia (APL) patients.

Acute promyelocytic leukemia (APL) is characterized cytogenetically by the presence of a reciprocal translocation between chromosomes 15 and 17 [t(15;17)(q22-q24;q11-q21)] in the bone marrow cells in the majority of patients. Cytogenetic evaluation of bone marrow cultures from patients with APL is often technically difficult, due to frequent difficult marrow aspiration and the suboptimal quality of cytogenetic preparations. This has important implications for the cytogenetic detection of residual disease. This study examined the proliferative ability of the recombinant human growth factors-stem cell factor (SCF), interleukin-6 (IL-6), interleukin-3 (IL-3), and granulocyte macrophage-colony stimulating factor (GM-CSF)-to determine if they would provide a consistent improvement over the standard cytogenetic culturing techniques in terms of mitotic index (MI). In all cases, the MI of the growth factor stimulated cultures showed a considerably higher (3.5-198 fold) and statistically significant (p < 0.01) increase compared to the unstimulated cultures. We conclude that the use of recombinant human growth factors is potentially an effective way of increasing the MI in bone marrow cultures from APL patients for the purposes of diagnosis and residual disease detection.

Bone Marrow↗

The effect of domestic water filters on water fluoride content.

The effect of filtration on water fluoride level was investigated in a study using commercially available filters. Testing was carried out in London (low fluoride), Braintree (optimum fluoride, naturally occurring) and Birmingham (optimum fluoride, artificially adjusted). It was found that none of the filters removed fluoride. In Birmingham, but not in either Braintree or London, there was a small, clinically insignificant increase in fluoride levels with filtration using two of the five filters. It is concluded that the water filtration systems tested will not affect the advantage offered by optimum water fluoride levels. Fluoride dietary supplements should not be prescribed for children living in optimal fluoride areas, irrespective of whether they use household filters.

Analysis of Variance↗

Management of acute myocardial infarction in Auckland.

AIM: To analyse the utilisation of therapies in coronary care units for patients with acute myocardial infarction. METHODS: An evaluation form was completed prospectively by a designated nurse in each coronary care unit of the four Auckland hospitals in 1993. RESULTS: One thousand and eighty one patients who were admitted with definite or probable acute myocardial infarction had a coronary care unit stay of 63.4 (SD 49.3) hours, and hospital stay of 7.3 (5.1) days. The mortality for definite myocardial infarction was 13.7% (< 70 years 7.1%). Coronary angiography was performed on 10% of patients during their hospital admission, and 4.9% underwent revascularisation. Thrombolytic therapy was administered to 52% (495/948) of patients with definite infarction and 4% had contraindications. Patients aged > or = 70 years (47% vs 55% p = 0.02) or diabetics (46% vs 56%, p = 0.04) were less likely to receive thrombolysis. The utilisation of aspirin and oral beta-blockers was 86% and 40%, respectively, in patients with definite infarction and both were used less frequently in patients > or = 70 years. Intravenous beta-blockers were administered to < 1% of patients. Angiotensin converting enzyme (ACE) inhibitors were prescribed in 21%, intravenous or long acting nitrates in 41% and calcium antagonists in 14%; the latter two therapies were used more frequently in patients > or = 70 years. There was no evidence of gender or ethnic bias for either investigation or treatment. CONCLUSION: On the basis of results of recent clinical trials, there may be under utilisation of some treatments for acute myocardial infarction including aspirin, thrombolytic therapy, beta-blockers and ACE inhibitors, while calcium antagonists may be over used.

Adrenergic beta-Antagonists↗