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Biomedical subjects

I Williams

Publications and source records attributed to I Williams.

At least 55 records · Page 3Linked to original sources

Drug development.

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Anti-Infective Agents↗

Proton MRS and quantitative MRI assessment of the short term neurological response to antiretroviral therapy in AIDS.

OBJECTIVE: To investigate MRI and proton spectroscopy changes in five patients with HIV associated dementia complex (HADC) treated with antiretroviral therapy. METHODS: Three markers were evaluated: (1) CSF/intracranial volume ratio; (2) T2 weighted signal ratio between parieto-occipital white and subcortical grey matter; and (3) metabolite ratios from long echo time (TE=135 ms) single voxel proton spectra of parieto-occipital white matter. RESULTS: Spectroscopic changes indicated initial increases in N-acetyl/(N-acetyl + choline + creatine) ratio (NA/(NA+ Cho+Cr)) and progression of atrophy after initiation of antiretroviral therapy in four of five patients. When the neurological status of the patients subsequently deteriorated (two of five patients), the NA/(NA+Cho+Cr) ratio also declined. CONCLUSIONS: Spectroscopic changes mirror reversible neuronal dysfunction. These objective, non-invasive techniques may be used for monitoring the neurological effects of antiretroviral drug therapy in patients with HADC.

AIDS Dementia Complex↗

Comparative evaluation of Wellhöfer ion chamber array and Scanditronix diode array for dynamic wedge dosimetry.

Normalised profiles have been measured using the Scanditronix diode array and the Wellhöfer ion chamber array for the Varian dynamic wedge. Agreement was of the order of 0.1% of central axis peak dose for an open beam at depth, 0.3% for a dynamic wedge field at depth, and up to 0.6% at the peak depth. The use of the arrays for data acquisition is discussed, including user interface limitations. Data reproducibility is determined to be of the order of 0.1% for both systems. The issue of beam hardening within dynamic wedges is discussed and resolved in terms of the dose-gradient effect. A method for interpolation between dynamic wedge profiles using open beam data is presented that allows construction of isodoses to an estimated accuracy of 0.7%. Finally a benchmark for comparison of different measuring systems based on quality assurance requirements for the enhanced dynamic wedge is suggested.

Particle Accelerators↗

Tibial insert undersurface as a contributing source of polyethylene wear debris.

Sixty-seven ultrahigh molecular weight polyethylene tibial inserts from cementless total knee arthroplasties were retrieved at autopsy and revision surgery and analyzed for evidence of articular and nonarticular surface wear after a mean implantation time of 62.8 months (range, 4-131 months). Polyethylene cold flow and abrasive wear on the nonarticular insert surface (undersurface) were assigned a wear severity score (Grade 0-4). The severity of articular wear was assessed quantitatively and graded. Corresponding prerevision radiographs were evaluated for evidence of tibial metaphyseal osteolysis and osteolysis around tibial fixation screws. Exact nonparametric conditional inference methods were used to establish correlations between different variables and the occurrence of tibial metaphyseal osteolysis. Severe Grade 4 wear of the tibial insert undersurface was associated with tibial metaphyseal osteolysis or osteolysis around fixation screws. Time in situ statistically was related to Grade 4 undersurface wear and tibial metaphyseal osteolysis. The occurrence of tibial osteolysis was not related statistically to articular wear severity, insert thickness, or implant type. The main articulation between the femoral implant and ultrahigh molecular weight polyethylene insert has been assumed to be the primary source of polyethylene debris contributing to osteolysis and total knee arthroplasty implant failure. The undersurface of the insert is an additional source of polyethylene debris contributing to tibial metaphyseal osteolysis. To lessen polyethylene debris produced at this modular interface, the tibial implant locking mechanism should fix the insert firmly to the metal backing to decrease relative micromotion. Because motion between the insert and metal backing may be inevitable, the wear characteristics of the inner tray surface should be optimized to minimize wear debris production at this other articulation.

Arthroplasty, Replacement, Knee↗

Safety, tolerance, and efficacy of atevirdine in asymptomatic human immunodeficiency virus-infected individuals.

Atevirdine is a nonnucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1). In this study we investigated the effect of atevirdine in asymptomatic antiretroviral naive HIV-infected patients with CD4+ cell counts of between 200 and 750 cells per mm3. Patients were randomized to receive 600 mg of atevirdine (n = 15) or a placebo (n = 15) three times a day for 12 weeks. There was no statistically significant effect of atevirdine on viral loads (HIV p24 antigen and HIV-1 RNA levels by PCR) or CD4+ cell counts. The data do not support the use of atevirdine as a monotherapy in the treatment of HIV-infected patients.

Adult↗

Multicenter comparison of three commercial methods for quantification of human immunodeficiency virus type 1 RNA in plasma.

Three procedures for the quantification of human immunodeficiency virus type 1 (HIV-1) RNA from plasma were compared at three laboratories. The comparison involved the Quantiplex branched DNA assay (version 1.0) by Chiron Diagnostics, the NASBA-QT assay by Organon Teknika, and the Amplicor Monitor assay by Roche Molecular Systems. The laboratories performed each of the three assays with the same sets of reconstructed HIV-1-infected human plasma samples, cross-sectionally collected clinical plasma samples and longitudinally collected plasma samples from patients starting zidovudine therapy. Analysis of the reconstruction panel results for interlaboratory variation demonstrated that no laboratory differences in results were detected for any of the assays. A comparison of the reproducibilities of duplicate samples analyzed by batch and in separate assay runs demonstrated that the reproducibilities of the test results were similar within one assay and appeared to be independent of the HIV-1 concentration. The best reproducibility was obtained with the Quantiplex assay, but all three assays demonstrated equal reliability, which was independent of batched or unbatched analysis of replicate samples. Differences in the absolute concentrations calculated were observed for the assays, in particular in the analysis of reconstructed samples. In all assays, similar changes in plasma HIV-1 RNA concentrations were determined for longitudinally collected clinical samples.

Biomarkers↗

Summary of track B: clinical science.

AIM: To review Track B on clinical science. Major topics covered were quantitative HIV-1 plasma RNA measurement, combination antiretroviral therapy, protease inhibitors, treatment of primary HIV-1 infection, HIV-1 drug resistance, future use of antiretroviral drugs, paediatric HIV-1 infection, opportunistic infections and HIV/AIDS in developing countries. QUANTITATIVE HIV-1 PLASMA RNA MEASUREMENT: Quantification of HIV-1 RNA is a predictor of progression of immune deficiency and death in HIV-infected adults and children, and is useful in monitoring response to antiretroviral therapy. THERAPY: Combination antiretroviral therapy is now the standard of care, although questions about optimal starting time and the best initial regimen remain unresolved. Protease inhibitors are a powerful new class of antiretroviral agents which in combination with other drugs can produce profound reductions in plasma HIV-1 RNA levels. Trials are in progress of combination antiretroviral therapy, including protease inhibitors, in persons recently infected with HIV-1 to assess the feasibility of permanent suppression or eradication of HIV-1. Adherence to therapy and drug resistance will become increasingly important subjects. CONCLUSIONS: The genuine improvements in patient management are out of reach to the majority of the world's HIV-infected persons, a conclusion with implications which dampened the optimism generated by the conference.

Adult↗

Day-case surgery in children under 2 years of age: experience in a district general hospital and survey of parental satisfaction.

One surgeon's experience of day-case paediatric surgery in a population aged less than 2 years at a district general hospital is reported. During a 6-year period from 1989 to 1994, 82 day-case operations were performed in 79 infants and young children. All children were managed by a multidisciplinary team including surgeon, paediatric anaesthetist and paediatric nurses. There was no mortality and minimal morbidity. A telephone survey of parents enquiring into satisfaction with all aspects of pre-, peri-, and post-operative care revealed that the procedures are well-accepted. The survey also showed that there was no increased utilization of primary health care professionals when day-case surgery is performed in this young age group. We conclude that paediatric day-case surgery is safe and well-tolerated by both infants and parents and is suitable for performance in non-specialist centres provided a team approach is adopted.

Ambulatory Surgical Procedures↗

A beta-linked mannan inhibits adherence of Pseudomonas aeruginosa to human lung epithelial cells.

Adherence through carbohydrate-binding adhesins is an early step in colonization of the lung by gram-negative organisms, and because published data indicate that binding involves mannose groups, we tested the ability of a beta-linked acetyl-mannan (acemannan) to inhibit adherence of Pseudomonas aeruginosa to cultures of human lung epithelial cells. Adherence of radiolabelled P.aeruginosa to A549 cells (a type II-like pneumocyte line) increased linearly with the duration of the incubation. Acemannan inhibited adherence of bacteria, and the extent of inhibition was related to the concentration of the mannan. Inhibition required continued contact between acemannan and the target epithelial cells; cells washed free of acemannan no longer discouraged bacterial binding. Comparison of binding between seven different strains of P.aeruginosa indicated that fewer mucoid than non-mucoid bacteria adhered, but binding of either phenotype was inhibited by acemannan. Mannose, methyl alpha-D-mannopyranoside, methyl beta-D-mannopyranoside and dextran did not affect adherence of any of the non-mucoid strains. Mannose inhibited adherence by one mucoid strain, but not the other, indicating differences between strains of the same phenotype. Since prior treatment of epithelial cells with concanavalin A did not affect acemannan-induced inhibition of bacterial adherence, we concluded that the inhibitory effect of acemannan probably does not involve mannose-containing receptors.

Analysis of Variance↗

Influences on control in diabetes mellitus: patient, doctor, practice, or delivery of care?

OBJECTIVE: To assess patient, doctor, practice, and process of care variables for their effect on glycaemic control in diabetes mellitus, and to quantify their relative effects. DESIGN: Search of general practice medical records, patient questionnaires and examination, doctor questionnaire, videotaping and analysis of consultations, and practice questionnaire. SETTING: 12 practices with 32 participating general practitioners in Nottinghamshire. SUBJECTS: 318 patients randomly selected from those with diabetes in each practice, 10 for each participating doctor. MAIN OUTCOME MEASURE: Glycaemic control as measured by random glycated haemoglobin A1c estimation (random haemoglobin A1 measurement). RESULTS: Glycaemic control was significantly related to the disease process as measured by years since diagnosis, treatment group, and number of diabetes related clinical events. Females had significantly worse control than males. Other patient factors, such as age, social class, lifestyle, attitudes, satisfaction, and knowledge, had no association with glycaemic control. Of all the doctor factors examined, only doctors who professed a special interest in diabetes achieved significantly better glycaemic control. Bigger and better equipped practices and those with a diabetic miniclinic had patients with significantly better glycaemic control, as did those with access to dietetic advice. Patients attending hospital clinics had worse glycaemic control, but this seemed to be attributable to the case mix and practice characteristics. Shared care did not contribute to the multiple linear regression model. CONCLUSION: Glycaemic control among diabetic patients in the community is related to such factors as treatment group, sex, and years since diagnosis; it is also related to the organisation and process of care. The findings support concentrating diabetic care on partners with special interests in diabetes in well equipped practices with adequate dietetic support.

Attitude of Health Personnel↗

Muscle disease, HIV and zidovudine: the spectrum of muscle disease in HIV-infected individuals treated with zidovudine.

Eleven patients with AIDS or AIDS-related complex who developed muscle-related symptoms whilst taking zidovudine were investigated. The clinical details of a further ten patients who did not undergo muscle biopsy are also outlined. The clinical features, quantitative muscle strength testing, electromyographic findings, serial creatine kinase levels, muscle biopsy appearance on light microscopy and the effects of zidovudine withdrawal and rechallenge are described. The spectrum of muscle disease encountered included four cases of frank myopathy diagnosed using clinical, electrophysiological and histological criteria, four patients with mild weakness and myalgia in whom muscle biopsies were normal, three patients with myalgia only and a mild increase in the interstitial cell infiltrate shown by biopsy. The patients presenting with myopathy showed no improvement on withdrawal of zidovudine but responded to immunosuppressive therapy with steroids and, in one case, thalidomide prescribed incidentally. At present, it is not yet possible to clinically define a specific zidovudine-induced myopathy that is distinct from the other effects of HIV infection on muscle structure and function. Our experience suggests that zidovudine may be implicated as a myotoxin in some patients, particularly those with myalgia and mild weakness. In those patients with severe weakness, and with biopsy findings of necrosis and inflammation, the drug effects may be difficult to separate from the primary effects of HIV.

AIDS-Related Complex↗