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Biomedical subjects

D M Williams

Publications and source records attributed to D M Williams.

424 records · Page 24Linked to original sources

Is home tooth bleaching gel cytotoxic?

Tooth whitening systems are widely used clinically and for home usage. The aim of this study was to determine the effects of two bleaching gels, each containing 10 percent and 15 percent carbamide peroxide, respectively, a 'bleaching gel' without carbamide peroxide, and carbamide peroxide alone on the viability of human endothelial cells in vitro in comparison with culture medium that acted as a negative control. The incubation period used was 30 minutes. A colorimetric viability assay (MTT assay) was employed. The results showed that the gel without carbamide peroxide is not cytotoxic compared to the negative control, while carbamide peroxide on its own and 10 percent and 15 percent carbamide peroxide bleaching gels were cytotoxic, but there were no significant differences (p greater than 0.05) among these latter three test groups. These data indicate that 10 percent and 15 percent carbamide peroxide bleaching gels are cytotoxic and that carbamide peroxide is the component responsible for this cytotoxic effect. This paper also discusses why this in vitro cytotoxic effect appears not to be significant in vivo.

Analysis of Variance↗

Bulk flow model for multislice magnetic resonance imaging sequences with phantom validation.

A simple conceptual model for describing the effects of one-dimensional bulk flow on image intensities is presented and validated using a multislice imaging sequence specific to one vendor. The model allows quantitative estimates of echo amplitudes versus velocity by using the equation of motion to follow the pulse history of fluid volumes influenced by the readout pulse for any slice of interest. Each affected volume is divided into equal elemental components and the state of each component is computed at discrete times in a pulse position-timing diagram until readout occurs. The final amplitude for the composite volume is determined by the signed summation of each of the elemental components. Validation of the quantitative model was performed by imaging a rotating bulk flow phantom centered at each of the slices of a multislice, partial saturation, spin-echo sequence. Effects due to rf field inhomogeneities were normalized by dividing the results of the dynamic scans by the corresponding static one. The results presented here are relatively insensitive to odd-echo dephasing (even echo rephasing).

Humans↗

Diagnosis of renal vascular disease with MR angiography.

Renal magnetic resonance (MR) angiography allows accurate evaluation of patients suspected to have renal artery stenosis without the risks associated with nephrotoxic contrast agents, ionizing radiation, or arterial catheterization. Other applications of renal MR angiography are mapping the vascular anatomy for planning renal revascularization, planning repair of abdominal aortic aneurysms, assessing renal bypass grafts and renal transplant anastomoses, and evaluating vascular involvement by renal tumors. A variety of pulse sequences provide complementary information about kidney morphology, arterial anatomy, blood flow, and renal function and excretion. Three-dimensional gadolinium-enhanced MR angiography can be combined with several other sequences to produce a comprehensive approach to renal MR angiography. This comprehensive approach is designed to allow hemodynamic characterization of renal artery stenosis with a single MR imaging examination that can be easily completed in 1 hour. Three-dimensional gadolinium-enhanced MR angiography demonstrates the renal arteries along with the abdominal aorta, iliac arteries, and mesenteric arteries in a 20-30-second acquisition that can be performed during breath holding. Numerous projections are reconstructed from a single three-dimensional volume of data acquired with a single injection of contrast material to obtain perpendicular and optimized views of each renal artery.

Anastomosis, Surgical↗

Flow cytometry in the preclinical development of biopharmaceuticals.

Novel biomarkers are often required in the preclinical development of biopharmaceuticals in order to characterize pharmacologic and toxicologic effects and to establish pharmacodynamic and pharmacokinetic relationships. Flow cytometry is uniquely suited for measurement of these biomarkers. Large numbers of single cells in a heterogeneous population can be rapidly identified and characterized with high accuracy and reproducibility. Cells are not damaged by the detection system and can be subsequently sorted for further morphologic or functional analysis. The availability of clinical instruments and a wide range of fluorescent probes have made this technology applicable for use in toxicologic clinical pathology. Flow cytometry has played an integral role in the development of a monoclonal antibody to human CD4 (keliximab, IDEC-CE9.1, SB 210396). Lymphocyte subset analysis and assays for expression, coating, and modulation of human CD4 were used for sequential assessment of the pharmacologic activity of keliximab in transgenic mice expressing human CD4.

Animals↗

Inhaled antibiotics in cystic fibrosis: a review.

OBJECTIVE: To provide an overview of aerosol drug therapy, including physical considerations and aerosol drug delivery systems, and to review clinical experience with inhaled antibiotics in cystic fibrosis (CF) when used as adjunctive therapy to intravenous therapy for acute pulmonary exacerbations and chronic, suppressive therapy. DATA SOURCES: A MEDLINE search (1966-1995) of English-language literature describing the use of inhaled antibiotics for the management of CF. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for possible inclusion in the review. Pertinent information as judged by the authors was selected for discussion. DATA SYNTHESIS: The use of inhaled antibiotics as adjunctive therapy to systemic therapy for acute exacerbations did not improve pulmonary function tests, increase hospital discharge rate, or permanently eradicate sputum Pseudomonas. Clinical trials of inhaled antibiotics as suppressive therapy yielded variable results. Individually, four trials documented a significant improvement in pulmonary function, three trials documented a slower decline in pulmonary function, and four trials reported a reduced frequency of hospitalizations. However, the trials were unable to collectively document a prolonged beneficial effect of inhaled antibiotics on pulmonary function, sputum bacterial density, and frequency of hospitalizations. CONCLUSIONS: Clinical trials conducted thus far suggest no role for inhaled antibiotics in the treatment of acute pulmonary exacerbations in patients with CF. Aerosolized antibiotics used as suppressive therapy may be useful in certain patients, but their use should be limited to select patients based on individual response to therapy. Additional long-term, well-controlled trials of inhaled antibiotics as suppressive therapy are needed before routine use can be recommended.

Administration, Inhalation↗

Multicenter evaluation of six methods for predicting warfarin maintenance-dose requirements from initial response.

Warfarin maintenance-dose requirements predicted by six mathematical methods based on initial response to therapy were compared with patients' actual dose requirements in a multicenter trial. Data were collected for patients who had received an initial regimen of warfarin sodium 10 mg orally every 24 hours for three days and for whom a prothrombin time (PT) had been determined 16-20 hours after the third dose. Patients' individual dose requirements and PT values were recorded during one to three follow-up visits after discharge from one of seven medical centers. Prothrombin ratios (patient PT divided by control PT) calculated on day 4 were used for maintenance-dose prediction by five methods; a sixth method was based on the cumulative warfarin dose-PT response curve up to a PT value of 20 seconds. For 54 men and 30 women who qualified for the study, 197 maintenance-dose-PT response measurements were recorded; 95 in the first four weeks of therapy, 76 during weeks 5-12, and 26 at 6-12 months after initial treatment. Prothrombin ratios were within the therapeutic range (PT 1.5-2.5 times the control value) in 154 observations, and the mean actual warfarin sodium maintenance dose associated with therapeutic response was 7.6 mg/day. For patients with therapeutic prothrombin ratios, dose predictions by the five methods using prothrombin ratios (PRs) correlated significantly with actual dose requirements. The formula that predicted doses numerically closest to the actual dose is as follows: Dose = 11.17 - 21.08 (log PR). Only 45 observations were obtained for the sixth prediction method, and the correlation between actual and predicted doses was not significant. Initial warfarin maintenance-dose requirements can be predicted effectively based on one PT determination after administration of three daily 10-mg doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Chlamydia trachomatis pneumonia in the severe combined immunodeficiency (SCID) mouse.

We have developed a model of pneumonia caused by the mouse pneumonitis agent (MoPn, murine Chlamydia trachomatis) in the C.B-17 severe combined immunodeficiency (SCID) mouse. In contrast to our prior models in the nude athymic (nu/nu) and heterozygous (nu/+) mouse, SCID mice lack B-cell function and gamma delta T-cell function. SCID mice were more susceptible to MoPn than nu/nu or nu/+ mice both by criteria of mortality and quantitative lung culture. SCID mice could be reconstituted with thymocytes to be more resistant to MoPn (in the absence of significant antibody production), but the protection was modest and less than that in T-cell reconstituted nu/nu mice in our previous studies. A nu/+ MoPn-specific T-cell clone with a Th1-like cytokine profile also provided modest but significant protection without significant antibody production. The SCID mouse is a useful model to study T-cell-mediated immunity to MoPn in a B cell and gamma delta T-cell-deficient environment.

Animals↗

Resolution of murine chlamydial genital infection by the adoptive transfer of a biovar-specific, Th1 lymphocyte clone.

MoPn-specific T-cell clones were isolated from a T-cell line that was capable of curing chlamydial genital infection by the Chlamydia trachomatis agent of mouse pneumonitis (MoPn) after adoptive transfer. Two clones (designated as 2.14-0 and 2.14-3) were characterized by flow cytometry techniques to be homogenous for L3T4, CD3, and alpha/beta T cell receptor (TcR) T-helper cell markers. The two clones were biovar specific, because they reacted to MoPn but not the Chlamydia psittaci agent of guinea pig inclusion conjunctivitis (GPIC) or C. trachomatis, serovar type E. Cytokine profile analysis, by a combination of bioassays, ELISA, and slot/Northern blotting for specific cytokine messenger RNAs, further revealed that cultures of antigen-stimulated clone 2.14-0 contained interleukin-2 (IL-2), tumor necrosis factor-alpha, and gamma interferon (a T helper 1 cell [Th1] profile). Clone 2.14-3 was also positive for gamma interferon, a level much lower than that of clone 2.14-0, and negative for IL-4 secretion, suggesting a Th1 profile as well. The ability of these clones to bring about the resolution of the chronic genital chlamydial infection of nude mice was tested by the adoptive transfer of 10(7) cells of each clone into the mice. By 4 weeks after cell transfer of clone 2.14-0, 81% of recipient nude mice (30 of 37) resolved the disease. In contrast, clone 2.14-3 or a control T-cell clone specific for a heterologous antigen were unable to resolve the infection in 20 recipients in each case, even after 100 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗