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Biomedical subjects

A C Williams

Publications and source records attributed to A C Williams.

At least 37 records · Page 2Linked to original sources
PubMed2004

Research in primary dental care part 4: measures.

An important part of the design process for any study is deciding how to assess and measure the phenomena you are aiming to research. In this article we will use the term outcome measure to indicate the tool or index that can be used to quantify, in an accurate and predictable way, the phenomenon under investigation. This might, for example, be a patient's opinion, the effect of a treatment, the outcome of an intervention, or the prevalence of an oral disease. The paper presents an overview of outcome measures which can be used in research. We will discuss the properties to look for in a measure, suggest suitable evidence-based measures and briefly introduce how to go about developing new measures, in particular, questionnaires.

Costs and Cost Analysis↗
PubMed2004

Selegiline increases heme oxygenase-1 expression and the cytotoxicity produced by dopamine treatment of neuroblastoma SK-N-SH cells.

Increased dopamine catabolism may be associated with oxidative stress and neuronal cell death in Parkinson's disease. The present study was carried out to examine the effect of dopamine on the expression of heme oxygenase-1 and -2 (HO-1 and HO-2) in human neuroblastomas (SK-N-SH cell line) and the effects of selegiline and antioxidants on this expression. Cells were kept with close control of pH and were incubated with varying concentrations of dopamine (0.1-100 microM) for 24 h. HO-1 and HO-2 cDNA probes were prepared by reverse transcription-polymerase chain reaction amplification. The mRNA expression of HO-1 and HO-2 was measured by Northern blot analysis. The levels of HO-1 mRNA increased after dopamine treatment, in a dose-dependent manner, in all cell lines studied, whereas levels of the two HO-2 transcripts did not. The HO-1 and HO-2 protein expression was analyzed by Western blotting. HO-1 protein was undetectable in untreated SK-N-SH cells and increased after treatment with dopamine. In contrast, the HO-2 protein (36 kDa) was detected in untreated cells and the levels did not change as a result of treatment. Alpha-tocopherol (10-100 microM) and ascorbic acid (100 microM) did not attenuate the effects of dopamine. Selegiline (10 microM) produced significant increase (P < 0.01) in the induction of HO-1 by dopamine (more than six times the control values). The increased expression of HO-1 following dopamine treatment indicates that dopamine produces oxidative stress in this cell line.

Blotting, Northern↗
PubMed2004

Research in primary dental care part 3: Designing your study.

Earlier articles in this series identified the importance of stating a clear research question as the first step in conducting research in primary dental care. The study design seeks to answer the research question. This article describes different types of study design and their application. A framework of the steps involved in designing each type of study are described, together with the situations in which they could be used. Useful resources and sources of information are provided.

Dental Care↗
PubMed2004

Functional significance of the pentose phosphate pathway and glutathione reductase in the antioxidant defenses of human sperm.

Glutathione peroxidase is one of the principal antioxidant defense enzymes in human spermatozoa, but it requires oxidized glutathione to be reduced by glutathione reductase using NADPH generated in the pentose phosphate pathway. We investigated whether flux through the pentose phosphate pathway would increase in response to oxidative stress and whether glutathione reductase was required to protect sperm from oxidative damage. Isotopic measurements of the pentose phosphate pathway and glycolytic flux, thiobarbituric acid assay of malondialdehyde for lipid peroxidation, and computer-assisted sperm analysis for sperm motility were assessed in a group of normal, healthy semen donors. Applying moderate oxidative stress to human spermatozoa by adding cumene hydroperoxide, H(2)O(2), or xanthine plus xanthine oxidase or by promoting lipid peroxidation with ascorbate increased flux through the pentose phosphate pathway without changing the glycolytic rate. However, adding higher concentrations of oxidants inhibited both the pentose phosphate pathway and glycolytic flux. At concentrations of 50 microg/ml or greater, the glutathione reductase-inhibitor 1,3-bis-(2-chloroethyl) 1-nitrosourea decreased flux through the pentose phosphate pathway and blocked the response to cumene hydroperoxide. It also increased lipid peroxidation and impaired the survival of motility in sperm incubated under 95% O(2). These data show that the pentose phosphate pathway in human spermatozoa can respond dynamically to oxidative stress and that inhibiting glutathione reductase impairs the ability of sperm to resist lipid peroxidation. We conclude that the glutathione peroxidase-glutathione reductase-pentose phosphate pathway system is functional and provides an effective antioxidant defense in normal human spermatozoa.

Antioxidants↗
PubMed2004

Research in primary dental care. Part 2: Developing a research question.

The first step in planning and conducting any research is identifying the research question, that is a testable statement of the question which the research aims to answer. In this article three distinct types of research question are identified: Descriptive questions (for example Who? What? Where? When?); Questions of relationships (How are two or more things related?); Questions of comparison (often these questions will ask about cause and effect). Examples are given of each type of research question. The process of devising a research question is described, in particular searching for relevant information, and evaluating the quality of the information obtained. A list of useful resources is provided.

Data Collection↗
PubMed2004

Interactions of surfactants (edge activators) and skin penetration enhancers with liposomes.

Incorporating edge activators (surfactants) into liposomes was shown previously to improve estradiol vesicular skin delivery; this phenomenon was concentration dependent with low or high concentrations being less effective. Replacing surfactants with limonene produced similar behaviour, but oleic acid effects were linear with concentration up to 16% (w/w), beyond which it was incompatible with the phospholipid. This present study thus employed high sensitivity differential scanning calorimetry to probe interactions of additives with dipalmitoylphosphatidylcholine (DPPC) membranes to explain such results. Cholesterol was included as an example of a membrane stabiliser that removed the DPPC pre-transition and produced vesicles with a higher transition temperature (T(m)). Surfactants also removed the lipid pre-transition but reduced T(m) and co-operativity of the main peak. At higher concentrations, surfactants also formed new species, possibly mixed micelles with a lower T(m). The formation of mixed micelles may explain reduced skin delivery from liposomes containing high concentrations of surfactants. Limonene did not remove the pre-transition but reduced T(m) and co-operativity of the main peak, apparently forming new species at high concentrations, again correlating with vesicular delivery of estradiol. Oleic acid obliterated the pre-transition. The T(m) and the co-operativity of the main peak were reduced with oleic acid concentrations up to 33.2mol%, above which there was no further change. At higher concentrations, phase separation was evident, confirming previous skin transport findings.

Calorimetry, Differential Scanning↗
PubMed2004

Research in primary dental care. Part 1: Setting the scene.

There is a growing trend for research to be conducted in primary health settings, to the benefit of patients and healthcare workers. This article provides an introduction and overview of a series which aims to facilitate research in general dental practice and to encourage general dental practitioners and other members of the dental team to become involved in these studies. The benefits of undertaking research are outlined, as well as barriers to becoming involved in such research. It is argued that many of these barriers can be overcome by encouraging dental practitioners to collaborate with established researchers in a variety of settings.

Dental Research↗
PubMed2004

Penciclovir solubility in Eudragit films: a comparison of X-ray, thermal, microscopic and release rate techniques.

The solubility of penciclovir (C(10)N(5)O(3)H(17)) in a novel film formulation designed for the treatment of cold sores was determined using X-ray, thermal, microscopic and release rate techniques. Solubilities of 0.15-0.23, 0.44, 0.53 and 0.42% (w/w) resulted for each procedure. Linear calibration lines were achieved for experimentally and theoretically determined differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRPD) data. Intra- and inter-batch data precision values were determined; intra values were more precise. Microscopy was additionally useful for examining crystal shape, size distribution and homogeneity of drug distribution within the film. Whereas DSC also determined melting point, XRPD identified polymorphs and release data provided relevant kinetics.

Acyclovir↗
PubMed2004

Patients' experiences after undergoing orthognathic surgery at NHS hospitals in the south west of England.

Patients are being increasingly involved in assessing the quality of care that they receive in the NHS. Our aim was to undertake a retrospective postal survey to evaluate their perception of the delivery of orthognathic surgery in the south west of the United Kingdom (UK) using a patient-centred measure. A total of 327 patients (53% response rate) participated. Although most participants (n = 249, 76%) reported that they were well-informed about what to expect during treatment, many reported that the symptoms of pain, swelling, or difficulty in eating that they experienced immediately post-operatively were worse than expected. A third also reported that it took them longer to recover from the operation than they had anticipated. Patients undergoing orthognathic surgery in the south west of the UK need more specific information about what to expect both immediately post-operatively and at home after discharge.

Adolescent↗
PubMed2004

The development of a patient-centered measure of the process and outcome of combined orthodontic and orthognathic treatment.

OBJECTIVE: The aim of this study was to develop a patient-based measure of the process and outcome of combined orthodontic and orthognathic care in the National Health Service in the UK. DESIGN: Identification of relevant dimensions through qualitative methods, design of form, determination of psychometric properties of the scale, specific readability, reliability and validity. SETTING: NHS hospitals in the South West Region. SUBJECTS: The sample comprised patients who had received combined orthodontic and orthognathic treatment between 01 January 1998 and 31 December 2000. Twenty-six participants (a 25% response rate) took part in four focus group meetings. Thirty subjects (65% response rate) took part in a pilot study to test the properties of the questionnaire. MAIN OUTCOME MEASURES: Six broad themes emerged from the focus groups. These formed the basis of the sections in the questionnaire. RESULTS: The questionnaire developed had a Flesch reading ease score of 72.9 or US grade level 4 equivalent to aged 9-10 years. Test-retest reliability gave kappa values for most questions that exceeded 0.4. Criterion validity of the measure was established by comparing responses to the questionnaire over two periods with a telephone interview on a sample of 30 patients. Criterion related validity was poor for nine of the 16 items. By contrast the construct validity of the questionnaire was satisfactory. CONCLUSION: A patient-based measure of the process and outcome of combined orthodontic and orthognathic treatment has been developed. This has sufficient validity and reliability for use in inter-center audit projects.

Attitude to Health↗
PubMed2004

Assisted reproductive technologies in europe encompass diverse and complex ethical viewpoints: issues to be considered in reporting research in human reproduction.

The many dimensions of the field of reproduction (clinical, scientific, social, ethical, legal) must be addressed by those with editorial responsibility for the major journals in the field. As the editorial team of the leading reproductive journal Human Reproduction, we have evolved processes that attempt to ensure a transparent but robust approach to complexities whose impact varies across international boundaries.

Cloning, Organism↗
PubMed2003

Psychological therapies for the management of chronic and recurrent pain in children and adolescents.

BACKGROUND: An increasing number of children suffer with pain that lasts for six months or longer. Traditional treatment for such pain has been pharmacological and/or physical. Increasingly, following developments in the field of adult chronic pain management, psychological therapies are being employed to treat children with chronic or recurrent pain. OBJECTIVES: To assess the effectiveness of psychological therapies in treating chronic or recurrent pain in children and adolescents, and to test the null hypothesis that psychological therapies are no more effective than placebo, waiting list control or standard medical care. SEARCH STRATEGY: Electronic searches of the Cochrane Register of Randomised Controlled Trials, MEDLINE (1966-1999), Social Sciences Citation Index (1981-1999) and PsycLit (1974-1999) were made. RCTs were also sought in references of all identified studies, meta-analyses and reviews, and first authors and experts within the field were contacted. Date of the most recent search: December 1999. SELECTION CRITERIA: RCTs with at least five participants in each study arm which compared psychological therapies with placebo, waiting list or standard medical care for children or adolescents with chronic or recurrent pain were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Data were inspected for heterogeneity. For homogeneous dichotomous data the odds ratio with 95% confidence interval were calculated on an intention to treat basis. MAIN RESULTS: Thirty papers were recovered, representing 28 RCTs. Of these, 18 were analysable and included a total of 808 patients, 438 of whom entered treatment conditions. Fifteen were trials of chronic or recurrent headache; two for recurrent abdominal pain; and one for sickle cell pain. Only pain experience data from 13 trials were meta-analysable. Two meta-analyses were conducted. The first analysis of single treatments versus controls gave a pooled odds ratio of 8.83 (95% CI 4.33 to 18.03; z=5.98, P < 0.00001, df = 12 ). The second analysis (combined treatment versus control) produced a similar estimate: pooled odds ratio = 8.64 ( 95% CI = 4.13 to 18.07; z-5.73, P < 0.00001, df = 9 ). Both analyses indicate that psychological treatment is effective when compared with a pooled group of control conditions. From the pooled data set the NNT was 2.32 (95%CI 1.96 to 2.88). REVIEWER'S CONCLUSIONS: There is very good evidence that psychological treatments, principally relaxation and cognitive behavioural therapy, are effective in reducing the severity and frequency of chronic headache in children and adolescents. There is at present no evidence for the effectiveness of psychological therapies in attenuating pain in conditions other than headache, and little evidence for the effectiveness of psychological therapies in improving non-pain outcomes.

Abdominal Pain↗
PubMed2003

Using skinfold calipers while teaching body fatness-related concepts: cognitive and affective outcomes.

Body composition testing has been advocated as part of fitness test batteries in an educational effort to promote health-related fitness, and to prevent public health problems like obesity. However, the measurement of the body composition of children and youth, especially involving the use of skinfold calipers, has raised concerns. In two experiments the cognitive and affective consequences of skinfold caliper use in a 7th grade (155 boys, 177 girls, total N = 332) health/physical education context were examined. Experiment 1 demonstrated that the students could be taught to accurately measure a partner and/or significantly learn body fatness-related concepts compared to controls. It was also shown that inexpensive plastic Fat Control calipers produced accurate measurements. Experiment 2 was designed to replicate the significant cognitive outcome effects, and also to test the hypothesis that psychological damage is a likely consequence of skinfold caliper use-and that hypothesis was refuted. Specifically, knowledge scores, and outcome scores on adapted affect scales (e.g., PANAS, MAACL), physical self-esteem scales (CY-PSPP) and on the Social Physique Anxiety Scale supported the premise that skinfold calipers can be used in an educational context to facilitate cognitive learning without causing adverse affective consequences.

Adipose Tissue↗
PubMed2003

Transcriptional upregulation of the insulin-like growth factor binding protein IGFBP-3 by sodium butyrate increases IGF-independent apoptosis in human colonic adenoma-derived epithelial cells.

Sodium butyrate (NaBt) and the pro-apoptotic IGFBP-3 protein, expressed at the top of the normal colonic crypt, have both been implicated in the regulation of apoptosis in colonic epithelial cells. Recent studies in human breast and hepatic cell lines have shown that NaBt can transcriptionally upregulate IGFBP-3 expression. However, the role of butyrate in the regulation of IGFBP-3 expression in the colon is less clear, with reports of both up- and downregulation of the IGFBP-3 protein in colorectal cancer cell lines. In this study we have shown that the level of IGFBP-3 protein expression in colonic epithelial cells correlates with the p53 status of the cells; wildtype p53 cells secrete higher levels of IGFBP3 protein than mutant p53 cell lines. Data presented shows that, when treated with a dose of NaBt that induced significant apoptosis (4 mM for 48 h), there was an upregulation of IGFBP-3 protein in both wildtype and mutant p53 expressing cell lines. The NaBt-induced increase in secreted IGFBP-3 protein was associated with transcriptional upregulation of the IGFBP-3 gene. Using a transfected derivative of the S/RG/C2 adenoma-derived cell line, which stably expressed exogenous IGFBP-3 protein at levels equivalent to that secreted by the 4 mM NaBt-treated parental line (1-3 ng/10(6) cells), we have shown a >2-fold increase in the sensitivity of the cells to NaBt-induced apoptosis when compared with the vector control and parental cell lines. Furthermore, inhibition of the secreted IGFBP-3 protein, by addition of neutralizing antibodies, resulted in a significant decrease in NaBt-induced apoptosis. These data suggest that IGFBP-3 may act as a positive regulator of NaBt-induced apoptosis in colonic epithelial cells, and represents a potentially important mechanism whereby the sensitivity of colonic epithelial cells to NaBt-induced apoptosis can be increased.

Adenoma↗
PubMed2003

Surgery for Parkinson's disease: lack of reliable clinical trial evidence.

There has been a striking resurgence of interest in surgery for Parkinson's disease (PD) with new targets identified and new procedures developed. This systematic review identified over 500 studies of surgery for PD published since 1990, including over 10 000 patients. However, the authors were unable to assess the value of PD surgery reliably because only seven randomised trials were identified including just 196 patients. Studies of surgery for PD have generally been of poor quality with too few patients, too short follow up, inappropriate choice of outcome measures, and lack of control groups. Much larger, randomised, controlled trials are needed to assess the longer term effects of surgery on patient rated quality of life and cost effectiveness.

Clinical Trials as Topic↗
PubMed2003

Expression of cysteine dioxygenase (EC 1.13.11.20) and sulfite oxidase in the human lung: a potential role for sulfate production in the protection from airborne xenobiotica.

AIMS: The lung is one of the major sites of phase I cytochrome P450 enzyme and phase II sulfotransferase expression, which together are thought to act as an enzymic barrier against the unimpeded transfer of airborne xenobiotics into the lung parenchyma and systemic circulation. Sulfate for conjugation is produced primarily from the oxidation of cysteine, begun by cysteine dioxygenase (CDO), and completed with the conversion of sulfite to sulfate via sulfite oxidase (SO). Little is known about the site of expression of these two enzymes in the alveoli of the human lung. METHODS: Antibodies and oligonucleotide probes raised against both CDO and SO were used for immunohistochemistry and in situ hybridisation, respectively, to investigate the expression of CDO and SO in human lung alveoli. RESULTS: CDO and SO were expressed in alveolar epithelial cells, which is also the site of expression of cytochrome P450 1B1. CONCLUSIONS: These results demonstrate that the two key enzymes in sulfate production are expressed in the same locale as phase I and phase II enzymes, and that these two enzymes may be involved in the production of sulfate for the maintenance of a metabolic barrier against the entry of airborne xenobiotics and the synthesis of important structural proteins and proteoglycans.

Air Pollutants↗
PubMed2002

Two large British kindreds with familial Parkinson's disease: a clinico-pathological and genetic study.

We present the findings of a study of two large unrelated kindreds with autosomal dominant Parkinson's disease. The affected members were assessed clinically and with [(18)F]6-fluorodopa-PET and were indistinguishable from patients with the sporadic form of Parkinson's disease. In one kindred, an affected member was examined subsequently at autopsy and Lewy bodies were present in a distribution typical of sporadic Parkinson's disease. These kindreds are distinct from other Parkinsonian kindreds with identified genetic loci (PARK1-4) and provide further evidence for genetic heterogeneity in familial Parkinson's disease.

Adult↗