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Biomedical subjects

C Williams

Publications and source records attributed to C Williams.

At least 37 records · Page 2Linked to original sources
PubMed2001

A virus binding assay for studying the antigenic landscape on intact, native, primary human immunodeficiency virus-type 1.

This protocol describes a simple assay that can be used to study the nature of exposure of antigenic epitopes and antigenic relatedness of different intact, native HIV-1 strains. The assay is based on the principle that mAbs coated on microtiter wells bind to epitopes on the surface of intact, native virions. The bound virion is then lysed to release p24, which is then quantitated (pg/ml) to give a measure of the amount of virion bound to the mAb. High p24 levels released after lysis correlate with high level capture of virions by mAbs, and as such, reflect good exposure of the epitope on the virion. Likewise, binding patterns of a specific mAb with different virus strains reveal information on their antigenic relatedness. In establishing this assay, the nature of exposure of antigenic epitopes and the antigenic relatedness of six intact, native HIV-1 virions of clades A, B, C, D, F and G were examined using anti-HIV-1 mAbs directed at epitopes in the V2, V3, CD4bd and C5 of gp120, and in clusters I and II of the gp41 region. Analysis of the binding data shows that mAbs directed at epitopes in the V3, C5 and gp41 Cluster I region bound best to the viruses examined, suggesting that these are the regions most exposed and conserved on intact, native HIV-1 virions of different clades. Epitopes in the V2 and CD4bd of gp120, and in gp41 cluster II, are not exposed on intact, native virions.

Antibodies, Monoclonal↗
PubMed2001

Flexible alignment of small molecules.

A method is presented for flexibly aligning small molecules. The method accepts a collection of small molecules with 3D coordinates as input and computes a collection of alignments. Each alignment is given a score, which quantifies the quality of the alignment both in terms of internal strain and overlap of molecular features. The results of several computational experiments on pairs of compounds with known binding conformations are used to systematically and objectively tune the parameters for the method. The results indicate the method's utility for the elucidation of pharmacophores and comparative field analysis.

Databases, Factual↗
PubMed2001

Concomitant chemotherapy and radiation therapy for cancer of the uterine cervix.

BACKGROUND: The National Cancer Institute (USA) alert in February 1999 stated that concomitant chemoradiotherapy should be considered for all patients with cervical cancer, based on evidence from five randomised controlled trials. OBJECTIVES: To review all known randomised clinical controlled trials (RCTs) comparing concomitant chemotherapy and radiation therapy with radiotherapy for locally advanced cervical cancer. SEARCH STRATEGY: We searched electronic databases, trials registers and reference lists of published trial reports and review articles were also searched. SELECTION CRITERIA: This review includes RCTs in cervical cancer comparing concomitant chemotherapy and radiotherapy with radiotherapy. In the experimental arm, further adjuvant chemotherapy was allowable. Hydroxyurea was considered inactive and allowable. Trials using radiosensitisers or radioprotectors in the experimental arm were excluded. DATA COLLECTION AND ANALYSIS: Two authors reviewed trials for inclusion and extracted data. For meta-analyses of time-to-event outcomes (survival, progression-free survival), a hazard ratio (HR) was extracted or estimated from trial reports, where possible. Only overall rates of local and distant recurrence were presented in many reports so only an odds ratios (OR) of recurrence rates could be calculated, which takes no account of time to recurrence or censoring. The HRs and ORs for individual trials were combined across all trials, using the fixed effect model. Few trials reported acute toxicity adequately. Data were therefore grouped and the number of toxic events was used to calculate a single OR for each site and grade. Late toxicity was rarely described so could only be reviewed qualitatively. MAIN RESULTS: Nineteen trials (17 published, two unpublished) were identified including 4580 patients, although due to patient exclusion and differential reporting 62-78% were available for the various analyses. The review strongly suggests chemoradiation improves overall survival and progression free survival, whether platinum was used or not with absolute benefits of 12% and 16% respectively. There was, however, statistical heterogeneity for these outcomes There was some evidence that the effect was greater in trials including a high proportion of stage I and II patients. Chemoradiation also showed significant benefit for both local and distant recurrence. Haematological and gastrointestinal toxicity was significantly greater in the concomitant chemoradiation group. Details of late morbidity were sparse. REVIEWER'S CONCLUSIONS: Concomitant chemotherapy and radiotherapy appears to improve overall survival and progression-free survival in locally advanced cervical cancer. It also reduces local and distant recurrence suggesting concomitant chemotherapy may afford cytotoxic and sensitisation effects. Some acute toxicity is increased, but data on long term side effects were sparse.

Combined Modality Therapy↗
PubMed2001

Comparison of nicardipine versus placebo to control hemodynamic responses during emergence and extubation.

OBJECTIVE: To compare 2 different doses of intravenous nicardipine versus placebo to control heart rate and blood pressure responses to emergence and extubation. DESIGN: Prospective, randomized, double-blind, placebo-controlled. SETTING: University hospital, single-institutional. PARTICIPANTS: Forty-five American Society of Anesthesiologists (ASA) class I through III adult patients. INTERVENTIONS: General endotracheal anesthesia was with oxygen and isoflurane and muscle relaxation. At the end of surgery, with at least 2 twitches present by nerve stimulator and end-tidal isoflurane <0.4%, reversal was accomplished with neostigmine and glycopyrrolate. Two minutes post-reversal, the study drug (nicardipine, 0.015 mg/kg; nicardipine, 0.03 mg/kg; or a saline placebo) was given. Heart rate and blood pressure were measured for every minute up to 10 minutes and at 15 minutes postreversal. MEASUREMENTS AND MAIN RESULTS: There were no significant differences among groups in age, gender, ASA class, weight, or heart rate. The nicardipine groups, 0.015 and 0.03 mg/kg, had lower blood pressure values than the placebo group. There was a significant difference in blood pressure among groups, with greater and more consistent attenuation of blood pressure occurring with the larger nicardipine dose. There were no episodes of hypotension or adverse events. CONCLUSIONS: Compared with placebo, both nicardipine doses attenuated blood pressure but not heart rate responses during emergence and extubation. Greater blood pressure control occurred with the larger nicardipine dose of 0.03 mg/kg.

Adult↗
PubMed2001

Regulation of the serotonin transporter by interacting proteins.

The serotonin transporter (SERT) plays a critical role in the maintenance of normal neurotransmission by serotonin [5-hydroxytryptamine (5-HT)]. Recent evidence suggests that SERT and other neurotransmitter transporters are tightly regulated. Activation of protein kinase C results in a decrease in SERT-mediated 5-HT uptake, which is due to an internalization of the transporter. However, to date little is known about the mechanism and proteins involved in the down-regulation of the transporter. One candidate SERT-regulatory protein is the SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein receptor) protein, syntaxin 1A (Syn1A), which has recently been implicated in the regulation of ion channels as well as the SERT-related gamma-aminobutyric acid- and glycine-transporters. Using 5-HT uptake assays, confocal microscopy and glutathione S-transferase (GST) pull-down assays we showed that Syn1A also interacts with SERT and alters the subcellular localization of the transporter, resulting in a reduction of 5-HT transport. In addition, we have used the yeast two-hybrid system to search for novel regulatory proteins that interact with the cytoplasmic N-terminal domain of SERT. By screening rat brain cDNA library we have identified six potential SERT-binding proteins. Here we also present progress towards the elucidation of the biological relevance of these proteins and their potential role for the regulation of the serotonin transporter.

Animals↗
PubMed2001

Pre-registration house officer rotations incorporating general practice: does the order of rotation matter?

CONTEXT: In relation to pre-registration house officer (PRHO) rotations incorporating general practice, previous research has recommended that where possible, no PRHO should undertake general practice as the first placement, because of the difficulties encountered. It was recognized that logistically, this could make such schemes almost unworkable. Within the context of a larger qualitative evaluation comparing how 24 PRHOs learned in hospital and general practice settings, the issue of rotation order was explored. METHODS: In-depth semistructured interviews were conducted with the 12 PRHOs who were involved in general practice rotations. They were interviewed at the beginning and end of the PRHO year, and following their return to hospital work after the general practice placement. RESULTS: Each rotation order had both advantages and disadvantages, with no particular rotation order being obviously better or worse for the PRHOs involved. CONCLUSIONS: This small qualitative evaluation has highlighted a number of advantages and disadvantages specific to each rotation order, and makes some practical recommendations to help alleviate the problems encountered. It is important that future evaluations of similar schemes consider this issue, as there are conflicting reports about the significance of the rotation order.

Attitude of Health Personnel↗
PubMed2001

A randomized, controlled, single-blind trial of teaching provided by a computer-based multimedia package versus lecture.

BACKGROUND: Computer-based teaching may allow effective teaching of important psychiatric knowledge and skills. AIMS: To investigate the effectiveness and acceptability of computer-based teaching. METHOD: A single-blind, randomized, controlled study of 166 undergraduate medical students at the University of Leeds, involving an educational intervention of either a structured lecture or a computer-based teaching package (both of equal duration). RESULTS: There was no difference in knowledge between the groups at baseline or immediately after teaching. Both groups made significant gains in knowledge after teaching. Students who attended the lecture rated their subjective knowledge and skills at a statistically significantly higher level than students who had used the computers. Students who had used the computer package scored higher on an objective measure of assessment skills. Students did not perceive the computer package to be as useful as the traditional lecture format, despite finding it easy to use and recommending its use to other students. CONCLUSIONS: Medical students rate themselves subjectively as learning less from computer-based as compared with lecture-based teaching. Objective measures suggest equivalence in knowledge acquisition and significantly greater skills acquisition for computer-based teaching.

Algorithms↗
PubMed2001

The doctor-patient relationship: from undergraduate assumptions to pre-registration reality.

OBJECTIVES: To describe the ways in which the doctor-patient relationship experienced by newly qualified pre-registration house officers (PRHOs) differed from their undergraduate expectations. DESIGN: Qualitative study in which in-depth semistructured interviews were carried out with each PRHO within 4-6 weeks of the start of their first job. SETTING: Three teaching hospitals, three district general hospitals and four general practices in south-east England. PARTICIPANTS: 24 newly qualified PRHOs. RESULTS: A number of differences were identified by PRHOs. These were caused in part by the impact of factors such as the shortage of time, which could lead to emotional 'blunting'. Some PRHOs were changing their ideas about what constitutes a 'good' doctor, and were redefining the meaning of a 'professional' relationship. The relationships of PRHOs with patients were also affected by the attitudes of their senior colleagues. For example, where PRHOs tried to maintain a patient-centred relationship, they could be identified by colleagues as working too slowly. PRHOs working in general practice were able to utilize and improve their communication skills with patients, but found it difficult to transfer these skills back into the hospital setting. CONCLUSIONS: Despite receiving substantial undergraduate education on how best to communicate with patients, a variety of factors conspired to prevent hospital-based PRHOs from utilizing this information. Building on these findings, a number of recommendations are made to help improve practice.

Communication↗
PubMed2001

The clinical and educational experiences of pre-registration house officers in general practice.

AIMS: To describe aspects of the clinical experience and educational supervision gained by pre-registration house officers (PRHOs) in general practice, and to relate these to the current General Medical Council (GMC) aims for general clinical training in general practice. DESIGN: Qualitative evaluation, part of which involved semistructured interviews with 12 PRHOs who were experiencing a general practice rotation. Interviews were conducted at the beginning and the end of the pre-registration year, and following return to hospital work after completion of the general practice placement. SETTINGS: Three teaching hospitals, two district general hospitals and six general practices in south-east England. PARTICIPANTS: 12 PRHOs who were involved in rotations incorporating a general practice placement. RESULTS: To varying degrees, the GMC aims for training in general practice were met for all the participants. All PRHOs recognized the value of the clinical experience and educational supervision they received in general practice. They particularly valued aspects such as having an individual training programme based on their own needs, and the interlinking of theory and practice, which aided learning. Most felt that having responsibility for their own patients acted as an important incentive for learning, and in general, PRHOs appreciated having the time to learn which general practice allowed. CONCLUSIONS: For the majority of PRHOs, the time spent in general practice was seen as a positive clinical and educational experience. In a variety of ways, the general practice placement encouraged PRHOs to develop the self-directed learning skills seen as essential to the lifelong learning advocated by the GMC. A number of recommendations are made to help improve the integration of the hospital and general practice components of these rotations.

Clinical Competence↗
PubMed2001

Occurrence and significance of gastric colonization during acid-inhibitory therapy.

There are now a wide variety of drugs available that are able profoundly to reduce the production of gastric acid. These drugs are currently widely prescribed for the treatment of peptic ulceration and gastro-oesophageal reflux disease. One of the main functions of gastric acid is to kill ingested bacteria. Colonization of the gastric lumen occurs in patients on anti-secretory medication, the degree of bacterial overgrowth depending upon the degree of elevation of the pH. There have been concerns that these bacteria may produce carcinogenic nitrosamines and increase the risk of gastric cancer, but there is at present no definitive evidence in support of this. A profound suppression of gastric acid may also facilitate the colonization of the upper small intestine, leading to deconjugation of the bile salts and malabsorption. There is some evidence that profound gastric acid suppression may decrease the number of ingested pathogens required to produce enteric disease. This chapter discusses these potential bacterial complications of therapeutic acid suppression and the evidence for them.

Achlorhydria↗
PubMed2001

Muscle soreness and damage parameters after prolonged intermittent shuttle-running following acute vitamin C supplementation.

Exercise-induced free-radical production may be partly responsible for muscle soreness and damage following demanding exercise. A number of studies have investigated the effect of antioxidant supplementation although there is a paucity of information regarding vitamin C. Therefore the aim of the present study was to investigate the effect of vitamin C supplementation on exercise-induced muscle soreness and damage. Nine habitually active males consumed a 1 g dose of vitamin C 2 h before exercise, and on another occasion consumed an identical placebo. The exercise comprised a 90 min intermittent shuttle-running test, which was designed to simulate the multiple-sprint sports. Vitamin C supplementation increased plasma concentrations of vitamin C before exercise, and plasma concentrations continued to increase during the shuttle-run to reach a peak of approximately 200 micromol x l(-1) immediately after exercise. However, muscle soreness, and markers of both muscle damage (creatine kinase and aspartate aminotransferase) and lipid peroxidation (malondialdehyde) were elevated to an equal extent after exercise in placebo and supplemented trials. Therefore acute supplementation with vitamin C had no beneficial effects although it is possible that such short-term vitamin C supplementation was ineffective because it occurred at an inappropriate time.

Administration, Oral↗
PubMed2001

Screening for amblyopia in preschool children: results of a population-based, randomised controlled trial. ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood.

INTRODUCTION: The rationale for preschool vision screening programmes has recently been questioned. Evidence about the effects of early treatment is needed, but it is not known how early the target conditions can reliably be detected. In this study, an intensive programme comprising several different screening methods, used at different ages up to 37 months, was compared with the usual practice of visual surveillance and ad hoc referrals. METHODS: Two groups were randomly selected from children in a population birth cohort study. The control group (n = 1461) received visual surveillance only. The intervention group (n = 2029) was offered in addition a programme of regular visual assessments by orthoptists testing visual acuity, ocular alignment, stereopsis and non-cycloplegic photorefraction. RESULTS: The intervention group programme yielded more children with amblyopia (1.6% vs. 0.5%, p < 0.01), and was more specific (95% vs. 92%, p < 0.01), than the control programme. The individual components of the intervention programme were compared. The cover test and visual acuity tests were poorly sensitive until the children were 37 months, but were always >99% specific. Photorefraction was more sensitive than acuity testing at all ages below 37 months, with specificity >95% at 31 and 37 months. CONCLUSIONS: Photorefraction would have detected more children less than 37 months of age with straight-eyed amblyopia than did visual acuity testing, but with more false positives. At 37 months, photorefraction plus a cover test would have been comparable in effectiveness to visual acuity testing plus a cover test.

Amblyopia↗
PubMed2001

Stereoacuity at age 3.5 y in children born full-term is associated with prenatal and postnatal dietary factors: a report from a population-based cohort study.

BACKGROUND: Observational studies suggested that breast-feeding benefits the visual development of preterm children, which has been attributed to the presence of docosahexaenoic acid (DHA) in breast milk but not most formula milks. Randomized studies showed that preterm children require a dietary supply of DHA in the first few weeks of life for optimal visual development, but it is unclear whether full-term children experience similar benefits from breast milk or DHA supplements. OBJECTIVE: The objective of this study was to compare stereoacuity at age 3.5 y in healthy, full-term children who were breast-fed and in similar children who had not been breast-fed after adjustment for socioeconomic status and maternal diet. DESIGN: Prospectively collected data on maternal diet during pregnancy (including intake of oily fish), the child's diet, and the socioeconomic status of the family were examined. Stereoacuity at age 3.5 y was assessed. RESULTS: Children who had been breast-fed for 4 mo were more likely to achieve high-grade stereopsis, or stereoscopic vision, than were children who had not been breast-fed (adjusted odds ratio: 2.77; 95% CI: 1.54, 4.97). The mother's antenatal blood DHA content was associated with her intake of oily fish (P < 0.0001). Children whose mothers ate oily fish during pregnancy were also more likely to achieve high-grade stereopsis than were children whose mothers did not eat oily fish (adjusted odds ratio: 1.57; 95% CI: 1.00, 2.45). CONCLUSIONS: The results of this study suggest that for full-term infants, breast-feeding is associated with enhanced stereopsis at age 3.5 y, as is a maternal DHA-rich antenatal diet, irrespective of later infant feeding practice.

Animals↗
PubMed2001

Written and computer-based self-help treatments for depression.

Patients and health purchasers are demanding the provision of effective and accessible mental health treatments. Psychotherapeutic approaches are popular with patients, but access to specialist psychotherapy services is often limited. Other ways of offering treatment within the time and resources available to most practitioners need to be considered. One possible solution is the use of structured self-help materials that address common mental disorders such as depression. Self-help treatments are available in a variety of formats such as books, CD-ROMS, audio and videotapes. Evidence exists for their effectiveness; however, a relatively neglected area has been a discussion of the educational aspects of such materials. Self-help materials aim to improve patient knowledge and skills in self-management. They require very clear educational goals and a content and structure that is appropriate for those who use them. Such work will enhance the credibility, take-up, and effectiveness of self-help materials within clinical settings.

Books↗
PubMed2001

Pre-registration house officers in general practice: the views of GP trainers.

BACKGROUND: Recent changes have led to an upsurge of interest in pre-registration rotations in general practice. In 1998, a national pilot programme of >40 new rotations incorporating general practice was implemented. OBJECTIVE: The aim of this study was to explore the experiences of GPs involved in the four pilot rotations established in South Thames region. METHODS: Semi-structured interviews were conducted with trainers and partners. RESULTS: The supervisory workload for pre-registration house officers (PRHOs) was much greater than that required by registrars. All GPs felt that increased remuneration was important for the future viability of the scheme. The majority of GPs remained supportive of the scheme, although a minority were concerned about the value of the experience gained by PRHOs. There were a few instances in which inadequacies in patient management had to be dealt with subsequently by trainers. The supervisory implications of such events will need to be addressed. CONCLUSION: This significant development in medical education has important implications for GPs and their patients which need further exploration through long-term evaluations.

Attitude of Health Personnel↗
PubMed2001

Lymphocytic hypophysitis in a man presenting with hypercalcemia.

A 59-year-old man with a 30-year history of type 2 diabetes mellitus presented with fatigue, confusion, and weight loss over a 3-month period. He was found to be hypercalcemic (11.8 mg/dL) and dehydrated, and his hypercalcemia improved with intravenous fluids. While in the hospital, he developed hyponatremia, hypoglycemia, and hypotension. He was found to have a subnormal cortisol level of 2.3 microg/dL at baseline, which increased to only 5.6 microg/dL 60 minutes after a 250-microg corticotropin intravenous stimulation test. The patient developed pneumonia and adult respiratory distress syndrome and died of an acute myocardial infarction. During the autopsy, he was found to have lymphocytic hypophysitis with a severe reduction in corticotropin-producing anterior pituitary cells. No malignancy was identified at autopsy. He is the first male patient to be described in the literature who presented with hypercalcemia caused by lymphocytic hypophysitis.

Autopsy↗