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Biomedical subjects

J G Williams

Publications and source records attributed to J G Williams.

At least 19 recordsLinked to original sources
PubMed2005

Fluorescence in situ hybridisation analysis of chromosomal aberrations in gastric tissue: the potential involvement of Helicobacter pylori.

In this series of experiments, a novel protocol was developed whereby gastric cells were collected using endoscopic cytology brush techniques, and prepared, such that interphase fluorescence in situ hybridization (FISH) could be performed. In total, 80 distinct histological samples from 37 patients were studied using four chromosome probes (over 32,000 cells analysed). Studies have previously identified abnormalities of these four chromosomes in upper GI tumours. Using premalignant tissues, we aimed to determine how early in Correa's pathway to gastric cancer these chromosome abnormalities occurred. Aneuploidy of chromosomes 4, 8, 20 and 17(p53) was detected in histologically normal gastric mucosa, as well as in gastritis, intestinal metaplasia, dysplasia and cancer samples. The levels of aneuploidy increased as disease severity increased. Amplification of chromosome 4 and chromosome 20, and deletion of chromosome 17(p53) were the more common findings. Hence, a role for these abnormalities may exist in the initiation of, and the progression to, gastric cancer. Helicobacter pylori infection was determined in premalignant tissue using histological analysis and PCR technology. Detection rates were comparable. PCR was used to subtype H. pylori for CagA status. The amplification of chromosome 4 in gastric tissue was significantly more prevalent in H. pylori-positive patients (n=7) compared to H. pylori-negative patients (n=11), possibly reflecting a role for chromosome 4 amplification in H. pylori-induced gastric cancer. The more virulent CagA strain of H. pylori was associated with increased disease pathology and chromosomal abnormalities, although numbers were small (CagA+ n=3, CagA- n=4). Finally, in vitro work demonstrated that the aneuploidy induced in a human cell line after exposure to the reactive oxygen species (ROS) hydrogen peroxide was similar to that already shown in the gastric cancer pathway, and may further strengthen the hypothesis that H. pylori causes gastric cancer progression via an ROS-mediated mechanism.

Aged↗
PubMed2005

Systematic review of prevalence studies of autism spectrum disorders.

AIM: To quantitatively examine the influence of study methodology and population characteristics on prevalence estimates of autism spectrum disorders. METHODS: Electronic databases and bibliographies were searched and identified papers evaluated against inclusion criteria. Two groups of studies estimated the prevalence of typical autism and all autism spectrum disorders (ASD). The extent of variation among studies and overall prevalence were estimated using meta-analysis. The influence of methodological factors and population characteristics on estimated prevalence was investigated using meta-regression and summarised as odds ratios (OR). RESULTS: Forty studies met inclusion criteria, of which 37 estimated the prevalence of typical autism, and 23 the prevalence of all ASD. A high degree of heterogeneity among studies was observed. The overall random effects estimate of prevalence across studies of typical autism was 7.1 per 10,000 (95% CI 1.6 to 30.6) and of all ASD was 20.0 per 10,000 (95% CI 4.9 to 82.1). Diagnostic criteria used (ICD-10 or DSM-IV versus other; OR = 3.36, 95% CI 2.07 to 5.46), age of the children screened (OR = 0.91 per year, 95% CI 0.83 to 0.99), and study location (e.g. Japan versus North America; OR = 3.60, 95% CI 1.73 to 7.46) were all significantly associated with prevalence of typical autism. Diagnostic criteria, age of the sample, and urban or rural location were associated with estimated prevalence of all ASD. CONCLUSIONS: Sixty one per cent of the variation in prevalence estimates of typical autism was explained by these models. Diagnostic criteria used, age of children screened, and study location may be acting as proxies for other study characteristics and require further investigation.

Age Factors↗
PubMed2004

Clinical guidelines online: do they improve compliance?

BACKGROUND: The introduction of intranet services in a district general hospital provided an opportunity to put evidence based national guidelines online to facilitate access and promote application of best practice in acute medical care. This study evaluated the effectiveness of this approach. METHOD: Local guidelines were made available online at ward terminals after they had been distributed in paper form. An interrupted time series design was used to evaluate the impact on compliance with three preselected guidelines, which addressed the management of suspected deep vein thrombosis, upper gastrointestinal bleeding, and stroke. This was supplemented by a qualitative assessment of the views of medical staff. RESULTS: There was a significant increase in the adherence to the guidelines for stroke when they were made available online, but this was not demonstrable for deep vein thrombosis or upper gastrointestinal bleeding. Qualitative interviews with junior medical staff and consultants after the study was completed revealed that there was confusion regarding the application of the guidelines for deep vein thrombosis and little active support from the gastroenterologists for the guidelines for upper gastrointestinal bleeding. The stroke guidelines were actively promoted by their author and widely supported. CONCLUSION: Making guidelines available online will not be effective unless they are actively promoted and represent a consensus view.

Algorithms↗
PubMed2003

Upper airways abnormalities and tracheal problems in Morquio's disease.

Morquio's disease is a metabolic disorder that can cause various respiratory abnormalities. Patients who live into adulthood are likely to develop upper airway problems and respiratory failure. With advances in home ventilation, these patients are increasingly likely to be referred to specialist respiratory units. We describe our experiences with two such patients.

Adult↗
PubMed2003

Can randomised trials rely on existing electronic data? A feasibility study to explore the value of routine data in health technology assessment.

OBJECTIVES: To estimate the feasibility, utility and resource implications of electronically captured routine data for health technology assessment by randomised controlled trials (RCTs), and to recommend how routinely collected data could be made more effective for this purpose. DATA SOURCES: Four health technology assessments that involved patients under care at five district general hospitals in the UK using four conditions from distinct classical specialties: inflammatory bowel disease, obstructive sleep apnoea, female urinary incontinence, and total knee replacement. Patient-identifiable, electronically stored routine data were sought from the administration and clinical database to provide the routine data. REVIEW METHODS: Four RCTs were replicated using routine data in place of the data already collected for the specific purpose of the assessments. This was done by modelling the research process from conception to final writing up and substituting routine for designed data activities at appropriate points. This allowed a direct comparison to be made of the costs and outcomes of the two approaches to health technology assessment. The trial designs were a two-centre randomised trial of outpatient follow-up; a single-centre randomised trial of two investigation techniques; a three-centre randomised trial of two surgical operations; and a single-centre randomised trial of perioperative anaesthetic intervention. RESULTS: Generally two-thirds of the research questions posed by health technology assessment through RCTs could be answered using routinely collected data. Where these questions required analysis of NHS resource use, data could usually be identified. Clinical effectiveness could also be judged, using proxy measures for quality of life, provided clinical symptoms and signs were collected in sufficient detail. Patient and professional preferences could not be identified from routine data but could be collected routinely by adapting existing instruments. Routine data were found potentially to be cheaper to extract and analyse than designed data, and they also facilitate recruitment as well as have the potential to identify patient outcomes captured in remote systems that may be missed in designed data collection. The study confirmed previous evidence that the validity of routinely collected data is suspect, particularly in systems that are not under clinical and professional control. Potential difficulties were also found in identifying, accessing and extracting data, as well as in the lack of uniformity in data structures, coding systems and definitions. CONCLUSIONS: Routine data have the potential to support health technology assessment by RCTs. The cost of data collection and analysis is likely to fall, although further work is required to improve the validity of routine data, particularly in central returns. Better knowledge of the capability of local systems and access to the data held on them is also essential. Routinely captured clinical data have real potential to measure patient outcomes, particularly if the detail and precision of the data could be improved.

Arthroplasty, Replacement, Knee↗
PubMed2003

Measuring the completeness and currency of codified clinical information.

OBJECTIVES: The paper describes how an objective score (CCscore) of the 'completeness' and 'currency' of codified clinical information relevant to the management of diabetes mellitus may be derived for individual practices. METHODS: A questionnaire was developed and administered to 35 practices and statistical methods were used to test for correlation between the prevalence for diabetes mellitus and the relevant CCscores RESULTS: No significant correlation could be found. CONCLUSIONS: The 'quality' of computer-stored information varies widely across English General practices for reasons that are incompletely understood. We demonstrated how CCscores may be calibrated for different 'views' of 'relevance', 'completeness', and 'currency' and yet be consistent across practices for a given 'view'. The potential value of this score and how it may contribute to our understanding of variation in 'information quality' are discussed.

Benchmarking↗
PubMed2002

Pre-operative assessment of anal fistulas using endoanal ultrasound.

OBJECTIVE: To study the accuracy of endoanal ultrasound in pre-operative assessment of cryptoglandular anal fistulas, with respect to the site of the internal opening, type and depth of the fistula tract. PATIENTS AND METHODS: A consecutive series of 151 patients with anal sepsis underwent pre-operative endoanal ultrasound assessment of a suspected anal fistula. Hydrogen peroxide was used to define the tract when there was doubt as to the course of the fistula. All patients subsequently had surgical exploration under anaesthesia, irrespective of findings at sonography. The site of the internal opening, depth and type of fistula were recorded at surgery, and concordance with the ultrasound was assessed. RESULTS: One hundred and forty-five patients were subsequently shown to have a fistula at surgical exploration. Type of fistula: Two thirds were transsphincteric (63%) and one third were inter sphincteric (32%), with a few submucosal, and supra sphincteric fistulas. Ultrasound correctly predicted surgical findings in 82% of patients (124/151). Concordance was highest for transsphincteric fistulas (87%). Internal opening: Accuracy of predicting the site of the internal opening was 93% (140/151). The commonest site for the internal opening was the midline posteriorly (49%), followed by the midline anteriorly (25%), the rest lay laterally. Fistula depth: Ultrasound and surgical assessment of the depth of fistulas was concordant in 120 of 145 patients (83%). CONCLUSIONS: Endoanal ultrasound has a high accuracy of predicting the site of internal opening of an anal fistula. Endoanal ultrasound is able to assess the type and depth of a fistula. This information is useful for pre-operative planning of fistula treatment.

Journal Article↗
PubMed2002

Shared care in gastroenterology: GPs' views of open access to out-patient follow-up for patients with inflammatory bowel disease.

OBJECTIVE: The aim of this study was to ascertain GPs' views about open access to out-patient follow-up for patients with inflammatory bowel disease (IBD). METHODS: Semi-structured interviews and a postal survey were carried out in general practices in West Glamorgan UK, each with at least one IBD patient taking part in a randomized trial of open access versus routine follow-up, which has been reported elsewhere. A total of 112 GPs from 53 general practices who referred the 180 study patients to specialist gastroenterological care in Neath or Swansea were included in the study. Main outcome measures were GPs' experience of the trial; preferences between methods of out-patient follow-up; and their views about enhancing open access follow-up. RESULTS: Sixty-nine GPs from 40 practices took part in the practice-specific data collection and 91 returned 156 patient-specific questionnaires. They expressed a strong preference for open access follow-up, for both specific patients (108/156 patients) and IBD patients in general (47/69 GPs). Preference for extending open access follow-up to other chronic conditions was not so strong (21/69 GPs). A substantial number of GPs considered their experience of the trial limited (30/69), and few GPs were aware of the shared care guideline distributed before the trial started (8/69). Few GPs encountered any problems in the management of the study patients (9/69) and <50% of the GPs used a Cumulative Encounter Form (29/69) developed for the study. Most GPs were supportive of giving patients written guidelines (56/69) and establishing a gastroenterological (GI) nurse practitioner (45/69). CONCLUSIONS: Open access follow-up of patients with IBD is supported by GPs. The approach would probably be improved by the distribution of written information to patients, the establishment of a GI nurse practitioner and an integrated approach between the nurse, hospital specialist, GP and patient.

Ambulatory Care↗
PubMed2002

A review of oesophageal manometry testing in a district general hospital.

Although several modalities are available to investigate oesophageal motility disorders, manometry is the gold standard. The procedure is increasingly available in district general hospitals but the clinical utility of this investigation in this setting remains unclear. The aim in this study was to evaluate the use and outcome of oesophageal manometry in a district general hospital. Data on 100 consecutive oesophageal manometry procedures were analysed, taking into account the referral pattern, indications, and results. The indications were gastro-oesophageal reflux disease (preoperative assessment before fundoplication) (58), dysphagia (28), chest pain (12), and epigastric pain (2). Diagnoses were made using predefined standard criteria and were as follows: normal (41), non-specific motility disorder (NSMD) (38), achalasia (15), diffuse oesophageal spasm (4), and scleroderma (2). Of the 58 patients who had undergone manometry as a preoperative assessment of oesophageal motility, 27 (47%) were abnormal. Twenty five (43%) had NSMD and two (3%) had achalasia. Forty eight of these preoperative cases were combined with 24 hour pH recording, which confirmed acid reflux in 35 (73%). The experience reported here reflects the published evidence that the use of manometry is changing. It is now more commonly used for assessment before antireflux surgery and for dysphagia, and the use in the assessment of chest pain is declining. The findings confirm the importance of eliminating achalasia before inappropriate antireflux surgery.

Adolescent↗
PubMed2001

A Dictyostelium nuclear phosphatidylinositol phosphate kinase required for developmental gene expression.

The generation of diacylglycerol (DAG) in response to receptor stimulation is a well-documented signalling mechanism that leads to activation of protein kinase C (PKC). Putative alternative effectors contain sequences that interact with DAGs, but the mechanisms of signal transduction are unknown. We have identified a Dictyostelium gene encoding a novel protein which contains a domain with high identity to the DAG-binding domain of PKC. It does not encode a PKC homologue as the conservation does not extend outside this region. We confirm that the proposed DAG-binding domain is sufficient to mediate interaction of a fusion protein with vesicles containing DAG. The protein also shows significant homology to mammalian phosphatidylinositol phosphate (PIP) kinases and we show that this domain has PIP kinase activity. The protein, PIPkinA, is enriched in the nucleus and abrogation of gene function by homologous recombination inhibits early developmental gene expression, blocking development at an early stage. Thus, we have identified a PIP kinase from Dictyostelium which is required for development, is a candidate effector for DAG and has the potential to synthesize nuclear PIP(2).

Animals↗
PubMed2001

The road to extinction is paved with good intentions: negative association of fish hatcheries with threatened salmon.

Hatchery programmes for supplementing depleted populations of fish are undergoing a worldwide expansion and have provoked concern about their ramifications for populations of wild fish. In particular, Pacific salmon are artificially propagated in enormous numbers in order to compensate for numerous human insults to their populations, yet the ecological impacts of this massive hatchery effort are poorly understood. Here we test the hypothesis that massive numbers of hatchery-raised chinook salmon reduce the marine survival of wild Snake River spring chinook, a threatened species in the USA. Based on a unique 25-year time-series, we demonstrated a strong, negative relationship between the survival of chinook salmon and the number of hatchery fish released, particularly during years of poor ocean conditions. Our results suggest that hatchery programmes that produce increasingly higher numbers of fish may hinder the recovery of depleted wild populations.

Animals↗
PubMed2001

Protein tyrosine phosphatase PTP1 negatively regulates Dictyostelium STATa and is required for proper cell-type proportioning.

The protein tyrosine phosphatase PTP1, which mediates reversible phosphorylation on tyrosine, has been shown to play an important regulatory role during Dictyostelium development. Mutants lacking PTP1 develop more rapidly than normal, while strains that overexpress PTP1 display aberrant morphology. However, the signalling pathways involved have not been characterised. In reexamining these strains, we have found that there is an inverse correlation between levels of PTP1 activity, the extent of tyrosine phosphorylation on Dictyostelium STATa after treatment with cAMP, and the proportion of the slug population exhibiting STATa nuclear enrichment in vivo. This suggests that PTP1 acts to attenuate the tyrosine phosphorylation of STATa and downstream STATa-mediated pathways. Consistent with this, we show that when PTP1 is overexpressed, there is increased expression of a prestalk cell marker at the slug posterior, a phenocopy of STATa null slugs. In ptp1 null strains, STATa tyrosine phosphorylation and nuclear enrichment in the slug anterior is increased. There is also a change in the prestalk to prespore cell ratio. Synergy experiments suggest that this is due to a cell-autonomous defect in forming the subset of prespore cells that are located in the anterior prespore region.

Animals↗
PubMed2001

Development and initial validation of the Effort Sense Rating Scale (ESRS): a self-perceived index of physical fitness.

BACKGROUND: The Effort Sense Rating Scale is a non invasive, easy to administer, self-assessment device for deriving an index of physical fitness comprising only aerobic and anaerobic power components. The scale originates from the notion that people who have experienced varying degrees of effort doing "everyday" tasks can accurately estimate the exertion required in fairly common, physically demanding "situations" when provided with an appropriate perceptual frame-of-reference. Estimations elicited in this way can be scaled and used to categorize fitness level. This article reports an initial validity study. Further development of this technique is in progress. SAMPLE: Forty volunteers from a university community, mainly students (17 women and 23 men), completed ESRS twice and then underwent submaximal aerobic (cycle ergometry: YMCA protocol) and anaerobic power (Wingate protocol) assessments. RESULTS: Nonparametric correlation coefficients between the Effort Sense Rating Scale and the aerobic power were r(s) = 0.47 (P < 0.05) and anaerobic power r(s) = 0.62 (P < 0.05). Interpreted at the category level there was 77.5% agreement between ESRS indices and category levels for measured fitness components. Readministration of the Effort Sense Rating Scale after 14 days prior to physical assessments showed 100% consistency in choice of rating items with some changes in assigned values (r(s) = 0.86, P < 0.01). CONCLUSIONS: Modifications to the equivalence and selection of fitness elements and wording of the effort-demanding "scenarios," the discriminative level of the fitness categories, and broadening the size and composition of the validation sample are required to further enhance the veracity of the scale. Appropriately tuned, this perception-based approach to self-assessment of physical fitness can provide a low-cost, meaningful device for baseline setting and progress monitoring by people either entering or continuing with an exercise program for health-related fitness purposes.

Activities of Daily Living↗
PubMed2001

Autologous plasmin enzyme in the surgical management of diabetic retinopathy.

PURPOSE: This is a pilot study to assess the use of autologous plasmin enzyme (APE) as an adjunct to vitreous surgery in eyes with advanced diabetic retinopathy. DESIGN: Prospective noncomparative interventional case series. PARTICIPANTS: Seven patients with advanced diabetic retinopathy selected at random from our practice population. METHODS: Seven eyes were treated with APE as an adjunct to standard vitreous surgery. Six eyes had macular tractional retinal detachments, and one eye had refractory macular edema. Three fellow eyes had standard vitreous surgery performed for macular tractional retinal detachments without APE. All 10 eyes had macular edema and background diabetic retinopathy. MAIN OUTCOME MEASURES: The main outcome measures included induction of a posterior vitreous detachment, retinal reattachment, improvement in visual acuity, and resolution of macular edema. RESULTS: All seven APE-treated eyes achieved spontaneous or easy removal of the posterior hyaloid including one eye that had vitreoschisis over areas of detached retina. All eyes treated with APE had resolution of intraretinal edema. Retinas of all eyes treated with APE were reattached. The three fellow eyes were treated by vitreous surgery without APE. Two of the three fellow eyes had reattached retinas, but none had resolution of intraretinal edema without further focal photocoagulation treatment. Mean visual acuity improvement was 0.7 logarithm of the minimum angle of resolution (LogMAR) units in APE-treated eyes and 0.1 LogMAR units in eyes without APE. The average follow-up period was 14 months. CONCLUSIONS: This pilot study suggests that APE may be beneficial in the surgical management of diabetic retinopathy.

Adult↗
PubMed2001

Tyrosine phosphorylation-independent nuclear translocation of a dictyostelium STAT in response to DIF signaling.

We describe a Dictyostelium STAT, Dd-STATc, which regulates the speed of early development and the timing of terminal differentiation. Dd-STATc also functions as a repressor, which directs graded expression of the ecmA gene in different prestalk cell populations. Developing Dictyostelium cells produce a chlorinated hexaphenone, DIF, which directs prestalk cell differentiation. Dd-STATc is tyrosine phosphorylated, dimerizes, and translocates to the nucleus when cells are exposed to DIF. Surprisingly, however, SH2 domain-phosphotyrosine interaction is not necessary for the DIF-induced nuclear translocation of Dd-STATc. In this respect, Dd-STATc activation resembles several recently described, noncanonical mammalian STAT signaling processes. We show instead that DIF mediates nuclear translocation via sequences located in the divergent, N-terminal half of the Dd-STATc molecule.

Amino Acid Sequence↗
PubMed2001

Review article: balsalazide therapy in ulcerative colitis.

Balsalazide is a 5-aminosalicylic acid (mesalazine) pro-drug which has an inert carrier molecule instead of the sulfapyridine moiety of sulfasalazine. It is designed to deliver 5-aminosalicylic acid to the colonic mucosa without the sulfapyridine-associated side-effects encountered with sulfasalazine. Several studies have confirmed the efficacy and patient tolerance of balsalazide. When compared to mesalazine at equivalent doses, it induced symptomatic and complete remission of acute ulcerative colitis in a greater proportion of patients. In particular, patients with resistant left-sided disease were shown to have a higher probability of achieving remission. Balsalazide was beneficial in patients with troublesome nocturnal symptoms. It has a similar efficacy in maintaining remission when compared to sulfasalazine and mesalazine. The advantage of balsalazide over other 5-aminosalicylic acid compounds is its superior patient tolerability with minimal side-effects.

Aminosalicylic Acids↗