Search PubMed⌕ Search

Biomedical subjects

S Richardson

Publications and source records attributed to S Richardson.

At least 19 recordsLinked to original sources

Detection of severe acute respiratory syndrome coronavirus in stool specimens by commercially available real-time reverse transcriptase PCR assays.

Three commercially available real-time reverse transcriptase PCR assays (the Artus RealArt HPA coronavirus LightCycler, the Artus RealArt HPA coronavirus Rotor-Gene, and the EraGen severe acute respiratory syndrome coronavirus POL assay) and three RNA extraction methodologies were evaluated for the detection of severe acute respiratory syndrome coronavirus RNA from 91 stool specimens. The assays' sensitivities were highest (58% to 75%) for specimens obtained 8 to 21 days after symptom onset. The assays were less sensitive when specimens were obtained less than 8 days or more than 21 days after the onset of symptoms. All assays were 100% specific.

Feces↗

Cyclosporine profiling with C2 and C0 monitoring improves outcomes after heart transplantation.

BACKGROUND: Cyclosporine (CsA) level at 2 hours post-dose (C2) is a more sensitive marker for rejection risk than trough (C0) level. A combination of C2 and C0 monitoring may prove optimal. METHODS: We compared efficacy and safety outcomes among 28 de novo heart transplant patients in whom both C2 and C0 monitoring were undertaken (Group 1), with a single CsA profile at Weeks 2 to 6, versus 28 historic controls monitored by only C0 (Group 2). Patients received anti-thymocyte globulin (ATG) induction with CsA, steroids and azathioprine maintenance therapy. RESULTS: The CsA microemulsion dose was significantly higher in Group 1 than Group 2 up to 3 months post-transplant. Mean C2 values in Group 1 at 3 and 12 months were 1,248 +/- 328 ng/ml and 1,039 +/- 362 ng/ml, respectively. One patient in Group 1 and 7 in Group 2 (25%) discontinued CsA, either due to CsA-related neurotoxicity or two or more episodes of early rejection. At 12 months, graft and patient survival were 100% in both groups. Six patients in Group 1 (21%) and 11 in Group 2 (39%) had at least one episode of biopsy-proven acute rejection (not significant). Over the first 12 months post-transplant, the proportion of biopsies showing Grade 3 rejection was 5% in Group 1 and 11% in Group 2 (p < 0.002). Gloerular filtration rate (GFR) was significantly lower in Group 1 than Group 2 at both 3 and 12 months. CONCLUSIONS: Combined use of C2 and C0 monitoring results in improved efficacy versus C0 monitoring alone. Regular measurement of C2 levels should be undertaken in de novo heart transplant recipients.

Adult↗

Screening for amblyopia in childhood.

BACKGROUND: Amblyopia is a reversible deficit of vision that has to be treated within the sensitive period for visual development. Screening programmes have been set up to detect this largely asymptomatic condition and refer children for treatment while an improvement in vision is still possible. The value of such programmes and the optimum protocol for administering them remain controversial. OBJECTIVES: The objective of this review was to evaluate the effectiveness of vision screening in reducing the prevalence of amblyopia. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Eyes and Vision Group Trials Register, on The Cochrane Library Issue 2, 2005, MEDLINE (1966 to May 2005 week 1) and EMBASE (1980 to 2005 week 19). No language restrictions were placed on these searches. No handsearching was done. SELECTION CRITERIA: We planned to analyse data from randomised controlled trials and cluster-randomised trials comparing the prevalence of amblyopia in screened versus unscreened populations. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study abstracts identified by the electronic searches. Full text copies of appropriate studies were obtained and, where necessary, authors were contacted. No data were available for analysis and no meta-analysis was performed. MAIN RESULTS: Despite the large amount of literature available regarding vision screening no trials designed to compare the prevalence of amblyopia in screened versus unscreened populations were found. Data currently under preparation may be available for updates to the review. AUTHORS' CONCLUSIONS: The lack of data from randomised controlled trials makes it difficult to analyse the impact of existing screening programmes on the prevalence of amblyopia. The absence of such evidence cannot be taken to mean that vision screening is not beneficial; simply that this intervention has not yet been tested in robust trials. To facilitate such trials normative data on age-appropriate vision tests need to be available and a consensus reached regarding the definition of amblyopia. In addition, the consequences of living with untreated amblyopia have yet to be quantified and a cost-benefit analysis carried out.

Amblyopia↗

Screening for correctable visual acuity deficits in school-age children and adolescents.

BACKGROUND: Although the benefits of vision screening seem intuitive, the value of such programmes in junior and senior schools has been questioned. In addition to this there exists a lack of clarity regarding the optimum age, and frequency at which to carry out screening. OBJECTIVES: The objective of this review is to evaluate the effectiveness of vision screening programmes carried out in schools in reducing the prevalence of undetected, correctable visual acuity deficits due to refractive error in school-age children. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials - CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) on The Cochrane Library (Issue 3 2004), MEDLINE (1966 to August 2004) and EMBASE (1980 to August 2004). No language or date restrictions were placed on these searches. To date it has not been possible to carry out any manual searches but it is hoped to include these in a future update. SELECTION CRITERIA: We planned to include randomised controlled trials including randomised cluster controlled trials. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed study abstracts identified by the electronic searches. No trials were identified that met the inclusion criteria. MAIN RESULTS: As no trials were identified, no formal analysis was performed. A narrative synthesis of other retrieved studies was undertaken in order to explain current practice. AUTHORS' CONCLUSIONS: At present there are no robust trials available that allow the benefits of school vision screening to be measured. The disadvantage of attending school with a visual acuity deficit also needs to be quantified. The impact of a screening programme will depend on the geographical, and socio-economic setting in which it is conducted. There is therefore clearly a need for well planned randomised controlled trials, in various settings, to be undertaken so that the potential benefits and harms of vision screening can be measured.

Adolescent↗

Frisby Davis distance stereoacuity values in visually normal children.

AIMS: To establish the range of normal distance stereoacuity in young children using the Frisby Davis distance stereo test (FD2). METHODS: Children passing preschool vision screening assessments underwent measurement of distance stereoacuity with the FD2 using a standard testing protocol. RESULTS: 59 visually normal children aged between 36 months and 68 months were recruited to this study. All 59 were able to understand the test requirements and were examined with the FD2 stereo test. Four (6.8%) had no measurable stereoacuity; 13 (24%) had stereoacuity measurable only at a 3 metre testing distance (mean 92.3 seconds of arc; SD 52.6). These children were significantly younger than the remaining 42 (76%) who demonstrated a stereoacuity response at a 6 metre testing distance (mean 29.6 seconds of arc; SD 13.1, p=0.008). CONCLUSION: The FD2 stereo test enables the measurement of distance stereoacuity in young children. There appears to be a maturational effect with distance stereoacuity improving between 36 months and 68 months. The data on age related normal values will provide a baseline from which to compare outcomes in clinical populations.

Aging↗

Hypoxia inducible factor-1 and facilitative glucose transporters GLUT1 and GLUT3: putative molecular components of the oxygen and glucose sensing apparatus in articular chondrocytes.

Articular cartilage is an avascular connective tissue in which the availability of oxygen and glucose is significantly lower than synovial fluid and plasma. Glucose is an important metabolic fuel and structural precursor that plays a key role in the synthesis of extracellular matrix macromolecules in articular cartilage. However, glucose concentrations in cartilage can fluctuate depending on age, physical activity and endocrine status. Chondrocytes are glycolytic cells and must be able to sense the quantities of oxygen and glucose available to them in the extracellular matrix and respond appropriately by adjusting cellular metabolism. Consequently chondrocytes must have the capacity to survive in an extracellular matrix with limited nutrients and low oxygen tensions. The molecular mechanisms responsible for allowing chondrocytes to adapt to these harsh environmental conditions are poorly understood. In this article we present a novel "dual" model of oxygen and glucose sensing in chondrocytes based on recent experimental data. This model incorporates the hypoxia-inducible factor alpha (HIF-1alpha) as an oxygen sensor and the hypoxia responsive facilitative glucose transporters, GLUT1 and GLUT3 as putative components of the glucose sensing apparatus in chondrocytes. Recent studies have shown that GLUT1 and GLUT3 are both expressed in chondrocytes and their HIF-1alpha-mediated transcription may be dually stimulated in response to hypoxia and low glucose conditions which in turn promote anaerobic glycolysis in favor of oxidative phosphorylation. This working model provides, for the first time, a unifying hypothesis to explain how chondrocytes might sense and respond to low oxygen tensions and alterations in extracellular glucose.

Animals↗

Efficacy of donepezil in mild cognitive impairment: a randomized placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of the acetylcholinesterase inhibitor donepezil in a placebo-controlled trial in patients with mild cognitive impairment (MCI). METHODS: A total of 270 patients with MCI were enrolled in a 24-week, multicenter, randomized, double-blind, placebo-controlled study. Patients were randomized to receive donepezil (n = 133; 5 mg/day for 42 days, followed by forced dose escalation to 10 mg/day) or placebo (n = 137). Primary efficacy measures were the New York University (NYU) Paragraph Delayed Recall test and the Alzheimer disease (AD) Cooperative Study Clinician's Global Impression of Change for MCI (ADCS CGIC-MCI). Secondary efficacy measures included the modified AD Assessment Scale-cognitive subscale (ADAS-cog), the Patient Global Assessment (PGA), and additional neuropsychologic measures. Efficacy analyses were performed on intent-to-treat (ITT) and fully evaluable (FE) populations. RESULTS: Primary efficacy measures of the NYU Paragraph Recall test and the ADCS CGIC-MCI did not show significant treatment effects in the ITT population. Some secondary measures showed effects favoring donepezil. More donepezil-treated patients showed improvements in ADAS-cog total scores, in tests of attention and psychomotor speed, and in PGA scores. More donepezil-treated than placebo-treated patients experienced adverse events, most of which were mild to moderate and transient. CONCLUSION: Although significant treatment effects were not seen in the primary efficacy measures, outcomes on secondary measures suggest promising directions for further evaluation of donepezil treatment in patients with MCI.

Aged↗

Medical event profiling of COPD patients.

PURPOSE: This analysis proposes appropriate descriptive and analytical statistical techniques to profile medical events requiring GP consultation using the example of chronic obstructive pulmonary disease (COPD). METHODS: Consultation patterns were examined for 1807 cases with a diagnosis compatible with COPD in 1998 and a group of controls matched by sex, age and practice from the General Practice Research Database, a nationally representative UK primary care database. Consulting patterns by Read code chapter and chapter subdivision were examined using cluster analysis, logistic regression and classification and regression trees (CART). RESULTS: CART and multivariate logistic regression analyses suggested that COPD patients were more likely to consult with pulmonary circulatory disease (multivariate OR: 7.46 (95% confidence intervals: 2.05, 20.01) ), non-COPD respiratory diseases (2.77 (2.28, 3.37)), mycoses (2.0 (1.43, 2.71)), 'symptoms or ill-defined conditions' (1.95 (1.68, 2.29)), or other forms of heart disease (1.84 (1.92, 2.64)), and less likely to consult with hypertensive diseases (0.73 (0.57, 0.96)). Regression also showed positive associations with digestive system diseases (OR: 1.31 (1.02, 1.68)) and negative associations with 'other viral or chlamydial disease' (0.16 (0.03, 0.88)). A borderline significance reduced risk for cancers was seen in univariate logistic regression analyses. Cluster analyses were not useful in discriminating between cases and controls. CONCLUSIONS: These analyses provide information about the natural history of COPD and could be used to help interpret or detect adverse drug reactions if repeated before and after introduction of a treatment. COPD can be considered a multicomponent disease with more frequent comorbidities than age- and gender-matched individuals without COPD.

Aged↗

The Newcastle Control Score: a new method of grading the severity of intermittent distance exotropia.

AIM: To describe the development and application of a novel scoring system for grading the severity of intermittent distance exotropia (IDEX) and its potential application as an intervention criterion for surgical intervention. METHODS: The Newcastle Control Score (NCS) for IDEX was developed by incorporating both subjective (home control) and objective (clinic control) criteria into a scale to grade severity. The score structure described was evaluated for interobserver and test-retest reliability. To determine an optimal score threshold for surgical intervention, 170 cases of IDEX were scored retrospectively. Cure rates for surgical and non-surgical cases were then compared according to preoperative or presenting scores. RESULTS: Interobserver and test-test reliability were good (r = 0.82 and r = 0.89 respectively). Total cure rate with surgery was 54% and without surgery 18% (chi(2) = 23.093, df = 1, p<0.001). Significantly fewer patients with NCS >/=3 achieved cure without surgery than those with NCS 2 (chi(2) = 3.362, df = 1, p<0.047). CONCLUSIONS: The NCS is a reliable method for grading the severity of IDEX and aids decisions regarding intervention. Patients with a score of 3 or more are unlikely to attain a cure without surgery.

Child↗

Interventions for intermittent distance exotropia.

BACKGROUND: The clinical management of intermittent distance exotropia has been discussed frequently in the literature but there is a lack of clarity regarding the indications for intervention, the most effective type and the optimum age at which it should be carried out. OBJECTIVES: The objective of this review is to assess intervention criteria, the effects of various surgical and non-surgical treatments in people with intermittent distance exotropia and to determine the significance of factors such as age with respect to outcome. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials - CENTRAL (which contains the Cochrane Eyes and Vision Group trials register) on the Cochrane Library (Issue 4 2002), MEDLINE (1966 to November 2002), EMBASE (1980 to November 2002) and LILACS (Latin American and Caribbean Literature on Health Sciences) (1966 to 2002). We manually searched the British Orthoptic Journal, proceedings of the European Strabismological Association (ESA), International Strabismological Association (ISA) and American Academy of Paediatric Ophthalmology and Strabismus meeting (AAPOS). We contacted researchers who are active in the field for information about further published or unpublished studies. There were no language restrictions in the manual or electronic searches. SELECTION CRITERIA: We planned to include randomised controlled trials of any surgical or non-surgical treatment for intermittent distance exotropia. DATA COLLECTION AND ANALYSIS: Each reviewer independently assessed study abstracts identified from database and manual searches. Reviewer analysis was then compared and full papers for appropriate studies were obtained. MAIN RESULTS: No studies were found that met our selection criteria and therefore none were included for analysis. REVIEWER'S CONCLUSIONS: The available literature consists mainly of retrospective case reviews. These are difficult to compare and analyse due to a large variation in the definition of intermittent distance exotropia, intervention criteria and outcome measures. However there seems to be general agreement that non-surgical treatment is most appropriate in small angle deviations or as a supplement to surgery. Studies were found supporting both early and late surgical intervention so the optimal timing of surgical intervention cannot be concluded. Recent work indicates that bilateral surgery may be the most effective surgical procedure in these cases. There is clearly a need for carefully planned clinical trials to be undertaken to improve the evidence base for the management of this condition.

Exotropia↗

Molecular characterization and partial cDNA cloning of facilitative glucose transporters expressed in human articular chondrocytes; stimulation of 2-deoxyglucose uptake by IGF-I and elevated MMP-2 secretion by glucose deprivation.

OBJECTIVE: Recent evidence suggests that human chondrocytes express several facilitative glucose transporter (GLUT) isoforms and also that 2-deoxyglucose transport is accelerated by cytokine stimulation. The aim of the present investigation was to determine if human articular chondrocytes express any of the recently identified members of the GLUT/SLC2A gene family and to examine the effects of endocrine factors, such as insulin and IGF-I on the capacity of human chondrocytes for transporting 2-deoxyglucose. DESIGN/METHODS: PCR, cloning and immunohistochemistry were employed to study the expression of GLUT/SLC2A transporters in normal human articular cartilage. The uptake of 2-deoxyglucose was examined in monolayer cultured immortalized human chondrocytes following stimulation with TNF-alpha, insulin and IGF-I. Levels of MMP-2 were assessed by gelatin zymography following glucose deprivation of alginate cultures. RESULTS: Using PCR we detected transcripts for eight glucose transporter isoforms (GLUTs 1, 3, 6, 8, 9, 10, 11 and 12) and for a fructose transporter (GLUT5) in human articular cartilage. Expression of GLUT1, GLUT3 and GLUT9 proteins in normal human articular cartilage was confirmed by immunohistochemistry. The uptake of 2-deoxyglucose was dependent on time and temperature, inhibited by cytochalasin B and phloretin, and significantly accelerated in chondrocyte cultures stimulated with IGF-I. However, 2-deoxyglucose uptake was unaffected by short and long-term insulin treatment, which ruled out a functional role for insulin-sensitive GLUT4-mediated glucose transport. Furthermore, secretion of MMP-2 was increased in alginate cultures deprived of glucose. CONCLUSIONS: The data supports a critical role for glucose transport and metabolism in the synthesis and degradation of cartilage.

Blotting, Western↗

Cancer risks in populations living near landfill sites in Great Britain.

Previous studies have raised concerns about possible excess risks of bladder, brain and hepatobiliary cancers and leukaemias near landfill sites. Several cancers have been implicated, but no consistent pattern has emerged. We present a large nationwide analysis of selected cancers near landfill sites in Great Britain. The base population comprised people living within 2 km of 9565 (from a total of 19 196) landfill sites that were operational at some time from 1982 to 1997, with populations living more than 2 km from a landfill as reference. Risks of cancers at the above sites were computed with adjustment for age, sex, year of diagnosis, region and deprivation. National post-coded registers provided a total of 341 856 640 person-years for the adult cancer analyses and 113 631 443 person-years for childhood leukaemia. There were 89 786 cases of bladder cancer, 36 802 cases of brain cancer, 21 773 cases of hepatobiliary cancer, 37 812 cases of adult leukaemia and 3973 cases of childhood leukaemia. In spite of the very large scale of this national study, we found no excess risks of cancers of the bladder and brain, hepatobiliary cancer or leukaemia, in populations living within 2 km of landfill sites. The results were similar if the analysis were restricted to landfill sites licensed to carry special (hazardous) waste. Our results do not support suggestions of excess risks of cancer associated with landfill sites reported in other studies.

Child↗

A Bayesian partition model for case-control studies on highly polymorphic candidate genes.

We present a new statistical model for the analysis of case-control or cohort studies examining a highly polymorphic candidate disease susceptibility gene. Many genotypes are possible for such a gene. Consequently, the average number of subjects having each genotype will be modest. If analyzed separately, the risks associated with most genotypes will be estimated imprecisely. Our Bayesian partition model clusters genotypes according to risk, only allowing partitions that satisfy a particular assumption about the joint effect of the two alleles making up a genotype. This assumption is genetically plausible, imposes structure on the set of genotype risks, and still leaves a highly flexible model. By Bayesian model averaging over partitions, the model becomes, in effect, a semiparametric model for genotype risk. It allows borrowing of strength, i.e., estimates of risk for one genotype are informed by the risk estimates of all the genotypes. We present the results of fitting the model to two datasets, one simulated and one genuine case-control study of the NAT1 gene and lung cancer, and compare it in a simulation study with a haplotype relative risk model. The partition model enables genotype risks to be estimated more accurately and the alleles to be ranked according to risk.

Bayes Theorem↗

Human articular chondrocytes express three facilitative glucose transporter isoforms: GLUT1, GLUT3 and GLUT9.

Glucose is an important metabolite and a structural precursor for articular cartilage and its transport has significant consequences for cartilage development and functional integrity. In this study the expression of facilitative glucose transporters (GLUTs) in human chondrocytes was investigated. Results showed that at least three GLUT isoforms (GLUT1, GLUT3 and GLUT9) are expressed by normal chondrocytes. Given the central role of glucose in chondrocyte physiology and metabolism, its regular provision via GLUTs will influence the metabolic activity and survival of chondrocytes in cartilage matrices.

Cartilage, Articular↗

Variable selection and Bayesian model averaging in case-control studies.

Covariate and confounder selection in case-control studies is often carried out using a statistical variable selection method, such as a two-step method or a stepwise method in logistic regression. Inference is then carried out conditionally on the selected model, but this ignores the model uncertainty implicit in the variable selection process, and so may underestimate uncertainty about relative risks. We report on a simulation study designed to be similar to actual case-control studies. This shows that p-values computed after variable selection can greatly overstate the strength of conclusions. For example, for our simulated case-control studies with 1000 subjects, of variables declared to be 'significant' with p-values between 0.01 and 0.05, only 49 per cent actually were risk factors when stepwise variable selection was used. We propose Bayesian model averaging as a formal way of taking account of model uncertainty in case-control studies. This yields an easily interpreted summary, the posterior probability that a variable is a risk factor, and our simulation study indicates this to be reasonably well calibrated in the situations simulated. The methods are applied and compared in the context of a case-control study of cervical cancer.

Analysis of Variance↗

Risk of adverse birth outcomes in populations living near landfill sites.

OBJECTIVE: To investigate the risk of adverse birth outcomes associated with residence near landfill sites in Great Britain. DESIGN: Geographical study of risks of adverse birth outcomes in populations living within 2 km of 9565 landfill sites operational at some time between 1982 and 1997 (from a total of 19 196 sites) compared with those living further away. SETTING: Great Britain. SUBJECTS: Over 8.2 million live births, 43 471 stillbirths, and 124 597 congenital anomalies (including terminations). MAIN OUTCOME MEASURES: All congenital anomalies combined, some specific anomalies, and prevalence of low and very low birth weight (<2500 g and <1500 g). RESULTS: For all anomalies combined, relative risk of residence near landfill sites (all waste types) was 0.92 (99% confidence interval 0.907 to 0.923) unadjusted, and 1.01 (1.005 to 1.023) adjusted for confounders. Adjusted risks were 1.05 (1.01 to 1.10) for neural tube defects, 0.96 (0.93 to 0.99) for cardiovascular defects, 1.07 (1.04 to 1.10) for hypospadias and epispadias (with no excess of surgical correction), 1.08 (1.01 to 1.15) for abdominal wall defects, 1.19 (1.05 to 1.34) for surgical correction of gastroschisis and exomphalos, and 1.05 (1.047 to 1.055) and 1.04 (1.03 to 1.05) for low and very low birth weight respectively. There was no excess risk of stillbirth. Findings for special (hazardous) waste sites did not differ systematically from those for non-special sites. For some specific anomalies, higher risks were found in the period before opening compared with after opening of a landfill site, especially hospital admissions for abdominal wall defects. CONCLUSIONS: We found small excess risks of congenital anomalies and low and very low birth weight in populations living near landfill sites. No causal mechanisms are available to explain these findings, and alternative explanations include data artefacts and residual confounding. Further studies are needed to help differentiate between the various possibilities.

Congenital Abnormalities↗

Acute childhood encephalitis and Mycoplasma pneumoniae.

In a prospective 5-year study of children with acute encephalitis, evidence of Mycoplasma pneumoniae infection was demonstrated in 50 (31%) of 159 children. In 11 (6.9%) of these patients, M. pneumoniae was determined to be the probable cause of encephalitis on the basis of its detection in cerebrospinal fluid (CSF) by polymerase chain reaction (PCR) or by positive results of serologic tests for M. pneumoniae and detection of the organism in the throat by PCR. CSF PCR positivity correlated with a shorter prodromal illness (P=.015) and lack of respiratory symptoms (P=.06). Long-term neurologic sequelae occurred in 64% of probable cases. Thirty children (18.9%) who were seropositive for M. pneumoniae but did not have the organism detected by culture or PCR had convincing evidence implicating other organisms as the cause of encephalitis, suggesting that current serologic assays for M. pneumoniae are not sufficiently specific to establish a diagnosis of M. pneumoniae encephalitis.

Acute Disease↗