Biomedical subjects

S White

Publications and source records attributed to S White.

At least 19 recordsLinked to original sources

PubMed2006

Ensembl 2007.

The Ensembl (http://www.ensembl.org/) project provides a comprehensive and integrated source of annotation of chordate genome sequences. Over the past year the number of genomes available from Ensembl has increased from 15 to 33, with the addition of sites for the mammalian genomes of elephant, rabbit, armadillo, tenrec, platypus, pig, cat, bush baby, common shrew, microbat and european hedgehog; the fish genomes of stickleback and medaka and the second example of the genomes of the sea squirt (Ciona savignyi) and the mosquito (Aedes aegypti). Some of the major features added during the year include the first complete gene sets for genomes with low-sequence coverage, the introduction of new strain variation data and the introduction of new orthology/paralog annotations based on gene trees.

Animals↗

PubMed2006

The impact of clinical audit on antibiotic prescribing in general dental practice.

OBJECTIVE: To reduce the number of antibiotics inappropriately prescribed by general dental practitioners, and to increase overall prescription accuracy. DESIGN: A prospective clinical audit carried out between September and March of 2002-3 and 2003-4. SETTING: General dental practices in Eastern England. SUBJECTS AND METHODS: The pre-audit antibiotic prescribing practices of 212 general dental practitioners were recorded over an initial six week period. On each occasion this included which antibiotic had been chosen, together with its dose, frequency and duration, as well as the clinical condition and reason for which the prescription had been raised. When related to prophylaxis, the patient's medical history was also noted. Following education on contemporary prescribing guidelines, presentations which illustrated the practitioners' previous errors, and the agreement of standards to be achieved, the process was repeated for another six weeks, and the results compared. RESULTS: In the pre-audit period, 2,951 antibiotic prescriptions were issued, and during the audit this was reduced by 43.6% to 1,665. The majority were for therapeutic reasons, with only 10.5% and 13.6% for medical prophylaxis during the pre-audit and audit periods respectively. Over both periods, amoxicillin and metronidazole were the two most commonly prescribed antimicrobials (63.4% and 21.2% respectively). In the pre-audit period, only 43% of all prescriptions were error free in dose, frequency, and/or duration of use, but this rose significantly to 78% during the audit. Equally, using contemporary published guidelines, out of all the prescriptions made in the pre-audit period, only 29.2% were deemed to be justified, as compared to 48.5% during the audit. CONCLUSIONS: Clinical audit, in conjunction with education, and prescribing guidelines can favourably change antibiotic prescribing patterns among general dental practitioners.

Anti-Bacterial Agents↗

PubMed2006

CASP and CONSORT.

Explore the source record for details and available documents.

Anti-Infective Agents, Local↗

PubMed2006

Autonomic control of bronchial blood flow and airway dimensions during strenuous exercise in sheep.

BACKGROUND: During exercise and recovery the transient and steady-state changes in autonomic activity regulating lower airway blood flow and dimensions are unknown. The aim of this study was to define changes in bronchial blood flow (Q(br)) and dimensions during moderate and strenuous exercise, and to analyse the role of vagal and sympathetic nerves. METHODS: Nine ewes (34-44kg) underwent left thoracotomy during general anaesthesia (thiopentone/isoflurane) and either (5 sheep=Group 1) a pulsed Doppler transducer was placed on the bronchial artery, or (4 sheep=Group 2) a pulsed Doppler transducer was placed on the bronchial artery, and transit-time and single crystal sonomicrometers were mounted on the left main bronchus. These measured continuously Q(br), bronchial circumference (Circ(br)) and wall thickness (Th(br)). Aortic pressure (P(a)) and central venous pressure catheters were placed in the superficial cervical artery and vein. Trained sheep exercised on a horizontal treadmill, i.e. Group 1, moderate exercise 2.2mph over 1.6, 6min recovery, for analysis of changes in Q(br) before and after cholinoceptor blockade; Group 2, strenuous exercise 4.4mph over 2, 10min recovery for analysis of changes in Q(br) and airway dimensions, before and after cholinoceptor plus alpha(1)-, alpha(2)-adrenoceptor blockade. beta-adrenoceptor systems were intact. RESULTS: In Group 1 during moderate exercise P(a) and heart rate (HR) rose. Q(br) and blood flow conductance (C(br)) fell immediately to 83% (P<0.001) before returning toward resting levels, but fell when exercise ceased to 89% (P<0.01) before recovering. Prior cholinoceptor blockade abolished the immediate fall in Q(br) and C(br), but not the recovery vasoconstriction. Later in recovery the bronchial bed dilated progressively over 6min (P<0.05). In Group 2 during strenuous exercise P(a) and HR rose substantially. Q(br) and C(br) fell to 68% and 54% (P<0.001), respectively, and there was early vasoconstriction in recovery. Circ(br) fell immediately and remained at 93% (P<0.01), and did not recover fully when exercise ceased. Th(br) did not change during or after exercise. Prior cholinoceptor plus alpha-adrenoceptor block caused P(a) and Q(br) to fall slightly during exercise, but the bronchovascular constriction during and after exercise was abolished, as was circumferential shortening in the airway. CONCLUSIONS: At exercise onset and steady-state, resetting the arterial baroreflex upward in sheep increases parasympathetic cholinergic vasoconstrictor activity and causes bronchial wall and bronchovascular smooth muscle contraction in concert with sympathetic adrenergic constriction of systemic vascular beds. Whether the known sigmoid baroreflex control of tracheal smooth muscle tension at rest is extended to tracheobronchial smooth muscle and its circulation during exercise is yet to be determined.

Acetylcholine↗

PubMed2006

Effects of graded exercise on bronchial blood flow and airway dimensions in sheep.

Exercise stimulus-response relationships for airway blood supply and dimensions have not been described in mammalian species. These relationships are vital for postulates concerning integrated reflex factors normally controlling the airways and which may underlie the asthma syndromes of exercise. This study defines airways stimulus-response relationships in exercising sheep. Ewes between 35 and 40kg were instrumented at left thoracotomy under thiopentone/isoflurane general anaesthesia. Pulsed Doppler ultrasonic transducers were mounted on the bronchial artery, and transit-time plus single-crystal sonomicrometers on the left main bronchus. These recorded simultaneously and continuously bronchial blood flow (Q(br)) and conductance (C(br)), bronchial circumference (Circ(br)) and wall thickness (Th(br)). In Protocol 1 (P1), four sheep ran duplicate 5min protocols on a horizontal treadmill at continuous step-up-and-down speeds of 1min duration, namely, 0.8, 1.6, 2.2, 1.6 and 0.8mph (moderate exercise), followed by 10min recovery. In P2, four sheep ran duplicate 2min protocols at constant 4mph (strenuous exercise), and in P3, one sheep ran duplicate protocols each of 3min at 2.2, 4.4 and 6mph (severe exercise). Regression analysis and repeated measures ANOVA were used to assess differences between times, runs and exercise intensity. In P1, airway effects were directly related to graded exercise effort sustained over 5min. Peak effects occurred at 2.2mph, except for Th(br). Heart rate and P(a) rose (to 156% and 111% of resting, respectively), and Q(br) and C(br) fell (to 83% and 75%; both P<0.001). Circ(br) fell to 96% (P=0.02), and Th(br) rose at low speeds early and late, and thinned at the highest speed. In P2 and P3 for all variables the steady-state effects were systematically greater than for P1 (4.4mph: C(br) to 43%, Circ(br) to 93%; 6.6mph: C(br) to 25%, Circ(br) to 82%). There was no significant recovery hyperaemia, but there was residual post-exercise bronchoconstriction. The exercise stimulus-response relationships from rest to a maximal 6mph for sheep airway circumference and its bronchial circulation are inverse and functionally constrictor.

Animals↗

PubMed2006

Proliferation, steroid receptors and clinical/pathological response in breast cancer treated with letrozole.

Sixty-three postmenopausal women with large primary breast cancers were treated with neoadjuvant letrozole (2.5 mg daily) for 3 months. Tumour samples were taken at diagnosis and after 10-14 days and 3 months treatment. Immunohistochemical staining for Ki67, oestrogen receptor (ER) and progesterone receptor (PgR) was performed and related to clinical (ClinR) and pathological responses (PathR) after 3 months treatment. ClinR was observed in 48 of 63 cases (76.2%) and PathR in 47 of 62 (75.8%). Pretreatment Ki67 scores were similar in responders (R) and non-responders (NR). Highly significant Ki67 decreases occurred in all tumour subgroups at 10-14 days (P<0.005). A significant difference in Ki67 scores at 10-14 days (P<0.007) was found between PathR and PathNR but not between ClinR and ClinNR. At 3 months, decreases from pretreatment Ki67 scores were highly significant in all tumour subgroups irrespective of response status. However, whereas Ki67 scores were significantly different between pathological R and NR (P = 0.009), the corresponding comparison of ClinR status was not. Significant decreases between 10-14 days and 3 months were found only in ClinR and PathR (P = 0.02 and 0.045, respectively). Treatment significantly reduced PgR expression at 14 days and 3 months (both P<0.0001), but the level of changes was not different between response status groups. In summary, letrozole produces rapid and profound decreases in expression of Ki67 and PgR but changes do not always correlate with clinical and pathological responses.

Aged↗

PubMed2006

Ensembl 2006.

The Ensembl (http://www.ensembl.org/) project provides a comprehensive and integrated source of annotation of large genome sequences. Over the last year the number of genomes available from the Ensembl site has increased from 4 to 19, with the addition of the mammalian genomes of Rhesus macaque and Opossum, the chordate genome of Ciona intestinalis and the import and integration of the yeast genome. The year has also seen extensive improvements to both data analysis and presentation, with the introduction of a redesigned website, the addition of RNA gene and regulatory annotation and substantial improvements to the integration of human genome variation data.

Animals↗

PubMed2006

Dioxins and polychlorinated biphenyls (PCBs) in fish oil dietary supplements: occurrence and human exposure in the UK.

Commercially available fish oil supplements sourced from retail outlets in the UK, as well as by mail order, were surveyed in 2000-02 for dioxin (PCDD/Fs) and polychlorinated biphenyl (PCB) content. Sampled products were representative of market share. The WHO-TEQ values for these products ranged from 0.18 to 8.4 ng kg-1 for SigmaPCDD/F and from 1.1 to 41 ng kg-1 for Sigma dioxin-like PCBs. The results suggest a downward trend in the levels of dioxins in fish oil supplements over the last decade, since levels for similar products ranged from 0.3 to 10 ng kg-1 for SigmaPCDD/F WHO-TEQ in 1996. Levels of ICES (International Council for the Exploration of the Seas) 7 PCBs in the current study ranged from 8.3 to 267 microg kg-1. Subsequent to this survey, European Union legislation has been introduced that includes a maximum limit of 2 ng kg-1 WHO-TEQ for dioxins in fish oil products for human consumption. Twelve of the 33 products reported here would have exceeded this limit. Negotiations are in progress to incorporate dioxin-like PCBs into the European Union regulations. When manufacturer-recommended doses were applied to the observed levels, the estimated upper bound human exposure to dioxins and dioxin-like PCBs from dietary intake of these products ranged from 0.02 to 7.1 pg WHO-TEQ kg-1 body weight day-1 for adults and from 0.02 to 10 pg WHO-TEQ kg-1 body weight day-1 for schoolchildren. This level rises to 1.8-8.9 pg WHO-TEQ kg-1 body weight day-1 for adults and 1.4-14 pg WHO-TEQ kg-1 body weight day-1 for schoolchildren when combined with the average exposure from the whole diet in 1997. Again, subsequent to this survey, the Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT) revised the UK tolerable daily intake (TDI) for mixtures of dioxins and dioxin-like PCBs from 10 to 2 pg WHO-TEQ kg-1 body weight day-1. This is in line with the tolerable weekly intake (TWI) of 14 pg WHO-TEQ kg-1 body weight set by the Scientific Committee on Food (SCF).

Dietary Supplements↗

PubMed2006

Bereaved adults with intellectual disabilities: a combined randomized controlled trial and qualitative study of two community-based interventions.

BACKGROUND: Bereaved adults with intellectual disabilities are known to experience prolonged and atypical grief which is often unrecognized. The aim of this project was to find an effective way to improve mental health and behavioural outcomes. METHODS: Subjects were randomized to two different therapeutic interventions: traditional counselling by volunteer bereavement counsellors, and an integrated intervention delivered by carers which offered bereavement specific support. Qualitative and quantitative methods were used to determine their effectiveness and efficacy. RESULTS: The counselling intervention resulted in measurable gains both clinically and in terms of quality of life; the second intervention proved impracticable in most settings and no improvement in mental health or behaviour resulted. CONCLUSIONS: Despite small numbers, the quantitative findings were highly significant, were supported by the qualitative data, and were of practical relevance to primary care practitioners and specialist mental health and intellectual disability staff.

Adult↗

PubMed2006

Factors in decision making following genetic counseling for pre-natal diagnosis of de novo chromosomal rearrangements.

A retrospective survey of genetic counselors was conducted in order to identify practice patterns and factors that influence a patient's decision making when a de novo translocation is diagnosed pre-natally. Different variables that influence patients' decisions about pregnancy management were assessed and compared. Specifically, the type of rearrangement and/or knowledge of the breakpoints, risks provided for abnormal outcome, anxiety, fetal ultrasound findings and personal reasons for parental decisions were evaluated. Our findings suggest that patient anxiety level significantly predicts pregnancy management decisions. This information may be of benefit in identifying potential areas of education for genetic counselors as well as other health care providers.

Abortion, Induced↗

PubMed2005

Improved molecular diagnosis of dystrophinopathies in an unselected clinical cohort.

Mutations in the DMD gene result in Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). Readily available clinical tests detect only deletions of one exon or greater, which are found in approximately 60% of cases. Mutational analysis of other types of DMD mutations, such as premature stop codons and small frameshifting insertions or deletions, has historically been hampered by the large size of the gene. We have recently reported a method that allows the rapid and economical sequencing of the entire coding region of the DMD gene, and that is more sensitive than methods based on single-strand conformational polymorphism (SSCP) screening or other preliminary screening steps. Here we use single condition amplification/internal primer (SCAIP) sequencing analysis, in combination with multiplex amplifiable probe hybridization (MAPH) analysis of duplications, to report the frequency of mutations in a large cohort of unselected dystrophinopathy patients from a single clinic. Our results indicate that 7% of dystrophinopathy patients do not have coding region mutations, suggesting that intronic mutations are not uncommon. The availability of rapid and thorough mutation analysis from peripheral blood samples, along with an improved estimate of the percentage of non-coding region mutations, will be of benefit for improved genetic counseling and in identification of cohorts for clinical trials.

Codon, Nonsense↗

PubMed2005

Australian experience of a modified schedule of FOLFOX with high activity and tolerability and improved convenience in untreated metastatic colorectal cancer patients.

This study determined the efficacy and safety of a modified FOLFOX regimen that improved patient convenience without compromising oxaliplatin dose intensity. A total of 62 patients with previously untreated metastatic colorectal cancer were enrolled to receive, entirely as outpatients, 2-weekly cycles of oxaliplatin 100 mg m(-2) i.v. over 2 h, together with leucovorin 400 mg m(-2) over 2 h, 5-fluorouracil (5-FU) 400 mg m(-2), bolus, followed by a 46-h infusion of 5-FU at 2.4 g m(-2). Treatment was given until progression or unmanageable toxicity. In all, 61 patients received > or =one oxaliplatin dose and a median of 11 treatment cycles (range 1-20 cycles); 22 (36%) reported grade 3/4 neutropenia and 13 patients (21%) experienced grade 3 neurotoxicity; 16 patients (26%) discontinued treatment due to disease progression or death, 15 (25%) due to neurotoxicity and six (10%) due to haematological toxicity. Of the 56 eligible patients, complete or partial responses were observed in 29 or 52% (95% confidence interval 38-65%). Median progression-free survival was 8.2 months (7.1-9.9) and median overall survival was 18.7 months (14.0-23.4). In our experience, a modified schedule of FOLFOX improves convenience without compromising efficacy or toxicity.

Adult↗

PubMed2005

Ensembl 2005.

The Ensembl (http://www.ensembl.org/) project provides a comprehensive and integrated source of annotation of large genome sequences. Over the last year the number of genomes available from the Ensembl site has increased by 7 to 16, with the addition of the six vertebrate genomes of chimpanzee, dog, cow, chicken, tetraodon and frog and the insect genome of honeybee. The majority have been annotated automatically using the Ensembl gene build system, showing its flexibility to reliably annotate a wide variety of genomes. With the increased number of vertebrate genomes, the comparative analysis provided to users has been greatly improved, with new website interfaces allowing annotation of different genomes to be directly compared. The Ensembl software system is being increasingly widely reused in different projects showing the benefits of a completely open approach to software development and distribution.

Animals↗

PubMed2005

Prognostic significance of alarm symptoms in patients with gastric cancer.

BACKGROUND: The aim of this study was to determine the incidence and spectrum of alarm symptoms in patients with newly diagnosed gastric cancer, and to examine the relationship between symptoms and outcome. METHODS: Three hundred consecutive patients with gastric adenocarcinoma were studied prospectively. The outcomes of 40 patients (13.3 per cent) without alarm symptoms (21 men; median age 69 years) were compared with those of the 260 patients (86.7 per cent) with alarm symptoms (175 men; median age 72 years). RESULTS: It was possible to perform an R0 gastrectomy more often in patients without alarm symptoms (21 patients; 52 per cent) than in those with alarm symptoms (71 patients; 27.3 per cent) (chi(2) = 10.35, 1 d.f., P = 0.001). The cumulative survival rate at 5 years was 38 per cent for patients without alarm symptoms versus 15.0 per cent for those with alarm symptoms (chi(2) = 10.18, 1 d.f., P = 0.001). In a multivariate analysis, distant metastasis (hazard ratio (HR) 2.73 (95 per cent confidence interval (c.i.) 2.04 to 3.66); P < 0.001), overall stage of cancer (HR 1.83 (95 per cent c.i. 1.53 to 2.19); P < 0.001) and persistent vomiting at diagnosis (HR 1.66 (95 per cent c.i. 1.26 to 2.18); P < 0.001) were independently associated with length of survival. CONCLUSION: Alarm symptoms are absent in a significant minority of patients with gastric cancer at diagnosis; these patients stand a better chance of curative surgery and long-term survival than those with alarm symptoms.

Adenocarcinoma↗

PubMed2005

Involving the community in cervical cancer prevention programs.

Underutilization of cervical cancer prevention services by women in the high-risk age group of 30-60 years can be attributed to health service factors (such as poor availability, poor accessibility, and poor quality of care provided), to women's lack of information, and to cultural and behavioral barriers. The Alliance for Cervical Cancer Prevention (ACCP) partners have been working to identify effective ways to increase women's voluntary participation in prevention programs by testing strategies of community involvement in developing countries. The ACCP experiences include developing community partnerships to listen to and learn from the community, thereby enhancing appropriateness of services; developing culturally appropriate messages and educational materials; making access to high-quality screening services easier; and identifying effective ways to encourage women and their partners to complete diagnosis and treatment regimens. Cervical cancer prevention programs that use these strategies are more likely to increase demand, ensure follow-through for treatment, and ultimately reduce disease burden.

Ambulatory Care↗

PubMed2005

Aromatase inhibitors: cellular and molecular effects.

Marked cellular and molecular changes may occur in breast cancers following treatment of postmenopausal breast cancer patients with aromatase inhibitors. Neoadjuvant protocols, in which treatment is given with the primary tumour still within the breast, are particularly illuminating. In Edinburgh, we have shown that 3 months treatment with either anastrozole, exemestane or letrozole produces pathological responses in the majority of oestrogen receptor (ER)-rich tumours (39/59) as manifested by reduced cellularity/increased fibrosis. Changes in histological grading may also take place, most notably a reduction in mitotic figures. This probably reflects an influence on proliferation as most tumours (82%) show a marked decrease in the proliferation marker, Ki67. These effects are generally more dramatic than seen with tamoxifen given in the same setting. Differences between aromatase inhibitors and tamoxifen are also apparent in changes in steroid hormone expression. Thus, immuno-staining for progesterone receptor (PgR) is reduced in almost all cases by aromatase inhibitors, becoming undetectable in many. This contrasts with effects of tamoxifen in which the most common change on PgR is to increase expression. Changes in proliferation occur rapidly following the onset of exposure to aromatase inhibitors. Thus, neoadjuvant studies with letrozole in which tumour was sampled before and after 14 days and 3 months treatment show that decreased expression of Ki67 occur at 14 days and, in many cases, the effect is greater at 14 days than 3 months. These early changes precede evidence of clinical response but do not predict for it. However, this study design has allowed RNA analysis of sequential biopsies taken during the neoadjuvant therapy. Based on clustering techniques, it has been possible to subdivide tumours into groups showing distinct patterns of molecular changes. These changes in tumour gene expression may allow definition of tumour cohorts with differing sensitivity to aromatase inhibitors and permit early recognition of response and resistance.

Anastrozole↗

PubMed2005

Use of surrogate markers of biological agents in air and settled dust samples to evaluate a water-damaged hospital.

UNLABELLED: An environmental survey was conducted in two hospital buildings in Montana, one of which had historical water incursion on the top floors and higher prevalence of reported respiratory symptoms that improved when the occupants were away from work. We measured culturable fungi and bacteria, fungal spores, endotoxin, and sub-micron particles in air; and culturable fungi and bacteria, endotoxin, markers of fungi (extra-cellular polysaccharides specific for Penicillium/Aspergillus, ergosterol, and beta(1-->3) glucans) and cat allergen in chair and floor dusts. For the analytes measured in air, the correlation coefficients ranged from 0.43 to 0.78 (P < 0.05). In chair dust, beta(1-->3) glucan concentrations correlated with culturable fungi and ergosterol concentrations. We found that sub-micron particles and markers of microbiological agents, but not culturable microbiological agents, were significantly positively associated with the building that had both historical water damage and higher prevalence of reported respiratory symptoms. Chair dust measurements tended to be higher in the non-complaint building. These results suggest that air and floor dust measurements of marker compounds may be better indicators of current health risk in a water-damaged environment than chair dust measurements or measurements of culturable fungi or bacteria in air or settled dust. PRACTICAL IMPLICATIONS: Detection and quantification of nonculture-based microbiological markers and/or agents of disease may be useful methods to assess microbial contamination and to more accurately evaluate microbial exposures in the indoor environment for exposure-response studies.

Air Microbiology↗

PubMed2005

Heart and mind: (2) psychotropic and cardiovascular therapeutics.

There is a plausible biological basis for the association between psychiatric morbidity and cardiovascular disease. Anxiety, panic disorder, and depression are common in patients with coronary heart disease and hypertension. Despite this evidence there is poor recognition of anxiety disorders and depression in primary care and hospital medical practice. Concern also surrounds the use of psychotropic drugs in patients with cardiovascular disease. In the first of the two articles on this subject, we highlighted the current evidence regarding the association between cardiovascular and psychotropic conditions. In this second article, we discuss the interaction of the drugs used in the management of these two varied but commonly coexistent group of diseases as well as their relative effects on either system. Finally, we summarise the data regarding the safe use of these medications based on the recommendations from the currently available evidence.

Cardiovascular Agents↗