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Biomedical subjects

R White

Publications and source records attributed to R White.

At least 19 recordsLinked to original sources
PubMed2006

A blinded, randomized, multicenter study of an intravenous Staphylococcus aureus immune globulin.

OBJECTIVES: Very low birth weight (VLBW) infants are vulnerable to nosocomial infections and subsequent morbidity; including infections caused by Staphylococcus aureus: 85% of nosocomial S. aureus infections are caused by capsular polysaccharide (CPS) types 5 and 8. Altastaph is a polyclonal investigational human immunoglobulin G (IgG) with high levels of opsonizing S. aureus CPS types 5 and 8 IgG. METHODS: A Phase 2 clinical trial to assess the safety and kinetics of Altastaph in VLBW infants. Neonates in this multicenter study were randomized to receive two identical 20 ml/kg i.v. infusions of either 0.45% NaCl placebo or 1000 mg Altastaph/kg. Each infant was followed for 28 days after the second infusion or until discharge. Serum S. aureus CPS types 5 and 8 IgG levels were measured preinfusion and at various times after each infusion. RESULTS: Of 206 neonates, 158 received both infusions. Adverse events were similar in the two treatment groups. Six subjects (3% in each group) discontinued owing to an adverse event. Geometric mean anti-type 5 IgG levels were 402 and 642 mcg/ml 1 day following infusion of the first (day 0) and Second (day 14) doses, respectively, in neonates < or =1000 g and slightly higher in neonates 1001 to 1500 g. Trough levels before second infusion were 188 mcg/ml. Type 8 IgG levels were similar. Geometric mean IgG levels among placebo recipients were consistently <2 and <5 mcg/ml for types 5 and 8 in both weight groups. Three episodes of S. aureus bacteremia occurred in each arm. CONCLUSIONS: Infusion of Altastaph in VLBW neonates resulted in high levels of specific S. aureus types 5 and 8 CPS IgG. The administration of this anti-staphylococcal hyperimmune globulin was well tolerated in this population.

Bacterial Capsules↗
PubMed2006

The nuclear receptor co-repressor RIP140 controls the expression of metabolic gene networks.

NRs (nuclear receptors) regulate the expression of specific gene networks in target cells by recruiting cofactor complexes involved in chromatin remodelling and in the assembly of transcription complexes. The importance of activating gene expression, in metabolic tissues, is well established, but the contribution of transcriptional inhibition is less well defined. In this review, we highlight a crucial role for RIP140 (receptor-interacting protein 140), a transcriptional co-repressor for NR, in the regulation of metabolic gene expression. Many genes involved in lipid and carbohydrate metabolism are repressed by RIP140 in adipose and muscle. The repressive function of RIP140 results from its ability to bridge NRs to repressive enzyme complexes that modify DNA and histones. In the absence of RIP140, expression from many metabolic genes is increased so that mice exhibit a lean phenotype and resistance to high-fat-diet-induced obesity and display increased glucose tolerance and insulin sensitivity. We propose that a functional interplay between transcriptional activators and the co-repressor RIP140 is an essential process in metabolic regulation.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Bristol COPD Knowledge Questionnaire (BCKQ): testing what we teach patients about COPD.

Health professionals recommend education of patients about COPD. There is no satisfactory instrument to measure their knowledge and therefore to assess the results of education. A multiple-choice questionnaire (BCKQ) has been designed and tested. Each of 13 topics contains five statements for which there is a right or wrong answer. Its validity and consistency has been assessed, and the test re-test reliability and responsiveness measured after an interval of eight weeks. A copy of the multiple-choice questionnaire is given in the Appendix. The questionnaire was judged by patients and health professionals to have good content and face validity. It has good internal consistency for the 65 items. (Cronbach's alpha 0.73). It can be completed and scored within twenty minutes. The average score in subjects who had not received prior education was 54.7%. In a group not receiving education there was good test-retest reliability (r = 0.71). Following an eight-week education programme there was a significant improvement of 18.3 percentage points, and most of the increase was maintained for six months without any further formal education. BCKQ is suitable for both clinical and research purposes. It will test knowledge that is appropriate for COPD patients and can be used as an assessment tool for individual patients, or as a broad cross-sectional survey instrument. It will enable the effectiveness of education to be assessed and will be of value in developing and comparing different educational interventions.

Aged↗
PubMed2005

Localization and movement of mineral oil in plants by fluorescence and confocal microscopy.

Fluorescence and confocal laser scanning microscopy were explored to investigate the movement and localization of mineral oils in citrus. In a laboratory experiment, fluorescence microscopy observation indicated that when a 'narrow' distillation fraction of an nC23 horticultural mineral oil was applied to adaxial and opposing abaxial leaf surfaces of potted orange [Citrus x aurantium L. (Sapindales: Rutaceae)] trees, oil penetrated steadily into treated leaves and, subsequently, moved to untreated petioles of the leaves and adjacent untreated stems. In another experiment, confocal laser scanning microscopy was used to visualize the penetration into, and the subsequent cellular distribution of, an nC24 agricultural mineral oil in C. trifoliata L. seedlings. Oil droplets penetrated or diffused into plants via both stomata and the cuticle of leaves and stems, and then moved within intercellular spaces and into various cells including phloem and xylem. Oil accumulated in droplets in intercellular spaces and within cells near the cell membrane. Oil entered cells without visibly damaging membranes or causing cell death. In a field experiment with mature orange trees, droplets of an nC23 horticultural mineral oil were observed, by fluorescence microscopy, in phloem sieve elements in spring flush growth produced 4-5 months and 16-17 months after the trees were sprayed with oil. These results suggest that movement of mineral oil in plants is both apoplastic via intercellular spaces and symplastic via plasmodesmata. The putative pattern of the translocation of mineral oil in plants and its relevance to oil-induced chronic phytotoxicity are discussed.

Biological Transport↗
PubMed2005

OPA3 mutation screening in patients with unexplained 3-methylglutaconic aciduria.

We have screened 13 patients with neurological abnormalities and 3-methylglutaconic aciduria (3MGA) for mutations in the OPA3 gene, which are known to be the cause of Costeff syndrome (optic atrophy, chorea and spasticity; type III 3MGA). We aimed to explore whether mutations in the OPA3 gene are present in patients with 3MGA but without classic Costeff syndrome. OPA3 mutations (IVS1-1G>C) were identified in 2 patients with the classic phenotype of type III 3MGA, but not in the other 11 patients with differing non-Costeff phenotypes associated with developmental delay and neurological signs and symptoms as described. We identified a previously described sequence variation in the OPA3 gene (c.231T>C) in 12/13 patients. The alteration was homozygous in 8/12 and heterozygous in 4/12. This alteration was also found in 60 of 98 normal control alleles. In a single patient, a novel sequence variation in the 5' UTR was identified, (c.-38A>G). Our studies suggest that the c.231T>C sequence variation is of no clinical significance, whereas the significance of the 5' UTR sequence variation remains open to speculation. Our study of the OPA3 gene in patients with 3MGA without Costeff syndrome suggests that mutations in OPA3 are not a common cause of 3MGA in the absence of signs of Costeff syndrome.

5' Untranslated Regions↗
PubMed2005

Harmonic analysis of force platform data in normal and cerebral palsy gait.

BACKGROUND: Examination of force platform data during gait is usually carried out in the time domain and is limited to selected points on the force-time graphs. Harmonic analysis allows examination of the whole waveform and has a greater potential for assessing the effects of treatment options. Therefore, the objectives of this study were to show the benefits of using harmonic analysis to determine the variability and symmetry of force platform data in normal and cerebral palsy gait. METHODS: Harmonic analysis was carried out on the foot to ground reaction force data recorded from a group of cerebral palsy children and a matched control group when they walked at their preferred walking speed. Statistical tests were used to assess this frequency domain data and to validate the reconstructed force-time curves. FINDINGS: The differences in the frequency domain parameters between the cerebral palsy and control groups were significant. The mediolateral force was the most variable and asymmetric parameter in the control group. Cerebral palsy gait was more variable and more asymmetric than normal gait. INTERPRETATION: This study has shown that the force platform data derived from clinical gait analysis can reveal more useful information in the frequency domain than the limited time domain information commonly used for analysing this type of data.

Algorithms↗
PubMed2005

Diagnostic accuracy of self collected vaginal specimens for human papillomavirus compared to clinician collected human papillomavirus specimens: a meta-analysis.

BACKGROUND/OBJECTIVES: Providing summary recommendations regarding self collection of vaginal specimens for human papillomavirus (HPV) testing is difficult owing to the wide range of published estimates for the diagnostic accuracy of this approach. To determine summary estimates from analyses of reported findings of the sensitivity, specificity and summary receiver operating characteristic curves (SROC) for self collected vaginal specimens for HPV testing compared to the reference standard, clinician collected HPV specimens. METHODS: Standard search criteria for a diagnostic systematic review were employed. Eligible studies were combined using a random effects model and summary ROC curves were derived for overall and for specific subgroups. RESULTS: Summary measures were determined from 12 studies. Six studies where patients used Dacron or cotton swabs or cytobrushes to obtain samples were pooled and had an overall sensitivity of 0.74 (95% CI 0.61 to 0.84) and specificity of 0.88 (95% CI 0.83 to 0.92), with diagnostic odds ratio of 22.3 and an area under the curve of 0.91. Self specimens using Dacron or cotton swabs or cytobrushes collected by women enrolled at referral clinics had an overall sensitivity of 0.81 (95% CI 0.65 to 0.91) and specificity of 0.90 (95% CI 0.80 to 0.95). Sensitivity and specificity of tampons ranged from 0.67-0.94 and 0.80-0.85 respectively. CONCLUSIONS: Our findings indicate that the combined sensitivity for HPV-DNA is more than 70% when patients use Dacron swabs, cotton swabs, or cytobrushes to obtain their own vaginal specimens for HPV-DNA evaluation. Self collected HPV-DNA swabs may be an appropriate alternative for low resource settings or in patients reluctant to undergo pelvic examinations.

Area Under Curve↗
PubMed2004

The Gene Ontology (GO) database and informatics resource.

The Gene Ontology (GO) project (http://www. geneontology.org/) provides structured, controlled vocabularies and classifications that cover several domains of molecular and cellular biology and are freely available for community use in the annotation of genes, gene products and sequences. Many model organism databases and genome annotation groups use the GO and contribute their annotation sets to the GO resource. The GO database integrates the vocabularies and contributed annotations and provides full access to this information in several formats. Members of the GO Consortium continually work collectively, involving outside experts as needed, to expand and update the GO vocabularies. The GO Web resource also provides access to extensive documentation about the GO project and links to applications that use GO data for functional analyses.

Animals↗
PubMed2004

Complications of pancreaticoduodenectomy after neoadjuvant chemoradiation in patients with and without preoperative biliary drainage.

BACKGROUND: It has been suggested that preoperative biliary drainage increases the risk of infectious complications of pancreaticoduodenectomy. AIMS: The aim of this study was to assess complications related to biliary stents/drains and postoperative morbidity in patients undergoing neoadjuvant chemoradiotherapy for periampullary cancer. PATIENTS: One hundred and eighty-four patients with periampullary neoplasms were prospectively selected for neoadjuvant external beam radiation therapy and 5-fluorouracil-based chemotherapy between 1995 and 2002. METHODS: The data were retrospectively completed and analysed with respect to biliary drainage, efficacy and complications of endoscopic biliary stents and postoperative morbidity. Patients who had undergone a surgical biliary bypass were excluded. RESULTS: Data were completed in 168 patients. One hundred and nineteen patients were treated with endoscopic biliary stents, 18 patients had a percutaneous biliary drain and 31 patients did not require biliary drainage. Hospitalisation for stent-related complications was necessary in 15% of the patients with endoscopic biliary stents. Seventy-two patients underwent pancreaticoduodenectomy. There was no significant difference in the rate of wound infections, intra-abdominal abscesses and overall complications between the groups with and without preoperative biliary drainage. CONCLUSIONS: Postoperative infectious complications are common in patients both with and without preoperative biliary drainage. A statistically significant difference in complication rates was not observed between these groups.

Adult↗
PubMed2004

Reviewing measures of outcome: reliability of data extraction.

RATIONALE, AIMS AND OBJECTIVES: Although there is wide acceptance of the necessary domains for the evaluation of measures of health outcome, there has been little development or evaluation of methods of data extraction, such as checklists. This study aimed to assess the inter-rater reliability of data extraction from published articles using a new electronic database developed for structured reviews of health outcome measures. METHODS: Domains considered important in the evaluation of measures of health outcome provided the foundation for a checklist for data extraction using a new electronic database. The database utilized Microsoft Access 2000 software (Microsoft Corporation, 2000). Following training, three independent reviewers extracted data from seven selected articles using the electronic database, and assessed article and measure quality against pre-defined criteria. Data extraction was compared for consistency and item content. Inter-reviewer agreement for categorical data was assessed by multiple kappa correlation. RESULTS: Analysis demonstrated strong agreement between reviewers for all aspects of data extraction. However, lack of clarity in published articles affected the ability to clearly identify measures of outcome. CONCLUSIONS: The high level of inter-reviewer agreement supports the use of multiple trained reviewers in data extraction for reviews of measures of outcome using the checklist and Access software described. The electronic database supports standardized data extraction from published articles, benefiting from the combination of data extraction and data entry in a single step. Adaptation of the database to support structured reviews of measures of outcome adopted in the evaluation of other health states is proposed.

Ankle Injuries↗
PubMed2003

Alpha-substituted hydroxamic acids as novel bacterial deformylase inhibitor-based antibacterial agents.

We report the synthesis and biological activity of analogues of VRC3375 (N-hydroxy-3-R-butyl-3-[(2-S-(tert-butoxycarbonyl)-pyrrolidin-1-ylcarbonyl]propionamide), an orally active peptide deformylase inhibitor. This study explores the structure-activity relationship of various chelator groups, alpha substituents, P(2)' and P(3)' substituents in order to achieve optimal antibacterial activity with minimal toxicity liability.

Amidohydrolases↗
PubMed2003

Neutralizing antibodies during treatment of secondary progressive MS with interferon beta-1b.

OBJECTIVE: To investigate the relationship between neutralizing antibodies (NAB) and disease progression, relapses, and MR measures of MS. METHODS: Sequential serum samples from all 718 patients of the European Study Group in Interferon beta-1b in Secondary Progressive MS were analyzed to investigate relations between NAB and disease progression, relapses, and MR measures. RESULTS: This study showed no attenuating effect of NAB development on progression in disability. The effects of NAB on relapse rate showed substantial variation, depending on the statistical approach and definition of positivity, though analyses comparing low- and high-NAB+ periods with NAB- periods suggested a titer-related effect. MR T2 lesion volume changes from baseline were significantly higher for NAB+ patients but remained lower than for placebo patients. A substantial proportion of NAB+ patients became NAB-. No untoward effect of NAB development on safety was observed. CONCLUSION: These results support the conclusion that even though high NAB titers appear to have impact on treatment efficacy with respect to relapses, treatment decisions should be based primarily on clinical grounds.

Adult↗
PubMed2003

Semi-rigid vs rigid glass fibre casting: a biomechanical assessment.

OBJECTIVES: To determine if semi-rigid synthetic casts provide any measurable advantages compared to rigid synthetic casts. BACKGROUND: Glass fibre bandages are now commonly applied immediately post-injury to provide rigid immobilisation of the limb, for both weight bearing and non-weight bearing casts. However, composite casts that have inherent flexibility are also available and it is claimed they provide some functionality. METHODS: Five members of the orthopaedic department each applied a rigid and a semi-rigid below elbow (Colles) and a below knee walking cast to a single volunteer subject. Joint immobilisation and functional movement was assessed using electrogoniometry and limb support using pressure transducers. RESULTS: Semi-rigid Colles casts provided slightly greater immobilisation at the wrist while allowing full finger function and greater support to the forearm during hand movements. Similarly, semi-rigid below knee walking casts produced greater immobilisation at the ankle while allowing more forefoot movement and were less of an impediment to walking. CONCLUSIONS: Semi-rigid casting techniques have measurable advantages compared to rigid synthetic casts and represent a further development in the conservative management of fractures and soft tissue injuries. RELEVANCE: Semi-rigid casting is a relatively new technique that can reduce some of the problems of rigid cast immobilisation and could potentially shorten the rehabilitation phase following injury. Information about the performance of these casts to assess their value in specific applications is very limited.

Ankle Injuries↗
PubMed2003

Carcinoid tumors of the gastrointestinal tract. A review and the Duke University institutional overview.

Carcinoid tumors are relatively rare neoplasms arising from the amine precursor uptake and decarboxylation (APUD) cells of the gastrointestinal tract and bronchial tree. Presenting symptoms vary by site of origin, and various modalities may be used to diagnose them. Initial treatment is surgical, with procedure depending upon site of origin. Several experimental therapies may be used in treatment of metastatic carcinoid tumors.

Antineoplastic Agents↗
PubMed2003

Anesthesia for endovascular repair of abdominal and thoracic aortic aneurysms: a review article.

Open repair of abdominal aortic aneurysms (AAA) and thoracic aortic aneurysms (TAA) are associated with significant morbidity and mortality. Endovascular aortic aneurysm repair (EVAAR) using a stent graft is a new alternative to traditional open repair. There are various types of anesthesia which can be utilized for EVAAR; specifically general endotracheal anesthesia, regional anesthesia, and monitored anesthesia care (MAC) with local anesthetic infiltrated at the incision site. Choice of anesthetic technique may be dependent upon a patient's co-existing diseases. We have prepared a review article discussing the various types of anesthesia available for this procedure, including the specifics of each technique and pros and cons of each option. The most often utilized technique appears to be general anesthesia, often times related to surgeon unfamiliarity with the EVAAR procedure. Regional techniques, including continuous epidural or continuous spinal anesthesia are utilized in some cases with very good results. This technique can provide more hemodynamic stability and better pain control than general alternative, MAC with local, is an extremely safe and effective technique for the EVAAR procedure, especially in patients with severe co-existing diseases. In addition, this technique also minimalizes sedation and post-operative analgesic requirements, decreases cardiopulmonary complications, and decreases overall hospital stay, thereby reducing cost.

Anesthesia, General↗