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Biomedical subjects

N Robertson

Publications and source records attributed to N Robertson.

At least 19 recordsLinked to original sources
PubMed2006

cisRED: a database system for genome-scale computational discovery of regulatory elements.

We describe cisRED, a database for conserved regulatory elements that are identified and ranked by a genome-scale computational system (www.cisred.org). The database and high-throughput predictive pipeline are designed to address diverse target genomes in the context of rapidly evolving data resources and tools. Motifs are predicted in promoter regions using multiple discovery methods applied to sequence sets that include corresponding sequence regions from vertebrates. We estimate motif significance by applying discovery and post-processing methods to randomized sequence sets that are adaptively derived from target sequence sets, retain motifs with p-values below a threshold and identify groups of similar motifs and co-occurring motif patterns. The database offers information on atomic motifs, motif groups and patterns. It is web-accessible, and can be queried directly, downloaded or installed locally.

Animals↗
PubMed2006

Psychological morbidity and problems of daily living in people with visual loss and diabetes: do they differ from people without diabetes?

AIMS: To examine psychological adjustment and changes in the activities of daily living in relation to visual loss in diabetes. METHODS: This was an incident cohort, longitudinal, observational study contrasting the adjustment of individuals with visual loss associated with diabetes and those whose visual loss arose from other conditions; in the year subsequent to registration for blindness and 12 months later, 124 individuals participated in the study (51 with diabetes and 73 without). Participants provided demographic and biomedical information, and completed the Brief COPE, Hospital Anxiety and Depression Scale, SF-36, Instrumental Activities of Daily Living scale and Social Avoidance and Distress Scale via interview. People with diabetes were compared with those without. RESULTS: Both diabetic and non-diabetic groups showed elevated and comparable levels of psychological morbidity, sustained over time. Significant differences in functional adjustment were found at initial interview: people with diabetes having more problems coping but these were no longer present 1 year later. CONCLUSIONS: There was a significant and enduring elevation of anxiety and depression in those who were newly registered blind or visually handicapped. Taking these findings into account, psychological assessment should be developed for all those experiencing visual loss.

Activities of Daily Living↗
PubMed2005

Tailored interventions to overcome identified barriers to change: effects on professional practice and health care outcomes.

BACKGROUND: Strategies to implement change in health professional performance have variable impact. A potential explanation is that the barriers to implementation are different in different settings and at different times. Change may be more likely if the strategies were specifically chosen to address the identified barriers. OBJECTIVES: To assess the effectiveness of strategies tailored to address specific, identified barriers to change in professional performance. SEARCH STRATEGY: We searched the Cochrane Effective Practice and Organisation of Care Group (EPOC) specialised register and pending files until end of December 2002. English language articles only were included. SELECTION CRITERIA: Randomised controlled trials (RCTs) that reported objectively measured professional practice or health care outcomes in which at least one group received an intervention designed (or tailored) to address prospectively identified barriers to change. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed quality. We also contacted study authors to obtain any missing information. Quantitative and qualitative analyses were undertaken. MAIN RESULTS: We included 15 studies. For Comparison 1 (an intervention tailored to address identified barriers to change compared to no intervention or an intervention(s) not tailored to the barriers), there was no consistency in the results and the effect sizes varied both across and within studies.A meta-regression of a subset of the included studies, using a classical approach estimated a combined OR of 2.18 (95% CI: 1.09, 4.34), p = 0.026 in favour of tailored interventions. However, when a Bayesian approach was taken, meta-regression gave a combined OR of 2.27 (95% Credible Interval: 0.92, 4.75), which was not statistically significant. AUTHORS' CONCLUSIONS: Interventions tailored to prospectively identify barriers may improve care and patient outcomes. However, from the studies included in this review, we were unable to determine whether the barriers were valid, which were the most important barriers, whether all barriers were identified and if they had been addressed by the intervention chosen. Based on the evidence presented in this review, the effectiveness of tailored interventions remains uncertain and more rigorous trials (including process evaluations) are needed. Further research needs to address explicitly the questions of identifying and addressing barriers.

Humans↗
PubMed2003

Anti-reflux surgery for the neonatal intensive care-dependent infant.

AIM: The benefit of anti-reflux surgery for gastro-oesophageal reflux (GOR) in early infancy is uncertain. The aim of this study was to assess the value of Nissen fundoplication in a group of infants with severe GOR. METHODS: 10 infants underwent Nissen fundoplication for gastro-oesophageal reflux following a failure of medical management. All had suffered life-threatening respiratory episodes as a consequence of gastro-oesophageal reflux, and were neonatal intensive care-dependent. Median (range) birth weight was 1.26 kg (0.48-3.8 kg), gestation 30 weeks (25-38 weeks); at surgery, weight was 3.25 kg (2.5-6.1 kg) at a corrected age of 11.5 weeks (term-22) weeks. For each infant, the success of enteral feeding and the level of support required pre- and post-operatively was compared, and where appropriate, the facilitation of palliative feeding was assessed. Median follow-up was 14 (3-36) months. RESULTS: No infant suffered intra-operative morbidity or mortality. One infant died within 1 month of surgery from a collapse unrelated to surgery. Eight of nine surviving infants were discharged from intensive care following extubation and the establishment of enteral feeding. One patient died of severe bronchopulmonary dysplasia 3 months post-surgery. One infant developed a gastrostomy site infection, and two required gastrostomy tube replacement within 6 months of surgery. All were thriving at follow-up. Two infants with a congenital myopathy died as a result of their muscle disease at 9 and 11 months post-operatively. CONCLUSIONS: Nissen fundoplication is a feasible, effective and safe operation in severe gastro-oesophageal reflux unresponsive to medical treatment in term and pre-term infants. It has an additional important role in facilitating safe palliative enteral feeding in infants with a diagnosis incompatible with survival into adulthood.

Female↗
PubMed2001

Potassium bis(4,5-dimercapto-1,3-dithiole-2-thionato)nickelate 1,4,7,10,13,16-hexaoxa-2,3:11,12-dibenzocyclooctadeca-2,11-diene propanone solvate.

In the title compound, K[Ni(C(3)S(5))(2)] x C(20)H(24)O(6).C(3)H(6)O, K(+) is incorporated in the cavity of the 1,4,7,10,13,16-hexaoxa-2,3:11,12-dibenzocyclooctadeca-2,11-diene (DB18c6) molecule and is coordinated by the six DB18c6 O atoms and the propanone O atom. Two [K(+)(DB18c6)[(CH(3))(2)CO]] units form a dimer which is aligned in a one-dimensional manner along the a axis through a face-to-face interaction between the benzene rings of neighboring DB18c6 molecules. [Ni(dmit)(2)](-) anions are also aligned along the a axis through side-by-side S.S interactions.

Journal Article↗
PubMed2001

Effects of ras and von Hippel-Lindau (VHL) gene mutations on hypoxia-inducible factor (HIF)-1alpha, HIF-2alpha, and vascular endothelial growth factor expression and their regulation by the phosphatidylinositol 3'-kinase/Akt signaling pathway.

Many oncogenes induce expression of vascular endothelial growth factor (VEGF), a key factor in tumor angiogenesis. Phosphatidylinositol 3'-kinase (PI3K)/Akt is a common signaling pathway for oncogenes and tumor suppressor genes and is involved in VEGF regulation. Because hypoxia is a major stimulus for VEGF production, we examined the effects of LY294002, a selective PI3K inhibitor, on hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha expression and on endogenous VEGF responses to hypoxia. A panel of breast cancer cell lines reflecting the different genetic changes occurring in human breast cancer was analyzed. LY294002 inhibited HIF-1alpha induction and phosphorylation under hypoxia. However, HIF-2alpha expression was not affected. Basal and hypoxia-inducible VEGF expression was reduced at both mRNA and protein levels by 50%. V12-ras overexpression resulted in an increase in hypoxia-induced HIF-1alpha and HIF-2alpha expression. This effect was blocked by PI3K inhibitor, demonstrating one mechanism for ras synergy with hypoxia-mediated induction of genes. The decreased HIF-1alpha expression was not dependent on VHL interaction because a renal carcinoma cell line with VHL mutation and constitutive high HIF-1alpha expression also showed down-regulation of HIF-1alpha after treatment with LY294002. These results have implications for the use of PI3K inhibitors to inhibit synergistic effects of hypoxia with a wide range of common oncogenes.

Basic Helix-Loop-Helix Proteins↗
PubMed2001

Multiple sclerosis in sibling pairs: an analysis of 250 families.

OBJECTIVES: To assess the potential contribution of genetic factors to clinical phenotype in multiple sclerosis. METHODS: Using a cohort of 262 pairs of coaffected siblings from 250 families with multiple sclerosis, intersibling concordance analysis was used to explore underlying genetic mechanisms in disease pathogenesis by assessing parameters of disease course, clinical presentation, age and year of onset, and measures of disability and handicap. RESULTS: Adjusted intraclass correlation coefficients were not significant for either age of onset or for year of first symptom. One third of sibling pairs were concordant for presenting symptom (81/262), a result that was non-significant. However, course type was identical in 50% of the sibling pairs (kappa=0.17 (95% confidence interval (95% CI) 0.08 to 0.26)) indicating a significant result. Severity of the disease at assessment, using the Kurtzke and CAMBS scales, demonstrated that whereas there was no agreement for relapse rate in the previous year within the sibship, there was significant concordance for measures of disability (kappa=0.11 (95% CI 0.04 to 0.19)), progression (kappa=0.09 (95% CI 0.01 to 0.18)) and handicap (kappa=0.08 (95% CI 0.02 to 0.14)). CONCLUSIONS: Within a sibship, the clinical presentation tends to be different. However, once established, concordance is more likely to be seen for the ultimate course, leading in the end to similar disability and handicap scores. These results are consistent with the hypothesis that genes influence both disease susceptibility and evolution in multiple sclerosis.

Activities of Daily Living↗
PubMed2001

Twenty-four hours of mild hypothermia in unsedated newborn pigs starting after a severe global hypoxic-ischemic insult is not neuroprotective.

Three to 12 h of mild hypothermia (HT) starting after hypoxia-ischemia is neuroprotective in piglets that are anesthetized during HT. Newborn infants suffering from neonatal encephalopathy often ventilate spontaneously and are not necessarily sedated. We aimed to test whether mild posthypoxic HT lasting 24 h was neuroprotective if the animals were not sedated. Thirty-nine piglets (median weight 1.6 kg, range 0.8-2.2 kg; median age 24 h, range 7-48 h) were anesthetized and ventilated and subjected to a 45-min hypoxic (FiO(2) approximately 6%) global insult (n = 36) or sham hypoxia (n = 3). On reoxygenation, 18 were maintained normothermic (NT, 39.0 degrees C) for 72 h, and 21 were cooled from 39 (NT) to 35 degrees C (HT) for the first 24 h before NT was resumed (18 experimental, three sham hypoxia). Cardiovascular parameters and intermittent EEG were documented throughout. The brain was perfusion fixed for neuropathology and five main areas examined using light microscopy. The insult severity (duration in minutes of EEG amplitude < 7 microV) was similar in the NT and HT groups, mean +/- SD (28 +/- 7.2 versus 27 +/- 8.6 min), as was the mean FiO(2) (5.9 +/- 0.7 versus 5.8 +/- 0.8%) during the insult. Six NT and seven HT piglets developed posthypoxic seizures that lasted 29 and 30% of the time, respectively. The distribution and degree of injury (0.0-4.0, normal-maximal damage) within the brain (hippocampus, cortex/white matter, cerebellum, basal ganglia, thalamus) were similar in the NT and HT groups (overall score, mean +/- SD, 2.3 +/- 1.5 versus 2.4 +/- 1.3) as was the EEG background amplitude at 3 h (13 +/- 3.5 versus 10 +/- 3.3 microV). The HT animals shivered and were more active. The sham control group (n = 3) shivered but had normal physiology and neuropathology. Plasma cortisol was significantly higher in the HT group during the HT period, 766 +/- 277 versus 244 +/- 144 microM at 24 h. Mild postinsult HT for 24 h was not neuroprotective in unsedated piglets and did not reduce the number of animals that developed posthypoxic seizures. Cortisol reached 3 times the NT value at the end of HT. We speculate that the stress of shivering and feeling cold interfered with the previously shown neuroprotective effect of HT. Research on the appropriateness of sedation during clinical HT is urgent.

Adult↗
PubMed2001

Randomised controlled trial of tailored strategies to implement guidelines for the management of patients with depression in general practice.

BACKGROUND: Various methods are available for implementing change in the clinical behaviour of general practitioners (GPs). Although passive dissemination of information is generally ineffective, other methods can be variably effective. Few studies have investigated the impact of tailored methods. AIM: To determine whether methods tailored to overcome obstacles to change using psychological theories are more effective than dissemination alone in the implementation of guidelines for depression among GPs. DESIGN OF STUDY: Randomised controlled trial. SETTING: Sixty general practices in England; 30 GPs in the control group, 34 in the intervention group. METHOD: Practitioners identified patients presenting with depression before and after the implementation of guidelines (control group n = 192 in the first data collection, n = 181 in the second; intervention group n = 210 in the first data collection and n = 197 in the second). The main outcome measures were: record of adherence to guideline recommendations in clinical records; proportion of patients with Beck Depression Inventory (BDI) score less than 11 at 16 weeks after diagnosis. RESULTS: In comparison with the control group, in the group of GPs receiving tailored implementation, there were increases in the proportions of patients assessed for suicide risk. In the intervention group, the proportion of patients with BDI scores of less than 11 at 16 weeks increased. CONCLUSION: Obstacles to implementation can be identified and strategies tailored to address them. The findings indicate a new approach for research to understand and develop methods of implementation.

Depressive Disorder↗
PubMed2000

Effect of IL-5, glucocorticoid, and Fas ligation on Bcl-2 homologue expression and caspase activation in circulating human eosinophils.

IL-5 is a potent eosinophil viability-enhancing factor that has been strongly implicated in the pathogenesis of IgE-mediated inflammation in vivo. Recently published data have suggested that IL-5 (and related cytokines) may act by altering the expression of the anti-apoptotic regulator Bcl-2 or its homologues, but this is controversial. The behaviour of the recently described pro-apoptotic cysteine proteases (caspases) in eosinophils after IL-5 treatment has not been explored. We examined the effect of IL-5 on the expression of four major Bcl-2 homologues, as well as on the expression/activation of key members of the caspase cell death cascade in cultured circulating human eosinophils. The effect of relevant inducers of eosinophil apoptosis (glucocorticoid and Fas ligation) on these regulatory proteins was also examined. We observed baseline expression of the anti-apoptotic Mcl-1 and pro-apoptotic Bax proteins in immunoblots of eosinophil lysates, but not Bcl-x, Bcl-2. IL-5 treatment had the effect of maintaining this basal level of expression over time without altering the balance of Bcl-2 homologues. The (upstream) caspase 8 and (downstream) caspase 3 proenzymes were detected in eosinophils at baseline, and were processed during spontaneous and stimulated eosinophil death. IL-5 completely blocked caspase processing in spontaneous and dexamethasone-induced cell death, and significantly slowed processing during Fas ligation. Our data do not support the theory that IL-5 acts by altering the balance of anti-apoptotic and pro-apoptotic Bcl-2 homologues, but suggest that it may act by regulating activation of the caspase cell death cascade.

Apoptosis↗
PubMed2000

Thyroglossal duct remnants.

Thyroglossal duct remnants presenting as a lump in the neck are usually called thyroglossal cysts. Meticulous dissection of the cyst and duct, along with the body of the hyoid bone (Sistrunk's operation) is necessary to avoid recurrence. The authors have reviewed the histology of 61 consecutive specimens diagnosed preoperatively as thyroglossal cysts and have found that a true cyst exists in only 46 per cent of cases.

Adolescent↗
PubMed1999

Protection of mice against challenge with foot and mouth disease virus (FMDV) by immunization with foliar extracts from plants infected with recombinant tobacco mosaic virus expressing the FMDV structural protein VP1.

A tobacco mosaic virus (TMV)-based vector has been used to express in plants the complete open reading frame coding for VP1, the major immunogenic protein of foot and mouth disease virus (FMDV). In vitro RNA transcripts were inoculated into Nicotiana benthamiana plants and detectable amounts of recombinant VP1 were identified by Western blot as soon as 4 days postinfection. Foliar extracts prepared from infected leaves were injected intraperitoneally into mice and all of the immunized animals developed a specific antibody response to both the complete virus particle and the major immunogenic region as determined by ELISA and Western blot analysis. Most importantly, all immunized mice developed a protective immune response against experimental challenge with virulent FMDV. To our knowledge, this is the first report showing the expression of a complete open reading frame of an antigenic foreign protein in plants, using a recombinant plant virus, in sufficient quantity to permit use of the crude plant extract as an experimental immunogen to protect animals against virus challenge.

Animals↗