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Biomedical subjects

Heather Powell

Publications and source records attributed to Heather Powell.

10 recordsLinked to original sources
PubMed2006

JAK2(V617F) and leukemic transformation in myelofibrosis with myeloid metaplasia.

Amongst 42 consecutive patients with leukemic transformation (LT) from myelofibrosis with myeloid metaplasia (MMM) 72% carried the JAK2(V617F) mutation. The mutation was observed at expected frequencies in all subtypes of MMM and acute myeloid leukemia. Although the patients with the mutation were younger and had a shorter interval to LT there was no difference in survival. Additionally, both the lack of mutation status progression in serial analysis (available in nine patients) and the low frequency of patients with high mutated allele burden suggest that LT arising from MMM is probably not dependent on changes in JAK2(V617F) mutation status.

Adult↗
PubMed2006

Initial corticosteroid therapy for asthma.

PURPOSE OF REVIEW: This review examines the commencement of maintenance pharmacotherapy for asthma: inhaled corticosteroids alone or in combination with long-acting beta2 agonists. RECENT FINDINGS: A systematic review of randomized controlled trials has examined the starting dose of inhaled corticosteroids (high, moderate, low) and the dose regimen (step down versus constant) in asthma. There was no significant difference in key asthma outcomes for step down compared with a constant inhaled corticosteroid dose. There was no significant difference between high or moderate dose inhaled corticosteroid groups (n=11) for morning peak expiratory flow, symptoms and rescue medication use. There may be a benefit from high-dose inhaled corticosteroids for airway hyperresponsiveness. There was a significant improvement in peak expiratory flow and nocturnal symptoms in favour of a moderate inhaled corticosteroid dose compared with low-dose treatment. Long-acting beta2 agonists combined with inhaled corticosteroids as initial asthma therapy has been examined in a systematic review of nine randomized controlled trials. Inhaled corticosteroids combined with long-acting beta2 agonists led to significant improvements in forced expiratory volume in 1 s, morning peak expiratory flow, symptom score and symptom-free days but no difference in exacerbations requiring oral corticosteroids. A randomized controlled trial of patients with uncontrolled asthma found a benefit of escalating doses of salmeterol/fluticasone compared with fluticasone on asthma control. SUMMARY: Initial inhaled corticosteroid therapy should begin with a constant, moderate dose. Initial therapy with long-acting beta2 agonist and inhaled corticosteroids achieves superior improvement in symptoms and lung function, and at a quicker rate than inhaled corticosteroids alone. There is no benefit in terms of reduced exacerbations unless an escalating inhaled corticosteroid dose strategy is used.

Administration, Inhalation↗
PubMed2005

Interleukin-10 gene expression in acute virus-induced asthma.

RATIONALE: Virus-induced asthma is characterized by marked neutrophil influx and eosinophil degranulation, suggesting a mode of immunopathogenesis different from that of allergen-induced asthma. OBJECTIVES: This study compared induced sputum cytokine responses in subjects with severe asthma exacerbation and respiratory virus infection with those of patients with stable asthma, healthy control subjects, and virus-infected nonasthmatic subjects. METHODS: Subject infection status and pulmonary history were established on the basis of common cold and asthma questionnaires, and lung function and atopy tests were performed. Respiratory virus infection was diagnosed by cell culture and direct polymerase chain reaction, using induced sputum. The induced sputum cellular profile was examined and cytokine gene expression was assessed by quantitative real-time polymerase chain reaction. RESULTS: A respiratory virus was detected in 78% of subjects with acute asthma. Specific viruses detected were rhinovirus (83%), influenza (15%), enterovirus (4%), and respiratory syncytial virus (2%). Virus-infected subjects with acute asthma or no asthma had increased RANTES (regulated on activation, normal T cell expressed and secreted) and macrophage inflammatory protein-1alpha messenger RNAs compared with other groups. Interleukin (IL)-10 mRNA was significantly increased in virus-infected acute asthma and reduced on recovery from acute asthma. IL-5, eotaxin, and IL-8 mRNA transcripts were similar across groups. CONCLUSIONS: Asthma exacerbation triggered by respiratory virus infection is characterized by increased IL-10 gene expression that may explain the suppressed eosinophil influx in acute asthma. Airway neutrophilia due to respiratory virus infection is associated with chemokine gene expression involving RANTES and macrophage inflammatory protein-1alpha.

Acute Disease↗
PubMed2004

Microstructural disassembly of calcium phosphates.

Microstructural factors may play a role in the osseointegration of calcium phosphates. In this paper, direct microstructural interactions between crystalline calcium phosphates and the biological milieu are reported. Degradation via exposure to osteoblast culture closely resembles in vivo interactions with subcutaneous tissues in a bovine model at early time periods. That these interactions were common to both experiments constitutes one of the few known examples of in vitro-in vivo correspondence. Interestingly, the degradation of phase pure hydroxyapatite (HA) in vitro was more rapid than that of biphasic HA in vivo. In both cases, grain extraction/pullout was frequently observed. This suggests a connection to smaller-scale observations of epitaxial CHA nucleation and growth on pre-existing HA grains. A microstructure in which the grain boundary is dissolving/corroding can apparently be disassembled by forces transmitted through biological structures. These observations are distinct from those of simple non-biological solutions and prove that biological environments can interact with the material beneath the ceramic-cell/ceramic-tissue interface. Many often ignored microstructural factors-grain size, shape, grain boundary strength and the presence of impurity phases-may in fact control degradation. We also suggest that even relatively modest initial grain sizes will, in combination with the mild/absent foreign body response to calcium phosphates, result in lengthy in vivo particle resistence.

Animals↗
PubMed2003

Inhaled corticosteroid doses in asthma: an evidence-based approach.

OBJECTIVE: To define the evidence for doses of inhaled corticosteroids in asthma and describe this in clinically meaningful, evidence-based terms. DATA SOURCE: Cochrane Database of Systematic Reviews. STUDY SELECTION AND DATA EXTRACTION: We identified systematic reviews of randomised controlled trials of dosing of inhaled corticosteroids in asthma. Data on efficacy and safety of different doses were extracted from meta-analyses and summarised as the number needed to treat (NNT) and number needed to harm (NNH). DATA SYNTHESIS: Inhaled corticosteroids were highly efficacious, with a relatively flat dose-response curve. Three patients needed to be treated with fluticasone 100 microg daily to prevent worsening asthma (NNT 3), and for fluticasone 1000 microg the NNT was 2.1 patients. The dose-response curve for side effects was steep. For a dose of fluticasone 100 microg, oral candidiasis developed in one of every 90 subjects treated (NNH 90). In contrast, the NNH for fluticasone 1000 microg and 2000 microg daily were 23 and 6, respectively. CONCLUSION: Level 1 evidence supports the use of low-dose inhaled corticosteroids in asthma. Clinicians should review doses of inhaled corticosteroids used for treating patients with asthma.

Administration, Inhalation↗
PubMed2003

Migration to a western country increases asthma symptoms but not eosinophilic airway inflammation.

The prevalence of asthma symptoms varies markedly throughout the world. However, the asthma mechanisms involved are not defined. Studying the effects of migration can help identify the reasons for this geographic variation. The aims of this study were to examine the prevalence of asthma symptoms, airway hyperresponsiveness (AHR), and induced sputum eosinophils in adolescents who migrate to Australia. The study was conducted in Sydney, Australia, where adolescent students completed a video symptom questionnaire, hypertonic saline challenge, sputum induction, and allergy skin testing. The 211 students had widely different cultural backgrounds, including Asian, South Pacific, Middle Eastern, European, and African countries. Among adolescents who were migrants to Australia, the prevalence of asthma symptoms was higher than that reported using a similar methodology in their country of origin. Asthma symptom prevalence was related to residence time in Australia. The prevalence of wheeze was 17.2% in recent arrivals, 20.5% in adolescents living in Australia for >2 years, and 36.3% in those living all their lifetime in Australia (P = 0.013). For every year of residence in Australia, there was an 11% increase in prevalence of current wheeze (odds ratio, 1.11; P = 0.02). This effect was not related to atopy, AHR, or eosinophilic airway inflammation. Sputum neutrophils were elevated in recent arrivals. In conclusion, adolescents who migrate to Australia report increased asthma symptoms, compared to their country of origin, and asthma symptoms are further increased for every additional year of residence in Australia. The development of wheeze after migration to Australia was independent of eosinophilic inflammation and consistent with noneosinophilic asthma mechanisms.

Adolescent↗
PubMed2003

Asthma education.

Education about asthma and self-management of asthma are now key recommendations of asthma management guidelines. A Cochrane systematic review of 12 RCTs found that limited education programmes that offer information about asthma but not self-management skills did not reduce hospitalisation rates or visits to the doctor for asthma. The positive outcomes from limited asthma education were a reduction in symptoms. Asthma self-management education which consists of information, self-monitoring, regular medical review, and a written action plan is effective and leads to a reduction in hospitalisation and ER visits for asthma, unscheduled doctors visits, days lost from work, episodes of nocturnal asthma, indirect costs and an improvement in quality of life. The effects were large enough to be of both clinical and statistical significance. While a structured asthma self-management programme is effective in a hospital setting, attempts to deliver these programmes in primary care have met with varying success.

Asthma↗
PubMed2002

Breakfast in the Pacific.

The Sixth Natural Language Processing Pacific Rim Symposium was held on 27--30 November 2001, at the National Center of Science, Tokyo, Japan.

Journal Article↗
PubMed2002

Nanoscale modifications of PET polymer surfaces via oxygen-plasma discharge yield minimal changes in attachment and growth of mammalian epithelial and mesenchymal cells in vitro.

Surface topography is believed to be a factor affecting cellular morphology, proliferation, and differentiation. The effect of surface roughness in the micron to supramicron range has been investigated previously. In the current study, the influence of nanoscale surface roughness was examined in terms of its effects on morphology, cytoskeleton expression, proliferation, differentiation, and apoptosis of three model cell types. Polyethylene terephthalate (PET) disks were etched using oxygen plasma to produce uniform and decidedly nanoscale levels of surface roughness. Three distinct types of cell lines-mouse 3T3-L1 preadipocytes, human JEG-3 choriocarcinoma cells, and human MCF-7 breast adenocarcinoma cells-were cultured on the plasma-treated disks. Untreated PET disks were used as a control. Cytoskeletal proteins (F-actin and cytokeratin) exhibited similar patterns of expression. Cell morphology also was similar on both surfaces. Cell growth kinetics for the three types of cells and hormone secretion from the JEG-3 cells were not significantly different from that of the controls (p > 0.05). However, the differentiation of preadipocyte 3T3-L1 cells into lipid-laden fat cells was modestly affected by nanoscale surface topography. In addition, 15-deoxy-Delta(12,14)-prostaglandin J(2) (15dPGJ(2))-induced apoptosis of the JEG-3 and MCF-7 cells revealed differences between the two surfaces. Plasma-treated surfaces showed more differentiated and apoptotic cells, respectively, compared to the controls. These results indicate that nanoscale roughness contributes in only moderate ways to cellular adhesion, proliferation, and differentiation in the cell lines tested.

3T3 Cells↗