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Biomedical subjects

P Weller

Publications and source records attributed to P Weller.

At least 19 recordsLinked to original sources
PubMed2004

Cough plate versus cough swab in patients with cystic fibrosis; a pilot study.

BACKGROUND: Accurate identification of lower respiratory tract pathogens is important in the management of cystic fibrosis patients. AIM: To evaluate the cough plate as an alternative method of obtaining respiratory samples for microbiological culture. METHODS AND RESULTS: Using sputum culture as the "gold standard", the cough plate method identified significantly more positive cases than either dry or moistened cough swabs. Of 20 patients who had a positive sputum culture, 16 had a positive culture on cough plate compared to seven positive cultures each on moistened swab and on dry swab respectively. CONCLUSIONS: In this study cough plates were more sensitive than cough swabs in isolating respiratory pathogens in sputum producers. As patients prefer it, the cough plate merits further evaluation, particularly in non-sputum producers.

Adolescent↗
PubMed2003

Quantification of carotenoids in chicken plasma after feeding free or esterified lutein and capsanthin using high-performance liquid chromatography and liquid chromatography-mass spectrometry analysis.

The present study reports about the plasma carotenoid levels of chickens achieved after feeding diets containing free and esterified lutein (from marigold) and capsanthin (from red pepper) by applying HPLC analyses using a RP-C30 column. Forty chickens were divided at random into four groups and were fed 2 wk with different diets after receiving a basal diet with a low carotenoid content for carotenoid depletion (3 wk). One group was fed a diet containing free lutein (G1), another group received a diet with esterified lutein (G2), two other diets contained free (R1) and esterified capsanthin (R2), respectively. To unequivocally identify plasma carotenoids, liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry analysis was applied, which had never been used as an analytical tool to evaluate the carotenoids of chicken plasma; HPLC chromatograms of chicken plasma following capsanthin feeding have not been presented. The study showed that not only lutein but also capsanthin appeared in the blood stream after feeding free or esterified xanthophylls, demonstrating that capsanthin esters were bioavailable. Quantitative analysis showed comparable concentrations of plasma lutein and capsanthin, respectively, no matter if free or esterified carotenoids were fed.

Animal Nutritional Physiological Phenomena↗
PubMed2001

Cystic fibrosis-related deaths in infancy and the effect of newborn screening.

Although newborn screening for cystic fibrosis (CF) is widely advocated, hard evidence in its favor is difficult to obtain, partly because of a dramatically improved life expectancy. Between 1985--1989 infants, born in Wales and the West Midlands were randomized to newborn CF screening by heel-prick immunoreactive trypsin (IRT) measurement or diagnosis by clinical presentation. Eligible children with CF who died in the first 5 years of life were identified from the local pediatricians and from the National UK CF Survey. In all, 230,076 infants were randomized to be screened, while 234,510 were unscreened. One hundred seventy-six CF children were identified, of whom 7 died in the first 5 years of life, 3 having presented with meconium ileus. Median age of diagnosis in the screened group was 8 weeks. On an intention to treat analysis, all 4 nonmeconium ileus-related deaths occurred in the unscreened group (Fisher's exact test, P < 0.05). However, the clinical presentation of 2 of these infants led to them being diagnosed prior to 8 weeks, i.e., earlier than would have been likely by screening. In conclusion, newborn screening has the potential to decrease infant CF deaths, but if it is to be successful, identification and treatment must occur as soon as possible after birth.

Cystic Fibrosis↗
PubMed2001

A case study of using artificial neural networks for classifying cause of death from verbal autopsy.

BACKGROUND: Artificial neural networks (ANN) are gaining prominence as a method of classification in a wide range of disciplines. In this study ANN is applied to data from a verbal autopsy study as a means of classifying cause of death. METHODS: A simulated ANN was trained on a subset of verbal autopsy data, and the performance was tested on the remaining data. The performance of the ANN models were compared to two other classification methods (physician review and logistic regression) which have been tested on the same verbal autopsy data. RESULTS: Artificial neural network models were as accurate as or better than the other techniques in estimating the cause-specific mortality fraction (CSMF). They estimated the CSMF within 10% of true value in 8 out of 16 causes of death. Their sensitivity and specificity compared favourably with that of data-derived algorithms based on logistic regression models. CONCLUSIONS: Cross-validation is crucial in preventing the over-fitting of the ANN models to the training data. Artificial neural network models are a potentially useful technique for classifying causes of death from verbal autopsies. Large training data sets are needed to improve the performance of data-derived algorithms, in particular ANN models.

Autopsy↗
PubMed2001

Ultrastructural localization of vesicle-associated membrane protein(s) to specialized membrane structures in human pericytes, vascular smooth muscle cells, endothelial cells, neutrophils, and eosinophils.

Vesicle-associated membrane proteins (VAMPs) are important to the trafficking of vesicles between membrane-bound intracytoplasmic organelles, in the facilitation of neurosecretion, and in constitutive and regulated secretion in non-neuronal cells. We used a pre-embedding ultrastructural immunonanogold method to localize VAMPs to subcellular sites in human cells of five lineages known to have cytoplasmic vesicles that may function in vesicular transport. We found VAMPs localized to caveolae in pericytes, vascular smooth muscle cells, and endothelial cells of venules, to the vesiculo-vacuolar organelle, recently defined in venular endothelial cells, to the vesicle-rich intergranular cytoplasm and secretory granule membranes of neutrophils, and to perigranular cytoplasmic secretory vesicles and secretory granule membranes in eosinophils. These specific localizations in five human vascular and granulocyte lineages support the notion that VAMPs have vesicle-associated functions in these cells.

Adult↗
PubMed2000

Technical description of the IBIS data library. Improved Monitoring for Brain Dysfunction in Intensive Care and Surgery.

The IBIS Data Library (DL) is an annotated data library that contains practically all the monitored data and other clinical information from critically ill patients during surgery and in intensive care. The data have been collected at three sites: the intensive care unit of the Kuopio University Hospital, Finland; Royal Brompton Hospital, London, UK; and St. Bartholomew's Hospital, London, UK. The purpose of the DL is to form the basis for development of biosignal interpretation methods in the Improved Monitoring for Brain Dysfunction in Intensive Care and Surgery project in the European Union (EU) BIOMED2 programme (BMH4-97-2570). The DL contains continuous electroencephalography signals, multimodal evoked potential recordings and diagnostic electrocardiography recorded during intensive care and surgery. In addition, signal types similar to those recorded during an earlier project, the EU-BIOMED1 project IMPROVE, are stored in the DL. In addition, trend data from patient monitors, laboratory data, annotations, nursing actions, and medications recorded and stored by a Patient Data Management System (PDMS) during routine care are included. The data obtained routinely are complemented by special annotations made by a physician who observes the patient during the data collection session. Annotations include, for example, assessment of the awareness of the patient and specific events during surgery not recorded routinely by the PDMS. Inclusion of information about the care plan and the aims of the care make the contents of the DL complete. The present paper describes the technical set-up used for recording of the DL and the contents of the DL. The paper also includes an appendix defining a new data format, the extended evoked potentials format, used for storage of sweep data in the DL.

Brain↗
PubMed2000

The IBIS system architecture. Improved Monitoring for Brain Dysfunction in Intensive Care and Surgery.

An efficient method of interfacing between patient related data and the signal processing methods used to interpret these data is a critical component for a successful patient monitor, particularly for use in high dependency environments. This paper describes the approach adopted in the IBIS project. The key elements of the system are first introduced. A multi-layer structure is then developed in which the outputs from one decision layer are used to enhance the information available for subsequent layers in the system. The resulting system is modular, robust, flexible and easy to modify.

Brain↗
PubMed1999

Functional and structural studies of wild type SOX9 and mutations causing campomelic dysplasia.

In humans, mutations in SOX9 result in a skeletal malformation syndrome, campomelic dysplasia (CD). The present study investigated two major classes of CD mutations: 1) point mutations in the high mobility group (HMG) domain and 2) truncations and frameshifts that alter the C terminus of the protein. We analyzed the effect of one novel mutation and three other point mutations in the HMG domain of SOX9 on the DNA binding and DNA bending properties of the protein. The F12L mutant HMG domain shows negligible DNA binding, the H65Y mutant shows minimal DNA binding, whereas the A19V mutant shows near wild type DNA binding and bends DNA normally. Interestingly, the P70R mutant has altered DNA binding specificity, but also bends DNA normally. The effects of the point mutations were interpreted using a molecular model of the SOX9 HMG domain. We analyzed the effects upon transcription of mutations resembling the truncation and frameshift mutations in CD patients, and found that progressive deletion of the C terminus causes progressive loss of transactivation. Maximal transactivation by SOX9 requires both the C-terminal domain rich in proline, glutamine, and serine and the adjacent domain composed entirely of proline, glutamine, and alanine. Thus, CD arises by mutations that interfere with DNA binding by SOX9 or truncate the C-terminal transactivation domain and thereby impede the ability of SOX9 to activate target genes during organ development.

Amino Acid Sequence↗
PubMed1998

Enhanced delayed matching performance in younger and older macaques administered the 5-HT4 receptor agonist, RS 17017.

Recent evidence indicates that the 5-HT4 subtype of serotonin receptor may modulate central cholinergic activity in regions of the mammalian CNS important to memory such as the frontal cortex, hippocampus and amygdala. These receptors could represent targets for drugs designed for the symptomatic therapy of Alzheimer's disease (AD) and other disorders of memory. In the present study, the binding activity of RS 17017 (previously described as a selective 5-HT4 agonist) was assessed across a number of neurotransmitter receptors and binding sites, pharmacokinetic data were obtained, and the compound was evaluated in macaques for mnemonic effects via a computer-assisted delayed matching-to-sample task (DMTS). Binding data confirmed the 5-HT4 selectivity of the compound, while pharmacokinetic results revealed low oral bioavailability, but a large volume of distribution of the compound. Significant and reproducible improvements in DMTS accuracy were observed after oral administration of the compound across a dose-effect series in both younger and older monkeys. The results suggest that RS 17017 offers a potential for memory enhancement in disorders involving cognitive decline, and are consistent with a role for central 5-HT4 receptors in memory. Improvements in DMTS performance in aged monkeys may have particular implications for neurodegenerative conditions such as AD, whereas positive results in the younger monkeys indicate that RS 17017 (or similar compounds) may have additional potential in the therapeutics of memory disorders not necessarily associated with advanced age.

Aging↗
PubMed1997

Growth during one year of treatment with fluticasone propionate or sodium cromoglycate in children with asthma.

The aim of this study was to compare accurately measured growth over 12 months in asthmatic children treated with either fluticasone propionate (FP) 50 micrograms twice daily (b.i.d.) or sodium cromoglycate (SCG) 20 mg four times daily (q.i.d.). After a 2-week run-in, asthmatic children aged 4-10 years from 15 UK centers were randomized in a 3:4 ratio to open-label FP (n = 52) or SCG (n = 70). After 8 weeks, those whose asthma was not adequately controlled were switched from SCG to FP or withdrawn. Standing height was measured (Holtain stadiometry) at baseline, after 8 weeks and at 6 weeks intervals thereafter for 1 year. Morning peak flows (PEFam) were recorded by patients for 2 weeks during baseline, and 1 week before each visit during treatment. Urinary free cortisol (24 h) was measured at baseline, 6 months, and 1 year. After 8 weeks, 22 patients were withdrawn from SCG group (and were switched to FP), and five patients were withdrawn from the FP group due to poor asthma control. A further 21 and 11 patients were withdrawn from the SCG and FP groups, respectively, during the course of the study. There were no significant differences between patients who received FP and SCG for 1 year (n = 34 and n = 26, respectively) in terms of height velocity adjusted for age and gender (HV), or height velocity standard deviation scores adjusted for gender (HVSDS). Mean HV (mean HVSDS) were 6.0 cm/yr (0.1) and 6.5 cm/yr (0.5) for FP and SCG, respectively. There were no treatment differences in mean 24 h urinary free cortisol levels at 6 and 12 months. Mean % predicted PEFam improved over 1 year in both groups but to a greater degree in the FP group. We concluded that growth was normal in mildly asthmatic children receiving FP (50 micrograms bid) for 1 year. There were fewer withdrawals and lung function improved to a greater extent in FP treated patients than in patients receiving SCG.

Administration, Inhalation↗
PubMed1996

Prediction of outcome in critically ill patients using artificial neural network synthesised by genetic algorithm.

BACKGROUND: Decisions about which patients to admit to intensive care and how long to keep them there are difficult. A flexible computer-based mathematical model which is sensitive to the complexity of intensive care medicine, and which accurately models prognosis, seems highly desirable. METHODS: We have created, optimised by genetic algorithms, trained, and evaluated the performance of an artificial neural network (ANN) in the clinical setting of systemic inflammatory response syndrome and haemodynamic shock. 258 patients were selected from an intensive care database of 4484 patients at a London teaching hospital and randomised to a network training set (168) and a test set (90). The outcome evaluated was death during that hospital admission and the performance of the neural net was compared (by receiver operating characteristic [ROC] curves and by Brier scores) with that of a logistic regression model. FINDINGS: Artificial neural network performance increased with successive generations; the best-performing ANN was created after 7 generations and predicted outcome more accurately than the logistic regression model (ROC curve area 0.863 vs 0.753). INTERPRETATION: In this study, ANNs have lent themselves particularly well to modelling a complex clinical situation; we suggest that this relates to their inherently flexible nature which accommodates interactions between the clinical input fields. In addition, we have demonstrated the value of a second computational technique (genetic algorithms) in "tuning" ANN performance. These techniques can potentially be implemented in individual intensive care units; the outcome models which they will generate will be sensitive to local practice. Analysis of such accurate clinical outcome models may empower clinicians with a hitherto unappreciated degree of insight into those elements of their clinical practice which are most relevant to their patients' outcome.

Adult↗
PubMed1995

Salmeterol xinafoate in children on high dose inhaled steroids.

BACKGROUND: Current UK and international guidelines on asthma management recommend that, in pediatric patients still symptomatic on treatment with high-dose inhaled corticosteroids, consideration should be given to the introduction of regular twice daily long-acting beta 2-agonists. OBJECTIVE: The purpose of this study was to assess the efficacy and safety of inhaled salmeterol xinafoate 50 micrograms bid via the Diskhaler when added to the existing treatment of children with moderate to severe asthma. METHODS: A 12-week multicenter, double-blind, placebo-controlled, parallel group study was conducted at 78 hospital centers throughout the United Kingdom, involving 210 asthmatic children aged between 4 and 16 years of age. Morning peak expiratory flow (PEF), evening PEF, night-time and daytime symptoms and relief medication usage were recorded daily by the patient or parent over a 12-week treatment period. RESULTS: Compared with placebo, the addition of salmeterol xinafoate to existing high dose inhaled corticosteroid treatment significantly improved mean morning PEF expressed as percent predicted (PEF-PP) during the first 4 weeks of treatment (median increase 6.5 percentage points P < .001). This effect persisted throughout the 12-week treatment period (P < .05). Both groups demonstrated an overall improvement in mean morning PEF-PP, 7.5 percentage points for salmeterol xinafoate and 4 percentage points for placebo. The mean evening PEF-PP followed a similar although less pronounced trend which was significant only during the first 4 weeks of treatment (P = .014). Daytime relief medication and recorded symptoms were reduced significantly in both groups. There was a greater improvement in the number of symptom-free days during the first 4 weeks (P < .01) and the last 4 weeks (P < .05) of treatment for salmeterol xinafoate. The overall incidence and nature of minor adverse events was similar in both groups. CONCLUSIONS: This study demonstrates that the addition of salmeterol xinafoate to inhaled corticosteroid therapy in symptomatic asthmatic children significantly improves morning PEF-PP, and reduces their symptoms and use of relief medication.

Administration, Inhalation↗