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Biomedical subjects

V Brown

Publications and source records attributed to V Brown.

At least 37 records · Page 2Linked to original sources
PubMed2001

The development of the Chemotherapy Symptom Assessment Scale (C-SAS): a scale for the routine clinical assessment of the symptom experiences of patients receiving cytotoxic chemotherapy.

The management of symptoms experienced by patients receiving cytotoxic chemotherapy influences quality of life during treatment. Symptom management may be improved through a structured approach to symptom assessment. This paper describes the development of the Chemotherapy Symptom Assessment Scale (C-SAS), a 24-item scale designed for the routine assessment of symptoms experienced by patients receiving cytotoxic chemotherapy. The scale development process focused both upon the psychometric properties and the clinical usefulness of the scale. Patients and health professionals played a significant role in item selection and scale design in order to maximise the clinical utility of the C-SAS.

Antineoplastic Agents↗
PubMed2001

Saccade target selection in visual search: the effect of information from the previous fixation.

This paper reports an analysis of saccades made during a task of visual search for a colour shape conjunction. The analysis concentrates on the saccade following the first saccade, thus complementing an earlier paper where the first saccades were analysed. The further analysis addresses the issue of what information might be held in trans-saccadic memory. As with the first saccade, incorrect second saccades tend to fall on distractors sharing one feature with the target. The proximity of the target to the fixation location immediately prior to the saccade is a very significant determinant of whether the saccade will reach the target. The results lead to the conclusion that in the majority of cases, choice of saccade destination is made afresh during each fixation with no carry-over from the previous fixation. However, in a small number of cases, second saccades are made after extremely brief fixation intervals. Although these saccades show a similar probability of reaching the target as those following longer fixations, it is argued that this sub-set of saccades are pre-programmed at the time of the preceding saccade.

Fixation, Ocular↗
PubMed2001

Rapid assessment of population size by area sampling in disaster situations.

In the initial phase of a complex emergency, an immediate population size assessment method, based on area sampling, is vital to provide relief workers with a rapid population estimate in refugee camps. In the past decade, the method has been progressively improved; six examples are presented in this paper and questions raised about its statistical validity as well as important issues for further research. There are two stages. The first is to map the camp by registering all of its co-ordinates. In the second stage, the total camp population is estimated by counting the population living in a limited number of square blocks of known surface area, and by extrapolating average population calculated per block to the total camp surface. In six camps selected in Asia and Africa, between 1992 and 1994, population figures were estimated within one to two days. After measuring all external limits, surfaces were calculated and ranged between 121,300 and 2,770,000 square metres. In five camps, the mean average population per square was obtained using blocks 25 by 25 meters (625 m2), and for another camp with blocks 100 by 100 m2. In three camps, different population density zones were defined. Total camp populations obtained were 16,800 to 113,600. Although this method is a valuable public health tool in emergency situations, it has several limitations. Issues related to population density and number and size of blocks to be selected require further research for the method to be better validated.

Africa↗
PubMed2001

Personal exposure to benzene and the influence of attached and integral garages.

Benzene is an air pollutant that is a recognised human carcinogen. An air quality standard has been established for ambient air in the UK to reduce the population's exposure. It has been estimated that about 70% of benzene emissions to air in the UK come from petrol vehicles. A number of studies, including the Avon Longitudinal Study of Pregnancy and Childhood in the UK, have found that benzene concentrations in homes with attached or integral garages tend to be higher than in those without such garages. The present paper reviews these studies and reports a detailed investigation of five homes with either an attached or an integral garage. Indoor and outdoor locations were monitored using diffusive sampling to determine the average benzene concentration over approximately 28 days each month for 18 consecutive months (June 1998-November 1999). For one of these homes, ten years of data had shown the indoor benzene concentration to be consistently higher than outdoors. Personal exposure monitoring of one adult in this home showed that the benzene concentration in the main bedroom was a better predictor of personal exposure than the concentration outdoors. In the homes where a car was regularly parked in the garage, 18-month average benzene concentrations of up to 101.3 micrograms m-3 were measured in the garage, which is more than six times the ambient air quality standard for benzene (16.25 micrograms m-3 running annual average). Mean benzene values in all cars and most of the garages studied exceeded the benzene standard. Mean benzene concentrations in the room above the garage ranged from 3.7 micrograms m-3 in one home, where the car was rarely parked in the garage, to 39.9 micrograms m-3 in another home where a car with high benzene emissions was parked in the garage for six of the 18 months monitored. The mean benzene concentration in the room above the garage in this latter home was nearly 2.5 times the ambient air standard. The study demonstrates that there is a potential for people to have a higher exposure to benzene as a result of living in a home with an attached or integral garage. An understanding of routes of personal exposure is important to develop effective policies to reduce risks to health.

Air Pollution, Indoor↗
PubMed2001

The repeatability of nonbronchoscopic bronchoalveolar lavage differential cell counts.

Airway inflammation in children can be assessed by nonbronchoscopic bronchoalveolar lavage (BAL). Little is known about the repeatability of cell counts in the BAL obtained. Children (n=43) attending for elective surgery were studied. Cell counts were obtained following a nonbronchoscopic lavage. Two samples were obtained with either: 1) the catheter wedged in the same position (n=21) or 2) the catheter reinserted and wedged again (n=22). Slides (n=30) from nonbronchoscopic lavage samples were selected at random and two independent observers counted 500 cells on each slide on two occasions. The repeatability of the lavage sampling and cell counting was assessed for different cell types. The inter- and intra-observer repeatability for the differential cell counting demonstrated that there was good repeatability for all cell types except lymphocytes (interobserver: Lin's concordance coefficient 0.42; repeatability coefficient 0.66). Quantification of eosinophil (%) was highly repeatable using either method (Lin's concordance coefficient 1) 0.99, 2) 0.95; repeatability coefficient 1) 0.58, 2) 1.36). Nonbronchoscopic lavage is a repeatable technique for the quantification of eosinophils. Variation in the sampling method can be reduced by taking two separate samples and averaging the differential cell counts. Furthermore, increasing the number of cells counted should ensure accurate quantification of lymphocytes.

Bronchoalveolar Lavage Fluid↗
PubMed2001

Antioxidants and protein carbonyls in bronchoalveolar lavage fluid of children: normal data.

Antioxidant-oxidant imbalances in bronchoalveolar lavage fluid (BAL) are thought to contribute to oxidative stress in respiratory disease. However, normal reference ranges for BAL antioxidants and oxidized proteins in children are not available. In this study, we recruited 124 children attending for elective surgery for a noninflammatory condition; 83 were nonasthmatic, nonatopic (N) and 41 were nonasthmatic, atopic (NA). A nonbronchoscopic lavage was performed and ascorbate, uric acid, alpha-tocopherol, and protein carbonyl (as a measure of oxidative damage) concentrations were determined in BAL fluid. The 95% reference range was 0.112-1.897 micromol/L for ascorbate, 0.149-2.163 micromol/L for urate, 0.0029-0.066 micromol/L for alpha-tocopherol, and 0.280-4.529 nmol/mg for protein carbonyls in BAL fluid. Age, gender, and exposure to environmental tobacco smoke did not affect the concentration of ascorbate, urate, alpha-tocopherol, or protein carbonyls. However, in multiple linear regression analyses, the type of home heating (glass-fronted fires or oil-fired central heating) was found to influence ascorbate and urate concentrations in the BAL fluid (ss-coefficient for ascorbate: 0.445, p = 0.031; for urate: 0.114, p = 0.001). There was no significant difference between the N and NA group in BAL fluid concentrations of ascorbate, urate, or protein carbonyls. The alpha-tocopherol concentration was significantly increased in the NA group (p = 0.037). Uric acid and alpha-tocopherol concentrations in BAL fluid and serum were not correlated. Intriguingly, serum and BAL ascorbate concentrations were significantly correlated (r = 0.297, p = 0.018, n = 63), which may offer an explanation for why supplementing the diet with vitamin C can improve asthma symptoms. Further studies will investigate the role of BAL antioxidant concentrations in children with inflammatory respiratory diseases.

Antioxidants↗
PubMed2000

Chronic cough in children: bronchoalveolar lavage findings.

Isolated chronic cough in childhood is a common complaint. Although the symptom cough is included in the definition of clildhood asthma, there is debate as to whether the majoritv of these children have asthma. The authors studied children with isolated chronic cough looking for evidence of airway inflammation typical of asthma, with increased numbers of airway eosinophils as assessed from bronchoalveolar lavage (BAL). The investigations were carried out on 23 children (median age: 6.7 yrs; range: 1.7-12.75 yrs), attending the Royal Belfast Hospital for Sick Children for elective surgery, who also had a chronic unexplained cough. Written informed consent was obtained from the parent(s) and a nonbronchoscopic BAL was performed. BAL samples were analysed for total and differential white cell counts and also for the inflammatory mediators, eosinophil cationic protein (ECP) and histamine. Results were compared with a group of normal nonatopic children and also a group of atopic asthmatic children, who had been recruited for other studies on airway inflammation. There was a small but statistically significant increase in BAL percentage eosinophils in the children with chronic cough compared with nonasthmatic controls (0.28% versus 0.10%, p=0.03). However, the children with cough had lower percentage eosinophils than the atopic asthmatic controls (0.28% versus 0.66%, p=0.01). Three out of 23 children with chronic cough had BAL eosinophils greater than the normal upper 95% reference interval in BAL. There was a small but statistically significant increase in percentage neutrophils in the children with cough compared with the nonasthmatic controls (5.85% versus 3.21%, p=0.03). Four out of the 23 children had BAL neutrophils greater than the normal upper 95% reference interval in BAL. The authors conclude that only a minority of children with chronic unexplained cough have asthmatic-type airway inflammation. It is speculated that the increased percentage neutrophils in bronchoalveolar lavage from children with cough could relate to underlying persistent airways infection.

Asthma↗
PubMed2000

Interleukin 15 mediates epithelial changes in celiac disease.

BACKGROUND & AIMS: Villous atrophy and crypt proliferation are key epithelial features of untreated celiac disease. We tried to define whether cytokines such as interleukin (IL)-15, IL-2, IL-4, and IL-7, which share chains of their receptors, could influence the epithelial modifications. METHODS: Duodenal biopsy specimens (14 treated and 13 untreated celiac patients, 7 controls) were cultured in vitro for 24 hours with or without gliadin (1 mg/mL), IL-15, IL-7, IL-4, or IL-2 (10 ng/mL). Tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma were also used in some specimens of untreated celiacs. Epithelial expression of Ki67, FAS, and transferrin receptor (TFR) was detected by immunohistochemistry, and apoptosis by TUNEL technique (percentage of positive enterocytes). IL-15-positive cells were detected by immunohistochemistry in celiac disease and control biopsy specimens; presence of IL-15 was also determined by semiquantitative polymerase chain reaction. RESULTS: Only IL-15 induced enterocyte expression of Ki67, TFR, and FAS in treated celiac (P<0.01 vs. medium) and enterocyte apoptosis in untreated celiac disease specimens. Anti-IL-15 monoclonal antibodies neutralized gliadin-induced enterocyte TFR and FAS expression in treated celiac and enterocyte apoptosis in untreated celiac disease specimens (P<0.05 vs. gliadin). IL-15-positive cells were increased in untreated celiacs (P<0.001 vs. treated celiacs and controls). CONCLUSIONS: IL-15 is involved in the modulation of epithelial changes in celiac disease, indicating that this cytokine has an unforeseen role in the pathologic manifestations of celiac disease.

Adolescent↗
PubMed1999

Famine in southern Sudan.

We provide baseline information and objective testimony on severe malnutrition and high mortality in the general population of southern Sudan that is affected by chronic civil war and severe famine.

Child, Preschool↗
PubMed1999

Expression of the 71 kDa dystrophin isoform (Dp71) evaluated by gene targeting.

To investigate the function of the major non-muscle dystrophin isoform, Dp71, we substituted a beta-galactosidase (betagal) reporter gene for Dp71 by homologous recombination in embryonic stem cells. Staining for betagal activity in chimeric mice revealed Dp71 promoter activity in glial cells in the CNS, in neurons of the inner nuclear and inner plexiform layers of the retina, and in the kidney tubules and collecting ducts. Our observations demonstrate that Dp71 is widely expressed in the adult CNS (retina, cerebellum, cerebral cortex, ependyma, and choroid) as well as the adult kidney epithelium and suggest a broad function for Dp71 in differentiated tissues.

Animals↗
PubMed1999

Serum eosinophil cationic protein (ECP): reference values in healthy nonatopic children.

BACKGROUND: Although serum ECP concentrations have been reported in normal children, there are currently no published upper cutoff reference limits for serum ECP in normal, nonatopic, nonasthmatic children aged 1-15 years. METHODS: We recruited 123 nonatopic, nonasthmatic normal children attending the Royal Belfast Hospital for Sick Children for elective surgery and measured serum ECP concentrations. The effects of age and exposure to environmental tobacco smoke (ETS) on the upper reference limits were studied by multiple regression and fractional polynomials. RESULTS: The median serum ECP concentration was 6.5 microg/l and the 95th and 97.5 th percentiles were 18.8 and 19.9 microg/l. The median and 95th percentile did not vary with age. Exposure to ETS was not associated with altered serum ECP concentrations (P = 0.14). CONCLUSIONS: The 95th and 97.5 th percentiles for serum ECP for normal, nonatopic, nonasthmatic children (aged 1-15 years) were 19 and 20 microg/l, respectively. Age and exposure to parental ETS did not significantly alter serum ECP concentrations or the normal upper reference limits. Our data provide cutoff upper reference limits for normal children for use of serum ECP in a clinical or research setting.

Adolescent↗
PubMed1999

Inflammatory mediators in bronchoalveolar lavage samples from children with and without asthma.

BACKGROUND: We investigated whether eosinophils and mast cells, found in the airways of children with wheeze, were activated during relatively asymptomatic periods. METHODS: A nonbronchoscopic bronchoalveolar lavage (BAL) procedure was performed on children presenting for an elective surgical procedure. Eosinophil-derived (eosinophil cationic protein, ECP) and mast cell-derived (histamine/tryptase) mediator concentrations were measured in the BAL fluid. A detailed history and serum immunoglobulin E were used to classify the children into four groups: atopic with and without asthma, viral-associated wheeze and normal controls. RESULTS: The ECP concentrations in BAL from atopic asthmatic subjects were significantly higher than those measured in BAL from normal controls (P < 0.01), no other groups differed significantly. Histamine concentrations were elevated in both the atopic asthmatic and viral-associated wheeze groups compared with controls (P < 0.02) and additionally higher concentrations were obtained in atopics with asthma compared with atopics without asthma (P < 0.03). Tryptase concentrations did not differ between groups, although the tryptase and histamine concentrations correlated significantly (r = 0.78, P < 0.0001). CONCLUSIONS: Elevated histamine concentrations were found in children with wheeze regardless of the aetiology, whereas ECP was only elevated in those asthmatics with atopy. This suggests that even in relatively quiescent periods, there is some on going activation of airway eosinophils in children with atopic asthma.

Adolescent↗
PubMed1999

Serum eosinophilic cationic protein and blood eosinophil counts for the prediction of the presence of airways inflammation in children with wheezing.

BACKGROUND: Serum eosinophilic cationic protein (ECP) concentrations may be useful noninvasive markers of airways inflammation in atopic asthma. However, the usefulness of serum ECP measurement for the prediction of airways inflammation in children with a history of wheezing is unknown. OBJECTIVE: To determine the test accuracy of serum ECP and blood eosinophil percentage as noninvasive markers of eosinophilic airways inflammation. METHODS: Bronchoalveolar lavage (BAL) fluid and peripheral blood samples for eosinophil percentages and serum ECP were obtained from children undergoing elective surgery and who gave a history of wheezing in the previous year. Sensitivity, specificity and likelihood ratios (LH) and the area under the curve (AUC) for the receiver operator characteristic (ROC) curve were calculated for each blood marker for the prediction of airways inflammation defined by a BAL eosinophil percentage > 0.86. Data were analysed on the basis of how recently symptoms had occurred. RESULTS: Seventy-seven children (median age 6.75 years) were studied. An AUC of 0.75 (log serum ECP concentration) and 0.76 (log blood eosinophil percentage) was obtained for predicting airways inflammation. A serum ECP > 13 microg/L yielded a LH of 4.4, whereas using a cutoff blood eosinophils > 4% yielded a LH of 1.9, for the prediction of elevated eosinophils in BAL. Serum ECP and eosinophil percentages in BAL and blood were lowest (not statistically significant) when last symptoms had occurred more than 12 weeks previously. CONCLUSIONS: Serum ECP and blood eosinophil percentages are useful markers for predicting eosinophilic airways inflammation in wheezing children.

Adolescent↗
PubMed1999

Elevated levels of a U4/U6.U5 snRNP-associated protein, Spp381p, rescue a mutant defective in spliceosome maturation.

U4 snRNA release from the spliceosome occurs through an essential but ill-defined Prp38p-dependent step. Here we report the results of a dosage suppressor screen to identify genes that contribute to PRP38 function. Elevated expression of a previously uncharacterized gene, SPP381, efficiently suppresses the growth and splicing defects of a temperature-sensitive (Ts) mutant prp38-1. This suppression is specific in that enhanced SPP381 expression does not alter the abundance of intronless RNA transcripts or suppress the Ts phenotypes of other prp mutants. Since SPP381 does not suppress a prp38::LEU2 null allele, it is clear that Spp381p assists Prp38p in splicing but does not substitute for it. Yeast SPP381 disruptants are severely growth impaired and accumulate unspliced pre-mRNA. Immune precipitation studies show that, like Prp38p, Spp381p is present in the U4/U6.U5 tri-snRNP particle. Two-hybrid analyses support the view that the carboxyl half of Spp381p directly interacts with the Prp38p protein. A putative PEST proteolysis domain within Spp381p is dispensable for the Spp381p-Prp38p interaction and for prp38-1 suppression but contributes to Spp381p function in splicing. Curiously, in vitro, Spp381p may not be needed for the chemistry of pre-mRNA splicing. Based on the in vivo and in vitro results presented here, we propose that two small acidic proteins without obvious RNA binding domains, Spp381p and Prp38p, act in concert to promote U4/U5.U6 tri-snRNP function in the spliceosome cycle.

Amino Acid Sequence↗
PubMed1999

Isolation of an FMRP-associated messenger ribonucleoprotein particle and identification of nucleolin and the fragile X-related proteins as components of the complex.

The loss of FMR1 expression due to trinucleotide repeat expansion leads to fragile X syndrome, a cause of mental retardation. The encoded protein, FMRP, is a member of a gene family that also contains the fragile X-related proteins, FXR1P and FXR2P. FMRP has been shown to be a nucleocytoplasmic shuttling protein that selectively binds a subset of mRNAs, forms messenger ribonucleoprotein (mRNP) complexes, and associates with translating ribosomes. Here we describe a cell culture system from which we can isolate epitope-tagged FMRP along with mRNA, including its own message, and at least six other proteins. We identify two of these proteins as FXR1P and FXR2P by using specific antisera and identify a third protein as nucleolin by using mass spectrometry. The presence of nucleolin is confirmed by both reactivity with a specific antiserum as well as reverse coimmunoprecipitation where antinucleolin antiserum immunoprecipitates endogenous FMRP from both cultured cells and mouse brain. The identification of nucleolin, a known component of other mRNPs, adds a new dimension to the analysis of FMRP function, and the approach described should also allow the identification of the remaining unknown proteins of this FMRP-associated mRNP as well as the other bound mRNAs.

Animals↗