Biomedical subjects

J F Price

Publications and source records attributed to J F Price.

At least 55 records · Page 3Linked to original sources

PubMed1996

Issues in adolescent asthma: what are the needs?

In the UK most children with asthma do not attend hospital clinics and continuity of care is provided by their general practitioner. However, those with severe asthma, most of whom will not grow out of their symptoms, need hospital-based care as well. As they progress through adolescence teenagers become increasingly uncomfortable in paediatric wards and outpatient clinics. They need clinics where they can meet the chest physician who will take on their care before they transfer to a clinic for adults (table 5). Adolescent asthmatic patients are a distinct group of patients with different treatment requirements from either paediatric or adult patients. It is important that physicians recognise adolescent needs and the importance of regular health checks, smoking, peer pressure, and the negotiation of treatment plans in this group of patients.

Adolescent↗

PubMed1996

Pulmonary dysfunction in cystic fibrosis is associated with oxidative stress.

The aim of this study was to determine whether a relationship exists between the circulating concentration of antioxidants, or markers of oxidative stress, and pulmonary function in cystic fibrosis patients. Plasma was obtained from 34 patients attending a cystic fibrosis clinic. Oxidative stress was investigated by measuring the concentrations of circulating lipid hydroperoxides and malondialdehyde (lipid peroxidation) and protein carbonyls (protein oxidation). Antioxidant status was determined from the plasma concentrations of alpha-tocopherol, ascorbic acid, uric acid and total sulphydryls. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and forced mid-expiratory flow (FEF25-75) were measured in 25 of the subjects by spirometry, and expressed as percentage predicted for normal height, weight and age. Lung function decreased significantly with age and was associated with decreased plasma alpha-tocopherol, ascorbic acid and sulphydryl concentrations. The reduction in pulmonary function correlated with elevated plasma malondialdehyde, but not with lipid hydroperoxide or protein carbonyl concentrations. Patients with severe lung dysfunction (FEV1 < 50% predicted) had higher plasma concentrations of lipid hydroperoxides than those with mild-to-moderate lung dysfunction (FEV1 > 50% pred). This study provides evidence that cystic fibrosis patients have inadequate antioxidant defences to cope with the elevated oxidative stress that they regularly experience. We believe that recurring oxidative lung injury contributes to the decline in pulmonary function in these patients.

Adolescent↗

PubMed1996

Cysteinyl leukotriene involvement in chronic lung disease in premature infants.

The pathophysiology of chronic lung disease (CLD) in premature infants who require mechanical ventilation and prolonged oxygen supplementation has been well-described but the underlying mechanisms are not understood. Our aim was to test the hypothesis that excess cysteinyl leukotriene (LT) production was a contributing factor in CLD. We compared LT production and lung function, at 7 months of age, in nine premature infants with CLD and in eight control infants without CLD. None of the control infants developed any neonatal respiratory problems, but two subsequently required bronchodilator therapy. Respiratory function was assessed by the measurement of thoracic gas volume (TGV), airways resistance (Raw) and functional residual capacity (FRC). Total cysteinyl LT production was quantified by measurement of leukotriene E4 (LTE4) in a spot urine sample. Although all patients were asymptomatic at follow-up, there was evidence of significant lung function abnormalities in infants with CLD. The CLD infants had significantly elevated TGV, Raw and FRC values reflecting airway obstruction when compared to the controls. Urinary LTE4 levels were significantly higher in the CLD infants when compared to the controls (geometric mean: 741 and 337 pmol.mmol-1 creatinine, respectively). There was no direct correlation between urinary LTE4 levels in the CLD group and TGV, Raw or FRC values. Although this study is small and a direct correlation between lung function and urinary leukotriene E4 was not demonstrated, pathological lung function and an enhanced urinary leukotriene E4 production in infants with chronic lung disease would tend to suggest that the cysteinyl leukotrienes were involved in the sequelae of this disease.

Airway Obstruction↗

PubMed1996

Hyperinsulinaemia: a risk factor for peripheral arterial disease in the non-diabetic general population.

BACKGROUND: Peripheral arterial disease is a common complication of diabetes mellitus, and hyperinsulinaemia has been associated with an increased incidence of intermittent claudication in diabetic subjects. Our aim was to investigate the relationship between hyperinsulinaemia and peripheral arterial disease in the non-diabetic general population. METHODS: Eighty-three cases with peripheral disease and 88 age- and sex-matched controls were selected from non-diabetic participants in the Edinburgh Artery Study, a survey of 1,592 men and women aged 55-74 years of randomly selected from the general population. RESULTS: Mean plasma insulin, 1 h after a 75 g oral glucose load, was higher in cases than in controls (73.6 versus 59.8 mU/l; P < 0.05). The relationship between insulin and disease was independent of blood pressure [odds ratio (OR) 2.04; 95% CI 1.11-3.74; P < or = 0.05] and partially independent of low- and high-density lipoprotein cholesterol and triglycerides (OR 1.86; 95% CI 0.99-3.48; P < or = 0.1). Mean 1 h insulin was higher in current or ex-smokers than in those who had never smoked (P < or = 0.05) and when smoking was added to the multivariate model, the relationship between insulin and disease diminished (OR 1.64; 95% CI 0.83-3.23; P > 0.1). CONCLUSIONS: In the non-diabetic general population, peripheral arterial disease is associated with post-glucose hyperinsulinaemia, independently of blood pressure, lipoproteins and triglycerides. Some of this association may be mediated by a relationship between hyperinsulinaemia and smoking.

Aged↗

PubMed1995

Cell viability and laminin-induced neurite outgrowth in cultures of embryonic chick neural tube cells: effects of cytosine-B-D-arabinofuranoside.

We have measured the effects of cytosine-beta-D-arabinofuranoside (AraC) on cell survival and neurite outgrowth in cultures of dissociated 4-6 day embryonic chick neural tube cells. High concentrations of AraC (greater than 100 microM) reduced neuronal cell survival and neurite outgrowth from viable cells. Concentrations normally used to inhibit mitotic cell division (1-10 microM) were toxic to the neurones cultured in serum free medium on a poly-DL-ornithine/laminin substrate. AraC does not appear to have a neurite promoting effect on dissociated neurones that are cultured in the presence of low numbers of non-neuronal cells. This suggests that the neurite promoting effects of AraC reported by others is likely to be through the non-neuronal cells that were an inherent feature of the culturing systems in these studies. AraC cytotoxicity was completely blocked by the addition of the competitive antagonist: 2'deoxycytidine (2'DC) but not by its metabolic precursor cytosine (cyt). We suggest that the acute effects of AraC on neurones which are actively growing neurites are the result of interference with lipid metabolism.

Animals↗

PubMed1995

Comparison of fluticasone propionate and sodium cromoglycate for the treatment of childhood asthma (an open parallel group study).

Inhaled corticosteroids are highly effective in the treatment of asthma at all ages and their use in younger children is increasing. As concerns exist about the long-term systemic side-effects of high dose inhaled corticosteroids, current guidelines continue to recommend sodium cromoglycate (SCG) as first line regular medication for children with frequent symptoms. Few published studies have compared the safety and efficacy of inhaled corticosteroids with SCG in children. This study compares SCG with the new inhaled corticosteroid, fluticasone propionate (FP), which has theoretical advantages over other currently available corticosteroids due to its negligible oral bioavailability. This was a randomized, open, multi-centre, parallel group comparison of 50 micrograms FP twice daily and 20 mg SCG four times daily over 8 weeks, preceded by a 2-week baseline period. Sixty-two general practices and two hospital centres enrolled 225 asthmatic children aged 4-12 years (110 received FP; 115 received SCG). Outcome measures improved in both groups, with a significant difference in favour of FP for the key variables of mean morning and evening % predicted PEFR and % of symptom-free days and nights. No significant difference was observed for FEV1, or relief medication use. Two children taking FP and 10 children taking SCG withdrew because of adverse events. This study showed that low dose FP was effective and superior to SCG in young children with mild-moderate asthma. Safety studies of longer duration are needed before changing the current recommendations for inhaled corticosteroid therapy.

Androstadienes↗

PubMed1995

Persistent increase in plasma and urinary leukotrienes after acute asthma.

Leukotrienes may mediate bronchoconstriction in asthma. Cysteinyl leukotriene production rises in vivo after allergen challenge, but few reports describe leukotriene concentrations in clinical asthma or in children. Using high performance liquid chromatography/radioimmunoassay, plasma and urinary leukotrienes in asthmatic children (aged 5-10 years) were measured during an acute exacerbation (peak expiratory flow (PEF) < 65%, n = 10) and one month later (PEF 74-169%, n = 9), and in non-atopic normal children (aged 1.3-13.2 years). In the asthmatics, geometric mean (95% confidence interval) plasma leukotriene B4 (LTB4) was 746 pg/ml (398 to 1403) acutely and 1026 pg/ml (662 to 1593) in remission, compared with 369 pg/ml (167 to 728) in the normal children (n = 14). Plasma cysteinyl leukotrienes were low or undetectable, but urinary leukotriene E4 (LTE4) was higher in the asthmatics during an acute episode (210 pmol/mmol creatinine, 101 to 454) and at follow up (179 pmol/mmol, 110 to 293), compared with the normal children (98 pmol/mmol, 81 to 118, n = 41). This persistent increase in plasma LTB4 and urinary LTE4 concentrations one month after a severe asthmatic episode suggests leukotriene production is related to chronic inflammation rather than to acute bronchoconstriction.

Acute Disease↗

PubMed1995

The effect of prolonged exposure to NO2 from birth on airways responsiveness in rabbits sensitized at birth.

Our aim was to determine whether daily exposure to 4 ppm nitrogen dioxide (NO2) from birth until 3 months of age influenced the development of airways hyperresponsiveness and atopic sensitivity in immunized rabbits. Littermate New Zealand white (NZW) rabbits were immunized within 24 h of birth by i.p. injection of house dust mite antigen in AI(OH)3 gel, and exposed to either ambient air or 4 ppm NO2 for 2 h.day-1, 5 days.week-1. At 3 months, bronchoalveolar lavage (BAL) and serum samples were obtained. Airways responsiveness was measured as the provocative concentrations (mg.ml-1) of histamine or methacholine required to elicit a 50% increase in airway resistance (RLPC50) and a 35% decrease in dynamic compliance (CdynPC35). There were no differences in total cell or differential cell counts recovered in BAL fluid between control and NO2 exposed animals. Airways responsiveness did not differ between groups of animals (histamine RLPC50 values: air (n = 15) versus NO2 (n = 13), respectively, 9.98 +/- 1.32 versus 16.43 +/- 1.45 mg.ml-1; CdynPC35 values: 16.60 +/- 1.44 versus 14.95 +/- 1.43 mg.ml-1; methacholine RLPC50 values: air (n = 14) versus NO2 (n = 12), respectively, 2.18 +/- 1.51 versus 2.21 +/- 1.32 mg.ml-1; CdynPC35 values: 2.64 +/- 1.41 versus 2.85 +/- 1.31 mg.ml-1). There was no difference in sensitization between groups of animals exposed to air or NO2, evaluated either by cutaneous responsiveness to intradermal antigen, or serum immunoglobulin E (IgE) levels assessed by the passive cutaneous anaphylaxis (PCA) reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗

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↗

PubMed1994

Atopic children with cystic fibrosis have increased urinary leukotriene E4 concentrations and more severe pulmonary disease.

BACKGROUND: We investigated the hypothesis that cysteinyl leukotriene (LT) production is altered in atopic patients with cystic fibrosis (CF). METHODS: Urinary LTE4 was measured in two groups of children with CF: atopic (ACF group, n = 22) and nonatopic (NACF group, n = 13); and in two groups of unaffected children, those with atopic asthma (AA group, n = 11) and nonatopic normal control subjects (NN group, n = 12). RESULTS: Atopic groups excreted significantly more urinary LTE4 (geometric means [95% confidence intervals] in picomoles per millimole creatinine), ACF group: 104 (73-147) and AA group: 195 (136-282) compared with NACF group: 19 (9-39) and NN group: 27 (15-48). The ACF group had significantly more airflow obstruction than the NACF group, with forced expiratory volume in 1 second (percent predicted, mean +/- SD) in ACF: 58 +/- 21 versus NACF: 81 +/- 23, and forced vital capacity (percent predicted, mean +/- SD) 72 +/- 17 versus 87 +/- 23, respectively. There were significant correlations between the degree of airflow obstruction, bronchodilator responsiveness, and urinary LTE4 concentration within the entire CF group. We used multiple regression analysis to assess the respective influence of age, atopy, sensitization to Aspergillus fumigatus, and colonization with Pseudomonas aeruginosa on urinary LTE4 concentration. The atopic state was the only significant variable associated with urinary LTE4 production in subjects with CF. CONCLUSIONS: The similarities in urinary LTE4 between ACF and AA groups suggest that the atopic state is the prime determinant of urinary LTE4 excretion. Enhanced cysteinyl LT production associated with atopy in CF may increase the severity of pulmonary disease.

Adolescent↗

PubMed1994

Growth and adrenal responsiveness with budesonide in young asthmatics.

Inhaled corticosteroid therapy for asthma is used increasingly from a pre-school age. Current knowledge of adverse systemic effects, however, is based on treatment of older children. Eighteen asthmatic children aged 4.5-7.4 years who had taken budesonide by Nebuhaler in doses averaging 200-1100 micrograms m-2 day-1 during the previous year were studied. Height velocities calculated over this period were no different from those of the normal population. Neither the velocities nor a modest delay in bone ages were related to budesonide dose. Every child responded normally to tetracosactrin. These young asthmatic children do not show a greater susceptibility to systemic effects from an inhaled corticosteroid than older counterparts.

Administration, Topical↗

PubMed1994

Specificity of ELISA for IgG subclass antibodies against inhalant antigens in early childhood.

ELISA is increasingly used to measure antibodies in new circumstances. Recently, it has been applied to the measurement of IgG subclass antibodies against common antigens in early childhood. These studies have raised concerns about the specificity of some of these assays. This paper details the results of experiments which have assessed the specificity of IgG1 binding to allergens of dust mite (Dermatophagoides pteronyssinus) and ryegrass (Lolium perenne) pollen by inhibition ELISA in the sera of 2-year-old children of atopic parents. Six sera which showed binding of IgG1 to D. pteronyssinus and six to L. perenne were used. All had IgG1 antibody against ovalbumin. In the children's sera, binding to D. pteronyssinus was substantially inhibited by preincubation with the homologous antigen, but not with ovalbumin, thereby confirming the specificity of the assay. However, suppression of IgG1 binding to L. perenne with the homologous antigen was comparatively small, and ovalbumin could cause an equivalent inhibition, indicating poor specificity. Furthermore, the level of IgG1 binding to L. perenne was closely correlated to the level of IgG1 binding to ovalbumin (r = 0.98; P < 0.001). When the assay was reversed, IgG1 binding to ovalbumin was only slightly inhibited by L. perenne, indicating that most antibody binding to ovalbumin was specific. Thus, binding IgG1 in both adult and child sera to D. pteronyssinus appeared to be specific, while child, but not adult, IgG1 binding to L. perenne showed poor specificity. This disparity may be due to differences in the affinities of the respective antibodies, and it illustrates the importance of determining assay specificity when making measurements in early childhood.

Adult↗

PubMed1994

Interleukin-1 alpha, soluble interleukin-2 receptor, and IgG concentrations in cystic fibrosis treated with prednisolone.

The cytokines interleukin-1 and interleukin-2 participate in the inflammatory response, and may contribute to hypergammaglobulinaemia G and the development of lung injury in cystic fibrosis. Anti-inflammatory treatment with corticosteroids may attenuate this response. The effect of a 12 week course of oral prednisolone on spirometry and serum concentrations of interleukin-1 alpha (IL-1 alpha), soluble interleukin-2 receptor (sIL-2R), and IgG was investigated in 24 children with cystic fibrosis. Prednisolone was administered, in a double blind and placebo controlled manner, at an initial dose of 2 mg/kg daily for 14 days and tapered to 1 mg/kg on alternate days for 10 weeks. The treated group (n = 12) experienced an increase in forced expiratory volume in one second and forced vital capacity at 14 days, however, these changes were smaller at 12 weeks. In the treated group, change in pulmonary function was associated with decreased serum IgG and cytokine concentrations. Prednisolone suppresses serum concentrations of these cytokines, which may participate in the inflammatory response, the excessive synthesis of IgG, and airflow obstruction observed in cystic fibrosis patients.

Adolescent↗

PubMed1994

A method for the long-term exposure of rabbits to environmental pollutant gases.

The aims of the present study were twofold. Firstly, we wanted to develop a system for the exposure of rabbits to pollutant gases that would monitor gas concentrations accurately, allow flexibility, be simple to operate, and could be constructed at relatively modest cost. Additionally, we wanted to determine whether the procedures necessary for the daily exposure of young rabbits had any detrimental effect on their development. Using the environmental exposure system that we developed, littermate New Zealand White rabbits, neonatally immunized to either Alternaria tenuis or house dust mite antigen were exposed 2 h daily, from within 24 h of birth until 3 months of age, to either 4 ppm nitrogen dioxide (NO2), or 5 ppm sulphur dioxide (SO2) or ambient air. The environmental exposure system consists of four sections; a stainless steel exposure chamber; an airflow monitoring and control system and gas delivery system; a gas detector and monitoring system; and an exhaust fan. Equilibration and wash-out times of gas were short and the gas mixing within the chamber atmosphere was uniform. Levels of gases were reliably maintained throughout the period of exposure within predetermined limits. The weights of the immunized, gas-exposed animals did not differ significantly from those of the immunized, air-exposed animals at any time throughout the 3 month period of exposure. At 3 months of age, the basal values for lung resistance and dynamic compliance did not differ between gas- and air-exposed rabbits. These values did not differ significantly from those obtained from naive animals of the same age. Our results suggest that we have developed a sensitive, reliable and simple environmental exposure and monitoring system. It is anticipated that the methodology described will allow the careful investigation of the effects of long-term exposure to pollutant gases from birth on the development of airways hyperresponsiveness.

Air Pollutants↗

PubMed1993

The use of inhaled steroids in young children.

There are apparently irreversible inflammatory changes in the airways of young adults with chronic asthma so a strong case can be made for starting anti-inflammatory treatment early. Corticosteroids have potent and diverse anti-inflammatory activity. High efficacy is established in school age children. Trials in pre-school children and infants have given more mixed results perhaps because of problems with administration. No clinically important systemic effects have been observed in children taking conventional doses of inhaled steroids.

Acute Disease↗

PubMed1993

Inhaled ipratropium bromide and terbutaline in asthmatic children.

Inhaled bronchodilator therapy in young asthmatic children reduces symptoms and improves lung function. After a single dose of therapy, however, lung function may still be abnormal, as evidenced by an elevated function residual capacity (FRC). The aims of this study were to assess if a second dose of bronchodilator therapy resulted in further improvement in lung function and to determine whether additional therapy was more effective if given as a second dose of a beta-adrenergic agonist or if instead an anticholinergic was used. Twenty-one asthmatics (median age 7.5 years) received in random order on two separate occasions, 1 week apart, either two doses of terbutaline (500 micrograms) or terbutaline plus ipratropium bromide (20 micrograms). FRC and peak expiratory flow rate (PEFR) were measured immediately prior to and then 20 min after each dose of bronchodilator therapy. In the group, overall FRC and PEFR improved after the first and second dose of bronchodilator, regardless of regime used, the response to the second dose, however, was smaller than the first dose. There was no significant difference overall between the two regimes in baseline FRC or PEFR, or FRC and PEFR measured after each dose of bronchodilator. Eight children failed to show a significant change in FRC following two doses of terbutaline, but seven of these eight did have a significant change in FRC in response to the combination of terbutaline and ipratropium bromide. We conclude that a second dose of bronchodilator therapy does further improve lung function. Our results suggest the more efficacious regime consists of a combination of single doses of ipratropium bromide and terbutaline.

Administration, Inhalation↗

PubMed1993

Asthma, growth and inhaled corticosteroids.

Linear growth can be divided into three phases: during infancy it is influenced mainly by nutrition; thereafter throughout childhood it comes under hormonal control; puberty constitutes the third phase. The pubertal growth spurt, which may account for up to 30 cm of linear growth, results from an increase in growth hormone pulse amplitude that is mediated by sex steroids. The rate of growth in childhood, onset of puberty and final height are determined by the impact of a range of environmental factors on genetic potential. These variables and the effect of asthma itself need to be taken into account when assessing the possible effect of inhaled corticosteroids on growth. Many asthmatic children have a slower growth rate than normal children, and a physiological delay in puberty which does not affect final adult height. Prolonged administration of oral corticosteroids retards growth. The mechanism is not fully understood, but may involve an indirect effect on growth hormone secretion following adrenal suppression. Short-term deceleration of growth has been demonstrated by knemometry in children taking inhaled corticosteroids, but there is no evidence of long-term growth suppression with conventional doses of inhaled corticosteroids. Growth should be monitored in children taking over 0.8 mg day-1 of inhaled corticosteroid, but the priority should be to treat the asthma adequately.

Administration, Inhalation↗

PubMed1993

Sputum tumour necrosis factor-alpha and leukotriene concentrations in cystic fibrosis.

It is postulated that a vigorous host inflammatory response in the cystic fibrosis lung contributes to lung injury. Tumour necrosis factor-alpha (TNF-alpha) may play a part in that process and in the generation of leukotrienes. Therefore, the relationships between sputum TNF-alpha, leukotriene concentration, and lung function abnormalities in 16 children with cystic fibrosis were investigated. Each subject provided sputum samples and performed spirometry. TNF-alpha was measured by enzyme linked immunosorbent assay; individual leukotrienes were separated using high performance liquid chromatography and quantified by radioimmunoassay. The geometric mean concentration of TNF-alpha was 129.7 pg/ml and 95% confidence interval 48.2 to 348.3. Mean (SEM) leukotriene B4 (LTB4) was 97.8 (22.9) pmol/g and total cysteinyl leukotrienes were 60.9 (14.8) pmol/g. Mean (SD) forced expiratory volume in one second (FEV1) of the group was 53 (15)% of predicted and forced vital capacity (FVC) was 65 (14)% of predicted. There was a significant positive correlation between TNF-alpha and both LTB4 and the total cysteinyl leukotriene sputum content. An inverse relationship existed between TNF-alpha and FEV1 and FVC. Moreover, a negative correlation was observed between sputum LTB4 and FEV1 and FVC. These results suggest that TNF-alpha and the leukotrienes may participate in the airways inflammation and airflow obstruction observed in cystic fibrosis subjects and support the hypothesis that TNF-alpha upregulates the 5-lipoxygenase pathway in vivo.

Adolescent↗