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J R Britton

Publications and source records attributed to J R Britton.

At least 55 records · Page 3Linked to original sources
PubMed1989

Effect of vasopressin on bronchial reactivity to histamine.

1. Recent evidence suggests that a high salt diet increases bronchial reactivity, but the underlying mechanism is unclear. 2. To determine whether alterations in circulating vasopressin might be responsible, we have studied the effect of an infusion of vasopressin on the airways of six normal and eight asthmatic subjects measuring the response as expiratory flow at 30% of vital capacity (V30P) in the normal subjects and as forced expiratory volume in 1s (FEV1) in the asthmatic subjects, in a double-blind, placebo-controlled, cross-over study. 3. Vasopressin, given as an infusion at a rate of 2 i.u./h for 1 h, followed by 4 i.u./h for a further hour, produced plasma concentrations of 12.8 and 17 ng/l, respectively, compared with 2.0 and 2.0 ng/l on placebo. 4. Airway reactivity to histamine was measured after 1 and 2 h as the provocative doses of histamine causing a 40% reduction in V30P (PD40V30P) in the normal subjects and a 20% reduction in FEV1 (PD20FEV1) in the asthmatic subjects. 5. There was a small increase in PD40V30P after both vasopressin and placebo in normal subjects (refractoriness) but no change in PD20FEV1 in the asthmatic subjects. 6. There was no significant difference between vasopressin and placebo in V30P or PD40V30P over the 2 h after the drug in the normal subjects or in FEV1 or PD20FEV1 over the 2 h after the drug in the asthmatic subjects. 7. We conclude that alterations in circulating vasopressin are unlikely to be responsible for the increase in bronchial reactivity when dietary salt intake is increased.

Adolescent↗
PubMed1989

What symptoms predict the bronchial response to histamine? Evaluation in a community survey of the bronchial symptoms questionnaire (1984) of the International Union Against Tuberculosis and Lung Disease.

A questionnaire developed by the International Union against Tuberculosis and Lung Disease (IUATLD) to assess bronchial symptoms has been tested for its ability to predict the bronchial response to histamine in adults aged 18-64 years living in two areas of southern England. A number of questions were found to be independently associated with increased reactivity in the first randomly selected half of the subjects. These symptoms included wheeze, waking at night with shortness of breath, tightness in the chest or shortness of breath when exposed to animals, dust or feathers and the non-specific symptom of persistent problems with breathing. A predictive score based on these symptoms was more sensitive and only slightly less specific than the question on wheeze alone in predicting the response to histamine in the second half of the subjects. Questions about asthma though more specific were considerably less sensitive than either. Symptoms did not differentiate between reactivity associated with positive skin tests and that associated with smoking.

Adult↗
PubMed1989

Minimal hydrolysis of epidermal growth factor by gastric fluid of preterm infants.

Epidermal growth factor (EGF), present in high concentrations in milk, may play a role in growth of the gastrointestinal tract. Resistance to proteolytic degradation in the stomach is necessary if ingested EGF is to function within the gastrointestinal tract. Although EGF stability to low pH and proteases predicts gastric survival, the extent of digestion in the stomach remains to be defined. Consequently, we measured gastric degradation of 125I-human recombinant EGF in preterm infants with an in vitro method in which EGF was incubated at 37 degrees C with stomach fluid at pH 1.8, 3.2, and 5.8 followed by analysis of degradation products. As maximal acid proteolytic activity is present one hour after feeding in preterm infants, fluid was obtained at that time from 18 infants with a mean gestational age at birth of 30.4 (3.0) (SD) weeks and a postnatal age of 26.3 (12.7) days at sampling. Incubations for up to 60 minutes revealed minimal loss of trichloroacetic acid precipitable radioactivity, in contrast to the substantial hydrolysis of iodinated casein which occurred under the same conditions. Chromatography of reaction mixtures on Sephadex G-25 showed a single major peak of radioactivity which coeluted with EGF. Epidermal growth factor also retained greater than 75% of its ability to bind to anti-EGF affinity columns and placental membrane receptors after incubation with gastric fluid. These data support the concept of substantial gastric survival of ingested EGF in a potentially biologically active form in preterm infants.

Epidermal Growth Factor↗
PubMed1989

Prostaglandin stability in human milk and infant gastric fluid.

Prostaglandins are present in breast milk and may protect and maintain intestinal epithelial cell integrity in developing mammals. In view of their very short half-life in other body tissues and fluids, studies were performed to determine prostaglandin stability in milk and gastric fluid. Tritiated prostaglandins E2 and F2 alpha were incubated for 30 min in whole milk, milk cells, and milk plasma obtained from mothers delivering at term and prematurely, and in preterm infant gastric fluid. Radioactivity chromatographic analysis revealed minimal degradation of PG in milk preparations and gastric fluid. Thus, milk may serve as an effective natural medium for PG delivery to the gastrointestinal tract. The cytoprotective effect of prostaglandins on the gastrointestinal tract may be related to their stability and lack of degradation in milk and gastric digestive juices.

Dinoprost↗
PubMed1989

The distribution of peak expiratory flow variability in a population sample.

Although serial peak expiratory flow (PEF) measurements are often used to assess the variability of airflow obstruction, the range of values to be expected in the general population has never been defined, nor is there any consensus as to how PEF variability should be expressed. We have compared PEF recordings made by 121 subjects selected at random from the population of a small town (Group A) and 221 subjects selected because of wheeze in the last year (Group B). Subjects were asked to record PEF every 2 h during waking hours for 7 days using a mini-Wright peak flow meter. Seven indices of PEF variability were derived for each subject and the range for each index determined. All indices showed a positively skewed distribution in the random sample. Two variability indices, standard deviation percent mean and amplitude percent mean, provided the greatest separation between subjects with both a diagnosis of asthma and wheeze in the last year and subjects with neither feature and also provided the highest intra-class correlation coefficients. We conclude that amplitude percent mean and standard deviation percent mean provide the best means of expressing PEF variability for epidemiological purposes, but that amplitude percent mean is more easily derived and appears to be the index of choice. PEF variability has a continuous distribution in the general population and no clear-cut division between asthmatic and nonasthmatic subjects can be defined.

Adolescent↗
PubMed1989

Validity and repeatability of the IUATLD (1984) Bronchial Symptoms Questionnaire: an international comparison.

The International Union against Tuberculosis and Lung Disease (IUATLD) Bronchial Symptoms Questionnaire (1984) was developed for use in studies of asthma and its reliability measured in an earlier survey in England. The association of the symptoms elicited by this questionnaire to bronchial response to histamine has also been described. This paper presents the results of studies of the questionnaire in four clinical centres in Europe. The reliability of the questionnaire and its ability to predict the bronchial response to histamine were compared for English, Finnish, French and German translations of the questionnaire in samples of diagnosed asthmatics and controls in Nottingham, Berlin, Helsinki and Paris. The answers to questions showed good repeatability, especially in Finland and Germany, particularly those questions on asthma and wheeze. The most sensitive symptom for predicting hyperresponsiveness was the question on wheeze, the most specific questions were those on waking at night with shortness of breath (Paris and Nottingham) and morning tightness (Helsinki and Berlin). This study shows that the IUATLD (1984) questionnaire may provide useful, valid and comparable data even in translation but these studies will need to be repeated in representative samples before such a possibility is accepted as fully demonstrated.

Adult↗
PubMed1989

A comparison of three measures of the response to inhaled methacholine.

In studies of asthma prevalence bronchial responsiveness has usually been measured as the provocative dose of bronchoconstrictor causing a 20% fall in FEV1 (PD20FEV1). This is relatively insensitive and only 10-20% of subjects in a general population sample will show such a response. Attempts to increase sensitivity, such as the use of the provocative dose causing a 10% fall in FEV1 (PD10FEV1), have not demonstrated any overall advantage, due to poorer repeatability. It has been suggested that measurement of bronchial reactivity using flow at low lung volumes measured from a partial flow volume curve is a more sensitive index of bronchoconstriction than PD20FEV1. If equally repeatable, it would have advantages in epidemiological practice. In 20 subjects with asthma, we compared the sensitivity and repeatability of PD10FEV1, PD20FEV1, and the provocative dose causing a 40% fall in flow at 30% of vital capacity (PD40V30P) following methacholine challenge. PD40V30P was more sensitive than both PD20FEV1 and PD10FEV1 by 1.48 and 0.35 doubling doses (DD) of methacholine, respectively. PD20FEV1 and PD40V30P showed equal repeatability, the 95% range for a single estimate of both being 2.02 DD. PD10FEV1 was less repeatable, with a 95% range of 2.35 DD. Values for the intraclass correlation co-efficient, which measures the ability of a test to discriminate between subjects, were 0.63, 0.79 and 0.69 for PD10FEV1, PD20FEV1, and PD40V30P, respectively. The increased sensitivity and comparable repeatability of measurement of bronchial reactivity for PD40V30P suggest that this method may be useful for studies of asthma prevalence.

Adult↗
PubMed1989

Transferrin degradation by gastrointestinal fluids of suckling and weanling rats.

Dietary transferrins are postulated to play a number of biological roles in the developing gastrointestinal tract. A prerequisite for such roles is survival in the gastrointestinal lumen. To evaluate luminal transferrin digestion during development, 125I-transferrin was incubated in vitro with luminal fluid from the stomach and small intestine of 12-day old suckling and 31-day old weanling rats, followed by analysis of degradation products. At both ages, the rate of degradation to trichloroacetic acid soluble material was maximum in the mid-jejunum and lowest in the stomach. Transferrin hydrolysis by weanling fluid was 2-10 times greater than suckling depending upon the particular segment. Chromatography of small intestinal reaction mixtures on Sephacryl S-200 revealed label eluting between intact transferrin and free iodine: two such peaks were generated with suckling fluid and one with weanling. Electrophoresis on SDS-polyacrylamide gels showed two major bands of Mr 69K and 20K; the former was the predominant reaction product with suckling intestinal fluid and the latter with weanling. Both methods showed small amounts of apparently intact transferrin. Results indicate substantial yet incomplete luminal degradation of transferrin which is more pronounced in the weanling than in the suckling. This survival is compatible with potential biological functioning of dietary transferrin or one of its breakdown products within the gastrointestinal tract.

Animals↗
PubMed1988

Rebound increase in bronchial responsiveness after treatment with inhaled terbutaline.

To investigate whether cessation of regular beta-agonist treatment results in an increase in bronchial responsiveness, two double-blind, randomised crossover studies were done. Subjects with mild asthma were investigated to determine the course of change in bronchial responsiveness, measured as the provocative dose (PD20) of histamine that caused a 20% fall in forced expiratory volume in 1 s after short-term and longer term treatment with an inhaled beta-agonist. In the first study in 8 subjects, 500 and 2000 micrograms terbutaline thrice in 1 day protected against histamine-induced bronchoconstriction, and the increase in PD20 compared with placebo remained high throughout the day and overnight. In the second study 8 subjects received placebo or terbutaline 750 micrograms thrice daily for 14 days. The protection afforded by terbutaline against histamine-induced bronchoconstriction on day 14 was less than that on day 1 by 40% in the morning and 82% in the afternoon. On day 15 PD20 was lower after stopping terbutaline than placebo, with a maximum difference of 1.5 (95% CI 0.6-2.5) doubling-doses of histamine 23 h after the end of treatment. Thus treatment with terbutaline for 1 day did not result in any rebound increase in bronchial responsiveness. Treatment for 2 weeks impaired the ability of terbutaline to protect against histamine-induced bronchoconstriction, and was followed by a rebound increase in bronchial responsiveness after cessation of treatment.

Adolescent↗
PubMed1988

Luminal hydrolysis of recombinant human epidermal growth factor in the rat gastrointestinal tract: segmental and developmental differences.

Epidermal growth factor (EGF), present in high concentrations in the milk of various species, is biologically active following oral administration to young animals. Although in vivo studies show gastrointestinal processing of dietary EGF during early postnatal development, the relative importance of luminal and mucosal digestion in such processing is undefined. To characterize the luminal metabolism of dietary EGF in the developing gastrointestinal tract, we incubated human recombinant 125I-EGF in vitro at 37 degrees with luminal fluid from the stomach and various segments of the small intestine of 12 day old suckling and 31 day old weanling rats and analyzed the resulting reaction products. The rate of EGF hydrolysis as determined by generation of acid soluble material was greater in weanling small intestine than in suckling, with maximal hydrolytic capacity observed in the mid-jejunum and ileum. Minimal hydrolysis was observed with stomach fluid from both age groups, and EGF retained its ability to elute as a single species on Sephadex G-25 columns and to bind to monospecific affinity columns and placental membrane receptors. Incubation with suckling small intestinal fluid produced little change in the chromatographic profile on Sephadex G-25, but a reduction in antibody and receptor binding was observed. In contrast, incubation with weanling small intestinal fluid yielded both a more pronounced loss of EGF-like material on G-25 columns and a greater reduction in receptor and antibody binding. We conclude that little luminal EGF degradation occurs in the rat stomach during the suckling and weanling periods, but that in the lumen of the small intestine breakdown increases during postnatal development.

Animals↗
PubMed1988

The effect of inhaled ouabain on bronchial reactivity to histamine in man.

To determine the role of Na/K ATPase in determining bronchial reactivity in man, we studied the effect of 1 mg inhaled ouabain on histamine reactivity in six normal and 10 asthmatic subjects in a placebo controlled, crossover study. sGaw was measured before and up to 2 h after drug, followed by a histamine challenge test to estimate the dose of histamine causing a 35% reduction in sGAW (PD35). sGAW values after ouabain and placebo did not differ significantly. Ouabain did not affect bronchial reactivity, geometric mean (95% CI) PD35 histamine values following ouabain and placebo were 8.98 (3.8-21.2) and 7.75 (3.2-18.7) mumol respectively in normal subjects and 0.46 (0.18-1.21) and 0.69 (0.22-2.13) in asthmatic subjects. We were thus unable to demonstrate a role for Na/K ATPase in determining bronchial reactivity to histamine in man.

Administration, Inhalation↗
PubMed1988

Comparison of histamine and methacholine for use in bronchial challenge tests in community studies.

Measurement of bronchial reactivity is widely used in epidemiological surveys. Histamine has been compared with methacholine inhalation challenge in two samples of adults from a small town to determine which is the better agent for use in community studies. Increasing doses of histamine and methacholine were given, up to a maximum of 4 and 12 mumol respectively, according to the method of Yan et al, the provocative dose of agonist causing a 20% fall in FEV1 (PD20) being measured. More subjects had a measurable PD20 with methacholine than with histamine, both in a random sample of 108 subjects (25 v 11 subjects, p less than 0.01) and in an additional 95 subjects selected because of wheeze in the last 12 months (67 v 48 subjects, p less than 0.01). Side effects were mild with both agents but histamine caused voice change in more subjects (21% v 11%). Repeatability was assessed in a further group of subjects with wheeze in the last year. The 95% range for a single estimation of PD20 in subjects with a measured PD20 on at least one occasion was +/- 2.5 doubling doses for histamine (n = 25) and +/- 2.1 doubling doses for methacholine (n = 33). Thus methacholine has advantages over histamine for community studies of bronchial reactivity as it is possible to use doses that produce more PD20 measurements with fewer side effects.

Adolescent↗
PubMed1988

Development of luminal protein digestion in suckling and weanling rats.

Because previous measurements of early postnatal, small intestinal fluid, proteolytic activity in man and animals have been contradictory, we characterized the development of luminal protein digestion using a sensitive assay in which iodinated bovine casein was incubated in vitro at 37 degrees C with luminal fluid flushed from the stomach and small intestine of 12-day-old suckling and 31-day-old weanling rats, followed by measurement of radioactivity in trichloroacetic acid-soluble material. Gastric proteolysis at pH 3.2 in the weanling rat was approximately 50-fold greater than that in the suckling rat. Analysis of stomach fluid acid-soluble casein degradation products of weanling rats by chromatography on G-50 Sephadex in the presence of sodium dodecyl sulfate revealed three peaks of radioactivity comprising 65, 18 and 12% of the total product in order of elution. In the jejunum at neutral pH, the proteolytic capacity of the weanling rat was approximately five times that of the suckling rat; such differences were more pronounced in the ileum, however, in which protein hydrolysis of weanling rats was 30-fold higher than that in the suckling rat. In the suckling rat, small intestine proteolytic activity was greater in the jejunum than in the ileum, but in the weanling rat greater protein hydrolysis was present in the ileum. Gel filtration analysis of reaction products in both intestinal segments and at both ages demonstrated two peaks, which constituted 60-70 and 15-23% of the acid-soluble material in order of elution.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1988

Corticosteroid increases gastrointestinal luminal proteolysis in suckling rats.

Although stress during the perinatal period may influence a number of enzymes in the gastrointestinal tract, the resulting effects on digestive processes are not completely understood. In suckling rats, corticosteroid administration increases levels of proteases in gastric mucosa and pancreas, but previous studies of unstimulated luminal fluid proteolytic activity suggest no effect. To re-evaluate this phenomenon, we injected suckling rats with cortisone acetate (5 mg/100 g body weight) subcutaneously daily on days 9-11 followed by sacrifice on day 12; littermates served as controls. Luminal fluid from stomach and small intestine was analyzed for proteolytic activity by a sensitive assay in which incubation in vitro with 125I-bovine casein was followed by measurement of radioactivity soluble in trichloroacetic acid. Cortisone acetate produced significant increases in luminal proteolytic activity in all gastrointestinal segments with the most dramatic effect observed in the ileum; this segment showed a more than 10-fold enhancement of proteolysis with steroid treatment. Analysis of acid-precipitable reaction products by electrophoresis in polyacrylamide gels containing sodium dodecyl sulfate also revealed enhancement of casein degradation by luminal fluid in all segments from steroid-treated animals. We conclude that corticosteroid increases luminal proteolysis in the gastrointestinal tract of the suckling rat. This phenomenon may have implications for steroid-induced premature closure to macromolecular absorption and protein digestive capacity during the perinatal period.

Animals↗
PubMed1988

The relation between change in airway reactivity and change in respiratory symptoms and medication in a community study.

Airway reactivity is known to increase in relation to the severity of asthma, and, in the community, hyperreactivity has been shown to be associated with respiratory symptoms such as wheezing and shortness of breath. However, the relation between change in airway reactivity and change in the severity of respiratory symptoms and change in the use of asthma medications within subjects has not been studied. We have investigated this relationship in a community population. In September 1984 and March 1985, the provocative dose of histamine producing a 20% fall in FEV1 (PD20) was measured, and respiratory symptoms and medication use assessed by questionnaire in 78 subjects taking part in a study of seasonal changes in airway reactivity. On both occasions, PD20 was negatively correlated with current frequency of wheezing, with the amount of asthma medication in regular use, and with the current general assessment of breathing problems. In the 45 subjects who had a PD20 value of 8 mumol or less on at least one of the two occasions tested, PD20 increased between September and March by 0.46 (SEM, 0.32) doubling doses of histamine (p = 0.16). Within subjects, change in PD20 was negatively correlated with change in the frequency of wheezing in the past month (p less than 0.005) and with change in medication use (p less than 0.05). This study demonstrates that PD20 is related to the severity of respiratory symptoms and medication use, and that change in airway reactivity within subjects in a community population is associated with changes in the frequency of wheezing and in the use of asthma medication.

Adult↗
PubMed1988

High-dose inhaled albuterol in severe chronic airflow limitation.

Higher doses of inhaled albuterol have been shown to cause slightly more bronchodilatation than standard doses from a metered-dose inhaler in patients with severe chronic airflow limitation. Higher doses, however, carry an increased risk of side effects, and the optimum dose balancing benefit and adverse effects have yet to be established. We have therefore looked at objective and subjective evidence of beneficial and adverse effects after 4 doses of albuterol in 30 patients with chronic bronchitis, severe airflow limitation, and less than 200 ml increase in FEV1 after 200 micrograms inhaled albuterol. Subjects were given placebo, 400 micrograms, 1 mg, 2 mg, and 4 mg albuterol by dry powder inhaler in random order on separate days in a double-blind study, and FEV1, relaxed VC, PEFR, 12-min walk distance, finger tremor, oxygen saturation, heart rate, and arrhythmias were measured at intervals over 6 h. With increasing doses of albuterol, there was a significant dose-related increase in FEV1, VC, and PEFR, the maximal mean changes being 196 ml, 480 ml, and 50 L/min, respectively. The duration of effect was longer with the higher doses. There was a dose-related increase in heart rate, tremor amplitude, and supraventricular ectopic beats and a dose-related fall in oxygen saturation. There was no drug-related effect on the frequency of ventricular ectopic beats either at rest or during the walk tests. The largest increases in walk distance occurred after the 1 and 2 mg doses and the least after the 4 mg dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗