Basophil-enriched leucocyte populations in an anti-IgE mediated protease degranulation assay.
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Adult↗
Biomedical subjects
J R Britton
Publications and source records attributed to J R Britton.
The effect of an oral leukotriene D4 antagonist L-649,923 on the response to inhaled antigen in asthma.
We have compared the effects of the leukotriene (LT) D4 antagonist L-649,923 and placebo on the airway response to antigen challenge in eight men with mild asthma known to have both an early and late response to inhaled antigen. Subjects ingested 1000 mg of L-649,923 or placebo in a randomized, double-blind protocol and, two hours later, inhaled the dose of antigen known to induce a 20% fall in FEV1. Pulmonary function (specific conductance, FEV1, peak expiratory flow rate, and maximal flow at 25% of vital capacity) was measured at intervals before and up to 9 hours after antigen. FEV1 fell in one subject after L-649,923 ingestion. L-649,923 in the other seven subjects caused no change in baseline pulmonary function, a small reduction in the early response to antigen for FEV1, peak expiratory flow rate, and maximal flow at 25% of vital capacity but not for specific airway conductance (six subjects only) and no effect on the late response. The mean maximum fall in FEV1 in the early response was 1.35 L after L-649,923 ingestion and 1.78 after placebo ingestion. This relatively small degree of protection by L-649,923 suggests either that L-649,923 is not a sufficiently potent antagonist to diminish the effect of endogenous LTD4 in vivo or that LTD4 does not play a major role in the airway response to antigen challenge.
Administration, Inhalation↗
Management of asthma in schools.
A questionnaire on asthma in schools was circulated to 291 Nottingham schools. The response rate was 91%. Three areas of concern were identified: are schools aware of all their asthmatic pupils; should children have more access to their medications in school; and do teachers need more guidance in supervising illnesses.
Adolescent↗
Descriptive epidemiology of bronchial reactivity in an adult population: results from a community study.
The bronchial response to inhaled histamine has been suggested as an epidemiological tool for assessing the prevalence of asthma, though the exact relationship between reactivity and asthma is unknown. Tests of bronchial reactivity to histamine were carried out in 511 subjects aged 18-64 years, randomly selected from the population in two areas of the South of England, who had returned questionnaires on respiratory symptoms. Bronchial reactivity to less than or equal to 8 mumol histamine was present in 14% and was associated with positive skin test responses to common allergens and with smoking history. Both of these relationships were in turn dependent on age, skin sensitivity being the more important determinant of reactivity in the young and smoking the more important in older subjects. Bronchial reactivity was least prevalent in the 35-44 year age group. No independent effect on reactivity of sex, social class, or area of residence was detected, and no significant effect from recent respiratory tract infections. Interpretation of the bronchial response to histamine in selected groups of subjects must take account of age, atopic state, and smoking history.
Adult↗
Estimation and repeatability of the response to inhaled histamine in a community survey.
Epidemiological problems arising from the absence of an agreed definition of asthma have led to the use of bronchial reactivity tests in community surveys of asthma prevalence. Since only a minority of the general population will develop bronchoconstriction in response to the dose of histamine considered acceptable for use in the community it is important to make maximum use of the data available. Several methods for summarising the information in the dose-response curve obtained from a histamine challenge test have been compared. A standardised histamine challenge test was administered to 797 subjects selected from two communities, and a repeat test to 106 subjects. The test was well accepted. For most subjects FEV1 rose initially after administration of histamine (median rise 100 ml), so maximum FEV1 was used as the baseline from which the 20% fall to achieve a PD20 was calculated. In order to use all the data rather than just two points on the FEV1-log dose graph, PD20 was estimated by means of curve fitting, and the values were compared with PD20 from linear interpolation. An exponential curve was found to fit the data well. Extrapolation from the maximum dose of 4 mumol up to 8 mumol was allowed in the estimation of PD20 by both methods. The curve fitting method gave slightly more reproducible PD20 values than did linear interpolation, and also gave more estimates in the range 0.03-8 mumol. The repeatability of PD20 compared well with that of asthmatic subjects tested in a clinical environment. Curve fitting has an advantage over linear interpolation in large community studies, for which analysis of data by computer is essential.
Adolescent↗
Luminal digestion of lactoferrin in suckling and weanling rats.
The development of luminal digestion of lactoferrin was evaluated in vitro by incubating 125I-labeled lactoferrin with 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 hydrolysis of lactoferrin at pH 3.2 in the weanling was 20-fold greater than that in the suckling. In the small intestine at neutral pH, luminal degradation of lactoferrin was minimal in the suckling but increased significantly after weaning, with maximal degradative capacity demonstrable in the midjejunum. Sephadex G-75 chromatography of intestinal acid-soluble breakdown products revealed two peaks of radioactivity, each comprising 40-45% of the total product; analysis of intestinal acid-precipitable products by polyacrylamide gel electrophoresis yielded several discrete lower molecular weight species. Food deprivation for 12 h/100 g body wt decreased lactoferrin degradation in the weanling jejunum and midjejunum. Our findings suggest that lactoferrin digestion may vary with respect to postnatal age of the organism, segment of the gastrointestinal tract, and dietary state. In the young animal, lactoferrin degradation is minimal, and consequently its potential for biological function may be high.
Acids↗
Response to inhaled histamine and 24 hour sodium excretion.
A relation between the prevalence of asthma and economic development has been suggested by studies in migrants and other surveys in developing countries. That this correlation might be partially explained by an increased intake of salt in the diet is supported by the observation that sales of table salt in the different regions of England and Wales are independently correlated with mortality from asthma for men and for children. As part of a wider survey of asthma 138 men living in two Hampshire villages and aged 18-64 were given a bronchial histamine challenge test and had their 24 hour urinary excretion of sodium measured. Bronchial reactivity was strongly related to 24 hour excretion of sodium after allowing for the effects of age, atopy, and cigarette smoking, there being on average a 10-fold difference in reactivity over the 95% range of sodium excretion recorded in the study. The data suggest that a high sodium diet may potentiate bronchial reactivity.
Adolescent↗
Milk protein quality in mothers delivering prematurely: implications for infants in the intensive care unit nursery setting.
Because reports comparing the nitrogen content of breast milk from mothers delivering prematurely and at term have conflicted, the present study sought to compare these milks during the first month of lactation with respect to total protein and the distribution of protein among individual protein species and amino acids. No significant differences in total protein concentration were established. However, immunoglobulin comprised a greater proportion of protein in preterm milk than in term milk. The major component of the milk casein fraction, beta-casein, was present in similar proportions in early term and preterm milk, yet increased with time in term milk but not preterm milk. Lactoferrin and lactalbumin were similar in both milks. Differences in amino acid composition were found for serine, arginine, and tyrosine. With respect to protein composition, preterm milk and term milk thus differ during the first month of lactation, and the different patterns of change in individual components suggest that factors other than milk volume contribute to protein content.
Amino Acids↗
Discordance of milk protein production between right and left mammary glands.
The cases of two lactating mothers whose milk from right and left mammary glands differed dramatically in protein concentration and composition are presented. The discordance in protein quality between the two breast milks underscores the need to sample both breasts in future studies of milk proteins and suggests that each breast may possess some degree of autonomy with respect to milk protein production.
Adult↗
Specific thromboxane synthetase inhibition and albumin excretion rate in insulin-dependent diabetes.
Albumin excretion rates (AER) were measured in 30 insulin-dependent diabetics during a 16-week double-blind, randomised, placebo-controlled study of the specific thromboxane synthetase inhibitor UK-38,485.6 of 15 subjects in the active group had microalbuminuria (defined as mean pretreatment AER 20-150 micrograms/min); in these patients AER fell from 32 +/- 3 micrograms/min to 11 +/- 1 micrograms/min at 8 weeks and 9 +/- 1 micrograms/min at 16 weeks. The AER rose again (to 29 +/- 8 micrograms/min) within 12 weeks of stopping the drug. There was no significant change in the 10 patients with microalbuminuria who received placebo. There was a strong correlation between change from baseline values and the baseline values themselves in the active, but not in the placebo group, and the change from baseline differed significantly between the two groups. There was no change in glycosylated haemoglobin or mean blood glucose levels during the study. In a separate study UK-38,485 caused significant suppression of thromboxane B2 synthesis in diabetic and non-diabetic subjects.
Adult↗
Efficacy of early newborn discharge in a middle-class population.
The safety of early newborn discharge was assessed by determining the incidence, time of onset, and nature or problems requiring hospitalization that appeared in the first two weeks of life among 1,735 consecutively born term infants in a private metropolitan hospital. Infants with and without abnormalities during the initial six-hour transitional period were compared. Of 1,583 initially well infants, 11 (0.7%) had problems other than jaundice develop that required hospitalization in the first three days of life. In contrast, 42 (28%) of the 152 infants with abnormal transitional periods required prolonged hospital care; this was statistically significant. The nature of the problems occurring before and after 72 hours was similar, jaundice being the most common and occurring with equal frequency in both periods. Most illness requiring hospitalization in the first three days of life could have been safely detected during an outpatient visit; these findings, in addition to a cost-benefit estimate, suggest that early discharge of initially well infants with careful follow-up may be an effective alternative to a traditional three-day stay.
Arizona↗
Resuscitation of the newborn infant.
Perinatal asphyxia may occur prior to or at the time of birth, leading to hypoxia and acidosis with persistence of the fetal circulatory pattern. Resuscitation facilitates transition to the adult circulatory pattern by restoring normal oxygenation, ventilation, and perfusion. Assessment of the degree of asphyxia should utilize the Apgar score, and resuscitation should proceed in a stepwise fashion to an extent determined by the degree of depression. Aspects of resuscitation unique to the newborn are reviewed, in addition to situations requiring specific intervention.
Anesthesia, Obstetrical↗
'Baby Doe' rulings-review and comment.
The recent controversy over the "Baby Doe" regulations issued by the Department of Health and Human Services represents the culmination of a dilemma that has faced the medical and legal professions for more than a decade. Although they have not been upheld by the courts, the regulations express the position that withholding treatment from defective newborns may constitute discrimination on the basis of handicap and advocate mechanisms for the reporting of such practices. Legislation regarding this issue is pending at both the national and state levels. The rulings have been disputed by many medical and professional groups, which are working to provide acceptable alternatives.
Arizona↗
The "Baby Doe" issue: developments at the state level.
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Arizona↗
Study of possible risk factors for severe retinopathy in non-insulin dependent diabetes.
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Blood Glucose↗
Macromolecular synthesis in T7 infected F' cells.
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Coliphages↗
Permeability lesions in male Escherichia coli infected with bacteriophage T7.
The abortive development of bacteriophage T7 in E. coli cells carrying F factors has previously been attributed to a lack of virus-directed modification of ribosomes in such cells. We find it unnecessary to postulate such translational control to explain the failure of T7 development. Instead, there is a general cessation of macromolecular syntheses around 8 min after T7 infection of F' cells. This cessation is correlated with a sudden outflow of the entire acid-soluble pool of phosphorus-containing compounds and loss of the ability to accumulate amino acids. Manifestation of these defects requires expression of at least one T7 gene and one episomal gene.
Autoradiography↗
Bronchoscopic evaluation of airway obstruction in campomelic dysplasia.
Campomelic dysplasia is a generalized disorder of cartilaginous growth and development, leading to early death from pulmonary insufficiency. We describe the airway dynamics as observed bronchoscopically in two affected infants. Both infants demonstrated anatomic compromise of the upper airway and diffuse laryngotracheobronchomalacia. Additionally, both had a characteristically small, bell-shaped thoracic cage. The abnormal airway dynamics produced serious inspiratory and expiratory obstruction in these infants and, in combination with the restrictive chest wall defect, led rapidly to the development of respiratory failure. While palliative procedures such as tracheostomy may temporarily improve airway dynamics, future respiratory tract insults may prove fatal.
Airway Obstruction↗