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Biomedical subjects

J R Britton

Publications and source records attributed to J R Britton.

At least 37 records · Page 2Linked to original sources

Dietary antioxidant vitamin intake and lung function in the general population.

We have investigated the relation between lung function and dietary intake of the antioxidant vitamins C and E in the general population in a cross-sectional survey of a random sample of adults from the electoral register of an administrative area of Nottingham. In 2,633 subjects 18 to 70 yr of age, we measured FEV1 and FVC, allergen skin sensitivity to grass pollen, cat fur, and Dermatophagoides pteronyssinus, pack-years smoking exposure by personal recall, and usual dietary intake of vitamins C and E by semiquantitative food frequency questionnaire. After adjustment for the effects of age, sex, height, mean allergen skin wheal diameter, and pack-years smoking history, both FEV1 and FVC were significantly and independently related to mean daily intake of vitamin C, such that a standard deviation (40 mg/d) higher vitamin C intake was associated with a 25.0 (95% CI, 5.2 to 44.8; p = 0.01) ml higher FEV1 and a 23.3 (0.94 to 45.7, p = 0.04) ml higher FVC. There was also an association between vitamin E intake and lung function, such that a standard deviation (2.2 mg) higher intake of vitamin E was associated with a 20.1 (1.3 to 40.4, p = 0.04) ml higher FEV1 and a 23.1 (1.0 to 45, p = 0.04) ml higher FVC. However, vitamin C and vitamin E intakes were significantly correlated (r = 0.29, p < 0.001), and after allowing for the effects of vitamin C there was no additional independent effect of vitamin E on either FEV1 or FVC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Heart-lung transplantation in cystic fibrosis: predictions for the next decade in England and Wales.

Heart-lung transplantation has become an established treatment for end stage respiratory failure secondary to cystic fibrosis. The success of this form of treatment, and the increasing survival of such patients, suggests there will be an increased need for transplantation over the next decade. We have used cystic fibrosis population predictions and all cause mortality data to estimate the number of cardio-pulmonary deaths, due to cystic fibrosis, over the next decade and to estimate the number of such patients who are likely to benefit from heart-lung transplantation. We estimate that there will be between 85 and 127 potential transplant recipients with cystic fibrosis each year over the next decade. During 1990, 1991 and 1992 there were less than 40 transplants each year in such patients. These data emphasize the need to expand transplantation services and to maintain the availability of donor organs.

Adolescent↗

Relation of pulmonary lymphangio-leiomyomatosis to use of the oral contraceptive pill and fertility in the UK: a national case control study.

BACKGROUND: Pulmonary lymphangioleiomyomatosis is a rare progressive disease of unknown aetiology affecting premenopausal women. Since the oral contraceptive pill has been implicated in its pathogenesis, a case control study was carried out to determine whether women with the disease were more likely to have taken the oral contraceptive pill, and whether the disease was associated with other conditions related to sex hormones including pregnancy, parity, and fibroids. METHODS: All chest physicians in the UK were asked for details of all live patients with pulmonary lymphangioleiomyomatosis; the patient's family doctor was then asked for four age and sex matched control subjects from their patient register. Details of lifetime use of the oral contraceptive pill, pregnancy, parity, history of fibroids, and smoking were obtained from cases and controls. Relative odds of exposure to potential risk factors were estimated by conditional logistic regression. RESULTS: Medical details were obtained from all 23 cases of lymphangioleiomyomatosis identified; questionnaires were completed by 21 cases (one by proxy) and by 46 matched controls of mean (SD) age 43 (10) and 44 (11) years, respectively. The patients had a mean age of 34 (9) years at onset of symptoms and a median (range) time of 2 (0-29) years from onset of symptoms to diagnosis. Compared with control subjects, cases did not differ in the use of the oral contraceptive pill (odds ratio (OR) 0.39, 95% CI 0.09 to 1.68), diagnosis of fibroids (OR 3.12; 95% CI 0.52 to 18.7), age of menarche, menstrual history, or lifetime smoking. They were, however, less likely to have been pregnant (OR 0.14, 95% CI 0.03 to 0.71) or to have had children (OR 0.13, 95% CI 0.03 to 0.67). More pregnancies had ended in spontaneous abortion (28% v 8%) but the proportion of women undergoing spontaneous abortion was similar in cases and controls (OR 2.13, 95% CI 0.47 to 9.3). CONCLUSIONS: This study does not support the hypothesis that use of the oral contraceptive pill is causally associated with the development of pulmonary lymphangioleiomyomatosis. Sex hormones may be involved, however, since patients were less likely to have been pregnant or to have had children, and tended to have had more spontaneous abortions and an increased incidence of fibroids.

Abortion, Spontaneous↗

Early discharge of the term newborn: a continued dilemma.

OBJECTIVE: To provide the pediatric practitioner with a summary of available data regarding the appropriate time of hospital discharge of the term newborn. METHODOLOGY: Published series on early discharge were critically reviewed. RESULTS: Heterogeneity and limitations of methodology and study design substantially limit conclusions that may be drawn from published studies. CONCLUSION: Early discharge recommendations of the American Academy of Pediatrics remain appropriate, and decisions regarding the timing of discharge of the well term newborn should be individualized and made by the practitioner based upon the medical, social, and economic aspects of each case.

Humans↗

Steroid sparing effect of nedocromil sodium in asthmatic patients on high doses of inhaled steroids.

Nedocromil sodium is a non-steroidal prophylactic agent developed for the management of asthma. We have assessed the steroid sparing potential of inhaled nedocromil sodium 4 mg four times daily in a randomized, double blind, placebo controlled study in 69 asthmatic subjects controlled on inhaled beclomethasone dipropionate in the dose range 1000-2000 micrograms daily. Following a 4 week run-in period subjects added nedocromil sodium or placebo by metered dose inhaler to their usual medication for a further 4 weeks. The dose of inhaled steroid was then reduced at fortnightly intervals according to a predetermined schedule, with monitoring of asthma severity, symptom scores, bronchodilator use and peak flow recordings. Sixty subjects entered the steroid reduction phase and achieved median (range) % decreases in steroid dose of 80 (17-100)% with nedocromil sodium compared to 65 (0-100)% with placebo (P = 0.34) with 14 patients in the nedocromil sodium group and 10 in the placebo group being withdrawn completely from inhaled steroids. Subjective global assessment scores were significantly better with nedocromil sodium (mean 2.14) than with placebo (2.93; P < 0.02) though there was no difference between individual daily symptom scores. In this study therefore in asthmatic patients controlled on high doses of inhaled steroids, nedocromil sodium was well tolerated but the small differences in steroid sparing effect between nedocromil and placebo were not statistically significant.

Administration, Inhalation↗

Factors affecting peak expiratory flow variability and bronchial reactivity in a random population sample.

BACKGROUND: Bronchial reactivity measurements are widely used in epidemiological studies to provide an objective marker of asthma. There are, however, several potential advantages of measuring peak expiratory flow (PEF) variability instead, particularly in large studies. PEF variability and bronchial reactivity were compared in a population sample to assess the relationships of the two measurements to factors known to be associated with airways disease, and to compare their response rates. METHODS: Subjects aged 18-65 were randomly selected from the electoral register of an administrative area in eastern England and randomised to attend either for a bronchial challenge test measuring the provocative dose of methacholine producing a 20% fall in FEV1 (PD20), or to measure PEF at two hourly intervals during waking hours for one week. Skin tests with common allergens were performed and a smoking history obtained. PEF variability was expressed as the amplitude % mean (highest - lowest x 100/mean). RESULTS: A total of 273 subjects (69%) collected a PEF meter but a completed record sheet was returned by only 247 (62%); this was still significantly more than the 202 subjects (54%) who attended for and successfully completed a challenge test. Amplitude % mean was higher in women than in men (9.7% v 8.5%). In multiple regression analysis amplitude % mean increased significantly with age, mean skin weal diameter, and with current smoking. The odds of having a PD20 below 24.5 mumol increased with mean skin weal diameter and were greater in current smokers. Neither age nor sex had a significant effect on bronchial reactivity but there were significant interactions between age and the effects of both smoking and atopy. CONCLUSIONS: The higher response rate associated with the use of PEF variability measurement, and the association with factors implicated in the pathogenesis of airways disease, suggest that PEF variability would be a useful measurement to employ in epidemiological studies.

Adolescent↗

Weight, length, head and chest circumference at birth in Phoenix, Arizona.

Standard percentile curves are presented for weight, length, head circumference and chest circumference at birth for a population of 27,963 singleton infants born between the gestational ages of 26 and 42 weeks at a large, private hospital in Phoenix, Arizona. At term, all four growth parameters were significantly greater in male than in female infants. These parameters were significantly reduced in infants born to mothers who smoked and increased in infants born to mothers with diabetes. Percentiles in all parameters were higher than in those of previous studies, suggesting that continued use of growth curves based on older data may result in misclassification of infants with respect to appropriateness of growth-for-gestational age.

Analysis of Variance↗

Comparison of PD20 with two alternative measures of response to histamine challenge in epidemiological studies.

Bronchial responsiveness to histamine or methacholine provides a useful objective measure for epidemiological studies of airways disease, but most people in a community population do not have a 20% fall in forced expiratory volume in one second (FEV1) with the highest dose administered. Histamine challenge data were analysed to compare the repeatability. Normality and separation of symptom groups of the early dose-response slope with provocative dose producing a 20% fall in FEV1 (PD20). Tests were continued until a 20% fall in FEV1 occurred, or 4 mumol had been given. Data were available for 510 randomly selected subjects, and for an additional 283 with wheeze. A repeat test was obtained in 104 individuals. PD20 was estimated by curve fitting, with extrapolation to 8 mumol. Least-squares slope of percentage decline in FEV1 on histamine dose was calculated, using all the measured points and two-point slope as the fall from the post-saline measurement to the maximum cumulative dose divided by the maximum dose. Log transformation of PD20 and shifted reciprocal transformations of slope produced constant variance. Over all subjects the three measures had similar repeatability; in subjects with PD20 > 8 mumol the intraclass correlation for two-point slope was only 0.26, but was 0.66 for least-squares slope. Neither measure of slope was normally distributed, but the distribution of log(PD20) was consistent with a censored normal distribution. In conclusion, least-squares slope is preferable to two-point slope for epidemiological studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Comparison of bronchial reactivity and peak expiratory flow variability measurements for epidemiologic studies.

Inclusion of a standardized measurement of airway function is important in epidemiologic studies of asthma to facilitate comparison between different studies. Bronchial reactivity is widely used in such studies, but measurement of peak expiratory flow (PEF) variability has a number of potential advantages. We compared PEF variability with methacholine challenge tests in a community population sample. Subjects selected at random (n = 95) and on the basis of having experienced wheeze in the last 12 months (n = 130) performed a challenge test with methacholine to a maximum dose of 12.25 mumol and made serial PEF recordings every 2 h for a week. PEF variability was expressed as mean daily maximum amplitude as a percentage of the mean (amplitude % mean). Increased bronchial reactivity and PEF variability were arbitrarily defined as values above the 10th or below the 90th percentiles in the random sample. A measurement of amplitude % mean was available from all 225 subjects, whereas only 115 (51%) had a measurable PD20 methacholine. PD20 measurements correlated weakly but significantly with amplitude % mean (r = -0.44, p less than 0.001). Increased values of both bronchial reactivity and PEF variability were related to the presence of respiratory symptoms in the week before testing. Asthma was more strongly related to increased bronchial reactivity than to PEF variability. Both measurements showed a strong association with atopy and the intraclass correlation coefficients (ratio of between-subject to total variance) were similar for both.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Biologically active polypeptides in milk.

Many biologically active polypeptides have been described in the milk of several species. Various functions for these polypeptides in addition to nutrition have been proposed in the maternal body and in the breast-fed infant. These polypeptides are derived from several sources and multiple factors control their secretion into milk as well as their fate in the mother and infant. An increasing body of evidence supports the concept that they may function physiologically.

Animals↗

Cystic fibrosis: current survival and population estimates to the year 2000.

BACKGROUND: Survival from cystic fibrosis is increasing rapidly. Estimates of the extent of this improvement should allow health care facilities to be planned to deal with the expanding population of patients with cystic fibrosis. Estimates of life expectancy are also essential if accurate information on current prognosis is to be given to parents of an affected child, or to prospective parents deciding whether to proceed with a pregnancy where the fetus may be affected. METHODS: Survival trends in the national data on cystic fibrosis have been analysed to produce estimates of the likely size of the cystic fibrosis population over the next decade and to predict the life expectancy of children born with cystic fibrosis in the years up to 1990. RESULTS: In England and Wales the estimated number of patients with cystic fibrosis is at present about 5200, of whom 3300 (63%) are aged under 16 years. By the year 2000 the total population will increase to 6000, with 3400 (57%) aged under 16. Thus the number of children with cystic fibrosis will remain fairly constant over the next 10 years, whereas adult numbers will increase by about 36% (from 1901 to 2577). The median life expectancy of children with cystic fibrosis born in 1990 is estimated to be 40 years, double that of 20 years ago. CONCLUSION: This study suggests that health service provision for children will not need to change substantially over the next 10 years whereas services for adults will need to increase by about a third. Parents can be counselled that the median life expectancy of a newborn child with cystic fibrosis is currently likely to be of the order of 40 years.

Age Factors↗

Bronchodilator, cardiovascular, and hypokalaemic effects of fenoterol, salbutamol, and terbutaline in asthma.

The airway response and cardiovascular and hypokalaemic effects of fenoterol, salbutamol, and terbutaline given in multiples of standard doses from metered-dose inhalers were studied in ten patients with mild asthma. In a double-blind, crossover, placebo-controlled study the subjects received 2, 6, and 18 puffs of each drug with intervals of 90 min, and forced expiratory volume in 1 s, heart rate, QTc interval, plasma potassium concentration, tremor, and bronchial reactivity to histamine were measured. All three drugs produced similar bronchodilatation. However, the rises in heart rate, QTc interval, and tremor and the fall in plasma potassium were greater after fenoterol than after salbutamol or terbutaline. The maximum mean (SD) increases in heart rate for fenoterol, salbutamol, and terbutaline were 29 (24) bpm, 8 (9) bpm, and 8 (14) bpm, respectively; falls in plasma potassium were 0.76 (0.62) mmol/l, 0.46 (0.32) mmol/l, and 0.52 (0.39) mmol/l, respectively. Fenoterol afforded no additional protection against histamine compared with salbutamol. These findings suggest that at doses based on those used in clinical practice fenoterol causes more adverse effects than salbutamol or terbutaline. The most likely explanation for these effects is that fenoterol has been marketed at a higher dose than the other beta 2-agonists; fenoterol may in addition be less selective for beta 2 receptors.

Adolescent↗

Liver disease in neonatal lupus erythematosus.

We report the cases of neonatal lupus erythematosus associated with significant hepatic involvement in three living infants and in one infant who died 3 hours after delivery. The three living infants had neonatal cholestasis as a major component of their clinical findings. Pathologic changes included giant cell transformation, ductal obstruction, and extramedullary hematopoiesis. Liver involvement has been noted incidentally in children with neonatal lupus erythematosus, but it has generally been attributed to hemodynamic compromise as a result of congenital heart block or systemic toxic reactions. We speculate that neonatal hepatitis proceeding to hepatic fibrosis may occur in neonatal lupus erythematosus, analogous to the occurrence of "idiopathic" congenital heart block. The neonatal hepatitis associated with neonatal lupus erythematosus is a form distinguishable from the "idiopathic" group. Liver involvement may be more common than was previously recognized, and prospective studies to look for maternal autoantibodies in idiopathic neonatal liver disease should be undertaken.

Antibodies, Antinuclear↗

Effect of sodium-transport inhibitors on airway smooth muscle contractility in vitro.

1. To determine whether alterations in membrane sodium transport in airway smooth muscle can alter its contractility, we studied the effect of ouabain (a Na+/K(+)-adenosine triphosphatase inhibitor) and amiloride on contractile responses in bovine trachea and human bronchial rings in a series of studies. 2. Ouabain (10(-6)-10(-4) mol/l) caused concentration-related contraction of bovine trachea with a maximum effect at 30 min; the mean increases in tension with 10(-6), 10(-5) and 10(-4) mol/l ouabain were 19, 27, and 32%, respectively, of the maximum response seen with 10(-3) mol/l histamine (n = 6). In human bronchial rings, ouabain (10(-5) mol/l) caused a mean contraction which was 40% of the maximum response to methacholine (n = 8). 3. Calcium-free fluid (plus ethylenediaminetetraacetic acid) and nifedipine (10(-5) mol/l) inhibited ouabain-induced contractions, suggesting that contraction was mediated in part by calcium entry via voltage-dependent calcium channels. Phentolamine (10(-5) mol/l) was without effect. 4. Ouabain (10(-5) mol/l) did not alter histamine responsiveness in bovine trachea or methacholine responsiveness in human bronchial rings. 5. Amiloride did not affect resting tone in bovine trachea but caused a concentration-dependent relaxation of bovine tracheal strips preconstricted with carbachol, 10(-3) mol/l amiloride relaxing strips completely over 15 minutes (n = 8).(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗

Effect of sodium-transport inhibitors on bronchial reactivity in vivo.

1. We have recently shown that ouabain, an inhibitor of Na+/K(+)-adenosine triphosphatase, causes contraction of bovine and human airways in vitro, and that amiloride causes relaxation and inhibits receptor-operated contraction in bovine trachealis. 2. To determine whether such drugs alter bronchial reactivity in vivo, we have studied the effect of oral digoxin (an inhibitor of Na+/K(+)-adenosine triphosphatase) and oral and inhaled amiloride on bronchial reactivity to histamine in three double-blind, placebo-controlled studies. 3. Histamine reactivity was measured as the provocative dose causing a 20% reduction in the forced expiratory volume in 1 s (PD20FEV1) or, when normal subjects were included, the provocative dose causing a 35% reduction in the specific airways conductance (PD35sGaw); the results are given as geometric mean values. 4. In study 1, 13 atopic asthmatic subjects were given 20 mg of oral amiloride or placebo on separate days. Two hours after the drug, the geometric mean PD20FEV1 for histamine was 0.43 mumol after amiloride and 0.54 mumol after placebo (95% confidence intervals for the difference: 0.9 to -0.2 doubling doses of histamine; P = 0.2). 5. In study 2, six normal and 24 atopic asthmatic men inhaled 10 ml of 10(-2) mol/l amiloride or diluent control in a crossover study. The mean values of PD35sGaw for histamine immediately after inhalation of amiloride and placebo were 3.0 mumol and 4.3 mumol, respectively, in the normal subjects (95% confidence intervals for the difference: -0.53 to 1.52 doubling doses, P = 0.2), and 0.33 mumol and 0.29 mumol in the asthmatic subjects (95% confidence intervals for the difference: -0.95 to 0.57 doubling doses; P = 0.6).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effects of social class, sex, and region of residence on age at death from cystic fibrosis.

To determine the time trend in age at death from cystic fibrosis and the independent effects of social class, sex, and region of residence mortality data for England and Wales from 1959 to 1986 were analysed. Median age at death increased from 6 months in 1959 to 17 years in 1986 and was higher in most years from 1970 in male patients (by one to six years) and in social classes with non-manual occupations (by one to 12 years). Independent odds ratios for death above the median age for the year of death (calculated for years from 1974, when regions of residence were coded by regional health authority area) were 1.47 (95% confidence interval 1.16 to 1.87) in male compared with female patients and 2.75 (2.16 to 3.52) in non-manual compared with manual social classes. The independent odds of death at above the median age also varied significantly among regions of residence by a ratio of up to 2.67. Social class, sex, and region of residence are all potential determinants of survival of patients with cystic fibrosis. Social class is particularly likely to confound the effect of management in specialist centres on survival.

Adolescent↗

Gastric luminal digestion of lactoferrin and transferrin by preterm infants.

Lactoferrin, a milk iron-binding protein, may play antimicrobial, iron-absorptive and growth-promoting roles in the developing gastrointestinal tract. To perform such functions, lactoferrin must survive digestive processes in the gut lumen in an active form. We investigated the gastric digestion of lactoferrin in addition to that of the other milk proteins, transferrin and casein, in preterm infants by measuring their degradation during incubation in vitro at 37 degrees C with gastric fluid at pH 1.8, 3.2 and 5.8. Fluid was obtained 1 h after a milk feeding, a time of maximum peptic activity, from 12 infants with a mean gestational age of 29.7 +/- 0.8 weeks at birth and a postnatal age of 24.7 +/- 3.2 days at sampling. Hydrolysis of all three proteins as indicated by generation of trichloroacetic acid soluble material from iodinated substrate was maximal at acid pH and declined by greater than 75% at pH 5.8, lactoferrin was less rapidly degraded than casein at low pH and transferrin breakdown was intermediate. Analysis of reaction mixtures by SDS-polyacrylamide gel electrophoresis showed degradation of lactoferrin and transferrin to low molecular weight products at pH 3.2 but minimal breakdown at pH 5.8. Several discrete fragments were generated at low pH, including species with molecular weights of 41,000-42,000 which may represent half-molecules. We conclude that dietary lactoferrin and transferrin may be degraded by preterm infant gastric fluid to discrete species, but that hydrolysis may be minimal at the prevailing postprandial pH. Consequently they may be rendered available for possible subsequent biological action within the infant.

Caseins↗