Heparin-induced release of lipase activity in the human forearm: an immunological study.

Low doses of heparin were injected into the brachial artery of three volunteers. The lipase activities in the deep vein of the same forearm, draining mainly muscle tissue, and in the artery were monitored over a 10-min period. Lipase activity, rapidly released by heparin in the deep vein, was immunologically similar to lipoprotein lipase (E.C. 3.1.1.3), i.e. (1) it did not react with antiserum against human post-heparin plasma hepatic lipase and (2) it was inhibited by an antiserum against bovine milk lipoprotein lipase, which cross reacts with human post-heparin plasma lipoprotein lipase. The evidence that human muscle contains lipoprotein lipase is discussed.

Circannual changes in plasma concentrations of immunoreactive retinol-binding protein and luteinizing hormone in male and female Japanese quail.

In a single experiment, lasting for 18 months, male and female quail were exposed to an annual cycle of artificial photoperiod synchronized with sunrise and sunset, and their plasma levels of immunoreactive retinol-binding protein (IRBP) and LH were monitored at frequent intervals. Plasma levels of both IRBP and LH showed a repeating annual cycle with maximal levels during the spring/summer, the period of reproductive activity and highest rate of egg-laying, and minimal levels during the autumn/winter. Plasma levels of IRBP and LH were significantly, but only weakly, correlated with each other. The possible role of LH in the regulation of plasma IRBP during reproduction is discussed. Evidence is presented that the proportion of IRBP which does not carry retinol (retinol-binding apoprotein; apoRBP) varies throughout the female breeding cycle and that the high apoRBP concentration noted in the spring/summer period may be related to the deposition of retinol in the egg.

Application of pyrolysis mass spectroscopy and SDS-PAGE in the study of the epidemiology of Pseudomonas cepacia in cystic fibrosis.

Representative isolates of Pseudomonas cepacia from 15 cystic fibrosis (CF) patients attending the Respiratory Unit of Alder Hey Childrens' Hospital were investigated by SDS-PAGE of whole-cell polypeptides and by pyrolysis mass spectroscopy (PMS). SDS-PAGE was less discriminatory than PMS. Eleven isolates were indistinguishable by PMS and considered to represent re-isolates of an endemic strain; four isolates were distinct from this group, and from one another. P. cepacia was first isolated on the unit in July 1989 from a patient who had attended a UK selection meeting for a Canadian CF camp. A ward and outpatient segregation policy was introduced, but colonisation of further patients occurred. In August 1991, the Adult CF Association recommended that all social activities involving colonised patients should cease. This, and an increased awareness amongst older CF patients of the risks of person-to-person transmission, was associated with a marked decline in new cases. Social activity and hospital admissions were compared for colonised patients during the year before colonisation with P. cepacia, and matched patients who did not acquire the endemic strain. This showed a significantly higher attendance at CF social events for colonised patients, but no significant association between colonisation and hospital admission. These results are strong indirect evidence that transmission of P. cepacia occurs through social contact outside the hospital environment.

Sorbitol and other polyols in lens, adipose tissue and urine in diabetes mellitus.

Sugars and polyols (glucose, fructose, sorbitol, inositol and pentitols) have been measured in urine, adipose tissue and lens in groups of diabetic and non-diabetic patients. The daily excretions of glucose, sorbitol and inositol were raised in the diabetics. There was a linear relation between 24 hour urinary excretion of glucose and hexitols (r = +0.87, p less than 0.001). In lens of diabetics there was an increase in glucose concentration, but not of fructose, sorbitol or inositol. Compounds readily detected in adipose tissue were inositol and glucose; in addition an unidentified carbohydrate was detected in adipose tissue that related to the concentration of tissue glucose. These results are discussed in relation to the possibility that tissue accumulation of polyols could be responsible for the secondary complications of diabetes such as cataracts.

Changes in airflow obstruction and oxygen saturation in response to exercise and bronchodilators in cystic fibrosis.

The airway response to exercise and inhaled terbutaline was assessed in 25 patients with cystic fibrosis (CF), seeking evidence for the possible deleterious effects of bronchial muscle relaxation. We postulated that "early" and "late" flows, taken from the full maximum expiratory flow volume curve, might move paradoxically in patients with unstable airways. Oxygen saturation was measured continuously; desaturation occurred early in exercise with partial recovery thereafter. This was unrelated to changes in expiratory airflow measurements. Both during and after exercise, and after inhaled bronchodilator, changes in expiratory airflow measurements were strikingly variable. Changes in individual measurements should be interpreted in relationship to the within-subject variability of the test in patients with CF. During exercise, there was a significant increase in mean FEV1; this was most marked in patients with worst lung function. Two patients (both with severe lung disease) showed paradoxical changes in early and late flows. After exercise, only two patients showed the asthmatic pattern of postexercise bronchoconstriction. After inhaled bronchodilator, the group as a whole showed small but statistically significant increases in expiratory airflow measurements. Those with highest baseline FEV1 had the greatest bronchodilator response; this is the opposite of the pattern observed in asthma. Paradox did not occur after bronchodilators and only one patient showed a significant fall in late expiratory airflow. This pattern of expiratory airflow changes is compatible with the concept of airway instability in which any beneficial effects of bronchial tone reduction are canceled out by the effects of compression of damaged airways rendered more compliant by loss of bronchial wall tone. We did not observe any clinically important deleterious effects from this mechanism.

Comparison of the occlusion and inflation techniques for measuring total respiratory compliance in sick, intubated infants.

Respiratory system compliance (Crs) can be used to assess lung stiffness in sick, intubated infants, avoiding the use of an esophageal balloon. Crs was assessed in a group of 15 sick, intubated infants using the occlusion and inflation techniques. The occlusion technique gave satisfactory results in 13 infants. Apneic pauses following occlusion were obtained in infants up to 10 months of age. Satisfactory measurements of Crs were obtained in all 15 infants using the inflation technique, but difficulty was experienced in obtaining data over the tidal volume range in three of them. A close agreement was found between the two methods of measuring Crs in the ten infants in whom a direct comparison was possible.

The accuracy of esophageal pressure measurements in convalescent and sick intubated infants.

Assessment of the esophageal pressure technique for measuring dynamic lung compliance (Cdyn) showed that accurate results were obtained in only 5 of 15 studies of sick intubated infants, whereas they were obtained in 6 of 6 studies of convalescent nonintubated infants. In sick infants, inaccuracy was due to large variations in esophageal pressure change (delta Pes) at different esophageal depths and difficulties validating Pes using the occlusion test. Methods of assessing lung stiffness that depend on the measurement of esophageal pressure are unreliable and should not be used in sick intubated infants.

Growth during one year of treatment with fluticasone propionate or sodium cromoglycate in children with asthma.

The aim of this study was to compare accurately measured growth over 12 months in asthmatic children treated with either fluticasone propionate (FP) 50 micrograms twice daily (b.i.d.) or sodium cromoglycate (SCG) 20 mg four times daily (q.i.d.). After a 2-week run-in, asthmatic children aged 4-10 years from 15 UK centers were randomized in a 3:4 ratio to open-label FP (n = 52) or SCG (n = 70). After 8 weeks, those whose asthma was not adequately controlled were switched from SCG to FP or withdrawn. Standing height was measured (Holtain stadiometry) at baseline, after 8 weeks and at 6 weeks intervals thereafter for 1 year. Morning peak flows (PEFam) were recorded by patients for 2 weeks during baseline, and 1 week before each visit during treatment. Urinary free cortisol (24 h) was measured at baseline, 6 months, and 1 year. After 8 weeks, 22 patients were withdrawn from SCG group (and were switched to FP), and five patients were withdrawn from the FP group due to poor asthma control. A further 21 and 11 patients were withdrawn from the SCG and FP groups, respectively, during the course of the study. There were no significant differences between patients who received FP and SCG for 1 year (n = 34 and n = 26, respectively) in terms of height velocity adjusted for age and gender (HV), or height velocity standard deviation scores adjusted for gender (HVSDS). Mean HV (mean HVSDS) were 6.0 cm/yr (0.1) and 6.5 cm/yr (0.5) for FP and SCG, respectively. There were no treatment differences in mean 24 h urinary free cortisol levels at 6 and 12 months. Mean % predicted PEFam improved over 1 year in both groups but to a greater degree in the FP group. We concluded that growth was normal in mildly asthmatic children receiving FP (50 micrograms bid) for 1 year. There were fewer withdrawals and lung function improved to a greater extent in FP treated patients than in patients receiving SCG.

Branhamella catarrhalis colonization in preschool asthmatics.

Branhamella catarrhalis has been associated with exacerbations of chronic bronchitis and asthma in adults. To investigate the possible role of B. catarrhalis in asthma of early childhood, we took posterior pharyngeal swabs from 24 normal children, 20 well asthmatics, and 20 acutely wheezy asthmatics, all between 1 and 4 years of age. On culture, 33% of the normal children were colonized with B. catarrhalis; colonization rates in the well asthmatics (70%) and in the wheezy asthmatics (75%) were significantly higher than in normals. The nature of this association requires further study.

Methicillin-resistant Staphylococcus aureus in children with cystic fibrosis: An eradication protocol.

A retrospective 12-year study (May 1988-July 2000) was undertaken in children with cystic fibrosis (CF) to evaluate 1) the magnitude of methicillin-resistant Staphylococcus aureus (MRSA) in these children; 2) the clinical impact of MRSA on CF; and 3) the efficacy of an MRSA protocol aimed at the eradication of the carrier state. The study maneuver comprised of 1) surveillance cultures of throat/rectum to detect the MRSA carrier state; 2) life-long cephradine rather than flucloxacillin to lift selection pressure; 3) topical application of oral and nebulized vancomycin for 5 days to clear the carriage of MRSA; and 4) a strict antistaphylococcal hygiene program, including handwashing and device policy. Fifteen children with CF (11 boys, with median age 117 months) positive for MRSA were enrolled. The current prevalence of MRSA among children with CF in our hospital is 6.5%. Of 15 children identified, only 12 (18 episodes of MRSA colonization) were treated according to protocol. Median age of MRSA acquisition was 73 months (interquartile range, 43-134 months). In 7 patients (55%), MRSA was eradicated. Of a total of 18 MRSA episodes, the protocol was successful in 10 episodes. The mean period of MRSA-free status was 12 months (range, 6-36 months). Pulmonary function (measured by FEV(1)) was not affected (68% of predicted before treatment, and 68% of predicted after treatment). All children were oropharyngeal carriers of both MRSA and ceftazidime-resistant P. aeruginosa. We believe that an effort has to be made to limit MRSA in CF clinics for the following reasons: 1) MRSA carriage in any individual is an abnormal condition; 2) limitation of systemic vancomycin use is desirable; 3) MRSA carriage may be a contraindication for lung transplantation; and 4) epidemiologically, a CF unit with a substantial MRSA problem functions as a source of dissemination for other patients.

Selective histamine blockade in childhood asthma; the effect of terfenadine on resting bronchial tone and exercise induced bronchoconstriction.

The orally active histamine H1 blocker terfenadine was investigated for its effect on resting bronchial tone and exercise induced bronchoconstriction in 20 asthmatic children by a double blind placebo controlled study. Terfenadine produced acute broncholidation with an average 32% improvement in FEV1 by 3 h. After exercise challenge terfenadine partially inhibited exercise induced bronchoconstriction. The maximum fall in PEFR after exercise was reduced from 32% after placebo to 21.5% after terfenadine. These results suggest that asthmatic children have background resting 'histamine tone' that is reversible by histamine H1 blockage.

Reversible bronchial dilatation in children: comparison of serial high-resolution computer tomography scans of the lungs.

INTRODUCTION: Bronchiectasis is generally considered irreversible in the adult population, largely based on studies employing bronchography in cases with a significant clinical history. It is assumed, that the same is true for children. Few studies have examined the natural history of bronchiectasis in children and diagnostic criteria on high-resolution computer tomography of the lungs are derived from studies on adults. Frequently, bronchiectasis is reported in children in cases where localised bronchial dilatation is present, incorrectly labelling these children with an irreversible life-long condition. OBJECTIVE: to evaluate changes in appearance of bronchial dilatation, unrelated to cystic fibrosis in children, as assessed by sequential high-resolution computer tomography (HRCT) of the lungs. METHODS: The scans of 22 children with a radiological diagnosis of bronchiectasis, seen at Alder Hey Children's Hospital between 1994 and 2000, who had at least two CT scans of the lungs were reviewed by a single radiologist, who was blinded to the original report. RESULTS: Following a median scan interval of 21 months (range 2-43), bronchial dilatation resolved completely in six children and there was improvement in appearances in a further eight, with medical treatment alone. DISCUSSION: A radiological diagnosis of bronchiectasis should be considered with caution in children as diagnostic criteria derived from studies in adults have not been validated in children and the condition is generally considered irreversible.

Association of spatial distribution of childhood respiratory morbidity with environmental dust pollution.

The objective of this study was to investigate the spatial distribution of respiratory morbidity and asthma in children in relation to high levels of airborne dust pollution. A cross-sectional survey of 2035 children (aged 5-11 yr) by parent-completed questionnaire, with concurrent monitoring of dust deposition rates in the vicinity of children's homes, was performed in 15 primary schools (5 in each of 3 areas of Merseyside). The main outcome measures were (1) doctor-diagnosed asthma, (2) parent-reported respiratory symptoms of recent excess cough, wheeze, and breathlessness, and (3) school absenteeism due to respiratory ill health. Proximity to the source of dust pollution was associated with increased prevalence of excess cough, breathlessness, school absence due to respiratory ill health, and doctor-diagnosed asthma, after adjusting for a range of socioeconomic, environmental, and other confounding factors. The adjusted odds for excess cough and breathlessness for children living within 2 km of the source (dock area) are estimated to be almost twice those for children living more than 2 km away: excess cough 1.9 (95% CI 1.4-2.6); breathlessness 1.9 (1.3-2.7); school absence 1.5 (1.2-1.9); and doctor-diagnosed asthma 1.5 (1.1-2.0). Excess cough was significantly associated with the mean annual dust deposition recorded in the vicinity of the child's home. The adjusted odds ratio for excess cough corresponding to an increase in mean annual dust deposition of 50 mg/m2/d was 3.1 (95% CI 1.1-8.2). These results suggest that airborne dust was associated with respiratory morbidity in these children, which could relate to the high prevalence of childhood doctor-diagnosed asthma in this community.

Targeting of dornase alpha therapy in adult cystic fibrosis.

Although dornase alpha (recombinant human DNase) can thin the viscid pulmonary secretions of cystic fibrosis (CF), clinical trials in groups of unselected patients have shown only modest average improvements in pulmonary function. The product is very expensive, so in conjunction with purchasers we designed selection criteria and a protocol for a 2-week trial to target CF individuals who might gain most benefit. Treatment was to be continued in those showing > or = 10% improvement in pulmonary function. Those who had a trial of dornase alpha were followed up for 2 years. Of 25 patients who had a 2-week trial of dornase alpha, 17 met the criteria for continuation (average gain in forced expiratory volume 37%). The 11 of these who were still alive at 2 years had a greater initial average FEV1 improvement than those who had died (45% versus 22%), and still had an average improvement of 31% at 2 years. The 8 patients who did not meet the criteria for continuation were older and had required fewer intravenous antibiotic courses. All these were alive at 2 years with unchanged clinical indices. This method of selection for dornase alpha treatment allows targeting to those who gain most benefit without disadvantaging the remaining patients. Furthermore, production of such guidelines in conjunction with purchasers obviates funding difficulties and allows rational prescribing.

Pulmonary function in children after neonatal meconium aspiration syndrome.

Eighteen children aged 6 to 11 years old who fulfilled criteria for the diagnosis of neonatal meconium aspiration syndrome were investigated to find out the prevalence of previous and current respiratory symptoms, and abnormal pulmonary function tests, chest radiographs, and ventilation scans. Eleven of the 18 had no respiratory symptoms and eight of these had normal pulmonary function on testing. Two had mild limitation of expiratory airflow that did not respond to treatment with bronchodilators, and one had exercise induced bronchospasm that responded to treatment with bronchodilators. Seven of the 18 had recurrent cough and wheezing compatible with a diagnosis of asthma, and five of these had appreciable exercise induced bronchospasm that responded to treatment with bronchodilators. None of the children with symptoms had a personal or family history of atopy or had had acute bronchiolitis. All chest radiographs were normal. We found a much higher prevalence of asthmatic symptoms and abnormal bronchial reactivity among survivors of neonatal meconium aspiration syndrome than in the general childhood population. Aspiration of meconium may have long term consequences for the developing respiratory tract and is associated with abnormal respiratory function in later childhood.

Fluorescein dilaurate test of exocrine pancreatic function in cystic fibrosis.

The fluorescein dilaurate test, a non-invasive test of exocrine pancreatic function, was carried out on 21 children with cystic fibrosis and pancreatic exocrine insufficiency, and 12 healthy siblings. The test clearly discriminated between the patients with cystic fibrosis and severe exocrine pancreatic insufficiency and the normal control subjects.