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Biomedical subjects

E Baraldi

Publications and source records attributed to E Baraldi.

At least 19 recordsLinked to original sources
PubMed2000

Metabolic and respiratory effects of theophylline in the preterm infant.

BACKGROUND: Methylxanthines are often administered to preterm infants for the treatment of apnoea. AIMS: To study the effects of theophylline on energy metabolism, physical activity, and lung mechanics in preterm infants. METHODS: Indirect calorimetry was performed for six hours before and after administration of a bolus of theophylline (5 mg/kg) in 18 preterm infants while physical activity was recorded with a video camera. Lung mechanics measurements were performed at baseline and 12 and 24 hours after theophylline treatment. RESULTS: Theophylline increased mean (SEM) energy expenditure by 15 (5) kJ/kg/day and augmented carbohydrate utilisation from 6.8 to 8.0 g/kg/day, but fat oxidation was unchanged. After theophylline treatment, preterm infants had faster respiration, lower transcutaneous CO2, and improved static respiratory compliance without increased physical activity. CONCLUSIONS: A bolus of 5 mg/kg theophylline increased energy expenditure independently of physical activity, increased carbohydrate utilisation, and improved respiratory compliance. The increased energy expenditure could be detrimental to the growth of the preterm infant.

Aminophylline↗
PubMed2000

Exhaled nitric oxide and exercise-induced bronchoconstriction in asthmatic children.

It is known that exhaled nitric oxide (ENO) is increased in asthmatic individuals, probably as an expression of airway inflammation, but no studies have been reported of ENO and exercise-induced bronchoconstriction (EIB). We assessed the effect of a treadmill exercise challenge on ENO concentration in 24 asthmatic children aged 11.2 +/- 0.4 yr (mean +/- SEM). According to the presence or absence of EIB, the children were divided into an EIB group (n = 10) and a non-EIB group (n = 14). ENO was measured with a single-breath reservoir technique. FEV(1), ENO, and heart rate were measured at baseline and 1, 6, 12, and 18 min after the end of exercise. We also measured ENO in 18 healthy control children aged 10.8 +/- 0.6 yr, of whom nine underwent an exercise challenge identical to that of the asthmatic children. After the exercise test, the mean decrease in FEV(1) was 34% in the EIB group and 5% in the non-EIB group. The EIB group had higher baseline ENO values (12.3 +/- 1.6 ppb) than the healthy children (6.1 +/- 0.2 ppb) (p < 0.01). The time course of ENO was similar in the EIB, non-EIB, and control groups, with no significant changes after exercise (p = NS). In the overall group of asthmatic children there was a significant correlation (r = 0.61, p < 0.01) between baseline (preexercise) ENO and magnitude of the maximal decrease in FEV(1) after exercise. In conclusion, our study shows that ENO levels do not change during acute airway obstruction induced by exercise challenge in asthmatic children. In addition, baseline ENO values correlate with the magnitude of postexercise bronchoconstriction, suggesting that NO may be a predictor of airway hyperresponsiveness to exercise.

Adolescent↗
PubMed1999

Structure of the PH domain from Bruton's tyrosine kinase in complex with inositol 1,3,4,5-tetrakisphosphate.

BACKGROUND: The activity of Bruton's tyrosine kinase (Btk) is important for the maturation of B cells. A variety of point mutations in this enzyme result in a severe human immunodeficiency known as X-linked agammaglobulinemia (XLA). Btk contains a pleckstrin-homology (PH) domain that specifically binds phosphatidylinositol 3,4,5-trisphosphate and, hence, responds to signalling via phosphatidylinositol 3-kinase. Point mutations in the PH domain might abolish membrane binding, preventing signalling via Btk. RESULTS: We have determined the crystal structures of the wild-type PH domain and a gain-of-function mutant E41K in complex with D-myo-inositol 1,3,4,5-tetra-kisphosphate (Ins (1,3,4,5)P4). The inositol Ins (1,3,4,5)P4 binds to a site that is similar to the inositol 1,4,5-trisphosphate binding site in the PH domain of phospholipase C-delta. A second Ins (1,3,4,5)P4 molecule is associated with the domain of the E41K mutant, suggesting a mechanism for its constitutive interaction with membrane. The affinities of Ins (1,3,4,5)P4 to the wild type (Kd = 40 nM), and several XLA-causing mutants have been measured using isothermal titration calorimetry. CONCLUSIONS: Our data provide an explanation for the specificity and high affinity of the interaction with phosphatidylinositol 3,4,5-trisphosphate and lead to a classification of the XLA mutations that reside in the Btk PH domain. Mis-sense mutations that do not simply destabilize the PH fold either directly affect the interaction with the phosphates of the lipid head group or change electrostatic properties of the lipid-binding site. One point mutation (Q127H) cannot be explained by these facts, suggesting that the PH domain of Btk carries an additional function such as interaction with a Galpha protein.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed1999

Reference values of exhaled nitric oxide for healthy children 6-15 years old.

Nitric oxide (NO) can be detected in human exhaled air, and its endogenous production is increased in patients with asthma. It may provide a noninvasive means for measuring airway inflammation. The aim of this study was to establish reference values for exhaled NO concentrations in a large number of healthy school-age children. We measured exhaled NO levels in 159 white healthy children (88 girls, 71 boys, age range 6-15 years) recruited from two public schools of Padua, Italy. Exhaled NO levels in exhaled gas were measured by a tidal breathing method with a chemiluminescence analyzer, and NO steady-state levels were recorded. Nasal NO levels were measured by direct sampling from the nose during mouth breathing. The mean concentration of endogenous NO in orally exhaled gas was 8.7 parts per billion (ppb) (95% confidence interval (C.I.), 8.1-9.2 ppb) and sampled data followed a log-normal distribution (Kolmogorov-Smirnov d = 0.77, P > 0.2). No difference was found between boys (mean value, 8.4 ppb; 95% C.I., 7.3-9.4 ppb) and girls (mean value, 8.9 ppb; 95% C.I., 7.9-9.9 ppb). No significant correlation was found between age, height, or spirometric data and exhaled NO levels (r < 0.2). The mean value of nasal NO concentrations was 216 ppb (95% C.I., 204-228 ppb). There was no correlation between exhaled and nasal NO values (r = 0.16, P = ns). In conclusion, this study establishes a reference range for exhaled NO values measured by a tidal breathing method in children between age 6-15 years. The observed levels are independent of age, gender, and lung function, and can be used to monitor airway inflammation in asthmatic children.

Adolescent↗
PubMed1999

The PH superfold: a structural scaffold for multiple functions.

Pleckstrin homology (PH) domains form a structurally conserved family that is associated with many regulatory pathways within the cell. Domains with a nearly identical fold are found in other families that share no sequence similarity, suggesting the existence of a stable PH superfold. The PH domains generally function as regulated membrane-binding modules that bind to inositol lipids and respond to upstream signals by targeting the host proteins to the correct cellular sites. The other domains with a similar fold, such as the phosphotyrosine binding domains, recognize protein ligands.

Amino Acid Motifs↗
PubMed1999

Renal distal tubular handling of sodium in central fluid volume homoeostasis in preascitic cirrhosis.

BACKGROUND/AIMS: Patients with preascitic liver cirrhosis have an increased central plasma volume, and, for any given plasma aldosterone concentration, they excrete less sodium than healthy controls. A detailed study of the distribution of sodium reabsorption along the segments of the renal tubule, especially the distal one, is still lacking in preascitic cirrhosis. METHODS: Twelve patients with Child-Pugh class A cirrhosis and nine control subjects (both groups on a normosodic diet) were submitted to the following investigations: (a) plasma levels of active renin and aldosterone; (b) four hour renal clearance of lithium (an index of fluid delivery to the loop of Henle), creatinine, sodium, and potassium; (c) dopaminergic activity, as measured by incremental aldosterone response to intravenous metoclopramide. RESULTS: Metoclopramide induced higher incremental aldosterone responses, indicating increased dopaminergic activity in patients than controls, which is evidence of an increased central plasma volume (+30 min: 160.2 (68.8) v 83.6 (35.2) pg/ml, p<0.01; +60 min: 140.5 (80.3) v 36. 8 (36.1) pg/ml, p<0.01). Patients had increased distal fractional sodium reabsorption compared with controls (26.9 (6.7)% v 12.5 (3. 4)% of the filtered sodium load, p<0.05). In the patient group there was an inverse correlation between: (a) absolute distal sodium reabsorption and active renin (r -0.59, p<0.05); (b) fractional distal sodium reabsorption and sodium excretion (r -0.66, p<0.03). CONCLUSIONS: These data suggest that in preascitic cirrhosis the distal fractional tubular reabsorption of sodium is increased and critical in regulating both central fluid volume and sodium excretion.

Adult↗
PubMed1999

Effect of natural grass pollen exposure on exhaled nitric oxide in asthmatic children.

Exhaled nitiric oxide (NO) is increased in exhaled breath of asthmatic patients. The aim of this study was to investigate the longitudinal changes of exhaled NO outside and during the pollen season in pollen-allergic asthmatic children. Twenty-one children (age 6 to 16 yr), with a seasonal allergic asthma sensitive to grass pollen, underwent measurements of exhaled NO and pulmonary function before (March), during (May), and after (November) the pollen season. Exhaled NO was measured by a tidal breathing method with a chemiluminescence analyzer and NO steady-state levels were recorded. The timing of the measurements during the pollen season was based on the atmospheric pollen count. Exhaled NO values of asthmatic children were compared with those of 21 sex- and age-matched healthy children. Pulmonary function and symptoms of asthma were also evaluated at each visit. The mean value of exhaled NO before the grass season was 12.7 +/- 5.1 ppb (mean +/- SD), significantly higher when compared with controls (7.8 +/- 2.7 ppb, p < 0.001). In the pollen season there was a significant (p < 0.001) twofold increase in exhaled NO (21.4 +/- 7.6 ppb) that, after the season, returned to values similar (12.8 +/- 5.8 ppb, p = NS) to those found before the season. There were no significant changes in FEV1 before and during the season (98.6% predicted versus 101% predicted, p = NS). We conclude that natural allergen exposure is related to an increase of exhaled NO in asthmatic grass pollen-allergic children even in absence of significant changes in airways function. We speculate that measurement of exhaled NO could be a sensitive noninvasive marker of asthma disease activity.

Adolescent↗
PubMed1999

Exhaled nitric oxide concentrations during treatment of wheezing exacerbation in infants and young children.

While it is known that exhaled nitric oxide (ENO) is increased in adults and school children with asthma exacerbation probably as an expression of disease activity, no studies have investigated whether this phenomenon also occurs in infants and young children with recurrent wheeze exacerbation. We measured ENO in 13 young children (mean age 20.2 mo) with recurrent wheeze (Group 1) during an acute episode and after 5 d of oral prednisone therapy. ENO was measured also in nine healthy control subjects (Group 2) (mean age 16.9 mo) and in six children with a first-time viral wheezy episode (Group 3) (mean age 11 mo). To measure ENO, infants inhaled NO-free air via a face mask from a reservoir and, through a nonrebreathing valve, exhaled in a collecting bag that was analyzed by chemiluminescence. To address the question of whether the levels of ENO collected in the bag are a reflection of the pulmonary airway, ENO determinations were performed in two healthy infants before and after tracheal intubation for elective surgery. During the acute episode of wheezing the mean (+/- SEM) value of ENO in children with recurrent wheeze (Group 1) was 14.1 +/- 1.8 ppb, almost threefold higher than in healthy control subjects (5.6 +/- 0.5 ppb, p < 0.001). After steroid therapy we found a mean fall of 52% in ENO (5.9 +/- 0.7 ppb, p < 0.01) compared with baseline values. ENO values measured before and after intubation in two infants were 6 ppb and 5 ppb in one child and 7 ppb and 6 ppb in the other one. The mean value of ENO of children with first-time wheeze (Group 3) was 8.3 +/- 1.3 ppb, significantly lower (p < 0.05) than the value of children with recurrent wheeze (Group 1). In conclusion, we describe a method to measure ENO in young children and show that infants with recurrent wheeze have elevated levels of ENO during exacerbation that rapidly decrease after steroid therapy. This suggests that, in these children, airway inflammation could be present at a very early stage.

Acute Disease↗
PubMed1999

Prevention of a first episode of variceal bleeding: role of duplex Doppler sonographic measurement of the acute response to beta-blockers.

The aim of our study was to assess whether acute variations in portal vein Doppler sonographic parameters induced by administration of a single beta-blocker agent are predictive of the long-term effects of these drugs in the prevention of a first episode of variceal bleeding. In 30 patients with liver cirrhosis at high risk for variceal bleeding, duplex Doppler sonographic parameters (maximal portal flow velocity, portal blood flow, and congestion index) were measured before and 4 h after the administration of 40 mg of propranolol. Twenty-three of these patients started chronic therapy with propanolol and were evaluated periodically (seven patients were excluded because they did not continue the therapy). The percentage of patients free from bleeding was 86.9% at the first year and 77.8% at the second year. Among a series of clinical, laboratory, and instrument-based parameters, the only one related to first bleeding, selected by the Cox regression model, was the percentage decrease in maximal portal flow velocity observed after initial administration of propranolol (P < 0.01). The best cutoff value for the percentage decrease in portal flow velocity (portal flow velocity test) was 12%. The prevalence of bleeding had been 25% (3 of 12) in patients with positive portal flow velocity test results (12% decrease or more), versus 64% (7 of 11) in patients with negative portal flow velocity test results. The actuarial probability of remaining free from bleeding (Kaplan-Meier analysis) was different in these two groups (log rank P < 0.01). The portal flow velocity test represents a safe and feasible method to predict the efficacy of beta-blockers in the prevention of a first bleeding episode in patients with cirrhosis. In patients with negative results on the portal flow velocity test, an alternative therapeutic approach should be considered.

Actuarial Analysis↗
PubMed1998

Conformational stability studies of the pleckstrin DEP domain: definition of the domain boundaries.

Pleckstrin is the major substrate of protein kinase C in platelets. It contains at its N- and C-termini two pleckstrin homology (PH) domains which have been proposed to mediate protein-protein and protein-lipid interactions. A new module, called DEP, has recently been identified by sequence analysis in the central region of pleckstrin. In order to study this module, several recombinant polypeptides corresponding to the DEP module and N- and C-termini extended forms have been expressed. Using circular dichroism (CD) and nuclear magnetic resonance (NMR) techniques, the domain boundaries have been determined that yield a soluble and folded pleckstrin DEP domain. This comprises 93 amino acids with an alpha/beta fold in agreement with secondary structure predictions. Stability studies indicate that the regions surrounding the DEP domain do not contribute to its stability suggesting that the phosphorylation sites at S113, T114 and S117 are in an unstructured region. Identification of the regions of pleckstrin that are folded shall facilitate determination of its structure and function.

Amino Acid Sequence↗
PubMed1998

Effect of atmospheric nitric oxide (NO) on measurements of exhaled NO in asthmatic children.

The measurement of exhaled nitric oxide concentrations [NO] may provide a simple, noninvasive means for measuring airway inflammation. However, several measurement conditions may influence exhaled NO levels, and ambient NO may be one of these. We measured exhaled NO levels in 47 stable asthmatic children age 5 to 17 years and in 47 healthy children, gender and age matched. Exhaled [NO] in expired air was measured by a tidal breathing method with a chemiluminescence analyzer, sampling at the expiratory side of the mouthpiece. NO steady-state levels were recorded. In order to keep the soft palate closed and avoid nasal contamination, the breathing circuit had a restrictor providing an expiratory pressure of 3-4 cm H2O at the mouthpiece. To evaluate the effect of [NO] in ambient air, measurements were randomly performed by breathing ambient air or NO-free air from a closed circuit. Breathing NO-free air, exhaled [NO] in asthmatics (mean +/- SEM) was 23.7 +/- 1.4 ppb, significantly higher (P < 0.001) than in healthy controls (8.7 +/- 0.4 ppb). Exhaled NO concentrations measured during ambient air breathing were higher (49 +/- 4.6 ppb, P < 0.001) than when breathing NO-free air (23.7 +/- 1.4 ppb) and were significantly correlated (r = 0.89, P < 0.001) with atmospheric concentrations of NO (range 3-430 ppb). These findings show that 1) exhaled [NO] values of asthmatic children are significantly higher than in healthy controls, and 2) atmospheric NO levels critically influence the measurement of exhaled [NO]. Therefore, using a tidal breathing method the inhalation of NO-free air during the test is recommended.

Adolescent↗
PubMed1998

Effect of topical steroids on nasal nitric oxide production in children with perennial allergic rhinitis: a pilot study.

It has been hypothesized that concentrations of exhaled nitric oxide (NO) may be related to the extent of cytokine-mediated airway inflammation. Recent findings indicate the nasal airways as an important site of NO production. Our objective was to evaluate whether children with allergic rhinitis show different nasal NO levels when compared with normal healthy subjects and the effect of topical steroids and anti-histamine therapy. We have measured the concentration of NO drawn from the nose of 21 children (5-17 years old) affected by perennial allergic rhinitis (house dust mite) out of therapy for at least 3 weeks. Thirteen children were then treated with nasal beclomethasone dipropionate (BDP) (400 micrograms daily) and eight subjects with nasal anti-histamine levocabastine (200 micrograms daily). Measurements were performed before and after 10 days of treatment. As a control group we evaluated 21 healthy children aged 5-15 years. To measure NO we used a chemiluminescence analyser. Before treatment the whole group of children with allergic rhinitis showed a mean (+/- SEM) nasal NO concentration of 267 +/- 18 ppb, significantly higher (P < 0.01) than the control group (186 +/- 15 ppb). The group of children treated with BDP showed, after 10 days of therapy, a significant (P < 0.05) decrease of nasal NO concentration (271 +/- 21 ppb vs. 212 +/- 20 ppb). Indeed, in the group treated with levocabastine, nasal NO concentrations did not present a significant difference (P not significant) compared with baseline (261 +/- 33 ppb and 252 +/- 31 ppb, respectively). These data suggest that (1) children with allergic rhinitis have higher levels of nasal NO than non-atopic controls and (2) intranasal steroid therapy significantly reduces nasal NO production in children with allergic rhinitis. We speculate that the allergic inflammatory response may influence the nasal NO levels and that NO measurements may be a useful marker of nasal inflammation.

Adolescent↗
PubMed1998

Endogenous dopaminergic activity in Child-Pugh A cirrhosis: potential role in renal sodium handling and in the maintenance of clinical compensation.

BACKGROUND: We studied the main determinants of aldosterone secretion in a group of 20 patients with biopsy-proven Child-Pugh A cirrhosis without previous ascites or diuretic consumption. METHODS: We evaluated the plasma levels of adrenocorticotrophic hormone (ACTH), active renin and aldosterone (both supine at 07.00 h and after 30 min of upright posture),and active renin and aldosterone responses 30 min and 60 min after the administration of metoclopramide, a dopamine DA2 antagonist (10 mg e.v.). Nine normal subjects were also submitted to the metoclopramide stimulation test. RESULTS: Compared with control subjects, the patients showed significantly greater incremental aldosterone responses both 30 min and 60 min after metoclopramide (+30 min: 157.5+/-73.3 vs. 83.5+/-32.2 pg mL(-1), P< 0003; +60 min: 142.1+/-87.2 vs. 36.8+/-39.0 pg mL(-1), P < 0-001). We found significant positive correlations between amplitude of aldosterone response 30 min after metoclopramide and 24-h urinary fractional excretion of sodium (r=0.61, P < 0.01) and basal morning aldosterone levels (r=0.69, P < 0.001). CONCLUSIONS: The higher incremental aldosterone responses observed after metoclopramide in cirrhotic patients are expressions of increased dopaminergic activity in these patients compared with control subjects. Moreover, the correlation we found between the degree of dopaminergic activity and 24-h urinary fractional excretion of sodium suggests a role for endogenous dopamine as a relevant mediator of natriuresis in cirrhosis, at least in patients with compensated disease.

Adrenocorticotropic Hormone↗
PubMed1998

Inhaled nitric oxide in hypoxaemic newborns who are candidates for extracorporeal life support.

The aim of this study was to evaluate the effect of inhaled nitric oxide (NO) in newborns with acute hypoxaemic respiratory failure and the impact of this NO therapy on survival and the need for extracorporeal membrane oxygenation (ECMO). A cohort of newborns with a gestational age of > or = 34 weeks and an oxygenation index (OI) > 25 were prospectively evaluated. Patients were given NO at an initial dose of 10 parts per million (ppm). Oxygenation parameters were evaluated prior and during NO inhalation. From January 1994 to December 1996, 20 infants were enrolled in the study. Based upon their outcome, patients were divided into two groups: survivors with no need for ECMO, group A (n=8) and survivors requiring ECMO or nonsurvivors, group B (n=12). All infants approached or met ECMO criteria before NO inhalation. Eight patients (40%) were successfully managed with NO and conventional treatment (group A). Newborns in this group showed a rapid and sustained improvement of systemic oxygenation during NO inhalation. Mean arterial oxygen tension (Pa,O2) increased significantly from 4.5 kPa (34 mmHg) (95% confidence interval (95% CI) 1.9-7.1 kPa (14.4-53.7 mmHg)) to 10.1 kPa (75.7 mmHg) (95% CI 6.5-13.6 kPa (49.1-1023 mmHg)) after 1 h and was 9.0 kPa (67.7 mmHg) (95% CI 7.1-11.0 kPa (53.1-82.4 mmHg)) at 24 h. Conversely, none of the oxygenation parameters improved in the 12 patients who ultimately required ECMO or died (group B). The results indicate that inhaled nitric oxide can improve systemic oxygenation in newborns with acute respiratory failure and may reduce the need for extracorporeal membrane oxygenation support in candidates. Lack of a rapid response to nitric oxide may be an early predictor of unfavourable short-term outcome, prompting a move towards alternative treatments.

Administration, Inhalation↗
PubMed1997

Home oxygen therapy in infants with bronchopulmonary dysplasia: a prospective study.

UNLABELLED: We followed the clinical course of 21 infants with bronchopulmonary dysplasia enrolled in a prospective home O2 therapy programme during a 4-year-period. Mean gestational age was 28.5 weeks (range, 25-36 weeks) and mean birth weight 1093 g (range 630-2750 g). Infants were regularly monitored to maintain pulse oximeter O2 saturation over 94%-95%. The source of O2 was liquid oxygen and was delivered by nasal cannula. During the follow up oxygenation was assessed by SatO2 measurement, cardiac function by Doppler echocardiography and respiratory function by the occlusion technique. All patients had an ophthalmological follow up. The mean age of the infants at discharge was 3.7 months (range 1.7-8.6) and mean weight 2830 g (range 2150-3780 g). At discharge 8 infants had right ventricular hypertrophy (RVH) and four of them had pulmonary hypertension. Mean duration of home O2 therapy was 97 days (range 15-320 days) and the mean age of discontinuation of O2 was 6.9 months (range 3-14.7 months). The cardiological follow up was benign: the ECG signs of RVH disappeared by 12 months of age in six out of eight infants and the right ventricular pulmonary pressure, as measured by the Doppler method, normalised in the four patients in whom it was detected. No relationship was found between respiratory mechanics and the duration of O2 therapy. Weight gain was poor with mean growth at the 3rd percentile for females and just below the 3rd percentile for males. Twelve of the 21 infants required 25 rehospitalizations. No one presented deterioration of retinopathy of prematurity that was present in 16 infants at discharge; at 12 months retinopathy was resolved in 14 infants. A total of 2025 hospital days were saved, representing a significant financial saving. CONCLUSION: Home O2 therapy permits the safe early discharge of O2-dependent BPD infants and it reduces significantly the length of time spent in hospital which represents a considerable financial saving.

Bronchopulmonary Dysplasia↗
PubMed1997

Corticosteroids decrease exhaled nitric oxide in children with acute asthma.

OBJECTIVES: Nitric oxide (NO) produced in human airways seems to have both homeostatic and proinflammatory actions in the respiratory system. NO production has been shown to be higher in the exhaled air of asthmatic adults than in normal subjects. The aim of this study was to evaluate exhaled NO production during asthma exacerbation in children and the effect of a rescue course of oral steroid therapy. STUDY DESIGN: We measured NO in the exhaled air of 16 children (8 girls and 8 boys, aged 6 to 13 years) with an acute asthmatic episode before and after 5 days of therapy with prednisone, and in 16 healthy children. To measure NO, children inhaled NO-free air and, breathing at tidal volume, exhaled in a circuit from which a chemiluminescence analyzer sampled continuously. To assess the effect of acute changes in bronchial caliber on exhaled NO levels, we measured NO before and after a positive bronchodilation test result with albuterol in seven children with asthma whose disease was stable. RESULTS: In the group with acute asthma (forced expiratory volume in 1 second 62% +/- 4.4% predicted, mean +/- SEM), NO levels were significantly higher (31.3 +/- 4.2 parts per billion [ppb]) than in healthy children (5.4 +/- 0.4 ppb, p < 0.001). Administration of prednisone (1 mg/kg per day orally) for 5 days resulted in a mean decrease of 46% +/- 4% in exhaled NO concentrations (16.5 +/- 2.3 ppb, p < 0.001) compared with baseline, accompanied by a significant improvement in lung function (forced expiratory volume in 1 second 90.7% +/- 4.3% predicted). However, in patients with asthma exhaled NO levels remained significantly higher than in control children (p < 0.001) after steroid treatment. When exhaled NO was measured before and after a positive result after bronchodilator reversibility testing, we found no difference in exhaled NO levels (24 +/- 3.8 ppb vs 23.8 +/- 3 ppb; difference not significant). This demonstrates that inhaled albuterol and acute changes in bronchial caliber do not affect exhaled NO measurement. CONCLUSIONS: These data show that children with asthma exacerbation have high levels of exhaled NO that rapidly decrease with oral steroid therapy. We suggest that measurement of exhaled NO may represent a noninvasive method of monitoring airway inflammation in children with asthma.

Acute Disease↗
PubMed1997

Photopheresis in paediatric patients with drug-resistant chronic graft-versus-host disease.

Photopheresis (ECP) is a new type of photochemotherapy, used for the treatment of oncological and autoimmune diseases. Lymphocytes are drawn from the patients by leukapheresis, treated with 8-methoxypsoralen (8-MOP) and ultraviolet light A (UVA) in an extracorporeal system and then reinfused. Skin exposure to 8-MOP and UVA (PUVA) has been shown to relieve cutaneous symptoms of graft-versus-host disease (GVHD) in bone marrow transplant (BMT) recipients. ECP, which is similar in some ways to PUVA, has been used in this study to treat four paediatric patients who developed chronic GVHD following BMT and in whom GVHD had failed to respond to conventional immunosuppressive therapy. Following ECP, skin lesions cleared almost completely and pulmonary function tests improved in two of three patients with cutaneous and lung involvement. Serum bilirubin and transaminases gradually normalized, and gammaGT decreased considerably in the remaining patient who had a severe cholestatic hepatopathy. The Karnofsky performance score increased to 90% in the three patients with positive responses to ECP and remained unchanged (40%) in the patient who did not respond. Immunosuppressive therapy was reduced in three patients and eventually discontinued in two. No significant side-effects were observed during the treatment. Our results suggest that ECP is a non-aggressive treatment that may benefit patients with chronic GVHD who do not respond to standard immunosuppressive therapy.

Adolescent↗