Effects of systemic glucocorticosteroids on peripheral neutrophil functions in asthmatic subjects: an ex vivo study

In 21 asthmatic subjects, several functions of isolated peripheral neutrophils (chemokinesis and chemotaxis toward 10% E. coli; superoxide anion generation after PMA; leukotriene B4 (LTB4) release from whole blood and isolated neutrophtls, before and after different stimuli) were evaluated during an acute exacerbation of asthma, and after 14 – 54 days of treatment with systemic glucocorticosteroids (GCS). During acute exacerbation, superoxide anion generation was higher in asthmatics than in eleven normal subjects (39.2 ± 14.1 vs. 25.2 ± 7.3 nmol, p < 0.05); there was a significant correlation between FEV1 (% of predicted) and neutrophil chemotaxis (r = −0.52, p = 0.04). After treatment, there was no significant change in all neutrophil functions, except for a decrease in neutrophil chemotaxis in subjects who showed an FEV1 increase > 20% after GCS treatment (from 131 ± 18 to 117 ± 21 μm, p = 0.005). Chemokinesis sicantly decreased in all subjects, and the changes significantly correlated with an arbitrary score of the total administered dose of GCS (r = 0.57, p < 0.05). These data suggest that neutrophil activation plays a minor role in asthma, and that treatment with GCS is not able to modify most functions of peripheral neutrophils in asthmatic subjects; chemotaxis seems to be related only to the severity of the asthma and it could reflect the improvement of the disease

Neonatal Gram Negative and Candida Sepsis Survival and Neurodevelopmental Outcome at the Corrected Age of 24 Months

Objectives: To evaluate the long term neurodevelopmental outcome of premature infants exposed to either gram- negative sepsis (GNS) or neonatal Candida sepsis (NCS), and to compare their outcome with premature infants without sepsis. Methods: Historical cohort study in a population of infants born at <30 weeks gestation and admitted to the Neonatal Intensive Care Unit (NICU) of the Academic Medical Center in Amsterdam during the period 1997-2007. Outcome of infants exposed to GNS or NCS and 120 randomly chosen uncomplicated controls (UC) from the same NICU were compared. Clinical data during hospitalization and neurodevelopmental outcome data (clinical neurological status; Bayley -test results and vision/hearing test results) at the corrected age of 24 months were collected. An association model with sepsis as the central determinant of either good or adverse outcome (death or severe developmental delay) was made, corrected for confounders using multiple logistic regression analysis. Results: Of 1362 patients, 55 suffered from GNS and 29 suffered from NCS; cumulative incidence 4.2% and 2.2%, respectively. During the follow-up period the mortality rate was 34% for both GNS and NCS and 5% for UC. The adjusted Odds Ratio (OR) [95% CI] for adverse outcome in the GNS group compared to the NCS group was 1.4 [0.4-4.9]. The adjusted ORs [95% CI] for adverse outcome in the GNS and NCS groups compared to the UC group were 4.8 [1.5-15.9] and 3.2 [0.7-14.7], respectively. Conclusions: We found no statistically significant difference in outcome at the corrected age of 24 months between neonatal GNS and NCS cases. Suffering from either gram -negative or Candida sepsis increased the odds for adverse outcome compared with an uncomplicated neonatal period

The Angiotensin Converting Enzyme Insertion/Deletion polymorphism is not associated with an increased risk of death or bronchopulmonary dysplasia in ventilated very low birth weight infants

BACKGROUND: The ACE gene contains a polymorphism consisting of either the presence (insertion, I) or absence (deletion, D) of a 287 bp alu repeat in intron 16. The D allele is associated with increased ACE activity in both tissue and plasma. The DD genotype is associated with risk of developing ARDS and mortality. The frequency of the D allele is higher in patients with pulmonary fibrosis, sarcoidosis and berylliosis. The role of this polymorphism has not been studied in the development of BPD in the premature newborn. METHODS: ACE I/D genotype was determined in 245 (194 African-American, 47 Caucasian and 4 Hispanic) mechanically ventilated infants weighing less than 1250 grams at birth and compared to outcome (death and/or development of BPD). RESULTS: The incidence of the D allele in the study population was 0.58. Eighty-eight (35.9%) infants were homozygous DD, 107 (43.7%) were heterozygous ID and 50 (20.4%) were homozygous II. There were no significant differences between genotype groups with respect to ethnic origin, birth weight, gestation, or gender. There was no effect of the ACE I/D polymorphism on mortality or development of BPD (O(2 )on 28 days or 36 weeks PCA). Secondary outcomes (intraventricular hemorrhage and periventricular leukomalacia) similarly were not influenced by the ACE ID polymorphism. CONCLUSIONS: The ACE I/D polymorphism does not significantly influence the development of BPD in ventilated infants less than 1250 grams

Surfactant phosphatidylcholine half-life and pool size measurements in premature baboons developing bronchopulmonary dysplasia

Because minimal information is available about surfactant metabolism in bronchopulmonary dysplasia, we measured half-lives and pool sizes of surfactant phosphatidylcholine in very preterm baboons recovering from respiratory distress syndrome and developing bronchopulmonary dysplasia, using stable isotopes, radioactive isotopes, and direct pool size measurements. Eight ventilated premature baboons received (2)H-DPPC (dipalmitoyl phosphatidylcholine) on d 5 of life, and radioactive (14)C-DPPC with a treatment dose of surfactant on d 8. After 14 d, lung pool sizes of saturated phosphatidylcholine were measured. Half-life of (2)H-DPPC (d 5) in tracheal aspirates was 28 +/- 4 h (mean +/- SEM). Half-life of radioactive DPPC (d 8) was 35 +/- 4 h. Saturated phosphatidylcholine pool size measured with stable isotopes on d 5 was 129 +/- 14 micro mol/kg, and 123 +/- 11 micro mol/kg on d 14 at autopsy. Half-lives were comparable to those obtained at d 0 and d 6 in our previous baboon studies. We conclude that surfactant metabolism does not change during the early development of bronchopulmonary dysplasia, more specifically, the metabolism of exogenous surfactant on d 8 is similar to that on the day of birth. Surfactant pool size is low at birth, increases after surfactant therapy, and is kept constant during the first 2 wk of life by endogenous surfactant synthesis. Measurements with stable isotopes are comparable to measurements with radioactive tracers and measurements at autopsy

Estimates of live-tree carbon stores in the Pacific Northwest are sensitive to model selection

<p>Abstract</p> <p>Background</p> <p>Estimates of live-tree carbon stores are influenced by numerous uncertainties. One of them is model-selection uncertainty: one has to choose among multiple empirical equations and conversion factors that can be plausibly justified as locally applicable to calculate the carbon store from inventory measurements such as tree height and diameter at breast height (DBH). Here we quantify the model-selection uncertainty for the five most numerous tree species in six counties of northwest Oregon, USA.</p> <p>Results</p> <p>The results of our study demonstrate that model-selection error may introduce 20 to 40% uncertainty into a live-tree carbon estimate, possibly making this form of error the largest source of uncertainty in estimation of live-tree carbon stores. The effect of model selection could be even greater if models are applied beyond the height and DBH ranges for which they were developed.</p> <p>Conclusions</p> <p>Model-selection uncertainty is potentially large enough that it could limit the ability to track forest carbon with the precision and accuracy required by carbon accounting protocols. Without local validation based on detailed measurements of usually destructively sampled trees, it is very difficult to choose the best model when there are several available. Our analysis suggests that considering tree form in equation selection may better match trees to existing equations and that substantial gaps exist, in terms of both species and diameter ranges, that are ripe for new model-building effort.</p

Knowledge and health care resource allocation: CME/CPD course guidelines-based efficacy.

BACKGROUND: Most health care systems consider continuing medical education a potential tool to improve quality of care and reduce disease management costs. Its efficacy in general practitioners needs to be further explored. OBJECTIVE: This study assesses the effectiveness of a one-year continuing medical education/continuing professional development course for general practitioners, regarding the improvement in knowledge of ARIA and GINA guidelines and compliance with them in asthma management. METHODS: Sixty general practitioners, covering 68,146 inhabitants, were randomly allocated to continuing medical education/continuing professional development (five residential events +four short distance-learning refresher courses over one year) or no training. Participants completed a questionnaire after each continuing medical education event; key questions were repeated at least twice. The Local Health Unit prescription database was used to verify prescription habits (diagnostic investigations and pharmacological therapy) and hospitalizations over one year before and after training. RESULTS: Fourteen general practitioners (46.7%) reached the cut-off of 50% attendance of the training courses. Knowledge improved significantly after training (p < 0.001, correct answers to key questions +13%). Training resulted in pharmaceutical cost containment (trained general practitioners +0.5% vs. controls +18.8%) and greater attention to diagnosis and monitoring (increase in spirometry +63.4%, p < 0.01). CONCLUSION: This study revealed an encouraging impact of educational events on improvement in general practitioner knowledge of guidelines and daily practice behavioral changes. Long-term studies of large populations are required to assess the effectiveness of education on the behavior of physicians in asthma management, and to establish the best format for educational events

Improving manual oxygen titration in preterm infants by training and guideline implementation

To study oxygen saturation (SpO2) targeting before and after training and guideline implementation of manual oxygen titration, two cohorts of preterm infants 21%. ABCs where oxygen therapy was given were identified and analyzed. After training and guideline implementation the %SpO2-wtr increased (median interquartile range (IQR)) 48.0 (19.6-63.9) % vs 61.9 (48.5-72.3) %; p 95% (44.0 (27.8-66.2) % vs 30.8 (22.6-44.5) %; p 95% did not decrease (73% vs 64%; ns) but lasted shorter (2 (0-7) vs 1 (1-3) minute; p < 0.004). CONCLUSION: Training and guideline implementation in manual oxygen titration improved SpO2 targeting in preterm infants with more time spent within the target range and less frequent hyperoxaemia. The durations of hypoxaemia and hyperoxaemia during ABCs were shorter. What is Known: • Oxygen saturation targeting in preterm infants can be challenging and the compliance is low when oxygen is titrated manually. • Hyperoxaemia often occurs after oxygen therapy for oxygen desaturation during apnoeas. What is New: • Training and implementing guidelines improved oxygen saturation targeting and reduced hyperoxaemia. • Training and implementing guidelines improved manual oxygen titration during ABC

Azithromycin in the extremely low birth weight infant for the prevention of Bronchopulmonary Dysplasia: a pilot study

<p>Abstract</p> <p>Background</p> <p>Azithromycin reduces the severity of illness in patients with inflammatory lung disease such as cystic fibrosis and diffuse panbronchiolitis. Bronchopulmonary dysplasia (BPD) is a pulmonary disorder which causes significant morbidity and mortality in premature infants. BPD is pathologically characterized by inflammation, fibrosis and impaired alveolar development. The purpose of this study was to obtain pilot data on the effectiveness and safety of prophylactic azithromycin in reducing the incidence and severity of BPD in an extremely low birth weight (≤ 1000 grams) population.</p> <p>Methods</p> <p>Infants ≤ 1000 g birth weight admitted to the University of Kentucky Neonatal Intensive Care Unit (level III, regional referral center) from 9/1/02-6/30/03 were eligible for this pilot study. The pilot study was double-blinded, randomized, and placebo-controlled. Infants were randomized to treatment or placebo within 12 hours of beginning mechanical ventilation (IMV) and within 72 hours of birth. The treatment group received azithromycin 10 mg/kg/day for 7 days followed by 5 mg/kg/day for the duration of the study. Azithromycin or placebo was continued until the infant no longer required IMV or supplemental oxygen, to a maximum of 6 weeks. Primary endpoints were incidence of BPD as defined by oxygen requirement at 36 weeks gestation, post-natal steroid use, days of IMV, and mortality. Data was analyzed by intention to treat using Chi-square and ANOVA.</p> <p>Results</p> <p>A total of 43 extremely premature infants were enrolled in this pilot study. Mean gestational age and birth weight were similar between groups. Mortality, incidence of BPD, days of IMV, and other morbidities were not significantly different between groups. Post-natal steroid use was significantly less in the treatment group [31% (6/19)] vs. placebo group [62% (10/16)] (p = 0.05). Duration of mechanical ventilation was significantly less in treatment survivors, with a median of 13 days (1–47 days) vs. 35 days (1–112 days)(p = 0.02).</p> <p>Conclusion</p> <p>Our study suggests that azithromycin prophylaxis in extremely low birth weight infants may effectively reduce post-natal steroid use for infants. Further studies are needed to assess the effects of azithromycin on the incidence of BPD and possible less common side effects, before any recommendations regarding routine clinical use can be made.</p

Can we improve outcome of congenital diaphragmatic hernia?

This review gives an overview of the disease spectrum of congenital diaphragmatic hernia (CDH). Etiological factors, prenatal predictors of survival, new treatment strategies and long-term morbidity are described. Early recognition of problems and improvement of treatment strategies in CDH patients may increase survival and prevent secondary morbidity. Multidisciplinary healthcare is necessary to improve healthcare for CDH patients. Absence of international therapy guidelines, lack of evidence of many therapeutic modalities and the relative low number of CDH patients calls for cooperation between centers with an expertise in the treatment of CDH patients. The international CDH Euro-Consortium is an example of such a collaborative network, which enhances exchange of knowledge, future research and development of treatment protocols