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Biomedical subjects

A E Curley

Publications and source records attributed to A E Curley.

8 recordsLinked to original sources
PubMed2006

A dose response study of inhaled nitric oxide in hypoxic respiratory failure in preterm infants.

BACKGROUND: Inhaled nitric oxide (iNO) is used widely in newborn infants with hypoxic respiratory failure, despite the known and theoretical toxicity of iNO, and a relative lack of information about appropriate doses. AIM: To determine whether a dose-response relationship existed for iNO in preterm infants. DESIGN: A four-period, four-dose, cross-over design was used with iNO given for 15 min in a randomised sequence in concentrations of 5, 10, 20 and 40 parts per million (ppm), with a minimum 5 min wash-out period. Data on ventilatory, blood gas and other physiological measurements were recorded before and at the end of each period. The relationship of clinical response with iNO dose and period was analysed using multivariate regression. SUBJECTS: Infants with gestational age < 34 weeks and < 28 days postnatal age with hypoxic respiratory failure were recruited. OUTCOME MEASURE: A clinically significant dose-response was defined as a rise in the post-ductal arterial oxygen tension (PaO(2)) of at least 3 kPa. RESULTS: Thirteen infants were recruited. At trial entry, ten were < 3 days of age; 11 were being treated with high frequency oscillatory ventilation; median (inter-quartile range) gestational age 27 (25-29) weeks; birthweight 983 (765-1120) g; oxygenation index 27.1 (21.8-28.8). Six infants (46%) showed a clinically significant response. After adjusting for period and patient effect, no evidence for an overall dose effect was identified (likelihood ratio test, p=0.34). CONCLUSION: No evidence of a dose-response relationship with iNO was found in this study of very preterm infants with respiratory failure.

Administration, Inhalation↗
PubMed2004

The role of matrix metalloproteinases -9 and -2 in development of neonatal chronic lung disease.

AIM: Matrix metalloproteinases (MMPs) -9 and -2 degrade type-IV collagen, a major constituent of lung basement membrane, and may have a role in the pathogenesis of neonatal chronic lung disease (CLD). We determined factors influencing MMP levels in neonatal bronchoalveolar lavage (BAL) fluid to establish whether an imbalance between MMP and its inhibitor could be implicated in CLD. METHODS: We measured MMP-9 and -2 and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels in 316 BAL fluid samples from 121 babies of gestational ages 23 to 42 wk over the first 14 d of life to determine effects of gestation and postnatal age. Median MMP-9, -2, TIMP-1 and MMP-9/TIMP-1 ratio in BAL were further studied in a subgroup of 85 babies <33 wk gestation to determine their ability to predict CLD and to establish effects of antenatal corticosteroid therapy (ANCS). RESULTS: MMP-9, -2 and TIMP levels did not vary with postnatal age over the first week. Median MMP-9 levels and MMP-9/TIMP-1 ratio increased with decreasing gestation in preterm babies. The MMP-9/TIMP-1 ratio was higher in babies who developed CLD, implying a proteinase/antiproteinase imbalance, but this association disappeared when controlled for gestational age. ANCS had no effect on BAL fluid MMP or TIMP levels. CONCLUSION: MMPs may have a role in the development of lung injury and fibrosis, but estimating their levels in the first week of life does not help with prediction of CLD.

Bronchoalveolar Lavage Fluid↗
PubMed2004

Chorioamnionitis increases matrix metalloproteinase-8 concentrations in bronchoalveolar lavage fluid from preterm babies.

OBJECTIVE: To determine the effects of chorioamnionitis and antenatal corticosteroids on matrix metalloproteinase-8 (MMP-8) concentrations in bronchoalveolar lavage (BAL) fluid from preterm babies in the first week of life. DESIGN: Prospective observational study. SETTING: Regional neonatal intensive care unit. PATIENTS: Thirty five ventilated preterm babies < 33 weeks gestation, seven of whom were born after chorioamnionitis, which was diagnosed histologically as the presence of inflammatory cells in the chorioamnionic plate. METHODS: MMP-8 was measured by enzyme linked immunosorbent assay (ELISA) in 90 serial BAL samples taken during the first six postnatal days. The median MMP-8 concentration for each baby was calculated. RESULTS: Median MMP-8 concentrations were higher in the chorioamnionitis group than in those without (43 v 5 ng/ml). Partial or complete courses of antenatal corticosteroids had no effect on MMP-8 concentrations. CONCLUSIONS: Higher concentrations of MMP-8 are found in BAL fluid from preterm babies from pregnancies complicated by chorioamnionitis. This type I collagenase may contribute to the lung injury that occurs in some babies with respiratory distress syndrome.

Adrenal Cortex Hormones↗
PubMed2001

The present status of exogenous surfactant for the newborn.

This year is the 20th anniversary of the first successful trial of exogenous surfactant for respiratory distress syndrome in the newborn and it is perhaps a good time to review recent advances in basic science and clinical practice as they relate to surfactant therapy.

Animals↗
PubMed2001

Type I collagenases in bronchoalveolar lavage fluid from preterm babies at risk of developing chronic lung disease.

OBJECTIVE: To assess whether increased collagenolysis precedes severe chronic lung disease (CLD). METHODS: Matrix metalloproteinase-1 (MMP-1) and MMP-8 (enzymes that degrade type I collagen, the main structural protein of lung extracellular matrix) were measured by enzyme linked immunosorbent assay in 100 bronchoalveolar lavage samples taken during the first 6 postnatal days from 45 ventilated preterm babies < 33 weeks gestation. The median value for each baby was calculated. CLD was defined as an oxygen requirement after the 36th week after conception. RESULTS: MMP-8 levels in bronchoalveolar lavage fluid were higher (median 13 ng/ml) in 20 babies who developed CLD than in 25 without CLD (median 2 ng/ml). No MMP-1 was detected in any sample. CONCLUSIONS: MMP-8 can be detected in bronchoalveolar lavage fluid from preterm babies, and higher levels are found in those who later develop CLD. MMP-8 may contribute to lung injury that occurs as a prelude to CLD.

Blood Gas Analysis↗
PubMed2000

[Treatment of very low birth weight infant: is it evidenced-based?].

AIM: To determine what percentage of therapeutic interventions for very low birth weight infants undergoing neonatal intensive care is evidence based. METHODS: The management of 80 very low birth weight infants admitted to our neonatal unit during 1998 was retrospectively reviewed. For each clinical diagnosis e.g. respiratory distress syndrome, patent ductus arteriosus or chronic lung disease all interventions were recorder. Each intervention was then categorised according to the level of supporting evidence. Level I was supported by evidence from randomised controlled trials or meta-analysis of multiple trials. Level II included interventions backed by convincing non-experimental evidence where randomised controlled trials would be unnecessary or unethical. Level III were treatments in common use without substantial supporting evidence. These categorizations were made after extensive researching of Medline, The Cochrane Database and the Randomised Controlled Trial Register, detailed hand-searching of the literature as well as using local expertise and knowledge. RESULTS: 943 separate interventions were recorded in the charts of the 80 babies. Overall 91.3% were shown to be evidence-based of which 58.7% were level I, 32.6% were level II and only 8.7% were level III. CONCLUSIONS: 91.3% of interventions for very low birth weight infants in our neonatal intensive care unit were evidence-based and only 8.7% had no substantial supporting evidence. Care of the very low birthweight infants is largely evidence-based.

Evidence-Based Medicine↗