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H L Halliday

Publications and source records attributed to H L Halliday.

At least 19 recordsLinked to original sources
PubMed2004

Intravenous indometacin in preterm infants with symptomatic patent ductus arteriosus. A population pharmacokinetic study.

AIMS: To characterize the population pharmacokinetics of indometacin in preterm infants with symptomatic patent ductus arteriosus and to investigate the influence of various factors on the response to treatment. METHODS: Data were collected from 35 infants (gestational age 25-34 weeks; postnatal age 1-77 days) in neonatal units in Belfast and Copenhagen. Infants received an initial course of up to three doses of intravenous indometacin (0.1-0.2 mg kg(-1)) as considered appropriate by the treating physician. For those infants who did not respond to therapy or in whom the ductus reopened, a second course was sometimes given. Population analysis of the 185 plasma concentrations obtained was conducted using NONMEM and pharmacokinetic and demographic differences between responders and nonresponders were compared. RESULTS: The concentration-time course of indometacin was best described by a one-compartment model. The final population parameter estimates of clearance (CL) and volume of distribution (V) (standardized to the median weight of 1.17 kg) were 0.00711 l h(-1) and 0.266 l, respectively. CL increased from birth by approximately 3.38% per day and V by approximately 1.47% per day. Concomitant digoxin therapy resulted in a 30% decrease in V. Interindividual variability in CL and V was 41% and 21%, respectively. Interoccasion variability for CL was 43%. Residual variability corresponded to a standard deviation of 0.148 mg l(-1). Closure occurred in 75% of infants with a plasma concentration > or = 0.4 mg l(-1) 24 h after the last dose. CONCLUSIONS: Dosing regimens for indometacin should take into account the weight and postnatal age of the infant and any concomitant digoxin therapy. The population estimates can be used to determine typical values of CL and V allowing the prediction of individualized doses of indometacin that should increase the probability of achieving a 24 h plasma concentration > or = 0.4 mg l(-1). Although the pharmacokinetic estimates will be affected by both interindividual and within-individual variation, it is anticipated that this approach will decrease the variability of exposure and optimize treatment outcome.

Cardiovascular Agents↗
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↗
PubMed2004

Characterization of the C-terminal region of molecular forms of human milk bile salt-stimulated lipase.

UNLABELLED: Bile salt-stimulated lipase (BSSL) in human milk exists in multiple molecular forms and it has been shown that approximately one-third of lactating mothers secrete two forms. AIM: to determine the structural features of BSSL that may give rise to this heterogeneity. METHODS: Oligosaccharides present in the proline-rich region in the C-terminus of BSSL were investigated using deglycosylating enzymes and lectin affinity probing to determine the origin of the multiple molecular forms. RESULTS: It was found that the variability in the molecular mass of BSSL is due predominantly to glycosylation. The molecular forms contain similar sugar chains; all forms possess the core disaccharide Galbeta1-3GalNAc and beta-D-galactose, fucose linked at alpha1-6 and sialic acid linkage alpha2-3 to galactose. CONCLUSION: The molecular mass difference in the BSSL molecular forms cannot be attributed to the type of carbohydrate moiety in the sugar chains of the N- and O-linked sites suggesting that the differences arise from the extent or quantity of glycosylation. The oligosaccharides in the C-terminal region contain Lewis x and b and, less prominently, Lewis a antigenic structures. Owing to the presence of these blood-group-related antigenic determinants, the C-terminal region of BSSL may have an adhesive function in cell-cell interactions.

Electrophoresis, Polyacrylamide Gel↗
PubMed2003

Randomized trial of novel tetracaine patch to provide local anaesthesia in neonates undergoing venepuncture.

BACKGROUND: Procedures such as venepuncture or heel prick are painful and may cause considerable stress to newborn infants. Topical local anaesthetics are effective for venepuncture but need to be applied for at least 60 min and the delivered dose will vary. We assessed a novel tetracaine-based self-adhesive patch in providing controlled local anaesthesia before venepuncture. METHODS: A placebo-controlled, double-blind trial was conducted using a tetracaine patch formulated from hydroxypropylcellulose discs (0.283 cm(2)) containing tetracaine (1 mg x cm(-2)) surrounded by a low tack pressure-sensitive adhesive backing layer. Thirty-two newborn infants of gestation 32-42 weeks (median 36 weeks), aged 3-18 days (median 6 days) were randomized to receive a tetracaine-containing patch or a placebo device applied to the dorsum of the hand 30 min before venepuncture to obtain blood samples. Pain was assessed in response to needle insertion using a validated adaptation of the neonatal facial coding score (NFCS) and the presence of crying. RESULTS: Of 15 tetracaine-treated neonates, 14 (93%) presented little or no pain in response to the procedure compared with six of 17 (35%) who had the placebo patch applied (P=0.01). CONCLUSIONS: The tetracaine patch produced effective pain relief during the venepuncture procedure in both term and pre-term infants. There were no adverse effects, either local or systemic.

Administration, Cutaneous↗
PubMed2003

Postnatal dexamethasone: what is the real cost-benefit ratio?

UNLABELLED: Postnatal corticosteroids given early after birth reduce the risk of chronic lung disease in preterm infants but are associated with an approximate doubling of the risk of adverse neurosensory outcomes. Corticosteroids given after 7-10 d of age appear not to have these increased risks of neurosensory sequelae and reduce time on the ventilator. CONCLUSION: Further research is needed to determine the lowest dose of corticosteroid that will improve lung function and minimize risks to the developing brain.

Brain↗
PubMed2003

Treatment strategies for bronchopulmonary dysplasia with postnatal corticosteroids in Europe: the EURAIL survey.

AIM: To survey practices in 14 European countries and describe strategies for the prevention and treatment of bronchopulmonary dysplasia with postnatal steroids (PNS). METHODS: In 1999-2000 questionnaires covering the use of PNS were sent to every neonatal unit taking very preterm newborns in charge, in population-based areas covering at least 20000 births annually. One questionnaire was sent to surveyed unit. The participating areas were chosen by an expert from each country participating in the Europe Against Immature Lung (EURAIL) study group. RESULTS: Responses to 331 questionnaires were received; the mean response rate by countries was 84% (range 64-100%). Teaching hospitals accounted for 19% of the responding units. The number of extremely premature newborns (less than 28 wk of gestation) admitted yearly to these units was 0 in 16%, < 20 in 62%, 20-39 in 11% and > 39 in 11%. Overall, 67% of the centres used PNS: 48% initiated treatment in non-intubated infants and 53% at 7-14 d. Treatment duration was 4-15 d in 62% and > 15 d in 21%. PNS administration was limited to intubated infants less often in smaller units [odds ratio (OR) 0.2, 95% confidence interval (95% CI) 0.1-0.6] and more often in non-teaching hospitals (OR 2.5, 95% CI 2.5-5.0). CONCLUSIONS: Although PNS have important side effects, they were still widely used in 1999 to treat or prevent chronic lung disease. Surprisingly, steroids are still prescribed in non-ventilated infants. PNS use should be based on guidelines derived from the evidence from randomized controlled trials. This evidence should be regularly updated and disseminated.

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

Study of maternal influences on fetal iron status at term using cord blood transferrin receptors.

AIMS: To determine effects of maternal iron depletion and smoking on iron status of term babies using serum transferrin receptors (STfR) and their ratio to ferritin (TfR-F index) in cord blood. METHODS: Iron, ferritin, STfR, and haemoglobin (Hb) concentration were measured and TfR-F index calculated in 67 cord /maternal blood pairs. Twenty six mothers were iron depleted (ferritin <10 microg/l) and 28 were smokers. RESULTS: Maternal iron depletion was associated with decreased cord ferritin (113 v 171 microg/l) and Hb (156 v 168 g/l) but no change in STfR or TfR-F index. Smoking was associated with increased cord Hb (168 v 157 g/l) and TfR-F index (4.1 v 3.4), and decreased ferritin (123 v 190 microg/l). Cord TfR-F index and Hb were positively correlated (r = 0.48). CONCLUSIONS: Maternal iron depletion is associated with reduced fetal iron stores but no change in free iron availability. Smoking is associated with increased fetal iron requirements for erythropoiesis.

Anemia, Iron-Deficiency↗
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↗
PubMed2001

A trial of recombinant human granulocyte colony stimulating factor for the treatment of very low birthweight infants with presumed sepsis and neutropenia.

OBJECTIVES: The primary objective was to investigate the safety of recombinant human granulocyte colony stimulating factor (rhG-CSF) for the treatment of very low birthweight infants (VLBW) with sepsis and relative neutropenia, specifically with regard to worsening of respiratory distress and thrombocytopenia and all cause mortality. Secondary objectives were to evaluate duration of ventilation, intensive care, and antibiotic use as markers of efficacy. DESIGN: Neonates (< or = 28 days) in intensive care, with birth weights of 500-1500 g, absolute neutrophil count (ANC) of < or = 5 x 10(9)/l, and clinical evidence of sepsis, were randomly assigned to receive either rhG-CSF (10 microg/kg/day) administered intravenously (n = 13), or placebo (n = 15) for a maximum of 14 days, in addition to standard treatment and antibiotics. All adverse events, oxygenation index, incidence of thrombocytopenia, all cause mortality, duration of ventilation, intensive care and antibiotic treatment, and ANC recovery were compared between the two groups. RESULTS: Adverse events and oxygenation index were not increased by, and thrombocytopenia was not attributable to, treatment with rhG-CSF. At 6 and 12 months postmenstrual age, there were significantly fewer deaths in the group receiving rhG-CSF (1/13 v 7/15; p < or = 0.038). There was a non-significant trend towards a reduction in duration of ventilation, intensive care, and antibiotic use in the rhG-CSF group. There was a significantly more rapid increase in ANC in the rhG-CSF treated babies (p < 0.001). CONCLUSIONS: In a small randomised placebo controlled trial in a highly selected group of neonates, adjuvant treatment with rhG-CSF increased ANC rapidly, and no treatment related adverse events were identified. Mortality at 6 and 12 months postmenstrual age was significantly lower in the treatment group. A large trial investigating efficacy in a similar group of neonates is warranted.

Anti-Infective Agents↗
PubMed2001

Cord blood transferrin receptors to assess fetal iron status.

OBJECTIVE: To study iron status at different gestational ages using cord blood serum transferrin receptors (STfRs). METHODS: STfRs, iron, ferritin, total iron binding capacity, haemoglobin, and reticulocytes were measured in 144 cord blood samples. The babies were divided into three groups according to gestation (26 very preterm (24-29 weeks); 50 preterm (30-36 weeks); 68 term (37-41 weeks)). RESULTS: Serum iron, ferritin, and total iron binding capacity were highest at term, whereas reticulocytes were highest in the very preterm. STfR levels were not influenced by gestation. Haemoglobin (r = 0.46; p < 0.0001) and reticulocytes (r = 0.42; p < 0.0001) were the only indices that independently correlated with STfR levels. CONCLUSIONS: STfR levels in cord blood are not directly influenced by gestation and probably reflect the iron requirements of the fetus for erythropoiesis.

Analysis of Variance↗
PubMed2001

Oxidative stress in lavage fluid of preterm infants at risk of chronic lung disease.

There is evidence that oxidative stress plays a role in the development of chronic lung disease (CLD), with immature lungs being particularly sensitive to the injurious effect of oxygen and mechanical ventilation. We analyzed total ascorbate, urate, and protein carbonyls in 102 bronchoalveolar lavage fluid samples from 38 babies (33 preterm, 24-36 wk gestation; 5 term, 37-39 wk gestation). Preterm babies had significantly decreasing concentrations of ascorbate, urate, and protein carbonyls during the first 9 days of life (days 1-3, 4-6, and 7-9, Kruskal-Wallis ANOVA: P = 0.016, P < 0.0001, and P = 0.010, respectively). Preterm babies had significantly higher protein carbonyl concentrations at days 1-3 and 4-6 (P = 0.005 and P = 0.044) compared with term babies. Very preterm babies (24-28 wk gestation) had increased concentrations of protein carbonyls at days 4-6 (P = 0.056) and significantly decreased ascorbate concentrations at days 4-6 (P = 0.004) compared with preterm babies (29-36 wk gestation). Urate concentrations were significantly elevated at days 1-3 (P = 0.023) in preterm babies who subsequently developed CLD. This study has shown the presence of oxidative stress in the lungs of preterm babies during ventilation, especially in those who subsequently developed CLD.

Antioxidants↗
PubMed2001

Oxidative stress and increased type-IV collagenase levels in bronchoalveolar lavage fluid from newborn babies.

Oxidative stress may increase lung permeability by up-regulation of matrix-metalloproteinase-9 (MMP-9), a type-IV collagenase that can disrupt alveolar basement membranes. We have compared a marker of oxidative stress (protein carbonyl residues) with levels of MMP-9 and its inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), in bronchoalveolar lavage samples from newborn babies. Bronchoalveolar lavage samples (n = 87, two from each time point) were taken in the first 6 postnatal days from 41 ventilated babies: 18 of <29 wk gestation, 10 of 29-36 wk, 9 term with persistent fetal circulation, and 4 term without lung disease. Respiratory disease severity at the time of bronchoalveolar lavage was assessed using the arterial-alveolar oxygen tension ratio. One sample from each time point was used for the measurement of MMP-9 by zymography and TIMP-1 by ELISA. The second sample was used to measure carbonyl group concentrations, also using an ELISA. Correlations were calculated between protein carbonyls, arterial-alveolar oxygen tension ratio, and MMP-9 and TIMP-1 concentrations. Significant correlations were found between carbonyl concentrations and arterial-alveolar oxygen tension ratio (r = -0.325, p = 0.0031, n = 81), MMP-9 (r = 0.331, p < 0.0029, n = 79), and TIMP-1 (r = 0.436, p < 0.0001, n = 87). Worsening respiratory disease in newborn babies is associated with increased carbonyl concentrations in neonatal bronchoalveolar lavage fluid, and these correlated with MMP-9 and TIMP-1 levels. Increased oxidative stress may damage the lung by increasing type-IV collagenase activity, causing disruption of the extracellular matrix.

Bronchoalveolar Lavage Fluid↗
PubMed2001

The effect of postnatal steroids on growth and development.

Single courses of prenatal corticosteroids have many beneficial effects including reduction in respiratory distress syndrome, intraventricular hemorrhage and neonatal mortality. Postnatal corticosteroids, however, have both beneficial and harmful effects. The beneficial effects include shortened time on the ventilator and a reduction in chronic lung disease. Dexamethasone treatment started within the first 4 days of life is associated with an increased risk of abnormal neurodevelopment including cerebral palsy. Other adverse effects include metabolic disturbances, cardiac hypertrophy, reduced growth and gastrointestinal perforation. The risks of early dexamethasone treatment in currently used doses outweigh the benefits. Further research is needed to determine the optimal corticosteroid drug, its dose and timing of administration to maximize benefit and reduce risk to a minimum. Other non-drug interventions should be used to minimize the risk of chronic lung disease in very preterm infants.

Adrenal Cortex Hormones↗