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Biomedical subjects

R Iles

Publications and source records attributed to R Iles.

At least 19 recordsLinked to original sources
PubMed2000

Inhaled steroids for neonatal chronic lung disease.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a chronic disorder associated with prematurity. Systemic steroids induce at least a temporary improvement in respiratory function, but are associated with adverse side effects. Inhaled steroids have fewer side effects. OBJECTIVES: To determine if inhaled corticosteroids are effective in alleviating the morbidity of bronchopulmonary dysplasia (BPD) compared to 0-placebo. SEARCH STRATEGY: We identified randomised, controlled trials (RCT) within the Cochrane Database, references from retrieved trials, hand searches of journals and contact with pharmaceutical companies and experts in this field. SELECTION CRITERIA: Only randomised controlled trials involving infants with chronic lung disease of prematurity and treated with inhaled steroids versus placebo were included. Patients receiving systemic corticosteroids were excluded. Co-interventions included antenatal systemic steroids, routine neonatal intensive care, ventilatory support, surfactant replacement therapy, diuretics and bronchodilators. DATA COLLECTION AND ANALYSIS: Four of the seven included trials were of good methodological quality. There were five parallel-group trials in ventilated infants. These were comparable in terms of population, co-interventions and need for increased inspired oxygen concentration. They differed in terms of type, dose and duration (7-28 days) of inhaled steroids. Two cross-over trials were performed in non-ventilated patients. MAIN RESULTS: The inability to extubate during treatment was markedly reduced in infants treated with inhaled steroids; Peto Odds Ratio (OR) 0.12, 95% Confidence Interval (CI) 0.03 to 0.43. There was heterogeneity in this finding, however, with one study that contributed 30% of the total number of patients reporting no successful extubations in either treatment arm over one week. The risk of sepsis appeared similar between the two groups (N=3, OR=0.72, 95%CI: 0.21 to 2.43). The small number of trials precluded analysis to examine the effect of differences in drug, duration of therapy, delivery system, co-interventions, and disease severity. Reduced oxygen requirements were reported in one of the two trials performed in non-ventilated infants, but inadequate data reporting precluded pooling of data. REVIEWER'S CONCLUSIONS: In ventilated infants with BPD, inhaled steroids administered for 1 to 4 weeks improved the rate of extubation with no apparent increase in the risk of sepsis. No firm conclusion could be derived with regard to the efficacy of inhaled steroids in non-ventilated infants.

Administration, Inhalation↗
PubMed1999

Crying significantly reduces absorption of aerosolised drug in infants.

AIM: Therapeutic aerosols are routinely used in the management of infant obstructive airways disease. Infants often become distressed during administration. The aim of this study was to determine the influence of distress and disease severity on the absorption of aerosolised drug in this age group. METHODS: Fifteen infants, eight with resolving chronic lung disease of prematurity (mean age, 13 months), and seven infants with normal birth histories (mean age, 11 months) were studied. Flow through small airways was assessed by measurement of partial forced expiratory flow volume curves. Each infant was then given a dose of 20 mg nebulised sodium cromoglicate via a Sidestream nebuliser and distress was graded as: 1, not distressed; 2, distressed. Infants were excluded if contact with the mask was lost for more than 10 seconds. Urine was collected for eight hours and analysed for excreted drug by radioimmunoassay. RESULTS: Sodium cromoglicate is absorbed by the respiratory epithelium, and undergoes renal (43%) and hepatic (57%) excretion. A mean of 0.43% of the total nebulised drug dose was excreted in the urine of the non-distressed infants compared with 0.11% of total dose in the distressed infants. Flow through the small airways was significantly reduced in infants with chronic lung disease of prematurity. Maximum flow at functional residual capacity did not correlate with the amount of drug in the urine, but the degree of distress did. CONCLUSION: To maximise absorption, nebulised drugs should be given to settled infants. The degree of airways disease does not influence drug absorption in this age group.

Administration, Inhalation↗
PubMed1999

Diversity in levels of intracellular total creatine and triglycerides in human skeletal muscles observed by (1)H-MRS.

We used (1)H-magnetic resonance spectroscopy to noninvasively determine total creatine (TCr), choline-containing compounds (Cho), and intracellular (IT) and extracellular (between-muscle fibers) triglycerides (ET) in three human skeletal muscles. Subjects' (n = 15 men) TCr concentrations in soleus [Sol; 100.2 +/- 8.3 (SE) mmol/kg dry wt] were lower (P < 0.05) than those in gastrocnemius (Gast; 125.3 +/- 9.2 mmol/kg dry wt) and tibialis anterior (TA; 123. 7 +/- 8.8 mmol/kg dry wt). The Cho levels in Sol (35.8 +/- 3.6 mmol/kg dry wt) and Gast (28.5 +/- 3.5 mmol/kg dry wt) were higher (P < 0.001 and P < 0.01, respectively) compared with TA (13.6 +/- 2. 4 mmol/kg dry wt). The IT values were found to be 44.8 +/- 4.6 and 36.5 +/- 4.2 mmol/kg dry wt in Sol and Gast, respectively. The IT values of TA (24.5 +/- 4.5 mmol/kg dry wt) were lower than those of Sol (P < 0.01) and Gast (P < 0.05). There were no differences in ET [116.0 +/- 11.2 (Sol), 119.1 +/- 18.5 (Gast), and 91.4 +/- 19.2 mmol/kg dry wt (TA)]. It is proposed that the differences in metabolite levels may be due to the differences in fiber-type composition and deposition of metabolites due to the adaptation of different muscles during locomotion.

Adult↗
PubMed1998

Liposome-mediated transfection of fetal lung epithelial cells: DNA degradation and enhanced superoxide toxicity.

Cationic liposomes, 1:1 (mol/mol) 1,2-dioleoyldimethylammonium chloride-1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, were used to transfect primary cultures of distal rat fetal lung epithelial cells with pCMV4-based plasmids. A DNA-to-lipid ratio of 1:10 to 1:15 (wt/wt) optimized DNA uptake over a 24-h exposure. At a fixed DNA-to-lipid ratio of 1:15, chloramphenicol acetyltransferase (CAT) reporter gene expression declined at lipid concentrations > 2.5 nmol/cm2 cell surface area, whereas DNA uptake remained concentration dependent. CAT expression peaked 48 h after removal of the liposome-DNA complex, declining thereafter. Reporter gene expression was increased, and supercoiled cDNA degradation was reduced by the addition of 0.2 mM nicotinamide and 10 microM chloroquine. Rat fetal lung epithelial cells transfected with two different expression cassettes had an increased susceptibility to superoxide-mediated cytotoxicity. This could be attributed to a nonspecific delivery of exogenous DNA or some other copurified factor. The DNA-dependent increase in superoxide-mediated cytotoxicity, but not basal levels of cytotoxicity, was inhibited by the addition of 0.2 mM nicotinamide and 10 microM chloroquine.

Animals↗
PubMed1997

Lung disease in mice with cystic fibrosis.

The leading cause of mortality and morbidity in humans with cystic fibrosis is lung disease. Advances in our understanding of the pathogenesis of the lung disease of cystic fibrosis, as well as development of innovative therapeutic interventions, have been compromised by the lack of a natural animal model. The utility of the CFTR-knockout mouse in studying the pathogenesis of cystic fibrosis has been limited because of their failure, despite the presence of severe intestinal disease, to develop lung disease. Herein, we describe the phenotype of an inbred congenic strain of CFTR-knockout mouse that develops spontaneous and progressive lung disease of early onset. The major features of the lung disease include failure of effective mucociliary transport, postbronchiolar over inflation of alveoli and parenchymal interstitial thickening, with evidence of fibrosis and inflammatory cell recruitment. We speculate that the basis for development of lung disease in the congenic CFTR-knockout mice is their observed lack of a non-CFTR chloride channel normally found in CFTR-knockout mice of mixed genetic background.

Animals↗
PubMed1997

Serum concentrations of cancer antigen 125, placental alkaline phosphatase, cancer-associated serum antigen and free beta human chorionic gonadotrophin as prognostic markers for epithelial ovarian cancer.

OBJECTIVE: To investigate the prognostic significance of elevated levels of cancer antigen 125 (CA125), placental alkaline phosphatase (PLAP), free beta human chorionic gonadotrophin (hCG) and cancer-associated serum antigen (CASA) in women with primary epithelial ovarian carcinoma. DESIGN: A two year follow up study of survival. SETTING: A tertiary care gynaecological oncology unit. PARTICIPANTS: One hundred and eleven women with histologically confirmed epithelial ovarian cancer. MAIN OUTCOME MEASURES: Survival over a two year period. RESULTS: Stage corrected log-rank chi 2 tests demonstrated a significant effect on survival for all four tumour markers (CA125 P = 0.0142; PLAP P < 0.0001; CASA P = 0.0098; hCG P = 0.0002). This was confirmed when each variable was fitted together with disease stage in Cox proportional hazard models. When fitted as multiple variables in a Cox proportional hazard model, the addition of free beta-hCG and CASA to disease stage, PLAP concentrations and CA125 levels did not demonstrate further prognostic value. CONCLUSIONS: Levels of all four markers correlate with survival in patients with epithelial ovarian cancer. The combination of PLAP and CA125 concentrations together with disease stage may be used to predict survival but the addition of hCG and CASA levels do not give additional prognostic information.

Adult↗
PubMed1997

Assessment of pulmonary function in resolving chronic lung disease of prematurity.

AIM: To investigate the longitudinal changes of interstitial and airways disease in resolving chronic lung disease of prematurity (CLD). METHODS: Thirty three infants were studied between 35 and 40 weeks of postconceptional age, and then at three monthly intervals throughout their first year. Measurements of mean arterial oxygen saturation (MSaO2) and its variability (delta MSaO2) were recorded. PaCO2 and PaO2 were determined while the infants breathed steady state 50% oxygen via a hood. From these, the alveolar arterial difference (A-a) DO2(50) was calculated. Airway disease was assessed by the measurement of partial forced expiratory flow volume curves (PEFC) to give Vmax Frc. RESULTS: The cohort mean +/- 95% confidence intervals measured between 35 and 40 weeks were for MSaO2 (89.25 +/- 1.87%, range 75-96.5%) and delta MSaO2 (4.79 +/- 0.8%, range 0.16-9.64%), PaCO2 (5.89 +/- 0.56 kpa, range 4.2-10.11 kpa), (A-a) DO2(50) (22.7 +/- 2.56 kpa, range 6.67-31.4 kpa) and VmaxFrc (41.5 +/- 8.65 mls/second, range 8.5-103.7 ml/second). The most significant improvement in all measurements occurred within the first three months (P = 0.05). An MSaO2 of less than 90% in room air at 1 year of age was predicted between 35 and 40 weeks postconceptional age by an (A-a) DO2(50) of greater than 29 kpa, with a sensitivity of 0.85 and a specificity of 0.88, and a PaCO2 greater than 7 kpa predicted a specificity of 0.78 and a sensitivity of 0.88. Predictions were strengthened by combining the above criteria and these then gave a sensitivity and specificity of 1. CONCLUSION: Measurements of (A-a) DO2(50) and PaCO2 taken between 35 and 40 weeks can be used to assess the degree of pulmonary dysfunction at 1 year. Quantification of the severity of CLD could be used as a measurable end point for early neonatal intervention studies.

Humans↗
PubMed1997

Urinary beta-core hCG: screening for aneuploidies in early pregnancy (11-14 weeks' gestation).

Initial studies at 17-22 weeks' gestation evaluating urinary beta-core human chorionic gonadotrophin (hCG) as a marker for Down's syndrome had suggested that it may have more potential than its serum counterpart. This study measured maternal urinary beta-core-hCG and creatinine at 11-14 weeks' gestation in a series of 26 aneuploidies (nine trisomy 21, five trisomy 18, four 45,X0, and eight others). The normal range for beta-core-hCG and beta-core-hCG/ creatinine was derived from 198 normal singleton pregnancies. Trisomy 18 cases (n = 5) had low maternal urinary beta-core-hCG creatinine levels (median 0.35 MOM, range 0.08-0.82 MOM). Whereas the other aneuploidies had no particular pattern; in particular, the trisomy 21 cases (n = 9) (median 1.16 MOM, range 0.3-4.74 MOM) did not differ significantly from 1 MOM. The findings imply that maternal urinary beta-core-hCG is not as discriminating for Down's syndrome between 11 and 14 weeks as later on in pregnancy.

Adult↗
PubMed1996

Infection with Ureaplasma urealyticum and Mycoplasma hominis and the development of chronic lung disease in preterm infants.

In a prospective cohort study in a tertiary referral neonatal intensive care unit, the endotracheal secretions of 40 consecutively intubated newborn infants, less than 31 weeks' gestation, were examined weekly for the genital mycoplasmas and all other common bacterial pathogens. Fifteen (37%) infants were positive for Ureaplasma urealyticum and/or Mycoplasma hominis. There were no differences in gestation, birthweight, use of surfactant, or time on ventilator between the culture-positive and negative babies. Thirteen (87%) of the culture-positive group developed chronic lung disease (CLD) compared with 11 (41%) of the negative group (p = 0.0196). Of those culture-positive, 37% were not identified on the first specimen taken at the time of admission. These data suggest a significant association between infection with the urogenital mycoplasma and CLD and also stress the need for repeated cultures to identify these organisms.

Chronic Disease↗
PubMed1996

Prediction of early outcome in resolving chronic lung disease of prematurity after discharge from hospital.

In an attempt to identify those infants with resolving chronic lung disease of prematurity (CLD) at greatest risk of sudden infant death syndrome or acute life threatening event (SIDS/ALTE), or readmission to hospital following discharge, recordings of arterial oxygen saturation were made on 35 infants. Recordings were collected while the infants were breathing room air. Movement artefact was excluded and the data analysed to provide the mean individual arterial oxygen saturation (MSaO2), and the variability of the mean individual oxygen saturation (delta MSaO2). These data were related to clinical outcome recorded over the three months following investigation. A MSaO2 less than 90% on discharge predicted hospital admission within three months with a sensitivity of 1 and a specificity of 0.76, and SIDS/ALTE with a sensitivity of 1 and a specificity of 0.75. A delta MSaO2 greater than 6% predicted SIDS/ALTE with a sensitivity 0.88 and specificity of 1. Infants with resolving chronic lung disease of prematurity who are at risk of increased morbidity and mortality can be assessed by accurate measurement of mean arterial saturation.

Bronchopulmonary Dysplasia↗
PubMed1994

Maternal serum human chorionic gonadotrophin and pregnancy-associated plasma protein A, markers for fetal Down syndrome at 8-14 weeks.

Maternal serum levels of human chorionic gonadotrophin and its subunits (intact, alpha, and free beta h CG) and pregnancy-associated plasma protein A (PAPP-A) were measured in 279 women between 8 and 14 weeks' gestation. This group included 23 pregnancies in which the fetus had Down syndrome (DS), diagnosed either at birth or during the second trimester (n = 17) or from chorionic villus sampling (CVS) (n = 6). Normal medians were determined from the 258 apparently normal pregnancies. The median levels of intact hCG (1.4 MOM) and free beta hCG (2.1 MOM) were significantly raised, whereas the median level of PAPP-A (0.39 MOM) was significantly lower in the DS pregnancies when compared with the control group. Levels of alpha hCG were similar in both the control and the DS pregnancies. Analysis of samples taken prior to 14 weeks' gestation demonstrated that only PAPP-A (0.34 MOM) was significantly altered in DS pregnancies. However, after the exclusion of DS cases diagnosed at CVS, the median intact hCG (1.56 MOM), free beta hCG (2.27 MOM), and alpha hCG (1.8 MOM) were all raised in DS pregnancies. This emphasizes the problem of the interpretation of biochemical markers when DS cases are diagnosed at CVS.

Biomarkers↗
PubMed1994

Dramatic increase in levels of placental protein 14 in amniotic fluid at 10-15 weeks' pregnancy.

Concentrations of placental protein 14 (PP14) were measured by radioimmunoassay in 103 amniotic fluid samples from 10 to 20 weeks of pregnancy. Low levels of PP14 were present at 10-12 weeks (median values 82-280 micrograms/l). After 12 weeks, the levels increased by two orders of magnitude to reach a peak at 18 weeks (median 11 mg/l). This pattern may reflect the obliteration of the extraembryonic coelom and direct apposition of the decidua with the chorio-amnion.

Amniotic Fluid↗
PubMed1992

The effects of metabolic inhibition and acidification on force production in the rat uterus.

The effects of hypoxia and intracellular acidification were examined on the mechanical properties of the non-pregnant and pregnant rat uterus. Isolated uteri were investigated during control conditions and in the presence of cyanide, to simulate hypoxia or the salts of weak acids and bases to change intracellular pH at constant external pH (pH 7.4). Both spontaneous contractions and high-K contractures (i.e. fully activated preparations) were investigated at 37 degrees C. In control solutions both pregnant and non-pregnant uteri were spontaneously active and gave a contracture when bathed with a high-K+ solution. When oxidative phosphorylation was inhibited by cyanide, spontaneous contractions were either greatly reduced or abolished. The effects on spontaneous contractions were more pronounced in the non-pregnant than the pregnant uterus. If high-K solution was added after cyanide had abolished spontaneous contractions, then a small amount of force was produced. High-K-induced contractures were not maintained in the presence of cyanide and quickly fell to baseline levels in both pregnant and non-pregnant uteri. All the effects of cyanide were fully reversible. When only intracellular pH was changed by adding weak acids (50 mM-butyrate or propionate), spontaneous contractions were greatly diminished or abolished in both pregnant and non-pregnant uteri. However, the application of weak acids had no effect upon the KCl-induced contractures in both pregnant and non-pregnant uteri. The effects of cyanide on the uterus include both an acidification and changes in metabolites, e.g. a fall in [ATP]. To investigate the changes in metabolites without a change in pHi, cyanide was applied with the weak base trimethylamine (40-50 mM). 31P Nuclear magnetic resonance spectroscopy was used to show that the alkalinization which occurs with trimethylamine alone abolished the acidification ordinarily associated with cyanide. Spontaneous and high-K-induced contractions were greatly reduced or abolished, i.e. the result was the same as with cyanide alone. This occurred in both pregnant and non-pregnant uteri. It is concluded that spontaneous force production is affected by both changes in metabolites (e.g. decreased [ATP] and increased inorganic phosphate) and pHi, and that both can depress activation of the uterus. Only the changes in metabolites can depress force production in fully activated preparation. The greater effect on force in the non-pregnant uterus compared to the pregnant uterus may be due to the lower initial levels of [ATP] and the greater fall in ATP seen in non-pregnant compared to pregnant uterus, and gestational changes in metabolism.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗