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P N LeSouef

Publications and source records attributed to P N LeSouef.

7 recordsLinked to original sources
PubMed2005

CD14 C-159T and early infection with Pseudomonas aeruginosa in children with cystic fibrosis.

Early acquisition of Pseudomonas aeruginosa is associated with a poorer prognosis in patients with cystic fibrosis. We investigated whether polymorphisms in CD14, the lipopolysaccharide receptor, increase the risk of early infection. Forty-five children with cystic fibrosis were investigated with annual bronchoalveolar lavage (BAL) and plasma sCD14 levels. Plasma sCD14 levels were significantly lower in children from whom P.aeruginosa was subsequently isolated (492.75 microg/ml vs. 1339.43 microg/ml, p = 0.018). Those with the CD14 -159CC genotype had a significantly increased risk of early infection with P.aeruginosa suggesting that CD14 C-159T plays a role in determining the risk of early infection with P.aeruginosa.

Australia↗
PubMed2001

Allele and genotype frequencies of polymorphic cytochromes P4502D6, 2C19 and 2E1 in aborigines from western Australia.

The polymorphisms of the important xenobiotic metabolizing enzymes CYP2D6, CYP2C19 and CYP2E1 have been studied extensively in a large number of populations and show significant heterogeneity in the frequency of different alleles/genotypes and in the prevalence of the extensive and poor metabolizer phenotypes. Understanding of inter-ethnic differences in genotypes is important in prediction of either beneficial or adverse effects from therapeutic agents and other xenobiotics. Since no data were available for Australian Aborigines, we investigated the frequencies of alleles and genotypes for CYP2D6, CYP2C19 and CYP2E1 in a population living in the far north of Western Australia. Because of its geographical isolation, this population can serve as a model to study the impact of evolutionary forces on the distribution of different alleles for xenobiotic metabolizing enzymes. Twelve CYP2D6 alleles were analysed. The wild-type allele *1 was the most frequent (85.81%) and the non-functional alleles (*4, * 5, * 16) had an overall frequency of less than 10%. Only one subject (0.4%) was a poor metabolizer for CYP2D6 because of the genotype *5/*5. For CYP2C19, the frequencies of the *1 (wild-type) and the non-functional (*2 and *3) alleles were 50.2%, 35.5% and 14.3%, respectively. The combined CYP2C19 genotypes (*2/*2, *2/*3 or *3/*3) correspond to a predicted frequency of 25.6% for the CYP2C19 poor metabolizer phenotype. For CYP2EI, only one subject had the rare c2 allele giving an overall allele frequency of 0.2%. For CYP2D6 and CYP2C19, allele frequencies and predicted phenotypes differed significantly from those for Caucasians but were similar to those for Orientals indicating a close relationship to East Asian populations. Differences between Aborigines and Orientals in allele frequencies for CYP2D6* 10 and CYP2E1 c2 may have arisen through natural selection, or genetic drift, respectively.

Alleles↗
PubMed1998

The elimination half-life of urinary cotinine in children of tobacco-smoking mothers.

Exposure to environmental tobacco smoke (ETS) is strongly associated with childhood morbidity. Cotinine, the major metabolite of nicotine, is a useful marker of tobacco smoke exposure. Cotinine levels in infants are higher than in older children or adults exposed to the same reported quantity of ETS. One hypothesis to explain this difference is that the urinary elimination half-life of cotinine is different between infants and older children. Urine was collected at admission, 12, 24 and 48 h, cotinine levels were subsequently measured and then standardized by correcting for creatinine excretion. Urinary elimination half-life of cotinine was calculated in 31 infants and 23 older children. The median half-life was 28.3 h (range 6.3-258.5 h) in infants, and 27.14 h (range 9.7-99.42 h) in older children. A Mann-Whitney U test showed no significant difference in the median half-life of cotinine between the two age groups (P = 0.18). Multivariate linear regression analysis demonstrated no significant relationship between half-life of cotinine and corrected cotinine level (P = 0.24). Our results support the hypothesis that higher cotinine levels in infants is due to greater exposure, rather than slower metabolism of cotinine.

Adolescent↗
PubMed1994

Pressure transmission across the respiratory system at raised lung volumes in infants.

Forced expiratory flow-volume (FEFV) curves can be generated from end-tidal inspiration in infants with use of an inflatable jacket. We have developed a technique to raise lung volume in the infant before generation of FEFV curves. Measurements of pressure transmission to the airway opening by use of static maneuvers have shown no change with increasing lung volume above end-tidal inspiration. The aim of this study was to determine, under dynamic conditions (i.e., during rapid thoracic compression), whether the efficiency of pressure transmission across the chest wall is altered by raising lung volume above the tidal range. Dynamic pressure transmission (Ptx,dyn) was measured in five infants (age 6-17 mo). Jacket pressure (Pj), esophageal pressure, and volume were measured throughout passive and FEFV curves at lung volumes set by 10, 15, and 20 cmH2O preset pressure. The group mean Ptx,dyn was 37 +/- 6% (SE) of Pj at end-tidal inspiration, and no change was seen with further increases in lung volume. However, a mean decrease in Ptx,dyn of 42% was evident throughout the tidal volume range (i.e., from end-tidal inspiration to end expiration). Isovolume static pressure transmission (Ptx,st) was measured in three of the five infants by inflation of the jacket in a stepwise manner with the airway closed. Measurements were made at end-tidal inspiration and lung volumes at 10, 15, and 20 cmH2O preset pressure. Resulting changes in Pj, esophageal pressure, and airway opening pressure were compared using linear regressions to determine Ptx,st.(ABSTRACT TRUNCATED AT 250 WORDS)

Cystic Fibrosis↗
PubMed1994

Improved detection of abnormal respiratory function using forced expiration from raised lung volume in infants with cystic fibrosis.

The raised volume rapid thoracic compression (RVRTC) technique is a recently developed method of measuring lung function in infants. The measurements of forced expiratory volume-time (FEVt) parameters from raised lung volumes have been shown to be less variable than maximal flow at functional residual capacity (VmaxFRC), obtained from the conventional rapid thoracic compression (RTC) technique. Measurements of VmaxFRC are highly variable, and may not be sensitive enough to detect a difference between normal infants and infants with cystic fibrosis (CF). The aim of this study was to determine whether the raised volume rapid thoracic compression technique could detect abnormal lung function in a group of CF infants with no current respiratory symptoms. Twelve CF infants were studied (median age 10.5 months, range 3-18 months), and compared to normative data collected previously on 26 healthy infants (median age 14 months, range 3-23 months). We found that VmaxFRC failed to detect any difference between the two groups. CF infants had significantly smaller FEV0.5 and FEV0.75 measurements at a lung volume set by 17.5 cmH2O predetermined inflation pressure (PP) both as raw values and when expressed as percentage predicted. We conclude that the raised volume rapid thoracic compression technique is a sensitive tool, able to detect abnormal lung function in infants with cystic fibrosis. This abnormality was not demonstrated by measurements derived from the conventional rapid thoracic compression technique in the tidal volume range.

Cystic Fibrosis↗
PubMed1984

Total resistance of the respiratory system in preterm infants with and without an endotracheal tube.

The passive compliance and resistance of the respiratory system were measured in 12 spontaneously breathing newborn infants before and after endotracheal extubation. End-inspiratory airway occlusions were used to relax the respiratory muscles, allowing occlusion pressure to be measured and respiratory system compliance and resistance to be calculated from the flow volume relationship of the subsequent passive expiration. Airway pressure was measured from an endotracheal tube or a face mask, expiratory flow from a pneumotachograph, and expiratory volume from the integrated flow signal. In six of the infants, diaphragmatic electromyography was also performed before and after extubation. Resistance and EMG findings were both decreased by extubation (mean decrease 43.9%, P less than 0.001 and 27.3%, P less than 0.05, respectively), but compliance was unchanged. Thus, by substantially increasing resistance, an endotracheal tube causes the diaphragm to increase its activity to maintain ventilation.

Airway Resistance↗