PubMed Health⌕ Search

Biomedical subjects

I A Laing

Publications and source records attributed to I A Laing.

At least 19 recordsLinked to original sources

Association of haplotypes of beta2-adrenoceptor polymorphisms with lung function and airway responsiveness in a pediatric cohort.

We evaluated the influence of haplotypes of beta(2)-adrenergic receptor (ADRB2) polymorphisms on lung function and airway responsiveness (AR) in a pediatric cohort recruited before birth and followed up to 11 years of age. The subjects (180) were the participants in a prospective study of lung function and AR. They have been assessed five times (at 1 month, 6 months, 12 months, 6 and 11 years of age) for lung function and AR. The two ADRB2 single nucleotide polymorphisms (SNPs): Arg16Gly and Gln27Glu were genotyped by PCR-RLFP and their haplotypes inferred using the program PHASE. An association between the haplotype arg16gln27 and the prevalence of positive AR was found at age 6 years (P = 0.009). The gly16gln27 haplotype was associated with higher FEV1 (P = 0.015) at age 6 and both higher FEV1 and FVC (P = 0.018 and P = 0.001, respectively) at age 11. In contrast, arg16gln27 was associated with both lower FEV1 and FVC (P = 0.028 and P = 0.011, respectively) at age 11. Children with the gly16gln27 haplotype were less likely to have asthma-ever or doctor-diagnosed asthma at age 11 (OR: 0.38; P = 0.019 and OR: 0.31; P = 0.041, respectively). In conclusion, haplotypes of beta(2)-adrenoceptor polymorphisms are associated with lung function, AR, and asthma susceptibility in childhood.

Airway Resistance↗

Association of CD14 promoter polymorphism with otitis media and pneumococcal vaccine responses.

Innate immunity is of particular importance for protection against infection during early life, when adaptive immune responses are immature. CD14 plays key roles in innate immunity, including in defense against pathogens associated with otitis media, a major pediatric health care issue. The T allele of the CD14 C-159T polymorphism has been associated with increased serum CD14 levels. Our objective was to investigate the hypothesis that the CD14 C-159T allele is protective against recurrent acute otitis media in children. The association between the CD14 promoter genotype and the number of acute otitis media episodes was evaluated both retrospectively and prospectively in a cohort of 300 children. Serotype-specific immunoglobulin G (IgG) antibody responses after pneumococcal vaccinations were examined according to CD14 genotype to compare immune responsiveness across genotypes. An age-dependent association was found: compared with that for CC homozygotes aged between 12 to 24 months, TT homozygotes had fewer episodes of acute otitis media (79 versus 41%, respectively; P = 0.004); this relationship was absent in older children. Additionally, TT homozygotes showed higher serotype-specific anti-pneumococcal IgG antibody levels. Our data suggest that genetic variation in CD14, a molecule at the interface of innate and adaptive immune responses, plays a key role in the defense against middle ear disease in childhood and in pneumococcal vaccine responsiveness. These findings are likely to be important to these and other immune-mediated outcomes in early life.

Age Factors↗

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↗

How has research in the last five years changed my clinical practice?

Although the practice of neonatology is increasingly evidence based, much of our assessment and treatment of newborn infants is still founded on experience, common sense, guesswork, and myth. Research may put a particular issue beyond dispute, but it often raises new questions. This review looks at the benefits of research in one area: temperature control.

Asphyxia Neonatorum↗

beta2 adrenoceptor Arg16Gly polymorphism, airway responsiveness, lung function and asthma in infants and children.

BACKGROUND: We have previously reported a relationship between increased airway responsiveness (AR) in infancy and reduced childhood lung function. OBJECTIVE: The current study aimed to determine whether the Arg16Gly polymorphism of the beta2 adrenoceptor (beta2AR) gene was important to this relationship. METHODS: A cohort that initially numbered 253 individuals underwent assessments of AR and lung function aged 1 month, 6 and 11 years; genotyping for polymorphisms of the beta(2)AR was performed. RESULTS: At 1 month of age, the genotype homozygous Arg16 (n=24) was associated with a mean increase in log dose-response slope (AR) of 0.27 [95% confidence interval (CI) 0.07, 0.49] compared with the genotype homozygous Gly16 (n=58), P=0.01. At 11 years of age, the genotype homozygous Arg16 (n=35) was associated with a mean reduction in the percentage of forced expiratory volume in 1 s of 5.3% [95% CI 0.3, 10.2] compared with the genotype homozygous Gly16 (n=65), P=0.03. There was no association between the Arg16Gly polymorphism and atopy or diagnosed asthma. However, nine of 69 individuals with the genotype homozygous Gly16 were admitted to hospital with asthma compared with five out of 111 individuals with the remaining genotypes (P<0.05). CONCLUSION: The Arg16Gly polymorphism may be important to the association between increased AR in infancy and reduced lung function in childhood and may also be a determinant of asthma severity in children but not asthma per se.

Asthma↗

A comparison of transcutaneous bilirubinometers: SpectRx BiliCheck versus Minolta AirShields.

BACKGROUND: Two devices are available for making transcutaneous estimates of serum bilirubin (SBR): the Minolta AirShields JM102 and the new SpectRx BiliCheck. OBJECTIVES: (a) To measure how well the readings produced by these devices agree with SBR measured in the laboratory; (b) to estimate for each device, the proportion of infants with clinical jaundice who would require blood sampling if the device was used as a screening tool to detect infants with SBR > or = 250 micromol/l. DESIGN: Prospective cohort study of jaundiced infants who required SBR at < or = 20 days of postnatal age. Those who had received phototherapy or exchange transfusion were excluded. SETTING: Tertiary neonatal service in South-East Scotland. INTERVENTIONS: Within 30 minutes of SBR sampling, transcutaneous bilirubinometry was performed using one Minolta and two SpectRx devices (designated A and B). RESULTS: Sixty-four neonates were enrolled, 19 of which were preterm (31-35 weeks). The 95% confidence intervals of a device reading corresponding to SBR were +/- 66.7, +/- 67.9, and +/- 66.4 micromol/l respectively. Using the devices to identify all SBR > or = 250 micromol/l would reduce SBR sampling by 23%, 16%, and 20% respectively. CONCLUSIONS: Given that SBR levels range from 50 to 400 micromol/l in jaundiced infants, the 95% confidence intervals of the devices are wide at +/- 67 micromol/l. The SpectRx can be used as a screening tool for hyperbilirubinaemia but there is no advantage in using it over the Minolta.

Bilirubin↗

As time goes by.

The timing of birth-related events may influence neonatal outcome and is often pivotal in medicolegal cases. This prospective observational study determined the variation in displayed time on timepieces in a regional maternity unit which could result in inaccuracies of time documentation. The mean (95% CI) difference between time displayed and true time was sec (+/- 2 min 4 sec) for delivery room clocks and +1 m 8 s (+/- 7 m 12 s) for resuscitation room clocks. The maximum discrepancy between delivery room and resuscitation room clocks was 7 m 52 s. The abilities of staff to estimate the duration of time passed was also assessed. The mean (95% CI) five-minute estimate was 4 m 52 s (+/- 3 m 12 s). These disparities could have considerable medicolegal significance, and should be taken into consideration in risk management studies. Maternity units should move towards synchronising all timepieces. Meanwhile, statements about the precise timing of events should be regarded with suspicion.

Delivery Rooms↗

Follow up care of bereaved parents after treatment withdrawal from newborns.

OBJECTIVE: To explore parents' experiences of bereavement care after withdrawal of newborn intensive care. DESIGN: Face to face interviews with 108 parents of 62 babies born over two calendar years in the East of Scotland. RESULTS: Only 22% were seen by six weeks after the death, 10% were not recalled before 6-11 months, and 8% were not seen at all in the first year. All except one couple saw the neonatologist who had cared for their baby. Only 33% remembered a neonatal nurse being present. Most (88%) were seen in the study hospital. Parents highlighted a number of specific needs. Appointments should be: (a) scheduled soon after the death of the baby and certainly within two months of the death irrespective of whether or not autopsy results are available; (b) with the named neonatologist; (c) in a setting away from the hospital if possible. Parents value: (a) efforts to find out how they are coping; (b) full frank information given sensitively to enable them to build up a cohesive picture of what happened and assess their future risks; (c) reassurance where possible, but half truths, false reassurances, and broken promises are unacceptable. CONCLUSIONS: Follow up care is a crucial part of the management of families from whose babies treatment has been withdrawn. Resources devoted to it should be re-examined to provide a service more in tune with parental need. In choosing the place, timing, and conduct of the meeting, staff should be sensitive to the expressed wishes of the parents themselves.

Adolescent↗

Consent to autopsy for neonates.

OBJECTIVES: To determine parents' views on autopsy after treatment withdrawal. DESIGN: Face to face interviews with 59 sets of bereaved parents (108 individual parents) for whose 62 babies there had been discussion of treatment withdrawal. RESULTS: All except one couple were asked for permission for postmortem examination; 38% refused. The main reasons for declining were concerns about disfigurement, a wish to have the child left in peace, and a feeling that an autopsy was unnecessary because the parents had no unanswered questions. The diagnosis, the age of the child, and the approach of the consultant appeared to influence consent rates. Of those who agreed to autopsies, 92% were given the results by the neonatologist concerned. Whether or not they had agreed to the procedure, at 13 months no parent expressed regrets about their decision. CONCLUSIONS: Autopsy rates in the East of Scotland stand at 62%. Parents' perceptions are an important element in consent to postmortem examination.

Adolescent↗

Deciding for imperilled newborns: medical authority or parental autonomy?

The ethical issues around decision making on behalf of infants have been illuminated by two empirical research studies carried out in Scotland. In-depth interviews with 176 medical and nursing staff and with 108 parents of babies for whom there was discussion of treatment withholding/withdrawal, generated a wealth of data on both the decision making process and the management of cases. Both staff and parents believe that parents should be involved in treatment limitation decisions on behalf of their babies. However, whilst many doctors and nurses consider the ultimate responsibility too great for families to carry, the majority of parents wish to be the final arbiters. We offer explanations for the differences in perception found in the two groups. The results of these empirical studies provide both aids to ethical reflection and guidance for clinicians dealing with these vulnerable families. They demonstrate the value of empirical data in the philosophical debate.

Asphyxia Neonatorum↗

Association between plasma CC16 levels, the A38G polymorphism, and asthma.

The effect of the A38G polymorphism on Clara cell secretory protein (CC16) gene expression and asthma was investigated by measuring plasma CC16 levels in 100 asthmatic and nonasthmatic children. Restriction digestion determined the A38G genotype and plasma CC16 levels were analyzed using a sensitive latex immunoassay. Asthmatics had lower mean plasma CC16 levels adjusted for age and gender (7.96 microg/L; 95% confidence interval [CI] = 6.79 to 9.31) than nonasthmatic subjects (9.98 microg/L; 95% CI = 8.83 to 11.26) (p = 0. 006). Similarly adjusted, mean plasma CC16 levels were also lower in 38A/38A (6.79 microg/L; 95% CI = 4.56 to 9.02) than 38G/38G subjects (10.01 microg/L; 95% CI = 7.90 to 12.12; p = 0.003). The odds ratio for asthma diagnosis of 38A/38A subjects was 4.78 (95% CI = 1.08 to 21.18; p = 0.04) compared with 38G/38G subjects. However, this was reduced when corrected from plasma CC16 level, suggesting that the odds of asthma was largely mediated through altered plasma CC16 levels. The 38A sequence was associated with reduced plasma CC16 levels and individuals with lower plasma CC16 levels were more likely to have asthma. This provides further evidence for a significant role of the CC16 gene, 38A allele in the development of asthma.

Adolescent↗

Clinical diagnosis of pneumothorax is late: use of trend data and decision support might allow preclinical detection.

Pneumothorax in the newborn has a significant mortality and morbidity. Early diagnosis would be likely to improve the outlook. Forty-two consecutive cases of pneumothorax that developed after admission to a tertiary referral neonatal medical intensive care unit over 4 y from 1993 to 1996 were reviewed. The time of onset of the pneumothorax was determined by retrospective evaluation of the computerized trend of transcutaneous carbon dioxide (tcpCO2) and oxygen tensions. The timing of the occurrence in the notes and x-rays determined the time of clinical diagnosis noted at the time. The difference was the time the condition was undiagnosed. The overall mortality before discharge was 45% (19 cases), four patients succumbing within 2 h. The median time (range) between onset of pneumothorax and clinical diagnosis was 127 min (45-660 min). In most cases, the endotracheal tube was aspirated and the transcutaneous blood gas sensor was repositioned, and in at least 40% of the cases, the baby was reintubated before the diagnosis was made. Reference centiles were constructed for level of tcpCO2 and slope of the trended tcpCO2 over various time intervals (in minutes) from 729 infants from 23 to 42 wk gestation who needed intensive care during the first 7 d of life from the same time period. The 5-min tcpCO2 trend slopes were compared in index and matched control infants. The presence of five consecutive and overlapping 5-min slopes greater than the 90th centile showed good discrimination for a pneumothorax (area under the receiver operating characteristic curve, 89%). We concluded that 1) the clinical diagnosis of pneumothorax was late, occurring when infants decompensate; 2) trend monitoring of tcpCO2 might allow the diagnosis to be made earlier if used properly; and 3) use of reference centiles of the trended slopes of tcpCO2 might be used for automatic decision support in the future.

Carbon Dioxide↗

Do phototherapy hoods really protect the neonate?

UNLABELLED: The objective of the current study was to evaluate the protection given to the eyes of neonates by an Amber 300 phototherapy hood during blue-light phototherapy from Drager Phototherapie 800 units, and to make recommendations for clinical practice. Hazard-weighted blue-light radiance of phototherapy lamps was measured inside neonatal incubators, with and without the use of a protective phototherapy hood. The study was carried out in a tertiary referral neonatal unit. No patients were involved. A mannequin was used as model of a jaundiced neonate being treated with blue-light phototherapy. The study shows that hazard-weighted blue-light radiance levels detectable from within the space enclosed by the hood may be several times greater than accepted industrial threshold limits for adults. CONCLUSIONS: Nursing and medical staff must ensure meticulous care in the positioning of infants, so that the caudal edge of the shadow cast by the hood is always at least 30 mm inferior to the infants' lower eyelids. The vulnerability of the neonatal retina and the relatively high levels of blue-light radiance visible from within the shadow of the hood may make it advisable to use more effective eye protection. Triple phototherapy using lamps at the foot-end of the incubator is clearly hazardous and should not be carried out unless the infant's eyes are protected by eye-patches.

Equipment Safety↗

Modulations in breathing patterns during intermittent feeding in term infants and preterm infants with bronchopulmonary dysplasia.

As infants with bronchopulmonary dysplasia (BPD) have difficulty maintaining adequate levels of oxygenation during rest, it was decided to investigate how the additional respiratory demands associated with nutritive feeding disrupt their breathing rates. The sucking and breathing patterns of six (three male, three female) preterm infants (between 23 and 29 weeks gestational age at birth), classified as having BPD were individually compared with the patterns observed in 12 (six male, six female) healthy term (control) infants (> or = 38 weeks gestational age at birth) with no known respiratory ailments. All infants were recruited from the neonatal unit at Simpson's Maternity Pavilion, Edinburgh, Scotland. In general, the breathing patterns recorded for the infants with BPD during the pause periods of intermittent feeding lacked the striking regularity observed in the term infants. It was found that the severity of the BPD affected breathing rates by significantly reducing the duration and the regularity of a breath (P<0.05) while sucking during the intermittent phase of feeding.

Bronchopulmonary Dysplasia↗

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↗

Association of polymorphisms within the tumour necrosis factor (TNF) genes and childhood asthma.

BACKGROUND: Tumour necrosis factor alpha (TNFalpha) is a potent modulator of immune and inflammatory responses, and has been implicated in a variety of autoimmune diseases, including asthma. Increased levels of TNFalpha have been detected in both sputa and bronchoalveolar lavage fluid of asthmatic subjects during acute attacks. Interindividual variation in TNFalpha levels may be genetically determined and polymorphisms within the TNF genes and nearby HLA Class II region have been associated with differences in TNFalpha production. OBJECTIVE: To investigate the association of differences in asthma-related phenotypes with two biallelic polymorphisms: a G to A substitution at position - 308 of the TNFalpha gene promoter (TNF1 and TNF2 alleles) and an NcoI polymorphism in the first intron of the lymphotoxin alpha gene (LT-alpha*1 and LT-alpha*2 alleles). METHODS: The regions of interest were amplified from genomic DNA using specific primers and PCR. Dot blot analysis was used for genotyping individuals for the TNFalpha - 308 polymorphism, while restriction enzyme digestion was used for genotyping individuals for the LT-alpha gene NcoI polymorphism. A case-control analysis was then performed on 74 asthmatic and 50 non-asthmatic unrelated children for each polymorphism. RESULTS: The TNFalpha - 308 TNF1 allele was present at a significantly higher frequency in cases than controls (OR= 2.4, P=0.003), and homozygosity for the TNF1 allele was associated with a fivefold increased risk of physician diagnosed asthma relative to the other genotypes (OR = 5.23, P = 0.004). The LT-alpha*2 allele showed similar associations, including an approximately fivefold higher risk of physician diagnosed asthma for LT-alpha*2 homozygotes (OR = 4.89, P = 0.019). Evidence of a significant linear trend in asthma risk across the three genotypes was found for both polymorphisms. CONCLUSION: These results suggest an important role for the TNFalpha gene or a linked locus in an inherited asthma diathesis.

Alleles↗