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Biomedical subjects

J Stocks

Publications and source records attributed to J Stocks.

At least 37 records · Page 2Linked to original sources

Analysis of tidal breathing parameters in infancy: how variable is TPTEF:TE?

During recent years there has been increasing interest in the measurement of tidal breathing parameters, such as the time to reach peak tidal expiratory flow as a proportion of total expiratory time (TPTEF:TE), and their application to population-based studies of the determinants of early respiratory morbidity. However, little is known about factors influencing the within and between-subject variability of these parameters. This study examines the influence of sedation on TPTEF:TE, estimates the optimal number of breaths and breath epochs required to measure TPTEF:TE, and assesses short-term repeatability of this parameter during the first year of life, taking account of age-related differences. Measurements were made in 266 healthy infants and young children (1 d to 19 mo old). Mean (SD) TPTEF:TE fell from 0.49 (0.11) in the first 2 wk of life to 0.34 (0.09) by 5 to 8 wk, remaining similar thereafter. Sedation with triclofos sodium (75 mg/kg) had no significant effect on TPTEF:TE, which was 0.33 (0.10) in 23 unsedated 6-wk-old infants and 0.32 (0.08) in 49 sedated infants of similar age and weight (95% CI for the difference: -0.05, 0.04). At least 10 breaths in each of two separate epochs from each infant were required to provide a representative estimate of TPTEF:TE. The mean (SD) difference between repeat measurements made 5 to 108 min apart was 0.02 (0.08) in 34 infants younger than 6 wk of age (95% limits of agreement: -0.15, 0.18) and -0.01 (0.04) (95% limits of agreement -0.09, 0.08) in 30 infants 6 wk and older.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors

A comparison of respiratory function in Afro-Caribbean and Caucasian infants.

Race is recognized as an important determinant of lung function in children and adults, but limited data exist for infants. Accurate interpretation of lung function tests during the neonatal period may depend on appropriate values for predicting normality. The aim of this study was to compare tidal breathing parameters, Hering-Breuer reflex (HBR) activity, and total respiratory compliance (Crs) in healthy newborn caucasian (white) and Afro-Caribbean (black) infants, to determine whether separate reference values were required for these two ethnic groups. Respiratory function was measured in 33 healthy black infants, 18 of whom were premature, and 33 healthy white infants matched for sex, gestational age, weight, postnatal age, and maternal smoking during pregnancy. There were no significant paired differences between black and white infants with respect to minute ventilation, respiratory frequency, the ratio of time to reach peak expiratory flow to total expiratory time, or HBR activity. Values of Crs were similar in black and white full-term infants (37.5 (SD 9.0) versus 35.0 (6.3) ml.kPa-1, respectively) suggesting that, in the immediate newborn period, separate reference values are not necessary for these parameters. However, Crs was somewhat lower in black than white preterm infants (26.0(5.2) versus 29.5(7.2) ml.kPa-1, this difference reaching statistical significance if results were expressed in relation to body weight (95% confidence interval of within-pair differences -4.0 to -0.02 ml.kPa-1 x kg-1; p < 0.05). We conclude that no separate reference values for tidal breathing, Hering-Breuer reflex activity or total respiratory compliance are required for white and black babies in the immediate newborn period.(ABSTRACT TRUNCATED AT 250 WORDS)

Black People

Effect of continuous negative extrathoracic pressure on respiratory mechanics and timing in infants recovering from neonatal respiratory distress syndrome.

Changes in respiratory mechanics and timing produced by continuous negative extrathoracic pressure (CNEP) of -0.6 kPa were assessed in 18 infants recovering from neonatal respiratory distress syndrome. The median gestational age was 28 wk (range 24-36 wk). All infants were recruited before discharge from neonatal intensive care and were measured at a median postnatal age of 58 d (range 10-127 d) and a median weight of 2.67 kg (range 1.99-3.77 kg). All had been treated for respiratory distress syndrome; 11 were diagnosed as having chronic lung disease. At the time of the study, all infants were stable breathing room air. There was a significant decrease of the respiratory rate in all but one infant from 63.6 +/- 10.0 to 49.3 +/- 9.1 breaths per min (mean +/- SD) during CNEP. This was predominantly due to a marked prolongation of the expiratory time. Passive respiratory mechanics were assessed using airway occlusion techniques. Whereas respiratory system compliance (Crs) did not change in the infants with a normal baseline measurement, there was a significant improvement of Crs in the 11 infants with low Crs values in atmosphere: In the latter, all of whom were very-low-birth-weight infants, Crs assessed by the multiple occlusion technique (mean +/- SD) corrected for body weight increased from 7.9 +/- 1.5 to 9.4 +/- 1.9 mL.kPa-1.kg-1 in CNEP (p = 0.012). There was no consistent change in respiratory system resistance in this population of 18 infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Female

Variability of plasma apolipoprotein (apo) A-II levels associated with an apo A-II gene polymorphism in monozygotic twin pairs.

A dimorphic MspI RFLP (alleles M1 and M2) in an Alu unit 528 base pairs downstream from the apolipoprotein A-II gene on chromosome 1 was investigated for associations with dyslipoproteinaemia or coronary atherosclerosis. No significant differences were observed between the allele frequencies in healthy random controls (M2 = 0.850, n = 70) and patients with primary hypertriglyceridaemia (M2 = 0.846, n = 52) or severe coronary atherosclerosis (M2 = 0.819, n = 47). The apolipoprotein A-II gene may also contribute to the regulation of plasma levels or composition of HDL in response to environmental changes. To study the effect upon apolipoprotein A-II variability, 42 monozygotic twin pairs were genotyped for the MspI RFLP. Pairs with the genotype M2M2 (n = 28) had significantly smaller within-pair differences in plasma apolipoprotein A-II levels (2.2 vs 5.8 mg/dl, P < 0.02; Mann-Whitney) than those with other genotypes (n = 14). The M2 allele may be in linkage disequilibrium with a functional mutation that restricts the variability of plasma apolipoprotein A-II in response to environmental conditions. This provides a new example of a 'variability' gene, one of an important group of loci which may alter responses to hypolipidaemic therapy and cardiovascular risk.

Adult

Assessment of passive respiratory compliance in healthy preterm infants: a critical evaluation.

The airway occlusion techniques for assessing passive respiratory mechanics have become well established methods in fullterm neonates and older infants. The single breath technique (SBT) is frequently used for assessing lung function in intubated infants on neonatal intensive care units. However, less is known about the reliability of these quick and noninvasive techniques in healthy preterm infants. The aim of this study was to evaluate these methods in healthy unintubated preterm infants to facilitate both establishment of reference values and more meaningful interpretation of lung function assessments in the neonatal unit. Forty-seven studies were attempted in 31 healthy preterm infants (gestational age 29-36 weeks; body weight 1.88 +/- 0.28 kg; mean +/- SD) during the first 2 weeks of life, using both the multiple occlusion technique (MOT) and the SBT. Whereas technically acceptable respiratory system compliance (Crs) data from either the MOT or the SBT were obtained on 37 occasions in 25 infants, satisfactory results from both techniques were achieved only on 22 occasions. In these infants mean +/- SD Crs was 28.1 +/- 5.2 mL kPa-1 when assessed by MOT and 29.1 +/- 6.0 mL kPa-1 when using the SBT. The mean difference between technically satisfactory paired Crs values obtained with MOT and SBT was less than 5% (range, +28 to -18%). By contrast, in infants in whom data were invalidated as a result of expiratory airflow braking, failure to relax or instability of the end-expiratory level, gross discrepancies occurred between the techniques.(ABSTRACT TRUNCATED AT 250 WORDS)

Female

Comparison of nitrogen washout and plethysmographic measurements of lung volume in healthy infants.

Functional residual capacity (FRC), the only lung volume to be assessed routinely in infants, can be measured using plethysmography or gas dilution. Although it is well recognized that both methods yield similar FRC values in healthy adults, gas dilution techniques have consistently produced lower values in healthy infants when compared with plethysmography. However, interpretation of this difference is difficult since data comparing the different techniques within the same infants have rarely been reported. We performed paired measurements of FRC using an automated open-circuit nitrogen washout technique (FRCN2) and whole-body plethysmography (FRCpleth) in 11 healthy infants with a median age of 12 months (range, 2 to 18 months). The mean (SD) FRC was 21.7 (4.0) ml/kg for the N2 washout and 25.6 (4.9) ml/kg for plethysmography. The mean within-subject difference between FRCN2 and FRCpleth was 3.9 (range, -0.3 to 7.2) ml/kg (p = 0.001). Both N2 washout and plethysmography yielded reproducible results, with the mean of the coefficients of variation (CV) being 3.6 and 3.9%, respectively. The results from these paired measurements support previously reported data from separate populations of infants which suggest that gas dilution techniques consistently yield smaller values for FRC than do those measured by plethysmography.

Female

Respiratory compliance in infants--a preliminary evaluation of the multiple interrupter technique.

Measurements of total respiratory system compliance (Crs) using the multiple occlusion technique (MOT) in spontaneously breathing infants can be difficult to interpret in the presence of an unstable end-expiratory level. Similarly, measurements using the passive flow volume technique (PFV) are invalidated if there is alinearity of the expiratory time constant (Trs), irrespective of respiratory effort. For possibly overcoming these problems, we assessed the feasibility of a technique using multiple interruptions of of a single expiration (MIT), obtaining several pairs of volume-pressure data, from one expiration, which relate to a single end-expiratory level. Crs was measured in 16 infants aged 0.5 to 20 months using the MOT, MIT, and PFV technique. The MOT and the MIT each failed in one (different) infant, both succeeding where the other failed. The PFV technique failed in five infants in whom no acceptable plateau of airway pressure during occlusion and no Trs could be obtained from a single breath. Failure to obtain a linear Trs was accompanied by failure of the MIT in only one infant. Individual differences between the MIT and the MOT were less than 9%. However, the PFV measurements varied from -16.3% and +25.7% of the values from MIT or MOT. The greatest differences between Crs values coincided with the greatest differences between volume intercepts of the extrapolated volume-pressure (MOT, MIT) and flow-volume (PFV) data. From this preliminary study, the MIT proved as successful as the MOT, requiring fewer occluded breaths to measure Crs. In infants with a rapid respiratory rate, the data from several expirations can be merged and analyzed as for the MOT.

Humans

Polymorphisms at the GLUT1 (HepG2) and GLUT4 (muscle/adipocyte) glucose transporter genes and non-insulin-dependent diabetes mellitus (NIDDM).

In order to determine the possible contribution of the GLUT1 (HepG2) glucose transporter gene to the inheritance of non-insulin-dependent diabetes mellitus (NIDDM), two restriction fragment length polymorphisms (RFLPs) and the related haplotypes at this locus were studied in 48 Italian diabetic patients and 58 normal subjects. Genotype frequencies for the XbaI polymorphism were significantly different between patients and controls (XbaI: chi 2 = 9.80, df = 2, P less than 0.0079). A significant difference was also found in the allele frequencies between NIDDM patients and controls (chi 2 = 9.39, df = 1, P less than 0.0022), whereas no differences were found for the StuI RFLP. No linkage disequilibrium was detected between the XbaI and StuI RFLPs in this sample. The analysis of the four haplotype frequencies (X1S1, X1S2, X2S1, X2S2) revealed a significant difference between diabetic patients and controls (chi 2 = 14.26, df = 3, P less than 0.002). By comparing single haplotype frequencies, a significant difference between the two groups was found for the X1S1 and X2S2 haplotypes. A two-allele RFLP at the GLUT4 (muscle/adipocyte) glucose transporter gene, detected with the restriction enzyme KpnI, was also examined; no differences were found between patients and controls for this RFLP. The finding of an association between polymorphic markers at the GLUT1 transporter and NIDDM suggests that this locus may contribute to the inherited susceptibility to the disease in this Italian population.

Adipose Tissue

Sib-pair analysis of adenosine deaminase locus in NIDDM.

Recently, linkage between the ADA gene locus and MODY, a subtype of NIDDM, has been reported. The possibility that the region of chromosome 20q containing the ADA locus also may play a role in susceptibility to NIDDM needs to be investigated. Therefore, we examined the linkage between the ADA locus and NIDDM in affected siblings of 50 European white diabetic pedigrees--21 Italian and 29 British. Departure from independent segregation of the disease and an Alu VpA polymorphism within the 5' flanking region of the ADA locus was tested in the affected sib-pairs with the APM statistical method. After DNA amplification by the PCR and PAGE, five alleles were identified in the ALU VpA tract at the ADA locus in the two populations. Allele frequencies did not differ significantly between the two populations (chi 2 = 2.426, P > 0.05 [NS]). Analysis of the 50 diabetic sib sets, and independently of the Italian and British groups of affected sib pairs, revealed no segregation distortion between the marker locus and NIDDM. We conclude that mutations within or around the ADA locus are unlikely to play a major role in the etiology of NIDDM.

Adenosine Deaminase

Lipoprotein lipase genotypes for a common premature termination codon mutation detected by PCR-mediated site-directed mutagenesis and restriction digestion.

We have developed a procedure for the determination of a common mutation in exon 9 of the human lipoprotein lipase (LPL) gene. The mutation is due to a C-G transversion which creates a premature termination codon (Ser447-Ter) and results in a truncated LPL molecule lacking the C-terminal dipeptide SER-GLY. The mutation can be detected by polymerase chain reaction (PCR) amplification of exon 9 using a modified 3' amplimer that produces a 140 bp product containing a site for the restriction enzyme Hinf-1 in the presence of the mutation (G allele). The G allele was in strong linkage disequilibrium with a Hind-III restriction fragment length polymorphism (RFLP) allele in intron 8. Genotype determinations for the mutation can be performed by PCR amplification of genomic DNA, digestion with Hinf-1, and analysis of the products by polyacrylamide gel electrophoresis. The allelic frequency of the Ser447-Ter mutation in normal male Caucasian controls was 0.11. The frequency of the mutation was lower in a group of subjects with primary hypertriglyceridemia compared to normolipidemic controls.

Adult

Genetic polymorphisms at the human liver/islet glucose transporter (GLUT2) gene locus in Caucasian and West Indian subjects with type 2 (non-insulin-dependent) diabetes mellitus.

The liver/islet glucose transporter (GLUT2) is mainly expressed in the hepatocytes of the liver and the beta-cells of the pancreatic islets and a defect in this transporter could lead to diabetic phenotypes, such as relative hypoinsulinaemia and reduced uptake and metabolism of glucose in the liver. DNA from unrelated individuals was digested with the restriction endonucleases Bgl-I and Taq-I followed by blotting and hybridisation with a 32P-labelled GLUT2 cDNA which revealed three restriction fragment length polymorphisms (RFLPs) (B1, T1 and T2) in both Caucasian and West Indian populations. Linkage analysis between these variant sites demonstrated that the alleles of these polymorphisms were in strong linkage disequilibrium. Disease association of genetic variants at the GLUT2 locus with type 2 diabetes was examined with these RFLPs in both Caucasian (n = 54) and West Indian (n = 46) populations with type 2 diabetes. There were no significant differences in the frequency of alleles, genotypes or haplotypes between diabetic patients and non-diabetic controls. However, there were significant differences in the allele frequencies of all these three polymorphisms between Caucasian and West Indian populations.

Aged

The effect of triclofos sodium sedation on respiratory rate, oxygen saturation, and heart rate in infants and young children.

Chloral hydrate is frequently used to sedate infants for lung function testing. While no effect on respiratory function has been demonstrated, a recent study has reported a fall in oxygen saturation (SaO2) following sedation in wheezy infants. This study was designed to assess the effects of the closely related but less gastrically irritant drug triclofos sodium on respiratory rate (RR), heart rate (HR), and SaO2 in infants without cardiopulmonary disease. Paired measurements using respiratory inductance plethysmography and pulse oximetry were obtained in 10 infants (4-19 months of age) during natural and sedated sleep. Following sedation with triclofos, mean RR rose by 1.9 breaths min-1 (95% confidence intervals [Cl] of the mean difference: 0.13-3.7 min-1). Mean heart rate rose by 5.5 beats min-1 (95% Cl: -0.9-11.9 min-1). Mean SaO2 fell by 0.68% (95% Cl -1.8-0.45%). None of these changes are considered to be of clinical importance, and only the change in RR reached statistical significance at the 5% level.

Procedural Sedation

Influence of sedation on the Hering-Breuer inflation reflex in healthy infants.

The airway occlusion technique for measuring passive respiratory mechanics in infants relies on an ability to evoke the Hering-Breuer inflation reflex (HBR). However, the persistence of this reflex beyond the early newborn period remains controversial. We have recently demonstrated that there is no change in the strength of this reflex during the first two months of life in healthy infants during natural sleep. Measurements beyond this immediate newborn period are difficult without sedation, but it is unclear whether sedation itself may influence this reflex. To investigate the influence of sedation, the HBR was measured in 66 healthy, full-term infants aged 4-8 weeks. Thirty-three infants were measured during natural sleep, and 33 after triclofos sodium sedation (75 mg.kg-1). The strength of the HBR was assessed from the change in expiratory time (TE) following brief end-inspiratory airway occlusion, as compared to TE during spontaneous breathing. The mean increase in TE following occlusion was 89.45% (SD, 29.8; range, 44-175) in infants sleeping naturally, and 92.42% (SD, 31.2; range, 34-179) in sedated infants. Using unpaired t tests, no statistically significant difference was found between groups (P = 0.7516). We conclude that the strength of the HBR in healthy infants is not influenced by sedation with triclofos sodium, in doses normally used for lung function testing.

Female