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Biomedical subjects

J Stocks

Publications and source records attributed to J Stocks.

At least 73 records · Page 4Linked to original sources

Analysis of high density lipoprotein apolipoproteins by capillary zone and capillary SDS gel electrophoresis.

We describe new methods for analyzing the apolipoproteins (apo) of the high density lipoproteins (HDL) of several species by two modes of capillary electrophoresis: size separation using a molecular sieving buffer, and capillary zone electrophoresis (CZE) using neutral coated capillaries. By either mode HDL apos were resolved within 25 min. Results for apoA-I and apoA-II mass agreed with those by electroimmunoassay; intra-assay coefficients of variation were 1.8-4.2%. The migration times of human, rat, rabbit, and bovine apoA-I during CZE were proportional to their net charge/Mr ratios. This enabled human and rabbit apoA-I to be quantified simultaneously in transgenic rabbit HDLs. CZE also resolved human apoA-I isoforms, deamidated apoA-I, and pro-apoA-I.

Animals↗

The Ser447-Ter mutation of the lipoprotein lipase gene relates to variability of serum lipid and lipoprotein levels in monozygotic twins.

Studies on monozygotic twins support a role for genetic determinants of plasma lipid, lipoprotein, and apolipoprotein levels. Gene variants of the enzyme lipoprotein lipase have been shown to associate with dyslipidemia and coronary artery disease. We assessed the gene-environment interaction by investigating the relationship between the lipoprotein lipase gene and plasma lipid, lipoprotein, and apolipoprotein variability and levels among 54 male monozygotic twin pairs (aged 18-28 years). The Ser447-Ter mutation (C-->G transversion) was associated with significantly smaller within-pair differences in plasma high density lipoprotein-cholesterol (CG [n = 10] vs. CC [n = 44], 3.7+/-5.3 mg/dl vs. 6.4+/-5.2 mg/dl, P < 0.03) and total cholesterol (CG [n = 10] vs. CC [n = 44], 7.9+/-9.4 mg/dl vs. 15.8+/-12.7 mg/dl, P < 0.05), indicating attenuated variability in response to environmental stimuli. This observation of a restrictive variability gene effect further supports a role for the lipoprotein lipase gene in the genetic regulation of lipids and lipoproteins and suggests that the Ser447-Ter mutation exerts multiple effects. This study also raises the possibility of a genetically determined responsiveness to dyslipidemia therapies.

Adolescent↗

Reproducibility of lung volume measurements.

Test reproducibility is an important consideration when interpreting results and should be set as a goal during data collection. Reproducibility criteria may need to be different for different subject groups and are instrument and procedure-dependent. Ideally, the within-subject variability for each lung volume and measurement technique used should be established for each laboratory. These values also need to be established for each different subject group (age and disease). At a minimum, test reproducibility should be monitored and controlled and each laboratory should define their between-day reproducibility of measurements on at least one "reference" subject from ongoing periodic (e.g., weekly or monthly) measurements as part of their laboratory's quality control programme. For plethysmographic measurements functional residual capacity (FRC)pleth multiple determinations and a corresponding test reproducibility criteria is probably justified.

Adult↗

Capillary electrophoresis to monitor the oxidative modification of low density lipoproteins.

A procedure has been developed that uses high performance capillary electrophoresis to monitor the changes in the electrophoretic mobility of low density lipoproteins (LDL) resulting from Cu2+-catalyzed lipid peroxidation. Using uncoated fused silica capillaries, methylglucamine-Tricine, pH 9.0, as electrophoresis buffer and a field strength of 350 V/cm, separation of native LDL and oxidized LDL could be achieved in 8-10 min. The electrophoretic mobility of native LDL under these conditions was 1.32 x 10(-4) cm2 x V(-1) x s(-1), and the migration time could be measured with a coefficient of variation of 0.44%. The increase in the electronegativity of LDLs during incubation with 10 microM Cu2+ for 0.25-2.0 h resulted in a progressive increase in migration time. Monitoring the absorbance of the migrating LDL particles at a wavelength of 234 nm showed a progressive increase in peak area, which paralleled that in diene conjugation measured spectrophotometrically. Electronegative LDL particles formed by modification with malondialdehyde could also be separated from native LDL particles under these conditions. This new procedure should be useful in studies of factors influencing low density lipoprotein oxidation in vitro and in vivo.

Copper↗

Lung development and early origins of childhood respiratory illness.

In the last two decades, 5 cohort studies have been initiated to examine the association of infant respiratory function with genetic and environmental risk factors, as well as with subsequent lower respiratory illness in early childhood. While the current complexity of respiratory function tests in this age group precludes study samples with sufficient power to examine more complex issues, information from these studies has provided an exciting adjunct to that available from the longer cohort studies. Premorbid alterations in airway function or lung development increase the risk of wheezing lower respiratory illnesses during the preschool years and the risk of impaired airway function at 5-6 years of age. In addition, gender differences in airway function and the response to maternal smoking have been observed. Larger collaborative population-based studies are needed to explore the environmental, genetic and immunological mechanisms responsible, but will depend on the development of less invasive tests of airway function appropriate for use in healthy infants.

Adolescent↗

Urinary antimony in infancy.

OBJECTIVE: To determine whether antimony may be detected in the urine during infancy and early childhood and its association with passive exposure to tobacco smoke, as assessed by urinary cotinine. DESIGN: Analysis of spare aliquots of urine collected from infants participating in studies of respiratory function and passive smoking. Urinary antimony was assayed using inductively coupled plasma mass spectroscopy in 201 urine specimens collected at different ages throughout the first two years of life from 122 term and 26 preterm infants. Urinary cotinine was measured using gas liquid chromatography. MAIN OUTCOME MEASURE: Urinary antimony concentrations. RESULTS: Absolute antimony concentrations varied widely between infants, being below the laboratory detection limit of 0.02 microgram/l in 7% of samples, below 0.5 microgram/l in 90.5%, and above the reference value of 1 microgram/l reported for non-occupationally exposed UK populations in 4%. Creatinine standardised antimony values were unrelated to postnatal age or urinary cotinine concentrations and were highest in urine collected from preterm infants within 24 hours of birth (geometric mean (95% confidence interval): 2.3 ng/mg (1.5 to 3.4)). CONCLUSIONS: Although antimony is present at very low concentrations in urine during infancy and early childhood, the relevance to health is uncertain. The higher levels found in preterm infants may reflect prematurity or fetal assimilation of antimony. Tobacco is unlikely to be an important source of environmental exposure to antimony during infancy and early childhood.

Aging↗

Infant respiratory function after RSV-proven bronchiolitis.

The mechanisms underlying the increased risk of wheezing in early childhood following acute bronchiolitis in infancy remain unclear. Previous studies have reported significant abnormalities in infant respiratory function after clinical recovery from bronchiolitis, but are difficult to interpret because of the frequent omission of a concurrent comparison group. Respiratory function was compared within pairs of previously healthy full-term caucasian infants admitted with a first episode of acute bronchiolitis to an inner London hospital, and age- and sex-matched control infants without prior wheezing, asthma, or lower respiratory illness who were recruited from local general practices. Respiratory function was measured in 29 control and 29 asymptomatic index infants, with measurements in the latter done at a median interval of 36 wk (range: 16 to 49 wk) after admission, when 16 (55%) had experienced subsequent wheezing. Index infants tended to be autumn-born and of shorter gestation than control infants, to have younger mothers, and to have been exposed to tobacco smoke. There were no statistically significant differences in plethysmographic FRC, initial inspiratory airway resistance (Raw), or respiratory system compliance (mean [index minus control] within-pair difference [95% confidence interval]: -11 ml [-29, 7 ml]; -0.2 kPa/L/s [-0.7, 0.4 kPa/L/s]; -8 ml/kPa [-21, 4 ml/kPa], respectively), but respiratory rate and time to peak tidal flow as a proportion of total expiratory time (tPTEF:tE) were significantly diminished in index as compared with control infants (-4.0 breaths/min [-7.6, -0.4 breaths/min], versus -0.035 [-0.066, -0.005], respectively). These findings suggest a better prognosis for infant lung function after acute bronchiolitis than reported previously. Longitudinal studies are needed to clarify whether subclinical alterations in airway function precede acute bronchiolitis.

Acute Disease↗

Influence of ethnicity and gender on airway function in preterm infants.

While maximal expiratory flow at functional residual capacity, calculated from partial expiratory flow volume curves (V'maxFRC), is a valuable measure of peripheral airway function in infants, limited data are available in preterm infants despite their high prevalence of respiratory problems. To investigate the influence of gender and ethnic group, V'maxFRC and other indices of respiratory function were measured in 28 black and 28 white preterm infants (50% female in each group) at time of discharge from the neonatal unit (mean [SD] weight 2.36 [0.3] kg, postnatal age 19 [9] d). No infant had any history of cardiorespiratory disease and all were born to non-smoking mothers. V'maxFRC tended to be higher in girls than boys (115 versus 94 ml.s-1 [95% CI: -5; 47]) but there was no significant difference in this parameter between black and white infants (111 versus 98 ml.s-1 [95% CI of difference: -12; 40]). Respiratory resistance (Rrs) was significantly lower in black than white infants (95% CI: -2.9; -0.4 kPa.L-1.s) and tended to be lower in female than male infants (95% CI: -2.3; 0.2 kPa.L-1.s). Similarly, time to peak tidal expiratory flow as a proportion of total expiratory time (tPTEF:tE) was significantly longer in black than white (95% CI: 0.06, 0.20) and in female than male (95% CI: 0.02, 0.15) infants. These findings suggest that certain parameters of airway function may be influenced by both ethnic group and gender in preterm infants, both of which should therefore be taken mw account when investigating the effects of disease and/or therapeutic interventions in this group.

Airway Resistance↗

A new microtransducer catheter for measuring esophageal pressure in infants.

Measurement of esophageal pressure, as a reflection of pleural pressure, is essential for assessment of dynamic lung mechanics in neonates and infants. Conventionally, an esophageal balloon or a fluid-filled catheter is used, but considerable skill is required to obtain accurate results. Both devices have problems, and failure to achieve valid occlusion tests have been reported, particularly in small infants with lung disease. Recently, a flexible #3 French gauge (FG) microtransducer catheter (MTC, Dräger Netherlands) has become available for medical monitoring. We have assessed the accuracy and feasibility of using this device for measuring lung mechanics in 51 spontaneously breathing infants and small children aged 1 day to 24 months (weight 1.35 to 12.0 kg), 9 of whom were healthy neonates, the remainder suffering from a variety of cardio-respiratory diseases, and in 18 sick ventilated infants (weight 0.6 to 4.0 kg). Positioning of the catheter was well tolerated by all infants. The ratio of esophageal to airway opening pressure changes (delta Pes:delta Pao) ranged from 0.94 to 1.09 [mean (SD) 1.013 (0.03)] for the spontaneously breathing infants and from 0.98 to 1.06 [mean (SD) 1.003 (0.02)] In the ventilated infants with no significant difference in this ratio between the two groups (p = 0.16). This new generation of catheter tip pressure transducers may provide a simpler and more reliable tool for assessing transpulmonary pressure changes in infants than has previously been available.

Catheterization↗

Delayed maturation of Hering-Breuer inflation reflex activity in preterm infants.

We have previously shown that the strength of the Hering-Breuer inflation reflex (HBIR) diminishes between 2 and 12 mo of age in full-term babies. The purpose of this study was to determine whether the onset of this decline had commenced by 3 to 4 mo of age in healthy full-term infants and whether preterm delivery influences the pattern of maturation. Serial measurements of HBIR activity using the end-inspiratory occlusion technique were made in 25 preterm and 27 full-term infants at matched postnatal and postconceptional ages during the first 6 mo of life. Although similar levels of reflex activity were observed at birth (mean +/- SD of 101.2% +/- 42.4% in preterm, and 101.0% +/- 33.9% in full-term infants), by 40 wk postconceptional age (PCA) (i.e., term equivalent) HBIR activity (mean +/- SD) had increased to 121.7% +/- 51.2% in preterm infants, which was significantly greater than that in full-term infants of similar PCA (95% CI of difference: 0.2; 41.2%). By 15 wk postnatal age (PNA), HBIR activity had decreased to 68.8% +/- 26.6% in full-term infants, but remained significantly higher in those delivered prematurely (87.8% +/- 32.7%). However, when measurements were repeated at approximately 4 mo after the expected rather than actual date of delivery, these differences were no longer evident (95% CI difference preterm-full-term: -21.2; 3.8%). This study suggests that important transitions in respiratory control mechanisms occur between 8 and 15 wk PNA in full-term infants and that these changes are delayed in preterm infants.

Aging↗

In vitro assessment of infant pulmonary function equipment.

Commercially available automated pulmonary monitors are used increasingly in neonatal intensive care units. However, detailed information regarding the static and dynamic accuracy of these monitors is rarely available. Collaboration between scientists, clinicians, and manufacturers is essential to establish improved technical standards and protocols for testing of equipment and for the development of more reliable neonatal pulmonary monitors. The aim of this study was to develop a protocol for the in vitro assessment of commercial infant pulmonary function equipment which could be applied within the laboratory to provide rapid feedback to the manufacturer. A recently released neonatal pulmonary monitor, the Bicore CP100 (software version 3.3), was selected for the development of this protocol. The deadspace and resistance of the measuring device were determined. The flow and airway pressure measuring systems were evaluated alone and connected to a tracheal tube for both static accuracy and frequency response. The pressure-volume relationship of the esophageal balloon was determined and its static accuracy and frequency response were assessed. The algorithms for on-line calculations were checked and their correct application confirmed by examination of an ASCII data print out. Finally, the pulmonary monitor was tested during intermittent positive pressure ventilation of a neonatal lung model of known compliance and resistance.

Algorithms↗

The single breath test in neonates: does pressurization of the pneumotachograph make a difference?

The single breath test for the measurement of respiratory system resistance and compliance in newborns consists of an end inspiratory occlusion which is subsequently released, allowing expiration to proceed through a pneumotachograph (PNT). The measured flow is then integrated to give volume. The simplicity of the test is one of the major reasons for its popularity. However, some investigators have cautioned against the use of an occlusion distal to the PNT because pressurization of the PNT may introduce artifacts in the flow measurement. Despite this caution, many commercial systems use a pressurized PNT. This study investigated the errors that would result from pressurization of the PNT by providing a step function of flow to two infant PNTs, a Fleisch #0 and a Hans Rudolph 4500, in the unpressurized and pressurized state. In each case there was an initial rapid rise of the flow signal, followed by some overshoot and oscillations that rapidly died out. The overshoot and oscillations for the Hans Rudolph PNT were greater when pressurized whereas pressurization had little effect on the Fleisch PNT. Unpressurized, the two were similar. In either case, the artifact introduced by pressurization of the PNT died out so quickly that it would have little effect on any measurement in an infant.

Airway Obstruction↗