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Biomedical subjects

J Stocks

Publications and source records attributed to J Stocks.

At least 55 records · Page 3Linked to original sources
PubMed2000

Specification for signal processing and data handling used for infant pulmonary function testing. ERS/ATS Task Force on Standards for Infant Respiratory Function Testing. European Respiratory Society/American Thoracic Society.

The aim of this present paper is to define minimal performance criteria for the separate items comprising signal processing and data handling used to measure respiratory function in infants. These guidelines cover numerous aspects including: signal processing, data handling and subsequent analysis, reporting of results, demographics and handling of reference values. Adherence to these guidelines should ensure that infant lung function measurements can be performed with an acceptable degree of safety, precision, and reproducibility. Furthermore, they will facilitate multicentre collection of data and the performance of clinical investigations.

Electronic Data Processing↗
PubMed1999

Analysis of apolipoproteins and lipoproteins by capillary electrophoresis.

Capillary electrophoresis provides a valuable analytical tool for the analysis of apolipoproteins and lipoproteins. Sodium dodecyl sulfate (SDS) capillary gel electrophoresis can resolve human and animal apolipoprotein (apo) A-I, apo A-II, apo E and apo A-IV in isolated high density lipoproteins (HDLs) and is capable of analysing HDL apo A-I and apo A-II content with a coefficient of variation (CV) of less than 5%. Capillary zone electrophoresis (CZE) using coated capillaries with Tricine-urea buffer can also be used for the analysis of HDL apolipoproteins and is also capable of resolving apo A-I isoforms, pro-apo A-I, mature apo A-I and deamidated apo A-I. Furthermore it can separate human A-I from endogenous rabbit A-I in transgenic rabbits expressing the human apo A-I gene. Capillary isoelectric focusing can also separate apo A-I isoforms. Analysis of charge-modified low density lipoprotein (LDL) (ox-LDL) produced by in vitro lipid peroxidation can be performed by CZE and the technique can be used to monitor simultaneous changes in the electrophoretic mobility and absorption spectra of LDL.

Animals↗
PubMed1999

A multicenter, randomized, double-blind, placebo-controlled trial of high-dose intravenous immunoglobulin for oral corticosteroid-dependent asthma.

To determine the efficacy of high doses of intravenous gammaglobulin (IVIG) for the treatment of severe, steroid-dependent asthma in patients between 6 and 68 years of age, a randomized, double-blind, placebo-controlled multicenter clinical trial was conducted in private and university hospitals in the United States. Patients were randomized to one of three treatment arms: 2 g IVIG/kg/month (16 patients); 1 g IVIG/kg/month (9 patients); or 2 g iv albumin (placebo)/kg/month (15 patients). The treatment consisted of seven monthly infusions followed by a posttreatment observation period. The primary outcome measurement was mean daily prednisone-equivalent dose requirements, determined during the observation month preceding initiation of treatment and compared to the month preceding the seventh infusion. Secondary clinical endpoints measured were pulmonary function, frequency of emergency room visits or hospitalizations, and number of days absent from school or work. When adjusted for body weight, the mean dose requirements fell by 33, 39, and 33% in the placebo, IVIG (1 g/kg), and IVIG (2 g/kg) treatment arms, respectively. The differences between therapies were not statistically different (P = 0.9728). The mean percentage-of-predicted FEV1 fell in all three treatment groups during the treatment period but there was no significant difference between treatment groups (P = 0.8291). There was also no significant difference in the percentage of subjects requiring emergency room visits or hospitalizations or missing days of work/school, among the three treatment groups. The trial was terminated prematurely after interim analysis determined the adverse experience rate was different between the three groups. Three patients, all randomized to the 2-g/kg IVIG dose group, were hospitalized with symptoms consistent with aseptic meningitis. In summary, in this randomized, double-blind, placebo-controlled multicenter study, high doses of IVIG did not demonstrate a clinically or statistically significant advantage over placebo (albumin) infusions for the treatment of corticosteroid-dependent asthma. Subgroup analysis failed to identify markers predicting responsiveness. High-dose IVIG can also be associated with a significant incidence of serious adverse events.

Administration, Oral↗
PubMed1999

Threshold for classification as a skin sensitizer in the local lymph node assay: a statistical evaluation.

For more than 15 years, the murine local lymph node assay (LLNA) has undergone development, evaluation and validation as an alternative approach to the predictive identification of skin sensitizing chemicals. The criteria by which sensitizing chemicals are distinguished from those without significant skin sensitising hazard were developed empirically and were based on experience rather than a mathematical formula or statistical method. The current practice is to classify, as skin sensitizers, those chemicals which at one or more test concentrations stimulate a threefold or greater increase in the proliferative activity in draining lymph node cells. Despite the apparent confirmation of the utility of this approach from the extensive data available, there has not previously been any attempt to substantiate the accuracy of this criterion. In this present investigations, data from 134 chemicals tested in the LLNA and in the guinea pig and/or for which there exists clear evidence relating to human skin sensitization potential, have been subjected to a rigorous statistical evaluation using Receiver Operating Characteristic (ROC) curves. Whether the analysis is based on a comparison with guinea pig or human data, the results indicate that the empirically derived threefold threshold is an acceptable practical value for hazard identification.

Animal Testing Alternatives↗
PubMed1999

Impaired airway function and wheezing in infancy: the influence of maternal smoking and a genetic predisposition to asthma.

This prospective community-based study of infants born in inner London was undertaken to examine the association between premorbid airway function and subsequent wheezing in the first year of life and to explore the influence on this association of a family history of asthma and maternal smoking during pregnancy. Healthy Caucasian term infants were recruited shortly after birth, and physician-diagnosed wheezing episodes were identified retrospectively from medical records. Specific airway conductance was determined from plethysmographic measurements of lung volume and airway resistance, before 13 wk and prior to any respiratory illness, in 101 infants, 28 of whom experienced at least one episode of wheezing during the first year. Mean (SD) specific airway conductance was significantly diminished in infants who subsequently wheezed: 2.02 (1.07) s-1. kPa-1 and 2.60 (0.93) s-1. kPa-1, respectively (p < 0.05), and in those with a first-degree relative with asthma: 1.98 (0.83) s-1. kPa-1 and 2.60 (1.0) s-1. kPa-1, respectively (p < 0.05), but not in those whose mothers smoked during pregnancy, in whom airway resistance was, however, significantly elevated (p < 0.05). The odds ratio (95% confidence interval [CI]) for wheezing was 2.1 (1.1 to 3.8) for every unit (s-1. kPa-1) decline in specific airway conductance (p = 0.02). After adjustment for premorbid airway function, the odds of wheezing were significantly increased in those with a family history of asthma (4. 3; 95% CI, 1.3 to 13.8; p = 0.016) and those exposed to maternal smoking during pregnancy (4.9; 95% CI, 1.6 to 15.0; p = 0.005). Our findings confirm previous reports that impaired premorbid airway function precedes and predicts wheezing in the first year. Among those with a genetic predisposition to asthma, alterations in airway geometry or tone may increase susceptibility to wheezing. Maternal smoking has important and potentially preventable adverse effects on somatic growth and respiratory morbidity in early life.

Airway Resistance↗
PubMed1999

Assessment of airway function using partial expiratory flow-volume curves: How reliable are measurements of maximal expiratory flow at frc during early infancy?

We investigated the extent to which measurements of maximal expiratory flow at FRC (V EmaxFRC) are influenced by the dynamic increase of FRC in young infants by superimposing partial forced expiratory flow-volume curves on those obtained after lung inflation to 2 kPa (20 cm H2O) in 12 infants during the first month of life. The elastic equilibrium volume (EEV) of the respiratory system was estimated by extrapolating the passive expiratory time constant (obtained after lung inflation but prior to forced deflation) to zero flow. There was a very strong relationship between V EmaxFRC (which ranged from 11 to 190 ml/s) and the extent to which FRC was dynamically increased above EEV (range: 0 to 5 ml/kg), r2 = 0.88. The results of this study suggest that, although V EmaxFRC remains a useful means of measuring peripheral airway function in infants, its values should be interpreted with caution during the neonatal period. In particular, the relatively high V EmaxFRC values reported in healthy newborn infants may reflect differences in breathing strategy rather than airway structure. More meaningful within- and between-infant comparisons of peripheral airway function may be obtained by calculating forced expiratory flows at a fixed interval (e.g., 3 ml/kg) above EEV, rather than at the FRC that is operational at the time of measurement.

Airway Resistance↗
PubMed1999

Lung function testing in infants.

During recent years, there has been rapid development in the availability and application of pulmonary function tests in infants and young children. Whereas original methods were based on adaptations of classical techniques, over the past decade there has been an increasing trend towards developing less complex techniques specifically for use in infants and young children. Interpretation of these measurements requires a knowledge of respiratory physiology, and may be confounded by an unstable end expiratory level, compliant chest wall, dominance of the upper airways, difficulty in achieving flow limitation in healthy infants, and the variability of respiratory, lung or airway resistance which increases the difficulty of assessing the significance of changes in resistance as a result of treatment or challenge. Nevertheless, with care, the assessment of respiratory function during infancy and early childhood can increase knowledge of the growth and development of the respiratory system, and our understanding of the patho-physiological processes underlying respiratory diseases in early life. They also have the potential to provide valuable objective outcome measures in the quest for effective preventive and therapeutic strategies in respiratory medicine.

Humans↗
PubMed1999

Respiratory function testing in early childhood: where have we come from and where are we going?

After an initially slow beginning, we are currently witnessing something of a revolution in the field of respiratory function testing during early childhood, both with respect to the number of techniques available and the applications to which they are being put. There is now an urgent need for international, collaborative efforts to develop more objective, standardized methods of assessment (including improved, properly validated equipment and software) and reliable reference data for this age group. This would improve our understanding of exactly what these tests are measuring, and facilitate the development of effective therapeutic and preventive strategies to minimize suffering from respiratory illness not only during early childhood but, hopefully, throughout life.

Child, Preschool↗
PubMed1999

Respiratory physiology during early life.

Despite the rapid adaptation to extrauterine life, the respiratory system of an infant is not simply a miniaturized version of that of an adult, since the rapid somatic growth that occurs during the first year of life is accompanied by major developmental changes in respiratory physiology. The highly compliant chest wall of the infant results in relatively low transpulmonary pressures at end expiration with increased tendency of the small peripheral airways to close during tidal breathing. This not only impairs gas exchange and ventilation-perfusion balance, particularly in dependent parts of the lung, but, together with the small absolute size of the airways, renders the infant and young child particularly susceptible to airway obstruction. Premature airways are highly compliant structures compared with those of mature newborns or adults. This increased compliance can cause airway collapse, resulting in increased airways resistance, flow limitation, poor gas exchange and increased work of breathing. Although there is clear evidence that airway reactivity is present from birth, its role in wheezing lower respiratory tract illnesses in young infants may be overshadowed by pre-existing abnormalities of airway geometry and lung mechanics, or by pathological changes such as airway oedema and mucus hypersecretion. Attempts to assess age-related changes in airway reactivity or response to aerosol therapy in the very young is confounded by changes in breathing patterns and the fact that infants are preferential nose breathers. There is increasing evidence that pre-existing abnormalities of respiratory function, associated with adverse events during foetal life (including maternal smoking during pregnancy), and familial predisposition to wheezing are important determinants of wheezing illnesses during the first years of life. This emphasizes the need to identify and minimize any factors that threaten the normal development of the lung during this critical period if respiratory morbidity throughout life is to be minimized.

Child, Preschool↗
PubMed1998

A comparison of the respiratory effects of sevoflurane and halothane in infants and young children.

BACKGROUND: This study compared the respiratory effects of sevoflurane with those of halothane in anesthetized infants and young children. METHODS: Infants were randomized to receive 1 minimum alveolar concentration (MAC) halothane or sevoflurane in a mixture of nitrous oxide and oxygen. Anesthetic management included the use of a laryngeal mask. Flow, airway pressure, and the end-tidal carbon dioxide pressure (PETCO2) were measured during spontaneous ventilation and airway occlusions. Respiratory inductive plethysmography was used to assess chest wall motion. RESULTS: Measurements were obtained in 30 infants and young children (mean (SD) age, 14.5 (5.9) months), 15 of whom received sevoflurane and 15 received halothane. Some respiratory depression, as indicated by a PETCO2 of 45 mmHg (6 kPa), was present in both groups. Minute ventilation and respiratory frequency were significantly lower during sevoflurane than halothane anesthesia (4.5 compared with 5.4 (1/ m2)/min, and 37.5 compared with 46.7 breaths/min, respectively, P < 0.05). There was no difference in respiratory drive, but the shape of the flow waveform differed according to anesthetic agent, with peak inspiratory flow reached later, and peak expiratory flow reached earlier, in the sevoflurane group. There was also significantly less thoracoabdominal asynchrony during sevoflurane anesthesia. CONCLUSIONS: Minute ventilation and respiratory frequency were lower in infants during 1 MAC sevoflurane in nitrous oxide than during halothane anesthesia. However, these differences may not be clinically relevant at these concentrations, given the modest increase in PETCO2. Differences in parameters of breath timing and shape between sevoflurane and halothane suggest different effects of these anesthetic agents on ventilatory control.

Anesthetics, Inhalation↗
PubMed1998

Distinct patterns of respiratory difficulty in young children with achondroplasia: a clinical, sleep, and lung function study.

AIM: Achondroplasia can result in respiratory difficulty in early infancy. The aim of this study was to document lung growth during infancy, together with the cause of any cardiorespiratory and sleep dysfunction. PATIENTS AND METHODS: Seventeen prospectively ascertained infants (14 boys and three girls) with respiratory symptoms starting before 1 year of age underwent clinical, sleep, and lung function studies. RESULTS: Three distinct groups were identified. Group 1 (n = 6) were the least symptomatic and only had obstructive sleep apnoea. Group 2 (n = 6) had obstructive sleep apnoea of muscular aetiology and, neurologically, hydrocephalus and a small foramen magnum were common. Group 3 (n = 5), the most severely affected group, all developed cor pulmonale, with three deaths occurring as a result of terminal cardiorespiratory failure. All five had obstructive sleep apnoea with a muscular aetiology (a small foramen magnum predominated) with severe or moderately severe gastro-oesophageal reflux. Initially, lung function studies found no evidence of restriction or reduced lung volumes standardised according to weight. However, with growth these infants had worsening function, with raised airway resistance and severe reductions in respiratory compliance. CONCLUSIONS: These groups appear to be distinct phenotypes with distinct anatomical aetiologies: "relative" adenotonsillar hypertrophy, resulting from a degree of midfacial hypoplasia (group 1); muscular upper airway obstruction along with progressive hydrocephalus, resulting from jugular foramen stenosis (group 2); and muscular upper airway obstruction, but without hydrocephalus, resulting from hypoglossal canal stenosis with or without foramen magnum compression and no jugular foramen stenosis (group 3). The aetiology of these abnormalities is consistent with localised alteration of chondrocranial development: rostral, intermediary and caudal in groups 1, 2, and 3, respectively.

Achondroplasia↗
PubMed1998

The Hering-Breuer reflex in anesthetized infants: end-inspiratory vs. end-expiratory occlusion technique.

Both end-inspiratory (EIO) and end-expiratory (EEO) occlusions have been used to measure the strength of the Hering-Breuer inflation reflex (HBIR) in infants. The purpose of this study was to compare both techniques in anesthetized infants. In each infant, HBIR activity was calculated as the relative prolongation of expiratory and inspiratory time during EIO and EEO, respectively. Respiratory drive was assessed from the change in airway pressure during inspiratory effort against the occlusion, both at a fixed time interval of 100 ms (P0.1) and a fixed proportion (10%) of the occluded inspiratory time (P10%). Twenty-two infants [age 14.3 +/- 6. 4 (SD) mo] were studied. No HBIR activity was present during EIO [-11.8 +/- 15.9 (SD) %]. By contrast, there was significant, albeit weak, reflex activity during EEO [HBIR: 27.2 +/- 17.4%]. A strong HBIR (up to 310%) was elicited in six of seven infants in whom EIO was repeated after lung inflation. P0.1 was similar during both types of occlusions, whereas mean +/- SD P10% was lower during EEO than during EIO: 0.198 +/- 0.09 vs. 0.367 +/- 0.15 kPa, respectively (P < 0.01). These data suggest a difference in the central integration of stretch receptor activity in infants during anesthesia compared with during sleep.

Anesthesia, Inhalation↗
PubMed1998

Analysis of forced expiratory maneuvers from raised lung volumes in preterm infants.

During recent years it has been suggested that forced expiratory measurements, derived from a lung volume set by a standardized inflation pressure, are more reproducible than those attained during tidal breathing when the rapid thoracoabdominal compression technique is used in infants. The aim of this study was to evaluate the feasibility of obtaining measurements from raised lung volumes in unsedated preterm infants. Measurements were made in 18 infants (gestational age 26-35 wk, postnatal age 1-10 wk, test weight 1.4-3. 5 kg). Several inflations [1.5-2.5 kPa (15-25 cmH2O)] were used to briefly inhibit respiratory effort before the rapid thoracoabdominal compression was performed. Conventional analysis of flows and volumes at fixed times and percentages of the forced expiration resulted in a relatively high variability in this population. However, by using the elastic equilibrium point (i.e., the passively determined lung volume, derived from passive expirations before the forced expiration) as a volume landmark, it was feasible to achieve reproducible results in unsedated preterm infants, despite their strong respiratory reflexes and rapid respiratory rates. Because this approach is independent of changes in expiratory time, expired volume, or applied pressures, it may facilitate investigation of the effects of growth, development, and disease on airway function in infants, particularly during the first weeks of life, when conventional analysis of forced expirations may be inappropriate.

Female↗
PubMed1998

Influence of volume dependency and timing of airway occlusions on the Hering-Breuer reflex in infants.

Both end-inspiratory (EIO) and end-expiratory (EEO) airway occlusions are used to calculate the strength of the Hering-Breuer inflation reflex (HBIR) in infants. However, the influence of the timing of such occlusions is unknown, as is the extent to which changes in volume within and above the tidal range affect this reflex. The purpose of this study was to compare both techniques and to evaluate the volume dependency of the HBIR in healthy, sleeping infants up to 1 yr of age. The strength of the HBIR was expressed as the ratio of expiratory or inspiratory time during EIO or EEO, respectively, to that recorded during spontaneous breathing, i.e., as the "inhibitory ratio" (IR). Paired measurements of the EIO and EEO in 26 naturally sleeping newborn and 15 lightly sedated infants at approximately 1 yr showed no statistically significant differences in the IR according to technique: mean (95% CI) of the difference (EIO - EEO) being -0.02 (-0.17, 0.13) during the first week of life and 0.04 (-0.14, 0.22) at 1 yr. During tidal breathing, a volume threshold of approximately 4 ml/kg was required to evoke the HBIR. Marked volume and age dependency were observed. In newborn infants, occlusions at approximately 10 ml/kg during sighs always resulted in an IR > 4, whereas a similar response was only evoked at 25 ml/kg in older infants. Age-related changes in the volume threshold may reflect maturational changes in the control of breathing and respiratory mechanics throughout the first year of life.

Age Factors↗
PubMed1998

Respiratory function among preterm infants whose mothers smoked during pregnancy.

We examined whether the adverse effects of prenatal exposure to tobacco on lung development are limited to the last weeks of gestation by comparing respiratory function in preterm infants whose mothers had and had not smoked during pregnancy. Maximal forced expiratory flow (Vmax FRC) and time to peak tidal expiratory flow as a proportion of total expiratory time (TPTEF:TE) were measured prior to discharge from hospital in 108 preterm infants (mean [SD] gestational age, 33.5 [1.8] wk), 40 of whose mothers had smoked during pregnancy. Infant urinary cotinine was less than 4 ng/ml in those born to nonsmokers, but it was as high as 458 ng/ml in exposed infants (p < 0.0001). TPTEF:TE was significantly lower in infants exposed to tobacco in utero (mean [SD], 0.369 [0.109]) when compared with those who were not (0.426 [0.135]) (p <= 0.02). Vmax FRC was also reduced in exposed infants (mean [SD], 85.2 [41.7] ml/s versus 103.8 [49.7] ml/s) (p = 0.07). After allowing for sex, ethnic group, body size, postnatal age, and socioeconomic status, TPTEF:TE remained significantly diminished in infants exposed prenatally to tobacco (p < 0.05). Thus, impaired respiratory function is evident in infants born on average 7 wk prior to the expected delivery date, suggesting that the adverse effects of prenatal exposure to tobacco are not limited to the last weeks of pregnancy.

Age Factors↗
PubMed1998

Validation of respiratory inductive plethysmography using the Qualitative Diagnostic Calibration method in anaesthetized infants.

The aim of this study was to compare tidal volume (VT) derived from the Qualitative Diagnostic Calibration (QDC) method (VT,QDC) with measurements from pneumotachography (VT,PN,T) in anaesthetized infants. Measurements were made during spontaneous (SV) and intermittent positive pressure (IPPV) ventilation, sighs and airway occlusions. The VT,DIF was the difference between VT,QDC and VT,PNT (%VT). The contribution of the ribcage (rc) to VT,QDC (%rc) and the thoracoabdominal phase lag were also derived. Twenty-eight infants, mean (SD) age 14.0 (6.2) months were studied. VT,QDC represented VT,PNT most closely when > or = 20 breaths were analysed. There was close agreement during SV immediately after the calibration period (95% limits of agreement (LA; QDC - PNT) -23, 3.0%). The 95% LA increased to -9.6, 10.2% after 10 min. Accuracy diminished during IPPV (95% LA -38, 31%), and sighs. During airway occlusions, when VT,PNT was zero, the 95% LA were -63, 4.1 mL x kg(-1). Mean phase lag was 36 and 2%, respectively, during SV and IPPV (p<0.05). The %rc appeared to be overestimated, being in excess of 50% in infants under 12 months. The Qualitative Diagnostic Calibration method used to estimate tidal volume in anaesthetized infants was limited by the need to analyse > or = 20 breaths and by a loss of within-subject accuracy if measurement conditions or pattern of breathing changed.

Anesthesia, General↗
PubMed1998

A collaborative study of infant respiratory function testing.

The aims of this study were to compare inter-observer variability within and between two specialized infant lung function testing centres and to develop a strategy for performing and analysing infant respiratory function tests to facilitate future collaborative trials. A protocol for data collection and analysis was developed using similar equipment and identical software. All raw data were exchanged on disk and analysed, blind to infant status. All data were cross-analysed by both centres to assess inter-observer variability. Outcome measures were functional residual capacity (FRCpleth), airway resistance (Raw) and maximal expiratory flow at FRC (V'max,FRC). Subjects were recruited from the multicentre UK extracorporeal membrane oxygenation (ECMO) Trial and measured at around 1 yr of age. Forty-two infants attended the Institute of Child Health, London and 36 attended the Leicester Royal Infirmary. The proportion of infants treated with ECMO or conventional management at each centre was similar. There were no significant differences between any of the outcome measures for infants tested at either centre. During a cross-analysis, the agreement between the two centres, within infant, was closer for V'max,FRC and FRCpleth (within 10%) than for the more variable measurements of Raw (within 20%). A collaborative approach to trials with infant respiratory function as an outcome measure appears feasible, providing that close attention is paid to study design, and participants in such trials maintain a standard approach to data collection and analysis.

Airway Resistance↗