Value of radiological follow up of childhood pneumonia.
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Biomedical subjects
Publications and source records attributed to J Y Paton.
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The role of the central and peripheral chemoreceptors in the hyperpnea of exercise has been controversial. We studied five children, age 6 to 11 yr, with absent hypercapneic and hypoxic ventilatory responses during wakefulness (congenital central hypoventilation syndrome, CCHS). Each child performed an incremental treadmill exercise test. Maximal oxygen consumption (VO2) and minute ventilation (VE) at maximal exercise were lower than but not significantly different from these values in a group of nine normal control children of similar age, height, and weight (VO2/kg, 33.7 +/- 5.0 versus 45.4 +/- 2.9 ml/kg/min, mean +/- SEM, NS; VE 28.3 +/- 7.3 versus 43.8 +/- 3.9 L/min, NS). Oxygen tension and saturation fell and CO2 tension rose significantly at maximal exercise in CCHS but not in control subjects. In contrast to control subjects, CCHS subjects increased VE largely by increasing respiratory frequency (f) rather than tidal volume (VT). In the oldest child, submaximal exercise tests at 50% VO2, with varying pacing rate, showed a significant positive relation between pacing rate and f, but not VT. Thus, VE was higher at the faster pacing rate. Further incremental testing in the two oldest subjects with recording of the pacing rate showed positive linear relations between pacing frequency and breathing frequency and between pacing frequency and VE up to a maximum pacing rate of 48 to 50 paces per 15 s. VE beyond this level varied randomly around the maximum level. We conclude that exercise-induced hyperpnea can occur in the absence of chemoreceptor function. In the CCHS children, limb movement is an important determinant of the ventilatory response to exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
To determine the most effective infection control procedure in preventing nosocomial infection with respiratory syncytial virus (RSV), we did a prospective controlled study of four infection-control strategies in four wards in a large paediatric hospital in the west of Scotland. All children under two years old admitted to four general wards during three winter RSV epidemics (1989-92) were screened for RSV infection (by nasopharyngeal aspirate and direct immunofluorescence) within 18 hours of admission. The main outcome measure was the occurrence of nosocomial infection, defined as the number of children initially RSV negative who became RSV positive 7 days or more after hospital admission (incubation period for RSV infection is 5-8 days). Without special precautions, there was a high rate of nosocomial RSV infection (26%). Nosocomial infection was significantly reduced by the combination of cohort nursing with the wearing of gowns and gloves for all contacts of RSV-infected children (p = 0.0022). Neither the use of gowns and gloves alone nor cohort nursing alone produced a significant reduction in cross-infection. In the final year, general clinical use of a policy of cohort nursing with gowns and gloves resulted in a reduction in the cross-infection rate by two-thirds of its original value (9.5% vs 26%). Combined with rapid laboratory diagnosis, cohort nursing and the wearing of gowns and gloves for all contacts with RSV-infected children can significantly reduce the risk of nosocomial RSV infection.
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Using an electronic inhaler timer device (Nebulizer Chronolog), compliance with the prescribed frequency of inhaled prophylactic medication in 14 asthmatic children was measured. Underuse occurred in 55% of study days while overuse occurred in only 2%. Such devices provide an important new tool for investigating inhaled drug compliance.
Theophylline is commonly believed to stimulate central respiratory centers. We studied the effect of oral theophylline therapy on ventilatory responses to hypercapnia and hypoxia during a double-blind placebo-controlled trial with a slow release oral theophylline preparation. We measured hypercapnic and hypoxic ventilatory responses using rebreathing techniques in 15 subjects (21 to 41 yr of age, with normal lung function) on three occasions: baseline, after 4 days of Drug 1, and after 4 days of Drug 2. For subjects receiving theophylline, the mean serum theophylline level was 11.3 + 1.3 (SE) micrograms/ml (range, 5.3 to 22.1). Unpleasant side effects were reported by 11 of the 15 subjects (nausea, jitteriness, and agitation) while receiving theophylline but not while receiving placebo. The mean hypercapnic ventilatory response with placebo was 4.3 +/- 0.9 L/min/mm Hg PACO2 and with theophylline it was 4.5 +/- 0.7 L/min/%SaO2 and with theophylline it was -2.7 +/- 0.4 L/min/%SaO2. Hypoxic responses for each subject were measured at similar PvCO2. There were no significant changes in ventilatory responses with theophylline. We conclude that theophylline use, at a dose sufficient to cause side effects, does not affect chemoreceptor responsiveness.
Digital clubbing and pulmonary function tests were measured in children, adolescents, and adults with chronic lung diseases to determine pulmonary function correlates with a quantitative measure of clubbing. The group had a mean age of 13.8 +/- 6.0 (SD) years, mean PaO2 of 81 +/- 21 mm Hg, and mean FEV1 of 60% +/- 26% predicted. Digital clubbing was diagnosed in 43 cases when the distal phalangeal depth to interphalangeal depth (DPD/IPD) ratio, measured on a finger cast, was greater than or equal to 1 (greater than 3 SD above mean from 85 controls; no history of pulmonary disease; mean age, 14.8 +/- 7.6). The PaO2 of patients with digital clubbing was 69.4 +/- 2.1 (SEM) mm Hg compared with 88.3 +/- 1.3 mm Hg in those without digital clubbing (P less than 0.0001). Digital clubbing was present in 39 of the 84 (46%) hypoxic patients (PaO2 less than or equal to 88) but only four of the 78 (5%) normoxic patients (P less than 0.0001). The DPD/IPD ratio was negatively correlated with PaO2 in subjects with cystic fibrosis and interstitial fibrosis. Weak negative correlations were seen for all other subjects except asthmatics. Overall, the DPD/IPD ratio was significantly correlated with PaO2 (r = -0.53; P less than 0.0001). The DPD/IPD ratio was correlated with other lung function abnormalities (increased RV, decreased FEV1, and FEF25%-75%) only for the subjects with cystic fibrosis. We conclude that digital clubbing is associated with hypoxemia and airway obstruction. The relation is seen most clearly in subjects with cystic fibrosis, possibly reflecting the prolonged duration of hypoxemia. Digital clubbing is rarely seen in normoxic subjects.
Sweat glands isolated from skin obtained from normal subjects and patients with cystic fibrosis (CF) were pre-loaded with 86Rb+ and superfused with a physiological salt solution and the rate of 86Rb+ efflux was measured as an indicator of cellular potassium permeability. Acetylcholine always evoked a permeability increase in the glands from control subjects and this response could be resolved into calcium-dependent and calcium-independent components. Sweat glands from CF patients did not show such consistent responses. In three individuals the glands were abnormally insensitive to acetylcholine but normal responsiveness was seen in a fourth case. It is proposed that CF can induce dysfunction of calcium-dependent control processes in sweat glands.
The sensitivity and specificity of direct immunofluorescence microscopy performed on Pernasal swab specimens and compared with those of nasopharyngeal aspirates were 93 and 99%, respectively. Posterior nasopharyngeal swabs applied immediately to microscope slides allow a rapid and simple screening procedure for the diagnosis of acute respiratory syncytial virus infections.
We studied the relation of gastro-oesophageal reflux with apnoea during sleep in 24 infants with antecedent respiratory abnormalities and/or proven gastrooesophageal reflux (GOR), by combined lower oesophageal pH and polygraphic monitoring. GOR, indicated by pH less than 4, was confirmed in 24 infants. There were no episodes of prolonged (greater than 20 s) central apnoea (CA). Fifty-six mixed or obstructive breathing episodes were identified in 12 infants (14 studies), of which 28 lasted between 3 and 6 s. Bradycardia (heart rate less than less than 80 beats/min for 10 s was not observed. There were 80 falls in transcutaneous oxygen (PtcO2 greater than 5 mmHg) but only 6 exceeded 10 mmHg and one 20 mmHg. There was no relationship between GOR and obstructive episodes in terms of frequency, duration or temporal occurrence, except in one infant. There were 1276 gross body movements, mainly during active or indeterminate sleep and, of these, 7% were associated with decreases in pH to less than 4. Movements occurred during the 60 s period preceding 83% of pH decreases greater than 1 pH unit compared to only 30% in the 60 s succeeding a pH drop. We conclude that, while GOR and obstructive episodes may co-exist in the patient groups studied, decreases in pH in the lower oesophagus do not usually induce either central or obstructive apnoea, and vice versa. Of the variables monitored, only gross body movements were temporally associated with pH drops, and usually preceded them.
Respiratory movements and heart rate were monitored continuously during the course of 2 h radionuclide studies to detect gastro-oesophageal reflux (GOR) in 22 infants following a milk feed. Twenty infants had GOR, to upper oesophageal/pharyngeal level in 19, and 17 had central apnoea between 3 and 15s. Prolonged central apnoea (greater than 20s) was not observed. Bradycardia, defined as a heart rate less than 80 beats/min for 10s or more, was observed in only 1 infant who did not have GOR. No correlation was found between the number or duration of reflux episodes and the frequency of respiratory pauses between 3 and 17s. When data from individual infants were examined a possible temporal relation between the occurrence of GOR and central apnoea was seen in only two infants; in each case, detailed examination suggested that apnoea was more closely associated with sleep than with GOR. Although the respiratory monitoring system did not include airflow sensors, the almost complete absence of bradycardia suggested that prolonged obstructive apnoeas did not occur. We conclude that any relation between GOR and central apnoeas less than 15 s is not of a direct cause/effect nature.
Infants with myelomeningocele have abnormalities in ventilatory control. To determine whether these persist into later life, we studied 14 patients with myelomeningocele and Arnold-Chiari malformation (age 18.0 +/- 0.8 (SE) years), and compared them with 14 control subjects (age 24.0 +/- 0.9 years). Pulmonary function and ventilatory muscle strength did not differ between patients with myelomeningocele and control subjects. Hypercapnic ventilatory responses were significantly lower in the group with myelomeningocele (1.98 L/min/mm Hg) compared with control values (3.33 L/min/mm Hg; p less than 0.01). Hypoxic ventilatory responses (-1.4 L/min/%oxygen saturation of hemoglobin in arterial blood) were not significantly different from control values (-2.14 L/min/%oxygen saturation). In control subjects the hypercapnic and hypoxic ventilatory responses were highly correlated with each other within subjects (r = 0.84; p less than 0.002) but not in those with myelomeningocele (r = 0.34; not significant). We concluded that adolescents and young adults with myelomeningocele have abnormalities in control of ventilation during sleep and wakefulness. We speculate that the Arnold-Chiari malformation interferes with central chemosensitivity (hypercapnic ventilatory response) and central integration of chemoreceptor output.
The association between gastro-oesophageal reflux and sleep state in 24 infants with confirmed or suspected gastro-oesophageal reflux was studied by monitoring both the pH in the lower oesophagus and polygraphic tracings made during sleep at night. Gastro-oesophageal reflux during the night was confirmed in 20 infants. Three hundred and sixteen precipitous drops of more than one unit of pH were recorded during the studies, 186 during periods of wakefulness. Of 130 drops in pH during sleep, 62 (48%) began during active sleep and 62 during indeterminate sleep. Of the latter, 56 (90%) were associated with brief gross body movements. Only five of the drops in pH (4%) began during quiet sleep. Gastro-oesophageal reflux stopped during active sleep on 56 occasions (43%), in indeterminate sleep in 62 (47%), and in quiet sleep in 12 (9%). Episodes of gastro-oesophageal reflux starting or ending in quiet sleep were uncommon. The occurrence of gastro-oesophageal reflux during active sleep may partly explain why reflux during sleep is a risk factor for pulmonary disease.
There is much debate relating to possible abnormalities in respiratory control mechanisms in infants considered at increased risk for sudden infant death syndrome (SIDS). The P0.1 occlusion technique was used to assess the central respiratory response to hyperoxic hypercapnia during quiet sleep in 21 normal infants, 13 siblings of SIDS victims, and 17 infants with apparent life threatening events. The slope of P0.1 plotted against carbon dioxide concentration increased exponentially with age, independent of body weight in each group. Birth weight has a significant effect on slope with a lower weight predisposing to a lower slope. Siblings as a group had a significantly lower slope at any given age than normal infants, whereas the infants who had had apparent life threatening events were not significantly different from the controls. As intragroup variation in both siblings and control groups greatly exceeded the significant intergroup differences observed, the technique cannot identify individual infants as belonging to one or other group.
Congenital central hypoventilation syndrome (CCHS) has been thought to be a disorder of central chemoreceptor responsiveness. Previous studies in CCHS have shown decreased or absent ventilatory responsiveness to both hypercarbia and hypoxia. However, hypoxic responsiveness during wakefulness has not been systematically studied. We studied hypoxic and hypercapnic ventilatory responses during wakefulness in five children with CCHS (6 to 11 yr of age). To measure the hypercapnic response, the children rebreathed a hyperoxic hypercapnic mixture until PaCO2 reached 56 to 69 mm Hg. For the hypoxic response, the children rebreathed a hypoxic gas mixture, at mixed venous PCO2, until SaO2 had fallen to less than 78%. We found that the ventilatory responses to hypercapnia and hypoxia were very variable (linear correlation coefficients ranging from -0.44 to +0.63 for hypercapnic responses and from -0.15 to +0.77 for hypoxic responses), with no significant change from baseline in response to either stimulus. There was no evidence of progressive ventilatory stimulation despite increasing stimulus. Additionally, these children had no subjective sensation of dyspnea or discomfort. This establishes that hypoxic and hypercapnic ventilatory control is absent during wakefulness. Chemoreceptor control (peripheral and central) is, therefore, defective in all states in children with CCHS. We speculate that the defect in CCHS lies in central integration of the central and peripheral chemoreceptor signals.
During radionuclide scans in 82 infants and children gastro-oesophageal reflux extending to the upper oesophageal/laryngeal level was detected in 636 one minute frames. Only 61 (9.6%) of these frames were associated with vomiting, defined as the appearance of milk at the mouth. Thus the absence of vomiting does not preclude appreciable gastro-oesophageal reflux.
Eleven normal term infants undergoing respiratory assessment involving rebreathing to produce progressive hypercapnia were studied by Doppler ultrasound examination of an anterior cerebral artery during the procedure. A linear increase in end tidal carbon dioxide concentration from 4.5% to a maximum of 8.5% was documented during a period of 4-5 min rebreathing. A corresponding elevation of transcutaneous carbon dioxide tension was shown in the two infants monitored in this way. In all cases the Pourcelot index fell with rising end tidal carbon dioxide concentration. This fall in Pourcelot index was due to an increase in the diastolic frequency of the Doppler waveform. These results are consistent with the view that Pourcelot index correlates with cerebral vascular resistance distal to the site of recording.
A clinical approach to infants who may have 'nearly missed' Sudden Infant Death Syndrome (SIDS) is suggested as appropriate whether or not the eventual conclusion is that there is no connection between these surviving infants and those who die of SIDS. A non-restrictive investigative approach has been applied to 57 infants with episodes causing similar levels of alarm and recourse to medical aid but not exclusively having documented apnoea or need for cardiopulmonary resuscitation. Similarities among patients in past history, recent minor symptoms, modes of presentation and positive investigations support the concept that they may show a common response to a variety of pathophysiologic stresses. Epidemiological similarities to SIDS cases support the suggestion that SIDS may be the end-stage inadequate response to such stresses. Future studies should address the reasons for 'inappropriate' collapse, its treatment and prevention and be alert to any resultant effect upon the incidence of SIDS or further evidence of a link between the conditions.