Nemaline myopathy as a cause of sleep hypoventilation.

Two siblings, a 14.5-year-old boy and his 11.5-year-old sister, with congenital nemaline myopathy presented with severe respiratory failure and, in the case of the older patient, with cor pulmonale and systemic hypertension. The children were treated initially by continuous mechanical ventilation, but after a few weeks they only required ventilation at night. At the start of treatment, both were found to have a decreased ventilatory response to CO2 which apparently improved during 4 to 5 years of follow-up treatment. It has not been possible to wean them from nocturnal mechanical ventilation, but during the daytime they attend school and function almost normally. It is postulated that respiratory failure in nemaline myopathy may not be related to the severity of the muscle weakness but may result from a disturbance of the feedback required for normal control of breathing.

Oxygen cost and oxygen uptake dynamics and recovery with 1 min of exercise in children and adults.

To test the hypothesis that O2 uptake (VO2) dynamics are different in adults and children, we examined the response to and recovery from short bursts of exercise in 10 children (7-11 yr) and 13 adults (26-42 yr). Each subject performed 1 min of cycle ergometer exercise at 50% of the anaerobic threshold (AT), 80% AT, and 50% of the difference between the AT and the maximal O2 uptake (VO2max) and 100 and 125% VO2max. Gas exchange was measured breath by breath. The cumulative O2 cost [the integral of VO2 (over baseline) through exercise and 10 min of recovery (ml O2/J)] was independent of work intensity in both children and adults. In above-AT exercise, O2 cost was significantly higher in children [0.25 +/- 0.05 (SD) ml/J] than in adults (0.18 +/- 0.02 ml/J, P less than 0.01). Recovery dynamics of VO2 in above-AT exercise [measured as the time constant (tau VO2) of the best-fit single exponential] were independent of work intensity in children and adults. Recovery tau VO2 was the same in both groups except at 125% VO2max, where tau VO2 was significantly smaller in children (35.5 +/- 5.9 s) than in adults (46.3 +/- 4 s, P less than 0.001). VO2 responses (i.e., time course, kinetics) to short bursts of exercise are, surprisingly, largely independent of work rate (power output) in both adults and children. In children, certain features of the VO2 response to high-intensity exercise are, to a small but significant degree, different from those in adults, indicating an underlying process of physiological maturation.

Oxygen uptake dynamics during high-intensity exercise in children and adults.

We hypothesized that the O2 uptake (Vo2) response to high-intensity exercise would be different in children than in adults. To test this hypothesis, 22 children (6-12 yr old) and 7 adults (27-40 yr old) performed 6 min of constant-work-rate cycle-ergometer exercise. Sixteen children performed a single test above their anaerobic threshold (AT). In a separate protocol, six children and all adults exercised at low and high intensity. Low-intensity exercise corresponded to the work rate at 80% of each subject's AT. High-intensity exercise (above the AT) was determined first by calculating the difference in work rate between the AT and the maximal Vo2 (delta). Twenty-five, 50, and 75% of this difference were added to the work rate at the subject's AT, and these work rates were referred to as 25% delta, 50% delta, and 75% delta. For exercise at 50% delta and 75% delta, Vo2 increased throughout exercise (O2 drift, linear regression slope of Vo2 as a function of time from 3 to 6 min) in all the adults, and the magnitude of the drift was correlated with increasing work rates in the above-AT range (r = 0.91, P less than 0.0001). In contrast, no O2 drift was observed in over half of the children during above-AT exercise. The O2 drifts were much higher in adults (1.76 +/- 0.63 ml O2.kg-1.min-2 at 75% delta) than in children (0.20 +/- 0.42, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Oral [13C]bicarbonate measurement of CO2 stores and dynamics in children and adults.

During exercise, less additional CO2 is stored per kilogram body weight in children than in adults, suggesting that children have a smaller capacity to store metabolically produced CO2. To examine this, tracer doses of [13C]bicarbonate were administered orally to 10 children (8-12 yr) and 12 adults (25-40 yr) at rest. Washout of 13CO2 in breath was analyzed to estimate recovery of tracer, mean residence time (MRT), and size of CO2 stores. CO2 production (VCO2) was also measured breath by breath using gas exchange techniques. Recovery did not differ significantly between children [73 +/- 13% (SD)] and adults (71 +/- 9%). MRT was shorter in children (42 +/- 7 min) compared with adults (66 +/- 15 min, P less than 0.001). VCO2 per kilogram was higher in the children (5.4 +/- 0.9 ml.min-1.kg-1) compared with adults (3.1 +/- 0.5, P less than 0.0001). Tracer estimate of CO2 production was correlated to VCO2 (r = 0.86, P less than 0.0001) and when corrected for mean recovery accurately predicted the VCO2 to within 3 +/- 14%. There was no difference in the estimate of resting CO2 stores between children (222 +/- 52 ml CO2/kg) and adults (203 +/- 42 ml CO2/kg). We conclude that orally administered [13C]bicarbonate can be used to assess CO2 transport dynamics. The data do not support the hypothesis of lower CO2 stores under resting conditions in children.

Failure of early postnatal dexamethasone to prevent chronic lung disease in infants with respiratory distress syndrome.

OBJECTIVE: To study the effect of early postnatal dexamethasone (days 1-3) on the incidence and severity of chronic lung disease in preterm infants with respiratory distress syndrome. METHODS: A multicentre, randomised, placebo controlled, blinded study was carried out in 18 neonatal intensive care units in Israel. The primary outcome measure was survival to discharge without requirement for supplemental oxygen therapy beyond 28 days of life. The secondary outcome measures were requirement for mechanical ventilation at 3 and 7 days, duration of ventilation or oxygen therapy, need for subsequent steroids for established chronic lung disease and incidence of major morbidities. RESULTS: The study consisted of 248 infants (dexamethasone n = 132; placebo n = 116). No differences were found in the outcome variables except for a reduction in requirement for mechanical ventilation at age 3 days in treated infants (dexamethasone 44%, placebo 67%; P = 0.001). Gastrointestinal haemorrhage, hypertension, and hyperglycaemia were more common in treated infants, but no life threatening complications, such as gastrointestinal perforation, were encountered. CONCLUSIONS: These data do no support the routine use of early postnatal steroids, but may justify further study in a selected, high risk group of infants.

Ethical problems in cardiac surgery for a lethal, congenital malformation.

The development of surgical procedures for increasingly complex and hitherto considered to be fatal and noncorrectible congenital heart disease has resulted in a re-evaluation of the ethical and social issues raised by the availability of such procedures. Three specific cases are used to illustrate some of the problems that may arise in different socioeconomic and geographic groups. It is suggested that the mere availability of the procedure does not necessarily either allow for or permit its logistical use without attention to the underlying ethical and social conditions.

Prenatal ritodrine administration and the incidence of respiratory distress syndrome in premature infants.

UNLABELLED: Prenatal exposure to ritodrine may be associated with a lower incidence of RDS in premature infants, independent of its effect on prolongation of pregnancy. OBJECTIVE: The purpose of this study was to assess the neonatal respiratory outcome of premature infants according to whether their mothers were treated prenatally with ritodrine. STUDY DESIGN: A retrospective review was done of all 247 infants born at 34 weeks of gestation or less in our hospital during a 6-year period. A multivariate logistic regression was used to adjust for possible confounding variables. RESULTS: Among the ritodrine-exposed infants respiratory distress syndrome developed in 9.5% (4/42) compared with 28% (57/205) in the unexposed group (p < 0.012; adjusted odds ratio 4.88, 95% confidence interval 1.27 to 18.70). The gestational age and birth weight were similar in the two groups. The incidence of transient tachypnea of the newborn and other neonatal complications was not statistically different between the two groups. CONCLUSION: Ritodrine was associated with a significantly lower incidence of respiratory distress syndrome in premature infants, independent of the effect of ritodrine on prolongation of pregnancy.

Adverse perinatal outcome in the older primipara.

Delayed childbearing has become common and has raised the awareness of the possible risks for the mother and the newborn infant. The increased maternal and neonatal risks have been attributed largely to the lack of proper prenatal care. The aim of this study was to assess whether advanced maternal age is a significant risk factor in mothers who receive good prenatal care. We matched 161 cases 1:1 according to the following criteria: maternal and paternal ethnic origin, chronic diseases, marital status, and smoking during pregnancy. Our results show that the older women had babies with a significantly higher incidence of low birth weight (< 2500 gm, p = 0.001), prematurity (< 37 weeks, p = 0.02), intrauterine growth retardation (p = 0.001), abruptio placentae (p = 0.002), and cesarean section (p < 0.001). The average hospital stay for the babies of the older mothers was longer than that for babies of the younger mothers (8.4 vs 6.1 days, p = 0.003), and the incidence of hospitalization for more than 3 days in the neonatal intensive care unit was increased (10.3% vs 2.2%). Logistic regression did not support maternal age of 35 years and older as being the single significant risk factor for adverse neonatal and maternal outcome. We conclude that maternal age older than 35 years entails a higher risk for the mother and her newborn infant, even when good prenatal care is taken.

The effect of mode of delivery on long-term outcome of very low birthweight infants.

A prospective 2-year neurodevelopmental follow-up was carried out on 69 very low birthweight (VLBW) infants (< 1501 g), born in the years 1985-87. The aim of the study was to determine whether there was a long-term advantage to cesarean section in these infants. The incidence of major disability and cognitive ability at 2 years of age were assessed, comparing modes of delivery. Cesarean section was performed in 38 out of 69 (55.1%) of the infants. Major disability was diagnosed in 11/69 (15.9%) of the children, of whom 7/38 (18.4%) were delivered by cesarean section, compared with 4/31 (12.9%) delivered vaginally. The difference, accounting for presentation and multiple birth was not statistically significant. Cognitive ability at 2 years of age was tested using the Mental Development Index (MDI) of the Bayley Scales, and was compared, according to mode of delivery, in 55 of 58 infants without major disability. There was no statistically significant difference between mean +/- S.E. in the MDI of 28 infants delivered by cesarean section (99.7 +/- 7.3) and that of 27 infants delivered vaginally (95.6 +/- 4). In summary, at 2 years of age, no clinically relevant benefit was found for VLBW infants who had been delivered by cesarean section.

Familial combined duodenal and jejunal atresia.

Combined duodenal and jejunal atresia is extremely uncommon. The familial occurrence of congenital duodenal and small bowel atresia is even more unusual. To the authors' knowledge, this is the first report of two siblings with simultaneous duodenal and jejunal atresia who underwent successful surgical repair. The report may support the genetic origin of some forms of high intestinal atresia.

Heart rate recovery from 1 minute of exercise in children and adults.

Previous studies demonstrated that the time required for oxygen uptake, CO2 production, and minute ventilation to return to baseline levels after 1-min bursts of exercise is different in children compared with adults. To test the hypothesis that the heart rate (HR) recovery time after exercise is also different in children compared with adults, we examined HR in 10 children (range 7-11 y old) and 12 adults (26-42 y old) for 10 min after 1 min of cycle ergometer exercise. Each subject exercised at work rates corresponding to 80% of the lactate or anaerobic threshold (AT), 50% of the difference between AT and maximal O2 uptake (delta), 100% of maximal uptake, and 125% of maximal uptake. Gas exchange was measured breath by breath. In adults, the HR recovery time increased significantly with work intensity as judged by the time constant of a single exponential curve fit to postburst-exercise HR [23 +/- 8 (SD) s at 80% AT, 55 +/- 16 at 50% delta, 74 +/- 13 at 100% of maximal uptake, and 83 +/- 20 at 125% of maximal uptake]. HR recovery time tended to increase with work intensity in children (16 +/- 7, 20 +/- 4, 23 +/- 7, and 27 +/- 9; for 80% AT, 50% delta, 100% of maximal uptake, and 125% of maximal uptake respectively), but to a much smaller extent, and the HR recovery time was significantly smaller in children in the high-intensity (above AT) range of exercise (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Maturation of ventilatory responses to 1-minute exercise.

To test the hypothesis that ventilatory responses to exercise mature during growth in healthy children, we examined CO2 production (VCO2) and minute ventilation (VE) before, during, and for 10 min after 1-min bursts of cycle ergometry exercise. Ten children (range: 7-11 y old) and 13 adults (26-42 y old) exercised at work rates corresponding to 50 and 80% of the anaerobic or lactate threshold, 50% of the difference between anaerobic threshold and maximum O2 consumption, 100% of maximum O2 consumption, and 125% of maximum O2 consumption (125% max). Gas exchange was measured breath by breath. Children recovered faster from high-intensity (above anaerobic threshold) exercise as judged by the time constant of single exponential curve-fits to postexercise VCO2 [55 +/- 10 s (1 SD) at 125%. max in children compared with 92 +/- 17 s at 125% max in adults; p less than 0.001] and VE (58 +/- 10 s at 125% max in children compared with 125 +/- 37 s in adults, p less than 0.001). Although we found no significant difference between VCO2 and VE recovery times in children, VE was significantly slower than VCO2 in adults for high-intensity exercise. Moreover, recovery times in adults increased with work intensity but were independent of them in children. Whereas the CO2 costs [calculated as total CO2 produced above baseline per unit work done (mL.J-1)] increased with work intensity in adults, no similar significant relationship was observed in children.(ABSTRACT TRUNCATED AT 250 WORDS)

The work-rate-dependent effect of carbon monoxide on ventilatory control during exercise.

The effect of low levels of carbon monoxide (CO) was studied during exercise in order to determine the work-rate dependent effect of CO breathing on exercise ventilation (VE). Ten normal subjects (aged 32.8 +/- 7.1 years) were studied during air breathing and air with added CO to bring carboxyhemoglobin (COHb) to approximately 11% and 20%. During the incremental exercise test, VE was not affected by CO breathing at work rates below the lactic acidosis threshold (LAT), defined as the O2 uptake above which CO2 is excreted by the lungs consequent to buffering of metabolic acid (not hyperventilation) (Beaver et al. (1986) J. Appl. Physiol. 60: 2020-2027). However, VE was increased above the LAT as work rate and COHb saturation were increased. At the end of constant work rate exercise, the increase in VE caused by increased COHb was positively correlated (r = 0.83, P less than 0.0001) with the increase in venous lactate sampled 2 min into recovery. This was complemented by a decrease in end-tidal PCO2 versus lactate (r = 0.76, P less than 0.0001). We conclude that the increase in exercise VE resulting from COHb levels up to 20%, is restricted to work rates above the LAT, and is proportionately higher, the greater the lactic acidosis.

Effect of increased metabolic rate on oxygen isotopic fractionation.

16O16O is preferentially used over 18O16O (a stable isotope of oxygen comprising about 0.2% of atmospheric O2) as oxygen is consumed during respiration in humans (Epstein and Zeiri, 1988, Proc. Natl. Acad. Sci. USA 85: 1727-1731). To test the hypothesis that oxygen isotopic fractionation is related to the metabolic rate, 8 healthy adults performed 5 min of constant work rate cycle ergometer exercise below and above their anaerobic threshold. Moreover, 3 subjects performed an incremental exercise to the limit of tolerance. Oxygen uptake (VO2) was measured breath by breath. Samples of the exhaled breath for oxygen isotope measurement were obtained at rest and at various times during exercise and recovery. Oxygen isotopic fractionation was determined by isotope ratio mass spectrometry and calculated as the ratio of the degree of fractionation to the oxygen consumed in the breath sample (Z value). For the constant work rate protocol, both low and high intensity exercise resulted in a significant decrease in Z compared to the rest values (P less than 0.01). However, for the high intensity exercise the reduction in fractionation was greater compared to the low intensity protocol (P less than 0.05). For the incremental test, there was a significant negative correlation between oxygen isotopic fractionation and VO2 expressed as percent of the maximal oxygen uptake (r = -0.91, P less than 0.0001). These data suggest that during exercise low-fractionating processes become more important as limiting steps for O2 transport.

Exchange transfusion in newborns via a peripheral artery and vein.

Exchange transfusion using a peripheral artery and vein was carried out 18 times in 17 newborn infants. The arteries use to withdraw blood were the radial [13], the ulnar [3] an the posterior tibial [2]. Infusion of blood was carried out simultaneously through a peripheral vein. There was no mortality or morbidity directly associated with the procedure. We recommend this technique for exchange transfusion in general, and especially in the very ill newborn.

The outcome of twin pregnancies after IVF.

It has been suggested that the high rates of prematurity, low birth weight, perinatal morbidity and mortality in in-vitro fertilization (IVF) infants are due to the increased frequency of multiple gestations in this population. The aim of our study was to test this hypothesis by comparing the outcome of IVF twins with that of twins born after spontaneously conceived pregnancies. The perinatal outcome of 40 IVF twins was compared with that of 80 control twins, matched for maternal age, parity and ethnic origin. IVF twins had a higher rate of prematurity (P = 0.03), their mean birth weight was significantly lower (P < 0.01) and the frequency of very low birth weight infants was much higher (P < 0.003). There was no neonatal mortality in the control group, whereas four IVF twins died (P < 0.01). Neonatal morbidity was significantly greater in IVF twins (P < 0.05). Oxygen therapy and mechanical ventilation were administered more frequently to IVF twins (P < 0.007 and P < 0.05). We conclude that twins conceived by IVF are at a significantly higher risk for prematurity and associated neonatal morbidity and mortality than spontaneously conceived twins.

13CO2 washout kinetics in acute hypercapnia.

The redistribution of CO2 and bicarbonate throughout the body following perturbations of normal respiration is not well described. We used tracer techniques to examine CO2-bicarbonate dynamics in an animal model in which acute hypercapnia was induced by hypoventilation. Eleven rabbits were anesthetized, tracheostomized, paralyzed and ventilated. In five animals PaCO2 was kept between 30 and 35 mmHg (control, C) while in six PaCO2 was held between 65 and 70 mmHg (acute hypercapnia, AH). A bolus of [13C]bicarbonate was given intravenously. Breath samples were obtained for 13CO2 by isotope ratio mass spectrometry and CO2 output (VCO2) was measured breath-by-breath for 240 min. There was no difference in the VCO2 between C [5.6 +/- 1.8 (SD) ml/min per kg] and AH (5.3 +/- 0.8). The 13CO2 washout for both C and AH was well fit by the sum of three exponentials. Only the time constant of the third (slowest) exponential was significantly longer in AH (103 +/- 11 min) compared with C (75 +/- 15, P less than 0.01). The mean residence time in AH (82 +/- 9 min) was significantly lower than in C (57 +/- 10, P less than 0.001). The estimated mass of exchangeable CO2 and bicarbonate was significantly greater in AH (443 +/- 37 ml per kg) compared with C (312 +/- 63, P less than 0.005). Compartmental analysis indicated that the increase in CO2-bicarbonate occurred primarily in the slowly exchanging pool. The data suggest that acute hypercapnia may be accompanied by a redistribution of exchangeable CO2 and bicarbonate in the body.