Enzymatically inactive red cell carbonic anhydrase B in a family with renal tubular acidosis.

An inactive mutant form of red cell carbonic anhydrase B is described in three members of a large kindred who manifest infantile renal tubular acidosis and nerve deafness. A combination of enzymatic and immunologic investigations permitted its detection, despite the fact that both antigenic and electrophoretic properties of the mutant were identical to those of the normal form.

Acute ventilator-induced vascular permeability and cytokine responses in isolated and in situ mouse lungs.

To determine the influence of experimental model and strain differences on the relationship of vascular permeability to inflammatory cytokine production after high peak inflation pressure (PIP) ventilation, we used isolated perfused mouse lung and intact mouse preparations of Balb/c and B6/129 mice ventilated at high and low PIP. Filtration coefficients in isolated lungs and bronchoalveolar lavage (BAL) albumin in intact mice increased within 20-30 min after initiation of high PIP in isolated Balb/c lungs and intact Balb/c, B6/129 wild-type, and p55 and p75 tumor necrosis factor (TNF) dual-receptor null mice. In contrast, the cytokine response was delayed and variable compared with the permeability response. In isolated Balb/c lungs ventilated with 25-27 cmH(2)O PIP, TNF-alpha, interleukin (IL)-1 beta, IL-1 alpha, macrophage inflammatory protein (MIP)-2, and IL-6 concentrations in perfusate were markedly increased in perfusate at 2 and 4 h, but only MIP-2 was detectable in intact Balb/c mice using the same PIP. In intact wild-type and TNF dual-receptor null mice with ventilation at 45 cmH(2)O PIP, the MIP-2 and IL-6 levels in BAL were significantly increased after 2 h in both groups, but there were no differences between groups in the BAL albumin and cytokine concentrations or in lung wet-to-dry weight ratios. TNF-alpha was not be detected in BAL fluids in any group of intact mice. These results suggest that the alveolar hyperpermeability induced by high PIP ventilation occurs very rapidly and is initially independent of TNF-alpha participation and unlikely to depend on MIP-2 or IL-6.

Effect of modulators of hypoxic pulmonary vasoconstriction on the response to inhaled nitric oxide in a neonatal model of severe pulmonary atelectasis.

Hypoxic pulmonary vasoconstriction (HPV) is an intrinsic mechanism that facilitates ventilation to perfusion matching and preservation of oxygenation. We investigated the neonatal HPV response from extensive atelectasis and tested the hypothesis that (I) the resulting hypoxemia is corrected by inhaled nitric oxide (NO); (2) the "pulmonary steal" of blood away from hypoxic area is further improved by modulators of the HPV. Intratracheal injection of steel beads in 32 piglets (7 to 20 days) resulted in atelectasis of 50% to 75% of the lungs. The piglets were then randomized to receive saline (control), indomethacin (IND) 2 mg/kg, doxapram (DOX) 0.5 mg/kg/h or almitrine (ALM) 4 micrograms/kg/min. After 30 minutes, all animals were subjected to NO at 40 ppm. Atelectasis resulted in severe impairment in oxygenation (PaO2 - 105 +/- 6 mm Hg, AaDO2 = 536 +/- 9 mm Hg; shunt fraction = 31% +/- 2%) and moderate pulmonary hypertension. Mean pulmonary artery pressure (PAP) increased to 35 +/- 0.8 mm Hg. NO reduced pulmonary vascular resistance (PVR) from 128 +/- 14 mm Hg/kg/mL/min to 74 +/- 9 mm Hg/kg/mL/min and improved gas exchange (PaO2 = 180 +/- 50 and AaDO2 = 438 +/- 50 mm Hg). Following the development of atelectasis, the peripheral chemoreceptor agonists (ALM and DOX) did not modify gas exchange and had no significant cardiovascular effect. ALM and DOX failed to enhance the response to NO. IND did not alter HPV, but prevented the improvement in gas exchange associated with NO-induced pulmonary vasodilation.

Decreased fetal activity and fetal heart rate changes after amniocentesis complicated by fetal hemorrhage.

A case is described in which amniocentesis caused placental injury, abruptic placenta, and fetal hemorrhage which caused fetal distress. This was primarily manifested by reduction of fetal movements and later by fetal heart rate deceleration. Emergency cesarean section was performed of monitoring the fetus after amniocentesis by assessment of fetal movements is stressed.

Plasma ascorbic acid levels in premature infants.

During gestation the fetus is abundantly provided with vitamin C, but inadequate postnatal provision of the vitamin may lead to early hypoascorbemia. Since premature newborns are often prevented from full alimentation for a considerable length of time, ascorbate deficiency may result. Plasma ascorbate levels of 20 premature newborns were determined during the first two weeks of life. Daily ascorbate intake of less than 5 mg/kg b. w. resulted in a decline of plasma ascorbate level from 1.56 +/- 0.15 mg/100 ml (mean +/- SEM) on the first day of life to a low level of 0.48 +/- 0.05 mg/100 ml by two weeks of age. An increase of daily ascorbate intake to 5--10 mg/kg b.w. resulted in a higher plasma concentration of 0.79 +/- 0.09 mg/100 ml (p less than 0.02) while parenteral supplementation of 50 mg vitamin C daily provided for a high plasma concentration of 2.7 +/- 0.46 mg/100 ml (p less than 0.005) when compared with the other two groups. Maturational and environmental factors may impose a higher demand for vitamin C during early premature life and therefore adequate amounts of the vitamin should be early provided.

Vitamin E and vitamin C plasma levels in premature infants following supplementation of vitamin C.

Our preliminary data suggest that supplementation of premature neonates with vitamin C is required to maintain adequate ascorbate plasma levels and may have a sparing effect on vitamin E metabolism. Further studies are required to validate our findings and evaluate the possible antioxidant advantage of ascorbic acid administration.

Cerebellar hemorrhage: a major morbidity in extremely preterm infants.

OBJECTIVE: To determine the impact of cerebellar hemorrhage (CH) on mortality and adverse neurodevelopmental (ND) outcome rates in extremely preterm infants admitted to a tertiary neonatal unit. STUDY DESIGN: A total of 1120 eligible infants (<28 weeks gestation) were born from 1998 to 2008 and had at least one cranial ultrasound. ND outcome was determined at 12 to 18 months corrected age. RESULTS: Most CH (75%) occurred in infants <25 weeks gestation. CH did not affect mortality rates, however, it was associated with both mental and motor impairments, with incidence rate ratios of 3.08 (1.71 to 4.84) and 2.12 (1.12 to 3.45), respectively. Moreover, the risk of cerebral palsy (CP) was increased in infants with CH involving the medial part of the cerebellum. CONCLUSION: Our findings substantiate recent reports about the cerebellum, highlighting its role in cognitive and executive functions, and associating early cerebellar injury not only with CP but also with learning, affective and behavioral disorders.

A practical and reliable method of measuring blood pressure in the neonate by pulse oximetry.

OBJECTIVE: We investigated the reliability of the plethysmographic waveform of the pulse oximeter to measure systolic blood pressure in sick neonates. METHODS: Fifty infants admitted to the neonatal intensive care unit, with indwelling arterial catheters placed for their ongoing care, were enrolled. Median gestational age was 31 weeks (range, 24 to 40 weeks), and the mean birth weight was 1711 gm (range, 546 to 3856 gm). Blood pressure was recorded by an oscillometric method as well as from a transducer connected to an arterial catheter. Additionally, pulse oximeter blood pressures were obtained by gradually inflating an appropriately sized blood pressure cuff in increments of 2 to 5 mm Hg, on the same extremity as the oximeter probe, until the waveform just disappeared. The cuff was then rapidly inflated another 20 mm Hg and then gradually deflated in increments of 2 to 5 mm Hg until the waveform reappeared on the oximeter screen display. The pulse oximeter blood pressures were calculated both as the blood pressure noted at disappearance of the pulse oximeter waveform and as the blood pressure noted by the average pulse oximeter blood pressure at the disappearance and reappearance of the waveform. The mean intraarterial systolic blood pressure was 54 mm Hg (range, 36 to 82 mm Hg). RESULTS: Blood pressures obtained by pulse oximetry showed a significantly better correlation with intraarterial measurements in comparison with those obtained by oscillometric instruments. Additionally, the limits of agreement (mean difference +/- 2 SD) between blood pressures obtained by intraarterial measurements and those obtained by pulse oximetry were within a clinically acceptable range as opposed to those obtained by the comparison of intraarterial and oscillometric methods. CONCLUSION: Measurements of blood pressure in the neonate by means of pulse oximetry waveform analysis are easily obtainable and more accurate than those obtained by the oscillometric method.

High plasma ascorbic acid levels in premature neonates with intraventricular hemorrhage.

The accumulation of ascorbic acid in the brain by active transport establishes a high brain-plasma gradient of the vitamin. An insult to the CNS may result in an efflux of ascorbate into the circulation with a consequent rise of plasma levels. We measured plasma ascorbic acid levels in premature neonates on days 1, 3, and 5 of life, and the infants underwent ultrasonographic examination to detect intracranial hemorrhage. Neonates with intraventricular hemorrhage sustained significantly higher plasma ascorbate levels than their controls. Infants with massive bleeding had higher levels than those with a smaller hemorrhage. These results suggest that an efflux of ascorbic acid into the circulation occurs secondary to intracranial hemorrhage.

High frequency chest wall compression in cats with normal lungs.

Ten anesthetized, paralyzed adult cats were ventilated by high frequency chest wall compression (HFCWC) at 3, 5, 7, and 9 Hz by means of a single chamber cuff enclosing the thorax from the axillae to the xyphisternum. The effects of HFCWC in terms of gas exchange, end-expiratory lung volume, and respiratory system compliance were compared to conventional intermittent positive pressure ventilation (IPPV) (30 breaths/mn). HFCWC and IPPV were compared at three levels of matched end-expiratory airway pressure [continuous positive airway pressure (CPAP)/positive end-expiratory pressure/(PEEP) of 0, 2, and 5 cm H2O]. In the absence of CPAP, HFCWC resulted in a marked decrease (up to 50%) in end-expiratory lung volume with significantly lower PaO2, lower compliance, and higher alveolar-arterial oxygen gradient than during IPPV. No differences in PaO2 and a-ADO2 were observed when HFCWC was combined to CPAP greater than or equal to 2 cm H2O. At frequencies below 9 Hz, PaCO2 became significantly lower during HFCWC + CPAP than during IPPV. During HFCWC + 2 cm H2O CPAP, lung volume was lower than during IPPV + 2 cm H2O and similar to the volumes observed during IPPV + 0 positive end-expiratory pressure. Additional studies in six cats at HFCWC + 3 cm H2O confirmed that CPAP greater than 2 cm H2O more than adequately compensated the decrease in lung volume associated with HFCWC alone. Peak cuff pressures between 14 and 17 cm H2O generated oscillary tidal volumes between 4.5 and 2.1 ml/kg. The size of the oscillatory volume was significantly affected by increasing frequencies (decrease in tidal volume) and increasing levels of positive airway pressure (increase in tidal volume). We conclude that in cats with normal lungs, HFCWC can provide for normal gas exchange, provided that it is combined with low level CPAP in order to prevent the occurrence of airway closure associated with HFCWC alone.

Air embolus following pulmonary interstitial emphysema in hyaline membrane disease.

Two cases of hyaline membrane disease are presented complicated by severe, interstitial emphysema and resulting in death from air embolus. This is consistent with the experimental evidence of other investigators that shows that such an air embolus may be more common complication of hyaline membrane disease than previously expected.

High-frequency positive-pressure ventilation in neonates.

Twenty-five newborn infants with severe respiratory failure responding poorly to conventional mechanical ventilation were switched to high-frequency positive-pressure ventilation (HFPPV) at 90 to 180 cycle/min (mean 158), an estimated tidal volume less than or equal to 3 ml/kg body weight, an inspiratory time of 0.1 sec, and a PEEP of 3 to 17 cm H2O. In all infants, HFPPV increased PaO2 (mean 66 torr) and decreased PaCO2 (mean 14 torr) within 1 h. Fourteen hours after onset of treatment, the FIO2 requirement had decreased from 1.0 to 0.6 in all infants. Mean airway pressure (Paw) with HFPPV was usually less than or equal to Paw during conventional ventilation. In spite of the often high level of PEEP used, pneumothorax occurred in only 2 infants and bronchopulmonary dysplasia in 1. Eighteen (72%) infants survived and none died of respiratory failure. The use of HFPPV might be beneficial in neonates with severe respiratory failure that responds poorly to conventional therapy.

Comparison of high-frequency negative-pressure oscillation with conventional mechanical ventilation in normal and saline-lavaged cats.

We modified a negative-pressure respirator to produce high-frequency, subatmospheric pressure oscillations around the chest. The effects of negative-pressure oscillation (NPO) on gas exchange, lung volume, compliance and cardiovascular variables were compared to those of conventional intermittent positive-pressure ventilation (IPPV) at 30 breath/min, using cats with normal and surfactant-depleted lungs. For frequencies in both normal lungs (1, 3, 4, 5, and 7 Hz) and saline-lavaged lungs (3, 5, and 7 Hz), peak inflating pressures were lower during NPO. Oxygenation was similar for both modes of ventilation. In cats with normal lungs, PaCO2 was significantly lower during NPO at 3 and 4 Hz (mean 24 torr) than during IPPV (mean 30 torr); normocapnia was maintained at the other frequencies. In damaged lungs, NPO and IPPV at 3 and 5 Hz resulted in similar CO2 removal, but PaCO2 was significantly higher during NPO at 7 Hz. Oscillatory tidal volumes decreased with increasing frequencies: in normal lungs, mean oscillatory tidal volume was 4.4 ml/kg at 1 Hz and 2.3 ml/kg at 7 Hz; in damaged lungs it was 6.5 ml/kg at 3 Hz and 3.2 ml/kg at 7 Hz. At 3 Hz and above, NPO was associated with a larger functional residual capacity than during sequences of IPPV matched for end-expiratory transthoracic pressure. There were no significant differences in respiratory system compliance, cardiac output, and pulmonary vascular resistance between both modes of ventilation. Further studies are warranted to investigate the potential clinical usefulness of NPO.

Aminophylline versus doxapram in weaning premature infants from mechanical ventilation: preliminary report.

A small, double-blind crossover study compared the efficacy of aminophylline and doxapram in ventilator weaning of eight premature infants recovering from respiratory distress syndrome (RDS). Although neither drug was significantly better than the other, four infants were weaned from mechanical ventilation after drug administration. It is suggested that drugs stimulating the respiratory center may aid in shortening the duration of mechanical ventilation in premature infants recovering from RDS.

High-frequency oscillatory ventilation versus conventional ventilation in a piglet model of early meconium aspiration.

OBJECTIVE: To compare the cardiopulmonary effects of high-frequency oscillatory ventilation (HFO) and conventional ventilation (CV) in a piglet model of meconium aspiration syndrome. DESIGN: Prospective, randomized control study. SUBJECTS: Piglets 1 to 2 wks of age. INTERVENTIONS: Meconium aspiration was induced in 30 piglets. They were then randomized to CV, HFO at 10 Hz, or HFO at 15 Hz. MEASUREMENTS AND MAIN RESULTS: Arterial blood gas, and systemic and pulmonary hemodynamics were measured serially. Airway opening pressure (P-Flex), static lung compliance (Crs), and trapped gas volume (TGV) were derived. Meconium instillation produced similar stable decreases in Crs (6.7 +/- 0.7 [SEM] to 4.7 +/- 0.4 mL/cm) and increases in pulmonary vascular resistance (68 +/- 6.4 vs. 91.9 +/- 8.5 mm Hg/mL/kg/min). A greater proportion of animals (40%, p< .007) remained hypercarbic during HFO at 15 Hz. Oxygenation indices were similar for all groups. In regards to high-frequency support, both power and deltaP were higher in the HFO at 15 Hz group (p< .001). When compared with both CV and HFO at 10 Hz, the TGV in the HFO at 15 Hz group was significantly higher following randomization to ventilator type. P-Flex was also greatest in the 15 Hz group, followed by the 10 Hz group and the CV group. Higher airway opening pressures, given identical compliance, suggest that HFO at 15 Hz resulted in greater large airway obstruction. With HFO's inherent low tidal volumes, progression of meconium to the distal airways may be delayed. CONCLUSIONS: Early institution of HFO at 15 Hz in meconium aspiration may exacerbate air trapping. HFO at lower rates may be the optimal method of respiratory support in meconium aspiration syndrome. HFO may extend the window of time available for removal of meconium.

Early diagnosis of necrotizing enterocolitis.

This study demonstrates that the diagnosis of necrotizing enterocolitis can sometimes be made before the full-blown clinical and radiographic findings are manifest. Of 12 infants with films available prior to diagnosis of the disease, nine had early selective dilatation of small bowel and little or no air in the colon. Necrotizing enterocolitis should be foremost in the differential diagnosis when this finding is coupled with signs such as abdominal distention, acidosis, and diarrhea.

Does the pattern of ventilation determine the degree of lung damage following intensive care of the newborn?

Lung function tests were performed on 14 infants 22 to 67 wk following mechanical ventilation of 6 h to 51 days and on 5 infants of comparable age who had been treated with continuous positive airway pressure (CPAP). Airway resistance increased (P less than 0.01) and specific airway conductance decreased (P less than 0.001) in the ventilated infants compared with the CPAP-treated group who were normal. The airway resistance and specific airway conductance were normal in two ventilated infants and in one CPAP-treated infant who were studied earlier in the neonatal period. There were no significant differences in thoracic gas volume between groups of ventilated and nonventilated babies studied initially or at follow-up. There was no relationship between lung damage and the following: peak inspiratory pressure, the duration of high pressure ventilation, the level of CPAP or its duration, or the duration of greater than 60% oxygen administration. The degree of lung damage was not related to the maximum ventilatory frequency used, but there was a significant correlation with the duration of rapid frequency ventilation. This study supports the view that barotrauma is a major cause of lung disease following neonatal intensive care.