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.

Heparinization of alimentation solutions administered through peripheral veins in premature infants: a controlled study.

A randomized controlled study was done to determine whether the addition of heparin (1 U/mL) to peripheral intravenous alimentation solutions would affect the incidence of phlebitis and duration of patency of intravenous catheters in premature infants. Twenty-two-gauge Teflon catheters were uniformly used. One hundred five catheters infused with heparin were placed in 13 infants, and 122 catheters were placed in the control group of 13 infants. The time, nature, and incidence of complications were noted for each infusion site. Infusion of heparin was found to double the duration of patency of intravenous catheters and to reduce significantly the incidence of phlebitis. No complications related to the administration of heparin were noted. Heparinization of intravenous alimentation solutions should therefore be considered in premature infants as a means of reducing the work load and incidence of complications associated with peripheral lines.

Aminophylline versus doxapram in idiopathic apnea of prematurity: a double-blind controlled study.

A double-blind controlled study, in two parts, was undertaken to compare the effectiveness of aminophylline and doxapram therapy in idiopathic apnea of prematurity. In the first part of this study, eight of 15 infants responded to doxapram therapy with complete cessation of apneic spells and six of 11 infants responded similarly to administration of aminophylline. These differences were statistically insignificant. In the second part of the study, assessment was made of whether the addition of doxapram to aminophylline therapy was effective in treatment of apnea of prematurity that had been unresponsive to aminophylline alone. Of ten infants who continued to have apneic spells during treatment with aminophylline, eight responded to the addition of doxapram with complete cessation of apnea. Nine infants received placebo in addition to aminophylline, and none had a reduction in frequency of apnea.

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.

Lung function in infancy and childhood following neonatal intensive care.

Pulmonary function studies were performed in 11 neonatal intensive care survivors both during infancy and later in childhood. Lung function was compared with the respiratory support given in the neonatal period. The mean +/- SE thoracic gas volume was 96 +/- 4% predicted in infancy and rose to 122 +/- 8% predicted during childhood (P less than 0.005). The specific airway conductance (SGaw) in infancy was 57 +/- 7% predicted and rose to 90 +/- 8% predicted in childhood (P less than 0.0025). Abnormalities in SGaw were found only in ventilated infants, and there was a negative logarithmic correlation between the treatment score in the neonatal period and the SGaw in both infancy and childhood. The data indicate a long-term improvement in airway conductance of moderately affected infants with the development of mild hyperinflation in childhood possibly resulting from residual small airway abnormalities despite a symptomless clinical course. The residual abnormalities in prematurely born infants were in proportion to the intensity of treatment required in the neonatal period.

Idiopathic gastrointestinal perforation in the neonate.

Spontaneous localized perforation of the gastrointestinal tract, unrelated to mechanical intestinal obstruction and with no evidence of necrotizing entrocolitis (NEC), occurred in 20 neonates. Three perforations were located in the stomach, 11 in the small intestine, and six in the colon. Maternal obstetric complications as well as prematurity and postnatal distress were common in these patients. The overall survival rate was 80%. There was no late gastrointestinal symptoms in the survivors. Whether idiopathic perforation of the gastrointestinal tract results from a localized form of NEC or from a distinct lesion of unknown etiology has not yet been ascertained. Some ideas concerning the etiology of this entity, as well as some diagnostic aspects are discussed.

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.

[Tolerance of moderate hypothermic therapy: it's effect on the neonatal cardiovascular system and particularly pulmonary and intestinal circulation]. / Tolérance de l'hypothermie thérapeutique modérée: son effet sur le système cardiovasculaire néonatal et notamment la circulation pulmonaire et intestinale.

We present a study in which we investigated the safety of therapeutic mild hypothermia on the neonatal cardiovascular system. In an attempt to mimic the state of affairs that may follow an hypoxic-ischemic insult, the effect of moderate hypothermia was studied under conditions where cardiovascular integrity was impaired. Newborn piglets where randomized to either receive a thromboxane A2 mimetic or an hypoxic inspiratory gas mixture. Periods of hypothermia (5 degrees C below normothermic level) preceded or were combined with those agents in a random manner. Isolated hypothermia decreased cardiac output by 25%, and increased pulmonary vascular resistance by 48%. Mesenteric blood flow and cerebral blood flow decreased by a similar magnitude (21 and 18% respectively). When hypothermia was combined with alveolar hypoxia or thromboxane, the increase in pulmonary vascular resistance (103 and 292% respectively) exceeded the increase produced by the sum of each individual component. In contrast neither hypoxia nor thromboxane potentiates the hypothermia induced decrease in mesenteric blood flow. Ileal mucosal blood flow remained stable for all conditions. We conclude that mild therapeutic hypothermia may be safe in conditions where cardiac function is impaired, but may be more hazardous when severe pulmonary hypertension is present.

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.