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The localization of monocytes to sites of inflammation is mediated by interactions with extracellular matrix components including fibronectin, a nonimmune opsonin with binding sites for collagen, fibrin, heparin, and cell surfaces. This study demonstrates that newborn infants' monocytes bind to both gelatin (i.e., denatured collagen) and matrix-bound fibronectin to a degree comparable to that of adult-derived cells.

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To test the hypothesis that restriction of sodium intake during the first 3 to 5 days of life will prevent the occurrence of hypernatremia and the need for administration of large fluid volumes, we prospectively and randomly assigned 17 babies (mean +/- SD: 850 +/- 120 gm; 27 +/- 1 weeks of gestation) to receive in blind fashion either daily maintenance sodium or salt restriction with physician-prescribed parenteral fluid intake. Maintenance-group infants received 3 to 4 mEq of sodium per kilogram per day; restricted infants received no sodium supplement other than with such treatments as transfusion. Sodium balance studies conducted for 5 days demonstrated that maintenance salt intake resulted in a daily sodium balance near zero, whereas sodium-restricted infants continued to excrete urinary sodium at a high rate, which promoted a more negative balance (average daily sodium balance -0.30 +/- 1.78 SD in maintenance group vs -3.71 +/- 1.47 mEq/kg per day in restriction group; p less than 0.001). Care givers tended to prescribe daily increases in parenteral fluids for the salt-supplemented infants, perhaps because serum sodium concentrations were elevated in these infants after the first day of the study (p less than 0.001). Hypernatremia developed in two sodium-supplemented infants (greater than 150 mEq/L), and hyponatremia developed in two sodium-restricted infants (less than 130 mEq/L); however, the restricted infants were more likely to have normal serum osmolality (p less than 0.05). Both groups of infants produced urine that was neither concentrated nor dilute, with a high fractional excretion of sodium; renal failure was not observed. The mortality rate was not affected, but the incidence of bronchopulmonary dysplasia was significantly less in the sodium-restricted babies (p less than 0.02). We conclude that in tiny premature infants, a fluid regimen that restricts sodium may simplify parenteral fluid therapy targeted to prevent hypernatremia and excessive administration of parenteral fluids.

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Phototherapy has been used to treat neonatal hyperbilirubinemia for more than three decades; however, it is only during the last ten years that an understanding of the mechanism of action of phototherapy has emerged. While visible light is known to photooxidize and photoisomerize bilirubin, recent data suggest that the formation of bilirubin structural isomers (lumirubin) is responsible for the decrement in serum bilirubin. This paper discusses current clinical recommendations for light dosage and wavelength and develops new guidelines based upon recent information of how light effects a reduction in the serum bilirubin concentration.

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Elastase activity and concentrations of alpha 1-proteinase inhibitor, albumin, and fibronectin were measured in bronchoaleolar lavage (BAL) fluid from ventilated lungs in preterm neonates with lung disease before and after treatment with dexamethasone or indomethacin. Treatment with dexamethasone was associated with a significant decrease in BAL elastase activity but no change in fibronectin, albumin, or alpha 1-proteinase inhibitor concentrations. In contrast, treatment with indomethacin was associated with an increase in BAL elastase activity and fibronectin concentration, with no change in albumin or alpha 1-proteinase inhibitor concentrations. Control groups showed no changes in these BAL fluid biochemical markers during a similar time period. These data indicate that treatment with corticosteroids decreases lung inflammation as measured by BAL elastase activity. Corticosteroid treatment may not inhibit the development of pulmonary fibrosis, because fibronectin concentrations in BAL fluid were unaffected. Indomethacin treatment may augment lung inflammation and fibrosis by increasing BAL elastase activity and fibronectin concentration.

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Eighteen very low birth weight premature infants born before 28 weeks gestation and weighing less than 1000 gm were evaluated prospectively for disturbances in serum electrolyte concentrations and for renal glomerular and tubular functions. Clinically symptomatic hyperkalemia resulting in significant electrocardiographic dysrhythmias developed in eight of these infants; 10 babies remained normokalemic. Peak serum potassium concentration ranged from 6.9 to 9.2 mEq/L in the hyperkalemic group; all potassium values in the normokalemic group were less than 6.6 mEq/L. Indices of renal glomerular function and urine output were similar in both groups; no infant had oliguria. Serum creatinine concentrations were the same in both groups (1.04 +/- 0.16 SD mg/dl in normokalemic vs 1.19 +/- 0.24 mg/dl in hyperkalemic infants, beta less than 0.2 at alpha = 0.05), and glomerular filtration rates did not differ significantly (6.29 +/- 1.78 ml/min/1.73 m2 in normokalemic vs 5.70 +/- 1.94 ml/min/1.73 m2 in hyperkalemic infants, beta less than 0.2 at alpha = 0.05). In contrast, indicators of tubular function revealed a significantly larger fractional excretion of sodium in hyperkalemic infants: 13.9 +/- 5.4% versus 5.6 +/- 0.9% in normokalemic control subjects (p less than 0.001). Hyperkalemic infants also had a tendency toward lower urine concentrations of potassium, although there was no significant difference in their net potassium excretion in comparison with that in the normokalemic group. We speculate that hyperkalemia in the tiny baby is in part the result of immature distal tubule function with a compromise in ability to regulate potassium balance.

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The effect of heparin dose and infusion rate on plasma lipids, lipases, and unbound bilirubin was investigated in 22 premature infants with physiologic jaundice. Infants were randomly assigned to receive low or high intravenous doses (24 vs 137.3 U/day) of heparin. Each patient then received 2 g/kg/day of 10% Intralipid on 2 successive days: one day during a 15-hour period and the other day over 24 hours, with the order assigned randomly. The results demonstrate a significantly greater change in serum-free fatty acids in infants receiving the high heparin dose during the 15-hour lipid infusion period. Lipoprotein lipase activity rose more with the high heparin dose and equally at either infusion rate. We conclude that lipid infusions of 2 g/kg/day with low heparin dosage infused over 24 hours resulted in less elevation in serum-free fatty acids. There were no adverse effects on unbound bilirubin at either infusion rate or heparin dosage.

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Plasma for fibronectin determinations was obtained from 39 neonates with uncomplicated respiratory distress syndrome (RDS) and from 15 infants with RDS who developed bronchopulmonary dysplasia (BPD). Tracheal lavage fibronectin and albumin concentrations were measured in 15 infants with RDS and 15 with BPD. Control plasma fibronectin values were obtained from 20 healthy preterm infants on days 1, 2, 3, 14, and 30 of life. Control tracheal lavage fibronectin and albumin concentrations were measured in 17 neonates of various gestational ages who required tracheal intubation for nonpulmonary indications. Mean plasma fibronectin concentrations from patients with RDS was 121 +/- 11 micrograms/ml on days 1, 2, and 3, versus control level of 163 +/- 12 micrograms/ml (P less than 0.01). Mean tracheal lavage fibronectin/albumin ratio was 3.8 +/- 0.6 ng per microgram of albumin on days 1 to 5 for infants with RDS, versus control level of 5.6 +/- 3.6 (P = NS). Tracheal lavage fibronectin/albumin ratio from patients with BPD was elevated at 16.3 +/- 5.0 ng fibronectin per microgram of albumin on days 14 to 21, and 23.6 +/- 7.4 on day 30 (P less than 0.05 versus control and and versus RDS days 1 to 10). Low plasma fibronectin concentrations early in RDS may contribute to the development of pulmonary capillary leak. High tracheal lavage fibronectin levels may foster the development of pulmonary fibrosis in patients with BPD.

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To establish guidelines for the routine use of diphtheria, tetanus, and pertussis (DTP) vaccine in preterm infants, we quantitated antibody responses of preterm infants to DTP and determined the nature and extent of side effects. Twenty-five preterm infants were immunized with 0.5 ml DTP vaccine at routine intervals. Term infants served as controls. Immediately before each immunization and 2 months after the third, DTP-specific antibodies were quantitated. Clinical side effects were determined by parental report. After the second immunization, 100% of preterm infants had evidence of specific antibody production against diphtheria, tetanus, and pertussis. The incidence of side effects was low, but irritability was significantly more common in preterm infants after the second immunization. These observations suggest that the initiation of primary immunization with DTP in preterm infants need not be delayed beyond 2 months of age.

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Twenty-two preterm infants (birth weight 850 +/- 220 gm) were randomly assigned to receive phototherapy either soon after birth or after the serum bilirubin concentration reached 5 mg/dl. Infants receiving prophylactic phototherapy were placed under lights at a significantly earlier age and lower serum bilirubin concentration than infants in the routine group (P less than 0.001). There was no significant difference between groups in peak serum bilirubin concentration, age at which it peaked, rate of rise in serum bilirubin concentration, or serum bilirubin concentration at any time during the study. Infants assigned to the prophylactic phototherapy group were under lights for a significantly longer time than those in the routine group (P less than 0.05). There was a significant rise in both configurational and structural photo-isomers (P less than 0.005) independent of serum bilirubin concentration after phototherapy in all patients. These data suggest that the clinical course of hyperbilirubinemia is not altered in infants with very low birth weight receiving prophylactic phototherapy compared with infants with phototherapy begun at a bilirubin concentration of 5 mg/dl.

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The purpose of our study was to compare the effects of narrow-spectrum blue light and broad-spectrum white light on the production of bilirubin photo-isomers in human infants with jaundice. Twelve preterm infants were studied under both white and blue light. Irradiance at 450 nm was controlled at 12 microW/cm2/nm for both light sources. Each light condition (white or blue) was administered for 12 hours. Bilirubin isomers (4Z,15E-bilirubin and lumirubin) were measured before therapy and after 12 hours of each sequential light condition. The percentage of 4Z,15E-bilirubin was greater under blue light than under white light (P less than 0.01) phototherapy. There was no significant difference in percentage lumirubin under white or blue light therapy. Our data indicate that blue light is more effective than white light in producing 4Z,15E-bilirubin in vivo. Our study demonstrates that when irradiance in the bilirubin absorbance spectrum is constant, the color of light (spectral distribution) will determine the relative concentrations of photo-isomers produced.

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To study the effects of two different heat shields commonly used under radiant warmers (thin plastic blanket vs a plastic body hood) on premature newborn infants, eight neonates were studied to measure insensible water loss and radiant power density at the skin under control and two shielded conditions. The body hood was found to diminish transmission of radiant heat to the infant's skin by 80%, absorbing heat and becoming warm (P less than 0.001). The plastic blanket absorbed only 15% of radiant warmer heat output (P less than 0.01). Insensible water loss was significantly less under the plastic blanket (1.88 +/- 0.4) ml/kg/hour) than under control (2.70 +/- 0.50 ml/kg/hour, P less than 0.01) and hood (2.86 +/- 0.32 ml/kg/hour, P less than 0.05) conditions. There was no decrease in insensible water loss under the hood compared to controls. This study demonstrates that a thin plastic blanket is the more effective shield against insensible water loss under a radiant warmer. Caution should be exercised with any shielding device to prevent interference with radiant heat delivery.

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Ten premature infants nursed on servocontrolled radiant warmer beds were studied in three environments designed to alter one or more factors affecting heat transfer (convection, evaporation, and radiation). In the control environment, infants were nursed supine on an open warmer bed. The second environment (walled chamber) was designed to reduce convection and evaporation by placing plastic walls circumferentially around the bed. In the third environment convection and evaporation were minimized by covering infants with a plastic blanket. Air turbulence, insensible water loss, and radiant warmer power were measured in each environment. There was a significant reduction in mean air velocity in the walled chamber and under the plastic blanket when compared to the control environment. A parallel decrease in insensible water loss occurred. In contrast, radiant power demand was the same for control and walled environments, but decreased significantly when infants were covered by the plastic blanket. This study suggests that convection is an important factor influencing evaporation in neonates nursed under radiant warmers. The thin plastic blanket was the most effective shield, significantly reducing radiant power demand.

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To determine the relationship between improvement in pulmonary function and diuresis in respiratory distress syndrome, ten consecutive premature infants requiring mechanical ventilation for severe RDS were studied. Every infant had a diuresis (output/intake greater than 80%), which began at 26 to 34 hours of life and which lasted for an additional 64-72 hours. The diuresis preceded significant improvement in AaDo2 and ventilator settings (IMV, PIP, PEEP) by 52 hours. There was a significant decrease in body weight among all study infants during the first four days of life despite an increase in fluid intake. This study suggests a relationship in RDS between improvement in oxygenation and removal of interstitial lung edema.

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We have developed an enzyme-linked monoclonal antibody inhibition assay to detect bacterial antigens in cerebrospinal fluid. The monoclonal antibody used in this immunodiagnostic test was produced by continuous cultures of hybrid myeloma cell lines. Using this assay, type III GBS antigen was detected in CSF specimens from 11 culture-proven cases of GBS meningitis and in the knee aspirate from an infant with GBS septic arthritis. Five spinal fluid specimens from meningitis due to other bacterial pathogens and ten other control samples were negative. The ELMIA detected streptococcal antigen at a concentration of 10 ng/ml, and is more sensitive and specific than currently used immunodiagnostic tests.

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A retrospective study of ten patients with infant botulism who received gentamicin or kanamycin suggests that aminoglycoside antibiotics potentiate muscular weakness and precipitate respiratory failure as late as 27 days after onset of the disease. Although it is difficult to separate progression of the disease from the effects of antibiotics, the rapidity of deterioration following aminoglycoside treatment and the rapidity of recovery following cessation of aminoglycoside therapy is highly suggestive. A review of five patients who received only penicillin or a semisynthetic derivative of penicillin did not reveal any temporal deterioration with onset of penicillin therapy or improvement with cessation of penicillin therapy.

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A controlled trial of the use of intermittent phototherapy for the treatment of hyperbilirubinemia in newborn infants is reported. Periods of illumination of (1) 15 minutes light on, 15 minutes light off, (2) 15 minutes on, 30 minutes off, and (3) 15 minutes on, 60 minutes off are as effective as is continuous illumunation. A comparison with previous trials of intermittent phototherapy is made and differences in results are explained using as a model the action of light on bilirubin.

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The appropriate therapy for methyprylon (Noludar) poisoning has remained controversial, owing to a lack of reliable pharmacologic data concerning the most effective way to remove the drug after a large ingestion. We recently employed peritoneal dialysis to treat a 16-year-old girl, who had ingested 6.3 gm of methypyrlon, and were able to recover more than 80% of the unmetabolized drug in the dialysate. Clinical recovery was complete within eight hours. This appears to be a safe and effective method to remove the drug in the child or adult with a serious intoxication.

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