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Seven newborns were treated with recombinant tissue plasminogen activator for arterial thromboses. Complete lysis occurred in four of seven and partial in two of seven patients. Serious bleeding complications were observed in two of seven patients. This and published experience suggest that successful lysis with recombinant tissue plasminogen activator occurs in most patients and that hemorrhagic complications are unusual but are not.

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To compare the efficacy of dopamine and dobutamine for the treatment of hypotension (mean arterial blood pressure, < or = 30 mm Hg) in preterm (< or = 34 weeks of gestation) infants with respiratory distress syndrome in the first 24 hours of life, we enrolled 63 hypotensive preterm infants in a randomized, blind trial. Inclusion criteria required an arterial catheter for measurement of mean arterial blood pressure, treatment with exogenous surfactant, and persistent hypotension after volume expansion with 20 ml/kg (packed erythrocytes if hematocrit < 0.40, 5% albumin if > or = 0.40). Intravenous study drug infusions were initiated at 5 micrograms/kg per minute and then increased in increments of 5 micrograms/kg per minute at 20-minute intervals until a mean arterial blood pressure > 30 mm Hg was attained and sustained for > or = 30 minutes (success) or a maximum rate of 20 micrograms/kg per minute was reached without resolution of hypotension (failure). The study groups at entry were comparable for birth weight, gestational age, postnatal age, gender, birth depression, hematocrit < 0.40, heart rate, oxygenation index, delivery route, maternal chorioamnionitis, and maternal magnesium or ritodrine therapy. No infants in the dopamine group had a treatment failure (0/31; 0%); (16%) of 32 infants failed to respond to dobutamine (p = 0.028). Success was attained at < or = 10 micrograms/kg per minute in 30 (97%) of 31 infants given dopamine and in 22 (69%) of 32 infants given dobutamine (p < 0.01). Among those treated successfully, the increase in mean arterial blood pressure was significantly higher in those given dopamine (mean, 11.3 vs 6.8 mm Hg; p = 0.003). We conclude that dopamine is more effective than dobutamine for the early treatment of hypotension in preterm infants with respiratory distress syndrome.

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The neutropenia often seen in infants of hypertensive mothers (IHMs) at < 12 hours of age has been associated with nosocomial infection in the first 18 days of life. To assess maternal hypertension as an independent factor for nosocomial infection, we compared 101 low birth weight (< or = 2.00 kg) IHMs to a concurrent birth weight-matched group of infants of normotensive mothers (INMs). Infants without differential leukocyte counts at < 12 hours of age were excluded, leaving 93 IHMs and 98 INMs. The incidence of neutropenia at < 12 hours among IHMs was not significantly different from that among INMs (42/92 (45%) vs 37/98 (38%)). Nosocomial infection was more frequent in neutropenic IHMs than in neutropenic INMs (12/42 vs 2/37; p = 0.007). Infection in IHMs included omphalitis (2 infants), pneumonia (4), and sepsis with or without meningitis (6); INMs had cellulitis (1) and sepsis (1). The underlying mechanism(s) for this predisposition remains to be elucidated, although limited data suggest that neutropenia may be more severe and prolonged among IHMs.

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To assess the previously reported association of intraventricular hemorrhage (IVH) with neutropenia, we prospectively followed during a 38-month study period infants with birth weight less than or equal to 1500 gm who survived greater than 72 hours and underwent serial cranial sonography and neutrophil counts for the first 14 days of life. Neutrophil counts were interpreted according to a widely employed reference range. Infants with conditions other than IVH reported to be associated with neutropenia (sepsis, maternal hypertension, 5-minute Apgar score less than or equal to 5) were excluded. Final study groups included 38 infants with IVH and 114 without IVH. No significant differences were found for birth weight, gestational age, respiratory distress syndrome, mechanical ventilation, prolonged rupture of membranes, patent ductus arteriosus, route of delivery, pneumothorax, or sex. The occurrence of neutropenia before 14 days of age was not significantly different between the groups (50% with IVH, 56% without IVH), nor were differences found at individual postnatal ages. Comparison of immature neutrophil count and immature/total neutrophil ratio also revealed no differences. The high incidence of neutropenia in our non-IVH group raises questions about application of these widely accepted reference ranges to very low birth weight infants.

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For an assessment of the efficacy of clindamycin in preventing bowel necrosis (intestinal gangrene or perforation), 42 premature infants with radiographically confirmed necrotizing enterocolitis (NEC) (pneumatosis, intraportal gas, or both) were randomly assigned to receive parenterally either ampicillin and gentamicin (control group, n = 22) or ampicillin, gentamicin, and clindamycin (n = 20), 20 mg/kg/d at 8-hour intervals for 10 to 14 days. Infants who had received antibiotics for greater than 24 hours before randomization and those developing intestinal gangrene or perforation less than 12 hours after randomization were excluded. Intestinal gangrene or perforation developed in four infants in the control group and six in the clindamycin group. Four in each group died of NEC. In the control group, one of 18 survivors developed a late stricture requiring surgical resection, whereas six of 15 survivors in the clindamycin group developed such strictures (P = 0.022). Routine inclusion of clindamycin in medical treatment of NEC does not reduce the frequency of intestinal gangrene or perforation and may be associated with an increase in late stricture formation.

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The clinical courses in 27 infants with culture or autopsy evidence of systemic candidiasis were reviewed. Twenty-two infants (group 1) had persistent signs of sepsis and clinical deterioration or died before institution of antifungal therapy. Five infants (group 2) improved markedly before culture results were reported, and recovered without systemic antifungal therapy. Fourteen infants in group 1 (64%) had central nervous system infection. Of four patients in whom CNS involvement was diagnosed only postmortem, antemortem cerebrospinal fluid from three was abnormal despite sterile cultures; no antemortem CSF was obtained in the other. In meningitis caused by susceptible organisms addition of flucytosine sterilized CSF within 5 days, although prior amphotericin monotherapy had been unsuccessful. Of 14 patients in group 1 who received systemic antifungal therapy, only one died with Candida infection. Toxicity from antifungal agents occurred in 11 of 13 successfully treated infants, but was reversible in every case except one by modifying the dosage. Our data indicate that (1) CNS infection is very common in infants with systemic candidiasis, (2) combined flucytosine-amphotericin therapy may facilitate treatment of CNS infection and should be the initial therapy for systemic candidiasis in infants, (3) Gram stains of CSF and urine enhance early diagnosis, (4) isolation of Candida from normally sterile body fluids in high-risk infants should be considered pathogenic and therapy initiated unless the clinical course strongly suggests otherwise, and (5) toxicity from antifungal agents is common but usually reversible.

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Concentrations of immunoglobulins G, M, and A were measured by double-antibody radioimmunoassay in morning milk samples collected during the first month postpartum from 35 mothers delivered of preterm infants and 14 mothers delivered of term infants. Mean concentrations of IgG (1.8, to 2.8 mg/gm protein) and IgM (2.8 to 11.7 mg/gm protein) were similar in milk from both groups of mothers. In contrast, IgA was present in significantly higher concentrations throughout the first month postpartum in milk from mothers delivered of preterm infants than in milk from those giving birth at term (P less than 0.01). To determine the effect of milk flow on IgA concentration, IgA was also measured in complete 24-hour milk collections; milk from mothers with preterm deliveries again contained significantly higher concentrations of IgA than milk from mothers with term deliveries (P less than 0.01). This higher IgA concentration was not secondary to method of milk expression. The concentration of IgA was found, however, to vary inversely with milk volume (P less than 0.01). Although mean values of milk volumes for the groups were not statistically different, the overall lower volumes of milk produced by mothers giving birth preterm resulted in comparable total IgA production per 24 hours. There were no differences in serum IgA concentrations of preterm infants fed their own mother's milk and comparable infants fed a cow milk formula, suggesting that IgA in milk is not absorbed from the intestine in significant amounts.

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