Tissue neutropenia: the newborn neutrophil in perspective.

The notion of tissue neutropenia due to impaired signal transduction secondary to decreased newborn neutrophil membrane receptor mobility allows intervention to improve neutrophil mobilization. New pharmacologic agents and biologic response modifiers show promise of increasing the newborn neutrophil's ability to respond to chemotactic signals. This approach will lead to the development of effective adjuvant therapy for neonatal sepsis.

The prognostic significance of age and pattern of metastases in stage IV-S neuroblastoma.

Stage IV-S neuroblastoma is a unique disseminated neoplasia characterized by remote disease to the liver, skin, or bone marrow. Stage IV-S patients have frequent spontaneous remissions and a 60% to 90% survival rate. Many investigators have recommended minimal or no therapeutic intervention; however, some patients do experience progressive disease and ultimately die of neuroblastoma. Many authors have commented on single prognostic factors such as age and site of metastatic involvement. Five newborns were recently seen at Walter Reed Army Medical Center with Stage IV-S neuroblastoma. Four of these children died of mechanical complications associated with massive hepatomegaly, prompting this review of Stage IV-S neuroblastoma to determine prognostic factors.

Irreversible neutrophil aggregation. A mechanism of decreased newborn neutrophil chemotactic response.

To investigate the neutrophil-neutrophil interactions of the newborn for possible clues to the etiology of decreased newborn neutrophil (PMN) chemotaxis, the authors compared adult and newborn C5a-induced PMN aggregation and chemotaxis at various PMN concentrations. Using Craddock's technique of C5a-induced aggregation, the authors found that the newborn lacks the normal biphasic aggregation-deaggregation seen in the adult, suggesting irreversible aggregation similar to that seen when adult PMNs are pretreated with cytochalasin-B. Chemotaxis of adult and newborn PMNs was studied with a modified Gallin radiolabel technique. A linear correlation between PMN concentration and corrected chemotactic response was found with both adult (r2 = 0.93) and newborn (r2 = 0.90) PMNs in the range 0.1 X 10(6) to 20 X 10(6) PMNs/ml. Random migration was not augmented by increased PMN concentration. The augmentation of newborn PMN chemotaxis was less than that of the adult (adult slope = 2426; newborn slope = 983). Irreversible newborn PMN aggregation may be the underlying event producing decreased PMN chemotaxis and interfering with the normal chemotactic augmentation caused by increased PMN concentration.

Diminished bacterial defences with intralipid.

'Intralipid', a lipid emulsion used in parenteral nutrition, impaired bacterial clearance and enhanced bacterial virulence in mice. In addition it inhibited the chemotaxis of human neutrophils in vitro. Intralipid may enhance the risk of bacterial sepsis in certain patients.

Decreased phytohemagglutinin-induced aggregation and C5a-induced chemotaxis of human newborn neutrophils.

Phytohemmagglutinin (PHA)-induced lectin aggregation, chemotactic response to C5a, and random migration were measured on paired samples of neutrophils obtained from human peripheral blood and cord blood of normal newborn infants. The mean aggregation rate (+/- 1 SD) of adult neutrophils with PHA was 16.8 +/- 4.4 vs. 12.0 +/- 3.6 for newborn neutrophils (P less than 0.005), and the mean percent aggregation of adult neutrophils was 56.2 +/- 9.2 vs. 45.6 +/- 8.3 for newborn neutrophils (P less than 0.005). Exposure to newborn plasma had no affect on adult neutrophil aggregation. Whereas vinblastine (VBL) decreased both the percent and rate of PHA-induced adult neutrophil aggregation, only the rate of newborn neutrophil aggregation was reduced by VBL. Newborn neutrophil chemotactic response to C5a, was reduced by 80% (P less than 0.0025), and showed a positive correlation with percent PHA-induced aggregation (r = 0.6037, P less than 0.05). On the other hand, random migration was not significantly reduced and did not correlate with PHA-induced aggregation. These observations suggest that the decreased chemotactic responsiveness of newborn neutrophils may be due to developmental membrane differences which adversely affect the number and/or availability of C5a resceptors. Lectin-induced aggregation studies of other chemotactic defects may identify similar differences.

Anthracycline cardiomyopathy in children: report of two cases.

Two children with leukemia are presented, each demonstrating an unusual aspect of anthracycline-induced cardiomyopathy. In the first patient (a 7-month-old female with acute monocytic leukemia) extremely young age and previous chemotherapy with a podophyllotoxin derivative, VP-16, may have prediposed the patient to fatal congestive heart failure at a total Daunorubicin dose of only 225 mg/m2. In the second patient, a delay of 4 1/2 years was not sufficient in preventing congestive heart failure resulting from the administration of additional anthracycline chemotherapy. We conclude that extremely young age and, possibly, prior therapy with VP-16 may be addition risk factors in the development of anthracycline cardiomyopathy. Also, we suggest that once an anthracycline agent has reached a toxic threshold for the myocardium, the heart may always be at risk to injury from additional Adriamycin or Daunorubicin therapy.