Ch. P. Speer

Decreased Adherence, Chemotaxis and Phagocytic Activities of Neutrophils from Preterm Neonates

ABSTRACT. Using microanalytic assays various phagocytic functions of separated neutrophils from preterm neonates (mean birthweight 1 506 g, n = 13) were simultaneously studied. Adherence of neutrophils to nylon fibre was decreased in cells from preterm infants (77.1 ± 3.1 %) when compared with adult controls (86.9 ± 2.1 %, mean ± 1 SD, p <0.05). In addition neutrophil chemotaxis in response to zymosan activated serum was reduced in preterm neonates (131.9 ± 19.7, adults 166.6 ± 11.1, p<0.001); directed migration towards Formyl‐Methionyl‐Leucyl‐Phenylalanine was also decreased (preterm neonates 93.4 ± 15, adults 111.1 ± 16.8, p<0.05). Preterm infants had a higher percentage of slow moving neutrophils when compared with adults (p< 0.001). Phagocytosis of Candida albicans was reduced in neutrophils from preterm neonates (phagocytic index: preterm neonates 41.4 ± 12.7, adults 83 ± 7.2). Adult neutrophils ingested more Candida per cell (p <0.001). Chemiluminescence, exocytosis of elastase and lactoferrin during uptake of opsonized zymosan was also reduced in neutrophils from preterm neonates. However, random migration, phagocytosis of Staphylococcus aureus and production of O‐2, in response to Phorbol myristate acetate or opsonized zymosan were identical in cells from either source. We conclude, that these abnormalities of neutrophils could predispose the preterm infant to serious and often overwhelming bacterial and fungal infections.

Sequential determination of CRP, α1-antitrypsin and haptoglobin in neonatal septicaemia

ABSTRACT. In 312 preterm and term newborn infants serum concentrations of C‐reactive protein (CRP), haptoglobin and α1‐antitrypsin were measured during several days by radial immunodiffusion. In addition white blood cell count and the ratio of band to total neutrophils (B/N‐ratio) were determined. In 12 infants with proven sepsis CRP was found elevated above the upper limit of the normal range (20 mg/l). Successful therapy was followed by a decrease of CRP concentration. In infants with suspected infection high CRP values were found in most cases. In contrast, haptoglobin and α1‐antitrypsin concentrations differed not significantly between the group of infants without infection, with proven and with suspected infection. White blood cell count and B/N‐ratio also were not appropriate for the early identification of bacterial infection in the newborn period.

Phagocytosis‐Associated Oxidative Metabolism in Human Milk Macrophages

ABSTRACT. Evidence exists that human milk macrophages, which are the most abundant cells in milk, play an important role in the protection of the newborn infant against infection. We investigated the oxidative metabolism of milk macrophages by measuring luminol‐dependent chemiluminescence, generation of superoxide anion ((K) and production of hydrogen peroxide (H2O2) in the resting state and after stimulation with opsonized zymosan or phor‐bol myristate acetate (PMA). Generally, macrophages generated luminol‐dependent luminescence, (O2‐) and H2O2 with either stimulus to a similar extent as did blood monocytes. In addition, macrophages killed Escherichia coli and Staphylococcus aureus as effectively as did blood monocytes (–75%, 120 min). Acidification of macrophages in milk (pH 1,30 min) only slightly reduced their PMA‐stimulated production of oxygen radicals. Bacterial killing by macrophages preincubated at pH 1 was about 70% that from controls maintained at pH 7. When macrophages were cultured for several days in endotoxin‐free medium, their ability to produce oxygen metabolites declined. By continuous treatment with bacterial LPS (10 ng/ ml), milk‐macrophages could be “primed” to release large amounts of oxygen intermediates. In addition, the Oi response of macrophages cultured without bacterial products could be partially restored by the addition of LPS to the culture. We conclude that milk macrophages are capable of releasing large amounts of oxygen metabolites, and could contribute to the protection of neonates against bacterial and fungal infections.

Phagocytic activities in neonatal monocytes

Monocytes play an essential role in cellular host defense as circulating phagocytes, as well as precursors of macrophages. We investigated the principal phagocytic activities in monocytes from cord blood of term infants by analysing adherence, random migration, chemotaxis, bactericidal activity, phagocytosis-associated chemiluminescence, production of superoxide anion (O2−) and generation of hydrogen peroxide (H2O2). All phagocytic functions of monocytes from neonates were shown quantitatively to be comparable to those of cells from healthy adult volunteers. The increased susceptibility of the human neonate to serious systemic infections cannot be related to an abnormality in monocyte function.

Intracerebral haemorrhages in surfactant treated neonates with severe respiratory distress syndrome : age at diagnosis, severity and risk factors

Within a randomized European multicentre trial the time of onset, severity and progression of intracerebral haemorrhages (ICH) were investigated prospectively by serial cranial ultrasonography in 343 ventilated infants with severe respiratory distress syndrome (RDS) following instillation of single or multiple doses of a natural porcine surfactant (Curosurf). In 148/343 infants (43%) ICH was diagnosed (grade I or II: 22%, grade III or IV: 21%). In 26 cases (8%) ICH was present on the ultrasound scan prior to surfactant instillation at a median age of 6h. Incidence and severity of ICH was similar after single- or multiple-dose surfactant treatment. Using a logistic regression model the following risk factors predictive of ICH were defined: low birth weight, allocation to certain hospitals, vaginal delivery, Apgar score≤6, rectal temperature on admission ≤36°C, primary anaemia, acidosis prior to treatment, RDS grade IV in pre-treatment chest films and poor response to surfactant treatmentOur study provides supportive evidence that multiple doses of Curosurf do not increase the risk for ICH as compared to single-dose administration.

Treatment of promyelocytic leukemia during pregnancy

SummaryIn spite of the fact that acute promyelocytic leukemia during pregnancy is rare and that there is little precedent in the literature for treatment with combined chemotherapeutic agents, the rate of success with current chemotherapeutic regimens is very encouraging. Judging from previous reports and our own experience, it is possible to give combination chemotherapy to pregnant women with AML/APL with the result that mother and infant survive, whereby the incidence of complication is within an acceptable range. No comprehensive studies on life-time teratogenic or carcinogenic effects are available at present.

Interdisciplinary treatment of necrotizing enterocolitis and spontaneous intestinal perforations in preterm infants

From January 1986 to December 1992, 13 patients with necrotizing enterocolitis (NEC) (Grade II‐III; Bell) were treated. The incidence was highest in the very immature infants with birth weight < 1000 g: 6/148 (4%). From onset, NEC was associated with clinical symptoms such as abdominal distension, bloody stools, retained gastric contents and septicemia. Indications of inflammation were seen in only 6 out of 13 patients at the time of diagnosis. No complications were seen in 10 patients during the acute phase. Two infants developed a bowel perforation and another one a gangrene. Immediate surgery was performed. In three other infants, elective surgery was performed because of colonic strictures. Twelve (92%) patients survived NEC. Five other VLBW infants developed spontaneous perforations of the bowel. The clinical presentation, laboratory and radiological findings differed greatly from those with NEC. Four infants survived. A primarily conservative therapeutic regime with close cooperation between the surgeon and pediatrician may be an alternative to early surgical intervention in NEC.

Diagnostic value of elastase-α1-proteinase inhibitor in cerebrospinal fluid

ABSTRACT‐ In this report we introduce CSF Elastase‐α1‐Proteinaseinhibitor as a valuable indicator for differentiating bacterial meningitis from aseptic meningitis and other neurological disorders. All patients (n = 26) with bacterial meningitis had increased CSF concentrations of E‐α1‐PI above the range of normal (range of reference values: 0.0–2.3 μg/1, n = 79; bacterial meningitis: 30–3490 μg/1, n = 26). Concentrations of E‐α1‐PI in bacterial meningitis were significantly elevated when compared with those in aseptic meningitis (0.0–194 μg/1, n = 37), polyneuropathy (0–23 μg/1, n = 24) and cerebrovascular attack (0–23.2 μg/1, n = 17).

Microcalorimetric determination of blood heat output in human neonates

Abstract Based on earlier results on a body size relationship of blood heat output in different mammalian species, an intra-specific comparison of blood heat output in human neonates and adults was made. To avoid taking additional blood samples from neonates, a resuspension technique was developed, allowing the use of material left over from clinical routine sampling. In 13 adult volunteers, microcalorimetric heat output ( x ± SEM ) was 48.1 ± 0.8 μW (mlblood)−1 or 105.6 ± 2.2 μW (mlcells)−1 in the whole blood and 47.3 ± 1.6 μW (mlsusp.)−1 or 104.0 ± 3.3 μW (mlcells)−1 in the resuspended samples, respectively, proving that the resuspension procedure did not alter the thermal power values. Using this technique on blood samples from 38 neonates in their first week of life, a heat output of 77.2 ± 3.1 μW (mlsusp.)−1 or 151.8 ± 5.9 μW (mlcells)−1 was found. This is significantly higher than in adults, and fits the body size relationship of blood heat output previously described for different mammalian species.

Glucuronyl transferase deficiency and mild hereditary spherocytosis: effect of splenectomy

In a 6-year-old girl an association of hereditary spherocytosis and a defect in hepatic bilirubin metabolism has been found. The patient suffered from mild compensated haemolytic anaemia and excessive hyperbilirubinaemia (maximum concentration 581 μmol/l), the serum activity of liver enzymes was slightly increased. Examination of the erythrocyte membrane proteins revealed a deficiency of the major membrane skeletal protein, spectrin (about 75% of normal) which is probably the basic genetic defect of hereditary spherocytosis. Examination of the patients family revealed a recessive mode of inheritance. The concentration of bilirubin conjugates in the patients serum was decreased due to a reduced UDP-glucuronyl transferase activity found in homogenates of liver tissue. Histological liver examination showed an intrahepatic cholestasis, which is a secondary and reversible alteration resulting from severe hyperbilirubinaemia. After splenectomy, normalization of the increased haemolysis and hepatic dysfunction was observed. The excessive hyperbilirubinaemia can be explained by the association of an increased bilirubin load due to haemolytic anaemia and the diminished hepatic conjugation of bilirubin.