Recurrent outbreaks of Serratia marcescens among neonates and infants at a pediatric department: an outbreak analysis.

PURPOSE: Serratia marcescens is a known cause of bloodstream infections (BSIs) and outbreaks in neonates receiving intensive care. Our aim was to analyze clinical and epidemiological characteristics of two outbreaks detected in our unit to prevent and control further epidemic infections. METHODS: Two episodes of BSI outbreaks in neonates have been investigated in a 20-month period at a pediatric department of a medical university in Hungary. We collected all S. marcescens strains that were isolated in the study period, and two strains that were isolated before the outbreaks. Strains were analyzed by pulsed-field gel electrophoresis (PFGE). Clinical data were collected for the BSIs during and between the outbreaks (n = 14). RESULTS: Out of the 28 S. marcescens isolates investigated by PFGE, 16 were blood isolates. All isolates represented four PFGE types. Pathogenic strains that caused epidemic BSIs were related to a single PFGE type (SM009). Strains with the same pulsotype could be detected before, between, and after the outbreak periods from surveillance cultures of neonates, and a water tap in the infant care unit despite intensive infection control measures. Case fatality rate of BSIs was 29%. Rate of complications in central nervous system was high: 3/14 neonates developed meningitis. CONCLUSIONS: Rapid spread and high mortality rate of S. marcescens infections necessitate a high suspicion when isolating this species in neonatal intensive care. Early identification of outbreaks is essential, that can be facilitated by determination of clonal relatedness using molecular methods, and with regular surveillance cultures of patients and environment.

Apoptosis in various organs of preterm infants: histopathologic study of lung, kidney, liver, and brain of ventilated infants.

Apoptosis, the well-characterized form of active programmed cell death, is a physiologic phenomenon in embryonal and fetal life in developing organs. Severe hypoxia, which occurs in most preterm infants, also leads to cell death, which may be necrotic or apoptotic. The aim of our study was to examine the incidence of apoptosis in various organs (such as lung, kidney, and brain) of preterm infants who suffered from clinically proven respiratory distress causing infantile respiratory distress syndrome (IRDS), cardiac failure, and periventricular leukomalacia (PVL). Twenty-four autopsy cases were studied histologically to detect the apoptotic ratio, which was performed on the basis of hematoxylin and eosin staining and validated by terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) reaction. Elevated apoptotic ratio was found in stages II, III, and IV of bronchopulmonary dysplasia (BPD) among alveolar and bronchiolar cells. The apoptotic activity was very low in stage I of BPD. High apoptotic ratio was detected in hypoxic injuries of the central nervous system (CNS) of preterm infants. Features of apoptosis were present in proximal and excreting tubules of the kidney. Significant elevation of apoptotic activity may play a role in the development of BPD, ischemic brain lesions, and renal failure.

Changes in echogenicity of spinal subarachnoid space associated with intracranial hemorrhage: new observations.

PURPOSE: The role of subarachnoid blood and secondary, sterile inflammation in the pathogenesis of posthemorrhagic hydrocephalus (PHH) is not well understood. The aims of this study were to study the frequency and rate of spread of blood into the spinal subarachnoid space (SSS) and to evaluate the relationship of this finding and PHH. MATERIALS AND METHODS: Nine premature babies with major intracerebral hemorrhage (ICH, grade 3 or higher), and ten premature infants with minor ICH (grade 1) or no evidence of ICH (control group) were identified and underwent serial cranial and spinal sonography at the time of initial diagnosis, 12-24 h after the ICH and weekly thereafter for at least 9 weeks. Sagittal and axial scans of the thoracolumbar spine were obtained and evaluated for the presence of echogenic debris in the dorsal SSS. Six additional patients who had cranial and spinal sonography died within the 1st week of life and underwent post-mortem examinations. RESULTS: The SSS was echo-free (normal) in all cases at the time of initial sonographic diagnosis of ICH. Within 24 h, all babies with major ICH had developed increased echogenicity of the cervical and thoracic SSS. Echogenicity of the SSS decreased gradually over several weeks. Although transient ventricular dilatation was present in every patient, only one patient had rapidly progressive PHH requiring shunt placement. Transient cysts of the cervicothoracic subarachnoid space were identified in two patients 6-7 weeks after ICH. The subarachnoid space remained echo-free in all control infants At autopsy, all four infants with echogenic spinal debris had blood or blood products in the spinal subarachnoid space, whereas two infants with echo-free spinal images did not. CONCLUSIONS: Spread of blood from the ventricular system into the spinal subarachnoid space after ICH is common and can be seen within 24 h of initial ICH. Subarachnoid blood is associated with post-hemorrhagic ventricular dilatation and transient spinal subarachnoid cyst formation.

Effects of purinergic agents on human mononuclear phagocytes are differentiation dependent. Implications for atherogenesis.

The differentiation-dependent expression of purinergic receptors for metabolically stable analogues of adenosine and ATP was studied in human mononuclear phagocytes (MNPs). Ligands of these receptors are able to modulate cellular cholesterol metabolism. In addition, the intracellular signal transduction pathways of the purinergic receptor system were examined. ATP gamma S, the metabolic stable analogue of ATP, was used as a P2 ligand, and 2-p-(2-carboxyethyl)phenylethylamino-5'-N-ethylcarboxamido adenosine (CGS 21680) and 5'-(N-ethylcarboxamido)adenosine (NECA) were used as P1 ligands in binding studies. Binding of [35S]ATP gamma S to MNPs at 4 degrees C revealed saturable low-affinity binding sites with a Kd of 868 +/- 52 nmol/L and Bmax of 7.3 +/- 0.4 pmol per 10(6) cells in 1-day cultured human MNPs and a Kd of 780 +/- 30 nmol/L and Bmax of 14.0 +/- 0.8 pmol per 10(6) cells in 7-day cultured human MNPs. The characterization of the P1 receptors on 1- and 7-day cultured human MNPs showed that they are expressed only on 7-day cultured human MNPs. The specific binding curve of the adenosine A2 receptor agonist [3H]CGS 21680 was biphasic, with a Kd1 of 33 +/- 15 nmol/L and a Kd2 of 90 +/- 10 nmol/L and with Bmax1 of 0.19 +/- 0.06 pmol per 10(6) cells and Bmax2 of 0.41 +/- 0.09 pmol per 10(6) cells, whereas NECA did not exhibit specific binding. The typical agonists for probing A1 receptor subtypes did not bind to 1- and 7-day cultured human MNPs, indicating that only A2 receptors are expressed on 7-day cultured human MNPs. ATP gamma S enhanced [Ca2+]i in 1- and 7-day cultured human MNPs in a concentration-dependent manner, whereas the P1 ligands, adenosine and CGS 21680, induced Ca2+ flux only in 7-day cultured MNPs. All three drugs increased intracellular cAMP levels in 7-day cultured human MNPs at a concentration of 10(-5) mol/L, whereas no effect was observed in 1-day cultured human MNPs. The uptake of fluorescently labeled acetylated low-density lipoprotein (LDL) in 7-day cultured human MNPs was inhibited by adenosine, CGS 21680, ATP, and ATP gamma S. No significant influence of these compounds was measured on the uptake of LDL, acetylated LDL, and high-density lipoprotein, in 1-day cultured MNPs. Our investigations indicate that the expression of P2y and A2 receptors is increased during differentiation of blood monocytes to macrophages.(ABSTRACT TRUNCATED AT 400 WORDS)

Endocytosis of oxidized LDL and reversibility of migration inhibition in macrophage-derived foam cells in vitro. A mechanism for atherosclerosis regression?

The ability of macrophage-derived foam cells to migrate from atherosclerotic lesions represents one potential mechanism for the regression of atherosclerosis. It is, however, generally recognized that the transformation of macrophages into foam cells results in greatly reduced migrational ability. In the present study, we set out to investigate the factors affecting migratory capability in foam cell-like cells with the use of an in vitro assay. Foam cell-like cells were prepared by incubating macrophages in the presence of oxidized low density lipoprotein (LDL). The transformation to a typical foam cell morphology was demonstrated by Nile red staining (light microscopy), and the mechanisms of binding, uptake, and intracellular processing of oxidized LDL were established by colloidal gold labeling on the ultrastructural level. With the in vitro assay, the migration of these foam cell-like cells was found to be markedly inhibited compared with untreated, control macrophages. However, zymosan-activated mouse serum restored migration in oxidized LDL-treated cells to levels similar to those of control cells. Restoration of migratory capacity was accompanied by alterations in the cytoskeleton system, especially in actin arrangement.

Inhibition of ACAT activity after 7-oxo-PGI2 treatment in cholesterol-fed rabbits.

It has been supposed that prostacyclin (PGI2) and its analogues have important antiatherogenic effects. The aim of this work was to test the effect of PGI2 and 7-oxo-PGI2- (a stable analogue of PGI2) (6) treatment on the acyl CoA: cholesterol-acyltransferase (ACAT) activity in the aortic wall of rabbits. The rabbits had been previously fed with cholesterol and treated with PGI2 and 7-oxo-PGI2 intravenously. Cholesterol feeding increased ACAT activity compared to the control group which was not fed with cholesterol: 16.84 nmol/mg prot./h and 10.03 nmol/mg prot./h, respectively. PGI2 treatment of the cholesterol fed group did not cause a significant decrease, while 7-oxo-PGI2 treatment significantly decreased aortic ACAT activity compared to the cholesterol-fed control group; 14.31 nmol/mg prot./h; 11.53 nmol/mg prot./h and 16.84 nmol/mg prot./h, respectively. The decrease found in the ACAT activity after PGI2 and 7-oxo-PGI2 treatment are new data for the protective effect of these agents against atherosclerosis.

[D-penicillamine does not affect the liver and kidney function in newborn infants nor the in vitro function of phagocytes]. / A D-penicillamin kezelés nem befolyásolja az újszülöttek máj- és vesefunkcióját, valamint in vitro a phagocyták müködését.

D-penicillamine was introduced to treat neonatal hyperbilirubinaemia in 1973 and to prevent retinopathy of prematurity in 1980. In this study we investigated the renal and liver functions of neonates treated with DPA and the in vitro effect of the drug on superoxide anion generation and beta-glucuronidase release as well as on phagocytic and intracellular killing activation on human peripheral blood granulocytes. Our data concerning the renal and liver functions before and after 3 to 4 days DPA treatment reveal no pathological change during short-term administration in the neonatal period. Furthermore, none of the examined DPA concentrations influenced the phagocytic or killing activity of neutrophils.

[In vivo migration of peritoneal macrophages, saturated with fats in vitro]. / In vitro zsírral telített peritoneális macrophagok in vivo migrációja.

Our experiments aimed at the in vitro development of cells similar to macrophage foam cells of vessel wall. Fatty macrophages were produced by Intralipid incubation of peritoneal macrophages and their motility was studied in vivo. Our results showed that fat-saturated, isotope and colloid-gold marked macrophages can get through the vessel wall, so they are able to in vivo migration.

[Clinical experiences with intravenous immunoglobulin therapy of infectious diseases in infancy and childhood]. / Klinische Erfahrungen mit der intravenösen Immunglobulintherapie septischer Krankheiten im Säuglings- und Kindesalter.

In 26 infants with severe sepsis antibacterial therapy was supplemented by the intravenous administration of immunoglobulins (Endobulin, Immuno AG, Vienna). Such therapy was indicated in 6 patients by the appearance of granulocytopenia during the treatment of their underlying disease, in 14 children by their very young age which was less than 2 years, and in 6 children by the failure of antibacterial therapy to produce the desired effect. Depending on the clinical picture of sepsis different organ manifestations were seen, purulent meningitis (10 cases) and pneumonia (9 cases) being the most frequent. In 24 patients immunoglobulin therapy led to complete recovery. In all 7 cases of purulent meningitis, the simultaneous administration of antibiotics and immunoglobulins was effective.