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Endogenously formed cytokines may play an important role in the development of meningitis, and it is necessary to understand in more detail inflammatory cascades involved in the disease process. We were interested to investigate biochemical changes which are inducible by interferon gamma. Therefore, we exa­mined concentrations of neopterin, tryptophan, kynurenine and interferon gamma in cerebrospinal fluid (CSF) of 11 children with bacterial or viral meningitis and of 20 children with febrile convulsions, who suffered from viral or bacterial disease not involving the central nervous system. Concentrations of neopterin (mean ± S.D.: 43.9 ± 34.6 nmol/l) kyunrenine (0.41 ± 0.56 μmol/l) and interferon gamma (0.64 ± 0.81 U/ml) levels were higher in CSF of children with meningitis than in those with febrile convulsions (all p

Immune stimulation due to secondary infection may enhance HIV replication and viraemia, since cellular activation of CD4+T-cells is required for viral replication. We describe a case of an 18 months old child, exposed intrauterinely to human immunodeficiency virus type 1 (HIV -1). During a period of various infections, which was followed by transient viraemia, decrease of CD4 + T -lymphocytes and increase of neopterin concentrations was registered. Disease progression may have occured due to activation of latent HIV-l in CD4+ T -lymphocytes/macrophages by secondary infections.

A significant increase in the incidence of allergy and asthma has been observed during the past decades. The background of this phenomenon has not been well explained, but changes in lifestyle and habits are heavily discussed as contributing factors. Among these is a too clean environment, which may predispose individuals to increased sensitivity to allergic responses. Also the increase in dietary supplements including preservatives and colorants may contribute to this. In vitro, we and others have shown in freshly isolated human peripheral blood mononuclear cells that antioxidant compounds like vitamins C and E as well as food preservatives and colorants exert significant suppressive effects on the Th1 immune activation cascade. The effects observed may be based on the interaction of antioxidant compounds with proinflammatory cascades involving important signal transduction elements such as nuclear factor-κB. Although only obtained in vitro, these results show an anti-inflammatory property of compounds which could shift the Th1-Th2-type immune balance towards Th2-type immunity. This review article discusses the potential role of increased use of antioxidant food supplements as well as preservatives and colorants in the increase in allergy and asthma in the Western world., (Copyright © 2011 S. Karger AG, Basel.)

Objective: To investigate the influence of culture proven intrauterine infection on preterm morbidity and to test the effect of antimicrobial treatment., Methods: Retrospective cohort study conducted between October 1997 and February 2001 in patients with preterm premature rupture of membranes or preterm labor. Vaginal swabs were sampled and amniocentesis for microbiologic culture of the amniotic fluid was performed. Patients with Ureaplasma urealyticum in the amniotic fluid were treated with josamycin. Infants were followed post partum according to birth weight, gestational age, APGAR score and infant morbidity., Results: In 49 eligible patients, 40% of cultures were positive, 22% for Ureaplasma urealyticum, 12% for other bacteria and 6% for candida. Children of mothers with positive amniotic fluid cultures had significantly lower gestational ages (26+4 weeks for Ureaplasma urealyticum [p=0.04] and 25+5 weeks for other microorganisms [p=0.0017] versus 28+6 weeks for mothers with negative amniotic fluid cultures) and lower birth weights (975 g [n.s.] and 828 g [p=0.0072] versus 1,041 g) but were appropriate for their gestational ages. 33.3% and 66.7% versus 24% of the children were mechanically ventilated [n.s.], duration of mechanical ventilation was 5.3 [p=0.02] and 10.1 days [p=0.04] versus 1.4 days, and prevalence of chronic lung disease was 38% and 33% versus 11% [n.s.]. Prevalence of severe intraventricular hemorrhage (12.5% [n.s.] and 33% [p=0.04] versus 3.4%) and nosocomial infections (50% for both groups of positive cultures versus 10.3% for negative cultures, p=0.02 and 0.03, respectively) was higher and median length of stay was significantly longer (121 [p=0.02] and 107 days [p=0.03] versus 60 days) in these patients. Maternal positive vaginal swab cultures were not associated with any of the above-mentioned factors. In none of the patients treated with macrolids for proven Ureaplasma urealyticum amnionitis could the microbes be eradicated., Conclusion: Maternal positive amniotic fluid cultures have been associated with lower gestational age and lower birth weight. Rate of infant morbidity was higher and length of stay was significantly longer in this group. Positive vaginal swabs were not predictive for infant morbidity. Treatment of mothers showing positive amniotic fluid cultures with macrolids was not effective.

A 2-year-old morbidly obese boy presented with early manifestation of vascular disease associated with several obesity-related features of the metabolic syndrome due to massive overfeeding. Ultrasound of the carotid arteries showed significant thickening of the intima media, perfusion magnetic resonance spectroscopy indicated cerebral microcirculation disturbance, and echocardiography revealed left ventricular hypertrophy. Thorough assessment of morbidly obese children seems to be of importance from early childhood on. Studies evaluating the prevalence of obesity-related metabolic and vascular comorbidities in very young morbidly obese children are warranted.

Background: Septic complications lead to a high mortality rate in very low birthweight infants (VLBWI). Therefore, prognostic markers for the development of sepsis attach importance to start an efficient therapy as early as possible., Aims: Functional and phenotypical variables of blood monocytes in the cord and peripheral blood were investigated to evaluate the parameters for predicting early-onset and late-onset sepsis (nosocomial infections)., Study Design: In a prospective study, 25 VLBWI were investigated., Methods: In the cord blood taken immediately after birth, the capacity of the monocytes to phagocytose non-opsonized E. coli bacteria by flow cytometry and the ex-vivo production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta and IL-6 (enzyme-linked immunoassay (ELISA)) after lipopolysaccharide (LPS) stimulation were measured. At the third day, the HLA-DR expression on the monocytes (flow cytometry) and the LPS-induced cytokine production were measured from the peripheral blood., Results: Five VLBWI already developed early septic complications after 24-72 h, while the other three infants had late-onset sepsis 10-18 days after birth. The prognostic significance for early-onset sepsis was highest for the decreased monocyte phagocytic capacity (sensitivity and specificity: 100%) and for the LPS-induced formation of TNF-alpha and IL-1 beta in cord blood. Moreover, in septic VLBWI, the HLA-DR expression on the monocytes was lowered on day 3 after birth. The prognostic significance for late-onset sepsis was highest for TNF-alpha and IL-1 beta levels in the peripheral blood on the third day after birth., Conclusions: The determination of phagocytosis in the cord blood seems to be a reliable parameter for predicting early-onset sepsis and offers the possibility for a forward start of an antibiotic therapy.

Objective: To assess the risk to second- and third-borns of developing perinatal infections based on a diminished first-line immune response in comparison to the first-born., Study Design: 11 sets of twins and 2 sets of triplets (27-39 weeks of gestation, 740-3,560 g birth weight) admitted consecutively to our neonatal care unit were investigated. All were delivered by cesarean section. Phagocytosis and the expression of TNF-alpha and IL-1 in cord blood were determined immediately and 72 h after birth from peripheral blood monocytes by FACS analysis and ELISA., Results: In all second- and third-borns, phagocytosis of cord blood monocytes was significantly decreased in comparison to the first-borns (p < 0.001, p < 0.015). 72 h after birth phagocytosis determined from peripheral blood showed no significant difference between the first-borns and the second- and third-borns. Cytokine expression revealed no significant differences dependent on birth order., Conclusion: We suggest that the observed temporarily diminished first-line immune response of second- and third-born multiplets might be the result of a short-term reduced cellular oxygenation during delivery, but has no influence on further immunological deficiency leading to a higher risk of perinatal infections., (Copyright 2002 S. Karger AG, Basel)

Background: It is known that plasma or serum viral load is high in vertically HIV-infected children during the first year of life, but the changes in these titers after the first birthday have not been described. Information on the natural history of circulating extracellular virus will be useful in elucidating the pathogenesis of pediatric HIV infection and in using viral load measurement to guide prognosis and therapy., Methods: We measured serum RNA by reverse transcriptase-polymerase chain reaction and immune complex-dissociated p24 antigen enzyme-linked immunosorbent assay over time in 48 unselected children followed in our clinics and analyzed the findings in relation to age and clinical outcome., Results: In first-available samples from the 48 children there was a gradual reduction in HIV RNA values with increasing age, with a slope of -0.21 log copy/ml/year (P < 0.001, R2 = 0.6022). This downward trend was seen in subsets of children with all degrees of immunodeficiency. The mean slope of repeated HIV RNA measurements in individual children was similarly in a downward direction (slope -0.11 (P = 0.007 for difference from zero)). The slope was more negative in children who were younger at baseline. Immune complex-dissociated p24 antigen values were much less predictable and predictive., Conclusions: Viral load in vertically infected children, measured by reverse transcriptase-polymerase chain reaction, falls very gradually over time, descending from very high titers at the end of the first year, and reaching values seen in horizontally infected adults at approximately 5 years of age.

A high percentage of HIV-1-infected infants and children in Romania are coinfected with hepatitis B virus. Little information is available on the impact of concurrent hepatitis B infection on the course of HIV-1 infection. We conducted a prospective cohort study over 1 year in a group of 68 HIV-1-infected infants and children to determine whether hepatitis B surface antigenemia, neopterin, and beta 2-microglobulin (B2M) predicted death. Among the 44 hepatitis B surface antigen-positive (HBsAg+) subjects at enrollment, 13 (30%) died during 1 year of follow-up. In comparison, two of 24 (8%) HBsAg-negative subjects died (RR = 7.7; p = 0.05). Higher initial serum concentrations of neopterin and B2M were negatively associated with survival. After stratifying by baseline clinical evidence of HIV-related disease, survival was negatively associated with HBsAg+ status (p = 0.04) in 33 children in stage P-2, adjusting for age, serum neopterin, and serum B2M levels. The results of this study suggest that serum neopterin is a marker for severity of clinical illness and that HBsAg+ status increases the mortality rate among children with clinical evidence of HIV infection.

Serologic markers of immune activation, neopterin and beta-2-microglobulin (B2M), have been shown to predict progressive human immunodeficiency virus type 1 (HIV-1) disease based on cohort studies in adults. Both parameters appear also to be valuable in distinguishing HIV-1 infants with progressive disease from asymptomatic infants and HIV-1 seronegative infants. In a cross-sectional study we examined the utility of neopterin and B2M testing in 135 infants of an orphanage in Romania, 69 of the infants (51%) were found to be HIV-1 antibody seropositive; 95% of the 135 infants were either hepatitis B virus (HBV) antigen or antibody seropositive. In the HIV-1 seronegative infants B2M was higher in those with HBV antigenaemia. Serum neopterin and B2M concentrations were higher in HIV-1 seropositive than in seronegative infants (p = 7 x 10(-12) and 1 x 10(-6)). Children with CDC stage P2 had only slightly higher neopterin and B2M values as compared to stage P1 (P = 0.04 and 0.08). Our study indicates that measurement of neopterin and B2M is useful to monitor HIV-1 infection, particularly in areas where laboratory facilities are limited. Both parameters continue to be associated with HIV-1 infection even when there is a high background rate of other infections.

The homage of 135 abandoned children in the city of Resita, south west Rumania, has been checked by a medical team from the University of Innsbruck for social, clinical and hyginical situation. The local government had applied for such an investigation. Most of the infections and other diseases are based on a dramatically bad hygienical situation. 52% of checked sera were HIV positiv by RIA and Western Blot, moreover 60% Hepatitis B antigen positiv. We assume a high rate of horizontal transmission of the HIV virus. One of the main clinical symptoms was maternal-deprivation syndrome, with an incidence of 80%. Consequences in personal policy of the homage as well as medical strategies have to follow.