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Biomedical subjects

M Xanthou

Publications and source records attributed to M Xanthou.

At least 19 recordsLinked to original sources

Prothrombotic factors in neonates with cerebral thrombosis and intraventricular hemorrhage.

AIM: To investigate whether the factor V Leiden mutation (FVL), the prothrombin gene G20210A variant or the methylenetetrahydrofolate reductase (MTHFR) C677T genotype are risk factors for central nervous system (CNS) thrombosis or intraventricular hemorrhage (IVH) in neonates. METHODS: Thirteen full-term infants with cerebral infarct documented with magnetic resonance imaging were assessed with the whole spectrum of assays for thrombophilia including the three DNA-based prothrombotic factors. The frequency of congenital defects was compared with that observed in 38 healthy full-term infants. The genetic defects were also assessed in 55 premature neonates, gestational age <32 wk, 17 of whom developed IVH, grade II-IV. The remaining 38 premature neonates without IVH were used as controls. RESULTS: In the CNS thrombosis group: a prothrombotic factor was detected in 53% of patients and an underlying disease or a triggering event in 61.5%. The frequency of FVL in thrombosed neonates was higher (23%) than in the group of healthy full-term infants (10.5%), although it did not reach statistical significance. IVH developed in 30.9% of premature neonates. Apart from several maternal or neonatal risk factors for IVH, FII G20210A was found in a considerably higher prevalence in the cohort of neonates with IVH (12%) than in those without (2%), although the difference was not statistically significant. CONCLUSION: The pathogenesis of cerebral thrombosis or IVH in neonates is multifactorial. Along with underlying diseases or triggering events, congenital prothrombotic factors (FVL or FII G20210A) showed a trend towards a higher frequency in full-term infants with CNS thrombosis or premature neonates with IVH than in controls. However, their contribution to neonatal cerebral thrombosis or IVH remains to be determined.

Birth Weight↗

Inflammatory mediators in perinatal asphyxia and infection.

AIM: To determine serum levels of interleukin-6 (IL-6), IL-1beta, tumor necrosis factor-alpha (TNF-alpha), soluble intercellular adhesion molecule-1 (sICAM-1) and C-reactive protein (CRP) in asphyxiated neonates and compare these inflammatory factors with those found in neonates with perinatal infection. METHODS: 88 neonates were studied, of whom 36 were asphyxiated, 18 were infected and the remaining 34 were controls. Peripheral blood samples were obtained on the 1st, 3rd and 5th postnatal days. RESULTS: Cytokines IL-6 and IL-1beta as well as sICAM-1 serum levels did not differ between asphyxiated and infected neonates; however, at most time periods, their values were significantly higher than controls. TNF-alpha was similar in the three groups of neonates. CRP serum values were significantly higher in the infected neonates than in the asphyxiated or control subjects. Among the 54 asphyxiated and infected neonates, 15 were considered as severe cases and 39 as mild. The severe cases, at most time periods, had significantly higher IL-6, IL-1beta and sICAM-1 levels compared with the mild ones. Through receiver operating characteristic curves the cut-off points, sensitivities, and specificities for distinguishing neonates at risk or at high risk for brain damage were established. CONCLUSION: Similar increases in serum levels of IL-6, IL-1beta and sICAM-1 were found in perinatally asphyxiated and infected neonates. As these increases correlated with the severity of the perinatal insults, neonates at high risk for brain damage might be detected.

Asphyxia Neonatorum↗

Early markers of brain damage in premature low-birth-weight neonates who suffered from perinatal asphyxia and/or infection.

We studied 57 low-birth-weight premature neonates, of whom 29 suffered from perinatal asphyxia and/or infection, while the remaining 28 did not and served as controls. We measured peripheral nucleated red blood cell (NRBC) absolute numbers as well as interleukin (IL)-1beta, IL-6 and tumour necrosis factor (TNF)-alpha cytokine serum levels at 24 h postnatally and on days 3 and 7 following birth. Fourteen of the asphyxiated/infected neonates and 12 controls had neurologic assessments at the corrected postnatal age of 18 months. We found NRBC absolute numbers and serum IL-1beta and IL-6 cytokine levels at 24 h postnatally to be significantly higher in neonates with perinatal asphyxia/infection than in the controls (p = 0.022, p = 0.036 and p = 0.037, respectively). TNF-alpha levels did not differ. Neurologic examination at the corrected postnatal age of 18 months showed 8 out of the 14 children who had been asphyxiated/infected as neonates to have abnormal findings, while 12 children who were used as controls during their neonatal period were normal. Abnormal neurologic findings correlated with high NRBC counts and IL-1beta and IL-6 levels at 24 h postnatally. In conclusion, increased NRBC counts and proinflammatory cytokine levels in asphyxiated/infected neonates represent early markers for subsequent neurologic impairment.

Asphyxia Neonatorum↗

Determination of slime-producing S. epidermidis specific antibodies in human immunoglobulin preparations and blood sera by an enzyme immunoassay: correlation of antibody titers with opsonic activity and application to preterm neonates.

Slime-producing Staphylococcus epidermidis is responsible for severe infections in immunocompromised patients and, particularly, in premature infants who are transiently deficient in IgG. A sulfated polysaccharide with molecular mass of 20-kDa (20-kDa PS) has been recognized as the major polysaccharide component and antigenic determinant of S. epidermidis extracellular slime layer. The presence of adequate amounts of antibodies to 20-kDa PS in patients' sera would be of importance to prevent or treat slime-producing S. epidermidis bacteremia. Administration of intravenous immunoglobulin (IVIG) is considered to be a reasonable IgG replacement therapy and has been widely used to prevent or treat neonatal sepsis. Clinical trials have shown conflicting results on the efficacy of IVIGs and this phenomenon has been attributed to the variability of IVIG preparations in the content and opsonic activity of IgG against microorganisms of clinical importance. Monitoring of antibodies to distinct bacterial macromolecules, which are species-specific and responsible for bacterial infections, has not been performed previously. A highly precise and repeatable enzyme immunoassay was developed to determine quantitatively the levels of antibodies against the 20-kDa PS of S. epidermidis slime. The amount of 20-kDa PS specific antibodies found in 27 lots of an IVIG preparation (Sandoglobulin) correlated well with their in vitro opsonic activity against slime-producing S. epidermidis. The majority of lots (75%) having titers higher than 200 units/ml showed significant opsonic activity (50-75%) towards slime-producing S. epidermidis. Sandoglobulin lots with titers higher than 200 units/ml of 20-kDa PS specific IgG were administered as a prophylactic agent to low-birth weight (lower than 1700 g) preterm neonates immediately after birth. The levels of total and 20-kDa PS specific IgG in neonates' blood sera were significantly higher than those found in the control group, even 10 days after the last infusion. The rate of slime-producing S. epidermidis bacteremia in neonates who received IVIG was also considerably lower than those in the control group. The results of this study suggest that specific IgG titers estimated by the developed enzyme immunoassay may well be indicative of the IVIG opsonic activity against slime-producing S. epidermidis. Furthermore, administration of Sandoglobulin with titers higher than a cut-off value of 200 units/ml may significantly protect preterm neonates against slime-producing S. epidermidis bacteremia.

Antibodies, Bacterial↗

Immune protection of human milk.

Human milk contains a very large number of specific and non-specific immunologic and nonimmunologic factors who provide passive and active protection to the newborn. The immunologic factors are either immunostimulatory or immunosuppressive. The immunostimulatory ones increase host defense mechanisms mainly against infective illness, and the immunosuppressive ones downregulate inflammation and the development of allergies. Furthermore, human milk has been found to promote intestinal growth and maturation and to have immunomodulating effects beyond infancy, later on in life. In conclusion, human milk represents a very valuable weapon for enhancing the immature immunologic system of the newborn and for strengthening its deficient host defense mechanisms against infective or other foreign agents.

Female↗

Indications of coagulation and/or fibrinolytic system activation in healthy and sick very-low-birth-weight neonates.

A combined hemostatic defect consisting of a reduction in certain procoagulants, anticoagulants (antithrombin III-ATIII-, protein C-PC-) and components of the fibrinolytic system (plasminogen-Plg-) was demonstrated in very-low-birth-weight infants (VLBW <1,500 g) with gestational age 26-32 weeks. Sixteen of them were healthy, 28 were suffering from RDS and 24 from septicemia. The hemostatic defect was more profound in the RDS group, nevertheless increased TAT (thrombin + ATIII complex) and/or PAP values (plasmin + a2-antiplasmin complex) was a more frequent finding in the septicemic group of infants (91.8 vs. 17.9%). Moderate-to-severe thrombocytopenia was detected in a higher percentage in the septicemic (70.8%) than in the RDS group (50%), and increased D-dimers were demonstrated in 34.8 and 28.6% of the infants, respectively. Elevated TAT or PAP values were not always associated with gross coagulation abnormalities, and advanced disseminated intravascular coagulation (DIC) was only documented in 16.7% of the septicemic and 7.1% of the RDS infants. None of the VLBW neonates presented with clinical evidence of thrombosis, although hemorrhagic manifestations were apparent in 34.8 and 14.3% of the neonates with septicemia or RDS, respectively, mainly due to DIC or severe thrombocytopenia. In conclusion, increased TAT and/or PAP values are good indicators of the in vivo activation of the hemostatic system, but still their impact on sick neonates morbidity and mortality remains unknown.

Antithrombin III↗

Human milk and intestinal host defense in newborns: an update.

In this update of the role of breast milk ingestion on passive and active protection of the human neonate, new observations and studies are presented that appear to support the concept that preterm and term infants should receive their mother's milk so far as possible. New objective evidence has been presented to support the role of breast milk in the protection of the newborn from intestinal and systemic infections. New concepts of the active role of breast milk growth factors on an accelerated development of the infant's own mucosal barrier function are presented, as well as preliminary data to support the role of breast milk growth factors in gut development. This new area of breast milk function, however, requires extensive clinical studies to support the practical value of breast milk in the development of the infant's own defenses.

Breast Feeding↗

In vivo distribution of human milk leucocytes after ingestion by newborn baboons.

The in vivo distribution of enterally administered human milk leucocytes labelled with indium hydroxyquinoline (111In) was studied in premature baboons. The animals were killed at 72 hours of age and tissue samples examined for radioactivity. Maximum activity was found in the luminal contents, and activity in the liver and spleen was higher than in bone marrow, the site where free isotope is normally deposited. These findings suggest that some intact milk leucocytes may cross from the gastrointestinal tract into the neonatal circulation. Also the high activity in gastrointestinal tissue that had been washed several times indicates that leucocytes adhere to mucosa or lie intramurally. We speculate that the presence of leucocytes in the gastrointestinal tract 60 hours after a single breast feed can provide an important defence mechanism against infection.

Animals↗

Outbreak of colonization of neonates with Enterobacter sakazakii.

An outbreak of colonization of 11 neonates with Enterobacter sakazakii occurred in a neonatal intensive care unit from the 10 September to 17 October 1984. During this period Ent. sakazakii was isolated from throat and rectal swabs and tracheal aspirates, but not from blood, of the neonates. The duration of colonization ranged from 2 to 8 weeks. The isolates were resistant to amikacin and to tobramycin, but sensitive to gentamicin. Four of the 11 colonized neonates had clinical signs of severe sepsis and one of meningitis and four died in spite of intensive chemotherapy. The source and the mode of spread of Ent. sakazakii remained unknown as it was not found on the hands of staff or in the inanimate environment of the unit. Ent. sakazakii may be implicated in severe infections in neonates and should be included when screening clinical specimens.

Bacteriological Techniques↗

Immunologic deficiencies in small-for-dates neonates.

Health is dependent upon good nutrition because of the interactions of immunologic function with nutritional status. Full-term neonates--and even more so prematures--present with various immaturities of their humoral and cellular immunologic mechanisms, particularly during the first days of life. Foetal growth retardation causes further deficiencies to the immature neonatal host defence mechanisms by decreasing thymic hormone activity and by reducing the numbers and activity of T and B-lymphocytes in their peripheral blood. Furthermore, very low levels of IgG 1 immunoglobulin and reduced bacteriocidal capacity of polymorphonuclear neutrophils have been found in small-for-dates neonates. Impaired immunocompetence in growth-retarded neonates is probably the main cause of the increased frequency and severity of infections they develop.

Adult↗

Antibody dependent cytotoxicity of human colostrum phagocytes.

Monocytes and polymorphonuclear neutrophils of human colostrum were identified using cytochemical staining procedures. The ability of colostral phagocytes to function in antibody dependent cellular cytotoxicity was found to be satisfactory at high effector/target cells ratio (20:1) Colostral monocytes showed a diminished cytotoxicity when compared to monocytes of adult or neonatal peripheral blood at low effector/target cells ratio (1:1). This could be due to the extensive fat ingestion by these cells or other inhibitory factors found in colostrum.

Antibody-Dependent Cell Cytotoxicity↗

Parental nutrition in sick low-birth-weight neonates.

T. P. N. (aminoacids-glucose-fat) or aminoacids and glucose (A-G.) was given to 49 premature low-birth-weight neonates through peripheral veins for 7--42 days. The T. P. N. infusate contained glucose 12--20.5 g/kg/day and a standard dose of 2 g/kg/day for aminoacids and fat. The patients formed 4 groups: Twenty neonates were healthy but unable to tolerate oral feeding. Ten of them (group A) received T. P. N. and ten (Group B) received only A-G. Twenty nine neonates suffered from serious illness: 14 of them (Group C) received T. P. N. and 15 (Group D) A-G. In healthy neonates the weight gain was significantly higher in those who received T. P. N. than in those who took the same amount of calories but with A-G only. The addition of fat in parenteral nutrition is necessary in order to achieve a weight gain similar to that of intrauterine period. Fat is even more necessary in sick low-birth-weight neonates because they were found to be unable to tolerate high doses of glucose. Only part of the energy intake of the sick neonates could be covered with A-G. The present study has shown that parenteral nutrition can safely be given to sick low-birth-weight neonates without serious complications.

Acid-Base Equilibrium↗

Cytotoxicity of lymphocytes in the newborn.

Antibody-dependent, phytohaemagglutinin-induced, and spontaneous cytotoxicity was studied in 44 term and 60 preterm newborn babies, all of whom were healthy and of normal weight for gestational age. Twenty-seven adults were used as controls. Antibody-dependent cytotoxicity was low in term babies particularly in the preterm ones during the first 4 days of life, but soon rose to adult levels. Phytohaemagglutinin-induced cytotoxicity was low both in term and preterm babies compared with adult levels, and remained lower throughout the neonatal period although it began to rise. Spontaneous cytotoxicity was lower in preterm babies than in term ones during the first 2 weeks of life, and lower too than in adults. These findings indicate decreased cytotoxic ability of neonatal leucocytes especially during the first 4 days of postnatal life particularly in preterm babies, suggesting either lack of effector cells or that the cells are functionally immature.

Antibody-Dependent Cell Cytotoxicity↗