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Biomedical subjects

L Sirota

Publications and source records attributed to L Sirota.

At least 37 records · Page 2Linked to original sources

Ibuprofen affects pro- and anti-inflammatory cytokine production by mononuclear cells of preterm newborns.

The in vitro effect of ibuprofen (IB) on the production of the proinflammatory cytokines interleukin (IL) 1beta, IL-6, and tumor necrosis factor alpha (TNF-alpha) and the anti-inflammatory cytokine IL-10 by cord blood mononuclear cells from preterm newborns was compared to that of peripheral blood mononuclear cells of adults. Mononuclear cells were incubated without or with lipopolysaccharide in the absence or presence of various concentrations of IB. The levels of IL-1beta, IL-6, TNF-alpha, and IL-10 in the supernatants were tested by ELISA. The mononuclear cells from the two groups responded to IB by an increased secretion of IL-6 and TNF-alpha and by a reduced production of IL-10. The pattern of response to the drug was similar following stimulation with lipopolysaccharide. The IL-1beta production was mostly unaffected by IB. It is suggested that in preterm newborns the differences observed in the in vitro proinflammatory cytokine production in response to IB, as observed in the present study, or to indomethacin, as reported previously, may affect various clinical outcomes using these two drugs.

Adult↗

CD14 receptor expression and lipopolysaccharide-induced cytokine production in preterm and term neonates.

CD14 expression and the capacity of mononuclear cells (MC) from preterm and term neonates to secrete the proinflammatory cytokines interleukin (IL) 1 beta, tumor necrosis factor alpha and IL-6 in response to lipopolysaccharide (LPS) was investigated and compared to that of adults. MC were incubated with various doses of LPS, and the cytokine level in the supernatants was tested. CD14 receptors on MC and the intensity of their expression were analyzed. MC of preterm and term neonates and adults responded to LPS with low, medium and high proinflammatory cytokine production, respectively. CD14 expression was lowest in preterm infants, intermediate in term infants and highest in adults. The difference between term and preterm neonates for both parameters was significant. The results suggest a possible correlation between the lower expression of CD14 receptor on neonatal cells and the reduced secretion of proinflammatory cytokines by these cells. This decreased production may possibly contribute to the low ability of neonates to develop fever.

Cells, Cultured↗

Effect of dexamethasone on IL-10 and IL-12p40 production in newborns and adults.

The effect of dexamethasone (DEX) on interleukin (IL)-10 and IL-12p40 production was examined in preterm newborns, term infants and was compared to that in adults. Mononuclear cells isolated from newborn cord blood (CBMC) and peripheral blood from adults (PBMC) were incubated with lipopolysaccharide in the absence or presence of DEX at concentrations between 10(-8) and 10(-5) M. Cytokine concentration in the supernatants was tested using ELISA kits. DEX induced a dose-dependent inhibition of IL-10 production by PBMC from adults whereas CBMC from newborns were mostly unaffected by the drug. DEX caused a dose-dependent inhibition of IL-12p40 secretion by cells of the three age groups, although to a different extent. Since IL-12 plays a critical role in the development of a protective immune response to fungal infection, it is conceivable that the inhibition of IL-12p40 secretion caused by DEX may contribute to the increased occurrence of fungal infections in preterms treated with this drug.

Adult↗

Effect of cefotaxime on cytokine production in newborns and adults in vitro.

The in vitro effect of cefotaxime on the production of interleukin (IL)-1beta, IL-2, IL-6 and tumor necrosis factor alpha (TNFalpha) was studied in term neonates and was compared with that of adults. The addition of cefotaxime caused a significant enhancement of IL-2 production by cells of both adults and neonates, and increased the secretion of TNFalpha by peripheral blood mononuclear cells (PBMC) of adults, whereas the synthesis of this cytokine by cord blood mononuclear cells (CBMC) of the newborns was not affected. In contrast with the described stimulatory effects of cefotaxime, this drug induced dose-dependent inhibition of the spontaneous and lipopolysaccharide (LPS)-induced IL-1beta production by cells of the two groups, but had no effect on the in vitro production of IL-6. These data suggest that cefotaxime, apart from its known antimicrobial activity, may modify the host immune response of both newborns and adults, via the alteration of cytokine production.

Adult↗

Beware the chopsticks gene.

Population stratification is a potential source of error in psychiatric genetics. New study designs and statistical methods can help guard against this problem. Molecular Psychiatry (2000) 5, 11-13.

Ethnicity↗

Effect of antibiotic therapy in preterm premature rupture of the membranes on neonatal mortality and morbidity.

The objective of this study was to evaluate the effect of prophylactic antibiotic treatment on prenatal and neonatal outcome after preterm premature rupture of the membranes (P-PROM). The study population consisted of 172 pregnant women admitted to the Rabin Medical Center in Israel with P-PROM at 23-34 gestational weeks. The patients were divided into two groups by mode of expectant management-prophylactic ampicillin and erythromycin (study group, n = 121) or observation only (control group, n = 51) and compared for neonatal outcome. There were no significant differences between the groups in age, gravidity, parity, or gestational age at admission. Significantly more women in the study group had an interval of more than 24 hours from onset of P-PROM to delivery (98 women, 81%) than the control group (32 women, 63%) (p = 0.001). The neonatal mortality rate was significantly lower in the study group (6.6%) than the control group (1 7.6%) (p = 0.03). The lower neonatal mortality rate associated with prophylactic antibiotic treatment in P-PROM has important clinical implications for the effectiveness of this type of management.

Adult↗

Placental transfer and decay of varicella-zoster virus antibodies in preterm infants.

OBJECTIVES: To compare the placental transfer of maternal varicella-zoster (VZV) antibodies to preterm and term infants and to investigate antibody decay during the first 6 months of life in the preterm infants. STUDY DESIGN: Maternal and umbilical cord blood samples were taken from 113 healthy mother-newborn pairs: 64 term (gestational age > or =37 weeks) and 49 preterm (gestational age < or =35 weeks). Premature infants were further tested at 1, 2, and 6 months. Anti-VZV antibody to membrane antigen was measured with the immunofluorescent technique. RESULTS: Preterm infants of gestational age < or =28 weeks had positive cord antibody and a geometric mean titer significantly lower than those in preterm infants of gestational age 29 to 35 weeks and term infants (25% vs 95% and 95%, respectively, P <.001 for each, and 2.5 +/- 2.2 vs 10.5 +/- 2.4 and 12.6 +/- 2.4, respectively, P <.001 for each). There was no difference between the preterm 29 to 35 weeks of gestation and term groups. Fetal-maternal ratios for both preterm groups were <1 and were significantly less than the fetal-maternal ratio in the term infants. The transfer of maternal antibodies to term infants was significantly greater than to the 29- to 35-week preterm infants (P =.01). At 2 months of age, 25% of 29- to 35-week preterm infants and no preterm infant < or =28 weeks had a positive titer. At 6 months of age, all preterm infants were seronegative, and the geometric mean titer in both groups declined to undetectable levels. CONCLUSION: Transplacental transfer of maternal VZV antibodies is diminished in preterm infants. VZV antibody levels are significantly lower in preterm infants born at < or =28 weeks' gestational age compared with those in preterm infants 29 to 35 weeks' gestational age and term infants. Anti-VZV titers decrease to undetectable levels in preterm infants by 6 months of age or earlier; thus these infants appear to be susceptible to chickenpox before the scheduled 12-month vaccination.

Antibodies, Viral↗

Clinical and laboratory impact of coagulase-negative staphylococci bacteremia in preterm infants.

UNLABELLED: A retrospective evaluation of the clinical and laboratory impact of coagulase-negative staphylococci (CONS) bacteremia in preterm infants was carried out. The study population included all preterm infants (n = 31) in whom two or more blood cultures were positive for CONS within a period of 4 d, with negative blood cultures 1 wk before and 1 wk after the CONS bacteremia. Clinical manifestations and the results of laboratory tests 7 d before and after the positive blood cultures, and on the first day of sepsis, were recorded and compared. During CONS bacteremia, the infants demonstrated apnoea and bradycardia (88%) and a need for oxygen (59%) and ventilatory support (69%). Significant laboratory findings were leukopenia below 5,000 cells/mm3 (12%), leukocytosis above 30,000 cells/mm3 (39%), and thrombocytopenia below 150,000/mm3 (25%). These clinical and laboratory manifestations differed significantly during the bacteremia infection compared with the week before and after. CONCLUSION: CONS bacteremia is a clinically significant infection in preterm infants, causing episodes of apnoea and bradycardia, and a need for ventilatory support.

Anti-Bacterial Agents↗

Congenital Volkmann-Lesser ischemic contracture of the upper limb.

Neonatal vascular compromise to limbs has been associated traditionally with perinatal injury of the brachial plexus, fracture of the clavicle or humerus, or iatrogenic causes. Congenital Volkmann's ischemic contracture is an exceptional etiology of ischemic limb in the newborn. Fewer than 10 cases had been described in the literature. The authors report a newborn presenting at birth with partial bluish discoloration of the right forearm. The clinical picture and laboratory studies lead to the diagnosis of congenital Volkmann-Lesser ischemic contracture.

Arm↗

Liver enzyme abnormalities in gram-negative bacteremia of premature infants.

BACKGROUND: Hyperbilirubinemia and liver enzyme abnormalities are commonly observed in sepsis. However, the frequency in premature neonates and the specific relation to gram-negative bacteria are not known. PATIENTS AND METHODS: Charts of all preterm infants who had positive blood cultures for either gram-negative bacteria or coagulase-negative staphylococci were reviewed. Neonates with gram-negative bacteremia (n = 54) were compared with neonates with coagulase-negative staphylococcal bacteremia (n = 31). In addition infants with gram-negative bacteremia and elevated liver enzymes (n = 25) were compared with infants with gram-negative bacteremia and normal liver enzymes (n = 29). RESULTS: Liver enzyme abnormalities accompanied 46.3% (25 of 54) of gram-negative bacteremia and 12.9% (4 of 31) of episodes of coagulase-negative staphylococcal bacteremia (P = 0.002). Serum concentrations of liver enzymes were significantly higher in infants with gram-negative bacteremia than in those with coagulase-negative staphylococcal bacteremia (P < 0.0001), but no difference in alkaline phosphatase serum values was observed. Infants with gram-negative bacteremia and elevated liver enzymes were not fed for a longer period than infants with gram-negative bacteremia and normal liver enzymes (7.3 +/- 6.3 days vs. 4.0 +/- 4.3 days, P = 0.03), and this was accompanied by significant conjugated hyperbilirubinemia (P < 0.0001). Ventilation, total parenteral nutrition and medications were not responsible for the observed differences. Klebsiella pneumoniae bacteremia was commonly associated with elevated liver enzymes (12 of 18), whereas none of the infants with Pseudomonas aeruginosa bacteremia had elevated liver enzymes. CONCLUSIONS: Gram-negative bacteremia is commonly associated with cholestasis in premature neonates. Liver enzyme abnormalities are more common than elevated conjugated bilirubin, not all gram-negative bacteria have the same effect and the lack of enteral feeding seems to play a more significant role than the administration of parenteral nutrition.

Bacteremia↗

Diode laser treatment of posterior retinopathy of prematurity.

AIMS: To study the efficacy of infrared diode laser for the treatment of posterior retinopathy of prematurity (ROP). METHODS: 48 eyes of 25 premature babies (mean birth weight 779 (SD 127.7) g; mean gestational age 25.5 (SD 1.47) weeks) with threshold ROP in zone I and posterior zone II were treated by the indirect infrared (810 nm) diode laser. Confluent burns were applied to the avascular retina. In 18 eyes, an additional row of laser burns was added posterior to the ridge. RESULTS: Favourable anatomical results were noted in 41 eyes (85.4%). ROP stage 5 developed in two eyes, ROP stage 4A developed in four eyes, and ROP stage 4B in one eye. Three of the eyes with stage 4A eyes were successfully buckled; the fourth was not operated on and remained demarcated by laser scars. No complications were noted. CONCLUSION: In this series, the diode laser was found to be a safe and effective treatment for posterior ROP.

Female↗

Controlled trial of immune response of preterm infants to recombinant hepatitis B and inactivated poliovirus vaccines administered simultaneously shortly after birth.

AIM: The study was conducted to evaluate the immunogenicity of an early, extra dose of enhanced inactivated poliovirus vaccine (IPV) administered simultaneously with recombinant hepatitis B vaccine (HBV) to preterm infants shortly after birth. METHODS: Three groups were studied. Fifty preterm infants received IPV intramuscularly within 24 hours of birth, in addition to routine recommended childhood immunisations. Fifty two preterm infants and 35 full term infants received routine immunisations only (routine vaccination timing: HBV at birth, 1 and 6 months of age; IPV at 2 and 4 months; oral polio vaccine (OPV) at 4 and 6 months; diphtheria-tetanus-pertussis (DTP) at 2, 4, and 6 months; and Haemophilus influenzae B vaccine at 2 and 4 months). Blood samples were taken at birth, 3 and 7 months of age from all infants, and at 1 month of age from preterm infants only. RESULTS: At birth, a lower percentage of both study and control preterm infants had antipoliovirus type 3 titres >/= 1:8 than full term infants. At 1 and 3 months of age significantly more early IPV infants had antipoliovirus type 3 titres >/= 1:8 than routinely vaccinated preterm infants (p < 0.05). At 7 months of age there were no significant differences in percentage of antipoliovirus titres >/= 1:8 or geometric mean times (GMTs) between the early IPV group and the routinely vaccinated preterm group. At 3 and 7 months of age, the percentage of positive antihepatitis B titres (>/= 1:10) and the GMT of the early IPV preterm group did not differ significantly from those of preterm controls. There was no significant difference in percentage of positive antihepatitis B titres between the early IPV group and full term controls at any time. GMTs for hepatitis B antibodies were significantly lower in the early IPV preterm group than in full term controls at 3 and 7 months of age. CONCLUSIONS: Administration of an additional dose of IPV simultaneously with routine HBV to preterm infants shortly after birth provides early protection from poliovirus and hepatitis B infection, and does not interfere with poliovirus antibody production at the age of 7 months.

Antibodies, Viral↗

Early postnatal dexamethasone treatment and increased incidence of cerebral palsy.

OBJECTIVE: To study the long term neurodevelopmental outcome of children who participated in a randomised, double blind, placebo controlled study of early postnatal dexamethasone treatment for prevention of chronic lung disease. METHODS: The original study compared a three day course of dexamethasone (n = 132) with a saline placebo (n = 116) administered from before 12 hours of age in preterm infants, who were ventilated for respiratory distress syndrome and had received surfactant treatment. Dexamethasone treatment was associated with an increased incidence of hypertension, hyperglycaemia, and gastrointestinal haemorrhage and no reduction in either the incidence or severity of chronic lung disease or mortality. A total of 195 infants survived to discharge and five died later. Follow up data were obtained on 159 of 190 survivors at a mean (SD) age of 53 (18) months. RESULTS: No differences were found between the groups in terms of perinatal or neonatal course, antenatal steroid administration, severity of initial disease, or major neonatal morbidity. Dexamethasone treated children had a significantly higher incidence of cerebral palsy than those receiving placebo (39/80 (49%) v. 12/79 (15%) respectively; odds ratio (OR) 4.62, 95% confidence interval (95% CI) 2.38 to 8.98). The most common form of cerebral palsy was spastic diplegia (incidence 22/80 (28%) v. 5/79 (6%) in dexamethasone and placebo treated infants respectively; OR 4.45, 95% CI 1.95 to 10.15). Developmental delay was significantly more common in the dexamethasone treated group (44/80 (55%)) than in the placebo treated group (23/79 (29%); OR 2. 87, 95% CI 1.53 to 5.38). Dexamethasone treated infants had more periventricular leucomalacia and less intraventricular haemorrhage in the neonatal period than those in the placebo group, although these differences were not statistically significant. Eleven children with cerebral palsy had normal ultrasound scans in the neonatal period; all 11 had received dexamethasone. Logistic regression analysis showed both periventricular leucomalacia and drug assignment to dexamethasone to be highly significant predictors of abnormal neurological outcome. CONCLUSIONS: A three day course of dexamethasone administered shortly after birth in preterm infants with respiratory distress syndrome is associated with a significantly increased incidence of cerebral palsy and developmental delay.

Anti-Inflammatory Agents↗

Skin barrier properties in different body areas in neonates.

OBJECTIVE: The aim of the study was to investigate skin barrier function in neonates in different anatomic sites during the first 2 days of life. DESIGN: The study population consisted of 44 healthy full-term newborn infants. Transepidermal water loss (TEWL), stratum corneum hydration (SCH), and skin surface pH were measured in different anatomic sites (forehead, flexor part of forearm, upper back, abdomen, inguinal region, palms, and soles) during the first 10 hours of life and 24 hours later. Measurements were recorded with a Tevameter, a Corneometer, and a skin pH meter with a flat glass electrode. Results were compared with those in 20 healthy adults. RESULTS: TEWL was lower in infants than in adults in the forehead, palms, soles, and higher in the forearms. It was significantly higher on day 1 than on day 2 in the soles, palms, and forearms, and in the forearm, palms, and inguinal region compared with the other anatomic sites. SCH was significantly lower in the infants on the forehead, back, and abdomen, and higher on the forearms and palms; it was significantly higher on the first day of life on the forearms and palms, and lower in the inguinal region. Skin surface pH was significantly higher in the infants in all body sites (>6.6 in most measurements). On day 2, it was significantly lower than on day 1, but still higher than in adults. SCH correlated positively with TEWL in the neonates but not in the adults. None of the variables were related to gestational age, sex, mode of delivery, or body weight. CONCLUSIONS: Changes take place in SCH, water loss, and pH in the first 2 days after birth, suggesting that the stratum corneum barrier is still in the process of adapting to extrauterine life. The significant anatomic variability in TEWL and SCH should be taken into account in evaluating the permeation of skin care products and topical medications in newborns.

Adult↗

Effect of indomethacin on IL-1beta, IL-6 and TNFalpha production by mononuclear cells of preterm newborns and adults.

The in vitro effect of indomethacin (IM) on the production of interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)alpha by cord blood mononuclear cells (CBMC) from preterm newborns was compared to that of peripheral blood MC of adults (PBMC). MC isolated from peripheral blood of adults (PBMC) and cord blood of preterm newborns (CBMC) were incubated without or with lipopolysaccharide (LPS) in the absence or presence of various concentrations of IM. The levels of IL-1beta, IL-6 and TNFalpha in the supernatants were tested by ELISA. MC isolated from preterm newborns were less sensitive to the in vitro effect of IM on IL-1beta and TNFalpha secretion than adult cells. While the spontaneous secretion of IL-1beta and TNFalpha and the production of TNFalpha induced by LPS were significantly increased following incubation of adult PBMC with IM, only the spontaneous synthesis of TNFalpha by CBMC of preterm newborns was affected by this drug. The in vitro production of IL-6 by MC in the two groups was not affected by the addition of IM. It is suggested that IM may affect the preterm's immune response. However, the role of the drug in the frequency and severity of infections in the neonatal intensive care unit needs further investigation.

Adult↗

[Prematurity as an interplay between psychological and biological risk factors leading to infant psychopathology].

Concepts such as risk factor, vulnerability, protective factor and resiliency have become central in the field of developmental psychopathology. The birth of a very-low-birth weight premature baby can be used as a paradigm of the interplay between these factors. Indeed, prematurity implies for both infant and parents, biological as well as psychological risk factors. They may interact in such a way that the child's emotional, cognitive and social development will deviate from normal. Understanding the psychological impact of premature birth includes reference to both the normal psychological processes that characterize pregnancy that are jeopardized by a premature, often traumatic delivery, and to the special significance of being a parent in the Special Care Nursery. The contrast between the expected appearance of the baby and that of the sick-looking, tiny premature, together with uncertainty about its medical status, often affect the parents' bonding process. In addition, parents must learn quickly to cope with issues such as total dependence on a very busy team, loss of control of the care of their baby, and their unclear roles as parents. Added to these risk factors are the specific neurobehavioral characteristics of premature babies, which often make it hard for parents to read their cues and respond to them properly. A clinical vignette illustrates the chain of psychological and biological events that lead to severe disturbance of the early parent-child relationship. It also brings up the question of psychosocial intervention in the Special Care Nursery, both in terms of early detection of families at risk and the types of intervention.

Adaptation, Psychological↗