Plasma levels of interleukin-6 and interleukin-10 in preterm neonates evaluated for sepsis

In a prospective study, plasma interleukin-6 (IL-6) and interleukin-10 (IL-10) levels were measured by enzyme-linked immunosorbent assay in 45 premature neonates (25–34 weeks gestational age) with signs and symptoms of suspected sepsis at 0, 12 and 24 h; C-reactive protein (CRP) was measured at 0–24 h after enrolment. Six subjects were excluded due to insufficient blood sampling. The remaining 39 neonates were assigned to one of three groups: 25 newborns with sepsis (blood culture positive), seven with pneumonia (positive results on broncho-alveolar lavage fluid culture and characteristic chest radiography) and seven with necrotising enterocolitis (NEC) (characteristic intestinal and radiological signs according to the criteria of Bell et al.). A group of 20 healthy preterm neonates represented control subjects. On admission, higher levels of IL-6, IL-10 and CRP were observed in neonates with sepsis: IL-6 (median 1500 pg/ml, range 487–10000 pg/ml), IL-10 (median 113 pg/ml, range 70–196 pg/ml), CRP (median 22 mg/l, range 4–80 mg/l); pneumonia: IL-6 (median 1500 pg/ml, range 747–8000 pg/ml, IL-10 (median 84 pg/ml, range 76–92 pg/ml), CRP (median 10 mg/l, range 8–33 mg/l) and NEC: IL-6 (median 6650 pg/ml, range 1595–7950 pg/ml), IL-10 (median 80 pg/ml, range 61–147 pg/ml), CRP (median 3 mg/l, range 2.8–8 mg/l) as compared to controls (IL-6 median 208 pg/ml, range 198–349 pg/ml; IL-10 median 36 pg/ml, range 19–50 pg/ml; CRP median <2 mg/l) (P < 0.05). In neonates with sepsis, IL-6 levels were significantly correlated with IL-10 levels (r=0.65; P=0.04) at the time of the second sample. The highest IL-6 levels were observed at onset, while IL-10 was predominant 12 h later. On admission, IL-10 and CRP levels were significantly higher in non-survivors (IL-10 median 507 pg/ml, range 422–753 pg/ml; CRP median 123 mg/l, range 20–219 mg/l) than in survivors (IL-10 median 76 pg/ml, range 61–143 pg/ml; CRP median 8 mg/l range 3–46 mg/l), while IL-10 levels were significantly higher (P < 0.05) also 12 h after admission (non-survivors: IL-10 median 600 pg/ml, range 538–800 pg/ml; survivors: IL-10 median 74 pg/ml, range 53–161 pg/ml). IL-6 and IL-10 levels were significantly correlated with CRP levels on admission (r=0.45; P=0.05). Conclusion Preterm neonates with sepsis, pneumonia or necrotising enterocolitis showed increased interleukin-6, interleukin-10 and C-reactive protein levels. High interleukin-10 concentration was associated with mortality and could be an early indicator of prognosis. Received: 21 November 2000 / Accepted: 23 January 2001     

Cord blood interleukin-10 levels are increased in preterm newborns

Cell-mediated immunosuppression due to interleukin (IL)-10 may contribute to normal pregnancy. By contrast, delivery is associated with a predominance of T-helper-1 (Th1) cytokines (IL-12, interferon-γ) and might be regarded as a graft rejection process. The aim of the study was to assess IL-10 and IL-12 levels in cord blood samples from newborns and their normal mothers in relation to the gestational age and type of delivery. Cord blood and serum samples were obtained from 31 term newborns (gestational age 38–42 weeks) and 40 preterm newborns (mean gestational age 32 weeks). Serum samples were obtained from 26 mothers of term newborns at birth. There were 18 term and preterm infants born by caesarean section. Measurements of IL-10 and IL-12 levels by ELISA were repeated in mothers 15 days after delivery and in 11 preterm infants (median 14 days of age). Cord blood IL-10 levels were significantly higher in preterm than in term newborns (median 17.0 versus 3.2 pg/ml, P = 0.0001), but were similar to term newborns and paired mothers (2.2 versus 1.0 pg/ml). Term and preterm newborns also showed similar cord blood IL-12 levels (median 349 versus 320 pg/ml), and these levels were significantly higher when compared to their paired mothers (median 14.5 pg/ml, P = 0.0003). Cord blood IL-10 levels showed a significant inverse correlation with gestational age (P = 0.0001). When preterm infants, at several weeks post-delivery, were compared to gestational age matched newborns, their IL-10 levels were similar (median 8.3 pg/ml) whereas IL-12 levels were clearly lower(147 pg/ml; P = 0.0007). The type of delivery (vaginal versus caesarean) did not influence cord blood IL-10 and IL-12 results. Conclusion Cord blood IL-10 levels are increased in preterm newborns and may be due to the immunosuppression occurring during pregnancy and to fetal immaturity because these levels are inversely correlated with gestational age. Received: 18 December 1998 and in revised form 12 October 1999 / Accepted: 25 October 1999     

Serum vascular endothelial growth factor: a new predictive indicator for the occurrence of coronary artery lesions in Kawasaki disease

We investigated serum vascular endothelial growth factor (SVEGF) levels in Kawasaki disease and determined whether these levels had any association with the development of coronary artery lesions. We measured SVEGF levels in 66 patients with Kawasaki disease, 18 patients with active infections and 18 afebrile controls. SVEGF levels of patients in the acute phase of Kawasaki disease (0.0–2003.6 pg/ml, median 59.87 pg/ml) were significantly higher than those of patients with active infections (0.0–45.2 pg/ml, median 8.10 pg/ml; P < 0.05) or afebrile controls (0.0–49.8 pg/ml, median 7.75 pg/ml; P < 0.05) and decreased to undetectable or low levels in the recovery phase (n=31, acute phase: 0.0–2003.6 pg/ml, median 62.50 pg/ml versus recovery phase: 0.0–146.5 pg/ml, median 26.90 pg/ml; P=0.0007) of the disease. There existed a positive correlation between SVEGF levels and serum C-reactive protein concentrations in the acute phase of Kawasaki disease (r _s =0.347, P=0.0051). In addition, SVEGF level and duration of fever were found to be major risk factors for the occurrence of coronary artery lesions by univariate (P=0.012 and P=0.003, respectively) and multivariate (P=0.037, OR 6.16 and P=0.0059, OR 7.59, respectively) analyses. Conclusion Serum vascular endothelial growth factor level, in combination with persistence of fever, could be a powerful predictor for the development of coronary aneurysms. Received: 16 March 1999 / Accepted: 30 November 1999     

TNF-α is a mediator of the anti-inflammatory response in a human neonatal model of the non-septic shock syndrome

The anti-inflammatory/immunoparalytic phase of the systemic inflammatory response syndrome (SIRS) following major insult (surgery, thermal/traumatic injury) is of major clinical importance in the neonate, during which the risk of infection is particularly great. Here, the mechanisms by which TNF-α production is suppressed in response to infection are largely unknown. We questioned whether TNF-α itself could be a critical mediator of this suppression. Monocytes, isolated from cord blood (n=3), were treated with LPS (100 ng/ml), TNF-α (10 ng/ml, +/− anti-TNF-α antibody) for 18 and 36 h. Cells were then restimulated with LPS (Gram −ve) or Pam-3-Cys (Gram +ve) for 24 h. This was also done in the presence of selective inhibitors of MAP kinases p38, MEK and JNK. TNF-α, IL-6, IL-10 and IL-8 were quantified by ELISA CD86 and HLA-DR expression were determined flow cytometrically. Cells stimulated with LPS for 24 h produced TNF-α (282 pg/ml), IL-10 (1,236 pg/ml), IL-6 (2,694 pg/ml) and IL-8 (2,144 pg/ml). In cells pre-exposed to TNF-α for 36 h, there was a significant suppression in TNF-α and IL-6 levels (9 and 221 pg/ml, respectively) (P<0.05) with minimal impact on IL-10 (1,206 pg/ml) and IL-8 levels (1,886 pg/ml). A similar effect was seen with Pam-3-Cys with a tenfold decrease in levels of TNF-α and IL-6 (86→8.5 pg/ml and 458→46 pg/ml, respectively) with no effect on IL-10 and IL-8 levels. Anti-TNF-α antibody negated this effect. Inhibition of p38 kinase reversed the TNF-α effect. Inhibition of the JNK and MEK kinases had no effect. A reduction in the expression of CD86 and HLA-DR was observed. This ex-vivo model of non-septic SIRS demonstrates that TNF-α, released during a major insult, can suppress subsequent monocyte responses to bacterial agents through p38 MAP kinase, making it a potential therapeutic target.     

Suppression of elevated plasma interleukin-8 levels due to total ischemia and reperfusion of the small intestine by luminal perfusion with fetal bovine serum

 A previous study demonstrated that continuous enteric luminal perfusion of fetal bovine serum (FBS) protects the small intestine from total ischemia/reperfusion injury (IRI) and increases the intestinal mass. In this study, we further investigated the changes in plasma interleukin-8 (IL-8) level caused by total ischemia/reperfusion of the small intestine and the effect of FBS on plasma IL-8 levels. A 3-h total ischemia was induced in a 15-cm segment of terminal ileum and then reperfusion was instituted. Luminal perfusion of FBS was conducted via an osmotic minipump connected to the stomach through a fine polyethylene tube, starting 3 days prior to total ischemia. The rats were killed after 10 and 30 min and 1 and 3 h of total ischemia, and 1, 6, and 12 h or 1, 2, and 3 days after initiation of reperfusion. Plasma IL-8 was measured by enzyme-linked immunosorbent assay. The results were compared among the FBS-treated and untreated groups. The plasma IL-8 level was elevated from 1 h of total ischemia to 6 h after initiation of reperfusion (P < 0.05) with a peak of 641.5 ± 36.9 pg/ml in the untreated group and 471.6 ± 42.2 pg/ml in the treated group. Luminal perfusion of FBS significantly suppressed plasma IL-8 levels after 1 h of total ischemia and 1 h after initiation of reperfusion (P < 0.05). The results suggest that FBS might play a role in the treatment of total IRI of the small intestine. Accepted: 21 March 2001     

Comparison of two inspiratory: expiratory ratios during high frequency oscillation

The aim of this study was to compare gas exchange and volume delivery during high frequency oscillation at two frequently used inspiratory:expiratory (I:E) ratios: 1:2 and 1:1, other oscillatory settings being kept constant. A group of 13 infants with respiratory distress syndrome, median gestational age 28 weeks (range 23–36) and postnatal age 1 day (range 1–8) were studied. At the I:E ratio of 1:1 compared to 1:2 the median paCO₂ was lower, P < 0.05 (30 mmHg, range 22–47 vs 34 mmHg, range 27–46) and the volume delivered higher, P < 0.01 (2.6 ml/kg, range 1.2–5.6 vs 2.0 ml/kg, range 1.0–3.9). There was no significant difference in oxygenation levels at the two I:E ratios. In a related in vitro study, changing the I:E ratio from 1:2 to 1:1 increased the mean airway pressure by a median of 8.6% (range 2.9–28.1%). Conclusion Routinely maintained longer expiratory than inspiratory times during high frequency oscillation should be discouraged. Received: 6 November 1998 / Accepted: 30 March 1999     

Phototherapy for neonatal hyperbilirubinemia affects cytokine production by peripheral blood mononuclear cells

The capacity of peripheral blood mononuclear cells (PBMC) to produce interleukin (IL) IL-1β, IL-2, IL-3, IL-6, IL-10 and tumor necrosis factor-α (TNFα) was examined in term newborns with hyperbilirubinemia after 24 hours' exposure to phototherapy (wave length 425–475 nm). The results were compared with those from untreated neonates. Fifty newborns spontaneously delivered at term were included in the study. Blood samples were collected from 20 newborns before and 24 h after phototherapy. The control group consisted of 30 neonates examined on two consecutive days. PBMC isolated from blood samples were incubated in vitro for cytokine production. The concentration of cytokines in the supernatants was tested using ELISA kits (for IL-1β, IL-6, IL-10 and TNFα), or by bioassays (for IL-2 and IL-3). Phototherapy caused a 70% increase in IL-2 secretion (123 ± 27 vs 208 ± 30 units/ml, P < 0.01) and 56% in IL-10 production (1.07 ± 0.19 vs 1.67 ± 0.33 ng/ml, P < 0.03), whereas the spontaneous secretion of IL-1β was reduced by 43% (13.7 ± 2.3 vs 7.3 ± 1.7 ng/ml, P < 0.02). In the control group the secretion of these cytokines was similar on the two consecutive days and did not differ significantly from secretion in the other group before phototherapy. On the other hand, lipopolysaccharide induced TNFα production was higher on the second day in the two groups of newborns irrespective of phototherapy (388 ± 58 vs 683 ± 88 pg/ml, P < 0.001, in the control group and 384 ± 75 vs 588 ± 91, P < 0.05, before and after phototherapy). The synthesis of IL-3 and IL-6 did not change significantly between the two days of the study. The results demonstrate that in addition to the well-known positive effect of phototherapy on the neonate serum bilirubin level, this treatment affects the function of the immune system in newborns via alterations in cytokine production. Received: 4 September 1997 / Accepted: 14 February 1998     

Elevated platelet activating factor in the tracheal aspirate at birth and signs of intra-uterine inflammation in infants with neonatal pulmonary emphysema

To investigate the pathophysiology of the neonatal pulmonary emphysema, we assayed platelet activating factor (PAF) in the tracheal aspirates of the low birth weight infants. A total of 29 neonates (birth weight <1750 g) who required mechanical ventilation were enrolled. Tracheal aspirates were obtained within 48 h and blood samples collected within 24 h of life. PAF was assayed on the basis of its ability to cause aggregation of washed rabbit platelets. PAF was significantly elevated in four infants who showed pulmonary emphysema within the 1st week of life (median 24 pg/g lipid phosphorus, range 9.9–200) compared with those detected in the other three groups of infants; infants with respiratory distress syndrome (RDS) in whom chronic lung disease (CLD) did not develop (median 1.8 pg/g lipid phosphorus, range 0–30; P < 0.05), infants without RDS nor CLD (median 0.64 pg/g lipid phosphorus, range 0–14; P < 0.05) and infants with other types of CLD (median 1.1 pg/g lipid phosphorus, range 0–1.8; P < 0.01). The four infants who developed pulmonary emphysema within the 1st week of life, had significantly elevated serum IgM and neutrophilia at birth. The increased amount of PAF in the tracheal aspirates shows the presence of inflammation in the lung at birth. The elevated serum IgM level and neutrophilia indicate that the inflammation begins in utero. Conclusion Our data suggest that neonatal pulmonary emphysema is caused by intra-uterine inflammation increasing platelet activating factor in the lungs. Platelet activating factor may play a role in aggravating the process of pulmonary emphysema. Received: 20 July 1998 / Accepted: 14 February 1999     

Cord blood levels of interleukin-6 and interleukin-8 for the immediate diagnosis of early-onset infection in premature infants

BACKGROUND: Cytokine plasma levels are suggested to be sensitive indicators of neonatal sepsis, but conventional assays are time consuming. This study aimed at evaluating the significance of cord blood levels of interleukin (IL)-6 and IL-8 determined by a fully automated random access assay within 90 min of admission to predict systemic bacterial infection. PATIENTS AND METHODS: Cord blood levels of IL-6 and IL-8 were determined in 71 mature and 100 premature infants by a chemiluminescence assay (Immulite). Patients were divided into four groups according to a clinical and laboratory scoring system. Group A: documented early-onset infection; group B: infection possible; group C: infection unlikely, and group D: healthy newborns. RESULTS: Median IL-6 levels in the subgroup of premature newborns were as follows: group A, 1,920 pg/ml (5-95% confidence interval 308-4,660 pg/ml); group B, 50 (15-102) pg/ml; group C, 21 (12-71) pg/ml, and group D, 8 (6-11) pg/ml. For IL-8, median levels for groups A-D were 289 (226-514) pg/ml, 87 (40-107) pg/ml, 44 (33-98) pg/ml and 21 (16-25) pg/ml, respectively. The difference between group A and the other groups was highly significant (IL-6 p < 0.0001, IL-8 p < 0.001). At a cut-off of 80 pg/ml, the sensitivity of IL-6 for the diagnosis of sepsis was 96% (specificity 95%). For IL-8 (cut-off 90 pg/ml), the sensitivity was 87% (specificity 94%). CONCLUSION: In premature infants, the diagnosis of an early-onset infection can be established or ruled out with a high level of confidence by measuring IL-6 or IL-8 levels from cord blood using a random access chemiluminescence assay.     

Clinical significance of plasma endothelin levels in patients with biliary atresia

Biliary atresia (BA) is the end-result of a destructive inflammatory process that affects intra- and extrahepatic bile ducts, leading to fibrosis and obliteration of the biliary tracts with the development of biliary cirrhosis and portal hypertension (PH). Endothelins (ET) are 21-amino-acid peptides of endothelial origin with potent vasoconstrictor activity that bind to various cells of the liver. Nothing is presently known about plasma ET levels in BA. The aim of this study was to determine the clinical significance of plasma ET levels in patients with BA after hepatic portoenterostomy (Kasai's procedure) and to correlate these with liver function tests (LFT) and PH. We measured plasma concentrations of ET in 19 patients with BA (5 boys and 14 girls; mean age 11.6 ± 5.5 years) after portoenterostomy and 10 age-matched controls. Patients were grouped according to outcome based on LFT: group A consisted of 9 patients with an ‘‘unfavorable outcome” and Group B 10 patients with a “favorable outcome”. The plasma ET levels were measured using a highly sensitive and specific enzyme immunometeric assay (EIA). No patient had ascites or hepatorenal syndrome. Plasma ET levels were significantly higher in patients with BA than in controls (3.42 ± 0.42 vs 1.75 ± 0.39 pg/ml, respectively; P < 0.01) and in patients in group A than in group B. (3.75 ± 0.25 vs 3.06 ± 0.23 pg/ml, respectively; P < 0.01). In group A, plasma ET levels were higher in patients with PH (n = 4) than in those without PH (n = 5) (3.99 ± 0.06 vs 3.64 ± 0.22 pg/ml, respectively; P < 0.05). We conclude that plasma ET levels are high in patients with BA, especially those with severe biliary cirrhosis, and that ET may partially contribute to development of PH in BA. The results of the present study also suggest that plasma ET concentrations may be a useful marker in the follow-up of patients with BA. Accepted: 12 September 1997     

Effect of elective antibiotic therapy on resting energy expenditure and inflammation in cystic fibrosis

Cystic fibrosis (CF) patients often present with malnutrition which may partly be due to increased resting energy expenditure (REE) secondary to inflammation. Both REE and tumour necrosis factor-alpha (TNF-α), as other markers of inflammation, are elevated during respiratory exacerbations and decrease after antibiotic treatment. However, the effect of antibiotic therapy on REE and inflammation in patients without respiratory exacerbation is not known. The aim of our study was to determine the effect of such an elective antibiotic therapy on REE, TNF-α, and other serum markers of inflammation. Twelve CF patients 5F/7M, age 15.9 ± 6.1 years, weight for height ratio 89 ± 8% without clinically obvious exacerbation and treated by intravenous antibiotics were studied. Both before (D0) and after (D14) treatment, pulmonary function tests were performed. REE was measured by indirect calorimetry and blood taken to measure inflammation parameters. Body weight increased by 1.1 kg from D0 to D14 (P < 0.001), composed of 0.3 kg fat mass and 0.8 kg fat-free mass (FFM). The forced expiratory volume at 1 s increased from 43 ± 15% of predicted at D0 to 51 ± 15% of predicted at D14 (P < 0.01). Mean REE was 41.1 ± 7.6 kcal/kg FFM per day at D0 and did not change significantly at D14 (40.6 ± 8.5 kcal/kg FFM per day). Serum markers of inflammation decreased from D0 to D14: C-reactive protein 17 ± 17 mg/l to 4 ± 7 mg/l (P < 0.05), elastase 62 ± 29 μg/l to 45 ± 18 μg/l (P < 0.02), orosomucoid acid 1.25 ± 0.11 g/l to 0.80 ± 0.15 g/l (P < 0.001), and TNF-α 37 ± 14 pg/ml to 29 ± 6 pg/ml (P = 0.05). Individual values showed a correlation between changes in REE and in TNF-α (P < 0.02). Conclusion The contribution of inflammation to energy expenditure is possible but appears to be minimal in cystic fibrosis patients treated by antibiotics on a regular basis in the absence of clinically obvious exacerbation. Received: 6 August 1998 and in revised form: 23 November 1998 / Accepted: 23 November 1998     

Prediction of extubation failure in preterm neonates

The aim of this study was to compare the results of lung function measurements made before and after extubation and ventilator settings recorded immediately prior to extubation with regard to their ability to predict extubation success in mechanically ventilated, prematurely born infants. Immediately after extubation all infants were nursed in an appropriate amount of humidified oxygen bled into a headbox. Functional residual capacity, spontaneous tidal volume and compliance of the respiratory system were measured both within 4 h before and within 24 h after extubation. The peak inspiratory pressure and inspired oxygen concentration immediately prior to extubation were recorded. The results were related to extubation failure: requirement for continuous positive airways pressure or re-ventilation within 48 h of extubation. A total of 30 infants, median gestational age 29 weeks (range 25–33 weeks) were studied at a median postnatal age of 3 days (range 1–6 days). Extubation failed in ten infants, who differed significantly from the rest of the cohort with regard to their post extubation functional residual capacity (FRC) (median 23, range 15.6–28.7 ml/kg versus 28.6, range 18.1–39.2 ml/kg, P < 0.01) and their requirement for a higher inspired oxygen concentration post extubation (median 0.30, range 0.21–0.40 versus 0.22, range 0.21–0.36, P < 0.05). An FRC of less than 26 ml/kg post extubation had the highest positive predictive value in predicting extubation failure. Conclusion A low lung volume performed best in predicting extubation failure when compared to the results of other lung function measurements and commonly used `clinical' indices, i.e. ventilator settings. A low gestational age, however, was a better predictor of extubation failure than a low lung volume. Received: 1 November 1998 / Accepted: 16 April 1999     

The relationship between procollagen-III-peptide and the severity of esophageal varices in children with biliary atresia after Kasai operation

Biliary atresia (BA) is a common cause of infantile cholestasis. Disease progression leads to intra hepaticfibrosis, and thus to the development of PH and EV. Our objective has been to study the relationship between procollagen-III-peptide (PIIIP) and the severity of EV in children with BA after Kasai operation. Children below 15 years of age (n=29) with BA after a Kasai operation were evaluated for EV by endoscopy. Healthy (n=26) children of the same age and sex distribution who participated in the hepatitis B vaccination program served as the controls. Serum PIIIP was determined by radioimmunoassay. The BA patients were classified on the basis of severity of EV (Paquet's classification) into three groups: group 1 (n=15) had grade 0, group 2 (n=8) grade 1–2, and group 3 (n=6) grade 3–4 EV. In group 3, serum PIIIP (2.9 ± 1.3 IU/ml) was significantly higher than in group 2 (1.5 ± 0.4 IU/ml) (P < 0.05). Serum PIIIP levels were increased in group 2 compared with group 1 (1.2 ± 0.4 IU/ml) and in group 1 compared with the control group (1.2 ± 0.2 IU/ml), but this difference was not significant. PIIIP levels increased with severity of the EV in the BA patients. Hence, high PIIIP levels may serve as a non invastive indicator of EV developing in postoperative BA patients. Accepted: 8 January 2001     

Plasma vascular endothelial growth factor level is a predictor of the severity of postoperative capillary leak syndrome in neonates undergoing cardiopulmonary bypass

 Capillary leak syndrome (CLS), characterized by extravascular fluid accumulation and significant organ dysfunction, is a serious complication in children undergoing cardiopulmonary bypass (CPB). We examined the relationship between plasma vascular endothelial growth factor (VEGF) levels and severity of CLS. The kinetics of VEGF in the plasma of 11 neonates and 7 older children undergoing CPB were investigated, correlating plasma VEGF levels and CLS clinical presentation. The degree of postoperative CLS was quantified by measuring parameters of extracellular volume and end-organ dysfunction. A chest-wall soft-tissue-width index (CSTWI) was designed in order to standardize the extracellular fluid accumulation. Most CLS parameters were significantly more prominent in the neonatal patients. Low plasma VEFG levels (>35 pg/ml) were found in 3 neonatal control patients and all but, sample from the older group patient. The neonates had significantly higher preoperative VEGF plasma levels (684.4 ± 559.1 pg/ml, P = 0.02), which decreased during the operation to levels below 35 pg/ml and increased again 24 h postoperatively to levels significantly higher than in the older patients (484 ± 270.3 pg/ml, P = 0.001). Multilinear regression analysis found preoperative VEGF levels to independently correlate with CLS as represented by CSTWI (P < 0.01, r = 0.726). Both the occurrence of post-CPB CLS and plasma VEGF levels pre- and postoperatively were thus higher in neonates than in children. Plasma VEGF level is a predictor of the severity of postoperative CLS. Accepted: 1 March 2000     

Lipid and lipoprotein profiles in children with familial hypercholesterolaemia: effects of therapy

In 71 children with familial hypercholesterolaemia the effect of dietary and/or medical treatment was evaluated. Initial total cholesterol and low density lipoprotein (LDL)-cholesterol levels were significantly lower in children who were consecutively treated by diet (Step-One-Diet) than in those who received additional medication. By dietary treatment, the median total cholesterol level (236.5 mg/dl; range 210–510 mg/dl) was reduced by 7.4% and the median LDL-cholesterol level (162 mg/dl; range 126–423 mg/dl) by 9.9%. By dietary and medical therapy, the median total cholesterol level (330 mg/dl; range 270–424 mg/dl) was reduced by 29.7% and the median LDL-cholesterol level (263 mg/dl; 192–333 mg/dl) by 25.9%. High density lipoprotein (HDL)-cholesterol and HDL 3 remained unchanged. HDL 2 showed a significant decrease of 15.6% up to 27 mg/dl (13–42 mg/dl) on medical treatment. Apolipoprotein A I levels did not change during therapy. Initial apolipoprotein B levels were significantly higher in children who were treated by diet and medication and were reduced by 28.9% by combined therapy. In 28 patients (39.4%) an excess of lipoprotein (a) was detected. Regarding the apolipoprotein E phenotype, 32.2% of the patients carried the risk gene ɛ4 in a hetero- or homozygous form. Conclusion Early dietary and/or medical treatment in hypercholesterolaemic children significantly ameliorates the lipoprotein status. The pretherapy lipoprotein status seems to prognosticate the effectiveness of therapy. Received: 16 April 1997 / Accepted in revised form: 27 May 1998     

Serum concentration of granulocyte colony stimulating factor in term and preterm infants

We measured serum granulocyte colony stimulating factor (GCSF) concentration and absolute neutrophil count in four groups of infants: (1) 15 healthy term newborn infants; (2) 21 healthy preterm newborn infants, with mean (SD) birth weight 1583 (533) g, and gestational age 32.0 (3.8) weeks; (3) 5 infected newborn infants; (4) 22 6-month-old control infants. Median (range) serum GCSF concentration was 132.2 (41.5–176.0) pg/ml in term infants, 51.5 (1.8–175.7) pg/ml in preterm infants and 138.9 (54.1–449.8) pg/ml in 6-month-old control infants, with a significant reduction in preterm infants, as compared to term and control infants. GCSF levels were significantly higher in the infected infants, as compared to healthy neonates. Conclusion A significant positive relationship was found in term and preterm infants between serum GCSF concentration and gestational age or birth weight. No relationship was found between serum GCSF concen tration and neutrophil count. The low GCSF baseline levels may contribute to the increased incidence and severity of infection in preterm infants. Received: 17 May 1996 and in revised form: 20 July 1996 / Accepted: 29 July 1996     

Short-term, high-dose testosterone treatment fails to reduce adult height in boys with constitutional tall stature

Height predictions based on three different methods (Bayley-Pinneau [BP], Tanner-Whitehouse Mark II [TW II], Roche-Wainer-Thissen [RWT]) were compared to adult heights in 19 males with constitutional tall stature previously treated with high-dose testosterone oenanthate for 6 months (group A) and 25 untreated tall males (group B). Their chronological ages (CA) at the initial evaluation of tall stature ranged from 12.1 to 16.6 years in group A and from 10.4 to 15.7 years in group B; at the time of assessment of adult height ages ranged from 18.0 to 26.5 years and from 18.4 to 25.1 years, respectively. Height measurements and predicted adult heights were expressed as height standard deviation scores (height SDS) for chronological age using the tables of Reinken and van Oost [14]. Height SDS in group A were 2.8 (range = 1.8–5.4) before testosterone treatment, 3.0 (range = 2.0–4.8) thereafter and finally 3.0 (range = 2.1–4.2) (P=NS) and in group B 2.7 (range = 0.5–4.3) and 2.4 (range = 1.3–3.5) (P=NS). A significant difference between adult height SDS and predicted height SDS according to BP was detected both in group A (3.0; range = 2.1–4.2 vs 3.6; range = 2.4–5.0; P≤0.004) and group B (2.4; range = 1.3–3.5 vs 3.0; range = 2.0–4.9; P≤0.0002), whereas no significant difference between adult height SDS and predicted height SDS according to TW II and RWT was found in either group. These data indicate that BP height predictions overestimated adult height in our patient group of treated and untreated males with constitutional tall stature. In contrast, the TW II and RWT methods were more accurate in predicting adult height in these patients, but also failed to demonstrate that testosterone therapy in boys with constitutional tall stature can be limited to a 6-month period in order to reduce adult height. Conclusion The widely used height prediction method of BP is inaccurate in boys with constitutional tall stature. High dose testosterone treatment fails to reduce adult height in these individuals when discontinued before complete closure of the epiphyses. Received: 30 January 1997 / Accepted: 20 June 1997     

Voiding urosonography: the study of the urethra is no longer a limitation of the technique

Background  Voiding urosonography (VUS) has proved to be a reliable method for the study of vesicoureteric reflux (VUR). Early reports considered it inadequate for imaging the male urethra. Objective  To determine the usefulness of contrast-enhanced VUS for the study of the urethra. Material and methods  A total of 208 children aged 2 days to 10 years underwent VUS to confirm or exclude VUR for different reasons (n = 150) or for follow-up (n = 58). Patients with unconfirmed suspicion of VUR (99 boys and 51 girls) also underwent VUS for the study of the urethra. Examinations were performed using a harmonic imaging mode specific for contrast (Levovist) enhancement. We used a 6–4-MHz convex probe and a transperineal and/or a transpelvic approach. Results  The neck of the bladder and the entire urethra were visualized in all patients (n = 150). The male urethra was considered normal in 95 boys (95.95%). We diagnosed posterior urethral valves in two patients, diverticulum of the prostatic utricle in one, and diverticulum of the anterior urethra in one. All abnormal cases were confirmed using conventional voiding cystourethrography. Conclusion  VUS can replace voiding cystourethrography as the method of choice for the initial study of suspected VUR in children. This work was presented at the 44th Annual Meeting of the European Society of Paediatric Radiology, Barcelona, Spain, 3–7 June 2007.     

Effect of antioxidant therapy on collagen synthesis in corrosive esophageal burns

To investigate the efficacy of antioxidant therapy on collagen synthesis in corrosive esophageal burns, 110 Sprague-Dawley rats were divided into five groups of 22 animals each. A standard esophageal caustic burn was produced by 1 ml of 10% sodium hydroxide solution for the rats in groups B to E; group A was instilled only with 0.9% saline after preparation of the distal esophageal segment. Group A animals (controls) were uninjured and untreated. Group B had untreated esophageal burns. Esophageal burns were treated in group C with vitamin E (10 mg/kg IM), in group D with vitamin C (10 mg/kg IP), and in group E with methylprednisolone (30 mg/kg IM) on each of 5 days. Eight rats from each group were killed 4 days after initiation of the study and the abdominal esophagus was studied for tissue malondialdehyde (MDA; μmol/g protein) levels. The other rats were killed 28 days after initiation of the study and determination of hydroxyproline (HP) (μg/g tissue) levels in esophageal tissue was performed for 8 rats in each group. Histopathologic evaluation was also performed in the other 6 rats from each group. MDA levels in esophageal tissue were significantly lower in groups C (9.24 ± 2.62, P < 0.01) and group E (6.26 ± 2.22, P < 0.001) than in group B (12.35 ± 1.80). HP levels were significantly lower in groups A (0.75 ± 0.21, P < 0.001), C (1.11 ± 0.15, P < 0.01), and E (0.96 ± 0.15, P < 0.001) than in group B (1.40 ± 0.20). Histopathologically, collagen deposition in the submucosa and tunica muscularis was lower in groups C and E than in group B (P < 0.05, and 0.01, respectively). Our results demonstrate that treatment with antioxidant drugs such as vitamin E and methylprednisolone decreased tissue HP levels, and thus inhibited new collagen synthesis and stricture formation in rats with alkali-induced caustic esophageal burns. Accepted: 16 February 2001     

乳凝集素对轮状病毒感染新生大鼠肠道分泌IL-2、IL-4及INF-γ的影响

Objective To explore the influence of laetadherin on gut contents level of IL-2,IL-4 and IFN-γ in newborn rats with rotavirus infection.Methods Forty-five ten-day-old SD rats were randomly divided into three groups: control group(group N), rotavirus infection group(group V), rotavirus infection and lactadherin group(group VL) .All the rats were fed with formula,group V and group VL were fed with rotavirus(1 x 106) on the first day,then group VL were fed 25 mg/d lactedberin when they started diarrhea, until recovery. Gut contents samples were taken before feeding(T1), with most serious diarrhea(T2),after recovery(T3),the level of IL-2,IL-4 and IFN-γ in the gut contents were detected by ELISA. Results At time of T1 gut contents level of IL-2,IL-4 and IFN-γ were no statistically significant differences.Gut contents level of IL-2 and INF-γ were higher in group N[(348.84± 45.44) pg/ml, (33.95 ± 5.76) pg/ml] than those in group V[(97.97 ± 7.22) pg/ml, (25.00 ± 8.32)pg/ml] and group VL[(70.00 ± 8.27)pg/ml, (20.53 ± 2.10) pg/ml] at time of T2(P < 0.05). At time of T3 gut contents level of IL-2 and INF-γ, were higher in group VL than those in group V[(369.83 ± 36.83)pg/ml, (42.59 ± 7.54) pg/ml vs. (293.59 ± 45.64) pg/ml, (31.35 ± 3.63)pg/ml, P < 0.05], but the differences between group VL and group N were not statistically significant. Conclusions Lactadherin could boost gut contents levd of IL-2 and INF-γ in rats with rotavirus inretctiom, it plays a certain positive role on anti-rotavirus infection.