Interactions of endotoxin with cortisol and acute phase proteins in septic shock neonates

CRP, alpha 1-acid glycoprotein and haptoglobin were studied in 13 septic shock neonates. Endotoxin was recovered from eight infants. Serum cortisol concentration from infants with endotoxemia (917 +/- 596 ng/ml) was significantly higher than that from infants without endotoxemia (398 +/- 239 ng/ml). Serum cortisol correlated well with immature neutrophil counts defined as the unit "band/neutrophil". Increased cortisol level and immature neutrophil counts preceded the elevation of CRP, alpha 1-acid glycoprotein and haptoglobin in four extremely premature neonates. We conclude that positive interactions between endotoxin, cortisol and acute phase protein synthesis are present in the initial period of infection, and delayed acute phase protein synthesis is suspected in extremely premature neonates.     

内皮素-1在新生儿缺氧缺血性脑病中的变化及意义

目的　探讨内皮素 - 1(ET - 1)在新生儿缺氧缺血性脑病 (HIE)中的变化及意义。方法　采用放射免疫法测定 2 0例正常小儿和 5 2例HIE患儿的血清及脑脊液 (CSF)中ET 1水平 ,并将HIE患儿分为轻、中、重 3组。结果　正常对照组血清ET 1为 6 8.71± 12 .0 3ng/L。轻、中、重度HIE血清ET 1在急性期分别为 98.38±12 .82ng/L ,10 7.2 1± 18.5 6ng/L ,119.5 6± 14.6 9ng/L ;恢复期分别为73.44± 11.79ng/L ,75 .73± 11.38ng/L ,83.92± 15 .99ng/L。HIE患儿急性期血清ET 1水平显著高于恢复期及正常对照组 ,P <0 .0 1。轻、中、重度HIE患儿急性期CSF中ET 1水平分别为 43.79± 7.14ng/L ,5 1.0 7± 11.19ng/L ,6 1.86± 13.5 5ng/L ;恢复期CSF中ET 1水平分别为 30 .79± 4.42ng/L ,33.0 7± 4.84ng/L ,39.5 0± 5 .5 6ng/L。急性期CSF中ET 1水平显著高于恢复期 ,均P <0 .0 1,且血清及CSF中ET 1水平与病情轻重密切相关。急性期HIE患儿血清和CSF中ET 1水平 ,重度组明显高于正常对照组P <0 .0 1及P <0 .0 5 ,尤以重度组升高显著 ;恢复期轻 ,中度组ET 1水平降至正常 ,而重度组仍维持在较高水平 ,且血清及CSF中ET 1水平与病情轻重密切相关。血清和CSF中ET 1水平与 1分钟Apgar评分呈显著负相关。 结论　ET 1在HIE的发     

Influence of Dopamine on Atrial Natriuretic Peptide Level in Premature Infants

ABSTRACT. The role of dopamine (DA) in the activation and/or release of atrial natriuretic peptide (ANP) was investigated in 11 premature infants during the early postnatal period. Mean plasma concentration of ANP and free DA level before DA infusion was 252.6±210 fmol/ml, and 0.4±0.2 ng/ml, respectively. DA infusion in a dose of 2μg/kg/min caused a rise in plasma free DA level to 59.7±21.5 ng/ml and a significant increase in GFR, diuresis, sodium excretion and fractional sodium excretion. The plasma concentration of ANP, however, remained unchanged (252.6±210.0 vs. 213±143.0 fmol/ml). Thus, our data failed to demonstrate a stimulatory effect of DA on ANP release in premature infants. The role of the high plasma concentration of ANP in preterm neonates immediately after birth has to be clarified.     

Lactoferrin in relation to acute phase proteins in sera from newborn infants with severe infections

Serum lactoferrin concentrations were elevated in 22 out of 49 newborn infants with suspected and verified severe bacterial as well as viral infections, suggesting that this protein resembled an acute phase reactant. In the infants suspected of having septicemia, high concentrations of C-reactive protein appeared to indicate a severe bacterial infection. Like lactoferrin, however, haptoglobin, orosomucoid, 1-antitrypsin and 1-antichymotrypsin discriminated only poorly or not at all between infants with severe bacterial infections and those in which such infections were unlikely. Thus, serum CRP concentrations remained the most valuable of the acute phase reactants tested as an aid in ruling out septicemia in the neonatal period.     

THE CONCENTRATIONS OF TOTAL CORTISOL AND CORTICOSTERONE IN MIXED CORD PLASMA

ABSTRACT: Homoki, J., Teller, W. M., Tschürtz, D., and Fazekas, A. T. A. (Department of Paediatrics, Division of Endocrinology and Metabolism, University of Ulm/Donau, BRD). The concentrations of total Cortisol and corticosterone in mixed cord plasma. Acta Paediatr Scand, 64:587, 1975.–Cortisol and corticosterone were determined in mixed umbilical cord plasma of 43 healthy full-term newborns. The method consisted of a combined thin-layer chromatographic-ftuorimetric procedure which proved to be specific and reliable. The mean concentration in cord plasma of Cortisol was 10.6±4.9 μ.g/100 ml, of corticosterone 1.8±0.8 μg/100 ml. The mean ratio cortisol/corticosterone F/B was 6.3±2.5. Neither the duration nor the time of day of delivery appeared to influence the concentration of Cortisol or corticosterone in umbilical cord plasma. Also, there was no significant difference between male and female infants. In 18 instances of a pathological course of gestation and/or delivery the mean Cortisol level was 9.1±4.7 μg/ml, the mean corticosterone level 2.2±9 μg/100 ml. The mean F/B ratio was slightly but not significantly decreased (4.2±1.4 μg/100 ml; p >0.05). It is speculated that the high corticosterone concentration in umbilical cord plasma reflects a defect in Cortisol biosynthesis (17α-hydroxylase deficiency) in the newborn, compared with later life.     

White blood cells and acute phase reactants in neonatal sepsis

No single diagnostic test for neonatal sepsis is both rapid and reliable. Combining leukocyte (wbc) counts with acute phase reactants (APR) enhances diagnostic accuracy. The most helpful wbc counts are leukopenia (less than 5.0 x 10(9)/l), increased immature/total neutrophils (greater than or equal to 0.2) and profound neutropenia (less than 1.0 x 10(9)). Of the APR, C-reactive protein responds most rapidly, but alpha 1-acid glycoprotein (orosomucoid), haptoglobin and mini-ESR (greater than or equal to 15 mm/h) are also useful. Rapid, quantitative determinations of APR are now available with nephelometric techniques. Abnormal wbc counts frequently appear before APR changes in group B streptococcal infection. Sequential determinations of wbc counts and APR may provide valuable diagnostic and prognostic information.     

早产儿血清维生素E浓度测定

目的　测定早产儿维生素E的二种异构体α 生育酚和γ 生育酚的血清浓度,探讨早产儿体内维 生素E的水平。方法　选取早产儿、正常足月儿各16例,采用库仑阵列电化学法检测血清中维生素E水平。结果 与正常足月儿对比,早产儿血清α 生育酚浓度(217±120ng/mLvs411±284ng/mL)和γ 生育酚浓度(889±460 ng/mLvs2177±1031ng/mL)明显降低,差异有显著性意义(均P<0.05)。结论　早产儿体内维生素E储藏量相 对较少,容易发生维生素E缺乏。早产儿出生后应及时补充维生素E。     

SEQUENTIAL DETERMINATION OF CRP, α1-ANTITRYPSIN AND HAPTOGLOBIN IN NEONATAL SEPTICAEMIA

ABSTRACT. In 312 preterm and term newborn infants serum concentrations of C-reactive protein (CRP), haptoglobin and α₁-antitrypsin were measured during several days by radial immunodiffusion. In addition white blood cell count and the ratio of band to total neutrophils (B/N-ratio) were determined. In 12 infants with proven sepsis CRP was found elevated above the upper limit of the normal range (20 mg/l). Successful therapy was followed by a decrease of CRP concentration. In infants with suspected infection high CRP values were found in most cases. In contrast, haptoglobin and α₁-antitrypsin concentrations differed not significantly between the group of infants without infection, with proven and with suspected infection. White blood cell count and B/N-ratio also were not appropriate for the early identification of bacterial infection in the newborn period.     

Free Urinary Cortisol Immunoreactive Levels in Premature and Full Term Infants

ABSTRACT. Urinary free immunoreactive Cortisol excretion was measured in 20 full term, 20 premature and 20 premature newborns of mothers who had been treated with 12 mg betamethasone 48 hours before delivery. In 10 full term newborns delivered normally, values were 40 ±20 nmol/mmol creatinine on the first, 23±8 on the second and 21±6 on the third day of life. In 10 full term newborns with stressful delivery, the corresponding values were 63±39, 44±33 and 32±17 nmol/mmol creatinine in the first three days of life. The levels of urinary free immunoreactive Cortisol of 10 premature newborns delivered without stress were 170±116, 91±75 and 70±61 nmol/mmol creatinine respectively, on days one, two and three of life. Ten premature infants with respiratory distress syndrome had values of 471 ± 187, 526±465 and 636±906 nmol/mmol creatinine, respectively. The 10 premature newborns whose mothers had received betamethasone, had urinary free immunoreactive Cortisol levels of 109±120, 55±42 and 66±84 nmol/mmol creatinine, lower than the other premature infants. This difference, however, was not statistically significant. We conclude that premature infants regardless of stress or normal labor have high urinary free immunoreactive Cortisol excretion, suggesting that prematurity per se is a potent stress.     

Aldosterone Concentrations in Dehydrated Infants

ABSTRACT. The mean serum aldosterone concentration of 37 infants with acute gastroenteritis and dehydration was markedly elevated on admission (mean ±SE 94.3±12.1 ng/ml) and approximated to normal values (18.2±3.7 ng/ml) following recovery from the acute disease (t=3.56 p<0.005). Serum aldosterone levels were significantly positively correlated with the percent weight loss (r=0.41, p<0.05) and with the blood urea nitrogen levels (r=0.55, p<0.001). There was no correlation between either serum sodium levels or blood osmolarity and aldosterone concentrations. Serum potassium levels were positively correlated with aldoster-one levels (r=0.53, p<0.001). These findings indicate that small infants when dehydrated respond appropriately with elevated aldosterone levels. The amount of body fluid depletion and hyperkalemia are the major factors determining the amount of aldosterone response.     

Early diagnosis of neonatal infection

In 93 preterm and term infants with proven neonatal septicemia and/or meningitis different leukocyte indexes were evaluated at onset of septicemia [absolute neutrophil count, immature neutrophil count, immature to total neutrophil ratio (I/T-ratio)]. 75% of the patients who developed septicemia within the first three days of life and 60% of all neonates with septicemia or meningitis could be identified by an elevated I/T-ratio, the most sensitive leukocyte count. Thrombocytopenia was observed in only 33% of the patients. Additional analysis of IgM and fibrinogen was neither helpful in identifying neonatal infections nor a valuable follow-up parameter of successful treatment. In contrast C-reactive protein (CRP) was increased in 88% of all infants with neonatal septicemia and/or meningitis at time of diagnosis; when used in combination neutrophil indexes and CRP even improved the sensitivity of a single laboratory screening test.     

新生儿缺氧缺血性脑病血浆肿瘤坏死因子-α与降钙素基因相关肽水平变化的研究

目的 探讨肿瘤坏死因子-α(TNF-α)和降钙素基因相关肽(CGRP)在新生儿缺氧缺血性脑病(HIE)中的变化及临床意义。方法 采用放射免疫分析法对38例HIE患儿和18例健康足月新生儿血浆TNF-α与CGRP水平进行了同期动态观察。结果 HIE患儿急性期TNF-α,CGRP水平分别为(1.12±0.42) ng/ml,(88.92±23.16) ng/ml;恢复期分别为(0.61±0.18) ng/ml,(68.39±19.32) ng/ml;对照组分别为(0.54±0.15) ng/ml,(66.2±14.54) ng/ml。急性期血浆TNF-α和CGRP水平较恢复期显著增高(P<0.01),并明显高于同期对照组水平(P<0.01),恢复期与正常对照组无显著差异,急性期不同程度HIE与对照组TNF-α,CGRP水平比较,重度HIE组TNF-α,CGRP分别为(1.28±0.41) ng/ml,(118.12±30.25) ng/ml;中度HIE组分别为(0.95±0.3) ng/ml,(86.49±24.36) ng/ml,轻度HIE组分别为(0.63±0.19) ng/ml,(68.31±18.38) ng/ml,重度组明显高于对照组、轻度组及中度组,中度组高于对照组和轻度组,轻度组与对照组无显著性差异。急性期患儿血浆TNF-α与CGRP呈直线正相关关系(r=0.513,P<0.05)。结论 TNF-α和CGRP参与了新生儿HIE的发病过程。急性期TNF-α的增高可能是促发HIE脑损伤的一个重要因素,而CGRP增高在HIE中对脑损伤可能具有一定的保护作用。     

Circulating concentrations of chemokines in cord blood, neonates, and adults

Chemokines are critical for the movement of leukocytes. Chemotaxis is deficient in neonates, particularly those delivered prematurely, and this likely contributes to their increased vulnerability to sepsis. The concentrations of circulating chemokines in neonates have not been reported, nor is it known whether low chemokine concentrations contribute to their defective chemotaxis. We hypothesized that serum concentrations of chemokines 1) would be lower in preterm than term neonates, and 2) would be lower in preterm and term neonates than adults. Samples were obtained from preterm and term neonates with normal neutrophil and eosinophil counts, umbilical cord blood samples from pregnancies without clinical evidence of intra-amniotic infection, and healthy adult volunteers. The concentrations of epithelial neutrophil activating peptide-78, growth-related oncogene-alpha, eotaxin, RANTES (regulated upon activation, normal T cell expressed and secreted), and macrophage inflammatory protein-1 alpha were measured using specific ELISA. Serum concentrations from preterm infants were either similar to or higher than those measured in term neonates and adults. We conclude that the chemotactic defect observed in premature neonates is not the result of diminished circulating concentrations of any of the specific chemokines we measured.     

Serum interleukin-1β in neonatal sepsis

Serum levels of interleukin-1β (IL-1β) in newborn infants with septicaemia were measured and possible relationships between the clinical course of the infants, causative micro-organisms and IL-1β levels were investigated in a prospective study. The study groups comprised 49 newborn infants (25 mature, 24 premature) with proven sepsis and 40 healthy newborn infants (20 mature, 20 premature). Serum IL-1β levels were measured using the IL-1β immunoradiometric assay. The levels were found to be lower in neonates with sepsis (median 0.1 pg/ml) than in healthy controls (median 27.9 pg/ml) ( p <0.001). Non-significant trends towards lower levels were observed in children with shock and in non-survivors. No correlation was found between IL-1β and postnatal age, gestational age or the study weight of the patients. There was no significant difference in the serum IL-1β level in septic patients infected with Gram-positive bacteria and those infected with Gram-negative bacteria. The results show that the concentration of IL-1β is significantly decreased in preterm and term neonates with sepsis.     

Analysis of Blood Spot 17α-Hydroxyprogesterone Concentration in Premature Infants—Proposal for Cut-Off Limits in Screening for Congenital Adrenal Hyperplasia—

Blood Spot 17α-hydroxyprogesterone (17-OHP) concentrations in neonates, especially in premature babies, were determined in relation to 1) the gestational age at birth, 2) the equivalent age of gestation at blood sampling and 3) the birth weight. The 17-OHP concentrations were found to be higher with prematurity. Accordingly, the cut-off limit in screening for congenital adrenal hyperplasia (CAH) in premature infants is proposed as 20 ng/ml. Ideal cut-off limits were set by the equivalent age of gestation at blood sampling. Cut-off limits on the basis of gestational age at birth and birth weight are also suggested, where the sampling age is not so advanced. The rate of false positivity in premature infants can be reduced by this method.     

Serum C-reactive protein in early diagnosis of bacterial infections in premature infants

Serum C-reactive protein (CRP) is known to be produced by full-term infants and children in many diseases causing severe inflammation. We examined the usefulness of CRP as an early indicator of bacterial infection in premature newborn infants. CRP was obtained from 100 patients enrolled in a prospective study. All babies were suspected of having bacterial infection (meningitis-septicaemia) because of complications during pregnancy and/or symptoms suggestive of infection during the perinatal period. CRP was measured with the radial immunodiffusion technique. Examinations were done daily as long as elevated serum CRP levels were found. 100% (6/6) of our patients with culture-proven bacterial infections showed elevated CRP values within 24 h after the first clinical or laboratory signs suggesting sepsis. In 52.3% (11/21) of cases most probably suffering from infection, CRP rose within 72 h after the appearance of other symptoms. Even extremely immature infants were able to react with elevated CRP concentrations. Peak values of CRP were independent of birth weight. On the other hand, only 2.7% (2/73) of babies without findings of infection had slightly elevated amounts of CRP for a short time. Thus, serum CRP levels are a helpful parameter for the early diagnosis of severe bacterial infection in premature infants.     

Concentration of C-reactive protein,procalcitonin and alpha-1-antitrypsin in blood of neonates and infants with signs of inflammation

We determined the concentration of C-reactive protein (CRP), procalcilonin (PCT) and alpha-1-antitrypsin (AAT) in blood of neonates and infants with suspected infection. Investigations were carried out in 88 children. Increased concentrations of CRP (>5mg/L). procalcitonin (>0.5ng/ml) and AAT (> 200mg/dl) were observed in: CRP - 24%. PCT- 46%, AAT - 49% of neonates in 70, 60 and 70% of infants. We concluded, that the examined parameters are good and sensitive markers of inflammation in neonates and infants.     

肌钙蛋白Ⅰ在新生儿胎粪吸入综合征并心肌损伤诊断中的意义

目的 探讨心肌肌钙蛋白Ⅰ(CTn-Ⅰ)在新生儿胎粪吸入综合征(MAS)并心肌损伤诊断中的意义。方法：用化学发光免疫法及酶法分别测定35例合并心肌损伤的MAS患儿、30例无心肌损伤的MAS患儿及15例正常对照组血清CTn-Ⅰ及CK-MB的水平。结果：心肌损伤组生后2～3 d CTn-Ⅰ浓度为(0.67±0.13) ng/ml,较MAS对照组［(0.07±0.05) ng/ml］和正常对照组［(0.07±0.03) ng/ml］明显升高,差异有显著性意义(P<0.05)。结论：CTn-Ⅰ是诊断新生儿MAS并心肌损伤的特异性指标之一。     

Changes of Fibrinolysis and Their Relationship with Pulmonary Artery Pressures in Neonates with Lung Diseases

目的　研究新生儿肺疾病的纤溶改变及其与肺动脉压力的关系。方法　用发色底物法测定 2 7例新生儿肺疾病患儿 (病例组 )及 2 5例正常新生儿 (对照组 )血浆组织纤溶酶原激活剂 (TPA)和纤溶酶原激活抑制物(PAI)活性变化 ;用超声多普勒方法测定肺动脉血流加速时间 (TPV)与右室射血时间 (RVET)之比值 (TPV/RVET) ,以此估计新生儿肺动脉压力 (TPV/RVET比值与肺动脉压力成反比 )。结果　病例组PAI活性 [(9.3±4 .1)AU× 10 -1/ml]明显高于对照组 [(5 .5± 3.0 )AU× 10 -1/ml],P <0 .0 1,TPV/RVET比值 (0 .2 9± 0 .0 5 )明显低于对照组 (0 .34± 0 .0 8) ,(P <0 .0 5 ) ;发生肺出血者肺动脉压力 [TPV/RVET (0 .2 3± 0 .0 2 ) ]显著升高 ,P <0 .0 5。肺出血恢复期新生儿TPA [(3.7± 1.7)IU× 10 -1/ml]及血小板 [(180± 30 )× 10 9/L]明显高于肺出血发生时 [TPA (1.8± 0 .7)IU× 10 -1/ml,血小板 (98± 39)× 10 9/L],(P <0 .0 1)。结论　新生儿肺疾病时由于肺动脉压力增高 ,肺血管内皮细胞破坏 ,导致TPA释放减少 ,PAI活性增高 ,纤溶活性降低。     

新生儿血清瘦素水平与生长发育关系研究

目的：探讨新生儿血清瘦素与生长发育的关系。方法：采用放射免疫法检测80例新生儿静脉血和脐血瘦素水平,其中66例足月儿分为大于胎龄儿(LGA)组18例,适于胎龄儿(AGA)组32例,小于胎龄儿(SGA)组16例。采用Rohrer’s指数=出生体重(g)×100/身长(cm)~3估测新生儿营养状态。结果：早产儿血清瘦素水平明显低于足月儿[(0.66±1.03)ng/ml vs(3.59±2.16)ng/ml],P<0.01;足月儿中AGA血清瘦素水平[(3.06±0.96)ng/ml]明显低于LGA[(4.03±2.22)ng/ml],而高于SGA[(1.13±1.98)ng/ml];足月新生儿血清瘦素水平与Rohrer’s指数、新生儿体重、胎龄呈显著正相关(r=0.61,0.68,0.62,P均<0.01)。结论：新生儿体内瘦素是反映新生儿的发育和营养状态的有用指标。[中国当代儿科杂志,2003,5(1):29-30]