全身炎症反应综合征新生儿的凝血功能研究

目的　探讨全身炎症反应综合征 (SIRS)新生儿凝血功能的变化及其临床意义。方法　符合SIRS诊断标准的新生儿 12 6例 ,在入院后 2 4h内进行新生儿危重病例评分 ,并采血测定凝血酶原时间 (PT)、凝血酶时间 (TT)、部分活化凝血活酶时间 (APTT)、D 二聚体 (DD)含量和血小板 (PLT)计数。分别以SIRS符合项数及预后、疾病严重程度分组 ,观察其与凝血功能紊乱间的关系。结果　随着SIRS符合项数的增加 ,SIRS新生儿中危重病例所占百分比及病死率明显增高 ,PT、TT、APTT、DD也增高 ,具有明显的相关性。存活组与死亡组间PT、TT、APTT差异无显著性意义 (P >0 0 5 ) ,死亡组DD显著高于存活组 (P <0 0 1)。危重症组PT、TT、APTT、DD与非危重症组比较 ,差异均具显著性意义 (P<0 0 1)。结论　SIRS新生儿存在凝血机制的活化 ,符合SIRS诊断标准项数越多 ,病情越重 ,凝血功能紊乱越显著 ,病死率越高。     

全身炎症反应综合征患儿凝血功能改变及其临床意义的探讨

目的 研究全身炎症反应综合征(SIRS)患儿出凝血系统的功能改变和临床意义及其对预后的影响.方法 采用前瞻性病例对照设计,按照小儿/新生儿SIRS新定义将收住ICU的患儿分为SIRS组(24例)、非SIRS组(21例),另设正常对照组(28例).SIRS组按预后再分为死亡组(10例)和生存组(14例),监测血小板计数(PLT)、凝血酶原时间(PT)、部分凝血酶原时间(APTT)、纤维蛋白原(FBG)、凝血酶-抗凝血酶复合物(TAT)、抗凝血酶Ⅲ(AT-Ⅲ)、蛋白C(PC)、血栓调节蛋白(TM)、D-二聚体(DD)、组织型纤溶酶原激活物(TPA)共10项反映凝血系统功能的指标.结果 (1)SIRS组中PT、APTT、TAT、TM、DD、TPA水平均较非SIRS组及对照组升高(P<0.05);AT-Ⅲ、PC水平均较非SIRS组及对照组降低(P<0.05),非SIRS组PC水平较对照组降低(P<0.05);PLT、FBG水平在SIRS组、非SIRS组及对照组之间比较差异无显著性(P>0.05);(2)SIRS患儿中,死亡组与生存组各出凝血指标间比较差异无显著性(P>0.05).结论 (1)SIRS患儿存在凝血功能异常,主要表现为凝血活化、抗凝活性的降低和纤溶系统的活化;(2)出凝血分子标志物是疾病早期针对性反映患儿凝血系统所处状态的良好指标;(3)分子标志物对预后的意义尚需大样本进行评估.     

Acute disseminated encephalomyelitis in conjunction with inflammatory bowel disease

Neurological complications in paediatric patients with inflammatory bowel disease (IBD) are rare. Most previous reports involve cerebral venous thrombosis, central nervous system vasculitis, or peripheral nerve inflammation. We report a child with active inflammatory bowel disease complicated by acute disseminated encephalomyelitis (ADEM). The child presented with acute neurological deficits following an exacerbation of colitis with evidence of lesions in the central nervous system white matter on magnetic resonance imaging. Ancillary investigations did not provide evidence of systemic infection, coagulation disorders, or vasculitis. In our case the colitis improved with immunosuppressive therapy, with a similar improvement in the white matter lesions showing almost complete resolution of the MR scan changes and no evidence of infarction. This case suggests that ADEM may be another extra intestinal manifestation of inflammatory bowel disease, probably associated with an autoimmune pathogenic mechanism.     

SIRS患儿VW因子、D-二聚体、CRP的变化与病情危重程度的关系

目的　 探讨不同程度全身炎症反应综合征 (SIRS)患儿血管性假血友病因子 (VW因子 )、D 二聚体 (D D)及C 反应蛋白 (CRP)的变化 ,与病情危重程度的关系。 方法 　符合SIRS一项诊断标准评一分 ,按SIRS评分将患儿分为SIRS2、SIRS3及SIRS4三组 ,每组各 2 0例。于急性期和恢复期抽血用ELISA法测定VW因子和D D ,免疫比浊法测定CRP ,并与非SIRS患儿进行比较。同时对SIRS患儿行危重症评分分为危重症组和非危重症组。 结果 　SIRS患儿急性期血VW因子、D D及CRP含量均增高 ,且随SIRS评分增加 ,升高程度更显著 ;三者在危重症组也明显高于非危重症组 (P均 <0 0 5 )。SIRS4组符合危重症标准及发生MODS的例数均高于SIRS3和SIRS2组 (SIRS4与SIRS2比较 ,P <0 0 5 )。 结论 　SIRS时血浆VW因子和D D明显升高 ,提示血管内皮细胞受到损伤 ,凝血功能出现紊乱 ,当SIRS程度加重、病情恶化时 ,升高的程度更显著。CRP水平可反映SIRS患儿体内炎症反应的程度 ,并与病情的危重程度密切相关。SIRS评分可作为临床判定患儿病情轻重的简便易行的指标 ,SIRS评分越高 ,提示病情越重 ,若结合血VW因子、D D或CRP水平可更准确地判定病情的危重程度。     

Nitric oxide and intestinal barrier failure.

The systemic inflammatory response syndrome (SIRS) is a leading cause of morbidity and mortality in adults and children. Various proinflammatory mediators have been implicated in the pathogenesis of SIRS; however, their mechanisms of action are poorly defined. Recent evidence suggests that nitric oxide (NO) plays a regulatory role in gut barrier function. Sustained upregulation of NO production in the intestine can lead to intestinal epithelial injury through the formation of peroxynitrite. Peroxynitrite can nitrate mitochondrial proteins and inhibit cellular respiration. The resultant changes in mitochondrial function lead to activation of the caspase cascade, subsequent DNA fragmentation, and enterocyte apoptosis. Enterocyte apoptosis results in a transient "bare area" in the intestinal epithelium where bacteria can attach and then penetrate the lamina propria. Bacteria that successfully escape the immune system may in turn incite a systemic inflammatory response.     

Extensive white matter involvement in hemorrhagic shock and encephalopathy syndrome

Reported is a case of hemorrhagic shock and encephalopathy syndrome (HSE) with extensive white matter involvement. A three year old, previously healthy boy was presented with an acute onset of fever, loss of consciousness and convulsions. He had disseminated intravascular coagulation, metabolic acidosis, non-ketotic hypoglycemia and hepatorenal dysfunction. The computed tomography (CT) scan of his head on the second day of illness demonstrated symmetric, extensive low-density areas in the cerebral and cerebellar white matter. The child died on the 13th hospital day. A post-mortem histopathological examination of the liver revealed centrilobular necrosis and infiltration of fatty acid droplets. The concentrations of serum 2′,5′-oligoadenylate synthetase and urinary neopterin were markedly elevated, indicating excessively activated cell-mediated immunity. This overproduction of inflammatory cytokines might play an important role in the pathogenesis of the brain lesion as well as in other clinical and laboratory manifestations. The patient had a decreased serum level of α1-antitrypsin, which may have been associated with the development of uncontrolled inflammation and coagulation disorder.     

International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics.

OBJECTIVE: Although general definitions of the sepsis continuum have been published for adults, no such work has been done for the pediatric population. Physiologic and laboratory variables used to define the systemic inflammatory response syndrome (SIRS) and organ dysfunction require modification for the developmental stages of children. An international panel of 20 experts in sepsis and clinical research from five countries (Canada, France, Netherlands, United Kingdom, and United States) was convened to modify the published adult consensus definitions of infection, sepsis, severe sepsis, septic shock, and organ dysfunction for children. DESIGN: Consensus conference. METHODS: This document describes the issues surrounding consensus on four major questions addressed at the meeting: a) How should the pediatric age groups affected by sepsis be delineated? b) What are the specific definitions of pediatric SIRS, infection, sepsis, severe sepsis, and septic shock? c) What are the specific definitions of pediatric organ failure and the validity of pediatric organ failure scores? d) What are the appropriate study populations and study end points required to successfully conduct clinical trials in pediatric sepsis? Five subgroups first met separately and then together to evaluate the following areas: signs and symptoms of sepsis, cell markers, cytokines, microbiological data, and coagulation variables. All conference participants approved the final draft of the proceedings of the meeting. RESULTS: Conference attendees modified the current criteria used to define SIRS and sepsis in adults to incorporate pediatric physiologic variables appropriate for the following subcategories of children: newborn, neonate, infant, child, and adolescent. In addition, the SIRS definition was modified so that either criteria for fever or white blood count had to be met. We also defined various organ dysfunction categories, severe sepsis, and septic shock specifically for children. Although no firm conclusion was made regarding a single appropriate study end point, a novel nonmortality end point, organ failure-free days, was considered optimal for pediatric clinical trials given the relatively low incidence of mortality in pediatric sepsis compared with adult populations. CONCLUSION: We modified the adult SIRS criteria for children. In addition, we revised definitions of severe sepsis and septic shock for the pediatric population. Our goal is for these first-generation pediatric definitions and criteria to facilitate the performance of successful clinical studies in children with sepsis.     

Fetal and neonatal origins of altered brain development

Abnormal development of the brain during fetal life is now thought to contribute to the aetiology of many neurological disorders that manifest throughout life. Many factors are likely to underlie such abnormal development including genetic makeup and an adverse intrauterine environment. This review will focus on prenatal hypoxic/ischaemic injury, inflammatory/infective insults and preterm birth. A range of experimental models have been used to characterize lesions formed in response to these insults and to determine mechanisms of damage resulting from such events. Relatively brief periods of fetal hypoxia result in neuronal death (cerebellum, hippocampus, and cerebral cortex), white matter damage and reduced growth of neural processes. These effects are more profound at mid than late gestation. Chronic mild placental insufficiency can result in fetal growth restriction and deficits in neural connectivity and myelination. Exposure of the preterm fetus to inflammatory agents causes brain damage particularly in the white matter and this is exacerbated by hypoxia. Premature birth without potentiating factors can result in subtle neuropathologies including cerebral white matter gliosis, hippocampal sclerosis and subarachnoid haemorrhage; the extent of the damage appears to be related to the regimen of ventilatory support. These studies show that the timing, severity and nature of specific insults are critical in determining the pattern of injury and thus the extent to which neurological function will be affected postnatally. Defining the causes, patterns and mechanisms of brain injury is crucial if we are to develop rational neuroprotective strategies to reduce the burden of altered brain growth and poor functional and behavioural outcomes.     

Systemic inflammatory response syndrome

Despite advances in perinatal care in the past decade, sepsis and its complications continue to present problems for the neonate, remaining a major cause of neonatal morbidity and mortality. Sepsis research is focusing on how the neonate (host) responds to bacteria. The newborn may develop a systemic reaction to bacteria that induces the release of substances known as inflammatory mediators. Termed the systemic inflammatory response syndrome (SIRS), this reaction is believed to be responsible for the signs and symptoms of sepsis. This article introduces the neonatal nurse to SIRS, providing an overview of various inflammatory mediators and cytokines, their clinical consequences, and potential new therapies in the management of SIRS.     

感染性腹泻致全身炎症反应综合征婴幼儿血小板参数、凝血功能研究

目的探讨感染性腹泻致全身炎症反应综合征(SIRS)患儿血小板参数、凝血功能关系。方法检测感染性腹泻伴全身炎症反应综合征患儿的血小板数目、平均体积、分布宽度、凝血酶原时间以及纤维蛋白原浓度等值。并与30例对照组比较。结果感染性腹泻的血小板参数、凝血指数及发生全身炎症反应综合征的对比均有显著性意义。结论监测血小板参数、凝血功能以及是否发生全身炎症反应综合征对于感染性腹泻的诊断和治疗有一定的临床意义。     

早期连续性血液净化在肠穿孔腹膜炎模型中改善全身炎症状况的作用

目的 观察早期连续性血液净化对幼猪肠穿孔腹膜炎诱导的全身炎症反应综合征(SIRS)的疗效,旨在探索新生儿肠穿孔腹膜炎治疗的新方法.方法 12只上海种小白猪,体重7～9 kg,雌雄不限.随机分为对照组(n=6)和治疗组(n=6).以盲肠手术穿孔诱导全身炎症反应综合征(SIRS),造模成功后治疗组行连续静脉-静脉血液透析滤过(CVVHDF)8 h.成模后,治疗2、4、8、16 h分别记录二组动物基础状态的心率、呼吸、血压、体温、外周血细胞计数和血气分析,采血检测TNF-α、IL-1β和IL-6含量.结果 所有动物经造模后4～6 h内均达SIRS标准.经分组行CVVH-DF 8h后,观察指标有明显变化的是:CVVHDF组的心率、呼吸、血压、血清TNF-α水平均较对照组明显降低(P＜0.05),而血清IL-6在CVVHDF组则较对照组升高(P=0.04).血氧分压、血细胞计数和血清IL-1β水平的变化在二组中无显著性差异.结论 本组动物实验的资料显示,在幼猪肠穿孔腹膜炎模型中,治疗的早期采用CVVHDF,可降低部分炎因子反应,对稳定SIRS动物的血流动力学有益处,但对SIRS的部分指标改善不显著.     

Hemodynamic disturbances in premature infants born after chorioamnionitis: association with cord blood cytokine concentrations

Chorioamnionitis and elevated cord blood inflammatory cytokine concentrations are associated with detectable disturbances of systemic and cerebral hemodynamics in premature newborns. Fifty-five infants (25-31 wk gestation) were enrolled. Chorioamnionitis was defined by placental histology. IL-6, IL-1beta, and tumor necrosis factor-alpha were quantified by ELISA. Blood pressure, heart rate, cardiac output, stroke volume, fractional shortening, and middle cerebral artery blood flow velocities were measured at 3 +/- 1 h after birth. Chorioamnionitis was evident in 22 placentas and was associated with increased IL-6 (p < 0.001), IL-1beta (p = 0.035), and heart rate (p = 0.027); and with decreased mean and diastolic blood pressure (p = 0.026 and p = 0.019, respectively). IL-6 concentration correlated inversely with systolic, mean, and diastolic blood pressures. Right ventricular cardiac output was elevated (p = 0.028) in infants with fetal vessel inflammation. Maternal temperature >or=38.0 degrees C and newborn immature-to-total white blood cell ratio >or=0.4 were associated with significant decreases in left ventricular fractional shortening (p = 0.001 and p = 0.005, respectively). Neither chorioamnionitis nor elevated cytokine concentrations were associated with changes in middle cerebral artery Doppler blood flow velocities. Chorioamnionitis and elevated cord blood IL-6 concentrations are associated with decreased blood pressure in premature newborns. Inflammation of the fetal vessels and nonspecific indicators of infection are associated with disturbances in cardiac function. Infants with chorioamnionitis and elevated cytokine concentrations do not manifest changes in cerebral Doppler indices within the first few postnatal hours. We speculate that cytokine-associated systemic hemodynamic disturbances in premature infants born after chorioamnionitis predispose such infants to perinatal brain injury.     

全身炎症反应综合征在新生儿肺出血时临床意义

为探讨全身炎症反应综合征(SIRS)在新生儿肺出血疾病演变与转归中的意义,将94例肺出血新生儿分为SIRS组68例和非SIRS组26例,比较其病死率及SIRS组中SIRS持续时间及各脏器功能不全等与肺出血的关系。结果提示,非SIRS组肺出血病死率远低于SIRS组(P<0.01);符合SIRS诊断标准项目4项者,病死率远高于2、3项者(P<0.05);随着功能不全器官数目的增多及器官损害的严重性,肺出血病死率不断增加。提示,SIRS的发生、持续时间、并发功能不全器官数目及器官损害的严重性,均影响肺出血的预后,为此必须预防和及早控制SIRS,防止其进一步恶化导致肺出血及多脏器功能衰竭。     

Melatonin reduces inflammation and cell death in white matter in the mid-gestation fetal sheep following umbilical cord occlusion

The premature infant is at increased risk of cerebral white matter injury. Melatonin is neuroprotective in adult models of focal cerebral ischemia and attenuates ibotenate-induced white matter cysts in neonatal mice. Clinically, melatonin has been used to treat sleep disorders in children without major side effects. The aim of this study was to investigate the protective and anti-inflammatory effects of melatonin in the immature brain following intrauterine asphyxia. Fetal sheep at 90 d of gestation were subjected to umbilical cord occlusion. Melatonin (20 mg/kg, n = 9) or vehicle (n = 10) was administered IV to the fetus, starting 10 min after the start of reperfusion and continued for 6 h. Melatonin treatment resulted in a slower recovery of fetal blood pressure following umbilical cord occlusion, but without changes in fetal heart rate, acid base status or mortality. The production of 8-isoprostanes following umbilical cord occlusion was attenuated and there was a reduction in the number of activated microglia cells and TUNEL-positive cells in melatonin treated fetuses, suggesting a protective effect of melatonin. In conclusion, this study shows that melatonin attenuates cell death in the fetal brain in association with a reduced inflammatory response in the blood and the brain following intrauterine asphyxia in mid-gestation fetal sheep.     

早产儿脑室旁白质损伤发病机制的研究进展

脑室旁白质损伤是早产儿特征性脑损伤,也是早产儿最重要的脑病类型之一。其病理变化主要包括脑白质的凝固性坏死、少突胶质细胞损伤、髓鞘损害、轴突损伤以及坏死部位出现反应性胶质化和小胶质细胞浸润等,这些病变与新生儿期后的神经系统后遗症密切相关。早产儿脑室旁白质软化的发病机制主要是与脑血管发育未成熟和少突胶质细胞前体细胞损伤易感性有关。本文通过文献复习对早产儿脑室旁白质损伤发病机制的研究进展进行概述,为临床预防和诊治提供理论依据。     

Thymus involution and cerebral white matter damage in extremely low gestational age neonates

BACKGROUND: Among newborns who die, those who have cerebral white matter damage are more likely than others to have thymus involution and low thymus weights. OBJECTIVE: We sought to evaluate in a population of preterm newborns who did not die if those who developed a cerebral white matter damage (as defined by an echolucency) are more likely than others to have thymus involution as assessed on chest radiographs. METHOD: The 89 infants whose data were evaluated were born before the 28th week of gestation, had at least one chest radiograph within the first 2 days of life (to determine thymus size), and at least one cranial ultrasonogram to assess for white matter echolucency. RESULTS: Eighty-five percent of these infants had a small thymus within the first 2 weeks of life. Median time to thymus involution in those born before the 26th week of gestation was 36 h, and in those born during or after the 26th week of gestation was 140 h. Infants who developed involution before the median time in their respective gestational age groups were classified as early involuters (group 1) and were compared to their peers with late/no involution (group 2). Infants with an echolucency were more likely to have had early involution than infants without an echolucency (89% vs. 44%) (p = 0.01). This relationship was not distorted by potential confounders. The echolucency odds ratio associated with early thymus involution was consistently above 8 in all strata of the sample. CONCLUSION: These results are consistent with the possibility that early thymus involution and neonatal white matter damage are not independent phenomena and may have common antecedents.     

Cerebral white matter damage in the preterm infant: pathophysiology and risk factors

Based on clinical, epidemiologic, and experimental studies, the aetiology of white matter damage, specifically periventricular leukomalacia (PVL), is multifactorial and involves pre- and perinatal factors possibly including genetic factors, hypoxic-ischaemic insults, infection, excess cytokines, free radical production, increased excitatory amino acid release, and trophic factor deficiencies. The article summarizes research findings about the aetiology of white matter damage and cerebral palsy in preterm infants. The information is organized according to specific antecedents, for which we present epidemiological and neurobiological data. The most important prenatal factor appears to be intrauterine infection. We discuss the evidence supporting the hypothesis that the foetal inflammatory response contributes to neonatal brain injury and later developmental disability. We recently established an animal model of excitotoxic lesions in the developing mouse brain. Brain damage was induced by intra-cortical injections of ibotenate, a glutamatergic agonist. When administered on post-natal day 5 ibotenate induced the formation of white matter cysts. Our animal model could be used to further explore the mechanisms involved in the formation of PVL. Potentially preventive strategies will be discussed.     

儿科加强医疗病房全身炎症反应综合征和多器官功能不全综合征的临床分析

目的应用新概念———全身炎症反应综合征（ＳＩＲＳ）和多器官功能不全综合征（ＭＯＤＳ）认识多器官功能衰竭（ＭＯＦ）。方法回顾性总结分析１９９５年１月～１９９７年１２月我院儿科加强监护病房收治的危重患儿，根据Ｈａｙｄｅｎ修订的ＳＩＲＳ诊断标准和全国小儿急诊学组拟定的ＭＯＦ诊断标准进行临床分析。结果全组３０４例患儿，符合ＳＩＲＳ标准２５２例，占８２．９％．原发病有感染性疾病和非感染性疾病。在ＳＩＲＳ和ＭＯＤＳ病程发展过程中部分患儿出现一过性肝、肾、胃肠道和脑等器官功能受损的表现，最终进展为ＭＯＤＳ共６５例，占２５．８％。ＭＯＤＳ的病死率为４３．１％（２８／６５）。发生ＭＯＤＳ的高危因素为入院危重评分＜７５分，明显高代谢反应和合并Ｃ反应蛋白，而与年龄无明显关系。结论ＳＩＲＳ和ＭＯＤＳ是小儿加强医疗病房中常见病症，病死率较高。ＳＩＲＳ和急诊学组制定的ＭＯＦ诊断标准简单实用，但应根据美国胸科协会和危重病医学会倡议将ＭＯＦ更名为ＭＯＤＳ。ＳＩＲＳ和ＭＯＤＳ进展至器官功能衰竭前存在器官功能受损的表现，应予高度重视并早期干预。     

SIRS and group-B streptococcal sepsis in newborns: pathogenesis and perspectives in adjunctive therapy

Clinical signs of systemic inflammation and suspected systemic infection are common in neonatal medicine. Yet, causative infectious organisms can only infrequently be isolated. In previously healthy infants at low risk of sepsis, group B streptococcus (GBS) is the most common isolate. In vitro and in vivo data suggest that immune cells from newborn infants have impaired antimicrobial properties against GBS. In contrast large amounts of inflammatory mediators are formed upon GBS challenge and Toll-like receptors (TLR) are critical host molecules in this context. Thus, the immune balance tilts towards inflammation, SIRS and sepsis. Adjunctive therapy of neonatal sepsis needs to adjust the inflammatory response without further impairing bacterial clearance. This article summarises the pathophysiological events leading to sepsis and suggests molecular targets for adjunctive therapy.