A critical analysis of outcome for children sustaining cardiac arrest after blunt trauma

Purpose: Injury is the leading cause of cardiac arrest in children older than 1 year. Previous findings suggest that children who require cardiopulmonary resuscitation (CPR) administered by paramedics for any reason rarely survive to hospital discharge. The authors evaluated the outcome of children sustaining cardiac arrest after blunt trauma in a Regional Pediatric Trauma Center. Methods: Children (age [lt ] 16) who underwent CPR in the field or in the emergency department (ED) after blunt trauma were identified from the trauma registry of a regional pediatric trauma center over a 3-year period (1997 to 2000). Patient demographics, rate of survival to discharge, factors influencing survival, and organ donation data were obtained from the trauma registry and medical record. Probability of survival (Ps) was calculated by TRISS analysis. Results: Twenty-five children were identified with a history of cardiac arrest after blunt injury (mean age; 3.3 years; range, 0.1 to 10; mean ISS, 30.7; range, 13-75; mean RTS, 1.58). Mean calculated Ps was 22.7%. However, only 2 (8%) survived. Death in the majority (91%) of the 23 patients who died occurred secondary to brain or spinal cord injury, and only 2 (9%) occurred as the result of exsanguinating hemorrhage. CPR was first performed in the field in 10 patients (40%), en route in 6 (24%), and in the ED in 9 (36%). Of the children who survived, both had vitals in the field, and CPR was administered initially in the ED. Mean length of ED resuscitation before death was 80 minutes. Of the children who died, organ donation occurred in only 3 (13%). The 2 survivors had no head injury and were discharged within 3 weeks of injury. Conclusions: Cardiopulmonary resuscitation after blunt injury in children rarely results in survival. The majority of deaths occur as a result of isolated intracranial injury and not exsanguinating hemorrhage. Although all children should receive aggressive resuscitation after injury, the need for CPR in the field portends a poor outcome. Furthermore, these data would suggest that prolonged or heroic efforts for children sustaining cardiac arrest in the field are not indicated.     

A processive versus a distributive mechanism of action correlates with differences in ability of normal and xeroderma pigmentosum group A endonucleases to incise damaged nucleosomal DNA

A DNA endonuclease, isolated from the nuclei of normal human and xeroderma pigmentosum complementation group A (XPA) cells, which recognizes predominately pyrimidine dimers, was examined for the mechanism by which it locates sites of damage on UVC-irradiated DNA. In reaction mixtures with low ionic strengths (i.e. lacking KCl), the normal and XPA endonuclease locate sites of UV damage on both naked and reconstituted nucleosomal DNA by different mechanisms. On both of these substrates, the normal endonuclease acts by a processive mechanism, meaning that it binds non-specifically to DNA and scans the DNA for sites of damage, whereas the XPA endonuclease acts by a distributive one, meaning that it randomly locates sites of damage on DNA. However, while both the normal and XPA endonucleases can incise UVC irradiated naked DNA, they differ in ability to incise damaged nucleosomal DNA. The normal endonuclease showed increased activity on UVC treated nucleosomal DNA compared with naked DNA, whereas the XPA endonuclease showed decreased activity on the damaged nucleosomal substrate. Since a processive mechanism of action is sensitive to the ionic strength of the micro-environment, the KCl concentration of the reaction was increased. At 70 mM KCI, the normal endonuclease switched to a distributive mechanism of action and its ability to incise damaged nucleosomal DNA also decreased. These studies show that there is a correlation between the ability of these endonucleases to act by a processive mechanism and their ability to incise damaged nucleosomal DNA; the normal endonuclease, which acts processively, can incise damaged nucleosomal DNA, whereas the XPA endonuclease, which acts distributively, is defective in ability to incise this substrate.      

A new amino acid mixture permits new approaches to the treatment of phenylketonuria

A new amino acid mixture for incorporation into medical foods for the treatment of hyperphenylalaninemia has been tested in a regular clinic. The mix is designed to be as unobtrusive as possible, consistent with good nutrition. After more than 1 year of trial as a beverage, we have shown that it is safe and well tolerated but that plasma phenylalanine is no better controlled than with some other products. The mix can be incorporated into a large number of different foods without affecting the taste. Occult monitoring of the quantity of medical foods purchased compared with the amounts reported to be consumed in diet histories provides an excellent way to monitor dietary compliance.     

Efficacy of left thoracoscopy and blunt mediastinal dissection during the Nuss procedure for pectus excavatum

Background/Purpose

The minimally invasive Nuss procedure is emerging as the preferred technique for repair of pectus excavatum. Original methods of pectus bar placement have been modified to improve safety and efficacy and avoid cardiothoracic complications. The currently reported modifications to facilitate retrosternal pectus bar placement include routine use of right thoracoscopy or a subxiphoid incision. The purpose of this article is to describe additional modifications of the Nuss procedure to improve safety and efficacy.

Methods

A retrospective analysis was performed on 51 patients who have had a thoracoscopic-assisted Nuss procedure at The Children's Hospital, Denver, Colo, between 1999 and 2002. Technical modifications included patient positioning, routine use of left thoracoscopy, and an Endo-kittner.

Results

Fifty-one patients have successfully undergone the Nuss procedure using the new modifications. Surgical time ranged from 45 to 120 minutes. There have been no intraoperative or postoperative bleeding complications. There have been 2 large pneumothoraces requiring needle thoracenteses in the operating room before extubation. No chest tubes were required postoperatively. Subjectively, all patients have been satisfied with their surgical correction. Average length of hospital stay was 4 to 6 days.

Conclusions

By using left chest thoracoscopy and Endo-kittner dissectors, the risk of cardiothoracic injury can be eliminated. Moreover, other methods to ensure safe substernal dissection are unnecessary.     

IL-1β induces an exaggerated pro- and anti-inflammatory response in peritoneal macrophages of children compared with adults

Children have a lower incidence of acute lung injury (ALI) compared with adults. Because ALI appears to be the end result of systemic hyperinflammation, children may either have 1) an attenuated pro-inflammatory response or 2) an augmented anti-inflammatory response compared with adults. The purpose of this study was to determine the IL-1-induced pro- and anti-inflammatory response of pediatric vs. adult peritoneal macrophages (PMs). We hypothesized that pediatric PMs would have an enhanced anti-inflammatory response compared with adult PMs. Human PMs were collected during elective laparoscopic procedures, cultured, and stimulated with IL-1. IL-6, IL-8, IL-10, and TNF production were determined by ELISA. Statistical analyses were by ANOVA; a P <0.05 was significant. Our results showed that IL-1 induced an 11-fold increase in IL-10 production in pediatric PMs (659±103 vs. 60±25 control, P <0.05). There was no IL-10 production in IL-1-stimulated adult PMs. IL-1-induced TNF production was greater in children compared with adults (2152±166 vs. 592±188, P <0.05). Similarly, IL-1-induced IL-6 production was greater in pediatric PMs compared with adults (532±3 vs. 444±52, P <0.05). There was no difference in IL-1-induced IL-8 production in children compared with adults. The IL-10:TNF ratio after IL-1 stimulation was 0.306±0.056 in pediatric macrophages and 0.020±0.015 in adult macrophages ( P <0.01). In conclusion, IL-1-induced IL-6 and TNF production were greater in pediatric than adult PMs. Furthermore, pediatric PMs had an 11-fold increase in IL-1-induced IL-10 production, while adult PMs did not produce IL-10. Therefore, IL-1 induces both a pro- and an anti-inflammatory response in pediatric PMs, whereas adult PMs produce only pro-inflammatory cytokines in response to IL-1. The exaggerated anti-inflammatory IL-10 response in children may be an important factor in the observed differences in ALI between children and adults.Presented at the International Symposium for Pediatric Surgical Research, Marseille, France, 3 October 2003Research supported by NIH Trauma Center Grant #P50GM49222–10 and NIH Training Grant T32 GM08315–12     

Toll-like receptor-4 signaling mediates pulmonary neutrophil sequestration in response to gram-positive bacterial enterotoxin

BACKGROUND: Toll-like receptors (TLRs) serve as mediators of innate immune responses to pathogen-associated molecular patterns (PAMPs) which include lipopolysaccharide (LPS) and staphylococcal enterotoxin B (SEB). TLR-4 is thought to act as the primary effector of LPS recognition and TLR-2 is thought to mediate responses to Gram-positive bacterial proteins. Chemokines such as macrophage inflammatory protein (MIP-2) are peptides that are responsible for lung neutrophil (PMN) sequestration following an infectious or inflammatory insult. Given the Gram-positive origin of SEB, we hypothesized that mice with altered TLR-4 signaling would exhibit no difference in lung PMN sequestration following SEB when compared to wild-type mice. METHODS: Wild-type and TLR-4 mutant mice were administered intratracheal saline, LPS (Escherichia coli 0.1 mg/kg), or SEB (1 mg/kg). After 24 h, lung PMN accumulation was determined by myeloperoxidase (MPO) assay and bronchoalveolar lavage fluid cell count (BALfcc). Total lung and BALf MIP-2 was measured by enzyme-linked immunosorbent assay. RESULTS: There was an increase in lung PMN accumulation (by both MPO and BALfcc) and MIP-2 following LPS and SEB in wild-type mice compared to saline-treated controls. In contrast, TLR-4 mice failed to exhibit an increase in lung MIP-2 or PMN accumulation following either LPS or SEB compared to wild-type mice. CONCLUSIONS: TLR-4 mutant mice are unresponsive to intratracheal LPS. SEB elicited an increase in lung MIP-2 and PMN accumulation in wild-type mice. However, TLR-4 mutant mice were protected from this process. This suggests that TLR-4 signaling may mediate the responses to other PAMPs in addition to LPS.     

B7-1和IL-12基因转染对肝癌细胞免疫原性的影响

目的 观察Ｂ７－１和ＩＬ－１２基因表达对人肝癌细胞免疫原性原影响。方法 分别将Ｂ７－１和ＩＬ－１２基因以逆转录病毒介导转染ＨｅｐＧ２细胞。阳性克隆细胞与健康人外周血淋巴细胞（ＰＢＬ）混合培养后,用流式细胞仪检测ＰＢＬ表面Ⅰ类人白细胞抗原（ＨＬＡ－Ⅰ）分子表达,以ＭＴＴ法检测ＰＢＬ的特异性杀伤活性Ｋ５６２细胞的活性。结果 混合ＨｅｐＧ２／Ｂ７－１ＨｅｐＧ２／ＩＬ－１２细胞组ＰＢＬ表面的ＨＬＡ－Ⅰ分子