The injured child is resistant to multiple organ failure: a different inflammatory response?

BACKGROUND: Although postinjury multiple organ failure (MOF) is a well-described phenomenon in adults, the incidence of this syndrome in children is unknown. The purpose of this study was to describe the incidence, course, and severity of pediatric postinjury MOF. We hypothesized that the incidence and severity of postinjury MOF in children would be less when compared with adults. METHODS: Patients were retrospectively identified from the trauma registry of a regional pediatric trauma center and an adult Level I trauma center with pediatric commitment for a 3-year period. All trauma patients less than 16 years old who survived for longer than 24 hours and had an Injury Severity Score > 15 were eligible. An accepted MOF score was used. Categorical variables were compared by chi2 and continuous variables by t test. A value of p< 0.05 was considered statistically significant. RESULTS: Of 534 patients identified, 334 (63%) were admitted for evaluation of isolated head injury and excluded from further analysis. The rate of postinjury MOF in children was found to be only 3%, with a low (17%) mortality when compared with historical adult data (50%). CONCLUSION: The incidence of postinjury MOF in the child is less than in the adult, given equivalent injury severity. These observations solidify the contention that postinjury MOF is rare in children, and is less severe when it occurs. Delineating the mechanism(s) whereby children are protected from postinjury MOF may provide insight into the development of strategies to prevent MOF in other age groups as well as various disease states.     

TNF receptor I mediates chemokine production and neutrophil accumulation in the lung following systemic lipopolysaccharide.

BACKGROUND: Tumor necrosis factor (TNF)-alpha is a critical effector of lipopolysaccharide (LPS)-induced acute lung injury, and its effects are mediated by two structurally related receptors, RI and RII. Cellular adhesion molecules and C-X-C chemokines (Keratinocyte chemoattractant (KC) and macrophage inflammatory protein [MIP]-2) regulate tissue neutrophil polymorphonuclear neutrophil (PMN) accumulation in a multitude of inflammatory states. We hypothesized that TNFRI signaling dictates PMN accumulation in the lung via regulation of chemokine molecule production. Therefore, the purposes of this study were to (1) delineate LPS-induced lung TNF-alpha production and (2) characterize the contribution of both TNF receptors to lung chemokine production and neutrophil influx following systemic LPS. METHODS: Wild-type or TNFRI and TNFRII knockout (KO) mice were injected with vehicle (saline) or LPS (Escherichia coli 0.5 mg/kg intraperitoneally). After 2, 4, 6, or 24 h, lungs were analyzed for TNF-alpha and chemokine (KC and MIP-2) protein expression (enzyme-linked immunosorbent assay) and PMN accumulation (myeloperoxidase assay). RESULTS: There was an increase in total lung TNF-alpha (vehicle, 5.0 +/- 1.2 pg/mg total protein vs LPS, 950 +/- 318; P < 0.05) after LPS. Lung chemokine production and PMN accumulation were also increased compared to vehicle-injected mice. Lung chemokine production and PMN accumulation were significantly lower in TNFRI KO, but not TNFRII KO, mice, despite no difference in TNF-alpha production (TNFRI KO, 925 +/- 301 vs TNFRII KO, 837 +/- 267, P = 0.82). CONCLUSIONS: Acute lung injury following systemic LPS administration is characterized by increased lung (1) TNF-alpha production, (2) C-X-C chemokine production, and (3) neutrophil accumulation. The maximal effect of LPS-induced lung neutrophil accumulation appears to be dependent upon the TNFRI receptor but not the TNFRII receptor. .     

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     

Lymphangiomas in children: MR imaging

Seventeen lymphangiomas in 15 patients were imaged with magnetic resonance (MR) to define the nature, extent, and anatomic relationships of these lesions. The MR and pathologic findings were then compared to determine the histologic basis for the signal-intensity characteristics of these lesions. The signal intensity of 13 lesions was similar to or slightly less than that of muscle on T1-weighted images and greater than that of fat on T2-weighted images. This appearance correlated with the presence of ectatic lymphatic channels containing clear fluid on histologic section. Four lymphangiomas had high signal intensity, approximately equal to that of fat, on T1-weighted images, reflecting the presence of clotted blood or small cystic spaces with a higher ratio of fat to fluid. Sixteen of 17 lesions had visible septations on MR images. The authors' experience suggests that most lymphangiomas have a characteristic appearance on MR images. The information obtained with MR imaging can help in providing a preoperative diagnosis, in planning surgical resection, and in defining recurrence.     

Ferrite particles for bowel contrast in MR imaging: design issues and feasibility studies

Diverse materials with varying physical and magnetic properties have been evaluated as gastrointestinal contrast agents for magnetic resonance (MR) imaging. Uniform marking of the small bowel remains the greatest challenge. Ferrites are magnetically active iron oxide particles that are miscible with water and cause loss of signal on MR images. The decrease in MR signal intensity produced by ferrites occurs with a wide range of iron concentrations (0.1-10 mM) and with both T1- and T2-weighted pulse sequences. These effects of ferrites are explained by predominant T2 shortening with negligible T1 effects. The ferrite preparation used in this study was stable in vitro, with little iron solubilized by acid. Intragastric administration of ferrite (5 mg of iron per kg in 6 ml) routinely marked the small bowel of rats. The authors conclude that ferrites represent a promising new class of contrast agents for gastrointestinal MR imaging.     

Electromyographic investigation of unstable patella before and after its realignment operation

Background:

Patellar dislocations are either due to superolateral contracture of the soft tissue or imbalance of the power between the vastus medialis (VM) and the vastus lateralis (VL). The imbalance of muscle power as an etiology of patellar dislocation has not been studied. Hence, we studied the recurrent, habitual and permanent dislocations of the patella with an electromyogram (EMG) of the vastus medialis, vastus lateralis, and pes anserinus, before and after realignment operations, to document the muscle imbalance and effectiveness of the realignment operation.

Materials and Methods:

An electromyographic investigation was carried out on the vastus medialis and vastus lateralis in nine recurrent, 20 habitual, and 13 permanent dislocations of the patella, before and after their realignment operations. Pes anserinus transposition, which acted as a medial stabilizer of the patella, was also investigated with an EMG study, to understand its role on patellar stability at 0°, 30°, 60°, 90°, 120°, 150°, and full flexion of the knee. The age of the patients varied from nine to 30 (mean 15) years. There were 24 males and 18 females. Twenty-six patellar dislocations were on the right and 16 were on the left side.

Results:

Electromyographic pictures reveal subnormal activity of the vastus medialis in all types of dislocations and similar activities of the vastus lateralis in permanent and habitual dislocations recorded pre operatively, which recovered to almost normal values postoperatively, at the mean one-year follow-up. Pes anserinus, which was used for medial stabilization of the patella after its realignment, maintained normal EMG activity before and after the operation.

Conclusion:

This study is significant for understanding the imbalance of muscle activities in patients with an unstable patella, which can be rectified without recurrence after pes anserinus transposition.     

Altered neutrophil function in the neonate protects against sepsis-induced lung injury

Background/Purpose: Neutrophils (PMNs) are well known effectors of lung injury after sepsis. The accumulation of PMNs into the lung is dependent on a complex cascade of events that includes the local production of chemokines. Interestingly, neonates are protected from lung injury after zymosan-induced sepsis. The authors hypothesized that this protection was caused by either altered PMN function or diminished lung chemokine production compared with the adult. Methods: Sepsis was induced in neonatal and adult rats by an intraperitoneal injection of zymosan. Animals were killed 24 hours later and lungs examined for PMN accumulation and function, chemokine production, and lung injury. Results: Septic neonates (SN) were protected from pulmonary edema when compared with septic adults (SA). Lung PMN number and chemokine (MIP-2) production increased in both septic neonates and adults when compared with vehicle (V) treated animals. Conversely, PMN function was decreased significantly in neonates when compared with adults. Conclusions: Despite equivalent lung PMN accumulation and chemotactic protein production, PMN function and lung injury in septic neonates was diminished when compared with that of adults. These findings suggest that neonates may be relatively protected from sepsis-induced lung injury caused by immature PMN function. J Pediatr Surg 37:1042-1047.