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Background: The operative versus nonoperative management of major pancreatic ductal injuries in children remains controversial. The computed tomographic (CT) scan may not be accurate for determination of location and type of injury. We report our experience with ductal injury including the recent use of acute endoscopic retrograde cholangiopancreatography (ERCP) for definitive imaging, and an endoscopically placed stent as definitive treatment. This has not been reported in children., Methods: In review of 14,245 admissions to a regional pediatric trauma center over a 14-year period, 18 patients with major ductal injuries from blunt trauma were noted. Records were reviewed for mechanism of injury, method of diagnosis, management, and outcome., Results: There were 10 girls and 8 boys, ranging in age from 2 months to 13 years. The most common mechanisms of injury were motor vehicle and bicycle crashes. Admission CT scan in 16 children was suggestive of injury in 11, and missed the injury in 5. Distal pancreatectomy was carried out in eight patients with distal duct injuries: one died of central nervous system injury. Nonoperative management in three proximal duct injuries suggested by initial CT scan and in three missed distal duct injuries resulted in pseudocyst formation in five survivors; one patient died of central nervous system injuries. Two children with minimal abdominal pain, normal initial serum amylase, and no initial imaging developed pseudocysts. Two of seven pseudocysts spontaneously resolved and five were treated by delayed cystogastrostomy. Two recent children with suggestive CT scans were definitively diagnosed by acute ERCP and treated by endoscopic stenting. Clinical and chemical improvement was rapid and complete and the stents were removed. Follow-up ERCP, CT scan, and serum amylase levels are normal 1 year after injury., Conclusion: Pancreatic ductal injuries are rare in pediatric blunt trauma. CT scanning is suggestive but not accurate for the diagnosis of type and location of injury. Acute ERCP is safe and accurate in children, and may allow for definitive treatment of ductal injury by stenting in selected patients. If stenting is not possible, or fails, distal injuries are best treated by distal pancreatectomy; proximal injuries may be managed nonoperatively, allowing for the formation and uneventful drainage of a pseudocyst.

Background: Rel/NF-kappaB, an oxidative stress-responsive transcription factor, participates transiently in the control of gene expression. The cellular mechanisms that mediate NF-kappaB activation during ischemia (and during reperfusion in the course of treating ischemia) are not known., Methods and Results: To investigate the NF-kappaB activation induced during oxidative stress, we examined human cardiac tissue obtained during surgical procedures requiring cardiopulmonary bypass. In vitro, we examined human umbilical vein endothelial cells (HUVECs) exposed to hypoxia, reoxygenation after hypoxia, or a reactive oxygen intermediate (H(2)O(2)). Electrophoretic mobility shift assays performed on right atrial tissue revealed prominent NF-kappaB activation after hearts had been exposed to ischemia and reperfusion. The assays also showed that NF-kappaB activation was observed in hypoxic HUVECs after reoxygenation and in cultures treated with H(2)O(2) (500 micromol/L). Pervanadate (200 micromol/L) also induced marked NF-kappaB activation in HUVECs, indicating that H(2)O(2)-induced NF-kappaB activation is potentiated by the inhibition of tyrosine phosphatases. Western blotting of cytoplasmic IkappaBalpha demonstrated that NF-kappaB activation induced by oxidative stress was not associated with IkappaBalpha degradation. In contrast, tumor necrosis factor-alpha-induced NF-kappaB activation occurred in concert with degradation of IkappaBalpha. Inhibition of IkappaBalpha degradation with a proteasome inhibitor, MG-115, blocked NF-kappaB activation induced by tumor necrosis factor-alpha; however, MG-115 had no effect on NF-kappaB activation during oxidative stress., Conclusions: This study demonstrated a stimulus-specific mechanism of NF-kappaB activation in endothelial cells that acts independently of IkappaBalpha degradation and may require tyrosine phosphorylation.

Background: Platelet-activating factor (PAF) is one of the most potent biological mediators of tissue injury. PAF acetylhydrolase (PAF-AH) is a recently isolated naturally occurring enzyme that hydrolyzes PAF and renders it inactive. We hypothesize that inhibition of PAF with PAF-AH will reduce myocardial ischemia-reperfusion (I/R) injury in vivo., Methods and Results: The coronary ligation model was used in New Zealand white rabbits. The large branch of the marginal coronary artery was occluded for 45 minutes, followed by 2 hours of reperfusion. Fifteen minutes before reperfusion, animals were given either 2 mg/kg of vehicle or of PAF-AH. At the completion of 120 minutes of reperfusion, percentage of necrosis, degree of neutrophil infiltration, and measurements of regional contractility were assessed. Data are expressed as the mean+/-SEM and compared by Student's t test or Mann-Whitney ANOVA. Both groups of animals showed an equivalent area at risk; however, 46.7+/-11% was necrotic in the animal treated with vehicle. In contrast, 20.9+/-7.0% was necrotic in the animals treated with PAF-AH (P<0.05). Systolic shortening and wall thickness were significantly greater in those animals treated with PAF-AH at 15, 30, 60, and 120 minutes of reperfusion (P<0.05). Quantification of neutrophil infiltration showed a 62% reduction in the PAF-AH treated animals compared with those treated with vehicle alone., Conclusions: PAF-AH is a potent cardioprotective agent in an in vivo model of I/R injury.

Introduction: Nonoperative management of solid organ injury from blunt trauma in children has focused concern on potential delays in diagnosis of hollow viscus injury with resultant increases in morbidity, mortality, and cost. This study of a large pediatric trauma database will review the issues of difficulty and/or delay in diagnosis as it relates specifically to definitive treatment and outcome., Methods: We surveyed 11,592 consecutive admissions to a designated pediatric trauma center from 1985 to 1997 to identify children with documented injury of the gastrointestinal (GI) tract from blunt trauma. The records were extensively analyzed specifically in regard to mechanism of injury, type and site of injury, time to diagnosis, operative treatment, complications, and final outcome., Results: The 79 children identified, 4 months to 17 years old, included 27 females and 52 males. Mechanism of injury included 15 restrained and 7 unrestrained passengers, 15 pedestrians, 15 child abuse victims, 10 bike handlebar intrusions, 8 discrete blows to the abdomen, 4 bike versus auto, 3 falls, and 2 crush injuries. There were 51 perforations, 6 avulsions, and 22 lesser injuries including contusions. Injury of the small bowel was most common, 44 cases, followed by the duodenum, 18 cases, colon, 17 cases, and stomach, 6 cases. In 45 children, diagnosis was made quickly by a combination of obvious clinical findings, plain x-ray and/or initial computed tomographic findings mandating urgent operative intervention. Diagnosis was delayed beyond 4 hours in 34 children, beyond 24 hours in 17 children and was made by persistent clinical suspicion, aided by delayed computed tomographic findings of bowel wall edema or unexplained fluid. The six deaths were caused by severe head injury. Complications included two delayed abscesses and two cases of intestinal obstruction. All 73 survivors left the hospital with normal bowel function., Conclusions: Injury to the GI tract from blunt trauma in children is uncommon (<1%). The majority of GI tract injuries (60%) are caused by a discrete point of energy transfer such as a seatbelt (19%), a handle bar (13%), or a blow from abuse (19%), or other blows and is unique to this population. Although diagnosis may be difficult and often delayed, this did not result in excessive morbidity or mortality. Safe and effective treatment of GI tract injuries is compatible with nonoperative management of most other injuries associated with blunt abdominal trauma in children, while reducing the risk of nontherapeutic laparotomy.

Background: One proinflammatory property observed during endothelial cell activation is the expression of the neutrophil adhesion molecule E-selectin on the surface of endothelial cells. An important regulatory element in endothelial cell E-selectin expression is the nuclear localization of the transcription factor nuclear factor (NK)-kappa B, which binds to and affects the function of several genes encoding proteins mediating inflammation., Methods and Results: In this study, we investigated the ability of pyrrolidine dithiocarbamate (PDTC), an agent that inhibits the nuclear localization of NF-kappa B, to (1) block endothelial cell E-selectin expression in vitro in response to tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, and lipopolysaccharide (LPS) and (2) reduce neutrophil infiltration in a rabbit model of systemic inflammation. As measured with the use of an enzyme-linked immunosorbent assay, TNF-alpha, IL-1, and LPS each induced a significant increase in surface expression of E-selectin in cultured human umbilical vein endothelial cells (HUVECs) compared with HUVECs treated with medium alone. In contrast, E-selectin surface expression was blocked in HUVECs pretreated with PDTC before TNF-alpha, IL-1, or LPS stimulation. NF-kappa B was present in HUVEC nuclei treated with TNF-alpha, whereas translocation of NF-kappa B to the nucleus was absent in TNF-alpha-treated HUVECs pretreated with PDTC. In vivo, rabbits pretreated with PDTC before LPS infusion showed significantly less neutrophil infiltration in the lungs, liver, and heart compared with animals infused with LPS alone. This correlated with a reduction in E-selectin expression in vivo., Conclusions: Our data suggest that NF-kappa B regulation of gene expression in the vascular endothelium may be an important cellular mechanism in endothelial cell activation.

The increased use of ultrasonography in the management and evaluation of pregnancy has provided a unique opportunity to observe the anatomy of the developing fetus from 12 weeks gestation until term. Twenty-eight surgically important anatomic abnormalities have been diagnosed in utero by sonographic examinations at our affiliated institutions over the past three and a half years. These include ascites (five cases), gastroschisis (four cases), omphalocele (three cases), sacrococcygeal teratoma, cystic hygroma, hydrocele, duodenal atresia, multicystic kidney (two cases each), and one each of jejunal atresia, conjoined twins, ureteropelvic junction obstruction, urethral valves, urethral agenesis, and hydronephrosis secondary to reflux. Prenatal diagnosis by ultrasonographic examination has signifcantly improved perinatal management. Elective caesarean section has benefited infants with lesions causing dystocia, such as sacrococcygeal teratoma, omphalocele, and conjoined twins. Advance notification of surgeons and neonatalogists has reduced the delays of postnatal evaluation and treatment that contribute, significantly, to complications and death. In addition, transfer of the pregnant mother carrying an infant with a significant surgical anomaly to a center with facilities for neonatal surgery and specialized postoperative care can be properly planned for in advance. In the near future, intrauterine fetal surgery or palliative intervention may provide increased salvage of patients with obstructive uropathy and diaphragmatic hernia, both of which carry high mortality rates secondary to in utero damage. Sonography has proven useful in following the dilatation of either intestinal or urinary tract structures in utero. In our hands, maternal sonography has improved the surgical care of the newborn and may open a new frontier of intrauterine fetal surgery in the future.

Although many birth defects pose a real threat to life if left uncorrected, the problem of ambiguous genitalia, if poorly or incorrectly handled, leads to a lifetime of unhappiness for both parent and child. The evaluation of these defects must be attended to with the same dispatch as any life threatening anomaly. A total of 18 children with ambiguous genitalia have been evaluated and treated in the past two years including nine females with virilizing adreno-genital syndrome, three infants with mixed gonadal dysgenesis, two infants with dysgenetic male pseudohermaphroditism, two males with severe perineal hypospadias, bifid scrotum, and undescended testicles, and two females with cloacal deformities. Precise diagnosis and most importantly proper gender assignments were made in 11 neonates by cytogenetic, biochemical, and miniaturized endoscopic techniques. Subsequent surgical reconstruction is governed by existing anatomy, not genetic sex, and has been completed in six children two to two and half years of age. Most are reconstructed as females with recession of the enlarged clitoris and vaginoplasty. Males with hypospadias are handled by standard techniques. Seven previously evaluated patients had been lost to follow-up for up to 13 years and were recently reconstructed. Surgical treatment in five older children with extreme virilization and moderate to severe gender confusion was technically successful but associated with pronounced emotional difficulties. Worse than delay in gender assignment, is making the wrong gender assignment, or failing to follow through with the original plan at an early age. Sample cases from each of these categories are presented in detail to illustrate the innovations in the diagnostic and therapeituc management of these children.