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Background : The utility, diagnostic yield and accuracy of lung biopsies in pediatric oncology patients are variable. Here we describe our preliminary results using intraoperative electromagnetic navigation bronchoscopy (IENB) for peripheral lung lesions to increase the surgical yield and accuracy in pediatric oncology patients. Methods : From May 2018 until October 2020 all surgical lung biopsies on pediatric oncology patients were performed using IENB technology. IENB and tattooing with methylene blue dye, Indocyanine green dye or both followed by Video-assisted Thoracoscopic Surgery (VATS) was performed in the same setting. Data were collected retrospectively. Data points included diagnosis, technical success, pathologic diagnosis and alteration in treatment management and complications. Results : A total of 10 biopsy procedures were performed on 8 patients during the study. The youngest patient was 7 years old. All had successful IENB with tattooing. All biopsies were diagnostic. No procedures were converted to open. There were no technical failures or procedure complications. One patient had a total of 11 biopsies, 6 from the right lung and 5 from the left, performed at 2 separate procedures. Another had 2 biopsies, one from the right lung and one from the left performed at the same operation. In 7 of the 8 patients treatment changes were made based on results of their biopsy. Conclusion : Here we present the first described experience of IENB and tattooing of peripheral lung lesions in the pediatric population. We have shown that IENB for peripheral lung lesion localization is a safe and effective technique in pediatric oncology.

Neuroblastoma is the most common non-central nervous system (CNS) solid malignant tumor in children. The surgical treatment of high-risk neuroblastoma presents a challenge, and the benefits of aggressive surgical resection have been called into question.To examine our experience with surgical resection of neuroblastoma.We report on a retrospective chart review of our preliminary surgical experience in 25 patients with neuroblastoma who underwent surgery performed by a single surgeon at two institutions over a 3 year period. Demographic data, including stage of tumor and risk stratification, were recorded. Primary outcome was total gross resection. Patients were followed for 3 years after surgery.We found that 80% of the patients, including those with high-risk neuroblastoma tumors, had total gross resection of their tumor with minimal operative morbidity and no mortality; 88% had greater than 90% resection of their tumor. Overall, 3 year survival was 84% (21/25).Resection of neuroblastoma, even large, high-risk, bilateral tumors, was possible when performed by surgical teams with considerable experience.

Background Congenital diaphragmatic hernia (CDH) is a common birth defect affecting 1 in 3000 births. It is characterised by herniation of abdominal viscera through an incompletely formed diaphragm. Although chromosomal anomalies and mutations in several genes have been implicated, the cause for most patients is unknown. Methods We used whole exome sequencing in two families with CDH and congenital heart disease, and identified mutations in GATA6 in both. Results In the first family, we identified a de novo missense mutation (c.1366C>T, p.R456C) in a sporadic CDH patient with tetralogy of Fallot. In the second, a nonsense mutation (c.712G>T, p.G238*) was identified in two siblings with CDH and a large ventricular septal defect. The G238* mutation was inherited from their mother, who was clinically affected with congenital absence of the pericardium, patent ductus arteriosus and intestinal malrotation. Deep sequencing of blood and saliva-derived DNA from the mother suggested somatic mosaicism as an explanation for her milder phenotype, with only approximately 15% mutant alleles. To determine the frequency of GATA6 mutations in CDH, we sequenced the gene in 378 patients with CDH. We identified one additional de novo mutation (c.1071delG, p.V358Cfs34*). Conclusions Mutations in GATA6 have been previously associated with pancreatic agenesis and congenital heart disease. We conclude that, in addition to the heart and the pancreas, GATA6 is involved in development of two additional organs, the diaphragm and the pericardium. In addition, we have shown that de novo mutations can contribute to the development of CDH, a common birth defect.

Background Congenital diaphragmatic hernia (CDH) is a prevalent major congenital anomaly with significant morbidity and mortality. Thirty to 40% mortality in CDH is largely attributed to pulmonary hypoplasia and pulmonary hypertension (PH). We hypothesized that the underlying genetic risk factors for hereditary PH are shared with CDH associated PH. Methods Participants were recruited as part of the Diaphragmatic Hernia Research & Exploration; Advancing Molecular Science (DHREAMS) study, a prospective cohort of neonates with a diaphragmatic defect enrolled from 2005 to 2012. PH affected patients with available DNA for sequencing had one of the following: moderate or severe PH on echocardiography at 3months of age; moderate of severe PH at 1month of age with death occurring prior to the 3month echocardiogram; or on PH medications at 1month of age. We sequenced the coding regions of the hereditary PH genes bone morphogenetic protein receptor type II ( BMPR2 ), caveolin 1 ( CAV1 ) and potassium channel subfamily K, member 3 ( KCNK3 ) to screen for mutations. Results There were 29 CDH patients with PH including 16 males and 13 females. Sequencing of BMPR2 , CAV1 , and KCNK3 coding regions did not identify any pathogenic variants in these genes. Type of study Prognosis study Level of evidence Level IV

Congenital diaphragmatic hernia (CDH) is characterized by incomplete formation of the diaphragm, occurring as either an isolated defect or in association with other anomalies. Genetic factors including aneuploidies and copy number variants are important in the pathogenesis of many cases of CDH, but few single genes have been definitively implicated in human CDH. In this study, we used whole exome sequencing (WES) to identify a paternally inherited novel missense GATA4 variant (c. 754C>T, p. R252W) in a familial case of CDH with incomplete penetrance. Phenotypic characterization of the family included magnetic resonance imaging (MRI) of the chest and abdomen demonstrating asymptomatic defects in the diaphragm in the two “unaffected” missense variant carriers. Screening 96 additional CDH patients identified a de novo heterozygous GATA4 variant (c.848G>A; p.R283H) in a non-isolated CDH patient. In summary, GATA4 is implicated in both familial and sporadic CDH, and our data suggests that WES may be a powerful tool to discover rare variants for CDH.

Available data comparing the management and outcome of right-sided (R-CDH) vs left-sided congenital diaphragmatic hernia (L-CDH) are inconsistent. Large-volume CDH studies are limited by small numbers of R-CDH or are confounded by compilations from multiple institutions with multiple treatment strategies. Consequently, they are underpowered to draw conclusions. To define the behavior and outcomes of R-CDH better, we report the largest single-institution series of R-CDH and ask if factors traditionally linked to poor prognosis in L-CDH were applicable to R-CDH.We reviewed a single institution's experience with 267 consecutive evaluable neonates with unilateral CDH repaired from 1990 to 2006, with specific focus on R-CDH. chi(2) tests were performed for disease-related categorical variables. Two-tailed unpaired t tests were used for continuous variables. Factors associated with morbidity and survival were determined by univariate regression. Statistical significance was set at P.05.Forty right-sided (15%) and 227 (85%) left-sided cases of CDH were identified. Prenatal diagnosis was made in 20 right-sided vs 170 left-sided defects (50% vs 75%, P.01). Survival was 22 of 40 in R-CDH compared with 175 of 227 in L-CDH (55% vs 77%, P.01). Extracorporeal membrane oxygenation was required in 16 right-sided and 33 left-sided cases (40% vs 15%, P.001). A diaphragmatic patch was used in 22 of 29 right-sided compared with 82 of 199 left-sided repairs (76% vs 41%, P.01); rates of abdominal wall prosthesis were also higher in right-sided hernias (38% vs 19%, P.05). No differences were detected in right-sided vs left-sided recurrences (14% vs 8%, P = .38), mean time from birth to operation (5.3 vs 4.8 days, P = .80), or presence of cardiac anomalies (15% vs 12%, P = .63). Morbidity persisting beyond 6 months of age was present in 16 of 22 R-CDH survivors compared with 76 of 175 L-CDH survivors (73% vs 43%, P.05). Among R-CDHs, prenatal diagnosis was the only factor to predict survival by univariate regression (P.01). Use of a prosthesis in the diaphragm (P.05) for R-CDH repair correlated with morbidity.Although previous reports suggest that associated anomalies, need for extracorporeal membrane oxygenation, and time to repair can influence L-CDH survival, these data do not support extrapolation to R-CDH survival. Right-sided CDH carries a disproportionately high morbidity and mortality. Prenatal diagnosis was the only factor predictive of R-CDH survival. Morbidity may correlate with use of prosthetic material for R-CDH repair. Right-sided CDH is a unique disease that may require a modified antenatal consultation.

Right-sided diaphragmatic defects represent less than 20% of all congenital diaphragmatic hernias (CDH). Recent data suggest that right CDH (R-CDH) may carry a disproportionately high morbidity as well as increased rates of extracorporeal support when compared with left CDH. Treatment of infants with R-CDH may be further complicated by anatomical distortion unique to right-sided defects. We report 2 cases of azygous vein cannulation in neonates with large isolated R-CDH. Both infants had postnatal deteriorations within 48 hours, met our criteria for extracorporeal membrane oxygenation (ECMO), and underwent venoarterial cannulations through the right neck. In each case, the venous cannula passed directly into the azygous vein and failed to provide adequate ECMO support. Echocardiography confirmed both cases of azygous cannulation. In one child, the right atrium was successfully cannulated after 90 minutes of extensive cannula manipulation. This child survived a 5-day ECMO course and is alive at 22-month follow-up. In the second child, despite prolonged efforts at cannula repositioning, cannulation of the right atrium was not achieved. We did not offer central cannulation because of a rapidly deteriorating clinical course, with expiration in several hours. At autopsy, a dilated azygous vein was evident as a result of inferior vena cava compression by a malpositioned liver. The possibility of azygous vein cannulation may be increased in neonates with R-CDH and has not been previously reported. When evaluating infants with R-CDH for ECMO, clinicians must recognize the possibility of azygous cannulation and its potentially lethal consequences, and should anticipate alternative venous cannulation.

We asked if fetal lung-to-head ratio (LHR) of 1.0 or lower or liver herniation had a statistical effect on survival or need for extracorporeal membrane oxygenation (ECMO), compared with LHR above 1.0 in patients with congenital diaphragmatic hernia (CDH). Methods Antenatal records of all patients diagnosed with CDH from January of 2002 to June of 2005 were examined. Inclusion criteria were isolated left-sided CDH and absence of significant cardiac or other anomalies/syndromes, treated solely at this institution. Lung-to-head ratio values were compared based on the value currently proposed for fetal intervention: LHR of 1.0 or lower vs LHR above 1.0. Outcome was assessed as survival (discharge to home) or need for ECMO. Results Twenty-eight patients met inclusion criteria. Overall survival was 86% (24/28). Postnatal survival in fetuses with LHR of 1.0 or lower (8/11) was not statistically different from LHR above 1.0 (16/17) (73% vs 94%, P = .114). The need for ECMO in the group with LHR of 1.0 or lower (3/11) was not significantly different from those with LHR above 1.0 (1/17) (27% vs 6%, P = .114). Herniation of the fetal liver into the chest did not affect survival or need for ECMO (P = .228). Conclusion Neither LHR of 1.0 or lower nor liver herniation identified a risk factor significant enough to warrant fetal intervention. Multicenter studies may be more appropriate to investigate this clinical problem.

Background/Purpose Congenital diaphragmatic hernia affects approximately 1 in every 2000 live births. The etiology of these diaphragmatic defects is unknown. Using mice with a targeted deletion of fibroblast growth factor 10 (FGF10), which display a complete lack of lung tissue, we have examined the relationship between lung hypoplasia and diaphragmatic development. Methods The diaphragms of FGF10 null mice were examined at 2 embryonic time-points and compared with their heterozygous and wild-type littermates. Results FGF10 null mice had phenotypically normal diaphragms when compared with wild-type littermates at both time-points studied. Conclusion Normal diaphragm development appears to occur independent of lung development in mice.

minal obstruction may occur. Recurrent suppurative pneumonia can occur due to obstruction. Our patient aspirated a chicken bone 4 years previously and underwent several rigid bronchoscopy attempts to extract the foreign body. She was admitted to the Istanbul Medical School after an episode of pneumonia and had dyspnea and audible wheezing because of near total airway obstruction diagnosed via bronchoscopy. Ibrahim Sersar and colleagues reported a series of 3300 patients, 3 of whom required bronchotomy because extraction of the inhaled foreign body failed. In another study, 164 patients underwent bronchoscopy for foreign body aspiration, and 6% of patients required surgical extraction. Early bronchoscopy has high successful rates in the extraction of foreign bodies. Bronchotomy is usually enough to extract the foreign body, which was performed after early bronchoscopy. Because of the delay in extraction, our patient required an extended operation, a segmental main bronchial resection with supra-aortic anastomosis. After unsuccessful attempts, a bronchotomy would have been a less-invasive procedure for this patient. Thus, we advise an early operation for organic foreign bodies.

The liver is the solid organ most commonly injured as a result of blunt abdominal trauma. Complete avulsion of the common hepatic duct is a rare and devastating type of hepatobiliary trauma. Here the authors report the case of a 7-year-old child who had complete biliary disruption as a result of an abdominal crush injury that was not diagnosed correctly preoperatively. The intraoperative diagnosis and treatment of this injury is discussed.

Polyorchidism is a rare diagnosis. When recovered, it is frequently found in combination with other urologic pathologies. We report the case of a 14-month-old child with imperforate anus who was found to have polyorchia during repair of his inguinal hernia. Although cryptorchidism is not an uncommon finding in patients with imperforate anus, polyorchidism has never been reported. This is an unusual presentation of a rare entity.

Rupture of the abdominal aorta from blunt trauma is rare and aortic biforcation tear is extremely rare. We will present the management of a 2 year old boy who suffered blunt abdominal trauma and was operated in urgent fashion in our institution.

Hyperoxia is commonly used in the treatment of newborn respiratory distress. Although essential and life saving, oxygen therapy can result in the development of lung injury. Oxygen toxicity is associated with the production of reactive oxidant species. Nitric oxide (NO) is an oxidant formed by the catalysis of L-arginine when acted upon by the enzyme nitric oxide synthase (NOS). We studied the differential effects of prolonged normobaric hyperoxia (FIO2 = .95, for 3, 4, and 5 days) on the two major NOS enzymes, constitutive endothelial cell NOS (ecNOS) and inducible NOS (iNOS). Hyperoxia led to a significant lung injury, as measured by pulmonary compliance studies. Hyperoxia did not increase serum NO production, measured as the concentration of nitrite and nitrate. However, hyperoxia did result in a small but significant increase in NO production in the bronchoalveolar lavage fluid, as measured by the products of nitrite and nitrate concentration. This increase in NO was not associated with an induction of whole lung iNOS, as measured by the conversion of L-[3H]arginine to L-[3H]citrulline or by Northern blot analysis. Hyperoxia significantly decreased ecNOS activity as measured by the conversion of L-[3H]arginine to L-[3H]citrulline. In addition, administration of the NOS inhibitor NG-nitro-L-arginine methyl ester worsened the injury, as measured by lung compliance and survival. Further studies need to be performed to determine whether this decrease in ecNOS activity during hyperoxia plays a role in the pathogenesis of hyperoxia-related lung injury.

Pulmonary oxygen injury is classified by the development of tissue and alveolar edema, surfactant dysfunction, lung inflammation, and decreased pulmonary compliance. In neonates prolonged oxygen therapy is associated with the development of bronchopulmonary dysplasia. Recombinant DNA technology makes it possible to experimentally explore the role of specific proteins in the development of pulmonary oxygen injury. However, in vivo experiments require sensitive ways of identifying pulmonary oxygen injury early in its development. We therefore compared the sensitivities of several experimental assays used to assess pulmonary injury. We found that changes in pulmonary compliance were the most sensitive and showed significant differences after 72 hr of exposure to normobaric hyperoxia (FiO2 = 0.95), which correlated with a small change in the histology of the mice lungs. The concentration of protein in the bronchoalveolar lavage fluid was less sensitive and did not differ significantly until after 96 hr of exposure. The survival in hyperoxia also did not worsen until after 96 hr. The lung wet/ dry weight ratios was the least sensitive assay and did not increase until after 5 days of exposure to normobaric hyperoxia. We conclude that a decrease in pulmonary compliance is an early indicator of pulmonary oxygen injury and may be a better way to study the mechanisms and mediators of pulmonary oxygen injury.

The effects of minimally invasive surgery (MIS) on postoperative nutrition and food intake have not been reported. We compare the effects of MIS access techniques on postoperative status by analyzing the changes in body weight and food intake in an immature mouse model. Immature 5- to 7-week-old male A/J mice underwent laparotomy under general inhalational anesthesia (n = 20/group). In addition, two other groups of mice underwent MIS using either pneumoperitoneum with carbon dioxide (CO2) or gasless suspension (n = 20/group). Operative and anesthetic times were equal for all groups. Body weight and the amount of food and water intake were recorded over a 2-week postoperative period. Data were analyzed statistically by ANOVA and p < 0.05 was considered to be significant. The postoperative percentage decrease in body weight was significantly greater after laparotomy than after either MIS or anesthetic control (−14.9 ± 3.6% vs. preoperative body weight, −11.0 ± 3.2% in pneumoperitoneum group, and −1...

Purpose To determine developmental outcomes and associated factors in patients with congenital diaphragmatic hernia (CDH) at 2 years of age. Methods This is a multicenter prospective study of a CDH birth cohort. Clinical and socioeconomic data were collected. Bayley Scales of Infant Development (BSID-III) and Vineland Adaptive Behavior Scales (VABS-II) were performed at 2 years of age. Results BSID-III and VABS-II assessments were completed on 48 and 49 children, respectively. The BSID-III mean cognitive, language, and motor scores were significantly below the norm mean with average scores of 93 ± 15, 95 ± 16, and 95 ± 11. Ten percent (5/47) scored more than 2 standard deviations below the norm on one or more domains. VABS-II scores were similar to BSID-III scores with mean communication, daily living skills, social, motor, adaptive behavior scores of 97 ± 14, 94 ± 16, 93 ± 13, 97 ± 10, and 94 ± 14. For the BSID-III, supplemental oxygen at 28 days, a prenatal diagnosis, need for extracorporeal membrane oxygenation (ECMO) and exclusive tube feeds at time of discharge were associated with lower scores. At 2 years of age, history of hospital readmission and need for tube feeds were associated with lower scores. Lower socioeconomic status correlated with lower developmental scores when adjusted for significant health factors. Conclusion CDH patients on average have lower developmental scores at 2 years of age compared to the norm. A need for ECMO, oxygen at 28 days of life, ongoing health issues and lower socioeconomic status are factors associated with developmental delays.

Expression of the inducible isoform of nitric oxide synthase (iNOS) contributes to the hypotension and vascular hyporeactivity in various models of shock induced by bacterial lipopolysaccharide (LPS). However, the role of iNOS in response to shock caused by live bacteria is more controversial. In the present study, we investigated the role of iNOS in a rat model of cecal ligation and puncture (CLP). CLP resulted in increased plasma nitrite/nitrate levels (up to 59 microM at 24 h) and increased pulmonary iNOS activity (up to 71 fmoles/mg/min at 12 h) and caused a significant vascular hyporeactivity at 18 h. The degree of NO production and iNOS induction was approximately 30% of that observed several hours after administration of LPS in the same species, and the degree of vascular hyporeactivity was less than that observed after LPS injection. Selective inhibition of iNOS with mercaptoethylguanidine (MEG) reduced plasma nitrite/nitrate levels, but did not prevent the development of vascular hyporeactivity, and did not improve survival in this model of CLP. Thus, CLP-induced sepsis causes low-level induction of iNOS, but factors other than iNOS are the crucial determinants of the vascular failure and mortality in this model.

Intestinal injury is a rare complication of lumbar disc surgery, resulting from inadvertent penetration of the anterior annulus fibrosus and anterior longitudinal ligament. Patients typically complain of abdominal pain and distention developing over the course of several days. Imaging with plain upright chest radiographs or abdominal computed tomography may demonstrate free air in the abdominal cavity. We report a case of intestinal perforation after microscopic lumbar discectomy and present the diagnostic postoperative imaging. In addition, we review the relevant literature and discuss techniques that may be employed to avoid this complication.

Background Congenital diaphragmatic hernia (CDH) is a common birth defect with significant morbidity and mortality. Although the aetiology of CDH remains poorly understood, studies from animal models and patients with CDH suggest that genetic factors play an important role in the development of CDH. Chromosomal anomalies have been reported in CDH. Methods In this study, the authors investigated the frequency of chromosomal anomalies and copy number variants (CNVs) in 256 parent–child trios of CDH using clinical conventional cytogenetic and microarray analysis. The authors also selected a set of CDH related training genes to prioritise the genes in those segmental aneuploidies and identified the genes and gene sets that may contribute to the aetiology of CDH. Results The authors identified chromosomal anomalies in 16 patients (6.3%) of the series including three aneuploidies, two unbalanced translocation, and 11 patients with de novo CNVs ranging in size from 95 kb to 104.6 Mb. The authors prioritised the genes in the CNV segments and identified KCNA2 , LMNA , CACNA1S , MYOG , HLX , LBR , AGT , GATA4 , SOX7 , HYLS1 , FOXC1 , FOXF2 , PDGFA , FGF6 , COL4A1 , COL4A2 , HOMER2 , BNC1 , BID , and TBX1 as genes that may be involved in diaphragm development. Gene enrichment analysis identified the most relevant gene ontology categories as those involved in tissue development (p=4.4×10−11) or regulation of multicellular organismal processes (p=2.8×10−10) and ‘receptor binding’ (p=8.7×10−14) and ‘DNA binding transcription factor activity’ (p=4.4×10−10). Conclusions The present findings support the role of chromosomal anomalies in CDH and provide a set of candidate genes including FOXC1 , FOXF2 , PDGFA , FGF6 , COL4A1 , COL4A2 , SOX7 , BNC1 , BID , and TBX1 for further analysis in CDH.

SUMMARY Congenital diaphragmatic hernia (CDH) is one of the most common congenital abnormalities. Children born with CDH suffer a number of co-morbidities, the most serious of which is respiratory insufficiency from a combination of alveolar hypoplasia and pulmonary vascular hypertension. All children born with CDH display some degree of pulmonary hypertension, the severity of which has been correlated with mortality. The molecular mechanisms responsible for the development of pulmonary hypertension in CDH remain poorly understood. Angiopoitein-1 (Ang-1), a central mediator in angiogenesis, participates in the vascular development of many tissues, including the lung. Although previous studies have demonstrated that Ang-1 might play an important role in the development of familial pulmonary hypertension, the role of Ang-1 in the development of the pulmonary hypertension associated with CDH is poorly understood. The aim of this study was to examine the role of the Ang-1 pathway in a murine model of CDH. Here, we report that Ang-1 appears important in normal murine lung development, and have established its tissue-level expression and localization patterns at key time-points. Additionally, our data from a nitrofen and bisdiamine-induced murine model of CDH suggests that altered expression patterns of Ang-1, its receptor Tie-2 and one of its transcription factors (epithelium-specific Ets transcription factor 1) might be responsible for development of the pulmonary vasculopathy seen in the setting of CDH.

Purpose Risk factors that predispose children with congenital diaphragmatic hernia (CDH) to recurrence remain poorly defined. We report a large series of recurrent CDH and ask whether prenatal patient factors or postnatal treatment variables better predict recurrence. Methods Two hundred thirty-eight neonates with unilateral CDH underwent repair from 1990 to 2006. Data were assessed by χ 2 and Mann-Whitney U tests. Multivariate regression identified independent predictors of recurrence. Statistical significance was set at P Results We identified 24 recurrences (10%). Median time from repair to recurrence diagnosis was 4.9 months. Patients with recurrence were older ( P = .02) and more often required abdominal wall patches at initial repair ( P = .01) compared to nonrecurrence patients. Postoperative length of stay (LOS) after initial repair ( P P = .01) were greater in recurrence patients. Use of diaphragm patch at initial repair was greater in patients with recurrence but only approached statistical significance ( P = .05). Only 2 variables independently predicted recurrence by multivariate regression as follows: abdominal (not diaphragm) wall patch during initial repair (odds ratio [OR] 3.50; P = .04) and postoperative LOS (OR, 1.012; P = .01). Conclusion Neonates at risk for CDH recurrence are better identified by postnatal treatment variables than by prenatal patient factors. Although age at repair and diaphragm patch use are greater in recurrence patients, the only factors to independently predict recurrence were postoperative LOS and abdominal wall patch use. These data can help optimize follow-up regimens.

Spinal muscular atrophy (SMA) is a common pediatric neuromuscular disorder caused by insufficient levels of the survival of motor neuron (SMN) protein. Studies involving SMA patients and animal models expressing the human SMN2 gene have yielded relatively little information about the earliest cellular consequences of reduced SMN protein. In this study, we have used severe- and mild-SMN2 expressing mouse models of SMA as well as material from human patients to understand the initial stages of neurodegeneration in the human disease. We show that the earliest structural defects appear distally and involve the neuromuscular synapse. Insufficient SMN protein arrests the post-natal development of the neuromuscular junction (NMJ), impairing the maturation of acetylcholine receptor (AChR) clusters into ‘pretzels’. Pre-synaptic defects include poor terminal arborization and intermediate filament aggregates which may serve as a useful biomarker of the disease. These defects are reflected in functional deficits at the NMJ characterized by intermittent neurotransmission failures. We suggest that SMA might best be described as a NMJ synaptopathy and that one promising means of treating it could involve maintaining function at the NMJ.

Perforated appendicitis is one of the most common diagnoses treated by pediatric surgeons. Although rare, a perforated appendix can present with a cutaneous fistula. Here we present the second reported case of perforated appendicitis presenting as an appendicoumbilical fistula.

A 6-year-old girl with hereditary multiple exostoses presented with spontaneous hemothorax and pericardial effusion. Chest computed tomographic scan showed left-sided costal exostoses protruding into the left side of the chest. She underwent successful thoracoscopic resection of 3 left rib exostoses and made a full recovery. This report illustrates this rare clinical scenario and reviews the previously published reports of this complication of costal exostoses.

The management of life-threatening congenital diaphragmatic hernia (CDH) has undergone significant change over the last two decades. When CDH was felt to be a surgical emergency treated promptly after birth, survival rates of 50% were typical. Recent changes in medical management of these patients prior to surgery have had a dramatic influence on clinical outcome with survival rates over 80%. This study was performed to assess under the current 80% survival rates whether there is predictive value in the appearance of the initial chest radiograph and clinical outcome in patients with CDH. Initial chest radiographs on 56 newborns with CDH were retrospectively reviewed for percent aeration of ipsilateral lung, percent aeration of contralateral lung, percent mediastinal shift, and content of hernia and correlated with clinical outcome. There was no significant relationship between radiographic analysis of the percent of ipsilateral lung aeration (P=0.43), contralateral aeration (P=0.52) mediastinal shift (P=0.18), or content of hernia and clinical outcome. All CDH lesions tend to “look the same” on radiographs, regardless of favorable or fatal outcome. Chest radiography serves to confirm the diagnosis of CDH, but does not predict outcome.

BACKGROUND: Pancreatic trauma occurs in up to 10% of all cases of blunt pediatric trauma. Here we attempted to identify markers of pancreatic injury in children and to assess our current diagnostic approach to pancreatic injury. METHOD: We performed a retrospective chart review of all patients with a pancreatic injury admitted to a Level I pediatric trauma center between January of 1980 and September of 1994. RESULTS: In all, 26 children were included. All pancreatic injuries were due to blunt trauma. Handlebar injuries were the most common mechanism of injury and resulted in a unique pattern of isolated pancreatic trauma, often complicated by the development of a pseudocyst. Computed tomographic scans, performed with intravenous and oral contrast and done in the acute setting, were 85% sensitive for diagnosing a pancreatic injury. CONCLUSIONS: Double contrast computed tomographic scan is a more sensitive test than ultrasound in diagnosing pancreatic injury. The constellation of abdominal pain, an elevated serum amylase and a handlebar mechanism of injury warrants hospitalization and a double contrast abdominal computed tomographic scan.

Objective To identify clinical factors associated with pulmonary hypertension and mortality in patients with congenital diaphragmatic hernia (CDH). Study design A prospective cohort of neonates with a diaphragm defect identified at one of seven collaborating medical centers was studied. Echocardiograms were performed at one month and three months of age and analyzed at a central core by two cardiologists independently. Degree of pulmonary hypertension and survival were tested for association with clinical variables using Fischers exact test, chi-square and regression analysis. Results 220 patients met inclusion criteria. Worse pulmonary hypertension measured at one month of life was associated with higher mortality. Other factors associated with mortality were need for extracorporeal membrane oxygenation (ECMO), patients inborn at the treating center and patients with a prenatal diagnosis of CDH. Interestingly, patients with right sided CDH did not have worse outcomes. Conclusions Severity of pulmonary hypertension is associated with mortality in CDH. Other factors associated with mortality were birth weight, gestational age at birth, inborn status and need for ECMO.

The inducible isoform of nitric oxide synthase (iNOS) is expressed in various organs, including the lung, during systemic endotoxemia. Overproduction of nitrix oxide (NO) by iNOS contributes significantly to the vascular failure and end-organ damage in endotoxemia. Using selective pharmacological inhibitors of iNOS, the purpose of this study was to define the role of iNOS in a rat model of endotoxin-induced pulmonary transvascular flux (TVF). Lung TVF was assessed by a method of Evans Blue permeability index (PI). Bacterial lipopolysaccharide (LPS) (15 mg/kg intraperitoneally [IP]) significantly increased pulmonary iNOS activity and serum levels of nitrite/nitrate (NO 2 /NO 3 ). This was accompanied by a significant elevation of the PI 6 hours after injection. Selective iNOS inhibition with either S-methyl isothiourea (SMT; 5 mg/kg IP) or aminoguanidine (AG; 20 mg/kg IP), administered 2 hours after LPS injection, significantly prevented the increase in PI associated with LPS injection. Similarly, inhibition of the induction of iNOS with dexamethasone (10 mg/kg IP), given 3 hours before LPS, also inhibited the increase in PI. All three treatments significantly prevented the increase in both lung iNOS activity and serum NO 2 /NO 3 associated with endotoxemia. In conclusion, the overproduction of NO generated by iNOS during systemic endotoxemia causes a vascular leak in the lung. Thus, it is speculated that selective inhibition of iNOS may be beneficial in preventing the development of acute respiratory failure in sepsis.

Inguinal and scrotal Wilms' tumors are extremely rare; only 15 cases have been reported to date. The authors report a case of inguinal Wilms' tumor (stage III), which occurred in a previously healthy 3 1/2-year-old boy who was staged and treated according to currently accepted National Wilms' Tumor Study III criteria. The exact embryological origin of this tumor has not been determined. However, there is evidence that the origin is more primitive than that of intrarenal Wilms' tumor.

Nitric oxide (NO), a paracrine-acting gas enzymatically synthesized from L-arginine, is a unique biologic mediator that has been implicated in a myriad of physiologic and pathophysiologic states. It is an important regulator of vascular tone and may be the mediator of the hemodynamic changes involved in sepsis and cirrhosis. In addition, there is increasing evidence that NO is involved in coagulation, immune function, inhibitory innervation of the gastrointestinal tract, protection of gastrointestinal mucosa, and the hepatotoxicity of cirrhosis. It has already been speculated that NO may represent a point of control or intervention in a number of disease states. The purpose of this paper is to provide the surgeon with a broad overview of the scientific and clinical aspects of this important molecule.

A four-year-old girl was brought to her pediatrician by her parents because of intermittent bilious emesis, which had started two weeks earlier. There were no other changes in her bowel or bladder habits, and she had not lost weight. Her parents reported that she occasionally pulled at and ate her hair, but they did not believe that this behavior was compulsive or obsessive (trichotillomania). Physical examination revealed a firm mass in the upper abdomen, but the rest of the examination was unremarkable. An upper gastrointestinal series revealed a large trichobezoar in the child's stomach and proximal small bowel (Panel A). . . .

Traditional medicine is the source of primary care for most Zimbabweans. N'angas (traditional healers) are consulted for their political and religious powers along with their healing powers. The Zimbabwe National Traditional Healers Association was formed and is officially recognized by the government and has a constitution along with departments of education and research. Each member pays annual dues. Herbal remedies are used. Most n'angas say they are possessed by a healing spirit which they invoke while treating the patient. These n'angas practice specialization--the extent to which the n'angas claim expertise, outside of which they will refer a patient to others. The referral and specialization practices of a select group of n'angas in and around the capital, Harare are studied. 30 n'angas from 7 suburbs of harare were interviewed personally at their place of practice in 1987. All 30 claimed to specialize in the treatment of certain illnesses. They specialized in spiritual, not just medical, problems. The n'angus referred to other n'angas for either or both of 2 reasons: 1) most referred patients for whom their treatment had failed; and 2) patients were referred for suffering an illness which that certain n'anga could not cure, usually because their healing spirit did not give them the cure. There were some things that the n'angas would only send to western medical practitioners and hospitals. These were mostly accidents or emergencies. "Abnormal illnesses" were never referred to Western practitioners and hospitals. "Abnormal illnesses" were caused by evil spirits such as "ngozi." The n'angas were divided over what to do about the acquired immunodeficiency syndrome (AIDS). 1 n'anga sand that he was so good at curing AIDS that he was flown to America to treat a patient. Others would send AIDS patients to hospitals. Most all Zimbabwe natives are descended from Shona and Ndebele cultures.