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Background: The currently utilized International Neuroblastoma Risk Group (INRG) staging system developed in 2009 uses image-defined risk factors as a measure of surgical risk, separating resectable neuroblastoma from those best preceded by chemotherapy. The previous International Neuroblastoma Staging System was based primarily on surgical findings. We hypothesized there would be a change to the role of the surgeon in neuroblastoma treatment in the more recent decade., Methods: This is a single center 20-year retrospective analysis of 104 patients with International Classification of Diseases-9 and -10 codes for neuroblastoma. Patient demographics, tumor site, cancer treatment modality, survival, biopsy technique, surgical intervention, and pathology staging were collected. Data was analyzed by analysis of variance (ANOVA) and Student's t test., Results: There was a decrease in open surgeries for extra-adrenal neuroblastomas in the later decade (77%, 31%, P = 0.01). There was a narrowing of the time interval to surgery in the later cohort, likely as a result of uniformity in surgical timing on treatment protocols relying on INRG staging., Conclusions: Our findings mirror changes in practice patterns globally. We found an increase in minimally invasive approaches but did not find a difference in the role of the surgeon under the INRG staging system., (© 2021. Children's Hospital, Zhejiang University School of Medicine.)

Chronic constipation is a common condition which may result in fecal impaction. A 13-year-old male with chronic constipation and encopresis presented with fecal impaction for three weeks. The impaction caused abdominal pain, distension, encopresis, and decreased oral intake. He was found in severe distress with non-pitting edema of his feet and ankles along with perineal edema. The pedal edema worsened after receiving a fluid bolus, so concern arose for venous compression or a thrombus. A Duplex Ultrasound demonstrated changes in the venous waveforms of the bilateral external iliac and common femoral veins without thrombosis. Manual disimpaction and polyethylene glycol 3350 with electrolytes resolved the pedal and perineal edema. Four months later, he had soft bowel movements without recurrence of the edema. A repeat Duplex Ultrasound was normal. We present a child in whom severe fecal impaction caused pelvic venous compression resulting in bilateral pedal and perineal edema.

The outcomes of patients admitted to the hospital following a sport-related concussion are largely unknown. Medical records of patients admitted to the pediatric trauma service between 2008 and 2011 after sustaining a sport-related concussion were reviewed. In all, 59 participants were in the high-velocity activities group, and 21 in the field or court sport group. Abnormal CT scans were found in 14 patients in the high-velocity group and 2 in the field or court sport group. The majority of participants in the field or court sport group were football players, all of whom had normal CT scans. Headache was predictive of an abnormal CT scan. Among the patients, 56% clinically improved and were discharged the following day. Patients with field or court sport-related concussion admitted to a pediatric trauma service appear to be at low risk for clinically significant intracranial pathology and do well in the acute setting., (© The Author(s) 2014.)

We compared proliferation (growth) and differentiation (development) related proteins in normal and hypoplastic fetal murine lungs. The hypoplastic lungs were created in CD-1 fetal mice by nitrofen exposure (25 mg per pregnant mouse given intragastrically on gestational day 8 [Gd8]), as published earlier. The lungs were harvested at Gd14, 16, 19 and from neonates. Immunoblot analyses were carried out for transcription factors (oncogenic proteins, nuclear receptor, and transmembrane receptor proteins) in severely hypoplastic murine fetal lungs with coexistent diaphragmatic hernia, and results were compared with those derived from normal lungs of equivalent age. These proteins have proposed roles in the regulation of proliferation and differentiation processes of fetal lungs. We have shown that the product of the oncogene c-myc was reduced in hypoplastic lungs at all stages of gestation, whereas c-Fos protein levels were variable. These proteins are known to regulate transcription of various developmental proteins, such as those responsible for proliferation and differentiation. Further, the nuclear transcription factors thyroid transcription factor-1 (TITF-1) and glucocorticoid receptor (GR) were reduced, and thyroid hormone receptor (TR) and retinoic acid receptors (RARs) were inhibited in severely hypoplastic lungs compared to normal lungs of equivalent gestational stage, except in neonatal lungs, where signals for RARs were seen. TITF-1 is known to localize in bronchial epithelial cells in developing lungs. It is restricted to type II pneumocytes with gestational development in the normal lungs and regulates surfactant proteins. Earlier, we have reported that surfactant proteins are reduced in hypoplastic lungs. In the current study, reduced GR and TITF-1 proteins may play a role in reducing surfactant proteins in the hypoplastic lungs. The significant inhibition in TR and RARalpha in the severely hypoplastic lungs reflects on affected epithelial cell maturation and alveolar formation, respectively. Altered RARbeta levels correlate with affected lung growth and branching morphogenesis of nitrofen-exposed lungs. A transmembrane receptor protein EGFR was reduced in hypoplastic lungs, suggesting the involvement of altered mesenchymal-epithelial signal transduction pathways. We conclude (1) Our data suggest altered levels of various nuclear transcription factors in the murine fetal hypoplastic lungs; (2) Reduced levels TITF-1 protein in hypoplastic lungs may have caused the functional immaturity of distal lung, immature airways and thus may affect overall differentiation of lungs. These results correlated with low levels of surfactant proteins in these lungs; (3) TR and RAR inhibition indicate their roles through reduced or retarded proliferation and differentiation processes in the severely hypoplastic lungs; (4) GR down-regulation in developing fetal murine hypoplastic lungs indicate delayed development, and GR up-regulation in affected neonates may be induced by stress/stretch caused at birth due to air-breathing; (5) Down- regulation of EGFR indicate altered mesenchymal-epithelial interactions and possible influence on lung proliferation and differentiation., (Copyright 2001 Wiley-Liss, Inc.)

Small Cell Lung Cancer (SCLC), a clinically aggressive cancer, accounts for approximately 25% of primary lung cancers. We carried out suppression subtractive hybridization (SSH), a PCR-based method for cDNA subtraction, between the human classic, NCI-H69 and variant, more aggressive NCI-N417 SCLC cell lines to isolate and characterize variable expression of genes, which may be responsible for differential degree of tumorigenicity of SCLC. Using NCI-N417 as a tester, we obtained 28 differentially expressed cDNA clones from a total of 60 arbitrarily picked clones. Among the 28 cDNA clones, 4 were unknown genes, 2 were fatty acid binding protein (FABP) with specific identification of mRNA for mammary-derived growth inhibitor (MDGI), 1 was human alpha-enolase, 4 were ribosomal proteins, 2 were structural genes, vimentin and moesin (membrane-organizing extension spike protein), and 9 were homologous with murine leukemia viruses, whereas 2 others had enhanced expression in NCI-H69 and A549 cell lines, and 4 were cell surface proteins and murine type C retrovirus. Expression of FABP/MDGI was significantly high in NCI-H417, which may influence mitosis and cell growth as implicated in other tissues, contrary to the conclusion drawn for the role of MDGI in human breast cancer. Higher expression of ribosomal proteins in NCI-N417 compared to NCI-H69 may have a role in differential tumorigenicity and metastatic ability. Further, we obtained 14 differentially expressed cDNA clones by reversing the tester and driver, using NCI-H69 as a tester. Of these 14 differential cDNAs, 5 were unknown genes, 2 were specific for keratins, others had similarities with protease inhibitor, human BAC clone, Alu RNA binding protein, and tumor expression-enhanced gene. Characterization of these differentially expressed cDNA clones will provide useful information in understanding of the genes responsible for differential tumorigenicity of SCLC., (Copyright 2000 Academic Press.)

Objective: To determine whether use of a primary pull-through would result in equivalent perioperative and long-term complications compared with the two-stage approach., Summary Background Data: During the past decade, the authors have advanced the use of a primary pull-through for Hirschsprung disease in the newborn, and preliminary results have suggested excellent outcomes., Methods: From May 1989 through September 1999, 78 infants underwent a primary endorectal pull-through (ERPT) procedure at four pediatric surgical sites. Data were collected from medical records and a parental telephone interview (if the child was older than 3 years) to assess stooling patterns. A similar group of patients treated in a two-stage fashion served as a historical control., Results: Mean age at the time of ERPT was 17.8 days of life. Comparing primary ERPT with a two-stage approach showed a trend toward a higher incidence of enterocolitis in the primary ERPT group compared with those with a two-stage approach (42.0% vs. 22.0%). Other complications were either lower in the primary ERPT group or similar, including rate of soiling and development of a bowel obstruction. Median number of stools per day was two at a mean follow-up of 4.1 +/- 2.5 years, with 83% having three or fewer stools per day., Conclusions: Performance of a primary ERPT for Hirschsprung disease in the newborn is an excellent option. Results were comparable to those of the two-stage procedure. The greater incidence of enterocolitis appears to be due to a lower threshold in diagnosing enterocolitis in more recent years.

We have shown that dexamethasone (Dex) accelerates maturation and differentiation of cultured fetal murine lungs (Cilley RE, Zgleszewski SE, Krummel TM, and Chinoy MR. Surg Forum 47: 692-695, 1996). We now demonstrate that although Dex inhibits thinning of acinar walls and secondary septa formation, it does, however, promote lung growth. CD-1 murine fetal lungs were cultured for 7 days in the presence and absence of 10 nM Dex. Dex-modulated genes were investigated and identified by differential display of mRNAs performed with specific anchor primer H-T(11)G and 24 arbitrary primers. Thirty-five differentially expressed cDNAs were isolated, subcloned, sequenced, and identified through BLAST searches. One of these cDNAs, termed Dex2, with enhanced expression in Dex-treated lungs, had 100% similarity with ras-recision gene (rrg), also known as the lysyl oxidase (LOX) gene that encodes lysyl oxidase. LOX gene is very highly conserved, with significant sequence similarity among mouse, rat, and human. Two other cDNAs, termed Dex1 and Dex4, were also identified as rrg, with 92 and 97% sequence similarity with the existing data bank sequence of rrg. LOX enzyme is known to downregulate p21(ras) protein and play a central role in the maturation of collagen and elastin in the extracellular matrix as well as modulate the cytoskeletal elements. Thus LOX may be important in lung developmental processes involving epithelial-mesenchymal interactions.

Background/purpose: The mechanisms by which static airway pressures in the developing lung affect development are unknown. The in vitro murine fetal lung model with airway ligation reproduces the phenomenon of intraluminal airway pressure in developing lungs. We have applied the technique of differential display of mRNAs to fetal murine lungs that were maintained in organ culture with and without tracheal ligation. The goal of this investigation was to identify genes that are induced or enhanced by airway pressure during lung development., Methods: Fetuses were harvested from CD-1 mice on gestational day (Gd) 14. The lungs were removed and trachea either transected or ligated and organ cultured for 7 days. Total RNA was extracted from cultured unligated controls and ligated lungs. Reverse transcription (RT) of the purified total RNA from each pooled sample was performed with anchor primer H-T11G or C and one of 24 arbitrary primers followed by polymerase chain reaction (PCR) of the RT mixtures. PCR products were electrophoresed on a DNA sequencing gel. Differentially expressed cDNA bands of interest were cut from the dried gel. Each cDNA was then reamplified. Reamplified cDNAs were extracted, PCR amplified, cloned, and sequenced for homology to existing sequences in the GenBank database., Results: Sequencing identified 4 differentially expressed genes enhanced by tracheal ligation: hepatoma-derived growth factor (HDGF), ribosomal protein S24, stathmin, and parathyroid hormone (PTH)., Conclusions: Genes enhanced by airway pressure or tracheal ligation are mitogenic for fibroblasts, correlate with cell proliferation, regulate cell proliferation and differentiation, and may play a role in growth in distal lung and type II cell differentiation. Further work is necessary to identify the mechanisms by which these genes influence lung maturational processes.

Background/purpose: The addition of growth factors EGF (epidermal growth factor) plus TGFbeta1 (transforming growth factor beta1; E + T) or dexamethasone (DEX) to normal murine fetal lungs in culture enhances lung development. In addition, ligation of the airway in lungs in organ culture, enhances lung development. Nitrofen (2,4-dichlorophenyl-p-nitrophenylether) administration to pregnant mice results in pulmonary hypoplasia in the offspring with many similarities to human hypoplastic lung conditions. This study investigates the effects of growth factors, dexamethasone, and airway ligation on the development of hypoplastic fetal murine lungs in whole-organ culture. We hypothesized that E+T, DEX, or airway ligation will enhance the development and maturation of hypoplastic murine fetal lungs in vitro., Methods: Time-dated pregnant CD-1 mice were given nitrofen, 25 mg, intragastrically at gestational day (Gd) 8. The dams were killed on Gd 14, and the fetuses were removed. The hypoplastic fetal lungs were excised, and the tracheae were transected. The lungs were cultured in serum-free BGJb media in the presence or absence of E+T (10 ng/mL + 2 ng/mL, respectively) or DEX (10 nmol/L). Some lungs were cultured for 7 days with the tracheae ligated., Results: Gross morphology under a dissecting stereomicroscope showed that the lungs were larger after E+T, DEX, or tracheal ligation. Histologically, the untreated lungs had progressed from the pseudoglandular stage to a canalicular-like stage with poorly differentiated airways. The E+T-treated lungs had better developed airway branching and small acini; however, thick mesenchyme persisted. The ligated lungs had well-developed airway branching and acinar structures. After DEX treatment the lungs were most developed with very well defined airway branching and expanded acinar structures; however, there was no secondary septation. Ultrastructurally, the hypoplastic lungs at Gd 14 and after 7 days in culture had no glycogen in their epithelial cells, no defined acinar formation, and had damaged mitochondria. The E+T-treated or tracheally ligated lungs had abundant type II cells, secreted lamellar bodies (LBs), and showed infrequent tubular myelin. Mitochondrial damage was noted in these lungs as in the untreated lungs. DEX-treated hypoplastic lungs showed large acini. The acinar walls were thick; however, they had type II cells with abundant LBs and intact mitochondria. The airways were noted to have differentiated cell types. Surfactant secretions in acinar spaces showed tubular myelin structures., Conclusions: E+T, tracheal ligation, or DEX accelerates lung development and maturation of hypoplastic fetal murine lungs compared with untreated controls. DEX had a greater effect with special reference to repair of mitochondrial damage. DEX not only accelerated lung development, but it may have reversed some of the effects nitrofen.

Background: Pulmonary hypertension (PH) after congenital diaphragmatic hernia (CDH) repair remains a significant cause of morbidity and mortality. Although treatment advances have improved overall survival, a new cohort of patients is surviving with PH beyond the postnatal period. Because the clinical entity of postnatal persistent pulmonary hypertension (PPHTN) in CDH patients has not been published, the authors undertook a retrospective study of our neonatal CDH experience to characterize this group of infants., Methods: Charts of all infants with CDH treated at this institution from January 1991 to June 1997 were reviewed (n = 51). Persistent pulmonary hypertension by echocardiographic (Echo) measurements at the time of discharge identified PPHTN patients. Control survivors had normal pulmonary artery pressures at discharge. Physiological parameters and the results of therapeutic interventions were analyzed to predict PPHTN., Results: Seven infants (four boys, three girls) had PPHTN at discharge. Significant differences with the control group were noted in length of stay, duration of intubation, and duration of nitric oxide therapy. Extracorporeal membrane oxygenation (ECMO) duration was not significantly different between the groups. By 12 months of age, PPHTN resolved in six patients (87%), and one died at 13 months. Regardless of therapy, two parameters showed 100% positive predictive value for identifying patients with PPHTN (P < .001): an Echo demonstrating PH at 2 months of age or continued oxygen requirement at 3 months. Oxygen requirement at 2 months had a 67% predictive value of PPHTN., Conclusions: With current treatment strategies for CDH, infants can survive with persistent pulmonary hypertension beyond the newborn period. The long-term survival rate is excellent, and normalization of pulmonary artery pressures can be expected. PPHTN can be predicted in those infants with Echo-defined pulmonary hypertension at 2 months.

The purpose of this study was to identify differentially expressed genes in normal and nitrofen-induced hypoplastic lungs in fetal mice. Such genes may play a role in the regulation of lung development. CD-1 pregnant dams were gavaged with 25 mg of nitrofen on gestational day (Gd) 8 to induce pulmonary hypoplasia and diaphragmatic hernia (DH). Normal and nitrofen-treated fetuses were removed on Gd 14 and Gd 16. Lungs were examined in all nitrofen-exposed fetuses and only those that had developed severely hypoplastic lungs with coexistent diaphragmatic hernia were taken for molecular analyses. RNA was extracted from normal and nitrofen-treated lungs, reverse transcribed, and PCR-amplified using 48 combinations of anchor and arbitrary primers for each condition. The resulting cDNAs from normal and hypoplastic lungs were run on 6% polyacrylamide differential display gels. In Gd 14 lungs, we observed 10 differentially expressed cDNA bands, of which 6 were identified to be inhibited and 4 were reduced in the hypoplastic lungs compared to normal fetal lungs. From the Gd 16 lungs, a total of 29 differentially expressed cDNA bands were found, of which 11 were reduced, 4 were inhibited, 11 were enhanced, and 3 were induced in the hypoplastic compared to the normal lungs. All 39 differentially expressed cDNAs were cloned, sequenced, and identified through BLAST searches. Among the sequences that were identified, results were as follows: 1) Hypoplastic Gd 14 lungs had two unknown cDNA sequences with reduced/inhibited expressions, whereas one was a known sequence having 77% similarity with a promoter region regulating various cytokines such as IL-1, IL-2, and IL-11. The expression of this sequence was inhibited in the hypoplastic lungs. This sequence also had similarity to lipid-binding proteins. 2) On Gd 16, hypoplastic lungs had one cDNA sequence with reduced expression which had 82% similarity with thyroid hormone receptor gene exon 1 and two other cDNA sequences with enhanced expressions. One of these enhanced cDNA sequences in hypoplastic lungs had 98% similarity with the fibroblast growth factor receptor-3 gene, and the other was an unknown sequence. Northern blot hybridizations were performed to confirm the differential expression of the two sequences of interest, which were identified as thyroid hormone receptor and fibroblast growth factor (FGF) receptor-3. Overall, out of a total of 39 RT-PCR products (i.e., cDNAs), the abundance of which was altered by nitrofen, 6 were found to be homologous to sequences in Gen Bank through BLAST searches. These 6 sequences became the products of interest, and 3 of these 6 products were similar to previously identified genes. Our results may shed some light on regulatory aspects of lung development and open avenues for treatment of hypoplastic lungs and other respiratory problems in human neonates.

Transforming growth factor-beta (TGF-beta), a potent inhibitor of epithelial cell proliferation, and epidermal growth factor (EGF), a mitogenic polypeptide that binds to cell surface receptors, are important regulators of cell differentiation; however, their distinct role(s) in lung development and their mechanisms of action are not well understood. We evaluated the effects of these factors on lung morphogenesis in murine fetal lungs at gestational day 14 (time:zero) and again after 7 days in culture. Baseline controls were cultured after tracheal transection in supplemented BGJb medium, and other tracheally transected lungs were cultured following addition of EGF (10 ng/ml BGJb), TGF-beta1 (2 ng/ml BFJb), or with both in combination added to the medium. The control lungs in culture had poorly developed airways and an absence of defined acinar structures. The addition of EGF resulted in hyperplasia of primary airways with stunted outgrowths, monopodial branching, and absence of distinct acinar structures. Addition of TGF-beta1 alone, led to significant elongation of primary airways, without normal airway branching; however, terminal dipodial branching was seen and the prospective pulmonary acini were well defined. Combination of these growth factors (GF) resulted in a more normal branching pattern and differentiation, suggesting their epigenetic role in lung morphogenesis and mutual interactive mechanisms that regulate lung development. These lungs had more abundant and larger lamellar bodies than those after other treatments. Control lungs remained immature with prominent glycogen aggregates with occasional dense lamellar bodies. The total protein and DNA contents were highest with EGF treatment, followed by combination treatment; these observations were supported by immunohistochemical localization of proliferating cell nuclear antigen, an indication of the proliferative state of tissues. All the surfactant proteins were relatively unaltered and their messages were up-regulated for SP-A, but down-regulated for SP-B and SP-C in the lungs treated with growth factors. In conclusion, we have demonstrated enhanced biochemical and structural development of lungs treated in vitro with GF, and propose that further research in this area may lead to therapeutic uses of GF alone or in combination with other agents for the treatment of newborn respiratory distress due to lung immaturity or hypoplastic lung development.

Studies on lung morphogenesis have indicated a role of homeobox (Hox) genes in the regulation of lung development. In the present study, we attempted to modulate the synthesis of Hoxb5 protein in cultured murine fetal lungs after mechanical or chemical stimuli. Murine fetuses at gestational day 14 (GD14) were removed from pregnant CD-1 mice, and lungs were excised and cultured for 7 days in BGJb media. The experimental groups were 1) untreated, unligated; 2) tracheal ligation; 3) supplemented media with either epidermal growth factor (EGF; 10 ng/ml), transforming growth factor (TGF)-beta 1 (2 ng/ml), dexamethasone (10 nM), EGF + TGF-beta 1, or EGF + TGF-beta 1 + dexamethasone. After 3 or 7 days, the cultured lungs were compared with in vivo lungs. Immunoblotting signals at 3 days in culture were stronger than those at 7 days. Western blot analyses showed that ligation, EGF, TGF-beta 1, and EGF + TGF-beta 1 downregulated Hoxb5 protein to approximately 20-70% of Hoxb5 protein levels in unligated, untreated cultured lungs. Furthermore, dexamethasone alone or in combination with EGF and TGF-beta 1 downregulated Hoxb5 protein by > 90% (P < 0.05) signal strength, similar to that seen in GD19 or in neonatal lungs. Immunostaining showed that Hoxb5 protein was expressed strongly in the lung mesenchyme at early stages in gestation. However, by GD19 and in neonates, it was present only in specific epithelial cells. A persistent level of Hoxb5 protein in the mesenchyme after EGF or TGF-beta 1 treatments or tracheal ligation was noted. Hoxb5 protein was significantly downregulated by EGF + TGF-beta 1, and it was least in lungs after dexamethasone or EGF + TGF-beta 1 + dexamethasone treatment. The decrease in Hoxb5 protein was significant only in the groups with dexamethasone added to the media. Thus immunostaining results parallel those of immunoblotting. The degree of Hoxb5 downregulation by dexamethasone or EGF + TGF-beta 1 + dexamethasone was similar to that seen in vivo in very late gestation, which correlated to the advancing structural development of the lung.

Purpose: The authors hypothesized that increased intraluminal pressure in the fetal stomach would enhance development in a murine organ culture model., Methods: Gestation day 14 (Gd14) fetal stomachs from time-dated pregnant CD-1 mice (term, 20 days) were maintained in organ culture for 7 days. Some stomachs were ligated at the gastroesophageal (GE) and pyloroduodenal (PD) junctions. Others were left unligated. Gd14, Gd16, and Gd18 stomachs were taken as well to compare organogenesis in vivo. Tissues were processed for histological, morphometric, and immunohistochemical analysis, as well as total protein and DNA determination., Results: The ligated stomachs were visibly distended compared with unligated stomachs in organ culture after 7 days. The length and width of the 7-day in vitro ligated stomachs were significantly increased compared with unligated (2.97+/-0.04 mm v 2.48+/-0.05 mm and 2.14+/-0.04 mm v 1.57+/-0.08 mm, respectively, P < .05). Mucosal epithelial cells showed nuclear polarization, and there was a distinct outer muscle layer in the ligated stomachs, but not in the unligated stomachs, which demonstrated pseudostratified epithelial cells in the mucosa. The ligated stomachs had increased in mucosal thickness compared with unligated (31.4+/-1.3 microm vs 24.9+/-0.9 microm, p < 0.05). The ligated stomachs also had significantly increased protein and DNA content when compared with unligated stomachs (65.8+/-3.1 microg and 23.3+/-1.2 microg v 55.0+/-2.7 microg and 19.0+/-1.2 microg, respectively, P < .05). However, there were no significant differences noted between the protein to DNA ratios. Immunohistochemical staining for proliferating cell nuclear antigen (PCNA), a marker for cell proliferation, demonstrated increased proliferative activity of the mucosal epithelial cells in the ligated stomachs., Conclusions: Esophageal and pyloric ligation enhanced the development of the fetal stomach in vitro in comparison with unligated stomachs cultured under similar conditions. Developmental characteristics of the ligated stomachs paralleled that of Gd16 stomachs in vivo.

To evaluate lung development at the level of gene expression, a comparison was made between normal and hypoplastic murine fetal lungs by using the mRNA differential display technique. We focused on altered gene expressions at gestational day (Gd) 19 in normal and hypoplastic murine lungs. Hypoplastic fetal lungs were created by gavaging pregnant mice at Gd8 with 25 mg of nitrofen (2,4-dichlorophenyl-p-nitrophenyl ether) [1]. Normal as well as gavaged mice were euthanized by an overdose of halothane at Gd19, and fetuses were removed by laparotomy. Lungs were excised and total RNA was extracted from normal and hypoplastic fetal lungs. Differential display technique was carried out using the RNAimage kit (GenHunter Corp., TN). Each reverse transcription and polymerase chain reaction (RT-PCR) was performed using one specific anchor primer H-T11M (5'HindIII-T11A/C/G3') and one arbitrary primer. We have used a total of 3 different anchor primers and 24 arbitrary primers for each sample. There were 20 differentially expressed cDNA clones, either induced, inhibited, enhanced, or reduced in hypoplastic fetal lungs as compared to normal. Of these, one clone (NL2) with reduced expression in Gd19 hypoplastic lungs had 100% homology with mouse nucleosome assembly protein I gene. Another clone (NT5) with induced expression in hypoplastic lungs is an unknown gene. Further, analyses of Northern blots of lungs from various gestational ages showed that the expression of NT5 was induced in hypoplastic lungs at Gd18, whereas in normal lungs it was first expressed at the neonatal stage and was increasingly expressed into adulthood. There is a single hybridized band, approximately 400 bp long for NT5 message. Dexamethasone induced expression of NT5 in normal Gd14 pseudoglandular lungs cultured for 7 days; however, different growth factors did not. Northern blot hybridization of multiple adult mice tissues showed NT5 expression in the lung, intestine, and spleen. The thyromimetic action of nitrofen and the interactive functional pathways of dexamethasone with T3 are known. Therefore, we suggest that the isolation and characterization of NT5 may provide valuable information on the regulation of lung development.

The authors have previously shown that murine fetal lungs can be maintained in serum-free whole organ culture and that airway ligation accelerates lung development. In spite of extensive use of lung organ culture systems, the vasculature of the unperfused lung in organ culture has not been studied. The aim of the present study was to compare organ cultures of heart-lung blocks with continuous perfusion of the pulmonary vasculature to those without perfusion, ie, whole lungs cultured without the attached heart. Time-dated pregnant CD-1 mice were killed on gestational day (Gd) 14. The fetuses were removed via laparotomy. Heart-lung blocks and whole lungs without the heart were excised under sterile conditions and cultured in BGJb media. Some of the heart-lungs and whole lungs underwent tracheal ligation whereas others were left with the trachea unligated allowing free egress of airway fluid. After 7 days, the cultured organs were processed for histology, ultrastructural analysis, and immunohistochemistry. (1) Lungs were fixed in 10% formalin, paraffin embedded, and processed for routine H&E staining. (2) Lungs were fixed in 2.5% glutaraldehyde in cacodylate buffer and processed for transmission electron microscopy. (3) Lungs were embedded in CRYOform and flash frozen for immunohistochemical localization of PECAM-1 (CD31) (PECAM-1, Platelet endothelial cell adhesion molecule-1, a selective endothelial cell marker). Our daily observations of the cultured organs showed that the heart maintained synchronized beating for all 7 days in culture. Perfusion of the pulmonary microvasculature was demonstrated. Light microscopically, H&E sections showed that fresh fetal Gd14 pseudoglandular lungs (time-zero) had a defined capillary network, which was more centrally localized and peripherally less developed. The presence of more numerous lung capillaries in the cultured heart-lung blocks was noted when compared with cultured lungs alone. Ultrastructurally, endothelial cells with intact structural integrity were identified only in cultured whole lungs with hearts. Immunohistochemical staining of the whole lungs with rat antimurine PECAM-1 monoclonal antibody performed on cryosections showed the presence of vasculature by specific PECAM-1 localization on endothelial cells. PECAM-1 labeling of capillaries was noted in Gd14 (time-zero) lungs. In addition, the lungs cultured with hearts, ie, perfused lungs, showed more well defined, distinct capillary networks stained with PECAM-1 antibody than unperfused lungs without hearts. Our results showed that microvasculature is present in murine fetal lungs at Gd14. After 7 days in organ culture, the maintenance of lung microvasculature was confirmed histologically, ultrastructurally, and immunohistochemically. The microvasculature in whole lungs cultured as perfused/beating heart-lung blocks was better maintained than the microvasculature of unperfused whole lungs cultured without hearts. A perfused whole lung organ culture model is attractive because the lung architecture is better maintained and may be useful in lung developmental studies as it mimics the in situ heart-lung functional physiological relationship.

Objective: Using an organ-culture fetal heart repair model, we explored fetal repair in tissues other than dermis., Methods: Wounded fetal mouse hearts of 14 and 18 days' gestation (term = 20 days), as well as hearts of 22 days' gestation (newborn), were maintained in serum-free medium. Specimens were fixed at 2, 7, and 11 days and then processed for histologic examination. Small fragments of fetal hearts from all time points were cultured as explants. The migration of cells from the periphery of the explants was compared at day 4, and the pattern of microfilaments in these cells was assessed., Results: In 14-day hearts (n = 18), tissue architecture was rapidly reestablished without an inflammatory response or scarring, constituting regenerative repair. In 18-day hearts (n = 18), no reestablishment of muscle fibers or wound closure occurred. In the 22-day explants (n = 12) the wounds closed by scarring. Cell migration from 14-day explants was 4.7 +/- 2.3 ocular units; from 18-day explants, it was 2.6 +/- 1.1 ocular units; and from 22-day explants, it was 0.9 +/- 0.4 ocular units. Microfilaments of 14-day cells were arranged at the periphery of the cell consistent with cardiomyocytes. Microfilaments of 18- and 22-day cells were arranged in parallel arrays (stress fibers) that were consistent with fibroblasts., Conclusions: We propose that regenerative healing of 14-day fetal hearts is by the migration of cardiomyocytes. At 18 and 22 days, cardiomyocytes are too differentiated and unable to migrate; hence cell migration is limited to resident fibroblasts, which are deficient at 18 days but sufficient at 21 days to be repaired by the scarring process.

Juvenile xanthogranuloma (JXG) is a rare lesion of the skin and deep tissues whose cytologic features have not previously been published. We report on 2 cases of JXG in patients aged 5 days and 5 yr who presented with an axillary mass and enlarged supraclavicular lymph node, respectively. Fine-needle aspiration and touch imprints made from the surgical biopsies yielded cellular specimens composed of histiocytes, multinucleated Touton-type giant cells, and variable admixtures of lymphocytes and eosinophils. One lesion was composed primarily of benign-appearing histiocytes with admixed multinucleated giant cells and a few lymphocytes. The second lesion consisted of a few histiocytes, occasional Touton giant cells, many lymphocytes, and scattered fibroblasts. The histiocytes were CD68-positive and S100-negative. Histologic follow-up confirmed the diagnosis of juvenile xanthogranuloma. One patient was lost to follow-up; the other is alive without evidence of recurrence 1 yr after surgery. We conclude that deep JXG has characteristic and diagnostic cytologic features.

Evidence exists from both congenital anomalies and animal models that normal fetal lung development is dependent on maintenance of fluid pressure within the developing "airways." Fetal tracheostomy, allowing free egress of airway fluids, results in lung hypoplasia, indicating that some airway distending pressure is required for normal lung development to occur. In contrast, fetal tracheal ligation, which increases fetal airway pressure, reverses lung hypoplasia in animal models. The authors' experiments test the hypothesis that large airway obstruction accelerates the development of murine lungs in vitro in whole-organ culture. Fetuses from time-dated pregnant CD-1 mice at day 14 of gestation were removed (term, 20 days), and the lungs were excised. The left bronchus of each lung was ligated (n = 26), after which the left lung was isolated and cultured at 37 degrees C (95% air, 5% CO2) in BGJb media supplemented with vitamin C and antibiotics. Some fetal lungs were cultured under similar conditions without bronchial ligation (n = 11). After 7 days in culture, the lungs were taken for various analyses. The lungs were fixed in either formaldehyde and processed for paraffin embedding for light microscopic evaluation and morphometric data collection, or were freshly minced and aliquots taken for total protein and DNA content. Several more ligated and unligated lungs were processed for ultrastructural analysis. Morphometric analysis on transverse sections of lungs showed significant differences in the lung tissue size, thickness, epithelial cell height, luminal areas, perimeters, and total number of airspaces (airway + primordial alveolar airspaces). It was evident that bronchial ligation promoted lung development. The ligated lungs displayed thinning of the primordial alveolar walls with cuboidal epithelial cells. The total number of airspaces per field was lower for better developed ligated lungs because of the increased area of airspaces compared with that of the unligated lungs. The dorsoventral tissue thickness (in micrometers) of the ligated lungs was significantly greater than that of the unligated lungs (124.1 +/- 7.0 v 89.6 +/- 8.0); the average outer perimeter of the primordial alveolar airspaces was greater for ligated lungs (404.56 +/- 19.0 microns v 256.85 +/- 17.0 microns). Similarly, the luminal diameter of the spaces of ligated lungs was almost double that of the unligated lungs (38.0 +/- 2.0 microns v 20.3 +/- 2.0 microns), as was the luminal surface area. The morphometric data, which suggest enhanced maturation of the ligated lungs, are supported by results of ultrastructural studies. Ligated lungs had significantly more lamellar bodies. Although total protein and DNA content were greater among the ligated lungs, the protein/DNA ratios did not differ among the groups. The intraluminal pressure (airway pressure) of ligated lungs was 2.9 mm Hg and 3.1 mm Hg at 2 and 4 days in organ culture; the respective pressures for unligated lungs were 1.0 mm Hg and 0.8 mm Hg. These data support the hypothesis that mechanical distending pressure resulting from airway obstruction not only improves pulmonary architecture but also accelerates lung development in vitro. Although these effects have been seen in in vivo models, this is the first proposed in vitro organ culture model. This model may prove to be a powerful tool for the study of molecular mechanisms of mammalian lung development with respect to mechanical and chemical (cytokines, hormones) stimuli.

Helicobacter pylori (Hp) was discovered in 1982 by the Australians Robin Warren and Barry Marshall. Initially rejected by a skeptical scientific community, it has since gained worldwide recognition as a clinically significant bacterium. The incidence of colonization with Hp increases with age, affecting approximately one third of the world's population. Hp is uniquely capable of surviving in the acid environment of the stomach, and has properties of adherence to epithelial cells that resist parastalsis. Strains of Hp associated with human disease produce specific cytotoxic proteins. After ingestion, there is a period of intense proliferation and ensuing gastric inflammation that may result in chronic gastritis. Hp infection in children may produce symptomatic antral gastritis or duodenal ulceration. The diagnosis of Hp infection is confirmed by gastric biopsy and culture, where the organism is recognized by its characteristic histological appearance. Treatment for Hp includes combinations of bismuth amoxicillin and metronidazole administered for several weeks. In adults, chronic infection with Hp is associated with chronic gastritis, achlorhydria, and gastric cancer. An organism that was unheard of 15 years ago is now recognized as a clinically significant pathological entity. The ultimate significance of Hp as an agent of disease remains to be seen.

Although fetal dermal repair is known to be fundamentally different from adult healing, the response to wounding in other organs is less well characterized. Scarless repair in mid-gestation dermis with a transition to adult-type healing at term has been shown in fetal organ culture. A lung explant culture system was used to investigate whether wound repair in the fetal lung shows characteristics similar to those found in fetal dermis. Lungs from 14-day and 18-day Cd-1 murine fetuses and 2-day-old newborns, (term = 20 days, n = 24) were wounded by linear incision and incubated at 37 degrees C, in a 21% O2, 5% CO2 environment, in BGJb supplemented with vitamin C and antibiotics. Medium was changed daily. Samples were fixed at 7 days and embedded in paraffin. Sections were stained with hematoxalyn-eosin and Masson Trichrome. Additional 14-day and 18-day samples were frozen in freon and immunohistochemical staining for TGF-beta performed. Other frozen tissues from each time point were homogenized and used to assay for endogenous TGF-beta levels by Western blot analysis. Histology showed reconstitution of tissue architecture across the wound in 14-day and 18-day specimens. In representative histological sections, intact bronchial architecture developed across the previous wound site. No cellular inflammatory response was observed, and collagen deposition was undetectable at the site of the wound by Trichrome staining. By 22 days the lung explants showed a much less ordered repair, including disorganized collagen deposition.(ABSTRACT TRUNCATED AT 250 WORDS)

Nitric oxide (NO) represents a new therapeutic modality for treating neonatal pulmonary hypertension and may obviate the need for extracorporeal membrane oxygenation (ECMO) in a number of cases of neonatal respiratory failure. Recently, the authors treated an infant with a congenital diaphragmatic hernia and pulmonary hypertension with NO on two separate occassions. During the initial period of stabilization, NO failed to reverse the pulmonary hypertension and prevent the development of progressive respiratory failure. After a successful course of ECMO, recurrent pulmonary hypertension developed that was successfully treated with continuous low-dose NO therapy for over 1 month. Prolonged administration of NO in varying doses titrated to clinical and echocardiographic parameters was well tolerated by the infant and prevented the need for a second run of ECMO.

The expression of the inflammatory adhesion molecules intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and endothelial leukocyte adhesion molecule-1, was studied in six infants with biliary atresia using an immunoperoxidase technique on frozen sections. Controls consisted of five patients with various conditions including total parenteral nutrition-induced cholestasis, choledochal cyst, viral hepatitis, metastatic carcinoma, and thrombotic thrombocytopenic purpura. None of the patients were in liver failure. Bile ducts from the control subjects did not express any of the inflammatory adhesion molecules on ductal epithelium. In marked contrast, all of the biliary atresia specimens demonstrated strong intercellular adhesion molecule-1 expression and occasional vascular cell adhesion molecule-1 staining on epithelial cell membranes of both intra- and extrahepatic ductal structures. Hepatocytes and sinusoidal lining cells including Kupffer cells showed a pattern of intense intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression in all specimens with active inflammation that could not differentiate the biliary atresia cases from the control group. Lymphocyte function-associated antigen-1 intensely stained the inflammatory cell infiltrate in the biliary atresia and inflamed control specimens. The strong expression of intercellular adhesion molecule-1 on biliary ductal epithelium in patients with biliary atresia suggests a potential role for this adhesion molecule in the pathogenesis of this devastating neonatal hepatic disorder.

Anterior gastric fundoplication (AGF) has been performed at the University of Michigan since 1988. To objectively evaluate the long-term efficacy of the AGF, the authors performed a study of children who had undergone AGF between June 1988 and June 1990 (n = 46). Six of them died of unrelated causes. Twenty-two consented to follow-up evaluation that included parental interview, physical examination, upper gastrointestinal series (UGI), 24-hour esophageal pH probe monitoring (EpH), and a liquid-phase gastric emptying study. Twenty patients (74%) remained asymptomatic, and only one child required reoperation. Four asymptomatic patients exhibited gastroesophageal reflux (GER) by UGI, and three others by EpH. Three children were noted to have delayed gastric emptying. These results compare favorably with data previously reported from this institution of a 5-year follow-up of children after Nissen fundoplication. There is a trend toward improved efficacy (87% v 74%; P = .12), decreased reoperation rate (4% v 14%; P = .11), and less severe complications. The present study shows that AGF is effective treatment for GER when evaluated by objective studies and is comparable in therapeutic efficacy and safety to the Nissen fundoplication.

This study was undertaken to evaluate factors predictive of postoperative outcome after general surgical (GS) procedures in patients with congenital heart disease (CHD). All patients with a diagnosis of CHD who underwent a GS procedure under general anesthesia during a consecutive 10-year period were considered eligible for the study The congenital heart defect was classified as either simple (ASD, VSD, PDA) or complex (endocardial cushion defects, transposition of the great vessels, tetralogy of Fallot), and the GS procedure as either major (intraperitoneal, intrathoracic, or vascular reconstructive) or minor (inguinal herniorrhaphy, vascular access). The overall mortality rate for the patient population was 12% (27 deaths among 226 procedures), minor procedures being associated with a 3% mortality rate (2 of 70 procedures), and major procedures with a 16% mortality rate (25 of 156 procedures). Incremental risk factors for mortality included a preoperative American Society of Anesthesiologists' (ASA) physical status class of IV or higher (P = .0003), a preoperative in-hospital stay of 10 or more days (P = .004), birth at a tertiary care center (P = .04), and emergency operations (P = .05). In the subgroup of patients less than 6 months old, weight of less than 2.4 kg at the time of surgery and a 1-minute Apgar score of less than 4 were additional independent risk factors (P = .04 and .01, respectively). By logistic analysis, previous corrective cardiac procedures, whether complete or palliative, did not significantly alter the postoperative outcome. The authors conclude that physiologically well-compensated patients with CHD can undergo elective operations at a low operative risk; however, poorly compensated patients undergoing urgent or emergent operations are at high risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: The purpose of this study was to review our experience and early follow-up with 15 one-stage pull-through procedures performed at the time of diagnosis in neonates and infants with Hirschsprung's disease., Methods: Historic chart review of all patients with the new diagnosis of Hirschsprung's disease seen at the C.S. Mott Children's Hospital at the University of Michigan, Ann Arbor, between June 1989 and June 1992 was performed. Progress notes, operative and anesthetic records, pathology reports, and outpatient follow-up notes were used for data collection., Results: Operative technique included a modified endorectal pull-through after determining the presence of ganglion cells by frozen section. No colostomies were performed before or after operation. Three patients had affected family members. All infants were born at term. Operation was performed within 24 hours of diagnosis and as early as 48 hours of age. Twelve patients had standard rectosigmoid disease, two had total colonic disease, and another had long-segment disease. Bowel function returned within 4 days of operation, and feeding was instituted by postoperative day 6 in all patients. All of the patients with rectosigmoid disease are doing well. Patients with long-segment or total colonic disease had more problems but are currently at home and doing well. Morbidity included two postoperative bowel obstructions and three patients with postoperative enterocolitis., Conclusions: A single definitive operation may be used to treat Hirschsprung's disease diagnosed in the newborn. Long-term follow-up in these patients is required.

Complications after nonoperative management of hepatic trauma are rare but include persistent biliary fistula in 4% of cases. Therapy usually involves surgical drainage or hepatic resection to control the fistula. The authors present a case of hepatic biliary fistula treated nonoperatively with percutaneous drainage and endoscopic sphincterotomy. A 16-year-old girl suffered a grade III parenchymal liver fracture to the right lobe in an automobile accident. She was hemodynamically stable with no coexistent injuries and was treated nonoperatively. Over 2 weeks her total bilirubin rose to 3.2 mg/dL, and alkaline phosphatase was 463 U/L. Ultrasound showed free intraperitoneal fluid, and 2 L of bilious fluid were retrieved by paracentesis. A radionuclide scan confirmed massive extravasation of isotope from the right lobe. Two drains percutaneously placed over the parenchymal fracture produced 500 to 600 mL of bile daily. Endoscopic retrograde cholangiopancreatography (ERCP) 1 week later showed a normal extrahepatic biliary system. A 1-cm sphincterotomy was performed without difficulty. Within 72 hours, percutaneous drains produced only 35 mL per day. The follow-up radionuclide scan showed no evidence of extrahepatic biliary extravasation, and 3 weeks later the drains were removed. Six months after the accident, results of the computerized tomography scan and liver function tests were normal. It was believed that endoscopic sphincterotomy reduced fistula output by decreasing the intrabiliary pressure caused by the ampulla, thus favoring internal drainage. This case demonstrates the effectiveness of endoscopic sphincterotomy as an alternative to direct surgical intervention for the management of posttraumatic biliary fistula.

Structural anomalies of the gastrointestinal tract and anterior abdominal wall diagnosed in the perinatal period often require prompt surgical intervention. This article highlights the pathophysiology, evaluation, and management of the more common lesions encountered in the neonate.

Video-assisted thoracoscopy was used to remove a bronchogenic cyst in a 6-year-old boy and a foregut duplication cyst in a 2-year-old girl. Access ports were placed along the site of a proposed thoracotomy incision and chest tube exit site. Thoracoscopic excision was uneventful, and each child left the hospital on the second postoperative day. Video-assisted thoracoscopy has a role in the evaluation and the definitive treatment of intrathoracic masses in children.

In models using both intact animals and isolated lungs of rats, rabbits, lambs, and dogs, application of high airway pressure and resultant lung overdistension has been shown to cause lung injury. Under pathological conditions, the more normal portions of the lung may be subjected to relative overdistension when supranormal airway pressures are used. A small animal model of lung overdistension is presented here to demonstrate that lung injury can be caused by moderate lung overdistension. Rats were anesthetized with Ketamine and pentobarbital. A tracheostomy was performed and arterial and central venous catheters placed. The animal was placed in a plethysmograph and an infant ventilator was used to provide mechanical ventilation. In the first experiment, animals in group A (n = 6, control) were ventilated at tidal volume (TV) of 5 mL/kg for 5 hours. Animals in group B (n = 6) were ventilated at TV 15 mL/kg for 60 minutes and then were returned TV of 5 mL/kg for the remainder of the experiment. Animals in group C (n = 5) were ventilated at TV 20 mL/kg for 60 minutes and then returned to TV 5 mL/kg. Static lung compliance and arterial blood gasses were measured. Wet and dry lung weight were obtained after sacrifice. In the second experiment, animals in group D (n = 4, control) were ventilated at TV 5 mL/kg for 240 minutes and killed. Animals in group E (n = 4) were ventilated at TV 20 mL/kg for 60 minutes, returned to TV 5 mL/kg, and killed at 240 minutes. Fluorescein-labeled albumin was administered to each animal prior to mechanical ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Intraarterial access is used to provide continuous monitoring of systemic arterial blood pressure and to provide access to sample arterial blood. The use of chronic indwelling arterial catheters became commonplace in the 1970s and was rapidly adapted to the care of infants and children. The placement of intraarterial catheters can be technically challenging for even the most experienced surgeon, especially in small infants. Arterial catheters can directly injure vessels, resulting in thrombosis or occlusion. Distal embolization or ischemia can also occur. Catheter flushing may cause retrograde flow with the potential for embolization at remote sites. Local insertion site complications, such as hematoma, hemorrhage, and infection, can occur. Arterial catheters can also be a source of systemic sepsis. Although the risks and complication rates are low, the potential for devastating injury exists and deserves the greatest respect whenever placement of an arterial catheter is contemplated.

Intraosseous infusion was used extensively for the parenteral administration of blood, fluids, and pharmacological agents in the 1940s. The technique was "discovered" and popularized again during the 1980s. Substances injected intraosseously are found rapidly in the central circulation. Drugs should be given in the equivalent dose used for intravenous administration. The preferred site for intraosseous infusion is the proximal tibia. Insertion is performed 1 to 3 cm below the tibial tuberosity on the flat anteromedial surface of the tibia. After about 5 years of age, the distal tibia or femur are the preferred sites. Needles made specifically for resuscitative intraosseous infusion are available. Increased awareness of the role of intraosseous infusion, familiarity with the technique of insertion, and careful use of landmarks to guide insertion should minimize complications.

Systemic oxygen delivery (DO2) is normally four to five times higher than oxygen consumption (VO2), and VO2 is independent of DO2. If DO2 is decreased to less than twice VO2, a state of anaerobic metabolism and supply dependency occurs. Some authors have reported that this biphasic relationship is altered in the adult respiratory distress syndrome or sepsis to a condition of continuous supply dependency. If that were true, it would affect both our understanding and management of metabolism during sepsis. Therefore we measured VO2 and DO2 in a dog peritonitis model. DO2 was regulated with controlled pericardial tamponade. During sepsis VO2 increased 28% from a mean baseline of 5.6 to 7.3 cc O2/kg/min (p less than 0.005). As progressive cardiac tamponade was applied during sepsis, the DO2/VO2 ratio fell. When the DO2/VO2 ratio was greater than 2.4, VO2 remained independent of DO2. At DO2/VO2 ratios less than 2.4, VO2 was dependent on the level of DO2, and it diminished rapidly as DO2 decreased. Oxygen saturation in mixed venous blood (SvO2) consistently reflected the DO2/VO2 ratio in a fashion similar to that in normal dogs. A ratio of DO2/VO2 of 2.4 corresponded with an SvO2 of 42% +/- 12%, which was identified as a statistically significant critical SvO2 that marked onset of VO2 supply dependence. In this dog septic model, VO2 is independent of DO2 when DO2 is adequate. A state of continuous supply dependency does not exist. SvO2 reflects the status of the DO2/VO2 relationship in the septic state.

In pentobarbital-anesthetized dogs, oxygen delivery (DO2) was measured by thermodilution cardiac output and cooximeter determined oxygen content, while oxygen consumption (VO2) was measured independently by spirometry. Oxygen delivery was decreased by isovolemic dilutional anemia, breathing hypoxic gas mixtures, or cardiac tamponade to reduce cardiac output. Baseline VO2 (cc/kg/min) for the three groups was 5.9 +/- 0.7 (anemia), 5.4 +/- 0.4 (hypoxia), and 5.6 +/- 0.1 (low C.O.) (NS). A critical level of oxygen delivery (DO2crit) was found at 9-10 cc/kg/min (anemia), 10-11 cc/kg/min (hypoxia), and 9-10 cc/kg/min (low C.O.) (NS.). Below this level, VO2 fell (became supply dependent) and lactic acidosis occurred, regardless of the mechanism of impaired oxygen delivery.

Abdominal aneurysms are rare in children and are usually found in association with congenital cardiac or aortic malformations, connective tissue disorders, trauma, or previous arterial catheter placement. A 4-year-old girl who had a common iliac artery aneurysm, who had no history of arterial catheter placement or trauma, and who had no evidence of Marfan's or Ehlers-Danlos syndrome, arteritis, coarctation of the aorta, or other diseases associated with childhood aneurysms is presented. Resection of the aneurysm and arterial reconstruction were performed without the use of prosthetic material or vein graft. Pathologic examination showed no evidence of inflammation or medial degeneration in any of the layers of the arterial wall. This is the fourth report found in the literature of documented idiopathic abdominal aneurysm in a child. The conditions associated with abdominal aneurysms in childhood are discussed, and the literature is reviewed.

Thirty-one arterial macroaneurysms in 23 pediatric-aged patients (16 boys and 7 girls) were treated at the University of Michigan. The average age at time of diagnosis was 10.2 years (range 6 months to 18 years). Vessels involved the aorta (4), as well as hepatic (1), splenic (2), gastroepiploic (1), renal (12), iliac (1), superficial femoral (4), popliteal (1), brachial (1), radial (2), and ulnar (2) arteries. Twelve children exhibited overt clinical manifestations including presence of a mass (7), local pain (3), hematemesis (1), and painless obstructive jaundice (1). Eleven children had asymptomatic lesions. Aneurysm existence was confirmed by arteriography or operation. All but one child underwent surgical therapy, with 20 long-term survivors (mean follow-up 3.5 years). One operative death occurred and one death occurred 6 years after surgery. This experience and a review of previously reported cases served as a basis for categorization of childhood aneurysmal disease as true aneurysms associated with (I) arterial infection, (II) giant-cell aortoarteritis, (III) autoimmune connective tissue disease, (IV) Kawasaki's disease, (V) Ehlers-Danlos syndrome or Marfan's syndrome, (VI) other forms of noninflammatory medial degeneration, (VII) arterial dysplasias, (VIII) congenital-idiopathic factors, as well as (IX) false aneurysms associated with extravascular events causing vessel wall injury or disruption. Knowledge of the varied clinicopathologic characteristics of arterial aneurysms in children is important in treating these patients.

Options for mechanical support of pediatric patients with severe heart failure who are awaiting transplantation or have undergone transplantation are limited. This report examines 3 patients placed on extracorporeal life support (ECLS) while awaiting transplantation and 3 patients who underwent transplantation and suffered subsequent heart failure due to rejection or postoperative myocardial dysfunction. The overall survival rate was 2 of 6. The 2 surviving patients had a failing transplanted heart. There were no survivors among the patients placed on ECLS as a bridge to transplantation. In each case a contraindication to transplantation developed before a donor heart could be obtained. The mean time of ECLS support was 147.5 hours (range, 70 to 370 hours). The ECLS circuit did not affect cyclosporin levels or antirejection therapy. Extracorporeal life support can be used to support pediatric cardiac transplant patients with biventricular failure due to acute rejection or postoperative dysfunction. Although the results have been discouraging, ECLS may still have a role as a bridge to transplantation. However, complications can develop during ECLS that may preclude transplantation.

A compact closed-circuit gas exchange monitor (GEM) was built for measurement of oxygen consumption (VO2) in ventilated infants. The GEM includes a ventilator-driven slave bellows, a CO2 scrubber, one-way valves to ensure unidirectional flow, and tubing to complete the small-volume low-compliance system, which fits easily between the ventilator (VENT) and the endotracheal tube (ETT). Oxygen consumption is measured by volume loss from a spirometer attached by a one-way valve. Pressure is monitored at the airway, and the VENT is adjusted to attain the desired pressure pattern. The system was leak tested by placing a 3-kg weight on the spirometer bell (continuous positive airway pressure = 20 cm H2O) and then ventilating with peak inspiratory pressures (PIP) of 60 cm H2O without leak. Bench testing for accuracy of volume loss was checked by ventilating the device into another calibrated spirometer and achieving equal volumes. First, four rabbits were studied to determine the range of ventilator backup rates (BUR = 0 to 60), inspiratory times (IT = .2 to .6 seconds), and airway pressures (up to 40/8 cm H2O) attainable by this device. Then six fasted rabbits weighing 2.2 to 4.0 kg were anesthetized with a ketamine-rompun mixture, underwent tracheostomy, and were placed on a pressure VENT. The BUR was set at 20/min and the IT at .5 seconds. The GEM was placed between the VENT and the ETT, and the PIP was adjusted to maintain PaCO2 between 30 and 40 torr, eliminating spontaneous respiration. Oxygen consumption was measured at five-minute intervals for one hour.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma of the esophagus continues to carry a very poor prognosis. Previous studies have rarely reported the exact cause of death in these patients. Twenty-five autopsies were retrospectively reviewed in patients with the diagnosis of carcinoma of the esophagus, noting the cause of death. Two-thirds of all patients with unresected middle-third lesions ultimately died as a result of direct extension of the tumor into the aorta or tracheobronchial tree. Other findings included a high incidence of second neoplasms (12%) and the lack of an antemortem diagnosis of esophageal cancer in three of four females in the series.

In a national registry, data were collected on 715 newborn patients with severe respiratory failure supported by extracorporeal membrane oxygenation (ECMO) in 18 neonatal centers. This represents almost all infants treated with ECMO between 1980 and 1987. Eighty-one percent of the patients survived. This result is statistically significantly better than any other treatment which produces less than 78.4% survival. The most common diagnoses were meconium aspiration (310 patients, 91% survived), respiratory distress syndrome (96 patients, 78% survived), diaphragmatic hernia (121 patients, 65% survived), and sepsis (64 patients, 72% survived). Average pre-ECMO characteristics were: age 59 hours; PaO2 42 torr, PaCO2 41 torr, pH 7.40; ventilator settings FiO2 1.0, pressure 45/4 cmH2O, rate 93. Technical complications occurred in 23.1%, and physiologic complications occurred in 65.6%. Results improved with experience. Survival rate for the first ten patients from each center was 73.5% compared to 83.7% for all subsequent patients. Survival rate did not, however, significantly differ after an institutional experience of 20 patients. These observations were made on a large cohort that could not be accumulated at an individual center. These results indicate that ECMO and lung rest is appropriate and successful treatment for newborn respiratory failure unresponsive to other means of management, and that almost all respiratory failure is reversible in near-term neonates.